Selpercatinib and capmatinib combination promotes sustained complete response in novel ISOC1-RET fusion lung cancer after resistance to RET inhibitor via MET amplification: Case Report.

RET fusions occur in 1-2% of non-small cell lung cancer. Selpercatinib and pralsetinib are selective RET inhibitors with significant improvement of outcome in patients with tumor harboring RET fusion; however, resistance mechanisms appear frequently, mainly driven by MAPK pathway bypass, secondary RET mutations, or in 5% via MET amplification. Co-inhibition of RET and MET is a compelling strategy for overcoming MET-dependent resistance to RET inhibitors and potentially other inhibitors. To our knowledge, this is the first report of a novel ISOC1-RET fusion lung cancer with a durable complete response to selpercatinib, with resistance via MET amplification, which was overcome by the successful combination of selpercatinib and capmatinib.

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Optimizing outcomes for patients with metastatic prostate cancer: insights from South East Asia Expert Panel.

AIMS: Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges. METHODS: Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations. RESULTS: The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance. CONCLUSION: Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC.

Consensus on diagnosis and management of non-metastatic castration resistant prostate cancer in Brazil: focus on patient, selection, treatment efficacy, side effects and physician's perception according to patient comorbidities

ABSTRACT Background: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. Objective: To present survey results on management of M0 CRPC in Brazil. Design, setting, and participants: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. Conclusions: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.

Consensus on diagnosis and management of non-metastatic castration resistant prostate cancer in Brazil: focus on patient, selection, treatment efficacy, side effects and physician's perception according to patient comorbidities.

BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.

Optimizing the treatment of metastatic castration-resistant prostate cancer: a Latin America perspective.

Prostate cancer is a significant burden and cause of mortality in Latin America. This article reviews the treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) and provides consensus recommendations to assist Latin American prostate cancer specialists with clinical decision making. A multidisciplinary expert panel from Latin America reviewed the available data and their individual experience to develop clinical consensus opinions for the use of life-prolonging agents in mCRPC, with consideration given to factors influencing patient selection and treatment monitoring. There is a lack of level 1 evidence for the best treatment sequence or combinations in mCRPC. In this context, consensus recommendations were provided for the use of taxane-based chemotherapies, androgen receptor axis-targeted agents and targeted alpha therapy, for patients in Latin America. Prostate-specific antigen (PSA) changes alone, during treatment, should be treated with caution; PSA may not be a suitable biomarker for radium-223. Bone scans and computed tomography are the standard imaging modalities in Latin America. Imaging should be prompted during treatment where symptomatic decline and/or significant worsening of laboratory evaluations are reported, or where a course of therapy has been completed and another antineoplastic agent is under consideration. Recommendations and guidance for treatment options in Latin America are provided in the context of country-level variable access to approved agents and technologies for treatment monitoring. Patients should be treated with the purpose of prolonging overall survival and preserving quality of life through increasing the opportunity to administer all available life-prolonging therapies when appropriate.

Preoperative and pathological staging of NSCLC: retrospective analysis of 291 cases.

OBJECTIVE: The objective of this study was to evaluate the accuracy of preoperative clinical staging with computed tomography in predicting the correct pathological stage. METHODS: Medical records of non-small cell lung cancer (NSCLC) patients treated, from 1990 to 2005 were reviewed. Clinical stage was based on routine preoperative clinical and imaging evaluation. Positron emission tomography was not routinely performed. Suspected lesions, that would preclude a surgical resection, were pathologically confirmed. The pathological stage was based on final postoperative or biopsy pathological assessment. A correlation table between clinical and pathological stages was generated. Cohen's kappa index, sensitivity, specificity, positive and negative predictive values and accuracy were calculated. RESULTS: Records of 291 patients were reviewed. Clinical stages Ia, Ib, IIa, IIb, IIIa, IIIb and IV were found respectively in 8.9%, 31.9%, 0.3%, 18.6%, 25.4%, 11% and 3.8%. Pathological staging was different from clinical staging in 33% (15% were upstaged and 18% downstaged). Sensitivity, specificity, positive and negative predictive values and accuracy for clinical staging were 78%, 69%, 82%, 64% and 67%, respectively. Cohen's kappa index was 0.574 (P < 0.001). CONCLUSION: Preoperative clinical staging presents limited efficacy for the correct staging of NSCLC patients from this sample of Brazilian population.

