FANCD2 Mutation in a Patient With Early Rectal Cancer Receiving Definitive Chemoradiation.
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ABSTRACT:
SUBMITTER: McDonald J
PROVIDER: S-EPMC8260782 | biostudies-literature | 2021 Sep-Oct
REPOSITORIES: biostudies-literature
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<i>FANCD2</i> Mutation in a Patient With Early Rectal Cancer Receiving Definitive Chemoradiation.
McDonald Jordan J Chuang Chine-Yu CY Hicks J Kevin JK Berry Darcy K DK Imanirad Iman I Rishi Anupam A Frakes Jessica M JM Hoffe Sarah E SE Felder Seth S
Advances in radiation oncology 20210521 5
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Project description:To analyze a single-center experience with locally advanced pancreatic cancer (LAPC) patients treated with chemoradiation (CRT) and to evaluate predictive variables of outcome.LAPC patients at our institution between 1997 and 2009 were identified (n = 109). Progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Cox proportional hazard models were used to evaluate predictive factors for survival. Patterns of failure were characterized, and associations between local progression and distant metastasis were explored.Median OS was 12.1 months (2.5-34.7 months) and median PFS was 6.7 months (1.1-34.7 months). Poor prognostic factors for OS include Karnofsky performance status ?80 (P = .0062), treatment interruption (P = .0474), and locally progressive disease at time of first post-therapy imaging (P = .0078). Karnofsky performance status ?80 (P = .0128), pretreatment CA19-9 >1000 U/mL (P = .0224), and treatment interruption (P = .0009) were poor prognostic factors for PFS. Both local progression (36%) and distant failure (62%) were common. Local progression was associated with a higher incidence of metastasis (P < .0001) and decreased time to metastasis (P < .0001).LAPC patients who suffer local progression following definitive CRT may experience inferior OS and increased risk of metastasis, warranting efforts to improve control of local disease. However, patients with poor pretreatment performance status, elevated CA19-9 levels, and treatment interruptions may experience poor outcomes despite aggressive management with CRT, and may optimally be treated with induction chemotherapy or supportive care. Novel therapies aimed at controlling both local and systemic progression are needed for patients with LAPC.
| S-EPMC3622285 | biostudies-other
Project description:Background and purposeTo evaluate longitudinal patient-reported distress in cervical cancer patients treated with definitive chemoradiation (CRT).Materials and methodsBetween 2011 and 2016, consenting cervical cancer patients treated with definitive CRT who completed ≥ 2 revised Edmonton Symptom Assessment System (ESAS-r) questionnaires at clinical visits, including baseline, were included. A linear mixed model was used to assess the longitudinal trend in ESAS-r. A minimal clinically important difference (MCID) for total ESAS-r score was defined as a change of 3-points for improvement and 4-points for deterioration. The proportion of patients with an MCID over time was described using moving averages. To test for changes, mixed effects logistic models were fitted, each of which included patient-specific random intercepts and random slopes.Results67 patients were eligible for analysis (736 ESAS-r assessments). Median (range) follow-up was 24 months (range: 15-45) and compliance at 12 months was 60% (40/67). There was a significant decrease in ESAS-r scores over time. Baseline ESAS-r was strongly predictive of ESAS-r at follow-up (p < 0.001). The proportion of patients with an MCID for improvement from baseline significantly increased over time (p < 0.001) and the proportion with an MCID for deterioration significantly decreased over time (p < 0.001). No predictors for distress were found.ConclusionsLong-term cervical cancer survivors experience distress that significantly improves over time to an extent expected to be clinically meaningful for patients. Implementing cervical cancer specific patient-reported outcome tools into practice could better inform patient needs.
| S-EPMC7186264 | biostudies-literature
Project description:The present study aimed to develop two nomograms in order to predict cancer-specific survival (CSS) and overall survival (OS) of patients with anal carcinoma receiving definitive chemoradiotherapy. Data from studies including patients with anal carcinoma, who were determined to be positive histologically and diagnosed between 2004 and 2010, were obtained from the Surveillance, Epidemiology, and End Results database. Significant prognostic factors for CSS and OS of patients were screened to develop nomograms through univariate and multivariate analyses. Nomograms were validated using internal and external data. The predictive abilities of the generated models were evaluated by concordance index (C-index) and calibration curves. Risk stratification was performed for patients with the same TNM stage. A total of 1,473 patients and six independent prognostic factors for CSS and OS, namely age, sex, ethnicity, marital status at diagnosis, T stage and N stage, were included in the nomogram calculations. Calibration curves demonstrated that nomogram prediction was in high accordance with actual observation. The C-indices of nomograms were greater than those of models based on the sixth edition of the American Joint Committee on Cancer TNM staging system for CSS prediction (training cohort, 0.72 vs. 0.70; validation cohort, 0.68 vs. 0.62) and OS (training cohort, 0.70 vs. 0.66; validation cohort, 0.68 vs. 0.62). Survival curves demonstrated significant survival differences among the different risk groups. Nomograms were more accurate than the conventional TNM staging system in prognosis prediction. In addition, survival performances of patients with the same TNM stage could be further distinguished by risk stratification, which provided individualized prediction for patients. These survival prediction methods may aid clinicians in patient counseling and in selecting more individualized therapeutic strategies.
| S-EPMC6960384 | biostudies-literature
Project description:ObjectiveIn selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread - MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT.Methods and materialsA PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed.ResultsIndividual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5 mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (p < 0.001.) The group of ypT1 had the smallest MIS, followed by the ypT3-4 group, while the ypT2 group had the largest MIS (p < 0.001). Regarding time interval between CRT and surgery, a statistically significant difference was seen when comparing the three time-interval groups (less than 8 weeks, 8-12 weeks, and more than 12 weeks), where waiting more than 12 weeks after CRT resulted in the largest MIS (p < 0.0001).ConclusionBased on this meta-analysis, in order to treat the MIS for 95% of rectal cancer patients after CRT, a Clinical Target Volume (CTV) margin of 5.5 mm from the lateral most edge of the macroscopic tumor would suffice. 80% of tumors showed no MIS and would not require an extra CTV margin for treatment. These findings support the feasibility of localized radiotherapy boosts for dose-escalation to improve response among patients with incomplete response after standard CRT and can also be applied in the surgical setting.
| S-EPMC7104917 | biostudies-literature
Project description:ObjectivePatient-reported distress (PRD) has not been well assessed in association with survival after radiation therapy (RT). The aims of this study were to evaluate the association between PRD level and survival after definitive RT and to identify the main causes of distress in definitive RT patients.Methods and materialsA total of 678 consecutive patients receiving definitive RT at our institution from April 2012 through May 2015 were included. All patients answered a PRD questionnaire that contained 30 items related to possible causes of distress, which could be rated from 1 (no distress) to 5 (high distress). Additionally, patients were asked to rate their overall distress level from 0 (no distress) to 10 (extreme distress). This overall distress level was our primary patient-reported distress measure and was examined as a continuous variable and as a categorical variable with 3 PRD levels (low, 0-3 [n = 295]; moderate, 4-6 [n = 222]; and high, 7-10 [n = 161]).ResultsAs a continuous variable in multivariable Cox regression analysis, a higher overall PRD level was associated with poorer survival after RT (hazard ratio [HR], 1.39; P = .004). As a categorical variable, compared with patients with low distress, survival was poorer for patients with moderate distress (HR, 1.62; P = .038) or high distress (HR, 1.49; P = .12), but the latter difference was not significant. When the moderate and high distress levels were combined, survival was significantly poorer compared with the low distress level (HR, 1.57; P = .034). The top 5 specific causes of distress that patients mentioned were "How I feel during treatment," "Fatigue," "Out-of-pocket medical costs," "Pain that affects my daily functioning," and "Sleep difficulties."ConclusionsPRD before or during RT is a prognostic factor associated with decreased survival. Distress screening guidelines and interventions should be implemented for patients receiving definitive RT.
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Project description:ObjectivesPoor responders to chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) can still have a good prognosis if the treatment strategy is changed in time. However, no reliable predictor of early-treatment response has been identified. The purpose of this study was to investigate the role of T2 relaxation time in magnetic resonance imaging (MRI) for the early prediction of a pathological response to CRT in LARC.MethodsA total of 123 MRIs were performed on 41 LARC patients immediately before, during, and after CRT. The corresponding tumor volume, T2 relaxation time, and apparent diffusion coefficient (ADC) values at different scan time points were obtained. The Mann-Whitney U test was used to compare the T2 relaxation time between pathological good responders (GR) and non-good responders (non-GR). The area under the curve (AUC) value was used to quantify the diagnostic ability of each parameter in predicting tumor response to CRT.ResultsTwenty-one (51%) and 20 (49%) were GRs and non-GRs, respectively. T2 relaxation time showed an excellent intraclass correlation coefficient (ICC) of > 0.85 at three-time points. It was significantly lower in the GR group than in the non-GR group during and after CRT. The early T2 decrease had a high AUC of 0.91 in differentiating non-GRs and GRs, similar to 0.90 of the T2 value after CRT.ConclusionsT2 relaxation time may help predict treatment response to CRT for LARC earlier, rather than having to wait until the end of CRT, thereby alleviating the physical burden for patients with no good response.
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Project description:The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15-27% patients with a pathological complete response (pCR)-defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5-6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm.
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Project description:Following definitive chemoradiation for anal squamous cell carcinoma (ASCC), patients face a variety of chronic issues including: bowel dysfunction, accelerated bone loss, sexual dysfunction, and psychosocial distress. The increasing incidence of this disease, high cure rates, and significant long-term sequelae warrant increased focus on optimal survivorship care following definitive chemoradiation. In order to establish our survivorship care model for ASCC patients, a multi-disciplinary team of experts performed a comprehensive literature review and summarized best practices for the multi-disciplinary management of this unique patient population. We reviewed principle domains of our survivorship approach: (1) management of chronic toxicities; (2) sexual health; (3) HIV management in affected patients; (4) psychosocial wellbeing; and (5) surveillance for disease recurrence and survivorship care delivery. We provide recommendations for the optimization of survivorship care for ASCC patients can through a multi-disciplinary approach that supports physical and psychological wellness.
| S-EPMC6737598 | biostudies-literature
Project description:BackgroundThe comparative effectiveness of trimodality therapy vs definitive chemoradiation for treating locally advanced esophageal cancer in older adults is uncertain. Existing trials lack generalizability to older adults, a population with heightened frailty. We sought to emulate a hypothetical trial comparing these treatments using real-world data.MethodsA cohort of adults aged 66-79 years diagnosed with locally advanced esophageal cancer between 2004 and 2017 was identified in the Surveillance Epidemiology and End Results-Medicare database. The clone-censor-weight method was leveraged to eliminate time-related biases when comparing outcomes between treatments. Outcomes included overall mortality, esophageal cancer-specific mortality, functional adverse events, and healthy days at home.ResultsA total of 1240 individuals with adenocarcinomas and 661 with squamous cell carcinomas were identified. For adenocarcinomas, the standardized 5-year risk of mortality was 73.4% for trimodality therapy and 83.8% for definitive chemoradiation (relative risk [RR] = 0.88, 95% confidence interval [CI] = 0.82 to 0.95). Trimodality therapy was associated with mortality risk reduction for squamous cell carcinomas (RR = 0.87, 95% CI = 0.70 to 1.01). The 1-year incidence of functional adverse events was higher in the trimodality group (adenocarcinomas RR = 1.40, 95% CI = 1.22 to 1.65; squamous cell carcinomas RR = 1.21, 95% CI = 1.00 to 1.49). Over 5 years, trimodality therapy was associated with 160 (95% CI = 67 to 229) and 177 (95% CI = 51 to 313) additional home days in individuals with adenocarcinomas and squamous cell carcinomas, respectively.ConclusionsCompared with definitive chemoradiation, trimodality therapy was associated with reduced mortality but increased risk of function-related adverse events. Discussing these tradeoffs may help optimize care plans.
| S-EPMC9623425 | biostudies-literature
Project description:We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m(-2) day(-1) is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m(-2) day(-1), reduced to 225 mg m(-2) day(-1) during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery.
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