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Interstitial brachytherapy (ISBT) is an effective option for delivering conformal high dose radiation to the target volume with better organ-at risk sparing but is thought to be more invasive and painful than other methods. This study investigated pain levels and opioid consumption in patients who received spinal anesthesia (SA) or general anesthesia (GA) for their ISBT.Patients that underwent ISBT from April 2014 to September 2018 were analyzed from a prospective institutional database. The most prevalent malignancies were cervical (45%), recurrent endometrial (27%) and vaginal (20%) cancers. Baseline patient characteristics, radiation treatment details, anesthesia records, and inpatient charts were obtained. Opioid consumption was quantified as oral morphine equivalent per day (OMEq/day) from implantation until removal. Pain score levels were collected by using an 11-point scoring system.Ninety nine patients received GA and 40 patients received SA as their anesthesia for ISBT. During their first admission, 76 patients (55%) required intravenous opioids. Patients receiving SA had significantly lower mean pain scores on the morning of their procedure 6 (Interquartile range [IQR] 2-8) vs. 0 (IQR: 0-1); p0.001]. Pain did not significantly differ between cohorts at any other time. During the first admission, SA patients had a lower median opioid usage of 23 (IQR: 9-47) mg/day compared to GA patients at 38 (IQR: 21-71) mg/day (p = 0.011). No difference in opioid consumption was seen during subsequent admissions.In patients undergoing ISBT, SA provides better immediate pain control post insertion compared to GA. Patients who received SA used lower amounts of opioids during their first ISBT insertion.

Introduction: Our objective was to assess the effect of 18F-DCFPyL prostate-specific membrane antigen (PSMA) positron emission tomography (PET) on the management and outcomes of patients receiving salvage radiotherapy following biochemical failure (BF) post-radical prostatectomy (RP) using a matched cohort analysis. Methods: A PSMA-PET cohort of patients with BF post-RP was identified through a prospective registry. Patients from this registry were included if they did not have disease outside of the pelvis and underwent salvage radiotherapy to the prostate and/or pelvis. Case-control matching was performed with a contemporary cohort of patients with BF post-RP without PSMA-PET information. Results: Forty-four patients were included in the PSMA-PET cohort and 80 were analyzed in the non-PSMA-PET cohort. The PSMA-PET cohort had a significantly higher pre-radiotherapy median prostate-specific antigen (PSA) of 0.48 ng/mL compared to 0.20 ng/mL in the non-PSMA-PET cohort (p0.99) and matched patients (p=0.808 and 0.808), respectively. Metastasis-free survival was significantly higher in the matched PSMA-PET cohort compared to the matched non-PSMA-PET cohort (p=0.046), although a higher proportion of patients in the non-PSMA-PET cohort underwent PSMA-PET restaging after BF (52 vs. 20%, p=0.08726). Conclusions: Our study showed that patients undergoing PSMA-PET scans after BF post-RP had a higher likelihood of pelvic nodal treatment at the time of salvage RT. Despite higher PSA levels at salvage, we identified no recurrence or survival differences.

To compare toxicities in relation to standard radiation treatments [conventional fractionation RT (CRT) and moderate hypofractionated RT (MRT)] with ultrahypofractionated RT (URT) in the treatment of patients with localized PCa.A searched was performed in Medline, Embase, Cochrane CENTRAL, and LILACS to January 2020 for studies comparing URT to CRT and/or MRT in relation to genitourinary (GU) and gastrointestinal (GI) toxicity in the treatment of patients with localized PCa. URT, MRT and CRT were defined as protocols delivering a daily dose of ≥5 Gy, 2.4-4.9 Gy, and2.4 Gy per fractions regardless total dose, respectively.Eight studies with 2929 patients with localized PCa were included in the analysis. These eight studies did not find any difference between URT and MRT/CRT groups in relation to acute GU toxicity (21.0% × 23.8%, RD -0.04; 95% CI -0.13, 0.06; p = 0.46; IThe present study suggests that acute GU/GI and late GU/GI toxicity are similar between URT and standard protocols. More studies with longer follow-ups directed to oncology outcomes are warranted before any recommendation on this topic.

