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To evaluate the change in parotid glands at mid-treatment during IMRT and the association between radiation dose to the parotid gland stem cell (PGSC) region and patient-reported xerostomia for patients with head and neck cancer (HNC). Patients who were treated from 2006–2012 at our institution with patient-reported xerostomia outcomes available at least 9 months following RT were included. PG and PGSC regions were delineated and the dose was estimated from the treatment plan dose distribution, using contours from pre- and mid-treatment CT scans. The association between radiation dose and volumetric changes was assessed using linear regression. Univariable logistic regression, logistic dose-response curves, and receiver operating characteristics (ROC) were used to examine the relationship between radiation dose and patient-reported xerostomia. Sixty-three patients were included, most treated with 70 Gy in 33 fractions; 34 patients had mid-treatment CT scans. Both contralateral and ipsilateral PGs had considerable volume reduction from baseline to mid-treatment (25% and 27%, respectively, both p <.001), significantly associated with mean PG dose (−0.44%/Gy, p =.008 and −0.54%/Gy, p <.001, respectively). There was a > 5 Gy difference in mean PG and PGSC dose for 8/34 patients at mid-treatment, with 6/8 (75%) reporting severe xerostomia. Xerostomia prediction based on whole PG or PGSC region dose showed similar performance (ROC AUC 0.754 and 0.749, respectively). The corresponding dose-response models also predicted similar risk of patient-reported xerostomia with mean dose to the contralateral PG (32.5%) or PGSC region (31.4%) at the 20 Gy QUANTEC-recommended sparing level. The radiation dose to the PGSC region did not show stronger association with patient-reported xerostomia compared to that of whole PG, possibly due to considerable anatomical changes identified at mid-treatment. This shift in the size and position of the PG warrants adaptive planning strategies to evaluate the true benefit of parotid stem cell sparing. [ABSTRACT FROM AUTHOR]

PURPOSE: Liver-directed therapy after transarterial chemoembolization (TACE) can lead to improvement in survival for selected patients with unresectable hepatocellular carcinoma (HCC). However, there is uncertainty in the appropriate application and modality of therapy in current clinical practice guidelines. The aim of this study was to develop a proof-of-concept, machine learning (ML) model for treatment recommendation in patients previously treated with TACE and select patients who might benefit from additional treatment with combination stereotactic body radiotherapy (SBRT) or radiofrequency ablation (RFA). METHODS: This retrospective observational study was based on data from an urban, academic hospital system selecting for patients diagnosed with stage I-III HCC from January 1, 2008, to December 31, 2018, treated with TACE, followed by adjuvant RFA, SBRT, or no additional liver-directed modality. A feedforward, ML ensemble model provided a treatment recommendation on the basis of pairwise assessments evaluating each potential treatment option and estimated benefit in survival. RESULTS: Two hundred thirty-seven patients met inclusion criteria, of whom 54 (23%) and 49 (21%) received combination of TACE and SBRT or TACE and RFA, respectively. The ML model suggested a different consolidative modality in 32.7% of cases among patients who had previously received combination treatment. Patients treated in concordance with model recommendations had significant improvement in progression-free survival (hazard ratio 0.5; P =.007). The most important features for model prediction were cause of cirrhosis, stage of disease, and albumin-bilirubin grade (a measure of liver function). CONCLUSION: In this proof-of-concept study, an ensemble ML model was able to provide treatment recommendations for HCC who had undergone prior TACE. Additional treatment in line with model recommendations was associated with significant improvement in progression-free survival, suggesting a potential benefit for ML-guided medical decision making. Proof of concept #ML decision support tool for adjuvant therapy selection for unresectable HCC. [ABSTRACT FROM AUTHOR]

Advanced cervical cancer treated with tandem and ovoids intracavitary/interstitial brachytherapy. Material and methods: FIGO stage IB1-IIIB locally advanced cervical cancer treated with intracavitary/interstitial brachytherapy via a tandem and ovoids hybrid applicator were analyzed. Median high-risk clinical target volume (HR-CTV), rate of tumor volume reduction, EQD2 D90, organ at risk doses, and outcomes were recorded. Univariable and multivariable Cox regression was applied for survival analysis, and logistic regression was used for toxicity analysis. Results: Seventy-one patients were identified. Median follow-up was 24.9 months, with a 2-year local control of 83.6%, loco-regional control of 72.0%, and overall survival of 88.6%. Median HR-CTV D90 was 87.4 Gy (IQR = 85.7-90.2). Median HR-CTV D90 > 90 Gy10 showed a trend toward improved local control (LC) (p = 0.19). Median HR-CTV was 37.9 cm3, and median V100 was 86.5%. A median HR-CTV of = 40 cm3 demonstrated worse loco-regional control (LRC) (p = 0.018) and progression-free survival (p = 0.021). Two-year LC and LRC for stage IIB patients with a median HR-CTV < 40 cm3 were significantly improved as compared to = 40 cm3 at 100% and 71.8%, respectively (p = 0.019) and 100% and 56.5%, respectively (p = 0.001). However, this trend was not statistically significant for stage IIIB patients. Higher percent per day reduction in HR-CTV during brachytherapy showed improved LRC (p = 0.045). Four percent of patients experienced acute grade 3 genitourinary toxicity, 1% late grade 3 genitourinary and 1% late grade 3 gastrointestinal toxicity. Conclusions: Tandem and ovoids intracavitary/interstitial brachytherapy provides satisfactory outcomes with modest toxicity. Higher HR-CTV D90 coverage demonstrated a trend toward improved tumor control. Tumor volume based on median HR-CTV = 40 cm3 at brachytherapy was prognostic for poor outcomes, even within initial FIGO stage groups warranting caution. [ABSTRACT FROM AUTHOR]

Background: Proton therapy is a promising advancement in radiation oncology especially in terms of reducing normal tissue toxicity, although it is currently expensive and of limited availability. Here we estimated the individual quality of life benefit and cost-effectiveness of proton therapy in patients with oropharyngeal cancer treated with definitive radiation therapy (RT), as a decision-making tool for treatment individualization.Methods and Materials: Normal tissue complication probability models were used to estimate the risk of dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis for 33 patients, comparing delivered photon intensity-modulated RT (IMRT) plans to intensity-modulated proton therapy (IMPT) plans. Quality-adjusted life years (QALYs) lost were calculated for each complication while accounting for patient-specific conditional survival probability and assigning quality-adjustment factors based on complication severity. Cost-effectiveness was modeled based on upfront costs of IMPT and IMRT, and the cost of acute and/or long-term management of treatment complications. Uncertainties in all model parameters and sensitivity analyses were included through Monte Carlo sampling.Results: The incremental cost-effectiveness ratios (ICERs) showed considerable variability in the cost of QALYs spared between patients, with median $361,405/QALY for all patients, varying from $54,477/QALY to $1,508,845/QALY between individual patients. Proton therapy was more likely to be cost-effective for patients with p16-positive tumors ($234,201/QALY), compared to p16-negative tumors ($516,297/QALY). For patients with p16-positive tumors treated with comprehensive nodal irradiation, proton therapy is estimated to be cost-effective in ≥ 50% of sampled cases for 8/9 patients at $500,000/QALY, compared to 6/24 patients who either have p16-negative tumors or receive unilateral neck irradiation.Conclusions: Proton therapy cost-effectiveness varies greatly among oropharyngeal cancer patients, and highlights the importance of individualized decision-making. Although the upfront cost, societal willingness to pay and healthcare administration can vary greatly among different countries, identifying patients for whom proton therapy will have the greatest benefit can optimize resource allocation and inform prospective clinical trial design. [ABSTRACT FROM AUTHOR]

