Effect of Radiation Doses to the Heart on Survival for Stereotactic Ablative Radiotherapy for Early-stage Non-Small-cell Lung Cancer: An Artificial Neural Network Approach.

INTRODUCTION: The cardiac radiation dose is an important predictor of cardiac toxicity and overall survival (OS) for patients with locally advanced non-small-cell lung cancer (NSCLC). However, radiation-induced cardiac toxicity among patients with early-stage NSCLC who have undergone stereotactic ablative radiotherapy (SABR) has been less well-characterized. Our objective was to assess the associations between cardiac radiation dosimetry and OS in patients with early-stage NSCLC undergoing SABR. MATERIALS AND METHODS: From 2009 to 2014, 153 patients with early-stage NSCLC had undergone SABR at a single institution. The maximum dose, mean dose, V10Gy, V25Gy, and V50Gy to 15 cardiac substructures and the whole heart were analyzed for their association with OS using the Kaplan-Meier method. An artificial neural network (ANN) analysis was performed to modulate confounding behaviors of dosimetric variables to predict for OS. RESULTS: A total of 112 patients were included in the present analysis. The right ventricle (RV) V10Gy most negatively predicted for OS, such that patients who had received a RV V10Gy dose < 4% had significantly longer OS than patients who had received a RV V10Gy does > 4% (5.3 years vs. 2.4 years). On ANN analysis, 74 input features, including cardiac dosimetry parameters, predicted for survival with a test accuracy of 64.7%. A repeat ANN analysis using dosimetry to dose neutral structure confirmed the predictive power of cardiac dosimetry. CONCLUSION: Cardiac dosimetry to subvolumes of the heart was associated with decreased OS in patients with early-stage NSCLC undergoing SABR. These data support the importance of minimizing the radiation dose to cardiac substructures. Further prioritizing the heart as an organ at risk might be warranted. Additionally, cardiac follow-up should be considered.

The impact of treatment package time on survival in surgically managed head and neck cancer in the United States.

OBJECTIVES: Delays in the initiation of postoperative radiation have been associated with worse outcomes; however, the effect of the overall treatment package time (interval from surgery through the completion of radiation) remains undefined. The purpose of this study was to determine the impact of package time on survival and to evaluate this effect among different subgroups of head and neck cancer patients. PATIENTS AND METHODS: In this observational cohort study, the National Cancer Database was used to identify 35,167 patients with resected nonmetastatic head and neck cancer who underwent adjuvant radiation from 2004 to 2014. Kaplan-Meier survival estimates and multivariate Cox regression analyses were performed to determine the effect of treatment package time on overall survival. RESULTS: Median package time was 96 days (interquartile range, 85-112 days). After adjusting for covariates, package times of 11 weeks or less were associated with improved survival (adjusted hazard ratio (aHR), 0.90; 95% confidence interval, 0.83-0.97) compared to an interval of 12-13 weeks, whereas package times of more than 14 weeks were associated with worse survival (aHR, 1.14, 1.14, and 1.22 for 14-15, 15-17, and >17 weeks, respectively). A significant interaction was identified between package time and disease site, nodal status, and stage. Specifically, patients with oropharyngeal tumors, advanced stage (III or IV) disease, or nodal involvement experienced more pronounced increases in mortality risk with delays in treatment time. CONCLUSIONS: Treatment package time independently impacts survival. This effect may be strongest for patients with oropharyngeal tumors or advanced stage disease.

Survival impact of treatment delays in surgically managed oropharyngeal cancer and the role of human papillomavirus status.

BACKGROUND: The impact of treatment delays on survival in oropharyngeal cancer and whether the effect varies by human papillomavirus (HPV) status have yet to be defined. METHODS: Retrospective analysis of the survival impact of time from diagnosis to surgery (DTS), surgery to radiation (SRT), and duration of radiation (RTD) for patients in the National Cancer Database with resected oropharyngeal cancer who underwent adjuvant radiation from 2010 to 2014. RESULTS: We identified optimal thresholds of 30, 40, and 51 days for DTS, SRT, and RTD, respectively, with treatment times exceeding these thresholds associated with significantly worse overall survival. Prolonged SRT and RTD were associated with mortality regardless of HPV status, although rising DTS was only predictive among patients with HPV-negative tumors. CONCLUSIONS: Treatment delays significantly impact survival in oropharyngeal cancer. The consequences of prolonged DTS may be stronger in HPV-negative than HPV-positive disease. These data serve as a foundation for future research and clinical management.

Risk Factors, Causes, and Costs of Hospital Readmission After Head and Neck Cancer Surgery Reconstruction.

IMPORTANCE: Thirty-day hospital readmissions have substantial direct costs and are increasingly used as a measure of quality care. However, data regarding the risk factors and reasons for readmissions in head and neck cancer surgery reconstruction are lacking. OBJECTIVE: To describe the rate, risk factors, and causes of 30-day readmission in patients with head and neck cancer following free or pedicled flap reconstruction. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study analyzed medical records from the Nationwide Readmissions Database of 9487 patients undergoing pedicled or free flap reconstruction of head and neck oncologic defects between January 1, 2010, and December 31, 2014. Data analysis was performed in October 2017. EXPOSURES: Pedicled or free flap reconstruction of an oncologic head and neck defect. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause readmissions. Secondary outcomes included risk factors, causes, and costs of readmission. Multivariate regression analyses were conducted to determine factors independently associated with 30-day readmissions. RESULTS: Among 9487 patients included in the study (6798 male; 71.7%), the median age was 63 years (interquartile range, 55-71 years), and the 30-day readmission rate was 19.4% (n = 1839), with a mean cost per readmission of $15 916 (standard error of the mean, $785). The most common indication for readmission was wound complication (26.5%, n = 487). On multivariate regression, significant risk factors for 30-day readmission were median household income in the lowest quartile (vs highest quartile: odds ratio [OR], 1.58; 95% CI, 1.18-2.11), congestive heart failure (OR, 1.68; 95% CI, 1.14-2.47), liver disease (OR, 2.02; 95% CI, 1.22- 3.33), total laryngectomy (OR, 1.40; 95% CI, 1.12-1.75), pharyngectomy (OR, 1.47; 95% CI, 1.08-2.01), blood transfusion (OR, 1.30; 95% CI, 1.04-1.64), discharge to home with home health care (vs routine: OR, 1.32; 95% CI, 1.04-1.67), and discharge to a nursing facility (vs routine: OR, 1.77; 95% CI, 1.30-2.40). CONCLUSIONS AND RELEVANCE: Using the Nationwide Readmissions Database, we demonstrate that approximately 1 in 5 patients undergoing head and neck cancer surgery reconstruction is readmitted within 30 days of surgery. Readmissions are most commonly associated with wound complications. Socioeconomic status, complex ablative procedures, and patient comorbidities are independent risk factors for readmission. These findings may be useful to clinicians in developing perioperative interventions aimed to reduce hospital readmissions and improve quality of patient care.

Comparing Outcomes of Patients With Early-Stage Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Frailty Status.

INTRODUCTION: Frailty of surgical patients has been associated with worse outcomes. There is limited literature discussing frailty in patients with lung cancer treated with stereotactic body radiotherapy (SBRT). This study assesses the relationship between frailty and overall survival (OS), tumor control, and toxicity in patients with early-stage non-small-cell lung cancer (NSCLC) treated with SBRT. PATIENTS AND METHODS: A retrospective review of patients with early-stage NSCLC treated with SBRT at a single institution between February 2009 and September 2014 was performed. A modified frailty index (mFI) of 8 variables was created, and patients were categorized as nonfrail (mFI ≤ 2) and frail (mFI > 2). OS, recurrence-free survival (RFS), local control (LC), regional control, and distant control (DC) were compared between frail and nonfrail patients by Kaplan-Meier analysis and log-rank tests. Univariate and multivariable analyses were conducted. RESULTS: One hundred forty cases of early-stage NSCLC were included, with 49 frail (35.0%) and 91 nonfrail (65.0%) subjects. OS was significantly lower in frail than nonfrail patients (P = .01) with 3-year OS of 59.3% versus 82.0%. LC and DC were significantly lower in frail than nonfrail patients (LC: P = .02, 3-year LC of 85.3% vs. 97.0%; DC: P = .03, 3-year DC of 80.6% vs. 93.4%), as was RFS (P = .01, 3-year RFS of 53.4% vs. 74.5%). Frailty remained a significant predictor for shorter OS on multivariable analysis (hazard ratio = 1.98; 95% confidence interval, 1.02-3.85; P = .04). CONCLUSION: Frailty is associated with reduced OS in early-stage NSCLC patients treated with SBRT. Characterizing frailty using an mFI before treatment could help guide treatment decision making and patient counseling.

Endoscopic Management of Subglottic Stenosis.

