scholarly journals Treatment of Canine Oral Melanoma with Adjuvant Chemotherapy and Immunotherapy

2021 ◽  
Vol 49 ◽  
Author(s):  
Gleidice Eunice Lavalle ◽  
Carla Emanuela Tertuliano Caires ◽  
Stéfane Valgas Teixeira ◽  
Rúbia Monteiro de Castro Cunha ◽  
Rubens Antônio Carneiro

Background: Melanoma is the most frequent cancer in the canine oral cavity. It shows an aggressive behavior, characterized by rapid and invasive growth and high metastatic potential. Metastasis is seen in more than 80% of dogs at time of death. Adjuvant therapy should be recommended because of potential recurrence and metastasis. Oral melanoma has a poor prognosis even when adjuvant treatments are used. There are some treatment options, but the high death rate due to the disease is still a challenge. The aim of this study was to assess the overall survival of dogs diagnosed with oral melanoma and treated with adjuvant chemotherapy and immunotherapy. Materials, Methods & Results:A retrospective analysis was carried out in 20 dogs with oral melanocytic or amelanocytic melanomas. Cases were staged according to a modified World Health Organization clinical staging system for canine oral malignant melanoma. Tumor size (T1: < 2 cm; T2: 2 - 4 cm; T3: > 4 cm), regional metastasis (N0: no metastasis; N1: metastasis) and presence of distant metastasis (M0: no metastasis; M1: metastasis) are evaluated. Then, cases were divided into 4 stages: I (T1 N0 M0), II (T2 N0 M0), III (T3 N0-1 M0, Tx N1 M0) and IV (Tx Nx M1). Diagnoses were confirmed with histopathological exam and immunohistochemistry (IHC) when necessary. In poorly differentiated neoplasms, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Animals were divided into 2 groups: dogs submitted to surgery alone were included in group 1 (G1); dogs submitted to surgery associated with adjuvant chemotherapy with four 21-day cycles of carboplatin (300 mg/m2) and immunotherapy with six 7-day cycles of interferon-α (3 x 106 IU/m2) were included in group 2 (G2). Twenty dogs diagnosed with oral melanoma were evaluated: 3 were included in G1 and 17 in G2. Considering clinical staging of the dogs: 7 stage II, 12 stage III and only 1 stage IV. There was no stage I patients. In poorly differentiated neoplasias, IHC was performed at the request of the submitting veterinarian using specific markers PNL-2 and Melan-A. Patient follow-up was obtained through the evaluation of patient records and telephone interviews with owners. The overall survival time (OS) was defined by the period (in days) between the date of surgical excision and the death caused by the disease. Median overall survival time was 86 days for animals in G1 and 894 days for animals in G2 (P = 0.01). Discussion: Carboplatin was considered an appropriate cytostatic drug to treat microscopic disease in oral melanoma. INF-α was chosen for immunotherapy in this study because it promotes immune system stimulation associated with an indirect antiproliferative effect on neoplastic cells. The association of INF-α and carboplatin resulted in a significant increase in overall survival, when compared to the literature, suggesting that association of chemotherapy and immunomodulation is an important strategy in the treatment of canine oral melanoma. Controlled prospective randomized trials are necessary to confirm the benefits of chemotherapy and immunotherapy association to treat canine oral melanoma. Adjuvant therapy with chemotherapy and immunotherapy was considered effective to increase overall survival and maintained quality of life of dogs diagnosed with oral melanoma.

2009 ◽  
Vol 32 (2) ◽  
pp. 180 ◽  
Author(s):  
Shen Xu-dong ◽  
Shen Zan ◽  
Zheng Shui-er ◽  
Tang Li-na ◽  
Yu Wen-xi ◽  
...  

Purpose: To determine the prognostic value of the expression of Ezrin, CD44 and Six1 genes in osteosarcoma tissues of Chinese patients. Methods: Fluorescent quantitative real-time PCR was applied to study the mRNA levels of Ezrin, CD44 and Six1 genes in 32 osteosarcoma patient samples and 10 adjacent normal tissues and MG63 osteosarcoma cell lines. The analysis of relationships between pulmonary metastasis and overall survival time were carried out based on the clinical data. Results: mRNA levels of Ezrin and Six1 genes in osteosarcoma tissues were higher than those in adjacent normal tissues (P=0.015, 0.025). The mRNA levels of Ezrin, CD44 and Six1 genes were closely correlated with Enneking GTM clinical staging, while no correlations were demonstrated between the mRNA level of these genes with sex, age, location or pathological types. In addition, we demonstrated that the high mRNA level of Ezrin gene was related to shorter lung metastasis-free and overall survival time of the Chinese patients with osteosarcoma (P < 0.001). Conclusion: Our data suggest that Ezrin, but not CD44 and Six1, could be a prognostic factor and a predictor of potential lung metastasis in osteosarcoma. Further large sample studies need to be done to confirm the potential value of Ezrin as a new therapeutic target.


