The aim of this study was to evaluate the clinical significance of studies with dual radiotracers, 18F-FDG and 18F-fluorocholine (18F-FCH), performed before and after 1 mo of sorafenib therapy, in patients with advanced hepatocellular carcinoma (HCC) for the prediction of 1-y survival. Methods: Patients with advanced HCC eligible for sorafenib therapy were recruited in the prospective open-label single-arm multicenter PREMETHEP trial (NCT02847468; 6 recruiting centers). Patients had to undergo 18F-FDG and 18F-FCH PET/CT before treatment initiation and 1 mo after to evaluate baseline and residual tumor metabolism. The following parameters were extracted from each scan: the SUVmax and tumor-to-normal-liver ratio (TNR) (SUVmax of the tumor divided by SUVmax of normal liver) for the more significant lesion, and the volumetric parameters of the intrahepatic tumor burden: metabolic tumor volume (MTV), total lesion glycolysis (TLG) for 18F-FDG, and total lesion choline kinase activity for 18F-FCH. The tumor metabolic response (change in SUVmax, TNR, MTV, TLG, and total lesion choline kinase activity) was also calculated. Patients were followed during 1 y after treatment initiation. Cox analysis was performed to determine predictors of death. Optimal thresholds for quantitative parameters were determined using logistic regressions with the Youden index method. Results: Among 61 patients included, 36 were considered for final analysis (all male; median age, 70 y). Twenty-one patients died during follow-up. On univariate analysis, a serum albumin level of less than 36 g/L and parameters reflecting high 18F-FDG tumor burden at baseline were significantly associated with death (TNR ≥ 1.5 [hazard ratio (HR), 7.6; 95% CI, 2.2-26.5; P = 0.001], MTV ≥ 18 cm3 [HR, 6.3; 95% CI, 2.1-19.3; P < 0.001], and TLG ≥ 53 [HR, 12.6; 95% CI, 2.9-55.2; P = 0.002]). In contrast, neither of the 18F-FCH parameters (baseline and follow-up) and clinical data had prognostic significance. On multivariate analysis, an MTV of at least 18 cm3 on baseline 18F-FDG PET/CT remained an independent predictor of death (HR, 6.6; 95% CI, 1.7-25.2; P < 0.001). Conclusion: Baseline metabolic tumor burden determined with 18F-FDG PET/CT is a strong prognostic biomarker in patients with advanced HCC receiving sorafenib therapy. 18F-FCH PET/CT does not provide additional prognostic information.

Importance:Stereotactic body radiotherapy (SBRT), most commonly delivered in 5 fractions, is an established treatment option for patients with localized prostate cancer. While efforts to further reduce treatment to fewer than 5 fractions are ongoing, the efficacy and tolerability of single high-dose SBRT remain to be established. Objective:To determine in men with localized prostate cancer whether a single-fraction SBRT can be a valid treatment option in terms of biochemical disease control and safety. Design, Setting, and Participants:This multicenter, single-arm, prospective, phase 1/2 nonrandomized clinical trial included men with localized prostate cancer at low or intermediate risk, with International Society of Urological Pathology grade group 1 or 2, and without significant tumor in the transitional zone. Participants were recruited between 2017 and 2022 in 5 academic centers in Europe and the US. Data were analyzed between February and May 2026. Intervention:Participants were treated with a 19-Gy single-fraction prostate SBRT with urethra-sparing and intrafraction motion control. Main Outcomes and Measures:The primary end point was biochemical relapse-free survival (bRFS) at 3 years (expected value of 96% included in the 95% CI). Secondary end points included occurrence of genitourinary (GU), gastrointestinal (GI), and sexual adverse events (AEs) and quality of life (QOL) assessment. Results:Among the 45 patients recruited (median age, 72 [range, 60-82] years), 43 were treated per protocol. After a median follow-up of 55.3 (IQR, 49.9-60.7) months, the estimated 3-year bRFS was 92.9% (95% CI, 85.4%-100%), meeting the primary end point. At 3 years, grade 2 GU and GI AEs were observed in 4 (9.8%) and 2 (4.9%) participants, respectively, with only a grade-3 proctitis observed in 1 patient at month 12. Grade 2 or higher erectile dysfunction increased from 9 of 42 patients (21.4%) at baseline to 15 of 39 (38.4%) at 3 years. A significant minimally clinically important change in Expanded Prostate Cancer Index Composite scores was observed in 6 (14%) and 12 (28%) participants for GU and sexual scores, respectively. The impact in GI bother scores was minimal. Conclusions and Relevance:In this multicenter phase 1/2 trial, a single-fraction 19-Gy urethra-sparing SBRT met the primary end point, achieving a 3-year bRFS of 92.9%, with grade 2 GU and GI AEs remaining below 10% and 5%, respectively, at 3 years. Longer follow-up is warranted to assess long-term disease control. Trial Registration:ClinicalTrials.gov Identifier: NCT03294889.

