Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer.

BACKGROUND: The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear. MATERIALS AND METHODS: We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test. RESULTS: Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI. CONCLUSION: TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.

Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study.

PURPOSE: Universal cancer peptide-based vaccine (UCPVax) is a therapeutic vaccine composed of two highly selected helper peptides to induce CD4+ T helper-1 response directed against telomerase. This phase Ib/IIa trial was designed to test the safety, immunogenicity, and efficacy of a three-dose schedule in patients with metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with refractory NSCLC were assigned to receive three vaccination doses of UCPVax (0.25 mg, 0.5 mg, and 1 mg) using a Bayesian-based phase Ib followed by phase IIa de-escalating design. The primary end points were dose-limiting toxicity and immune response after three first doses of vaccine. Secondary end points were overall survival (OS) and progression-free survival at 1 year. RESULTS: A total of 59 patients received UCPVax; 95% had three prior lines of systemic therapy. No dose-limiting toxicity was observed in 15 patients treated in phase Ib. The maximum tolerated dose was 1 mg. Fifty-one patients were eligible for phase IIa. The third and sixth dose of UCPVax induced specific CD4+ T helper 1 response in 56% and 87.2% of patients, respectively, with no difference between three dose levels. Twenty-one (39%) patients achieved disease control (stable disease, n = 20; complete response, n = 1). The 1-year OS was 34.1% (95% CI, 23.1 to 50.4), and the median OS was 9.7 months, with no significant difference between dose levels. The 1-year progression-free survival and the median OS were 17.2% (95% CI, 7.8 to 38.3) and 11.6 months (95% CI, 9.7 to 16.7) in immune responders (P = .015) and 4.5% (95% CI, 0.7 to 30.8) and 5.6 months (95% CI, 2.5 to 10) in nonresponders (P = .005), respectively. CONCLUSION: UCPVax was highly immunogenic and safe and provide interesting 1-year OS rate in heavily pretreated advanced NSCLC.

Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?

BACKGROUND: Nowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown. AIM: The aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR). METHODS: Analysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020. RESULTS: All patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found. CONCLUSIONS: LR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.

Standard 6-week chemoradiation for elderly patients with newly diagnosed glioblastoma.

Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72-77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I-II and III-IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5-17.5), median OS was 11.7 months (CI 95%: 10-13 months). Median PFS was 9.5 months (CI 95%: 9-10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for "real-life" elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.

Survival of Patients with Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small Cell Lung Cancer Treated beyond the Second Line in the Tyrosine Kinase Inhibitor Era.

BACKGROUND: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. METHODS: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. RESULTS: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53-37.6) and the median follow-up duration was 40.83 months (range 11.33-88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. CONCLUSIONS: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients.

Anti-PD-1 antibodies prolong survival of performance status (PS) 0-1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3-4 patients is unknown. Conse- cutive PS 3-4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3-4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1-7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41-63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1-3.2). Median OS was 4.4 months (95%CI, 0.5-8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9-14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7-13.8, p = 0.003) predicted worse survival. PS improvement from 3-4 to 0-1 (n = 9) led to a median 43-month (95%CI, 0-102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

Treatment strategies and safety of rechallenge in the setting of immune checkpoint inhibitors-related myositis: a national multicentre study.

OBJECTIVES: The occurrence of immune-related myositis (irM) is increasing, yet there are no therapeutic guidelines. We sought to analyse the current therapeutic strategies of irM and evaluate the outcomes of immune checkpoint inhibitors (ICIs) rechallenge. METHODS: We conducted a nationwide retrospective study between April 2018 and March 2020 including irM without myocardial involvement. Depending on the presence of cutaneous signs or unusual histopathological features, patients were classified into two groups: typical or atypical irM. Therapeutic strategies were analysed in both groups. The modalities and outcomes of ICI rechallenge were reviewed. RESULTS: Among the 20 patients, 16 presented typical irM. Regardless of severity, most typical irM were treated with steroid monotherapy (n = 14/16) and all had a complete response within ≤3 weeks. The efficacy of oral steroids for non-severe typical irM (n = 10) was the same with low-dose (≤0.5 mg/kg/day) or high-dose (1 mg/kg/day). Severe typical irM were successfully treated with intravenous methylprednisolone. Atypical irM (n = 4) had a less favourable evolution, including one irM-related death, and required heavy immunosuppression. ICIs were safely reintroduced in nine patients presenting a moderate (n = 6) or a severe (n = 3) irM. CONCLUSION: Our data highlight that steroid monotherapy is an effective treatment for typical irM, either with prednisone or with intravenous methylprednisone pulses depending on the severity. The identification of unusual features is important in determining the initial therapeutic strategy. The outcomes of rechallenged patients are in favour of a safe reintroduction of ICI following symptom resolution and creatin kinase (CK) normalization in moderate and severe forms of irM.

One-year survival in patients with solid tumours discharged alive from the intensive care unit after unplanned admission: A retrospective study.

PURPOSE: Outcomes in cancer patients after unplanned ICU admission was reassessed. METHODS: retrospective cohort of patients with solid tumours admitted to ICU over a 10 years period. RESULTS: 622 patients (age 62 [53-70]) were analysed. The most common primary sites of cancer were lung (n = 133; 21.4%) and digestive tract (n = 126; 20.2%) The ICU mortality rate was 22.2% (n = 138). Among 470 ICU survivors, the 1-year mortality was 41.3% (95% CI, 36-45.9) (n = 167). Factors independently associated with 1-year mortality were ICU admission after 2010 (HR 0.53 (0.37-0.76), p < .001), disease status (respectively, HR = 1.88 (1.0.2-3.45), p = .002) for locally advanced cancer and HR = 2.23 (1.35-3.67), p = .003) for metastatic cancer), poor performance status (HR = 1.58 (1.08-2.31), p = .019), newly diagnosed cancer at ICU admission (HR = 2.02 (1.28-3.20), p = .003), inability to receive oncologic treatment after ICU discharge (HR = 5.34 (3.49-8.18), p < .001) and decision to withhold life-sustaining treatment during ICU stay (HR = 2.34 (1.50-3.65), p < .001). CONCLUSIONS: Among the factors associated with one-year mortality after ICU discharge, the possibility of receiving oncologic treatment after ICU discharge seems crucial.

Efficacy of Immune Checkpoint Inhibitors in Lung Sarcomatoid Carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer prognosis but have not been evaluated specifically in sarcomatoid carcinoma (SC), a rare lung cancer subtype with poor prognosis. As such, our study sought to retrospectively assess the efficacy of ICI in SC. METHODS: All consecutive patients with centrally confirmed SC treated using ICI as a second-line treatment or beyond between 2011 and 2017 were enrolled. Programmed death-ligand 1 (PD-L1) tumor expression was assessed using immunohistochemistry (SP263 clone) and the tumor mutational burden (TMB) with the Foundation One panel. TMB was considered high if it was greater than or equal to 10 mutations per megabase. RESULTS: Overall, 37 patients with SC were evaluated, predominantly men (73%) with a median age of 63.2 years (36.8-79.7) and who were current or former smokers (94.6%). Immunotherapy (nivolumab, 86.5% of cases) was given as a second-line treatment in 54% of the patients and as third-line treatment or beyond in 46% of the patients. The objective response rate was 40.5% and disease control rate was 64.8%, regardless of PD-L1 status. Median overall survival was 12.7 months (range: 0.3-45.7). One-third of patients exhibited early progression. The median PD-L1 expression was 70% (0-100). There was a trend toward higher PD-L1 expression in responsive diseases, with an objective response rate of 58.8% in patients with PD-L1+ and 0% in the one patient with PD-L1- (p = 0.44). The median TMB was 18 (4-39) mutations per megabase, with 87.5% of the cases displaying a high TMB. There was a trend toward higher TMB in responders versus stable or progressive diseases (p = 0.2). CONCLUSIONS: Patients with SC exhibited high response rates and prolonged overall survival under ICI treatment. These data support the prospective investigation of ICI in patients with SC who are under first-line treatment.

A First-in-Human Phase I Study of INVAC-1, an Optimized Human Telomerase DNA Vaccine in Patients with Advanced Solid Tumors.

