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Pamela A. Davol, 76 Mildred Avenue, Swansea, MA  02777-1620.
pdavol@labbies.com


Cancer In The Canine

Cancer Letters

A compilation of selected letters from my archives addressing issues pertaining to various forms of cancer.

Contents:

Acanthhomatous epulis (1 entry)
Chemodectoma (2 entries)

Fibrosarcoma (2 entries)
Hemangiosarcoma (4 entries)
Histiocytosis and Histiocytic sarcoma (1 entry)
Insulinoma (1 entry)
Intestinal tumor (Non-classified) (1 entry)
Lung Cancer (Lung Adenocarcinoma) (1 entry)
Lymphoma/Lymphosarcoma (3 entries)
Mast Cell Tumors (4 entries)
Mast Cell Tumor (Mastocytoma) vs. Histiocytoma (1 entry)
Meningiomas
(1 entry)
Nasal Cavity tumors (1 entry)
Neurofibromas (1 entry)
Oral Malignant Melanoma (1 entry)
Osteosarcoma (1 entry)
Sarcomas (Malignant Mesenchymomas  and Myxosarcomas
) (1 entry)
Squamous Cell Carcinoma (1 entry)
Tumor on the Leg (Non-classified) (1 entry)

Fibrosarcoma

"Our young Kerry Blue has just been found to have a fibrosarcoma. We are looking for a specialist ...to discuss treatment options with and, if the options/chances of survival are promising and humane, someone to do the treatment. Do you have any suggestions? Also, do you have any thoughts regarding the best treatment for this type of malignancy in such a young animal? Thank you for your consideration...."

Fibrosarcomas, in general, can be very invasive to the local surrounding tissues but do not often have a high rate of metastasis. Typical treatment for fibrosarcomas includes wide-margin surgical excision to ensure that all the cancer is removed. In many cases, fibrosarcoma can be cured with surgery alone. Often, however, when fibrosarcomas occur on limbs, their is difficulty in performing this type of excision to an effective extent, so a surgeon may recommend amputation. When amputation is not desired, or in some cases of fibrosarcomas occurring in dogs under 2 years (which have a tendency to be more invasive) radiation therapy has been effective at controlling disease. Radiation therapy, however, is most effective for fibrosarcoma when combined with hyperthermia or surgery/chemotherapy. For this reason, a Veterinary Medical School would provide the best treatment options in regard to available resources and most current treatment options. You might try contacting David J. Waters, DVM, PhD, Veterinary Oncologic Surgery, Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana 47907 e-mail: waters@vet.purdue.edu  

___________________________

 "My 16 year old beagle was just diagnosed with mandibular fibrocarcinoma. Although the vet has recommended a partial removal of the lower jaw, I am not convinced, given the age of my pet, that I want to put her through such a radical procedure. I have not yet picked up the lab results to see just how far the cancer has spread. In researching this type of cancer, I see that fibrocarcinomas can be responsive to radition therapy, perhaps controlling the cancer an average of 12 months. Given the age of my pet, I am leaning towards radiation therapy at this point. I'd like your opinion on this. Thanks in advance for your time...."

 Fibrosarcomas of the mandible are tumors with a high rate for local invasion and destruction of tissue. (Mandibular fibrsarcomas) also tend to metastasize. If (your dog) were a young or middle-aged dog, then I would agree with your vet in recommending an aggressive approach to therapy such as mandibulectomy and even adjuvant therapy with radiation and/or chemotherapy. Wide surgical excision is required to reduce risk of recurrence. I don't know how much of (your dog's) mandible is involved and how much excision would be necessary. Given (your dog's) age, I fear that surgery of this nature may compromise her further without necessarily providing any benefits of increasing survival time (primarily because of the possibility of occult metastasis). Radiation therapy alone has provided a palliative approach for fibrosarcoma in dogs who are not candidates for surgery and in some cases remission of the disease. Radiation therapy alone has provided an average of about one year in terms of survival compared to no treatment. Surgery combined with radiation has provided longer survival times in some cases. Results of any therapy, however, will depend on whether or not metastasis has already occurred (which may or may not be detectable at this time). This of course is only my opinion and I recommend that you seek the opinion(s) of one or more other veterinarians, preferably one who specializes in oncology.


Acanthomatous epulis

"I have a 14 year old Scottie dog who has been dx'd with an acanthomatous epulis of the mandible. I'm interested in any info about the use of bleomycin for treatment of this. Your article was the only place i've been able to find it referenced. Apparently there are no radiation facilities available here for dogs and a mandibulectomy does not sound like something i'd want to put him through. Thank you very much."

Epulides are the most common benign tumors of the oral cavity and arise from the periodontal connective tissue. There are different classifications of epulides with acanthomatous being the most prevalent (comprising 40% of diagnosed epulides). Epulides do not metastasize but they can be locally aggressive, particularly acanthomatous epulides that can cause significant degeneration of adjacent bone regions. One concern encountered with acanthomatous epulides is that they are sometimes difficult to differentiate from squamous cell carcinoma (SCC) which are malignant tumors with the potential (low to moderate risk) to metastasize.

The most common therapy for epulides is wide-margin surgical excision and/or radiation therapy. Unfortunately, of the different classifications of epulides, acanthomatous epulides have the highest incidence for very rapid and repeated recurrence following surgical excision. Because radiation therapy may not be available in all clinical establishments, alternatively, intralesional administration of bleomycin has been found to cause regression of these epulides and inhibit acanthomatous epulides from recurring, similar to results obtained with radiation treatment. Yoshida and colleagues have presented several papers on bleomycin therapy for epulides:

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9826279&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10487228&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9921754&dopt=Abstract

 

Follow-up:

"Thank you for responding! I've forwarded the information to (my vet). Do you feel that it is worth a try since radiation is not available here and mandibulectomy seems too much to ask of a 14 year old dog? I feel that the general consensus of veterinarians is that the pets do better with the surgery than the "owners" do -- i just feel that since there's a high rate of recurrence even with surgery that i just don't want to do that. I don't understand why it (bleomycin) sounds so good in the Yoshida studies but there's no mention of it anywhere else!? Can you shed any light on that for me? Is information available as to dosages, procedures, etc. if the bleomycin is something we decide to try? I very much appreciate any and all information."

In regard to your specific questions:

>>>Do you feel that it is worth a try since radiation is not available here and mandibulectomy seems too much to ask of a 14 year old dog?

I think that risks to benefits must be weighed for each possible approach. Clearly, older dogs run higher risks related to anesthesia required for surgery. Additionally, hemimandibulectomy is a quite involved surgery that typically results in long-term physical and functional deformity. According to Yoshida's observations, intralesional administration of bleomycin resulted in no observable adverse reactions. Under these circumstances, and in light of the reported success of intralesional bleomycin administration, this may offer a viable alternative to surgery with lower risk for complications.

>>> i just feel that since there's a high rate of recurrence even with surgery that i just don't want to do that.

Recurrence is high in patients that receive only wide-marginal surgical excision of the acanthomatous epulides. In contrast, hemimandibulectomy is generally curative.

>>>I don't understand why it (bleomycin) sounds so good in the Yoshida studies but there's no mention of it anywhere else!?

Actually, bleomycin is commonly used either alone or in combination with radiation therapy for many oral forms of cancer, particularly squamous cell carcinoma. Many of the studies being conducted on oral cancers have come out of Japan, where there is a higher prevalence of oral cancers. The Japanese have been using bleomycin, radiation, and surgery for many years now in the treatment of these tumors. Japan has some of the top oncology specialists in this area of treatment. Unfortunately, however, in medicine, there are limitations that occur in regard to dissemination and acquisition of information. There is simply not enough time for those in general practice to sift through all the clinical data that becomes available on a daily basis in all the different areas of medicine. Additionally, Yoshida et al.'s report on intralesional administration of bleomycin (a novel approach, since bleomycin is typically administered intravenously for treatment of oral cancers) only documented results for 4 dogs. Though all four dogs had complete remissions, a study group of this size constitutes only anecdotal observations (i.e. these results may not represent the therapeutic response that would be encountered in the general population of the dogs diagnosed with epulides).

>>>Is information available as to dosages, procedures, etc. if the bleomycin is something we decide to try?

Yoshida used 5 mg bleomycin administered once per week intralesionally for 3 to 8 weeks, longer if necessary. Your vet will be able to access the complete procedure in the reference paper I provided to you earlier.


Neurofibroma

" I have an eleven years old boxer,a female...,which is very sick. In April,last year,she suffered a surgical intervention for a tumore of soft tissue situated on her left cheek.The hystopathological exam showed a "NEUROFIBROMA". After five months the tumore reappeared and the byopsy said "cancer-neurofibrosarcoma". She suffered a second surgical intervention in which she lost her left eye,the orbit and a part of the zygomatic arch.The vet tried to stop the evolution using specific anti cancer drugs such as Vincristine,Adriamycine,Ciclofosfamide. She felt very bad and I had to interrupt the treatment. Meanwhile,the hystopathological exam of the extirpated tumore (eye, orbit...) said 'Schwannoma' (NEUROFIBROMA, NO CANCER). She was O.K. till December when I saw the tumore starting to grow again. In January, a third intervention left her without a part of her masseter muscle. In spite of all these,she feels O.K.,her behaviour is normal,she eats,she plays (her physical condition is excellent) - she's happy. Her blood tests and echographic exams of the internal organes are O.K. too. The problem is that now  I see the tumore beginning to grow,and the vet is out of answers ... Could you,please,tell us what can we do to stop the evolution of the tumore? Do you know any other treatment? I thought that,as long as she is fighting with the disease and wants to live, I have to help her, I have to do everything is possible; I own her that!..."

I wish I had good news for you, but as you may know at this point, neurofibroma is an extremely difficult form of cancer to cure. Though it does not have a high metastatic rate (spreading to distant organs), it is extremely locally invasive and even when it appears that the entire tumor is excised, neurofibroma will still, in most cases, recur. The most anyone can hope to accomplish is to slow the progression of the disease. Surgery and systemic chemotherapy are palliative options that you have already explored. Because (your dog) has already undergone extensive surgery at this point and because she did not tolerate the side-effects of systemic chemotherapy very well, the options are becoming fewer.

Recently, there have been reports in the literature describing a novel approach of electrochemotherapy for the treatment of neurofibroma in dogs. This type of treatment entails combining intratumoral injection (directly into the tumor) of cisplatin followed by administration of electrical pulses to the tumor, which facilitates the drug to enter the tumor cells and thus render its toxic effects. Because cisplatin is delivered locally to the tumor, there are lower risks for any side-effects to the patient. Additionally, since (your dog) has not previously been administered cisplatin therapy, there is a likelihood that she would be a candidate for this type of therapy (i.e. if she had previously received cisplatin there is a risk that her tumor has already manifested resistance to cisplatin therapy).

The following is an abstract from a publication by Dr. Nataša Tozon on use of electrochemotherapy in dogs. Your vet may wish to contact Dr. Tozon (tozonna@mail.vf.uni-lj.si)  for consultation on this matter:     

Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats. Tozon N, Sersa G, Cemazar M. University of Ljubljana, Veterinary Faculty, Small Animal Clinic, Slovenia. Anticancer Res 2001 Jul-Aug;21(4A):2483-8.