QuestionCan stereotactic body radiotherapy (SBRT) be delivered safely and effectively as a single fraction of 19 Gy for patients with localized prostate cancer?FindingsIn this phase 1/2 nonrandomized clinical trial including 45 patients with localized prostate cancer, the primary hypothesis was confirmed, with the estimated 3-year biochemical relapse-free survival meeting the predefined primary end point. Treatment was well tolerated, and treatment-related adverse events as well as quality-of-life outcomes assessed over the first 3 years demonstrated the safety and good tolerability of single-fraction SBRT.MeaningThese results suggest that single-fraction SBRT is a feasible and well-tolerated treatment strategy that warrants further investigation as a potential option for carefully selected patients with localized prostate cancer. This nonrandomized clinical trial evaluates the efficacy and tolerance of single-fraction stereotactic body radiotherapy in men with localized prostate cancer. ImportanceStereotactic body radiotherapy (SBRT), most commonly delivered in 5 fractions, is an established treatment option for patients with localized prostate cancer. While efforts to further reduce treatment to fewer than 5 fractions are ongoing, the efficacy and tolerability of single high-dose SBRT remain to be established.ObjectiveTo determine in men with localized prostate cancer whether a single-fraction SBRT can be a valid treatment option in terms of biochemical disease control and safety.Design, Setting, and ParticipantsThis multicenter, single-arm, prospective, phase 1/2 nonrandomized clinical trial included men with localized prostate cancer at low or intermediate risk, with International Society of Urological Pathology grade group 1 or 2, and without significant tumor in the transitional zone. Participants were recruited between 2017 and 2022 in 5 academic centers in Europe and the US. Data were analyzed between February and May 2026.InterventionParticipants were treated with a 19-Gy single-fraction prostate SBRT with urethra-sparing and intrafraction motion control.Main Outcomes and MeasuresThe primary end point was biochemical relapse-free survival (bRFS) at 3 years (expected value of 96% included in the 95% CI). Secondary end points included occurrence of genitourinary (GU), gastrointestinal (GI), and sexual adverse events (AEs) and quality of life (QOL) assessment.ResultsAmong the 45 patients recruited (median age, 72 [range, 60-82] years), 43 were treated per protocol. After a median follow-up of 55.3 (IQR, 49.9-60.7) months, the estimated 3-year bRFS was 92.9% (95% CI, 85.4%-100%), meeting the primary end point. At 3 years, grade 2 GU and GI AEs were observed in 4 (9.8%) and 2 (4.9%) participants, respectively, with only a grade-3 proctitis observed in 1 patient at month 12. Grade 2 or higher erectile dysfunction increased from 9 of 42 patients (21.4%) at baseline to 15 of 39 (38.4%) at 3 years. A significant minimally clinically important change in Expanded Prostate Cancer Index Composite scores was observed in 6 (14%) and 12 (28%) participants for GU and sexual scores, respectively. The impact in GI bother scores was minimal.Conclusions and RelevanceIn this multicenter phase 1/2 trial, a single-fraction 19-Gy urethra-sparing SBRT met the primary end point, achieving a 3-year bRFS of 92.9%, with grade 2 GU and GI AEs remaining below 10% and 5%, respectively, at 3 years. Longer follow-up is warranted to assess long-term disease control.Trial RegistrationClinicalTrials.gov Identifier: NCT03294889

Abstract Background Lymphopenia has been associated with poor outcomes in metastatic breast cancer (BC), but its prognostic relevance in early-stage disease remains unclear. This study aimed to evaluate the prognostic value of baseline lymphopenia in patients with non-metastatic BC using data from the prospective French CANTO cohort (NCT01993498). Methods 10,854 patients with baseline absolute lymphocyte count (ALC) were analysed. Lymphopenia was defined as ALC < 1.0 × 10⁹ cells/L, measured before any cancer treatment. Relapse-free survival (RFS), overall survival (OS), and treatment-related toxicities were assessed using Kaplan-Meier estimates, piecewise-Cox regression models, and cause-specific hazard analyses considering pre-specified time periods. Results Baseline lymphopenia was observed in 342 patients (3.1%). It was associated with ECOG performance status > 0, hypoalbuminemia, and prior neoplasia. Lymphopenia correlated with inferior 5-year RFS (89.1% vs. 92.9%) and OS (92.5% vs. 96.4%). In multivariable analyses, lymphopenia was associated with increased risk of early relapse during the first 24 months (HR = 2.11; 95%CI: 1.28–3.48; p = 0.003), but not beyond, and no independent prognostic impact on OS was observed. No significant differences were found in surgical complications or chemotherapy dose intensity, though granulocyte colony-stimulating factor use was higher among lymphopenic patients. Conclusion Baseline lymphopenia is uncommon in early BC but may serve as a marker of early relapse risk. Although it does not independently predict long-term survival, its presence could reflect underlying tumour aggressiveness or patient frailty. These findings support further investigation of lymphocyte subpopulations to refine prognostic stratification in early BC. Trial registration Approved by French ethics committee in 2011 (ID-RCB:2011-A01095- 36,11–039 /NCT01993498 [20FEB2012]).

Abstract In the tumour microenvironment, IL-1α promotes neoangiogenesis, matrix remodelling, tumour proliferation, chemoresistance, and metastases. Highly expressed in human colorectal cancers, IL-1α is associated with poor prognosis. XB2001, a fully human monoclonal antibody neutralizing IL-1α, was evaluated for safety and preliminary efficacy with trifluridine/tipiracil (FTD/TPI) and bevacizumab in metastatic colorectal cancer patients previously treated with oxaliplatin- and irinotecan-based chemotherapies. This single institution, phase 1 study used a 3 + 3 design to assess XB2001 at doses of 250 mg, 500 mg and 1000 mg every 14 days, associated with FTD/TPI 35 mg/m² (days 1–5 and 8-12, every 28 days) (NCT05201352). The Maximum Tolerated Dose of XB2001 + FTD/TPI was then associated in combination with bevacizumab (5 mg/kg, days 1 and 15). Safety, efficacy, pharmacokinetics and pharmacodynamics were assessed. Seventeen patients (median age: 67.4 years) were enroled. No patient exhibited dose-limiting toxicity at any dose. The most common treatment-related adverse events (TRAE) of any grade (G) were diarrhoea (35.3%), nausea (47.1%) and anaemia (35.3%). G3-4 TRAE were neutropenia (17.6%) hypertension and infection (5.9% each). The RP2D (recommended phase 2 dose) of XB2001 was 1000 mg. The disease control rate was 76%, with 23% of patients achieving an objective response, including one complete response. Response and longer progression-free survival were associated with a decrease in serum IL-6 levels during therapy. High intratumoral IL-1α expression at baseline and CD8/PD-L1 infiltration are associated with a better progression-free survival. The combination of XB2001 with FTD/TPI and bevacizumab is feasible and safe, and showed encouraging clinical activity in chemotherapy-resistant mCRC.

Background: Synchronous bilateral breast cancer (sBBC) is a rare occurrence. There is currently no consensus on the optimal management strategy for this condition, particularly when there is discordance between the clinical or biological presentations. Some studies have reported that sBBC is associated with poorer outcomes compared to unilateral breast cancer. The objective of this study was to describe the incidence, clinical, pathological and biological presentations, treatments and outcomes of sBBC in the prospective CANTO cohort. Methods: We reviewed and included patients (pts) diagnosed with sBBC in CANTO, a French prospective cohort study which enrolled 12012 women with localized invasive breast cancer. Data on clinical and pathological patterns, locoregional and systemic treatments were collected. Pts characteristics were compared with those of patients with unilateral cancers. Survival endpoints were event free survival (EFS) and overall survival (OS). Results: Of the 11341 analyzable pts of the cohort, 259 had sBBC (2.3%). Median age was 60.4y, vs 56.4y in pts with unilateral BC (p<.0001). Of those, 30.9% (79 pts) had a first-degree family history of breast cancer, vs 22.2% in pts with unilateral BC (p=.001). However, the proportion of BRCA mutations was similar in both groups (7.8% out of 90 tested pts vs 10% out of 2592 tested pts, p=.48). Median body mass index was slightly higher in the sBBC pts (25.7 vs 24.8, p=.003). Concordant bilateral stage I and stage II disease was observed in 32% and 13.7% of sBBC pts, respectively. Discordant stage I/II, II/III and I/III disease was observed in 36.3%, 7.8% and 5.5% of pts, respectively. Conversely, pathological subtypes were predominantly concordant: 75.6% of pts had bilateral carcinoma of non-specific type (NST) while 10.5% had bilateral invasive lobular carcinoma. Bilateral ER+ RP+/HER2-, HER2 overexpressed/amplified and triple negative subtypes were identified in 77.4%, 2.8% and 1.6% of pts, respectively. Molecular subtype was discordant in 18.2% of cases. Tumor grade was concordant in 66.9% of pts (grade 2 or 3: 58.4%), while Ki67 was ≤30% in 80.5% of pts. Locoregional and systemic treatments were tailored to stage and pathological subtype of each side. Overall, 22.2% of pts underwent a bilateral mastectomy, 73.6% had bilateral radiotherapy and 64.7% received neoadjuvant and/or adjuvant chemotherapy. After a median follow-up of 60 months, median EFS and OS were not reached: OS and EFS at 5y were approximately 90% and 80%, respectively, regardless of discordance in stage, molecular subtype, or grade. Furthermore, EFS and OS were identical whether patients had bilateral or unilateral BC. Conclusions: Women with sBBC were more likely to be overweight and older, and to have a family history of breast cancer than pts with unilateral BC. However, there was no evidence of a higher frequency of genetic predisposition. Approximately half of sBBC pts had discordant stages at diagnosis, in contrast to the majority of cases, which exhibited similar pathological and biological presentations. It can be observed that the locoregional and systemic treatments were adapted to the stage and presentation of the disease. It is of note that the prognosis was not influenced by stage or pathological discordance, or bilaterality. Citation Format: Augusta d'Huy, Julie Blanc, Anne-Laure Martin, Dominique Delmas, Jean Zeghondy, Laurence Vanlemmens, Courèche Kaderbhai, Anne Kieffer, Baptiste Sauterey, Olivier Tredan, Christelle Levy, Inès Vas-Luis, Aurélie Bertaut, Paul Cottu. Characteristics, treatments and outcomes of localized synchronous bilateral breast cancers in the CANTO French prospective cohort study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-12-18.

PurposeA phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m(2) and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC).MethodsIn phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m(2)), 5-fluorouracil (2400 mg/m(2) for 46 h), oxaliplatin (85 mg/m(2)) and irinotecan (70 mg/m(2) administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity.Results32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%).ConclusionThe combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials.Clinical trial registrationNCT03795311 (clinicaltrials.gov).

BackgroundSarcomas are rare cancer with a heterogeneous group of tumors. They affect both genders across all age groups and present significant heterogeneity, with more than 70 histological subtypes. Despite tailored treatments, the high metastatic potential of sarcomas remains a major factor in poor patient survival, as metastasis is often the leading cause of death. Currently, metastatic risk assessment relies mainly on histological grading; yet, this method has limitations due to the disease’s heterogeneity. Advances in genomic and transcriptomic research have identified potential molecular signatures, but these approaches lack reproducibility and prognostic reliability. Therefore, new biomarkers are essential for improving risk prediction and therapy adaptation. Recent studies highlight that sarcoma cells secrete extracellular vesicles, particularly small extracellular vesicles (sEVs). These nanovesicles, abundant in bodily fluids such as blood, urine, and saliva, play a crucial role in tumor development, growth, and metastasis. sEVs contain proteins and nucleic acids that mirror tumor characteristics. Given their presence in blood, sEVs offer a promising avenue for noninvasive molecular cancer analysis via liquid biopsy. Preliminary studies in Ewing sarcoma have shown substantial alterations in sEV-derived transcripts, underscoring their potential in tracking disease progression and treatment efficacy. ObjectiveThis study aims to investigate whether sEVs can serve as reliable biomarkers for monitoring sarcoma progression and predicting recurrence risk. MethodsThis prospective, multicentric pilot study will enroll adult patients diagnosed with localized or metastatic liposarcomas, leiomyosarcomas, or undifferentiated pleomorphic sarcomas at 3 French cancer centers. The study’s primary goal is to quantify sEVs and analyze their protein and RNA content in the blood of patients with localized or metastatic sarcomas before and after the treatment. sEVs will be isolated from plasma samples, and protein and microRNA concentration will be determined. Research will last, on average, 6 months for patients with localized sarcoma and 4 months for patients with metastatic sarcoma. ResultsWe expect to identify differences in exosome levels based on disease stage and observe correlations between exosome dynamics and treatment response. If confirmed, these findings could establish sEVs as noninvasive biomarkers for monitoring therapy effectiveness and disease progression in patients with sarcoma. ConclusionsThis study could establish a novel, noninvasive biomarker for sarcoma prognosis and treatment monitoring. If successful, a nationwide study will be launched to confirm findings in a larger patient cohort, potentially revolutionizing sarcoma management and improving patient outcomes. Trial RegistrationClinicalTrials.gov NCT03800121; https://clinicaltrials.gov/ct2/show/study/NCT03800121 International Registered Report Identifier (IRRID)DERR1-10.2196/63718

Background: In HER2-positive (HER2+) metastatic breast cancer (MBC), the clinical presentation at metastatic diagnosis (dg), de novo (dnMBC) or recurrent (rMBC), is an independent prognostic factor. In contemporary clinical trials, the proportion of patients (pts) with dnMBC is high, likely due to improvements in the efficacy of (neo)adjuvant therapy. ESME-MBC, a national cohort of real-world data, recruiting pts consecutively treated for MBC in all comprehensive cancer centers in France since 2008, allows capturing of this evolution over time. Methods: We selected pts with HER2+ (immunohistochemistry, IHC 3+ or ISH amplified) MBC diagnosed between 2008 and 2022, excluding pts whose hormone receptor (HR) and HER2 status were unknown and those who did not receive systemic treatment for MBC. We compared clinicopathologic characteristics based on presentation at metastatic dg (dnMBC i.e. metastasis found within 6 months from initial diagnosis, or rMBC). We evaluated the trends in presentation according to year of MBC dg (YOD) using a Cochran-Armitage test, and studied factors associated with first-line progression-free survival (PFS1) and overall survival (OS) using multivariable Cox models. Results: Among the 35,687 pts in the ESME MBC cohort, 5,573 pts were treated for HER2+ MBC, including 2,800 (50.2%) with rMBC and 2,773 (49.8%) with dnMBC. Most pts were women (99.4%) with a median age of 57 years (range, 19-97). Compared with rMBC pts, dnMBC pts had significantly more often a premenopausal status (41.6% vs 35.9%, p <0.0001), have a BMI ≥30 (23.5% vs 17.8%; p <0.0001) and have ductal tumors (86.8% vs 78.8%; p <0.0001). In dnMBC pts compared with rMBC pts, there