Is the breast-conserving treatment with radiotherapy appropriate in mutation carriers? Long-term results and review of the literature

International audienceAs tumours in mutation carriers might be more sensitive to radiation, we investigated after long-term follow-up whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after breast-conserving treatment (BCT). and genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone BCT and radiotherapy. Patients were matched to 261 controls with sporadic breast cancer according to age at diagnosis and year of treatment. Controls were followed up for at least as long as the interval between diagnosis and genetic screening in familial cases. Rates of ipsilateral and contralateral cancer between groups were compared by the log-rank test. The mutations occurred in 20.6% of tested patients. Tumours in mutation carriers were more likely to be grade III ( < 10) and oestrogen receptor negative ( = 0.005) than in non-carriers and controls. Overall median follow-up was 161 months. There was no significant difference in ipsilateral tumours between mutation carriers, non-carriers and controls ( = 0.13). On multivariate analysis, age was the most significant predictor for ipsilateral recurrence ( < 10). The rate of contralateral cancer was significantly higher in familial cases: 40.7% (mutation carriers), 20% (non-carriers), and 11% (controls) ( < 10). After 13.4 years of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers than in non-carriers or controls. As tumours in mutation carriers might be more sensitive to radiation, BCT is a possible treatment option

Selection criteria for early breast cancer patients in the DBCG proton trial – The randomised phase III trial strategy

Background and purpose Adjuvant radiotherapy of internal mammary nodes (IMN) improves survival in high-risk early breast cancer patients but inevitably leads to more dose to heart and lung. Target coverage is often compromised to meet heart/lung dose constraints. We estimate heart and lung dose when target coverage is not compromised in consecutive patients. These estimates are used to guide the choice of selection criteria for the randomised Danish Breast Cancer Group (DBCG) Proton Trial.Materials and methods 179 breast cancer patients already treated with loco-regional IMN radiotherapy from 18 European departments were included. If the clinically delivered treatment plan did not comply with defined target coverage requirements, the plan was modified retrospectively until sufficient coverage was reached. The choice of selection criteria was based on the estimated number of eligible patients for different heart and lung dose thresholds in combination with proton therapy capacity limitations and dose-response relationships for heart and lung.Results Median mean heart dose was 3.0 Gy (range, 1.1-8.2 Gy) for left-sided and 1.4 Gy (0.4-11.5 Gy) for right-sided treatment plans. Median V17Gy/V20Gy (hypofractionated/normofractionated plans) for ipsilateral lung was 31% (9-57%). The DBCG Radiotherapy Committee chose mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37% as thresholds for inclusion in the randomised trial. Using these thresholds, we estimate that 22% of patients requiring loco-regional IMN radiotherapy will be eligible for the trial.Conclusion The patient selection criteria for the DBCG Proton Trial are mean heart dose ≥ 4 Gy and/or lung V17Gy/V20Gy ≥ 37%

Proton Therapy for Breast Cancer:A Consensus Statement From the Particle Therapy Cooperative Group Breast Cancer Subcommittee

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved

Evidence-based Review on the Use of Proton Therapy in Lymphoma From the Particle Therapy Cooperative Group (PTCOG) Lymphoma Subcommittee.

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Recent advances in breast cancer radiotherapy: Evolution or revolution, or how to decrease cardiac toxicity?

Radiation therapy has a major role in the management of breast cancers. However, there is no consensus on how to irradiate and on volume definitions, and there are strong differences in strategies according to different centers and physicians. New treatment protocols and techniques have been used with the principal purpose of decreasing lung and heart toxicity and adapting radiation treatment to patients’ anatomy. There is evidence that indicates internal mammary chain radiotherapy should be used carefully and that high quality techniques should be used for decreasing the dose delivered to the heart. This review of the literature presents the state of the art on breast cancer radiotherapy, with special focus on the indications, techniques, and potential toxicity

Applications of new irradiation modalities in patients with lymphoma: Promises and uncertainties

New highly conformal irradiation modalities have emerged for treatment of Hodgkin lymphoma. Helical tomotherapy offers both intensity-modulated irradiation and accurate patient positioning and was shown to significantly decrease radiation doses to the critical organs. Here we review some of the most promising applications of helical tomotherapy in Hodgkin disease. By decreasing doses to the heart or the breast, helical tomotherapy might decrease the risk of long-term cardiac toxicity or secondary breast cancers, which are major concerns in patients receiving chest radiotherapy. Other strategies, such as debulking radiotherapy prior to stem cell transplantation or total lymphoid irradiation may be clinically relevant. However, helical tomotherapy may also increase the volume of tissues that receive lower doses, which has been implicated in the carcinogenesis process. Prospective assessments of these new irradiation modalities of helical tomotherapy are required to confirm the potential benefits of highly conformal therapies applied to hematological malignancies

Eribulin combined with radiation therapy in a young patient re-irradiated for a new lesion of breast cancer

International audienceEribulin is widely used in the treatment of metastatic breast cancer, with a manageable toxicity profile. This aggressive disease often requires systemic and local treatments, comprising surgery or radiotherapy. However, eribulin is usually discontinued during radiation therapy due to the lack of data concerning the safety of this combination, especially in the setting of repeat locoregional radiation therapy. Our patient was diagnosed with ER positive invasive ductal carcinoma of the left breast initially treated by surgery, radiation therapy, chemotherapy, and hormone therapy. She then received various lines of chemotherapy for multiple triple-negative relapses in the left axillary region. Since October 2020, she has been treated by eribulin. In order to improve local control, it was decided to add local radiation therapy to the region of recurrence in addition to systemic therapy. She underwent radiation therapy concomitantly with eribulin from February to March 2021. Treatment was very well tolerated, and no acute toxicity was reported. This is the first published case of repeat locoregional radiation therapy in combination with eribulin

Could helical tomotherapy do whole brain radiotherapy and radiosurgery?

Whole brain radiotherapy (WBRT) remains the standard management of breast cancer patients with brain metastases, allowing for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity. In highly selected breast cancer patients, stereotaxic radiotherapy demonstrates a very good local control with a low toxicity. With the purpose of improving the efficacy/toxicity ratio, we report the association of integrated boost with WBRT in a breast cancer patient with brain metastases. Two and a half years after completion of helical tomotherapy (HT), the patient experienced clinical and radiological complete remission of her brain disease. No delayed toxicity occurred and the patient kept her hair without need of radiosurgical procedure. The HT provided a high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged