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Comorbidity, Radiation Duration, and Pretreatment Body Muscle Mass Predict Early Treatment Failure in Taiwanese Patients with Locally Advanced Oral Cavity Squamous Cell Carcinoma after Completion of Adjuvant Concurrent Chemoradiotherapy.

ABSTRACT: Few prospective cohort trials have evaluated the potential risk factors of early treatment failure of locally advanced oral cavity squamous cell carcinoma (LAOCSCC) patients following the completion of postoperative adjuvant concurrent chemoradiotherapy (CCRT). We collected clinicopathological variables, nutrition-inflammatory markers and total body composition data assessed by dual-energy X-ray absorptiometry (DXA) before and after CCRT. A factor analysis was used to reduce the number of DXA-derived parameters. Cox proportional hazard models were applied to determine the risk factors associated with early treatment failure defined as tumor progression or death within 180 days of CCRT completion. A total of 69 patients were eligible for analysis. After CCRT, the body weight, body mass index, nutritional markers, and muscle mass decreased, whereas C-reactive protein level increased. Five factors reflecting different body composition statuses were identified. A total of 21 patients (30.4%) developed early treatment failure. Comorbidities (hazard ratio ((HR)), 2.699; 95% confidence interval ((CI)), 1.005-7.913; p = 0.044), radiation duration (HR, 1.092; 95% CI, 1.015-1.174; p = 0.018) and the pretreatment body muscle mass (HR, 0.578; 95% CI, 0.345-0.957; p = 0.037) independently contributed to early treatment failure. Comorbidities, longer radiation duration, and lower pretreatment body muscle mass are predictive factors for early treatment failure in LAOCSCC patients following postoperative adjuvant CCRT completion.

SUBMITTER: Lin YC

PROVIDER: S-EPMC8306647 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1-4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p?<?0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p?=?0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45-1.56; p?=?0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37-1.72, p?=?0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98-4.87; p?=?0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Project description:PurposeInduction chemotherapy plus concurrent chemoradiotherapy and concurrent chemoradiotherapy alone are both standard treatment regimens for managing locally advanced nasopharyngeal carcinoma. However, the results of comparisons between them in clinical trials vary. Therefore, we designed this meta-analysis to illustrate their advantages and disadvantages in patients with locally advanced nasopharyngeal carcinoma.MethodsWe thoroughly searched the PubMed, EMBASE, and Cochrane Library databases and then merged the effect indicators of hazard ratios and risk ratios using RevMan 5.1.ResultsSeven randomized controlled trials totaling 2,319 patients were included in our research. The synthesized results showed that induction chemotherapy plus concurrent chemoradiotherapy improved overall survival (HR = 0.75, 95% CI: 0.63-0.89, P = 0.001), progression-free survival (HR = 0.69, 95% CI: 0.60-0.80, P < 0.001), distant metastasis-free survival (HR = 0.65, 95% CI: 0.53-0.80, P < 0.001) and locoregional recurrence-free survival (HR = 0.68 95%, CI: 0.54-0.86, P = 0.001) versus concurrent chemoradiotherapy alone. It also increased the risk of anemia, thrombocytopenia, and neutropenia during concurrent chemoradiotherapy. However, the incidence of leukopenia and mucositis was similar in induction chemotherapy and induction chemotherapy plus concurrent chemoradiotherapy. Furthermore, the subgroup analysis showed better survival outcomes with induction chemotherapy plus concurrent chemoradiotherapy than with concurrent chemoradiotherapy alone in the triweekly cisplatin subgroup (all P < 0.01), whereas induction chemotherapy plus concurrent chemoradiotherapy could only improve progression-free survival and locoregional recurrence-free survival in the weekly cisplatin subgroup (HR = 0.78, P = 0.02; and HR = 0.66, P = 0.03, respectively).ConclusionsInduction chemotherapy plus concurrent chemoradiotherapy improved survival outcomes in patients with locally advanced nasopharyngeal carcinoma versus concurrent chemoradiotherapy. For the weekly cisplatin regimen subgroup, it did not improve remote control or overall survival versus concurrent chemoradiotherapy alone, warranting further clarification.

Project description:BackgroundThe optimal sequencing of chemotherapy and radiotherapy after breast surgery was largely studied but remains controversial. Concurrent chemo-radiotherapy is a valuable method for adjuvant treatment of breast cancer which is under ongoing research program in our hospital. We are evaluating the feasibility of the concomitant use of chemotherapy retrospectively.MethodsTwo hundred forty four women having breast cancer were investigated in a retrospective study. All patients were either treated by radical surgery or breast conservative surgery. The study compares two adjuvant treatments associating concomitant chemotherapy and radiotherapy. In the first group (group A) the patients were treated by chemotherapy and radiotherapy in concomitant way using anthracycline (n = 110). In the second group (group B) the patients were treated by chemotherapy and radiotherapy in concomitant way using CMF treatment (n = 134). Chemotherapy was administered in six cycles, one each 3 weeks. Radiotherapy delivered a radiation dose of 50 Gy on the whole breast (or on the external wall) and/or on the lymphatic region. The Kaplan-Meier method was used to estimate the rates of disease free survival, loco-regional recurrence-free survival and overall survival. The Pearson Khi2 test was used to analyse the homogeneity between the two groups. The log-rank test was used to evaluate the differences between the two groups A and B.ResultsAfter 76.4 months median follow-up (65.3 months mean follow up), only one patient relapsed to loco-regional breast cancer when the treatment was based on anthracycline. However, 8 patients relapsed to loco-regional breast cancer when the treatment was based on CMF. In the anthracycline group, the disease free survival after 5 years, was 80.4% compared to 76.4% in the CMF group (Log-rank test: p = 0.136). The overall survival after 5 years was 82.5% and 81.1% in the anthracycline and CMF groups respectively (Log-rank test: p = 0.428). The loco-regional free survival at 5 years was equal to 98.6% in group A and 94% in group B (Log-rank test: p = 0,033). The rate of grade II and grade III anaemia was 13.9% and 6.7% in anthracycline group and CMF group respectively (Khi2-test: p = 0.009). The rate of grade II and grade III skin dermatitis toxicity was 4.5% in the group A and 0% in the group B (Khi2-test: p = 0.013).ConclusionFrom the 5 years retrospective investigation we showed similar disease free survival and overall survival in the two concurrent chemo-radiotherapy treatments based on anthracycline and CMF. However in the loco-regional breast cancer the treatment based on anthracycline was significantly better than that of the treatment based on CMF. There was more haematological and skin dermatitis toxicity in the anthracycline group.

Project description:BackgroundThis retrospective study aimed to investigate whether the pretreatment hemoglobin-to-platelet ratio (HPR) could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (C-CRT) for locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsORN cases were reported from the records of LA-NPC patients who had oral examinations before and after C-CRT. The pretreatment HPR values were calculated on the first day of C-CRT. The connection between HPR values and ORN occurrences was determined using receiver operating characteristic curve analysis. The primary endpoint was the relationship between the pretreatment HPR values and post-C-CRT ORN incidence rates, while secondary endpoints included the identification of other putative ORN risk factors.ResultsWe distinguished 10.9% incidences of ORN during the post-C-CRT follow-up period among 193 LA-NPC patients. The optimal cutoff for pre-C-CRT HPR was 0.48 that grouped the patients into two HPR groups with fundamentally different post-C-CRT ORN incidence rates: Group 1: HPR ≤ 0.48 (N = 60), and Group 2: HPR > 0.48 (N = 133). The comparative analysis indicated a significantly higher ORN incidence in HPR ≤ 0.48 group (30%; P < 0.001). The other factors associated with meaningfully increased ORN rates included the presence of pre-C-CRT ≥ 5 teeth extractions, mandibular volume receiving ≥ 64 Gy, post-C-CRT tooth extractions, mean mandibular dose ≥ 50.6 Gy, and C-CRT to tooth extraction interval > 5.5 months.ConclusionLow pretreatment HPR levels were independently and unequivocally linked to significantly increased incidence of ORN post-C-CRT. Pre-C-CRT HPR levels may be used to estimate the incidence of ORN and be useful for taking preventive and therapeutic measures in these patients such as monitoring oral hygiene with strict follow-up, avoidance of unnecessary tooth extractions, particularly after C-CRT, and use of more rigorous mandibular RT dose limits.

Project description:BackgroundConcurrent chemoradiotherapy is the standard of care for locally advanced cervical cancer. Concurrent chemoradiotherapy with programmed blockade of the cell death-1/programmed cell death-ligand 1 pathway may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. PRIMARY OBJECTIVE:The CALLA trial is designed to determine the efficacy and safety of the programmed cell death-ligand 1 blocking antibody, durvalumab, with and following concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in women with locally advanced cervical cancer. STUDY HYPOTHESIS:Durvalumab concurrent with and following concurrent chemoradiotherapy will improve progression-free survival in patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IVA cervical cancer compared with concurrent chemoradiotherapy alone. TRIAL DESIGN:CALLA is a phase III, randomized, multicenter, international, double-blind, placebo-controlled study. Patients will be randomized 1:1 to receive either durvalumab (1500?mg intravenously (IV)) or placebo every 4 weeks for 24 cycles. All patients will receive external beam radiotherapy with cisplatin (40?mg/m2) IV or carboplatin (area under the curve 2) IV once a week for 5 weeks, followed by image-guided brachytherapy. MAJOR INCLUSION/EXCLUSION CRITERIA:The study will enroll immunotherapy-naïve adult patients with histologically confirmed cervical adenocarcinoma, cervical squamous, or adenosquamous carcinoma FIGO 2009 stages IB2-IIB node positive and stage IIIA-IVA with any node stage. Patients will have had no prior definitive surgical, radiation, or systemic therapy for cervical cancer. PRIMARY ENDPOINT:The primary endpoint is progression-free survival (assessed by the investigator according to Response Evaluation Criteria in Solid Tumors v1.1, histopathological confirmation of local tumor progression or death). SAMPLE SIZE:Approximately 714 patients will be randomized 1:1 to receive either durvalumab + concurrent chemoradiotherapy or placebo + concurrent chemoradiotherapy. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:Patient enrollment is continuing globally with an estimated completion date of April 2024. TRIAL REGISTRATION:NCT03830866.

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Comorbidity, Radiation Duration, and Pretreatment Body Muscle Mass Predict Early Treatment Failure in Taiwanese Patients with Locally Advanced Oral Cavity Squamous Cell Carcinoma after Completion of Adjuvant Concurrent Chemoradiotherapy.

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