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A multidisciplinary approach to the management of tongue cancer is vital for achieving optimal patient outcomes. Nursing and allied health professionals play essential roles within the team. We developed symposia comprising a series of online lectures offering a detailed perspective on the role each discipline and consumer perspective has in the management of patients with tongue cancer. The topics, including epidemiology and prevention, diagnosis, treatment planning, surgery, adjuvant care, and the management of recurrent or metastatic disease, were thoroughly examined. The symposia highlighted the significance of fostering collaboration and continuous learning through a multidisciplinary approach. This initiative should be relevant to healthcare professionals, researchers, and policymakers striving to enhance patient outcomes in tongue cancer care through innovative collaboration.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC. METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC. KEY CONTENT AND FINDINGS: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy. CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targete

BACKGROUND AND OBJECTIVE: In radiotherapy (RT) for locally advanced cervical cancer, high soft tissue contrast on magnetic resonance imaging (MRI) can ensure accurate delineation of target volumes (TVs) and optimal dose distribution to the RT target and organs at risk (OAR). MRI-guided adaptive RT (MRIgART) is a novel technology that revises RT plans according to anatomical changes occurring throughout the treatment to improve target coverage and minimise OAR toxicity. This review aims to assess the evidence and gaps of MRI use in RT planning and MRIgART in the treatment of cervical cancer, as well as challenges in its clinical implementation. METHODS: Ovid Medline and PubMed were searched using keywords for MRI in RT for cervical cancer. After applying the inclusion and exclusion criteria, the initial search was deduced to 32 studies. A total of 37 final studies were reviewed, including eight additional articles from references. KEY CONTENT AND FINDINGS: In the primary studies, TVs and organ motion were assessed before, during, and after treatment. MRI was used to investigate dose distribution and therapeutic response to the treatment in association with its outcome. Lastly, rationales for MRIgART were evaluated. CONCLUSIONS: It was concluded that MRI enables accurate target delineation, assessment of organ motion and interfraction changes, and monitoring of treatment response through dynamic parameters. Enhanced target coverage and reduced OAR irradiation through MRIgART can improve local control and the overall outcome, although its rationales against the logistical challenges need to be evaluated on further research.

BACKGROUND: Pancreatic cancer is a malignancy with one of the poorest prognoses amongst all cancers. Patients with unresectable tumours either receive palliative care or undergo various chemoradiotherapy regimens. Conventional techniques are often associated with acute gastrointestinal toxicities, as adjacent critical structures such as the duodenum ultimately limits delivered doses. Stereotactic body radiotherapy (SBRT) is an advanced radiation technique that delivers highly ablative radiation split into several fractions, with a steep dose fall-off outside target volumes. AIM: To discuss the latest data on SBRT and whether there is a role for magnetic resonance-guided techniques in multimodal management of locally advanced, unresectable pancreatic cancer. METHODS: We conducted a search on multiple large databases to collate the latest records on radiotherapy techniques used to treat pancreatic cancer. Out of 1229 total records retrieved from our search, 36 studies were included in this review. RESULTS: Studies indicate that SBRT is associated with improved clinical efficacy and toxicity profiles compared to conventional radiotherapy techniques. Further dose escalation to the tumour with SBRT is limited by the poor soft-tissue visualisation of computed tomography imaging during radiation planning and treatment delivery. Magnetic resonance-guided techniques have been introduced to improve imaging quality, enabling treatment plan adaptation and re-optimisation before delivering each fraction. CONCLUSION: Therefore, SBRT may lead to improved survival outcomes and safer toxicity profiles compared to conventional techniques, and the addition of magnetic resonance-guided techniques potentially allows dose escalation and conversion of unresectable tumours to operable cases.

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th−95th percentiles in weeks 1−4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies.

Proton therapy (PT) is a promising development in radiation oncology, with the potential to further improve outcomes for patients with squamous cell carcinoma of the head and neck (HNSCC). By utilizing the finite range of protons, healthy tissue can be spared from beam exit doses that would otherwise be irradiated with photon-based treatments. Current evidence on PT for HNSCC is limited to comparative dosimetric analyses and retrospective single-institution series. As a consequence, the recognized indications for the reimbursement of PT remain scarce in most countries. Nevertheless, approximately 100 PT centers are in operation worldwide, and initial experiences for HNSCC are being reported. This review aims to summarize the results of the early clinical experience with PT for HNSCC and the challenges that are currently faced.

Oesophageal cancer is the ninth most common cancer diagnosed, and seventh most common cause of cancer-related deaths worldwide. Despite significant advances in imaging, surgery, radiotherapy and systemic therapy over the past few decades, treatment outcomes in patients with localised oesophageal cancer remain suboptimal with a 5-year overall survival of less than 50%. Current treatment guidelines recommend surgery with/without pre-operative chemotherapy or chemoradiotherapy for patients with localised resectable disease. Hence, definitive radiotherapy (with or without chemotherapy) has predominantly been reserved for those who are deemed unsuitable for surgery. The role of radiotherapy in definitive management of oesophageal cancer has been recognised since the 1960s. The addition of concurrent chemotherapy has shown to improve treatment outcomes and has remained standard of care since the RTOG 85-01 and Intergroup 0123 trials. This review discusses the current literature on definitive radiotherapy with/without chemotherapy for localised oesophageal cancer, and evaluates current radiation modalities and technological developments in radiotherapy planning and delivery. We will provide an overview on the literature for definitive chemoradiotherapy in oesophageal cancer, the epidemiological and treatment response differences between squamous cell carcinoma and adenocarcinoma of the oesophagus, followed by a review of the current literature on different radiation treatment modalities (intensity modulated radiotherapy, brachytherapy and proton therapy) and the use of different imaging modalities for radiation treatment planning.

