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Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: closed (30 June 2020) | Viewed by 18559

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Dr. Jordan M. Cloyd

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Guest Editor

Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA
Interests: multimodality therapy; neoadjuvant therapy; gastrointestinal and hepatopancreatobiliary cancers; neuroendocrine tumors; surgery; patient-centered outcomes
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Special Issue Information

Dear Colleagues,

Gastrointestinal and hepatopancreatobiliary cancers are aggressive malignancies that require multidisciplinary treatment approaches. As novel therapies are regularly introduced, the optimal treatment approaches for these aggressive cancers is becoming increasingly complex. For localized cancers, neoadjuvant and adjuvant approaches are increasingly being applied. For patients with advanced disease, combination regimens and multimodality approaches are being utilized with increasing frequency. However, the indications for and outcomes of multimodality therapy for these cancers require additional research. This Special Issue aims to focus on advances in multimodality therapies for patients with gastrointestinal and hepatopancreatobiliary cancers, including the evaluation of novel treatment regimens, patient-centered outcomes, short-term safety, and long-term efficacy of such treatments.

Dr. Jordan Cloyd
Guest Editor

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Keywords

pancreatic cancer
hepatocellular carcinoma
colon cancer
gallbladder cancer
gastric cancer
esophageal cancer
cholangiocarcinoma
neoadjuvant therapy
adjuvant therapy
neuroendocrine tumor

Published Papers (6 papers)

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Research

16 pages, 1723 KiB

Open AccessArticle

Treatment Patterns for Gastroesophageal Junction Adenocarcinoma in the United States

by Bradford J. Kim, Yi-Ju Chiang, Prajnan Das, Bruce D. Minsky, Mariela A. Blum, Jaffer A. Ajani, Jeannelyn S. Estrella, Wayne L. Hofstetter, Ching-Wei D. Tzeng, Brian D. Badgwell, Paul F. Mansfield and Naruhiko Ikoma

J. Clin. Med. 2020, 9(11), 3495; https://doi.org/10.3390/jcm9113495 - 29 Oct 2020

Cited by 7 | Viewed by 1763

Abstract

Despite the increasing incidence of gastroesophageal junction adenocarcinoma (GEJA), the optimal treatment strategy for the disease remains unknown. The objective of this study was to describe treatment patterns for GEJA in the United States. The National Cancer Database was searched to identify all patients who underwent resection of the lower esophagus, abdominal esophagus, and/or gastric cardia for GEJA between 2006 and 2016. Patients were grouped by clinical disease stage: early localized (L; T1-2N0), locally advanced (LA; T3-4N0), regional (R; T1-2N+), or regionally advanced (RA; T3-4N+). The search identified 28,852 GEJA patients. The dominant age range was 60–69 years (39%). Most patients were men (85%), and most were white (92%). Most L patients (69%) underwent upfront surgery, whereas most LA, R, and RA patients received neoadjuvant therapy (NAT; 86%, 80%, and 90%, respectively). Among patients who received NAT, 85% received chemoradiotherapy. Adjuvant therapy was relatively uncommon across all groups (15–20%). In the LA, R, and RA groups, overall survival was greater in patients who received NAT compared to upfront surgery (p < 0.001). With the exception of patients with early localized node-negative disease, most GEJA patients receive neoadjuvant chemoradiotherapy despite the lack of prospective trials reporting survival benefit over chemotherapy alone. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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14 pages, 796 KiB

Open AccessArticle

Pattern of Recurrence and Patient Survival after Perioperative Chemotherapy with 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) for Locally Advanced Esophagogastric Adenocarcinoma in Patients Treated Outside Clinical Trials

by Torben Glatz, Rasmus Verst, Jasmina Kuvendjiska, Peter Bronsert, Heiko Becker, Jens Hoeppner and Birte Kulemann

J. Clin. Med. 2020, 9(8), 2654; https://doi.org/10.3390/jcm9082654 - 16 Aug 2020

Cited by 19 | Viewed by 2940

Abstract

Background: The 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) protocol provides superior oncologic results compared to other perioperative chemotherapeutic protocols for the treatment of non-metastatic esophagogastric cancer (EGAC). Survival and the pattern of recurrence of EGAC after FLOT and curative tumor resection are analyzed in a collective of patients treated outside clinical trials. Methods: Two-hundred-seventy-seven patients with EGAC (cT3-4 and/or cN+) were treated with perioperative FLOT-chemotherapy plus curative surgery between 2009 and 2018. Data were analyzed retrospectively from a prospective database. Results: Two-hundred-twenty-eight patients were included in the analysis. Postoperative in-hospital mortality was 2%. The median survival was 61–months, and median recurrence-free survival was 42 months. Multivariate analysis identified postoperative nodal status and T-stage as independent predictors of improved overall and recurrence-free survival. Administration of adjuvant chemotherapy failed to be significant for overall survival but was an independent predictor of recurrence-free survival. Recurrence occurred after a median of 9 months (range 1–46 months). Eighty-nine percent of recurrence occurred during the first 24 months. The rate of local recurrence was low. After surgery for gastric cancer, the major recurrence site was peritoneal carcinomatosis (56%), while esophageal cancer recurred mostly as metastasis to distant organs (78%). The specific site of recurrence had no impact on overall survival time. Conclusion: Real-life application of FLOT shows oncologic results comparable to clinical trials. Recurrence after FLOT and surgery for EGAC occurs predominantly early within the first two years after surgery and in the form of distant organ metastasis for esophageal tumors or peritoneal carcinomatosis for gastric tumors. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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12 pages, 1716 KiB

Open AccessArticle

Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomized Controlled Trials

by Jordan M. Cloyd, Victor Heh, Timothy M. Pawlik, Aslam Ejaz, Mary Dillhoff, Allan Tsung, Terence Williams, Laith Abushahin, John F. P. Bridges and Heena Santry

J. Clin. Med. 2020, 9(4), 1129; https://doi.org/10.3390/jcm9041129 - 15 Apr 2020

Cited by 85 | Viewed by 4862

Abstract

The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61–0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59–0.91; BR: HR 0.51 95% CI 0.28–0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61–0.98; chemotherapy alone: HR 0.68, 95% CI 0.54–0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82–1.04, I² = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18–1.93, I² = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47–2.91, I² = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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13 pages, 1856 KiB

Open AccessArticle

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review

by Eliza W. Beal, Lorena P. Suarez-Kelly, Charles W. Kimbrough, Fabian M. Johnston, Jonathan Greer, Daniel E. Abbott, Courtney Pokrzywa, Mustafa Raoof, Byrne Lee, Travis E. Grotz, Jennifer L. Leiting, Keith Fournier, Andrew J. Lee, Sean P. Dineen, Benjamin Powers, Jula Veerapong, Joel M. Baumgartner, Callisia Clarke, Harveshp Mogal, Marti C. Russell, Mohammed Y. Zaidi, Sameer H. Patel, Vikrom Dhar, Laura Lambert, Ryan J. Hendrix, John Hays, Sherif Abdel-Misih and Jordan M. Cloyd Show full author list Hide full author list

J. Clin. Med. 2020, 9(3), 748; https://doi.org/10.3390/jcm9030748 - 10 Mar 2020

Cited by 27 | Viewed by 2856

Abstract

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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13 pages, 1215 KiB

Open AccessArticle

Neoadjuvant Chemoradiotherapy and Larynx-Preserving Surgery for Cervical Esophageal Cancer

by Kun-Yao Dai, Yu-Chao Yu, Yi-Shing Leu, Chih-Wen Chi, Mei-Lin Chan, Chung-Hsin Tsai, Huan-Chau Lin, Wen-Chien Huang and Yu-Jen Chen

J. Clin. Med. 2020, 9(2), 387; https://doi.org/10.3390/jcm9020387 - 01 Feb 2020

Cited by 9 | Viewed by 2588

Abstract

Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. This study evaluated the feasibility of neoadjuvant CCRT as a larynx preservation strategy for treating cervical esophageal squamous cell carcinoma (SCC) by a multidisciplinary team. Fifteen patients with cervical esophageal SCC who received neoadjuvant CCRT and radical surgery at our institution were reviewed. All patients received CCRT using the intensity-modulated radiation therapy with 48 Gy to gross tumor and 43.2 Gy to regional lymphatic basin in 24 fractions. Side effects, clinical tumor responses, pathological responses, and surgical margin status were analyzed. Pathological T down-staging was noted in seven patients (46.7%); pathological complete response was achieved in three patients (20%). Fourteen patients (93.3%) had larynx preservation; eight patients (53.3%) achieved negative surgical margins. The 2-year overall survival, local relapse-free survival, and regional relapse-free survival were 50.6%, 62.2%, and 47.5%, respectively. Neoadjuvant CCRT and larynx-sparing surgery are feasible and tolerable in patients with cervical esophageal SCC. Prospectively designed studies for large patient groups and long-term follow-up results are needed for validating this multimodality therapy. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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12 pages, 351 KiB

Open AccessArticle

Prognostic Factors for Overall Survival in Advanced Intrahepatic Cholangiocarcinoma Treated with Yttrium-90 Radioembolization

by Michael Köhler, Fabian Harders, Fabian Lohöfer, Philipp M. Paprottka, Benedikt M. Schaarschmidt, Jens Theysohn, Ken Herrmann, Walter Heindel, Hartmut H. Schmidt, Andreas Pascher, Lars Stegger, Kambiz Rahbar and Moritz Wildgruber

J. Clin. Med. 2020, 9(1), 56; https://doi.org/10.3390/jcm9010056 - 25 Dec 2019

Cited by 32 | Viewed by 2965

Abstract

Purpose: To evaluate factors associated with survival following transarterial ⁹⁰Y (yttrium) radioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods: This retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in patients with advanced ICC following resin microsphere TARE. Patients were included either after failed previous anticancer therapy, including relapse after surgical resection, or for having a minimum of 25% of total liver volume affected by ICC. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier analysis was performed to analyze survival followed by cox regression to determine independent prognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age 62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while 63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI: 6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis. Cox regression revealed the extent of liver disease to one or both liver lobes being associated with survival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC had significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced liver disease was observed. Discussion: Survival after ⁹⁰Y TARE in patients with advanced ICC primarily depends on disease extent. Only limited prognostic factors are associated with a general poor overall survival. Full article

(This article belongs to the Special Issue Multimodality Therapy of Gastrointestinal and Hepatopancreatobiliary Cancers)

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