Germ Cell Cancer Group Research Articles

700P Detection of circulating tumor DNA and chromosome 3p25.3 gain in relapsed/refractory germ cell tumors and impact of salvage high-dose chemotherapy: Results from the Italian Germ Cell Cancer Group 04 study

700P Detection of circulating tumor DNA and chromosome 3p25.3 gain in relapsed/refractory germ cell tumors and impact of salvage high-dose chemotherapy: Results from the Italian Germ Cell Cancer Group 04 study

Factors Determining Survival of Patients with Germ Cell Tumor (Single Institutional Experience)

Objective: To determine the 5-year overall survival of all the germ cell tumour stages and to identify prognostic factors affecting advanced and metastatic disease outcomes in our institution.
 Study Design: Cross-sectional analytical study.
 Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from 2008 to 2013.
 Methodology: We analyzed the overall survival (OS) of the whole study population and sub-analyzed metastatic disease according to the International germ cell cancer group (IGCCCG), and their overall survival was calculated. Clinical, radiological, biochemical, and histopathological evaluation was used to identify risk factors determining disease outcome.
 Results: After analysing 186 male patients with germ cell tumours, 5-year overall survival for stages I, II, and III was 99%, 72%, and 62%, respectively. IGCCCG subgroup analysis showed that five-year overall survival for seminoma was slighter worse than non-seminoma. Five-year overall survival for reasonable risk and intermediate-risk seminoma was 68% and 46%, respectively. For non-seminoma, good, intermediate, and poor-risk categories carried five-year OS as 94%, 61%, and 49%, respectively. The presence of liver/brain metastasis, size of residual disease, primary mediastinal tumour, and tumor marker failure to decline post-chemotherapy were poor prognostic factors for metastatic disease.
 Conclusion: While identifying stages in germ cell tumours and classifying metastatic patients according to IGCCCG, individual factors including the location of the primary tumor, brain/ liver metastasis, a failure of tumor markers to decline less than 20% after the first chemotherapy cycle and size of residual disease are considered poor prognostic signs.

Incidence and clinical pattern of contralateral synchronous and metachronous germ cell testicular cancer

BackgroundIncidence of a second testicular tumor is higher in patients diagnosed with testicular cancer than in the general population. As incidence of unilateral germ cell cancer is increasing worldwide and most of these patients are cured, a growing number of patients at risk of developing a contralateral testis cancer is expected. ObjectiveTo analyze clinical and histological characteristics, as well as the absolute and cumulative incidence of a second testicular cancer in a cohort of 3,834 patients diagnosed with germ cell testicular cancer between I/1994 and I/2018 in 18 referral hospitals of the Spanish Germ Cell Cancer Group. MethodsPatients were treated according to stage and year of diagnoses. Contralateral testis biopsy was not routinely performed, according to European Association of Urology rules. Follow-up of the contra lateral testis consists of a physical exam only and an annual optional testicular ultrasound for 10 years. ResultsMedian age of the patients included was 32 years (18–82). With a median follow-up of 61 months (0–240), 67/3,834 patients (1.74%) were diagnosed with a second testicular tumor. The second testicular tumor was synchronic (diagnosed within 6 months of the first orchiectomy) in 19 patients, and metachronous in 48. Pathology of the second tumor was reported as a seminomatous testis tumor in 47 patients and a nonseminomatous cancer in 20. Cumulative incidence of contralateral testicular cancer was 2% at 5 years, and 4% (IC 95% 3%–5%) at 14 years. Younger age was a risk factor for developing a second testicular tumor (P = 0.006), whereas chemotherapy reduced the risk for a metachronous testicular cancer (P = 0.046). Within our cohort, 6 families with testicular cancer aggregation (more than 2 tumors in the same family) were identified. ConclusionsIncidence of second testicular neoplasm in this cohort of 3,834 patients was similar to that which has been reported in other countries. Metachronous tumors and seminomas are more common. Follow-up of the contralateral testis is mandatory, as well as adequate information for patients to prevent a second neoplasm if feasible, and to detect and treat it as soon as possible.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.

Patterns of relapse and treatment outcome after active surveillance or adjuvant carboplatin for stage I seminoma: a retrospective study of the Spanish Germ Cell Cancer Group.

