Radiotherapy for breast cancer.

In early breast cancer, adjuvant moderately hypofractionated regimens are recommended for both whole breast, partial breast and locoregional irradiation which abbreviates the overall treatment time, as argued in this review. Gating is recommended as well as the use of a simultaneous integrated boost when indicated. A tangential field set-up is standard, however, for challenging cases volumetric modulated arc therapy techniques, or referral for proton therapy, may be considered. In the metastatic setting, stereotactic radiotherapy is a promising treatment option for oligometastatic disease.

Through Clinicians Eyes: Use of an In-consultation Patient Decision Aid in Radiation Treatment for Early Breast Cancer. A Qualitative Study.

INTRODUCTION: Shared decision making (SDM) has become a crucial element on the political agenda and represents a vital aspect of modern healthcare. However, successful implementation of SDM highly depends on the attitude of clinicians towards SDM. The overall aim of our study was to explore the experience of oncologists and nurses with SDM using the Decision Helper, an in-consultation decision aid, at four Danish radiotherapy departments. METHODS: Semi-structured interviews were conducted with 20 clinicians. The participants were selected using purposive sampling to include nurses and oncologists, male and female, with different levels of experience with SDM and clinical work. The analysis was a data-driven, iterative process with inductive coding of all interviews and meaning condensation. RESULTS: Two main themes emerged: "Using the Decision Helper changes the consultation" and "Change of attitude among Danish oncologists." Each of the two themes included four elaborative subthemes, which are reported with supporting citations in this paper. In brief, the use of SDM and the Decision Helper should ideally be adjusted to the individual patient and depends highly on the oncologist. The participants described ambitions towards "making the right decision for this patient at this time." The healthcare system, however, has pitfalls that may hinder SDM, e.g., rigid interpretation of guideline-based recommendations. CONCLUSION: Using an in-consultation Decision Helper has the potential for individualized, structured patient engagement in decision making. There is a need for patient decision aids in clinical guidelines to ensure patient engagement in decision making.

Shared decision making with breast cancer patients - does it work? Results of the cluster-randomized, multicenter DBCG RT SDM trial.

BACKGROUND AND PURPOSE: Shared decision making (SDM) is a patient engaging process advocated especially for preference-sensitive decisions, such as adjuvant treatment after breast cancer. An increasing call for patient engagement in decision making highlights the need for a systematic SDM approach. The objective of this trial was to investigate whether the Decision Helper (DH), an in-consultation patient decision aid, increases patient engagement in decisions regarding adjuvant whole breast irradiation. MATERIAL AND METHODS: Oncologists at four radiotherapy units were randomized to practice SDM using the DH versus usual practice. Patient candidates for adjuvant whole breast irradiation after breast conserving surgery for node-negative breast cancer were eligible. The primary endpoint was patient-reported engagement in the decision process assessed with the Shared Decision Making Questionnaire (SDM-Q-9) (range 0-100, 4 points difference considered clinical relevant). Other endpoints included oncologist-reported patient engagement, decisional conflict, fear of cancer recurrence, and decision regret after 6 months. RESULTS: Of the 674 included patients, 635 (94.2%) completed the SDM-Q-9. Patients in the intervention group reported higher level of engagement (median 80; IQR 68.9 to 94.4) than the control group (71.1; IQR 55.6 to 82.2; p < 0.0001). Oncologist-reported patient engagement was higher in the invention group (93.3; IQR 82.2 to 100) compared to control group (73.3; IQR 60.0 to 84.4) (p < 0.0001). CONCLUSION: Patient engagement in medical decision making was significantly improved with the use of an in-consultation patient decision aid compared to standard. The DH on adjuvant whole breast irradiation is now recommended as standard of care in the Danish guideline.

Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.

BACKGROUND AND PURPOSE: Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. MATERIAL AND METHODS: Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. RESULTS: All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. INTERPRETATION: The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.

The King is in the altogether: Radiation therapy after oncoplastic breast surgery.

Breast cancer is the most common malignancy, and the majority of the patients are diagnosed at an early disease stage. Breast conservation is the preferred locoregional approach, and oncoplastic breast conservation surgery is becoming more popular. This narrative review aims to discuss the challenges and uncertainties in target volume definition for postoperative radiation after these procedures, to improve radiation therapy decisions and encourage multidisciplinary.

End-to-end framework for automated collection of large multicentre radiotherapy datasets demonstrated in a Danish Breast Cancer Group cohort.

Large Digital Imaging and Communications in Medicine (DICOM) datasets are key to support research and the development of machine learning technology in radiotherapy (RT). However, the tools for multi-centre data collection, curation and standardisation are not readily available. Automated batch DICOM export solutions were demonstrated for a multicentre setup. A Python solution, Collaborative DICOM analysis for RT (CORDIAL-RT) was developed for curation, standardisation, and analysis of the collected data. The setup was demonstrated in the DBCG RT-Nation study, where 86% (n = 7748) of treatments in the inclusion period were collected and quality assured, supporting the applicability of the end-to-end framework.

Difference between planned and delivered radiotherapy dose to the internal mammary nodes in high-risk breast cancer patients.

Background and purpose: Chest wall movement during radiotherapy can impact the delivered dose to the internal mammary nodes (IMN) in high-risk breast cancer patients. Using portal imaging and dose reconstruction we aimed to examine the delivered IMN dose coverage. Material and methods: Cine MV images were recorded for 39 breast cancer patients treated with daily image-guided radiotherapy (IGRT) in deep-inspiration breath-hold (DIBH). On the final frame of each cine MV recording the chest wall was matched with the Digitally Reconstructed Radiograph (DRR) from the treatment plan. The geometrical chest wall error was determined in the imager-plane perpendicular to the cranio-caudal direction, rounded to integer millimeters, and binned. For each 1 mm bin, an isocenter-shifted treatment plan was recalculated assuming that the projected error observed in the cine MV image was caused by anterior-posterior chest wall movement in the IMN region. A weighted plan sum yielded the IMN clinical target volume receiving at least 90% dose (V90_CTVn_IMN). Results: The mean number of cine MV observations per patient was 36 (range 26-55). Most patients (67%) had on average a posterior chest wall position at treatment compared to planned. This translated into a change in the delivered median V90_CTVn_IMN of -0.7% (range, -11.9-2.9%; p < 0.001). The V90_CTVn_IMN reduction was greater than 9% in three patients. No clinically relevant differences were found for the mean lung dose or mean heart dose. Conclusion: Using cine MV images, we found that the delivered V90_CTVn_IMN was significantly lower than planned. In 8% of the patients, the V90_CTVn_IMN reduction exceeded 9%.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Radiation-Induced Toxicity Risks in Photon Versus Proton Therapy for Synchronous Bilateral Breast Cancer.

Purpose: This study compares photon and proton therapy plans for patients with synchronous bilateral early breast cancer and estimates risks of early and late radiation-induced toxicities. Materials and Methods: Twenty-four patients with synchronous bilateral early breast cancer receiving adjuvant radiation therapy using photons, 3-dimensional conformal radiation therapy or volumetric modulated arc therapy, were included and competing pencil beam scanning proton therapy plans were created. Risks of dermatitis, pneumonitis, acute esophageal toxicity, lung and breast fibrosis, hypothyroidism, secondary lung and esophageal cancer and coronary artery events were estimated using published dose-response relationships and normal tissue complication probability (NTCP) models. Results: The primary clinical target volume V95% and/or nodal clinical target volume V90% were less than 95% in 17 photon therapy plans and none of the proton plans. Median NTCP of radiation dermatitis ≥ grade 2 was 18.3% (range, 5.4-41.7) with photon therapy and 58.4% (range, 31.4-69.7) with proton therapy. Median excess absolute risk (EAR) of secondary lung cancer at age 80 for current and former smokers was 4.8% (range, 0.0-17.0) using photons and 2.7% (range, 0.0-13.6) using protons. Median EAR of coronary event at age 80, assuming all patients have preexisting cardiac risk factors, was 1.0% (range, 0.0-5.6) with photons and 0.2% (range, 0.0-1.3) with protons. Conclusion: Proton therapy plans improved target coverage and reduced risk of coronary artery event and secondary lung cancer while increasing the risk of radiation dermatitis.

Internal Mammary Node Irradiation in Patients With Node-Positive Early Breast Cancer: Fifteen-Year Results From the Danish Breast Cancer Group Internal Mammary Node Study.

PURPOSE: The Danish Breast Cancer Group Internal Mammary Node study demonstrated improved 8-year overall survival (OS) with internal mammary node irradiation (IMNI) in patients with node-positive early breast cancer. Here, we present long-term results from the Danish Breast Cancer Group Internal Mammary Node study cohort. PATIENTS AND METHODS: This nationwide, prospective cohort study allocated patients with node-positive early breast cancer to adjuvant radiotherapy with or without IMNI depending on cancer laterality. Patients with right-sided cancer received IMNI. Patients with left-sided cancer were treated without IMNI because of risk of radiation-induced heart disease. Other treatment was independent of laterality. The primary study end point was OS. Secondary end points were distant recurrence and breast cancer mortality. Analyses were by intention to treat. RESULTS: During 2003-2007, 3,089 women were allocated to IMNI (right-sided, n = 1,491) or no IMNI (left-sided, n = 1,598). With a median follow-up of 14.8 years, 589 patients with and 701 patients without IMNI had died. The corresponding 15-year OS rates were 60.1% and 55.4%. The adjusted hazard ratio (HR) for death was 0.86 (95% CI, 0.77 to 0.96; P = .007) in favor of IMNI. The 15-year risk of developing distant recurrence was 35.6% (523 recurrences) and 38.6% (602 recurrences) with vs. without IMNI (adjusted HR, 0.88 [95% CI, 0.79 to 0.99; P = .04]). The 15-year breast cancer mortality with IMNI was 31.7% (467 deaths) compared with 33.9% (537 deaths) without IMNI (adjusted HR, 0.88 [95% CI, 0.78 to 1.00; P = .05]). The distribution of other deaths was similar across groups. CONCLUSION: In patients with node-positive early breast cancer treated with IMNI or without IMNI depending on breast cancer laterality, IMNI reduced the risk of distant recurrence and death from breast cancer, thereby improving long-term survival.

Postmastectomy radiotherapy in high-risk breast cancer patients given adjuvant systemic therapy. A 30-year long-term report from the Danish breast cancer cooperative group DBCG 82bc trial.

BACKGROUND: Between 1982 and 1990 the Danish Breast Cancer Cooperative Group (DBCG) conducted a randomized trial in high-risk pre- and postmenopausal (<70 years) breast cancer patients comparing mastectomy plus adjuvant systemic therapy alone versus the same treatment plus postoperative irradiation. AIM: To present a comprehensive analysis of the complete DBCG 82bc study with a 30-year long-term follow-up of the cancer therapeutic effect and survival, together with an additional focus on the potential long-term life-threatening morbidity related to cardiac irradiation and/or the risk of secondary cancer induction. METHODS: A total of 3083 patients with pathological stage II and stage III breast cancer were after mastectomy randomly assigned to receive adjuvant systemic therapy and postoperative irradiation to the chestwall and regional lymph nodes (1538 pts), or adjuvant systemic therapy alone (1545 pts). Pre- and menopausal patients (DBCG 82b) received 8-9 cycles of CMF with an interval of 4 weeks, whereas postmenopausal patients (DBCG 82c) received tamoxifen 30 mg daily for one year. The median follow-up time was 34 years. The primary endpoints were loco-regional recurrence (LRR) and overall mortality, and the secondary endpoints were distant metastasis, breast cancer mortality, and irradiation related late morbidity. RESULTS: Overall the 30-year cumulative incidence of loco-regional recurrence was 9% in irradiated patients versus 37% in non-irradiated patients who received adjuvant systemic therapy alone (HR: 0.21 [95% cfl 0.18-0.26]). Distant metastasis probability at 30 years was 49% in irradiated patients compared to 60% in non-irradiated (HR: 0.77 [0.70-0.84]). Consequently, these figures resulted in a reduced breast cancer mortality: 56% vs 67% (HR: 0.75 [0.69-0.82], and overall mortality (81% vs 86% at 30 years (p < 0.0001), HR: 0.83 [0.77-0.90] in favor of irradiation. Radiotherapy did not result in any significant excess death of other courses, such as ischemic heart disease, HR: 0.82 [0.58-1.18]; nor secondary lung cancer HR: 1.44 [0.92-2.24], or other non-cancer related death HR: 1.15 [0.92-1.45]. CONCLUSION: The study definitely demonstrate that optimal long-term treatment benefit of high-risk breast cancer can only be achieved if both loco-regional and systemic tumor control are aimed for. Therefore, radiotherapy has an important role in the multidisciplinary treatment of breast cancer. The PMRT treatment did not result in excess ischemic heart damage, nor in other non-breast cancer related death.

Spot-scanning proton therapy for targets with adjacent cardiac implantable electronic devices - Strategies for breast and head & neck cancer.

BACKGROUND AND PURPOSE: Cardiac implantable electronic device (CIED) malfunctions can be induced by secondary neutron dose from spot-scanning proton therapy. A recent in-vitro study investigating secondary neutron dose to CIEDs up to 7 mSv per fraction found that exposure of secondary neutrons in this range was clinically manageable. This study presents decision algorithms proposed by a national expert group for selection of patients with breast and head & neck (H&N) cancer with CIEDs adjacent to target for proton therapy based on the 7 mSv threshold. METHODS AND MATERIALS: Ten patients with breast cancer and five with H&N cancer were included in the study. Five patients with breast cancer received photon therapy with CIED and proton plans were retrospectively created. The remaining patients received proton therapy without CIED and a worst-case position of a virtual CIED was retrospectively delineated. Secondary neutron dose was estimated as ambient dose equivalent H*(10) using Monte Carlo simulations. RESULTS: For patients with breast cancer and with contralateral CIED, the secondary neutron dose to the CIED was below 7 mSv per fraction for CTV < 1500 cm3 in 2 Gy fractions and CTV < 1000 cm3 in 2.67 Gy fractions. The secondary neutron dose to the CIED was below 7 mSv per fraction for all patients with H&N cancer. CONCLUSIONS: Simulations of neutron exposure suggest that proton therapy is feasible for most patients with CIED adjacent to target. This forms the basis for decision algorithms for selection of patients with CIED for proton therapy.

European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer.

High-quality randomised clinical trials testing moderately fractionated breast radiotherapy have clearly shown that local control and survival is at least as effective as with 2 Gy daily fractions with similar or reduced normal tissue toxicity. Fewer treatment visits are welcomed by patients and their families, and reduced fractions produce substantial savings for health-care systems. Implementation of hypofractionation, however, has moved at a slow pace. The oncology community have now reached an inflection point created by new evidence from the FAST-Forward five-fraction randomised trial and catalysed by the need for the global radiation oncology community to unite during the COVID-19 pandemic and rapidly rethink hypofractionation implementation. The aim of this paper is to support equity of access for all patients to receive evidence-based breast external beam radiotherapy and to facilitate the translation of new evidence into routine daily practice. The results from this European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus state that moderately hypofractionated radiotherapy can be offered to any patient for whole breast, chest wall (with or without reconstruction), and nodal volumes. Ultrafractionation (five fractions) can also be offered for non-nodal breast or chest wall (without reconstruction) radiotherapy either as standard of care or within a randomised trial or prospective cohort. The consensus is timely; not only is it a pragmatic framework for radiation oncologists, but it provides a measured proposal for the path forward to influence policy makers and empower patients to ensure equity of access to evidence-based radiotherapy.

Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.

BACKGROUND: The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. MATERIAL AND METHODS: Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. RESULTS: The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. CONCLUSION: This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.