Comparing 90-Day Postoperative Mortality After Neoadjuvant Proton-Based Versus Photon-Based Chemoradiotherapy for Esophageal Cancer

PURPOSE: Evidence suggests that proton-beam therapy (PBT) results in less toxicity and postoperative complications compared to photon-based radiotherapy in patients who receive chemoradiotherapy followed by esophagectomy for cancer. Ninety-day mortality (90DM) is an important measure of the postoperative (nononcologic) outcome as proxy of quality-of-care. We hypothesize that PBT could reduce 90DM compared to photon-based radiotherapy. MATERIALS AND METHODS: From a single-center retrospective database patients treated with chemoradiotherapy before esophagectomy for cancer were selected (1998-2022). Univariable logistic regression was used to study the association of radiotherapy modality with 90DM. Three separate methods were applied to adjust for confounding bias, including multivariable logistic regression, propensity score matching, and inverse probability of treatment weighting. Stratified analysis for the age threshold that maximized the difference in 90DM (ie, ≥67 vs \u3c67 \u3eyears) was performed. RESULTS: A total of 894 eligible patients were included and 90DM was 5/202 (2.5%) in the PBT versus 29/692 (4.2%) in the photon-based radiotherapy group ( CONCLUSION: No statistically significant difference was observed in postoperative 90DM after esophagectomy for cancer between PBT and photon-based neoadjuvant chemoradiotherapy. However, among older patients a signal was observed that PBT may reduce 90DM risk

Esophageal Cancer Outcomes After Definitive Chemotherapy With Intensity Modulated Proton Therapy

PURPOSE: The effectiveness of intensity-modulated proton therapy (IMPT) for esophageal cancer treated with definitive concurrent chemoradiation therapy remains inadequately explored. We investigated long-term outcomes and toxicity experienced by patients who received IMPT as part of definitive esophageal cancer treatment. PATIENTS AND METHODS: We retrospectively identified and analyzed 34 patients with locally advanced esophageal cancer who received IMPT with concurrent chemotherapy as a definitive treatment regimen at The University of Texas MD Anderson Cancer Center from 2011 to 2021. The median IMPT dose was 50.4 GyRBE in 28 fractions; concurrent chemotherapy consisted of fluorouracil and/or taxane and/or platinum. Survival outcomes were determined by the Kaplan-Meier method, and toxicity was scored according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median age of all patients was 71.5 years. Most patients had stage III (cT3 cM0) adenocarcinoma of the lower esophagus. At a median follow-up time of 39 months, the 5-year overall survival rate was 41.1%; progression-free survival, 34.6%; local regional recurrence-free survival, 78.1%; and distant metastasis-free survival, 65.0%. Common acute chemoradiation therapy-related toxicities included hematologic toxicity, esophagitis (and late-onset), fatigue, weight loss, and nausea (and late-onset); grade 3 toxicity rates were 26.0% for hematologic, 18.0% for esophagitis and 9.0% for nausea. No patient had grade ≥3 wt loss or radiation pneumonitis, and no patients had pulmonary fibrosis or esophageal fistula. No grade ≥4 events were observed except for hematologic toxicity (lymphopenia) in 2 patients. CONCLUSION: Long-term survival and toxicity were excellent after IMPT for locally advanced esophageal cancer treated definitively with concurrent chemoradiation therapy. When available, IMPT should be offered to such patients to minimize treatment-related cardiopulmonary toxicity without sacrificing outcomes

Feasibility and first results of the 'Trials-within-Cohorts' (TwiCs) design in patients undergoing radiotherapy for lung cancer

Background: 'Trials-within-Cohorts' (TwiCs), previously known as 'cohort multiple randomized controlled trials' is a pragmatic trial design, supporting an efficient and representative recruitment of patients for (future) trials. To our knowledge, the 'COhort for Lung cancer Outcome Reporting and trial inclusion' (COLOR) is the first TwiCs in lung cancer patients. In this study we aimed to assess the feasibility and first year results of COLOR. Material and Methods: All patients diagnosed with lung cancer referred to the Radiotherapy department were eligible to participate in the ongoing prospective COLOR study. At inclusion, written informed consent was requested for use of patient data, participation in patient-reported outcomes (PROs), and willingness to participate in (future) trials. Feasibility was studied by assessing participation and comparing baseline PROs to EORTC reference values. First-year results of PROs at baseline and 3 months after inclusion were evaluated separately for stereotactic body radiotherapy (SBRT) and conventional radiotherapy patients. Results: Of the 338 eligible patients between July 2020 and July 2021, 169 (50%) participated. Among these, 127 (75%) gave informed consent to PROs participation and 110 (65%) were willing to participate in (future) trials. The inclusion percentage dropped from 77% to 33% when the information procedure was switched from in-person to by phone (due to COVID-19 pandemic measures). Baseline PROs for physical and cognitive functioning were comparable in COLOR patients compared to the EORTC reference values. No significant changes in PROs were observed 3 months after inclusion, except for a slight increase in pain scores in the SBRT group ( n  = 97). Conclusions: The TwiCs-design appears feasible in lung cancer patients with fair participation rates (although negatively impacted by the COVID-19 pandemic). With a planned expansion to other centers, the COLOR-study is expected to enable multiple (randomized) evaluations of experimental interventions with important advantages for recruitment, generalizability, and long-term outcome data collection

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

WHO grade I meningiomas that show regrowth after gamma knife radiosurgery often show 1p36 loss

Abstract WHO grade I meningiomas occasionally show regrowth after radiosurgical treatment, which cannot be predicted by clinical features. There is increasing evidence that certain biomarkers are associated with regrowth of meningiomas. The aim of this retrospective study was to asses if these biomarkers could be of value to predict regrowth of WHO grade I meningiomas after additive radiosurgery. Forty-four patients with WHO grade I meningiomas who underwent additive radiosurgical treatment between 2002 and 2015 after Simpson IV resection were included in this study, of which 8 showed regrowth. Median follow-up time was 64 months (range 24–137 months). Tumors were analyzed for the proliferation marker Ki-67 by immunohistochemistry and for deletion of 1p36 by fluorescence in situ hybridization (FISH). Furthermore, genomic DNA was analyzed for promoter hypermethylation of the genes NDRG1–4, SFRP1, HOXA9 and MGMT. Comparison of meningiomas with and without regrowth after radiosurgery revealed that loss of 1p36 (p = 0.001) and hypermethylation of NDRG1 (p = 0.046) were correlated with regrowth free survival. Loss of 1p36 was the only parameter that was significantly associated with meningioma regrowth after multivariate analysis (p = 0.01). Assessment of 1p36 loss in tumor tissue prior to radiosurgery might be considered an indicator of prognosis/regrowth. However, this finding has to be validated in an independent larger set of tumors

Erratum to: Methods for evaluating medical tests and biomarkers

The original MEMTAB Abstracts in Diagnostic and Prognostic Research contains the incorrect year on individual abstracts in the PDF [1].“Diagnostic and Prognostic Research 2016” under the correspondence line should therefore have been written as “Diagnostic and Prognostic Research 2017” as the journal did not launch until 2017