Squamous Cell Carcinoma

"I saw your web site and decided to write to you about my black standard poodle who has been diagnosed with squamous cell carcinoma in two toes (different back paws). The first digit of each toe was taken off and tested and it showed carcinoma. Is the protocol to take the entire toe off? If radiation is done, can it be done on the affected toes instead of taking the toes off? I cannot find much literature about this. There is a veterinary oncologist ... near where I live, but she does not do radiation. I was just wondering if you had dealt with this type of cancer and if so, what was done. I realize every case is different, but any information would help. Our dog is female and 7-1/2 years old. About 1-1/2 years ago she had an entire toe removed from her right back paw but the veterinary said that it was necessary because when she dislodged her toenail, part was forced back into the toe and eventually it had to be removed. I believe that it could have been the carcinoma at that time but the toe wasn't tested. Any help or information you could give me would be greatly appreciated. Our poodle is a part of our family and we want to do everything we can for her. Thank you..."

Squamous cell carcinoma (SCC) of the claw arises from the germinal claw epithelium and is the most common tumor affecting the toes in the dog. It arises most commonly in black dogs and there appears to be a genetic predisposition for this cancer particularly in certain bloodlines of Labradors and Standard Poodles. Usually in these two breeds, the cancer may gradually progress to involve multiple toes over a period of several years. Typically, however, SCC tumors of the claw grow very slowly and have a low incidence of metastasis. Amputation is the most common treatment for this tumor. Prognosis for cure or prolonged disease-free survival with surgical-amputation is good. If regional lymph node metastasis has occurred by the time SCC is diagnosed, then the veterinary oncologist may recommend lymph node excision or limb amputation to prevent further spread of disease. The folowing are abstracts from two peer-reviewed articles on SCC of the claw:

1) J Am Vet Med Assoc 1995 Sep 15;207(6):726-8 Evaluation of dogs with digit masses: 117 cases (1981-1991). Marino DJ, Matthiesen DT, Stefanacci JD, Moroff SD Department of Surgery, Animal Medical Center, New York, NY 10021, USA.

2) J Am Vet Med Assoc 1992 Sep 1;201(5):759-61 J Am Vet Med Assoc 1992 Oct 1;201(7):1090 Treatment by digital amputation of subungual squamous cell carcinoma in dogs: 21 cases (1987-1988). O'Brien MG, Berg J, Engler SJ Department of Surgery, School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

Since most SCC tumors of the claw are localized with low incidence of metastasis, surgical treatment alone has been the successful, first-line treatment against this disease. As such, there is an absence of clinical studies exploring radiation therapy alone or in combination with surgery for SCC of the claw, however, radiation treatment is effective against other SCC's which are more widespread and are considered a higher metastatic risk.


Osteosarcoma

"My wife and I have a Lab mix, just short of 8 years who was just diagnosed with osteosarcoma. We are hoping that (our dog) might be a candidate for a limb sparing treatment, and also hoping that someone with your experience could recommend a vet or site for this treatment. This is a tough one; would appreciate any help you can give."

Limb sparing surgery is a viable option for dogs that meet certain clinical criteria:

tumor confined to the leg and involving less than 50% of the bone
the primary tumor site has been intensively pre-treated with chemotherapy and/or radiation or will receive post-treatment with one or both of these (exception includes small stage I tumors that are confined to the medullary canal that may not require pre- or post- adjuvant therapy.)

There have been considerable advances in the treatment of osteosarcoma over the past decade. Most of these advances have been achieved by a group of surgeons, led by Dr. Stephen Withrow at The Animal Cancer Center at Colorado State University. Because, however, limb-sparing surgery is such a dynamic approach to this disease, there are few teams that have the required expertise for such surgery.

One option is to contact Dr. Withrow who may be able to refer you to colleagues in your area who might have experience with this procedure: http://www.cancercure.colostate.edu/

I hope this information provides some assistance to you.

___________________________________

Tumor on the Leg (Non-classified)

"Our golden was diagnosed with cancer on his leg about two months ago, since then the growth has increased in size about four-fold. They say he is too old (13 years) for amputation; however, I am not convinced that other treatments are not available. (He) is mentally as active as he has always been, he looks forward to his meals, does his daily business with regularity, and still loves the company of the house cats. Is there not anything we can do for this faithful old family pet? Our vet said amputation is the only alternative, but states his age is adetriment. I am not certain that it is time to throw in the towel. Any information you can provide will be greatly appreciated..."

You did not mention the type of cancer that (your dog) was diagnosed with. If it is a form of cancer that has a high potential for metastasis, then I can understand your vet's hesitation to perform surgery. Because of the possibility of micrometastases (in the case of osteosarcoma, about 90-95% of dogs will have metastases at the time they are diagnosed with the bone tumor), your vet is probably concerned about the stress of the surgery and its effects on (your dog's) subsequent ability to cope with wide-spread disease. If (your dog) already has detectable metastasis (usually to the lungs), then palliative surgery (perhaps using a local anesthetic) may be used to reduce the tumor burden. This will not cure the problem, and the tumor will grow back usually requiring another tumor removal at a later time. In regard to possible alternative therapies, much would depend on the type of tumor that (your dog) has. If you question your vet's decision, I recommend that you get a second opinion, perhaps from a veterinary oncologist if there is one available to you. If nothing more, then a second opinion may satisfy your concerns that you are doing all that you possibly can to help (your dog). Unfortunately, even when treatments are available, they may compromise quality of life (with toxicity and debilitation) without providing much gain in terms of prolonging life, especially in geriatric dogs. It is with this understanding that many vets may recommend no treatment, however, it never hurts to get a second opinion.


Lung Cancer (adenocarcinoma)

"I have been searching the internet and reading your webpages about cancer in dogs, but I am unable to find anywhere on the web much information about adenocarcinoma in the lung of a dog. My beautiful 11 year 10 mo. old lab mix was recently diagnosed with this. Prior to bringing him in for a dog bite from a neighbor's dog, he was his usual HYPER, healthy, active self, hiking in mountains and playing with my other two dogs of similar age. He infact was the most hyper of us all. The tumor is a large mass with a small metastisis to either the other lung lobe or within the same lobe (hard to tell due to lobar consolidation). The vets assured that through abdominal xrays and biopsy, the tumor is confined to the lung. But there have been differing opinions on whether surgery can be successful - the internist says that the spread is not via lymph node; the oncologist says that until you do surgery, it is not possible to tell if the metastisis within the lung is via blood vessel or lympth node. His blood workup is excellent - all within normal range for his age. No prior problems ever. Totally healthy and loved dog. He has been on prednisone 15 mg 2x per day for five days, followed by a reduction to 15 mg 1x per day since yesterday. He is doing great on prednisone; eats, chews rawhide, has no side effects, walks in woods one to three hours per day. He's like a less hyper version of himself. No coughing or any problems. Can you help me in any way ; I don't expect a diagnosis, but I am desperate for opinions, information, etc. from anyone who knows anything... I accept that if he is to die, I'd rather he live out his days happily as opposed to pain from rigors of intervention. BUT... given how well he is doing on the prednisone (I know it only masks what is going on) vis-a-vis how awful, anorexic and feverish he was in the ten days it took to get him diagnosed and on it - I am wondering if the doctors in their haste and business (I never got a real consultation on the facts of his case with an oncologist - they were all too busy) maybe left some stone unturned. Specifically, given his prior health and good response to prednisone, might surgery followed by chemo work? Have you heard of cases where the animal after such treatment, can live up to a year or more? The oncologist ...said that because of the metastisis (not knowing if it was blood or lympth borne), even though confined to the lung, the prognosis might be only two to four months. But I don't think he had all of the facts of this particular dog when he made that general statement. I in no way have problems with (the) workup; I just want to turn every stone in case I am missing some kernel of hope..."

I'm so sorry to hear about your beloved (dog). I know how frustrated and helpless you must be feeling. Because there is evidence that metastasis may have already occurred and given the age of your dog, I can understand your veterinarian's hesitation to proceed with surgery at this point. There may be possible alternatives to surgery, however, which may provide (your dog) with some help without the high risk of toxicity associated with conventional systemic chemotherapy. Dr. David Vail and colleagues at the Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison (email: vaild@svm.vetmed.wisc.edu ) published results last year on a study exploring the therapeutic efficacy of the anticancer drugs, taxol and doxorubicin (both of these drugs have efficacy against adenocarcinoma), delivered to lung tumors in dogs by inhalation. The results of the study were quite promising and showed low risk for toxic side-effects compared to when these drugs are administered by the usual systemic method. You might try e-mailing Dr. Vail or have your veterinary oncologist contact him or one of his colleagues to consult on this method of treatment. The following is the abstract from Dr. Vail's paper:

Clin Cancer Res 1999 Sep;5(9):2653-9 Inhalation chemotherapy for macroscopic primary or metastatic lung tumors: proof of principle using dogs with spontaneously occurring tumors as a model. Hershey AE, Kurzman ID, Forrest LJ, Bohling CA, Stonerook M, Placke ME, Imondi AR, Vail DM Department of Medical Sciences, University of Wisconsin-Madison 53706, USA. 

Another group has been using a similar inhalation therapy using immunotherapy with interleukin-2 (see the following abstract below). For more info on this treatment, you can contact Dr. Jeffrey Klausner, Department of Small Animal Clinical Sciences, e-mail: klaus001@tc.umn.edu .

Cancer 1997 Apr 1;79(7):1409-21 Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Khanna C, Anderson PM, Hasz DE, Katsanis E, Neville M, Klausner JS Department of Small Animal Clinical Sciences, University of Minnesota, St. Paul 55108, USA.

Some other information associated with primary lung tumors and prognostic factors as well as surgical treatment of lung metastasis associated with osteosarcoma and patient outcomes (be aware that osteosarcoma is a highly mestatic disease and, in general, is much more invasive than adenocarcinoma; I've included the info because the results of this study showed some significant benefits of surgery against the lung metastasis):

J Am Vet Med Assoc 1997 Dec 1;211(11):1422-7 Evaluation of prognostic factors for dogs with primary lung tumors: 67 cases (1985-1992). McNiel EA, Ogilvie GK, Powers BE, Hutchison JM, Salman MD, Withrow SJ Comparative Oncology Unit, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.

Vet Surg 1993 Mar-Apr;22(2):105-9 Resection of pulmonary metastases in canine osteosarcoma: 36 cases (1983-1992). O'Brien MG, Straw RC, Withrow SJ, Powers BE, Jameson VJ, Lafferty M, Ogilvie GK, LaRue SM Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523. 

I hope this information helps. Remember, it never hurts to get a second opinion. Some doctors may be more conservative when it comes to treating a geriatric dog. In cases where the treatment may provide more harm than benefit, this approach is understandable. However, occassionally, there may be some new therapies with low risk to quality-of-life for which a doctor may not yet be familiar.


Mast Cell Tumors

"I found your site while researching mast cell cancer for my Lab... I have one question I haven't found any info on: Is there any difference in the behavior of the lipoma-like mast cell tumors vs the more common ulcerated types? My 12 12/2 yr old Lab had 2 mast cell tumors removed..Another lump was removed last week and there is another there (scrotum) that I am trying to decide how to handle. The recent test results show: "...moderately differentiated grade 2 mast cell tumor. Especially those in this location are generally aggressive and have very unpredictable behavior. May recur as well as metastasize. Prognosis is guarded." I am trying to make an educated decision for my dear old dog (he is in good shape and spirits otherwise) - wondering if you've seen any info regarding differences by outward "type". He had the first lump for years - vet thinking it was a lipoma that did not need to be removed. Every lump so far he has thought was not cancer until the report comes back - now we assume the other is. Anyway, not to go on forever - he already does not fit most of the studies/cases I have read about and thought you may be able to point me to more "unusual" cases I can research..."

Ulceration of tumors does correlate with a more invasive phenotype and poor prognosis: see

J Vet Intern Med 1999 Sep-Oct;13(5):491-7 Prednisone and vinblastine chemotherapy for canine mast cell tumor--41 cases (1992-1997). Thamm DH, Mauldin EA, Vail DM. Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA.

Among other factors that have been found to have a significant impact upon survival of dogs with mast cell tumors are the histological grade of the tumor and recurrence of tumors following excision. In regard to histology, the more differentiated the tumor (the closer it resembles normal cell type) the better the prognosis. As such, tumors that tend to be diploid (twice the normal number of chromosomes) have a better prognosis than tumors that are aneuploid (multiple times the number of normal chromosomes). Interestingly, one study found that the mast cell tumors that occur within a particular dog often demonstrate a similar histological pattern within that dog:

Ayl RD, Couto CG, Hammer AS, Weisbrode S, Ericson JG, Mathes L. Correlation of DNA ploidy to tumor histologic grade, clinical variables, and survival in dogs with mast cell tumors.Vet Pathol 1992 Sep;29(5):386-90:

Therefore, a dog that develops a fairly differentiated mast cell tumor at one point in time and then later develops another mast cell tumor at another point in time, that second tumor will often demonstrate the same histological pattern as the first. Therefore, it may be expected that dogs with low-grade (diploid), well-differentiated tumors would have a better anticipated survival than dogs with high-grade (aneuploid), poorly differentiated tumors. The greatest risk is that which occurs as a result of metastasis. If Ayl et al's. findings are indeed the norm for mast cell tumors, then based on (your dog's) previous history, it could be predicted that these tumors may be less invasive, however, the longer a tumor is allowed to remain in the host, the greater the risk for mutations that may alter the histology and thus lead to a more invasive cell type. Therefore, the truth of the matter is: no one knows for sure how this will progress. My opinion and this is an opinion of the Lab lover and not the cancer researcher: if one of my Labbies was in the same position, healthy and happy in all other aspects, normal appetite, etc. I would have a chest and abdominal x-ray taken. If all was clear, I would proceed to have the scrotal tumor removed, (and I would probably request to have the entire scrotal sac removed at the same time). Then I would probably re-x-ray every 6 months. If, on the other hand, the chest, abdomen or both views indicated the presence of metastases, then I would probably not do surgery, maybe place my Labbie on prednisone, see:

J Vet Med Sci 1997 Nov;59(11):995-1001. Inhibitory effects of glucocorticoids on proliferation of canine mast cell tumor.Takahashi T, Kadosawa T, Nagase M, Mochizuki M, Matsunaga S, Nishimura R, Sasaki N.Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, Japan.

...and allow him to live out what ever time of quality life he had remaining. Of course there are other experimental therapeutic regimens that may be considered. You might check out the following articles:

J Vet Intern Med 1999 Sep-Oct;13(5):491-7. Prednisone and vinblastine chemotherapy for canine mast cell tumor--41 cases (1992-1997).Thamm DH, Mauldin EA, Vail DM. Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 53706, USA.

Clin Cancer Res 1998 Sep;4(9):2207-18. Photodynamic therapy of naturally occurring tumors in animals using a novel benzophenothiazine
photosensitizer.
Frimberger AE, Moore AS, Cincotta L, Cotter SM, Foley JW.The Harrington Oncology Program, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts 01536, USA.

Vet Radiol Ultrasound 1998 Jan-Feb;39(1):57-62. Radiation therapy for incompletely resected canine mast cell tumors.LaDue T, Price GS, Dodge R, Page RL, Thrall DE. Department of Companion Animal and Special Species Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.

I hope these references address some of your questions.

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"We have a six year old Golden Retriever that was diagnosed with cutaneous mast cell tumor on a hind toe . The diagnostic procedure was performed on fluid extracted from a fairly small lump . The test showed frequent heavily granulated generally well differentiated tumor cells . My question is --who would you recommend as the highest qualified most up-to -date Oncologist . Thank you in advance for your help . Ps. Our dog is scheduled for surgery this Tuesday."

There are several factors that you mention that suggest a favorable prognosis: 1) the biopsy showed the tumor to be well-differentiated indicating that the cells, though malignant, are still very similar to the normal cells they originated from and therefore, have a lower incidence of metastasis; 2) the tumor is on a limb and not the torso (tumors localized to the limbs have a lower incidence of recurring once excised. Because tumor recurrence after excision is associated with a poorer prognosis, tumors on the limbs are generally considered to carry a more favorable prognosis); and 3) (your dog) is still a young dog and young dogs are better able to tolerate cancer treatments. Additionally, you did not mention whether or not the tumor was an ulcerative tumor. If the tumor is more cyst-like (fully encapsulated) and not sore-like in its appearance, this also is a good sign in terms of treatment outcome and prognosis. During (your dog's) surgery, the veterinary surgeon will perform a wide surgical excision, removing the tumor as well as a wide area of the normal tissue that surrounds the tumor. As a precaution, the surgeon will also usually excise a regional lymph node so that it can be examined by the pathologist for evidence of tumor metastasis (a condition that would indicate the need for a more aggressive treatment protocol). In (your dog's) situation where the tumor is well-differentiated, the vet may not recommend "adjuvant" therapy to reduce incidence of recurrence. For example, if the tumor were moderately-differentiated, which carries a higher incidence for recurrence after surgical excision, radiation therapy would be recommended to reduce the likelihood of the tumor coming back after surgery. When dealing with a well-diferentiated tumor most vets will stand on surgery alone, then if the tumor recurs, they will utilize surgery and radiation. Of course, each time that the tumor recurs, it usually is more aggressive in nature. Therefore, the question becomes: Does one over-treat a low-grade tumor to ensure that it doesn't return, or treat according to grade and risk incomplete eradication? This is a judgement call and the reason why obtaining more than one opinion comes in handy. Dealing with cancer, I personally believe that over-treatment is the best option more often than not for several reasons, one of those being that pathology diagnosis has its limitations in regard to sampling an accurate representative of cells from a tumor population. Therefore, it is possible for a tumor to be "under-graded". Therefore, in the situation of a young, healthy dog, I personally would want to over-treat to make sure I eradicated everything the first time. But I am not an expert in mast cell tumors, that is why I recommend that you speak to someone who is. Dr. Karri Meleo  is an expert oncologist in mast cell tumors and their treatment. You might consider setting up a consultation with Dr. Meleo to evaluate (your dog's) condition. Since any radiation therapy would be put off for several weeks to allow for surgical wound healing, there is not an immediate rush, but I would call the office now because it may take awhile to get an appointment. Here are a few of her papers: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10909459&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9002168&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8947870&dopt=Abstract

Alternatively, you can find a list of veterinary oncologists by searching the following site: http://www.vin.com/vetquest/index0.html When performing the search, be sure to enter your state in the "state" box and "oncology" in the "choose category" box. I hope this info helps. You might also like to read the following info on mast cell tumors: http://vetinfo.com/dmastcell.html

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"In your "Part 2. Veterinary Oncology and the Dog" , under the heading, Skin Cancer and Treatment, you mention injections of deionized water at the site of the tumor being found to control recurrence of tumors. Case at hand: 8yr 3mo old black lab/pointer male. He had a mast cell tumor removed 2 wks ago from just below the tear duct area of the left eye. We were not able to get it all. The oncologist is recommending 1 month of radiation, MWF. I have read that daily radiation vs. MWF really increases the longevity--mean numbers being 62mo vs.12mo. She is not willing to do the daily radiation because of low manpower. I am now researching to see if I can find a place close enough to take the dog for daily radiation. Not being a vet myself, I could not tell from your article if I could expect the same result from doing the deionized water injections instead of the radiation. Have any studies been done comparing the two? Could I , in your opinion, choose the water injections instead of the radiation with same results--tumor non-recurrence and longevity and health? If so, how many injections and at what intervals would you recommend the treatment be done? I have been told the dog will have to be put to sleep each radiation treatment or highly aenesthetized. What is your opinion of increased danger to the dog if I choose daily radiation instead of MWF? "

Though there have been some reports about deionized water inhibiting recurrence of mast cell tumors, the best results are typically accomplished in those cases where surgery has resulted in complete excision of the primary tumor. Additionally, there appears to be some variability in efficacy of this treatment. Results of radiation therapy are more consistent and therefore radiation has become the routine adjuvant therapy to surgery for treatment of mast cell tumors. As you have read, probably in LaDue et al's paper, daily radiation provided additional increase in efficacy over 3X per week fractionated treatments related to inhibiting recurrence and prolonging survival.

It also never hurts to have a second opinion. Even if you are unable to schedule a daily dosing regimen, earlier studies exploring fractionated radiation have shown a considerable increase in survival out to between 19 and over 60 months in some dogs. In these earlier cases, survival of treated dogs did correlate with several variables including the clinical grade, stage and location of the tumors. Therefore, if your dog's tumor was well-differentiated with no evidence of metastasis to regional lymph nodes, 3X per week may be sufficient to control local recurrence. Moderately-differentiated tumors have a greater risk for recurrence and occult metastasis and therefore are often considered candidates for more aggressive therapy if the patient's underlying health does not contraindicate the use of aggressive therapy.

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"I have gotten two distinctly different answers. My chocolate lab had a level one mast cell tumor removed from her abdomen two weeks ago. The vet, who I like and have always trusted, told me we found it early, AND that "these types of tumors are slow to spread". So keeping a sharp eye should any return we would bring her in for lumpectomy, and all should be fine. OK, well now I see on a message board someone saying the opposite "mast cell tumors are viscous and spread rapidly to organs". Can I have your opinion? I will note,,,, she is 6 yrs old, she suffers from seizures, at this point the vet believes these to be epilepsy, she is on phenobarb twice a day, due to her seizures becoming life threatening (lasting long periods of time and coming in clusters). Any info you can pass along would be helpful, I find lots of info on epilepsy, but not much on the mast cell tumors."

In general, mast cell tumors do have a potential for metastasis (malignancy); however, read my specific comments below in regard to your dog. Wide-surgical excision and biopsy of regional lymph nodes (to detect early metastasis) is recommended for mast cell tumors.

Prognosis for mast cell tumors will be dependent upon several factors:

1) tumor grade (well-differentiated tumors, those whose cells look and behave like normal mast-cells when examined at biopsy, are less invasive and carry a better prognosis than moderately-differentiated or poorly-differentiated tumors); when your vet said that these kinds of tumors are slow to spread he was referring to the tumor level, not mast cell tumors in general (the other people you were talking to were making generalizations and not considering what the biopsy report showed). Your vet was correct: level one suggests that your dog's tumor was well-differentiated which suggests a low risk for recurrence. However, even well-differentiated tumors have a potential for recurrence and metastasis and in the absence of lymph node screening during this first surgery, it's hard to assure freedom of risk to your dog (though most veterinary oncologists would not routinely consider adjuvant therapy for this tumor grade). Other factors are also important to consider:

2) complete surgical excision (recurrence of the tumor after excision suggests a guarded prognosis); if the pathologist noted that the biopsy margins were clear of tumor, then this is a good sign

3) location of the tumor (tumors located on the extremities have a better prognosis than those located on the torso, since when surgically removed, there are fewer cases of recurrence of tumors on the extremities); since your dog's tumor was located on the torso, this may suggest a higher risk for recurrence. As your vet suggested, keep a close eye on any new developments. If there is recurrence, then early detection, surgical excision (be sure to request lymph node biopsy if a second surgery is required) and adjuvant therapy should be considered (keep in mind that each time these tumors recur they are usually more aggressive-i.e. higher level)

4) tumor appearance (ulcerated mast cell tumors are typically more invasive and carry a poorer prognosis compared to mast cell tumors that appear as enclosed nodules). If your dog's tumor was an enclosed nodule, this is also a good sign. Surgery is the treatment for mast cell tumors. In those instances where biopsy suggests a moderately or poorly differentiated mast cell tumor, then the veterinary oncologist will usually recommend radiation therapy as an adjuvant treatment to surgery (to prevent recurrence of the tumor). In cases where metastasis to the regional lymph nodes is detected, then immunosuppressive therapy with corticosteroids may be used to slow the progression of systemic disease.