Introduction: Radical prostatectomy (RP) is a standard treatment modality for localized prostate cancer. Biochemical failure after RP is usually evaluated with whole-body imaging to exclude distant metastatic disease, and pelvic magnetic resonance imaging (MRI) to detect local recurrence in the prostatectomy bed. The goal of this study is to correlate disease characteristics and demographic data in patients with rising prostate-specific antigen (PSA) after RP to determine association with MRI-detected cancer recurrence. Methods: Sixty-four patients who underwent pelvic MRI for rising PSA after RP and had complete clinical and pathological data available were included. Using Chi-squared testing, we analyzed PSA levels, pathological disease characteristics (prostate cancer risk group, Gleason score, extracapsular extension, positive surgical margin, seminal vesicle involvement, perineural invasion, lymphovascular invasion, and PSA level before MRI), time from surgery to biochemical failure, and patient demographic characteristics as potential predictors of MRI-detected local recurrence. Results: Definite MRI-detected local recurrence was observed in 17/64 patients (27%). Eleven (17%) patients had a suspicious lesion with the differential of scarring, retained seminal vesicle, or recurrent cancer. Thirty-six (56%) patients had no evidence of tumor in the prostate bed or pelvis on MRI. Patient race was associated with likelihood of detecting a prostate nodule on MRI (p=0.04), with African American patients having 82% lower odds of MRI-detected tumor recurrence compared with white patients (p=0.045). No other tumor or patient characteristic was significantly associated with MRI-detected recurrence. Conclusions: African American patients with biochemical failure after RP are less likely to have MRI-detectable recurrence in the prostate bed compared with white patients. [ABSTRACT FROM AUTHOR]

The National Cancer Institute's Radiation Research Program, in collaboration with the Radiosurgery Society, hosted a workshop called Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy on August 20 and 21, 2018 to bring together experts in experimental and clinical experience in these and related fields. Critically, the overall aims were to understand the biological underpinning of these emerging techniques and the technical/physical parameters that must be further defined to drive clinical practice through innovative biologically based clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS. Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan–Meier methods were used to compare actuarial survival estimates. Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3–4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68–0.96), p=.018). For patients with early stage disease (T1–2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86–1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30–45 Gy was seen for increasing doses up to 55–60 Gy, but not beyond 60 Gy. Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55–60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease. [ABSTRACT FROM AUTHOR]

Purpose: Here we explore the prognostic value of baseline step count data captured using wearable devices for patients treated with definitive chemoradiation therapy for locally advanced non-small cell lung cancer (NSCLC).Methods and Materials: Patients with locally advanced NSCLC wore a commercial fitness tracker during a course of definitive, concurrent chemoradiation therapy as part of a clinical trial. Baseline step count average was defined as the average daily step total from study enrollment until completion of the first week of radiation therapy. Based on data from healthy individuals, study subjects were categorized as inactive (below the 25th percentile), moderately active (25th to 75th percentile), or highly active (above the 75th percentile). Fisher's exact test was used to examine activity level as a predictor of hospitalization during radiation therapy and of completing the planned radiation therapy course without delay exceeding 1 week. Median progression-free survival (PFS) and overall survival (OS) durations were estimated using the Kaplan-Meier method. Inactivity was tested as a predictor of PFS and OS using Cox proportional hazards models.Results: Fifty subjects met eligibility criteria. Nine (18%) were categorized as highly active, 23 (46%) were moderately active, and 18 (36%) were inactive. Inactive subjects were more likely to be hospitalized during the radiation therapy course than other subjects (50% vs 9%, P = .004) and less likely to complete radiation therapy without delay exceeding 1 week (67% vs 97%, P = .006). Median PFS duration was 5.3 months for inactive subjects and 18.3 months for others (hazard ratio for inactivity = 5.10, P < .001). Median OS duration was 15.0 months for inactive subjects and not reached for others (hazard ratio = 3.91, P = .004). Performance status was not a significant predictor of PFS or OS.Conclusions: Baseline activity level measured using wearable devices may help identify patients with NSCLC who are fit for concurrent chemoradiation therapy and can predict clinical outcomes in this setting. [ABSTRACT FROM AUTHOR]

Purpose: Understanding the pathways and gateways to leadership and challenges faced by individuals in such roles can inform efforts to promote diversity and equity. We sought to describe the professional experiences and personal characteristics of academic radiation oncology (RO) chairs and to evaluate whether differences exist by gender.Methods and Materials: Anonymous surveys were distributed to 95 chairs of RO departments during the 2016 annual meeting of the Society of Chairs of Academic Radiation Oncology Programs. The surveys included 28 closed-ended questions and the Leadership Practices Inventory. Results were analyzed by gender using χ2 tests, rank-sum, and t tests (significance P < .05).Results: A total of 72 chairs responded (61 male, 10 female, 1 declined to identify gender) for a response rate of 76%. There were no significant gender differences in age, academic rank, publications, or prior leadership positions held at the time of the first chair appointment, but female respondents held significantly greater total direct funding from extramural grants than their male counterparts (median, $1.89 million [interquartile range, $0.5-$5 million] vs $0.25 million [interquartile range, $0-$1.0 million]; P = .006). Women were more likely to have spouses employed outside the home at time of their first chair appointment than men were, with a trend toward women experiencing greater difficulty relocating. Men and women identified budgeting and resource allocation as their greatest professional challenges. There were no gender differences in the Leadership Practices Inventory-identified leadership domains or professional goals.Conclusions: Female RO chairs are as equally qualified as men in terms of productivity or leadership skills, but they face distinct challenges in the context of a gender-structured society. The observation of higher grant funding among women at the time of chair appointment suggests a possible need for interventions such as unconscious bias training to ensure that selection processes do not unnecessarily hold women to a higher standard. [ABSTRACT FROM AUTHOR]

Management of gynecologic brachytherapy(BT) procedural pain or discomfort varies across institutions. Data suggest women experience symptoms of acute stress disorder and post-traumatic stress disorder (PTSD), as high as 30-41%, following BT with spinal/epidural anesthesia (AS)1. We sought to determine the prevalence of post-BT PTSD in our locally advanced cervical cancer (LACC) patients and differences based on the type of AS. We queried an IRB-approved institutional database for eligible women who received HDR-BT for LACC (intracavitary(IC), interstitial(IS), or hybrid intracavitary/interstitial(IC/IS)) from 1/1/2015 to 9/30/2021. Eligibility also included age >= 18 years old, ability to hear and speak well enough to complete the questionnaires in English, and no prior cancer history. Contact was attempted for each eligible patient. Enrolled patients completed two validated questionnaires by phone: 1) Impact of Event Scale-Revised, and 2) EORTC QLQ-CX24. Open commentary was offered. We utilized the Impact Event Scale-Revised with the replacement of the word "event" with "brachytherapy" to assess PTSD symptoms as published by Kirchheiner et al.1 A cutoff score above 33 was chosen to represent probable PTSD.2 Scores ranging from 24-32 were considered probable partial PTSD.3 56 patients met eligibility, and 21 patients aged 30-69 years old enrolled. Reasons for non-enrollment included disinterest, no working phone number, and inability to contact despite multiple attempts. FIGO stage ranged from 1B1-IVA. Five patients identified as Black or African American, 6 Hispanic, 2 Asian, 14 unknown or unavailable race, 9 unknown or unavailable ethnicity. The mean time since treatment was 3.27 years (1.5-6). 17 women were treated for intact CC. 4 patients were treated postoperatively. 9 patients were treated with IC applicators for intact CC, and 5 were treated with IC/IS applicators. 3 patients were treated with an IS implant for intact CC. 12 women were treated for intact CC with oral narcotics and anxiolytics, while 2 women were treated with conscious sedation (SD). 3 patients treated with an IS implant received general AS for implant placement. 4 patients treated with IC BT postoperatively received no SD or AS. The mean Impact of Event Scale score was 16.62 (0-73). 3 women had scores above 33, qualifying for a probable diagnosis of PTSD. 3 women had scores ranging from 24-32, suggesting partial PTSD. 6 women in total had scores above 24, equating to a partial to full PTSD symptom rate of 28.6% (95%CI: 11.3%, 52.2%). Small sample size precluded an analysis of SD technique and its association with PTSD. Open commentary of the BT highlighted the patient experience and emotional state (Table 1). Partial to full PTSD symptoms were present in 28.6% of women treated with HDR-BT for LACC. Challenges included loss to follow-up, successful contact, and recall bias given the retrospective approach. Further prospective study into the relationship between HDR gynecologic BT SD practices and PTSD is warranted.References: 1.doi:10.1016/j.ijrobp.2014.02.0182.doi:10.1016/j.brat.2003.07.0103.doi: 10.1007/978-0-387-70990-1_10 [ABSTRACT FROM AUTHOR]

