Immunotherapy with nivolumab for the treatment of soft tissue sarcoma with pulmonary metastasis: A case report.

Sarcomas are an unusual group of tumors, accounting for ~1% of cancer in adults. Immunotherapy has been shown to be a potential therapeutic option for the management of patients with cancer. However, there is still insufficient information on the action of immunotherapy on sarcomas. A 16-year-old male patient, diagnosed in December 2013 with grade III soft-tissue sarcoma in the right arm, was admitted to a private oncology service after relapse following surgical treatment. The patient underwent chemotherapy with ifosfamide plus adriamycin for 4 cycles, associated with adjuvant radiotherapy, followed by a new resection to remove the residual lesion. A year later, imaging tests identified pulmonary micronodules, and a new resection was performed. After immunohistochemical evaluation of biopsy, a large presence of programmed cell death 1 ligand 1 (PD-L1) marker was identified in tumor tissue and immunotherapy with nivolumab was performed. At present, the patient is in immunotherapeutic treatment (42 cycles), presenting an excellent general condition and without any symptoms, and a decrease in neoplastic lung masses. The literature recommends three cycles of anthracycline plus ifosfamide as adjuvant therapy to surgical treatment. Combined surgery plus adjuvant therapy has shown benefits in malignant tumors. Immunotherapy is an important therapeutic option for soft-tissue sarcomas with high programmed cell death protein 1 (PD-1)/PD-L1 expression. Treatment for high grade soft tissue sarcoma (STS) is still limited, due to tumor heterogeneity, and further studies are needed to consolidate the possibility of using immunotherapy to treat these neoplasms. When significant levels of specific biomarkers are present in tumor tissue, immunotherapy may be beneficial as shown by the present case report.

E-cigarettes and cancer patients.

The increasing popularity and availability of electronic cigarettes (i.e., e-cigarettes) in many countries have promoted debate among health professionals as to what to recommend to their patients who might be struggling to stop smoking or asking about e-cigarettes. In the absence of evidence-based guidelines for using e-cigarettes for smoking cessation, some health professionals have urged caution about recommending them due to the limited evidence of their safety and efficacy, while others have argued that e-cigarettes are obviously a better alternative to continued cigarette smoking and should be encouraged. The leadership of the International Association for the Study of Lung Cancer asked the Tobacco Control and Smoking Cessation Committee to formulate a statement on the use of e-cigarettes by cancer patients to help guide clinical practice. Below is this statement, which we will update periodically as new evidence becomes available.

Gefitinib and celecoxib in advanced metastatic gastrointestinal tumors: a pilot feasibility study.

BACKGROUND: This pilot, open-label study examined the safety and tolerability (primary objective) and efficacy (secondary objective) of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in combination with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, in patients with advanced or refractory gastrointestinal (GI) tumors of epithelial origin. METHODS: Patients were administered gefitinib (250 mg/day) plus celecoxib (400 mg twice daily). In the event of toxicity, dose interruptions were permitted and a single celecoxib dose reduction was allowed. RESULTS: Thirty patients (median age 60 years) with primary colorectal (25 patients), pancreatic (3 patients), esophageal (1 patient), or gall bladder (1 patient) tumors were recruited, 29 of whom had received prior chemotherapy. Adverse events (AEs) were generally mild and consisted mainly of acne, diarrhea, and nausea. Few severe AEs were noted. There were no withdrawals or deaths due to AEs. Dose reductions for celecoxib were reported for five patients, in three cases due to toxicity. Stable disease was confirmed in 12 patients (40%), with progressive disease in 18 patients (60%). CONCLUSIONS: After study completion, safety issues relating to the long-term use of COX-2 inhibitors have been raised. However, in this pilot study, the combination of gefitinib and celecoxib was generally well tolerated in patients with advanced GI cancer.

Neuroendocrine and biologic features of primary tumors and tissue in pulmonary large cell carcinomas.