You can read more about mast cell tumors at: http://www.labbies.com/cancer2.htm#Skin_Cancer .  You might also consider obtaining a second opinion from a veterinary oncologist, if nothing more then to ensure that you have considered all your options.

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Mast Cell Tumor (Mastocytoma) vs. Histiocytoma

"My friend's dog has a lump on his paw. When they took him to the vet they were told it could be one of two things either histiocytoma or mastocytoma. We wondered if you knew the difference between the two and could you explain in simple terms."

A diagnosis of histiocytoma or mast cell tumor will be dependent upon the origin of the cell type from which the tumor developed. Both histiocytes and mast cells are cells involved in immunity. Histiocytes may be macrophages (a type of white blood cell) or dendrites, dependent upon the differentiation of their intermediate precursor cells (that is, both histiocyte types develop from a common precursor cell in the bone marrow, but along the way to maturation, histiocytes may undergo two different types of differentiation leading to either a macrophage histiocyte or a dendritic histiocyte). The macrophage type is involved in ingesting (phagocytosing) foreign "invaders". The dendritic type is involved in processing and presenting antigens to T-lymphocytes to elicit an antigen-specific immune response.

Mast cells are also involved in immune response, but these cells secrete histamine and heparin, chemicals that will attract other immune surveillance cells to the site of infection, and are therefore involved in the inflammatory response.

Tumors involving these cell types frequently appear similar by outward appearance, however, histiocytoma is more frequently observed in young dogs under the age of 3 years. If the dog is older than 3 years, a biopsy is recommended to differentiate between histiocytoma and mast cell tumor because mast cell tumors have a greater potential for invasiveness (malignancy). In some instances cutaneous (skin) histiocytoma may be associated with a disease known as systemic histiocytosis, which affects multiple organs and often requires immunosuppressive (corticosteroid) therapy.

Histiocytomas do not metastasize (they are benign) and will usually spontaneously regress within several weeks without any treatment. They will sometimes recur. If the tumor does not regress, or if it should begin to enlarge, surgical excision and biopsy (with regional lymph node biopsy to detect early metastasis) are recommended since histiocytic sarcomas, a highly malignant tumor derived from histiocytes, may also present as a solitary, rapidly growing nodule.

Mast cell tumors also present as nodules on the skin, but unlike histiocytomas, these tumors do have a potential for metastasis (malignancy). Wide-surgical excision and biopsy of regional lymph nodes (to detect early metastasis) is recommended for mast cell tumors. Prognosis for mast cell tumors will be dependent upon several factors:

1) tumor grade (well-differentiated tumors, those whose cells look and behave like normal mast-cells when examined at biopsy, are less invasive and carry a better prognosis than moderately-differentiated or poorly-differentiated tumors);

2) complete surgical excision (recurrence of the tumor after excision suggests a guarded prognosis);

3) location of the tumor (tumors located on the extremities have a better prognosis than those located on the torso, since when surgically removed, there are fewer cases of recurrence of tumors on the extremities);

4) tumor appearance (ulcerated mast cell tumors are typically more invasive and carry a poorer prognosis compared to mast cell tumors that appear as enclosed nodules) . Surgery is the treatment for mast cell tumors.

In those instances where biopsy suggests a moderately or poorly differentiated mast cell tumor, then the veterinary oncologist will usually recommend radiation therapy as an adjuvant treatment to surgery (to prevent recurrence of the tumor). In cases where metastasis to the regional lymph nodes is detected, then immunosuppressive therapy with corticosteroids may be used to slow the progression of systemic disease.


Insulinoma

"I am looking for help with my 11 year old dog (mixed breed--small Collie/Retreiver) who has been diagnosed with an insulinoma (insulin secreting tumor of the pancreas). His ultrasound shows a diffused tumor area (not a defined mass) with no evidence of it spreading to other organs yet. Surgery seems like a risky option considering his age, likelihood of recurrence and weakened state because of hypoglycemia.   I need help with figuring out what kind of diet he needs--there is very conflicting information out there. He has been on Prednisone now for about 10 >days, which makes him anxious and bloated. Also, he has been on Rimadyl for about 3 years for a hip condition. Otherwise, he's always been a very healthy dog. I want info on alternative supplements,(anything which may slow or stop growth of his tumor) or anything that might help him. "

Though surgery is currently the treatment of choice for insulinoma, as you are aware, there are two points made regarding your dog's individual case that precludes this option: the first, of course, is age which puts your dog at high risk for developing complications during and after surgery; and the second is the observation that your dog's neoplasia is diffuse as opposed to nodular. Nonetheless, there are other options of treatment available for your dog, which I will briefly describe here. If you have not already done so, you might consider discussing these options with your veterinarian or a veterinarian oncologist who may be able to further elaborate on these approaches in direct context to your dog's case and provide you with risk assessments for their use in your dog.

Streptozotocin (Zanasar) is a drug in the early clinical investigation stage that selectively kills pancreatic beta cells and is being used for treatment of insulinoma. Because it is a relatively new drug, its therapeutic use should be limited to those dogs with confirmed insulinoma (pathology diagnosis) or in those dogs demonstrating symptoms of hypoglycemia. Response rate to Streptozotocin is about 30% with variable duration. Toxicities associated with this drug include acute renal failure as well as nausea and vomiting. These toxicities are greatly reduced or circumvented by administering large volumes of fluid therapy during and following administration of the drug and administering antiemetic drugs such as butorphanol (Torbugesic; to inhibit nausea), respectively.

Another similar drug that targets pancreatic beta cells is Alloxan. This drug also requires concurrent administration of fluid therapy to prevent renal damage. This drug has about a 50% rate of controlling hypoglycemia with an average duration of about 3-4 months. Doxorubicin (Adriamycin) has been used extensively to treat various cancers in dogs and may also be used to treat dogs with insulinoma. In humans, doxorubicin is used to treat insulinoma. Unfortunately, data from studies exploring its success rate specifically against insulinoma in dogs are not available. However, because this drug is used so frequently in dogs, dosing regimens have been well explored to determine the best schedule for acquiring efficacy and reducing toxic side-effects.

In regard to using diet in an attempt to control symptoms associated with insulinoma: High protein diets that are also high in fat and carbohydrates are currently recommended for the dog with insulinoma. Feeding should be done by providing small meals 3-4 times per day. The combination of small, frequent meals and prednisone treatment is often successful for controlling symptoms, however, your veterinarian may at some point need to increase dosage of the pred if symptoms cease to be controlled. In cases where the combination is effective at controlling symptoms, your vet may be able to reduce dosage of the pred.

Other drugs that may be helpful for controlling symptoms associated with insulinoma include: Diazoxide (Proglycem), a non-diuretic agent that decreases insulin secretion, promotes glucose production, and inhibits cellular uptake of glucose. This drug is available in tablet or liquid form so that it can be easily administered by the owner. Starting dose is 5 mg/kg twice/day (maximum dose = 30 mg/kg). Side-effects include anorexia, vomiting and diarrhea, but these may be reduced by administering the drug with food. Other side-effects include hyperglycemia, bone marrow suppression, and sodium retention (this latter contraindicates the use of this drug in dogs with heart disease).

In those dogs that may not respond to Diazoxide alone, administering hydrochlorothiazide, a diuretic that enhances the effects of Diazoxide may be administered in combination with Diazoxide to increase efficacy. Octreotide acetate[OA] (Sandostatine) is an analogue of a somatostatin-hormone that inhibits secretion of insulin. Response rates in a very small study of dogs with insulinoma were 75% with documented decreases in serum insulin concentrations. No serious side-effects were observed, although 1 out of the 8 dogs treated did develop diabetes mellitus. Recommended dosage is 1-2 g/kg administered by subcutaneous injection 2-3 times/day. Though it is impossible to predict which dogs will benefit from treatment with OA, because it appears safe with no toxicities observed, some clinicians are recommending this drug particularly in those dogs that are not candidates for surgery or who may not be able to tolerate toxicities associated with other drug regimens.

A reference for the above information is: Meleo KA and Caplan ER. Treatment of Insulinoma in the Dog, Cat, and Ferret. In Kirk's Current Veterinary Therapy XIII (JB Bonagura, ed), WB Saunders Co., Philadelphia, 1999, pp 357-361.


Lymphoma

"Our dog, an eleven year old Staffordshire Bull Terrier was diagnosed with Generalised Lymphosarcoma/ Lymphoma Grade 5a with B-cells. She has for the last seven weeks been on a COP Induction Protocol and is now in complete remission. We have read on your web site that longer remission times have been achieved with other protocols such as ACOPA and Madison-Wisconsin. We also understand that you are one of the leading authorities on the subject. We would therefore be very grateful to know your views on whether we should change at this stage or continue with the Low Dose COP Maintenance Protocol."

First, I'm very sorry to hear of (your dog's) diagnosis, but it's heartening to hear that she has attained disease remission. Second, I thank you for your inquiry and your consideration, however, I consider myself far removed from being an authority in the field of clinical veterinary oncology. I am happy to share what knowledge I do have in this area, however, the information I do provide should only be used as supplemental information. Any decisions made on your part in the treatment of (your dog) should be done so under the guidance of your own veterinarian. The protocol that (your dog) is currently receiving is one of the oldest and mildest therapies for treatment of lymphoma. It is usually selected for those dogs diagnosed with low-grade lymphoma or those dogs that are considered to be at high risk for toxic side-effects induced by more dose-intense protocols. Because (your dog) is a geriatric patient and age-related conditions can predispose to decreased drug-tolerance, your veterinarian probably selected this protocol because s/he believed that the COP protocol provided a reasonable potential for remission and remission-duration without compromising (your dog's) quality of life. When considering remission duration for more treatment-intensive protocols it is important to note that in many instances these protocols, although extending remission duration by 6 months-1 year, often compromise the overall quality of life by causing drug-related side effects. Therefore, the question that many veterinarians and owners must consider becomes: is it better to provide 6 months of quality disease-free life or 8-10 months (possibly) of poor-health? Additionally, severe and immediate-life-threatening toxic side-effects associated with more dose-intensive regimens in older dogs often necessitates that treatment be discontinued. Should this be the case, premature-discontinuation of the protocol would nullify any therapeutic advantage over a milder regimen while further compromising the underlying health of the patient. For this reason, advanced drug protocols such as ACOPA and Madison-Wisconsin, which are associated with much higher toxicity risks, are usually used in younger dogs that are better able to tolerate and thus successfully continue treatment rather than in older patients. That said, there is some recent data regarding dosing of cytoxan (cyclophosphamide [CTX]) that may have some relevance to (your dog's) COP treatment. There are two possible dosing schedules for the CTX portion of the COP protocol that (your dog) is currently receiving: a high-dose administered once every three weeks and a low-dose administered every other day on a weekly basis. You indicated that (your dog) is on a low-dose schedule and based on recent findings this low-dose schedule may have added benefits over the high-dose schedule. One of the major limitations to the success of agents such as CTX is the occurrence of drug resistance within the tumor cells. A recent study indicates that low-dose, frequent administration of CTX (metronomic dosing) may circumvent this ability of tumor cells to develop resistance to treatment through its antiangiogenic effect (targeting and destroying blood vessels to starve tumors) rather than its cytotoxic effect (direct killing of the tumor cells). In this study, frequent low-dose administration of the CTX provided superior efficacy against recurrence of tumors in murine models. Although this has not yet been explored in dogs, this suggests that there may be some advantages, in relation to antiangiogenic effects, to prevent disease relapse using the frequent, low-dose administration of CTX over the high-dose intermittent therapy with CTX in the COP protocol. You can read more about this approach at: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10766175&dopt=Abstract

