Chemotherapy followed by half-body radiation therapy for canine lymphoma

A protocol of induction chemotherapy followed by half-body radiation therapy for treatment of lymphoma was used in 94 dogs. Seventy-three (78%) dogs achieved complete remission. Substage (P = .011) and phenotype (P = .015) were identified as predictors of complete remission rate. Of these, 52 dogs received half-body irradiation. Cranial and caudal halves received a total dose of 8.0 Gy, given in 2 fractions of 4.0 Gy on consecutive days with cobalt-60 photons and a 3-week interval between halves. Median 1st remission for these dogs was 311 days. Anemia was identified as the only predictor for length of 1st remission (P = .024). Toxicoses after half-body irradiation generally were mild and infrequent and included myelosuppression and gastrointestinal signs. Thirty-one dogs relapsed and 20 resumed treatment with induction followed by maintenance chemotherapy. Seventeen (85%) dogs achieved a 2nd complete remission. Median overall remission for all 52 dogs was 486 days. Results of this study suggest that half-body radiation therapy after induction chemotherapy is well tolerated and might increase remission duration compared with conventional protocols that use chemotherapy alone, but this increase might not be long enough to be clinically relevant or to justify application of the method described herein.     

CHEMOTHERAPY FOLLOWED BY ABDOMINAL CAVITY IRRADIATION FOR FELINE LYMPHOBLASTIC LYMPHOMA

Combination chemotherapy is standard care for feline lymphoma, although clinically relevant improvements in remission duration are unlikely to result from manipulations of chemotherapy agents alone. Lymphopoietic tissues generally are sensitive to radiation, and support for chemoradiotherapy as a treatment for lymphoma is found in both humans and dogs. The goal of this prospective pilot study was to determine the normal tissue tolerance to 15 Gy total abdomen fractionated radiation therapy following induction chemotherapy in cats with lymphoblastic lymphoma. Eight cats with lymphoblastic gastrointestinal or multicentric lymphoma confined to the abdominal cavity were treated with a 6‐week combination chemotherapy protocol followed 2 weeks later by whole‐abdomen radiation therapy consisting of 10 daily fractions of 1.5 Gy. Treatment was well tolerated; renal insufficiency documented in one cat at the start of radiation therapy progressed to stable chronic renal failure. One cat not in complete remission at the time of radiation therapy relapsed 2 weeks later, one cat with multicentric lymphoma relapsed with hepatic large granular lymphoma, and one cat was euthanatized 3 weeks following completion of radiation therapy for other reasons; no evidence of lymphoma or radiation toxicoses was identified on post mortem evaluation. The remaining five cats remain in remission at least 266 days after starting therapy; median remission duration has not been reached (range, >266 to >1332 days). Results of this study suggest that 15 Gy total abdomen fractionated radiation therapy after induction chemotherapy is tolerated satisfactorily. This protocol is suitable for further testing to quantify efficacy.     

RESPONSE OF NINETEEN CATS WITH NASAL LYMPHOMA TO RADIATION THERAPY AND CHEMOTHERAPY

The records of 19 cats treated for stage I nasal lymphoma with radiation therapy and chemotherapy were reviewed to determine response to therapy, treatment outcome and possible prognostic indicators. All cats were treated with megavoltage radiation therapy to a total dose ranging from 22 to 48 Gy (median dose = 42 Gy). All cats were prescribed at least 6 months of multiagent chemotherapy. The median progression-free interval for all cats was 945 days (31 months). Two cats did not achieve clinical remission. Of 17 cats evaluable for relapse, 10 (58.8%) were progression free during the entire follow-up period. Four cats (23.5%) suffered local recurrence, while three (17.6%) experienced distant relapse. The median survival time was 955 days (31.4 months). The only variable found to have a significant negative impact on survival was destruction of the cribriform plate before therapy (P= 0.002). The long progression free and survival times reported here indicate that cats with stage I nasal lymphoma treated with aggressive local and systemic therapy can have a favorable outcome when compared with other anatomic forms of lymphoma. Despite strong clinical responses to the multimodality therapy used, the fact that three (17.6%) cats relapsed distantly supports the recommendation that treatment with radiation therapy alone is insufficient until further prospective studies can be performed.     

Radiotherapy in the management of localized mucocutaneous oral lymphoma in dogs: 14 cases

Oral mucocutaneous lymphoma is rare in dogs. Surgery and chemotherapy do not usually provide effective long-term control. The objective of this study was to retrospectively evaluate survival of dogs with localized oral lymphoma treated with radiation therapy. The medical database of three institutions was searched for dogs with diagnosis of oral lymphoma treated with radiotherapy. Dogs with evidence of systemic disease were excluded. Survival was calculated with the Kaplan-Meier method and prognostic variables analysed with log-rank test. Fourteen dogs were included in the study. Mean survival was 1129 days [95% confidence interval (CI) 711-1546] with median survival of 770 days. The overall response of radiotherapy was 67% (five complete and three partial responses). A survival advantage was seen in dogs with no evidence of lymph node metastasis (P = 0.002) and that achieved a complete response to radiation therapy (P = 0.013). Radiation therapy was a well-tolerated and effective treatment for localized oral lymphoma.     

A Comparison of Doxorubicin and COP for Maintenance of Remission in Cats With Lymphoma

Thirty-eight cats with lymphoma were treated with vincristine, cyclophosphamide, and prednisone (COP). They were randomized at entry to receive maintenance chemotherapy consisting of either single-agent doxorubicin or continued COP therapy, starting on week 4 of treatment and continuing for 6 months or until relapse. Eighteen cats achieved complete clinical remission after COP induction chemotherapy. The median remission duration for 11 cats continuing to receive COP was 83 days, which was significantly shorter than for 7 cats that received doxorubicin (281 days). Thus, doxorubicin should be considered a well-tolerated and efficacious agent for the maintenance of remission in cats with lymphoma.     

Comparison of 3 protocols for treatment after induction of remission in dogs with lymphoma

BACKGROUND: The optimal treatment after inducing complete remission (CR) in dogs with lymphoma has not been established. HYPOTHESIS: After inducing CR with L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisone (L-CHOP); consolidation with either half-body radiation therapy (HBRT); or lomustine (CCNU) and mechlorethamine, vincristine, procarbazine, prednisone (MOPP) would improve first remission duration compared with continuing a CHOP-based protocol for an additional 4 months. ANIMALS: Dogs with stage III-V lymphoma. METHODS: Prospective clinical trial in which dogs initially were treated with an 8-week induction protocol that consisted of L-CHOP. Dogs in CR after induction were then allocated to 1 of 2 consolidation arms. A chemotherapy consolidation arm consisted of 2 treatments with CCNU and 1 cycle of MOPP. A HBRT arm consisted of 2 sequential 8.0-Gy fractions to the cranial and caudal half-body separated by 30 days. Vincristine was given between fractions. Results of the consolidation arms also were compared with a historical group treated with the same 8-week induction protocol followed by CHOP therapy until week 24. RESULTS: Overall, 67% of the dogs were in CR after 8 weeks of induction chemotherapy and were compared. Fifty-two dogs were in the historical arm, 23 in the CCNU/MOPP arm, and 27 in the HBRT arm. No difference in first remission duration was found among groups. Median first remission duration for the historical, CCNU/MOPP, and HBRT arms were 307, 274, and 209 days, respectively (P = .28). Overall second CR rate was 82% and was not different among groups (all P > or = .58). Overall remission duration (P = .28) and survival time (P = .48) were not different among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Consolidation with either CCNU/MOPP or HBRT showed no advantage over a standard CHOP-based protocol.     

Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: a pilot study

Feline head and neck squamous cell carcinoma (SCC) is a loco‐regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials.     

Response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol: 38 cases (1996-2003)

OBJECTIVE: To determine response rates and survival times for cats with lymphoma treated with the University of Wisconsin-Madison chemotherapy protocol. DESIGN: Retrospective study. ANIMALS: 38 cats with lymphoma. PROCEDURE: Medical records were reviewed, and information on age, sex, breed, FeLV and FIV infection status, anatomic form, clinical stage, and survival time was obtained. Immunophenotyping was not performed. RESULTS: Mean +/- SD age of the cats was 10.9 +/- 4.4 years. Overall median survival time was 210 days (interquartile range, 90 to 657 days), and overall duration of first remission was 156 days (interquartile range, 87 to 316 days). Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first remission or survival time. Eighteen of the 38 (47%) cats had complete remission, 14 (37%) had partial remission, and 6 (16%) had no response. Duration of first remission was significantly longer for cats with complete remission (654 days) than for cats with partial remission (114 days). Median survival time for cats with complete remission (654 days) was significantly longer than median survival time for cats with partial remission (122 days) and for cats with no response (11 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a high percentage of cats with lymphoma will respond to treatment with the University of Wisconsin-Madison chemotherapy protocol. Age, sex, anatomic form, and clinical stage were not significantly associated with duration of first response or survival time, but initial response to treatment was.     

A preliminary assessment of whole-body radiotherapy interposed within a chemotherapy protocol for canine lymphoma

Six dogs with spontaneously occurring, previously untreated lymphoma were treated with half‐body radiation therapy (RT) doses interposed in a CHOP‐based 25‐week chemotherapy regimen. Chemotherapy‐related toxicities were as expected and were mildly increased in severity post‐RT compared with pre‐RT. Treatment was delayed by 1–2 weeks per delay in four dogs due to chemotherapy‐related neutropenia. Radiation therapy was administered in two consecutive day fractions of 4 Gray to the cranial and caudal halves of the body 4 weeks apart. Radiation‐related toxicities consisted of lethargy, alopecia, diarrhoea of less than 2‐day duration and average decreases in neutrophil counts of 50%. Late effects from RT were not evident. Median remission and survival times for the six dogs were 455 and 560 days, respectively. The protocol was well tolerated and should be studied further to evaluate the potential therapeutic gain of the addition of RT to chemotherapy for the treatment of canine lymphoma.     

Recurrent adenocarcinoma in a ferret

A 4.5-year-old, neutered male ferret with a history of recurrent adenocarcinoma in the preputial region was given 2 radiation treatment courses designed to control the rapidly growing neoplasm. The tumor regressed completely after the first 3.5-week course of therapy. The ferret remained clinically disease-free for 4 months, at which time small masses were noticed in the inguinal area and the original tumor site. A second course of therapy was administered, which again resulted in complete clinical regression of the neoplasm. However, the duration of remission was brief. Local recurrence and abdominal metastasis were observed within 2 months of the completion of therapy.     

RADIOTHERAPY WITH AND WITHOUT CHEMOTHERAPY FOR LOCALIZED LYMPHOMA IN 10 CATS

A retrospective study was undertaken to determine the efficacy of radiotherapy with and without chemotherapy for treatment of localized lymphoma in 10 cats. Tumor location included nasal cavity (3 cats), retrobulbar area (3 cats), mediastinum (1 cat), subcutaneous tissue (1 cat), maxilla (1 cat) and mandible (1 cat). Six cats were treated with radiation alone and 4 cats also received chemotherapy during and/or after radiotherapy. Complete remission was achieved locally in 8 of 10 cats, whereas 2 cats had partial remission. Five of the 6 cats treated with radiotherapy alone achieved complete remission. Overall mean and median remission times for the 8 cats with complete remission were 123 weeks and 114 weeks, respectively (range 4 to 277 weeks). Three of the 8 cats have been in complete remission for more than 131 weeks and are still alive. Three cats achieving complete local remission developed lymphoma outside the radiation field. One cat had recurrence at the site of irradiation. Results of the retrospective study suggest that radiotherapy with and without chemotherapy may be effective for the treatment of localized lymphoma in the cat.     

Chemoimmunotherapy for canine lymphosarcoma

A total of 157 dogs with lymphosarcoma were available for study; 67 were treated. All of the treated dogs were given 4 drug combinations and 20 of them also were given autogenous vaccine. Sixty (90%) of the dogs treated with multiple drugs improved clinically. Of the dogs with clinical improvement, 48 (80%) had either complete or partial remission; of these, 32 (67%) had complete remission. Clinical staging proved useful in increasing the accuracy of prognosis, whereby dogs in less advanced stages of disease responded better to therapy, with a higher percentage of complete clinical remissions and longer survival. The mean survival time of the 47 dogs treated with drugs alone was 138 days, which compared with a mean survival time of 30 days for 34 nontreated dogs. Dogs subjected to chemotherapy and immunotherapy had a mean survival time of 341 days. Dogs in complete remission at time of vaccination survived significantly (P less than 0.01) longer than did dogs treated with drugs and vaccinated while not incomplete remission.     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.     

Piroxicam, mitoxantrone, and coarse fraction radiotherapy for the treatment of transitional cell carcinoma of the bladder in 10 dogs: a pilot study

Ten dogs with transitional cell carcinoma (TCC) of the bladder were treated with a combination of once-weekly coarse fraction radiation therapy (six weekly fractions of 5.75 Gray [Gy]), mitoxantrone chemotherapy, and piroxicam. All dogs completed the radiation therapy protocol, and only minimal side effects were observed. Only two (22%) dogs achieved a measurable partial response; however, 90% of the dogs had amelioration of their urinary clinical signs. The median survival time for all dogs was 326 days. While this treatment protocol was well tolerated, the response rate and overall survival duration was not superior to reports using mitoxantrone and piroxicam without radiation therapy in dogs with TCC.     

Principles of treatment for canine lymphoma

Canine lymphoma is one of the most commonly diagnosed canine neoplasms. It is helpful to classify lymphoma anatomically, because these forms each have common histories and clinical signs. Anatomic forms include multicentric, alimentary, mediastinal, and cutaneous forms. Because lymphoma is a systemic disease, systemic chemotherapy is the most appropriate modality for its treatment. Lymphoma cells are sensitive to chemotherapy, and complete remission rates are high when these patients are treated with conventional chemotherapy. Treated dogs maintain a good quality of life, and treatment can provide resolution of many presenting signs and abnormalities. The fundamental goals of chemotherapy are to induce a durable remission and to re-induce a remission after one or more relapses. Other therapies, such as surgery and radiation therapy, are appropriate in certain situations. Prognostic factors will also be summarized.     

Treatment of dogs with lymphoma using a 12-week, maintenance-free combination chemotherapy protocol

BACKGROUND: Treatment of lymphoma in dogs by long-term chemotherapy has favorable results. However, the efficacy of short-term, maintenance-free treatment protocols on remission and survival times in dogs has not been determined. HYPOTHESIS: That treatment using a 12-week chemotherapy protocol would be associated with satisfactory treatment outcome in dogs with lymphoma. ANIMALS: 77 dogs with histologically or cytologically confirmed diagnosis of lymphoma. METHODS: Prospective clinical trial in which dogs were treated with a 12-week chemotherapy protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, and prednisolone. RESULTS: Complete remission rate was 76.3%. Multivariate logistic regression analysis revealed that clinical substage (P = .006) and immunophenotype (P = .003) had a significant influence on the likelihood of a dog achieving complete remission. Median duration of first complete remission was 243 days (range 19-1,191 days). The 6-month, 1-year, and 2-year remission rates were 68%, 28%, and 16%, respectively. In the multivariate analysis of patient variables, immunophenotype (P = .022) revealed a significant influence on first remission duration. Toxicosis was mild with the exception of 1 treatment-associated death. CONCLUSIONS AND CLINICAL IMPORTANCE: In this group of dogs the 12-week maintenance-free chemotherapy protocol was well tolerated and had satisfactory results.     

Canine intranasal tumours treated with alternating carboplatin and doxorubin in conjunction with oral piroxicam: 29 cases

Few veterinary studies have evaluated the response to chemotherapy treatment of canine intranasal tumours, while many have focused on the efficacy of radiation therapy. Given the higher costs and limited access to radiation therapy, alternative treatment options are needed. The study describes a cohort of dogs with histologically confirmed intranasal tumours treated with chemotherapy as a sole therapy. This retrospective study was conducted using data from the Melbourne Veterinary Specialist Centre (MVSC) database between 2004 and 2017. Dogs with a histologically confirmed intranasal tumour who received chemotherapy treatment were included. Signalment, presenting signs, tumour type, chemotherapy details, adverse events (AEs) and survival times were reviewed. Twenty‐nine dogs met the inclusion criteria. Overall median survival time for dogs in the study was 234 days (range 12‐1698 days). Median survival for dogs with adenocarcinoma or carcinoma (n = 12) was 280 days, transitional cell carcinoma (n = 6) 163 days, squamous cell carcinoma, anaplastic carcinoma or undifferentiated carcinoma (n = 7) 59 days and all sarcomas (n = 4) 448 days. Adverse events were reported following 28% of treatments and 69% of dogs experienced at least one AE. Twenty four per cent of all dogs experienced grade 3 or 4 toxicities. The chemotherapy protocol was generally well tolerated. The study suggests potential benefit in the use of chemotherapy for dogs with adenocarcinoma, carcinoma and sarcoma.     

A retrospective study of canine oral extramedullary plasmacytoma over a 15-year period (July 2004–July 2019): Treatment,histologic parameters and clinical outcomes

A total of 45 cases of canine oral extramedullary plasmacytomas (EMPs) presented to a tertiary referral institution over a 15-year period were examined. Histologic sections of 33 of these cases were examined for histopathologic prognostic indicators. Patients underwent variable treatment including surgical intervention, chemotherapy and/or radiation therapy. Long term survival was observed in the majority of dogs with a median survival time of 973 days (2–4315 days). However, almost 1/3 of dogs had progression of plasma cell disease, including two cases with myeloma-like progression. Histologic characterization of these tumours did not reveal criteria to predict tumour malignancy. However, cases without tumour progression did not exceed 28 mitotic figures in ten 400× fields (2.37 mm²). All cases with tumour related death showed at least moderate nuclear atypia. Oral EMPs may represent a local manifestation of systemic plasma cell disease or singular focal neoplasia.     

Survival Analysis of 97 Cats with Nasal Lymphoma: A Multi-Institutional Retrospective Study (1986–2006)

Background: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists.
Hypothesis: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy.
Animals: Records from 97 cats diagnosed with NLSA were examined.
Methods: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT + chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT + chemotherapy (n = 60), RT alone (n = 19), or chemotherapy alone (n = 18).
Results: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia ( P < .001), and positive independent prognostic variables were a complete response to therapy ( P < .001) and total radiation dose >32 Gy ( P = .03).
Conclusions and Clinical Importance: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.