Testicular germ cell tumour risk by occupation and industry: a French case-control study - TESTIS.

OBJECTIVE: Testicular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18-45 years. METHODS: The TESTIS study is a multicenter case-control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d'Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression. RESULTS: A positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6-2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4-51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8-5; OR≥2 years 1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings. CONCLUSIONS: Our findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development. TRIAL REGISTRATION NUMBER: NCT02109926.

Synchronous brain metastases as a poor prognosis factor in clear cell renal carcinoma: a strong argument for systematic brain screening.

PURPOSE: Brain metastases (BM) usually represent a poor prognostic factor in solid tumors. About 10% of patients with renal cancer (RCC) will present BM. Local therapies such as stereotactic radiotherapy (SRT), whole brain radiotherapy (WBRT), and surgery are used to achieve brain control. We compared survival between patients with synchronous BM (SynBM group) and metachronous BM (MetaBM group). METHODS: It is a retrospective study of patients with clear cell renal cell carcinoma (ccRCC) and BM treated with TKI between 2005 and 2019 at the Centre Léon Bérard in Lyon. We collected prognostic factors: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, the TNM stage, the histological subtypes and the Fuhrman grade. Overall survival (OS) was defined from diagnosis of metastatic ccRCC to death. Brain progression-free survival (B-PFS) was defined from focal brain therapy to brain progression or death. RESULTS: 99 patients were analyzed, 44 in the SynBM group and 55 in the MetaBM group. OS in the MetaBM group was 49.4 months versus 19.6 months in the SynBM group, p = 0.0002. The median time from diagnosis of metastasic disease to apparition of BM in the MetaBM group was 22.9 months (4.3; 125.7). SRT was used for 101 lesions (66.4%), WBRT for 25 patients (16.4%), surgery for 21 lesions (13.8%), surgery followed by radiation for 5 lesions (3.3%). B-PFS for all patients was 7 months (IC95% [5.0-10.5]). CONCLUSIONS: Survival of patients with synchronous BM is inferior to that of patients with metachronous BM. Outcome is poor in both cases after diagnosis of BM. Brain screening should be encouraged at time of diagnosis of metastatis in ccRCC.

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.

BACKGROUND: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. METHODS: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. CONCLUSIONS: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

IMPDH1/YB-1 Positive Feedback Loop Assembles Cytoophidia and Represents a Therapeutic Target in Metastatic Tumors.

Recently, cytoophidium, a nonmembrane-bound intracellular polymeric structure, has been shown to exist in various organisms, including tumor tissues, but its function and mechanism have not yet been examined. Examination of cytoophidia-assembled gene inosine monophosphate dehydrogenase (IMPDH) and cytidine triphosphate synthetase (CTPS) mRNA levels showed that only IMPDH1 levels were significantly higher in the clear cell renal cell carcinoma (ccRCC). IMPDH1 was positively correlated with the metastasis-related gene Y-box binding protein 1 (YB-1) and served as an independent prognostic factor in ccRCC. Kaplan-Meier analysis indicated that patients with tumors that expressed high IMPDH1 levels had a shorter overall survival (OS) and disease-free survival (DFS). Furthermore, detection of cytoophidia by immunofluorescence staining in ccRCC tissues showed that IMPDH1-assembled cytoophidia are positively associated with tumor metastasis. Mechanistically, IMPDH1 and YB-1 formed an autoregulatory positive feedback loop: IMPDH1 maintained YB-1 protein stabilization; YB-1 induced IMPDH1 expression by binding to the IMPDH1 promoter motif. Functionally, IMPDH1-assembled cytoophidia physically interacted with YB-1 and translocated YB-1 into the cell nucleus, thus correlating with ccRCC metastasis. Our findings provide the first solid theoretical rationale for targeting the IMPDH1/YB-1 axis to improve metastatic renal cancer treatment.

Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors.

BACKGROUND: Vascular endothelial growth factor (VEGF) directed therapies are being used in a large number of advanced tumors. Metastatic renal cell carcinoma (mRCC) is highly dependent on the VEGF pathway; VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKI) and humanized VEGF monoclonal antibody have been registered for clinical use in advanced renal cell carcinoma. The VEGFR TKI, pazopanib, with a rather manageable toxicity profile, was preferred to sunitinib by mRCC patients. We investigate the combination of pazopanib and bevacizumab to determine the maximum tolerated dose (MTD) in mRCC and other advanced solid tumors. METHODS: In this bicentric phase I trial with a 3 + 3 + 3 dose-escalation design, patients received oral pazopanib once daily plus intravenous infusion of bevacizumab every 2 weeks from D15, at one of the four dose levels (DL) planned according to the occurrence of dose limiting toxicities (DLT). 400 and 600 mg pazopanib were respectively combined with 7.5 mg/kg bevacizumab in DL1 and DL2, and 600 and 800 mg pazopanib with 10 mg/kg bevacizumab in DL3 and DL4. Tumor response was evaluated every 8 weeks. Blood samples were assayed to investigate pazopanib pharmacokinetics. RESULTS: Twenty five patients including seven mRCC were enrolled. Nine patients received the DL1, ten received the DL2. No DLT were observed at DL1, five DLT at DL2, and 3 DLT in the six additional patients who received the DL1. A grade 3 microangiopathic hemolytic anemia syndrome was observed in four (16%) patients. Five (22%) patients achieved a partial response. The mean (range) plasmatic concentrations of 400 and 600 pazopanib were respectively 283 (139-427) and 494 (227-761) µg.h/mL at Day 1, and 738 (487-989) and 1071 (678-1464) µg.h/mL at Day 15 i.e. higher than those previously reported with pazopanib, and were not directly influenced by bevacizumab infusion. CONCLUSIONS: The combination of pazopanib and bevacizumab induces angiogenic toxicity in patients without any pre-existing renal or vascular damage. Even if a marginal efficacy was reported with five (22%) patients in partial response in different tumor types, the toxicity profile compromises the development of this combination. TRIAL REGISTRATION: The study was retrospectively registered on ClinicalTrials.gov (number NCT01202032 ) on 2010, Sept 14th.

Haemoglobin level increase as an efficacy biomarker during axitinib treatment for metastatic renal cell carcinoma: a retrospective study.

BACKGROUND: Axitinib is used after failure of first line treatment for metastatic renal cell carcinoma (mRCC). A known side effect is the increase of haemoglobin level (HbL) during treatment with a suspected correlation with better outcome. Our objective was to examine whether HbL increase during the first three months of axitinib treatment is associated with better prognosis. METHODS: Retrospective multicentre analysis including patients with mRCC treated with axitinib for at least three months from 2012 to 2014. Progression-free survival (PFS) was analysed by a Cox model according to gender, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic score, high blood pressure (hBP), and maximum increase in HbL within the first three months of treatment. RESULTS: Ninety-eight patients were analysed (71% men; median age at treatment initiation: 62 years; IMDC: 24%, 50%, and 26% in the favourable, intermediate, and poor-risk group, respectively). Patients received axitinib for a median of 8 months. During the first three months, the median increase of HbL was +2.3 g/dL (-1.1; 7.2). Fifty-six (57%) patients developed hBP. In multivariate analysis, after adjustment for performance status (P < 0.0001) and gender (P = 0.0041), the combination of HbL increase ≥2.3 g/dL and any grade hBP was significantly associated with longer PFS (HR = 0.40, 95%CI [0.24; 0.68]). CONCLUSIONS: Early HbL increase during axitinib treatment combined with hBP is an independent predictive factor of PFS. These results require validation in a prospective setting.

Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology.

In 2010, the International Society of Geriatric Oncology (SIOG) developed treatment guidelines for men with prostate cancer who are older than 70 years old. In 2013, a new multidisciplinary SIOG working group was formed to update these recommendations. The consensus of the task force is that older men with prostate cancer should be managed according to their individual health status, not according to age. On the basis of a validated rapid health status screening instrument and simple assessment, the task force recommends that patients are classed into three groups for treatment: healthy or fit patients who should have the same treatment options as younger patients; vulnerable patients with reversible impairment who should receive standard treatment after medical intervention; and frail patients with non-reversible impairment who should receive adapted treatment.

Bone Metastases in Non-Seminomatous Germ Cell Tumors: A 20-Year Retrospective Analysis.