PURPOSE: To describe the baseline and serial tumor microbiome in HPV-associated oropharynx cancer (OPC) over the course of radiotherapy (RT). METHODS: Patients with newly diagnosed HPV-associated OPC treated with definitive radiotherapy +/- concurrent chemotherapy were enrolled in this prospective study. Using 16S rRNA gene sequencing, dynamic changes in the tumor site microbiome during RT were investigated. Surface tumor samples were obtained before RT and at week 1, 3 and 5 of RT. Radiological primary tumor response at mid-treatment was categorized as complete (CR) or partial (PR). RESULTS: Ten patients were enrolled, but 9 patients were included in the final analysis. Mean age was 62 years (range: 51-71). As per AJCC 8th Ed, 56%, 22% and 22% of patients had stage I, II and III, respectively. At 4-weeks, 6 patients had CR and 3 patients had PR; at follow-up imaging post treatment, all patients had CR. The baseline diversity of the tumoral versus buccal microbiome was not statistically different. For the entire cohort, alpha diversity was significantly decreased over the course of treatment (p = 0.04). There was a significant alteration in the bacterial community within the first week of radiation. Baseline tumor alpha diversity of patients with CR was significantly higher than those with PR (p = 0.03). While patients with CR had significant reduction in diversity over the course of radiation (p = 0.01), the diversity remained unchanged in patients with PR. Patients with history of smoking had significantly increased abundance of Kingella (0.05) and lower abundance of Stomatobaculum (p = 0.03) compared to never smokers. CONCLUSIONS: The tumor microbiome of HPV-associated OPC exhibits reduced alpha diversity and altered taxa abundance over the course of radiotherapy. The baseline bacterial profiles of smokers vs. non-smokers were inherently different. Baseline tumor alpha diversity of patients with CR was higher than patients with PR, suggesting that the microbiome

PURPOSE: To investigate multiple deep learning methods for automated segmentation (auto-segmentation) of the parotid glands, submandibular glands, and level II and level III lymph nodes on magnetic resonance imaging (MRI). Outlining radiosensitive organs on images used to assist radiation therapy (radiotherapy) of patients with head and neck cancer (HNC) is a time-consuming task, in which variability between observers may directly impact on patient treatment outcomes. Auto-segmentation on computed tomography imaging has been shown to result in significant time reductions and more consistent outlines of the organs at risk. METHODS: Three convolutional neural network (CNN)-based auto-segmentation architectures were developed using manual segmentations and T2-weighted MRI images provided from the American Association of Physicists in Medicine (AAPM) radiotherapy MRI auto-contouring (RT-MAC) challenge dataset (n = 31). Auto-segmentation performance was evaluated with segmentation similarity and surface distance metrics on the RT-MAC dataset with institutional manual segmentations (n = 10). The generalizability of the auto-segmentation methods was assessed on an institutional MRI dataset (n = 10). RESULTS: Auto-segmentation performance on the RT-MAC images with institutional segmentations was higher than previously reported MRI methods for the parotid glands (Dice: 0.860 ± 0.067, mean surface distance [MSD]: 1.33 ± 0.40 mm) and the first report of MRI performance for submandibular glands (Dice: 0.830 ± 0.032, MSD: 1.16 ± 0.47 mm). We demonstrate that high-resolution auto-segmentations with improved geometric accuracy can be generated for the parotid and submandibular glands by cascading a localizer CNN and a cropped high-resolution CNN. Improved MSDs were observed between automatic and manual segmentations of the submandibular glands when a low-resolution auto-segmentation was used as prior knowledge in the second-stage CNN. Reduced auto-segmentation performance was obse

BACKGROUND: This study aimed to evaluate the prognostic value of pre-treatment NLR in patients with oropharyngeal cancer. METHODS: Patients who completed definitive radiotherapy (RT) for oropharyngeal cancer and had blood counts taken pre-RT from 2002 to 2013 were included. NLR was calculated as total neutrophil/lymphocytes. Survival rates were estimated using the Kaplan-Meier method. Univariable and multivariable analyses were conducted with linear and Cox regression methods. NLR was analysed posteriori and dichotomised on the discovered median. RESULTS: Eight hundred and forty-eight patients were analysed. The median pre-RT NLR was 3. Patients with NLR of <3 had improved overall survival (OS) than those with NLR ≥ 3 (5-year OS 85 vs 74%, p < 0.0001). OS differences remained significant when stratified according to HPV status (HPV-positive p = 0.011; HPV-negative p = 0.003). Freedom from any recurrence (FFR), locoregional control (LRC) and freedom of distant recurrence (FDR) were better in those with NLR < 3. The negative impact of elevated pre-RT NLR on OS (HR = 1.64, p = 0.001), FFR (HR = 1.6, p = 0.006) and LRC (HR = 1.8, p = 0.005) remained significant on multivariable analysis. CONCLUSIONS: Pre-RT NLR is an independent prognostic factor in patients with oropharyngeal cancer regardless of HPV status. Patients with lower NLR had more favourable OS and disease control.

Radiomics is a promising technique for discovering image based biomarkers of therapy response in cancer. Reproducibility of radiomics features is a known issue that is addressed by the image biomarker standardisation initiative (IBSI), but it remains challenging to interpret previously published radiomics signatures. This study investigates the reproducibility of radiomics features calculated with two widely used radiomics software packages (IBEX, MaZda) in comparison to an IBSI compliant software package (PyRadiomics). Intensity histogram, shape and textural features were extracted from 334 diffusion weighted magnetic resonance images of 59 head and neck cancer (HNC) patients from the PREDICT-HN observational radiotherapy study. Based on name and linear correlation, PyRadiomics shares 83 features with IBEX and 49 features with MaZda, a sub-set of well correlated features are considered reproducible (IBEX: 15 features, MaZda: 18 features). We explore the impact of including non-reproducible radiomics features in a HNC radiotherapy response model. It is possible to classify equivalent patient groups using radiomic features from either software, but only when restricting the model to reliable features using a correlation threshold method. This is relevant for clinical biomarker validation trials as it provides a framework to assess the reproducibility of reported radiomic signatures from existing trials.

BACKGROUND: A possible surveillance model for patients with head and neck cancer (HNC) who received definitive radiotherapy was created using a partially observed Markov decision process. The goal of this model is to guide surveillance imaging policies after definitive radiotherapy. METHODS: The partially observed Markov decision process model was formulated to determine the optimal times to scan patients. Transition probabilities were computed using a data set of 1508 patients with HNC who received definitive radiotherapy between the years 2000 and 2010. Kernel density estimation was used to smooth the sample distributions. The reward function was derived using cost estimates from the literature. Additional model parameters were estimated using either data from the literature or clinical expertise. RESULTS: When considering all forms of relapse, the model showed that the optimal time between scans was longer than the time intervals used in the institutional guidelines. The optimal policy dictates that there should be less time between surveillance scans immediately after treatment compared with years after treatment. Comparable results also held when only locoregional relapses were considered as relapse events in the model. Simulation results for the inclusive relapse cases showed that <15% of patients experienced a relapse over a simulated 36-month surveillance program. CONCLUSIONS: This model suggests that less frequent surveillance scan policies can maintain adequate information on relapse status for patients with HNC treated with radiotherapy. This model could potentially translate into a more cost-effective surveillance program for this group of patients.

In treatment planning, multiple imaging modalities can be employed to improve the accuracy of tumor delineation but this can be costly. This study aimed to compare the interobserver consistency of using dual energy computed tomography (DECT) versus magnetic resonance imaging (MRI) for delineating tumors in the head and neck cancer (HNC) re-irradiation scenario. Twenty-three patients with recurrent HNC and had planning DECT and MRI were identified. Contoured tumor volumes by seven radiation oncologists were compared. Overall, T1c MRI performed the best with median DSC of 0.58 (0-0.91) for T1c. T1c MRI provided higher interobserver agreement for skull base sites and 60 kV DECT provided higher interobserver agreement for non-skull base sites.

PURPOSE/OBJECTIVE: Radiation-induced lymphopenia has been associated with poor survival outcomes in certain solid tumors such as esophageal, lung, cervical and pancreatic cancers. We aim to determine the effect of treatment-related lymphopenia during radiotherapy on outcomes of patients with oropharyngeal cancer. MATERIALS/METHODS: A retrospective analysis of all patients who completed definitive radiotherapy for oropharyngeal cancer at The University of Texas MD Anderson Cancer Center and had blood counts taken during radiotherapy from 2002 to 2013 were included. Patient, tumor and treatment characteristics, clinical outcomes and lymphocyte counts during radiotherapy were recorded. Lymphopenia was graded according to the CTCAE v4.0. Survival rates were estimated using the Kaplan-Meier method and compared with log-rank tests. RESULTS: 850 patients were evaluated. The median age was 57 years. The majority of the cohort had p16/HPV-positive disease (71%), 8% had HPV-negative disease and 21% were unknown. The median radiation total dose was 70 Gy. 45% of patients had induction chemotherapy, and 87% had concurrent chemotherapy. 703 (83%) patients developed ≥grade 3 (G3) lymphopenia and 209 (25%) had grade 4 (G4) lymphopenia during radiotherapy. The median follow-up was 59 months; the 5-year overall survival rate was 81%. There were no significant differences in overall survival rates nor in disease control rates, in those who developed G3/G4 lymphopenia compared with those who did not. No significant effect of lymphopenia on survival was observed when analyzed according to p16/HPV status. CONCLUSION: In this large cohort of patients with oropharyngeal cancer, the development of lymphopenia during radiotherapy did not impact outcomes.

PURPOSE: To automate the estimation of swallowing motion from 2D MR cine images using deformable registration for future applications of personalized margin reduction in head and neck radiotherapy and outcome assessment of radiation-associated dysphagia. METHODS: Twenty-one patients with serial 2D FSPGR-MR cine scans of the head and neck conducted through the course of definitive radiotherapy for oropharyngeal cancer. Included patients had at least one cine scan before, during, or after radiotherapy, with a total of 52 cine scans. Contours of 7 swallowing related regions-of-interest (ROIs), including pharyngeal constrictor, epiglottis, base of tongue, geniohyoid, hyoid, soft palate, and larynx, were manually delineated from consecutive frames of the cine scan covering at least one swallowing cycle. We applied a modified thin-plate-spline robust-point-matching algorithm to register the point sets of each ROI automatically over frames. The deformation vector fields from the registration were then used to estimate the motion during swallowing for each ROI. Registration errors were estimated by comparing the deformed contours with the manual contours. RESULTS: On average 22 frames of each cine scan were contoured. The registration for one cine scan (7 ROIs over 22 frames) on average took roughly 22 minutes. A number of 8018 registrations were successfully batch processed without human interaction after the contours were drawn. The average registration error for all ROIs and all patients was 0.36 mm (range: 0.06 mm- 2.06 mm). Larynx had the average largest motion in superior direction of all structures under consideration (range: 0.0 mm- 58.7 mm). Geniohyoid had the smallest overall motion of all ROIs under consideration and the superior-inferior motion was larger than the anterior-posterior motion for all ROIs. CONCLUSION: We developed and validated a deformable registration framework to automate the estimation of swallowing motion from 2D MR cine scans.

PURPOSE: To report on the feasibility and performance of conventionally fractionated multileaf collimator (MLC)-based robotic stereotactic body re-irradiation of the head and neck region using MLC-based Cyberknife (CK) technology. METHODS: Patients treated for recurrent or second primary head and neck cancer (HNC) with curative proton therapy to a target volume > 30 cm3 between 2011 and 2015 were included. MLC-based CK plans were generated using the CK M6 InCise2 MLC system. Dose statistics from MLC-based CK plans were compared to proton beam therapy (PBT) plans according to the following metrics: target coverage, target homogeneity index, gradient index, Paddick conformity index (CI), prescription isodose volume (PIV), treatment time (tTime) for one fraction as well as doses to organs at risk (OAR). Wilcoxon signed-rank test was used to compare dose metrics. RESULTS: Eight patients were included; the tumor sites included: salivary glands, pharynx (oropharynx, hypopharynx and retropharynx) and sinonasal cavities. Five of 8 patients were treated with multifield optimisation intensity modulated proton therapy, 3 were treated with passive scattering proton therapy. Median dose was 67 Gy (range 60-70) in 32 fractions (range 30-35). The median high-dose planning target volume (PTV) was 45.4 cm3 (range 2.4 - 130.2 cm3) and the median elective PTV was 91.9 cm3 (range 61.2 - 269.7 cm3). Overall, the mean target coverage (mean 98.3% vs. 96.2% for CK vs. PBT, respectively), maximum dose to PTV (mean 111% vs. 111%, p = 0.2) and mean dose to PTV (mean 104% vs. 104%) were similar across modalities. Highly conformal plans were achieved with both modalities, but mean CI was better with PBT (0.5 vs. 0.6 for CK vs. PBT, p = 0.04). Homogeneity and gradient indexes were similar between the 2 modalities; mean tTime with PBT and CK was 17 vs. 18 min, respectively (p = 0.7). Case-based study revealed that CK and PBT plans allowed for excellent sparing of OAR, with some clinical scenarios

PURPOSE: The use of magnetic resonance imaging (MRI) in radiotherapy treatment planning has rapidly increased due to its ability to evaluate patient's anatomy without the use of ionizing radiation and due to its high soft tissue contrast. For these reasons, MRI has become the modality of choice for longitudinal and adaptive treatment studies. Automatic segmentation could offer many benefits for these studies. In this work, we describe a T2-weighted MRI dataset of head and neck cancer patients that can be used to evaluate the accuracy of head and neck normal tissue auto-segmentation systems through comparisons to available expert manual segmentations. ACQUISITION AND VALIDATION METHODS: T2-weighted MRI images were acquired for 55 head and neck cancer patients. These scans were collected after radiotherapy computed tomography (CT) simulation scans using a thermoplastic mask to replicate patient treatment position. All scans were acquired on a single 1.5 T Siemens MAGNETOM Aera MRI with two large four-channel flex phased-array coils. The scans covered the region encompassing the nasopharynx region cranially and supraclavicular lymph node region caudally, when possible, in the superior-inferior direction. Manual contours were created for the left/right submandibular gland, left/right parotids, left/right lymph node level II, and left/right lymph node level III. These contours underwent quality assurance to ensure adherence to predefined guidelines, and were corrected if edits were necessary. DATA FORMAT AND USAGE NOTES: The T2-weighted images and RTSTRUCT files are available in DICOM format. The regions of interest are named based on AAPM's Task Group 263 nomenclature recommendations (Glnd_Submand_L, Glnd_Submand_R, LN_Neck_II_L, Parotid_L, Parotid_R, LN_Neck_II_R, LN_Neck_III_L, LN_Neck_III_R). This dataset is available on The Cancer Imaging Archive (TCIA) by the National Cancer Institute under the collection "AAPM RT-MAC Grand Challenge 2019" (https://doi.org/10.7937

