Intensity-modulated Radiotherapy Research Articles

Prevalence of hypopituitarism in survivors of adult onset, primary, non-pituitary, brain tumours treated with intensity-modulated radiotherapy

Prevalence of hypopituitarism in survivors of adult onset, primary, non-pituitary, brain tumours treated with intensity-modulated radiotherapy

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co.

Evaluating the Effects of Prostate Radiotherapy Intensified with Pelvic Nodal Radiotherapy and Androgen Deprivation Therapy on Myelosuppression: Single-Institution Experience.

Prostate cancer (PCa) management commonly involves the utilization of prostate radiotherapy (PRT), pelvic nodal radiotherapy (PNRT), and androgen deprivation therapy (ADT). However, the potential association of these treatment modalities with bone marrow (BM) suppression remains inadequately reported in the existing literature. This study is designed to comprehensively evaluate the risk of myelosuppression associated with PRT, shedding light on an aspect that has been underrepresented in prior research. We conducted a retrospective analysis of 600 patients with prostate cancer (PCa) treated with prostate radiotherapy (PRT) at a single oncology center between 2007 and 2017. Patients were categorized into four cohorts: PRT alone (n = 149), PRT + ADT, (n = 91), PRT + PNRT (n = 39), and PRT + PNRT + ADT (n = 321). To assess the risk of myelosuppression, we scrutinized specific blood parameters, such as hemoglobin (HGB), white blood cells (WBCs), neutrophils (NEUT), lymphocytes (LYM), and platelets (PLT) at baseline, mid-treatment (mRT), immediately post-RT (pRT), 1 month post-RT (1M-pRT), and 1 year post-RT (1Y-pRT). The inter-cohort statistical significance was evaluated with further stratification based on the utilized RT technique {3D conformal radiotherapy (3D-CRT), and intensity-modulated radiation therapy (IMRT)}. Significant statistical differences at baseline were observed in HGB and LYM values among all cohorts (p < 0.05). Patients in the PRT + PNRT + ADT cohort had significantly lower HGB at baseline and 1M-pRT. In patients undergoing ADT, BMS had a significant impact at 1M-pRT {odds ratio (OR) 9.1; 95% Confidence Interval (CI) 4.8-17.1} and at 1Y-pRT (OR 2.84; CI 1.14-7.08). The use of 3D-CRT was linked to reduced HGB levels in the PRT + PNRT + ADT group at 1 month pRT (p = 0.015). Similarly, PNRT significantly impacted BMS at 1M-pRT (OR 6.7; CI 2.6-17.2). PNRT increased the odds of decreased WBC counts at 1Y-pRT (OR 6.83; CI: 1.02-45.82). Treatment with any RT techniques (3D-CRT or IMRT), particularly in the PRT + PNRT and PRT + PNRT + ADT groups, significantly increased the odds of low LYM counts at all time points except immediately pRT (p < 0.05). Furthermore, NEUT counts were considerably lower at 1M-pRT (p < 0.05) in the PRT + PNRT + ADT group. PLT counts were significantly decreased by PRT + PNRT + ADT at mRT (OR 2.57; 95% CI: 1.42-4.66) but were not significantly impacted by the RT technique. Treatment with PRT, ADT, PNRT, and 3D-CRT is associated with BMS. Despite this statistically significant risk, no patient required additional interventions to manage the outcome. While its clinical impact appears limited, its importance cannot be underestimated in the context of increased integration of novel systemic agents with myelosuppressive properties. Longer follow-up should be considered in future studies.

Efficacy and safety of MR-guided adaptive simultaneous integrated boost radiotherapy to primary lesions and positive lymph nodes in the neoadjuvant treatment of locally advanced rectal cancer: a randomized controlled phase III trial

BackgroundIn locally advanced rectal cancer (LARC), optimizing neoadjuvant strategies, including the addition of concurrent chemotherapy and dose escalation of radiotherapy, is essential to improve tumor regression and subsequent implementation of anal preservation strategies. Currently, dose escalation studies in rectal cancer have focused on the primary lesions. However, a common source of recurrence in LARC is the metastasis of cancer cells to the proximal lymph nodes. In our trial, we implement simultaneous integrated boost (SIB) to both primary lesions and positive lymph nodes in the experimental group based on magnetic resonance-guided adaptive radiotherapy (MRgART), which allows for more precise (and consequently intense) targeting while sparing neighboring healthy tissue. The objective of this study is to evaluate the efficacy and safety of MRgART dose escalation to both primary lesions and positive lymph nodes, in comparison with the conventional radiotherapy of long-course concurrent chemoradiotherapy (LCCRT) group, in the neoadjuvant treatment of LARC.MethodsThis is a multi-center, randomized, controlled phase III trial (NCT06246344). 128 patients with LARC (cT3-4/N+) will be enrolled. During LCCRT, patients will be randomized to receive either MRgART with SIB (60–65 Gy in 25–28 fractions to primary lesions and positive lymph nodes; 50–50.4 Gy in 25–28 fractions to the pelvis) or intensity-modulated radiotherapy (50–50.4 Gy in 25–28 fractions). Both groups will receive concurrent chemotherapy with capecitabine and consolidation chemotherapy of either two cycles of CAPEOX or three cycles of FOLFOX between radiotherapy and surgery. The primary endpoints are pathological complete response (pCR) rate and surgical difficulty, while the secondary endpoints are clinical complete response (cCR) rate, 3-year and 5-year disease-free survival (DFS) and overall survival (OS) rates, acute and late toxicity and quality of life.DiscussionSince dose escalation of both primary lesions and positive nodes in LARC is rare, we propose conducting a phase III trial to evaluate the efficacy and safety of SIB for both primary lesions and positive nodes in LARC based on MRgART.Trial registrationThe study was registered at ClinicalTrials.gov with the Identifier: NCT06246344 (Registered 7th Feb 2024).

Executive Summary of the American Radium Society Appropriate Use Criteria for NSCLC in a Central/Ultracentral Location: Systematic Review and Guidelines

IntroductionDefinitive radiation therapy is considered standard therapy for medically inoperable early-stage NSCLC. Nevertheless, for patients with tumors located near structures such as the proximal tracheobronchial tree, esophagus, heart, spinal cord, and brachial plexus, the optimal management regimen is controversial. The objective was to develop expert multidisciplinary consensus guidelines on managing medically inoperable NSCLC located in a central or ultracentral location relative to critical organs at risk. MethodsCase variants regarding centrally and ultracentrally located lung tumors were developed by the 15-member multidisciplinary American Radium Society (ARS) Thoracic Appropriate Use Criteria (AUC) expert panel. A comprehensive review of the English medical literature was performed from January 1 1946 to December 31 2023 to inform consensus guidelines. Modified Delphi methods were used by the panel to evaluate the variants and procedures, with at least three rating points from median defining agreement/consensus. The guideline was then approved by the ARS Executive Committee and released for public comment per established ARS procedures. ResultsThe Thoracic ARS AUC Panel identified 90 relevant references and obtained consensus in all variants. Radiotherapy alone was considered appropriate, with additional immunotherapy to be considered primarily in the clinical trial setting. Hypofractionated radiotherapy in eight to 18 fractions was considered appropriate for ultracentral lesions near the proximal tracheobronchial tree, upper trachea, and esophagus. For other ultracentral lesions near the heart, great vessels, brachial plexus, and spine, or for non-ultracentral but still central lesions, five-fraction stereotactic body radiation therapy was also considered an appropriate option. Intensity-modulated radiotherapy was considered appropriate and three-dimensional–conformal radiotherapy inappropriate for all variants. Other treatment planning techniques to decrease the risk of overdosing critical organs at risk were also considered. ConclusionsThe ARS Thoracic AUC panel has developed multidisciplinary consensus guidelines for various presentations of stage I NSCLC in a central or ultracentral location.

KEAP1-mutant atypical meningioma: illustrative case.

