Cerenkov free micro-dosimetry in small-field radiation therapy technique.

Objective. Optical fiber-based scintillating dosimetry is a recent promising technique owing to the miniature size dosimeter and quality measurement in modern radiation therapy treatment. Despite several advantages, the major issue of using scintillating dosimeters is the Cerenkov effect and predominantly requires extra measurement corrections. Therefore, this work highlighted a novel micro-dosimetry technique to ensure Cerenkov-free measurement in radiation therapy treatment protocol by investigating several dosimetric characteristics.Approach.A micro-dosimetry technique was proposed with the performance evaluation of a novel infrared inorganic scintillator detector (IR-ISD). The detector essentially consists of a micro-scintillating head based on IR-emitting micro-clusters with a sensitive volume of 1.5 × 10-6mm3. The proposed system was evaluated under the 6 MV LINAC beam used in patient treatment. Overall measurements were performed using IBATMwater tank phantoms by following TRS-398 protocol for radiotherapy. Cerenkov measurements were performed for different small fields from 0.5 × 0.5 cm2to 10 × 10 cm2under LINAC. In addition, several dosimetric parameters such as percentage depth dose (PDD), high lateral resolution beam profiling, dose linearity, dose rate linearity, repeatability, reproducibility, and field output factor were investigated to realize the performance of the novel detector.Main results. This study highlighted a complete removal of the Cerenkov effect using a point-like miniature detector, especially for small field radiation therapy treatment. Measurements demonstrated that IR-ISD has acceptable behavior with dose rate variability (maximum standard deviation ∼0.18%) for the dose rate of 20-1000 cGy s-1. An entire linear response (R2= 1) was obtained for the dose delivered within the range of 4-1000 cGy, using a selected field size of 1 × 1 cm2. Perfect repeatability (max 0.06% variation from average) with day-to-day reproducibility (0.10% average variation) was observed. PDD profiles obtained in the water tank present almost identical behavior to the reference dosimeter with a build-up maximum depth dose at 1.5 cm. The small field of 0.5 × 0.5 cm2profiles have been characterized with a high lateral resolution of 100µm.Significance. Unlike recent plastic scintillation detector systems, the proposed micro-dosimetry system in this study requires no Cerenkov corrections and showed efficient performance for several dosimetric parameters. Therefore, it is expected that considering the detector correction factors, the IR-ISD system can be a suitable dose measurement tool, such as in small-field dose measurements, high and low gradient dose verification, and, by extension, in microbeam radiation and FLASH radiation therapy.

Neoadjuvant chemotherapy for breast cancer: Pathologic response rates but not tumor size, has an independent prognostic impact on survival.

AIM: We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. METHODS: From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). RESULTS: A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal-B Her2-negative and triple-negative (TN) subtypes, cN1 status, older age, and no-pCR had an independent negative prognostic value. Overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) were not significantly different for cT0-1 compared to cT2 stages. In Cox-model adjusted on in-breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in-breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2-positive tumors (HR = 11.706), as well as in Luminal-B Her2-negative tumors on MFS (HR = 2.223) and for Luminal-A on RFS (HR = 4.465) and MFS (HR = 4.185). CONCLUSION: Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (<2 cm), even in absence of clinically suspicious lymph nodes. Residual lymph node disease after NAC is the most powerful adverse prognostic factor.

Omission of Completion Axillary Lymph Node Dissection for Patients with Breast Cancer Treated by Upfront Mastectomy and Sentinel Node Isolated Tumor Cells or Micrometastases.

Omission of completion axillary lymph node dissection (cALND) in patients undergoing mastectomy with sentinel node (SN) isolated tumor cells (ITC) or micrometastases is debated due to potential under-treatment, with non-sentinel node (NSN) involvement detected in 7% to 18% of patients. This study evaluated the survival impact of cALND omission in a cohort of breast cancer (BC) patients treated by mastectomy with SN ITC or micrometastases. Among 554 early BC patients (391 pN1mi, 163 ITC), the NSN involvement rate was 13.2% (49/371). With a median follow-up of 66.46 months, multivariate analysis revealed significant associations between cALND omission and overall survival (OS, HR: 2.583, p = 0.043), disease-free survival (DFS, HR: 2.538, p = 0.008), and metastasis-free survival (MFS, HR: 2.756, p = 0.014). For Her2-positive or triple-negative patients, DFS was significantly affected by cALND omission (HR: 38.451, p = 0.030). In ER-positive Her2-negative BC, DFS, OS, recurrence-free survival (RFS), and MFS were significantly associated with cALND omission (DFS HR: 2.358, p = 0.043; OS HR: 3.317; RFS HR: 2.538; MFS HR: 2.756). For 161 patients aged ≤50 years with ER-positive/Her2-negative cancer, OS and breast cancer-specific survival (BCSS) were notably impacted by cALND omission (OS HR: 103.47, p = 0.004; BCSS HR: 50.874, p = 0.035). These findings suggest a potential negative prognostic impact of cALND omission in patients with SN micrometastases or ITC. Further randomized trials are needed.

Postoperative Outcomes of Pre-Pectoral Versus Sub-Pectoral Implant Immediate Breast Reconstruction.

INTRODUCTION: Immediate breast reconstruction (IBR) techniques are rapidly evolving. We compared the results from a single-center implant IBR cohort between subpectoral and prepectoral implants with and without a mesh. METHODS: We analyzed all complications and grade 2-3 complications, the implant loss rate, the surgery time, the length of stay (LOS), patient satisfaction, the interval time to adjuvant therapy and cost, with a comparison between subpectoral and prepectoral implant IBR. RESULTS: Subpectoral implant IBR was carried out in 529 mastectomies (62.0%) and prepectoral in 324, with a significant increase in prepectoral placement in recent years. Mesh was used in 176 prepectoral placements (54.3%). Any grade of complication was reported in 147 mastectomies (17.2%), with a significantly higher rate for prepectoral implant IBR (p = 0.036). Regression analysis showed that prepectoral implant was not significantly associated with any grade of complication or with grade 2-3 complications. Prepectoral implant IBR was associated with a significantly shorter operative time and lower LOS. Grade 2-3 complications were significantly associated with lower satisfaction. Higher costs were significantly associated with the subpectoral placement and mesh. A complication rate predictive score identified five groups with a significant increase in grade 2-3 complications. CONCLUSIONS: Prepectoral-M-IBR increased over time with no difference in complication rates compared to subpectoral-M-IBR. Prepectoral implant placement can be considered a safe technique.

Does Breast Surgery Type Alter Incidental Axillary Irradiation? A Dosimetric Analysis of the "Sentinel Envahi et Randomisation du Curage" SERC Trial.

BACKGROUND: An incidental axillary dose of adjuvant radiotherapy using tangential beams is usually given after breast-conserving surgery for breast cancer. The goal of this sub-study was to evaluate this incidental dose in the setting of post-mastectomy radiotherapy (PMRT) according to two different radiotherapy techniques. METHODS: Patients participating in a randomized SERC trial who received PMRT in a single center were included. We collected the incidental axillary dose delivered to the Berg level 1 using different dosimetric parameters and compared two techniques using Student's t-test: three-dimensional conformal radiotherapy (3D-CRT) and volumetric arc therapy (VMAT). RESULTS: We analyzed radiotherapy plans from 52 patients who received PMRT from 2012 to 2021. The mean dose delivered to the Berg level 1 was 37.2 Gy. It was significantly higher with VMAT than with 3D-CRT-43.6 Gy (SD = 3.1 Gy) versus 34.8 Gy (SD = 8.6 Gy) p < 0.001. Eighty-four percent of the Berg level 1 was covered by 40 Gy isodose in the VMAT group versus 55.5% in the 3D-CRT group p < 0.001. CONCLUSIONS: On the Berg level 1, PMRT gives a dose at least equivalent to the one given by post-breast-conserving surgery radiotherapy, making it possible to limit completion axillary lymph node dissections in select pN1a patients treated with a mastectomy. Modern radiotherapy techniques like VMAT tend to increase this incidental dose.

Triple-negative and Her2-positive breast cancer in women aged 70 and over: prognostic impact of age according to treatment.

Background: Elderly breast cancer (BC) patients have been underrepresented in clinical trials whereas ~60% of deaths from BC occur in women aged 70 years and older. Only limited data are available on the prognostic impact of age according to treatment, especially in the triple-negative (TN) and Her2-positive because of the lower frequency of these subtypes in elderly patients. We report herein the results of a multicenter retrospective study analyzing the prognostic impact of age according to treatment delivered in TN and Her2-positive BC patients of 70 years or older, including comparison by age groups. Methods: The medical records of 31,473 patients treated from January 1991 to December 2018 were retrieved from 13 French cancer centers for retrospective analysis. Our study population included all ≥70 patients with TN or Her2-positive BC treated by upfront surgery. Three age categories were determined: 70-74, 75-80, and > 80 years. Results: Of 528 patients included, 243 patients were 70-74 years old (46%), 172 were 75-80 years (32.6%) and 113 were >80 years (21.4%). Half the population (51.9%, 274 patients) were TN, 30.1% (159) Her2-positive/hormone receptors (HR)-positive, and, 18% (95) Her2-positive/endocrine receptors (ER)-negative BC. Advanced tumor stage was associated with older age but no other prognostic factors (tumor subtype, tumor grade, LVI). Adjuvant chemotherapy delivery was inversely proportional to age. With 49 months median follow-up, all patient outcomes (overall survival (OS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and recurrence-free survival (RFS)) significantly decreased as age increased. In multivariate analysis, age >80, pT2-3 sizes, axillary macrometastases, lymphovascular involvement, and HR-negativity tumor negatively affected DFS and OS. Comparison between age >80 and <=80 years old showed worse RFS in patients aged > 80 (HR=1.771, p=0.031). Conclusion: TN and Her2-positive subtypes occur at similar frequency in elderly patients. Older age is associated with more advanced tumor stage presentation. Chemotherapy use decreases with older age without worse other pejorative prognostic factors. Age >80, but not ≤80, independently affected DFS and OS.