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The Common Terminology Criteria for Adverse Events (CTCAE) is the standard for provider-based rating of adverse events in oncology, but its reliability for symptomatic adverse events is low. Patient-reported outcome (PRO) data might improve the inter-rater reliability of CTCAE assessments. We investigated whether providers' access to PRO data enhances the inter-rater reliability of CTCAE ratings and the detection of symptomatic adverse events. This multinational, open-label, randomised controlled trial was done in 11 hospitals in ten countries. Adults (aged ≥18 years) with any cancer diagnosis receiving chemotherapy, immunotherapy, or radiotherapy of curative or palliative intent were eligible. Patients were randomly assigned (1:1) to the intervention group (in which providers saw patients' PRO data as they were doing CTCAE assessments) or the control group (in which providers did not have access to PRO data) within each centre through a minimisation algorithm and a weighted cutoff; no additional stratification factors were applied. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and 16 additional items from the EORTC Item Library, covering 17 symptomatic adverse events. Two independent providers (oncologists or trained nurses) did CTCAE ratings. The primary endpoint was the inter-rater reliability of CTCAE ratings, expressed as intraclass correlation coefficients (ICCs), for all patients with complete assessments. The trial was registered at ClinicalTrials.gov (NCT04066868) and is now closed. Between Feb 10, 2020, and Dec 6, 2024, a total of 1067 patients were enrolled (538 in the control group and 529 in the intervention group), with full data from 512 patients in the control group and 501 in the intervention group included in the analysis. Median age was 59 years (IQR 46–68); 558 (55·1%) of 1013 were female and 455 (44·9%) were male. Most had good functional status (403 [79%] of 512 had ECOG 0–1 in the control group and 371 [74%] of 501 in the intervention group). The most common cancer types were haematological (control group: 137 [27%] of 512; intervention group: 131 [26%] of 501), breast (control group: 118 [23%]; intervention group: 107 [21%]), and gastrointestinal (control group: 98 [19%]; intervention group: 89 [18%]). Inter-rater reliability was significantly higher in the intervention group for 13 of 17 symptomatic adverse events, with the largest differences for memory impairment (ICC 0·176; p<0·0001), irritability (0·161; p<0·0001), concentration impairment (0·157; p<0·0001), depression (0·126; p=0·0012), and anxiety (0·109; p=0·0018). There was no significant difference for pain, diarrhoea, fatigue, and peripheral sensory neuropathy.. Availability of PRO data to providers for CTCAE rating improves the consistency of provider-based symptomatic adverse event detection in patients with cancer. PRO data supports reliable assessment of treatment-related toxicity, highlighting the value of integrating PRO data into clinical evaluations within cancer trials. EORTC Quality of Life Group.

Abstract Previous studies identified recurrent fusion and duplication events in pediatric low-grade glioma (pLGG). In addition to their role in diagnosis, the presence of these events aid in dictating therapy and predicting patient survival. Clinically, BRAF alterations are most commonly identified using fluorescent in situ hybridization (FISH). However, this method is costly, labor-intensive and does not identify nonBRAF events. Here, we evaluated the NanoString nCounter gene expression system for detecting 32 of the most commonly reported fusion/duplication events in pLGG. The assay was validated on 90 pLGG samples using FISH as the gold standard and showed sensitivity and specificity of 97% and 98%, respectively. We next profiled formalin-fixed paraffin-embedded preserved biopsy specimens from 429 pLGG cases. 171 (40%) of the cases within our cohort tested positive for a fusion or duplication event contained within our panel. These events, in order of prevalence, were KIAA1549-BRAF 16;9 (89/171, 52.0%), KIAA1549-BRAF 15;9 (42/171, 24.6%), KIAA1549-BRAF 16;11 (14/171, 8.2%), FGFR1-TACC1 17;7 (13/171, 7.6%), MYBL1 duplication (5/171, 2.9%), KIAA1549-BRAF 18;10 (4/171, 2.3%), KIAA1549-BRAF 15;11 (2/171, 1.2%), FAM131B-BRAF 2;9 (1/171, 0.6%), and RNF130-BRAF 3;9 (1/171, 0.6%). This work introduces NanoString as a viable clinical replacement for the detection of fusion and duplication events in pLGG.