PURPOSE: The purpose of this study was to compare self-reported health-related quality of life (QoL) and symptom burden in early stage tonsillar carcinoma patients treated with unilateral (URT) and bilateral radiotherapy (BRT). METHODS AND MATERIALS: This is a secondary analysis of a larger study assessing patient reported outcomes in human papillomavirus (HPV) oropharyngeal cancer (OPC) patients. Recruited patients were ≥12 months from completion of radiotherapy. This analysis included only patients with T1-2, N1-2b tonsil cancer and excluded patients with base of tongue involvement or recurrent disease. QoL and patient reported toxicity was measured using the EORTC QLQ-C30 module and the MDASI-HN. RESULTS: Patients were enrolled from November 2018 to May 2019. Of the 136 patients recruited to the main study, 43 were eligible for this substudy (22 URT, 21 BRT), with a median age and follow up of 58.2 and 3.0 years respectively. The two groups were balanced with respect to patient, tumor and treatment factors with the exception of higher rates of T2 disease (27% v 71%, p = 0.006) and more extensive GTV nodal volumes (11.0 v 25.5cc, p = 0.006) in the BRT group.BRT patients had lower global health status/QoL (84 v 69, p = 0.0005) and social functioning scores (93 vs 78, p = 0.033) on the EORTC QLQ-C30, and higher symptom severity (0.6 vs. 2.0, p = 0.001) and symptom interference scores (0.8 vs. 2.0, p = 0.010) on the MDASI-HN. Four of the six largest differences observed on MDASI-HN items were attributable to radiotherapy technique (dry mouth, mucous, difficulty swallowing/chewing and taste), with corresponding dose differences to the respective organs (contralateral parotid, oral cavity and pharyngeal constrictors). In every instance, severity of symptoms was worse on average for patients treated with BRT. CONCLUSIONS: In the highly conformal radiotherapy era, BRT in early HPV tonsillar cancer survivors has an enduring impact on long-term QoL and toxicity.

PURPOSE: To report cancer control outcomes and health-related quality of life (HRQoL) outcomes after highly conformal skull-based re-irradiation (re-RT). METHODS: Patients planned for curative intent re-RT to a recurrent or new skull base tumor were enrolled. HRQoL were assessed using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT) and the anterior skull base surgery quality of life (ASBQ) questionnaires. RESULTS: Thirty-nine patients were treated with stereotactic body RT or intensity modulated RT. Median follow-up was 14 months. Progression free survival was 71% at 1-year. There was mild clinically significant worsening of fatigue, lack of appetite and drowsiness (MDASI-BT), and physical function (ASBQ) at the end of RT, followed by recovery to baseline on subsequent follow-ups. Subjective emotions were clinically improved at 12 months, with patients reporting feeling less tense/nervous. CONCLUSION: Conformal skull base re-RT is associated with mild immediate deterioration in physical function followed by rapid and sustained recovery.

BACKGROUND: The current study was performed to assess the efficacy of surveillance imaging in patients with head and neck cancer (HNC) who are treated definitively with radiotherapy. METHODS: Eligible patients included those with a demonstrable disease-free interval (≥1 follow-up imaging procedure without evidence of disease and a subsequent visit/imaging procedure) who underwent treatment of HNC from 2000 through 2010. RESULTS: A total of 1508 patients were included. The median overall survival was 99 months, with a median imaging follow-up period of 59 months. Of the 1508 patients, 190 patients (12.6%) experienced disease recurrence (107 patients had locoregional and 83 had distant disease recurrence). A total of 119 patients (62.6%) in the group with disease recurrence were symptomatic and/or had an adverse clinical finding associated with the recurrence. Approximately 80% of patients with locoregional disease recurrences presented with a clinical finding, whereas 60% of distant disease recurrences were detected by imaging in asymptomatic patients. Despite the earlier detection of disease recurrence via imaging, those patients in the group of patients with clinically detected disease recurrence were significantly more likely to undergo salvage therapy compared with those whose recurrence was detected on imaging (odds ratio, 0.35). There was no difference in overall survival noted between those patients with disease recurrences that were detected clinically or with imaging alone. Approximately 70% of disease recurrences occurred within the first 2 years. In those patients who developed disease recurrence after 2 years, the median time to recurrence was 51 months. After 2 years, the average number of imaging procedures per patient for the detection of a salvageable recurrence for the imaging-detected group was 1539. CONCLUSIONS: Surveillance imaging in asymptomatic patients with HNC who are treated definitively with radiotherapy without clinically suspicious findin

BACKGROUND: The objective of the current study was to characterize the incidence, pattern, and impact on oncologic outcomes of retropharyngeal lymph node (RPLN) involvement in HPV-associated oropharyngeal cancer (OPC). METHODS: Data regarding patients with HPV-associated OPC who were treated at The University of Texas MD Anderson Cancer Center with intensity-modulated radiotherapy from 2004 through 2013 were analyzed retrospectively. RPLN status was determined by reviewing pretreatment imaging and/or reports. Outcomes analysis was restricted to patients with lymph node-positive (+) disease. Kaplan-Meier survival estimates were generated and survival curves were compared using the log-rank test. Bayesian information criterion assessed model performance changes with the addition of RPLN status to current American Joint Committee on Cancer staging. Competing risk analysis compared modes of disease recurrence. RESULTS: The incidence of radiographic RPLN involvement was 9% (73 of 796 patients) and was found to vary by primary tumor site. The 5-year rates of freedom from distant metastases (FDM) and overall survival were lower in patients with RPLN(+) status compared with those with RPLN-negative (-) status (84% vs 93% [P = .0327] and 74% vs 87% [P = .0078], respectively). RPLN(+) status was not found to be associated with outcomes on multivariate analysis. Bayesian information criterion analysis demonstrated that current American Joint Committee on Cancer staging was not improved with the inclusion of RPLN. Locoregional and distant disease recurrence probabilities for those patients with RPLN(+) status were 8% and 13%, respectively, compared with 10% and 6%, respectively, for those with RPLN(-) status. RPLN(+) status portended worse 5-year FDM in the low-risk subgroup (smoking history of <10 pack-years) and among patients who received concurrent chemotherapy but not induction chemotherapy. CONCLUSIONS: RPLN(+) status was associated with worse overall survival and FDM on

BACKGROUND: MRI-guided radiotherapy planning (MRIgRT) may be superior to CT-guided planning in some instances owing to its improved soft tissue contrast. However, MR images do not communicate tissue electron density information necessary for dose calculation and therefore must either be co-registered to CT or algorithmically converted to synthetic CT. No robust quality assessment of commercially available MR-CT registration algorithms is yet available; thus we sought to quantify MR-CT registration formally. METHODS: Head and neck non-contrast CT and T2 MRI scans acquired with standard treatment immobilization techniques were prospectively acquired from 15 patients. Per scan, 35 anatomic regions of interest (ROIs) were manually segmented. MRIs were registered to CT rigidly (RIR) and by three commercially available deformable registration algorithms (DIR). Dice similarity coefficient (DSC), Hausdorff distance mean (HD mean) and Hausdorff distance max (HD max) metrics were calculated to assess concordance between MRI and CT segmentations. Each DIR algorithm was compared to DIR using the nonparametric Steel test with control for individual ROIs (n = 105 tests) and for all ROIs in aggregate (n = 3 tests). The influence of tissue type on registration fidelity was assessed using nonparametric Wilcoxon pairwise tests between ROIs grouped by tissue type (n = 12 tests). Bonferroni corrections were applied for multiple comparisons. RESULTS: No DIR algorithm improved the segmentation quality over RIR for any ROI nor all ROIs in aggregate (all p values >0.05). Muscle and gland ROIs were significantly more concordant than vessel and bone, but DIR remained non-different from RIR. CONCLUSIONS: For MR-CT co-registration, our results question the utility and applicability of commercially available DIR over RIR alone. The poor overall performance also questions the feasibility of translating tissue electron density information to MRI by CT registration, rather than addressing this nee

BACKGROUND: The aim of this study was to determine the interdisciplinary agreement in identifying the post-operative tumor bed. METHODS: Three radiation oncologists (ROs), four surgeons, and three radiologists segmented post-operative tumor and nodal beds for three patients with oral cavity cancer. Specialty cohort composite contours were created by STAPLE algorithm implementation results for interspecialty comparison. Dice similarity coefficient and Hausdorff distance were utilized to compare spatial differentials between specialties. RESULTS: There were significant differences between disciplines in target delineation. There was unacceptable variation in Dice similarity coefficient for each observer and discipline when compared to the STAPLE contours. Within surgery and radiology disciplines, there was good consistency in volumes. ROs and radiologists have similar Dice similarity coefficient scores compared to surgeons. CONCLUSION: There were significant interdisciplinary differences in perceptions of tissue-at-risk. Better communication and explicit description of at-risk areas between disciplines is required to ensure high-risk areas are adequately targeted.

This study highlights gamma knife stereotactic radiosurgery (GK-SRS) as boost therapy in a patient with adenoid cystic carcinoma of the parotid involving the skull base and invasion of the facial nerve. Using GK-SRS, dose to the brainstem and temporal lobe were reduced when compared to less conformal radiotherapy techniques.

BACKGROUND: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). METHODS: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DISCUSSION: Multiple methods for safe treatment de-esc

Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control. Therefore, there is increasing interest in exploring different techniques and/or modality of radiotherapy and dose/fractionation. Stereotactic radiotherapy, which employs a hypofractionated regimen, has the potential advantage of delivering a high dose of radiation to the tumor in a short period of time (typically over 5 days) with minimal dose to the surrounding normal structures. Particle therapy such as proton and carbon ion therapy are being explored as potential radiation modality that could cause greater biological damage to the tumor compared to photon treatment, with rapid dose falloff resulting in minimal to no dose to adjacent structures. This review will discuss the current literature and emerging roles of stereotactic radiotherapy and particle therapy in pancreatic cancer.

BACKGROUND: Magnetic resonance imaging (MRI) has improved capacity to visualize tumor and soft tissue involvement in head and neck cancers. Using advanced MRI, we can interrogate cell density using diffusion weighted imaging, a quantitative imaging that can be used during radiotherapy, when diffuse inflammatory reaction precludes PET imaging, and can assist with target delineation as well. Correlation of circulating tumor cells (CTCs) measurements with 3D quantitative tumor characterization could potentially allow selective, patient-specific response-adapted escalation or de-escalation of local therapy, and improve the therapeutic ratio, curing the greatest number of patients with the least toxicity. METHODS: The proposed study is designed as a prospective observational study and will collect pretreatment CT, MRI and PET/CT images, weekly serial MR imaging during RT and post treatment CT, MRI and PET/CT images. In addition, blood sample will be collected for biomarker analysis at those time intervals. CTC assessments will be performed on the CellSave tube using the FDA-approved CellSearch® Circulating Tumor Cell Kit (Janssen Diagnostics), and plasma from the EDTA blood samples will be collected, labeled with a de-identifying number, and stored at - 80 °C for future analyses. DISCUSSION: The primary objective of the study is to evaluate the prognostic value and correlation of weekly tumor response kinetics (gross tumor volume and MR signal changes) and circulating tumor cells of mucosal head and neck cancers during radiation therapy using MRI in predicting treatment response and clinical outcomes. This study will provide landmark information as to the utility of CTCs ('liquid biopsy) and tumor-specific functional quantitative imaging changes during treatment to guide personalization of treatment for future patients. Combining the biological information from CTCs and the structural information from MRI may provide more information than either modality alone. In additi

BACKGROUND: The purpose of this study was to present our experience with retropharyngeal node reirradiation using highly conformal radiotherapy (RT). METHODS: A retrospective screen of 2504 consecutively irradiated patients with head and neck malignancies between 2005 and 2015 identified 19 patients who underwent reirradiation for retropharyngeal node metastasis. Clinical and toxicity outcomes were assessed in these patients. RESULTS: Thirteen patients (68%) had squamous cell carcinoma. Eleven patients (58%) received conventionally fractionated intensity-modulated radiotherapy (IMRT) or proton therapy, and 8 patients (42%) received single-fractionated or hypofractionated stereotactic RT. Fourteen patients (74%) received chemotherapy. Median follow-up was 14.7 months. The 1-year local control, locoregional control, overall survival, and progression-free survival rates were 100%, 94%, 92%, and 92%, respectively. Three patients (16%) experienced acute grade 3 toxicity and occurred in those treated with IMRT. There was no late grade ≥3 toxicity. CONCLUSION: Retropharyngeal node reirradiation with conformal therapy is well tolerated and associated with excellent short-term disease control.

Cancers of the nasal cavity and septum are associated with poor prognosis and are usually treated with surgery followed by post-operative radiotherapy with or without concurrent chemotherapy. Definitive radiotherapy is used in cases where the tumor is unresectable, patient is unfit for surgery, and/or the patient declines surgical intervention. Here, we present a case of a patient, who for non-medical reasons, opted to have non-surgical management of his rapidly progressing nasal cavity tumor. He was successfully treated with concurrent chemoradiotherapy utilizing a combination of intensity modulated proton therapy (IMPT) with passive scatter boost to reduce dose to the adjacent critical neural structures. Post-treatment clinical examination and imaging demonstrated complete clinical and metabolic response at the primary site and neck. This case highlights the use of IMPT and passive scatter boost in combination to achieve delivery of therapeutic dose to nasal cavity tumor and neck whilst limiting dose to numerous adjacent organs-at-risk.

Adenoid cystic carcinoma (ACC) is generally treated with surgical resection followed by postoperative radiotherapy. In cases where surgical management is precluded due to the location of the tumor and/or patient factors, radiation therapy can be offered to achieve local control. Here, we present a case of unresectable Stage T4N0 ACC of the nasopharynx with skull base and intracranial extension treated with intensity modulated proton therapy (IMPT), which achieved good local control with no significant late toxicity.

BACKGROUND: This prospective study aims to determine the impact of PET/CT on radiotherapy planning and outcomes in patients with oesophageal cancer. METHODS: All patients underwent PET/CT scanning in the radiotherapy treatment position, and received treatment planned using the PET/CT dataset. GTV was defined separately on PET/CT (GTV-PET) and CT (GTV-CT) datasets. A corresponding PTV was generated for each patient. Volumetric and spatial analysis quantified the proportion of FDG-avid disease not included in CT-based volumes. Clinical data was collected to determine locoregional control and overall survival rates. RESULTS: 13 (24.1%) of 57 accrued patients had metastatic disease detected on PET. Median follow up was 4 years. FDG-avid disease would have been excluded from GTV-CT in 29 of 38 patients (76%). In 5 patients, FDG-avid disease would have been completely excluded from the PTV-CT. GTV-CT underestimated the cranial and caudal extent of FDG-avid tumour in 14 (36%) and 10 (26%) patients. 4-Year overall survival and locoregional failure free survival were 37% and 65%. CONCLUSIONS: PET/CT altered the delineation of tumour volumes when compared to CT alone, and should be considered standard for treatment planning. Although clinical outcomes were not improved with PET/CT planning, it did allow the use of smaller radiotherapy volumes.

