Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Background and purpose: Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. Materials and methods: We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Results: Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). Conclusion: HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

The Influence of Surgical Complexity and Center Experience on Postoperative Morbidity After Minimally Invasive Surgery in Gynecologic Oncology: Lessons Learned from the ROBOGYN-1004 Trial.

BACKGROUND: This study was a secondary analysis of the ROBOGYN-1004 trial conducted between 2010 and 2015. The study aimed to identify factors that affect postoperative morbidity after either robot-assisted laparoscopy (RL) or conventional laparoscopy (CL) in gynecologic oncology. METHODS: The study used two-level logistic regression analyses to evaluate the prognostic and predictive value of patient, surgery, and center characteristics in predicting severe postoperative morbidity 6 months after surgery. RESULTS: This analysis included 368 patients. Severe morbidity occurred in 49 (28 %) of 176 patients who underwent RL versus 41 (21 %) of 192 patients who underwent CL (p = 0.15). In the multivariate analysis, after adjustment for the treatment group (RL vs CL), the risk of severe morbidity increased significantly for patients who had poorer performance status, with an odds ratio (OR) of 1.62 for the 1-point difference in the WHO performance score (95 % CI 1.06-2.47; p = 0.027) and according to the type of surgery (p < 0.001). A focus on complex surgical acts showed significant more morbidity in the RL group than in the CL group at the less experienced centers (OR, 3.31; 95 % CI 1.0-11; p = 0.05) compared with no impact at the experienced centers (OR, 0.87; 95 % CI 0.38-1.99; p = 0.75). CONCLUSION: The findings suggest that the center's experience may have an impact on the risk of morbidity for patients undergoing complex robot-assisted surgical procedures.

Stereotactic body radiotherapy as a viable treatment on extracranial oligometastases in melanoma patients: a retrospective multicentric study.

Introduction: Stereotactic radiotherapy (SBRT) potentially has a role in the management of oligometastatic melanoma. However, literature with data specific to this management is very limited. The objectives of this study were to evaluate the time to local control (LC) of extra-cranial melanoma metastases after SBRT treatment and to help establish if SBRT is a useful therapy for oligometastatic melanoma. Methods: A retrospective study was conducted with data collected from two referral centers in France between 2007 and 2020. The oligometastatic status of patients was reported based on the latest recommendations with a maximum of three lesions prior to treatment. Results: A total of 69 patients receiving SBRT for 88 oligometastatic melanoma metastases were included. The median follow-up time was 42.6 months. Most patients were treated for metachronous oligometastatic lesions. Occurrence of oligoprogression, oligorecurrence, and oligopersistence was reported in 42.0%, 39.1%, and 17.4% of cases, respectively. Treated lesions were mostly pulmonary (40.6%), followed by lymph node (34.8%) and hepatic sites (24.6%). Progression-free survival at 1, 2, and 3 years were 47.0% (35-59), 27.0% (16-39), and 25.0% (15.0-37.0), respectively. Time to LC rates at 1, 2, and 3 years were 94.2% (87.0-98.1), 90.3% (81.3-96.1), and 90.3% (81.3-96.1), respectively. Overall survival at 1, 2, and 3 years were 87% (76.0-93.0), 74.0% (76.0-93.0), and 61.0% (47.0-73.0), respectively. Only 17.4% of patients experienced acute, grade 1 or grade 2 toxicities with no reports of grade 3 or higher toxicities. Conclusion: SBRT demonstrated efficacy in managing melanoma patients with extracranial oligometastases and showed an overall low toxicity profile. Future randomized studies are needed to establish the role of SBRT in therapeutic approaches for patients with oligometastatic melanoma.

Consore: A Powerful Federated Data Mining Tool Driving a French Research Network to Accelerate Cancer Research.

BACKGROUND: Real-world data (RWD) related to the health status and care of cancer patients reflect the ongoing medical practice, and their analysis yields essential real-world evidence. Advanced information technologies are vital for their collection, qualification, and reuse in research projects. METHODS: UNICANCER, the French federation of comprehensive cancer centres, has innovated a unique research network: Consore. This potent federated tool enables the analysis of data from millions of cancer patients across eleven French hospitals. RESULTS: Currently operational within eleven French cancer centres, Consore employs natural language processing to structure the therapeutic management data of approximately 1.3 million cancer patients. These data originate from their electronic medical records, encompassing about 65 million medical records. Thanks to the structured data, which are harmonized within a common data model, and its federated search tool, Consore can create patient cohorts based on patient or tumor characteristics, and treatment modalities. This ability to derive larger cohorts is particularly attractive when studying rare cancers. CONCLUSIONS: Consore serves as a tremendous data mining instrument that propels French cancer centres into the big data era. With its federated technical architecture and unique shared data model, Consore facilitates compliance with regulations and acceleration of cancer research projects.

Incidence and characteristics of chronic postsurgical pain at 6 months after total mastectomy under pectoserratus and interpectoral plane block combined with general anesthesia: a prospective cohort study.

INTRODUCTION: Chronic postsurgical pain (CPSP) occurs in 20%-30% of patients who undergo total mastectomy (TM) performed under general anesthesia alone and significantly affects the quality of life. Pectoserratus and interpectoral plane block have been reportedly combined with general anesthesia to control immediate postoperative pain after TM. Our prospective cohort study aimed to evaluate the incidence of CPSP after TM when pectoserratus and interpectoral plane block were combined with general anesthesia. METHODS: We recruited adult women scheduled to undergo TM for breast cancer. Patients planned for TM with flap surgery, those who underwent breast surgery in the past 5 years, or those presenting with residual chronic pain after prior breast surgery were excluded. After general anesthesia induction, an anesthesiologist performed pectoserratus and interpectoral plane block with a ropivacaine (3.75 mg/mL) and clonidine (3.75 µg/mL) in 40 mL of 0.9% sodium chloride. The primary endpoint was the occurrence of CPSP-defined as pain with a Numeric Rating Scale Score of ≥3, either at the breast surgical site and/or at axilla, without other identifiable causes-evaluated during a pain medicine consultation at 6 months post TM. RESULTS: Overall, 43/164 study participants had CPSP (26.2%; 95% CI: 19.7 to 33.6); of these, 23 had neuropathic type of pain (53.5%), 19 had nociceptive (44.2%), and 1 had mixed (2.3%) type of pain. CONCLUSION: Although postoperative analgesia has significantly improved in the last decade, there is still need for improvement to reduce CPSP after oncologic breast surgery. TRIAL REGISTRATION NUMBER: NCT03023007.

A systematic review of recent phase-II trials in refractory or recurrent osteosarcoma: Can we inform future trial design?

BACKGROUND/OBJECTIVE: To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis. METHODS: A systematic review of trials registered on trial registries between 01/01/2017-14/02/2022. Comparison of 98 trials identified between 2003 and 2016. Publication search/analysis for both periods, last update on 01/12/2022. RESULTS: Between 2017 and 2022, 71 phase-II trials met our selection criteria (19 osteosarcoma-specific trials, 14 solid tumor trials with and 38 trials without an osteosarcoma-specific stratum). The trial number increased over time: 13.9 versus 7 trials/year (p = 0.06). Monotherapy remained the predominant treatment (62% vs. 62%, p = 1). Targeted therapies were increasingly evaluated (66% vs. 41%, P = 0.001). Heterogeneity persisted in the trial characteristics. The inclusion criteria were measurable disease (75%), evaluable disease (14%), and surgical remission (11%). 82% of the trials included pediatric or adolescent patients. Biomarker-driven trials accounted for 25% of the total trials. The survival endpoint use (rather than response) slightly increased (40% versus 31%), but the study H1/H0 hypotheses remained heterogeneous. Single-arm designs predominated over multiarm trials (n = 7). Available efficacy data on 1361 osteosarcoma patients in 58 trials remained disappointing, even though 21% of these trials were considered positive, predominantly those evaluating multi-targeted kinase inhibitors. CONCLUSION: Despite observed changes in trial design and an increased number of trials investigating new therapies, high heterogeneity remained with respect to patient selection, study design, primary endpoints, and statistical hypotheses in recently registered phase II trials for osteosarcoma. Continued optimization of trial design informed by a deeper biological understanding should strengthen the development of new therapies.

Impact of histamine-2 antagonist shortage on the incidence of hypersensitivity reactions to paclitaxel: a reconsideration of premedication protocols in France (PACLIREACT Study).

PURPOSE: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. METHODS: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. RESULTS: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). CONCLUSION: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A.

