Peritoneal Carcinomatosis of Rare Ovarian Origin Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Multi-Institutional Cohort from PSOGI and BIG-RENAPE.

PURPOSE: Ovarian cancer is the most common deadly cancer of gynecologic origin. Patients often are diagnosed at advanced stage with peritoneal metastasis. There are many rare histologies of ovarian cancer; some have outcomes worse than serous ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with recurrence. This study was designed to assess the impact of CRS and HIPEC on survival of patient with peritoneal metastasis from rare ovarian malignancy. METHODS: A prospective, multicentric, international database was retrospectively searched to identify all patients with rare ovarian tumor (mucinous, clear cells, endometrioid, small cell hypercalcemic, and other) and peritoneal metastasis who underwent CRS and HIPEC through the Peritoneal Surface Oncology Group International (PSOGI) and BIG-RENAPE working group. The postoperative complications, long-term results, and principal prognostic factors were analyzed. RESULTS: The analysis included 210 patients with a median follow-up of 43.5 months. Median overall survival (OS) was 69.3 months, and the 5-year OS was 57.7%. For mucinous tumors, median OS and DFS were not reached at 5 years. For granulosa tumors, median overall survival was not reached at 5 years, and median DFS was 34.6 months. Teratoma or germinal tumor showed median overall survival and DFS that were not reached at 5 years. Differences in OS were not statistically significant between histologies (p = 0.383), whereas differences in DFS were (p < 0.001). CONCLUSIONS: CRS and HIPEC may increases long-term survival in selected patients with peritoneal metastasis from rare ovarian tumors especially in mucinous, granulosa, or teratoma histological subtypes.

Response to anti-programmed cell death protein-1 antibodies in men treated for platinum refractory germ cell cancer relapsed after high-dose chemotherapy and stem cell transplantation.

INTRODUCTION: Treatment options for patients with platinum refractory metastatic germ cell tumours (GCT) relapsing after high-dose chemotherapy and autologous stem cell transplantation are limited and survival is poor. Antibodies directed against programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are currently assessed within clinical trials. We present updated data on our experience with checkpoint inhibitors as a compassionate use off-label treatment attempt for highly-pretreated patients with GCT and provide an overview of the current literature on PD-L1 expression in this rare tumour entity. PATIENTS AND METHODS: We analysed all patients with platinum refractory GCT treated with checkpoint inhibitors at our institutions between 2015 and 2017. Data were retrieved retrospectively from the patient charts. RESULTS: Seven patients were treated with nivolumab or pembrolizumab. Four patients received single-dose treatment and died shortly afterwards due to tumour progression; the remaining three patients received treatment for at least 6 months. No significant treatment toxicity was observed. Long-term tumour response was achieved in two of the three patients, both of them highly positive for PD-L1 staining. INTERPRETATION: We consider checkpoint inhibition to be efficient in carefully selected patients with platinum refractory GCT. However, predictive markers associated with tumour response are not yet known and larger prospective clinical trials are warranted.

Utilization of retroperitoneal lymph node dissection for testicular cancer in the United States: Results from the National Cancer Database (1998-2011).

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States. MATERIALS AND METHODS: The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time. RESULTS: A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P≤0.001) over the study period. CONCLUSIONS: The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period.

The efficacy of radio-frequency ablation for metastatic lung or liver tumors of male germ cell tumors as an alternative minimally invasive therapy after salvage chemotherapy.

BACKGROUND: The aim of this study was to assess the efficacy of radio-frequency ablation (RFA) for metastatic lung or liver tumors of germ cell tumors (GCTs) after chemotherapy. METHODS: RFA with computed tomography guidance and monitoring was performed in 24 patients with 48 metastatic lung or liver tumors of GCTs. Group A consisted of 9 patients with tumor marker normalization after salvage chemotherapy and group B consisted of 15 patients without tumor marker normalization in spite ofintensive treatment. RESULTS: Out of 48 tumors, 41 tumors in 21 patients were evaluated for the efficacy of the RFA treatment. Of the 41 tumors, successful ablation was achieved in 34 (82.9 %). The patients in group A had significantly better survival than the patients in group B (p = 0.0003). In group A, all 9 patients are still alive with no evidence of disease (NED). Patients with a solitary tumor had significantly better survival than those with multiple tumors (p = 0.0247). In group B, 2 patients are alive with NED, 1 patient is alive with disease, and the remaining 12 patients have died a tumor-related death. Three cases of pneumothorax requiring intubation were observed. CONCLUSIONS: RFA is less invasive than surgery and is an effective treatment option for curative and palliative therapy as an alternative to invasive salvage surgery for post-chemotherapeutic metastatic lung or liver lesions from GCT.

Clinical features, presentation, and tolerance of platinum-based chemotherapy in germ cell tumor patients 50 years of age and older.

BACKGROUND: Germ cell tumors (GCTs) primarily affect adolescent and young adult men. Detailed clinical and treatment characteristics in older men are lacking. METHODS: Patients with GCT seen over a 20-year period at Memorial Sloan-Kettering Cancer Center were identified. Primary tumor site and histology were compared for patients aged ≥ 50 years at diagnosis versus younger men. For patients aged ≥ 50, individual chart review was performed and treatment delays, changes, and toxicities were recorded for those treated with first-line chemotherapy. RESULTS: Of 4235 diagnoses of GCT, 3999 (94.4%) were made at age < 50 versus 236 (5.6%) at age ≥ 50. Compared with patients diagnosed before age 50, older men more frequently had seminoma (62.7% versus 36.7%) and less frequently, nonseminoma (34.7% versus 63.2%) (P < .0001). Predominant histology switched from nonseminoma to seminoma around age 35. Distribution of primary sites also differed for older versus younger men (testis: 89.4% versus 92.9%; retroperitoneal: 3.8% versus 0.7%; CNS 0% versus 1.7%) except for mediastinal primary tumors, which remained constant across age groups. Fifty patients age ≥ 50 received first-line platinum-based chemotherapy; 30 experienced complications leading to treatment discontinuation, delay ≥ 7 days, or regimen change. Twenty-two (44%) patients experienced neutropenic fever, 6 despite prophylactic growth factor support. Estimated 5-year survival for chemotherapy-treated patients was 84.9%. CONCLUSIONS: Men aged ≥ 50 years comprise less than 10% of GCT diagnoses and have distinct clinical and histological characteristics as compared with younger patients. Although complications from chemotherapy occur frequently in older men, prognosis remains excellent when risk-directed treatment is administered with curative intent.

Patterns of relapse after chemotherapy in patients with high-risk non-seminomatous germ cell tumor.

OBJECTIVES: We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. METHODS: 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. RESULTS: At relapse, 24% of the patients presented with an isolated elevation in serum tumor markers, 26% with pathologic radiologic confirmation with negative tumor markers, and 42% with elevated tumor markers and radiologically confirmed progression. Relapse was detected by clinical symptoms in 8%. 46% relapsed within 3 months and 97% within 2 years. Relapse pattern did not correlate with tumor marker status or metastasis location prior to chemotherapy, line of chemotherapy, response status after chemotherapy or time point of relapse. CONCLUSION: In high-risk GCT patients, relapse after chemotherapy is detected either by tumor marker elevation alone, radiologic imaging alone or both, in one third each. Close monitoring including serum tumor markers, radiologic imaging and clinical examination appears warranted within the first 2 years.

Linfadenectomía lumboaórtica laparoscópica para cáncer testicular no seminomatoso estadio clínico I / Laparoscopic lumbo-aortic lymph-node dissection in clinical stage i non-seminomatous testicular germ-cell tumors

Reportar la morbilidad y resultados oncológicos de la Linfadenectomía Lumboaórtica por vía laparoscópica (LLA lap) en pacientes portadores de tumor de células germinales no seminomatoso (TCGNS) estadio I, operados en el Hospital Ramón Barros Luco Trudeau. Pacientes y Métodos: Entre octubre de 2005 y agosto de 2008, 29 pacientes con TCGNS estadio I, fueron sometidos a LLA lap. No se realizó selección de pacientes en relación a los hallazgos anatomopatológicos o a la presencia de factores de riesgo. La Linfadenectomía retroperitoneal fue realizada por el mismo cirujano, respetando los límites descritos por Weissbach y Boedefeld. Resultados: De los 29 pacientes operados, el procedimiento fue completado en su totalidad por vía laparoscópica. La pérdida sanguínea promedio fue de 27,7 cc (5–250). No fue necesaria tranfusión sanguínea. El tiempo operatorio promedio fue de 170 min (150–240). El número de ganglios resecados promedio fue de 12,8 (4–25). El tiempo de hospitalización fue de 2 días. Se registró una complicación vascular intraoperatoria, que se manejo satisfactoriamente sin necesidad de conversión. Se preservó la eyaculación anterograda en la totalidad de los pacientes. Cuatro pacientes (13,8 por ciento) tuvieron estadio patológico IIa y recibieron quimioterapia adyuvante con Cisplatino, Etopósido y Bleomicina. Durante un periodo de seguimiento promedio de 19 meses (2-36) ninguno de los pacientes ha presentado recidiva. Conclusión: La Linfadenectomía Lumboaórtica por vía Laparoscópica ha demostrado ser una excelente herramienta de estadificación, la cual ofrece una alternativa mínimamente invasiva a la cirugía convencional abierta. Los resultados de la serie, durante el periodo de seguimiento, demuestran su equivalencia oncológica a la cirugía abierta, sumándose los beneficios de la técnica laparoscópica que incluyen, una menor morbilidad y una mejoría tanto en la visualización intraoperatoria, resultado estético como en la calidad de vida del paciente.

To report the morbidity and oncological results of laparoscopic lumbo-aortic lymph-node dissection (LLA lap) in clinical stage I non-seminomatous testicular germ cell tumors (TCGNS), operated at the Hospital Ramón Barros Luco Trudeau.Patients and Methods: Between October 2005 and August 2008, 29 patients with stage I TCGNS, underwent LLA lap. No patient selection was made in relation to the pathological findings or the presence of risk factors. Retroperitoneal lymphadenectomy was performed by the same surgeon within the limits described by Weissbach and Boedefeld. Results: The procedure was completed in its entirety with laparoscopic procedure. The average blood loss was 27.7 cc (5-250). There was no blood tranfusion. The average operative time was 170 min (150-240). The average number of lymph nodes resected was 12.8 (4-25). The hospitalization time was 2 days. There was an intraoperative vascular complication, which satisfactorily manage without conversion to open surgery. Antegrade ejaculation was preserved in all patients. 4 patients (13.8 percent) had pathological stage II received adjuvant chemotherapy with cisplatin, etoposide and bleomycin. During an average follow-up period of 19 months (2-36) none of the patients presented recurrence. Conclusion: The laparoscopic lumbo-aortic lymph-node dissection has proven to be an excellent staging tool, which offers a minimally invasive alternative to conventional open surgery. The results of the series during the follow-up period, demonstrate oncological equivalence to open surgery, adding the benefits of laparoscopic technique including a lower morbidity and an improvement in intraoperative visualization, aesthetic result and the quality of patient’s life.

High-dose cisplatin and VP-16 with bleomycin, in the management of advanced metastatic germ cell tumors.

Intensive combination chemotherapy consisting of cisplatin 40 mg/m2 daily X 5, VP-16 200 mg/m2 daily X 5 and bleomycin 15 mg/m2 every week was administered to 29 patients (22 previously untreated and seven previously treated) with poor prognosis germ cell tumors. Eighty-six per cent of the previously untreated patients obtained CR and 5% PR. Seventeen patients (77%) are alive without evidence of disease after a median observation time of 11 months (range 1+-19+ months) after treatment. Seventy-one per cent of the previously treated patients obtained CR and 14% PR. Six patients are still alive and four (57%) without evidence of disease after a median observation time of 9 months (range 3+-12+ months) after treatment. Toxicity was severe in both groups. In 73% of the cycles WBC was below 1.0 X 10(9)/1, and in 74% of the cycles thrombocytes was below 25 X 10(9)/1. Ninety-one per cent had at least one incidence with culture negative neutropenic fever, and in four patients bacteremia was documented. Kidney function decreased (median 33%) in previously untreated patients as measured by 51Cr-EDTA clearance. Ototoxicity was observed in around 60% of the patients (two patients has required the use of a hearing aid) and neurotoxicity in around 40%. Neurotoxicity was mild in most cases. The results of the present investigation are encouraging and justify an aggressive therapeutic approach to patients with poor prognosis germ cell tumors. The toxicity is substantial, but manageable, and only a prospective randomized study can substantiate whether this excess in toxicity can be translated into an improved survival and cure.