While genetic testing of tumors is commonly used to inform the selection of systemic therapies, there is limited evidence for the application of radiotherapy for brain cancer. Recent studies have shown that Kelch-like ECH-associated protein 1 (KEAP1), a key regulator of cellular responses to oxidative and electrophilic stress, is associated with radioresistance in multiple cancer types. Several studies have reported the clinical significance of KEAP1 mutation in brain metastasis; however, the effect of KEAP1 mutations on radioresponse in meningioma has never been reported. The authors present the case of a 40-year-old female with a KEAP1 mutation-positive atypical meningioma that was initially treated with resection followed by intensity-modulated radiation therapy (IMRT). Recurrence was observed at 15 months, requiring reoperation and adjuvant stereotactic radiosurgery (SRS). An excellent treatment response was observed at 7 months post-SRS with an improvement in reported symptoms, although bevacizumab was required for the resolution of radiation necrosis observed 2 months post-SRS. To the authors' knowledge, this is the first report of KEAP1-mutant meningioma, including its clinical course after comprehensive management. Notably, treatment included multimodal radiotherapy with IMRT followed by SRS. SRS led to an excellent treatment response at the 7-month follow-up. However, radiation necrosis developed after both radiotherapy treatments, suggesting that radiological modification can be beneficial in patients with KEAP1 mutations. https://thejns.org/doi/10.3171/CASE24387.

Evaluation of Inverse Planned and Forward Planned Intensity Modulated Radiotherapy Techniques in Breast Cancer

Introduction: The objective of this study is to compare the dosimetric parameters of radiation to the whole breast between the two intensity-modulated radiotherapy (IP IMRT) techniques, i.e. Inverse planned IMRT (IP IMRT) and Forward Planned IMRT (FP IMRT) with regard to target coverage (PTV) and irradiation of organs at risk (OAR). Material and Methods: Plain and Contrast enhanced computed tomography (CECT) datasets were created for 41 patients treated with whole breast radiation therapy. CT simulation and treatment is performed using deep inspiratory breath hold technique (DIBH). Radiotherapy treatment Planning is done using Eclipse Treatment Planning System (version 13.7) with a prescription dose of 40 Gy in 15#. The developed treatment plans were subjected to objective comparison of PTV and OARs using dose volume histograms (DVH). Results: IP IMRT plans provided better coverage (99.5% vs 97.6%), comparable though higher maximum dose (Dmax 45.0 VS 44.1 Gy), higher hot spot (PTV105% 49.2 vs 33), lower volumes receiving 20, 25, 30 Gy (V20, V25, V30) for heart, more homogeneous (homogeneity index 0.10 vs. 0.14) and conformal dose distribution (conformity Index 1.0 vs 0.98) compared to FP IMRT. Regarding OAR dosimetry it is observed that FP IMRT showed reduced mean dose to Coronary artery (LADCA), Contralateral Lung (CL), Contralateral breast (CB) along with reduction in low dose region (V5) to all OARs under study. It was also observed that Monitor units used and planning time were lower for FP IMRT. Conclusion: On weighing different dosimetric factors, both the techniques have displayed their own advantages and disadvantages. Choosing a planning technique needs to be customized taking into consideration various factors such as breast topography, size and volumes of breast, availability of expertise planning skills and resources.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy Versus Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Men with localized prostate cancer may receive either photon-based intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT). The PARTIQoL trial (NCT01617161) demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT with PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. Patients with low- or intermediate-risk prostate cancer were randomly assigned to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the Expanded Prostate Index Composite score 24 months after radiation therapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. Between July 2012 and November 2021, 450 patients were successfully accrued. Patients were randomly assigned to either PBT (N = 226) or to IMRT (N = 224); 13 were ineligible or withdrew before treatment. The median age of 437 analyzed patients was 68 years (range, 46-89 years). A total of 41% of patients had low-risk and 59% had intermediate-risk disease. In total, 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. 48% of patients used a rectal spacer. For patients receiving PBT, pencil beam scanning was used in 48%. PBT and IMRT arms were balanced for baseline variables. Despite significant challenges, the PARTIQoL trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase 3 randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer follow-up and secondary endpoints.

