Selective de-implementation of routine in vivo dosimetry.

As cone-beam computed tomography (CBCT) has become the localization method for a majority of cases, the indications for diode-based confirmation of accurate patient set-up and treatment are now limited and must be balanced between proper resource allocation and optimizing efficiency without compromising safety. We undertook a de-implementation quality improvement project to discontinue routine diode use in non-intensity modulated radiotherapy (IMRT) cases in favor of tailored selection of scenarios where diodes may be useful. After analysis of safety reports from the last 5 years, literature review, and stakeholder discussions, our safety and quality (SAQ) committee introduced a recommendation to limit diode use to specific scenarios in which in vivo verification may add value to standard quality assurance (QA) processes. To assess changes in patterns of use, we reviewed diode use by clinical indication 4 months prior and after the implementation of the revised policy, which includes use of diodes for: 3D conformal photon fields set up without CBCT; total body irradiation (TBI); electron beams; cardiac devices within 10 cm of the treatment field; and unique scenarios on a case-by-case basis. We identified 4459 prescriptions and 1038 unique instances of diode use across five clinical sites from 5/2021 to 1/2022. After implementation of the revised policy, we observed an overall decrease in diode use from 32% to 13.2%, with a precipitous drop in 3D cases utilizing CBCT (from 23.2% to 4%), while maintaining diode utilization in the 5 selected scenarios including 100% of TBI and electron cases. By identifying specific indications for diode use and creating a user-friendly platform for case selection, we have successfully de-implemented routine diode use in favor of a selective process that identifies cases where the diode is important for patient safety. In doing so, we have streamlined patient care and decreased cost without compromising patient safety.

Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations.

The KEYNOTE-522 study is a practice-changing phase III randomized study that demonstrated that the addition of pembrolizumab to polychemotherapy improves outcomes in patients with high-risk early-stage triple-negative breast cancer (TNBC). This regimen is highly efficacious with unprecedented pathologic complete response (pCR) rates, and clinically meaningful improvements in event-free survival (EFS). However, the combination is also associated with significant high-grade treatment-related toxicity. The backbone regimen deviated from common practice, including the addition of carboplatin, lack of dose dense anthracyclines, and adjuvant capecitabine for residual disease, thus brining important questions regarding real-world translation of these results. This brief report practically addresses some of the most relevant questions physicians and patients face in optimizing care using the best available evidence.

Breast cancer survivorship care plans: what are they covering and how well do they align with national guidelines?

PURPOSE: Survivorship care plans (SCPs) provide key information about cancer treatment history and follow-up recommendations. We describe the completeness of breast cancer SCPs and evaluate guideline concordance of follow-up recommendations. METHODS: We analyzed 149 breast cancer SCPs from two sites, abstracting demographics, cancer/treatment details, surveillance plans, and health promotion advice. SCP recommendations and provided information were compared to American Cancer Society/American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in > 90% of the plans included patient age; relevant providers; cancer stage; treatment details; and physical exam, mammogram, and health promotion recommendations. SCP components completed less frequently included post-treatment symptoms/side effects (67%). All SCPs at the community site were uniform but had the potential for oversurveillance if visits occurred every 3 months in years 1-2 or every 6 months in years 3-5 with multiple cancer providers. The academic site recommended three predominant patterns of follow-up: (1) primary care provider every 6-12 months; (2) cancer team every 3-6 months (year 1), every 6-12 months (years 4-5); and (3) alternating oncology providers every 3-6 months (years 1-2) then every 6 months. Compared to guidelines, these patterns recommend under- and oversurveillance at various times. Mammography recommendations showed guideline concordance (annual) for 84%, oversurveillance for 10%, and were incomplete for 6%. SCPs of only 12/79 (15%) women on aromatase inhibitors recommended guideline-concordant bone density testing. CONCLUSIONS: SCP content is more complete for demographic and treatment summary information but has follow-up recommendation gaps. Efforts to improve follow-up recommendations are needed.

Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study.

BACKGROUND: Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the molecular mechanisms of RT-related pain remain unclear. The current study aimed to identify susceptibility loci and enriched pathways for clinically relevant acute post-RT pain, defined as having moderate to severe pain (pain score ≥ 4) at the completion of RT. METHODS: We conducted a genome-wide association study (GWAS) with 1,344,832 single-nucleotide polymorphisms (SNPs), a gene-based analysis using PLINK set-based tests of 19,621 genes, and a functional enrichment analysis of a gene list of 875 genes with p < 0.05 using NIH DAVID functional annotation module with KEGG pathways and GO terms (n = 380) among 1112 breast cancer patients. RESULTS: About 29% of patients reported acute post-RT pain. None of SNPs nor genes reached genome-wide significant level. Four SNPs showed suggestive associations with post-RT pain; rs16970540 in RFFL or near the LIG3 gene (p = 1.7 × 10-6), rs4584690, and rs7335912 in ABCC4/MPR4 gene (p = 5.5 × 10-6 and p = 7.8 × 10-6, respectively), and rs73633565 in EGFL6 gene (p = 8.1 × 10-6). Gene-based analysis suggested the potential involvement of neurotransmitters, olfactory receptors, and cytochrome P450 in post-RT pain, whereas functional analysis showed glucuronidation (FDR-adjusted p value = 9.46 × 10-7) and olfactory receptor activities (FDR-adjusted p value = 0.032) as the most significantly enriched biological features. CONCLUSIONS: This is the first GWAS suggesting that post-RT pain is a complex polygenic trait influenced by many biological processes and functions such as glucuronidation and olfactory receptor activities. If validated in larger populations, the results can provide biological targets for pain management to improve cancer patients' quality of life. Additionally, these genes can be further tested as predictive biomarkers for personalized pain management.

Acute toxicity outcomes and dosimetric implications from incidental irradiation of adjacent tissues in tangent field hypofractionated breast radiotherapy.

PURPOSE: Adjacent tissues-in-beam (TIB) may receive substantial incidental doses within standard tangent fields during hypofractioned whole breast irradiation (HF-WBI). To characterize the impact of dose to TIB, we analyzed dosimetric parameters of TIB and associated acute toxicity. MATERIALS AND METHODS: Plans prescribed to 40.5 Gy/15 fractions from 4/2016-1/2018 were evaluated. Structures of interest were contoured: (1) TIB: all tissues encompassed by plan 30% isodose lines, (2) breast, (3) non-breast TIB (nTIB): TIB minus contoured breast. Volumes of TIB, breast, and nTIB receiving 100%-107% of prescription dose (V100-V107) were calculated. Twelve patient- and physician-reported acute toxicities were prospectively collected weekly. Correlations between volumetric and dosimetric parameters were assessed. Uni- and multivariable logistic regressions evaluated toxicity grade changes as a function of TIB, breast, and nTIB V100-V107 (in cm3). RESULTS: We evaluated 137 plans. Breast volume was positively correlated with nTIB and nTIB V100 (rho = 0.52, rho = 0.30, respectively, both p < 0.001). V107 > 2 cm3 were noted in 14% of breast and 21% of nTIB volumes. On multivariable analyses, increasing breast and nTIB V100 significantly raised odds of grade 2+ dermatitis and burning/twinging pain, respectively; increasing nTIB V105 elevated odds of hyperpigmentation and burning pain; and increasing nTIB V107 raised odds of burning pain. Threshold volumes for >6-fold odds of developing burning pain were TIB V105 > 100 cm3 and V107 > 5 cm3. CONCLUSIONS: For HF-WBI, doses to nTIB over the prescription predicted acute toxicities independent of breast doses. These data support inclusion of TIB as a region of interest in treatment planning and protocol design.

Association between C-reactive protein and radiotherapy-related pain in a tri-racial/ethnic population of breast cancer patients: a prospective cohort study.

BACKGROUND: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer. METHODS: During 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for pre- and post-RT pain. Pre- and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain. RESULTS: In 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre- and post-RT pain, while 23% of patients had RT-related pain. Both pre- and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RT-related pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity. CONCLUSIONS: This is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

PURPOSE: Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). METHODS: Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1-5 fractions of 5-18 Gray. Kaplan-Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated. RESULTS: In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ≥ grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. CONCLUSIONS: Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.

Adoption of an incident learning system in a regionally expanding academic radiation oncology department.

AIM AND BACKGROUND: We describe a successful implementation of a departmental incident learning system (ILS) across a regionally expanding academic radiation oncology department, dovetailing with a structured integration of the safety and quality program across clinical sites. MATERIALS AND METHODS M: Over 6 years between 2011 and 2017, a long-standing departmental ILS was deployed to 4 clinical locations beyond the primary clinical location where it had been established. We queried all events reported to the ILS during this period and analyzed trends in reporting by clinical site. The chi-square test was used to determine whether differences over time in the rate of reporting were statistically significant. We describe a synchronous development of a common safety and quality program over the same period. RESULTS: There was an overall increase in the number of event reports from each location over the time period from 2011 to 2017. The percentage increase in reported events from the first year of implementation to 2017 was 457% in site 1, 166.7% in site 2, 194.3% in site 3, 1025% in site 4, and 633.3% in site 5, with an overall increase of 677.7%. A statistically significant increase in the rate of reporting was seen from the first year of implementation to 2017 (p < 0.001 for all sites). CONCLUSIONS: We observed significant increases in event reporting over a 6-year period across 5 regional sites within a large academic radiation oncology department, during which time we expanded and enhanced our safety and quality program, including regional integration. Implementing an ILS and structuring a safety and quality program together result in the successful integration of the ILS into existing departmental infrastructure.

Impact of race, ethnicity, and socioeconomic factors on receipt of radiation after breast conservation surgery: analysis of the national cancer database.

INTRODUCTION: Many eligible women with invasive breast cancer do not receive recommended adjuvant radiation (RT), despite its role in local control and overall survival. We examined trends in RT use over 10 years, and the impact of sociodemographic factors on the receipt of standard-of-care RT, using the National Cancer Database (NCDB). MATERIALS/METHODS: Women under age 70 with invasive breast cancer who underwent BCS from 2004 to 2014 were analyzed. Receipt of RT was evaluated in the whole cohort and by time period to identify temporal trends. Multiple logistic regression models were used to assess associations between factors such as race, insurance status, ethnicity, and receipt of RT. RESULTS: A total of 501,733 patients met eligibility criteria. The percentage of patients undergoing adjuvant RT increased from 86.7% in 2004 to 92.4% in 2012, and then decreased in 2013 and 2014 to 88.9%. On univariate analysis, patients of white race were significantly more likely to receive RT compared with patients of black race (90.4% vs 86.9%, p < 0.0001), as were non-Hispanic women compared to Hispanic patients (90.2% vs. 85.3%, p < 0.0001). On multivariate analysis, race, ethnicity, insurance status, education level, and age remained significantly associated with receipt of RT. On temporal analysis, gaps remained stable, with no significant improvements over time. CONCLUSIONS: This analysis suggests a recent decline in guideline-concordant receipt of RT in women under 70, and persistent disparities in the use of RT after BCS by race, ethnicity, and socioeconomic factors. These findings raise concern for a recent detrimental change in patterns of care delivery.

Bringing Big Data to the Forefront of Healthcare Delivery: The Experience of Carolinas HealthCare System.

The use of big data to transform care delivery is rapidly becoming a reality. To deliver on the promise of value-based care, providers must know the key drivers of wellness at the patient and community levels, as well as understand resource constraints and opportunities to improve efficiency in the health-care system itself. Data are the linchpin. By gathering the right data and finding innovative ways to glean knowledge, we can improve clinical care, advance the health of our communities, improve the lives of our patients, and operate more efficiently. At Carolinas HealthCare System-one of the nation's largest health-care systems, with nearly 12 million patient encounters annually at more than 900 care locations-we have made substantial investments to establish a centralized data and analytics infrastructure that is transforming the way we deliver care across the continuum. Although the impetus and vision for our program have evolved over the past decade, our efforts coalesced into a strategic, centralized initiative with the launch of the Dickson Advanced Analytics (DA) group in 2012. DA has yielded significant gains in our ability to use data, not only for reporting purposes and understanding our business but also for predicting outcomes and informing action.While these efforts have been successful, the path has not been easy. Effectively harnessing big data requires navigating myriad technological, cultural, operational, and other hurdles. Building a program that is feasible, effective, and sustainable takes concerted effort and a rigorous process of continuous self-evaluation and strategic adaptation.

Adjuvant radiation use in older women with early-stage breast cancer at Johns Hopkins.

PURPOSE: In 2004, The National Comprehensive Cancer Network (NCCN) Guidelines incorporated omission of radiation therapy after breast-conservation surgery in women ≥70 years old with stage I, estrogen receptor-positive breast cancer who plan to receive endocrine therapy. One study demonstrated wide variation in implementing this change across 13 NCCN institutions. We evaluated the practice pattern at our institution. METHODS: We identified women ≥70 years old treated at our institution from 2009 to 2014. We calculated radiation therapy omission rate in those meeting the guidelines. We explored associations between radiation therapy omission, year of diagnosis, and patient characteristics with Wilcoxon rank sum tests and Fisher's exact tests. RESULTS: A total of 667 women met the inclusion criteria, and 117 (18 %) were candidates for radiation therapy omission. Mean age among the 117 was 76.3 years (Range: 70-95). Overall radiation therapy omission rate was 36.8 %, but varied greatly by year of diagnosis (Range: 7.7-54.5 %). This variation persisted after excluding women who did not receive endocrine therapy (Mean: 39.0 %, Range: 0.0-75.0 %). Factors associated with higher radiation therapy omission rates included older age and not having pathological nodal evaluation. The radiation therapy omission rate did not vary by race, tumor type, grade, or size. CONCLUSIONS: The implementation of the NCCN guideline has not been consistent at our institution. Our data suggest that other tools should be considered to apply the guidelines more consistently. We have implemented a quality improvement protocol that incorporates life expectancy estimate and geriatric assessment in women meeting the NCCN guideline at our institution.

FDG Avidity and Tumor Burden: Survival Outcomes for Patients With Recurrent Breast Cancer.

OBJECTIVE: The objective of this study was to assess the value of quantitative PET parameters in the prediction of survival for patients with recurrent breast cancer. MATERIALS AND METHODS: We conducted a retrospective study of 78 women who had recurrent breast cancer identified by biopsy or follow-up examinations from 2000 to 2012. The maximum and peak standardized uptake values (SUVmax and SUVpeak, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for each recurrent lesion at primary, nodal, and distant metastatic sites, with the use of the gradient segmentation method. The optimum cutoff point (i.e., the value with the maximum Youden index, defined as sensitivity plus specificity minus 1) was calculated using the ROC curve. The median follow-up duration was 28.5 months (range, 0-94 months). The primary outcome measure was overall survival (OS). Kaplan-Meier survival plots and Cox regression analyses were performed. RESULTS: The mean (± SD) values noted for the study population were as follows: an SUVmax of 6.70 ± 4.1, an SUVpeak of 5.12 ± 3.4, total lesion glycolysis of all recurrent lesions (TLGtotal) of 359.73 ± 1114.4 g, and metabolic tumor volume of all recurrent lesions (MTVtotal) of 68.04 ± 144.9 mL. The mean OS for patients who died was 25.5 months, whereas for patients who survived, it was 36.7 months (p = 0.04). Univariate analysis showed that age (p = 0.02), optimum SUVmax (p = 0.006), SUVpeak (p = 0.006), and TLGtotal (p = 0.034) were associated with OS; however, none of the factors remained statistically significant in multivariate analysis. Kaplan-Meier survival analysis was performed, and the SUVmax (threshold, 2.9; hazard ratio [HR], 5.2 [95% CI, 1.6-16.7]; p = 0.002), SUVpeak (threshold, 2.34; HR, 4.3 [95% CI, 1.5-12]; p = 0.002), and TLG (threshold, 11.85 g; HR, 2.8 [95% CI, 1.0-7.1]; p = 0.025) were statistically significant predictors of death during follow-up. An integrated risk stratification model with FDG avidity (SUVmax) and MTVtotal divided into three subgroups of patients predicted patient survival outcomes (HR, 2.48 [95% CI, 1.38-4.46]; p = 0.005, by log-rank test). CONCLUSION: FDG PET-determined SUVmax, SUVpeak, and TLG values and an integrated risk stratification scheme using FDG avidity and total tumor burden appear to provide prognostic survival information for patients with recurrent breast cancer.

Intrathoracic extensive-stage small cell lung cancer: assessment of the benefit of thoracic and brain radiotherapy using the SEER database.

BACKGROUND: Extensive-stage small cell lung cancer (ESCLC) includes metastatic disease and locally advanced disease confined to the thorax that cannot be encompassed in a typical radiation portal. We assessed and then compared the benefits of thoracic radiotherapy (TRT) and/or brain radiotherapy (BRT) on overall survival (OS) between the intrathoracic (T-ESCLC) and metastatic (M-ESCLC) groups using the Surveillance Epidemiology and End Results database. METHODS: TRT and BRT data were available for 10150 patients treated from 1988-1997. The T-ESCLC group included 1774 patients. The Kaplan-Meier method was used to estimate OS and the proportional hazards model was used to estimate OS hazard ratios for prognostic factors including age, gender, race, tumor size, T/N stage, TRT, and BRT. RESULTS: The 2-year OS for T-ESCLC was 7.8 % compared to 3 % in the M-ESCLC group (p < 0.001). In the T-ESCLC group, TRT and BRT were delivered to 750 and 102 patients, respectively. The 2-year OS was 13 % in the TRT group compared to 4.1 % in the no-TRT group (p ≤ 0.001) and 22.5 % in the BRT group compared to 7 % in the no-BRT group (p < 0.001). In the M-ESCLC group, TRT and BRT were delivered to 3093 and 1887 patients, respectively. The 2-year OS was 4.4 % in the TRT group compared to 2.8 % in the no-TRT group (p < 0.001) and 4.3 % in the BRT compared to 2.6 % in the no-BRT group (p < 0.001). Age, gender, TRT and BRT were significant OS prognostic factors in both groups. CONCLUSIONS: Our study suggests that T-ESCLC is a disease entity distinct from M-ESCLC. Prospective studies to determine whether TRT should be recommended for the thoracic-only subgroup are warranted.

Bringing Big Data to the Forefront of Healthcare Delivery: The Experience of Carolinas HealthCare System.

The use of big data to transform care delivery is rapidly becoming a reality. To deliver on the promise of value-based care, providers must know the key drivers of wellness at the patient and community levels, as well as understand resource constraints and opportunities to improve efficiency in the healthcare system itself. Data are the linchpin. By gathering the right data and finding innovative ways to glean knowledge, we can improve clinical care, advance the health of our communities, improve the lives of our patients, and operate more efficiently. At Carolinas HealthCare System-one of the nation's largest healthcare systems, with nearly 12 million patient encounters annually at more than 900 care locations-we have made substantial investments to establish a centralized data and analytics infrastructure that is transforming the way we deliver care across the continuum. Although the impetus and vision for our program have evolved over the past decade, our efforts coalesced into a strategic, centralized initiative with the launch of the Dickson Advanced Analytics (DA2) group in 2012. DA2 has yielded significant gains in our ability to use data, not only for reporting purposes and understanding our business but also for predicting outcomes and informing action.While these efforts have been successful, the path has not been easy. Effectively harnessing big data requires navigating myriad technological, cultural, operational, and other hurdles. Building a program that is feasible, effective, and sustainable takes concerted effort and a rigorous process of continuous self-evaluation and strategic adaptation.

Neoadjuvant Therapy for Early-Stage Breast Cancer: Current Practice, Controversies, and Future Directions.

Research in the fields of surgical, medical, and radiation oncology has changed the landscape of neoadjuvant therapy in breast cancer, yet many areas of controversy still exist. When considering whether a patient is a candidate for neoadjuvant therapy, ideally the initial assessment should be multidisciplinary in nature and should include clinical, radiographic, and pathologic evaluation. Optimization of systemic therapy is dependent upon identifying the patient's breast cancer subtype; the best approach may include targeted agents, as well as the determination of eligibility for enrollment into clinical trials that incorporate novel therapeutics or predictive biomarkers. This article will review a variety of surgical and radiation-based strategies for management of early-stage breast cancer, including surgical options involving the breast and axilla, and the role of radiation based on response to systemic therapy. Key areas of controversy include the ideal systemic treatment for different breast cancer subtypes, the surgical and radiotherapeutic approaches for management of the axilla, and the role of pathologic response rates as a surrogate for survival in drug development.

Racial and ethnic disparities in the diagnosis of breast cancer: changes in presenting stage in minority populations in Florida during 1981-2009.

We assessed whether presenting breast cancer stage has changed over time in Florida, and whether there is variation in this change with respect to race, ethnicity, and socioeconomic status (SES). Data were obtained from the Florida Cancer Data System. We included females with invasive breast cancer and complete information on race, ethnicity, and SES during 1981-2009 (n = 226,651). Associations between categorical variables were examined using Chi-square tests. Predictors of SEER stage at diagnosis (local, regional, and distant) were modeled with multinomial ordinal logistic regression models. There was a significant increase in local disease and a decrease in regional and distant disease at presentation (p < 0.0001) over the time period assessed. Compared to whites, black patients continue to have lower odds of local presentation (OR 0.73, 95% CI 0.63, 0.85), as do Hispanic patients (OR 0.80, 95% CI 0.76, 0.84) compared to non-Hispanics. The increase in local stage at diagnosis was greater for black than white patients, as was the decrease in regional and distant disease (p < 0.001). Hispanic women also had significant increase in localized disease and decrease in regional and distant disease (p < 0.001), but there was little difference in the change compared to non-Hispanic women. Localized breast cancer stage at diagnosis has become more common over time in all groups. Significant disparity persists, with black and Hispanic patients being less likely to present with localized disease than white patients overall. There was a greater change for black versus white patients, resulting in a narrowing in the racial gap in stage at diagnosis.

The Peaks and Valleys of Photon Versus Proton Spatially Fractionated Radiotherapy.

Spatially-fractionated radiotherapy (SFRT) delivers high doses to small areas of tumor while sparing adjacent tissue, including intervening disease. In this review, we explore the evolution of SFRT technological advances, contrasting approaches with photon and proton beam radiotherapy. We discuss unique dosimetric considerations and physical properties of SFRT, as well as review the preclinical literature that provides an emerging understanding of biological mechanisms. We emphasize crucial areas of future study and highlight clinical trials that are underway to assess SFRT's safety and efficacy, with a focus on immunotherapeutic synergies. The review concludes with practical considerations for SFRT's clinical application, advocating for strategies that leverage its unique dosimetric and biological properties for improved patient outcomes.

Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study.

We report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104). The Kaplan-Meier method was used to estimate time-to-event distributions. Cox proportional hazard methods were used to estimate hazard ratios (HRs) and tests for significance for event times. 561 patients were enrolled in cohort 1 and 104 in cohort 2. After central pathology review, 26% in cohort 1 were recategorized as high-grade and 26% in cohort 2 as low- or intermediate-grade. Mean DCIS size was similar at 7.5 mm in cohort 1 and 7.8 mm in cohort 2. Surgical margin was ≥3 mm in 96% of patients, and about 30% received tamoxifen. Median follow-up was 19.2 years. There were 104 IBEs, of which 54 (52%) were invasive. The IBE and invasive IBE rates increased in both cohorts up to 15 years, then plateaued. The 20-year IBE rates were 17.8% for cohort 1 and 28.7% for cohort 2 (p = 0.005), respectively. Invasive IBE occurred in 9.8% and 15.1% (p = 0.09), respectively. On multivariable analysis, IBE risk increased with size and was higher in cohort 2, but grade and margin width were not significantly associated with IBE. For patients with DCIS treated with excision without radiation, the rate of IBE increased with size and assigned cohort mostly in the first 15 years.

Omission of Radiotherapy After Breast-Conserving Surgery for Women With Breast Cancer With Low Clinical and Genomic Risk: 5-Year Outcomes of IDEA.

PURPOSE: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors. METHODS: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS. RESULTS: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively. CONCLUSION: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project.

INTRODUCTION: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. METHODS AND ANALYSIS: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently.The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. ETHICS AND DISSEMINATION: Ethical approval for the consensus process will be obtained from the Queen's University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. REGISTRATION: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854).