Improving IMRT delivery efficiency using intensity limits during inverse planning

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135056/1/mp5545.pd

Identifying Patients Whose Symptoms Are Underrecognized During Treatment With Breast Radiotherapy

Importance: Understanding whether physicians accurately detect symptoms in patients with breast cancer is important because recognition of symptoms facilitates supportive care, and clinical trials often rely on physician assessments using Common Toxicity Criteria for Adverse Events (CTCAE). Objective: To compare the patient-reported outcomes (PROs) of patients with breast cancer who received radiotherapy from January 1, 2012, to March 31, 2020, with physicians\u27 CTCAE assessments to assess underrecognition of symptoms. Design, Setting, and Participants: This cohort study included a total of 29 practices enrolled in the Michigan Radiation Oncology Quality Consortium quality initiative. Of 13 725 patients with breast cancer who received treatment with radiotherapy after undergoing lumpectomy, 9941 patients (72.4%) completed at least 1 PRO questionnaire during treatment with radiotherapy and were evaluated for the study. Of these, 9868 patients (99.3%) were matched to physician CTCAE assessments that were completed within 3 days of the PRO questionnaires. Exposures: Patient and physician ratings of 4 symptoms (pain, pruritus, edema, and fatigue) were compared. Main Outcomes and Measures: We used multilevel multivariable logistic regression to evaluate factors associated with symptom underrecognition, hypothesizing that it would be more common in racial and ethnic minority groups. Results: Of 9941 patients, all were female, 1655 (16.6%) were Black, 7925 (79.7%) were White, and 361 (3.6%) had Other race and ethnicity (including American Indian/Alaska Native, Arab/Middle Eastern, and Asian), either as self-reported or as indicated in the electronic medical record. A total of 1595 (16.0%) were younger than 50 years, 2874 (28.9%) were age 50 to 59 years, 3353 (33.7%) were age 60 to 69 years, and 2119 (21.3%) were 70 years or older. Underrecognition of symptoms existed in 2094 of 6781 (30.9%) observations of patient-reported moderate/severe pain, 748 of 2039 observations (36.7%) of patient-reported frequent pruritus, 2309 of 4492 observations (51.4%) of patient-reported frequent edema, and 390 of 2079 observations (18.8%) of patient-reported substantial fatigue. Underrecognition of at least 1 symptom occurred at least once for 2933 of 5510 (53.2%) of those who reported at least 1 substantial symptom. Factors independently associated with underrecognition were younger age (younger than 50 years compared with 60-69 years: odds ratio [OR], 1.35; 95% CI, 1.14-1.59; P \u3c .001; age 50-59 years compared with 60-69 years: OR, 1.19; 95% CI, 1.03-1.37; P = .02), race (Black individuals compared with White individuals: OR, 1.56; 95% CI 1.30-1.88; P \u3c .001; individuals with Other race or ethnicity compared with White individuals: OR, 1.52; 95% CI, 1.12-2.07; P = .01), conventional fractionation (OR, 1.26; 95% CI, 1.10-1.45; P = .002), male physician sex (OR, 1.54; 95% CI, 1.20-1.99; P = .002), and 2-field radiotherapy (without a supraclavicular field) (OR, 0.80; 95% CI, 0.67-0.97; P = .02). Conclusions and Relevance: The results of this cohort study suggest that PRO collection may be essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since physicians in this study systematically missed substantial symptoms in certain patients, including younger patients and Black individuals or those of Other race and ethnicity, improving symptom detection may be a targetable mechanism to reduce disparities

Toward Improving Patients\u27 Experiences of Acute Toxicity From Breast Radiotherapy: Insights From the Analysis of Patient-Reported Outcomes in a Large Multicenter Cohort

PURPOSE: Understanding acute toxicities after whole-breast radiotherapy is important to inform patients, guide treatment decisions, and target supportive care. We evaluated patient-reported outcomes prospectively collected from a cohort of patients with breast cancer. METHODS: We describe the maximal toxicity reported by 8,711 patients treated between 2012 and 2019 at 27 practices. Multivariable models identified characteristics associated with (1) breast pain, (2) bother from itching, stinging/burning, swelling, or hurting of the treated breast, and (3) fatigue within 7 days of completing whole-breast radiotherapy. RESULTS: Moderate or severe breast pain was reported by 3,233 (37.1%): 1,282 (28.9%) of those receiving hypofractionation and 1,951 (45.7%) of those receiving conventional fractionation. Frequent bother from at least one breast symptom was reported by 4,424 (50.8%): 1,833 (41.3%) after hypofractionation and 2,591 (60.7%) after conventional fractionation. Severe fatigue was reported by 2,008 (23.1%): 843 (19.0%) after hypofractionation and 1,165 (27.3%) after conventional fractionation. Among patients receiving hypofractionated radiotherapy, younger age (P \u3c .001), higher body mass index (BMI; P \u3c .001), Black (P \u3c .001) or other race (P = .002), smoking status (P \u3c .001), larger breast volume (P = .002), lack of chemotherapy receipt (P = .004), receipt of boost treatment (P \u3c .001), and treatment at a nonteaching center predicted breast pain. Among patients receiving conventionally fractionated radiotherapy, younger age (P \u3c .001), higher BMI (P = .003), Black (P \u3c .001) or other race (P = .002), diabetes (P = .001), smoking status (P \u3c .001), and larger breast volume (P \u3c .001) predicted breast pain. CONCLUSION: In this large observational data set, substantial differences existed according to radiotherapy dose fractionation. Race-related differences in pain existed despite controlling for multiple other factors; additional research is needed to understand what drives these differences to target potentially modifiable factors. Intensifying supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity

Use of Chemotherapy in Patients Receiving Hypofractionated Whole-Breast Irradiation: An Analysis within a State-Wide Quality Consortium

Purpose/Objective(s): Randomized clinical trials support the use of hypofractionated whole breast irradiation (H-WBI) in select patients with early stage breast cancer following breast conserving surgery. Patients who received chemotherapy (CHT) are not well represented on these trials. This study investigates whether receiving CHT prior to WBI is associated with increased toxicity or worse cosmetic outcomes. Materials/Methods: We identified 7,014 women in a state-wide radiation oncology quality consortium database who received WBI with a surgical cavity boost between 11/2011 and 8/2018. Toxicity data were available for 6,870 patients. Significant acute toxicity was defined as patient-reported moderate/severe breast pain (≥4/10), physician-reported CTCAE ≥grade 2 breast pain, or the development of moist desquamation between 7 days prior to and 42 days following the completion of radiotherapy. We determined rates of physician-reported fair/poor cosmetic outcome per the Harvard criteria in 2,012 patients who had ≥1 year of follow-up. Rates of significant acute toxicity and fair/poor cosmetic outcome were compared among patients receiving conventionally fractionated treatment (C-WBI) or H-WBI. Multivariable modeling, adjusting for age, race, BMI, breast volume, separation along the central axis, comorbidity index, smoking status, radiation planning technique, breast D50, triple negative breast cancer, pTis disease, treatment at an academic institution, and receipt of CHT, were used to quantify the strength of association, given as an odds ratio [95%CI], between patient or treatment related factors and clinical endpoints. Results: C-WBI and H-WBI most commonly comprised 45-50.4 Gy in 25-28 fractions and 40-42.72 Gy in 15-16 fractions, respectively. A boost of 10-16 Gy in 5-8 fractions and 10 in 4 fractions was most common for C-WBI and H-WBI, respectively. CHT was administered prior to radiation therapy in 1266 (35%) of the 3,628 patients who received C-WBI and in 558 (17%) of the 3,242 patients who received H-WBI. Crude rates of significant acute toxicity were 43% and 40% for patients receiving CHT followed by C-WBI and C-WBI without CHT, respectively, and 29% and 27% for patients receiving CHT followed by H-WBI and H-WBI without CHT, respectively. CHT was not associated with worse acute toxicity for patients receiving C-WBI (OR=0.94 [0.79-1.12], p=0.50) or H-WBI (OR=0.79 [0.63-1.00], p=0.054). CHT was not associated with increased rates of fair/poor cosmetic outcomes at 1 year (OR=1.21 [0.82-1.78], p=0.33), independent of fractionation. Conclusion: In this large, multi-center cohort, rates of significant acute toxicity and fair/poor cosmetic outcomes were not worse in patients receiving chemotherapy prior to whole breast irradiation, compared to patients who did not receive chemotherapy, regardless of fraction size

The impact of chemotherapy on toxicity and cosmetic outcome in patients receiving whole breast irradiation: an analysis within a state-wide quality consortium

PURPOSE: We investigated whether the use of chemotherapy prior to whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxicity or worse cosmetic outcome compared to WBI alone. METHODS AND MATERIALS: We identified 6,754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a state-wide consortium. We reported rates of four toxicity outcomes: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxicity measure (including moist desquamation and either patient-reported or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at one year following WBI. Successive multivariable models were constructed to estimate the impact of chemotherapy on these outcomes. RESULTS: Rates of moist desquamation, patient-reported pain, composite acute toxicity, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2,859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3,895 patients receiving HWBI. Receipt of chemotherapy prior to CWBI was not associated with higher rates of patient-reported pain, composite acute toxicity, or impaired cosmetic outcome compared to CWBI without chemotherapy but was associated with more moist desquamation (OR=1.32 [1.07-1.63], p=0.01). Receipt of chemotherapy prior to HWBI was not associated with higher rates of any of the four toxicity outcomes compared to HWBI alone. CONCLUSIONS: In this cohort, use of chemotherapy prior to WBI was generally well tolerated. CWBI with chemotherapy, but not to HWBI with chemotherapy, was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at one year were comparable in patients receiving chemotherapy prior to either CWBI or HWBI. These data support the use of HWBI following chemotherapy

Time trends and predictors of heart dose from breast radiation therapy in a large consortium of community and academic practices

Observational studies suggest that the risk of cardiac toxicity increases with increasing radiation dose to the heart, without a threshold for this effect. Although a recent systematic review summarized heart doses in the published literature, less is known about the range of heart doses delivered in routine practice in the United States today. The goal of this study was to assess the current state of cardiac sparing in a large prospective observational cohort, and to determine how cardiac dose varies by practice setting, technique, and patient characteristics

Are We Missing Acute Toxicities Associated with Hypofractionated Breast Irradiation? A Report from a Large Multi-Center Cohort Study

Purpose/Objective(s): The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) has been established through multiple randomized trials. However, data on acute toxicities associated with HF-WBI remain more limited. Since 2013, our group has prospectively collected data on acute toxicities associated with HF-WBI based on weekly evaluation during treatment and assessment at 1 month after completion of radiotherapy. In October 2015, we intentionally shifted the post-treatment assessment time-point from 1 month to 2 weeks post-completion of treatment. This change was intended to evaluate whether a closer follow-up (f/u) might result in the detection of otherwise unobserved acute toxicities for patients receiving HF-WBI. In this study we report whether 2-week f/u has resulted in increased sensitivity for detecting acute toxicity as compared with 4-wk f/u. Materials/Methods: We prospectively compared acute toxicity for patients treated with HF-WBI at 25 participating institutions. We compared patients treated between 1/1/2013 and 8/31/2015 (before 2-week f/u up was adopted – “4 wk f/u cohort”) to patients treated between 1/1/2016 – 8/31/2018 (after adoption of a 2-week f/u – “2 wk f/u cohort”). Acute toxicity was considered the maximum reported composite toxicity from 7 days prior to the completion of radiotherapy until 42 days (6 weeks) following completion. Composite toxicity was defined as self-reported or physician-assessed moderate or severe breast pain, and/or physician-assessed presence of moist desquamation. Multivariable logistic regression models were used to assess difference in toxicity by cohort using ASTRO HF-WBI 2018 Guideline v. 2011 Guideline, and further adjusted for BMI, breast volume, race, presence of comorbidity, smoking status, and use of IMRT. Results: 2243 patients who received post-lumpectomy radiation and boost were analyzed, 1369 patients in the 2-wk f/u cohort and 874 in the 4-wk f/u cohort. Occurrence of composite acute toxicity was similar between the 2 cohorts, 28.4% for 2-wk f/u cohort vs 26.9% for the 4-wk f/u cohort, adjusted p=0.66. When analyzing only patients who met all ASTRO HF-WBI Guideline v. 2011 criteria, no difference in acute toxicity was noted; 26.5% with 2-wk f/u vs 25.0% with 4-wk f/u, adjusted p=0.83. Finally, with 2 wk f/u compared with 4 wk f/u, additional acute toxicities were not detected for patients who were younger \u3c50 years (p=0.72), received chemotherapy (p=0.93), had ductal carcinoma in-situ (p=0.13), or had separation \u3e25 cm, (p=0.43), yet otherwise guideline compliant. Conclusion: A closer post-treatment follow-up for patients receiving HF-WBI did not reveal a significant increased incidence of acute toxicities at 2 weeks compared to 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI and the appropriateness of the interval of follow-up