PURPOSE: Human telomerase reverse transcriptase (hTERT) is highly expressed in >85% of human tumors and is thus considered as a good tumor-associated antigen candidate for vaccine development. We conducted a phase I study to investigate the safety, tolerability, clinical response, and immunogenicity of INVAC-1, a DNA plasmid encoding a modified hTERT protein in patients with relapsed or refractory solid tumors. PATIENTS AND METHODS: INVAC-1 was either administered by intradermal route followed by electroporation or by Tropis, a needle-free injection system. Safety and tolerability were monitored by clinical and laboratory assessments. Progression-free survival and overall survival were reported using Kaplan-Meier survival analysis. Immunogenicity was studied by ELISpot, Luminex, and Flow Cytometry. RESULTS: Twenty-six patients were treated with INVAC-1 administered at three dose levels (100, 400, and 800 µg). Vaccination was well tolerated and no dose-limiting toxicity was reported. One treatment-related grade 3 SAE was reported. Fifty-eight percent of patients experienced disease stabilization. PFS was 2.7 months, median OS was 15 months, and 1-year survival was reached for 65% of patients. INVAC-1 vaccination stimulated specific anti-hTERT CD4 T-cell response as well as cytotoxic CD8 T-cell response. No evidence of peripheral vaccine-induced immunosuppression was observed. CONCLUSIONS: INVAC-1 vaccination was safe, well tolerated, and immunogenic when administered intradermally at the three tested doses in patients with relapsed or refractory cancers. Disease stabilization was observed for the majority of patients (58%) during the treatment period and beyond.See related commentary by Slingluff Jr, p. 529.

Women, thrombosis, and cancer.

Venous thromboembolism (VTE) is a major common complication in cancer patients. Risk-adapted thromboprophylaxis and antithrombotic therapy for patients diagnosed with VTE can reduce the recurrence of VTE events. Thrombotic risk varies according to cancer type, stage, and comorbidities. The current review analyzes most recent data and provides clinical guidance for the management of women with cancer-associated thrombosis.

Abiraterone in metastatic castration-resistant prostate cancer: Efficacy and safety in unselected patients.

BACKGROUND: Abiraterone acetate (AA), an androgen biosynthesis inhibitor, is now a standard of care for men with metastatic, castration-sensitive and castration-resistant prostate cancer (mCRPC). Data exploring real-world toxicity and outcomes are scarce. METHODS: Retrospective study on unselected patients with mCRPC on AA plus steroids. RESULTS: 93 patients were included in the study. Median duration of treatment by AA was 7.5 months (95% CI 5.7-12) among the 58 patients pretreated with chemotherapy, versus 12.7 months ( 95% CI 8.2-35.9) among the 33 chemo-naive patients. Median survivals would reach 13.4 months (95% CI 10.2-19.1) and 36.4 months (95% CI 24.7-41.5) respectively. Rates of hypokalemia, peripheral edema, hypertension, cardiac failure, and overall survival assessments in patients with and without prior chemotherapy were similar to that previously reported in phase 3 randomized trials. The median survival time without adverse event of special interest was 7.5 months for hypokalemia and hypertension, and 5.3 months for liver-function test abnormalities (it was not reached for cardiac disorders). CONCLUSION: Our findings provide further evidence for the survival benefits of AA with a low frequency of additional adverse events among unselected patients. In patients who have not developed hypokalemia or a transaminase increase within 7.5 and 5.3 months respectively, a lighter systematic monitoring may be considered.

Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer.

Nivolumab for the treatment of advanced nonsmall cell lung cancer (NSCLC) evaluated in phase III trials showed 50% progression at first evaluation, but better overall survival (OS), suggesting regained efficacy of treatments given thereafter. We aimed to evaluate the efficacy of nivolumab and of next treatment received after nivolumab progression in patients with advanced NSCLC. Our multicentre retrospective study included all patients receiving nivolumab between January and December 2015. The primary end-point was progression-free survival (PFS) of treatment given after nivolumab. The 303 patients had the following characteristics: median age 63 years, 69% males, 92% smokers, 67% performance status 0-1 and 61% adenocarcinoma. Nivolumab was given as second-line treatment in 40% of patients. With 13.7 months of median follow-up, nivolumab PFS and OS were 2.6 and 11.3 months, respectively. At the cut-off analysis 18% were controlled under nivolumab, 14% were deceased and 5% were lost to follow-up under nivolumab. Among the 191 (63%) patients eligible for post-nivolumab (PN) treatment, 115 (38%) received further treatment and were characterised by better performance status (p=0.028) and by receiving more injections of nivolumab (p=0.001). Global PN-OS and PN-PFS were 5.2 and 2.8 months, respectively. Drugs most frequently used after nivolumab were gemcitabine (23%), docetaxel (22%) and erlotinib (16%), with median PFS of 2.8, 2.7 and 2.0 months, respectively. Nivolumab produced similar efficacy as in phase III trials, although patients received nivolumab later and had worse performance status. 38% received treatment after nivolumab progression with efficacy comparable to historical second-line trials.

Circulating oncometabolite D-2-hydroxyglutarate enantiomer is a surrogate marker of isocitrate dehydrogenase-mutated intrahepatic cholangiocarcinomas.

Therapeutic resources are limited for advanced biliary tract cancers and prognosis remains poor. Somatic mutations in isocitrate dehydrogenase (IDH)1/2 gene are found in 5-36% of patients with intrahepatic cholangiocarcinoma (ICC). The mutant forms of IDH1/2 catalyse the non-reversible accumulation of 2-hydroxyglutarate (2HG). Increasing numbers of indirect or direct-targeted therapies are developed to IDH1/2 mutations and could be assisted by a routinely feasible, rapid and inexpensive serum 2HG measurement by liquid chromatography coupled to tandem mass spectrometry. By comparing eight patients with an IDH1/2-mutated ICC to nine patients with wild-type IDH1/2 ICC, we found significantly higher levels of 2HG in patients with IDH1/2 mutations versus the wild-type group (median, 10.9 vs. 0.8 µmol/L, p = 0.0037). D and L-2HG enantiomer levels significantly differed between the two groups with a higher level of D-2HG (p < 0.0001) in patients with IDH1/2 mutations. Accordingly, the D/L ratio was markedly higher in the patients with IDH1/2 mutations compared with the wild-type group (38.0 vs. 0.9 µmol/L, p < 0.0001). D-2HG measurement ensured 100% sensitivity and specificity at a cut-off of 0.6 µmol/L. D-2HG levels were correlated with tumour burden and tumour response to treatment with IDH-targeted therapies or indirect therapies. D-2HG serum level measurement by liquid chromatography coupled to tandem mass spectrometry is a sensitive, specific, precise (a coefficient of variation <10% and an accuracy >95%), fast (9 min run per sample) and inexpensive surrogate marker of IDH1/2 somatic mutation in ICC. Systematic measurement in patients with ICC may facilitate access to, and monitoring of, IDH-driven therapies.

MET Exon 14 Alterations and New Resistance Mutations to Tyrosine Kinase Inhibitors: Risk of Inadequate Detection with Current Amplicon-Based NGS Panels.

INTRODUCTION: Targeted therapies such as tyrosine kinase inhibitors (TKIs) have dramatically improved the treatment of lung adenocarcinoma, and detection of activating mutations of genes such as EGFR or anaplastic lymphoma kinase gene (ALK) is now mandatory in the clinical setting. However, additional targetable alterations are continuously being described and forcing us to adapt our detection methods. Here we have evaluated the ability of eight amplicon-based next-generation sequencing (NGS) panels to detect the recently described mesenchymal epithelial transition factor (MET) exon 14 (METex14) alterations or new mutations conferring resistance to TKIs. METHODS: A total of 191 tumor samples from patients with NSCLC were screened for METex14 mutations by Sanger sequencing, and 62 additional cases were screened by Sanger sequencing and two amplicon-based NGS panels. In silico comparison of eight commercially available targeted NGS panels was also performed for the detection of METex14 alterations or ALK, ROS1, or EGFR resistance mutations. RESULTS: NGS analysis of the positive METex14 cases revealed a false-negative case because of amplicon design. Moreover, in silico analysis revealed that none of the eight panels considered would be able to detect more than 63% of literature-reported cases of METex14 mutations and similar limitations would be expected with new ALK, ROS1, or EGFR resistance mutations. CONCLUSIONS: We have illustrated major limitations of commercially available amplicon-based DNA NGS panels for detection of METex14 and recently described resistance mutations to TKIs. Documented choice of available panels and their frequent reevaluation are mandatory to deliver the most accurate data to the clinician for therapeutic decisions.