PURPOSE In this study, we propose combining three-dimensional (3D) transrectal ultrasound (TRUS) and 3D transabdominal ultrasound (TAUS) images of gynecologic brachytherapy applicators to leverage the advantages of each imaging perspective, providing a broader field-of-view and allowing previously obscured features to be recovered. The aim of this study was to evaluate the feasibility of fusing these 3D ultrasound (US) perspectives based on the applicator geometry in a phantom prior to clinical implementation. METHODS In proof-of-concept experiments, 3D US images of application-specific multimodality pelvic phantoms were acquired with tandem-and-ring and tandem-and-ovoids applicators using previously validated imaging systems. Two TRUS images were acquired at different insertion depths and manually fused based on the position of the ring/ovoids to broaden the TRUS field-of-view. The phantom design allowed "abdominal thickness" to be modified to represent different body habitus and TAUS images were acquired at three thicknesses for each applicator. The merged TRUS images were then combined with TAUS images by rigidly aligning applicator components and manually refining the registration using the positions of source channels and known tandem length, as well as the ring diameter for the tandem-and-ring applicator. Combined 3D US images were manually, rigidly registered to images from a second modality (magnetic resonance (MR) imaging for the tandem-and-ring applicator and X-ray computed tomography (CT) for the tandem-and-ovoids applicator (based on applicator compatibility)) to assess alignment. Four spherical fiducials were used to calculate target registration errors (TREs), providing a metric for validating registrations, where TREs were computed using root-mean-square distances to describe the alignment of manually identified corresponding fiducials. An analysis of variance (ANOVA) was used to identify statistically significant differences (p

External beam radiotherapy is an effective curative treatment option for localized prostate cancer, the most common cancer in men worldwide. However, conventionally fractionated courses of curative external beam radiotherapy are usually 8–9 weeks long, resulting in a substantial burden to patients and the health-care system. This problem is exacerbated in low-income and middle-income countries where health-care resources might be scarce and patient funds limited. Trials have shown a clinical equipoise between hypofractionated schedules of radiotherapy and conventionally fractionated treatments, with the advantage of drastically shortening treatment durations with the use of hypofractionation. The hypofractionated schedules are supported by modern consensus guidelines for implementation in clinical practice. Furthermore, several economic evaluations have shown improved cost effectiveness of hypofractionated therapy compared with conventional schedules. However, these techniques demand complex infrastructure and advanced personnel training. Thus, a number of practical considerations must be borne in mind when implementing hypofractionation in low-income and middle-income countries, but the potential gain in the treatment of this patient population is substantial., Conventionally fractionated external beam radiotherapy is an effective treatment for localized prostate cancer, but long treatment programmes result in a substantial burden to patients and the health-care system, which is particularly problematic in low-income and middle-income countries (LMICs) where health-care resources might be scarce and patient funds limited. Here, the authors discuss the outcomes and benefits of hypofractionation — in terms of both oncology and economics — and how it could be used to improve prostate cancer care in LMICs., Key points The global burden of prostate cancer is increasing and prostate cancer is becoming a major source of health-care burden in low-income and middle-income countries (LMICs).Radiotherapy is an essential treatment modality in the management of prostate cancer. However, radiotherapy resources are lacking in LMICs, resulting in excess morbidity and mortality.Hypofractionated radiotherapy schedules offer an opportunity to maintain excellent treatment outcomes while shortening curative radiotherapy courses. This approach expands the treatment capacity and could improve crucial access in communities with limited radiotherapy resources.Initial investments are required for technological upgrades, such as intensity-modulated radiotherapy and image-guided radiotherapy, as well as in specialized training in order to optimally provide hypofractionated treatment. Discussion amongst government agencies and device manufacturers is essential to lower these costs.Personnel training and access to external consultation are critical resources for developing radiotherapy centres. Information and communication technologies enable remote guidance between developing and developed radiotherapy centres.In the long term, hypofractionation programmes result in long-term cost savings and simultaneously expand patient access to a curative modality in the management of prostate cancer.

Decipher is a genomic classifier (GC) prospectively validated post-prostatectomy. Herein, we validate the performance of the GC in pre-treatment biopsy samples within the context of three randomized phase III high-risk definitive radiotherapy trials.A pre-specified analysis plan (NRG-GU-TS006) was approved to obtain formalin-fixed paraffin-embedded tissue from biopsy specimens from the NRG biobank from patients enrolled on the NRG/RTOG 9202, 9413, and 9902 phase III randomized trials. After central review, the highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays and GC scores were obtained. The primary objective was to validate the independent prognostic ability for the GC for distant metastases (DM), and secondary for prostate cancer-specific mortality (PCSM) and overall survival (OS) with Cox univariable (UVA) and multivariable analyses (MVA).GC scores were obtained on 385 samples, of which 265 passed microarray quality control (69%) and had a median follow-up of 11 years (interquartile range, 9, 13). In the pooled cohort, on UVA, the GC was shown to be a prognostic factor for DM (per 0.1 unit; sHR 1.29, 95%CI 1.18-1.41, p0.001), PCSM (sHR 1.28, 95%CI 1.16-1.41, p0.001), and OS (HR 1.16, 95%CI 1.08-1.22, p0.001). On MVA, the GC (per 0.1 unit) was independently associated with DM (sHR 1.22, 95%CI 1.09-1.36), PCSM (sHR 1.23, 95%CI 1.09-1.39), and OS (HR 1.12, 95%CI 1.05-1.20) after adjusting for age, PSA, Gleason score, cT-stage, trial, and randomized treatment arm. GC had similar prognostic ability in patients receiving short-term or long-term androgen-deprivation therapy (ADT) but the absolute improvement in outcome varied by GC risk.This is the first validation of a gene expression biomarker on pre-treatment prostate cancer biopsy samples from prospective randomized trials and demonstrates an independent association of GC score with DM, PCSM, and OS. High-risk prostate cancer is a heterogeneous disease state and GC can improve risk stratification to help personalize shared decision-making.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Purpose/objectives High dose rate (HDR) interstitial brachytherapy (ISBT) boost is integral for definitive radiation treatment of primary vaginal cancer. Technological advances with CT or MRI guidance provide improved precision and ability to treat more extensively invasive tumors over historical techniques, but reported experience is limited. We sought to provide updated outcome and toxicity data for women with primary vaginal cancer undergoing treatment with a modern ISBT technique. Material/methods Databases of primary vaginal carcinoma patients treated at two Canadian academic cancer institutions were combined including patient, tumor and treatment characteristics, and survival outcomes and toxicity data. Descriptive statistics, survival estimates based on the Kaplan-Meier method, and univariable/multivariable Cox proportional hazards regression analyses are reported. Results Between 2002 and 2017, 67 women with primary vaginal cancer were treated with 3D HDR ISBT. FIGO stage distribution was I (22.4%), II (50.8%), III (17.9%), IVa (9.0%). All patients received external beam radiotherapy and HDR ISBT of 500–750 cGy per fraction over 2–4 fractions. Median follow-up was 2.68 years (95% confidence interval: 2.04–6.04). Cumulative rate of grade 3–4 genitourinary/gastrointestinal toxicity was 10.4%. Four patients developed vaginal fistula. Progression-free survival at 2 and 3 years was 73.5% and 66.4% for all patients, 78.3% and 75.0% for stage I-II and 61.6% and 46.2% for stage III-IVa, respectively (log-rank p = 0.252). Conclusions Use of 3D image-guided HDR ISBT boost was safe and resulted in improved survival outcomes compared to historical rates in this series of primary vaginal cancer patients. Prospective study is warranted to better define clinical and dosimetric predictors of local control.

Purpose To investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methods Data from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. Results A total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. Conclusion Short-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

Cervical cancer is a deadly disease and the COVID-19 pandemic has the potential to further impact its lethality. Hypofractionated radiotherapy could mitigate this impact, however robust data in cervical cancer setting still is lacking. Information provided here could help institutions in reducing radiotherapy fractions for cervical cancer patients.

Purpose To compare CTVHR and OAR dimensions and inter-rater agreement between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) images in IB cervical cancer patients. Methods IB cervical cancer patients treated with (chemo)radiotherapy plus MR-guided brachytherapy (BT) were prospectively enrolled in this study. Radiation oncologists contoured CTVHR and OARs in pre-BT MR images (MRI) and intra-operative TRUS images. These contours were subsequently compared in regard to volume and dimension. Contour inter-rater agreement analysis was also investigated using kappa index (KI). Stata 15.0 was used for statistical analysis and a p-value Results TRUS CTVHR volumes were statistically smaller than the respective MRI contoured volumes. TRUS CTVHR thickness was found to be consistently smaller than MRI contours in all patients. No statistical difference was seen in width and height between the two different imaging modalities. MRI contours had a median KI of 0.66 (range: 0.56–0.77) while TRUS-based contours had a median KI of 0.64 (range: 0.47–0.77). Bladder and rectum had very satisfactory KI in both imaging modalities. Vaginal contours had moderate agreement in MR (0.52) and in TRUS images (0.58). Conclusion TRUS images allow good visualization of CTVHR and OARs in IB cervical cancer patients. Inter-rater contour variability was comparable between TRUS and MR images. TRUS is a promising modality on its own for image-guided BT.

Background and purpose To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. Materials and methods 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). Results Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9–6.6) years. Median baseline PSA was 7.3 (5.3–9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75–7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1–6.1; p = 0.037) and APP4 (HR 2.3, 1.1–4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4–12.4; p = 0.010) and APP4 (HR 3.7, 1.4–10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9–135.3; p Conclusion APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.

Purpose To describe a technique of penile surface mold high-dose-rate (HDR) brachytherapy and early outcomes. Methods and Materials Five patients diagnosed with a T1aN0 squamous cell carcinoma of the penis were treated using a penile surface mold HDR brachytherapy technique. A negative impression of the penis was obtained using dental alginate. CT images were acquired of the penile impression; subsequently, a virtual model of the patient's penis was generated. The positive model was imported into a computer-assisted design program where catheter paths were planned such that an optimized offset of 5 mm from the penile surface was achieved. The virtual model was converted into a custom applicator. A total dose of 40 Gy was delivered in 10 fractions. Patients were followed at 1, 3, 6, and 12 months after treatment and then every 6 months thereafter. Toxicities were reported using Common Terminology Criteria for Adverse Events v4.0. Results All patients tolerated treatment well. Acute Grade 2 skin reactions were observed within the first month after treatment. Median followup was 35 months. Late Grade 1 skin toxicities were observed. One patient experienced a urethral stricture requiring dilatation. Two patients developed local recurrence. Conclusion This technique allows the delivery of penile HDR brachytherapy as an outpatient procedure with minimal discomfort to the patient during each application and is a repeatable and accurate setup. This technique warrants validation in larger series with longer followup.

Purpose To evaluate standardized uptake value (SUV) stability on pretreatment and intratreatment 18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in patients undergoing definitive CRT for head and neck cancer (HNC). Methods Primary tumor and nodal volumes of interest (VOIs) from HNC patients were contoured on the pretreatment and intratreatment PET-CT by two independent observers. SUV stability was measured with intersection calculations (DICE, overlap fraction, center to center) between the VOIs at threshold levels of 50%, 60%, 70%, 80%, and 90% of the SUV maximum. Results The mean calculated DICE of the 50%, 60%, 70%, 80%, 90% SUV threshold was 0.53, 0.48, 0.41, 0.28, and 0.12, respectively. The mean calculated overlap fraction was 0.71, 0.65, 0.58, 0.43, and 0.2, respectively. Center-center difference demonstrates spatial variability of 7.8, 8.2, 8.6, 9.5, and 11.2 mm for these SUV subvolumes of interest. Conclusions HNC subvolumes defined by SUV thresholding technique in FDG PET-CT imaging do not remain physically stable during (chemo)RT. Highlights All pretreatment and intratreatment SUV thresholds (50%-90%) overlap indexes are low during the course of (chemo)radiation. Pretreatment and intratreatment center to center variation further corroborates that all FDG threshold volumes do not remain stable during treatment. No difference in SUV threshold stability was seen between p16 positive and negative tumors.

Purpose Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration. Methods and Materials Ten patients with intermediate-risk prostate cancer, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively contour the DIL onto the TRUS image using mpMRI as reference. The contours were analyzed for concordance using simultaneous truth and performance level estimation algorithm. Similarity indices, DIL volumes, and distance between centroid positions were measured to compare the consensus contours against the contours from ROs and the automated algorithms; registration time between all contouring methods was recorded. Results MR2US registration had the highest dice coefficients among all patients with a mean of 0.80 ± 0.13 in comparison to rigid (0.65 ± 0.20) and B-Spline (0.51 ± 0.30). The distance between centroid positions between simultaneous truth and performance level estimation contour and MR2US, rigid, and B-Spline contours were 5 ± 2, 7 ± 5, and 18 ± 11 mm, respectively. The average registration time was significantly shorter for MR2US (11 ± 2 s) and rigid algorithm (7 ± 1 s) compared to ROs (227 ± 27 s) and B-Spline (199 ± 38 s). Conclusions The efficacy of integrating an MRI-delineated DIL into a TRUS-based BT workflow has been validated in this study. The MR2US software is fast and accurate enough to be used for DIL identification in prostate HDR-BT.

Key Points Question What is the hemoglobin transfusion threshold and target recommended for patients with cervical cancer undergoing curative-intent radiotherapy (RT)? Findings In this international Delphi consensus study, 39 experts in gynecologic radiation oncology did not agree on a hemoglobin transfusion threshold, highlighting significant variability in clinical practice. For both external beam RT and brachytherapy, a hemoglobin transfusion target of 9 or more g/dL and less than 12 g/dL, respectively, was agreed on by an 89% consensus. Meaning A liberal packed red blood cell transfusion strategy was recommended by consensus to overcome hypoxia-induced radioresistance in patients with cervical cancer receiving curative RT., Importance Packed red blood cell (PRBC) transfusions are used to treat anemia in patients with cervical cancer undergoing radiotherapy (RT) owing to concerns of hypoxia-induced radioresistance. In the absence of high-quality evidence informing transfusion practices for patients receiving external beam RT (EBRT) and brachytherapy, various arbitrary hemoglobin target levels are used worldwide. Objective To develop consensus statements to guide PRBC transfusion practices in patients with cervical cancer receiving curative-intent RT with EBRT and brachytherapy. Design, Setting, and Participants This international Delphi consensus study was completed between November 1, 2019, and July 31, 2020. A total of 63 international clinical experts in gynecologic radiation oncology were invited; 39 (62%) accepted and consented to participate. Consensus building was achieved using a 3-round anonymous Delphi consensus method. Participants rated their agreement or disagreement with statements using a 5-point Likert scale. An a priori threshold of 75% or more was required for consensus. Main Outcomes and Measures The preplanned primary outcome of this study was to assess hemoglobin transfusion thresholds and targets for both EBRT and brachytherapy by expert consensus. Results Response rates of 100% (39 of 39), 92% (36 of 39), and 97% (35 of 36) were achieved for the first, second, and third rounds of surveys, respectively. Twenty-three experts (59%) practiced in Canada, 11 (28%) in the United States, 3 (8%) in South America, 1 (3%) in Europe, and 1 (3%) in Asia. Consensus was reached for 44 of 103 statements (43%), which were combined to form the final 27-statement consensus guideline. No specific hemoglobin transfusion threshold was agreed on by consensus for EBRT or brachytherapy. By consensus (89% [31 of 35]), a hemoglobin transfusion target for patients who receive a PRBC transfusion should be 9 g/dL or more and less than 12 g/dL. Conclusions and Relevance This study presents the first international expert consensus guideline informing PRBC transfusion practices for patients with cervical cancer undergoing EBRT and brachytherapy. A minimum hemoglobin transfusion target of 9 g/dL was endorsed to balance tumor radiosensitivity with appropriate use of a scarce resource. Randomized clinical trials are required to evaluate the optimal transfusion threshold and target that maximize clinical benefit in this patient population., This international Delphi consensus study developed consensus statements to guide packed red blood cell transfusion practices for patients with cervical cancer receiving curative-intent radiotherapy with external beam radiotherapy and brachytherapy.

Background Radiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients. Methods In this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain. Discussion This study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT. Trial registration ClinicalTrials.gov Identifier: NCT04221165. Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

PURPOSE/OBJECTIVE(S) To validate the association between body composition and all-cause mortality in men treated with radiation therapy for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to help classify patients by risk of all-cause mortality. MATERIALS/METHODS All participants of NRG/RTOG 9406 and NRG/RTOG 0126 with archived computed tomography that extended cranially to include the L4-L5 interface were included. Muscle mass and muscle density were estimated by measuring the cross-sectional area and average attenuation of the paired psoas muscles on a single slice at the level of L4-L5. Bone density was estimated by measuring the average attenuation of the vertebral body cancellous bone on a single slice at mid-L5. Adipose tissue density was estimated by measuring the average attenuation of the subcutaneous adipose tissue on a single slice at L4-L5. Survival analyses, including Cox proportional hazards models, were performed to assess the relationship between body composition variables and all-cause mortality. Recursive partitioning (RPA) was utilized to create a classification tree to classify NRG/RTOG 0126 participants by risk of death, and the discriminant ability of the classification model was validated using the NRG/RTOG 9406 data set. RESULTS Data from 2,066 men was included in this study (864 from NRG/RTOG 9406 and 1,202 from NRG/RTOG 0126). A total of 648 men died in the follow-up period and 51 (7.9%) were due to PCa. Psoas area, psoas density, and vertebral body density were individually associated with overall survival. In the final multivariable model, psoas area, comorbidity score, and age were associated with overall survival (Table). The RPA yielded a classification tree with 4 prognostic groups determined by age, comorbidity, and psoas cross-sectional area. When the RPA classification was applied to the NRG/RTOG 9406 validation set the discriminant ability was preserved (P < 0.001 groupwise log-rank). CONCLUSION The results of this study strongly support that body composition is related to all-cause mortality in men with localized PCa, with most deaths due to causes other than PCa. The inclusion of psoas cross-sectional area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction. This study also confirms the feasibility of performing body composition analysis using archived CT scans using NRG Oncology clinical trial data sets. These methods can be applied to other NRG Oncology data sets to further explore how body composition is related to patient outcomes.

Purpose/Objective(s) Adjuvant radiation plays a significant role in reducing locoregional recurrences in uterine cancers. Standard treatment consists of daily radiation for 5 weeks which can be challenging for patients and the healthcare system, especially during the COVID pandemic. Hypofractionated radiotherapy has been evaluated and established in other pelvic malignancies. This study aims to evaluate the acute urinary and bowel toxicities, and patient reported outcomes following stereotactic hypofractionated adjuvant radiation for endometrial cancer. Materials/Methods This is a prospective phase I/II trial in which patients with endometrial cancer planned for adjuvant radiation received 30 Gy in 5 fractions, every other day or once weekly. Treatment was delivered at two centers with volumetric arc radiation therapy with a body-vacuum immobilization, bowel enema and 3D image-guidance. Toxicity assessment, outcomes and patient reported quality of life (QOL, EORTC core QLQ-C30 and endometrial EN24) were collected at baseline, fractions (F) 3 and 5, and at regular follow-up intervals. Higher scores represent better global QOL/health status or worse symptoms (scale 0 – 100). Changes in QOL over time were investigated with linear mixed-effects models. A P-value threshold of 0.05 was used for statistical significance. A change in QOL score of ≥ 10 points was considered clinically significant. Results The median age of the 41 enrolled patients is 66 (range: 51 – 88). Histologies included 29 endometrioid adenocarcinoma, 8 serous/clear cell, 1 carcinosarcoma, and 3 dedifferentiated. Thirty patients had stage 1 disease while 3 had stage 2 and 8 stage 3. Seven patients received sequential chemotherapy and 3 had additional vault brachytherapy. Median follow-up is 9 months, with worst toxicity (GI or GU) of grade 1 and 2 in 63% and 24% respectively. No patients have experienced a grade 3 or higher toxicity. Patient-reported diarrhea and gastrointestinal domain scores were statistically significantly worse than baseline at F5 (mean paired difference = 27.2; 8.7, P Conclusion Stereotactic hypofractionated radiation for uterine cancers is feasible and well-tolerated with short-term follow-up. Longer follow-up and future randomized studies are needed to further evaluate this treatment.

Brachytherapy is often used in gynecologic cancer treatment to provide high radiation doses to tumors and spare nearby healthy tissues. Intracavitary applicators, including tandem-and-ovoid and tandem-and-ring, are commonly used to position the radioactive sources appropriately. Three-dimensional (3D) transrectal ultrasound (TRUS) imaging has been demonstrated to allow for consistent delineation of the clinical target volume; however, the ability to visualize applicators and relevant structures following applicator insertion has not been investigated. We propose the use of a 3D TRUS system to visualize applicators at the time of placement. In two patient images, the key components of the tandem-and-ovoid applicators were clearly visualized, as well as the uterus, cervix, and vagina, with the potential to identify the tumor and organs-at-risk in these images. Although the tandem-and-ring applicator (one patient) obscured the cervix and anterior anatomy, the posterior applicator edges were visualized and we propose combining the 3D TRUS image with a 3D transabdominal ultrasound (TAUS) image for more complete visualization of the necessary structures. We designed a multimodality application-specific pelvic phantom to assess the feasibility of the image fusion and performed preliminary feasibility assessment on a tandem-and-ovoids applicator and a tandem-and-ring applicator with an interstitial ring cap. The resulting phantom images showed promising features for future image fusion. Intraoperative assessment of applicator placement has the potential to improve the treatment quality and reduce the risk of complications from overexposure of nearby normal tissues, as well as provides a promising approach for accessible image-guided brachytherapy, facilitating broader adoption to healthcare cost-constrained settings.

Background Transoral surgery (TOS), particularly transoral robotic surgery (TORS) has become the preferred modality in the United States for the treatment of early stage oropharyngeal cancer, largely due to assumptions of fewer toxicities and improved quality of life compared to primary radiotherapy (RT). However, these assumptions are based on retrospective analysis, a subset of which utilize primary RT groups not limited to T1-2 stage tumors for which transoral robotic surgery is FDA approved. Thus, there is potential for underestimating survival and overestimating toxicity, including treatment related mortality, in primary RT. Methods Consecutive cases of early T-stage (T1–T2) oropharyngeal cancer presenting to the London Health Sciences Centre between 2014 and 2018 treated with RT or chemoradiation (CRT) were reviewed. Patient demographics, treatment details, survival outcomes and toxicity were collected. Toxicities were retrospectively graded using the Common Terminology Criteria for Adverse Events criteria. Results A total of 198 patients were identified, of which 82% were male and 73% were HPV-positive. Sixty-eight percent of patients experienced a grade 2 toxicity, 48% a grade 3 and 4% a grade 4. The most frequent toxicities were dysphagia, neutropenia and ototoxicity. The rates of gastrostomy tube dependence at 1 and 2 years were 2.5% and 1% respectively. There were no grade 5 (fatal) toxicities. HPV-positive patients experienced improved 5-year overall survival (86% vs 64%, p = 0.0026). Conclusions Primary RT or CRT provides outstanding survival for early T-stage disease, with low rates of severe toxicity and feeding tube dependence. This study provides a reference for comparison for patients treated with primary transoral surgery.

Background Patients with high-risk prostate cancer are at increased risk of lymph node metastasis and are thought to benefit from whole pelvis radiotherapy (WPRT). There has been recent interest in the use of hypofractionated radiotherapy in treating prostate cancer. However, toxicity and cancer outcomes associated with hypofractionated WPRT are unclear at this time. This phase II study aims to investigate the impact in quality of life associated with hypofractionated WPRT compared to conventionally fractionated WPRT. Methods Fifty-eight patients with unfavourable intermediate-, high- or very high-risk prostate cancer will be randomized in a 1:1 ratio between high-dose-rate brachytherapy (HDR-BT) + conventionally fractionated (45 Gy in 25 fractions) WPRT vs. HDR-BT + hypofractionated (25 Gy in 5 fractions) WPRT. Randomization will be performed with a permuted block design without stratification. The primary endpoint is late bowel toxicity and the secondary endpoints include acute and late urinary and sexual toxicity, acute bowel toxicity, biochemical failure-, androgen deprivation therapy-, metastasis- and prostate cancer-free survival of the hypofractionated arm compared to the conventionally fractionated arm. Discussion To our knowledge, this is the first study to compare hypofractionated WPRT to conventionally fractionated WPRT with HDR-BT boost. Hypofractionated WPRT is a more attractive and convenient treatment approach, and may become the new standard of care if demonstrated to be well-tolerated and effective. Trial registration This trial was prospectively registered in ClinicalTrials.gov as NCT04197141 on December 12, 2019.

Background Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck. Methods This is a multicentre phase II study randomizing 90 patients with T1–4 N0–2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL. Discussion This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials. Trial registration Clinicaltrials.gov identifier: NCT03997643. Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Purpose To determine factors associated with need for post-procedural catheterization in prostate cancer patients treated with 15 Gy high dose-rate brachytherapy boost (HDR-BT). Material and methods Patients treated with 15 Gy HDR-BT followed by EBRT were retrospectively evaluated for development of urinary retention and hematuria requiring catheterization in the first 30 days post procedure. Clinical characteristics and treatment details were obtained and used as independent variables under study. Univariable and multivariable logistic regression analysis were used to determine predictors of post brachytherapy complications and a classification tree for risk of urinary retention was created using recursive partitioning analysis (RPA). Results A total of 425 patients treated with 15 Gy HDR-BT were included in this analysis. 27 patients (6.3%) required catheter placement due to acute urinary retention and thirteen other patients (3%) developed hematuria requiring urinary catheter insertion ± continuous bladder irrigation. Number of needles, prostate volume and prior use of ADT, alpha-blockers or 5α-reductase inhibitors were statistically associated with urinary retention in the univariable logistic regression analysis. In multivariable analysis, prostate volume, previous use of alpha-blocker, and use of ADT remained significant. In the RPA, populations were identified in which the rate of urinary retention ranged from 2% to 50% depending on presence of one or more of these risk factors. Conclusion The overall rate of acute urinary complications post HDR brachytherapy is low, but the individual risk of urinary retention can increase depending on the number of risk factors present. A more patient-directed retention risk estimation can be performed by using the classification risk tree presented here.

We present the case of a woman diagnosed with coronavirus disease 2019 (COVID-19) while undergoing chemoradiation for locally advanced cervix cancer. This diagnosis had implications for the treatment of her cancer, and a number of important decisions had to be made. We present the issues that arose and how her oncologic care was managed.

Recent phase II clinical trials suggest that stereotactic ablative radiation therapy (SABR) can potentially improve survival for patients with oligometastatic cancer. However, these studies have mostly enrolled primaries other than gynecologic malignancies. While level I evidence is limited, recent publications exploring the use of SABR for oligometastatic gynecologic cancers have indicated a potential role for this treatment in para-aortic lymph node recurrences, and in visceral and brain metastases. The use of SABR for recurrences in the pelvis presents a number of challenges as these patients have often received previous radiation treatment. In these settings, care must be taken to avoid trespassing normal tissue tolerance with SABR leading to toxicity, especially as the potential benefit of SABR in this setting is not based on high-level evidence. Although SABR is feasible and in general safe for oligometastatic gynecologic malignancies, insufficient data are available to indicate whether it is associated with improved survival. Clinical judgment that incorporates patient and tumor factors is needed to determine if SABR is appropriate for selecting patients. Future directions include combining SABR with novel systemic therapies, determining optimal sequencing of treatments, and generating more robust randomized data pertaining to the use of SABR for oligometastatic gynecologic cancers.