2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Ge Zhang ◽  
Wan-Li Liu ◽  
Lin Zhang ◽  
Jun-Ye Wang ◽  
Miao-Huan Kuang ◽  
...  

The indoleamine 2,3-dioxygenase-(IDO-) mediated microenvironment plays an important role in tumor immune escape. However, the inhibitory effects of IDO on the CD8+tumour-infiltrating lymphocytes (CD8+TILs) in esophageal squamous cell carcinoma (ESCC) have not been clarified yet. Here, we found that the level of IDO expression in ESCC tumor specimens correlated with a reduction in the number of CD8+TILs. Patients with high IDO expression and a low number of CD8+TILs had significantly impaired overall survival time. IDO expression and functional enzyme activity in ESCC cell lines could be induced by IFNγ. When exposed to the milieu generated by IDO-expressing Eca109 cells, the CD8+TILs were suppressed in proliferation, and their cytolytic functions against target tumor cells were lost. These results suggested that impairing CD8+TIL functions by IDO expressed in ESCC possibly contributed to the finding that patients with higher IDO expression have more aggressive disease progression and shorter overall survival time.


2021 ◽  
Vol 11 (1) ◽  
pp. 20-28
Author(s):  
D.  M. Kuchin ◽  
Ya.  I. Kolesnik ◽  
H.  G. Torgomyan ◽  
V.  E. Zagainov

Purpose. To identify major factors affecting the overall survival (OS). To select the cohort of patients with the best prognosis.Materials and methods. A retrospective analysis included data of 268 patients, 128 men and 140 women, with median age of 59±10,53 (30 to 83) years. For multivariate analysis of survival, patients were selected who underwent pancreaticoduodenectomy (PD) for ductal adenocarcinoma of the pancreatic head.Results. Our study demonstrated that histologically verified vascular invasion (detected only in 30 % of patients who underwent PD with resection of the major vessels) statistically significantly affected the OS. The increased CA19-9 level over 500 U / L (detected in 32,3 % of cases) is the factor that significantly worsens the OS. Patients with high grade adenocarcinoma have significantly better survival rates compared with patients who have moderately or poorly differentiated adenocarcinoma (p = 0.014; median 26 months, 95 % CI 4.4–47.6 versus median 17 months, 95 % CI 15–19, an median: 13 months, 95 % CI 5–21, respectively). Also, the use of adjuvant chemotherapy has a positive effect on long-term outcomes (p = 0.0001; median 26 months, 95 % CI 21.7–30.3 versus median 13 months, 95 % CI 11.3–14.7).Conclusion. A well-differentiated tumor and the use of adjuvant chemotherapy significantly increase the OS of patients. Poorly differentiated tumor, CA19-9 level over 500 U / mL and the histologically confirmed vascular invasion significantly worsen the prognosis of these patients.


Author(s):  
Maegan L. Watson-Skaggs ◽  
Tracy L. Gieger ◽  
Hiroto Yoshikawa ◽  
Michael W. Nolan

Abstract OBJECTIVE To describe clinical outcomes in cats with insulin resistance and acromegaly treated with stereotactic radiosurgery (SRS). ANIMALS 14 client-owned cats. PROCEDURES Medical records of cats with insulin resistance and acromegaly treated with SRS (17 Gy) between August 2013 and November 2019 at a single institution were reviewed. Kaplan-Meier analysis was used to evaluate overall survival time. RESULTS Acute adverse effects of SRS included somnolence (n = 2) and alopecia (1). Delayed adverse effects of SRS included unspecified neurologic complications (n = 1; 481 days), seizures (1; 1,541 days), and hypothyroidism (1; 64 days). Exogenous insulin requirements decreased in 10 of the 14 cats, with a median time to lowest insulin dose of 399 days (range, 42 to 879 days). Complete diabetic remission was achieved in 3 cats. The median overall survival time was 741 days (95% CI, 353 to 1,129 days). Six cats were still alive at the end of the study period, with a median follow-up time of 725 days. In 7 of the 8 cats that had died, death was presumptively attributed to acromegaly owing to continued insulin resistance, organ failure, or altered neurologic status. CLINICAL RELEVANCE The SRS protocol was well tolerated and associated with survival times similar to those reported previously. Most cats had decreased exogenous insulin requirements after SRS. Latency to an endocrine response was highly variable, emphasizing the need for careful ongoing diabetic monitoring of acromegalic cats after pituitary gland irradiation.


