Surgical resection, intraoperative radiotherapy and immediate plastic reconstruction: A good option for the treatment of distal extremity soft tissue sarcomas

AimTo show three patients with soft tissue sarcomas of distal extremities conservatively treated after tumor-board discussion, involving margin-free surgery, exclusive intraoperative radiotherapy, and immediate reconstruction.BackgroundCurrent guidelines show clear and robust recommendations regarding the composition of the treatment of sarcomas of extremities. However, little evidence exists regarding the application of these treatments depending on the location of the primary neoplasia. Tumors that affect the distal extremities present different challenges and make multidisciplinary discussions desirable.Methods/ResultsWe reported 3 patients who were approached with a conservative intention, after tumor board recomendation. The goals from the treatment performed were aesthetic and functional preservation, while enruring locoregional control. We had wound healing complications in 2 of the cases, requiring additional reconstruction measures. Patients are followed up for 24, 20 and 10 months; local control is 100%, and functional preservation is 100%.ConclusionsDespite being a small series, it was sufficient to illustrate successful multidisciplinary planning, generating a therapeutic result with improved quality of life for patients who had an initial indication for extremity amputation

A phase II study of first-line nivolumab in patients with advanced cutaneous squamous-cell carcinoma

Introdução: O carcinoma de células escamosas (CEC) de pele figura dentre as mais frequentes neoplasias diagnosticadas mundialmente, demonstrando um aumento em sua incidência ao longo das últimas décadas. Para pacientes não candidatos ao tratamento locorregional com intuito curativo, o uso de bloqueadores de correceptores imunes com anticorpos monoclonais anti-programmed death receptor 1 (PD-1) despontou como promissora estratégia de tratamento. Nesse estudo, buscou-se investigar a atividade do agente anti-PD-1 nivolumabe (NIVO) em pacientes com CEC de pele avançado. Pacientes e métodos: Trata-se de um estudo de fase II aberto, de braço único, com o objetivo de determinar a eficácia e a segurança do NIVO em pacientes com CEC de pele avançado sem tratamentos sistêmicos prévios. NIVO foi administrado na dose de 3mg/kg a cada 14 dias até progressão de doença, toxicidade limitante, ou 12 meses de tratamento. O desfecho primário do estudo foi a taxa de resposta objetiva (TR) em 24 semanas, de acordo com critérios RECIST 1.1. Desfechos secundários incluíram segurança, duração de resposta, sobrevida livre de progressão (SLP) e sobrevida global (SG). Resultados: Vinte e quatro pacientes com o diagnóstico de CEC avançado foram incluídos no estudo, com uma mediana de idade da amostra de 74 anos (intervalo: 48 a 93 anos). Os sítios primários mais frequentes foram cabeça/pescoço (41,7%) e tronco (29,2%), e 10 pacientes (41,7%) receberam radioterapia previamente à inclusão no estudo. Todos os 24 pacientes foram incluídos na avaliação de resposta, e a TR em 24 semanas foi 58,3% (14/24). Após uma mediana de seguimento de 17,6 meses, a mediana de duração de resposta não foi atingida, e as medianas de SLP e SG estimadas foram 12,7 e 20,7 meses, respectivamente. A exposição prévia à radioterapia se associou a piores desfechos em análise univariada (p=0,035). Eventos adversos relacionados ao tratamento de qualquer grau e grau 3 ou superior ocorreram em 21 pacientes (87,5%) e 6 pacientes (25%), respectivamente, e um paciente descontinuou NIVO em função de toxicidades limitantes. Conclusões: NIVO resultou em expressiva atividade antitumoral, respostas duradouras e boa tolerância em pacientes com CEC de pele avançado sem tratamentos prévios. Os resultados desse estudo fornecem evidências adicionais para embasar o uso de bloqueadores de correceptores imunes como a estratégia padrão no tratamento do CEC de pele avançadoIntroduction: Cutaneous squamous-cell carcinoma (cSCC) is among the most frequent malignancies worldwide, and an increasing incidence has been documented over the past decades. For those not amenable to treatment with curative intent, immune checkpoint (ICP) blockade with anti-programmed death receptor 1 (PD-1) antibodies emerged as a promising therapeutic option. In this study, we sought to investigate the activity of the anti-PD-1 agent nivolumab (NIVO) in patients (pts) with advanced cSCC (AcSCC). Patients and Methods: We conducted a single-arm, open-label, phase II study to evaluate the safety/efficacy of NIVO in systemic-treatment-naïve pts with AcSCC. NIVO at 3mg/kg was administered every 2 weeks until disease progression, unacceptable toxicity or 12 months (mo) of treatment. The primary endpoint was the best objective response rate (bORR) at 24 weeks as per RECIST 1.1 criteria. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Results: Twenty-four pts with AcSCC were enrolled, with a median age of 74 years (range 48-93). Most frequent primary sites were head and neck (41.7%) and trunk (29.2%), and 10 pts (41.7%) had received prior radiation-therapy. All 24 pts were evaluable for response, and the bORR at 24 weeks was 58.3% (14/24). With a median follow-up of 17.6 mo, median duration of response has not been reached, and the estimated median PFS and OS were 12.7 and 20.7 mo, respectively. Prior exposure to radiotherapy was associated with worse outcomes (p=0.035, univariate analysis). Treatment-related AEs of any grade and grade 3 occurred in 21 pts (87.5%) and 6 pts (25%), respectively, and 1 patient discontinued NIVO due to toxicities. Conclusions: NIVO resulted in robust antitumor activity, sustained responses and good tolerability in systemic-treatment-naïve pts with AcSCC. These data provide further evidence to support the use of ICP as the standard treatment of AcSC

