New perspectives in platininum based chemotherapy

Since its clinical introduction cisplatin has had a major impact on the improvement of cancer treatment. Because of its curative potential in a selected number of tumor types cisplatin has become one of the most widely used anticancer drugs. ... Zie: Summary

Early ageing after cytotoxic treatment for testicular cancer and cellular senescence: Time to act

Treatment of testicular cancer (TC) has an exceptionally high success rate compared to other cancer types; even in case of metastasized disease, 80-90 % of TC patients can be cured. Consequently, attention has been drawn to a potential downside of this treatment success: late adverse treatment effects such as the accelerated development of otherwise age-associated features like cardiovascular disease and second malignancies. Underlying mechanisms are poorly understood. Emerging data suggest that cytotoxic treatment induces cellular senescence, resulting in secretion of inflammatory factors contributing to this early ageing phenotype. Molecular and cellular characterization of this early ageing will enhance understanding the pathogenesis of TC treatment-induced morbidity and contribute to better recognition and prevention of late effects. In this review, we describe clinical manifestations of the early ageing phenotype among TC survivors, and subsequently focus on potential underlying mechanisms. We discuss the clinical implications and describe perspectives for future research and intervention strategies

Long-term effects of testicular cancer treatment and implications for follow-up

Testicular cancer is treatable. The current five-year survival rate is &gt; 90%. Testicular cancer is usually diagnosed before the age of 40, and patients can live another 40 to 50 years after successful treatment. However, there is an increased risk of long-term and late effects of this treatment. Second primary malignancies and cardiovascular disease are the most common and potentially life-threatening. Others include nephrotoxicity, neurotoxicity, impaired fertility, hypogonadism, chronic fatigue and psychosocial problems. Little is known about the underlying mechanisms and the genetic susceptibility to the various side effects, which makes it difficult to identify patients at high risk of certain late effects. We present the current state of affairs regarding various long-term somatic and psychosocial effects after treatment and formulate recommendations for general medical evaluations, which should start at the start of treatment and continue after completion of treatment and follow-up.</p

Posterior retroperitoneoscopic resection of recurrent nonseminomatous tumor mass:a case report of the surgical procedure

Treatment of stage II-IV nonseminomatous testicular germ cell tumors (NSTGCTs) consists of cisplatin-based combination chemotherapy and, when present, resection of residual retroperitoneal tumor mass (RRTM) by conventional laparotomy or laparoscopy. In case of a retroperitoneal recurrence, a second conventional or laparoscopic procedure may be challenging. A case of late relapse after prior conventional resection of a RRTM and tailor-made surgical management with a posterior retroperitoneoscopic resection (PRR) is reported. A posterior retroperitoneoscopic RRTM resection was performed in a 26-year-old male with a history of stage IIC NSTGCT, presenting with a late left-sided retroperitoneal relapse, 6 years after initial treatment. Postoperative course was uneventful and at 1-year follow-up the patient had no evidence of disease. Reoperative surgery by a minimal invasive retroperitoneoscopic approach should be considered as an alternative for patients with a recurrent retroperitoneal tumor mass of a NSTGCT.</p

Laparoscopic Resection of Residual Retroperitoneal Tumor Mass in Advanced Nonseminomatous Testicular Germ Cell Tumors; a Feasible and Safe Oncological Procedure

Ten-year oncological experience of the University Medical Center Groningen with conventional laparotomy (C-RRRTM) and laparoscopy (L-RRRTM) is described concerning resection of residual retroperitoneal tumor masses (RRTM) in a large series of patients with advanced nonseminomatous testicular germ cell tumors (NSTGCT). 150 consecutive patients with disseminated NSTGCT required adjunctive surgery after combination chemotherapy. L-RRRTM was scheduled in 89 and C-RRRTM in 61 patients. Median residual tumor diameter was 20 mm in the L-RRRTM versus 42 mm in the C-RRRTM group (p <0.001). Conversion rate was 15% in the L-RRRTM group. Perioperative complications occurred in 5 patients (6%) in the L-RRRTM and 7 (12%, NS) in the C-RRRTM group. Median duration of L-RRRTM was 156 minutes vs. 221 minutes for C-RRRTM (p <0.001). 17/89 patients in the L-RRRTM group had postoperative complications versus 18/61 patients in the C-RRRTM group (NS). Median postoperative stay in the L-RRRTM group was 2 vs. 6 days in the C-RRRTM group (p <0.001). During a median follow-up of 79 months, 27 patients had recurrences: 8 (9%) in the L-RRRTM group and 19 (31%) in the C-RRRTM group (p <0.001). Laparoscopic resection of RRTM for advanced NSTGCT is feasible and an oncologically safe option in appropriately selected patients

Therapeutic targeting and patient selection for cancers with homologous recombination defects

Introduction: DNA double-strand breaks (DSBs) are toxic DNA lesions that can be repaired by non-homologous end-joining (NHEJ) or homologous recombination (HR). Mutations in HR genes elicit a predisposition to cancer; yet, they also result in increased sensitivity to certain DNA damaging agents and poly (ADP-ribose) polymerase (PARP) inhibitors. To optimally implement PARP inhibitor treatment, it is important that patients with HR-deficient tumors are adequately selected. Areas covered: Herein, the authors describe the HR pathway mechanistically and review the treatment of HR-deficient cancers, with a specific focus on PARP inhibition for BRCA1/2-mutated breast and ovarian cancer. In addition, mechanisms of acquired PARP inhibitor resistance are discussed. Furthermore, combination therapies with PARP inhibitors are reviewed, in the context of both HR-deficient and HR-proficient tumors and methods for proper patient selection are also discussed. Expert opinion: Currently, only patients with germline or somatic BRCA1/2 mutations are eligible for PARP inhibitor treatment and only a proportion of patients respond. Patients with HR-deficient tumors caused by other (epi)genetic events may also benefit from PARP inhibitor treatment. Ideally, selection of eligible patients for PARP inhibitor treatment include a functional HR read-out, in which cancer cells are interrogated for their ability to perform HR repair and maintain replication fork stability