Radiation nanosensitizers in cancer therapy-From preclinical discoveries to the outcomes of early clinical trials.
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ABSTRACT:
SUBMITTER: Bilynsky C
PROVIDER: S-EPMC8780058 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Immunotherapies are rapidly entering the clinic as approved treatments for diverse cancer pathologies. Radiation therapy is an integral partner in cancer therapy, commonly as part of complicated multimodality approaches that optimize patient outcomes. Preclinical studies have demonstrated that the success of radiation therapy in tumor control is due in part to immune mechanisms, and that outcomes following radiation therapy can be improved through combination with a range of immunotherapies. However, preclinical models of cancer are very different from patient tumors, and the way these preclinical tumors are treated is often very different from standard of care treatment of patients. This review examines the preclinical and clinical data for the role of the immune system in radiation therapy outcomes, and how to integrate preclinical findings into clinical trials, using ongoing studies as examples.
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Project description:To report the early clinical outcomes of combining intensity-modulated radiation therapy (IMRT) and intensity-modulated proton therapy (IMPT) in comparison with IMRT alone in treating oropharynx cancer (OPC) patients. The medical records of 148 OPC patients who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center, were retrospectively reviewed. During the 5.5 weeks' RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity-score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. With the median follow-up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, the IMRT/IMPT combination group experienced grade ≥ 3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p < 0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p = 0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p = 0.021); and AQA in 47.4% and 21.1% (p = 0.016), respectively. In multivariate logistic regression, grade ≥ 3 mucositis was significantly less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.027 and 0.024, respectively). AQA score ≥ 3 was also less frequent in the IMRT/IMPT combination group, both before and after PSM (p = 0.085 and 0.018, respectively). In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.
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Project description:In the era of precision medicine, radiation medicine is currently focused on the precise delivery of highly conformal radiation treatments. However, the tremendous developments in targeted therapy are yet to fulfill their full promise and arguably have the potential to dramatically enhance the radiation therapeutic ratio. The increased ability to molecularly profile tumors both at diagnosis and at relapse and the co-incident progress in the field of radiogenomics could potentially pave the way for a more personalized approach to radiation treatment in contrast to the current ''one size fits all'' paradigm. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiation therapy, however, most have failed to show benefit, which is arguably due to limited preclinical data. Several key molecular pathways could theoretically enhance therapeutic effect of radiation when rationally targeted either by directly enhancing tumor cell kill or indirectly through the abscopal effect of radiation when combined with novel immunotherapies. The timing of combining molecular targeted therapy with radiation is also important to determine and could greatly affect the outcome depending on which pathway is being inhibited.
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Project description:Patient accrual into cancer clinical trials remains at low levels. This survey elicited attitudes and practices of cancer clinicians towards clinical trials.The 43-item Clinicians Attitudes to Clinical Trials Questionnaire was completed by participants in an intervention study aimed at improving multi-disciplinary involvement in randomised trials. Responses from 13 items were summed to form a research-orientation score.Eighty-seven clinicians (78%) returned questionnaires. Physicians, more often than surgeons, chose to prioritise prolonging a patient's life, recruited ≥50% of patients into trials and attended more research-focussed conferences. Clinicians at specialist centres were more positive about trials with no-treatment arms than those at district general hospitals, more likely to believe clinician, rather than patient reluctance to participate was the greater obstacle to trial accrual, and preferred national and international to local recognition. Clinicians belonging to breast and colorectal teams were less disappointed about not enrolling patients in trials and more accepting of no-treatment arm trials. Research orientation was higher in physicians than surgeons and higher in specialist centres than district hospitals.This study provides greater understanding of clinicians' attitudes to trials. Results have been used to inform training interventions for clinicians targeting the problem of low and selective accrual.
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Project description:The number of people in the United States living with Alzheimer disease (AD) is growing, resulting in significant clinical and economic impact. Substantial research investment has led to drug development in stages of AD before symptomatic dementia, such as preclinical AD. Although there are no treatments approved for preclinical AD, there are currently 6 phase 3 clinical trials for preclinical AD treatments. In this article, we review these clinical trials and highlight considerations for future coverage decisions. In line with the definition of preclinical AD, enrollment in these trials focuses on cognitively unimpaired patients that are at high risk of AD because of family history and then genetic testing or brain imaging. Enrollment in most of these trials also allows for younger patients, including those aged under 65 years. Primary clinical trial endpoints focus on cognition often 4 or more years after treatment. Secondary endpoints include other measures of cognition and function, as well as biomarkers. Review of these trials brings to light a few potential considerations when covering these new medications in the future. First, novel and potentially costly approaches involving genetic testing and/or positron emission tomography imaging may be needed to identify appropriate patients and should be developed efficiently. Second, the long duration of these clinical trials suggest that there may be a need for alternative payment approaches in the United States that encourage early payers to pay for a medication for which the long-term benefits may not be realized until after the beneficiary is no longer with the health plan. Third, the value of AD treatments may differ across populations, creating a potential role for indication-based or population-based contracting. Finally, considering the potentially high budgetary impact and little real-world evidence for a new drug class, payers and manufacturers may want to consider outcomes-based payment approaches and coverage with evidence development to mitigate uncertainty about the value of the treatment demonstrated in well-defined populations in clinical trials versus more heterogeneous real-world settings. DISCLOSURES: This work was funded through a generous gift from the Global CEO Initiative on Alzheimer Disease. Hung reports grants from Agency for Healthcare Research and Quality and Pharmaceutical Research and Manufacturers of America outside the submitted work and past employment at CVS Health and BlueCross BlueShield Association. McClellan is an independent board member on the boards of Johnson & Johnson, Cigna, Alignment Healthcare, and Seer; co-chairs the Accountable Care Learning Collaborative and the Guiding Committee for the Health Care Payment Learning and Action Network; and receives fees for serving as an advisor for Cota and MITRE. Hamilton Lopez and Schneider have nothing to disclose. Part of this work was presented at the 2019 AMCP Nexus Meeting, October 29-November 1, 2019, in National Harbor, MD.
| S-EPMC10391091 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-03-03 | GSE113380 | GEO
Project description:Radiation therapy significantly reduces by at least 70% the relative risk of local and regional recurrences for breast cancer after surgery. A positive influence on overall survival has been clearly demonstrated, especially for patients with a high absolute risk for locoregional recurrences. However, this is partially counterbalanced by late toxicity (dependent upon the radiation dose) especially to cardiac structures. Apart from this toxicity, a clear influence of radiation-therapy-related factors on functional and cosmetic outcome has also been demonstrated. Over time, technical improvements have led to a marked reduction in dose to the neighbouring organs, with a consequent drop in acute and late toxicity. This has also allowed the introduction of shorter radiation schedules, lowering the burden of treatment to the patient and the hospital. Several tools, techniques and guidelines have been developed to optimise the balance between the desired reduction in recurrence rates and side effects. The multidisciplinary team should discuss all available treatment options for every individual breast cancer patient. Individualisation of the selection of the optimal combination of treatments, depending on patient and tumour-related factors, is of utmost importance. Apart from direct tumour-related outcomes, cosmesis and potential side effects have to be taken into account. Counselling should include known risk factors for survival and complications, including comorbidity.
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Project description:BackgroundThe role of radiaotion therapy in resectable gastric cancer patients without distant metastases remains controversial. This retrospective analysis was performed to identify whether resectable gastric cancer patients without distant metastases might benefit from radiation.ResultsThe results of the Kaplan-Meier analysis and log-rank test showed that a total of 3309 patients had a MST of 29.0 months, a 1-year survival rate of 74.7%, and a 3-year survival rate of 45.5%. Among them, the MST of the "RPS" group and the "RAS" group were significantly longer compared with that of the "No Radiation" group (32.7vs 32.9 vs 25.3 months, P < 0.05). The 1-year survival rates were 83.7%, 83.5% and 65.6% for the "RPS", "RAS" and "No radiation" groups, respectively (P < 0.05) and the 3-year survival rates were 52.6%, 63.6% and 44.9%, respectively (P < 0.05). The multivariate Cox proportional hazard regression analysis showed that radiation was an independent prognostic factor.Materials and methodsA total of 5744 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer without distant metastases from 2010 to 2013 were included. Patients were divided into three groups as follows: patients who underwent radiation after surgery ("RAS" group), patients who underwent radiation prior to surgery ("RPS" group) and patients who did not undergo radiation ,only surgery performed ("No radiation'"group).ConclusionsThis retrospective analysis demonstrated that "RPS" or "RAS"alone were independent prognostic factors for survival improvement in selected gastric cancer patients without distant metastases.
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