Intratumor Heterogeneity of KIT Gene Mutations in Acral Lentiginous Melanoma.

Melanoma is an aggressive skin malignancy, and the acral lentiginous melanoma (ALM) subtype affects non-sun-exposed sites such as the volar surface of the hands and feet and the subungual region and is most common in Asians, Hispanics, and Afro-descendants. The presence of different clones within the same tumor seems to influence the aggressiveness of tumors. Patients with mutations in the KIT gene have shown a good response to tyrosine kinase inhibitor therapy. We tested the hypothesis of intratumor heterogeneity through analysis of KIT gene mutations in ALM and determined the correlation between KIT mutations and demographic, clinical, and histopathological variables. Twenty-five ALM samples were examined. We selected up to four different regions per tumor for sequencing by the Sanger method for analysis of KIT gene exon 11 and exon 13 mutations. Advanced lesions were predominant, and the main histopathological characteristics of lesions were Breslow index >4.0 mm (17/25, 68%), Clark level IV/V (21/25, 84%), ulceration (16/25, 64%), and >3 mitoses/mm (8/25, 32%). KIT gene mutations were detected in 11/25 cases (44%), and all these 11 cases displayed intratumor heterogeneity, that is, at least 2 tumor regions had different mutational profiles. The predicted effect of most mutations detected was detrimental to protein function. No significant correlations between histopathological variables and either KIT mutations or intratumor heterogeneity were observed. The hypothesis of intratumor heterogeneity of KIT gene mutations in acral lentiginous melanoma was supported.

Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K.

The choice of appropriate therapeutic strategies may be influenced by intratumor heterogeneity and makes cancer treatment considerably more challenging. We aimed to evaluate the heterogeneity of BRAF exon 15 mutations in different areas of acral lentiginous melanoma (ALM). The entire exon 15 was sequenced in 4 different areas of paraffin-embedded samples from 26 patients with ALM. A total of 26 of 49 cases of ≥1 mm in depth of ALM identified by clinical, anatomical, and pathological data fulfilled the inclusion and exclusion criteria for this study. Tumors had a mean Breslow depth of 7.2 mm and an average mitotic index of 3 mitosis/mm. Mutations distinct from the common V600E and V600K were detected in 31%, and intratumor heterogeneity was observed in 31% of samples. Interestingly, 63.5% of all mutations had been previously associated with cancer. Most (62.5%) of the missense BRAF exon 15 mutations found in the ALM samples examined here were deemed "detrimental" for protein function according to at least 2 functional prediction programs, and 3 mutations (37.5%) were predicted to be "neutral," with no effect on protein function. BRAF exon 15 mutations were detected frequently in ALM and displayed heterogeneity, a finding to be further investigated.

Monitoramento auditivo em adultos submetidos à quimioterapia com carboplatina / Auditory monitoring in adults undergoing chemotherapy with carboplatin / Monitoreo del oído en adultos sometidos a quimioterapia con carboplatino

Objetivo: Caracterizar a audição de pacientes adultos submetidos à quimioterapia com carboplatina por meio de exames audiológicos em dois momentos durante o tratamento quimioterápico. Métodos: Prospectivo e observacional. Participaram da pesquisa seis sujeitos adultos entre 53 e 59 anos e 11 meses, em tratamento quimioterápico com carboplatina submetidos a uma bateria de exames audiológicos. Os dados foram analisados por meio do teste ANOVA, teste z para proporções e Teste de Wilcoxon. O valor de significância adotado foi de 5% (p≤0,05). Resultados: Um aumento nos limiares auditivos foi observado, sobretudo nas frequências mais altas, porém não houve significância. Também foi observado aumento na relação sinal/ruído das emissões otoacústicas evocadas transientes e por produto de distorção, porém sem significância estatística. Conclusão: Não foram observadas mudanças estatisticamente significantes quanto aos limiares auditivos e as respostas das emissões otoacústicas, no entanto pode-se notar um aumento nos limiares audíveis, especialmente nas altas frequências, bem como aumento da amplitude de respostas nas emissões otoacústicas.

Purpose: To characterize the hearing of adult patients undergoing chemotherapy with carboplatin using two sequential audiological tests during chemotherapy treatment. Methods: Prospective and observational. The participants were six adult subjects between 53 and 59 years and 11 months, undergoing chemotherapy treatment with carboplatin subjected to a battery of audiological exams. Data were analyzed using the ANOVA test, z test for proportions and Wilcoxon signed-ranks test. The adopted significance was 5% (p ≤ 0.05). Results: An increase in hearing thresholds was observed, particularly in the higher frequencies, but there was no significance. It was also observed an increase in the signal / noise ratio of transient evoked otoacoustic emissions and for distortion product, but without statistical significance. Conclusion: No statistically significant changes regarding the hearing thresholds and responses of otoacoustic emissions were observed, however it could be noted an increase in hearing thresholds, especially at high frequencies, as well as the increased amplitude on the responses in otoacoustic emissions.

Objetivo: Caracterizar la audición de pacientes adultos sometidos a quimioterapia con carboplatino a través de pruebas audiológicas dos veces durante la quimioterapia. Métodos: Estudio prospectivo observacional. Los participantes fueron seis sujetos adultos de entre 53 y 59 años y 11 meses, sometidos a quimioterapia con carboplatino sometido a una batería de pruebas audiológicas. Los datos se analizaron mediante la prueba de ANOVA, prueba z para proporciones y prueba de los rangos con signo de Wilcoxon. La significancia fue del 5% (p ≤ 0,05). Resultados: fueron observados un aumento de los umbrales de audición, en particular en las frecuencias más altas, pero no identificaron significación. También se observó un aumento de la relación señal / ruido de emisiones otoacústicas evocadas transitorias y productos de distorsión, pero sin significación estadística. Conclusión: Los cambios estadísticamente significativos con respecto a los umbrales de audición y las respuestas de las emisiones otoacústicas, fueron observadas sin embargo es posible que observe un aumento de los umbrales audibles, especialmente a altas frecuencias, así como una mayor gama de respuestas de las emisiones otoacústicas.

Quality Oncology Practice Initiative Can Guide and Improve Oncology Providers' Training in Brazil.

PURPOSE: It has become crucial to translate scientific findings and to find ways by which to mobilize local resources to improve the quality and accessibility of cancer care in developing countries. This study seeks to provide insight into challenge through examining differences in clinician documentation of patients with cancer treated at a Brazilian Public University Hospital. METHODS: ASCO Quality Oncology Practice Initiative (QOPI) measures were used to examine the care provided in the departments of breast, colorectal, lymphoma, gynecology, and lung cancers. For this study, data from a representative sample of patients receiving chemotherapy in the previous month were extracted and quality of cancer care indicators examined. RESULTS: Certain elements of medical care were consistently and appropriately documented, including cancer diagnosis and stage, chemotherapy planning, administration, and summary. In general, considering the specific cancer management measures, patients received recommended care in accordance with recognized guidelines. Despite this, a number of important gaps in care were identified, including the assessment and treatment of pain, documentation of chemotherapy intention, symptom and toxicity management, patients' psychosocial status, and provision of a treatment summary at care completion. CONCLUSION: These findings are encouraging in terms of adherence to core treatment guidelines in cancer care in Brazil. However, results suggest important opportunities for improving care across a number of domains, many of which represent a challenge throughout both developing and developed countries. This study may also provide preliminary guidance for enhancing educational and training programs for professionals and students alike, to implement high-quality, comprehensive cancer care.

Brazilian data of renal cell carcinoma in a public university hospital.

PURPOSE: Among renal malignancies, renal cell carcinoma (RCC) accounts for 85% of cases. Stage is a relevant prognostic factor; 5-year survival ranges from 81% to 8% according to the stage of disease. The treatment is based on surgery and molecularly targeted therapy has emerged as a choice for metastatic disease. MATERIALS AND METHODS: Retrospective study by reviewing the medical records of patients with RCC treated in the last 10 years at UNIFESP. The primary end point of this trial was to evaluate the overall survival (OS) of the patients. The secondary end point was to evaluate the progression-free survival (PFS) after nephrectomy. RESULTS: 118 patients with RCC were included. The mean age was 58.3 years, 61.9% men; nephrectomy was performed in 90.7%, clear cell was the histology in 85.6%, 44 patients were classified as stage IV at diagnosis. Among these, 34 had already distant metastasis. 29 patients were treated with sunitinib. The median OS among all patients was 55.8 months. The median PFS after nephrectomy was 79.1 months. Sarcomatoid differentiation HR29.74 (95% CI, 4.31-205.26), clinical stage IV HR1.94 (95% CI, 1.37-2.75) and nephrectomy HR0.32 (95% CI, 0.15-0.67) were OS prognostic factors. Sunitinib had clinical activity. CONCLUSIONS: Patients treated in our hospital achieved median OS compatible with literature. Nevertheless, this study has shown a high number of patients with advanced disease. For patients with advanced disease, treatment with sunitinib achieved median OS of 28.7 months, consistent with the literature.

Brazilian data of renal cell carcinoma in a public university hospital

ABSTRACT Purpose Among renal malignancies, renal cell carcinoma (RCC) accounts for 85% of cases. Stage is a relevant prognostic factor; 5-year survival ranges from 81% to 8% according to the stage of disease. The treatment is based on surgery and molecularly targeted therapy has emerged as a choice for metastatic disease. Materials and Methods Retrospective study by reviewing the medical records of patients with RCC treated in the last 10 years at UNIFESP. The primary end point of this trial was to evaluate the overall survival (OS) of the patients. The secondary end point was to evaluate the progression-free survival (PFS) after nephrectomy. Results 118 patients with RCC were included. The mean age was 58.3 years, 61.9% men; nephrectomy was performed in 90.7%, clear cell was the histology in 85.6%, 44 patients were classified as stage IV at diagnosis. Among these, 34 had already distant metastasis. 29 patients were treated with sunitinib. The median OS among all patients was 55.8 months. The median PFS after nephrectomy was 79.1 months. Sarcomatoid differentiation HR29.74 (95% CI, 4.31-205.26), clinical stage IV HR1.94 (95% CI, 1.37-2.75) and nephrectomy HR0.32 (95% CI, 0.15-0.67) were OS prognostic factors. Sunitinib had clinical activity. Conclusions Patients treated in our hospital achieved median OS compatible with literature. Nevertheless, this study has shown a high number of patients with advanced disease. For patients with advanced disease, treatment with sunitinib achieved median OS of 28.7 months, consistent with the literature.