Forecasting patient-specific dosimetric benefit from daily online adaptive radiotherapy for cervical cancer.

Objective. Adaptive Radiotherapy (ART) is an emerging technique for treating cancer patients which facilitates higher delivery accuracy and has the potential to reduce toxicity. However, ART is also resource-intensive, Requiring extra human and machine time compared to standard treatment methods. In this analysis, we sought to predict the subset of node-negative cervical cancer patients with the greatest benefit from ART, so resources might be properly allocated to the highest-yield patients.Approach. CT images, initial plan data, and on-treatment Cone-Beam CT (CBCT) images for 20 retrospective cervical cancer patients were used to simulate doses from daily non-adaptive and adaptive techniques. We evaluated the coefficient of determination (R2) between dose and volume metrics from initial treatment plans and the dosimetric benefits to theBowelV40Gy,BowelV45Gy,BladderDmean,andRectumDmeanfrom adaptive radiotherapy using reduced 3 mm or 5 mm CTV-to-PTV margins. The LASSO technique was used to identify the most predictive metrics forBowelV40Gy.The three highest performing metrics were used to build multivariate models with leave-one-out validation forBowelV40Gy.Main results. Patients with higher initial bowel doses were correlated with the largest decreases in BowelV40Gyfrom daily adaptation (linear best fit R2= 0.77 for a 3 mm PTV margin and R2= 0.8 for a 5 mm PTV margin). Other metrics had intermediate or no correlation. Selected covariates for the multivariate model were differences in the initialBowelV40GyandBladderDmeanusing standard versus reduced margins and the initial bladder volume. Leave-one-out validation had an R2of 0.66 between predicted and true adaptiveBowelV40Gybenefits for both margins.Significance. The resulting models could be used to prospectively triage cervical cancer patients on or off daily adaptation to optimally manage clinical resources. Additionally, this work presents a critical foundation for predicting benefits from daily adaptation that can be extended to other patient cohorts.

Competing causes of death and medical comorbidities among patients with human papillomavirus-positive vs human papillomavirus-negative oropharyngeal carcinoma and impact on adherence to radiotherapy.

IMPORTANCE: Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. OBJECTIVE: To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. MAIN OUTCOMES AND MEASURES: Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. RESULTS: Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). CONCLUSIONS AND RELEVANCE: Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

Clinical response of pelvic and para-aortic lymphadenopathy to a radiation boost in the definitive management of locally advanced cervical cancer.

PURPOSE: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. METHODS AND MATERIALS: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response, assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. RESULTS: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. CONCLUSIONS: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.

The equivalent dose contribution from high-dose-rate brachytherapy to positive pelvic lymph nodes in locally advanced cervical cancer.

PURPOSE: Definitive radiation therapy for locally advanced cervical cancer involves external beam radiation therapy (EBRT) and high-dose-rate (HDR) brachytherapy. There remains controversy and practice pattern variation regarding the optimal radiation dose to metastatic pelvic lymph nodes (LNs). This study investigates the contribution of the pelvic LN dose from HDR brachytherapy. METHODS AND MATERIALS: For 17 patients with 36 positive pelvic LNs, each LN was contoured on a computed tomography (CT) plan for EBRT and on brachytherapy planning CTs using positron emission tomographic images obtained before chemoradiation. The mean delivered dose from each plan was recorded, and an equivalent dose in 2-Gy fractions (EQD2) was calculated. A Student's t test was performed to determine if the mean delivered dose is significantly different from the mean prescribed dose and EQD2. RESULTS: The average prescribed dose from the total EBRT was 54.09 Gy. The average prescribed HDR dose to International Commission on Radiation Units point A was 26.81 Gy. The average doses delivered to the involved LNs from EBRT and brachytherapy were 54.25 and 4.31 Gy, respectively, with the corresponding EQD2 of 53.45 and 4.00 Gy. There was no statistically significant difference (p < 0.05) between the mean delivered and the prescribed doses for EBRT and between the delivered dose and the EQD2 for EBRT and brachytherapy. CONCLUSIONS: Our study shows that the HDR contribution is 7% (4.00 Gy) of the total EQD2 (57.45 Gy). The HDR contribution should be accounted for when prescribing the EBRT boost dose to pelvic LNs for the optimal therapeutic dose.