Even if (your dog) should experience a relapse, try to remain optimistic: Just recently I was contacted by a gentleman whose dog was in her 4th remission from lymphoma. As long as she is assessed as having a generally "good" underlying health, then your veterinarian will probably recommend moving her to an advanced drug combination such as COPLA. Although considered an "advanced drug combo," unlike ACOPA and Madison-Wisconsin, COPLA has a relatively low-rate of toxic side-effects and is better tolerated in geriatric dogs. Additionally, this protocol has been found to induce remissions even in those dogs that have relapsed on milder protocols. Response of rescued, relapsed-patients is about 75-80% with a median response of up to 1 year. There are other potential rescue drugs that demonstrate mild side-effects, however, they provide lower response rates and shorter remissions compared to COPLA. Mitoxantrone has been used as salvage chemotherapy in human patients with non-Hodgkin's lymphoma. Studies in dogs diagnosed with relapsing lymphoma indicate that this drug when used alone is fairly well tolerated and offers a response rate of about 47% with a median response duration of about 84 days. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9773407&dopt=Abstract

Another drug, Lomustine [CCNU; 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea)] also demonstrates limited efficacy at controlling relapse of lymphoma in dogs with a response rate of about 27% and median duration of 86 days. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10499719&dopt=Abstract

Another issue that may be of interest to you is the monitoring of serum alpha 1-acid glycoprotein (AGP) concentrations as a means to predict early relapse of lymphoma. A recent publication by KA Hahn et al. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10200796&dopt=Abstract

suggests that rising concentrations of AGP might serve as an early warning of relapse before clinical disease becomes evident. Earlier detection and thus early intervention with treatment may increase the success rate of rescue protocols to re-induce remission. Finally, there is often much speculation whether cancer may be controlled through special dieting, and a recent publication in the journal Cancer suggests that supplementing the dog's diet with mehaden fish oil and arginine increases disease-free survival (after doxorubicin-induced remission) and survival time in dogs diagnosed with lymphoma. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10760770&dopt=Abstract

I hope this information addresses some of your questions and perhaps provides some new insights for you.

Follow-up:

"You may remember that some time ago you were kind enough to offer your advice regarding our eleven year old Staffordshire Bull Terrier. We are now six months on from her diagnosis of Lymphoma and generally she is doing very well. Just to recap, she started on the COP protocol in September and achieved a complete remission. Then just before Christmas, after we suspected that she was beginning to come out of remission, she started on Doxorubicin and L'Asparaginase. She received three of these at three weekly intervals and experienced very few problems. Six weeks ago the oncologist decided to give her the third one and then wait six weeks until the fourth one. This was in the hope that it would double the length of time she could receive the doxorubicin before risking heart problems. Therefore after three weeks we gave her a high dose (three times the usual) of Cyclophosphamide, after a CBC which was normal, and waited another three weeks for the Doxorubicin. When we went back to the oncologist last thursday (she) seemed to be feeling very well but unfortunately he felt that she had just begun to come out of remission again. He felt the nodes were slightly enlarged but they were not huge and not as big as the two previous occassions. He gave her the fourth dose of Doxorubicin and L'Asparaginase and we have arranged to go back in two weeks time to assess her progress and the options. The oncologist is still hoping that the Doxorubicin will work and is happy to give her the eight doses and risk the toxicity because her general health is so good. The ECG was normal. All this raises a number of questions which you may be able to help us with. Firstly do you think that she is now resistant to the Doxorubicin or is it possible that it was simply too long a gap between the last two doses. Secondly how long would normally go by before we could expect to see her Lymph Nodes go down again if the she has gone back into remission.  It is now three days and although they do seem smaller to me they are still noticeable. Her behaviour is quite normal. Generally she is less tired and has been going out for lots of walks as usual. If they do not go down completely before we go back to the oncologist would it be worth giving another dose of Doxorubicin or would this be unlikely to work. We have also read that even though Doxorubicin has not worked giving Dacarbazine as well can help overcome the resistance to Doxorubicin. Is this correct. And if not what other alternatives would you feel were best to try. The oncologist has mentioned Lomustine. However from what I have read Mitoxantrone might offer better chances of another remission. Another thing that we are unclear about is whether having given one of these rescue drugs, say Lomustine, we can also give another one later on if that does not work. "

I certainly do remember you and (your dog). I am so glad to hear that she has been doing well. When dealing with lymphoma, recurrence following remissions is one of those things that is to be expected, however, at least 70% of dogs will experience a subsequent remission once treatment is re-initiated. So as long as (she) is feeling well, there are still options available for her. Typically, when relapse occurs, many veterinarians will first attempt to address recurrence by returning to the initial induction protocol (original treatment schedule used when lymphoma was first diagnosed) to try to induce another remission. Then, if this fails, an indication of drug resistance, a rescue protocol is initiated. Doxorubicin with dacarbazine (ADIC protocol) is one of the oldest rescue protocols. This drug combination appears to have synergistic effects against cancer. However, studies that have explored response rate of this rescue protocol have focused on dogs that did not receive doxorubicin in the initial treatment regimen. Despite this, veterinarians will still use the ADIC protocol in dogs with previous exposure to doxorubicin. One concern, however, is the potential for cumulative effects of doxorubicin in dogs that have received prior treatment with this drug. Therefore, these dogs should be monitored carefully for cardiac toxicity. There is a chemoprotective iron-chelating agent called ICRF-187 that has been found to minimize cumulative cardiotoxicity associated with doxorubicin treatment in dogs. This might be something to keep in mind.

In regard to dacarbazine, careful monitoring of liver and kidney function is recommended during its use. Vomiting and diarrhea are common side-effects of dacarbazine. There are other rescue protocols but they are very aggressive and have severe side-effects that can result in up to 35% mortality rate. Mitoxantrone has had superior results to lomustine in terms of overall response rates (47% compared to 27%, respectively), however, both drugs appear to yield comparable remission durations (84-86 days) once response occurs. Taken together, therefore, mitoxantrone might be considered the more preferable choice.

In regard to cross-over resistance, this is a major concern in chemotherapy because typically cancer cells that develop resistance to one drug will also demonstrate resistance to other drugs. That is one of the reasons that even when subsequent remissions occur, duration is usually shortened. Therefore, prolonging remission may be dependent upon incorporating other therapeutic approaches with standard chemotherapy. For example, there is clinical evidence supporting the use of the monoclonal antibody, Mab 231, in dogs with lymphoma once they experience remission through chemotherapy. Mab 231 appears to prolong remission durations in these dogs. There is also some indication that "metronomic" dosing (daily, low-dose administration) with cyclophosphamide (CTX) may also prolong remission. This metronomic schedule takes advantage of the antiangiogenic properties of CTX (to target vasculature for tumor inhibition) rather than its cytotoxic properties (to directly target cancer cells). As such, this regimen has the advantage of targeting tumors independent of CTX drug resistance (which is important in the case of relapsed dogs who may have already received treatment with CTX). Unfortunately, CTX can cause potentially fatal side effects and right now there isn't much information regarding a low dose schedule in dogs that would provide both efficacy and safety. Other possibilities include immunotherapy with cytotoxic T cells or high dose radiation followed by CD34+ stem cell transplantation. These latter options are a bit more extravagant and are in the experimental stage, however, they are potentially viable options.

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"Our 10 year old mixed black lab was brought to the Vet's office 2 weeks ago for lethargy and vomiting. We were told that his abdomen was filled with fluid as well as his chest. They extracted 1 liter of fluid from the abdomen and 100 cc of fluid out of his chest cavity. They then took an ultrasound of his abdomen & chest and we were told that he has both an abdominal mass of cancer and it has spread to the chest. There is metasties throughout him. .. When the doctor got the fluid results back, she called it lymphoma. He has been given Prednisone 30 mg. I asked about the Chemo - b/c they do this at the animal hospital, and they thought not, b/c of the wide-spread of the cancer & how the chemo could make him much sicker. Is there any vitamin, herb or drug I can ask her about to extend his life. With the prednisone he is acting normal. I know this does not last long, though. Any answers will be helpful. "

Lymphoma presents very suddenly and is very rapid in its progress. The pred can help for a time, as you know. Additionally, removing fluid periodically from the chest and abdomen can help to ease discomfort and perhaps buy more time. In regard to supplements, there have been some studies on the use of fish oil supplements (omega-3 fatty acids) in dogs with lymphoma. In one study, administering these supplements to dogs before and during doxorubicin-induced disease remissions significantly increased disease-free intervals. In another study investigating the effects of omega-3 fatty acids on human patients with terminal cancers, supplementation inhibited symptoms of cancer cachexia (the devastating wasting process that occurs in cancer patients caused by decreased protein synthesis and increased degradation of skeletal muscle believed to be associated with a factor produced by cancer cells), thus providing a better quality of life during end-stage disease. Cod liver oil contains a high concentration of omega-3 fatty acids. Alternatively, several formulated products are also available for dietary supplementation, such as: 3-V Caps Skin Formula, 6 oz. liquid or capsules http://www.medi-vet.com/fattyacids.asp The former study conducted in humans that I mentioned was conducted as a phase I trial to determine maximum tolerated dose in human patients. The supplement was very well tolerated even at high doses and it was determined that the maximum dose that would not produce any side-efects (diarrhea and gastrointestinal irritation) was 0.3 g omega-3 fatty acids/kg per day. Your vet may also wish to attempt dose escalation to achieve the maximal benefits of supplementation. Though this will not cure or necessarily slow down the progress of the disease, it may assist him in terms of coping with the disease metabolically.


Nasal Cavity Tumors

"Our 9 year old German Shepherd was diagnosed today with nasal respiratory carcinoma. We would like to know what we can do, if anything to treat this cancer. If nothing, then we would like to know what to expect and when, what we should and shouldn't do, what can we do to make his last days more comfortable ,such as feeding him raw steak, and when we need to be ready to put him down. About 2 months ago we noted what appeared to be a tooth abscess on his right, top canine (104). Our vet gave him a round of Antirobe, then Baytril before sending us to a specialist who placed him on Clavamox. After two weeks, the tooth was extracted. The specialist noted lots of abscess material but little sign of infection. Some tissue was sent out for histopath. (Our dog) currently has a lump with the area of an egg on his snout. The specialist suspects the cavity is filling up with abscess material again and recommended we contact an oncologist. It has been almost a week from the surgery and (his) appetite is strong. We switched to soft food from dry and he really likes it. He is fairly energetic and jumps at the chance to go for a walk. He seems about 90% recovered from the operation. I would greatly appreciate any suggestions you can offer and thank you for the information filled web site."