were more visceral involvement in absence of central nervous system (CNS) disease (54.1% vs 42.6%; p <0.0001), and less CNS involvement (4.7% vs 16.9%; p <0.0001), respectively. HR-positive status was similar in both categories (dnMBC vs rMBC, 60.5% vs 59.7%, p= 0.54) while HER2 score 3+ on IHC was more frequent in dnMBC (86.8% vs 82.5%, p <0.0001). Types of therapy by dnMBC and rMBC differed: first-line anti-HER2 treatment + chemotherapy +/- endocrine therapy (ET), anti-HER2 treatment + ET, anti-HER2 treatment alone or no anti-HER2 treatment in 88.4% and 66.6%, 3.2% and 6.6%, 1.6% and 7.6%, and 6.8% and 19.1% of pts, respectively. The proportion of rMBC significantly decreased from 63.5% in 2008 to 32.9% in 2022 (Cochran–Armitage test; p < 0.0001), whereas the proportion of HR+ tumors significantly increased from 53.2% in 2008 to 68.3% in 2022 (Cochran–Armitage test; p < 0.0001) both in dnMBC (50.0% to 67.0%) and rMBC (55.0% to 70.9%) pts from 2008 to 2022 (Cochran–Armitage test; p=0.0197 and 0.0008, respectively). With a median follow-up of 82.8 months (mo) (95%CI: 79.7-84.6), the median OS of dnMBC vs rMBC pts were 72.5 mo (95%CI: 66.4-77.3) vs 43.8 mo (95%CI: 41.6-46.4) and the median PFS1 were 18.9 mo (95%CI: 17.7-20.3) vs 9.4 mo (95%CI: 8.9-9.9). In the multivariable analysis, dnMBC was associated with better OS (adjusted hazard ratio (aHR): 0.65 (95%CI: 0.61-0.70); p < 0.001) and PFS1 (aHR: 0.64 (95% CI: 0.60-0.68); p < 0.001). In both categories of pts, HR- status, older age at metastatic diagnosis, presence of CNS disease, and multiple metastases were independently associated with poorer OS and PFS1. HER2 3+ status was an independent favorable factor for PFS1 in both dnMBC and rMBC pts, and for OS in dnMBC pts only. Conclusion: Between 2008 and 2022, in a large national cohort of pts with HER2+ MBC, we observed an epidemiological shift from a majority of rMBC pts to a vast majority of dnMBC pts, along with an increase in the proportion of HR+ pts among those with HER2+ cancer. Patients with dnMBC experienced significantly longer PFS1 and OS than those with rMBC. Attention to dnMBC vs rMBC enrollment in studies of HER2+ MBC is needed in the design and contextualization of study results. Citation Format: Thomas Grinda, Amélie Lusque, Stefania Morganti, David Pasquier, Aurélie Bertaut, Thierry Petit, Thomas Bachelot, Monica Arnedos, Fanny Le Du, Vincent Massard, Anthony Gonçalves, Caroline Bailleux, Jean-Sebastien Frenel, Paul Cottu, Christelle Levy, Aude-Marie Savoye, Nathalie Olympios, Marie-Ange Mouret-Reynier, Harold J. Burstein, Heather A. Pearsons, Lise Bosquet, Thomas Filleron, Suzette Delaloge, William Jacot, Nancy U. Lin. Trends in Presentation of HER2+ Breast Cancer: A Retrospective study of De Novo Versus Recurrent Metastatic Breast Cancer (MBC) in the Real-World French National ESME Cohort (2008-2022) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-08-03.

INTRODUCTION/BACKGROUND:Breast cancer affects over 61,000 women annually in France. While only 5-10% of breast cancers are hereditary, BRCA1/2 mutations significantly increase the lifetime risk of breast and ovarian cancer, with cumulative invasive breast cancer risks of 72% (BRCA1) and 69% (BRCA2) by age 80. Surgical management in this population is crucial, as it directly impacts quality of life (QoL). However, prospective comparative data on surgical strategies are lacking. MATERIALS AND METHODS:This prospective study analyzed data from the CANTO cohort to assess the impact of different surgical approaches on QoL in BRCA1/2 mutation carriers diagnosed with invasive breast cancer. Four surgical options were compared: breastconserving surgery (BCS), mastectomy, immediate breast reconstruction (IBR), and delayed breast reconstruction (DBR). Patient-reported outcomes were evaluated over time, focusing on body image, future perspective, sexual functioning, and physical symptoms. RESULTS:BCS and IBR were associated with better preservation of body image throughout follow-up. DBR significantly improved body image, future perspective, and sexual functioning beginning at the time of surgery. Breast and arm symptoms were overall moderate, but mastectomy resulted in increased arm symptoms, likely due to the higher rate of axillary lymphadenectomy. CONCLUSION:When feasible, BCS should be preferred for BRCA1/2 mutation carriers, as it best preserves QoL. For patients requiring mastectomy, IBR is a valuable option, while DBR offers long-term benefits in body image and psychosocial well-being. Psychological support and structured postsurgical rehabilitation are strongly recommended to alleviate symptoms and optimize patient quality of life.

