Outcomes in older adults with metastatic esophageal and gastric carcinoma treated with palliative chemotherapy.

BACKGROUND: The incidence of esophageal and gastric carcinoma (GEC) in elderly patients is increasing, yet patients ≥75 years have historically been underrepresented in clinical trials. We sought to investigate palliative chemotherapy administration patterns and survival outcomes in older adults. MATERIALS AND METHODS: A retrospective analysis identified patients aged 65-74 (young-old) and ≥75 years (older-old) diagnosed with advanced GEC. Patient and tumor characteristics were recorded, with descriptive analysis, time-to-event data analysis using Kaplan-Meier curves and multivariate Cox proportional hazards regression analysis performed. RESULTS: One hundred and ninety-eight "young-old" and 109 'older-old' patients were identified. Patient characteristics were similar between groups except for Charlson Co-morbidity Index (CCI), with lower co-morbidities in the "young-old" compared to "older-old" cohort (P < .001; CCI = 0 in 103 (52%) "young-old" vs 31 (28%) "older-old"). The primary diagnosis in both groups was adenocarcinoma. 119 (60%) "young-old" and 25 (23%) "older-old" patients received chemotherapy (P < .001). Performance status was the primary explanation for chemotherapy non-receipt in both cohorts; age was the explanation in 21 (25%) "older-old" patients and none in the "young-old" patients. PFS for first-line systemic therapy in "young-old" patients was 6.4 (95% CI 5.9-7.6) versus 7.5 months (95% CI 5.1-11.3) in "older-old" patients (P = .69) whilst respective OS was 12.3 (95% CI 10.1-15.5) and 10.4 months (95% CI 9.0-14.6) (P = .0816). Toxicity prompted chemotherapy cessation in 17 (15%) "young-old" and 3 (13%) "older-old" patients (P = .97). Multivariate analysis identified CCI and ECOG performance status as predictive for PFS and OS, respectively. No causative relationship was identified with other variables. CONCLUSION: Our study of real-world older-adults show that significant number of "older-old" patients with GEC do not receive chemotherapy. Among "older-old" adults who do receive systemic therapy, outcomes are comparable; this underscores the importance of geriatric assessment-guided care and suggests that age alone should not be a barrier to receipt of chemotherapy in patients with advanced GEC.

Development and validation of an MR-driven dose-of-the-day procedure for online adaptive radiotherapy in upper gastrointestinal cancer patients.

Objective.To develop and validate a dose-of-the-day (DOTD) treatment plan verification procedure for liver and pancreas cancer patients treated with an magnetic resonance (MR)-Linac system.Approach.DOTD was implemented as an automated process that uses 3D datasets collected during treatment delivery. Particularly, the DOTD pipeline's input included the adapt-to-shape (ATS) plan-i.e. 3D-MR dataset acquired at beginning of online session, anatomical contours, dose distribution-and 3D-MR dataset acquired during beam-on (BON). The DOTD automated analysis included (a) ATS-to-BON image intensity-based deformable image registration (DIR), (b) ATS-to-BON contours mapping via DIR, (c) BON-to-ATS contours copying through rigid registration, (d) determining ATS-to-BON dosimetric differences, and (e) PDF report generation. The DIR process was validated by two expert reviewers. ATS-plans were recomputed on BON datasets to assess dose differences. DOTD analysis was performed retrospectively for 75 treatment fractions (12-liver and 5-pancreas patients).Main results.The accuracy of DOTD process relied on DIR and mapped contours quality. Most DIR-generated contours (99.6%) were clinically acceptable. DICE correlated with depreciation of DIR-based region of interest mapping process. The ATS-BON plan difference was found negligible (<1%). The duodenum and large bowel exhibited highest variations, 24% and 39% from fractional values, for 5-fraction liver and pancreas. For liver 1-fraction, a 62% variation was observed for duodenum.Significance.The DOTD methodology provides an automated approach to quantify 3D dosimetric differences between online plans and their delivery. This analysis offers promise as a valuable tool for plan quality assessment and decision-making in the verification stage of the online workflow.

Gastro-Esophageal Cancer: Can Radiomic Parameters from Baseline 18F-FDG-PET/CT Predict the Development of Distant Metastatic Disease?

We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline 18F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent 18F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, 18F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.

Non-additive effects of electrical stimulation of the dorsolateral prefrontal cortex and the vestibular system on muscle sympathetic nerve activity in humans.

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes.

Current guidelines, challenges and future recommendations for regulation of stem cell research and therapy: a commentary.

In recent years, Malaysia has seen a surge in stem cell therapy for various medical conditions. However, the regulation of stem cell research and therapy in Malaysia faces several challenges such as the emergence of unregulated clinics and a lack of specific legislation. Some urgent measures, including enactment of specific laws, strengthened monitoring, as well as increased public awareness and education, are crucial. Therefore, stem cell therapy regulation requires concerted efforts by the policymakers, regulator bodies and healthcare professionals. This commentary discusses the current guidelines and challenges in Malaysian stem cell therapy regulation and proposes some future recommendations that could pave the way for responsible progress of stem cell research and therapy globally.

Current Applications of PET/MR: Part I: Technical Basics and Preclinical/Clinical Applications.

Positron emission tomography/magnetic resonance (PET/MR) imaging has gone through major hardware improvements in recent years, making it a reliable state-of-the-art hybrid modality in clinical practice. At the same time, image reconstruction, attenuation correction, and motion correction algorithms have significantly evolved to provide high-quality images. Part I of the current review discusses technical basics, pre-clinical applications, and clinical applications of PET/MR in radiation oncology and head and neck imaging. PET/MR offers a broad range of advantages in preclinical and clinical imaging. In the preclinic, small and large animal-dedicated devices were developed, making PET/MR capable of delivering new insight into animal models in diseases and facilitating the development of methods that inform clinical PET/MR. Regarding PET/MR's clinical applications in radiation medicine, PET and MR already play crucial roles in the radiotherapy process. Their combination is particularly significant as it can provide molecular and morphological characteristics that are not achievable with other modalities. In addition, the integration of PET/MR information for therapy planning with linear accelerators is expected to provide potentially unique biomarkers for treatment guidance. Furthermore, in clinical applications in the head and neck region, it has been shown that PET/MR can be an accurate modality in head and neck malignancies for staging and resectability assessment. Also, it can play a crucial role in diagnosing residual or recurrent diseases, reliably distinguishing from oedema and fibrosis. PET/MR can furthermore help with tumour characterization and patient prognostication. Lastly, in head and neck carcinoma of unknown origin, PET/MR, with its diagnostic potential, may obviate multiple imaging sessions in the near future.

Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis.

BACKGROUND: Patient-reported outcomes measures (PROM) are self-reflections of an individual's physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC). In this study, we examined the association between the ESAS score and overall survival (OS) in patients with GEC, the prognostication difference between ESAS and Eastern Cooperative Oncology Group (ECOG), and assessed the correlation between PRFS and the physician-reported ECOG performance status (PS). METHODS: The study was a retrospective cohort study of 211 patients with GEC with localized (stages I-III) and metastatic disease who completed at least one baseline ESAS prior to treatment. Patients were grouped into 3 cohorts based on ESAS score. OS was assessed using the Kaplan-Meier method, and the concordance index (c-index) was calculated for ESAS and physician-reported ECOG. The agreement between PRFS and physician-ECOG was also assessed. RESULTS: In total, 211 patients were included. The median age was 60.8 years; 90% of patients were ECOG PS 0-1; 38% of patients were stages I-III, while 62% were de novo metastatic patients. Median OS in low, moderate, high symptom burden (SB) patients' cohorts was 19.17 m, 16.39 mm, and 12.68 m, respectively (P < .04). The ability to predict death was similar between physician-ECOG and ESAS (c-index 0.56 and 0.5753, respectively) and PRFS and physician-ECOG (c-index of 0.5615 and 0.5545, respectively). The PS agreement between patients and physicians was 50% with a weighted Kappa of 0.27 (95% CI: 0.17-0.38). CONCLUSION: Patient's SB seems to carry a prognostic significance. ESAS and physician-reported ECOG exhibit comparable prognostic values. Physicians and patients can frequently have divergent opinions on PS. ESAS takes a patient-centered approach and should be encouraged in practice among patients with GEC as an additional tool for prognostication.

Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies.

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.

Differential control of sympathetic outflow to muscle and skin during physical and cognitive stressors.

PURPOSE: Sympathetic nerve activity towards muscle (MSNA) and skin (SSNA) regulates various physiological parameters. MSNA primarily functions in blood pressure and flow, while SSNA operates in thermoregulation. Physical and cognitive stressors have been shown to have effects on both types of sympathetic activity, but there are inconsistencies as to what these effects are. This article aims to address the discrepancies in the literature and compare MSNA and SSNA responses. METHODS: Microelectrode recordings were taken from the common peroneal nerve in 29 participants: MSNA (n = 21), SSNA (n = 16) and both MSNA and SSNA (n = 8). Participants were subjected to four different 2-min stressors: two physical (isometric handgrip task, cold pressor test) and two cognitive (mental arithmetic task, Stroop colour-word conflict test), the latter of which saw participants separated into responders and non-responders to the stressors. It was hypothesised that the physical stressors would have a greater effect on MSNA than SSNA, while the cognitive stressors would operate conversely. RESULTS: Peristimulus time histogram (PSTH) analysis showed the mental arithmetic task to significantly increase both MSNA and SSNA; the isometric handgrip task and cold pressor test to increase MSNA, but not SSNA; and Stroop test to have no significant effects on changing MSNA or SSNA from baseline. Additionally, stress responses did not differ between MSNA and SSNA in participants who had both sets of data recorded. CONCLUSIONS: This study has provided evidence to support the literature which claims cognitive stressors increase sympathetic activity, and provides much needed SSNA data in response to stressors.

Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: a real-world analysis of clinical and pathologic characteristics and outcomes.

BACKGROUND: Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients. METHODS: single-center retrospective study of GEC treated from 2007 to 2021. Clinicopathologic characteristics and treatment modalities were reviewed. Survival was calculated from the date of CNS diagnosis until date of death/last follow-up using the Kaplan-Meier method. A multivariable Cox proportional hazards regression model was used. RESULTS: Of 3283 GEC patients, 100 (3.04%) were diagnosed with BrM and 20 with LMC (0.61%). Patients with known human epidermal growth factor receptor 2 (HER2) status (N = 48), 60% were HER2 positive (defined as IHC 3 + or IHC 2+/FISH+). Among LMC patients most were signet-ring subtype (85%), and only 15% (2/13) were HER2 positive. Median survival was 0.7; 3.8; and 7.7 months in BrM patients treated with best supportive care, radiation, and surgery, respectively (p < 0.001). In LMC, median survival was 0.7 month in patients who had best supportive care (7/19) and 2.8 months for those who had whole brain radiation therapy (p = 0.015). Multivariate analysis showed worse outcomes in ECOG ≥ 2 (p = 0.002), number of BrM ≥ 4 (p < 0.001) and number of metastatic sites (p = 0.009). CONCLUSION: HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.

Outcome of Hypofractionated Palliative Radiotherapy Regimens for Patients With Advanced Head and Neck Cancer in Tikur Anbessa Hospital, Ethiopia: A Prospective Cohort Study.

PURPOSE: Head and neck cancers (HNCs) are the third most commonly treated cancer with radiation in Ethiopia. Most patients present with advanced stage and are not candidates for curative treatment. The objective of our study is to assess the outcome of hypofractionated palliative radiotherapy (RT) for advanced HNCs in a resource-limited setting. MATERIALS AND METHODS: Patients with histology-proven advanced HNC candidates for hypofractionated palliative RT were enrolled. Three regimens were allowed: 44.4 Gy in 12 fractions, 30 Gy in 10 fractions, and 20 Gy in five fractions. Response to treatment was assessed at baseline and at 4 weeks after treatment completion. The Kaplan-Meier curve was used to measure the survival. RESULTS: Between January 2022 and January 2023, 52 patients were enrolled and 25 patients were eligible for outcome assessment. Index symptoms include pain, bleeding, dysphagia, respiratory distress, and others in 25, 13, 10, 6, and 17 patients, respectively. Complete relief of the top three symptoms include pain in 52% of patients, hemostasis in 84% of patients, and dysphagia in 30% of patients. Objectively, 64% of patients attained partial response. For 48% of patients, their quality of life (QoL) improved in one parameter of the physical scores. Moreover, 64% of patients showed improvement in three parameters. The global functional score improved in 80% of patients. One patient had grade 3 xerostomia. At the end of the study period, 44% of patients died. The median survival after radiation was 9 months (95% CI, 7.2 to 10.8). CONCLUSION: All palliative hypofractionated regimens used were effective in terms of symptom control, tumor response rate, and QoL, and were well tolerated. This makes it appropriate for our setup because the majority of patients require palliation.

Establishing a robust radioligand therapy program: A practical approach for North American centers.

Radioligand therapy (RLT) is a targeted approach to treating cancer that has been shown to be safe and effective in a variety of disease states, including gastroenteropancreatic neuroendocrine tumors, lymphoma, and most recently, advanced prostate cancer. In the United States, patient access to this therapy is currently variable. Implementation of new RLT programs and expansion of existing programs are needed to broaden patient access to and standardize the delivery of RLT, especially as new therapies are introduced into clinical practice. Drawing from experience in establishing RLT programs in different settings, we have developed practical recommendations for building and implementing a robust RLT program. In this review, we present our recommendations for minimal requirements and optimal requirements, as well as system considerations, and special issues associated with implementing an RLT program in North American centers.

The Intersection of ChatGPT, Clinical Medicine, and Medical Education.

As we progress deeper into the digital age, the robust development and application of advanced artificial intelligence (AI) technology, specifically generative language models like ChatGPT (OpenAI), have potential implications in all sectors including medicine. This viewpoint article aims to present the authors' perspective on the integration of AI models such as ChatGPT in clinical medicine and medical education. The unprecedented capacity of ChatGPT to generate human-like responses, refined through Reinforcement Learning with Human Feedback, could significantly reshape the pedagogical methodologies within medical education. Through a comprehensive review and the authors' personal experiences, this viewpoint article elucidates the pros, cons, and ethical considerations of using ChatGPT within clinical medicine and notably, its implications for medical education. This exploration is crucial in a transformative era where AI could potentially augment human capability in the process of knowledge creation and dissemination, potentially revolutionizing medical education and clinical practice. The importance of maintaining academic integrity and professional standards is highlighted. The relevance of establishing clear guidelines for the responsible and ethical use of AI technologies in clinical medicine and medical education is also emphasized.

Top-down control of vestibular inputs by the dorsolateral prefrontal cortex.

The vestibular apparatus provides spatial information on the position of the head in space and with respect to gravity. Low-frequency sinusoidal galvanic vestibular stimulation (sGVS), a means of selectively changing the firing of vestibular afferents, induces a frequency-dependent perception of sway and, in some individuals, induces nausea. Given that vestibular afferents project to the insular cortex-which forms part of the vestibular cortex-and that the insula receives inputs from the dorsolateral prefrontal cortex (dlPFC), we tested the hypothesis that electrical stimulation of the dlPFC can modulate vestibular inputs. Sinusoidal electrical stimulation (± 2 mA, 0.08 Hz, 100 cycles) was delivered via surface electrodes over (1) the mastoid processes alone (sGVS), (2) electroencephalogram (EEG) site F4 (right dlPFC) and the nasion or (3) to each site concurrently (sGVS + dlPFC) in 23 participants. The same stimulation protocol was used in a separate study to investigate EEG site F3 (left dlPFC) instead of F4 in 13 participants. During sGVS, all participants reported perceptions of sway and 13 participants also reported nausea, neither sensation of which occurred as a result of dlPFC stimulation. Interestingly, when sGVS and dlPFC stimulations were delivered concurrently, vestibular perceptions and sensations of nausea were almost completely abolished. We conclude that the dlPFC provides top-down control of vestibular inputs and further suggests that dlPFC stimulation may provide a novel means of controlling nausea.

Advances and Challenges in Trials of Local Therapy for Patients With Oligometastatic or Oligoprogressive Disease.

The paradigm of oligometastatic disease (OMD), characterized by a limited number of metastases potentially amenable to local therapies, presents unique opportunities and challenges in clinical trial design and implementation. Although local ablative therapies, such as stereotactic body radiation therapy, have shown promise in improving outcomes for patients with OMD, there is a lack of large-scale randomized phase III trials supporting their widespread use. This paper outlines the key challenges in trial design and implementation in the oligometastatic setting, including appropriate patient selection, the definition of the oligometastatic state, trial design considerations, endpoint selection, and logistical considerations related to enrollment and follow-up. We suggest potential strategies to address these challenges, emphasizing the importance of a comprehensive, patient-centric approach, and the integration of multidisciplinary teams in trial design and implementation. The aim is to encourage the design of well-structured clinical trials, ultimately refining best practices and enhancing patient outcomes in the management of OMD.

Combination of clinical, radiomic, and "delta" radiomic features in survival prediction of metastatic gastroesophageal adenocarcinoma.

Objectives: To identify combined clinical, radiomic, and delta-radiomic features in metastatic gastroesophageal adenocarcinomas (GEAs) that may predict survival outcomes. Methods: A total of 166 patients with metastatic GEAs on palliative chemotherapy with baseline and treatment/follow-up (8-12 weeks) contrast-enhanced CT were retrospectively identified. Demographic and clinical data were collected. Three-dimensional whole-lesional radiomic analysis was performed on the treatment/follow-up scans. "Delta" radiomic features were calculated based on the change in radiomic parameters compared to the baseline. The univariable analysis (UVA) Cox proportional hazards model was used to select clinical variables predictive of overall survival (OS) and progression-free survival (PFS) (p-value <0.05). The radiomic and "delta" features were then assessed in a multivariable analysis (MVA) Cox model in combination with clinical features identified on UVA. Features with a p-value <0.01 in the MVA models were selected to assess their pairwise correlation. Only non-highly correlated features (Pearson's correlation coefficient <0.7) were included in the final model. Leave-one-out cross-validation method was used, and the 1-year area under the receiver operating characteristic curve (AUC) was calculated for PFS and OS. Results: Of the 166 patients (median age of 59.8 years), 114 (69%) were male, 139 (84%) were non-Asian, and 147 (89%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The median PFS and OS on treatment were 3.6 months (95% CI 2.86, 4.63) and 9 months (95% CI 7.49, 11.04), respectively. On UVA, the number of chemotherapy cycles and number of lesions at the end of treatment were associated with both PFS and OS (p < 0.001). ECOG status was associated with OS (p = 0.0063), but not PFS (p = 0.054). Of the delta-radiomic features, delta conventional HUmin, delta gray-level zone length matrix (GLZLM) GLNU, and delta GLZLM LGZE were incorporated into the model for PFS, and delta shape compacity was incorporated in the model for OS. Of the treatment/follow-up radiomic features, shape compacity and neighborhood gray-level dependence matrix (NGLDM) contrast were used in both models. The combined 1-year AUC (Kaplan-Meier estimator) was 0.82 and 0.81 for PFS and OS, respectively. Conclusions: A combination of clinical, radiomics, and delta-radiomic features may predict PFS and OS in GEAs with reasonable accuracy.

The Feasibility of Quality Assurance in the TOPGEAR International Phase 3 Clinical Trial of Neoadjuvant Chemoradiation Therapy for Gastric Cancer (an Intergroup Trial of the AGITG/TROG/NHMRC CTC/EORTC/CCTG).

PURPOSE: The TOPGEAR phase 3 trial hypothesized that adding preoperative chemoradiation therapy (CRT) to perioperative chemotherapy will improve survival in patients with gastric cancer. Owing to the complexity of gastric irradiation, a comprehensive radiation therapy quality assurance (RTQA) program was implemented. Our objective is to describe the RTQA methods and outcomes. METHODS AND MATERIALS: RTQA was undertaken in real time before treatment for the first 5 patients randomized to CRT from each center. Once acceptable quality was achieved, RTQA was completed for one-third of subsequent cases. RTQA consisted of evaluating (1) clinical target volume and organ-at-risk contouring and (2) radiation therapy planning parameters. Protocol violations between high- (20+ patients enrolled) and low-volume centers were compared using the Fisher exact test. RESULTS: TOPGEAR enrolled 574 patients, of whom 286 were randomized to receive preoperative CRT and 203 (71%) were included for RTQA. Of these, 67 (33%) and 136 (67%) patients were from high- and low-volume centers, respectively. The initial RTQA pass rate was 72%. In total, 28% of cases required resubmission. In total, 200 of 203 cases (99%) passed RTQA before treatment. Cases from low-volume centers required resubmission more often (44/136 [33%] vs 13/67 [18%]; P = .078). There was no change in the proportion of cases requiring resubmission over time. Most cases requiring resubmission had multiple protocol violations. At least 1 aspect of the clinical target volume had to be adjusted in all cases. Inadequate coverage of the duodenum was most common (53% major violation, 25% minor violation). For the remaining cases, the resubmission process was triggered secondary to poor contour/plan quality. CONCLUSIONS: In a large multicenter trial, RTQA is feasible and effective in achieving high-quality treatment plans. Ongoing education should be performed to ensure consistent quality during the entire study period.

Renal cell carcinoma in kidney transplant recipients: incidence, trends, clinical management & outcomes.

OBJECTIVE: To describe the incidence, characteristics, clinical management, and outcomes of renal cell carcinoma (RCC) among a large, single-centre cohort of kidney transplant recipients (KTR). METHODS: We conducted an observational cohort study looking at KTR transplanted between January 2000-December 2017 (n = 2443) with ≥ 1 year of follow-up. Simultaneous kidney/pancreas transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of RCC. Characteristics and management of RCC were examined using descriptive statistics. Risk factors and clinical outcomes were analyzed using Cox regression models. RESULTS: The incidence of RCC among our cohort was 0.32 per 100 person-years, 2.1% of all KTRs. Almost half (47.1%) of cases occurred within 4 years post-transplant. The majority of cases were T1a (86.3%), clear-cell (45.1%), and in the native kidney (80.4%). KTR diagnosed with RCC had a twofold higher incidence of other malignancies versus KTR without RCC. Overall mortality, but not cancer-specific mortality, at 2- and 5-years post-transplant was threefold higher among KTR with RCC than those without. CONCLUSIONS: Incidence of RCC among our KTR was slightly higher than the general population; majority of cases occur in the native kidneys and are low stage, low grade. Indolent histologic variants were more common than the general population. KTR with RCC had a higher incidence of other malignancies. Overall, but not cancer-specific, mortality was higher among KTRs diagnosed with RCC.

Clinical Outcomes of Patients with Metastatic Breast Cancer Treated with Hypo-Fractionated Liver Radiotherapy.

PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.