Importance: Optimal management of subglottic stenosis has not been established. Endoscopic techniques include balloon dilation, radial incisions with carbon dioxide laser or cold knife, and combinations of techniques. Adjunctive measures include mitomycin application and glucocorticoid injection. Objective: To determine whether surgical technique or adjunctive measures are associated with duration between surgical procedures. Design, Setting, and Participants: Adult patients with subglottic stenosis treated endoscopically between 1995-2015 at a quaternary academic medical center were identified. Patients with isolated subglottic (cricotracheal) stenosis 18 years and older were included. Patients with prior open surgical procedures, prior laryngeal surgical procedures, glottic stenosis, or vocal fold paralysis were excluded. Interventions: Patients underwent endoscopic procedures including laser radial incisions, balloon dilation, or both, with some patients receiving topical mitomycin, glucocorticoid injection, or both. Main Outcomes and Measures: Time interval between endoscopic treatments. Results: A total of 101 patients (mean [SD] age, 52.3 [15.9] years; 77.2% female) were included in the analysis, with etiologies including idiopathic (47 [46.5%]), intubation (31 [30.7%]), granulomatosis with polyangiitis (9 [8.9%]), and other autoimmune diseases (6 [5.9%]). Among the 219 operations, both laser and balloon dilation were used in 117 (53.4%), while balloon dilation alone was used in 96 (43.8%) and laser alone in 6 (2.7%). Mitomycin application and steroid injection were used in 144 (65.8%) and 93 (42.5%) cases, respectively. Mitomycin application was associated with improvement in the mean interval to next procedure from 317 to 474 days (absolute difference, 157 days; 95% CI, 15-299 days). Advanced grade of stenosis, dilation technique, and steroid injection did not significantly alter the surgical intervals. Conclusions and Relevance: Endoscopic surgery for subglottic stenosis is a critical aspect of patient management. Neither surgical technique nor grade of stenosis was seen to alter the surgical intervals. Mitomycin application was associated with an extended time interval between endoscopic treatments.

Clinical Outcomes for Patients with Gleason Score 9-10 Prostate Adenocarcinoma Treated With Radiotherapy or Radical Prostatectomy: A Multi-institutional Comparative Analysis.

BACKGROUND: The long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons. OBJECTIVE: To compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP. DESIGN, SETTING, PARTICIPANTS: Retrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). RESULTS AND LIMITATIONS: The median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p<0.0001). Five-yr and 10-yr distant metastasis-free survival rates were significantly higher with EBRT+BT (94.6% and 89.8%) than with EBRT (78.7% and 66.7%, p=0.0005) or RP (79.1% and 61.5%, p<0.0001). The 5-yr and 10-yr CSS and OS rates were similar across all three cohorts. CONCLUSIONS: Radiotherapy and RP provide equivalent CSS and OS. Extremely dose-escalated radiotherapy with ADT in particular offers improved systemic control when compared with either EBRT or RP. These data suggest that extremely dose-escalated radiotherapy with ADT might be the optimal upfront treatment for patients with biopsy GS 9-10 CaP. PATIENT SUMMARY: While some prostate cancers are slow-growing requiring many years, sometimes decades, of follow-up in order to compare between radiation and surgery, high-risk and very aggressive cancers follow a much shorter time course allowing such comparisons to be made and updated as treatments, especially radiation, rapidly evolve. We showed that radiation-based treatments and surgery, with contemporary standards, offer equivalent survival for patients with very aggressive cancers (defined as Gleason score 9-10). Extremely-dose escalated radiotherapy with short-course androgen deprivation therapy offered the least risk of developing metastases, and equivalent long term survival.

Anatomic and dosimetric changes in patients with head and neck cancer treated with an integrated MRI-tri-60Co teletherapy device.

OBJECTIVE: Prior studies have relied on CT to assess alterations in anatomy among patients undergoing radiation for head and neck cancer. We sought to determine the feasibility of using MRI-based image-guided radiotherapy to quantify these changes and to ascertain their potential dosimetric implications. METHODS: 6 patients with head and neck cancer were treated with intensity-modulated radiotherapy (IMRT) on a novel tri-60Co teletherapy system equipped with a 0.35-T MRI (VR, ViewRay Incorporated, Oakwood Village, OH) to 66-70 Gy in 33 fractions (fx). Pre-treatment MRIs on Fx 1, 5, 10, 15, 20, 25, 30 and 33 were imported into a contouring interface, where the primary gross tumour volume (GTV) and parotid glands were delineated. The centre of mass (COM) shifts for these structures were assessed relative to Day 1. Dosimetric data were co-registered with the MRIs, and doses to the GTV and parotid glands were assessed. RESULTS: Primary GTVs decreased significantly over the course of IMRT (median % volume loss, 38.7%; range, 29.5-72.0%; p < 0.05) at a median rate of 1.2%/fx (range, 0.92-2.2%/fx). Both the ipsilateral and contralateral parotid glands experienced significant volume loss (p < 0.05, for all) and shifted medially during IMRT. Weight loss correlated significantly with parotid gland volume loss and medial COM shift (p < 0.05). CONCLUSION: Integrated on-board MRI can be used to accurately contour and analyze primary GTVs and parotid glands over the course of IMRT. COM shifts and significant volume reductions were observed, confirming the results of prior CT-based exercises. Advances in knowledge: The superior resolution of on-board MRI may facilitate online adaptive replanning in the future.