Purpose: Developing a quantitative decision-support strategy estimating the impact of normal tissue complications from definitive radiation therapy (RT) for head and neck cancer (HNC). We developed this strategy to identify patients with oropharyngeal HNC who may benefit most from receiving proton RT.Methods and Materials: Recent normal tissue complication probability (NTCP) models for dysphagia, esophagitis, hypothyroidism, xerostomia, and oral mucositis were used to estimate NTCP for 33 patients with oropharyngeal HNC previously treated with photon intensity modulated radiation therapy (IMRT). Comparative proton therapy plans were generated using clinical protocols for HNC RT at a collaborating proton center. Organ-at-risk (OAR) doses from photon and proton RT plans were used to calculate NTCPs; Monte Carlo sampling 10,000 times was used for each patient to account for model parameter uncertainty. The latency and duration of each complication were modeled from calculated NTCP, accounting for age-, sex-, smoking- and p16-specific conditional survival probability. Complications were then assigned quality-adjustment factors based on severity to calculate quality-adjusted life years (QALYs) lost from each complication.Results: Based on our institutional-delivered photon IMRT doses and the achievable proton therapy doses, the average QALY reduction from all HNC RT complications for photon and proton therapy was 1.52 QALYs versus 1.15 QALYs, with proton therapy sparing 0.37 QALYs on average (composite 95% confidence interval, 0.27-2.53 QALYs). Long-term complications (dysphagia and xerostomia) contributed most to the QALY reduction. The QALYs spared with proton RT varied considerably among patients, ranging from 0.06 to 0.84 QALYs. Younger patients with p16-positive tumors who smoked ≤10 pack-years may benefit most from proton therapy, although this finding should be validated using larger patient series. A sensitivity analysis reducing photon IMRT doses to all OARs by 20% resulted in no overall estimated benefit with proton therapy with -0.02 QALYs spared, although some patients still had an estimated benefit in this scenario, ranging from -0.50 to 0.43 QALYs spared.Conclusions: This quantitative decision-support strategy allowed us to identify patients with oropharyngeal cancer who might benefit the most from proton RT, although the estimated benefit of proton therapy ultimately depends on the OAR doses achievable with modern photon IMRT solutions. These results can help radiation oncologists and proton therapy centers optimize resource allocation and improve quality of life for patients with HNC. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether a response assessment using mid-treatment computed tomography (CT) scans during definitive radiation therapy (RT) for oropharyngeal head and neck cancer can predict for locoregional recurrence (LRR).Methods and Materials: Head and neck cancer patients who receive RT at our institution undergo CT repeat scans at the 15th fraction, with treatment replanning in the case of an inadequate dose to gross disease or an increased dose to organs at risk. A retrospective cohort analysis was performed of 96 consecutive patients with oropharyngeal cancer treated from 2007 to 2015 with mid-treatment repeat CT scans available. The primary disease volume and involved lymph node volume were delineated on the pre- and mid-treatment CT scans. Univariable and multivariable Cox proportional hazards regression analyses were used to evaluate the efficacy of the mid-treatment reduction in tumor volume as a predictor of LRR. Risk stratification was performed by dichotomizing the patients into high- and low-risk groups according to the mid-treatment response and p16 status and smoking history.Results: With a median follow-up of 34 months, 14 patients experienced LRR. The median reduction in the total tumor volume was 18.7% (interquartile range 8.4%-30.9%). A reduction in total tumor volume greater than the median was an independent predictor of LRR (hazard ratio 0.22, 95% confidence interval 0.05-0.89; P = .020). The reduction in primary tumor volume was an even stronger predictor of LRR (hazard ratio 0.11, 95% confidence interval 0.02-0.57; P = .002). Stratifying patients into a high-risk group for those with a reduction in the total tumor volume at mid-treatment at or less than the median, p16 negative status, and smoking status of >10 pack-years and a low-risk group for those without these factors, we found a clear separation in Kaplan-Meier curves, with actuarial 3-year locoregional control, progression-free survival, and overall survival rates for the high-risk patients of 45.7%, 38.2%, and 71.8% compared with 90.7%, 70.6%, and 89.8% for low-risk patients, respectively (P ≤ .021 for all).Conclusions: Our results have shown that the treatment response from an early assessment using mid-treatment CT scans is an independent predictor of LRR and can be used to effectively distinguish high- and low-risk patients, allowing for risk-adaptive treatment stratification at the midway point. [ABSTRACT FROM AUTHOR]

Purpose: To perform a prospective trial examining positron emission tomography (PET)-based, dose-painted intensity modulated radiation therapy (IMRT) in the setting of locally advanced non-small cell lung cancer (NSCLC).Methods and Materials: Patients with stage IIB-III NSCLC were treated with 25 fractions of dose-painted IMRT. Tumors or lymph nodes with metabolic tumor volume exceeding 25 cm3 were deemed "high risk" and received 65 Gy. Smaller lesions were treated with 57 Gy or 52.5 Gy (after November 2014). Patients received concurrent weekly carboplatin (area under the curve = 2) and paclitaxel (45 mg/m2). The primary study endpoint was the absence of high residual metabolic activity (maximum standardized uptake value > 6) in treated lesions on PET 12 to 16 weeks after completion of IMRT.Results: Thirty-five subjects with 116 hypermetabolic lesions were eligible for analysis. The primary endpoint was met for 24 of 30 patients (80%) who underwent posttreatment PET, satisfying our efficacy objective. With a median follow-up duration of 23.8 months for living patients, progression in a lesion targeted with radiation therapy has been observed in 5 patients (14%). Treating progression in other sites and death without progression as competing risks, 2-year cumulative incidence rates of local disease progression in high-risk lesions (n=24) and low-risk lesions (n=92) are 9% and 3%, respectively. The actuarial rate of overall survival at 2 years is 52%.Conclusions: Dose-painted IMRT based on pretreatment PET metrics with concurrent chemotherapy yields high rates of metabolic response and local disease control for locally advanced NSCLC. Future trials should test this approach to maximize the therapeutic ratio of thoracic radiation therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine whether patients with Oropharyngeal Squamous Cell Carcinoma (OPSCC) treated with Transoral Robotic Surgery (TORS) have similar survival to patients treated with definitive RT.Materials and Methods: Using the National Cancer Database (NCDB) registry, we identified patients with newly diagnosed clinical T1-T2, N0-N2b OPSCC between 2010 and 2014. A multivariable logistic regression was utilized to determine the association between chemotherapy use and primary treatment modality (TORS vs definitive RT). Kaplan Meier survival analysis was used to estimate overall survival. Propensity score matching was utilized to address selection bias.Results: We identified 17,150 patients, of which 14,470 (84.4%) received primary RT and 2,680 (15.6%) underwent TORS. The median follow-up for the cohort was 31.4 months. Propensity score matching demonstrated similar 5-year OS for patients treated with either definitive RT or TORS (81% vs 84%, log rank p = 0.10). There was no difference in survival outcomes by treatment selection (TORS or definitive RT) in either HPV positive or HPV negative subtypes. Patients treated with TORS were less likely to receive chemotherapy compared to patients treated with definitive RT and this was also demonstrated in a propensity matched analysis (OR: 0.09, 95%CI 0.078-0.12, p < 0.001). Only 68.4% of TORS treated patients underwent adjuvant RT, compared to 100% of patients in the primary RT cohort (p < 0.001).Conclusions and Relevance: For patients with OPSCC, TORS results in similar OS outcomes and is associated with decreased chemotherapy and RT use compared to definitive RT. Our results demonstrate the feasibility of TORS in a select subgroup of OPSCC patients. [ABSTRACT FROM AUTHOR]

Objective: To analyze nutritional factors and compliance with dietary recommendations for associations with overall survival (OS) and progression-free survival (PFS) in patients receiving definitive RT for laryngeal and oropharyngeal cancers.Materials/methods: We identified 352 patients with non-metastatic laryngeal (146) and oropharyngeal (206) cancer treated with definitive RT between 2004 and 2013. Disease and patient characteristics, treatment information, sarcopenia based on muscle areas at L3 level on CT, compliance with the nutritional program, and clinical outcomes data were tabulated. Descriptive statistics, Kaplan-Meier survival analysis, and log rank tests were performed, and Cox regression models were used to examine predictors of OS and PFS.Results: The median follow-up for the entire cohort was 22.86 months. The actuarial rates for OS were 91, 86, and 73% at years 1, 2, and 5, respectively. Of patients with abdominal CT prior to starting RT, 70.9% (112/158) were sarcopenic with a median muscle mass index of 48.2 (range 30.4-70.9) for males and 35.9 (range 24.6-53.2) for females. The majority (85.8%) of patients met with a dietitian during their course of RT and 62.6% of these patients were compliant with the nutritional program. Compliance with the nutritional program resulted in 27% (HR 0.73, 95% CI 0.43-1.26) protection from death (did not reach significance) and 31% (HR 0.69, 95% CI 0.50-0.94) significant protection from disease progression. Higher pretreatment BMI was associated with a lower risk of death (HR 0.94, 95% CI 0.90-0.99) and disease progression (HR 0.96, 95% CI 0.93-0.99).Conclusion: Laryngeal and oropharyngeal cancer patients treated with definitive RT who are compliant with regular dietetic counseling and contact appear to have improved outcomes.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Purpose: Acute radiation dermatitis (RD) is a disfiguring and painful rash that occurs in up to 95% of patients receiving radiation therapy (RT) for cancer. Treatment for RD varies among practitioners with no evidence-based gold standard for management. While a multi-disciplinary approach has been utilized to manage other cancer-related toxicities, RD is most often managed by the treating radiation oncologist.Methods: This study evaluated the referral practices of radiation oncologists to dermatologists for management of RD utilizing a survey of radiation oncologists across the USA. The goal was to identify the referral practices of radiation oncologists for RD and any barriers to a multidisciplinary approach.Results: Of the 705 respondents, 15% reported ever referring patients to dermatology. Private practitioners referred significantly less than providers in academic or oncology centers (p < 0.01). Practitioners in urban settings were more likely to refer (p < 0.01), and radiation oncologists in the Southeastern USA were less likely to refer (p < 0.01).Conclusions: Lack of timely access to dermatologists in various geographic areas in addition to radiation oncologists' preference to treat RD are barriers to multidisciplinary management of RD. Inclusion of dermatologists and wound care specialists in cancer treatment teams could improve patient care and stimulate needed research into strategies for treatment and prevention of RD. [ABSTRACT FROM AUTHOR]

Purpose: A lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. We sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URMs) in these influential positions.Methods and Materials: From March to June 2016, we conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was used to invite all chairs who were women (n = 13) or URMs (n = 3) and 11 male chairs who were not URMs. Multiple analysts coded the verbatim transcripts.Results: Five themes were identified: (1) commitment to DEI promotes quality health care and innovation; (2) gaps remain despite some progress with promoting diversity in RO; (3) women and URM faculty continue to experience challenges in various career domains; (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race; and (5) expansion of the career pipeline is needed.Conclusions: The chairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school. [ABSTRACT FROM AUTHOR]

Purpose: Due to the inconclusive evidence for available treatment options, management of radiation dermatitis (RD) varies among practitioners. This study defines and reviews the current treatment patterns for RD in the USA, providing guidance for practicing physicians as well as directions for future research.Methods: An online survey of 21 questions was emailed to all 5626 members of the 2013 American Society for Radiation Oncology (ASTRO) directory, which included radiation oncologists, residents, fellows, physician assistants, nurse practitioners, registered nurses and other care providers. The questions were designed to evaluate demographics of responders, their training and comfort in the management RD, and their patterns of care regarding prophylaxis and treatment of RD. Data was analyzed using simple summary and descriptive statistics.Results: Out of the 5626 emails sent, we were left with 709 physician respondents for our analysis, or a response rate of 12.9%. Although 84.7% of physicians felt that RD had a moderate or large impact on patients' quality of life during cancer treatment, only 30.1% received special training or specific instructional courses in treating RD during their medical training in residency or fellowship. Eighty-nine percent of surveyed physicians rely on observational and/or anecdotal findings to guide treatment decisions, and 51.4% reported using evidence-based treatments.Conclusion: The results of our study show that there is great variability in the topical agents and dressings used in practice by radiation oncologists to prevent and treat RD. This information may be useful to other practitioners to develop their own personal recommendations and can guide further research into strategies to prevent and treat radiation dermatitis. [ABSTRACT FROM AUTHOR]

The importance of emotional intelligence (EI) in physicians has attracted attention as researchers begin to focus on the relationship of EI to retention, promotion, and productivity among academic physicians. However, to date, no formal evaluation of EI has been conducted among current department chairs. The objectives of this study were to assess the EI of current chairs of academic radiation oncology departments and to correlate EI with a self-reported assessment of burnout. The authors invited 95 chairs of academic radiation oncology departments to participate in a survey, approved by an institutional review board, consisting of the Trait Emotional Intelligence Questionnaire Short Form (TEIQue-SF) and the abbreviated Maslach Burnout Inventory (a-MBI). TEIQue-SF scores were evaluated for correlation with respondents' demographics and self-reported burnout scores on the a-MBI. Sixty chairs responded to the survey, for a response rate of 63.2%. The median (interquartile range) TEIQue-SF for the responding cohort was 172 (155-182) out of a maximum possible score of 210. The a-MBI emotional exhaustion and depersonalization subscores were low, with median (interquartile range) scores of4 (2.25-6.75) and 1 (0-2.75) out of maximum possible scores of 18 and 30, respectively. Higher TEIQue-SF global scores were weakly correlated with decreased burnout. The study results show that academic radiation on- cology chairs had a high EI and low rates of self-reported burnout. EI may be of increasing importance with respect to recruitment and retention of academic medical leaders. [ABSTRACT FROM AUTHOR]

Purpose: To perform a prospective trial testing the feasibility and utility of acquiring activity data as a measure of health status during concurrent chemoradiotherapy.Methods and Materials: Ambulatory patients who were planned for treatment with concurrent chemoradiotherapy with curative intent for cancers of the head and neck, lung, or gastrointestinal tract were provided with activity monitors before treatment initiation. Patients were asked to wear the devices continuously throughout the radiation therapy course. Step count data were downloaded weekly during radiation therapy and 2 and 4 weeks after radiation therapy completion. The primary objective was to demonstrate feasibility, defined as collection of step counts for 80% of the days during study subjects' radiation therapy courses. Secondary objectives included establishing step count as a dynamic predictor of unplanned hospitalization risk.Results: Thirty-eight enrolled patients were treated with concurrent chemoradiotherapy. Primary diagnoses included head and neck cancer (n=11), lung cancer (n=13), and a variety of gastrointestinal cancers (n=14). Step data were collected for 1524 of 1613 days (94%) during patients' radiation therapy courses. Fourteen patients were hospitalized during radiation therapy or within 4 weeks of radiation therapy completion. Cox regression modeling demonstrated a significant association between recent step counts (3-day average) and hospitalization risk, with a 38% reduction in the risk of hospitalization for every 1000 steps taken each day (hazard ratio 0.62, 95% confidence interval 0.46-0.83, P=.002). Inferior quality of life scores and impaired performance status were not associated with increased hospitalization risk.Conclusion: Continuous activity monitoring during concurrent chemoradiotherapy is feasible and well-tolerated. Step counts may serve as powerful, objective, and dynamic indicators of hospitalization risk. [ABSTRACT FROM AUTHOR]

Objective:Fractionated stereotactic radiotherapy (FSRT) is a relatively new option for the treatment of brain metastases. We performed a quantitative systematic review to determine if local control (LC) following is affected by FSRT dosing regimen.Methods:We reviewed articles describing LC following FSRT for brain metastases. LC data from each study were extracted from actuarial survival curves and aggregated to form a single data set. LC curves were generated using the Kaplan–Meier method. Log-rank testing and Cox proportional hazards modelling were utilized to test for associations between the biologically effective dose (BED) and LC. Tumour control probability modelling was performed to illustrate the relationship between the BED and the likelihood of LC after FSRT.Results:10 studies (720 metastases) met inclusion criteria. Prescription doses ranged from 18 to 42 Gy, delivered in 3–12 fractions (BED range: 29–100 Gy10). 1- and 2-year actuarial LC rates were 80% and 69%, respectively. Increasing BED was associated with improved LC (HR = 0.77 per increase of 10 Gy10, p = 0.009). Tumour control probability models demonstrated that the BEDs of 40, 50 and 60 Gy10 yield predicted 1-year LC rates of 73%, 78% and 84%, respectively. The BEDs of 40, 50 and 60 Gy10 yield 2-year LC rates of 62%, 69% and 81%, respectively.Conclusion:FSRT provides high rates of LC for patients with brain metastases. We found evidence for a dose–response relationship that should be explored in prospective trials. [ABSTRACT FROM AUTHOR]

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models.Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging 18F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapy dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size.Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion.Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the modeled probability of tumor control and organ at risk toxicities in locally advanced cervical cancer in patients treated by external beam radiation plus brachytherapy using intracavitary combined with interstitial brachytherapy (IC/IS) vs. intracavitary brachytherapy (IC) alone. Material and methods: Twenty cervical cancer patients with a mean HR-CTV volume of 47.4 cm3 and a mean width of 54 mm were planned with both IC/IS and IC brachytherapy alone. A probit model was utilized to model 3-year (3-yr) local control rate (LC), 3-yr cancer specific survival rate (CSS), and the adverse effect (AE) of the organ at risk by using a modeled data set from multiple institutions. Modeling results were used to estimate the LC, CSS, and AE of the treatments in this study. Results: Using the IC/IS technique, an EQD2 increase of 12.3 Gy to D90 (from 76.1 Gy to 88.3 Gy) of HR-CTV is expected to increase 3-yr LC and 3-yr CSS by 12.5%, and 11.0%, respectively. Comparing IC/IS to IC alone, the expected G2+ AE were 7.7% vs. 7.9% for the bladder, and 5.9% vs. 6.8% for the rectum. Conclusions: The IC/IS technique improved dose coverage to the HR-CTV without significantly increasing dose to 2 cm3 of the organ at risk (OAR) surrounding it. With different regimens of EBRT combined with BT, IC/IS can be used to increase the probability of LC and CSS, or decrease the risk of AE. [ABSTRACT FROM AUTHOR]

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control ( p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control ( p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands. [ABSTRACT FROM AUTHOR]

Purpose: To examine associations between radiation therapy (RT) noncompliance and clinical outcomes.Methods and Materials: We reviewed all patients who completed courses of external beam RT with curative intent in our department from the years 2007 to 2012 for cancers of the head and neck, breast, lung, cervix, uterus, or rectum. Patients who missed 2 or more scheduled RT appointments (excluding planned treatment breaks) were deemed noncompliant. Univariate, multivariable, and propensity-matched analyses were performed to examine associations between RT noncompliance and clinical outcomes.Results: Of 1227 patients, 266 (21.7%) were noncompliant. With median follow-up of 50.9 months, 108 recurrences (8.8%) and 228 deaths (18.6%) occurred. In univariate analyses, RT noncompliance was associated with increased recurrence risk (5-year cumulative incidence 16% vs 7%, P<.001), inferior recurrence-free survival (5-year actuarial rate 63% vs 79%, P<.001), and inferior overall survival (5-year actuarial rate 72% vs 83%, P<.001). In multivariable analyses that were adjusted for disease site and stage, comorbidity score, gender, ethnicity, race, and socioeconomic status (SES), RT noncompliance was associated with inferior recurrence, recurrence-free survival, and overall survival rates. Propensity score-matched models yielded results nearly identical to those seen in univariate analyses. Low SES was associated with RT noncompliance and was associated with inferior clinical outcomes in univariate analyses, but SES was not associated with inferior outcomes in multivariable models.Conclusion: For cancer patients being treated with curative intent, RT noncompliance is associated with inferior clinical outcomes. The magnitudes of these effects demonstrate that RT noncompliance can serve as a behavioral biomarker to identify high-risk patients who require additional interventions. Treatment compliance may mediate the associations that have been observed linking SES and clinical outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the implication of surgical clips in tumor bed variation during multi-lumen balloon (MLB)-based accelerated partial breast irradation. It mentions the application of surgical clips as surrogates for the tumor bed. It examines the dosimetric impact due to geometric variation in tumor bed.

Purpose Within a multifraction high-dose-rate vaginal cuff brachytherapy course, we determined if individual variations in organ at risk (OAR) volume and cylinder insertion geometry (CIG) impacted dose and whether planned minus fractional (P − F) differences led to a discrepancy between planned dose and delivered dose. Methods and Materials We analyzed vaginal cuff brachytherapy applications from consecutive patients treated with three fractions of 5 Gy after each undergoing a planning CT and three repeat fractional CTs (fCTs). Rectal and bladder D 2ccs and volumes were recorded in addition to the x (in relationship to midplane) and y (in relationship to the table) angles of CIG. Paired t-tests and multiple regression analyses were performed. Results Twenty-seven patients were identified. In comparing the planning CT vs. mean fCT rectal volumes, bladder volumes, x angles, and y angles, only bladder volume was significantly different (planned volume higher, t = 2.433, p = 0.017). The cumulative mean planned OAR D 2cc vs. delivered D 2cc was only significantly different for the bladder (planned dose lower, t = −2.025, p = 0.053). Regression analysis revealed planned rectal D 2cc ( p < 0.0003) and a positive (posterior) y insertion angle ( p = 0.015) to significantly impact delivered rectal D 2cc . Additionally, P − F rectal volume ( p = 0.037) was significant in determining rectal delivered dose. Conclusions A more posterior y angle of insertion was found to increase rectal D 2cc leading us to believe that angling the vaginal cylinder anteriorly may reduce rectal dose without significantly increasing bladder dose. Although attention should be paid to OAR volume and CIG to minimize OAR dose, the clinical significance of P − F changes remains yet to be shown. [ABSTRACT FROM AUTHOR]

We report our experience of establishing planning objectives to achieve dose coverage, conformity, and dose falloff for spine stereotactic body radiation therapy (SBRT) plans. Patients with spine lesions were treated using SBRT in our institution since September 2009. Since September 2011, we established the following planning objectives for our SBRT spine plans in addition to the cord dose constraints: (1) dose coverage—prescription dose (PD) to cover at least 95% planning target volume (PTV) and 90% PD to cover at least 99% PTV; (2) conformity index (CI)—ratio of prescription isodose volume (PIV) to the PTV < 1.2; (3) dose falloff—ratio of 50% PIV to the PTV (R 50% ); (4) and maximum dose in percentage of PD at 2 cm from PTV in any direction (D 2cm ) to follow Radiation Therapy Oncology Group (RTOG) 0915. We have retrospectively reviewed 66 separate spine lesions treated between September 2009 and December 2012 (31 treated before September 2011 [group 1] and 35 treated after [group 2]). The χ 2 test was used to examine the difference in parameters between groups. The PTV V 100% PD ≥ 95% objective was met in 29.0% of group 1 vs 91.4% of group 2 ( p < 0.01) plans. The PTV V 90% PD ≥ 99% objective was met in 38.7% of group 1 vs 88.6% of group 2 ( p < 0.01) plans. Overall, 4 plans in group 1 had CI > 1.2 vs none in group 2 ( p = 0.04). For D 2cm , 48.3% plans yielded a minor violation of the objectives and 16.1% a major violation for group 1, whereas 17.1% exhibited a minor violation and 2.9% a major violation for group 2 ( p < 0.01). Spine SBRT plans can be improved on dose coverage, conformity, and dose falloff employing a combination of RTOG spine and lung SBRT protocol planning objectives. [ABSTRACT FROM AUTHOR]

An efficient and simple class solution is proposed for hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) planning using the Volumetric Arc Therapy (VMAT) delivery technique following the NRG Oncology protocol NRG-CC001 treatment planning guidelines. The whole-brain planning target volume (PTV) was subdivided into subplanning volumes that lie in plane and out of plane with the hippocampal-avoidance volume. To further improve VMAT treatment plans, a partial-field dual-arc technique was developed. Both the arcs were allowed to overlap on the in-plane subtarget volume, and in addition, one arc covered the superior out-of-plane sub-PTV, while the other covered the inferior out-of-plane subtarget volume. For all plans ( n = 20), the NRG-CC001 protocol dose-volume criteria were met. Mean values of volumes for the hippocampus and the hippocampal-avoidance volume were 4.1 cm 3 ± 1.0 cm 3 and 28.52 cm 3 ± 3.22 cm 3 , respectively. For the PTV, the average values of D 2% and D 98% were 36.1 Gy ± 0.8 Gy and 26.2 Gy ± 0.6 Gy, respectively. The hippocampus D 100% mean value was 8.5 Gy ± 0.2 Gy and the maximum dose was 15.7 Gy ± 0.3 Gy. The corresponding plan quality indices were 0.30 ± 0.01 (homogeneity index), 0.94 ± 0.01 (target conformality), and 0.75 ± 0.02 (confirmation number). The median total monitor unit (MU) per fraction was 806 MU (interquartile range [IQR]: 792 to 818 MU) and the average beam total delivery time was 121.2 seconds (IQR: 120.6 to 121.35 seconds). All plans passed the gamma evaluation using the 5-mm, 4% criteria, with γ > 1 of not more than 9.1% data points for all fields. An efficient and simple planning class solution for HA-WBRT using VMAT has been developed that allows all protocol constraints of NRG-CC001 to be met. [ABSTRACT FROM AUTHOR]

Introduction. Radiation recall dermatitis (RRD) is a phenomenon that occurs in previously irradiated areas shortly after administration of a chemotherapeutic agent. As the use of sorafenib expands, the incidence of radiation recall dermatitis induced by sorafenib will likely increase. Here, we report on a patient who developed RRD and describe his clinical characteristics along with a review of the literature. Case Presentation. Our patient was treated with palliative radiation therapy (RT) to a painful metastatic hepatocellular carcinoma lesion in the right forearm. He completed his radiation course with grade 1 dermatitis, which had resolved by the time he was started on sorafenib 400 mg twice daily 7 days afterwards. On the 21st day after RT, he presented with desquamation and erythema in the previously irradiated area of the right forearm, consistent with RRD. The sorafenib was discontinued and his symptoms subsequently resolved with conservative topical management. Conclusions. Although the pathophysiologic mechanism of sorafenib-related radiation recall dermatitis remains to be investigated, practitioners should be aware of its presence and management in order to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose To quantify the frequency of patient noncompliance in an urban radiation oncology department and identify predictors of noncompliance. Methods and Materials We identified patients treated with external beam radiation therapy (RT) with curative intent in our department from 2007 to 2012 for 1 of 7 commonly treated malignancies. Patients who missed 2 or more scheduled RT appointments were deemed “noncompliant.” An institutional database was referenced to obtain clinical and demographic information for each patient, as well as a quantitative estimate of each patient's socioeconomic status. Logistic regression was used to identify factors associated with RT noncompliance. Results A total of 2184 patients met eligibility criteria. Of these, 442 (20.2%) were deemed “noncompliant.” On multivariate analysis, statistically significant predictors of noncompliance included diagnosis of head-and-neck, cervical, or uterine cancer, treatment during winter months, low socioeconomic status, and use of a long treatment course (all P <.05). Conclusion This is the first large effort examining patient noncompliance with daily RT. We have identified demographic, clinical, and treatment-related factors that can be used to identify patients at high risk for noncompliance. These findings may inform future strategies to improve adherence to prescribed therapy. [ABSTRACT FROM AUTHOR]

Purpose To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined. Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results Average (±SD) planned bladder volume was 299.7 ± 68.5 cm 3 . Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm 3 (range, 74.3-251.4 cm 3 ). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm 3 ; P =.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV_Bowel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient. [ABSTRACT FROM AUTHOR]

We sought to determine if single-dose external beam radiation therapy (EBRT) could modulate the expression signature of T-cell costimulatory and coinhibitory molecules in human prostate cancer (PCa) cell lines in vitro. We investigated the functional impact of irradiated PCa cells with a modulated costimulatory profile on responder T-cell activity. We used three PCa cell lines (DU145, PC3, and LNCaP) and two epithelial cell lines from noncancerous prostate and lung tissue. After 72 hours of EBRT, surface expression of four immunostimulatory molecules (CD70, CD275/ICOSL, CD134L/OX40L, and CD137L/41BBL) and two immunosuppressive markers (CTLA-4/CD152 and PD-L1/CD274) were evaluated by flow cytometry. We evaluated the impact of several radiation doses and the longevity of modulated expression. We examined the functional impact of radiation-induced modulation of cancer cells by cytotoxic T cells (CTL) cytotoxicity and ELISPOT assay for interferon-gamma (IFN-γ) production. Last, we evaluated whether IFN-γ-induced PD-L1 expression could be reversed by EBRT. After 10 Gy EBRT, expression of OX40L and 41BBL increased in all three PCa cell lines; expression of CD70 and ICOSL increased in PC3 cells. Conversely, a decrease in PD-L1 expression in DU145 and PC3 cells was detectable up to 144 hours after EBRT. No PD-L1 was detected in LNCaP. Epithelial cells from normal prostate were not modulated by radiation. CTL cytolytic activity and IFN-γ production were enhanced by interaction with irradiated PCa cells. Finally, EBRT failed to prevent IFN-γ-induced upregulation of PD-L1. We demonstrate that a single dose of EBRT increased surface expression of costimulatory molecules and decreased the expression of coinhibitory molecules in human PCa cell lines. Changes in irradiated tumor cells led to functional enhancement of T-cell activity, despite EBRT failing to reduce IFN-γ-induced expression of PD-L1. These data suggest that combining radiotherapy with T-cell stimulating immunotherapy may be an attractive strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the variations of multi-lumen balloon (MLB)-based brachytherapy from simulation day to treatment day and their dosimetric impacts during accelerated partial breast irradiation (APBI). Material and methods: A total of 42 CT images scanned from seven patients were evaluated with regards to daily variation due to of: 1) internal uncertainty: size and shape of balloon, seroma volume; 2) geometrical uncertainty-random: length of each catheter was measured for each fraction (total 70); 3) geometrical uncertainty-systematic: virtual systematic errors were tested by offsetting dwell positions. The original plans (as group A) had a mean value of 96.8% on v95 of the PTV_Eval. Plans were rerun (as group B) such that the mean value of the v95 was relaxed to 90.4%. By applying the reference plan to each daily CT image, variations of target coverage under different sources of error were evaluated. Results: Shape and size of the balloon had means of < 1 mm decreased in diameter and < 0.4 cm³ decreased in volume; the mean seroma volume increased by 0.2 cm³. This internal variation has a mean of < 1% difference for both V95 and V95. The geometrical uncertainty made a mean deviation of 2.7 mm per root of sum of square. It caused the degradations of V90 and v95 by mean values of 1.0% and 1.2%, respectively. A systematic error of 3 mm and 4 mm would degrade both of V90 and v95 by 4% and 6%, respectively. The degradations on target coverage of the plans in group A were statistically the same as those in group B. Conclusions: Overall, APBI treatments with MLB based brachytherapy are precise from day to day. However, minor variation due to daily treatment uncertainties can still degrade tumor bed coverage to an unacceptable coverage when V95 of the original plan is close to 90%. [ABSTRACT FROM AUTHOR]

Purpose: Controversy exists whether the prostate-specific antigen (PSA) bounce phenomenon following definitive radiation for prostate cancer has prognostic significance. Here, we perform a meta-analysis to determine the association between PSA bounce and biochemical control after brachytherapy alone. Material and methods: We reviewed Medline, EMBASE, and CENTRAL citations through February 2012. Studies that recorded biochemical failure rates in bouncers and non-bouncers were included. Hazard ratios describing the impact of bounce on biochemical failure were extracted directly from the studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. A random effects model was used in cases of significant effect heterogeneity (p < 0.10 using Q test). Results: The final analysis included 3011 patients over 6 studies treated with brachytherapy. Meta-analysis revealed that patients experiencing PSA bounce after brachytherapy, conferred a decreased risk of biochemical failure (random effects model HR = 0.42, 95% CI: 0.30-0.59; p < 0.001). Conclusions: Our meta-analysis determined that PSA bounce predicts for improved biochemical control following brachytherapy. To our knowledge, this is the first study describing this effect. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Radiation induced cranial nerve palsy (RICNP) involving the lower cranial nerves (CNs) is a serious complication of head and neck radiotherapy (RT). Recommendations for delineating the lower CNs on RT planning studies do not exist. The aim of the current study is to develop a standardized methodology for contouring CNs IX–XII, which would help in establishing RT limiting doses for organs at risk (OAR). Methods: Using anatomic texts, radiologic data, and guidance from experts in head and neck anatomy, we developed step-by-step instructions for delineating CNs IX–XII on computed tomography (CT) imaging. These structures were then contoured on five consecutive patients who underwent definitive RT for locally-advanced head and neck cancer (LAHNC). RT doses delivered to the lower CNs were calculated. Results: We successfully developed a contouring atlas for CNs IX–XII. The median total dose to the planning target volume (PTV) was 70Gy (range: 66–70Gy). The median CN (IX–XI) and (XII) volumes were 10c.c (range: 8–12c.c) and 8c.c (range: 7–10c.c), respectively. The median V50, V60, V66, and V70 of the CN (IX–XI) and (XII) volumes were (85, 77, 71, 65) and (88, 80, 74, 64) respectively. The median maximal dose to the CN (IX–XI) and (XII) were 72Gy (range: 66–77) and 71Gy (range: 64–78), respectively. Conclusions: We have generated simple instructions for delineating the lower CNs on RT planning imaging. Further analyses to explore the relationship between lower CN dosing and the risk of RICNP are recommended in order to establish limiting doses for these OARs. [ABSTRACT FROM AUTHOR]

Background and purpose: Rectal toxicity presents a significant limiting factor in prostate radiotherapy regimens. This study evaluated the safety and efficacy of an implantable and biodegradable balloon specifically designed to protect rectal tissue during radiotherapy by increasing the prostate-rectum interspace. Patients and methods: Balloons were transperineally implanted, under transrectal ultrasound guidance, into the prostate-rectum interspace in 27 patients with localized prostate cancer scheduled to undergo radiotherapy. Patients underwent two simulations for radiotherapy planning--the first simulation before implant, and the second simulation seven days post implant. The balloon position, the dimensions of the prostate, and the distance between the prostate and rectum were evaluated by CT/US examinations 1 week after the implant, weekly during the radiotherapy period, and at 3 and 6 months post implant. Dose-volume histograms of pre and post implantation were compared. Adverse events were recorded throughout the study period. Results: Four of 27 patients were excluded from the evaluation. One was excluded due to a technical failure during implant, and three patients were excluded because the balloon prematurely deflated. The balloon status was evaluated for the duration of the radiotherapy period in 23 patients. With the balloon implant, the distance between the prostate and rectum increased 10-fold, from a mean 0.22 ± 0.2 cm to 2.47 ± 0.47 cm. During the radiotherapy period the balloon length changed from 4.25 ± 0.49 cm to 3.81 ± 0.84 cm and the balloon height from 1.86 ± 0.24 cm to 1.67 ± 0.22 cm. But the prostate-rectum interspace distance remained constant from beginning to end of radiotherapy: 2.47 ± 0.47 cm and 2.41 ± 0.43 cm, respectively. A significant mean reduction in calculated rectal radiation exposure was achieved. The implant procedure was well tolerated. The adverse events included mild pain at the perineal skin and in the anus. Three patients experienced acute urinary retention which resolved in a few hours following conservative treatment. No infections or thromboembolic events occurred during the implant procedure or during the radiotherapy period. Conclusion: The transperineal implantation of the biodegradable balloon in patients scheduled to receive radiotherapy was safe and achieved a significant and constant gap between the prostate and rectum. This separation resulted in an important reduction in the rectal radiation dose. A prospective study to evaluate the acute and late rectal toxicity is needed. [ABSTRACT FROM AUTHOR]

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy. [ABSTRACT FROM AUTHOR]

