In April 2010, sipuleucel-T became the first anticancer vaccine approved by the United States Food and Drug Administration. Different from the traditional chemotherapy agents that produce widespread cytotoxicity to kill tumor cells, anticancer vaccines and immunotherapies focus on empowering the immune system to overcome the tumor. The immune system consists of innate and adaptive components. The CD4+ and CD8+ T cells are the most crucial components of the adaptive arm of the immune system that act to mediate antitumor responses. However, T-cell responses are regulated by intrinsic and extrinsic mechanisms, which may interfere with effective antitumor responses. Many anticancer immunotherapies use tumor-associated antigens as vaccines in order to stimulate an immune response against tumor cells. Sipuleucel-T is composed of autologous mononuclear cells incubated with a fusion protein consisting of a common prostate cancer antigen (prostatic acid phosphatase) linked to an adjuvant (granulocyte-macrophage colony-stimulating factor). It is postulated that when the vaccine is infused into the patient, the activated antigen-presenting cells displaying the fusion protein will induce an immune response against the tumor antigen. In a recent randomized, double-blind, placebo-controlled, phase III clinical trial, sipuleucel-T significantly improved median overall survival by 4.1 months in men with metastatic castration-resistant prostate cancer compared with placebo. Although overall survival was improved, none of the three phase III clinical trials found a significant difference in time to disease progression. This, along with cost and logistic issues, has led to an active discussion. Although sipuleucel-T was studied in the metastatic setting, its ideal place in therapy is unknown, and clinical trials are being conducted in patients at different stages of disease and in combination with radiation therapy, antiandrogen therapy, and chemotherapy. Various other anticancer vaccines and immunotherapies for other tumor types are currently under investigation and in clinical trials. These immunotherapies were formulated to incorporate tumor-associated antigens aimed at stimulating effector T-cell responses or to block regulatory mechanisms that suppress the function of effector T cells. Additional studies will determine how these therapies can best improve clinical outcomes in patients with cancer.

Objective To characterize the incidence, onset, management, predictors, and clinical impact of mTOR inhibitor associated noninfectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma. Patients and methods Retrospective review of 310 patients with metastatic renal cell carcinoma who received temsirolimus and/or everolimus between 6/1/2007 and 10/1/2010. Clinical correlations were made with serial radiologic imaging. Fisher’s exact, Wilcoxon rank sum, and logistic regression analysis were performed to evaluate the association of NIP with demographic or clinical factors. Log rank and Cox proportional hazards regression analysis were used for the time-to-event analysis. Results NIP occurred in 6% of temsirolimus and 23% of everolimus treated patients. Symptoms included cough, dyspnea, and fever (median of two and three symptoms per patient, respectively). Median NCI-CTCAE pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had significantly longer time on treatment (median 4.1 months vs 2 months) and overall survival (OS) (median 15.4 months vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis. Conclusions An increased incidence of NIP was observed in everolimus treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

Background Renal neuroendocrine tumors (NET), comprising carcinoid tumors and small cell carcinomas, are a rare group of neoplasms. The rarity of these tumors poses a diagnostic and therapeutic challenge. Our purpose was to characterize the cases treated at a tertiary cancer center and to evaluate patients' outcomes with the available treatment modalities. Methods This is a retrospective study of patients with renal NET seen at The University of Texas MD Anderson Cancer Center between January 1, 2001, and January 1, 2011. Patient and tumor data were analyzed by descriptive statistical methods. Results Three cases of carcinoid tumors and six cases of small cell carcinoma were identified. The median age at diagnosis was 53 years for patients with carcinoid and 65 years for patients with small cell carcinoma. The most common presenting symptoms were back pain, flank pain, and hematuria. The morphological appearance of the tumor cells and their immunohistochemical reactivity for neuroendocrine markers and cytokeratin helped establish the diagnosis. Nephrectomy was the mainstay of treatment for carcinoid tumors, yielding good long-term results, even in the presence of metastases. Surgery and chemotherapy were utilized for small cell carcinoma of the kidney. The median overall survival for patients with small cell carcinoma of the kidney was 17.3 months. Conclusion Renal carcinoid tumors are indolent and are associated with prolonged survival, while small cell carcinomas of the kidney are aggressive tumors with relatively short overall survival. Although palliative in nature, cytotoxic chemotherapy is the mainstay of therapy and is best given before surgery.

BackgroundNonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes.ResultsOur institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease.Materials and MethodsIn this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations.ConclusionsOur data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.

A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria.