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PURPOSE For patients with breast cancer undergoing breast conservation, escalating the dose (boost) of radiation to the lumpectomy cavity after whole-breast irradiation (WBI) reduces ipsilateral breast recurrence (IBR) but extends treatment duration. This phase III trial investigated whether boost delivery during WBI versus after WBI provides noninferior IBR and preserves cosmetic appearance. METHODS NRG/RTOG 1005 randomly assigned patients at higher risk for IBR after lumpectomy and axillary surgery to either a sequential boost of 12 Gy in six fractions(F) or 14 Gy in 7F after WBI of 50 Gy in 25F or 42.7 Gy in 16F (sequential arm) or a concurrent boost of 8 Gy in 15F of 0.53 Gy per day with WBI of 40 Gy in 15F (concurrent arm) using 3-dimensional conformal radiation therapy (RT) or intensity-modulated RT. Based on 1.59% 5-year IBR for the sequential arm, defining the noninferiority margin as a hazard ratio upper limit on the 90% CI of 2.12, 2,312 patients provide 80% power for noninferiority of IBR as first recurrence for the concurrent arm. Secondary end points included disease-free survival and overall survival, adverse events (AEs), and cosmetic outcomes. RESULTS Between May 24, 2011, and June 20, 2014, 2,354 patients were randomly assigned, with 2,255 eligible for analysis (sequential arm, n = 1,118; concurrent arm, n = 1,137). With median follow-up of 7.3 years, there were 56 IBR events; 5- and 7-year IBR were 2.1% and 2.2% on the sequential arm and 1.9% and 2.6% on the concurrent arm, respectively. The noninferiority criterion was met: HR (90% CI): 1.31 (0.84 to 2.04), P = .037. No differences were observed in AEs, cosmetic outcomes, or survival between arms. CONCLUSION Concurrent boost during WBI results in noninferior IBR compared with sequential boost without worsening toxicity or cosmetic outcomes and reduces overall treatment time.

ABSTRACT Immune checkpoint‐inhibitors (ICIs) have revolutionized and significantly improved cancer care through remarkable efficacy, but significant adverse effects have been observed. Among these, ICI‐induced myocarditis with myositis/myasthenia gravis overlap syndrome represents a life threatening, severe immune‐related adverse event that clinicians need to be aware of and be able to diagnose rapidly given its aggressive course. We present two patients who were treated with ICIs and subsequently developed said syndrome. Both patients experienced significant cardiac and neuromuscular manifestations and despite high‐dose intravenous steroids, intravenous immunoglobulin, and other adjunctive therapies, both patients rapidly deteriorated and elected to withdraw care. Additionally, we review the pathophysiology, diagnosis and management of ICI‐induced myocarditis with myositis/myasthenia gravis overlap syndrome. Overall, the overlap syndrome has a poor prognosis and high mortality rates requiring prompt recognition, discontinuation of ICIs and initiation of immunosuppressive therapies.

Introduction: Genomic variations among individuals can greatly affect their responses to different medications. Pharmacogenomics is the area of study that aims to understand the relationship between these various genetic variations and subsequent drug responses. Many medications used to optimize cardiovascular health are affected by these genetic variants and these relationships can subsequently impact dosing strategies in patients. Objective: This study aims to review the current literature on the clinical applications ofpharmacogenomics for commonly used cardiovascular medications such as Warfarin, Clopidogrel, Statins, Beta Blockers, and ACE-I/ARBs. Methods: Databases like PubMed were accessed to gather background information on pharmacogenomics and to collect data on relationships between genetic variants and subsequent drug response. Information on clinical applications and guidelines was obtained by accessing the CPIC and DPWG databases. Results: This article describes the most up-to-date data on pharmacogenomics relating to commonly used cardiovascular medications. It also discusses the clinical application of pharmacogenomic data as it pertains to medication selection/dosing by detailing current guidelines published by organizations such as the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group. Conclusion: In conclusion, this paper will help medical providers not only better understand pharmacogenomics but also apply it in their day-to-day practice. Clinical guidelines relating to the application of pharmacogenomic data were discussed both in text and graphical format, allowing providers to confidently select medications and adjust doses for common cardiovascular medications so that patients receive the maximum therapeutic benefit with minimal toxicity.

Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan–Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8–6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Objectives: Patients with recurrent and metastatic head and neck cancer (HNC) have limited treatment options. ‘QuadShot’ (QS), a hypofractionated palliative radiotherapy regimen, can provide symptomatic relief and local control and may potentiate the effects of immune checkpoint inhibitors (ICIs). We compared outcomes of QS ± concurrent ICIs in the palliative treatment of HNC. Materials and Methods: We identified patients who received ≥three cycles of QS from 2017 to 2022 and excluded patients without post-treatment clinical evaluation or imaging. Outcomes for patients who received QS alone were compared to those treated with ICI concurrent with QS, defined as receipt of ICI within 4 weeks of QS. Results: Seventy patients were included, of whom 57% received concurrent ICI. Median age was 65.5 years (interquartile range [IQR]: 57.9–77.8), and 50% patients had received prior radiation to a median dose of 66 Gy (IQR: 60–70). Median follow-up was 8.8 months. Local control was significantly higher with concurrent ICIs (12-month: 85% vs. 63%, p = 0.038). Distant control (12-month: 56% vs. 63%, p = 0.629) and median overall survival (9.0 vs. 10.0 months, p = 0.850) were similar between the two groups. On multivariable analysis, concurrent ICI was a significant predictor of local control (HR for local failure: 0.238; 95% CI: 0.073–0.778; p = 0.018). Overall, 23% patients experienced grade 3 toxicities, which was similar between the two groups. Conclusions: The combination of QS with concurrent ICIs was well tolerated and significantly improved local control compared to QS alone. The median OS of 9.4 months compares favorably to historical controls for patients with HNC treated with QS. This approach represents a promising treatment option for patients with HNC unsuited for curative-intent treatment and warrants prospective evaluation.

Background and purpose: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. Materials and methods: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0–69.96). Results: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25–90%). The median dose homogeneity index was 1.07 (range: 1.03–1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0–75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. Conclusions: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

Introduction: Oncology societies have been contributing guidelines/recommendations to the limited yet growing body of literature in cardio-oncology. Research Questions: What are the levels of evidence (LOE) and classes of recommendation (COR) for cardiology-specific recommendations produced by major oncology societies? Methods: We reviewed cardiology-specific recommendations published by the American Society of Clinical Oncology (ASCO), American Society of Hematology (ASoH), NCCN (National Comprehensive Cancer Network), and European Society of Cardiology (ESC). LOE and COR were noted for each recommendation. Results: The US oncologic societies have made 81 cardiac-specific recommendations (ASCO: 54 (67%); ASoH: 14 (17%); NCCN; 13 (16%) (Tables 1-3). For ASCO, 26 (48%) were COR 1, 23 (43%) COR 2, and 5 (9%) COR 3 supported by LOE A (9%), LOE B (39%), and LOE C (52%). For ASoH, 1(8%) was COR 1, 11(85%) COR 2, and 1(8%) COR 3 supported by LOE B (7%), and LOE C (93%). NCCN made 13 COR 2 recommendations and did not provide LOE classification. The most common recommendations addressed baseline (20%) and serial (24%) assessment, specific imaging modalities (9%), chemotherapy dosing (19%), and radiation therapy (20%). Most recommendations were unique without discrepant statements, but there were some redundancies. ESC produced 271 cardio-oncology recommendations (155 COR 1; 111 COR 2; 5 COR-3) with 3% LOE A, 21% LOE B, and 76% LOE C. The major areas for ESC recommendations included baseline (18%) and serial (33%) assessment, and medications (29%). Conclusions: Oncology and cardiology professional society guidelines have provided 352 cardiac related recommendations in the setting of cancer treatment and 73% have the lowest LOE. In this developing field with a limited evidence base, close collaboration between cardiologists and oncologists will be required to provide a cohesive set of recommendations for the cardiac issues associated with cancer treatment.