BACKGROUND: Prostate cancer management involves a balance between the risks of cancer death against those from other causes. To evaluate the performance of several comorbidity indices in predicting comorbid death in a prostate cancer radiotherapy cohort. METHODS: 2,131 men with localised prostate cancer treated with radical radiotherapy between 1999 and 2007 were studied. Tumour features, androgen deprivation usage, age, number of prescription medications (PMN) and Adult Comorbidity Evaluation-27 Index (ACE-27) were recorded. Death from prostate cancer (DPC) and death from other causes (DOC) were analysed as competing causes of death using a competing risks model, with discrimination assessed using the concordance index. RESULTS: ACE-27 scores correlated with patient's PMN (median PMN = 2). Tumour features were independent of ACE-27 scores. Estimated cumulative incidences of DOC and DPC at 10 years were 16.4% and 7.7% respectively. In the low/intermediate risk group (n = 1026) there was a 3.4-fold predominance of DOC inside 10 years (cumulative incidence: 15.8% DOC vs 3.4% DPC). High-risk men had approximately equal rates of DPC and DOC at 10 years. Multivariable analysis showed age, ACE-27 score ≥ 1 and PMN to have significant associations with DOC (P < 0.002 for all). A multivariable model incorporating all 3 variables resulted in C-Index = 0.646. CONCLUSION: Age, ACE-27 score and PMN act as independent prognostic factors for DOC in prostate cancer patients and can improve patient's life expectancy prediction.

PURPOSE: We evaluated the geometric and dosimetric-based distribution of mucosal and nodal recurrences in patients with metastatic head and neck squamous cell carcinoma to cervical lymph nodes of unknown primary after intensity modulated radiation therapy using validated typology-indicative taxonomy. METHODS AND MATERIALS: We reviewed the data of 260 patients who were irradiated between 2000 and 2015 and had a median follow-up time for surviving patients of 61 months. The mucosal and nodal recurrences were manually delineated on computed tomography images demonstrating the recurrences. The images were overlaid on the treatment plan using deformable image registration. The locations of the recurrences were determined relative to the original planning target volumes and doses using centroid-based approaches. Subsequently, the pattern of failures were classified into 5 types based on combined spatial and dosimetric criteria: A (central high dose), B (peripheral high dose), C (central elective dose), D (peripheral elective dose), and E (extraneous dose). For patients with type A failure with simultaneous nontype A lesions, the overall pattern of failures was defined as type A. RESULTS: Thirty-two patients had mucosal or nodal recurrences. The most common clinical nodal stage was N2b (66%). Preradiation therapy neck dissections were performed in 6 patients. The median dose delivered to clinical tumor volume 1 was 66 Gy. The majority (84%) had total/partial pharyngeal mucosa elective irradiation. Twenty-three patients had nodal recurrences, 8 had mucosal recurrences, and 1 had both nodal and mucosal recurrences. Twenty-one patients (91%) had type A nodal failure, and 7 of the mucosal failures (89%) were type C. CONCLUSIONS: The majority of nodal recurrences occurred within the high-dose area, demanding the need for identification of radioresistant areas within malignant nodes. Future studies should focus on either dose escalation of high-risk volumes or novel radiosensiti

Cases of synchronous prostate and colorectal adenocarcinomas have been sporadically reported. There are case reports on patients with synchronous prostate and rectal cancers treated with external beam radiotherapy alone or combined with high-dose rate brachytherapy boost to the prostate. Here, we illustrate a patient with synchronous prostate and rectal cancers treated using the volumetric arc therapy (VMAT) technique. The patient was treated with radical radiotherapy to 50.4 Gy in 28 fractions to the pelvis, incorporating the involved internal iliac node and the prostate. A boost of 24 Gy in 12 fractions was delivered to the prostate only, using VMAT. Treatment-related toxicities and follow-up prostate-specific antigen and carcinoembryonic antigen were collected for data analysis. At 12 months, the patient achieved complete response for both rectal and prostate cancers without significant treatment-related toxicities.

A first toxicity identification evaluation (TIE) was conducted in three phases using the Microtox(R) test to identify the major toxicant(s) in effluent discharged from a dyeing plant in Hong Kong. In Phase I toxicity characterization indicated that anions were likely to be the major toxicants for the entire effluent. In Phase II concentrations of sulfite and other anions in the original and the anion exchange resin-treated effluent samples were determined by ion chromatography. Anions, which were found in the effluent at comparatively high concentrations and were suspected of being responsible for the toxicity to luminescent bacteria, were selected for further study in Phase III. Investigation in Phase III using the spiking and mass balance approaches confirmed that the sulfite ion was the major toxicant in the effluent. (C) 2003 Wiley Periodicals, Inc.