Abstract Background: To evaluate outcomes of postneoadjuvant chemoradiotherapy (NACTRT) wait and watch strategy (WWS) in distal rectal cancers. Methods: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR respectively) post-NACTRT and wished for nonsurgical treatment option of WWS were included in this study. Patients were observed with 3 monthly MRI, sigmoidoscopy, and digital rectal examination (DRE) for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), nonregrowth recurrence-free survival, and overall survival (OS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). Results: Sixty-one consecutive patients post-NACTRT, achieving cCR [44 (72%)] and nCR [17 (28%)], respectively, were identified. All patients received pelvic radiotherapy to a dose of 45-50Gy conventional fractionation with concurrent Capecitabine. Additional boost dose with either external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with disease, as they refused surgery. The overall OPR, nonregrowth recurrence-free survival, OS was 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastasectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). Conclusion: The wait-and-watch strategy is a safe nonoperative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Background: Radiation therapy (RT) for postoperative residual or progressive non-functioning pituitary adenomas (NFPAs) has excellent long-term local control (LC) although its use has been limited because of the potential late toxicity related to radiation treatments. Newer techniques have led to better precision. Objective: The objective of the study was to review the institutional outcomes of NFPA treated with postoperative RT. Methods and Materials: One hundred forty-seven patients of NFPA were treated at our institution from 2006 to 2018. Ninty-one patients who received RT post-surgery were included in the analysis. RT was delivered to a dose of 45Gy in 25 fractions over 5 weeks using contemporary RT techniques. Patients with residual disease or recurrence after debulking surgery were treated with RT. Magnetic resonance imaging (MRI) for response was available in 70 patients. Effects of age, gender, cavernous sinus invasion (CSI), bony erosion, number of surgeries, MIB index, p53 status, and RT technique on overall survival (OS) were analyzed. Results: The median follow-up of the patients was 86.5 months (IQR: 53-126). The 10y OS was 88.9%. Of the 70 patients who had follow-up MRI, the 10y LC post-adjuvant RT was 97.1%. On univariate analysis, multiple surgeries were associated with better OS compared to patients who underwent single surgery (P = 0.012), and the presence of both bony erosion and CSI was significantly associated with poorer OS (P = 0.028). Conclusion: Radiotherapy after debulking surgery in a select group of patients with NFPA gives excellent tumor control and survival. The presence of extrasellar extensions results in poor clinical outcomes.

IntroductionThere has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.Methods and analysisThis is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.DiscussionThe trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.Ethics and disseminationThe trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.Trial registration numberRegistered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018

Purpose: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. Materials and Methods: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). Results: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). Conclusion: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

PurposeTo report clinical outcomes of salvage re-irradiation (re-RT) in recurrent/progressive ependymoma.MethodsMedical records of patients treated with curative-intent re-RT as multi-modality management for recurrent/progressive ependymoma were analyzed retrospectively. The linear-quadratic model was used to provide estimates of biologically effective dose (BED) of irradiation using an α/β value of 2 for late CNS toxicity for each course of irradiation and summated to derive cumulative BED without correcting for the assumed recovery.ResultsA total of 55 patients (median age 10 years at index diagnosis) treated with curative-intent re-RT between 2010 and 2018 were included. Median time to first recurrence was 29 months with an inter-quartile range (IQR) of 16–64 months. Majority (n = 46, 84%) of patients underwent surgical re-excision of recurrent disease. Median interval from first course of irradiation (RT1) to second course (RT2) was 35 months (IQR = 26–66 months) with a median re-RT dose of 54 Gy in 30 fractions (range 40–60 Gy), resulting in median cumulative equivalent dose in 2 Gy fraction (EQD2) of 106.2 Gy (range 92.4–117.6 Gy). Volume of re-RT was based on location and pattern of relapse, comprising uni-focal (n = 49, 89%), multi-focal (n = 3, 5.5%), or craniospinal irradiation (CSI) in 3 (5.5%) patients respectively. Thirty-six (66%) patients received platinum-based salvage chemotherapy either before or after RT2. At a median follow up of 37 months (range 6–80 months), the Kaplan–Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) for the entire study cohort were 40% and 51% respectively. Gross total resection at recurrence; early salvage re-RT (prior to chemotherapy, if any); and longer (> 2 years) disease-free interval (DFI) were associated with better survival outcomes. Salvage re-RT was generally well tolerated with only 3 (5.5%) patients developing symptomatic radiation necrosis necessitating corticosteroids.ConclusionExtent of re-excision, sequence/timing of re-RT, and DFI impact upon outcomes in curative-intent, multi-modality salvage therapy for recurrent ependymoma.