Outcome of Patients with Renal Cell Carcinoma and Multiple Glandular Metastases Treated with Targeted Agents.

PURPOSE: Pancreatic metastases (PM) from renal cell carcinoma (RCC) have been associated with long-term survival. The aim of this study was to evaluate the outcome of RCC patients with multiple glandular metastases (MGM) treated with targeted therapies (TTs). METHODS: Sixty-four MGM patients treated between 1993 and 2014 were retrospectively identified from a database of 274 RCC patients with PM from 11 European centers. The survival of MGM patients was compared with that of both patients with PM only and a cohort of 325 RCC patients with non-GM (control group) treated with TTs. Survival was estimated using the Kaplan-Meier method and was statistically compared using the log-rank test. RESULTS: Fifty-six patients (88%) had at least 2 MGM, 7 patients (11%) had 3 MGM and 1 patient had 4 MGM, while non-GM were present in the remaining patients. The median overall survival (OS) was 54.2 months for MGM and 73.4 months for patients with PM only. The median OS in the control group was 22.7 months and statistically inferior to both MGM (p < 0.001) and PM patients (p < 0.001). CONCLUSION: MGM from RCC are associated with a remarkable survival. Despite some limitations, these findings suggest that GM might be considered a predictor of a favorable prognosis.

Clinical Impact of Pancreatic Metastases from Renal Cell Carcinoma: A Multicenter Retrospective Analysis.

Pancreatic metastases from renal cell carcinoma are uncommon and their prognostic significance is not well defined. In this analysis we evaluated the outcome of patients with pancreatic metastases treated with either targeted therapies or local treatment to the pancreas. Patients with pancreatic metastases from renal cell carcinoma treated between 1993 and 2014 were identified from 11 European centers. Clinical records were retrospectively reviewed. Kaplan-Meier method and log-rank test were used to evaluate progression-free survival and overall survival. Cox's proportional hazard models were used for survival analysis. In total, 276 PM patients were evaluated, including 77 (28%) patients treated by either surgery or radiotherapy to the pancreas, and 256 (93%) who received systemic therapy. Median time from nephrectomy to diagnosis of pancreatic metastases was 91 months (IQR 54-142). Disease control rate after first-line TTs was 84%, with a median progression-free survival of 12 months (95% CI 10-14). Median overall survival was 73 months (95% CI 61-86) with a 5-year OS of 58%. Median OS of patients treated with local treatment was 106 months (95% CI 78-204) with a 5-year overall survival of 75%. On multivariable analysis, nephrectomy (HR 5.31; 95%CI 2.36-11.92; p<0.0001), Memorial Sloan Kettering/International Metastatic RCC Database Consortium prognostic score (HR 1.45, 95% CI 0.94-2.23 for intermediate vs good vs risk; HR 2.76 95%, CI 1.43-5.35 for poor vs good risk p = 0.0099) and pancreatic local treatment (HR 0.48; 95%CI 0.30-0.78 p = 0.0029) were associated with overall survival. Difference in median OS between patients with PM and that reported in a matched-control group of mRCC patients with extrapancreatic metastases was statistically significant (p < .0001). Pancreatic metastases from renal cell carcinoma usually occur years after nephrectomy, are associated with an indolent behavior and a prolonged survival. Targeted therapies and locoregional approaches are active and achieve high disease control rate.

Prophylaxis of venous thromboembolism in cancer patients.

Venous thromboembolism (VTE) is an independent prognostic factor and the second leading cause of death in cancer patients. VTE is however a largely preventable disease when thromboprophylaxis is appropriately used. As recommended worldwide by international Clinical Practice Guidelines, cancer patients undergoing surgery or hospitalization for acute medical illness or with reduced mobility should benefit from thromboprophylaxis, in the absence of bleeding or other contraindications to anticoagulants. Thromboprophylaxis in cancer outpatients receiving systemic therapies is still under debate, except for pancreatic ambulatory cancer patients where prophylaxis confers a sustained reduction in VTE. Numerous strategies are currently developed to improve VTE prophylaxis practices in cancer patients, and to elucidate the best appropriate anticoagulant regimen for each individual cancer patient.

[Molecular biology of castration-resistant prostate cancer]. / Bases de biologie moléculaire du cancer de la prostate résistant à la castration.

Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer.