Volumetric changes of the parotid gland during IMRT based on mid-treatment imaging: implications for parotid stem cell sparing strategies in head and neck cancer.

BACKGROUND: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Referral practices to dermatologists for the treatment of radiation dermatitis in the USA: a call for a multidisciplinary approach.

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.

Human papillomavirus, radiation dose and survival of patients with anal cancer.

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.

Pretreatment financial toxicity predicts progression-free survival following concurrent chemoradiotherapy for locally advanced non-small-cell lung cancer.

Aim: Financial toxicity (FT) describes patients' burden from out-of-pocket medical treatment costs. We studied associations between patient-reported pretreatment FT, socioeconomic status and clinical outcomes for locally advanced non-small-cell lung cancer (LA-NSCLC) patients. Methods: Patients received chemoradiotherapy for locally advanced non-small-cell lung cancer and completed the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) quality of life assessment before treatment. One question asks whether patients experience 'financial difficulties'. We tested FT and socioeconomic status (SES) as predictors of progression-free survival (PFS) and overall survival (OS). Results: A total of 43 patients were included. Median follow-up for surviving patients was 15 months. A total of 19 patients (44%) experienced disease progression and 17 patients (40%) died. Increasing FT was associated with shorter PFS (p = 0.011). FT did not predict overall survival (p = 0.67). Conclusion: Higher pretreatment FT is associated with shorter PFS.

Neoadjuvant radiation therapy for the management of myoepithelial carcinoma of the upper extremity.

Myoepithelial tumors of the soft tissue are a rare tumor displaying myoepithelial elements and lacking obvious ductal differentiation. The rarity of these precludes any evidence-based consensus regarding optimal management. Nevertheless, the current approach to these lesions begins with amputation or complete excision. The efficacy of neoadjuvant or adjuvant radiation therapy or chemotherapy has not been established. Here, we present the first report to the authors' knowledge of neoadjuvant radiation therapy for the treatment of this rare soft tissue neoplasm and review the management and outcomes of published cases of myoepithelial carcinoma. A patient with a soft tissue myoepithelial carcinoma that declined both amputation and chemotherapy was treated with neoadjuvant radiation therapy and wide surgical excision followed by a brachytherapy boost to the resected tumor bed. Neoadjuvant radiation therapy resulted in an excellent response with extensive treatment-related changes consisting predominantly of fibrosis, hyalinization and hemorrhage and only 10% residual viable myoepithelial carcinoma present in the surgical specimen.

The impact of dietary regimen compliance on outcomes for HNSCC patients treated with radiation therapy.

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.

Practice patterns for the prophylaxis and treatment of acute radiation dermatitis in the United States.

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.

Emotional Intelligence and Burnout in Academic Radiation Oncology Chairs.

EXECUTIVE SUMMARY: 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 of 4 (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 oncology 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.

Management algorithm for HIV-associated parotid lymphoepithelial cysts.

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.

Machine Learning-Based Prediction of Hospitalization During Chemoradiotherapy With Daily Step Counts.

Importance: Toxic effects of concurrent chemoradiotherapy (CRT) can cause treatment interruptions and hospitalizations, reducing treatment efficacy and increasing health care costs. Physical activity monitoring may enable early identification of patients at high risk for hospitalization who may benefit from proactive intervention. Objective: To develop and validate machine learning (ML) approaches based on daily step counts collected by wearable devices on prospective trials to predict hospitalizations during CRT. Design, Setting, and Participants: This study included patients with a variety of cancers enrolled from June 2015 to August 2018 on 3 prospective, single-institution trials of activity monitoring using wearable devices during CRT. Patients were followed up during and 1 month following CRT. Training and validation cohorts were generated temporally, stratifying for cancer diagnosis (70:30). Random forest, neural network, and elastic net-regularized logistic regression (EN) were trained to predict short-term hospitalization risk based on a combination of clinical characteristics and the preceding 2 weeks of activity data. To predict outcomes of activity data, models based only on activity-monitoring features and only on clinical features were trained and evaluated. Data analysis was completed from January 2022 to March 2023. Main Outcomes and Measures: Model performance was evaluated in terms of the receiver operating characteristic area under curve (ROC AUC) in the stratified temporal validation cohort. Results: Step counts from 214 patients (median [range] age, 61 [53-68] years; 113 [52.8%] male) were included. EN based on step counts and clinical features had high predictive ability (ROC AUC, 0.83; 95% CI, 0.66-0.92), outperforming random forest (ROC AUC, 0.76; 95% CI, 0.56-0.87; P = .02) and neural network (ROC AUC, 0.80; 95% CI, 0.71-0.88; P = .36). In an ablation study, the EN model based on only step counts demonstrated greater predictive ability than the EN model with step counts and clinical features (ROC AUC, 0.85; 95% CI, 0.70-0.93; P = .09). Both models outperformed the EN model trained on only clinical features (ROC AUC, 0.53; 95% CI, 0.31-0.66; P < .001). Conclusions and Relevance: This study developed and validated a ML model based on activity-monitoring data collected during prospective clinical trials. Patient-generated health data have the potential to advance predictive ability of ML approaches. The resulting model from this study will be evaluated in an upcoming multi-institutional, cooperative group randomized trial.

