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This study aimed to evaluate the safety and efficacy of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. It also investigates the changes in immune markers after treatment. This is an open-label, single-arm, single-institution phase 2 clinical trial. A total of 21 patients with newly diagnosed resectable esophageal cancer (cT1-2N+ / cT3-4aN0-3 M0) received 2 cycles of tislelizumab (200mg every 3 weeks for 2 cycles) concurrent with chemoradiotherapy. Radical esophagectomy was conducted within 4-6 weeks after neoadjuvant therapy. Baseline and pre-surgery PET/CT scans were performed to assess treatment response. Primary endpoints included pathological response rate (pCR) and major pathological response rate (MPR), the secondary endpoints were disease free survival and safety. Exploratory endpoints include molecular imaging research and immunological markers alterations in tumor microenvironment and circulating to further explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. A total of 21 patients were enrolled, and all received neoadjuvant tislelizumab combined with chemoradiotherapy, with 19 patients underwent radical esophagectomy. One patient underwent radical chemoradiotherapy due to lymph node metastases after neoadjuvant therapy. One patient died of pneumonia before surgery. Among 19 patients who underwent surgery, R0 was 100% (19/19),10 achieved pCR (52.6%), and 14 achieved MPR (73.7%). Most of treatment-related adverse event (TRAE) were grade 1-2. Grade ≥3 TRAEs included 1 anemia, 1 leukopenia, 1 neutropenia, 1 liver damage, 1 thrombocytopenia, and 1 elevated cardiac troponin T. A significant reduction in SUVmax of tumor was observed in both pCR and no-pCR patients after treatment. And SUVmax in no-pCR patients tended to be higher than pCR patients. Following neoadjuvant treatment, a significant increase of CD4+ T cells, CD8+ T cells, and memory T cells was observed within the TME. Patients with pCR had significant increase in the infiltration of CD4+ T cells, CD8+ T cells, and CD4+ Tm cells in tumor area. And significant increase in circulating CD4+ T cells, CD4+ effector memory T cells, and M1 macrophages was found after treatment. Moreover, a notably higher presence of CD4+ Tem cells and DC cells is observed in patients achieving pCR. Neoadjuvant tislelizumab combined with chemoradiotherapy for locally advanced ESCC has promising efficacy and good safety and enhances tumor immune infiltration and immunologic memory. [ABSTRACT FROM AUTHOR]

The objective of the study was to compare geometrical differences of target volumes based on four-dimensional computed tomography ( 4DCT) maximum intensity projection ( MIP) and 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/ CT) images of primary thoracic esophageal cancer for radiation treatment. Twenty-one patients with thoracic esophageal cancer sequentially underwent contrast-enhanced three-dimensional computed tomography ( 3DCT), 4DCT, and 18 F-FDG PET/CT thoracic simulation scans during normal free breathing. The internal gross target volume defined as IGTVMIP was obtained by contouring on MIP images. The gross target volumes based on PET/CT images ( GTVPET) were determined with nine different standardized uptake value ( SUV) thresholds and manual contouring: SUV ≥ 2.0, 2.5, 3.0, 3.5 ( SUV n); ≥20%, 25%, 30%, 35%, 40% of the maximum (percentages of SUVmax, SUV n%). The differences in volume ratio ( VR), conformity index ( CI), and degree of inclusion ( DI) between IGTVMIP and GTVPET were investigated. The mean centroid distance between GTVPET and IGTVMIP ranged from 4.98 mm to 6.53 mm. The VR ranged from 0.37 to 1.34, being significantly ( P < 0.05) closest to 1 at SUV2.5 (0.94), SUV20% (1.07), or manual contouring (1.10). The mean CI ranged from 0.34 to 0.58, being significantly closest to 1 ( P < 0.05) at SUV2.0 (0.55), SUV2.5 (0.56), SUV20% (0.56), SUV25% (0.53), or manual contouring (0.58). The mean DI of GTVPET in IGTVMIP ranged from 0.61 to 0.91, and the mean DI of IGTVMIP in GTVPET ranged from 0.34 to 0.86. The SUV threshold setting of SUV2.5, SUV20% or manual contouring yields the best tumor VR and CI with internal-gross target volume contoured on MIP of 4DCT dataset, but 3DPET/CT and 4DCT MIP could not replace each other for motion encompassing target volume delineation for radiation treatment. [ABSTRACT FROM AUTHOR]

SUMMARY We used pathological examination as golden standard to determine whether 3-deoxy-3-18F-fluorothymidine positron emission tomography/computed tomography (FLT PET/CT) can detect regional lymph node metastasis in untreated thoracic esophageal squamous cell carcinoma and additionally performed 18F-fluorodeoxyglucose (FDG) PET/CT for direct comparison with that of FLT. Twenty-two patients with thoracic esophageal squamous cell carcinoma underwent dual-tracer PET/CT examinations before surgery. The results of reviewing CT images and side-by-side FDG PET and FLT PET images for the diagnosis of locoregional lymph node metastasis were compared prospectively in relation to pathologic findings. All patients underwent esophagectomy and lymphadenectomy. Pathologic examination confirmed nodes positive for metastasis in 16 patients and 47 of 424 excised nodes. The uptake of FDG (median SUVmax, 5.4; range, 2.4-10.6) in locoregional lymph nodes metastases was significantly higher than that of FLT (median SUVmax, 2.8; range, 1.3-4.6). There were 14 false-positive nodes in FDG PET/CT and only 3 in FLT PET/CT; 8 false-negative nodes in FDG PET/CT, while there were 12 false negative nodes in FLT PET/CT. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FLT PET/CT were 74.47%, 99.20%, 96.46%, 92.11%, and 96.89%, respectively, whereas those of FDG PET/CT were 82.98%, 96.29%, 94.81%, 82.98%, and 96.29%, respectively. P-values were 0.450, 0.014, 0.313, 0.050, and 0.555, respectively. FLT uptake in regional lymph nodes of esophageal carcinoma is significantly lower compared with FDG uptake. FLT PET/CT has fewer false-positive findings and higher specificity compared with FDG PET/CT. [ABSTRACT FROM AUTHOR]

SUMMARY The purpose of this study was to evaluate hypoxia in esophageal squamous cell carcinoma (SCC) with 18F-fluoroerythronitroimidazole positron emission tomography/computed tomography (18F-FETNIM PET/CT). We determined an imaging threshold for hypoxia, quantified the spatiotemporal variability of hypoxia in untreated tumor, and evaluated the ability of 18F-FETNIM PET to predict clinical response following concurrent chemoradiotherapy (CCRT). Twenty-eight consecutive patients with inoperable SCC of the esophagus were consecutively accrued between April 2007 and June 2010. The first 10 patients received two pretreatment 18F-FETNIM PET/CT scans on separate days. The remaining 18 patients only underwent 18F-FETNIM PET/CT once before CCRT. The ratio of the maximum standardized uptake value (SUVmax) of 336 normal tissue regions (i.e. heart, lung, brain, or muscle) to the mean standardized uptake value (SUVmean) of the respective patient's spleen was calculated, and the imaging threshold for hypoxia defined as the level of uptake demonstrated by less than 5% of tissue regions. Among the patients with two pretreatment scans, each pair of scans was compared with respect to location and intensity of uptake to assess for baseline spatiotemporal variability. Logistic regression analysis was used to determine whether pretreatment imaging characteristics are predictive of clinical response. The mean and median ratios of the SUVmax of tissue : SUVmean of spleen were nearly identical, and 95% of the ratios fell below 1.3. The mean Dice similarity coefficient for the hypoxic volumes on pretreatment PET scans acquired in the same patient on different days was 0.12 (range, 0.05-0.21). Individuals' tumor SUVmax and SUVmean did not vary significantly, but on average, the geometric centers of hypoxic regions shifted 15 mm (range, 8-20 mm) from the first pretreatment scan to the second. SUVmax was the imaging characteristic most predictive of treatment response ( P= 0.041), with high SUVmax associated with poor clinical response. 18F-FETNIM PET/CT can depict hypoxia in esophageal SCC. Prior to CCRT, tumor hypoxia demonstrates spatial variability on different days, although overall 18F-FETNIM uptake remains similar. Baseline SUVmax may be predictive of treatment response. [ABSTRACT FROM AUTHOR]

The survival advantage of radiotherapy (RT) for patients with metastatic esophagus cancer has not been adequately evaluated. This study aims to find out the role of RT for metastatic esophagus cancer and to find the different effect for RT to esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). This study included 5,970 metastatic esophagus cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database, registered from January 2004 to December 2013. Propensity score (PS) analysis with 1:1 nearest neighbor matching method was used to ensure well-balanced characteristics of all comparison groups by histological types. The Kaplan-Meier and Cox proportional hazardous models were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% confidence interval (CI). Generally speaking, EAC did not get survival benefit from RT (median OS for RT group vs. no-RT group—8.0, 7.6–8.4 vs. 9.0, 8.5–9.5, P  = 0.073), whereas RT for metastatic ESCC did significantly improve OS (median OS for RT group vs. no-RT group—8.0, 7.4–8.6 vs. 7.0, 6.4–7.6, P  = 0.044). Therefore, compared with adenocarcinoma, ESCC could get more survival benefit from RT. [ABSTRACT FROM AUTHOR]