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Simple Summary: Induction chemotherapy followed by PET-adapted consolidation chemoradiotherapy has been ex-plored with success in the clinical trial setting for patients with high-risk gastroesophageal adeno-carcinoma. This study demonstrates that this strategy can be associated with high rate of pathologic complete response (pCR), sterilization of lymph node basin (ypN0), and margin-negative resection (R0) in high risk patients. Overall survival is favorable for patients who show metabolic response to 5-FU based chemotherapy and continue this during chemoradiation Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: The impact of adjuvant sequential chemoradiotherapy (CRT) on survival in resected pancreatic ductal adenocarcinoma (PDAC) remains unclear and warrants further investigation. Methods: NCDB patients with R0/R1 resected PDAC who received adjuvant chemotherapy without CRT or followed by CRT per RTOG-0848 protocol were included. Cox regression for 5-year overall survival (OS) was performed and used to construct a pathologic nomogram in patients who did not receive CRT. A risk score was calculated and patients were divided into low-risk and high-risk groups. Patients from each risk stratum were matched for the receipt of CRT to assess the added benefit of CRT on survival. The Kaplan–Meier analysis was performed to compare OS. Results: A total of 7146 patients were selected, 1308 (18.3%) received CRT per RTOG-0848. Cox regression concluded grade, T stage, N stage, node yield < 12, R1, and LVI as significant predictors of 5-year OS which were used to construct the risk score. Matched analysis in low-risk patients (score 0–79) showed no difference in OS between CRT vs. no CRT (47.6 ± 5.7 vs. 45.1 ± 3.9 months; p = 0.847). OS benefit was 3% at 1 year, − 4% at 2 years, and 4% at 5 years. In high-risk patients (score 80–100), median OS was higher in CRT vs. no CRT (24.8 ± 0.7 vs. 21.7 ± 0.8 months; p = 0.043). Absolute OS benefit was 13% at 1 year, 5% at 2 years, and − 1% at 5 years. Conclusion: CRT has a short-lived impact on OS in resected PDAC that is only evident in high-risk patients. In this subset, survival benefit peaks at 1 year and subsides at 3 to 5 years following PDAC resection. [ABSTRACT FROM AUTHOR]

Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? Recently, a shorter duration of adjuvant therapy in colon cancer has been studied within the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration, with the primary aim of reducing morbidity while not sacrificing oncologic outcome.21 On the basis of favorable results demonstrating the noninferiority of 3 months of capecitabine plus oxaliplatin in patients with T3N1 colon cancer, it is plausible that rectal cancer chemotherapy treatment duration may be affected in the coming years. Historically, most patients received an empirical treatment strategy, with little role for tumor response assessment after neoadjuvant therapy. PROSPECT: Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced Rectal Cancer Undergoing Surgery. [Extracted from the article]

Introduction: To develop a radiomic‐based model to predict pathological complete response (pCR) and outcome following neoadjuvant chemoradiotherapy (NACRT) in oesophageal cancer. Methods: We analysed 68 patients with oesophageal cancer treated with NACRT followed by esophagectomy, who had staging 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET) and computed tomography (CT) scans performed at our institution. An in‐house data‐chjmirocterization algorithm was used to extract 3D‐radiomic features from the segmented primary disease. Prediction models were constructed and internally validated. Composite feature, Fc = α * FPET + (1 − α) * FCT, 0 ≤ α ≤ 1, was constructed for each corresponding CT and PET feature. Loco‐regional control (LRC), recurrence‐free survival (RFS), metastasis‐free survival (MFS) and overall survival (OS) were estimated by Kaplan–Meier analysis, and compared using log‐rank test. Results: Median follow‐up was 59 months. pCR was achieved in 34 (50%) patients. Five‐year RFS, LRC, MFS and OS were 67.1%, 88.5%, 75.6% and 57.6%, respectively. Tumour Regression Grade (TRG) 0–1 indicative of complete response or minimal residual disease was significantly associated with improved 5‐year LRC [93.7% vs 71.8%; P = 0.020; HR 0.19, 95% CI 0.04–0.85]. Four sepjmirote pCR predictive models were built for CT alone, PET alone, CT+PET and composite. CT, PET and CT+PET models had AUC 0.73 ± 0.08, 0.66 ± 0.08 and 0.77 ± 0.07, respectively. The composite model resulted in an improvement of pCR predicting power with AUC 0.87 ± 0.06. Stratifying patients with a low versus high radiomic score showed clinically relevant improvement in 5‐year LRC favouring low‐score group (91.1% vs. 80%, 95% CI 0.09–1.77, P = 0.2). Conclusion: The composite CT/PET radiomics model was highly predictive of pCR following NACRT. Validation in larger data sets is warranted to determine whether the model can predict clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. Methods In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. Results A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. Conclusion The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. Clinical Trial Registration NCT02935309 [ABSTRACT FROM AUTHOR]