The Impact of Radiotherapy Delay in Breast Conservation Patients Not Receiving Chemotherapy and the Rationale for Dichotomizing the Radiation Oncology Time-Dependent Standard into Two Quality Measures

Abstract

Introduction: The Commission on Cancer/National Quality Forum breast radiotherapy quality measure establishes that for women < 70 years, adjuvant radiotherapy after breast conserving surgery (BCS) should be started < 1 year from diagnosis. This was intended to prevent accidental radiotherapy omission or delay due to a long interval between surgery and chemotherapy completion, when radiation is delivered. However, the impact on patients not receiving chemotherapy, who proceed from surgery directly to radiotherapy, remains unknown.

Patients and methods: Patients aged 18-69, diagnosed with stage I-III breast cancer as their first and only cancer diagnosis (2004-2016), having BCS, for whom this measure would be applicable, were reviewed from the National Cancer Database.

Results: Among 308,521 patients, the median age was 57.0 years, and > 99% of all patients were compliant with the measure. The cohort of interest included 186,650 (60.5%) patients not receiving chemotherapy, with a mean age of 57.9 years. Of these, 90.5% received external beam radiotherapy (EBRT) and 9.5% brachytherapy. Among them, 24.9% started radiotherapy > 8 weeks after surgery. In a multivariable model, delay from surgery to radiotherapy increased the hazard ratios for overall survival to 9.0% (EBRT) per month and 3.0% (brachytherapy) per week.

Conclusion: While 99.9% of patients undergoing BCS without chemotherapy remain compliant with the current quality measure, 25% have delays > 8 weeks to start radiation, which is associated with impaired survival. These data suggest that the current quality measure should be dichotomized into two, with or without chemotherapy, in order to impel prompt radiotherapy initiation and maximize outcomes in all patients.

© 2021. Society of Surgical Oncology.

Figures

Figure 1.

STROBE diagram of inclusions and exclusions.

Figure 2.. Histograms of days from definitive surgery to the start of radiotherapy (RT).

Panel A. All patients combined. The x-axis for days from definitive surgery to start of RT is truncated at 365 days arbitrarily. This cut point is not the same as the Dx to RT compliance cutpoint. Panel B. Patients subdivided by those not receiving (top) and receiving (bottom) chemotherapy Panel C. Patients not receiving chemotherapy, subdivided by type of RT administered: external beam radiotherapy (EBRT) vs brachytherapy.

Figure 2.. Histograms of days from definitive surgery to the start of radiotherapy (RT).

Panel A. All patients combined. The x-axis for days from definitive surgery to start of RT is truncated at 365 days arbitrarily. This cut point is not the same as the Dx to RT compliance cutpoint. Panel B. Patients subdivided by those not receiving (top) and receiving (bottom) chemotherapy Panel C. Patients not receiving chemotherapy, subdivided by type of RT administered: external beam radiotherapy (EBRT) vs brachytherapy.

Figure 2.. Histograms of days from definitive surgery to the start of radiotherapy (RT).

Panel A. All patients combined. The x-axis for days from definitive surgery to start of RT is truncated at 365 days arbitrarily. This cut point is not the same as the Dx to RT compliance cutpoint. Panel B. Patients subdivided by those not receiving (top) and receiving (bottom) chemotherapy Panel C. Patients not receiving chemotherapy, subdivided by type of RT administered: external beam radiotherapy (EBRT) vs brachytherapy.

Figure 3.. Overall survival plots by increasing levels of adjustment.

Panel A. Overall survival (OS) by surgery-radiotherapy (RT) interval for patients who received EBRT (left) or brachytherapy (right), estimated using Kaplan-Meier methods. Panel B. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models without covariates. Hazard ratio estimate for longest vs shortest interval group is 2.36 (95%CI=2.10–2.65, p<0.001) for EBRT and 1.49 (95%CI=1.03–2.13, p=0.035) for brachytherapy. From separate Cox models with the surgery-RT interval as a continuous variable, unadjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001) for EBRT and HR for a 1 week difference = 1.02 (95%CI 1.00–1.04, p=0.0229) for brachytherapy. Panel C. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with adjustment for age, race, and Charlson comorbidity index (CCI). Adjusted hazard ratio estimate for longest vs shortest interval group is 2.43 (95%CI 2.17–2.73, p<0.001) for EBRT and 1.59 (95%CI 1.10–2.31, p=0.014) for brachytherapy. From separate age, race and CCI-adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001, same as univariate) for EBRT and HR for a 1 week difference = 1.03 (95%CI 1.01–1.05, p=0.0084) for brachytherapy. Panel D. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with further adjustment for age, race, Charlson comorbidity index, urban/rural setting, transfer of care, facility volume, ER/PR status, tumor size, lymph node positivity, grade, endocrine therapy, and year of diagnosis (with year of diagnosis as a restricted cubic spline while others are categorical). Adjusted hazard ratio estimate for longest vs shortest interval group is 1.40 (95%CI 1.23–1.59, p<0.001) for EBRT and 1.46 (95% CI 0.99–2.17, p=0.057) for brachytherapy. From separate adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.09 (95%CI 1.07–1.11, p<0.0001) for EBRT, and adjusted HR for a 1 week difference = 1.03 (95%CI 1.00–1.05, p=0.0175) for brachytherapy.

Figure 3.. Overall survival plots by increasing levels of adjustment.

Panel A. Overall survival (OS) by surgery-radiotherapy (RT) interval for patients who received EBRT (left) or brachytherapy (right), estimated using Kaplan-Meier methods. Panel B. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models without covariates. Hazard ratio estimate for longest vs shortest interval group is 2.36 (95%CI=2.10–2.65, p<0.001) for EBRT and 1.49 (95%CI=1.03–2.13, p=0.035) for brachytherapy. From separate Cox models with the surgery-RT interval as a continuous variable, unadjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001) for EBRT and HR for a 1 week difference = 1.02 (95%CI 1.00–1.04, p=0.0229) for brachytherapy. Panel C. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with adjustment for age, race, and Charlson comorbidity index (CCI). Adjusted hazard ratio estimate for longest vs shortest interval group is 2.43 (95%CI 2.17–2.73, p<0.001) for EBRT and 1.59 (95%CI 1.10–2.31, p=0.014) for brachytherapy. From separate age, race and CCI-adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001, same as univariate) for EBRT and HR for a 1 week difference = 1.03 (95%CI 1.01–1.05, p=0.0084) for brachytherapy. Panel D. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with further adjustment for age, race, Charlson comorbidity index, urban/rural setting, transfer of care, facility volume, ER/PR status, tumor size, lymph node positivity, grade, endocrine therapy, and year of diagnosis (with year of diagnosis as a restricted cubic spline while others are categorical). Adjusted hazard ratio estimate for longest vs shortest interval group is 1.40 (95%CI 1.23–1.59, p<0.001) for EBRT and 1.46 (95% CI 0.99–2.17, p=0.057) for brachytherapy. From separate adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.09 (95%CI 1.07–1.11, p<0.0001) for EBRT, and adjusted HR for a 1 week difference = 1.03 (95%CI 1.00–1.05, p=0.0175) for brachytherapy.

Figure 3.. Overall survival plots by increasing levels of adjustment.

Panel A. Overall survival (OS) by surgery-radiotherapy (RT) interval for patients who received EBRT (left) or brachytherapy (right), estimated using Kaplan-Meier methods. Panel B. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models without covariates. Hazard ratio estimate for longest vs shortest interval group is 2.36 (95%CI=2.10–2.65, p<0.001) for EBRT and 1.49 (95%CI=1.03–2.13, p=0.035) for brachytherapy. From separate Cox models with the surgery-RT interval as a continuous variable, unadjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001) for EBRT and HR for a 1 week difference = 1.02 (95%CI 1.00–1.04, p=0.0229) for brachytherapy. Panel C. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with adjustment for age, race, and Charlson comorbidity index (CCI). Adjusted hazard ratio estimate for longest vs shortest interval group is 2.43 (95%CI 2.17–2.73, p<0.001) for EBRT and 1.59 (95%CI 1.10–2.31, p=0.014) for brachytherapy. From separate age, race and CCI-adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001, same as univariate) for EBRT and HR for a 1 week difference = 1.03 (95%CI 1.01–1.05, p=0.0084) for brachytherapy. Panel D. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with further adjustment for age, race, Charlson comorbidity index, urban/rural setting, transfer of care, facility volume, ER/PR status, tumor size, lymph node positivity, grade, endocrine therapy, and year of diagnosis (with year of diagnosis as a restricted cubic spline while others are categorical). Adjusted hazard ratio estimate for longest vs shortest interval group is 1.40 (95%CI 1.23–1.59, p<0.001) for EBRT and 1.46 (95% CI 0.99–2.17, p=0.057) for brachytherapy. From separate adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.09 (95%CI 1.07–1.11, p<0.0001) for EBRT, and adjusted HR for a 1 week difference = 1.03 (95%CI 1.00–1.05, p=0.0175) for brachytherapy.

Figure 3.. Overall survival plots by increasing levels of adjustment.

Panel A. Overall survival (OS) by surgery-radiotherapy (RT) interval for patients who received EBRT (left) or brachytherapy (right), estimated using Kaplan-Meier methods. Panel B. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models without covariates. Hazard ratio estimate for longest vs shortest interval group is 2.36 (95%CI=2.10–2.65, p<0.001) for EBRT and 1.49 (95%CI=1.03–2.13, p=0.035) for brachytherapy. From separate Cox models with the surgery-RT interval as a continuous variable, unadjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001) for EBRT and HR for a 1 week difference = 1.02 (95%CI 1.00–1.04, p=0.0229) for brachytherapy. Panel C. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with adjustment for age, race, and Charlson comorbidity index (CCI). Adjusted hazard ratio estimate for longest vs shortest interval group is 2.43 (95%CI 2.17–2.73, p<0.001) for EBRT and 1.59 (95%CI 1.10–2.31, p=0.014) for brachytherapy. From separate age, race and CCI-adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.19 (95%CI 1.17–1.21, p<0.0001, same as univariate) for EBRT and HR for a 1 week difference = 1.03 (95%CI 1.01–1.05, p=0.0084) for brachytherapy. Panel D. Overall survival curves for EBRT (left) and brachytherapy(right) patients, estimated from Cox models with further adjustment for age, race, Charlson comorbidity index, urban/rural setting, transfer of care, facility volume, ER/PR status, tumor size, lymph node positivity, grade, endocrine therapy, and year of diagnosis (with year of diagnosis as a restricted cubic spline while others are categorical). Adjusted hazard ratio estimate for longest vs shortest interval group is 1.40 (95%CI 1.23–1.59, p<0.001) for EBRT and 1.46 (95% CI 0.99–2.17, p=0.057) for brachytherapy. From separate adjusted Cox models with the surgery-RT interval as a continuous variable, adjusted HR for a 1 month difference = 1.09 (95%CI 1.07–1.11, p<0.0001) for EBRT, and adjusted HR for a 1 week difference = 1.03 (95%CI 1.00–1.05, p=0.0175) for brachytherapy.