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Cancers
Special Issues
Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology
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Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 10156

Special Issue Editors

Dr. Daniel A. Anaya

E-Mail Website
Guest Editor
Moffitt Cancer Center, Tampa, FL, USA
Interests: cholangiocarcinoma (bile duct cancer); colon cancer; colorectal cancer; gallbladder cancer; liver cancer; neuroendocrine tumor; rectal cancer; small intestine cancer
Dr. Andrew J. Sinnamon

E-Mail Website
Guest Editor
Moffitt Cancer Center, Tampa, FL, USA
Interests: gastrointestinal carcinoid tumor; pancreatic cancer

Special Issue Information

Dear Colleagues,

With a growing focus on multimodality therapy for a variety of gastrointestinal cancers, there has been a movement to emphasize therapies in the neoadjuvant setting. One major potential advantage of this approach is the ability to study treatment effects of therapies for tumors in their original location. However, with an ever-expanding array of novel treatments, including, but not limited to, immune and targeted therapies, the study of treatment response becomes increasingly complex. Research efforts are needed to improve our understanding of tumor response biology and the subsequent prognostic and therapeutic implications. This Special Issue focuses on recent efforts (original research and reviews) to study tumor responses to oncologic therapy across gastrointestinal oncology.

Dr. Daniel A. Anaya
Dr. Andrew J. Sinnamon
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tumor regression
  • treatment response
  • clinical response
  • pathologic response
  • neoadjuvant therapy

Published Papers (6 papers)

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Research

Jump to: Review

12 pages, 1069 KiB  
Article
Frequency of Common and Uncommon BRAF Alterations among Colorectal and Non-Colorectal Gastrointestinal Malignancies
by Amit Mahipal, Michael H. Storandt, Emily A. Teslow, Ellen Jaeger, Melissa C. Stoppler, Zhaohui Jin and Sakti Chakrabarti
Cancers 2024, 16(10), 1823; https://doi.org/10.3390/cancers16101823 - 10 May 2024
Viewed by 342
Abstract
Background: The predictive and prognostic role of BRAF alterations has been evaluated in colorectal cancer (CRC); however, BRAF alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of BRAF alterations among [...] Read more.
Background: The predictive and prognostic role of BRAF alterations has been evaluated in colorectal cancer (CRC); however, BRAF alterations have not been fully characterized in non-CRC gastrointestinal (GI) malignancies. In the present study, we report the frequency and spectrum of BRAF alterations among patients with non-CRC GI malignancies. Methods: Patients with CRC and non-CRC GI malignancies who underwent somatic tumor profiling via a tissue-based or liquid-based assay were included in this study. Gain-of-function BRAF alterations were defined as pathogenic/likely pathogenic somatic short variants (SVs), copy number amplifications ≥8, or fusions (RNA or DNA). Results: Among 51,560 patients with somatic profiling, 40% had CRC and 60% had non-CRC GI malignancies. BRAF GOF alterations were seen more frequently in CRC (8.9%) compared to non-CRC GI malignancies (2.2%) (p < 0.001). Non-CRC GI malignancies with the highest prevalence of BRAF GOF alterations were bile duct cancers (4.1%) and small intestine cancers (4.0%). Among BRAF GOF alterations, class II (28% vs. 6.8%, p < 0.001) and class III (23% vs. 14%, p < 0.001) were more common in non-CRC GI malignancies. Among class II alterations, rates of BRAF amplifications (3.1% vs. 0.3%, p < 0.001) and BRAF fusions (12% vs. 2.2%, p < 0.001) were higher in non-CRC GI malignancies compared to CRC. Conclusions: Non-CRC GI malignancies demonstrate a distinct BRAF alteration profile compared to CRC, with a higher frequency of class II and III mutations, and more specifically, a higher incidence of BRAF fusions. Future studies should evaluate clinical implications for the management of non-CRC GI patients with BRAF alterations, especially BRAF fusions. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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10 pages, 1054 KiB  
Article
Induction Fluorouracil-Based Chemotherapy and PET-Adapted Consolidation Chemoradiation with Esophagectomy for High-Risk Gastroesophageal Adenocarcinoma
by Andrew J. Sinnamon, Rutika Mehta, Samir Saeed, Gregory Y. Lauwers, Russell F. Palm, Jessica M. Frakes, Sarah E. Hoffe, Jobelle J. Baldonado, Jacques P. Fontaine and Jose M. Pimiento
Cancers 2023, 15(17), 4375; https://doi.org/10.3390/cancers15174375 - 1 Sep 2023
Viewed by 833
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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21 pages, 9322 KiB  
Article
Exploring Core Genes by Comparative Transcriptomics Analysis for Early Diagnosis, Prognosis, and Therapies of Colorectal Cancer
by Md. Ariful Islam, Md. Bayazid Hossen, Md. Abu Horaira, Md. Alim Hossen, Md. Kaderi Kibria, Md. Selim Reza, Khanis Farhana Tuly, Md. Omar Faruqe, Firoz Kabir, Rashidul Alam Mahumud and Md. Nurul Haque Mollah
Cancers 2023, 15(5), 1369; https://doi.org/10.3390/cancers15051369 - 21 Feb 2023
Cited by 5 | Viewed by 2591
Abstract
Colorectal cancer (CRC) is one of the most common cancers with a high mortality rate. Early diagnosis and therapies for CRC may reduce the mortality rate. However, so far, no researchers have yet investigated core genes (CGs) rigorously for early diagnosis, prognosis, and [...] Read more.
Colorectal cancer (CRC) is one of the most common cancers with a high mortality rate. Early diagnosis and therapies for CRC may reduce the mortality rate. However, so far, no researchers have yet investigated core genes (CGs) rigorously for early diagnosis, prognosis, and therapies of CRC. Therefore, an attempt was made in this study to explore CRC-related CGs for early diagnosis, prognosis, and therapies. At first, we identified 252 common differentially expressed genes (cDEGs) between CRC and control samples based on three gene-expression datasets. Then, we identified ten cDEGs (AURKA, TOP2A, CDK1, PTTG1, CDKN3, CDC20, MAD2L1, CKS2, MELK, and TPX2) as the CGs, highlighting their mechanisms in CRC progression. The enrichment analysis of CGs with GO terms and KEGG pathways revealed some crucial biological processes, molecular functions, and signaling pathways that are associated with CRC progression. The survival probability curves and box-plot analyses with the expressions of CGs in different stages of CRC indicated their strong prognostic performance from the earlier stage of the disease. Then, we detected CGs-guided seven candidate drugs (Manzamine A, Cardidigin, Staurosporine, Sitosterol, Benzo[a]pyrene, Nocardiopsis sp., and Riccardin D) by molecular docking. Finally, the binding stability of four top-ranked complexes (TPX2 vs. Manzamine A, CDC20 vs. Cardidigin, MELK vs. Staurosporine, and CDK1 vs. Riccardin D) was investigated by using 100 ns molecular dynamics simulation studies, and their stable performance was observed. Therefore, the output of this study may play a vital role in developing a proper treatment plan at the earlier stages of CRC. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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Review

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15 pages, 12913 KiB  
Review
Clinical Tools for Rectal Cancer Response Assessment following Neoadjuvant Treatment in the Era of Organ Preservation
by Amalia J. Stefanou, Sophie Dessureault, Julian Sanchez and Seth Felder
Cancers 2023, 15(23), 5535; https://doi.org/10.3390/cancers15235535 - 22 Nov 2023
Cited by 1 | Viewed by 941
Abstract
Local tumor response evaluation following neoadjuvant treatment(s) in rectal adenocarcinoma requires a multi-modality approach including physical and endoscopic evaluations, rectal protocoled MRI, and cross-sectional imaging. Clinical tumor response exists on a spectrum from complete clinical response (cCR), defined as the absence of clinical [...] Read more.
Local tumor response evaluation following neoadjuvant treatment(s) in rectal adenocarcinoma requires a multi-modality approach including physical and endoscopic evaluations, rectal protocoled MRI, and cross-sectional imaging. Clinical tumor response exists on a spectrum from complete clinical response (cCR), defined as the absence of clinical evidence of residual tumor, to near-complete response (nCR), which assumes a significant reduction in tumor burden but with increased uncertainty of residual microscopic disease, to incomplete clinical response (iCR), which incorporates all responses less than nCR that is not progressive disease. This article aims to review the clinical tools currently routinely available to evaluate treatment response and offers a potential management approach based on the extent of local tumor response. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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14 pages, 753 KiB  
Review
Neoadjuvant Immunotherapy for Patients with dMMR/MSI-High Gastrointestinal Cancers: A Changing Paradigm
by Muhammet Ozer, Charan Thej Reddy Vegivinti, Masood Syed, Morgan E. Ferrell, Cyndi Gonzalez Gomez, Svea Cheng, Jennifer Holder-Murray, Tullia Bruno, Anwaar Saeed and Ibrahim Halil Sahin
Cancers 2023, 15(15), 3833; https://doi.org/10.3390/cancers15153833 - 28 Jul 2023
Cited by 1 | Viewed by 3338
Abstract
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response [...] Read more.
Immune checkpoint inhibitors have revolutionized the management of mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) gastrointestinal cancers, particularly colorectal cancer. Cancers with the MMR-D/MSI-H genotype often carry a higher tumor mutation burden with frameshift alterations, leading to increased mutation-associated neoantigen (MANA) generation. The dramatic response seen with immune checkpoint inhibitors (ICIs), which are orchestrated by MANA-primed effector T cells, resulted in the rapid development of these novel therapeutics within the landscape of MSI-H gastrointestinal cancers. Recently, several clinical trials have utilized ICIs as potential neoadjuvant therapies for MSI-H gastrointestinal cancers and demonstrated deep clinical and pathological responses, creating opportunities for organ preservation. However, there are potential challenges to the neoadjuvant use of ICIs for certain disease types due to the clinical risk of overtreatment for a disease that can be cured through a surgery-only approach. In this review article, we discuss neoadjuvant management approaches with ICI therapy for patients with MSI-H gastrointestinal cancers, including those with oligometastatic disease. We also elaborate on potential challenges and opportunities for the neoadjuvant utilization of ICIs and provide further insight into the changing treatment paradigm of MMR-D/MSI-H gastrointestinal cancers. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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11 pages, 719 KiB  
Review
Interpretation of Tumor Response Grade following Preoperative Therapy for Gastric Cancer: An Overview
by Vasileios Tsagkalidis, Maryjka B. Blaszczyk and Haejin In
Cancers 2023, 15(14), 3662; https://doi.org/10.3390/cancers15143662 - 18 Jul 2023
Cited by 1 | Viewed by 1594
Abstract
Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying [...] Read more.
Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis. Full article
(This article belongs to the Special Issue Clinical and Pathologic Response to Therapy in Gastrointestinal Oncology)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Current tools for clinical response measurement and patient selection in the era of organ preservation following total neoadjuvant therapy in rectal cancer
Authors: Seth I. Felder
Affiliation: Moffitt Cancer Center, Tampa, United States

Title: Clinical management of anal SCC with or without clinical response to chemoradiotherapy
Authors: Julian A. Sanchez
Affiliation: Moffitt Cancer Center, Tampa, United States

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