Predictive Factors for Cancer Treatment Delay in a Racially Diverse and Socioeconomically Disadvantaged Urban Population.

PURPOSE: Incremental delays in time to treatment initiation (TTI) have been shown to cause a proportional, increased independent risk of disease-specific mortality for breast cancer, colorectal cancer (CRC), head and neck cancer (HNC), non-small-cell lung cancer (NSCLC), and pancreatic cancer. Studies suggest that delays are associated with racial and socioeconomic disparities. We evaluated associations between patient factors and TTI to identify those associated with delay. MATERIALS AND METHODS: This is a retrospective cohort study at an urban community-based academic center of patients diagnosed with or referred for curative-intent treatment of breast cancer, CRC, HNC, NSCLC, and pancreatic cancer from January 2019 to December 2021. Variables of interest included Charlson Comorbidity Index (CCI) score, insurance type, language preference, and inpatient admission 30 days before diagnosis. Factors associated with TTI delay, defined as TTI ≥ 30 days, were assessed using multivariable logistic regression. RESULTS: Among 2,543 patients (69% female), the mean age was 63.4 years and the median TTI was 25 days (IQR, 6-44). Within multivariable models, patients treated as outpatient and not admitted 30 days before diagnosis experienced statistically significant greater delay for CRC (odds ratio [OR], 2.82; 95% CI, 1.71 to 4.66) and NSCLC (OR, 2.11; 95% CI, 1.31 to 3.39). Higher CCI score was associated with delay for HNC (OR, 2.63; 95% CI, 1.04 to 6.66) and NSCLC (OR, 1.75; 95% CI, 1.14 to 2.71). For breast cancer, uninsured and Spanish-speaking patients (OR, 1.79; 95% CI, 1.21 to 2.67) experienced increased TTI. CONCLUSION: Care coordination/compliance (eg, inpatient 30 days before diagnosis), clinical (eg, medical comorbidities), and socioeconomic (eg, uninsured status) predictors for delayed TTI were identified and may inform delay minimizing interventions. Our data support evidence that TTI delays are associated with demographic and socioeconomic disparities. Existing disparities are likely exacerbated by delays that disproportionately affect patients with care coordination/compliance issues, multiple comorbidities, and lower socioeconomic status.

Predictors of Financial Toxicity in Patients Receiving Concurrent Radiation Therapy and Chemotherapy.

Purpose: Financial toxicity (FT) is a significant concern for patients with cancer. We reviewed prospectively collected data to explore associations with FT among patients undergoing concurrent, definitive chemoradiation therapy (CRT) within a diverse, urban, academic radiation oncology department. Methods and Materials: Patients received CRT in 1 of 3 prospective trials. FT was evaluated before CRT (baseline) and then weekly using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire Core-30 questionnaire. Patients were classified as experiencing FT if they answered ≥2 on a Likert scale question (1-4 points) asking if they experienced FT. Rate of change of FT was calculated using linear regression; worsening FT was defined as increase ≥1 point per month. χ2, t tests, and logistic regression were used to assess predictors of FT. Results: Among 233 patients, patients attended an average of 9 outpatient and 4 radiology appointments over the 47 days between diagnosis and starting CRT. At baseline, 52% of patients reported experiencing FT. Advanced T stage (odds ratio, 2.47; P = .002) was associated with baseline FT in multivariate analysis. The mean rate of FT change was 0.23 Likert scale points per month. In total, 26% of patients demonstrated worsening FT during CRT. FT at baseline was not associated with worsening FT (P = .98). Hospitalization during treatment was associated with worsening FT (odds ratio, 2.30; P = .019) in multivariate analysis. Conclusions: Most patients reported FT before CRT. These results suggest that FT should be assessed (and, potentially, addressed) before starting definitive treatment because it develops early in a patient's cancer journey. Reducing hospitalizations may mitigate worsening FT. Further research is warranted to design interventions to reduce FT and avoid hospitalizations.

