Project description:Immunizations have influenced the epidemiology of numerous gastrointestinal cancers. Human papillomavirus (HPV) is a common sexually transmitted infection (STI). Although most infections are transient and asymptomatic, persistent infections with oncogenic strains of HPV can progress to cervical, anal, penile, vaginal, vulvar, and oropharyngeal cancers. The introduction of HPV vaccinations has drastically reduced incidences of HPV-vaccine related infections and HPV related cervical cancers. The vaccine has proven to be safe and effective however, HPV vaccination rates have yet to reach target goals in the U.S. and many countries worldwide have not incorporated the vaccine into national immunization programs. The first successful nationwide vaccination program was employed against hepatitis B virus (HBV) in Taiwan in 1984 and demonstrated a statistically significant decrease in the incidence of hepatocellular carcinoma (HCC) in the 6 to 10 years after implementation of universal HBV vaccinations in infants. Twenty-year follow-up studies have continued to demonstrate statistically significant decreased rates of HBV related HCC among vaccinated populations. Despite the successful decrease in incidence of HBV-related HCC, efforts to create an effective prophylactic vaccination against hepatitis C virus (HCV) to prevent chronic HCV infection and its associated morbidity, including HCV-related HCC, have to date been unsuccessful.
Project description:There are limited patient-reported outcome (PRO) data tracking changes in toxicity in patients actively undergoing radiotherapy. Between 2015-2019, acute toxicity was prospectively measured in 698 patients undergoing a 5-week course of pelvic radiotherapy for gynecologic cancers using a weekly PRO questionnaire. Our questionnaire was able detect a pattern of onset and resolution of acute gastrointestinal (GI) and genitourinary (GU) toxicity in 27 out of 32 questions. Logistic regression analysis showed that increasing GI and GU toxicity at week 2 could predict for severe toxicity at week 5. However, due to a low number of severe events, univariate results could not be productively added to a multivariate model. We observed a >70% response rate for all sections of the questionnaire, except for questions on sexual and vaginal health, which had a 13% average response rate. By demonstrating that PRO data can be used to track acute toxicity during radiotherapy, there is a need to further examine how this tool may be implemented in the clinic to provide complex, adaptive care, such as early side effect management, and modifying radiation delivery in real-time.
Project description:The purpose of this study is to describe type and extent of organ specific late adverse effects in patients undergoing surgery for colorectal cancer with peritoneal metastases and after surgery for colorectal cancer with involvement of the urinary bladder.
Project description:PurposeRadiotherapy (RT) causes an inflammatory reaction of the tissue which leads to fibrosis and reduced functioning of the pelvic organs. Few studies have shown significant relationships between side effects and RT in uterine tumors. Here, the urological, lymphedema, pelvic pain and gastrointestinal (GI) symptoms were studied before and after RT in patients with primary uterine tumors using the EORTC QLQ-EN24, specifically designed for uterine cancer patients.MethodsThis prospective cohort study comprised patients with primary uterine tumors who received pelvic radiotherapy (RT). A total of 43 patients were included from May 2014 to February 2019. Patients completed the questionnaires for global health status and functioning before the start of RT and at 3 and 12 months after RT.ResultsWe found a significant worsening of the urological symptoms 3 months after RT which persisted up to 12 months after RT compared to baseline values prior to start of RT (p = 0.007). An exacerbation of the urinary symptoms was seen in patients with vaginal brachytherapy/boost compared to patients with pelvic RT at 12 months after RT (p = 0.053). The severity of lymphedema symptoms increased from RT start to 12 months after RT (p = 0.019) and the pelvic pain were higher at 3 months after RT compared to before RT (p = 0.004). Also, the level of GI symptoms was significantly higher 12 months after RT compared to the RT start (p < 0.001).ConclusionsThe urologic, lymphedema, pelvic pain and GI symptoms all increase after RT.
Project description:In recent years, there has been rapid adaption of proton beam radiotherapy (RT) for treatment of various malignancies in the gastrointestinal (GI) tract, with increasing number of institutions implementing intensity modulated proton therapy (IMPT). We review the progress and existing literature regarding the technical aspects of RT planning for IMPT, and the existing tools that can help with the management of uncertainties which may impact the daily delivery of proton therapy. We provide an in-depth discussion regarding range uncertainties, dose calculations, image guidance requirements, organ and body cavity filling consideration, implanted devices and hardware, use of fiducials, breathing motion evaluations and both active and passive motion management methods, interplay effect, general IMPT treatment planning considerations including robustness plan evaluation and optimization, and finally plan monitoring and adaptation. These advances have improved confidence in delivery of IMPT for patients with GI malignancies under various scenarios.
Project description:IntroductionPatients receiving radiotherapy are at risk of developing radiotherapy-related insufficiency fractures, which are associated with increased morbidity and pose a significant burden to patients' quality of life and to the health system. Therefore, effective preventive techniques are urgently required. The RadBone randomised controlled trial (RCT) aims to determine the feasibility and acceptability of a musculoskeletal health package (MHP) intervention in women undergoing pelvic radiotherapy for gynaecological malignancies and to preliminary explore clinical effectiveness of the intervention.Methods and analysisThe RadBone RCT will evaluate the addition to standard care of an MHP consisting of a physical assessment of the musculoskeletal health, a 3-month prehabilitation personalised exercise package, as well as an evaluation of the fracture risk and if required the prescription of appropriate bone treatment including calcium, vitamin D and-for high-risk individuals-bisphosphonates. Forty participants will be randomised in each group (MHP or observation) and will be followed for 18 months. The primary outcome of this RCT will be feasibility, including the eligibility, screening and recruitment rate, intervention fidelity and attrition rates; acceptability and health economics. Clinical effectiveness and bone turnover markers will be evaluated as secondary outcomes.Ethics and disseminationThis study has been approved by the Greater Manchester East Research Ethics Committee (Reference: 20/NW/0410, November 2020). The results will be published in peer-reviewed journals, will be presented in national and international conferences and will be communicated to relevant stakeholders. Moreover, a plain English report will be shared with the study participants, patients' organisations and media.Trial registration numberNCT04555317.
Project description:PurposeTo investigate the effect of reduced margin pelvic radiotherapy on gastrointestinal toxicity and outcomes in gynecological cancer.Materials and methodsThis retrospective study analyzed data of 590 patients who underwent hysterectomy and adjuvant pelvic radiotherapy between 2010 and 2020 at two tertiary centers. The pelvic nodal region was delineated based on a reduced margin definition or the Radiation Therapy Oncology Group (RTOG) guidelines. All patients were treated with intensity-modulated radiotherapy with imaging guidance. Gastrointestinal toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) and the Patient-Reported Outcome version (PRO-CTCAE).ResultsOverall, 352 (59.7%) and 238 (40.3%) patients underwent RTOG and reduced margin pelvic radiotherapy, respectively. Median follow-up was 6.4 years (IQR: 3.7-9.6). Reduced margin pelvic radiotherapy significantly lowered the radiation dose to the small bowel. For CTCAE grade ≥ 2 or 3, acute gastrointestinal toxicity was lower in the reduced margin group than in the RTOG group (16.4% vs. 33.5%, p < 0.001; 2.9% vs. 8.5%, p < 0.001). The reduced margin group reported less severe acute gastrointestinal toxicity (PRO-CTCAE score ≥ 3) than the RTOG group (12.5% vs. 28.7%, p < 0.001). Late grade 3 gastrointestinal toxicity was lower in the reduced margin group than in the RTOG group (0.8% vs. 4.8%, p = 0.006). The 5-year pelvic recurrence-free survival and disease-free survival in the RTOG and reduced margin pelvic radiotherapy groups were 97.4% and 97.9% (p = 0.55) and 80.7% and 83.5% (p = 0.18), respectively.ConclusionReduced margin pelvic radiotherapy decreased acute and late gastrointestinal toxicity and achieved favorable outcomes.
Project description:BackgroundA predictive assay for late radiation toxicity would allow more personalized treatment planning, reducing the burden of toxicity for the more sensitive minority, and improving the therapeutic index for the majority. In a previous study in prostate cancer patients, the γ-H2AX foci decay ratio (γ-FDR) was the strongest predictor of late radiation toxicity. The current study aimed to validate this finding in a more varied group of patients with pelvic cancer. Additionally, the potential correlation between the γ-FDR and patient-reported outcomes was investigated.MethodsProstate and gynecological cancer patients with ≥ 24 months of follow-up were included in the current analysis. Toxicity was evaluated by physician (CTCAE version 4) and patient (EORTC questionnaires). γ-FDRs were determined in ex vivo irradiated lymphocytes. Correlation between γ-FDR and toxicity was assessed using both linear and logistic regression analyses. The highest toxicity grade recorded during follow-up was used. The association between global quality of life and γ-FDR was tested by comparing the change in quality of life over time in patients with γ-FDR < or ≥ 3.41, a previously established threshold.ResultsEighty-eight patients were included. Physician-assessed and patient-reported cumulative grade ≥ 2 toxicity was 25% and 29%, respectively; which is much lower than in the previous cohort (i.e., 51% CTCAE grade ≥ 2). Patients with toxicity exhibited less favorable dose-volume parameters. In men, these parameters showed significant improvement compared to the previous cohort. The proportion of patients with a low γ-FDR increased with severity of toxicity, but this trend was not statistically significant. In addition, a γ-FDR < 3.41 was not correlated with the development of moderate to severe toxicity. Post-treatment decline in global quality of life was minimal, and similar for patients with γ-FDR < or ≥ 3.41.ConclusionsIn the present study, the γ-H2AX foci decay ratio could not be validated as a predictor of late radiation toxicity in patients with pelvic cancer. Improved radiotherapy techniques with smaller irradiated bladder and bowel volumes have probably resulted in less toxicities. Future studies on genetic markers of toxicity should be powered on these lower incidences. We further recommend taking persistency, next to severity, into consideration.
Project description:Background and purposeTo determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+).Methods and materialsTwo groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5-25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed.ResultsPMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05).ConclusionWhilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.
Project description:Improvements in the understanding of cancer biology have led to therapeutic advances in the treatment of gastrointestinal cancers. Drugs which target the vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways have led the way in colon cancer. Monoclonal antibodies (mAbs) such as bevacizumab, ramucirumab, cetuximab, and panitumumab, have improved progression free survival and overall survival (OS) for colorectal cancers and were quickly adopted. Human epidermal growth factor receptor 2 (HER2) has demonstrated significant benefit for gastroesophageal cancers and in the setting of HER2 amplification, trastuzumab in combination with chemotherapy has become the standard of care. However, responses have not been as durable nor as robust as once hoped. Mechanisms of resistance for each of these biologic compounds have been hypothesized and are in the process of being better elucidated. This review will approach the innate and acquired mechanisms of resistance of the above compounds. Additionally, we will explore some ongoing clinical trials to capitalize on the mechanisms of resistance in the hopes of retaining the promise of targeting these pathways.