In the era of therapeutic de-escalation, the opportunity to move from systematic axillary lymph node dissection (ALND) to sentinel lymph node biopsy in axillary node-positive breast cancer patients after neoadjuvant systemic therapy (NST) is currently considered. The purpose of this study was to identify FDG-PET parameters associated with axillary pathological complete response (pRAx) in the most proliferative tumor subtypes, eg Triple Negative (TN) and HER2-amplified. Patients with newly-diagnosed TN or HER2-amplified breast cancer, with pathologically-proven axillary node metastasis, no distant metastasis and indication of NST were prospectively included from September 2017 to December 2021. Sequential FDG-PET/CT scans were performed at baseline and after one cycle of NST. Metabolic parameters at baseline and their changes (Delta in

Background:Cancer-associated fibroblasts (CAFs) are a component of the tumor microenvironment, influencing tumor behavior and progression. This meta-analysis aims to describe the prognostic value of CAF biomarkers in colorectal cancer (CRC). Methods:A systematic search of the existing literature was performed in Medline and Embase on CAF immunohistochemical (IHC) biomarkers and their association with disease-free survival (DFS) and overall survival (OS). The selection of studies was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Population, Intervention, Comparator, Outcome criteria. The quality of the included articles was assessed using the Newcastle-Ottawa Scale. Results:A total of 3,535 records were identified, of which 84 were selected for the qualitative review and 59 (N = 15,396 patients) were included in the final meta-analysis. In general, CAF biomarker expression was associated with poor prognosis, with high heterogeneity among studies. Significant results for DFS were found for cluster of differentiation (CD) 163, matrix metalloproteinase 9 (MMP-9), and tenascin C. The following markers were significantly associated with OS: CD163, MMP-9, periostin, and vimentin. Conclusion:Several CAF IHC biomarkers, particularly CD163, MMP-9, periostin, and vimentin, significantly associated with prognosis in CRC, could be proposed as surrogates for the phenotypical characterization of the tumor microenvironment.

Background We aimed to generate a model of cancer-related fatigue (CRF) of clinical importance two years after diagnosis of breast cancer building on clinical and behavioral factors and integrating pre-treatment markers of systemic inflammation. Methods Women with stage I-III HR+/HER2- breast cancer were included from the multimodal, prospective CANTO cohort (NCT01993498). The primary outcome was global CRF of clinical importance (EORTC QLQ-C30≥40/100) two years after diagnosis (year-2). Secondary outcomes included physical, emotional, and cognitive CRF (EORTC QLQ-FA12). All pre-treatment candidate variables were assessed at diagnosis, including inflammatory markers (interleukin [IL]-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, interferon gamma, IL-1 receptor antagonist, TNF-α, and C-reactive protein), and were tested in multivariable logistic regression models implementing multiple imputation and validation by 100-fold bootstrap resampling. Results Among 1208 patients, 415 (34.4%) reported global CRF of clinical importance at year-2. High pre-treatment levels of IL-6 (Quartile 4 vs.1) were associated with global CRF at year-2 (adjusted Odds Ratio [aOR]: 2.06 [95% Confidence Interval 1.40-3.03]; p=0.0002; AUC=0.74). Patients with high pre-treatment IL-6 had unhealthier behaviors, including being frequently either overweight or obese (62.4%; mean BMI 28.0 [SD 6.3] Kg/m2) and physically inactive (53.5% did not meet WHO recommendations). Clinical and behavioral associations with CRF at year-2 included pre-treatment CRF (aOR vs no: 3.99 [2.81-5.66]), younger age (per 1-year decrement: 1.02 [1.01-1.03]), current smoking (vs never: 1.81 [1.26-2.58]), and worse insomnia or pain (per 10-unit increment: 1.08 [1.04-1.13], and 1.12 [1.04-1.21], respectively). Secondary analyses indicated additional associations of IL-2 (aOR per log-unit increment:1.32 [CI 1.03-1.70]) and IL-10 (0.73 [0.57-0.93]) with global CRF and of C-reactive protein (1.42 [1.13-1.78]) with cognitive CRF at year-2. Emotional distress was consistently associated with physical, emotional, and cognitive CRF. Conclusions This study proposes a bio-behavioral framework linking pre-treatment systemic inflammation with CRF of clinical importance two years later among a large prospective sample of survivors of breast cancer.