Loïc Chaigneau

Background/Objectives: Metronomic cyclophosphamide (MCP) is sometimes used for advanced soft-tissue sarcoma (STS) when standard therapies are unsuitable. We assessed its activity and safety in routine practice. Methods: This French three-center retrospective study included 60 adults with unresectable or metastatic STS who started MCP in 2008–2021. Patients received oral cyclophosphamide 50 mg twice daily on days 1–7 of 14-day cycles; 12 (20%) also received prednisolone during treatment weeks. The primary endpoint was progression-free survival (PFS). Results: Median age was 70 years; 55% had ECOG performance status 2–3. Median PFS and overall survival (OS) were 2.6 months (95% CI, 1.8–3.6) and 6.4 months (95% CI, 4.2–9.3), respectively. The objective response rate was 5.0% (3/60; exact 95% CI, 1.0–13.9%) and the disease control rate was 21.7% (13/60; exact 95% CI, 12.1–34.2%); ten patients (16.7%) were not radiologically evaluable. In 21 patients aged >65 years treated in the first- or second-line setting, median PFS and OS were 3.2 and 7.7 months. Treatment-related adverse events were documented in 16 patients (26.7%), with no grade ≥3 events recorded. Conclusions: Intermittent low-dose MCP showed limited antitumor activity but favorable clinician-documented short-term tolerability in this multicenter cohort. Alongside prospective evidence, the results do not support routine use in unselected patients. MCP may retain an individualized palliative role when established systemic therapy is unsuitable.

Objectives: This study aimed to fill the data gap regarding the prevalence of germline (g) BRCA1/2 mutations in patients with metastatic breast cancer (mBC) in France. Methods: A prospective gBRCA1/BRCA2 mutation analysis was proposed to all patients with mBC treated in seven French centers between 19 February and 30 November 2015. The BRCA TrueTM test (Pathway Genomics^®, San Diego, CA, USA) analyzed the coding and flanking regions of BRCA1 and BRCA2 genes using next-generation sequencing, Sanger sequencing, and multiplex ligation-dependent probe amplification. Results: Among 407 included mBC patients, 11 (2.7%) carried pathogenic gBRCA1/2 mutations. Of these, five (45%) would not have met standard criteria for genetic screening. Compared with non-carriers, gBRCA1/2 carriers were significantly younger at mBC diagnosis (47.5 vs. 60.7 years, p = 0.0006), had higher-grade tumor histology (p = 0.044), and had a higher rate of contralateral recurrence (36.4% vs. 11.6%, p = 0.035), with comparable adjusted survival (median overall survival 74.9 vs. 100.1 months, p = 0.97). Variants of uncertain significance were identified in 17 (4.2%) patients. Conclusions: The 2.7% prevalence of gBRCA1/2 mutations in this prospective French mBC cohort was relatively low. Nearly half of the mutation carriers would not have been routinely referred for oncogenetic counseling, underscoring the potential value of broader genetic screening in this population.

Background and Method: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer is correlated with accelerated tumor progression and an unfavorable clinical outcome. Since the introduction of trastuzumab in 2002, the treatment of HER2-positive breast cancer has been revolutionized, leading to significant improvements in survival. This retrospective, multicenter study aimed to describe the characteristics of patients with HER2-positive metastatic breast cancer (MBC) who maintained disease control for a minimum of three years after first-line therapy with trastuzumab and/or pertuzumab combined with chemotherapy. Results: Among 280 eligible patients, 48 (17.5%) were classified as long-term responders. The study population primarily consisted of women with a median age of 56.7 years at diagnosis; de novo metastatic presentation was observed in approximately 70% of cases. An objective response rate of nearly 90% was observed, with a median duration of response of 5.8 years. Median progression-free survival was 11.0 years [95% CI: 6.6—not reached], and median overall survival was not reached [95% CI: 10.9—not reached]. Furthermore, about 15% of patients were able to discontinue systemic therapy without immediate disease progression. Discussion and Conclusions: These findings indicate the potential of achieving prolonged disease control in a subset of patients with HER2-positive MBC, raising questions about therapeutic intensification and potential treatment discontinuation strategies. This study underscores the need for future research to identify predictive factors of durable response and assess the feasibility of adaptive treatment strategies, including planned treatment discontinuation.

Introduction: Soft tissue sarcomas (STSs) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available after the conventional first-line regimen. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS. This led to a FDA approval in 2015, but real-world evidence is still required, complementary to the pivotal phase II and III trials. Methods: One hundred twenty-six patients with STS, treated by trabectedin between 2002 and 2019, were analyzed in this retrospective study, in two French centers. The effects of trabectedin on survival, response, and toxicity were described. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin. Results: Three median cycles were administered per patient (1–79). Among the 113 patients analyzed for efficacy, the median progression-free survival was 3.0 months (95% CI: 2.3–4.8), with an overall survival of 12.3 months (95% CI: 10.2–16.9). The rate of disease control was 46% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression-free survival and overall survival of 13.3 months (95% CI: 2.3–18.7) and 27.8 months (95% CI: 3.2–64.7), respectively. Adverse events were manageable. Discussion and Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma. Combinatory regimens are under clinical trials to optimize the place of this chemotherapy.

IntroductionGastrointestinal stromal tumors represent the most frequently encountered primary mesenchymal tumors. Whereas the liver and the peritoneum are known to be the preferential metastasis sites, no therapeutic standard has yet been established for the management of bone metastases because of their very low incidence. We report a unique example of a single humerus metastasis of a jejunal gastrointestinal stromal tumor.Case presentationWe report the case of a 72-year-old European woman whose jejunal gastrointestinal stromal tumor was resected in 2013 and treated during the following 3 years with imatinib (400 mg daily). In 2018, she developed a single humeral bone lesion that was identified as a gastrointestinal stromal tumor metastasis. After 7 months of imatinib intake, reconstructive surgery was performed. Pathologists confirmed the satisfactory histological regression and assessed the complete tumor resection. The patient is still on imatinib maintenance therapy, with no recurrence reported so far. She fully recovered the upper limb function after following an appropriate rehabilitation program.DiscussionCurrent literature and published case reports indicate that bones are one of the rarest locations of gastrointestinal stromal tumor metastasis (about 1%), with occurrence mainly in the spine. Patients initially diagnosed with gastrointestinal stromal tumor of the small intestine and stomach are more likely to suffer from bone metastasis, compared with other gastrointestinal stromal tumor locations. The median overall survival rate is higher for patients with isolated bone metastasis compared with those having liver metastasis. Metastasis occurs on average 4 years after the primary, but it may take up to 20 years, emphasizing the need for long-term clinical and radiological monitoring. Although specific guidelines for such cases have not yet been established, we suggest that a multimodal concerted approach involving surgery or radiotherapy associated with tyrosine kinase inhibitor intake should be considered.ConclusionBones are one of the rarest locations of gastrointestinal stromal tumor metastasis. A multidisciplinary collaboration was set up to allow conservative surgery of our patient after several months of imatinib treatment. A year and a half later, the patient is still in complete remission. This specific case supports the concept of an intermediate stage between local and oligometastatic disease that should be managed with a curative aim, as much as possible.

Background: Soft tissue sarcomas (STS) are a rare and heterogenous group of tumors, with poor prognostic, judging from their frequency to relapse. Few drugs are available. Since 2007, trabectedin got approval after failure of anthracyclines and ifosfamide, for advanced or metastatic STS.Patients and Methods: This retrospective study describes effects of trabectedin on survival, response, and toxicity, in STS patients. One hundred twenty-nine patients treated between 2002 and 2019 were analysed, from two French centers. All patients were tested for toxicities, and efficacy was assessed in patients exposed to at least 2 cycles of trabectedin.Results: Three median cycles were administered per patient (1-79). Among the 115 patients analysed for efficacy, the median progression free survival was 3.0 months [CI_95%: 2.3 – 4.7], with an overall survival of 11.9 months [CI_95%: 10.2 – 16.6]. The rate of disease control was 45.2% at the end of treatment. Myxoid liposarcoma (n = 11) was the histology subtype that benefited most from this chemotherapy with median progression free survival and an overall survival of 13.3 months [CI_95%: 2.3 – 18.7] and 27.8 months [CI_95%: 3.2 – 64.7], respectively. Adverse events were manageable. Conclusion: Efficacy of trabectedin is confirmed in terms of clinical benefit and low toxicity, especially for myxoid liposarcoma.

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07–0.70, p = 0.01 and HR 0.38; 95% CI 0.15–0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.

Brain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases. We performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index. The original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status. The Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.