On behalf of the co-authors, I wish to submit our systematic review and meta-analysis entitled 'Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer: a systematic review and meta-analysis' for consideration to publish in the Annals of Surgery.Previously, we have shown that nCRT consisting of carboplatin and paclitaxel with 41.4 Gy radiotherapy significantly improves survival, compared to surgery alone (van Hagen et al, N Engl J Med 2012; Shapiro et al, Lancet Oncol 2015). After this nCRT regimen plus surgery, nearly a third (29%) of patients has a pathologically complete response in the resection specimen. This provides a rationale for an active surveillance approach, in which patients are subjected to frequent clinical investigations after nCRT, and esophagectomy is offered only to those with a proven locoregional recurrence without distant metastases. It is unknown which diagnostic tests are adequate for detecting residual disease after nCRT. The current study evaluates current literature on the accuracy of endoscopic biopsies, endoscopic ultrasound (EUS) and 18 F-fluoro-2-deoxy-D-glucose positron emission tomography with or without computed tomography (18F-FDG PET(-CT)) for detecting residual disease, which are the major diagnostic techniques used for response evaluation in current clinical practice.Since three diagnostic modalities are evaluated, the primary search term yielded 65 eligible articles for systematic review. Including essential references, we exceeded your reference limitation of 75 with 19 additional references. We believe that this manuscript is of interest to the readers of Annals of Surgery because it discusses a timely and relevant topic in the surgical field of esophageal cancer.The manuscript has not been published and is not under consideration for publication elsewhere. No funding was received for this contribution and we do not have any conflicts of interest. Please do not hesitate to contact us, should you have any questions or comments.

BackgroundThe course of health-related quality of life (HRQOL) during and after completion of neoadjuvant chemoradiotherapy (nCRT) for esophageal or junctional carcinoma is unknown.MethodsThis study was a multicenter prospective cohort investigation. Patients with esophageal or cancer to be treated with nCRT plus esophagectomy were eligible for inclusion in the study. The HRQOL of the patients was measured with European Organization for Research and Treatment of Cancer QLQ-C30, QLQ-OG25, and QLQ-CIPN20 questionnaires before and during nCRT, then 2, 4, 6, 8, 10, 12, 14, and 16 weeks after nCRT and before surgery. Predefined end points were based on the hypothesized impact of nCRT. The primary end points were physical functioning, odynophagia, and sensory symptoms. The secondary end points were global quality of life, fatigue, weight loss, and motor symptoms. Mixed modeling analysis was used to evaluate changes over time.ResultsOf 106 eligible patients, 96 (91%) were included in the study. The rate of questionnaires returned ranged from 94% to 99% until week 12, then dropped to 78% in week 16 after nCRT. A negative impact of nCRT on all HRQOL end points was observed during the last cycle of nCRT (all p < 0.001) and 2 weeks after nCRT (all p < 0.001). Physical functioning, odynophagia, and sensory symptoms were restored to pretreatment levels respectively 8, 4, and 6 weeks after nCRT. The secondary end points were restored to baseline levels 4–6 weeks after nCRT. Odynophagia, fatigue, and weight loss improved after nCRT compared with baseline levels at respectively 6 (p < 0.001), 16 (p = 0.001), and 12 weeks (p < 0.001).ConclusionAfter completion of nCRT for esophageal cancer, HRQOL decreases significantly, but all HRQOL end points are restored to baseline levels within 8 weeks. Odynophagia, fatigue, and weight loss improved 6–16 weeks after nCRT compared with baseline levels.Electronic supplementary materialThe online version of this article (10.1245/s10434-019-07779-w) contains supplementary material, which is available to authorized users.

Background After curatively intended neoadjuvant chemoradiotherapy (nCRT) according to CROSS plus surgery for esophageal cancer, 29% of patients have a pathologic complete response. Active surveillance after nCRT, in which patients undergo frequent clinical examinations and where esophagectomy is only offered to those with a locoregional regrowth without distant metastases, has been proposed as novel treatment option. This study provides a systematic review and meta-analysis of the literature regarding the accuracy of endoscopic biopsies, endoscopic ultrasound (EUS) and 18F-FDG PET(-CT) for detecting residual disease after nCRT for esophageal cancer. Methods A systematic literature search in Embase, Medline, Cochrane and Web of Science was performed. Two reviewers independently collected studies on the diagnostic accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) for detecting residual disease after nCRT at the primary tumor site or in regional lymph nodes for potentially curable esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC). Histopathological examination of the resection specimen was the reference standard. Study quality was appraised with the QUADAS-2 tool. Sensitivity and specificity values were calculated and pooled using meta-analyses. Subgroup analyses were performed to investigate possible sources of heterogeneity. Results 60 studies were included for qualitative analysis and 40 for quantitative analysis. For detecting residual disease at the primary tumor site, 11 studies evaluated endoscopic biopsies, 11 described EUS qualitatively, 14 evaluated PET qualitatively, 12 evaluated PET quantitatively, 6 of them using SUVmax and 6 of them using DSUVmax. Summary sensitivity values were 0.36 (95%CI 0.27–0.45), 0.97 (95%CI 0.94–0.98), 0.74 (95%CI 0.66–0.81), 0.68 (95%CI 0.61–0.74) and 0.68 (95%CI 0.54–0.79), respectively. Summary specificity values were 0.93 (95%CI 0.85–0.97), 0.09 (95%CI 0.04–0.19), 0.52 (95%CI 0.40–0.63), 0.70 (95%CI 0.61–0.78), 0.70 (95%CI 0.60–0.78) and respectively. For detecting residual malignant lymph nodes, 11 studies evaluated EUS with a summary sensitivity of 0.68 (95%CI 0.54–0.80) and a summary specificity of 0.58 (95%CI 0.45–0.70). Subgroup analyses demonstrated that sensitivity of endoscopic biopsy, PET DSUVmax and EUS for nodal was higher in SCC than in AC. Conclusion Current literature suggests insufficient accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) as individual modalities for detecting residual disease after nCRT for potentially curable esophageal cancer. Disclosure All authors have declared no conflicts of interest.

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