Active surveillance (AS) and adjuvant chemotherapy (AC) with carboplatin are valid alternatives for managing stage I seminoma, and most relapses can be cured with cisplatin-based chemotherapy. However, some reports suggest that AC may modify the classical pattern of recurrences. We analyzed all relapses observed in a series of 879 patients with stage I seminoma included in 4 consecutive studies of the Spanish Germ Cell Cancer Group. After a median follow-up of 67months, recurrences were detected in 56/467 (12%) low-risk cases on AS and 13/412 (3%) high-risk cases after AC (p < 0.001). The objective was to describe clinical features, treatment and outcome. Univariate comparisons were performed between both groups. No significant differences were found between relapses on AS and those after AC in terms of time to relapse (13 vs 17months), size (26 vs 27mm), location (retroperitoneum in 88% vs 85%), and method of detection (computed tomography in 77% vs 69%). Treatment consisted of chemotherapy (etoposide + cisplatin ± bleomycin) in 89% and 92%, respectively. Late relapses (after > 3years) were seen in 11% vs 7.7% (p = NS) and second or successive recurrences in 1.8 vs 23% (p < 0.05). With a median follow-up of 130 moths, two patients died of seminoma-unrelated causes (AS group) and the rest are alive and disease-free. In the setting of a risk-adapted treatment of stage I seminoma, the administration of two courses of AC in patients with tumor size > 4cm and/or rete testis invasion is associated with a higher incidence of second recurrences but does not significantly modify the pattern of relapses or their outcome.

☆Corrigendum to “Recommendations for surveillance and follow-up of men with testicular germ cell tumors: A multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica” [Crit. Rev. Oncol. Hematol. 137 (2019) (May) 154–164

☆Corrigendum to “Recommendations for surveillance and follow-up of men with testicular germ cell tumors: A multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica” [Crit. Rev. Oncol. Hematol. 137 (2019) (May) 154–164

Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3).

BackgroundMetastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life‐threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population.MethodsData were collected from mGCT patients receiving first‐line platinum‐based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long‐axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed.ResultsData from 1135 patients were collected. Median age was 31 years (range 10‐74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001).ConclusionsLarge RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.

Risk of Venous Thromboembolism in Patients Receiving First-Line Chemotherapy for Disseminated Germ Cell Tumours - a Multi-Site Retrospective Cohort Study as Part of the Global Germ-Cell Cancer Group (G3) Consortium

Risk of Venous Thromboembolism in Patients Receiving First-Line Chemotherapy for Disseminated Germ Cell Tumours - a Multi-Site Retrospective Cohort Study as Part of the Global Germ-Cell Cancer Group (G3) Consortium

984P - Prognosis of anaemia in disseminated testicular germ cell tumours. On behalf of the Spanish Germ Cell Cancer Group (SGCCG)

BackgroundDespite improvements in diagnosis and aggressive chemotherapy treatment, a proportion of young patients are still dying from germ cell cancer (GCC). We aim to identify additional prognostic factors that help to select patients that might benefit from new treatment strategies. Anaemia is prognostic in several tumours. Thus, our objective was to address the prognostic significance of anaemia in disseminated testicular GCC. MethodsA multicentre, observational, retrospective study of patients with disseminated testicular GCC receiving first-line platinum-containing chemotherapy between 2000-2014, pooled from the Spanish Germ-Cell Cancer Group registry and another 3 tertiary hospitals. All patients with haemoglobin level available at diagnosis were selected for the analysis. We used the Cox-proportional hazard model to identify prognostic factors. Results665 consecutive patients from 18 centres were included for analysis. The patient distribution according to the International Germ Cell Cancer Collaboration Group (IGCCCG) classification was: 427, 125 and 113 patients for good, intermediate and poor risk categories, respectively. Hb<10g/dL (anaemia) was observed in 22 (3%) patients and was associated with worse PFS (p<0.001) and OS (p<0.001). Anaemia was more frequently observed in the poor prognostic group (good risk: 1.4%, intermediate risk: 2.6% and poor risk: 13.1%, p<0.001), and in the multivariate analysis we observed an interaction between anaemia and the IGCCCG classification. We then analysed the prognostic significance of anaemia in each risk group. Anaemia remained as an independent prognostic factor in the poor risk group both for PFS (HR=2.18, 95%CI: 1.02-4.64; p=0.04) and for OS (HR=3.29, 95%CI: 1.42-7.65; p=0.006). No effect was observed in the good and intermediate risk group, although statistical power was limited in these subgroups due to the low number of patients with anaemia and events. ConclusionsIn our series, Hb<10g/dL at diagnosis was an independent prognostic factor in poor risk disseminated testicular GCC. Future collaborative studies in order to validate these finding in an independent cohort are needed. Legal entity responsible for the studyThe Spanish Germ Cell Cancer Group (SGCCG). FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Treatment and Outcome of Patients with Stage IS Testicular Cancer: A Retrospective Study from the Spanish Germ Cell Cancer Group.

