Locoregional Ablative Radiation Therapy for Patients With Breast Cancer Unsuitable for Surgical Resection.

PURPOSE: Patients with breast cancer who are unsuitable for surgical resection are typically managed with palliative systemic therapy alone. We report outcomes of 5-fraction ablative radiation therapy for nonresected breast cancers. METHODS AND MATERIALS: This is a retrospective analysis of an institutional registry of patients with breast cancer who were unsuitable for resection and underwent 35 to 40 Gy/5 fractions to the primary breast tumor or regional lymph nodes from 2014 to 2021. Primary outcomes were cumulative incidence of local failure and grade ≥3 toxicity (Common Terminology Criteria for Adverse Events, version 5.0). RESULTS: We reviewed 57 patients who received 61 treatment courses (median age of 81 years; range, 38-99). Unresectable tumor (10%), patient refusal (18%), medical inoperability (35%), and metastatic disease (37%) were the causes of not having surgery. Five patients (8%) had previously undergone adjuvant locoregional radiation therapy. Fifty-four percent (n = 33/61) of treatment courses targeted the breast only, 31% (n = 19/61) both the breast and lymph nodes, and 15% (n = 9/61) the lymph nodes only. Sixty-seven percent (n = 35/52) of the courses that targeted the breast were delivered with partial breast irradiation and 33% (n = 17/52) with whole breast radiation therapy (median dose of 25 Gy in 5 fractions) ± simultaneous integrated boost to the primary tumor. Most primary tumors (65%, n = 34/52) and target lymph nodes (61%, n = 17/28) were treated with a dose of 35 Gy in 5 fractions. Most treatments (52%) were delivered with intensity modulated radiation therapy (IMRT). Radiation therapy was delivered daily (20%), every other day (18%), twice weekly (36%), or weekly (26%). The 2-year cumulative incidence of local failure was 11.4% and grade≥3 toxicity was 15.1%. The grade ≥3 toxicity was 6.5% for IMRT treatments, versus 7.7% for non-IMRT treatments targeting partial breast or lymph nodes (hazard ratio, 1.13, P = .92), versus 38.9% for non-IMRT treatments targeting the entire breast (hazard ratio, 6.91, P = .023). All grade ≥3 toxicity cases were radiation dermatitis. No cases of brachial plexopathy were observed. CONCLUSIONS: Thirty-five to 40 Gy in 5 fractions is a safe and effective breast stereotactic body radiation therapy (SBRT) regimen and may be an attractive option for patients who are not surgical candidates. Highly conformal techniques (ie, IMRT or partial breast irradiation) were associated with a reduced risk of toxicity and should be the preferred treatment approaches.

Treatment times for delivering adjuvant breast radiotherapy at a cancer centre in Ontario, Canada.

BACKGROUND: Time is a valuable commodity that impacts hospital flow, patient experience and economic resources. This study aims to identify factors that affect daily treatment time over a course of radiation therapy (RT) in patients who underwent adjuvant breast RT. METHODS: In all adjuvant breast/chestwall RT patients treated from October 2017 to May 2018, daily set-up, beam delivery time, and overall treatment times were collected. A multivariable linear regression analysis was conducted to identify significant predictive factors related to treatment time. A general linear regression model was used to determine whether there was a learning curve effect throughout the course of treatment that decreased treatment time as patient and staff familiarity with the treatment procedure increased. RESULTS: A total of 567 patients were included with a median age of 61 years. The average overall treatment time for 2-field and 4-field RT was 8.3 (SD 2.4) and 13.1 (SD 5.6) minutes, respectively. Factors that significantly increased overall treatment times in patients prescribed 2-field RT were: bilateral techniques, breath-hold (BH) techniques, prone techniques (PR), reverse decubitus techniques (RD), wide tangents techniques, the use of bolus and number of segments delivered. (p < 0.05). Factors that significantly increased overall treatment times in patients who received 3-field and 4-field RT were: wide tangents volumes, a higher number of monitor units (MUs), bilateral techniques and BH techniques (p < 0.05). Older patients (≥60) who underwent 3-field and 4-field RT demonstrated a statistically significant increase in set-up time (p < 0.0001). Overall treatment time decreased from 10.0 to 9.3 min over the course of treatment, suggesting a minor learning curve (p = 0.009). CONCLUSION: The use of bilateral RT, BH, PR, RD, wide tangents, bolus, increasing treatment volumes, and increasing plan complexity were associated with increased treatment times. Future research should quantify the impact of other factors (BMI, mobility, patient care assessments, and imaging protocols) and utility of technological tools (time-predicting models, machine learning tools, and operations research models) on treatment time to optimize RT scheduling and improve resource management.

Effect of Supine vs Prone Breast Radiotherapy on Acute Toxic Effects of the Skin Among Women With Large Breast Size: A Randomized Clinical Trial.

Importance: Women with large breast size treated with adjuvant breast radiotherapy (RT) have a high rate of acute toxic effects of the skin. Breast RT in the prone position is one strategy that may decrease these toxic effects. Objective: To determine if breast RT in the prone position reduces acute toxic effects of the skin when compared with treatment in the supine position. Design, Setting, and Participants: This phase 3, multicenter, single-blind randomized clinical trial accrued patients from 5 centers across Canada from April 2013 to March 2018 to compare acute toxic effects of breast RT for women with large breast size (bra band ≥40 in and/or ≥D cup) in the prone vs supine positions. A total of 378 patients were referred for adjuvant RT and underwent randomization. Seven patients randomized to supine position were excluded (5 declined treatment and 2 withdrew consent), and 14 patients randomized to prone position were excluded (4 declined treatment, 3 had unacceptable cardiac dose, and 7 were unable to tolerate being prone). Data were analyzed from April 2019 through September 2020. Interventions: Patients were randomized to RT in the supine or prone position. From April 2013 until June 2016, all patients (n = 167) received 50 Gy in 25 fractions (extended fractionation) with or without boost (range, 10-16 Gy). After trial amendment in June 2016, the majority of patients (177 of 190 [93.2%]) received the hypofractionation regimen of 42.5 Gy in 16 fractions. Main Outcomes and Measures: Main outcome was moist desquamation (desquamation). Results: Of the 357 women (mean [SD] age, 61 [9.9] years) included in the analysis, 182 (51.0%) were treated in the supine position and 175 (49.0%) in prone. There was statistically significantly more desquamation in patients treated in the supine position compared with prone (72 of 182 [39.6%] patients vs 47 of 175 [26.9%] patients; OR, 1.78; 95% CI, 1.24-2.56; P = .002), which was confirmed on multivariable analysis (OR, 1.99; 95% CI, 1.48-2.66; P < .001), along with other independent factors: use of boost (OR, 2.71; 95% CI, 1.95-3.77; P < .001), extended fractionation (OR, 2.85; 95% CI, 1.41-5.79; P = .004), and bra size (OR, 2.56; 95% CI, 1.50-4.37; P < .001). Conclusions and Relevance: This randomized clinical trial confirms that treatment in the prone position decreases desquamation in women with large breast size receiving adjuvant RT. It also shows increased toxic effects using an RT boost and conventional fractionation. Trial Registration: ClinicalTrials.gov Identifier: NCT01815476.

Case series of radiation pneumonitis in breast cancer.

BACKGROUND: Radiation pneumonitis (RP) is a potentially severe inflammatory reaction that occurs in approximately 1-16% of breast cancer patients treated with radiation (RT). METHODS: Case histories and patient demographics were collected from 4 patients who received either hypofractionated (42.56 Gy in 16 fractions) or conventionally fractionated (50 Gy in 25 fractions) RT for breast cancer at a cancer centre from 2018-2020 and experienced clinically symptomatic RP. Lung dose parameters including mean lung dose, V5, and V20 were collected from institutional planning software and compared to institutional guidelines. RESULTS: The 4 cases were all female, aged 42-73 years old and received 2- or 4-field RT with wide or high tangent techniques. The most common symptoms in patients who developed RP were exertional dyspnea and dry cough. Corticosteroid doses in the daily range of 40-60 mg were the primary treatment followed by a highly variable tapering schedule. Two patients experienced a recurrence of symptoms after initial treatment and were restarted on corticosteroids. Patients had several predisposing risk factors including administration of wide tangents, chemotherapy with cyclophosphamide and/or taxanes, age>65 years, and comorbidities such as diabetes. DISCUSSION: Identification of RP is difficult as evidenced by the large gap in time between the appearance of RP symptoms to treatment with corticosteroids in several patients. Irregular tapering schedules may contribute to symptom recurrence. Three of the four patients treated with 4-field wide tangents exceeded the 35% dose constraint for ipsilateral lung V20 or V17.5. CONCLUSION: Careful radiation planning and review of lung dose constraints is essential to reduce risk of RP. Greater standardization of steroid tapering practices is recommended.

Dosimetry and outcomes in patients receiving radiotherapy for synchronous bilateral breast cancers.

BACKGROUND: Synchronous bilateral breast cancer (SBBC) is rare and there is little evidence describing organs at risk (OAR) and limits to the heart and lungs caused by radiotherapy (RT). Quantifying mean heart dose (MHD) and mean lung dose (MLD) from RT in this patient cohort may lead to better understanding of doses to OAR and resultant effects on clinical outcomes. The primary objective was to assess median MHD and MLD in SBBC, while secondary aims included analyses of 1) factors associated with MHD and MLD, 2) V5 and V20 values and 3) factors associated with clinical outcomes. METHODS: Patients planned for adjuvant bilateral whole breast/chest wall (WB) RT from a single institution treated in 2011-2018 were included. Median MHD and MLD (Gy) were stratified by hypofractionated (42.56 Gy/16 fractions, HFRT) and conventional fractionation (50 Gy/ 25 fractions, CFRT) and summarized separately based on the following treatments: 1) locoregional RT, WB tangential RT either 2) no boost 3) sequential boost or 4) simultaneous integrated boost. MHD, MLD, lung V5 and V20 values, and demographics were collected. Linear regression analyses identified factors associated with MHD and MLD and factors associated with clinical outcomes. RESULTS: A total of 88 patients were included. The median MHD for HFRT and CFRT was 1.99 Gy and 2.94 Gy, respectively. The median MLD for HFRT and CFRT was 6.00 Gy and 10.08 Gy, respectively. MHD and MLD were significantly associated with the occurrence of a cardiac or pulmonary event post-radiation. Patients who had a mastectomy or tumoral muscle involvement were more likely to develop a local recurrence, metastasis or new primary while patients who had a lumpectomy or tumor with a positive estrogen receptor status were less likely to experience these events. CONCLUSIONS: Further investigation should be conducted to identify SBBC RT techniques that mitigate dose to OARs to improve clinical outcomes in bilateral breast patients.

Quantitative Effect of Bolus on Skin Dose in Postmastectomy Radiation Therapy.

BACKGROUND: In postmastectomy radiation therapy (PMRT), some centres prescribe the use of a tissue-equivalent bolus to the skin to reduce the risk of chest wall recurrence. The addition of bolus causes an increase in the skin dose, which may lead to increased risk of radiodermatitis. Radiodermatitis can decrease patients' overall quality of life, bringing into question the benefit of using the bolus. The purpose of this retrospective chart review was to quantify the increase in skin dose associated with the use of bolus in the PMRT setting. MATERIALS AND METHODS: We evaluated 70 patients who underwent PMRT at our institution during 2012-2018. Two similar treatment plans were generated for each patient: one with bolus and one without. Skin dose-volume histogram values were evaluated, and statistical analysis was performed using MATLAB R2015b. RESULTS: There was no significant difference in the maximum skin dose within a depth of 5 mm for bolus versus nonbolus plans (P = 0.4). However, within a depth of 3 mm, bolus plans had a maximum skin dose 7% ± 2.5% higher than the nonbolus plans (P < .00001). Mean skin dose within depths of 3 and 5 mm were both significantly higher (P < .00001) for bolus plans. The photon beam energy and chest wall separation showed minimal or no effect on skin dose. CONCLUSION: Given the differing opinions in the literature regarding the role for bolus in PMRT, there is still uncertainty of the optimal treatment method. This retrospective study demonstrates a 20%-30% reduction in mean skin dose when bolus is not used.

Factors Affecting Mean Heart Dose in Patients Receiving Breast Radiotherapy from 2011 to 2018 in a Single Institution.

INTRODUCTION: Breast cancer radiotherapy (RT) can increase the risk of cardiac disease with increasing dose; as such, reducing excessive dosage to the heart is a concern for clinicians. The purpose of the present study was to assess mean heart dose (MHD) in patients with breast cancer receiving RT, where it was hypothesized that MHD decreased over time. METHODS: Patients planned for adjuvant unilateral whole breast/chest wall RT from 2011 to 2018 were included for a retrospective chart-review at a single-institution, academic center. MHD (Gy) was summarized by laterality, fractionation, and heart-sparing techniques. RESULTS: A total of 4,687 patients were included. The median MHD for left-sided conventional RT (50 Gy in 25 fractions) was 2.16 Gy across all years, decreasing until 2015 and increasing after. Median MHD for left-sided hypofractionated RT (42.6 Gy in 16 fractions) was 1.47 Gy, also decreasing until 2015 and increasing after. The increase in MHD after 2015 was attributed to a significant increase in the use of wide tangents (including internal mammary chain) after 2015 (P < .0001). Several treatment factors were associated with higher MHD in both right- and left-sided cancers, including locoregional RT, high tangents, wide tangents, bolus, heart shielding, treatment to the chest wall, higher volume of tissue irradiated by tangential fields, higher baseline breast separation values, and smaller heart volume. After adjusting for laterality and fractionation in the multivariate analysis, locoregional RT, wide tangents, heart shielding, boost, treatment to the chest wall, higher volume of tissue irradiated by tangential fields, higher baseline breast separation, and lower heart volume were significantly associated with higher MHD (P < .0001). DISCUSSION/CONCLUSIONS: MHD should be considered when determining the most appropriate RT techniques for both right- and left-sided cancers as higher MHD was significantly associated with various treatment techniques and patient factors.