Recent advances in understanding antitumor immunity [version 1; referees: 3 approved]

The term “antitumor immunity” refers to innate and adaptive immune responses which lead to tumor control. Turning the immune system into a destructive force against tumors has been achieved in a broad range of human cancers with the use of non-specific immunotherapies, vaccines, adoptive-cell therapy, and, more recently with significant success, through blockade of immune checkpoints. Nevertheless, the efficacy of these approaches is not universal, and tools to identify long-term responders and primarily refractory patients are warranted. In this article, we review recent advances in understanding the complex mechanisms of antitumor immunity and how these developments can be used to address open questions in a setting of growing clinical indications for the use of immunotherapy

Aspergillosis in a Patient Receiving Temozolomide for the Treatment of Glioblastoma

Leukopenia and selective CD4+ lymphopenia represent major adverse events associated with the use of temozolomide (TMZ), an oral alkylating agent incorporated in the treatment of glioblastoma (GBM). The increased risk of opportunistic infections, including those caused by Pneumocystis jiroveci and cytomegalovirus, has been previously described in the literature. Here we report the case, the first to our knowledge, of a patient with pulmonary invasive aspergillosis immediately after the completion of chemoradiation with TMZ for GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had excellent response to systemic voriconazole. This case illustrates that TMZ can be associated with severe opportunistic infections, presumably associated with T lymphocyte immune dysfunction, and patients exposed to this agent should be carefully monitored

Response to Paclitaxel in an Adult Patient with Advanced Kaposiform Hemangioendothelioma

Background: Kaposiform hemangioendothelioma (KHE) is a rare neoplasm of vascular origin that typically arises from the skin or soft tissues as a solitary tumor. The optimal therapy for this disease is still unknown. We report the case of an adult patient presenting with metastatic KHE of the spleen, who had a partial response after treatment with paclitaxel. Case Presentation: A 36-year-old man presented in November 2012 with a nontraumatic rupture of the spleen. A splenectomy was performed, and the pathology was consistent with a nonspecific vascular proliferation. Follow-up scans revealed lytic bone lesions and liver metastasis. A biopsy of the liver was performed and confirmed KHE. The decision was made to proceed with treatment with gemcitabine and docetaxel, which was discontinued due to myelotoxicity. The patient was then transferred to our institution, and a pathology review supported the diagnosis of metastatic KHE. His disease remained stable until February 2014, when he developed progression in the liver. Chemotherapy was restarted with paclitaxel, and a partial response was documented after 3 cycles. Unfortunately, disease progression occurred after 24 weeks, and subsequent treatments included prednisone, doxorubicin, interferon-α, gemcitabine, and ifosfamide, without any response. The patient developed Kasabach-Merritt phenomenon and passed away 1 week later due to a major gastrointestinal bleeding. Conclusions: This case report suggests that paclitaxel could be considered as a treatment option for advanced KHE, a rare condition for which no standard treatment exists

Tumor Reduction with Pazopanib in a Patient with Recurrent Lumbar Chordoma

Introduction. Chordomas are rare malignancies of bone origin that occur in the axial skeleton, typically the skull base and lumbar/sacral regions. Although often classified as low-grade neoplasms, its locally infiltrative behavior may result in significant morbidity and mortality. Optimal surgical resection may be curative, but up to 50% of the cases relapse within 5 years, and currently there are no systemic treatments approved in this setting. A large proportion of these tumors express stem-cell factor receptor (c-KIT) and platelet-derived growth factor receptors (PDGFRs), providing a rationale for the use of tyrosine-kinase inhibitors (TKIs). Case report. A 27-year-old male presented with recurrent chordoma of the lumbar spine 4 years after initial diagnosis. Salvage therapies in the interval included repeat resections and radiation therapy. He ultimately developed multifocal recurrence not amenable to complete excision or reirradiation. A comprehensive genomic profiling assay was performed and revealed nondrugable alterations. Decision was made to proceed with systemic treatment with pazopanib 800 mg/day, resulting in tumor reduction (−23.1% reduction in size) and prolonged disease control. Conclusion. For this patient with a multiple recurrent chordoma and limited treatment options, pazopanib resulted in sustained clinical benefit following initial tumor reduction

Combination of irinotecan and a platinum agent for poorly differentiated neuroendocrine carcinomas

Extrapulmonary poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and highly aggressive neoplasm for which the optimal chemotherapy remains unclear. The objective of this study was to evaluate the outcomes of patients with PDNEC treated with cisplatin and irinotecan (IP) and perform a review of the literature. From 2008 to 2012, patients with advanced PDNEC (Ki67≥20%) who received the IP combination were selected for analysis. Radiologic responses were determined through Response Evaluation Criteria In Solid Tumors criteria. Twenty-eight patients were included. The median age at diagnosis was 57 years and the most common presentation was pancreatic PDNEC. Twenty-five patients (89%) received chemotherapy with cisplatin and irinotecan and three received carboplatin and irinotecan. Forty-six percent of the patients achieved objective response and the median time to tumor progression was 3.7 months. The median overall survival was 11.7 months. Thirteen patients (46%) had treatment interruptions or dose reductions due to grade 3/4 toxicity. This retrospective cohort of advanced extrapulmonary PDNEC patients suggests that the IP combination is feasible and resulted in similar response rate and median survival to other treatments previously reported