Stage IS testicular cancer is defined by the persistence of elevated serum tumor markers, including α-fetoprotein and/or β-human chorionic gonadotropin, after orchiectomy without radiological evidence of metastatic disease. Current treatment recommendations include cisplatin based chemotherapy up front but the recommendations are based on limited single center series. We retrospectively analyzed clinical and pathological characteristics, and long-term outcomes in 110 patients uniformly treated with primary chemotherapy between 1994 and 2016. The primary objective was to evaluate long-term disease-free survival. We also explored factors associated with the need for additional treatment. The elevated prechemotherapy tumor markers were α-fetoprotein in 48% of cases, β-human chorionic gonadotropin in 14%, and α-fetoprotein and β-human chorionic gonadotropin in 38%. Median α-fetoprotein and β-human chorionic gonadotropin values were 71 ng/ml and 80 mIU/ml, respectively. The IGCCCG (International Germ Cell Cancer Collaborative Group) prognostic classification was good in 94% of cases. Mixed nonseminomatous germ cell tumor was found in 78% of cases. Of the patients 103 achieved a complete response to chemotherapy. In 6 patients radiological signs of progressive disease developed during chemotherapy, while 8 experienced relapse after an initial complete response. At a median followup of 108 months 108 patients were alive and disease-free. Five and 10-year disease-free survival rates were 87% and 85%, respectively. The predominance of embryonal carcinoma in the primary tumor was the only factor associated with the probability of needing additional therapy. Stage IS testicular cancer is more commonly associated with elevated α-fetoprotein, an IGCCCG good prognosis and mixed nonseminomatous germ cell tumor. Treatment with cisplatin based chemotherapy leads to cure in most cases. However, a proportion of patients require the integration of additional therapies, including more frequently when embryonal carcinoma is not predominant.

Recommendations for surveillance and follow-up of men with testicular germ cell tumors: a multidisciplinary consensus conference by the Italian Germ cell cancer Group and the Associazione Italiana di Oncologia Medica.

No compelling evidence is available about surveillance and follow-up of patients with testicular germ cell tumour (TGCT). In the light of the best clinical evidence, the Italian Germ cell cancer Group (IGG) and the Associazione Italiana di Oncologia Medica (AIOM) set up a multidisciplinary national consensus conference, involving 42 leading experts and 3 TGCT survivors. A minimum of 50% of votes was required in order to achieve a consensus recommendation on 29 questions. Recommendations have been summarized in three tables, divided by stage I seminoma, stage I nonseminoma and the advanced disease, which may be useful for clinicians to appropriately choose the clinical investigation and its timing during the surveillance and follow-up of TGCT patients based on an accurate estimation of their risk of disease relapse. The IGG-AIOM consensus recommendations may help clinicians to choose appropriate clinical investigations for the surveillance and follow-up of TGCT patients.

Questioning the Value of Fluorodeoxyglucose Positron Emission Tomography for Residual Lesions After Chemotherapy for Metastatic Seminoma: Results of an International Global Germ Cell Cancer Group Registry.

Residual lesions after chemotherapy are frequent in metastatic seminoma. Watchful waiting is recommended for lesions < 3 cm as well as for fluorodeoxyglucose (FDG) positron emission tomography (PET)-negative lesions ≥ 3 cm. Information on the optimal management of PET-positive residual lesions ≥ 3 cm is lacking. We retrospectively identified 90 patients with metastatic seminoma with PET-positive residual lesions after chemotherapy. Patients with elevated α-fetoprotein or nonseminomatous histology were excluded. We analyzed the post-PET management and its impact on relapse and survival and calculated the positive predictive value (PPV) for PET. Median follow-up time was 29 months (interquartile range [IQR], 10 to 62 months). Median diameter of the largest residual mass was 4.9 cm (range, 1.1 to 14 cm), with masses located in the retroperitoneum (77%), pelvis (16%), mediastinum (17%), and/or lung (3%). Median time from the last day of chemotherapy to PET was 6.9 weeks (IQR, 4.4 to 9.9 weeks). Post-PET management included repeated imaging in 51 patients (57%), resection in 26 patients (29%), biopsy in nine patients (10%) and radiotherapy in four patients (4%). Histology of the resected specimen was necrosis in 21 patients (81%) and vital seminoma in five patients (19%). No biopsy revealed vital seminoma. Relapse or progression occurred in 15 patients (17%) after a median of 3.7 months (IQR, 2.5 to 4.9 months) and was found in 11 (22%) of 51 patients on repeated imaging, in two (8%) of 26 patients after resection, and in two (22%) of nine patients after biopsy. All but one patient who experienced relapse were successfully treated with salvage therapy. The PPV for FDG-PET was 23%. FDG-PET has a low PPV for vital tumor in residual lesions after chemotherapy in patients with metastatic seminoma. This cautions against clinical decisions based on PET positivity alone.

