Dataset Information

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.

ABSTRACT:

Purpose

Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen.

Methods and materials

Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications.

Results

After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%.

Conclusions

This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.

SUBMITTER: Poppe MM

PROVIDER: S-EPMC7373304 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose Conventionally fractionated postmastectomy radiation therapy (PMRT) takes approximately 5 to 6 weeks. Data supporting hypofractionated PMRT is limited. We prospectively evaluated a short course of hypofractionated PMRT, in which therapy was completed in 15 treatment days. Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes, followed by an optional mastectomy scar boost of four fractions of 3.33 Gy. Our primary end point was freedom from any grade 3 or higher toxicities. We incorporated early stopping criteria on the basis of predefined toxicity thresholds. Results We enrolled 69 women with stage II to IIIa breast cancer, of whom 67 were eligible for analysis. After a median follow-up of 32 months, there were no grade 3 toxicities. There were 29 reported grade 2 toxicities, with grade 2 skin toxicities being the most frequent (16 of 67; 24%). There were two patients with isolated ipsilateral chest wall tumor recurrences (2 of 67; crude rate, 3%). Three-year estimated local recurrence-free survival was 89.2% (95% CI, 0.748 to 0.956). The 3-year estimated distant recurrence-free survival was 90.3% (95% CI, 0.797 to 0.956). Forty-one patients had chest wall reconstructions; three had expanders removed for infection before radiation therapy. The total rate of implant loss or failure was 24% (9 of 38), and the unplanned surgical correction rate was 8% (3 of 38), for a total complication rate of 32%. Conclusion To our knowledge, our phase II prospective study offers one of the shortest courses of PMRT reported, delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost. We demonstrated low toxicity and high local control with this schedule. On the basis of our data, we have designed a cooperative group phase III prospective, randomized trial of conventional versus hypofractionated PMRT that will activate soon.

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Project description:PurposeTo report 5-year outcomes of a phase 2 trial of hypofractionated whole breast irradiation (HF-WBI) completed in 3 weeks, inclusive of a sequential boost.Methods and materialsWomen with stage 0-IIIA breast cancer (ductal carcinoma in situ through T2N2a) were enrolled on a prospective, phase 2 trial of accelerated HF-WBI. We delivered a whole breast dose of 36.63 Gy in 11 fractions of 3.33 Gy, with an equivalent dose to the regional nodes when indicated, followed by a tumor bed boost of 13.32 Gy in 4 fractions of 3.33 Gy over a total of 15 treatment days. The primary endpoint was locoregional control; secondary endpoints included acute/late toxicity and physician-assessed and patient-reported breast cosmesis.ResultsBetween 2009 and 2017, we enrolled 150 patients, of whom 146 received the protocol treatment. Median age was 54 years (range, 33-82) and median follow-up was 62 months. Patients with higher-risk disease comprised 59% of the cohort, including features such as young age (33% ≤50 years), positive nodes (13%), triple-negative disease (11%), and treatment with regional nodal irradiation (11%) and/or neoadjuvant/adjuvant chemotherapy (36%). Five-year estimated locoregional and distant control were 97.7% (95% confidence interval [CI], 93.0%-99.3%) and 97.9% (95% CI, 93.6%-99.3%), respectively. Five-year breast cancer-specific and overall survival were 99.2% (95% CI, 94.6%-99.9%) and 97.3% (95% CI, 91.9%-99.1%), respectively. Acute/late grade 2 and 3 toxicities were observed in 30%/10% and 1%/3% of patients, respectively. There were no grade 4 or 5 toxicities. Physicians assessed breast cosmesis as good or excellent in 95% of patients; 85% of patients self-reported slight to no difference between the treated and untreated breast.ConclusionsOur phase 2 trial offers one of the shortest courses of HF-WBI; at 5 years of follow-up there continues to be excellent locoregional control and low toxicity with favorable cosmetic outcomes in a heterogeneous cohort of patients.

Project description:PurposeThis phase 1 trial aimed to identify the maximally tolerated hypofractionated dose schedule for postoperative radiation therapy (PORT) after radical prostatectomy. Secondary objectives included biochemical control and quality of life (QoL) measures.Methods and materialsPatients were treated on 1 of 3 dose levels (DLs): 56.4 Gy in 20 fractions (DL1), 51.2 Gy in 15 fractions (DL2), and 44.2 Gy in 10 fractions (DL3). Treatment was delivered to the prostate bed without pelvic nodal irradiation. Dose escalation followed a standard 3 + 3 design with an expansion for 6 additional patients at the maximally tolerated hypofractionated dose schedule. Acute dose-limiting toxicity (DLT) was defined as grade 3 toxicity lasting >4 days within 21 days of PORT completion; late DLT was defined as grade 4 gastrointestinal (GI) or genitourinary (GU) toxicity.ResultsBetween January 2018 and August 2019, 15 patients underwent radiation treatment: 3 on DL1, 3 on DL2, and 9 on DL3. The median follow-up was 24 months. There were no DLTs, and the maximally tolerated hypofractionated dose schedule was identified as DL3. Two of the 15 patients (13.3%) experienced biochemical failure (prostate-specific antigen >0.1). Ten of 15 patients (67%) had grade 2+ acute toxicities, consisting of transient GI toxicities. Three patients experienced late grade 2+ GI toxicity, and 5 patients experienced late grade 2+ GU toxicity. Late grade 3 GU toxicity occurred in 2 patients. There were no grade 4+ acute or late toxicities. There were no significant differences in GI measures of QoL, however, there was an increase in GU symptoms and corresponding decrease in GU QoL between 12 and 24 months.ConclusionsThe maximum tolerated hypofractionated dose schedule for hypofractionated PORT to the prostate bed was determined to be 44.2 Gy in 10 daily fractions. The most frequent clinically significant toxicities were late grade 2+ GU toxicities, which corresponded to a worsening of late GU QoL.

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Project description:PurposeTo assess the long-term quality of life (QoL) outcomes from a phase 3 trial comparing 2 modes of intensity modulated radiation therapy (IMRT): conventional IMRT (CIMRT) versus hypofractionated IMRT (HIMRT) in patients with localized prostate cancer.Methods and materialsBetween 2002 and 2006, 303 men with low-risk to high-risk prostate cancer were randomized to 76 Gy in 38 fractions (CIMRT) versus 70.2 Gy in 26 fractions (HIMRT). QoL was compared by use of the Expanded Prostate Cancer Index Composite (EPIC), the International Prostate Symptom Score (IPSS), and EuroQoL (EQ5D) questionnaires. The primary outcome of the QoL analysis was a minimum clinically important difference defined as a 0.5 standard deviation change from baseline for each respective QoL parameter. Treatment effects were evaluated with the use of logistic mixed effects regression models.ResultsA total of 286, 299, and 218 patients had baseline EPIC, IPSS, or EQ5D data available and were included in the analysis. Overall, there was no statistically significant difference between the 2 treatment arms in terms of EPIC, IPSS, or EQ5D scores over time, although there was a trend toward lower EPIC urinary incontinence scores in the HIMRT arm. More patients in the HIMRT arm had a lower EPIC urinary incontinence score relative to baseline versus patients in the CIMRT arm with long-term follow-up. On multivariable analysis, there was no association between radiation fractionation scheme and any QoL parameter. When other clinical factors were examined, lymph node radiation was associated with worse EPIC hormonal scores versus patients receiving no lymph node radiation. In general, QoL outcomes were generally stable over time, with the exception of EPIC hormonal and EQ5D scores.ConclusionsIn this randomized prospective study, there were stable QoL changes in patients receiving HIMRT or CIMRT. Our results add to the growing body of literature suggesting that HIMRT may be an acceptable treatment modality in clinically localized prostate cancer.