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Automatic contouring algorithms may streamline clinical workflows by reducing normal organ-at-risk (OAR) contouring time. Here we report the first comprehensive quantitative and qualitative evaluation, along with time savings assessment for a prototype deep learning segmentation algorithm from Siemens Healthineers. The accuracy of contours generated by the prototype were evaluated quantitatively using the Sorensen-Dice coefficient (Dice), Jaccard index (JC), and Hausdorff distance (Haus). Normal pelvic and head and neck OAR contours were evaluated retrospectively comparing the automatic and manual clinical contours in 100 patient cases. Contouring performance outliers were investigated. To quantify the time savings, a certified medical dosimetrist manually contoured de novo and, separately, edited the generated OARs for 10 head and neck and 10 pelvic patients. The automatic, edited, and manually generated contours were visually evaluated and scored by a practicing radiation oncologist on a scale of 1-4, where a higher score indicated better performance. The quantitative comparison revealed high (> 0.8) Dice and JC performance for relatively large organs such as the lungs, brain, femurs, and kidneys. Smaller elongated structures that had relatively low Dice and JC values tended to have low Hausdorff distances. Poor performing outlier cases revealed common anatomical inconsistencies including overestimation of the bladder and incorrect superior-inferior truncation of the spinal cord and femur contours. In all cases, editing contours was faster than manual contouring with an average time saving of 43.4% or 11.8 minutes per patient. The physician scored 240 structures with > 95% of structures receiving a score of 3 or 4. Of the structures reviewed, only 11 structures needed major revision or to be redone entirely. Our results indicate the evaluated auto-contouring solution has the potential to reduce clinical contouring time. The algorithm's performance is promising, but human review and some editing is required prior to clinical use. [ABSTRACT FROM AUTHOR]

Background Method Results Conclusion Treatment planning is currently a patient specific, time‐consuming, and resource demanding task in radiotherapy. Dose‐volume histogram (DVH) prediction plays a critical role in automating this process. The geometric relationship between DVHs in radiotherapy plans and organs‐at‐risk (OAR) and planning target volume (PTV) has been well established. This study explores the potential of deep learning models for predicting DVHs using images and subsequent human intervention facilitated by a large‐language model (LLM) to enhance the planning quality.We propose a pipeline to convert unstructured images to a structured graph consisting of image‐patch nodes and dose nodes. A novel Dose Graph Neural Network (DoseGNN) model is developed for predicting DVHs from the structured graph. The proposed DoseGNN is enhanced with the LLM to encode massive knowledge from prescriptions and interactive instructions from clinicians. In this study, we introduced an online human‐AI collaboration (OHAC) system as a practical implementation of the concept proposed for the automation of intensity‐modulated radiotherapy (IMRT) planning.The proposed DoseGNN model was compared to widely employed DL models used in radiotherapy, including Swin Transformer, 3D U‐Net CNN, and vanilla MLP. For PTV, DoseGNN achieved the mean absolute error (MAE) of Dmax${D}_{max}$, Dmean${D}_{mean}$, D95${D}_{95}$, and D1${D}_1$ between true plans and predicted plans that were 64%, 53%, 64%, 61% of the best baseline model. For the worst case among OARs (left lung, right lung, chest wall, heart, spinal cord), DoseGNN achieved the mean absolute error of Dmax${D}_{max}$, Dmean${D}_{mean}$, D50${D}_{50}$ that were 85%, 91%, 80% of the best baseline model. Moreover, the LLM‐empowered DoseGNN model facilitates seamless adjustment to treatment plans through interaction with clinicians using natural language.We developed DoseGNN, a novel deep learning model for predicting delivered radiation doses from medical images, enhanced by LLM to allow adjustment through seamless interaction with clinicians. The preliminary results confirm DoseGNN's superior accuracy in DVH prediction relative to typical DL methods, highlighting its potential to facilitate an online clinician‐AI collaboration system for streamlined treatment planning automation. [ABSTRACT FROM AUTHOR]

Purpose: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer.Methods and Materials: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level.Results: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively.Conclusions: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT. [ABSTRACT FROM AUTHOR]

BACKGROUND Radiation treatment volumes in head and neck squamous cell carcinoma (HNSCC) are controversial. The authors report the outcomes, patterns of failure, and quality of life (QOL) of patients who received treatment for HNSCC using intensity-modulated radiation therapy (IMRT) that eliminated the treatment of contralateral retropharyngeal lymph nodes (RPLNs) in the clinically uninvolved neck. METHODS A prospective institutional database was used to identify patients who had primary oral cavity, oropharyngeal, hypopharyngeal, laryngeal, and unknown primary HNSCC for which they received IMRT. There were 3 temporal groups (generations 1-3). Generation 1 received comprehensive neck IMRT with parotid sparing, generation 2 eliminated the contralateral high level II (HLII) lymph nodes, and generation 3 further eliminated the contralateral RPLNs in the clinically uninvolved neck. Patterns of failure and survival analyses were completed, and QOL data measured using the MD Anderson Dysphagia Inventory were compared in a subset of patients from generations 1 and 3. RESULTS In total, 748 patients were identified. Of the 488 patients who received treatment in generation 2 or 3, 406 had a clinically uninvolved contralateral neck. There were no failures in the spared RPLNs (95% confidence interval, 0%-1.3%) or in the high contralateral neck (95% confidence interval, 0%-0.7%). QOL data were compared between 44 patients in generation 1 and 51 patients in generation 3. QOL improved both globally and in all domains assessed for generation 3, in which reduced radiotherapy volumes were used ( P < .007). CONCLUSIONS For patients with locally advanced HNSCC, eliminating coverage to the contralateral HLII lymph nodes and contralateral RPLNs in the clinically uninvolved side of the neck is associated with minimal risk of failure in these regions and significantly improved patient-reported QOL. Cancer 2014;120:3994-4002. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The purpose of the proposed study is to evaluate the effectiveness and safety of low-dose paclitaxel with timed thoracic radiotherapy (TTR) for local control by inducing maximum radiosensitization through G2-M phase cell cycle arrest, followed by full dose adjuvant chemotherapy with gemcitabine and carboplatin for eradication of possible micrometastasis in unresectable stage III non-small cell lung cancer (NSCLC). Materials and methods: This is a single-center, non-randomized prospective phase II study. Patients with unresectable stage III NSCLC were treated with paclitaxel 15mg/m2 IV, followed by TTR 6h later on Monday/Wednesday/Friday, and TTR only on Tuesday/Thursday mornings (total 55Gy). Full dose adjuvant chemotherapy consisted of intravenous carboplatin (AUC 5) on day 1, gemcitabine 1000mg/m2 on days 1 and 8, every 21 days for 4 cycles. The primary endpoint was overall survival (OS). Secondary endpoints were overall response rate (ORR), and toxicities. Results: Twenty-seven patients were eligible for the study. Patient characteristics were: 19 males (70%); median age 67 years (range 39–82); 15 (56%) stage IIIB; 89% with ECOG performance status ≥1. Three-year OS was 16.7% in all patients, and 27.3% in patients received three or more cycles of adjuvant chemotherapy, respectively. ORR was 63%. Grade 3 toxicities during paclitaxel plus concurrent TTR phase were radiation esophagitis (11%) and radiation pneumonitis (4%), no grade 4 toxicities occurred. One grade 5 hemoptysis. Grade 3/4 toxicities during adjuvant gemcitabine/carboplatin were pneumonitis (22%), anemia (30%), neutropenia (22%), and thrombocytopenia (33%), one grade 5 neutropenic fever. Conclusion: Low-dose paclitaxel with concurrent TTR is an effective chemoradiotherapy regimen in unresectable stage III NSCLC. Improved survival benefit was observed in patients who have received three or more cycles of full dose adjuvant chemotherapy, yet, gemcitabine related radiation pneumonitis and hematological toxicities limited adjuvant chemotherapy delivery. [Copyright &y& Elsevier]

Objective: To evaluate the immediate effects of neoadjuvant androgen deprivation therapy (NADT) on health-related quality of life (HRQOL) among patients undergoing radiation therapy (RT) for newly diagnosed prostate cancer. Methods: The Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium is a prospective multi-institutional study. HRQOL is measured with the Expanded Prostate Cancer Index Composite-26 questionnaire. Differences in patient-reported HRQOL were observed between pretreatment and 2 months after NADT start (and before definitive RT) with significant differences evaluated by paired t test. Results: From among 450 patients who completed the Expanded Prostate Cancer Index Composite-26 before and 2 months after NADT start, 71 received NADT before proceeding with definitive RT. Patients receiving NADT experienced significant impairment in vitality/hormonal (P <.0001) and sexual (P <.0001) HRQOL after NADT initiation. The mean ± standard deviation vitality/hormonal score fell from an average of 94.1 ± 9.7 before NADT to 78.7 ± 16.3 two months after NADT initiation; and sexual HRQOL fell from a mean of 51.7 ± 31.1 pretreatment to 32.3 ± 26.1 after NADT initiation. Both these HRQOL domain changes exceeded the thresholds for clinical significance. Patients receiving NADT also experienced a significant impairment in urinary continence (P = .024), although this difference did not meet the criteria for clinical significance. Conclusion: In this analysis, patients receiving NADT experience significant impairment in sexual and vitality/hormonal HRQOL even before starting definitive RT. The significant effect of this therapy on HRQOL needs to be considered before initiating NADT in men where there is no clear evidence of clinical benefit. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oropharyngeal squamous cell carcinoma (SCC) rates have been increasing significantly in recent years, despite a decreasing incidence of head and neck cancer in general. Oropharyngeal SCC has many characteristics that are distinct from other head and neck cancers, and thus it is important to focus specifically on cancers arising in this region, with the goal of improving patient outcomes. One important goal is to identify those patients who are likely to fail standard therapy and who could potentially benefit from alternative or targeted treatments. METHODS: In the current study, the prognostic value of microRNAs (miRNAs) was evaluated in patients with oropharyngeal SCC. miRNAs are small, noncoding RNAs that are master regulators of many important biological processes. In total, 150 oropharyngeal tumors were analyzed using the recently developed quantitative polymerase chain reaction-based method for miRNA expression profiling. In addition, the expression of miRNAs was also compared with human papillomavirus (HPV) transcriptional activities. RESULTS: The current study identified 6 miRNAs that were found to be significantly associated with cancer survival. A combined expression signature of these miRNAs was prognostic of oropharyngeal SCC, independent of common clinical features or HPV status. CONCLUSIONS: This new miRNA signature was experimentally validated in an independent oropharyngeal SCC cohort. Furthermore, 5 HPV-related miRNAs were identified, which may help to characterize HPV-induced cancers including both oropharyngeal and cervical SCC. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background. To characterize the lung tumor volume response during conventional and hypofractionated radiotherapy (RT) based on diagnostic quality CT images prior to each treatment fraction. Methods. Out of 26 consecutive patients who had received CTon- rails IGRT to the lung from 2004 to 2008, 18 were selected because they had lung lesions that could be easily distinguished.The time course of the tumor volume for each patient was individually analyzed using a computer program. Results. The model fits of group L (conventional fractionation) patients were very close to experimental data, with a median Δ% (average percent difference between data and fit) of 5.1% (range 3.5-10.2%).The fits obtained in group S (hypofractionation) patients were generally good, with a median Δ% of 7.2% (range 3.7-23.9%) for the best fitting model. Four types of tumor responses were observed-Type A: "high" kill and "slow" dying rate; Type B: "high" kill and "fast" dying rate; Type C: "low" kill and "slow" dying rate; and Type D: "low" kill and "fast" dying rate. Conclusions. The models used in this study performed well in fitting the available dataset. The models provided useful insights into the possible underlying mechanisms responsible for the RT tumor volume response. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Help identify and define potential normal tissue dose constraints to minimize the mortality and morbidity of hypofractionated lung radiotherapy. Materials and methods: A method to generate isodose-based constraints and visually evaluate treatment plans, based on the published peer reviewed literature and the linear quadratic model, is presented. The radiobiological analysis assumes that the linear quadratic model isvalid up to 28Gy per fraction, the α/β ratio is 2 for the spinal cord and brachial plexus, 4 for pneumonitis, 4 or 10 for acute skin reactions depending on treatment length, and 3 for late complications in other normal tissues. A review of the literature was necessary to identify possible endpoints and normal tissue constraints for thoracic hypofractionated lung radiotherapy. Results: Preliminary normal tissue constraints to reduce mortality and morbidity were defined for organs at risk based upon hypofractionated lung radiotherapy publications. A modified dose nomenclature was introduced to facilitate the comparison of hypofractionated doses. Potential side effects from hypofractionated lung radiotherapy such as aortic dissection, neuropathy, and fatal organ perforation rarely seen in conventional treatments were identified. The isodose-based method for treatment plan analysis and normal tissue dose constraint simplification was illustrated. Conclusions: The radiobiological analysis based on the LQ method, biologically equivalent dose nomenclature, and isodose-based method proposed in this study simplifies normal tissue dose constraints and treatment plan evaluation. This may also be applied to extrathoracic hypofractionated radiotherapy. Prospective validation of these preliminary thoracic normal tissue dose constraints for hypofractionated lung radiotherapy is necessary. [Copyright &y& Elsevier]

Purpose: To determine the important clinical/pathologic prognostic factors and optimal treatment of malignant parotid tumors.Methods and materials: This study was a retrospective chart review of 163 patients treated for malignant parotid tumors at two institutions. Of the 163 patients, 91 were treated with surgical resection and radiotherapy (RT), 56 were treated with surgery alone, and 13 were treated with RT alone. The median follow-up was 5.1 years (range, 0–37 years).Results: Locoregional recurrence occurred in 37% of surgery-only, 11% of surgery plus RT, and 15% of RT-only patients (p = 0.001, Pearson''s chi-square test). Cox proportional hazard multivariate analysis revealed that increasing age and higher stage were each statistically significantly (p < 0.05) associated with a poorer overall 5-year survival and cause-specific survival. Only increasing age and the absence of adjuvant RT were shown in Cox proportional hazard multivariate analysis to impact negatively on local failure–free survival.Conclusion: In Cox proportional hazards multivariate analysis, only increasing age and stage were statistically significant prognostic factors for survival. The addition of RT to surgery did not improve overall survival but did reduce locoregional recurrence and improve local failure–free survival. [Copyright &y& Elsevier]

Background: Deep learning (DL) techniques have been extensively applied in medical image classification. The unique characteristics of medical imaging data present challenges, including small labeled datasets, severely imbalanced class distribution, and significant variations in imaging quality. Recently, generative adversarial network (GAN)‐based classification methods have gained attention for their ability to enhance classification accuracy by incorporating realistic GAN‐generated images as data augmentation. However, the performance of these GAN‐based methods often relies on high‐quality generated images, while large amounts of training data are required to train GAN models to achieve optimal performance. Purpose: In this study, we propose an adversarial learning‐based classification framework to achieve better classification performance. Innovatively, GAN models are employed as supplementary regularization terms to support classification, aiming to address the challenges described above. Methods: The proposed classification framework, GAN‐DL, consists of a feature extraction network (F‐Net), a classifier, and two adversarial networks, specifically a reconstruction network (R‐Net) and a discriminator network (D‐Net). The F‐Net extracts features from input images, and the classifier uses these features for classification tasks. R‐Net and D‐Net have been designed following the GAN architecture. R‐Net employs the extracted feature to reconstruct the original images, while D‐Net is tasked with the discrimination between the reconstructed image and the original images. An iterative adversarial learning strategy is designed to guide model training by incorporating multiple network‐specific loss functions. These loss functions, serving as supplementary regularization, are automatically derived during the reconstruction process and require no additional data annotation. Results: To verify the model's effectiveness, we performed experiments on two datasets, including a COVID‐19 dataset with 13 958 chest x‐ray images and an oropharyngeal squamous cell carcinoma (OPSCC) dataset with 3255 positron emission tomography images. Thirteen classic DL‐based classification methods were implemented on the same datasets for comparison. Performance metrics included precision, sensitivity, specificity, and F1$F_1$‐score. In addition, we conducted ablation studies to assess the effects of various factors on model performance, including the network depth of F‐Net, training image size, training dataset size, and loss function design. Our method achieved superior performance than all comparative methods. On the COVID‐19 dataset, our method achieved 95.4%±0.6%$95.4\%\pm 0.6\%$, 95.3%±0.9%$95.3\%\pm 0.9\%$, 97.7%±0.4%$97.7\%\pm 0.4\%$, and 95.3%±0.9%$95.3\%\pm 0.9\%$ in terms of precision, sensitivity, specificity, and F1$F_1$‐score, respectively. It achieved 96.2%±0.7%$96.2\%\pm 0.7\%$ across all these metrics on the OPSCC dataset. The study to investigate the effects of two adversarial networks highlights the crucial role of D‐Net in improving model performance. Ablation studies further provide an in‐depth understanding of our methodology. Conclusion: Our adversarial‐based classification framework leverages GAN‐based adversarial networks and an iterative adversarial learning strategy to harness supplementary regularization during training. This design significantly enhances classification accuracy and mitigates overfitting issues in medical image datasets. Moreover, its modular design not only demonstrates flexibility but also indicates its potential applicability to various clinical contexts and medical imaging applications. [ABSTRACT FROM AUTHOR]

Purpose: In radiotherapy planning, manual contouring is labor‐intensive and time‐consuming. Accurate and robust automated segmentation models improve the efficiency and treatment outcome. We aim to develop a novel hybrid deep learning approach, combining convolutional neural networks (CNNs) and the self‐attention mechanism, for rapid and accurate multi‐organ segmentation on head and neck computed tomography (CT) images. Methods: Head and neck CT images with manual contours of 115 patients were retrospectively collected and used. We set the training/validation/testing ratio to 81/9/25 and used the 10‐fold cross‐validation strategy to select the best model parameters. The proposed hybrid model segmented 10 organs‐at‐risk (OARs) altogether for each case. The performance of the model was evaluated by three metrics, that is, the Dice Similarity Coefficient (DSC), Hausdorff distance 95% (HD95), and mean surface distance (MSD). We also tested the performance of the model on the head and neck 2015 challenge dataset and compared it against several state‐of‐the‐art automated segmentation algorithms. Results: The proposed method generated contours that closely resemble the ground truth for 10 OARs. On the head and neck 2015 challenge dataset, the DSC scores of these OARs were 0.91±0.02, 0.73±0.10, 0.95±0.03, 0.76±0.08, 0.79±0.05, 0.87±0.05, 0.86±0.08, 0.87±0.03, and 0.87±0.07 for brain stem, chiasm, mandible, left/right optic nerve, left/right submandibular, and left/right parotid, respectively. Our results of the new weaving attention U‐net (WAU‐net) demonstrate superior or similar performance on the segmentation of head and neck CT images. Conclusions: We developed a deep learning approach that integrates the merits of CNNs and the self‐attention mechanism. The proposed WAU‐net can efficiently capture local and global dependencies and achieves state‐of‐the‐art performance on the head and neck multi‐organ segmentation task. [ABSTRACT FROM AUTHOR]

Caribbean small island developing states are becoming increasingly vulnerable to compounding disasters, prominently featuring climate-related hazards and pandemic diseases, which exacerbate existing barriers to cancer control in the region. We describe the complexities of cancer prevention and control efforts throughout the Caribbean small island developing states, including the unique challenges of people diagnosed with cancer in the region. We highlight potential solutions and strategies that concurrently address disaster adaptation and cancer control. Because Caribbean small island developing states are affected first and worst by the hazards of compounding disasters, the innovative solutions developed in the region are relevant for climate mitigation, disaster adaptation, and cancer control efforts globally. In the age of complex and cascading disaster scenarios, developing strategies to mitigate their effect on the cancer control continuum, and protecting the health and safety of people diagnosed with cancer from extreme events become increasingly urgent. The equitable development of such strategies relies on collaborative efforts among professionals whose diverse expertise from complementary fields infuses the local community perspective while focusing on implementing solutions. [ABSTRACT FROM AUTHOR]

Purpose: The research is to develop a novel CNN‐based adversarial deep learning method to improve and expedite the multi‐organ semantic segmentation of CT images and to generate accurate contours on pelvic CT images. Methods: Planning CT and structure datasets for 120 patients with intact prostate cancer were retrospectively selected and divided for tenfold cross‐validation. The proposed adversarial multi‐residual multi‐scale pooling Markov random field (MRF) enhanced network (ARPM‐net) implements an adversarial training scheme. A segmentation network and a discriminator network were trained jointly, and only the segmentation network was used for prediction. The segmentation network integrates a newly designed MRF block into a variation of multi‐residual U‐net. The discriminator takes the product of the original CT and the prediction/ground‐truth as input and classifies the input into fake/real. The segmentation network and discriminator network can be trained jointly as a whole, or the discriminator can be used for fine‐tuning after the segmentation network is coarsely trained. Multi‐scale pooling layers were introduced to preserve spatial resolution during pooling using less memory compared to atrous convolution layers. An adaptive loss function was proposed to enhance the training on small or low contrast organs. The accuracy of modeled contours was measured with the dice similarity coefficient (DSC), average Hausdorff distance (AHD), average surface Hausdorff distance (ASHD), and relative volume difference (VD) using clinical contours as references to the ground‐truth. The proposed ARPM‐net method was compared to several state‐of‐the‐art deep learning methods. Results: ARPM‐net outperformed several existing deep learning approaches and MRF methods and achieved state‐of‐the‐art performance on a testing dataset. On the test set with 20 cases, the average DSC on the prostate, bladder, rectum, left femur, and right femur were 0.88 (±0.11), 0.97 (±0.07), 0.86 (±0.12), 0.97 (±0.01), and 0.97 (±0.01), respectively. The average HD (mm) on these organs were 1.58 (± 1.77), 1.91 (±1.29), 3.14 (±2.39), 1.76 (±1.57), and 1.92 (±1.01). The average surface HD (mm) on these organs are 2.11 (±2.03), 2.36 (±2.43), 3.05 (±2.11), 1.99 (±1.66), and 2.00 (±2.07). Conclusion: ARPM‐net was designed for the automatic segmentation of pelvic CT images. With adversarial fine‐tuning, ARPM‐net produces state‐of‐the‐art accurate contouring of multiple organs on CT images and has the potential to facilitate routine pelvic cancer radiation therapy planning process. [ABSTRACT FROM AUTHOR]

The not-for-profit organization La LIGA Nacional Contra el Cáncer, with its hospital Instituto de Cancerología (INCAN), is responsible for cancer treatment of much of the indigent population in Guatemala, a country with a population of 16 million. Annually, approximately 70% of patients at INCAN are seen in late stages of cancer, which places a great strain on the hospital's limited resources. Private clinics account for 75% of radiation therapy centers in Guatemala and have considerable resources. However, private facilities are fee-based, which creates a barrier for low-income patients; this is an especially significant problem in Guatemala, which has the highest income inequalities and poverty rates in Latin America. This article describes a project on the transition from cobalt to a Halcyon radiation therapy system at INCAN through a partnership with the US Agency for International Development's Office of American Schools and Hospitals Abroad (USAID/ASHA), Washington University in St. Louis (WUSTL), industry partner Varian Medical Systems, and the US National Nuclear Security Administration to provide access to state-of-the-art radiation therapy technology while increasing the overall treatment capacity for the underserved population of Guatemala. [ABSTRACT FROM AUTHOR]

Currently, there is limited data on the comparative effectiveness of radiation therapy (RT) vs. chemoradiation (CHT) for high-grade T1 (HGT1) non-muscle invasive bladder cancer (non-MIBC). Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio (HR): 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Background: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. Methods: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. Results: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P < .008). Conclusion: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesisgenerating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies. [ABSTRACT FROM AUTHOR]

Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue α/β ratio divided by the tumor α/β times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified. [ABSTRACT FROM AUTHOR]

The addition of a brachytherapy (BT) boost to external beam radiotherapy (EBRT) reduces recurrence risk in men with high-risk prostate cancer (PCa) and may reduce PCa-mortality for Gleason grade group 5 (GG5). Whether the extent of pattern five, a risk factor for distant metastases, impacts the benefit of a BT boost is unclear. Men with localized GG5 PCa treated with (1) EBRT or (2) EBRT+BT between 2010 and 2016 were identified in the National Cancer Database. EBRT monotherapy group received conventionally fractionated (1.8−2.0 Gy per fraction) ≥74 Gy or moderately hypofractionated (2.5−3.0 Gy per fraction) ≥60 Gy. EBRT + BT group received conventionally fractionated ≥45 Gy or moderately hypofractionated ≥37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT; none received chemotherapy, immunotherapy, or surgery. OS was compared using Kaplan-Meier, log-rank test, and multivariable Cox proportional hazards in the overall cohort, followed by subgroups based on primary versus secondary pattern 5. Propensity score- and exact-matching was used to corroborate results. A total of 8260 men were eligible: EBRT alone (89%) versus EBRT + BT (11%). 5-year OS for EBRT versus EBRT + BT was 76.3% and 85.0%, respectively (p = 0.002; multivariable adjusted HR 0.84, 95% CI 0.65−0.98; p = 0.04). These results remained consistent after propensity score and exact matching. The OS advantage of a BT boost was more prominent in men with Gleason 4 + 5 PCa (p = 0.001) and not observed in men with Gleason 5 + 5 or 5 + 4 PCa. Extent of pattern five may be useful in appropriately selecting men for EBRT+BT and should be considered as a pre-randomization stratification variable for future clinical trial design. [ABSTRACT FROM AUTHOR]

Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa_R, Adnexa_L, Prostate, SeminalVesc, PenileBulb, Femur_R, and Femur_L. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research. [ABSTRACT FROM AUTHOR]

Background: To evaluate the daily total error shift patterns on post-prostatectomy patients undergoing image guided radiotherapy (IGRT) with a diagnostic quality computer tomography (CT) on rails system.Methods: A total of 17 consecutive post-prostatectomy patients receiving adjuvant or salvage IMRT using CT-on-rails IGRT were analyzed. The prostate bed's daily total error shifts were evaluated for a total of 661 CT scans.Results: In the right-left, cranial-caudal, and posterior-anterior directions, 11.5%, 9.2%, and 6.5% of the 661 scans required no position adjustments; 75.3%, 66.1%, and 56.8% required a shift of 1 - 5 mm; 11.5%, 20.9%, and 31.2% required a shift of 6 - 10 mm; and 1.7%, 3.8%, and 5.5% required a shift of more than 10 mm, respectively. There was evidence of correlation between the x and y, x and z, and y and z axes in 3, 3, and 3 of 17 patients, respectively. Univariate (ANOVA) analysis showed that the total error pattern was random in the x, y, and z axis for 10, 5, and 2 of 17 patients, respectively, and systematic for the rest. Multivariate (MANOVA) analysis showed that the (x,y), (x,z), (y,z), and (x, y, z) total error pattern was random in 5, 1, 1, and 1 of 17 patients, respectively, and systematic for the rest.Conclusions: The overall daily total error shift pattern for these 17 patients simulated with an empty bladder, and treated with CT on rails IGRT was predominantly systematic. Despite this, the temporal vector trends showed complex behaviors and unpredictable changes in magnitude and direction. These findings highlight the importance of using daily IGRT in post-prostatectomy patients. [ABSTRACT FROM AUTHOR]

The available dose/volume/outcome data for rectal injury were reviewed. The volume of rectum receiving ≥60Gy is consistently associated with the risk of Grade ≥2 rectal toxicity or rectal bleeding. Parameters for the Lyman-Kutcher-Burman normal tissue complication probability model from four clinical series are remarkably consistent, suggesting that high doses are predominant in determining the risk of toxicity. The best overall estimates (95% confidence interval) of the Lyman-Kutcher-Burman model parameters are n = 0.09 (0.04–0.14); m = 0.13 (0.10–0.17); and TD50 = 76.9 (73.7–80.1) Gy. Most of the models of late radiation toxicity come from three-dimensional conformal radiotherapy dose-escalation studies of early-stage prostate cancer. It is possible that intensity-modulated radiotherapy or proton beam dose distributions require modification of these models because of the inherent differences in low and intermediate dose distributions. [Copyright &y& Elsevier]

Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation.Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping.Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than approximately 1.0 Gy/fraction were most strongly associated with severe acute mucositis and dysphagia in the FDA models.Conclusions: FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations. FDA is recommended for use in normal tissue complication probability modeling. [ABSTRACT FROM AUTHOR]

Current recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa. The National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios. Median follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10−7) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10−8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82). In a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS. [ABSTRACT FROM AUTHOR]

Summary Background Due to unique biology and prognosis, precise identification of predictive parameters is critical for p16+ oropharyngeal squamous cell carcinoma (OPSCC). Prior studies showing absence of prognostication from extracapsular spread (ECS) and/or high N-classification in surgically-treated p16+ OPSCC necessitate new, evidence-based prognosticators. Methods A prospectively assembled cohort of 220, transoral surgery + neck dissection ± adjuvant therapy-treated, p16+ OPSCC patients was analyzed. Disease recurrence and disease-specific survival (DSS) were primary endpoints. Results Median follow-up was 59 (12–189) months. Distribution of metastatic node numbers was: 0 in 9.5% ( n = 21), 1 in 33.6% ( n = 74), 2 in 17% ( n = 38), 3 in 14.5% ( n = 32), 4 in 8.2% ( n = 18), and ⩾ 5 in 17% ( n = 37). ECS was recorded in 80% ( n = 159), and N2c–N3 in 17% ( n = 38). Adjuvant radiotherapy and chemoradiotherapy was administered in 44% and 34%. Recurrence developed in 22 patients (10%); 4 local, 5 regional, 2 regional and distant, and 11 distant. The 3- and 5-year DSS estimates were 94.6% and 93%. Multivariable logistic regression identified ⩾ 5 nodes and T3–T4 classification as predictors for recurrence. In multivariable Cox analyses, ⩾ 5 nodes, T3–T4 classification and margins were prognostic for DSS. ECS, N2c–N3 classification and smoking were not prognostic. Conclusions Metastatic node number, not ECS or high N-classification is an independent nodal predictor of outcomes in surgically-treated p16+ OPSCC patients. Despite high DSS (~80%), closer surveillance for recurrence is recommended for patients with ⩾ 5 metastatic nodes. [ABSTRACT FROM AUTHOR]

Definitive treatment options for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost ± androgen deprivation therapy (ADT). The role of brachytherapy ± ADT in the absence of EBRT is not well defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to BT±ADT for UIR-PCa. Men with UIR-PCa diagnosed between 2004 and 2015 were identified in the National Cancer Database (NCDB). Inverse propensity of treatment weighting was used to balance covariables that influenced treatment allocation and outcomes, and propensity-weighted multivariable analysis (MVA) using Cox regression modeling was used to compare OS hazard ratios. A total of 11,721 men were stratified into four treatment groups: (1) BT without ADT (n = 4,535), (2) BT+ADT (n = 1,303), (3) EBRT+BT (n = 3,446), or (4) EBRT+BT+ADT (n = 2,437). Relative to patients treated with BT alone, BT+ADT (Hazard Ratio (HR): 0.86 [95% Confidence Interval (CI): 0.76–0.99], p = 0.03), EBRT+BT (HR: 0.79 [0.70–0.88], p = 0.00002), and EBRT+BT+ADT (HR: 0.76 [0.67–0.85], p = 0.000003) were associated with improved OS on MVA. Relative to BT alone, EBRT+BT correlated with improved OS on weight-adjusted MVA (HR: 0.82 [0.75–0.89], p = 0.000005). 10-year OS for BT vs. EBRT+BT was 62.4% [60.1–64.7] vs. 69.3% [67.5–71.2], respectively (p < 0.0001). EBRT+BT correlated with improved OS relative to BT alone in men with UIR-PCa, reaffirming current NCCN recommendations recommending EBRT+BT over BT alone. While prior studies reported no benefit to adding EBRT to BT with optimal implant dosimetry, this study suggests men benefit from EBRT in a population of variable implant quality. [ABSTRACT FROM AUTHOR]

Purpose: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT).Methods and Materials: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741). Patients were treated with dose-escalated RT with or without ADT. The primary outcome was time to metastasis.Results: The CCR score prognosticated metastasis with a hazard ratio (HR) per unit score of 2.22 (95% confidence interval [CI], 1.71-2.89; P < .001). The CCR score better prognosticated metastasis than NCCN risk group (CCR, P < .001; NCCN, P = .46), CAPRA score (CCR, P = .002; CAPRA, P = .59), or CCP score (CCR, P < .001; CCP, P = .59) alone. In bivariable analyses, CCR score remained highly prognostic when accounting for ADT versus no ADT (HR, 2.18; 95% CI, 1.61-2.96; P < .001), ADT duration as a continuous variable (HR, 2.11; 95% CI, 1.59-2.79; P < .001), or ADT given at or below the recommended duration for each NCCN risk group (HR, 2.19; 95% CI, 1.69-2.86; P < .001). Men with CCR scores below or above the multimodality threshold (CCR score, 2.112) had a 10-year risk of metastasis of 3.7% and 21.24%, respectively. Men with below-threshold scores receiving RT alone had a 10-year risk of metastasis of 3.7%, and for men receiving RT plus ADT, the 10-year risk of metastasis was also 3.7%.Conclusions: The CCR score accurately and precisely prognosticates metastasis and adds clinically actionable information relative to guideline-recommended therapies based on NCCN risk in men undergoing dose-escalated RT with or without ADT. For men with scores below the multimodality threshold, adding ADT may not significantly reduce their 10-year risk of metastasis. [ABSTRACT FROM AUTHOR]

In the era of COVID-19, there has been a large shift toward delivering larger doses of radiation over fewer treatments using stereotactic body radiation therapy (SBRT). There is a radiobiologic basis for using SBRT, as prostate cancer cells are more sensitive to higher doses of radiation delivered over fewer treatments. Here we show that men with unfavorable intermediate-risk prostate cancer treated with SBRT lived significantly longer when treated with SBRT relative to longer courses of radiotherapy. While we await results from several ongoing clinical trials, this study lends support to the use of SBRT in men with unfavorable intermediate-risk prostate cancer. Background: Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in =5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ~44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). Methods: Men with UIR-PCa treated with SBRT (35-40Gy in =5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (=60Gy in 2.4-3.2Gy/fraction; biologically effective doses =120) were identified in the National Cancer Database (NCDB). Unweighted and propensityweighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. Results: Of 28,028 men with UIRPCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT + ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT + ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT. Conclusion: SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: External beam radiation therapy (EBRT) dose escalation has been tested in multiple prospective trials. However, the impact on patient reported outcomes (PROs) associated with higher doses of EBRT remain poorly understood. We sought to assess the differences in PROs between men treated with a dose of 70.2 Gy versus 79.2 Gy of EBRT for prostate cancer.Methods and Materials: The phase 3 clinical trial RTOG 0126 randomized 1532 patients with prostate cancer between March 2002 and August 2008 to 79.2 Gy over 44 fractions versus 70.2 Gy over 39 fractions. Eligible patients participated in the PRO data collection. PROs completed included the International Index of Erectile Function Questionnaire (IIEF), Functional Alterations due to Changes in Elimination (FACE), and the Spitzer Quality of Life Index (SQLI). The timepoints for the IIEF were collected pre-entry and at 6, 12, and 24 months. The FACE and SQLI were collected pre-entry and at 3, 6, 12, 18, and 24 months. The impact of EBRT dose to normal structures (penile bulb, rectum, and bladder) on PROs was also examined. Mixed effects models were used to analyze trends across time.Results: In total, 1144 patients completed baseline IIEF forms and of these, 56%, 64%, and 61% completed the IIEF at 6, 12, and 24 months, respectively; 1123 patients completed the FACE score at baseline and 50%, 61%, 73%, 61%, and 65% completed all 15 items for the FACE metric at timepoints of 3, 6, 12, 18, and 24 months, respectively. Erectile dysfunction at 12 months based on the single question was not significantly different between arms (38.1% for the standard dose radiation therapy arm vs 49.7% for the dose escalated radiation therapy arm; P = .051). Treatment arm (70.2 vs 79.2) had no significant impact on any PRO metrics measured across all collected domains. Comprehensive dosimetric analyses are presented and reveal multiple significant differences to regional organs at risk.Conclusions: Compliance with PRO data collection was lower than anticipated in this phase 3 trial. Examining the available data, dose escalated EBRT did not appear to be associated with any detriment to PROs across numerous prospectively collected domains. These data, notwithstanding limitations, add to our understanding of the implications of EBRT dose escalation in prostate cancer. Furthermore, these results illustrate challenges associated with PRO data collection. [ABSTRACT FROM AUTHOR]

Motivation Predicting early in treatment whether a tumor is likely to respond to treatment is one of the most difficult yet important tasks in providing personalized cancer care. Most oropharyngeal squamous cell carcinoma (OPSCC) patients receive standard cancer therapy. However, the treatment outcomes vary significantly and are difficult to predict. Multiple studies indicate that microRNAs (miRNAs) are promising cancer biomarkers for the prognosis of oropharyngeal cancer. The reliable and efficient use of miRNAs for patient stratification and treatment outcome prognosis is still a very challenging task, mainly due to the relatively high dimensionality of miRNAs compared to the small number of observation sets; the redundancy, irrelevancy and uncertainty in the large amount of miRNAs; and the imbalanced observation patient samples. Results In this study, a new machine learning-based prognosis model was proposed to stratify subsets of OPSCC patients with low and high risks for treatment failure. The model cascaded a two-stage prognostic biomarker selection method and an evidential K-nearest neighbors classifier to address the challenges and improve the accuracy of patient stratification. The model has been evaluated on miRNA expression profiling of 150 oropharyngeal tumors by use of overall survival and disease-specific survival as the end points of disease treatment outcomes, respectively. The proposed method showed superior performance compared to other advanced machine-learning methods in terms of common performance quantification metrics. The proposed prognosis model can be employed as a supporting tool to identify patients who are likely to fail standard therapy and potentially benefit from alternative targeted treatments.   Availability and implementation: Code is available in https://github.com/shenghh2015/mRMR-BFT-outcome-prediction. [ABSTRACT FROM AUTHOR]

Background: Improved prognostication of oropharyngeal squamous cell carcinoma (OPSCC) may facilitate individualized patient management. The goal of this study was to develop and validate a prognostic signature based on microRNA sequencing (miRNA-seq) analysis.Methods: We collected tumor specimens for miRNA-seq analysis from OPSCC patients treated at Washington University in St Louis (n = 324) and Vanderbilt University (n = 130). OPSCC patients (n = 79) from The Cancer Genome Atlas Program were also included for independent validation. Univariate and multivariable Cox regression analyses were performed to identify miRNAs associated with disease outcomes. All statistical tests were 2-sided.Results: By miRNA-seq profiling analysis, we identified a 26-miRNA signature. Based on computed risk scores of the signature, we classified the patients into low- and high-risk groups. In the training cohort, the high-risk group had much shorter overall survival compared with the low-risk group (hazard ratio [HR] = 3.80, 95% confidence interval [CI] = 2.37 to 6.10, P < .001). Subgroup analysis further revealed that the signature was prognostic for HPV-positive OPSCCs (HR = 3.07, 95% CI = 1.65 to 5.71, P < .001). Multivariable analysis indicated that the signature was independent of common clinicopathologic factors for OPSCCs. Importantly, the miRNA signature was a statistically significant predictor of overall survival in independent validation cohorts (The Cancer Genome Atlas Program cohort: HR = 6.05, 95% CI = 2.10 to 17.37, P < .001; Vanderbilt cohort: HR = 7.98, 95% CI = 3.99 to 15.97, P < .001; Vanderbilt HPV-positive cohort: HR = 8.71, 95% CI = 2.70 to 28.14, P < .001).Conclusions: The miRNA signature is a robust and independent prognostic tool for risk stratification of OPSCCs including HPV-positive OPSCCs. [ABSTRACT FROM AUTHOR]

Limited data are available on the effect of treatment delays for initiating chemoradiotherapy (CRT) for muscleinvasive bladder cancer. We used the National Cancer Database and found that 1387 patients had started CRT < 90 days after transurethral resection of bladder tumor (TURBT) compared with 197 with delayed CRT (≥ 90 days after TURBT). On multivariable analysis, delayed CRT was not associated with differences in overall survival. These results suggest that short, strategic treatment delays during a pandemic can be considered based on clinician judgment. Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making to ensure that the benefit of early intervention for muscle-invasive bladder cancer exceeds the risk of contracting COVID-19 in the clinical setting. It is unknown whether treatment delays for patients eligible for curative chemoradiation (CRT) compromise long-term outcomes. Patients and Methods: We used the National Cancer Data Base to investigate whether there is an association between a ≥ 90-day delay from transurethral resection of bladder tumor (TURBT) in initiating CRT and overall survival. We included patients with cT2-4N0M0 muscle-invasive bladder cancer from 2004 to 2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped on the basis of timing of CRT: ≤ 89 days after TURBT (earlier) vs. ≥ 90 and < 180 days after TURBT (delayed). Results: A total of 1387 (87.5%) received earlier CRT (median, 45 days after TURBT; interquartile range, 34-59 days), and 197 (12.5%) received delayed CRT (median, 111 days after TURBT; interquartile range, 98-130 days). Median overall survival was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95%CI, 19.75-34.24) for earlier. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long‐term bowel‐associated quality of life (QOL) in men after radiotherapy (RT) for prostate cancer with and without the use of rectal hydrogel spacer. Patients and Methods: The patients' QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) and mean changes from baseline in EPIC domains were evaluated. A total of 215 patients from a randomised multi‐institutional trial of RT, with or without hydrogel spacer, with a QOL endpoint were pooled with 165 non‐randomised patients from a single institution with prospective QOL collection in patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre‐treatment baseline in the bowel domain were tested using repeated measure logistic models with a pre‐specified threshold for clinically significant declines (≥5 equivalent to MIDx1 and ≥10 equivalent to MIDx2). Results: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men with >24 months of follow‐up [median (range) 39.5 (31–71.4) months]. Treatment with spacer was associated with less decline in average long‐term bowel QOL (89.4 for control and 94.7 for spacer) with differences at >24 months meeting the threshold of a MID difference between cohorts (bowel score difference from baseline: control = −5.1, spacer = 0.3, difference = −5.4; P < 0.001). When evaluated over time men without spacer were more likely to have MIDx1 (5 points) declines in bowel QOL (P = 0.01). At long‐term follow‐up MIDx1 was 36% without spacer vs 14% with spacer (P <0.001; odds ratio [OR] 3.5, 95% CI 1.7–6.9) while MIDx2 was seen in 19% vs 6% (P = 0.008; OR 3.6, 95% CI 1.4–9.1). The use of spacer was associated with less urgency with bowel movements (P = 0.002) and fewer loose stools (P = 0.009), as well as less bother with urgency (P = 0.007) and frequency of bowel movements (P = 0.009). Conclusions: In this pooled analysis of QOL after prostate RT with up to 5 years of follow‐up, use of a rectal spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long‐term follow‐up. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic. [ABSTRACT FROM AUTHOR]

Objectives: We investigated how tonsillectomy during childhood may influence the distribution of human papillomavirus (HPV) positive cancer of the tonsils in adult life using p16 as a surrogate marker for HPV infection. Study Design: Retrospective observational study. Methods: A total of 280 patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) and known p16 status were eligible for this study. Each participant was called to obtain the childhood tonsillectomy history. Respondents were subgrouped by p16 status and the primary tumor location. Patient demographic and clinical information was analyzed for association with Fisher's exact and Wilcoxon rank sum tests. Location of tumor was modeled using univariate (UVA) and multivariate (MVA) logistic regression with associated odds ratios (OR) and 95% confidence intervals. Results: Of the 280 patients, 115 (41%) were respondents: 104 (90.4%) were p16 positive and 11 (9.6%) were p16 negative. For p16 positive patients, we observed a majority (93%) of intact tonsils in those with tonsil cancer, compared to 45% of intact tonsils in patients with p16 positive cancer elsewhere in the oropharynx (P <.001). MVA logistic regression showed that female gender (OR = 4.16, P =.0675), prior smoking history (OR = 2.6, P =.0367), and intact tonsils (OR = 15.2, P <.0001) were associated with tonsillar OPSCC. Conclusion: We found that patients with p16 positive OPSCC at a non‐tonsil site were much more likely to have had prior tonsillectomy vs those with p16 positive OPSCC arising within the tonsil. Nevertheless, we do not advocate tonsillectomies as a public health policy to reduce HPV‐related OPSCC. Level of Evidence: 6 [ABSTRACT FROM AUTHOR]

Purpose: High-dose-rate brachytherapy (HDR-BT) delivered in a single fraction as monotherapy is a potential treatment modality for low- and intermediate-risk prostate cancer (LIR-PC); however, outcome data with this technique remain limited. Here we describe our institutional HDR monotherapy experience and report the efficacy and toxicity of this treatment. Material and methods: LIR-PC patients who received a definitive single fraction HDR-BT during 2013-2017 were retrospectively identified. The intended HDR monotherapy dose was 19 Gy in one fraction. Acute (< 90 days) and late (≥ 90 days) toxicity was assessed using CTCAE version 4.03. Trends in prostate-specific antigen (PSA) and American Urological Association (AUA) symptom scores after treatment were assessed using Bayesian linear mixed models. The Kaplan-Meier method was used to evaluate biochemical failure-free survival (BFFS). Results: 28 patients with median follow-up of 23.6 months were identified. The median age at treatment was 65 years (48-83). The NCCN risk groups were low in 14, favorable intermediate in 10, and unfavorable intermediate in 4 patients. There were 5 (18%) and 0 (0%) acute grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities, respectively, and one (4%) acute grade 3 GU toxicity. There were no late grade 3 toxicities, and 5 (18%) and 0 (0%) late grade 2 GU and GI toxicities respectively. PSA values and AUA symptom scores decreased significantly after treatment. There were 3 biochemical failures with the two- and three-year BFFS of 90.7% and 80.6%, respectively. Conclusions: Early results from a single institution suggest that single fraction HDR-BT with 19 Gy has limited toxicity, although with suboptimal biochemical control. [ABSTRACT FROM AUTHOR]

Purpose: Monotherapy with high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy are both recommended modalities for prostate cancer. The choice between HDR and LDR is dependent on patient, physician, and hospital preferences. We sought to identify treatment patterns and factors associated with receipt of HDR or LDR monotherapy. Material and methods: We queried the National Cancer Database (NCDB) for patients with localized low- or intermediate-risk prostate cancer treated with HDR or LDR monotherapy. Descriptive statistics were used to analyze patterns of HDR vs. LDR. Patient characteristics were correlated with HDR vs. LDR using multivariable logistic regression. Results: We identified 50,326 patients from 2004-2014: LDR 37,863 (75.2%) vs. HDR 12,463 (24.8%). Median follow-up was 70.3 months. The overall use of monotherapy declined over time. HDR application declined relative to LDR. In 2004, 27.0% of cases were HDR compared to 19.2% in 2014. Factors associated with increased likelihood of HDR on multivariable analysis included: increasing age (OR: 1.01, 95% CI: 1.01-1.01), cT2c disease (OR: 1.25, 95% CI: 1.11-1.41), treatment at an academic center (OR: 2.45, 95% CI: 2.24-2.65), non-white race (OR: 1.34, 95% CI: 1.27-1.42), and income > $63,000 (OR: 1.73, 95% CI: 1.59-1.88). LDR was more common in 2010-2014 (OR: 0.59, 95% CI: 0.54-0.65), Charlson-Deyo comorbidity index > 0 (OR: 0.89, 95% CI: 0.84-0.95), and for patients receiving hormone therapy (OR: 0.88, 95% CI: 0.83-0.93). No difference in prostate-specific antigen (PSA) or Gleason score and receipt of HDR vs. LDR was observed. Mean overall survival was 127.0 months for HDR and 125.4 for LDR, and was not statistically different. Conclusions: We observed an overall decrease in brachytherapy (BT) monotherapy use since 2004 for localized prostate cancer. Despite similar survival outcomes, the use of HDR monotherapy declined relative to LDR. [ABSTRACT FROM AUTHOR]

Abstract Background Despite existing evidence that human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis compared to HPV-negative OPSCC, randomized studies have yet to report the effect of de-escalating radiation therapy (RT) dose for definitive treatment. The aim of this study was to assess the effectiveness of dose de-escalated RT (DDRT) vs. standard dose RT (SDRT) in patients with HPV-positive OPSCC. Methods This was an observational study using the National Cancer Database (Year 2010–2014) to identify patients who had HPV-positive OPSCC and were treated with definitive RT or chemo-RT. Patients undergoing surgery were excluded. Patients receiving ≥50 Gy, but <66 Gy were categorized as receiving DDRT. Patients receiving ≥66 Gy were categorized as receiving SDRT. Inverse probability of treatment weighting (IPTW) using propensity scores was used to balance the two groups. Kaplan–Meier analysis was used to estimate overall survival (OS). Subset analyses in patients receiving RT alone and concurrent chemo-RT were also performed. Multivariable Cox proportional hazards modeling was used to evaluate factors associated with OS. Results 759 patients with HPV-positive OPSCC were identified: 104 received DDRT and 655 received SDRT. The median follow-up was 30.5 (2.4–81.4) months. After IPTW-adjusted analysis, there was no difference in the 3-yr OS between the two groups (82.2% vs. 79.3%; P = 0.85). In the subset of patients receiving concurrent chemoradiotherapy, IPTW-adjusted analysis also did not show a difference in the 3-yr OS between the two groups (83.1% vs. 79.6%; P = 0.83). On multivariable analysis, DDRT was not associated with an inferior OS (HR 0.88; 95% CI, 0.53–1.47; P = 0.63). Conclusions In this study, DDRT was not associated with an inferior OS compared to SDRT in patients with HPV-positive OPSCC. Randomized clinical trials to address DDRT in this patient population are currently ongoing. [ABSTRACT FROM AUTHOR]