Purpose. Transoral robotic surgery (TORS) has increased in popularity in the management of squamous cell carcinoma of the head and neck. However, TORS does not address the neck or retropharyngeal nodes (RPN). In the current report, we highlight the impact of the lack of adjuvant radiotherapy on RPN recurrence after TORS. Materials and Methods. A 58-year-old Caucasian male presented with squamous cell carcinoma of the head and neck of unknown primary. He was offered radiotherapy as a definitive management for clinical stage T0N2aM0, stage IVA, but he opted to left neck dissection. Follow-up PET-CT scan revealed recurrence in the left base of tongue and right level II lymph node. He was offered radiotherapy which he declined and opted to TORS and right neck dissection. Follow-up PET-CT scan showed recurrence in left RPN for which he underwent salvage concurrent chemoradiotherapy to 70 Gy. Results. After a followup of 9 months from the date of salvage chemoradiotherapy completion, the patient is with no evidence of disease. Conclusions. TORS followed by adjuvant radiotherapy seems reasonable in the context of squamous cell carcinoma of the head and neck due to the odds of RPN involvement. Further reports are warranted to optimize post-TORS adjuvant treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of breast size on dose-volume histogram parameters and clinical toxicity in whole-breast hypofractionated radiation therapy using intensity modulated radiation therapy (IMRT). Materials and Methods: In this retrospective study, all patients undergoing breast-conserving therapy between 2005 and 2009 were screened, and qualifying consecutive patients were included in 1 of 2 cohorts: large-breasted patients (chest wall separation >25 cm or planning target volume [PTV] >1500 cm3) (n=97) and small-breasted patients (chest wall separation <25 cm and PTV <1500 cm3) (n=32). All patients were treated prone or supine with hypofractionated IMRT to the whole breast (42.4 Gy in 16 fractions) followed by a boost dose (9.6 Gy in 4 fractions). Dosimetric and clinical toxicity data were collected and analyzed using the R statistical package (version 2.12). Results: The mean PTV V95 (percentage of volume receiving >= 95% of prescribed dose) was 90.18% and the mean V105 percentage of volume receiving >= 105% of prescribed dose was 3.55% with no dose greater than 107%. PTV dose was independent of breast size, whereas heart dose and maximum point dose to skin correlated with increasing breast size. Lung dose was markedly decreased in prone compared with supine treatments. Radiation Therapy Oncology Group grade 0, 1, and 2 skin toxicities were noted acutely in 6%, 69%, and 25% of patients, respectively, and at later follow-up (>3 months) in 43%, 57%, and 0% of patients, respectively. Large breast size contributed to increased acute grade 2 toxicity (28% vs 12%, P=.008). Conclusions: Adequate PTV coverage with acceptable hot spots and excellent sparing of organs at risk was achieved by use of IMRT regardless of treatment position and breast size. Although increasing breast size leads to increased heart dose and maximum skin dose, heart dose remained within our institutional constraints and the incidence of overall skin toxicity was comparable to that reported in the literature. Taken together, these data suggest that hypofractionated radiation therapy using IMRT is a viable and appropriate therapeutic modality in large-breasted patients. [Copyright &y& Elsevier]

Abstract: Purpose: To study the influence of timing of postseed implant imaging on rectal dose–volume parameters for cesium-131 (131Cs) seed prostate implants. Methods and Materials: Fifteen patients were treated in our institution with combination 131Cs brachytherapy followed by pelvic external beam radiation therapy for intermediate to high-risk prostate cancers. For all patients, CT scans were scheduled at 7 days (CT7) and again at 2 months for external beam radiation therapy simulation purpose (CT60) postseed implantation. Comprehensive postseed implant dosimetry was performed for both CT7 and CT60 scans. In each case, dose–volume histogram parameters, rectal separation (the distance between the center of posterior most seed and most anterior rectal wall), and posterior row activity (the total activity implanted within 2–4mm anterior to the posterior wall of the prostate) data were collected. The absolute rectal volumes receiving 100% and 110% prescription dose were also collected. Results: Rectal dose correlated strongly with rectal separation (p <0.001). The mean change in rectal separation between CT7 and CT60 scans was 1.1 (±1.7) mm, and the corresponding change in 0.1-cc rectal dose was 18 (±26.5) Gy. Posterior row activity did not correlate with rectal dose (p =0.51). The mean volume of rectum that receives between 100% and 110% of the prescription dose (RV100 and RV110) increased twofold, between CT7 and CT60 evaluations (0.03 [±0.06] cc vs. 0.07 (±0.05) cc, respectively, p =0.06). Conclusions: Our study has demonstrated that rectal doses after 131Cs seed implants are influenced by the timing of postseed imaging. This may be a consequence of prostatic and periprostatic edema resolution. [Copyright &y& Elsevier]

Purpose: Anatomic changes and positional variability during intensity-modulated radiation therapy (IMRT) for head and neck cancer can lead to clinically significant dosimetric changes. We report our single-institution experience using an adaptive protocol and correlate these changes with anatomic and positional changes during treatment. Methods and Materials: Twenty-three sequential head and neck IMRT patients underwent serial computed tomography (CT) scans during their radiation course. After undergoing the planning CT scan, patients underwent planned rescans at 11, 22, and 33 fractions; a total of 89 scans with 129 unique CT plan combinations were thus analyzed. Positional variability and anatomic changes during treatment were correlated with changes in dosimetric parameters to target and avoidance structures between planning CT and subsequent scans. Results: A total of 15/23 patients (65%) benefited from adaptive planning, either due to inadequate dose to gross disease or to increased dose to organs at risk. Significant differences in primary and nodal targets (planning target volume, gross tumor volume, and clinical tumor volume), parotid, and spinal cord dosimetric parameters were noted throughout the treatment. Correlations were established between these dosimetric changes and weight loss, fraction number, multiple skin separations, and change in position of the skull, mandible, and cervical spine. Conclusions: Variations in patient positioning and anatomy changes during IMRT for head and neck cancer can affect dosimetric parameters and have wide-ranging clinical implications. The interplay between random positional variability and gradual anatomic changes requires careful clinical monitoring and frequent use of CT- based image-guided radiation therapy, which should determine variations necessitating new plans. [ABSTRACT FROM AUTHOR]

Abstract: Intensity-modulated radiation therapy (IMRT) has been applied for treatments of primary head with neck nodes, lung with supraclavicular nodes, and high-risk prostate cancer with pelvis wall nodes, all of which require large fields. However, the design of the Varian multileaf collimator requires fields >14 cm in width to be split into 2 or more carriage movements. With the split-field technique, both the number of monitor units (MUs) and total treatment time are significantly increased. Although many different approaches have been investigated to reduce the MU, including introducing new leaf segmentation algorithms, none have resulted in widespread success. In addition, for most clinics, writing such algorithms is not a feasible solution, particularly with commercial treatment planning systems. We introduce a new approach that can minimize the number of split fields and reduce the total MUs, thereby reducing treatment time. The technique is demonstrated on the Eclipse planning system V7.3, but could be generalized to any other system. [Copyright &y& Elsevier]

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters ≤20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy® linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3® high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R50-R100 (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV50) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a 'V' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R50-R100 and NTV50 initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters ≤20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55±0.79 with HI 1.23±0.06; the average R50-R100 was 0.41±0.08, 0.55±0.10, and 0.65±0.09 cm, respectively, for tumors ≤20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system. [ABSTRACT FROM AUTHOR]

Background: To evaluate and compare the biological impact on different proposed margin recipes for the same geometric uncertainties for intra-hepatic tumors with different tumor cell types or clinical stages. Method: Three different margin recipes based on tumor motion were applied to sixteen IMRT plans with a total of twenty two intra-hepatic tumors. One recipe used the full amplitude of motion measured from patients to generate margins. A second used 70% of the full amplitude of motion, while the third had no margin for motion. The biological effects of geometric uncertainty in these three situations were evaluated with Equivalent Uniform Doses (EUD) for various survival fractions at 2 Gy (SF2). Results: There was no significant difference in the biological impact between the full motion margin and the 70% motion margin. Also, there was no significant difference between different tumor cell types. When the margin for motion was eliminated, the difference of the biological impact was significant among different cell types due to geometric uncertainties. Elimination of the motion margin requires dose escalation to compensate for the biological dose reduction due to the geometric misses during treatment. Conclusions: Both patient-based margins of full motion and of 70% motion are sufficient to prevent serious dosimetric error. Clinical implementation of margin reduction should consider the tumor sensitivity to radiation. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study. [Copyright &y& Elsevier]