Diagnostic Value of the Texture Analysis Parameters of Retroperitoneal Residual Masses on Computed Tomographic Scan after Chemotherapy in Non-Seminomatous Germ Cell Tumors.

After chemotherapy, patients with non-seminomatous germ cell tumors (NSGCTs) with residual masses >1 cm on computed tomography (CT) undergo surgery. However, in approximately 50% of cases, these masses only consist of necrosis/fibrosis. We aimed to develop a radiomics score to predict the malignant character of residual masses to avoid surgical overtreatment. Patients with NSGCTs who underwent surgery for residual masses between September 2007 and July 2020 were retrospectively identified from a unicenter database. Residual masses were delineated on post-chemotherapy contrast-enhanced CT scans. Tumor textures were obtained using the free software LifeX. We constructed a radiomics score using a penalized logistic regression model in a training dataset, and evaluated its performance on a test dataset. We included 76 patients, with 149 residual masses; 97 masses were malignant (65%). In the training dataset (n = 99 residual masses), the best model (ELASTIC-NET) led to a radiomics score based on eight texture features. In the test dataset, the area under the curve (AUC), sensibility, and specificity of this model were respectively estimated at 0.82 (95%CI, 0.69-0.95), 90.6% (75.0-98.0), and 61.1% (35.7-82.7). Our radiomics score may help in the prediction of the malignant nature of residual post-chemotherapy masses in NSGCTs before surgery, and thus limit overtreatment. However, these results are insufficient to simply select patients for surgery.

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study.

BACKGROUND: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. OBJECTIVE: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. RESULTS AND LIMITATIONS: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). CONCLUSIONS: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. PATIENT SUMMARY: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.

Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy.

BACKGROUND: The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. PATIENTS AND METHODS: This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. RESULTS: Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. CONCLUSION: In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence.

Improving outcomes of childhood and young adult non-Hodgkin lymphoma: 25 years of research and collaboration within the framework of the European Intergroup for Childhood Non-Hodgkin Lymphoma.

The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.

Results of a 20 Year Retrospective Analysis of Early-Stage Cervical Cancer: Should 3 cm Be Considered the New Ariadne's Thread in Early Cervical Cancer Treatment?

(1) This study aims to evaluate the overall survival (OS) and recurrence-free survivals (RFS) and assess disease recurrence of early-stage cervical cancer (ESCC) patients treated with minimally invasive surgery (MIS). (2) This single-center retrospective analysis was performed between January 1999 and December 2018, including all patients managed with MIS for ESCC. (3) All 239 patients included in the study underwent pelvic lymphadenectomy followed by radical hysterectomy without the use of an intrauterine manipulator. Preoperative brachytherapy was performed in 125 patients with tumors measuring 2 to 4 cm. The 5-year OS and RFS rates were 92% and 86.9%, respectively. Multivariate analysis found two significant factors associated with recurrence: previous conization with HR = 0.21, p = 0.01, and tumor size > 3 cm with HR = 2.26, p = 0.031. Out of the 33 cases of disease recurrence, we witnessed 22 disease-related deaths. Recurrence rates were 7.5%, 12.9%, and 24.1% for tumors measuring ≤ 2 cm, 2 to 3 cm, and > 3 cm, respectively. Tumors ≤ 2 cm were mostly associated with local recurrences. Tumors > 2 cm were frequently associated with common iliac or presacral lymph node recurrences. (4) MIS may still be considered for tumors ≤ 2 cm subject to first conization followed by surgery with the Schautheim procedure and extended pelvic lymphadenectomy. Due to the increased rate of recurrence, a more aggressive approach might be considered for tumors > 3 cm.

Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database.

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

Pain in desmoid-type fibromatosis: Prevalence, determinants and prognosis value.

The aim of this study is to evaluate the prevalence, determinants and prognostic value of pain at diagnosis in patients with desmoid-type fibromatosis (DF). We selected patients from the ALTITUDES cohort (NCT02867033), managed by surgery, active surveillance or systemic treatments, with pain assessment at diagnosis. Patients were invited to fill QLQ-C30 questionnaire and Hospital Anxiety Depression Scale. Determinants were identified using logistic models. Prognostic value on event-free survival (EFS) was evaluated using the Cox model. Overall, 382 patients were included in the current study (median age: 40.2 years; 117 men). The prevalence of pain was 36%, without significant difference according to first-line treatment (P = .18). In the multivariate analysis, pain was significantly associated with tumor size >50 mm (P = .013) and tumor site (P < .001); pain was more frequent in the neck and shoulder locations (odds ratio: 3.05 [1.27-7.29]). Pain at baseline was significantly associated with poor quality of life (P < .001), depression (P = .02), lower performance status (P = .03) and functional impairment (P = .001); we also observed a nonsignificant association with anxiety (P = .10). In the univariate analysis, baseline pain was associated with poor EFS; the 3-year EFS was 54% in patients with pain compared to 72% in those without pain. After adjustment for sex, age, size and line of treatment, pain was still associated with poor EFS (hazard ratio: 1.82 [1.23-2.68], P = .003). One third of recently diagnosed patients with DF experienced pain, especially those with larger tumors and neck/shoulder locations. Pain was associated with unfavorable EFS after adjustment for the confounders.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Stage I Clear Cell and Serous Uterine Carcinoma: What Is the Right Adjuvant Therapy?

This single-center study aimed to retrospectively evaluate the survival outcomes of patients with FIGO stage I clear cell and serous uterine carcinoma according to the type of adjuvant treatment received. The data were collected between 2003 and 2020 and only patients with stage I clear cell or serous uterine carcinoma treated with primary surgery were included. These were classified into three groups: No treatment or brachytherapy only (G1), radiotherapy +/- brachytherapy (G2), chemotherapy +/- radiotherapy +/- brachytherapy (G3). In total, we included 52 patients: 18 patients in G1, 16 in G2, and 18 in G3. Patients in the G3 group presented with poorer prognostic factors: 83.3% had serous histology, 27.8% LVSI, and 27.8% were FIGO stage IB. Patients treated with adjuvant radiotherapy showed an improved 5-year overall survival (OS) (p = 0.02) and a trend towards an enhanced 5-year progression-free survival (PFS) (p = 0.056). In contrast, OS (p = 0.97) and PFS (p = 0.84) in the chemotherapy group with poorer prognostic factors, were similar with increased toxicity (83.3%). Radiotherapy is associated with improved 5-year OS and tends to improve 5-year PFS in women with stage I clear cell and serous uterine carcinoma. Additional chemotherapy should be cautiously considered in serous carcinoma cases presenting poor histological prognostic factors.

Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Late toxicity comparison of alkylating-based maintenance regimen with cyclophosphamide (VAC) vs ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro-EWING99-R1 in France.

In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2 , ifosfamide = 59.4 g/m2 ) and 88 in VAI (ifosfamide = 97.1 g/m2 ). With a median follow-up of 10 years (range = 5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, P = .63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%-7.6%) and 34.8% (95% CI = 26.8%-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P = .02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P < .01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro-EWING99-R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE-VAC or VDC/IE (vincristine-doxorubicin-cyclophoshamide/ifosfamide-etoposide).

Ergonomic Assessment of the Surgeon's Physical Workload During Robot-Assisted Versus Standard Laparoscopy in a French Multicenter Randomized Trial (ROBOGYN-1004 Trial).

BACKGROUND: Standard laparoscopy (SL) is responsible for musculoskeletal disorders in surgeons because of poor ergonomic positions, which could be reduced by robot-assisted laparoscopy (RAL) owing to the surgeons' seated position. One of the aims of the ROBOGYN-1004 study (NCT01247779) was to evaluate surgeons' workloads during real-time procedures of gynecological oncological surgery. METHODS: Patients with gynecological cancer eligible for minimally invasive surgery were recruited from 13 French centers between December 2010 and December 2015. Physical workload was evaluated using the Borg scale every hour over the surgery duration and the perception of workload evaluated using NASA-TLX at the end of surgery. RESULTS: A total of 369 patients were recruited, of whom 176 underwent RAL and 193 underwent SL (per-protocol analysis). Posture during SL was significantly more challenging for all body parts except the back. There was an increase in discomfort over time (up to 4 h) for the hands and arms, neck, and legs in SL compared with RAL. Perceived physical activity and abilities were rated higher in SL than in RAL (p < 0.01), whereas perceived personal performance was higher in SL (p < 0.01). Perceived physical effort during surgery was lower in RAL than in SL. CONCLUSIONS: RAL improves the perception of physical workload. Compared with SL, the perceived effort is lower in RAL regardless of the complexity of the surgery.