In regard to prognosis, much will depend upon the exact type of tumor that (your dog) has and the tumor-grade. For example, adenocarcinomas, in general, tend to be less invasive than squamous cell carcinomas. Additionally, tumors that are characterized as being well- to moderately-differentiated (meaning that they still have many of the characteristics of the normal cells from which they originated) will have a better expected outcome in terms of disease-survival compared to tumors that are either poorly-differentiated or undifferentiated (tumor cells that have lost all characteristics of the normal cell type). This information should have been included on the pathology report, therefore, your vet may be able to provide you with further insight in this area. Average survival time of dogs with nasal cavity tumors ranges from 0-8 months (average survival being 3 months) and is dependent upon the tumor type and grade. Nasal cavity carcinomas do not tend to be highly metastatic tumors in most cases, however, they will invade local bone and tissue over a period of time. How quickly this occurs will depend on the invasiveness of the individual tumor.

In addition to symptoms associated with local invasion of the tumor (i.e. nasal discharge, sneezing and/or facial deformity), if invasion proceeds from the nasal cavity into the skull, one may expect neurological abnormalities to occur. Neurological symptoms may include some of the following: seizures, behavior changes, weakness or paralysis, loss of coordination, and/or loss of vision. Typically, surgery followed by radiation therapy is the prescribed treatment for dogs with nasal cavity tumors. Radiation therapy will provide some control over tumor invasion, neurological symptoms (should they appear), and pain. Additionally, in general, conventional radiation therapy can be expected to increase survival time by an average 3 months (average survival time for: adenocarcinomas= 12 months; squamous cell or undifferentiated tumors= 6 months). Clinical researchers at the College of Veterinary Medicine at the University of Florida have reported on an experimental procedure called 192iridium brachytherapy to target nasal cavity tumors in dogs. This procedure entails implanting a device in the nasal cavity of the dog in the location of the excised tumor. The clinicians later place radioactive "seeds" into this devise for a particular time period which will allow for specific delivery of radiation to the surrounding tissue. Results with this technique have been variable and on the average did not provide a significant benefit over the conventional radiation methods; however, one dog in this study did remain disease-free for greater than 19 months.

A dog's demeanor is usually the best indicator of his illness. The fact that (your dog) is still hungry, strong, and active should be viewed as positive signs at this point and suggests that (he) may further benefit from conventional radiation therapy. If your veterinarian has not referred you to a radiation-oncologist, the following site will provide you with a list of oncologists in your area: http://www.vin.com/vetquest/index0.html When performing the search, be sure to enter your state in the "state" box and "oncology" in the "choose category" box.

When cancer patients, both humans and dogs, give up the fight, it is usually evident to those around them. Typically, the patient withdraws and refuses food. If the dog is considered in the final-stages of terminal cancer, no supportive therapy is provided at this point and some owners will elect euthanasia. Likewise, if conditions secondary to the cancer are affecting quality of life (in the case of nasal cavity tumors: respiratory distress or severe neurologic side-effects caused by the invading tumor), the owner may also intercede. Anticipating the need to make this decision can place quite a strain on the owner. Keep in mind that for all our logic and medical advancements, some decisions are still best made from the heart. Therefore, in (your dog's) case, trust your judgment: you will know when it is time.


Histiocytosis

"My dog has cancer . He is a rot ,age 7years 8months has been in good shape except for allergies. About three weeks ago he stop eating his dry dog food and then would not eat canned . Now he is on hamburger meat . After x-rays by my local vet two large tumors appeareed on his lungs just above the heart . For a second opinion I took him to Med vet .They confirmed the cancer type as histiocytosis(sp) and describe it as very aggressive and located in lungs liver and splen No cure recommended but advised it could slowed by taking ccnu,lomustine. I,m not sure what to do . (He) has been a number one dog and I don't want ,what ever time is left , to be at a dimished level."

There are actually two types of histiocytic malignancies that effect dogs: histiocytic sarcoma (HS) and malignant histiocytosis (MH). The first of these, HS, is a rapidly growing, solitary and locally aggressive soft-tissue mass that may develop in an extremity or in an organ. Though HS may metastasize, especially in the late stages of the disease, typically the tumor remains locally aggressive and destroys surrounding tissue. The second of these, MH, presents as a widespread (multicentric) disease with lesions often presenting in multiple organ sites. Both forms of histiocytic tumors are rapid growing and aggressive. Recommended treatment for HS is complete surgical excision of the tumor mass with biopsy of regional lymph nodes to assess whether or not metastasis has already occurred. Better prognosis is expected in HS dogs that have the entire tumor removed and show no evidence of lymph node metastasis at the time of surgery. The widespread distribution of disease associated with MH, typically rules out surgery as a viable form of treatment. Unfortunately, generally speaking, treatment of either HS or MH with chemotherapy is not often very successful. Radiation therapy, however, has been successfully used in some cases of HS. Because of the aggressive nature of these malignancies, even when conventional therapies such as chemotherapy or radiation are used, the prognosis usually remains very poor. Keep in mind, however, that prognosis is based upon general observation and some dogs may respond better to therapy than others. Additionally, there have been some advancements in experimental therapy to treat histiocytic malignancies.

(Your dog) is still fairly young and if he is in otherwise general good health and spirit, you might wish to consider treatment options. Based upon your description of (his) condition, it appears that he has the MH form of this disease. Typically, conventional therapy is used first and if there is no improvement then experimental therapies are then considered; however, in this case where chemotherapy is only expected to be palliative at best, you may wish to discuss with your oncologist using experimental treatment now while he is not suffering from serious secondary conditions related to the disease and thus able to better tolerate treatment. A group at the Wistar Institute and Veterinary Oncology Services and Research Center in Pennsylvania have used the cytotoxic T-cell line TALL-104 to treat MH and were able to achieve long-term remissions in 4 out of the 4 dogs treated that had been diagnosed with MH; some of the dogs demonstrated complete remissions. The other positive part of this method of therapy was that none of the dogs demonstrated or experienced any significant side-effects (toxicities) during the treatment. If you or your oncologist wish to look into this therapy further, I recommend that you contact: Daniela Santoli, Ph.D. The Wistar Institute  Email: santoli@wista.wistar.upenn.edu Dr. Santoli's paper on TALL-104 is:

Visonneau S, Cesano A, Tran T, Jeglum KA, Santoli D. Successful treatment of canine malignant histiocytosis with the human major histocompatibility complex nonrestricted cytotoxic T-cell line TALL-104. Clin Cancer Res 1997 Oct;3(10):1789-97 The abstract of this paper can be viewed at: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9815565&dopt=Abstract

I hope this information provides some assistance to you.


Hemangiosarcoma

"I have 2 beautiful dogs (my 2 sons ) my oldest is a Yellow Labrador and my youngest a Golden Retriever who looks more like an Irish Setter. My question is in regard to (the latter). Although your Site is more about Labs I do hope that you might be able to give me some information about hemangiosarcoma. My (Golden) was just diagnosed with this type of Cancer. We had a biopsy done on a big bump. Our Vet also had a chest X-Ray taken and discovered growth on his lungs. His diagnosis was grave. But he referred us to an oncologist and I am trying to get information on the internet about this type of cancer but most of my searches came up with no information. Would you please be so kind and give me an idea where to look or what kind of literature I can turn to, to get some information."

I'm sorry to hear about (your Golden). I will try to provide you with some information on this form of cancer, however, as you have already been told, (your dog's) prognosis is grave. Unfortunately, this is one form of cancer that has not responded favorably to clinical intervention. I explain this because I think it will be important for you to take this into consideration when deciding upon treatment options. Hemangiosarcomas (HSA) are malignant, mesenchymal tumors; those that arise from supportive soft tissue structures. HSA can arise from the surface of the skin (cutaneous) or the underlying tissues (subcutaneous). Cutaneous HSA is frequently cured by surgery using wide-surgical excision of the primary tumor. In contrast, subcutaneous HSA and those HSA tumors arising from the connective tissue of internal organs are frequently very difficult to completely eradicate by surgical excision because they invade and infiltrate the underlying and adjacent tissues. Unfortunately, these tumors are highly aggressive with a high metastatic (distant spread) potential. As such, subcutaneous HSA is typically not successfully treated by surgery alone, and even with subsequent adjuvant therapy (chemotherapy and/or radiation therapy following surgery), HSA usually recurs. Treatment of disseminated HSA (tumor that has already spread from the original tumor site), therefore, is not directed at cure but most often is directed toward palliation (slowing down progression of the disease to provide a longer quality-life for the patient). In some cases, this palliative approach can be quite effective at significantly increasing the survival time for some HSA dogs while causing minimal, tolerable side-effects; this is particularly true if the dog is in otherwise good, general health and thus more able to tolerate more aggressive treatment regimens. On the average, dogs with incompletely excised primary tumor or tumor that has metastasized have a survival of about 172 days with adjuvant therapy. Without therapy, average survival from the time of diagnosis is about 60 days. This poor prognosis is consistent with the highly aggressive nature of this cancer-type, with patients usually succumbing to secondary tumors developing from metastasis.

Though there are currently new, experimental approaches being investigated for treatment of HSA, from a clinical standpoint, most oncologists will first use a treatment that has been proven effective in earlier cases of this disease. Only when conventional treatment fails are novel, experimental therapies utilized. In this instance, the most effective conventional therapy for treatment of incompletely operable or metastatic HSA in dogs is the VAC protocol (Vincristine-Days 8 and 15, Doxorubicin-Day 1, Cyclophosphamide-Day 1 combination/ cycle repeated on Day 22 for a total of 3-5 cycles). In instances where underlying health may predispose to more severe side-effects from chemotherapy, doxorubicin as a single agent has also been used to treat HSA. Response rate to chemotherapy is expected to be variable from patient to patient, often dependent upon the aggressiveness of the individual cancer. Interestingly, the more aggressive the tumor, the more effective doxorubicin is at controlling the disease. This is because doxorubicin works by targeting cells that are rapidly dividing; the more active the tumor, the better the chance for doxorubicin to effectively kill the tumor cells. Recent studies have utilized surgery combined with inhalation therapy with doxorubicin for the purpose of targeting lung metastases associated with HSA. This approach results in reduction/inhibition of systemic side-effects associated with the typical intravenous route of doxorubicin administration. In clinical studies, this approach has also shown excellent results for reducing lung metastases. The following are a list of reference links to abstracts that you might find helpful:

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8947871&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11012108&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10830540&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10499645&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9815908&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7704483&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8114034&dopt=Abstract

You can also access other publications by clicking on "Related Articles" in the upper right hand corner of each of the above abstracts.

Whenever viewing the statistics, it is important to keep in mind that each patient will respond on the individual level to therapy. Sadly, I receive many letters from owners who have dogs with cancer. Though many of these dogs do succumb, either to their disease or through the compassionate intercession of their owners, I also receive many letters of success stories; in some instances, these are true miracle stories, because "statistically-speaking" some of these dogs diagnosed with the most aggressive forms of cancer should not be alive...yet they are alive and still enjoy quality lives. When reviewing the survival data for dogs undergoing treatment for HSA, even the survival times reported for what are considered "successful" treatments may appear discouraging. However, there are many variables that will play a role in survival time, therefore, if you should decide to pursue treatment options, the key is to try to determine the best treatment that offers the greatest likelihood for increased survival time, and then just take one day at a time.

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"I just saw an article you copywrited in 1999 entitled >"Treating Cancer in the Canine". The topic of hemangiosarcoma is unfortunately of great immediate interest to me and my family. If there is ANY updated information, insight or suggestions you can offer us, it would be very much appreciated.

Our 9-1/2 year old black lab recently had a tumor removed from behind his left shoulder. The lab results indicated that he has hemangiosarcoma (HSA) and that there were cancer cells even in the margins that were removed. Our vet said that HSA typically starts on the spleen or another internal organ. Strangely though, chest and abdominal x-rays as well as abdominal ultrasound did not show any internal masses at all.

Since the primary site appeared to be the shoulder, we decided to have (our dog) undergo a 2nd surgery 3 weeks ago to remove the deltoid and tricep muscles. He is recovering very well and fortunately, the margins removed this time were totally free from diseased cells. Given that the primary site has been removed and that there are no other apparent masses at this point, we are now faced with the decision of whether to give him chemotherapy or not. Our vet is in consultation with a researcher at the University of Guelph who has had some success in using thalidomide to treat HSA (although his research is limited to dogs with the splenic version). Another option that faces us is an IV injection of doxorubicin every 3 weeks for 5 treatments. We know there are other combinations of chemo drugs but this seems to be the most manageable.

(Our dog) is an otherwise very healthy and enthusiastic dog with no other medical conditions. It is hard to close the book on him at this point. However, we want to stay within "reason" and not cause him undue discomfort for our benefit. Given your experience, do you feel that it would be beneficial to use thalidomide or doxorubicin to arrest the growth and spread of any cancer cells at this stage? I have been hurriedly trying to find as much updated info (re: efficacy, side effects, etc.) as I can on this topic to help us make an informed decision. So far the findings have been slim and mostly related to splenic HSA. I appreciate you taking the time to read this email and would welcome ANY suggestions or insight that you may have. "

I understand your desire to learn as much as you can about your treatment options, and hopefully I'll be able to sufficiently address some of your questions.

In a retrospective study, Ward et al. back in 1994 found that dogs bearing hemangiosarcomas that involved hypodermal tissues (deep tissues of the skin and muscular tissue) demonstrated significantly shorter survival periods due to metastasis (following excision of tumors) compared to dogs with more superficial skin tumors in which surgery alone appeared to be curative. These findings, along with the highly invasive and metastatic nature of these tumors, suggest that these tumors warrant adjuvant chemotherapy following surgery. The fact that (your dog's) second surgery demonstrated clear surgical margins is good news: clinical studies have demonstrated that complete excision of the primary tumor significantly increases survival time in these dogs. However, one study examining outcome for scapular hemangiosarcomas indicated that even with complete surgical excision of the primary tumor, distant metastases eventually present. Therefore, based on the general guarded prognosis for dogs with hemangiosarcomas, adjuvant chemotherapy is an option that should definitely be considered.

Doxorubicin is probably the drug used most often as an adjuvant to surgery for HSA. Average survival time for dogs that had primary tumors completely excised and underwent adjuvant therapy with doxorubicin (30 mg/m2 IV q 3 weeks for 5 treatments 10 to 14 days after the tumor removal) showed an average survival time of 267 days with 20% of the dogs still alive one year out. As to novel adjuvant therapies, if you have not already done so, you might be interested in reading the following recent review by Clifford et al. that discusses these potential treatment options in relation to HSA (these treatments, however, are only now undergoing investigation so much is still not known about doing and efficacy): http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11012108&dopt=Abstract

In regard to novel therapies, however, these treatments are typically only utilized when proven, conventional therapies fail. Efficacy of thalidomide as an adjuvant therapy for cancer has not been established. Though it does appear to provide palliative benefits to cancer patients in terms of reducing symptoms associated with the cancer syndrome (weight loss, nausea, night sweats, etc.), I am not aware whether or not a benefit for thalidomide as an adjuvant has been demonstrated at this point...at least in regard to using thalidomide alone (current clinical studies are exploring its efficacy when combined with other chemotherapeutic regimens.) As such, in the absence of studies showing efficacy of thalidomide as an adjuvant to surgery for inhibiting or delaying recurrence of disease, from an oncological standpoint, conventional treatment with doxorubicin would be the first adjuvant regimen employed.

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"I have an 8 year old female dog.. Some say she is a shepherd mix, some say a husky mix. She collapsed while we were playing ball. I took her to the vet immediately. Her spleen was removed. I brought her home. She is doing great, like nothing ever happened. Then came the dreaded news. Her biopsy report revealed hemangiosarcoma. I'm told on average a dog can have quality life for 4-6 months, and in some cases even longer. Like I already typed, (she) is fine, but I'm a wreck. I'm contemplating chemotherapy, but from what I've been reading on the internet and hearing, it appears to me that chemo wouldn't help her at all. She is so happy now. I'm giving her so much love and attention and she is loving it. I do not want to see her suffer, and I will put her down (as hard as it will be) when I have to.  If chemo would buy her more time and at the same time misery and pain, then chemo would be out of the question. Can you please give me some of your insight to this crisis I'm dealing with? "

I know you must have many questions and are probably feeling very uncertain of how to proceed at this point. Though I am a research scientist exploring the biochemistry of human cancers as well as investigating the potential of new drugs and combinations of drugs for the treatment of cancers, I have not dealt directly with hemangiosarcoma. I am glad to share what information I do have on hemangiosarcoma, however, my advice is that you consult with a veterinarian oncologist to discuss therapeutic options for (your dog).

If your veterinarian has not already referred you or does not know of an oncologist in your area, the following web site may be of some help for locating one in your area: http://www.vin.com/vetquest/index0.html (When performing the search, be sure to enter your state in the "state" box and "oncology" in the "choose category" box.)

The success of surgery (splenectomy) alone to treat hemangiosarcoma of the spleen will depend upon whether or not the cancer was confined to this organ. If all of the cancer was removed, then prognosis is excellent. Unfortunately, because of the insidious metastatic nature of this type of cancer, even when hemangiosarcoma appears to be localized to the spleen (Stage 1 or Stage 2), clinical studies exploring survival for dogs treated with surgery alone show a great margin of variability in terms of life expectancy. This suggests that occult (undetected) metastasis has already occurred in many clinical cases prior to surgery being performed.

One study exploring survival in 32 dogs treated with surgery alone reported a median survival of about 86 days. However, the range of survival for the 32 dogs in this study was from 14 to 470 days (1). When one compares treatment with surgery alone to treatment with surgery followed by adjuvant combination chemotherapy (such as doxorubicin plus cyclophosphamide), in one reported study the median survival increases to 250 days (overall mean = 403 days) in dogs with stage I localized disease (2); overall median survival of dogs, independent of stage (stage I, II, and III combined), was 202 days (overall mean = 285 days). Based on these clinical studies there does appear to be an advantage for utilizing adjuvant chemotherapy when treating hemangiosarcoma. I understand your concerns regarding (your dog's) quality of life and they are valid concerns. Cyclophosphamide, for one, can cause serious side-effects when used in aggressive dosing regimens. Typically, however, combining agents allows for a lower effective dose and fewer associated toxicities. Clinical studies that have combined cyclophosphamide with doxorubicin to treat hemangiosarcoma have reported only mild to moderate side effects that the patients were able to tolerate with or without supportive care. Naturally, geriatric dogs that have underlying health complications related to old-age are usually not considered good candidates for chemotherapy because their organ functions, apart from the disease, are often compromised or failing. However, at 8 years of age, (your dog) is still a relatively young dog and appears, based on your description, to live a healthy life apart from the cancer. Her system, therefore, may be able to tolerate a moderate, adjuvant chemotherapy regimen while her underlying health is still uncompromised by the cancer. Alternatively, a relatively new and experimental approach for treating with cyclophosphamide called "metronomic dosing" (3,4) provides continual or frequent low-dose administration of the drug to utilize its antiangiogenic properties (the ability to inhibit new blood vessel formation for which tumors are dependent upon for their growth) rather than its cytotoxic properties. This approach has been used in a few human cancer cases that have undergone remission. The metronomic dosing method is utilized as "prevention" against cancer recurrence. I am not aware of any cases, however, that have used this method for hemangiosarcoma. The above references can be accessed by the following links:

1) http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9728473&dopt=Abstract   2)http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8114034&dopt=Abstract   3)http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10766175&dopt=Abstract 4)http://www.jci.org/cgi/content/full/105/8/1045?view=full&pmid=10772648

I hope this information is of some use to you.

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"I was searching the internet for more information on tumor masses in the spleen for Labradors and your website was very helpful. My 12-year-old Labrador is scheduled for a splenectomy . It is my vet's opinion after doing x-rays and blood tests that we attempt to remove the mass as quickly as possible. Of course, being the typical lab owner that has major concern over my dog, it seems to me like an attempt first to diagnose whether or not the cancer is malignant through use of ultrasound would be less invasive. However, my vet is very competent and I'm trying to trust his judgement in removing the mass ASAP, even though its making me nuts. If you have any opinion as to whether or not further tests should be done prior to surgery, please e-mail me as soon as possible."

Except in instances of spread of the tumors (which can often be seen on x-ray imaging, as well), determining the nature of tumors by diagnostic imaging alone is not always possible. If this is a malignant condition, the earlier the tumors are removed, the better in terms of preventing spread of disease and thus prolong survival. It is for this reason that your vet, most likely finding on x-ray that the tumors were confined to the spleen, decided that (your dog) was a good candidate for possible surgical cure. This does not guarantee that tumors will not recur in the future in other organs (if occult metastases are already present..which would at this point be too small to detect by any diagnostic procedures), but the earlier the primary tumor(s) is(are) removed the greater the chance of stopping metastasis from occurring. Therefore, the urgency with which your vet addressed (your dog's) condition was well warranted and if (your dog) is strong enough to recover from the surgery, even if the biopsy suggests that the tumors are malignant (such as hemangiosarcoma), removing the spleen may prolong (your dog's) lifespan compared to if surgery had not been performed.


Chemodectoma

"I read your interesting web site and wonder if you have any experience in treating chemodectoma (tumor attached to a heart vein) with alternative therapies? Or just if you have any experience with this type of cancer. Any input appreciated. "

Surgery is the current therapeutic approach to chemodectoma, and unfortunately I am unaware of any alternative therapies. As you may know, complications associated with surgery can pose quite a risk. I, therefore, recommend that you contact: Dr. D.J. Krahwinkel, DVM, MS Professor of Surgery and Head of the Department of Small Animal Clinical Sciences Email: djk@utk.edu

Dr. Krahwinkel and colleagues have published on the surgical treatment of chemodectoma and may be able to offer you guidance regarding potential treatment options. (refer to the following paper:)

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9301745&dopt=Abstract

My best hopes.

 

Follow-up

"Thank you so much for your opinion. This is a 14 year old whippet. Performed the pericardectomy in November to release fluid formed by tumor but, due to the tumor location, it cannot be removed. Since surgery, he has been doing remarkably well - eating well, good spirits, etc."

I'm glad to hear that your dog performed so well after the surgery. I realize that he is an old boy, but I've never liked the policy of ignoring potential treatment options because of a patient's age. Therefore, I just thought I'd pass on some additional info.

Although not with chemodectoma, there has been a report for treatment of another heart tumor (mesothelioma) with adjuvant chemotherapy after surgery. The study used intrathoracic cisplatin combined with intravenous doxorubicin. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10476526&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8114034&dopt=Abstract

This adjuvant approach has been used in humans, as well, particularly in cases of incomplete surgical resection of the tumor. In this instance where the surgeon was unable to resect any of your dog's tumor, chemotherapy may offer a possible option (since cisplatin is well known for its ability to cause regression of some tumors). There are, of course, toxicities associated with cisplatin use which older dogs are less likely to tolerate as well as younger dogs. However, if the underlying health of the dog is otherwise sound, then chemotherapy might be something to consider while the patient is not yet compromised by the tumor.