A Risk-Adapted Approach to Patients with Stage I Seminoma according to the Status of Rete Testis: The Fourth Spanish Germ Cell Cancer Group Study

Objective: The aim of this study was to assess a risk-adapted strategy for stage I seminoma guided by the presence of rete testis invasion. Methods: Between January 2013 and December 2015, a total of 135 consecutive patients with stage I seminoma from 18 Spanish tertiary hospitals were included in a prospective multicenter study. Median patient age was 38 years (range 22–60). Preoperative beta-human chorionic gonadotropin was elevated in 9.6% of patients. Rete testis invasion was present in 47.4% of patients. After orchiectomy, subjects with rete testis invasion were treated with 2 courses of adjuvant carboplatin (area under the curve of 7, with 21-day interval). Those without this risk factor were managed by surveillance. Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Results: After a median follow-up time of 33 months, only 6 relapses were recorded (5 on surveillance, 1 after carboplatin). These cases were rescued with BEP or EP chemotherapy, and all 135 patients are currently disease free without sequelae. Three-year DFS was 92.0 and 98.2% for patients on surveillance and after carboplatin, respectively. Three-year OS was 100%. Conclusion: A risk-adapted approach based on rete testis invasion as a single risk factor is feasible and yielded an excellent outcome with a 3-year DFS of 94.9%.

IGG practice guidelines on germ cell tumor in adult male patients.

Germ cell tumors are rare neoplasms that affect young males. Nearly 99% of patients with localized stage I disease and nearly 80% of patients with metastatic disease can be cured. Even patients who relapse following chemotherapy can achieve a long-term survival in approximately 30-40% of cases. The main objective in early stages and in good prognosis patients has changed in recent years, and it has become of major importance to reduce treatment-related morbidity without compromising the excellent long-term survival rate. In poor prognosis patients, there is a correlation between the experience of the treating institution and the long-term clinical outcome of the patients, particularly when the most sophisticated therapies are needed. So far, of utmost importance is the information from updated practice guidelines for the diagnosis and treatment of germ cell tumors. The Italian Germ cell cancer Group (IGG) has developed the following clinical recommendations, which identify the current standards in diagnosis and treatment of germ cell tumors in adult males.

High-dose chemotherapy (HDCT) plus peripheral-blood stem-cell transplant (PBSCT) for patients (pts) with relapsed germ-cell tumors (GCT) and active brain metastases (mets).

4558 Background: The optimal management of progressive brain mets in pts with GCT remains unsettled. Treatment options include chemotherapy, stereotactic or whole brain radiation (XRT), surgery, or a combination thereof. Global germ cell cancer group analysis suggested multimodality therapy improves survival probabilities in pts with brain mets at relapse (JCO.2016;1;34(4):345-51). We report our experience on managing 25 consecutive pts with relapsed GCT and progressive brain mets undergoing HDCT with PBSCT at Indiana University from 2006-2016. Methods: All pts received HDCT consisting of carboplatin 700 mg/m2 days 1-3 and etoposide 750 mg/m2 i.v. days 1-3 followed by PBSCT on day 5 for upto 2 cycles. Pts were treated with craniotomy, XRT, chemotherapy alone, or a combination of modalities. Patient and disease characteristics, management of brain mets, and outcomes were measured. Platelet transfusions were given to maintain platelet counts &gt; 30,000 and goal of &gt; 50,000 in those with signs of hemorrhage. Results: Patient characteristics and outcomes are summarized in Table 1. Median age was 27.7 years (range, 16-48). All pts had progressive brain mets at time of starting HDCT. AFP ranged 1.6 to 1130, hCG 0.5 to 25601. At median follow-up of 24.8 months (range 2.5 to 118.5 months), 11 pts (44%) were alive with NED, 2 pts were alive with relapsed disease, and 12 pts died of disease progression. 17/18 patients developed progressive CNS mets despite radiation and/or craniotomy and of those, 8 are alive with NED. Toxicity was as previously published with this regimen (N Engl J Med 2007;357:340-8). Conclusions: Patients with relapsed GCT with progressing brain mets, including those with prior locoregional therapy, are curable with HDCT. [Table: see text]

FDG PET scan (PET) positive residual lesions after chemotherapy (chemo) for metastatic seminoma: Results of an International Global Germ Cell Cancer Group (G3) registry.

