Organ at risk dose-volume metrics in a series of hypofractionated breast radiotherapy with integrated boost.

Dose and volume metrics to organs at risk are used for evaluation and optimization in radiotherapy planning. However, the numerous choices of metrics can be confusing. In a series of patients treated with hypofractionation and an integrated boost for breast cancer, we aim to determine if a parsimonious selection of representative metrics can be identified. The dosimetries of 42 patients receiving 42 Gy to the breast, with or without nodal irradiation, and 51 Gy integrated boost to tumor bed in 15 fractions were reviewed. For each organ-heart, lungs, and contralateral breast-cumulative dose-volume histograms were used to extract values for 3 basic metric classes: Two additional classes were considered: Pearson correlation coefficient R was calculated between pairs of values within each basic class and with the 2 additional classes for each organ. The interquartile ranges of correlations for D.yy, Vrel.xx, and Vabs.xx were as follows: The mean dose correlated with all basic classes for the heart and lungs, and with dose D.yy and volumes at Vrel.10-Vabs.10 for the contralateral breast. The standard deviation correlated with Vrel.xx and Vabs.xx for the heart and lungs (R ≥ 0.70). Among the D.yy, D.50 (median dose) correlated with the mean and standard deviation for all organs (R = 0.65-0.96). The mean, standard deviation, and median doses were the preeminent correlators. These statistics appear to be parsimonious representatives of doses to organs. Further studies with other radiotherapy series will be necessary to validate these observations.

Economic evaluation and budget-impact of accelerated partial breast irradiation (APBI) versus standard or hypofractionated whole breast irradiation (WBI) in postmenopausal women with early-stage breast cancer. Results from the French SHARE randomized trial.

PURPOSE: This economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. MATERIALS AND METHODS: We compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. RESULTS: At three years, the average cost per patient was €2,549 (±1,954) in the APBI arm and €4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million€ cost saving. CONCLUSION: APBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.

Pelvic insufficiency fractures after intensity modulated radiation therapy combined with chemotherapy for cervix carcinoma: Incidence and impact of bone mineral density.

Background and Purpose: The aim of this study was to evaluate the incidence and predictive factors of Pelvic Insufficiency Fractures (PIFs) occurring after Intensity Modulated Radiation Therapy (IMRT) combined with chemotherapy for locally advanced cervical cancer (CC). Material and methods: Medical records of patients receiving radio-chemotherapy with IMRT between 2010 and 2020 for advanced CC were reviewed. PIFs were detected during follow-up on pelvic Magnetic Resonance Imaging (MRI) or Computed Tomography (CT). The cumulative incidence rate of PIFs and its confidence interval were calculated at 2 and 5 years of follow-up. Pre-therapeutic Bone Mineral Density (BMD) (g/cm3) was evaluated on CT simulation for sacrum and the fourth lumbar (L4) vertebrae. Sacrum dosimetric parameters (V30Gy, V40Gy, D50%, Dmean) were analyzed. Results: 136 patients were included. The median follow-up was 4.4 years. Median dose of D50% and V40Gy sacrum were 35.2 Gy (20.6-46.4) and 32.2% (7.2-73.4) respectively. The 2-year and 5-year cumulative incidence rates were 15.7% (95% CI: 9.88-22.71) and 22% (95% CI: 14.58-30.45) respectively. Median time interval between RT completion and PIFs' detection was 11.5 months (IQR: 7.4-22.3). Univariate analysis showed that older age (p < 0.01), postmenopausal status at baseline (p < 0.01), and lower sacral and spinal BMD at baseline (respectively p < 0.001 and p < 0.01) were significantly associated to all sites of PIFs, and lower sacral BMD with sacral fractures (p < 0.001). Conclusion: Post-IMRT PIFs were detected in 18.4% of patients with locally advanced CC. Individual predisposing factors as older age, postmenopausal status, decreased bone density on the CT simulation were mainly predictive.

[Treatments for rare ovarian tumors: What's new?] / Avancées thérapeutiques dans la prise en charge des tumeurs rares malignes ovariennes.

Even if each rare ovarian tumor (ROT) has a low incidence, the sum of all these entities represents almost the half of all ovarian neoplasms. Thus, development of dedicated clinical trial emerged as a prerequisite to improve their managements. Owing to the spreading of dedicated institutional networks and (supra)national collaborations, the number of clinical trials has increased the past few years, with different types of trials; while some focused on specific molecular features, others assessed innovative molecules. Furthermore, relevant randomized clinical trials were designed as a mean to position new treatment options. Currently, innovative molecular-driven trials, based on master protocol trials are emerging and may shed light towards the improvement of personalized medicine regarding ROT.

