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Neoadjuvant Chemoradiotherapy for Gastrointestinal Cancer

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Dr. Daniel Martin

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Guest Editor

1. Department of Radiotherapy and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany
2. German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Frankfurt, Germany
3. Frankfurt Cancer Institute (FCI), Goethe University Frankfurt, Frankfurt, Germany
Interests: gastrointestinal cancers; chemoradiotherapy; radiotherapy

Special Issue Information

Dear Colleagues,

We are pleased to invite you to a Special Issue of Cancers covering neoadjuvant chemoradiotherapy (CRT) for gastrointestinal (GI) cancer, focusing on rectal cancer, esophageal cancer, gastric cancer, and pancreatic cancer. Neoadjuvant CRT has been a cornerstone in the treatment of many GI cancers, aiming for downstaging in order to improve surgical outcome and enhance survival. As a prime example, CRT has been a mainstay in rectal cancer in order to reduce local recurrences after surgery and also adds the possibility of organ preservation using a watch and wait approach after reaching a complete clinical response after neoadjuvant treatment. Pancreatic cancer, a challenging entity due to its aggressive nature, offers the possibility to include CRT in a multimodal treatment approach, especially in borderline resectable cases.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but
not limited to) the following: clinical trials, novel combinations of systemic therapies, immunotherapy, and radiotherapy, novel strategies for applying radiotherapy in order to minimize toxicities and/or improve treatment results, as well as the role of molecular markers in refining treatment strategies.

I look forward to receiving your contributions.

Dr. Daniel Martin
Guest Editor

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13 pages, 632 KB

Open AccessArticle

Esophagectomy Versus Active Surveillance After Complete Response in Locally Advanced Esophageal Cancer: Retrospective Analysis

by Efrat Gur, Meroslav Lutsyk, Tomer Meirson, Noor Abu Hjool, Dror Limon, Yosef Landman, Oded Icht, Baruch Brenner and Yulia Kundel

Cancers 2025, 17(24), 3926; https://doi.org/10.3390/cancers17243926 - 8 Dec 2025

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Abstract

Background/Objectives: Esophageal cancer (EC) remains highly lethal. The standard management of locally advanced disease includes neoadjuvant chemoradiotherapy (nCRT) followed by surgery. However, the role of esophagectomy in patients achieving clinical complete response (cCR) after nCRT remains uncertain. Methods: We conducted a retrospective study at the Davidoff Cancer Center, Rabin Medical Center (2013–2023). Patients with thoracic EC (adenocarcinoma and squamous cell carcinoma) stage cT2–4a, N+, M0 who received nCRT (cisplatin/5-FU or CROSS regimen with 41.4–50.4 Gy) were included. Patients with cCR, defined by negative biopsies, endoscopic ultrasound, and PET-CT, were managed with surgery or surveillance. Survival was analyzed using Kaplan–Meier and Cox regression. Results: Of 252 patients treated with nCRT, 118 achieved cCR. Seventy underwent surgery, with 47% (33 patients) achieving pathological complete response (pCR), and 48 were managed with surveillance. Five-year overall survival (OS) was 48% with surveillance and 49% with surgery; disease-free survival (DFS) was 36% vs. 43%. No significant differences were observed in OS (HR = 0.75, 95% CI 0.47–1.26) or DFS (HR = 0.88, 95% CI 0.55–1.41). In patients ≤70 years, surgery conferred an OS and DFS benefit (HR = 0.44, p = 0.03). No benefit was observed in patients >70 years, where outcomes trended against surgery. On multivariable analysis, older age (p = 0.005) and female sex (p = 0.007) were independent predictors of OS. Conclusions: In younger patients (≤70 years), surgery yielded significant survival benefit, supporting its role as the preferred treatment. In patients >70 years, surveillance produced comparable or superior outcomes, suggesting deferral of surgery may avoid morbidity without compromising survival. Age-specific tailoring of management is essential. Full article

(This article belongs to the Special Issue Neoadjuvant Chemoradiotherapy for Gastrointestinal Cancer)

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16 pages, 546 KB

Open AccessArticle

Real-World Outcomes Between Perioperative Chemotherapy (FLOT) and Preoperative Concurrent Chemoradiotherapy (CROSS) in Localized Esophageal and Esophagogastric Junction Adenocarcinoma: A Retrospective Cohort Study

by Jirapat Wonglhow, Hui-Li Wong, Cuong Duong, John Spillane, David S. Liu, Trevor Leong, Julie Chu and Michael Michael

Cancers 2025, 17(18), 2962; https://doi.org/10.3390/cancers17182962 - 10 Sep 2025

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Abstract

Background: The management of localized esophageal and esophagogastric junction (EGJ) adenocarcinomas remains challenging. Although perioperative chemotherapy with the fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) regimen or preoperative concurrent chemoradiotherapy with carboplatin and paclitaxel (CROSS) regimen followed by surgery are standard options, the optimal approach is still debated. This study evaluated real-world outcomes of perioperative FLOT versus preoperative CROSS in such patients. Methods: A retrospective cohort study was conducted at a tertiary cancer center in Australia, including patients treated with FLOT or CROSS between 2014 and 2024. Multivariate Cox regression models adjusted for baseline differences, including demographics, tumor stage, differentiation, location, and surgical resection. Results: Among 70 patients, 15 received FLOT and 55 received CROSS. Median overall survival (OS) was 30.3 months for FLOT and 37.5 months for CROSS (p = 0.75). Median event-free survival (EFS) was not reached in the FLOT group and was 14.8 months in the CROSS group (p = 0.49). After multivariate adjustment, differences in OS and EFS were not significant. Compared to FLOT, CROSS was associated with higher treatment completion and response rates. CROSS also led to greater pathological tumor and nodal downstaging, as well as higher rates of complete pathological response. Conclusions: Both FLOT and CROSS appear to be effective treatment options for localized esophageal and EGJ adenocarcinomas. CROSS may offer advantages in terms of treatment tolerability and tumor response, and may be particularly suitable for patients with bulky tumors or reduced performance status. Owing to the limited sample size and follow-up, these findings should be interpreted cautiously. Personalized treatment decisions should be guided by multidisciplinary discussions, considering tumor characteristics, patient condition, and access to adjuvant immunotherapy. Full article

(This article belongs to the Special Issue Neoadjuvant Chemoradiotherapy for Gastrointestinal Cancer)

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