Background and purpose: Declining prostate brachytherapy utilization has been reported in several studies, despite strong evidence for efficacy and safety compared to alternatives. We sought to evaluate contemporary trends in brachytherapy, external beam radiotherapy (EBRT) and prostatectomy utilization in a publicly funded healthcare system. Materials and methods: Men with localized prostate cancer diagnosed and treated between 2006 and 2017 in Ontario, Canada were identified using administrative data. Men received EBRT, brachytherapy (monotherapy or boost) or prostatectomy as initial definitive management. Multivariable logistic regression evaluated patient-, tumour-, and provider-factors on treatment utilization. Results: 61,288 men were included. On multivariable regression, the odds of receiving brachytherapy boost increased 24% per year (odds ratio [OR]:1.24, 95% CI 1.22–1.26, p < 0.01), brachytherapy monotherapy increased 3% per year (OR:1.03, 95% CI:1.02–1.04, p < 0.01), and prostatectomy declined by 6% per year (OR:0.94, 95% CI 0.93–0.95, p < 0.01). Treatment year was not significant on multivariable modelling of EBRT. In a separate multivariable model limited to those who received radiotherapy, if the first radiation oncologist seen performed brachytherapy, the OR of receiving brachytherapy monotherapy over EBRT was 5.66 (95% CI: 5.11–6.26, p < 0.01) and 2.88 (95% CI: 2.60–3.19, p < 0.01) for brachytherapy boost over EBRT alone. Substantial geographic, provider and patient variation in treatment receipt was observed. Conclusion: We found increasing brachytherapy utilization, largely driven by increasing utilization of brachytherapy boost. To our knowledge, this is the first report of increasing brachytherapy use in the era of dose escalated EBRT.

Purpose Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively. Methods and Materials Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D90, Dmean, V150, and V200 to the prostate and DIL were reported. For urethra and rectum, D10 and V80 were reported. Results Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans. Conclusion The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D90 and Dmean. A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy.

Purpose To determine the dosimetric impact of organ and implant motion/deformation in the context of adaptive planning in image-guided gynecologic brachytherapy using a 3-fraction transperineal approach. Methods and materials Twenty-six patients were analyzed. Each patient was treated with three fractions given over a 24-h period using a single insertion. A planning CT scan (±MRI) was acquired before the first fraction. A verification scan was taken within 1 h following the second fraction. A single plan was delivered for Fractions 1 and 2 with an adaptive plan delivered for Fraction 3. Two evaluation frameworks were established. Framework 1 investigated the effects of motion/deformation from both implant and organs. Framework 2 investigated the impact of implant motion/deformation alone. Differences in high-risk clinical target volume (HRCTV) D90%, V100%, and bladder/rectum D2cc were assessed. Results From implant to verification, the HRCTV D90% and V100% decreased significantly (5.0%, p Conclusions Adaptive planning represents an important aspect of perineal-based interstitial image-guided brachytherapy given in three fractions; its absence would result in plan degradation.

Purpose The purposes of this study were to investigate the pattern of relapse in patients with low- or intermediate-risk prostate cancer treated with 19-Gy high-dose-rate brachytherapy (HDR-BT) and to calculate the dose received by the area of recurrence. Methods and Materials Patients included in this analysis were treated under a Phase II randomized trial that evaluated the role of 19-Gy HDR-BT monotherapy in low- and intermediate-risk prostate cancers. Multiparametric prostate MRI and prostate biopsy were performed in patients with suspicious local recurrence. The site of local relapse was compared with the initial site of disease. The dose received by the site of recurrence was investigated through registration of the posttreatment multiparametric prostate MRI with the HDR-BT treatment plan. Results Eight of 87 treated patients were found to have local recurrence after 19-Gy HDR-BT. Seven of the eight recurrences were at the site of initial bulk disease. Seven patients were found to have a more aggressive histology in the posttreatment biopsy. The mean volume of prostate that had received 100% of prescription dose was 97%. Mean dose to area of recurrence was 29.1 Gy, whereas dose to 98% and dose to 90% of the recurrence were 21.6 Gy and 23.2 Gy, respectively. Conclusions The relapse pattern after a single 19-Gy HDR-BT is predominantly associated with the site of initial disease. This lends some rationale to future strategies of further focused dose escalation to initial site of disease, notwithstanding the fact that the calculated biologically equivalent dose using linear–quadratic assumptions is already very high.