Estadiamentos pré-operatório e patológico do CPNPC: análise retrospectiva de 291 casos / Preoperative and pathological staging of NSCLC: retrospective analysis of 291 cases

OBJECTIVE: The objective of this study was to evaluate the accuracy of preoperative clinical staging with computed tomography in predicting the correct pathological stage. METHODS: Medical records of non-small cell lung cancer (NSCLC) patients treated, from 1990 to 2005 were reviewed. Clinical stage was based on routine preoperative clinical and imaging evaluation. Positron emission tomography was not routinely performed. Suspected lesions, that would preclude a surgical resection, were pathologically confirmed. The pathological stage was based on final postoperative or biopsy pathological assessment. A correlation table between clinical and pathological stages was generated. Cohen's kappa index, sensitivity, specificity, positive and negative predictive values and accuracy were calculated. RESULTS: Records of 291 patients were reviewed. Clinical stages Ia, Ib, IIa, IIb, IIIa, IIIb and IV were found respectively in 8.9 percent, 31.9 percent, 0.3 percent, 18.6 percent, 25.4 percent, 11 percent and 3.8 percent. Pathological staging was different from clinical staging in 33 percent (15 percent were upstaged and 18 percent downstaged). Sensitivity, specificity, positive and negative predictive values and accuracy for clinical staging were 78 percent, 69 percent, 82 percent, 64 percent and 67 percent, respectively. Cohen's kappa index was 0.574 (P < 0.001). CONCLUSION: Preoperative clinical staging presents limited efficacy for the correct staging of NSCLC patients from this sample of Brazilian population.

OBJETIVO: O objetivo do presente estudo foi avaliar a eficácia do estadiamento clínico pré-operatório com tomografia computadorizada com o estadiamento patológico. MÉTODOS: Entre 1990 e 2005, foram revisados retrospectivamente os prontuários dos pacientes com câncer de pulmão não-pequenas células (CPNPC). O estágio clínico foi baseado em exames pré-operatórios de imagem. Tomografia por emissão de pósitrons não foi incluída na rotina de exames pré-operatórios. Lesões suspeitas, que contra-indicassem a ressecção cirúrgica curativa, foram confirmadas patologicamente. O estágio patológico foi considerado aquele baseado na análise patológica pós-operatória ou em biópsia de lesão suspeita. Foi gerada uma tabela de correlação entre estágio clínico e patológico. Foram calculados o índice kappa de Cohen, a sensibilidade, a especificidade, o valor preditivo positivo e negativo, e a acurácia. RESULTADOS: 291 prontuários de pacientes foram revisados. Os estágios Ia, Ib, IIa, IIb, IIIa, IIIb e IV foram encontrados em 8,9 por cento, 31,9 por cento, 0,3 por cento, 18,6 por cento, 25,4 por cento, 11 por cento e 3,8 por cento, respectivamente. Estágio patológico foi diferente do estágio clínico em 33 por cento dos pacientes (15 por cento foram sobre-estadiados e 18 por cento sub-estadiados). Sensibilidade, especificidade, valor preditivo positivo e negativo, e acurácia foram 78 por cento, 69 por cento, 82 por cento, 64 por cento e 67 por cento, respectivamente. O índice kappa de Cohen foi de 0,574 (P < 0,001). CONCLUSÃO: O estadiamento clínico pré-operatório apresenta eficácia limitada no estadiamento dos pacientes com CPNPC.

Aggressive multimodality treatment in transitional cell carcinoma of the parafallopian tube: report of 2 cases and review of the literature.

BACKGROUND: Primary carcinoma of the fallopian tube is a rare and aggressive cancer. Information regarding its epidemiologic, biologic, and prognostic characteristics is limited; consequently, no standard treatment has been developed. We report the case histories of 2 women with transitional cell carcinoma (TCC) of the parafallopian tube treated with aggressive multimodality therapy, and the literature is reviewed. CASES: Two women presented with stage IIB TCC of the parafallopian tube. Both were treated with cytoreductive surgery followed by adjuvant intravenous chemotherapy with cisplatin, gemcitabine, and paclitaxel. Our consolidation treatment consisted of intraperitoneal chemotherapy using the same agents, and 1 patient also received additional hyperthermic chemotherapy with docetaxel. Both patients remain free of disease. CONCLUSION: In these 2 cases, an aggressive, multimodality regimen proved to be feasible and effective in treating TCC of the parafallopian tube.