BACKGROUND: Because biological behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and angiogenesis, p21(waf1/cip1) and microvessel density have been targeted as potentially useful tumor markers. We sought to validate the importance of p21(waf1/cip1) and microvessel density and study their interrelationship, analyzing clinical factors, subclassifications, and tumor and stromal markers. METHODS: We examined p21(waf1/cip1) and other markers in tissue from 61 patients with surgically excised large cell carcinomas. The amount of tumor staining for p21(waf1/cip1) and microvessel density was evaluated by immunohistochemistry and morphometry. The study outcome was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that after surgical excision, histologic subtypes were significantly related to survival time (p = 0.02), but quantitative staining of the tumor for p21(waf1/cip1) and microvessel density added prognostic information and these variables were more strongly prognostic than histologic subtype (p = 0.00). Cut points at the median staining of 3.5% and 3.0% for p21(waf1/cip1) and microvessel density, respectively, divided patients into two groups with distinctive survival times. Patients with p21(waf1/cip1) staining of more than 3.5% and microvessel density staining of more than 3.0% had a median survival time of 14 months. CONCLUSIONS: Tumor staining for p21(waf1/cip1) and microvessel density in resected large cell carcinomas and certain other types of lung tumors was strongly related to survival. Patients with more than 3.0% staining in their tumors were at high risk of death from lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.

COX-2, MMP-9, and Noguchi classification provide additional prognostic information about adenocarcinoma of the lung. A study of 117 patients from Brazil.

We report immunohistochemical staining results for cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in primary tumors of 117 patients with resected adenocarcinoma of the lung (median follow-up, 20 months). For COX-2, we graded the degree of tumor staining according to the sum of staining intensity and the proportion of cells staining. For MMP-9, we used morphometry to quantify cytoplasmic staining. We used the Cox proportional hazards model to analyze overall survival. With only 29 patients censored at last follow-up, after controlling for the effect of pathologic stage, staining for COX-2 and MMP-9 and subtype of tumor were related significantly to survival (P < 6 x 10(-5)). The effects of COX-2 and MMP-9 were opposite. Whereas any staining for COX-2 decreased the hazard and increased survival time, increased staining for MMP-9 increased the hazard and decreased survival time. The results also suggested that staining for COX-2 decreases with dedifferentiation. Our results suggest that staining for the combination of COX-2 and MMP-9 and categorizing tumors into papillary and nonpapillary types may provide important prognostic information for patients with resected adenocarcinoma of the lung; it is possible that these 3 variables could aid decisions about postoperative adjuvant treatment.

Imunodeficiência comum variável (hipogamaglobulinemia de início tardio ou hipogamoglobulinemia adquirida): seguimento inicial de 11 casos / Common variable immunodeficiency (hypogammaglobulinemia of late onset or acquired hypogammaglobulinemia): initial follow-up of 11 cases

O presente trabalho faz a avaliaçäo clínico-laboratorial de 11 pacientes com imunodeficiência comum variável, seguidos no Serviço de Imunopatologia do HC/FMUSP. A idade destes pcientes variou de oito a 45 anos, com tempo médio de doença de 12,6 anos e de diagnóstico de 4,3 anos. Manifestaçöes infecciosas, principalmente de vias aéreas e digestivas, ocorreram em todos os pacientes. Poliadenomegalia ocorreu em sete, hepatomegalia em seis, esplenomegalia em cinco e artralgia em quatro pacientes. Todos os casos apresentaram IgG sérica < 250 mg dl. IgA < 33 mg/dl e IGM < 31 ml/dl, exceto um paciente com IgM de 176 mg/dl. Os títulos de iso hemaglutininas foram < 1/20, exceto em um paciente. A determinaçäo de linfócitos B no sangue périférico revelou níveis normais em três, elevados em um e diminuidos em cinco pacientes. Cinco apresentaram testes cutâneos tardios positivos a pelo menos um dos antígenos testados (PPD, varidase (SK-SD), Tricofitina e Levedurina). A avaliaçäo da relaçäo CD-4/CD-8 obtida no sangue periférico foi <1 em oito e > 1 em três. Observou-se também déficit da funçäo NK, paralelamente a uma depressäo da atividade proliferativa de células mononucleares estimuladas por lectinas (PHA, Con-A e PWM). A associaçäo destas duas disfunçöes foi comum, sugerindo um possível papel de linfócitos T reguladores na imunopatogênese da doença nestes pacientes. Os dados obtidos demonstraram a diversidade das manifestaçöes clínicas e imunológicas desta doença, que pode ser notada ente pacientes diferentes e mesmo no seguimento de um único paciente. Em nossos casos a doença apresentou um caráter evolutivo, com uma disfunçäo primariamente humoral seguida por distúrbios da imunidade celular que resultaron em pior prognóstico e dificuldades progressivas na terapêutica...