Improving Adjuvant Liver-Directed Treatment Recommendations for Unresectable Hepatocellular Carcinoma: An Artificial Intelligence-Based Decision-Making Tool.

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.

A positron emission tomography radiomic signature for distant metastases risk in oropharyngeal cancer patients treated with definitive chemoradiotherapy.

BACKGROUND AND PURPOSE: Disease recurrence and distant metastases (DM) are major concerns for oropharyngeal cancer (OPC) patients receiving definitive chemo-radiotherapy. Here, we investigated whether pre-treatment primary tumor positron emission tomography (PET) features could predict progression-free survival (PFS) or DM. METHODS AND MATERIALS: Primary tumors were delineated on pre-treatment PET scans for patients treated between 2005 and 2018 using gradient-based segmentation. Radiomic image features were extracted, along with SUV metrics. Features with zero variance and strong correlation to tumor volume, stage, p16 status, age or smoking were excluded. A random forest model was used to identify features associated with PFS. Kaplan-Meier methods, Cox regression and logistic regression with receiver operating characteristics (ROC) and 5-fold cross-validated areas-under-the-curve (CV-AUCs) were used. RESULTS: A total of 114 patients were included. With median follow-up 40 months (range: 3-138 months), 14 patients had local recurrence, 21 had DM and 38 died. Two-year actuarial local control, distant control, PFS and overall survival was 89%, 84%, 70% and 84%, respectively. The wavelet_LHL_GLDZM_LILDE feature slightly improved PFS prediction compared to clinical features alone (CV-AUC 0.73 vs. 0.71). Age > 65 years (HR = 2.64 (95%CI: 1.36-5.2), p = 0.004) and p16-negative disease (HR = 3.38 (95%CI: 1.72-6.66), p < 0.001) were associated with poor PFS. A binary radiomic classifier strongly predicted DM with multivariable HR = 3.27 (95%CI: 1.15-9.31), p = 0.027, specifically for patients with p16-negative disease with 2-year DM-free survival 83% for low-risk vs. 38% for high-risk patients (p = 0.004). CONCLUSIONS: A radiomics signature strongly associated with DM risk could provide a tool for improved risk stratification, potentially adding adjuvant immunotherapy for high-risk patients.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: tumor dose inhomogeneity, conformity, and dose fall off.

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 < or = 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 < or = 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 < or = 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.

Multi-scale regularization approaches of non-parametric deformable registrations.

Most deformation algorithms use a single-value smoother during optimization. We investigate multi-scale regularizations (smoothers) during the multi-resolution iteration of two non-parametric deformable registrations (demons and diffeomorphic algorithms) and compare them to a conventional single-value smoother. Our results show that as smoothers increase, their convergence rate decreases; however, smaller smoothers also have a large negative value of the Jacobian determinant suggesting that the one-to-one mapping has been lost; i.e., image morphology is not preserved. A better one-to-one mapping of the multi-scale scheme has also been established by the residual vector field measures. In the demons method, the multi-scale smoother calculates faster than the large single-value smoother (Gaussian kernel width larger than 0.5) and is equivalent to the smallest single-value smoother (Gaussian kernel width equals to 0.5 in this study). For the diffeomorphic algorithm, since our multi-scale smoothers were implemented at the deformation field and the update field, calculation times are longer. For the deformed images in this study, the similarity measured by mean square error, normal correlation, and visual comparisons show that the multi-scale implementation has better results than large single-value smoothers, and better or equivalent for smallest single-value smoother. Between the two deformable registrations, diffeormophic method constructs better coherence space of the deformation field while the deformation is large between images.

Predictors of prostate bed recurrence on magnetic resonance imaging in patients with rising prostate-specific antigen after radical prostatectomy.

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.

Individualized quality of life benefit and cost-effectiveness estimates of proton therapy for patients with oropharyngeal cancer.

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.