4521 Background: Residual disease is a frequent finding after chemo for metastatic seminoma. Watchful waiting is recommended for residual lesions &lt; 3 cm or lesions ≥3 cm with negative PET. Data on the optimal management of PET positive residual lesions is lacking. Methods: A retrospective analysis within the G3 Group identified 91 patients (pts) from 9 countries with metastatic seminoma and residual PET positive lesions after chemo. Pts with elevated AFP ( &gt; 2xULN) or non-seminomatous components at diagnosis were excluded. We analyzed the post PET management chosen and its impact on relapse and survival. Results: Median follow-up was 29 (IQR 10 – 64) months. Median age at diagnosis was 41 (range 19 – 69) years. The primary tumor was gonadal in 68 pts (76%), retroperitoneal in 12 pts (13%) and mediastinal in 10 pts (11%). Prior to chemo the median size of the largest metastasis was 10 (range 1.4 – 23) cm, 67 pts (74%) had elevated LDH and 51 pts (57%) elevated HCG. Median diameter of the largest residual mass was 4.8 (range 1.1 – 14) cm mainly located in the retroperitoneum (77%), pelvis (15%), mediastinum (16%) or lung (4%). Median time from last day of chemo to PET was 7 (IQR 4 – 10) weeks. Post PET management was repeated imaging in 46 pts (51%), resection in 32 pts (35%), biopsy in 9 pts (10%) and radiotherapy in 4 pts (4%). Histology of the resected specimen was necrosis only in 25 (78%) and vital seminoma in 7 cases (22%). No biopsy revealed vital seminoma. Relapses occurred after a median of 3.7 (IQR 2.5 – 4.9) months in 16 pts (18%): 2/9 (22%) after biopsy, 12/46 (26%) on repeated imaging and 2/32 (6%) after resection (one necrosis, one &lt; 10% vital seminoma). Site of relapse was the area of residual disease in 14 pts (88%) and additional distant relapse (one bone, one lung) in 2 pts (12%). All relapsed pts received successful salvage chemo apart from one who died from treatment and two pts who are alive with ongoing treatment. Conclusions: PET positive post chemo residual lesions in seminoma pts are false positive in about 75%. Relapses in PET positive pts occur early and can be salvaged with chemo. Further analysis is needed to identify risk factors for relapse.

Prognostic Significance of Venous Thromboembolic Events in Disseminated Germ Cell Cancer Patients

Disseminated germ cell cancers are at high risk of developing thromboembolic complications. We evaluated the prognostic value of venous thromboembolic events (VTE) in disseminated germ cell cancer. Patients with germ cell cancer receiving upfront platinum-containing chemotherapy between 2004 and 2014 were pooled from the Spanish Germ Cell Cancer Group (SGCCG) registry and reviewed for the presence of VTE. Results were validated in an independent international group of patients. We used a penalized Cox proportional hazards model including VTE as a time-varying covariate to identify and validate prognostic factors. All statistical tests were two-sided. The SGCCG registry identified 416 patients from 14 referral institutions. With a median follow-up of 49 months, VTEs were observed in 9% of patients (n = 38). Events occurred at diagnosis, during chemotherapy, and after chemotherapy in 2.6%, 5.0%, and 1.4% of patients, respectively. VTE was associated with shorter progression-free survival (PFS; hazard ratio [HR] = 2.29, 95% confidence interval [CI] = 1.18 to 4.47, P = .02) and overall survival (OS; HR = 5.14, 95% CI = 2.22 to 11.88, P < .001). In multivariable analysis, the effect was consistent in the intermediate-risk group, both for PFS (HR = 9.52 95% CI = 2.48 to 36.58, P < .001) and OS (HR = 12.84, 95% CI = 2.01 to 82.02, P = .007). VTE at diagnosis is also an adverse prognostic variable for progression-free survival (HR = 4.64, 95% CI = 2.04 to 10.54, P < .001) and for overall survival (HR = 6.28, 95% CI = 1.68 to 17.10, P= .01). These results were validated in an independent international cohort that included 241 patients from four hospitals. VTE is an independent adverse prognostic factor in disseminated germ cell cancers, in particular for the intermediate prognostic group of the International Germ Cell Cancer Collaborative Group classification. The presence of VTE at diagnosis has also prognostic significance and should be further explored in future prognostic classifications.

High Dose Chemotherapy with Autologous Stem Cell Transplant in Treatment of Germ Cell Tumors: A Systematic Review and Meta-Analysis

Background:Cure rates for the poor risk, relapsed and refractory germ cell tumors are only 25 % with conventional dose chemotherapy. High Dose Chemotherapy (HDCT) followed by rescue stem cell transplant has since been studied in randomized controlled trails for the IGCCG poor risk group patients and for the relapsed and refractory testicular cancer patients. We conducted a meta-analysis of all prospective Phase II and III trials studying the role of high dose chemotherapy in germ cell tumors.Methods:Literature search was conducted using methods described in the PRISMA statement. Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials(CENTRAL) and Cochrane Database of Systematic Review (CDSR) were searched from the inception of these databases till present. We performed a meta-analysis using Comprehensive Meta-analysis 3.0 using random effects model. The heterogeneity was assessed using I2values and sensitivity analysis was performed to explain the heterogeneity where present.Results:After a comprehensive literature search 4440 studies were identified and finally 35 studies were included in the final analysis. 14 studies involving 905 patients with IGCCG poor risk germ cell cancer were treated with high dose chemotherapy. 44 % (398) patients were able to achieve CR with HDCT with HR of o.48 (0.33-0.62) p=0.75. The overall survival (OS) and Progression free survival (PFS ) were 0.62 (0.54-0.69, p=0.004) and 0.60 (0.52-0.68 p=0.011) respectively.21 studies involving 1153 patients with relapsed and or refractory germ cell cancer were identified. CR rate with HDCT was 32 % (374 patients) with HR of 0.32 (0.26-0.40, p=0.00). The results for OS failed to show any significant results with HR of 0.52 (0.44-0.60, p=0.67) but was significant for PFS with HR of 0.60 (0.52-0.67, p=0.01).Conclusion:High dose chemotherapy followed by HSCT showed significant OS and PFS for IGCCG poor risk category germ cell tumors and significant CR and PFS for relapsed and or refractory germ cell cancer group. DisclosuresAnwer:Incyte: Speakers Bureau; Seattle Genetics: Other: Advisory Board Participant.

779PD - Large retroperitoneal lymphadenopathy (RPLN) and increased risk of venous thromboembolism (VTE) in patients (pts) with metastatic germ cell tumours (mGCT): a global germ cell cancer group (G3) study

779PD - Large retroperitoneal lymphadenopathy (RPLN) and increased risk of venous thromboembolism (VTE) in patients (pts) with metastatic germ cell tumours (mGCT): a global germ cell cancer group (G3) study

Consensus Recommendations from the Spanish Germ Cell Cancer Group on the Use of High-dose Chemotherapy in Germ Cell Cancer

BackgroundHigh-dose chemotherapy (HDCT) has been studied in several clinical scenarios in advanced germ cell cancer (GCC). ObjectiveTo establish a clinical practice guideline for HDCT use in the treatment of GCC patients. Design, setting, and participantsAn expert panel reviewed information available from the literature. The panel addressed relevant issues concerning and related to HDCT. The guideline was externally reviewed by two international experts. Results and limitationsThe efficacy of HDCT has been demonstrated in selected GCC patients. The most conclusive evidence comes from retrospective analyses that need to be interpreted with caution. HDCT can cure a significant proportion of heavily treated GCC patients. When indicated, sequential HDCT with regimens containing carboplatin and etoposide, as well as peripheral stem-cell support, is recommended. There is no conclusive evidence to recommend HDCT as first-line therapy. According to a multinational retrospective pooled analysis, HDCT might be superior to conventional CT as first salvage treatment in selected patients. There is an urgent need for prospective clinical trials addressing the value of HDCT in GCC patients who experience failure on first-line cisplatin-based CT. In patients who progress on conventional-dose salvage CT, HDCT should be considered. Treatment of these patients at experienced centers is strongly recommended. ConclusionsIt has been demonstrated that HDCT cures selected GCC patients who experience disease progression on conventional rescue regimens. The panel recommends the inclusion of GCC patients in randomized clinical trials including HDCT. Patient summaryThis consensus establishes clinical practice guidelines for the use and study of high-dose chemotherapy in patients with germ cell cancer.