2020 ◽  
Author(s):  
Gerardo I. Magallanes-Garza ◽  
Sandra K. Santuario-Facio ◽  
Arlina F. Varela-Varela ◽  
Servando Cardona-Huerta ◽  
Pablo Ruiz-Flores ◽  
...  

Abstract Background: Studies of molecular changes occurring before and after neo-adjuvant chemotherapy (NCT) for breast cancer may unveil genetic biomarkers to predict therapy response. This study aimed at identifying genomic changes in breast primary tumors of patients under NCT. Gene expression changes were correlated with pathological response and survival.Methods: Gene expression profiles in tissue samples from pre and post NCT were obtained by a non-supervised classification analysis. Thirty-nine patients were classified according to their response to the chemotherapy as pathologic complete responders or non-responders (pCR and no-pCR, respectively). Overall survival was assessed by comparing gene expression values before NCT using the Log-rank (Mantel-Cox) test. Results: A signature constituted by 43 genes was obtained to stratify pCR and no-pCR patients after NCT (FC = + 3, FDR p -value < 0.0298). These genes were involved in regulation of the mitotic nuclear division and the anaphase-promoting complex-dependent catabolic process. Remarkably, over-expression of NUSAP1 and KIAA0101 were associated to poor overall survival. Conclusions: A new expression signature evaluating response for the neo-adjuvant chemotherapy stratified pathological response. The expression levels of NUSAP1 and KIAA0101 before and after the neo-adjuvant therapy may be useful to predict overall survival.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4587-4587
Author(s):  
Luca Laurenti ◽  
Francesco Autore ◽  
Barbara Vannata ◽  
Idanna Innocenti ◽  
Francesco Santini ◽  
...  

Abstract Abstract 4587 Chronic Lymphocytic Leukemia (CLL) is the most common lymphoprolipherative disorder of the elderly population in Western countries. It shows a highly variable clinical course. In fact, some patients may die within few months from the diagnosis because of CLL itself or disease-related complications. Other patients do not require any treatment for many years and have a long-standing disease. Many of them could die because of disease different from CLL. The identification of subgroups of patients with peculiar features predictive of the clinical behaviour of the disease is important. This retrospective analysis has the purpose to study patients affected by CLL, diagnosed and followed at our single centre of Haematology, focusing our attention on their causes of death. We selected 340 patients affected by CLL from our data-base, diagnosed from January 1999 to December 2010 and followed until March 2012. We distinguished the causes of death in two groups: one related to CLL (as progression of the disease, evolution to Richter's Syndrome, infections due to chemotherapy) and the other not related to CLL (i.e. cardiovascular diseases, solid tumours, old age). Statistical analysis, conducted using SPSS version 16.0 for Windows and “GraphPad Prism” GraphPad Software Inc., compared these two groups and tried to select other subgroups. We recorded 69 deaths: 47 related to CLL (68.1%) and 22 unrelated to CLL (31.9%). The median age of death of our cohort of patients was 76 years (range 40–92); those patients with a CLL-related death (related pts) died at a median age of 76 years (range 40–89) and the patients with a CLL-unrelated death (unrelated pts) died at a median age of 76 years (range 61–92). No differences in terms of median age of death were found analysing the data by gender. Also, considering the overall survival time from diagnosis to death, it was 58 months (range 9–155) in the related group and 43 months (range 14–121) in the unrelated group (p=0.185). When divided our population by the disease behaviour, we obtained 3 subgroups of patients: patients who progressed and died for CLL related causes (group A), patients who progressed and died for CLL unrelated causes (group B) and patients who did not progress and died for CLL unrelated causes (group C) (Table 1). The only statistical significant difference was found among the median overall survival times in un-progressive patients who died for non CLL related causes (p=0.043). The median age of death was not affected by the cause of death in our CLL population. Moreover, patients with un-progressive CLL showed an overall survival time shorter than the progressive CLL subgroups. Patients with un-progressive CLL probably had a shorter survival because unrelated CLL diseases could are more difficult aggressive than CLL itself. Table 1. group A group B group C p N° patients 47 13 9 Median age at diagnosis (years) (range) 70 (39–85) 71 (56–83) 77 (67–86) n.s. Median age at death (years) (range) 76 (40–89) 75 (61–84) 79 (68–92) n.s. Overall survival time (months) (range) 58 (9–155) 48 (18–121) 22 (14–78) 0.043 Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 716-716
Author(s):  
Danish Shahab ◽  
Emmanuel M. Gabriel ◽  
Kristopher Attwood ◽  
Valerie Francescutti ◽  
Wen Wee Ma ◽  
...  

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.


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