Cally, a 14-year-old, spayed female, domestic shorthair cat, presented to the Oncology Service at HopeVS for consultation for recently diagnosed gastrointestinal large cell lymphoma. Cally had a 1-month history of weight loss and progressively worsening appetite. She also had 2-3 days of hematemesis and pica. She was taken to the primary care vet where routine blood work and abdominal x-rays were found to be normal. Abdominal ultrasound was recommended which revealed a mass effect in the stomach and enlarged gastric lymph nodes, aspirates confirmed large cell lymphoma upon cytology review by a pathologist.
Lymphoma, a cancer of the immune system, is one of the most common cancers diagnosed in cats. Feline lymphoma may occur in various anatomic forms, with gastrointestinal being one of the most common forms(1, 2). Feline gastrointestinal lymphoma is divided into three main forms based on cell size, immunophenotype, and mucosal architecture(2). Enteropathy-associated T-cell lymphoma (EATCL) Type II is most often a small cell lymphoma which is confined to the mucosal layer of the small intestines and generally carries a good prognosis with an average survival time of 29 months when treated with steroids and Chlorambucil. The second main form is EATCL Type I, a large cell lymphoma in approximately 60% of cases, occurring in the submucosal and muscularis layers of the small intestine. This form of lymphoma carries a poor prognosis with average survival time of 1.5 months when treated with multiagent chemotherapy protocol. The third main form is B cell gastrointestinal lymphoma, a large cell form in 100% of cases, occurring in the submucosal and muscularis layers of the stomach, ileum and ileocecocolic junction. This form of lymphoma carries a poor prognosis with the average survival time of 3.5 months when treated with multiagent chemotherapy protocols.
Treatment of choice for feline large cell lymphoma is multiagent chemotherapy protocol, often L’CHOP or L’COP-based protocols are used(1). These protocols alternate L’asparaginase, vincristine (or vinblastine), cyclophosphamide, +/- doxorubicin. Steroids (prednisone or prednisolone) are incorporated into the chemotherapy protocol.
As outlined above, cats with gastric lymphoma, such as Cally, may have an estimated survival time of 3-4 months with L’CHOP protocol(2). In Cally’s case ultrasound results revealed a gastric mass and enlarged gastric lymph nodes. No ultrasound abnormalities were noted in other regions of the gastrointestinal tract. Cytology confirmed large cell lymphoma. Histopathology was recommended to further evaluate cellular characteristics, mucosal architecture, and immunophenotype; however Cally’s owners declined surgical biopsies. We recommended L’CHOP treatment protocol and serial ultrasound exams to monitor tumor response to treatment. In addition to traditional treatment for the cancer, we discussed incorporating acupuncture into Cally’s protocol, with the goal of reducing potential chemotherapy and tumor-induced nausea, improve appetite, and support the immune system(3).
Human and veterinary studies have demonstrated the benefit of acupuncture for conditions including: pain(3-6), immune dysregulation and inflammation(7-8), and nausea(9-10). In 1998, the National Institutes of Health (NIH) published a consensus report summarizing research findings which confirmed positive benefit on the effectiveness of acupuncture for chemotherapy-induced nausea as well as post-operative pain secondary to tumor removal in people(11). This report sparked major interest in acupuncture as a compliment to physician-based Western Medicine. Since 1998 there has been a surge in funding to support research evaluating the molecular mechanisms and the clinical benefits of acupuncture(12). As more and more positive research is published, Western medicine practitioners are gaining confidence in using this modality as a tool in their tool-belt. It is not surprising that the top tier, world-renowned U.S. Cancer Institutes such as, Dana-Farber in Boston, Sloan-Kettering in New York, and MD Anderson in Houston, all have integrative medicine programs closely associated with their Cancer Centers.
Research from physician-based medicine supports the use of this modality for the human oncology patient. Three of many studies were chosen to be summarized here. The first study is a three-armed, randomized, prospective clinical trial published in The Journal of the American Medical Association(10). Women with high grade mammary carcinoma, treated with high-dose myeloablative chemotherapy, were randomly assigned to three separate groups: anti-emetic alone, anti-emetic with electroacupuncture, anti-emetic with acupuncture at non-therapeutic locations on the body. The study found that women in the anti-emetic with electroacupuncture group had significantly less vomiting episodes compared to women in the two other groups (anti-emetic alone and anti-emetic with non-therapeutic acupuncture)(10).
The second study, published in The Journal of Supportive Care in Cancer evaluates the effectiveness of acupuncture at alleviating nausea in children with solid tumors who were receiving high dose chemotherapy(13). Eleven children were studied for a total of 22 chemotherapy cycles. The children were divided into two groups: group 1 received anti-emetic along with acupuncture and group 2 received anti-emetic alone. The amount of anti-emetic therapy used by each patient was documented (baseline and any additional needed) as well as a daily diary of emesis episodes, nausea scores and changes in body weight. The benefits of acupuncture with respect to the reduction of additional antiemetic medication were observed. The study found that acupuncture enabled patients to experience reduced levels of nausea and vomiting during chemotherapy.
The third study published in The Journal of Alternative and Complementary Medicine, investigated the effect of acupuncture on white blood cell count and absolute neutrophil count in patients with ovarian cancer receiving myelosuppressive chemotherapy(14). Patients received therapeutic acupuncture versus non-therapeutic acupuncture while undergoing chemotherapy. Acupuncture was given 2–3 times per week for a total of 10 sessions, starting 1 week before the second cycle of chemotherapy. White blood cell count, absolute neutrophil count and plasma granulocyte colony-stimulating factor (G-CSF ) were assessed weekly for one month. Results indicated that the median white blood cell count in the therapeutic acupuncture group was significantly higher than in the non-therapeutic acupuncture group after adjusting for baseline value, (8600 cells/μL, range: 4800–12,000 versus 4400 cell/μL, range: 2300–10,000) (p = 0.046). In addition the incidence of grade 2-4 leukopenia was less in the therapeutic acupuncture arm than in the non-therapeutic acupuncture arm (30% versus 90%; p = 0.02). The median leukocyte nadir, neutrophil nadir, and recovering absolute neutrophil counts were all higher but not statistically significantly different (p = 0.116–0.16), after adjusting for baseline differences. There were no statistically significant differences in plasma G-CSF between the two groups. In conclusion a clinically relevant trend of higher WBC values during one cycle of chemotherapy was observed in patients with ovarian cancer receiving therapeutic acupuncture during myelosuppressive chemotherapy. This suggests a potential myeloprotective effect of acupuncture.
In veterinary medicine, there are multiple research reports demonstrating the benefit of acupuncture at alleviating pain(3, 15-19) and nausea(9) for the veterinary patient. There is however, a paucity of data evaluating the benefits of acupuncture for the veterinary oncology patient. The good news is that there is data in the human literature which supports acupuncture as a beneficial adjunct therapy to traditional treatment for the cancer patient. By applying what we know from human medicine to the veterinary patient, veterinarians are able to further develop the field, embark on potential clinical research projects to help improve the scientific database, and most importantly, provide well rounded care for our cancer patients.
Cally went on to receive the L’CHOP protocol in which she received chemotherapy weekly along with acupuncture. Most common acupuncture points used include: Bai-Hui, GV 14, BL 23/20/21/17, ST 36. The goal of these acupuncture points was to reduce potential chemotherapy and tumor-induced nausea, improve appetite, and balance the immune system. After the first month of chemotherapy, a recheck ultrasound confirmed strong partial remission based on smaller tumor size. Cally was continued on this therapy. During the course of her disease and treatment she never experienced low white blood cell counts and had only intermittent regurgitation of hairballs but no vomiting and no pica. We continued to monitor the tumor response via serial ultrasound exams every 8-10 weeks. Eight-months after initial diagnosis she presented with acute onset of vomiting. Ultrasound exam confirmed progression of disease in the form of another gastric mass, which occurred within a short time frame as ultrasound exam 4-weeks prior revealed normal stomach wall thickness. Due to the severity of clinical symptoms associated with the relapse lymphoma, the clients declined further treatment and elected humane euthanasia.
In summary, Cally experienced low level of side effects from the tumor and from chemotherapy treatment as well as a longer than anticipated remission period with gastric lymphoma. She tolerated acupuncture treatment well. This case report demonstrates that acupuncture may be used in conjunction with chemotherapy in the feline patient with large cell lymphoma.
Submitted by: Kate Vickery, VMD, MS, DACVIM (Oncology), CVA
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