Background: Non-seminomatous germ cell tumors (NSGCTs) represent a rare yet the most prevalent malignancy among young men. Bone metastases (BMs) are exceedingly uncommon in this neoplasm, and available data regarding the initial disease presentation, survival outcomes, and prognostic significance of BMs are limited. Methods: We conducted a retrospective analysis of 40 NSGCT patients with BMs treated between 2001 and 2021 in our tertiary care center. The cohort was stratified into synchronous (n = 29) and metachronous (n = 11) groups based on the presence of BM at diagnosis or only at relapse, respectively. We assessed overall survival (OS), progression-free survival (PFS), disease presentation, and treatments. Results: After a median follow-up of 93 months, the 5-year PFS and OS rates were 37.6% and 53.9% in the synchronous group and 18.2% and 36.4% in the metachronous group, respectively. At the initial diagnosis, most patients were classified into the IGCCCG poor prognostic group (n = 34, 85%). BMs were mostly asymptomatic (n = 23, 57.5%), involved the spine (n = 37, 92.5%), and could become visible only after disease response (n = 4, 10%). A pathological examination of resected bone lesions after first-line treatment revealed necrosis (n = 5, 71.4%), teratoma, or seminoma (both n = 1, 14.3%). At first relapse, eight patients in the synchronous group did not experience bone recurrence, while eight patients experienced recurrence at the initial affected bone site. Conclusions: In NSGCT patients, BMs often present asymptomatically and may initially be unnoticed. However, these patients may have a poorer prognosis compared to those in the IGCCCG poor prognostic group. Further studies including control groups are needed to assess the independent prognostic significance of BMs.

KIR2DL2/DL3+NKs and Helios+Tregs in Peripheral Blood Predict Nivolumab Response in Patients with Metastatic Renal Cell Cancer.

PURPOSE: To identify predictive factors of nivolumab sensitivity, peripheral blood NKs and regulatory T-cell (Treg) were evaluated in patients with metastatic renal cell carcinoma (mRCC) enrolled in the REVOLUTION trial. EXPERIMENTAL DESIGN: Fifty-seven mRCCs being treated with nivolumab, as at least second-line of therapy, and 62 healthy donors were longitudinally evaluated (0-1-3-6-12 months) for peripheral NKs and Tregs, phenotype, and function. Multivariable logistic regression was conducted to identify the independent predictors. The 0.632+ internal cross-validation was used to avoid overfitting. The best cutoff value based on a 3-month clinical response was applied to progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves for PFS and OS were produced. RESULTS: At pretreatment, mRCCs displayed high frequency of NKp46+NKs, NKp30+NKs, KIR2DL1+NKs, KIR2DL2/DL3+NKs, and PD1+NKs with reduced NK degranulation as well as high frequency of Tregs, PD1+Tregs, Helios+Tregs, and ENTPD1+Tregs. Responder patients, identified as a clinical response after 3 months of treatment, presented at pretreatment significantly low CD3+, high KIR2DL2/DL3+NKs, high PD1+Tregs, and high Helios+Tregs. Upon multivariate analysis, only KIR2DL2/DL3NKs and Helios+Tregs held as independent predictors of nivolumab responsiveness. The KIR2DL2/DL3+NKs >35.3% identified patients with longer OS, whereas the Helios+Tregs >34.3% displayed significantly longer PFS. After 1-month of nivolumab, responder patients showed low CD3+, high NKs, KIR2DL2/DL3+NKs, and ICOS+Tregs. Among these subpopulations, CD3+ and KIR2DL2/DL3+NKs held as independent predictors of nivolumab efficacy. Low CD3+ (≤71%) was significantly associated with longer PFS, whereas high KIR2DL2/DL3+NKs (>23.3%) were associated with both PFS and OS. CONCLUSIONS: Pretreatment evaluation of Helios+Tregs/KIR2DL2/DL3+NKs and 1-month posttreatment CD3+/ KIR2DL2/DL3+NKs will predict nivolumab response in mRCCs.

Direct-to-participant recruitment of mothers and infants: A strategic approach during challenging pandemic times.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (e.g., smart phones) available to researchers and patients. This approach functions under the assumption that a participant has access to a device that connects to the internet such as a smart phone, tablet, or computer. Researchers are then able to transition a typical paper-based, in-person model to an electronic-based, siteless, remote study. This article describes the challenges clinicians and researchers faced when implementing a direct-to-participant study approach during the COVID-19 pandemic. The lessons learned during this study of infant populations could help increase efficiency of future trials, specifically, by lessening the burden on participants and clinicians as well as streamlining the process for enrollment and data collection. While direct-to-adult participant recruitment is not a novel approach, our findings suggest that studies attempting to recruit the infant population may benefit from such a direct-to-participant approach.

Real World Data of Diagnosis, Survival, and Treatment Outcomes in Patients With Metastatic Non Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Metastatic non clear cell renal cell carcinoma (nccRCC) is an heterogenous group, usually excluded from phase 3 trials. We report real life data of prognosis and systemic management of those patients. METHODS: We retrospectively included 102 metastatic nccRCC patients (unspecified papillary, n = 10; type 1 and 2 papillary n = 10 and n = 32; translocation RCC, n = 9; chromophobe, n = 14; collecting duct, n = 14) treated between 2006 and 2020. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Among patients who underwent pathological review, 40.8% presented a complete histological discordance. First line treatments were mainly tyrosine kinase inhibitor (60.8%), combination including immunotherapy (7.8%) or combination of chemotherapy (13.7%). Median ORR ranged from 0% in unspecified papillary RCC to 42.9% in type 1 papillary RCC. Median PFS ranged from 2.9 months in collecting duct carcinoma to 10.9 months in type 1 papillary RCC. Median OS ranged from 6.8 months in collecting duct carcinoma to 29.1 months in MiT family translocation RCC. Thirty (29.4%) patients were included in a treatment trial during their treatment course. CONCLUSION: Metastatic nccRCC patients have variable prognosis due to heterogeneity of histological subtypes. Their diagnosis and access to therapeutic innovation remain suboptimal. Dedicated prospective trials are needed.

Rationale for Prostate-Specific-Membrane-Antigen-Targeted Radionuclide Theranostic Applied to Metastatic Clear Cell Renal Carcinoma.

Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC.

Parental occupations at birth and risk of adult testicular germ cell tumors in offspring: a French nationwide case-control study.

Background: Testicular germ cell tumors (TGCT) are the most frequent cancer in young men in developed countries. Parental occupational exposures during early-life periods are suspected to increase TGCT risk. The objective was to estimate the association between parental occupations at birth and adult TGCT. Methods: A case-control study was conducted, including 454 TGCT cases aged 18-45 from 20 French university hospitals, matched to 670 controls based on region and year of birth. Data collected from participants included parental jobs at birth coded according to the International Standard Classification of Occupation-1968 and the French nomenclature of activities-1999. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. Results: Paternal jobs at birth as service workers (OR = 1.98, CI 1.18-3.30), protective service workers (OR = 2.40, CI 1.20-4.81), transport equipment operators (OR = 1.96, CI 1.14-3.37), specialized farmers (OR = 2.66, CI 1.03-6.90), and maternal jobs as secondary education teachers (OR = 2.27, CI 1.09-4.76) or in secondary education (OR = 2.35, CI 1.13-4.88) were significantly associated with adult TGCT. The risk of seminoma was increased for the above-mentioned paternal jobs and that of non-seminomas for public administration and defence; compulsory social security (OR = 1.99, CI 1.09-3.65); general, economic, and social administration (OR = 3.21, CI 1.23-8.39) for fathers; and secondary education teacher (OR = 4.67, CI 1.87-11.67) and secondary education (OR = 3.50, CI 1.36-9.01) for mothers. Conclusion: Some paternal jobs, such as service workers, transport equipment operators, or specialized farmers, and maternal jobs in secondary education seem to be associated with an increased risk of TGCT with specific features depending on the histological type. These data allow hypotheses to be put forward for further studies as to the involvement of occupational exposures in the risk of developing TGCT, such as exposure to pesticides, solvents, or heavy metals.

Approaches for enhancing the informativeness and quality of clinical trials: Innovations and principles for implementing multicenter trials from the Trial Innovation Network.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Implementation of a Prevention Program Based on Adapted Physical Activity and Recommendations for Adolescents and Young Adults with Cancer: PREVAPAJA Study.

Purpose: In Europe, 20,000 Adolescent and Young Adults (AYAs) aged 15-25 years are diagnosed with cancer annually. Although prognosis is good, AYA cancer survivors are at greater risk of second primary cancers, cardiovascular disease, and various long-term effects. Benefits of physical activity (PA) in AYAs reported in current studies remain difficult to generalize; none has been performed in France. This single-arm intervention study tested the feasibility of combining hospital-based supervised and home-based unsupervised physical activity sessions (PAS) and providing cancer prevention recommendations for AYAs. Methods: The AYAs attended PAS concomitant to treatment and participated in one face-to-face prevention interview. PA (international physical activity questionnaire), 6-min walk distance (6MWD), sedentarity, anthropometrics, quality of life (QoL), and fatigue were assessed at baseline (T1) and end of intervention (T2). PA, satisfaction and cancer prevention behaviors were assessed 1 year after baseline (T3). Results: Fifty-nine AYAs (mean 19 years) participated in the study. Acceptability and attrition were 80% and 12%, respectively. Between T1 and T2, 6MWD and global QoL improved (p < 0.001), and fatigue decreased (p = 0.003). Total PA improved and sitting time decreased (p < 0.001) overall (T1-T3). Assessment at T3 showed interindividual differences in how participants considered risk factors (e.g., more attention to PA, UV exposures, nutrition). Conclusion: Combined supervised and unsupervised home-based PAS in AYAs undergoing cancer treatment is acceptable and feasible. The program contributes to maintaining and improving physical fitness and QoL, while reducing fatigue and other cancer and treatment symptoms. Larger randomized controlled trials are needed to confirm these results.

Sarcoid-like granulomatosis and testicular germ cell tumor: the 'Great Imitator'.

OBJECTIVES: Only a few case reports and small case series of patients with sarcoidosis or sarcoid-like reaction and testicular germ cell tumors (GCT) have been reported in the literature. We performed a retrospective study of patients with testicular GCT managed at the Centre Léon-Bérard, who presented granulomatosis. METHODS: We performed a computerized search to identify all male patients with both a diagnosis of sarcoidosis or granuloma and testicular tumors seen at the Centre Léon-Bérard between 1992 and 2008. RESULTS: A total of 13 patients were identified among the 1,182 patients with testicular tumors. The median age at diagnosis of testicular GCT was 25.5 years. Six patients had stage I disease, 2 patients had stage IIb and 5 patients had stage III. Sarcoid-like granulomatosis was found in 9 patients at the time of initial diagnosis and in 4 patients during follow-up. Sarcoidosis presented mainly as pulmonary disease without severe organ involvement, with a benign evolution. CONCLUSION: We advise caution in the interpretation of clinical and histological findings in these patients. Sarcoid-like granulomatosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis of metastatic testicular tumors.

Efficacy of trabectedin for advanced sarcomas in clinical trials versus compassionate use programs: analysis of 92 patients treated in a single institution.

Trabectedin was recently approved for patients failing doxorubicin, the standard treatment for advanced/metastatic sarcoma. This retrospective study aimed to compare trabectedin efficacy between compassionate use in unselected patients and clinical trials. From May 1999 to January 2006, 92 patients were treated at the Centre Léon Bérard, either in phase II studies or on a named patient compassionate basis. All cases were retrospectively analyzed to assess trabectedin efficacy in terms of response, progression-free, and overall survival.The objective response rate was 10% (N=9): 4% (N=2) for patients treated in compassionate use program and 16% (N=7) for those in clinical trials (P=0.18); 26 (28%) patients had stable disease for at least 6 months, 11 (23%) in the compassionate group and 15 (33%) in clinical trials. Median progression-free and overall survivals were, respectively, 2.2 [95% confidence interval (CI): 1.9-3.6] and 8.9 (95% CI: 6.4-14.2) months for all patients, 2.3 (95% CI: 1.9-4.3) and 10.4 (95% CI: 6.9-24.2) months for patients in clinical trials and 1.8 (95% CI: 1.4-3.4) and 6.4 (95% CI: 3.3-14.2) months for patients under compassionate treatment. In this retrospective analysis, the reported grade 3-4 toxicities were increased transaminase (34 patients, 37%) and neutropenia (38 patients; 42%). Higher efficacy was observed in phase II studies than with compassionate treatment, but no significant difference remained after adjustment in multivariate analysis for performance status, a well-established prognosis factor. The safety and tolerability of trabectedin shown in clinical trials is confirmed for patients in real-life situation treated in compassionate use programs, but its benefit is higher for patients with performance status 0-1.

Long-term oncological outcome after post-chemotherapy retroperitoneal lymph node dissection in men with metastatic nonseminomatous germ cell tumour.

OBJECTIVE: To determine whether conformity to standard recommendations of retroperitoneal lymph node dissection (RPLND) after chemotherapy for testicular and primary retroperitoneal nonseminomatous germ cell tumours (NSGCT) and completeness of surgical excision have an effect on oncological outcome. PATIENTS AND METHODS: This was a retrospective study of patients with testicular and primary retroperitoneal NSGCT, with initial involvement of RPLNs, treated between June 1992 and December 2002 in one institution. We reviewed the clinical, surgical and histological charts of 151 such patients who had a RPLND after first-line platinum-based chemotherapy. The recommendations used to define conformity to RPLND standards were: the indication based on initial and residual lymph node size, shrinkage, extension of dissection and completeness of resection. RESULTS: RPLND conformed to standard recommendations in 70 of the 151 (46%) patients. Conformity was complete for the surgeon who operated on 48 patients and was 26% of the others. Fifteen patients (10%) relapsed in the retroperitoneum, 14 of whom had initial lymph nodes of > or =5 cm. Two patients (3%) relapsed in the group of 70 patients with conformed and complete RPLND, vs 13 (16%) in the 81 with conformed but incomplete resection or with non-conformed and complete or incomplete RPLND. After a median (range) follow-up of 77 (1.3-186.5) months 132 patients were alive with no evidence of disease, 18 died and one was alive with progressive disease. The limitations of this study were the relatively few patients and that it was retrospective. CONCLUSION: There was conformity of RLNPD to the recommendations, and completeness of resection, in half of the patients operated; this might have an effect on oncological outcome. Our data suggest that patients should be treated in tertiary centres.

Qualitative, Exploratory, and Multidimensional Study of Telepresence Robots for Overcoming Social Isolation of Children and Adolescents Hospitalized in Onco-Hematology.

Purpose: Treatment of pediatric cancers and hematological malignancies requires long periods of isolation in a sterile room. To promote family connections, telepresence robots have been made available in the homes of hospitalized patients. Our aim was to evaluate the perceived benefits and difficulties encountered by users and their families in terms of family dynamics. We also evaluated the presence of the robot on the medical caregivers' therapeutic relationship and organization of daily care. Methods: An observational study was undertaken with semistructured face-to-face interviews of 17 patients (aged 7 to 25 years) and their parents conducted by a psychologist on day +15 after provision of the robot and then after the patients had gone home, as well as face-to-face interviews of 15 caregivers by a philosopher before the robots were made available and at day +21. Results: One of the main perceived benefits expressed by the patients was maintenance of a connection with their siblings and retention of their role in the family. For parents, the device provided reassurance of being able to stay in touch with their child. The nursing staff indicated that the devices allowed them to develop more than a professional relationship with the child and to interact with their extended family. Limitations of the virtual nature of the nursing staff/family relationship were also noted, such as potential frustration for patients when they witness things that they cannot access and a degree of concern for the parents during periods of disconnection. Conclusions: This study revealed an overall perceived benefit for patients, their families, and caregivers. It also highlighted relevant issues and it provides guidelines for broader application of such devices.

Management of bladder cancer in older patients: Position paper of a SIOG Task Force.

Median age at bladder cancer (BC) diagnosis is older than for other major tumours. Age should not determine treatment, and patients should be fully involved in decisions. Patients should be screened with Mini-Cog™ for cognitive impairment and the G8 to ascertain need for comprehensive geriatric assessment. In non-muscle invasive disease, older adult patients should have standard therapy. Age does not contraindicate intravesical therapy. Independent of age and fitness, patients with muscle-invasive BC should have at least cross-sectional imaging. Data suggest extensive undertreatment in older adult patients, leading to poor outcomes. Standard treatment for a fit patient differs between countries. Radical cystectomy and trimodality therapy are first-line options. Radical cystectomy patients should be referred to an experienced centre and prehabilitation is mandatory. Older adult patients should be considered for neoadjuvant and adjuvant therapy, according to guidelines. In urinary diversion, avoiding bowel surgery for reconstruction of the lower urinary tract significantly reduces complications. If a patient is unfit for or refuses standard treatment, RT alone, or TURBT in selected cases should be considered. In metastatic BC, older adult patients should receive standard systemic therapy, depending on fitness for cisplatin and prognosis. Efficacy and tolerability of immunotherapy (IO) appears similar to younger patients. Second line IO is standard in platinum pre-treated patients, with benefit and tolerability in the older adult similar to younger patients. The toxicity profile seems to favour IO in the older adult but more data are needed. Patients progressing on IO may respond to further systemic treatment. In metastatic disease, palliative care should begin early.