Dose prediction for cervical cancer in radiotherapy based on the beam channel generative adversarial network

BackgroundExisting deep learning methods, such as generative adversarial network (GAN) technology, face challenges when dealing with mixed datasets, which involve a combination of Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT). This issue significantly complicates the application of dose prediction in the field of radiotherapy. In this study, we propose a novel approach called beam channel GAN (Bc-GAN) to address the task of radiation dose prediction for mixed datasets. Bc-GAN introduces a dose prediction calculation method that requires less precision. By defining an approximate range for dose prediction, Bc-GAN limits the physical range of GAN prediction, resulting in more reasonable dose distribution predictions. MethodsWe adopt a beam angle weighting method to determine the beam angle in the dose calculation. The dose of the beam with the highest weight is calculated using medical images and is then inputted into the artificial intelligence dose prediction model as the input channel. Additionally, we collect data from a total of 346 patients with Cervical Cancer (CC) for dataset. After cleaning the data, we exclude 51 cases with incomplete organ delineation, leaving us with 295 cases (IMRT: VMAT = 137:158) randomly divided into three sets: the training set, the validation set, and the test set, with proportions of 205:60:30, respectively. The assessment of model predictions was conducted via an analysis of dose distributions on the tomographic plane, dose volume histogram (DVH), and dosimetric parameters within the target zones and organs at risk (OAR). ResultsAfter DVH analysis, minimal discrepancy was found between predicted and actual dose distributions in PTV and OAR. The predicted distribution aligned with clinical standards. Dosimetric parameters for PTV were generally lower in the predicted model, except for homogeneity index (HI) (0.238 ± 0.024, P = 0.017) and Dmax (53.599 ± 0.710 Gy, P = 1.8e-05). The prediction model varied in estimating doses for six organs. Specifically, small intestine showed higher V20 (67.92 ± 51.64 %, P = 0.019) and V30 (57.171 ± 1.213 %, P = 0.024) than manual planning. A similar trend was seen in colon's V30 (37.13 ± 61.14 %, P = 0.016). However, predicted bladder V30 (87.51 ± 41.44 %, P = 2.03e-16) was lower, indicating significant dosimetric differences. ConclusionOverall, this study presents an innovative prediction method for CC in radiotherapy using the Bc-GAN model, addressing the challenges posed by different radiotherapy techniques. The proposed approach allows IMRT and VMAT in radiotherapy to be used as training sets, enabling the potential for large-scale engineering and commercialization applications of artificial intelligence (AI). The Bc-GAN-based prediction method for CC in radiotherapy not only reduces the amount of data needed for the training set but also expedites the model generation process. This approach can be applied to guide the development of clinical radiation therapy plans. Furthermore, future studies should consider extending the dose prediction method to encompass other types of tumors.

Weekly Image Guidance in Patients With Cervical Cancer Treated With Intensity-Modulated Radiation Therapy: Results of a Large Cohort Study.

Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients. The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities. IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

The Dose Difference of Dominant Intraprostatic Lesions (DILs) Defined by Magnetic Resonance-Guided and arc-based Intensity Modulated Radiation Therapy (IMRT), and the Association between Dose Difference and Recurrent Prostate Cancer.

There is growing evidence that local recurrence after radiotherapy often occurs within the dominant intraprostatic lesions (DILs) in prostate cancer. This study aimed to evaluate the dose difference between DILs defined by Magnetic Resonance-guided and arc-based Intensity Modulated Radiation Therapy (IMRT) and to assess the association between the dose difference and biochemical recurrence-free survival. Between 2015 and 2019, 48 prostate cancer patients with DILs visible from multiparametric Magnetic Resonance Imaging (mpMRI) underwent arc-based IMRT with 70 Gy (2.5 Gy each fraction) to the prostate gland. Pretreatment mpMRI DILs contoured the prostate gland retrospectively. Biochemical recurrence was 8.3%. There was a significant difference between the median dose of DILs from MRI-guided imaging, 69.22 Gy, and the median dose of the whole prostate from arc-based IMRT which was 67.09 Gy (p < 0.001*). The Kaplan-Meier survival curve compared by log-rank test showed an escalation dose of at least 2 Gy tends to improve biochemical recurrence-free survival. However, this tendency did not reach statistical significance (p = 0.2). The dose distribution within DILs defined by mpMRI is significantly higher than the whole prostate dose from arc-based IMRT. Escalation doses in DILs tend to improve biochemical recurrence-free survival, further validation in larger patient cohorts with extended follow-up is warranted.

