Risk of Lymphedema Following Contemporary Treatment for Breast Cancer: An Analysis of 7617 Consecutive Patients From a Multidisciplinary Perspective.

OBJECTIVE: The aim of this study was to identify the comprehensive risk factors for lymphedema, thereby enabling a more informed multidisciplinary treatment decision-making. SUMMARY BACKGROUND DATA: Lymphedema is a serious long-term complication in breast cancer patients post-surgery; however, the influence of multimodal therapy on its occurrence remains unclear. METHODS: We retrospectively collected treatment-related data from 5549 breast cancer patients who underwent surgery between 2007 and 2015 at our institution. Individual radiotherapy plans were reviewed for regional nodal irradiation (RNI) field design and fractionation type. We identified lymphedema risk factors and used them to construct nomograms to predict individual risk of lymphedema. Nomograms were validated internally using 100 bootstrap samples and externally using 2 separate datasets of 1877 Asian and 191 Western patients. RESULTS: Six hundred thirty-nine patients developed lymphedema during a median follow-up of 60 months. The 3-year lymphedema incidence was 10.5%; this rate increased with larger irradiation volumes (no RNI vs RNI excluding axilla I-II vs RNI including axilla I-II: 5.7% vs 16.8% vs 24.1%) and when using conventional fractionation instead of hypofractionation (13.5% vs 6.8%). On multivariate analysis, higher body mass index, larger number of dissected nodes, taxane-based regimen, total mastectomy, larger irradiation field, and conventional fractionation were strongly associated with lymphedema (all P < 0.001). Nomograms constructed based on these variables showed good calibration and discrimination internally (concordance index: 0.774) and externally (0.832 for Asian and 0.820 for Western patients). CONCLUSIONS: Trimodality breast cancer treatment factors interact to promote lymphedema. Lymphedema risk can be decreased by deintensifying node dissection, chemotherapy regimen, and field and dose of radiotherapy. Deescalation strategies on a multidisciplinary basis might minimize lymphedema risk.

Solitary Plasmacytoma Treated by Lenalidomide-Dexamethasone in Combination with Radiation Therapy: Clinical Outcomes.

PURPOSE: The study evaluates the results of the concurrent use of lenalidomide-dexamethasone with intensity modulated radiation therapy (IMRT) for solitary plasmacytoma in terms of toxicity and outcome. METHODS AND MATERIALS: Forty-six patients were treated for histologically proven solitary plasmacytoma (SP) between June 2007 and June 2018 in our Department (Curie Institute, Paris, France). All patients received IMRT. The median total dose was 40 Gy (range, 40-46). Prescription of concurrent lenalidomide-dexamethasone with radiation therapy was left to the discretion of the referring hematologist-oncologist and started the first day of radiation therapy for 4 cycles. RESULTS: Twenty-seven solitary plasmacytoma were treated with IMRT alone and 19 with lenalidomide-dexamethasone in association with IMRT. At 5 years, the local control, multiple myeloma-free survival (MMFS), and progression-free survival (PFS) rates were 96.3%, 85.4%, and 60%. MMFS and PFS were significantly higher in the IMRT plus lenalidomide-dexamethasone group compared with IMRT alone group (100% vs 77.1%, P = .02 and 81.7% vs 48.4%, P = .047, respectively). No major toxicity was found in either group. CONCLUSIONS: Lenalidomide-dexamethasone in association with IMRT in the treatment of solitary plasmacytoma is safe and improves MMFS and PFS. Further prospective and comparative studies are needed to confirm these results.

Brain metastases and treatment: multiplying cognitive toxicities.

INTRODUCTION: Thirty per cent of cancer patients develop brain metastases, with multiple combination or sequential treatment modalities available, to treat systemic or central nervous system (CNS) disease. Most patients experience toxicities as a result of these treatments, of which cognitive impairment is one of the adverse events most commonly reported, causing major impairment of the patient's quality of life. Areas covered: This article reviews the role of cancer treatments in cognitive decline of patients with brain metastases: surgery, radiotherapy, chemotherapy, targeted therapies, immunotherapies and hormone therapy. Pathological and molecular mechanisms, as well as future directions for limiting cognitive toxicities are also presented. Other causes of cognitive impairment in this population are discussed in order to refine the benefit-risk balance of each treatment modality. Expert opinion: Cumulative cognitive toxicity should be taken into account, and tailored to the patient's cognitive risk in the light of the expected survival benefit. Standardization of cognitive assessment in this context is needed in order to better appreciate each treatment's responsibility in cognitive impairment, keeping in mind disease itself impacts cognition in this context.

Cardiotoxicity associated with radiotherapy in breast cancer: A question-based review with current literatures.

Radiotherapy is an indispensable unit of multidisciplinary treatment of breast cancer. Although the application of modern techniques has led to a significantly reduction in radiation-induced heart disease, it is still recognized as the leading causes of morbidity and mortality among breast cancer survivors. With the growing number of long-term survivors, it is important to understand the cardiovascular risks associated with radiotherapy. Questions exist regarding the existence or not of a safe radiation threshold dose that the heart (or its substructures) can receive and strategies to minimize risk of radiation. This paper aims to review the current understanding of radiation-induced cardiotoxicity and try to give answers to those unsettled issues based on current literatures.

Use of helical tomotherapy in locally advanced and/or metastatic breast cancer for locoregional treatment.

OBJECTIVE: Helical tomotherapy (HT) is a new promising tool whose use remains to be studied. This work assesses its impact for local irradiation in terms of side effects, as well as tumour control in locally advanced (LABC) and metastatic breast cancer (MBC). METHODS: We retrospectively reviewed data of 66 patients with LABC and MBC. Patients received standard fractionated radiotherapy by HT, with or without concurrent systemic treatment. RESULTS: The median age was 60 years (28-77). The median follow-up of the population was 35.9 months (10.6-95.8). For 91% of patients, HT was concomitant with systemic treatments. Three patients experienced grade 3 skin toxicity and all had concurrent 5FU-vinorelbine. One patient who was receiving concurrent treatment with trastuzumab-pertuzumab had a decreased left ventricular ejection fraction by 14%. No late cardiac or lung toxicity was observed. A clinical benefit was observed in 75% of cases. At 2 months after HT, we observed tumour regression in 7/8 patients, as following: 1 complete, 4 partial responses, and 2 stable disease. The median survival for MBC group was 64.4 months (42.6-65.8) and 21.1 (6.1-36.1) months for LABC. CONCLUSION: This study suggests that the use of HT is well tolerated and feasible with a multimodal strategy that includes concurrent systemic treatments for patients with LABC and MBC. Advances in knowledge: The survival of LABC and MBC increases and new safe tools are needed to determine optimal strategies of treatment. To our knowledge, this is the first paper describing the use of HT for this population.

The use of helical tomotherapy in the treatment of early stage breast cancer: indications, tolerance, efficacy-a single center experience.

PURPOSE: to evaluate our experience in terms of local control, survival, adverse effects in patients treated by adjuvant helical tomotherapy (HT) for breast cancer (BC). RESULTS: We studied 179 consecutive patients with 194 treated breasts with adjuvant HT. Median follow-up was 38.1 months. Median age was 53 years. Chemotherapy was administered to 83% of patients. All 133 hormone receptor positive tumours received hormonal therapy. As concurrent treatment, apart from trastuzumab monotherapy, 6 patients received systemic therapy concomitant to RT. The HT was generally well tolerated with mostly grade 1 and 2 skin reactions and esophagitis. Only 3% grade III early skin reactions. At last follow-up, there were 2 local recurrences, 1 regional lymph node (LN) recurrence and 6 with metastatic progression. The 5-year progression-free survival was 90.5% (95% CI 84.2-97.3). MATERIALS AND METHODS: A retrospective study of all patients treated by HT between 2009 and 2015 was done. Patients excluded were those with: breast implants, advanced or metastatic BC, recurrent disease. All patients received breast+/-boost or chest wall irradiation and most received with LN irradiation. Dose constraints for organs at risk were defined using optimization scale developed in our Department. Evaluation of early and late toxicity was done using Common Terminology Adverse Criteria Events v.4.0. CONCLUSIONS: HT can be used for a well selected group of breast cancer as bilateral tumours, complex anatomy and target volumes where the conventional radiation therapy techniques cannot ensure an optimal dose distribution. Longer follow-up is necessary to confirm and validate these results.

The use of new delineation tool "MIRADA" at the level of regional lymph nodes, step-by-step development and first results for early-stage breast cancer patients.

OBJECTIVE:: To describe the practical procedure of implementation and optimization of delineation using "Mirada" software, as well as evaluation of the automatic segmentation for the daily practice of lymph nodes (LN) and organs at risk (OARs) in early stage breast cancer patients. METHODS:: 40 patients' CT scans in treatment position were selected and recontoured according to the European Society of Therapeutic Radiation Oncology guidelines. The atlas of data set was then created for automatic delineation. 30 patients with breast/chest wall and lymph nodes regions irradiated were recruited for evaluation. With the same treatment position, the CT scan images were acquired and then contoured by the MIRADA system automatically as well as by the radiation oncologist manually (as the reference). The conformity index (CI) was used to evaluate the concordance between both of them. RESULTS:: The mean time for manual contour was 24.1 ± 5.1 and 26.4 ± 2.8 min for the LN and the OARs respectively. All the volumes of interest were contoured using the software (including corrections) in 30 min, which reduced the time of delineation of target volumes and OAR by about 40%. Of the 30 cases evaluated, the mean CI of 5 principal OARs showed ≥0.8. While the automatic contour of LN was less satisfactory with mean CI of 0.43 ± 0.1 (0.23-0.52). CONCLUSION:: For the breast cancer patients, the studied software permitted to save time for delineation with acceptable OAR contours. The improvement of LN regions contour is needed. More cases and further evaluation are needed for the system to realize its routine use. ADVANCES IN KNOWLEDGE:: It's the first description and evaluation of the automatic delineation and segmentation system for the breast cancer.