Purpose: To quantify the relative motion of pelvic and groin lymph nodes (PLN and GLN) and define indicative margins for image-guided radiotherapy based on bony anatomy for the frog-leg position (FLP) and groin immobilization board (GIB). Materials and Methods: Twenty patients with planning computed tomography (CT) scan and on treatment cone beam CTs (median = 8) for groin and pelvic radiotherapy were included in the study. Of these nine were treated with FLP and eleven with GIB. The PLN and GLN regions on the left and right were outlined in each scan. Systematic and random uncertainties were determined along with correlations between the motions of these regions. The clinical target volume to planning target volume (PTV) margins required to take motion into account was calculated for each immobilization. Results: The mean shifts for PLN and GLN were lesser but not statistically lower using GIB over FLP. There was significant concordance in the vertical, longitudinal and lateral motion of the pelvis and right groin (P = 0.015, 0.09 and 0.049, respectively), pelvis and left groin (P = 0.001, 0.048, and 0.006, respectively) and between left and right groin (P = 0.013, 0.01 and 0.07, respectively) for FLP and not GIB. The PTV margins required by Van Herk and Stroom's formula were reduced from 11 mm and 9 mm to 6 mm and 5 mm for pelvis; 12 mm and 11 mm to 7 mm and 6 mm for groin, respectively, using FLP over GIB. Conclusions: GIB brings concordance in shifts between pelvis and groin and between bilateral groins, thereby reducing the required PTV margins.

Objective: Sporadic optic chiasmatic-hypothalamic gliomas (OCHGs), though histologically low-grade tumors, manifest as aggressive neoplasms radiologically, leading to difficulty in diagnosis. Molecular alterations of the BRAF gene are detectable in a majority of sporadic OCHGs. The purpose of our study was to elucidate the characteristic imaging features of sporadic OCHGs and to investigate whether imaging phenotypes could potentially correlate with specific BRAF gene alterations associated with these tumors. Methods: We retrospectively reviewed baseline magnetic resonance (MR) images and medical records of 26 patients with histopathologically proven sporadic OCHGs. MR imaging (MRI) features were systematically evaluated. Statistical analysis was performed to determine whether there was a significant association between imaging findings and BRAF molecular alterations. Results: Twenty-two cases (84.6%) presented with solid-cystic masses, while four (15.4%) presented with purely solid lesions. In all 26 cases, the solid component revealed central necrosis; there was minimal necrosis in 11 cases (42.3%), moderate in 8 (30.7%), and marked in 7 (26.9%). The presence of multiple cysts (>4) and minimal necrosis showed a significant association with BRAFV600E mutation (P < 0.005). Marked necrosis in the solid component significantly correlated with BRAF wild genotype (P < 0.001). The presence of a single peripheral cyst significantly correlated with BRAF fusion (P = 0.04). Conclusion: Sporadic OCHGs have a distinctive appearance on imaging. The solid-cystic composition coupled with varying degrees of central necrosis are clues to the radiological diagnosis of this entity and can facilitate early recognition in clinical practice. Imaging could potentially serve as a non-invasive predictor of the BRAF alteration status, thereby serving as a prognostic marker and guiding personalized management.

Long-course chemoradiation followed by a brachytherapy boost is one of the acceptable treatment options for watch-and-wait (W&W) eligible rectal cancer patients. However, MRI acquisition, planning, and treatment delivery delays can affect patient satisfaction and treatment success. This study used the classical quality improvement methodology to optimise the MRI-based rectal brachytherapy process. A multidisciplinary core team was formed, including a radiation oncologist, radiologist, medical physicist, specialist technologist and nurse. Data on wait times from MRI to brachytherapy treatment were collected for patients receiving rectal brachytherapy between August and November 2022. We aimed to reduce the number of days of the gap between the planning MRI day and the treatment delivery day from a median (D ) and mean (D ) of 14 and 15 days, respectively, to < 1 day each (primary goal) and to increase the number of same-day treatments (D ) from currently 0% to at least 70% (secondary goal) by 31 January 2023. The balancing measure was treatment errors or delays. Quality improvement measures were implemented using the Plan-Do-Study-Act (PDSA) cycles. The post-implementation data at PDSA 1 and 2 from 14 patients each were analysed. The post-change D , D and D improved to 3, 3 days and 35.7% for PDSA 1. This further improved to zero, 0.2 days and 78.9%, respectively, for PDSA 2. A sustained shift in the process was apparent on a control run chart, suggesting sustainability. Further in the sustenance phase, the D , D and D were maintained at 0.3, 0 days and 74%, respectively, for over 42 patients. Using the classical quality improvement methodology, we sustainably reduced the delay between the planning MRI day and the treatment delivery day. These strategies may serve as a model for other institutions implementing MRI-based brachytherapy programmes for the W&W approach in suitable rectal cancer patients.