Prognostic implications of HIF-1α expression in anal squamous cell carcinoma treated with intensity-modulated radiotherapy (IMRT)

BackgroundHypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor activated under hypoxic conditions, known to regulate genes associated with tumor survival, progression, and response to therapy. This study aimed to evaluate the prognostic significance of HIF-1α expression in patients with anal squamous cell carcinoma (ASCC) undergoing chemoradiation therapy. MethodsWe conducted a retrospective analysis of 28 ASCC patients treated with intensity-modulated radiotherapy (IMRT) at our center from 2009 to 2022. HIF-1α expression was assessed via immunohistochemistry on formalin-fixed paraffin-embedded tissue specimens. Quantitative analysis of HIF-1α expression was performed, and its relationship with clinical outcomes, including disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and overall survival (OS), was examined using Cox regression models. Furthermore, ASCC tissue specimens from 17 patients were analyzed for potential PIK3CA mutations using Sanger sequencing. ResultsHigh HIF-1α expression was significantly associated with poorer DFS (p = 0.005), LRRFS (p = 0.012), and OS (p = 0.009). HIF1α expression was marginally significantly higher in males compared to females (p = 0.056) while there was no significant difference found based on tumor stage or p16 status. However, a positive correlation was identified between BMI and HIF-1α levels (Pearson correlation r = 0.5, p = 0.0084), suggesting a link between metabolic status and tumor hypoxia. Only one patient exhibited a PIK3CA mutation, preventing a reliable assessment of its correlation with HIF-1α expression. ConclusionOur findings underscore the importance of HIF-1α as a potential biomarker for predicting survival outcomes in ASCC patients treated with chemoradiation. The association between higher BMI and increased HIF-1α expression may provide insights into the interplay between metabolic health and tumor biology in ASCC. Further studies with larger cohorts are needed to validate these findings and explore targeted therapies focusing on HIF-1α modulation.

Long-term results of induction chemotherapy for non-operable esophageal squamous cell carcinoma followed by concurrent chemoradiotherapy: a single-centre experience.

This study aimed to investigate the long-term clinical outcomes and toxicities of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) vs. CCRT alone in patients with non-operable esophageal squamous cell carcinoma (ESCC). Between 2008 and 2022, 271 ESCC patients who received definitive CCRT based on intensity modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) were enrolled. Through a propensity score-matched (PSM) method, 71 patients receiving IC and CCRT were matched 1:1 to patients who received CCRT alone. The Kaplan-Meier method and Cox proportional hazards model were applied to analyze survival and prognosis. The IC + CCRT group had no improvement in 5-year overall survival (OS) rate, recurrence-free survival (RFS) rate, and distant metastasis-free survival (DMFS) rate (all p > 0.05) compared with the CCRT group. The 5-year OS rate (65.6% vs. 17.6% vs. 29.3%, p < 0.001), RFS rate (65.6% vs. 17.6% vs. 26.9%, p < 0.001), and DMFS rate (62.5% vs. 10.3% vs. 27.2%, p < 0.001) of the IC good responders were significantly higher than that of the IC poor responders and CCRT group. Multivariate analysis revealed that total radiotherapy time (≥ 49 days) and stage III/IV were independent predictive factors of OS, RFS, and DMFS. No significant differences were observed in the rates of grade 3-4 toxicities between both groups. Our results showed the addition of IC to CCRT was not superior to CCRT in unselected ESCC patients, while IC responders could benefit from this regime without an increase in toxicities.

Safety of Pelvic and Abdominal Radiation Therapy for Patients With Inflammatory Bowel Disease: A Dosimetric Analysis of Acute Bowel Toxicity

ObjectivesInflammatory bowel disease (IBD) has been considered a relative contraindication to radiation therapy (RT) due to the potential greater risk of RT-induced toxicities. This study aims to assess acute toxicity outcomes in patients with IBD treated with abdominal/pelvic RT. MethodsAfter institutional review board approval, patients with IBD who received RT to the abdomen/pelvis were identified from an institutional research repository and their electronic medical records were reviewed. The IBD cohort was matched 1:1 with controls according to all of the following: radiotherapy, gender, disease site, age, and year of RT. Acute toxicity was defined as toxicity occurring within 3 months of RT. Primary outcomes were assessed via univariable logistic regression models and predicted probability of acute toxicity and acute gastrointestinal (GI) toxicity were plotted for the most significant covariates. IBD and control control cohorts were compared on demographic and toxicity variables using chi-square/Fisher's exact tests and Kruskal-Wallis tests where appropriate. ResultsWe identified 62 patients with median age of 64 years (interquartile range [IQR] 54-70) who received RT from 2006-2022. Patients were treated with intensity-modulated RT (38; 61.3%), 3-dimensional conformal RT (12; 19.4%), and stereotactic body RT/brachytherapy (12; 19.4%). After RT, 28 (45.2%) and 23 (37.1%) patients experienced grade ≥2 acute (any) and acute GI toxicity, respectively. Higher overall RT dose and RT dose to small bowel were found to be signicantly associated with increased risk of grade ≥2 acute toxicities (OR=1.041 per unit Gy, 95% CI 1.005-1.084, p=0.034 and OR=1.046, 95% CI 1.018-1.082, p=0.003, respectively). Between IBD and control cohorts, there were no significant differences in grade ≥2 acute (any) and acute GI toxicities (p=0.710 and p=0.704, respectively). ConclusionIn patients with IBD treated with abdominal/pelvic RT for malignancy, RT was effective and well-tolerated. RT treatment planning should carefully consider the location(s) of IBD inflammation and dose to bowel structures, in particular, dose to small bowel.

Prognostic Study of Inflammatory Markers in Nasopharyngeal Carcinoma Patients Receiving Intensity-Modulated Radiotherapy.

Inflammatory markers in the blood have been linked to tumor prognosis, but their specific prognostic significance in nasopharyngeal carcinoma (NPC) patients undergoing intensity-modulated radiotherapy (IMRT) is not well established. This study aims to evaluate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in this patient population. A total of 406 non-metastatic NPC patients were included in the study. NLR, PLR, and LMR were stratified according to their average values. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis was performed to evaluate the associations of NLR, PLR, and LMR with PFS and OS. Patients with NLR > 2.78had worse PFS (P = 0.008) and OS (P < 0.001); PLR > 162.48 was related to lower PFS (P = 0.018) but not OS (P = 0.29); LMR > 5.05 showed no significant difference in PFS and OS compared to LMR ≤ 5.05 (P values were 0.13 and 0.94, respectively). Multivariate analysis indicated that NLR was an independent prognostic factor for PFS (HR, 1.674; 95% CI, 1.006-2.784; P = 0.047) and OS (HR, 4.143; 95% CI, 2.111-8.129; P = 0.000), while PLR and LMR did not demonstrate significant associations with PFS and OS. This study identifies NLR as a novel and independent prognostic indicator for NPC patients receiving IMRT, offering valuable insights that could inform future clinical decision-making. In contrast, PLR and LMR did not demonstrate significant prognostic value in this context.

Real-World Implementation of Simulation-Free Radiation Therapy (SFRT-1000): A Propensity Score-Matched Analysis of 1000 Consecutive Palliative Courses Delivered in Routine Care.

The feasibility of simulation-free radiation therapy (SFRT) has been demonstrated but information regarding its routine care impact and scalability is lacking. In this single-institution, retrospective cohort study, all patients receiving palliative radiation therapy at an Australian tertiary cancer center were eligible for consideration of SFRT unless mask immobilization, a stereotactic technique, or a definitive dose was indicated. Coprimary endpoints were SFRT utilization, impact on consultation-to-RT time, and on-couch treatment duration. Timing metrics were compared with a contemporary local cohort that received simulation-based palliative radiation therapy using unadjusted Wilcoxon rank-sum tests and a propensity score-matched regression. Electronic patient-reported outcomes captured 2-week toxicity and pain response. Between April 2018 and February 2024, 2849 palliative radiation courses were delivered, of which 1904 were eligible. Of the 1904 courses, 1000 (52.5% SFRT utilization) received SFRT, including 668 using intensity-modulated radiation therapy/volumetric-modulated arc therapy. A total of 788 individual patients received SFRT and the median age was 71 years (IQR, 61-80) with 59% being male and 42% being Eastern Collaborative Oncology Group 2-4. SFRT utilization increased from 41% to 54% between years 2018-2019 and 2022-2024. SFRT reduced median consultation-to-RT time from 7.0 to 5.1 days (P < .0001) corresponding to an adjusted average treatment effect in the treated of -2.1 days (95% CI, -2.8 to -1.3). SFRT increased median on-couch treatment duration from 17.8 to 20.5 minutes (P < .0001; adjusted average treatment effect in the treated 2.6 minutes, 95% CI, 1.3-3.9). Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade 3 acute toxicity was 9% and at 4 weeks after RT, patients with moderate/severe pain at baseline (≥5/10) had a mean pain reduction of 3.5 points (7.1-3.6; P < .0001). Using widely available technologies, the SFRT-1000 cohort demonstrates routine care scalability with patient-centered and workflow benefits. SFRT is an attractive new paradigm implementable in most settings following adaptation to local requirements. Thus, SFRT opens new avenues to potentially improve access to palliative RT, which remains a global area of need.

Late effects following HSCT for childhood ALL: A national single-center study using three different modalities of delivery of total body irradiation.

Total body irradiation (TBI) is a pivotal part of conditioning prior to hematopoietic stem cell transplantation (HSCT) for childhood acute lymphoblastic leukemia (ALL), yet evidence is sparse regarding the effect of TBI delivery techniques on acute and late toxicities. In a national cohort of pediatric HSCT-recipients, we compared three TBI schedules; 12Gray (Gy) delivered as (i) 4Gy daily fractions from 2008 to 2011 (n=12); (ii) 2Gy fractions twice daily with two-dimensional (2D) planning technology from 2012 to 2015 (n=16); and (iii) 2Gy twice daily with three-dimensional (3D) planning intensity-modulated radiotherapy (IMRT) from 2016 to 2020 (n=14). The 5-year event-free survival was 75.0%, 81.3%, and 81.3% in Cohorts 1, 2, and 3, respectively. Acute toxicity assessed as maximum ferritin and C-reactive protein during the first 3months post HSCT did not differ between cohorts, nor did the time to first hospital discharge (median 28, 32, and 31days, p=.25). The incidences of acute graft-versus-host disease (GvHD) (66%, 56%, 71%) and chronic GvHD (25%, 31%, 14%) were comparable. Pulmonary function assessed by spirometry did not differ significantly. The 5-year cataract-free survival was 33.3%, 79%, and 100% in Cohorts 1, 2, and 3, respectively. We found a nonsignificant tendency toward more endocrinopathies in Cohort 1 compared to Cohorts 2 and 3. The change of modality did not result in more relapses. More fractionation led to improvement with a lower incidence of cataract and a tendency toward fewer endocrinopathies. The effect of 3D-planning-IMRT technology requires further evaluation in larger studies.

Impact of Reference Selection on Gamma Analysis in Patient-Specific Quality Assurance for Monte Carlo-Based Treatment Planning Systems.

