The therapeutic landscape of metastatic renal cell carcinoma (mRCC) has evolved considerably with the introduction of immune checkpoint inhibitors (ICIs) and VEGFR-targeted therapies, leading to unprecedented improvements in survival. As durable responses and deep remissions become more frequent, the question of how to optimize treatment intensity has gained prominence. Therapeutic de-escalation, through reduced dose intensity, extended dosing intervals, treatment interruption, or integration of local therapies, has emerged as a promising approach to mitigate chronic toxicity, preserve quality of life, and reduce healthcare costs without compromising oncologic outcomes. Pharmacokinetic and pharmacodynamic data provide a strong biological rationale for immunotherapy de-escalation, with ICIs achieving sustained PD-1/PD-L1 receptor occupancy that persists for weeks after infusion. Historical observations, such as prolonged responses after nivolumab discontinuation, together with modern evidence from trials like OMNIVORE, TITAN-RCC, STAR, and ongoing initiatives (PDIGREE, MOIO), support the feasibility of treatment reduction in selected responders (Table 1). De-escalation may also be facilitated by consolidative local therapies, including metastasectomy, stereotactic radiotherapy, and delayed nephrectomy, that can increase complete response rates and prolong treatment-free survival. Identifying candidates for de-escalation requires integrating clinical response depth, metastatic patterns, and emerging biomarkers. Minimal residual disease assessment using circulating tumor DNA, as recently demonstrated in prospective studies, may refine patient selection and inform optimal timing for treatment interruption. Despite encouraging retrospective and early prospective data, robust randomized trials remain essential to define standardized strategies. Overall, treatment de-escalation represents a key step toward personalized, value-based care in mRCC.

Targeted therapies (TT) represent a major breakthrough in oncology, with nearly one hundred agents now available, half of which are administered orally. While their efficacy is unquestionable, their safety profile, particularly cardiovascular (CV), requires close attention. Indeed, the frequency and presentation of these CV toxicities vary according to the TT: arterial hypertension with VEGFR inhibitors, thromboembolic events with abemaciclib, left ventricular dysfunction with osimertinib or BRAF/MEK inhibitors, QTc prolongation with ribociclib or vandetanib, and metabolic disorders (dyslipidemia, hyperglycemia) with PI3K/AKT/mTOR pathway inhibitors. Although severe events remain relatively uncommon, they may impact the continuation of a treatment crucial for cancer prognosis. Data from clinical trials, complemented by pharmacovigilance and real-world studies, now provide a clearer picture of these complications. Prevention and management rely on recent European Society of Cardiology recommendations including initial CV risk assessment (HFA-ICOS score), close clinical and paraclinical monitoring, and tailored management of toxicities. In this setting, cardio-oncology is emerging as an essential discipline, aiming to reconcile anticancer efficacy with cardiovascular safety. A multidisciplinary approach involving oncologists, cardiologists, primary care physicians, and patients is key. Patient education, optimization of risk factors, and individualized monitoring are the cornerstones of optimal care.

Metastatic osteosarcoma (MOS) has a poor prognosis, and few treatment options. This multicentre observational study provides real-world data on treatment patterns of patients with MOS in France. The primary objective was to describe treatment modalities of patients with MOS aged ≥12 years treated in 11 reference network centers. Secondary objectives were to assess time to next treatment (TTNT), overall survival (OS) and prognostic factors for TTNT and OS. From 2008 to 2018, 262 patients with MOS were included; 88 patients were metastatic at diagnosis, and 174 patients had a metastatic relapse. Median age at diagnosis was 26 (12-86). A total of 227 (86.6%) patients received systemic treatment in the metastatic setting, and 75 (28.6%) patients received more than two lines. Overall, 153 (58.4%) patients underwent at least a loco-regional procedure, and 50 patients (19.1%) participated in a clinical trial in the metastatic setting. Median OS from metastasis diagnosis was 21.5 months [95% CI 18.9-27.0], 23.0 months [95% CI 15.0-31.1] in the synchronous cohort, and 21.4 months [95% CI 18.7-29.7] in the metachronous cohort. Median TTNT was 8.2 months [95% CI 6.7-9.9], 5.7 months [95% CI 4.2-7.2], 3.7 months [95% CI 3.0-4.3], and 2.9 months [95% CI 1.8-3.9] in first, second, third, and fourth line. It was 7.6 months [95% CI 5.1-12.5], 6 months [95% CI 3.6-8.7], and 4.8 months [95% CI 2.9-7.5] for tyrosine kinase inhibitors such as regorafenib or cabozantinib in first, second, and third line. In MOS, the benefit of chemotherapy after first line is limited. TKIs show encouraging activity from first line. Inclusion in clinical trials should be prioritized.

BACKGROUND AND OBJECTIVE:Lenvatinib's activity after immune checkpoint inhibitors (ICI) combination therapy in renal cell carcinoma (RCC) remains unknown. We aimed to describe the real-world outcomes of patients with metastatic RCC (mRCC) treated with lenvatinib after failure of the prior standard of care. METHODS:Multicenter retrospective study including patients with mRCC treated with lenvatinib-based therapies beyond first-line therapy between 2020 and 2024. The primary endpoints were objective response rate (ORR) and time-to-treatment failure (TTF). Secondary endpoints included disease control rate (DCR), overall survival (OS), and safety. RESULTS:We included 133 patients, with a median age of 61 years. Clear-cell was the main subtype (82.0 %). Before lenvatinib treatment, 15.8 %, 51.9 %, and 27.8 % of patients showed favorable, intermediate, and poor risk disease, respectively, according to the International Metastatic RCC Database Consortium (IMDC). Moreover, patients received a median of 3 previous lines of treatment, including ICIs (90.2 %) and cabozantinib (90.2 %). Lenvatinib was given alone (45.9 %) or in combination with everolimus (33.8 %), pembrolizumab (18.0 %) or investigational agents (2.3 %). The ORR and DCR were 29.1 % and 67.7 %, respectively, with no differences between regimens or lines of treatment. With a median follow-up time of 13.5 months, the median TTF and OS were 6.2 and 9.6 months. Toxicity was manageable with dose modifications required in 34.6 %. The discontinuation rate was 9.8 %, with one toxic death. CONCLUSION:Lenvatinib-based regimens were active and safe for heavily pre-treated patients with mRCC. These findings provide evidence to support its use in daily practice.

The CABONEXT study is the first multicenter retrospective analysis evaluating subsequent systemic therapies after cabozantinib-based treatment in metastatic renal cell carcinoma (mRCC). This interim analysis includes 77 patients receiving subsequent treatments across two cohorts: after cabozantinib–nivolumab first-line treatment (Group A) and after ICI-based first-line treatment followed by cabozantinib (Group B). Time to subsequent treatment failure (TTF) and disease control rate (DCR) remain higher in Group A with a median TTF of 5 months (vs. 3.4 months in Group B) and a DCR of 86% (vs. 48%). Second-generation TKIs, mostly axitinib or lenvatinib, seemed to be the best option in Group B compared to other treatments including everolimus or first-generation TKIs (HR = 3.82, 95%CI [1.64; 8.93], p = 0.1). These findings already emphasize the need for innovative therapies targeting resistance mechanisms and optimal treatment sequences. Along with ongoing accrual, further analyses are expected.

BACKGROUND:Trabectedin, which is approved for advanced soft tissue sarcoma management, has a complex mechanism of action, but can be classified as an alkylating agent. The need to maintain a high relative dose intensity (RDI) is not clearly established in this clinical setting. METHODS:We conducted a retrospective study in five expert centers to compare the progression-free survival (PFS) and overall survival (OS) of patients with advanced L-Sarcomas (liposarcomas or leiomyosarcoma) according to the RDI calculated over the first three cycles (RDI < 80% and RDI ≥ 80%). Comparisons of patients' characteristics were done using Chi-2, Fisher exact, and Wilcoxon tests. Associations between PFS/OS and RDI were estimated and tested in Cox models. RESULTS:Out of 332 patients treated with trabectedin between 09/1999 and 12/2021, 244 have received at least 3 cycles before progression. Among these 244 patients, the median RDI during the first 3 cycles was 83% (range, 48%-106%), the mean RDI was 81% (±14%) and 106 patients had RDI < 80%. An RDI < 80% was more frequently observed in patients treated in a center with a high volume of activity (82/169, 49%, vs. 24/75, 32%, p = 0.02), in patients who had previously received pazopanib (12/18, 67%, vs. 94/225, 42%, p = 0.04), and in patients who experienced grade 3 neutropenia during the first cycle (56/77, 73% vs. 35/127, 28%, p < 0.001). PFS did not significantly differ according to RDI (p = 0.08): HR(< 80%/≥ 80%) = 0.79 (95% CI, 0.61-1.03), median PFS = 8.4 months (7.0-9.3) when RDI < 80% vs. 5.9 months (4.4-6.8) when RDI ≥ 80%. We observed no significant difference in terms of OS (p = 0.53): HR(< 80%/≥ 80%) = 0.92 (95% CI, 0.70-1.20), median OS = 18.2 months (15.6-23.4) when RDI < 80% vs. 15.8 months (13.2-19.7) when RDI ≥ 80%. CONCLUSION:This retrospective study does not support a link between high trabectedin RDI and PFS or OS for advanced L-sarcoma patients.

Metastatic chondrosarcoma (MCS) has a poor prognosis, and treatment options are scarce in this rare disease. This multicenter observational study provides real‐world data on treatment patterns of patients with MCS in France. Treatment characteristics, outcomes in terms of time to next treatment (TTNT) and overall survival (OS), and prognostic factors of patients ≥12‐year‐old treated for a MCS in nine French reference network centers were retrieved from the French Sarcoma Group prospective database. From 2008 to 2018, 127 patients with MCS were included, 31 were metastatic from diagnosis (synchronous cohort), 89 had a metastatic relapse, and 7 had locally advanced unresectable disease, of whom 4 developed secondary metastases (metachronous cohort). Median age at diagnosis was 61 years (14–90), 58.9% of patients received a systemic treatment with a median of 2 lines (1–6), 40.3% had a locoregional procedure on metastasis, and 9.7% of patients participated in a clinical trial at least once in the metastatic setting. Median OS from metastatic diagnosis was 12.7 months [95%CI 8.2, 14.9], without significant difference between the metachronous and synchronous cohorts. Median TTNT was 4.6 months [95%CI 3.0, 5.9], 3.4 months [95%CI 2.7, 4.8], and 3.4 months [95%CI 2.0, 7.9] in first, second, and third lines, respectively. In MCS, benefits of chemotherapies are very limited. Tyrosine kinase inhibitors such as regorafenib or pazopanib show some activity from first line. Locoregional treatment of metastasis is associated with survival and should be proposed when feasible. Inclusion in clinical trials should be prioritized.

Non-small cell lung cancer (NSCLC) is the most common cause of brain metastasis (BM). Little is known about immune checkpoint inhibitor activity in the central nervous system, especially in patients receiving monotherapy for tumors with a tumor proportion score (TPS) ≥ 50%. This noninterventional, retrospective, multicenter study, conducted with the GFPC, included treatment-naïve patients strongly positive for PD-L1 (TPS ≥ 50%) with BM receiving first-line single-agent pembrolizumab treatment between May 2017 and November 2019. The primary endpoints were centrally reviewed intracranial overall response rates (ORRs), centrally reviewed intracranial progression-free survival (cPFS), extracranial PFS, and overall survival were secondary endpoints. Forty-three patients from five centers were included. Surgical or local radiation therapy was administered to 31 (72%) patients, mostly before initiating ICI therapy (25/31). Among 38/43 (88.4%) evaluable patients, the intracranial ORR was 73%. The median PFS was 8.3 months. The cerebral and extracerebral median PFS times were 9.2 and 5.3 months, respectively. The median OS was 25.5 months. According to multivariate analysis, BM surgery before ICI therapy was the only factor significantly associated with both improved PFS (HR = 0.44) and OS (HR = 0.45). This study revealed the feasibility and outcome of front-line pembrolizumab treatment in this population with BM.

In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2). Fourteen patients (56%) had concomitant extracerebral metastases, primarily in group 2. Eight (32%) had oligometastatic disease, with seven in group 1. Over half received chemotherapy and pembrolizumab as first-line treatment. BM surgical resection occurred in twelve (80%) patients in group 1 and one in group 2. Median cerebral progression-free survival was 10 months: 12 in group 1 and 5 in group 2. Median overall survival was 25 months: not reached in group 1 and 6 months in group 2. This case series highlights survival outcomes for patients with inaugural BM, a demographic underrepresented in pivotal trials. Oligometastatic disease and symptomatic BM as initial signs seem associated with better prognosis due to increased use of multimodal local approaches. Combining local approaches with first-line ICI+/− chemotherapy appears to improve survival in brain metastatic NSCLC. A literature review was conducted to explore key questions regarding upfront ICI alone or in combination with systemic drugs or local approaches in brain metastatic NSCLC.

Lung cancers with ALK rearrangement represent less than 5% of all lung cancers. ALK inhibitors are currently used to treat first-line metastatic non-small cell lung cancer with ALK rearrangement. Compared to chemotherapy, ALK inhibitors have improved progression-free survival, overall survival, and quality of life for patients. The results of several phase 3 studies with a follow-up of over 6 years suggest that the life expectancy of these patients treated with targeted therapies is significantly higher than 5 years and could approach 10 years. Nevertheless, these treatments induce haematological toxicities, including neutropenia. Few data are available on neutropenia induced by ALK inhibitors and on the pathophysiological mechanism and therapeutic adaptations necessary to continue the treatment. Given the high efficacy of these treatments, managing side effects to avoid treatment interruptions is essential. Here, we have reviewed the data from published clinical studies and case reports to provide an overview of neutropenia induced by ALK inhibitors.

Introduction: Cancer patients are at high risk of developing septic shock (SSh) and are increasingly admitted to ICU given their improved long-term prognosis. We, therefore, compared the prognosis of cancer and non-cancer patients with SSh. Methods: We conducted a monocentric, retrospective cohort study (2013–2019) on patients admitted to ICU for SSh. We compared the clinical characteristics and management and studied short- and long-term mortality with ICU and in-hospital mortality and 1-year survival according to cancer status. Results: We analyzed 239 ICU stays in 210 patients, 59.5% of whom were men (n = 125), with a median age of 66.5 (IQR 56.3–77.0). Of the 121 cancer patients (57.6% of all patients), 70 had solid tumors (33.3%), and 51 had hematological malignancies (24.3%). When comparing ICU stays of patients with versus without cancer (n = 148 vs. n = 91 stays, respectively), mortality reached 30.4% (n = 45) vs. 30.0% (n = 27) in the ICU (p = 0.95), and 41.6% (n = 59) vs. 35.6% (n = 32) in hospital (p = 0.36), respectively. ICU length of stay (LOS) was 5.0 (2.0–11.3) vs. 6.0 (3.0–15.0) days (p = 0.27), whereas in-hospital LOS was 25.5 (13.8–42.0) vs. 19.5 (10.8–41.0) days (p = 0.33). Upon multivariate analysis, renal replacement therapy (OR = 2.29, CI95%: 1.06–4.93, p = 0.03), disseminated intravascular coagulation (OR = 5.89, CI95%: 2.49–13.92, p < 0.01), and mechanical ventilation (OR = 7.85, CI95%: 2.90–21.20, p < 0.01) were associated with ICU mortality, whereas malignancy, hematological, or solid tumors were not (OR = 1.41, CI95%: 0.65–3.04; p = 0.38). Similarly, overall cancer status was not associated with in-hospital mortality (OR = 1.99, CI95%: 0.98–4.03, p = 0.06); however, solid cancers were associated with increased in-hospital mortality (OR = 2.52, CI95%: 1.12–5.67, p = 0.03). Lastly, mortality was not significantly different at 365-day follow-up between patients with and without cancer. Conclusions: In-hospital and ICU mortality, as well as LOS, were not different in SSh patients with and without cancer, suggesting that malignancies should no longer be considered a barrier to ICU admission.

Background: According to guidelines, all patients with sarcoma must be managed from initial diagnosis at expert sarcoma centers. However, in everyday practice, the time interval to an expert center visit can be long, which delays presentation to an expert multidisciplinary tumor board and increases the risk of inappropriate management, negatively affecting local tumor control and prognosis. The advent of mobile health offers an easy way to facilitate communication and cooperation between general health care providers (eg, general practitioners and radiologists) and sarcomas experts. We developed a mobile app (Sar'Connect) based on the algorithm designed by radiologists from the French Sarcoma Group. Through a small number of easy-to-answer questions, Sar'Connect provides personalized advice for the management of patients and contact information for the closest expert center.Objective: This retrospective study is the first to assess this mobile app's potential benefits in reducing the time interval for patient referral to an expert center according to the initial clinical characteristics of the soft tissue tumor.Methods: From May to December 2021, we extracted tumor mass data for 78 patients discussed by the multidisciplinary tumor boards at 3 centers of the French Sarcoma Group. We applied the Sar'Connect algorithm to these data and estimated the time interval between the first medical description of the soft tissue mass and the referral to expert center. We then compared this estimated time interval with the observed time interval. Results: We found that the use of Sar'Connect could potentially shorten the time interval to an expert center by approximately 7.5 months (P<.001). Moreover, for half (31/60, 52%) of the patients with a malignant soft tissue tumor, Sar'Connect could have avoided inappropriate management outside of the reference center. We did not identify a significant determinant for shortening the time interval for referral.Conclusions: Overall, promoting the use of a simple mobile app is an innovative and straightforward means to potentially accelerate both the referral and management of patients with soft tissue sarcoma at expert centers.

According to guidelines, all sarcoma patients must be managed from initial diagnosis at expert sarcoma centers. However, in everyday practice, the time interval to an expert center visit can be long, which delays presentation to an expert multidisciplinary tumor board (MTB) and increases the risk of inappropriate management, negatively affecting local tumor control and prognosis. The advent of mobile health (mHealth) offers an easy way to facilitate communication and cooperation between general health care providers (e.g., general practitioners and radiologists) and sarcomas experts. We developed a mobile application (Sar’Connect) based on the algorithm designed by radiologists from French Sarcoma Group. Through a small number of easy-to-answer questions, Sar’Connect provides personalized advice for management of patients and contact information on the closest expert center. This retrospective study is the first to assess this mobile application’s benefits in reducing the time interval for patient referral to an expert center according to the initial clinical characteristics of the soft tissue tumor. We extracted tumor mass data for 78 patients discussed by MTBs of three centers of French Sarcoma Group. We applied the Sar’Connect algorithm to these data and estimated the time interval to expert center referral; then, we compared this estimated time interval with the observed time interval. We found that the use of Sar’Connect shortened the time interval to a referral center by approximately 7.5 months. Moreover, for half of patients with a malignant soft tissue tumor, Sar’Connect avoided inappropriate management outside of the reference center. We did not identify a significant determinant for shortening the time interval for referral. Overall, promoting the use of a simple mobile application is an innovative and straightforward means to accelerating both the referral and management of soft tissue sarcoma patients in expert centers.

Introduction Immune checkpoint inhibitors (ICIs) can induce adverse neurological effects. Due to its rarity as an adverse effect, meningitis has been poorly described. Therefore, meningitis diagnosis and management can be challenging for specialists. Moreover, meningitis can be an obstacle to resuming immunotherapy. Given the lack of alternatives, the possibility of reintroducing immunotherapy should be discussed on an individual basis. Here, we present a comprehensive systematic review of meningitis related to ICIs. Review We performed a search for articles regarding immune-related meningitis published in PubMed up to November 2021 with the MeSH terms "meningitis" and "immune checkpoint" using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. We summarized the studies not only by category but also based on whether it was a primary article or case report to provide a systematic overview of the subject. We reviewed a total of 38 studies and herein report the clinical experiences, pharmacovigilance data and group knowledge from these studies. Conclusion This review summarizes the existing information on immune-related meningitis and the possibility of reintroducing immunotherapy after the development of central neurological side effects. To the best of our knowledge, there is little information in the literature to guide clinicians on decisions regarding whether immunotherapy should be continued after a neurological adverse event occurs, especially meningeal events. This review emphasizes the necessity of systematic examinations, steroid treatment (as a cornerstone of management) and the need for further exploratory studies to obtain a clearer understanding of how to better manage patients who experience these side effects. The findings summarized in this review can help provide guidance to practitioners who face this clinical situation.

PEComas is a family of rare mesenchymal tumors. This systematic review aims to better understand the natural history of advanced PEComas. After a search on the PubMed database and main oncology meeting libraries according to the PRISMA guidelines, 88 articles reported in the English literature were included. Data on clinical and histological features, treatments and outcomes were collected. To identify risk factors, univariate and multivariate analyses were performed. Seven cohorts of patients and 124 individual patients were identified. Focusing on case reports, most patients were metastatic, and the median overall survival (OS) of the entire cohort was 60 months (95%CI 33; NA). Risk factors significantly associated with OS in the multivariate analysis were the presence of metastasis at diagnosis (HR: 2.59, 95%CI 1.06; 6.33, p = 0.036) and the grouped-Bleeker's risk category (HR: 4.66; 95%CI 1.07; 20.19; p = 0.039). In the metastatic population, only the presence of lymph node metastasis was associated with OS (HR: 3.11; 95%CI 1.13; 8.60, p < 0.05). Due to a lack of events, it was not possible to conclude on other factors. This review of the literature highlights the heterogeneity of literature data and shows the great diversity of clinical management strategies.