Biomarkers Associated with Lymph Nodal Metastasis in Endometrioid Endometrial Carcinoma.

INTRODUCTION: Lymph node metastasis is determinant in the prognosis and treatment of endometrioid endometrial cancer (EEC) but the risk-benefit balance of surgical lymph node staging remains controversial. OBJECTIVE: Describe the pathways associated with lymph node metastases in EEC detected by whole RNA sequencing. METHODS: RNA-sequencing was performed on a retrospective series of 30 non-metastatic EEC. N+ and N- patients were matched for tumoral size, tumoral grade and myometrial invasion. RESULTS: Twenty-eight EECs were analyzable (16 N+ and 12 N-). Bioinformatics Unsupervised analysis revealed three patterns of expression, enriched in N+, mix of N+/N- and enriched in N-, respectively. The cluster with only N+ patient overexpressed extra cellular matrix, epithelial to mesenchymal and smooth muscle contraction pathways with respect to the N- profile. Differential expression analysis between N+ and N- was used to generate a 54-genes signature with an 87% accuracy. CONCLUSION: RNA-expression analysis provides a basis to develop a gene expression-based signature that could pre-operatively predict lymph node invasion.

Neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer: Safety and efficacy of reverse sequence compared to standard technique?

BACKGROUND: The reverse sequence of neoadjuvant chemotherapy, preoperative radiotherapy, mastectomy then immediate breast reconstruction is currently proposed for selected patients with locally advanced breast cancer. Few studies have compared it to the standard sequence of neoadjuvant chemotherapy, mastectomy and radiotherapy with or without differed reconstruction. Our study compares overall (OS) and recurrence-free (RFS) survivals of breast cancer patients treated with reverse sequence compared to the standard technique. METHODS: In this retrospective, single center study at a Comprehensive Cancer Center in France, patients were included if: female, age <65y, had received neoadjuvant chemotherapy, mastectomy and radiotherapy, and were M0. Outcomes for patients treated by reverse sequence (RS) are compared to those for patients treated by standard sequence (ST). Data was collected from medical records. RESULTS: From January 2009 to April 2018, 222 eligible patients were treated, 46 by RS and 176 by ST. Mean follow-up was 61.7 months. Five-year OS and RFS did not differ between groups. 5-yr OS: 88.4% 95%CI [74.1-95.0] for RS and 81.5% 95%CI [74.0-87.0] for ST (P = 0.4412); 5-yr RFS: 78.3% 95%CI [61.9-88.3] for RS and 70.1% 95%CI [62.2-76.7] for ST (P = 0.3003). Overall treatment time was significantly shorter in the RS group, and the rate of severe surgical complications did not differ between groups. CONCLUSIONS: For locally advanced breast cancer patients with an indication for radiation therapy the reverse sequence offers similar safety and efficacy results as the standard treatment while allowing immediate breast reconstruction. However, careful patient selection is necessary, particularly with regard to preoperative lymph node invasion.

Treatment and outcomes in patients with central nervous system metastases from breast cancer in the real-life ESME MBC cohort.

AIM: The aims of the present study were to describe treatment patterns and survival outcomes in patients with central nervous system metastases (CNSM) selected among metastatic breast cancer (MBC) patients included in a retrospective study from the Epidemiological Strategy and Medical Economics (ESME) MBC cohort. METHODS: Neurological progression-free survival (NPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Significant contributors to NPFS were determined using a multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 42.8 months, of 16 701 patients included in the ESME MBC database, CNSM were diagnosed in 24.6% of patients. The most frequent treatments after diagnosis of CNSM were whole-brain radiotherapy (WBRT) (45.2%) and systemic treatment (59.3%). Median OS and NPFS were 7.9 months (95% CI: 7.2-8.4) and 5.5 months (95% CI: 5.2-5.8), respectively. In multivariate analysis, age >70 years (vs <50 years; HR = 1.40; 95% CI: 1.24-1.57), triple-negative tumours (vs HER2-/HR+; HR = 1.87; 95% CI: 1.71-2.06), HER2+/HR-tumours (vs HER2-/HR+; HR = 1.14; 95% CI: 1.02-1.27), ≥3 metastatic sites (vs < 3; HR = 1.32; 95% CI: 1.21-1.43) and ≥3 previous treatment lines (vs < 3; HR = 1.75; 95% CI: 1.56-1.96) were detrimental for NPFS. A time interval between selection and CNSM diagnosis superior to 18 months (vs <9 months; HR = 0.88; 95% CI: 0.78-0.98) was associated with longer NPFS. CONCLUSIONS: This study describes current treatment patterns of MBC patients in a "real life" setting. Despite advances in stereotactic radiation therapy, most of the patients still received WBRT. More research is warranted to identify patient subsets for tailored treatment strategies.

Use of FDG-PET to guide dose prescription heterogeneity in stereotactic body radiation therapy for lung cancers with volumetric modulated arc therapy: a feasibility study.

BACKGROUND: The aim of this study was to assess if FDG-PET could guide dose prescription heterogeneity and decrease arbitrary location of hotspots in SBRT. METHODS: For three patients with stage I lung cancer, a CT-simulation and a FDG-PET were registered to define respectively the PTVCT and the biological target volume (BTV). Two plans involving volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) were calculated. The first plan delivered 4 × 12 Gy within the PTV(CT) and the second plan, with SIB, 4 × 12 Gy and 13.8 Gy (115% of the prescribed dose) within the PTV(CT) and the BTV respectively. The Dmax-PTV(CT) had to be inferior to 60 Gy (125% of the prescribed dose). Plans were evaluated through the D95%, D99% and Dmax-PTV(CT), the D2 cm, the R50% and R100% and the dice similarity coefficient (DSC) between the isodose 115% and BTV. DSC allows verifying the location of the 115% isodose (ideal value = 1). RESULTS: The mean PTV(CT) and BTV were 36.7 (±12.5) and 6.5 (±2.2) cm3 respectively. Both plans led to similar target coverage, same doses to the OARs and equivalent fall-off of the dose outside the PTV(CT). On the other hand, the location of hotspots, evaluated through the DSC, was improved for the SIB plans with a mean DSC of 0.31 and 0.45 for the first and the second plans respectively. CONCLUSIONS: Use of PET to decrease arbitrary location of hotspots is feasible with VMAT and SIB for lung cancer.

Pulsed-dose-rate brachytherapy for uterine cervix carcinoma: 10 years of experience with 226 patients at a single institution.

PURPOSE: To analyze the long-term results of pulsed-dose-rate (PDR) brachytherapy (BT) in cervical carcinoma patients treated at a single institution. METHODS AND MATERIALS: All patients with histopathologically proven Stages IB-IVA cervical carcinoma, treated at our institution with PDR intracavitary BT between April 1996 and November 2007, were included in this retrospective analysis. All patients underwent primary pelvic radiotherapy (45 Gy) with concomitant chemotherapy from 1999 and PDR intracavitary BT (16 Gy to the clinical target volume), followed by hysterectomy in 124 patients. RESULTS: Two hundred twenty-six patients received radiochemotherapy and BT. With a median followup of 81.7 months, the 5-year overall survival, disease-free survival, and local control (LC) were 67%, 65%, and 80%, respectively; seventy-seven relapses were observed including 38 local recurrences. Multivariate analysis showed earlier FIGO (International Federation of Gynecology and Obstetrics) stage and absence of nodal involvement to be associated with better overall and disease-free survivals. Use of three-dimensional image-guided BT planning and absence of nodal involvement were associated with better LC in the multivariate analysis. Late Grade ≥3 toxicity was experienced by 22 patients (9.7%), consisting of gastrointestinal toxicity for 6 patients, urinary tract for 10 patients, lymphatics for 3 patients, and vaginal toxicity for 3 patients. CONCLUSIONS: This study demonstrates excellent LC rates with few late side effects with PDR BT for cervix carcinoma, similar to those reported in the literature with historical standard low-dose-rate BT.

[Advanced endometrial carcinoma: primary debulking surgery or neoadjuvant chemotherapy?]. / Cancers de l'endomètre de stades avancés : chirurgie première ou chimiothérapie néoadjuvante ?

Endometrial cancers with peritoneal spread are stage IVB of FIGO classification. Their pattern is similar to that of ovarian cancer. Optimal debulking surgery and chemotherapy are predictor of better overall and disease free survival. Despite the poor outcome, there is a need for new treatment options. Recommended management for this group of patients should consist of surgical cytoreduction followed by chemotherapy. There may be a role for neoadjuvant chemotherapy followed by interval surgery in selected subgroups of patients.