Our study aimed to establish a standardized methodology for selecting "reference" and "evaluated" distributions in gamma analysis for Monte Carlo (MC) based intensity modulated treatment plans. Evaluation of importance of reference selection in MC based and non MC based treatment planning systems were analysed using a study classification. Three categories were utilized to analyzed gamma passing rates across using different treatment planning systems (TPS) and detectors for thirty five patients. Category 1 utilized MC-based Monaco TPS plans and a 2 dimensional(2D) I'mRTMatriXX detector. Category 2 employed non-MC-based Eclipse TPS plans, assessed with a 2D I'mRTMatriXX detector. In Category 3, MC-based Monaco TPS plans were validated using a Dolphin detector. All plans were subjected to analysis using gamma criteria, which considered a dose difference of 3% and a distance to agreement of 3mm. Additionally, another set of gamma criteria was employed, with a dose difference of 3% and a distance to agreement of 2mm. An introduced Asymmetric factors in both 2D and 3D analysis will quantify the asymmetric nature of gamma based on the choice of "reference" distribution. For 2D Gamma analysis, MC-based Monaco TPS and I'mRTMatriXX showed a consistent positive Zk2D trend for all patients, with significant p-values below 0.01 for both gamma passing criteria. In contrast, non-MC based Eclipse TPS exhibited varied Zk2D results, with non-significant p-values. In 3D Gamma analysis, all patients exhibited positive Zk3D values with significant p-values below 0.01 when "references" were swapped. The Pearson correlation between asymmetricity and isodose volumes was notably high at 0.99 for both gamma criteria. Our study highlights the imperative of using MC-based TPS as the definitive "reference" in gamma analysis for patient specific quality assurance of intensity modulated radiation therapy, emphasizing that variations can mislead results, especially given gamma analysis's sensitivity to MC calculation noise.

RRx-001 Affects Multiple Toxicities in Patients Receiving Concomitant Chemoradiation for Head and Neck Cancers: Observations of the PREVLAR Phase II Trial

PURPOSE Phase IIa trial results suggested that RRx-001, an nucleotide-binding domain-like receptor protein 3 inhibitor and nuclear factor erythroid 2–related factor 2 activator, attenuated severe oral mucositis (SOM) in patients treated with concomitant chemoradiation (CRT) for oral cancer (OC) and oropharyngeal cancer (OPC). Given the shared pathobiology of CRT injury among other exposed tissues, we initiated a secondary analysis of reported adverse events (AEs) to assess RRx-001's potential benefit on non-SOM regimen-related toxicities. METHODS PREVLAR was an open-label randomized trial that has been completed and published. Patients were treated with CRT for locally advanced OC or OPC. Arms 1-3 received doses of RRx-001 twice a week beginning 2 weeks before the start of CRT. Arm 2 (n = 11) received additional RRx-001 once during weeks 2 and 5. Arm 3 (n = 13) received RRx-001 once a week for the first 6 weeks of CRT. Arm 4 (n = 10) received CRT only. Patients received standard intensity modulated radiation therapy (daily fractions of 2-2.2 Gy/minimum cumulative dose of 55 Gy) plus cisplatin. Comprehensive toxicity assessment was based on reported AEs graded using Common Terminology Criteria for Adverse Events v5.0 and categorized with the Medical Dictionary for Regulatory Activities. A two-sided Fisher's exact test was performed to compare AE incidences between RRx-001 arms and standard of care in a secondary analysis of the data. Overall false-positive rate in Fisher's exact test was controlled via Hochberg's adjustment method. RESULTS Compared with the control cohort, patients receiving RRx-001 demonstrated fewer AEs attributable to their CRT regimen. Statistically significant differences in AE incidences favoring RRx-001 were dependent on the RRx-001 dosing regimen. CONCLUSION This secondary analysis suggests that RRx-001 infusion may reduce multiple, biologically related AEs associated with a standard CRT regimen. More broadly, it suggests that it is possible that agents that effectively target central pathobiology targets may mitigate more than one toxicity.

24 Hypofractionated Intensity Modulated Radiation Therapy and Weekly Gemcitabine is an Effective and Safe Curative Treatment in Muscle Invasive Bladder Cancer: Long-Term Results

24 Hypofractionated Intensity Modulated Radiation Therapy and Weekly Gemcitabine is an Effective and Safe Curative Treatment in Muscle Invasive Bladder Cancer: Long-Term Results