Objective: To evaluate radiation-induced lymphopenia associated with unilateral vs. bilateral neck radiation and to test post-treatment neutrophil to lymphocyte ratio (NLR) as a prognostic clinical biomarker.Methods: This was a single academic center retrospective review of palatine tonsil squamous cell cancer patients treated with post-operative intensity modulated radiation therapy (IMRT) from 1997 to 2013. Absolute lymphocyte count (ALC) and NLR were evaluated during and after radiation for up to a year. Correlations of lab values with loco-regional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were assessed.Results: Ninety-nine patients with median follow up 5.8 years had ALC recorded at least at baseline and within one year of starting RT. Acute grade 3-4 lymphopenia (<10 weeks from RT start) occurred in 79% of bilateral neck RT patients (n = 70) and 58% of unilateral neck RT patients (n = 29), p = 0.03. There was no significant difference in late grade 3-4 (p = 0.12) lymphopenia. In a multivariable Cox regression model, acute NLR > 11.875 correlated with worse OS (HR = 4.4, 95% CI 1.2-16). Late NLR > 6.875 independently correlated with significantly worse FFDM (HR = 16, 95% CI 1.9-137) and OS (HR = 12, 95% CI 3.0-48).Conclusions: Unilateral neck radiation may prevent acute iatrogenic immunosuppression. In exploratory analyses, elevated post-treatment NLR was associated with risk for distant metastases and death. [ABSTRACT FROM AUTHOR]

Abstract: Prostate cancer (PCa) is one of the most common malignancies associated with bone metastases, and palliative radiation therapy (RT) is an effective treatment option. A total of 2641 patients were identified with PCa and bone metastases at diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as short course ([SC‐RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long course ([LC‐RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient characteristics were correlated with fractionation scheme using logistic regression. Overall survival was analyzed using the Kaplan‐Meier method, log‐rank test, Cox proportional hazards models, and propensity score‐matched analyses. A total of 2255 (85.4%) patients were included in the LC‐RT group and 386 (14.6%) patients in the SC‐RT group. SC‐RT was more common in patients over 75 years age (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32‐2.20), treatment at an academic center (OR: 1.76, 1.20‐2.57), living greater than 15 miles distance to treatment facility (OR: 1.38, 1.05‐1.83), treatment to the rib (OR: 2.99, 1.36‐6.60), and in 2014 (OR: 1.73, 1.19‐2.51). RT to the spine was more commonly long course (P < .0001). In the propensity‐matched cohort, LC‐RT was associated with improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC‐RT remains the most common treatment fractionation scheme for palliative bone metastases in PCa patients. Use of palliative SC‐RT is increasing, particularly in more recent years, for older patients, treatment at academic centers, and with increasing distance from a treatment center. [ABSTRACT FROM AUTHOR]

Abstract: The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone. [ABSTRACT FROM AUTHOR]

Background: The authors hypothesized that unilateral intensity-modulated radiotherapy (IMRT) would decrease toxicity compared with bilateral IMRT for patients with lateralized palatine tonsillar cancer and a neck classification of N0 to N2b, with similar oncological outcomes.Methods: A total of 154 patients were treated with postoperative IMRT from 1997 through 2013. Data were collected prospectively from 2005 to 2013 and retrospectively collected before 2005. Of those patients with lateralized primary and N0 to N2b disease, 48 received unilateral IMRT (group 1) and 59 received bilateral IMRT (group 2); a total of 47 patients had nonlateralized primary or N2c to N3 disease and received bilateral IMRT (group 3).Results: The median follow-up was 5.5 years. The 5-year locoregional control rates were similar in group 1, group 2, and group 3 (100%, 96%, and 94%, respectively; pooled comparison: P = .39 and group 1 vs group 2 comparison: P = .19). The 5-year overall survival rates were similar in group 1, group 2, and group 3 (85%, 79%, and 76%, respectively; pooled comparison: P = .60 and group 1 vs group 2 comparison: P = .25). There were no contralateral neck recurrences noted among unilaterally treated patients. Unilateral IMRT reduced acute toxicity and improved patient-reported quality of life compared with bilateral IMRT.Conclusions: Unilateral IMRT appears to reduce acute toxicity and achieves oncological outcomes similar to those of bilateral IMRT in selected patients with lateralized palatine tonsillar cancer with a neck classification of N0 to N2b. Cancer 2017;123:4594-4607. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Randomized data has shown a lower risk of recurrence with the addition of a brachytherapy (BT) boost in men with intermediate- and high-risk prostate cancer treated with external beam radiotherapy (EBRT) and concomitant androgen deprivation therapy (ADT). The inclusion of ADT with BT-based dose escalation is controversial, and professional guidelines support adding or excluding ADT for men with unfavorable intermediate risk prostate cancer treated with EBRT plus a BT boost. However, inclusion of ADT in men with intermediate risk prostate cancer may become more routine after results from RTOG 0815, and its impact on BT utilization in this population is unclear. Herein, we investigate the landscape of BT boost utilization in men with unfavorable intermediate risk prostate treated with EBRT and ADT in the United States. Men ≥ 18 years diagnosed with clinical stage T1-2N0M0, PSA < 20, and Gleason grade group 3 prostate cancer between 2004-2017 were analyzed from the National Cancer Database. Those missing risk-stratification or treatment data were excluded. Eligible patients were grouped into the following cohorts based on primary radiation treatment modality: (i) EBRT alone or (ii) EBRT plus BT boost. EBRT monotherapy group received conventionally fractionated (1.8-2.0 Gy per fraction) ≥ 74 Gy or moderately hypofractionated (2.5-3.0 Gy per fraction) ≥ 60 Gy. EBRT plus BT boost group received conventionally fractionated ≥ 45 Gy or moderately hypofractionated ≥ 37.5 Gy, and either LDR or HDR BT. All patients received concomitant ADT. Cochran-Armitage was used to evaluate radiation modality treatment trends over time, and multivariable logistic regression was used to identify sociodemographic predictors of treatment. Among the eligible cohort, 46,490 (82%) were treated with EBRT alone and 10,236 (18%) were treated with EBRT plus BT boost. Median (range) age was 70 years (38-90). Between 2004 to 2017, there was a significant decline in annual use of a BT boost, from 24.5% in 2004 to 16.4% in 2017 (p<0.001). On MVA, Black race (adjusted OR 0.85, 95% CI 0.79-0.90, P<.0001), Medicaid insurance (aOR 0.67, 95% CI 0.57-0.78, P<.0001), and Charlson-Deyo comorbidity index > 1 (aOR 0.78, 95% CI 0.61-0.99, P=0.04) were associated with decreased odds of receiving a BT boost. Private insurance (aOR 1.11, 95% CI 1.05-1.18, P=.001), treatment at an academic institution (aOR 1.25, 95% CI 1.12-1.39, p<.0001), and Charlson-Deyo comorbidity index 0 (aOR 1.07, 95% CI 1.00-1.15, P=.04) were associated with increased odds of receiving a BT boost. For men with unfavorable intermediate risk prostate cancer, utilization of a BT boost has significantly declined in the United States over the past two decades. Black and uninsured men have been at particularly high risk of undertreatment. Future studies aimed at identifying which men with intermediate-risk prostate cancer (e.g. based on genomic classifier or magnetic resonance imaging) derive the greatest oncologic benefit from a BT boost with EBRT and ADT is warranted to appropriately identify those who may be at risk of undertreatment with its exclusion. Additionally, future initiatives are needed to close the disparity gap in access and/or delivery of this efficacious treatment for Black and uninsured men, an overall undertreated population. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC).Materials and Methods: Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n=30) and trial 2 with APF (n=30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF.Results: No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25-95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p=0.37). In human papillomavirus (HPV)-related OPSCC (n=34), the CIDD at 52months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n=25), the CIDD at 52months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p=0.80; OS: p=0.30).Conclusion: This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF. [ABSTRACT FROM AUTHOR]

Objective: The purpose of our study is to compare oncologic and functional outcomes of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) patients, in the presence and absence of planned radiation to the primary bed following transoral surgery (TOS), stratified by T-classification.Methods: Retrospective cohort study of 261, T1-T4, consecutively TOS-treated OPSCC patients.Results: At a median follow-up of 61months, local recurrence (LR) occurred in 6 (2.3%)patients (3 each in T1-T2 and T3-T4 groups), of which 5 had tumors in the tongue base and one in the tonsil. Of patients not receiving planned primary bed radiation, LR occurred in 3% of T1-T2s versus 17% of T3-T4s. In patients with T1-T2 tumors, Absolute Risk Reduction of LR with primary bed radiation was 3.26% (95% CI: -0.37%, 7%); Number Needed to Treat to prevent one LR was 31 (95% CI: 14.5, 271). Absolute Risk Increase for gastrostomy-tube with primary bed radiation was 34.4% (95% CI: 24%, 45%); Number Needed to Harm was 3 (95% CI: 2.2, 4.2), i.e., for every three patients with T1-T2 tumors receiving primary bed radiation, one had a gastrostomy-tube.Conclusions: Elimination of primary bed radiation in margin-negative resected, T1-T2 p16-positive OPSCC was not associated with significant compromise of local control, and correlated with superior swallowing preservation, assessed using gastrostomy rate as a surrogate. Lack of primary bed radiation in T3-T4 tumors associated with significantly increased LR rates. [ABSTRACT FROM AUTHOR]

Objectives: We previously reported the efficacy of nab-paclitaxel added to cisplatin, 5-FU, and cetuximab (APF-C) followed by concurrent high dose bolus cisplatin and radiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). In this phase II trial, we determined the efficacy of APF (without cetuximab) followed by CRT in similar patients.Materials and Methods: Eligible patients had stage III-IV oropharynx (OP), larynx, or hypopharynx SCC and adequate organ function and performance status. T1 tumors were excluded. Patients were treated with three cycles of APF followed by CRT. Efficacy endpoints included two-year disease-specific survival (DSS), progression-free survival (PFS), overall survival (OS), and relapse rate.Results: Thirty patients were enrolled. Most patients were smokers (77%) with bulky T3/4 (73%) and N2/3 (83%) tumors. Analyses were stratified for human papilloma virus (HPV) status: HPV-related OPSCC (n=17; 57%) and HPV-unrelated HNSCC (n=13; 43%). With a minimum follow-up of 21months, relapse occurred in 1 (3%) patient. Two-year DSS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year PFS was 94% in HPV-related OPSCC and 100% in HPV-unrelated HNSCC. Two-year OS was 94% in HPV-related OPSCC and 92% in HPV-unrelated HNSCC. Causes of death were relapse (1), treatment-related mortality (1), and co-morbidity (1). Two patients with HPV-unrelated HNSCC treated with APF declined CRT and remained free of relapse at 36 and 28months of follow-up.Conclusion: This phase II trial demonstrated favorable two-year DSS, PFS, and OS and a low relapse rate in HPV-unrelated HNSCC and HPV-related OPSCC treated with APF followed by CRT. [ABSTRACT FROM AUTHOR]

Purpose: For the first time, MRI-guided radiation therapy systems can acquire cine images to dynamically monitor in-treatment internal organ motion. However, the complex head and neck (H&N) structures and low-contrast/resolution of on-board cine MRI images make automatic motion tracking a very challenging task. In this study, the authors proposed an integrated model-driven method to automatically track the in-treatment motion of the H&N upper airway, a complex and highly deformable region wherein internal motion often occurs in an either voluntary or involuntary manner, from cine MRI images for the analysis of H&N motion patterns. Methods: Considering the complex H&N structures and ensuring automatic and robust upper airway motion tracking, the authors firstly built a set of linked statistical shapes (including face, face-jaw, and face-jaw-palate) using principal component analysis from clinically approved contours delineated on a set of training data. The linked statistical shapes integrate explicit landmarks and implicit shape representation. Then, a hierarchical model-fitting algorithm was developed to align the linked shapes on the first image frame of a to-be-tracked cine sequence and to localize the upper airway region. Finally, a multifeature level set contour propagation scheme was performed to identify the upper airway shape change, frame-by-frame, on the entire image sequence. The multifeature fitting energy, including the information of intensity variations, edge saliency, curve geometry, and temporal shape continuity, was minimized to capture the details of moving airway boundaries. Sagittal cine MR image sequences acquired from three H&N cancer patients were utilized to demonstrate the performance of the proposed motion tracking method. Results: The tracking accuracy was validated by comparing the results to the average of two manual delineations in 50 randomly selected cine image frames from each patient. The resulting average dice similarity coefficient (93.28% ± 1.46%) and margin error (0.49 ± 0.12 mm) showed good agreement between the automatic and manual results. The comparison with three other deformable model-based segmentation methods illustrated the superior shape tracking performance of the proposed method. Large interpatient variations of swallowing frequency, swallowing duration, and upper airway crosssectional area were observed from the testing cine image sequences. Conclusions: The proposed motion tracking method can provide accurate upper airway motion tracking results, and enable automatic and quantitative identification and analysis of in-treatment H&N upper airway motion. By integrating explicit and implicit linked-shape representations within a hierarchical model-fitting process, the proposed tracking method can process complex H&N structures and low-contrast/resolution cine MRI images. Future research will focus on the improvement of method reliability, patient motion pattern analysis for providing more information on patientspecific prediction of structure displacements, and motion effects on dosimetry for better H&N motion management in radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a favorable prognosis. As a result, de-escalation clinical trials are under way. However, approximately 10% of patients will experience distant recurrence even with standard-of-care treatment. Here, we sought to identify novel biomarkers to better risk-stratify HPV-positive patients with OPSCC.Methods and Materials: Gene expression profiling by RNA sequencing (RNA-seq) and quantitative polymerase chain reaction was performed on HPV-positive OPSCC primary tumor specimens from patients with and without distant metastasis (DM).Results: RNA-seq analysis of 39 HPV-positive OPSCC specimens revealed that patients with DM had 2-fold higher E6 gene expression levels than did patients without DM (P=.029). This observation was confirmed in a validation cohort comprising 93 patients with HPV-positive OPSCC. The mean normalized E6 expression level in the 17 recurring primary specimens was 13 ± 2 compared with 8 ± 1 in the remaining 76 nonrecurring primaries (P=.001). Receiver operating characteristic analysis established an E6 expression level of 7.3 as a cutoff for worse recurrence-free survival (RFS). Patients from this cohort with high E6 gene expression (E6-high) (n=51, 55%) had more cancer-related deaths (23% vs 2%, P<.001) and DM (26% vs 5%, P<.001) than did patients with low E6 gene expression (E6-low) (n=42, 45%). Kaplan-Meier survival analysis revealed that E6-high had worse RFS (95% vs 69%, P=.004) and cancer-specific survival (97% vs 79%, P=.007). E6-high maintained statistical significance in multivariate regression models balancing surgery, chemotherapy, nodal stage, and smoking status. Gene set enrichment analysis demonstrated that tumors with high E6 expression were associated with P53, epidermal growth factor receptor, activating transcription factor-2, and transforming growth factor-β signaling pathways.Conclusion: High E6 gene expression level identifies HPV-positive OPSCC patients with 5-fold greater risk of distant disease recurrence and worse cancer-specific survival. Validation in a multi-institutional prospective clinical trial is required to assess the utility of E6 gene expression as a clinically useful prognostic biomarker. [ABSTRACT FROM AUTHOR]

Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas ( TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas ( HNSCC) including oropharyngeal squamous cell carcinoma ( OPSCC) and other subtypes. In this study, we analyzed mi RNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified mi RNAs were further tested with an independent cohort. mi RNA-seq data from TCGA was also analyzed to identify prognostic mi RNAs in oral cavity squamous cell carcinoma ( OSCC) and laryngeal squamous cell carcinoma ( LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four mi RNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four mi RNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-mi RNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care. [ABSTRACT FROM AUTHOR]