Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study.

BACKGROUND: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. METHODS: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. DISCUSSION: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. TRIAL REGISTRATION: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Impact of Endoscopic Ultrasonography on 18F-FDG-PET/CT Upfront Towards Patient Specific Esophageal Cancer Treatment.

INTRODUCTION: In patients with potentially resectable esophageal cancer (EC), the value of endoscopic ultrasonography (EUS) after fluorine-18 labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG-PET/CT) is questionable. Retrospectively, we assessed the impact of EUS after PET/CT on the given treatment in EC patients. METHODS: During the period 2009-2015, 318 EC patients were staged as T1-4aN0-3M0 with hybrid 18F-FDG-PET/CT or 18F-FDG-PET with CT and EUS if applicable in a nonspecific order. We determined the impact of EUS on the given treatment in 279 patients who also were staged with EUS. EUS had clinical consequences if it changed curability, extent of radiation fields or lymph node resection (AJCC stations 2-5), and when the performed fine-needle aspiration (FNA) provided conclusive information of suspicious lymph node. RESULTS: EUS had an impact in 80 (28.7%) patients; it changed the radiation field in 63 (22.6%), curability in 5 (1.8%), lymphadenectomy in 48 (17.2%), and FNA was additional in 21 (7.5%). In patients treated with nCRT (n = 194), EUS influenced treatment in 53 (27.3%) patients; in 38 (19.6%) the radiation field changed, in 3 (1.5%) the curability, in 35 (18.0%) the lymphadenectomy, and in 17 (8.8%) FNA was additional. EUS influenced both the extent of radiation field and nodal resection in 31 (16.0%) nCRT patients. CONCLUSIONS: EUS had an impact on the given treatment in approximately 29%. In most patients, the magnitude of EUS found expression in the extent of radiotherapy target volume delineation to upper/high mediastinal lymph nodes.

Lhermitte sign and myelopathy after irradiation of the cervical spinal cord in radiotherapy treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The goal of this work was to examine toxicity and risk factors after irradiation of the cervical spinal cord. PATIENTS AND METHODS: A total of 437 patients irradiated for a laryngeal and oropharyngeal carcinoma were eligible (median follow-up 27 months). Spinal cord contouring was defined differently over time as anatomically defined spinal cord area (SCA) and the spinal cord on CT (SC) with a margin of 3 or 5 mm (SCP3/SCP5). RESULTS: None developed chronic progressive radiation myelopathy (CPRM) (maximum spinal dose 21.8-69 Gy); 3.9% (17/437) developed a Lhermitte sign (LS) with a median duration of 6 months (range 1-30 months) and was reversible in all patients. Risk factors for developing LS were younger age (52 vs. 61 years, p < 0.001), accelerated RT (12/17 patients, p < 0.005), and dose-volume relationships for SCA with ≥ 45 Gy of 14.15 cm(3) and 7.9 cm(3) for patients with and without LS, respectively. CONCLUSION: LS is more frequently observed in younger patients and in patients treated with accelerated radiotherapy. A dose-volume relationship was seen for V45 in the case of SCA. For higher doses, no clear dose-volume relationships were observed.

Looking at individual symptoms: the dynamic network structure of depressive symptoms in cancer survivors and their preferences for psychological care.

PURPOSE: The majority of depressed cancer survivors do not receive psychological care, possibly because offered care does not align with their experiences and preferences. We examined (1) which depressive symptoms cancer survivors would like to receive psychological care for; (2) how distinct depressive symptoms are related to each other in the contemporaneous and temporal network of depressive symptoms; and (3) whether survivors' care needs correspond to the interconnectedness of these specific symptoms. METHOD: Fifty-two cancer survivors suffering from at least mild depressive symptoms and were not receiving psychological care filled out a baseline questionnaire about their care needs for distinct depressive symptoms, followed by ecological momentary assessments (EMA) assessing depressive symptoms (14 days, five times a day). Multi-level vector autoregression analysis was used to estimate associations between distinct depressive symptoms as well as their centrality within the network. RESULTS: Cancer survivors most strongly preferred to receive care for fatigue, feeling down, little enjoyment, and sleep problems. Fatigue, together with worry and lack of concentration, most strongly predicted the onset of other symptoms. Little enjoyment and feeling down were two of the most central symptoms (i.e., strongly connected to other symptoms) in the contemporaneous network and were most strongly influenced by other symptoms in the temporal network. CONCLUSIONS: Clinicians can offer specific interventions that target fatigue, as these played an important role in the onset of symptoms and would align with survivors' needs. IMPLICATIONS FOR CANCER SURVIVORS: Offering such symptom-specific care may increase the uptake of psychological interventions in cancer survivors.

A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy.

BACKGROUND: Isolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients. MATERIAL AND METHODS: A systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method. RESULTS: Of the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion -5.7, 95% CI [-13.7; 2.3]). CONCLUSIONS: Salvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.