Intestinal Tumor (Non-classified)

"I came across your website while looking for information on the treatment of canine cancer. Our dog had a malignant tumor removed from his intestinal tract yesterday. However, a very low hematocrit is leading our veterinarian to believe that it has spread to his bone marrow. By Sunday, we should have the results of the tests samples she removed . We are hoping to bring him home in a few days and I'm looking for a realistic course of treatment that would put the cancer into remission. Our dog is a 10 year old Pembroke Welsh Corgi. There are hundreds of websites that talk about this subject, but I was hoping that you might have some direct knowledge or information I can access about the treatments that work, etc I do not want to put him through an aggressive treatment--his veins are small and I don't want him to suffer. My wife and I decided that we would look to use any Rxs that are orally introduced. Any help you can give me would be gratefully appreciated. "

Therapeutic options will be based upon diagnosis of the primary tumor, which was removed from the intestinal tract. Different tumor types are often targeted more efficiently with certain drugs, therefore, once your veterinarian receives the pathology report, she will know which treatment protocol will provide (your dog) with the best therapeutic success. In regard to the anemia, tumors can lead to low red blood cell counts for several different reasons, not always of which will necessarily be bone marrow invasion. Large, ulcerated tumors often bleed and may lead to anemia due to blood loss. In the absence of bone marrow biopsy to identify metastatic infiltration of the bone marrow, blood tests showing an absence of reticulocytes (immature red blood cells) could indicate a condition of non-regenerative anemia which may be associated with either bone marrow infiltration or nutritional deficiencies often observed in cancer patients (particularly in patients with gastrointestinal cancers because these cancers often interfere with normal absorption of nutrients). Bone marrow biopsy will provide the most definitive answer as to whether this anemia is due to cancer metastasis, however, if you are concerned about submitting (your dog) to further invasive procedures, your veterinarian will probably suggest a more conservative approach. Now that the primary tumor has been removed and once (your dog) stabilizes, your vet may prescribe supplemental vitamin B12 injections (a vitamin required for red blood cell production which is often deficient in cancer patients) to stimulate bone marrow production of red blood cells. Follow-up bloodwork should provide an indication of whether this was a case of regenerative (bone marrow uncompromised) anemia due to secondary conditions related to the tumor or non-regenerative anemia (resulting from bone marrow compromise).

Your concerns regarding treatment are understandable and are those shared by many pet owners confronted with this disease in their beloved pets. Since (your dog's) tumor type was unknown at the time that you e-mailed me, I cannot provide specific information regarding treatment options at this point. When considering options, however, my best advice is to take into consideration the underlying health of the patient as well as the benefits to risks of treatment in regard to the anticipated outcome of treatment. For example, if (your dog) is an otherwise healthy 10 year old and a treatment option provides high success of prolonged survival, though perhaps there may be a brief period of acceptable side-effects from treatment, then benefits of therapy may considerably outweigh risks. If, however, (your dog's) underlying health is compromised and treatment options would only compromise that health further without clear indications for prolonged survival then the risks are probably not worth taking and a shortened, quality life may be considered better than a briefly prolonged, sickly life.


Oral Malignant Melanoma

"I have a 9 year old male black lab-golden retiever mix, weight is 70 lbs. He had a malignant oral melanoma removed from the back of his mouth. I understand his prognosis is not good. I read the following in your web page:"Gene Therapy in Canine Cancer". I am very interested in any and all potential treatments available, including chemotherapy and especially the aforementioned gene therapy."

Much of the gene therapy work referred to in my article was conducted in other countries (France and Switzerland), however, I refer you to the following paper: Dow SW, Elmslie RE, Willson AP, Roche L, Gorman C, Potter TA. In Vivo Tumor Transfection with Superantigen plus Cytokine Genes Induces Tumor Regression and Prolongs Survival in Dogs with Malignant Melanoma. J Clin Invest 1998 Jun 1;101(11):2406-14

This research was conducted in the lab of Terry Potter, Ph.D. Dr. Potter's biosketch and contact information can be accessed at: http://www.uchsc.edu/sm/immuno/potter.html

Perhaps Dr. Potter may be able to provide you with additional information and possible options regarding gene therapy. Other recent papers exploring other therapeutic options for targeting refractory melanoma: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11345308&dopt=Abstract http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11007934&dopt=Abstract


Sarcomas (Malignant Mesenchymomas  and Myxosarcomas)

"I'm hoping you might be able to help me....my Mother's dog was just diagnosed as having Triple Cell Sarcoma in the connective tissues. Her vet did not answer my Mother's questions and I was hoping you might be able to give me some suggestions as to where I might look on the internet."

Sarcomas are malignant tumors that develop from cells that make up the following mesenchymal (tissues located between the skin and the internal organs) structures: connective tissues, fatty tissues, blood vessels, lymphatic structures (immune system) and muscle. Sarcomas may be fleshy, soft tumors or fibrous and firm dependent upon their cellular origin. The characterization of "triple cell" is more of a descriptive classification rather than a tumor type and actually applies to many sarcomas. This is because sarcoma tumors have a tendency to develop not from a single cellular origin, but from a mixture of various mesenchymal cell types. That is to say, a sarcoma of the connective tissue will often be found to be made up of cancer cells not only originating from connective tissues, but also of cancer cells from perhaps the blood vessels and/or muscles as well as other mesenchymal tissue. Such sarcomas are most often either "malignant mesenchymomas" or "myxosarcomas" and are very rare tumor types in dogs.

Because these tumor types rarely occur in dogs, there have been no clinical trials exploring the most effective treatment regimens for prolonging survival or comparisons made between treatment options. Therefore, the clinical approach to treatment is one that applies to treatment of sarcomas in general. Like most sarcomas, these tumors are insidious and frequently are not detected until they are large enough to interfere with normal function or mobility. Though they may appear encapsulated, or contained, sarcomas typically invade surrounding normal tissue and bone, which can make them extremely difficult to completely remove by surgical excision without removing large areas of underlying structures (dependent upon the location of the tumor, complete surgical excision may be impossible). Accordingly, surgical excision alone is frequently unsuccessful for complete eradication of the tumor and thus, there is a high incidence for tumor recurrence at the site of the surgery. Sarcomas are, however, responsive to radiation therapy. Success of radiation therapy alone, however, for complete regression of tumor will depend on the size of the tumor and the dose of the radiation administered (dose may be limited by the location of the tumor). Combination of surgery and radiation therapy with or without adjuvant chemotherapy is, therefore, frequently utilized for treatment of sarcomas. However, sarcomas have the potential to metastasize (spread to distant organs). The most common sites of sarcoma metastases are the lungs and the lymph nodes; and metastases are an important consideration because they will produce limitations to successful treatment. Therefore, during surgical excision of the primary sarcoma tumor, biopsy of the regional lymph nodes and x-rays of the lungs are recommended to determine if metastasis has already occurred. The presence of detectable metastases would warrant the use of systemic chemotherapy as an adjuvant to surgery and radiation therapy. Even if metastases are not detected, the veterinary oncologist may recommend adjuvant chemotherapy as a precaution against the development of metastases at a later time.

Prognosis for sarcoma patients and outcome of treatment is more dependent upon certain characteristics of the individual tumor. For example, sarcomas that have a histologic characteristic of being "well-differentiated" have a better prognosis than those whose cancer cells are "poorly-differentiated" because well-differentiated cancer cells typically behave more closely like their normal cell counterparts: growing more slowly and having less likelihood for invading surrounding tissue or metastasizing to distant organs. This characteristic of a tumor is known as the "grade" and this information is very important when considering how aggressively a patient should be treated. The pathologist who examines the tumor biopsy will indicate the tumor grade in the pathology report. Histological identification and determination of grade of sarcoma tumors, however, can sometimes be difficult. Because these tumors are made up of various cell types, some of which may have a faster rate of cellular growth even when they are normal cells (as in the case of cartilage cells, it is sometimes easy to misdiagnose a particular sarcoma as highly aggressive (particularly if it contains components of cartilage) when it may actually be only a low-grade tumor or may even be benign.

Another factor that influences outcome when considering sarcomas includes location of the primary tumor. Sarcomas that are located on the extremities have a better prognosis than those located near or on the trunk of the body. This is because tumors on the extremities can be removed by amputation or by wide surgical excision followed by higher doses of radiation. The ability to treat extremity tumors aggressively reduces the likelihood of tumor recurrence. Tumors on the trunk, however, are often difficult to completely excise and the potential for damage to underlying critical organs by high-dose radiation presents limitations to aggressive treatment intervention. As such, tumors on the body have a higher risk for recurrence. This presents further implications regarding long-term prognosis because each time a tumor recurs the more invasive (higher grade) it usually becomes with each recurrence. There are many factors that must be considered in light of the individual patient when determining the most effective treatment regimen as well as evaluating, realistically, the chances for success. Therefore, consultation with a veterinarian who specializes in the field of oncology is essential for providing all the information necessary that will help your mother decide on a course of action. Because some treatment options may temporarily lead to undesirable side-effects, it will be important for the veterinary oncologist to assess whether treatment offers long-term benefits that would outweigh the short-term effects on quality-of-life in some cases. For this reason, it is important to find an oncologist who is not only knowledgeable in approach to the disease, but also compassionate in regard to the patient's quality-of-life and the owner's concern for preserving such.

For more information on sarcomas, you might try the following link: http://oncolink.upenn.edu/disease/rhabdo/


Meningiomas

"Have you ever dealt with meningiomas....my dog recently went thru brain surgery for this and we are heading for chemo this month...I am still in the dark on a lot... and if you have, what have you experienced....your expertise would be appreciated.."

Meningiomas are benign tumors that originate from cells that make-up the outer covering of the brain. Accordingly, these tumors do not metastasize, however, their location can cause symptoms, as you are probably aware, associated with their growth and subsequent pressure on underlying brain. Surgery is the typical treatment for menigiomas and provides the best outcome in patients who have operable tumors or who are good candidates for surgery. For tumors in which only partial resection is possible, low-dose fractionated radiation treatment is frequently used as an adjuvant therapy to surgery for targeting residual tumor. Because of the location of these tumors and the inability for many chemotherapeutic drugs to cross the blood-brain barrier, standard chemotherapy has not been found to be effective against meningiomas in dogs (therefore, I'm not sure what chemotherapeutic regimen your veterinarian is going to be using, unless, perhaps it is a modified drug delivery system -- ie. using osmotic BBB disruption, bradykinin modulation, or liposome delivery or direct intracerebral infusion; additionally and unfortunately, some drugs like alpha-interferon which have been studied as adjuvant treatments for meningiomas in humans with some suggestion of adjuvant effectiveness, have not been explored for efficacy in dogs with meningiomas.). Use of steroids has also been found to be virtually ineffective.

Radiation therapy is therefore typically the primary adjuvant therapy (or the primary treatment particularly in patients with inoperable tumors or who are poor candidates for surgery because of poor underlying health. In clinical studies, mean survival time of dogs undergoing therapy with radiation alone ranged from 21 to 50 weeks dependent upon the location of the tumor (comparable to surgical treatment alone; in some cases, combination treatment with surgery and radiation has been found to double the survival time anticipated for just surgical treatment alone). Some dogs (about 14%) did experience effects of radiation toxicity.


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