A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.

MRE11 liberates cGAS from nucleosome sequestration during tumorigenesis.

Oncogene-induced replication stress generates endogenous DNA damage that activates cGAS-STING-mediated signalling and tumour suppression1-3. However, the precise mechanism of cGAS activation by endogenous DNA damage remains enigmatic, particularly given that high-affinity histone acidic patch (AP) binding constitutively inhibits cGAS by sterically hindering its activation by double-stranded DNA (dsDNA)4-10. Here we report that the DNA double-strand break sensor MRE11 suppresses mammary tumorigenesis through a pivotal role in regulating cGAS activation. We demonstrate that binding of the MRE11-RAD50-NBN complex to nucleosome fragments is necessary to displace cGAS from acidic-patch-mediated sequestration, which enables its mobilization and activation by dsDNA. MRE11 is therefore essential for cGAS activation in response to oncogenic stress, cytosolic dsDNA and ionizing radiation. Furthermore, MRE11-dependent cGAS activation promotes ZBP1-RIPK3-MLKL-mediated necroptosis, which is essential to suppress oncogenic proliferation and breast tumorigenesis. Notably, downregulation of ZBP1 in human triple-negative breast cancer is associated with increased genome instability, immune suppression and poor patient prognosis. These findings establish MRE11 as a crucial mediator that links DNA damage and cGAS activation, resulting in tumour suppression through ZBP1-dependent necroptosis.

Single-cell and spatial profiling identify three response trajectories to pembrolizumab and radiation therapy in triple negative breast cancer.

Strategies are needed to better identify patients that will benefit from immunotherapy alone or who may require additional therapies like chemotherapy or radiotherapy to overcome resistance. Here we employ single-cell transcriptomics and spatial proteomics to profile triple negative breast cancer biopsies taken at baseline, after one cycle of pembrolizumab, and after a second cycle of pembrolizumab given with radiotherapy. Non-responders lack immune infiltrate before and after therapy and exhibit minimal therapy-induced immune changes. Responding tumors form two groups that are distinguishable by a classifier prior to therapy, with one showing high major histocompatibility complex expression, evidence of tertiary lymphoid structures, and displaying anti-tumor immunity before treatment. The other responder group resembles non-responders at baseline and mounts a maximal immune response, characterized by cytotoxic T cell and antigen presenting myeloid cell interactions, only after combination therapy, which is mirrored in a murine model of triple negative breast cancer.

INDIVIDUAL ARTICLE: USCOM Algorithm for the Prevention and Management of Cutaneous Immunotherapy-Related Adverse Events.

BACKGROUND: In 2023, nearly 2 million patients will be diagnosed with cancer in the United States and at least 40% will be eligible for treatment with an immune checkpoint inhibitor (ICI). Cutaneous immune related adverse events (cirAEs) from ICIs are common and include pruritus as well as maculopapular, eczematous, bullous, lichenoid, and psoriasiform reactions. All clinicians interfacing with cancer patients must expedite proper evaluation and diagnosis, treatment, and/or consultation that supports the need for evidence-directed guidelines. MATERIALS AND METHODS: A panel of advisors was selected, and a systematic literature review generated foundational evidence to develop a treatment algorithm for cirAEs via a modified Delphi process. Iterations of the algorithm were performed until the group met consensus. RESULTS: An algorithm that tailors the management of cirAEs was developed based on the CTCAE v.5 grading of skin disorders. Representative clinical images and suggested diagnostic measures, supplement the algorithm. CONCLUSION: Recognition and treatment of cirAEs guided through a multidisciplinary, physician-developed algorithm will limit disruption of immunotherapy, optimize quality of life, and enhance overall outcomes in patients treated with ICIs. J Drugs Dermatol. 2023;22:11(Suppl 1):s3-10.

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.

Lung cancer screening an asbestos exposed population: Existing lung cancer risk criteria are not sufficient.

BACKGROUND AND OBJECTIVE: Asbestos is a major risk factor for lung cancer, with or without tobacco smoke exposure. Low dose computed tomography (LDCT) screening for early lung cancer is effective but only when targeting high risk populations. This study aimed to analyse the effectiveness of LDCT screening in an asbestos exposed population and to compare lung cancer screening program (LCSP) eligibility criteria. METHODS: Participants in an asbestos health surveillance program, the Western Australia Asbestos Review Program, underwent at least one LDCT scan and lung function assessment as part of annual review between 2012 and 2017. Lung cancer cases were confirmed through linkage to the WA cancer registry. Theoretical eligibility for different screening programs was calculated. RESULTS: Five thousand seven hundred and two LDCT scans were performed on 1743 individuals. The median age was 69.8 years, 1481 (85.0%) were male and 1147 (65.8%) were ever-smokers (median pack-year exposure of 20.0). Overall, 26 lung cancers were detected (1.5% of the population; 3.5 cases per 1000 person-years of observation). Lung cancer was early stage in 86.4% and four (15.4%) cases were never smokers. Based on current lung screening program criteria, 1299 (74.5%) of this population, including the majority (17, 65.4%) of lung cancer cases, would not have been eligible for any LCSP. CONCLUSION: This population is at raised risk despite modest tobacco exposure. LDCT screening is effective at identifying early-stage lung cancer in this population and existing lung cancer risk criteria do not capture this population adequately.

United States Cutaneous Oncodermatology Management (USCOM) II: A Multidisciplinary-Guided Algorithm for the Prevention and Management of Acute Radiation Dermatitis in Cancer Patients.

BACKGROUND: Among the 1,918,030 patients in the United States estimated to be diagnosed with cancer in 2022, approximately 50% will require radiation therapy (RT) as part of their treatment plan. Radiation dermatitis (RD) is the most common side effect of RT, particularly in patients with breast, head, neck, and anal cancers, with a wide spectrum in the severity and degree of RD that develops in an individual and considerable heterogeneity in the management of RD. In addition, few contemporaneous treatment algorithms exist for the prevention and treatment of RD, underscoring the need to develop uniform, evidence-directed guidelines. MATERIALS AND METHODS: A modified Delphi process was used to develop a treatment algorithm (USCOM II) that expanded upon a previous algorithm (USCOM I) for the management of RD. A panel of multidisciplinary advisors was selected, and a systematic literature search with key terms was conducted to identify publications on RD. Subsequently, the literature was graded according to the strength of evidence for the recommendation. The advisors convened to review the results and assemble the algorithm. Further iterations on the algorithm were obtained until 100% group consensus was achieved. RESULTS: An algorithm that tailors the management of RD, based on the CTCAE v.5 grading of RD and the presence of moist desquamation, was developed. Unique features include photographs illustrating the clinical spectrum of RD to supplement the algorithm and the integration of medically based recommendations with over-the-counter (OTC) skincare regimens that include cleansing, moisturizing, and photoprotection. CONCLUSION: Acute RD, when suboptimally managed, can lead to symptoms of pruritus and pain, decreased quality of life and morbidity, and treatment interruptions. When RD is severe or prolonged, it can delay the receipt of a full therapeutic course of RT. Enhanced patient education on the prevention of RD and clarity of treatment recommendations through a multidisciplinary, physician-developed algorithm may help prevent and manage the various adverse effects and improve the overall care of patients receiving RT. J Drugs Dermatol. 2022;21:11(Suppl 1):s3-14.

Radiation Therapy for Low-Risk Breast Cancer: Whole, Partial, or None?

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.The following case represents a relatively common clinical scenario of a postmenopausal female patient who presents with low-risk, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative, early-stage, left-sided breast cancer to discuss the role of postoperative radiation (RT) following wide local excision (WLE) and sentinel node biopsy. The spectrum of choices, ranging from omission of RT, accelerated partial breast irradiation (PBI), whole-breast radiation therapy, and the nuances of various dose/fractionation regimens for each option, are discussed in the context of the Danish Breast Cancer Study Group (DBCSG) PBI trial published in this issue, with additional review of other key trials that inform these treatment recommendations. After consideration of the clinical-pathologic features in the framework of the existing data and an in-depth discussion taking into consideration the patient's preferences/goals, the decision was made to deliver moderately hypofractionated RT (40 Gy/15 fractions) to a PBI volume, in concordance with the DBCSG-PBI trial.

Radiation Modality (Proton/Photon), Timing, and Complication Rates in Patients With Breast Cancer Receiving 2-Stages Expander/Implant Reconstruction.

PURPOSE: Our purpose is to explore the effect of postmastectomy radiation therapy (PMRT) modality and timing on complication rates in breast cancer patients receiving immediate 2-stages expander/implant. METHODS AND MATERIALS: We reviewed the charts of 661 patients who underwent immediate 2-stages expander/implant with/without PMRT at our institution from 2000 to 2019. Patients were divided into 3 cohorts: no radiation, PMRT to expanders (RTE), and PMRT to implants after expander exchange (RTI). PMRT was delivered either with 3-dimensional conformal photon with or without chest wall boost (CWB) or proton therapy. Reconstruction complications were defined as infection/necrosis requiring debridement, capsular-contracture requiring capsulotomy, and reconstruction failure requiring prothesis removal. Logistic regression and Cox models were used to assess the effect of different radiation therapy modalities on complication rates and local control. RESULTS: Among 661 patients, 309 (46.7%) received PMRT, 220 of the 309 (71.2%) received RTE before exchange, and 89 (28.8%) received RTI after exchange. Seventeen out of 309 (5.5%) patients received proton therapy. The complications among RTE versus RTI cohorts were 22.7% versus 15.7% for infection/necrosis, 13.6% versus 19.1% for capsular-contracture, and 39.5% versus 31.5% for overall reconstruction failure, respectively. Among proton patients, 8/17 (47%) developed capsular contracture compared with 16.4% (24/146) and 10.3% (15/146) in CWB and non-CWB groups, respectively. Adjusted multivariable analysis showed no significant difference between RTI and RTE in terms of infection/necrosis and capsular contracture. Yet, RTE significantly increased overall reconstruction failure compared with RTI (39.5% vs 31.5%; odds ratio [OR], 2.11; P = .02). Protons significantly increased capsular contracture compared with both CWB and non-CWB groups (OR, 5.4; P = .01 and OR, 10.9; P < .001, respectively). Moreover, proton significantly increased overall reconstruction failure. The 5-year local control rates were 95.3% and 97.7% for RTE and RTI, respectively (hazard ratio, 1.2; P = .7). CONCLUSIONS: Early radiation to the expander before the exchange to implant significantly increased overall reconstruction failure without improving local control. Protons significantly increased capsular contracture rates and overall reconstruction failure leading to more revision surgeries.

Immunotherapy Combined with Radiation Therapy in Breast Cancer: A Rapidly Evolving Landscape.

Immune checkpoint inhibitors (ICI) can have significant anticancer activity, and are approved for many different cancer types, including breast cancer. In breast cancer, programmed cell death 1 (PD-1) inhibitors in combination with chemotherapy have demonstrated significant clinical benefit in early-stage and metastatic settings; however, these combinations can have significant side effects, and there are still many breast cancer patients who do not respond to these approaches. Novel combinations with immunotherapy are needed to improve responses. Given the effects of radiation therapy (RT) on the tumor micro-environment, combinations of RT with immune checkpoint blockade are active areas of investigation. In this review, we discuss experience ICI in breast cancer, including current clinical indications, emerging data in combination with RT, and ongoing studies exploring optimal dosing of RT, and novel combinations with other therapeutics.

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1-3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1-3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1-3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.

Risk of Developing Breast Reconstruction Complications: A Machine-Learning Nomogram for Individualized Risk Estimation with and without Postmastectomy Radiation Therapy.

BACKGROUND: The purpose of this study was to create a nomogram using machine learning models predicting risk of breast reconstruction complications with or without postmastectomy radiation therapy. METHODS: Between 1997 and 2017, 1617 breast cancer patients undergoing mastectomy and breast reconstruction were analyzed. Those with autologous, tissue expander/implant, and single-stage direct-to-implant reconstruction were included. Postmastectomy radiation therapy was delivered either with three-dimensional conformal photon or proton therapy. Complication endpoints were defined based on surgical reintervention operative notes as infection/necrosis requiring débridement. For implant-based patients, complications were defined as capsular contracture requiring capsulotomy and implant failure. For each complication endpoint, least absolute shrinkage and selection operator-penalized regression was used to select the subset of predictors associated with the smallest prediction error from 10-fold cross-validation. Nomograms were built using the least absolute shrinkage and selection operator-selected predictors, and internal validation using cross-validation was performed. RESULTS: Median follow-up was 6.6 years. Among 1617 patients, 23 percent underwent autologous reconstruction, 39 percent underwent direct-to-implant reconstruction, and 37 percent underwent tissue expander/implant reconstruction. Among 759 patients who received postmastectomy radiation therapy, 8.3 percent received proton-therapy to the chest wall and nodes and 43 percent received chest wall boost. Internal validation for each model showed an area under the receiver operating characteristic curve of 73 percent for infection, 75 percent for capsular contracture, 76 percent for absolute implant failure, and 68 percent for overall implant failure. Periareolar incisions and complete implant muscle coverage were found to be important predictors for infection and capsular contracture, respectively. In a multivariable analysis, we found that protons compared to no postmastectomy radiation therapy significantly increased capsular contracture risk (OR, 15.3; p < 0.001). This was higher than the effect of photons with electron boost versus no postmastectomy radiation therapy (OR, 2.5; p = 0.01). CONCLUSION: Using machine learning, these nomograms provided prediction of postmastectomy breast reconstruction complications with and without radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Current advances in immune checkpoint inhibitor combinations with radiation therapy or cryotherapy for breast cancer.

PURPOSE: Immune checkpoint inhibition (ICI) has demonstrated clinically significant efficacy when combined with chemotherapy in triple negative breast cancer (TNBC). Although many patients derived benefit, others do not respond to immunotherapy, therefore relying upon innovative combinations to enhance response. Local therapies such as radiation therapy (RT) and cryotherapy are immunogenic and potentially optimize responses to immunotherapy. Strategies combining these therapies and ICI are actively under investigation. This review will describe the rationale for combining ICI with targeted local therapies in breast cancer. METHODS: A literature search was performed to identify pre-clinical and clinical studies assessing ICI combined with RT or cryotherapy published as of August 2021 using PubMed and ClinicalTrials.gov. RESULTS: Published studies of ICI with RT and IPI have demonstrated safety and signals of early efficacy. CONCLUSION: RT and cryotherapy are local therapies that can be integrated safely with ICI and has shown promise in early trials. Randomized phase II studies testing both of these approaches, such as P-RAD (NCT04443348) and ipilimumab/nivolumab/cryoablation for TNBC (NCT03546686) are current enrolling. The results of these studies are paramount as they will provide long term data on the safety and efficacy of these regimens.

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method.

US Cutaneous Oncodermatology Management (USCOM): A Practical Algorithm.

BACKGROUND: An increasing number of patients survive or are living with cancer. Anticancer treatments frequently have cutaneous adverse events (cAEs) that may severely impact patients' quality of life and interrupt anticancer treatment. The US Cutaneous Oncodermatology Management (USCOM) project aims to improve cancer patients' and survivors' quality of life by offering tools for preventing and managing cAEs. METHODS: An algorithm was designed to reduce the incidence of cAEs, treat cAEs, and maintain healthy skin using general measures and over-the-counter agents to support all healthcare providers treating oncology patients, including physicians, nurses, pharmacists, and advanced providers. The panel used a modified Delphi approach, developed, discussed, and reached a consensus on statements and an evidence-based algorithm. RESULTS: The USCOM algorithm includes education on cAEs for patients and clinicians supporting prevention, treatment, and maintenance using skincare measures before, during, and after cancer treatment. A skincare regimen including hygiene, moisturization, and sun protection products should be safe and effective in helping to minimize cAEs and improving skin conditions such as erythema, xerosis, pruritus, and photosensitivity. The number and quality of studies evaluating skincare formulations and regimens for cAEs are increasing, but the evidence on the benefits of specific formulations is still scarce. CONCLUSIONS: The algorithm focuses on general measures and skincare to prevent or reduce the severity of cAEs. Increased awareness of cAEs by the multidisciplinary team treating and guiding the cancer patient throughout their care may improve patient outcomes. J Drugs Dermatol. 2021;20:9(Suppl):s3-19.

Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer.

Breast cancer has historically been a disease for which immunotherapy was largely unavailable. Recently, the use of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for the treatment of advanced/metastatic triple-negative breast cancer (TNBC) has demonstrated efficacy, including longer progression-free survival and increased overall survival in subsets of patients. Based on clinical benefit in randomized trials, ICIs in combination with chemotherapy for the treatment of some patients with advanced/metastatic TNBC have been approved by the United States (US) Food and Drug Administration (FDA), expanding options for patients. Ongoing questions remain, however, about the optimal chemotherapy backbone for immunotherapy, appropriate biomarker-based selection of patients for treatment, the optimal strategy for immunotherapy treatment in earlier stage disease, and potential use in histological subtypes other than TNBC. To provide guidance to the oncology community on these and other important concerns, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew upon the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for breast cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence-based and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with breast cancer.

The use of bolus in postmastectomy radiation therapy for breast cancer: A systematic review.

PURPOSE: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT. RESULTS: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus. CONCLUSIONS: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT.