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Current Oncology
Special Issues
Total Neoadjuvant Therapy for Rectal Cancer
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Total Neoadjuvant Therapy for Rectal Cancer

A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Gastrointestinal Oncology".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 4530

Special Issue Editors

Dr. Alexander De Vries

E-Mail Website
Guest Editor
Department of Radio Oncology, Hospital Feldkirch, 6800 Feldkirch, Austria
Interests: radio-oncology; rectal cancer; neoadjuvant; adjuvant; palliative radiotherapy
Dr. Gudrun Piringer

E-Mail Website
Guest Editor
Department for Hematology and Oncology, Kepler University Hospital, 4020 Linz, Austria
Interests: general oncology; gastrointestinal cancer; neoadjuvant–adjuvant–palliative

Special Issue Information

Dear Colleagues,

Neoadjuvant chemoradiation followed by total mesorectal excision results in optimized local treatment with local recurrence rates of less than 10% in locally advanced rectal cancer (LARC); however, neoadjuvant chemoradiation does not consistently improve overall survival, and distant metastases still occur in one-third of patients. Total neoadjuvant therapy (TNT) is a novel approach for LARC and has been intensively investigated in recent years. The optimal treatment sequence is, however, a matter of debate and until now no overall survival benefit has been reported. Guidelines incorporate TNT as the preferred treatment for LARC. However, the TNT protocols used, as well as the inclusion criteria, are different. Many unanswered questions remain, such as which chemotherapy regimen is the best (induction or consolidation chemotherapy, short-course radiotherapy or long-course radiochemotherapy before or after chemotherapy); whether adjuvant chemotherapy is necessary (TNT for all rectal cancers or defined high-risk patients, avoidance of surgery); do molecular markers play a role in upfront therapy decisions; and is the method of watching and waiting preferred? Furthermore, the value of circulating tumor DNA in the treatment of patients with advanced rectal cancer is within the focus of the research interest.

For this Special Issue of Current Oncology, submissions that summarize and identify differences from the TNT concepts used, discussion about the best TNT concepts, and future investigations from different perspectives in the therapy of locally advanced rectal cancer are sought.

We look forward to receiving your contributions.

Dr. Alexander De Vries
Dr. Gudrun Piringer
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. Current Oncology is an international peer-reviewed open access monthly 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 2200 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

  • total neoadjuvant therapy
  • radiotherapy in rectal cancer
  • induction/consolidation chemotherapy
  • ctDNA in rectal cancer
  • immunotherapy in rectal cancer
  • watch-and-wait in rectal cancer

Published Papers (3 papers)

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Research

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11 pages, 643 KiB  
Article
Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database
by Megan Mai, Jodi Goldman, Duke Appiah, Ramzi Abdulrahman, John Kidwell and Zheng Shi
Curr. Oncol. 2024, 31(3), 1291-1301; https://doi.org/10.3390/curroncol31030097 - 29 Feb 2024
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Abstract
Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to [...] Read more.
Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7–15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13–1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15–16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice. Full article
(This article belongs to the Special Issue Total Neoadjuvant Therapy for Rectal Cancer)
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13 pages, 3399 KiB  
Article
Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort
by Georg W. Wurschi, Stefan Knippen, Thomas Ernst, Claus Schneider, Herry Helfritzsch, Henning Mothes, Yves Liebe, Martin Huber and Andrea Wittig
Curr. Oncol. 2023, 30(6), 5366-5378; https://doi.org/10.3390/curroncol30060407 - 31 May 2023
Cited by 2 | Viewed by 1815
Abstract
Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy–TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime [...] Read more.
Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy–TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II–III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials. Full article
(This article belongs to the Special Issue Total Neoadjuvant Therapy for Rectal Cancer)
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Review

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17 pages, 624 KiB  
Review
Adoption of Total Neoadjuvant Therapy in the Treatment of Locally Advanced Rectal Cancer
by Madison L. Conces and Amit Mahipal
Curr. Oncol. 2024, 31(1), 366-382; https://doi.org/10.3390/curroncol31010024 - 10 Jan 2024
Viewed by 1521
Abstract
Local and metastatic recurrence are primary concerns following the treatment of locally advanced rectal cancer (LARC). Chemoradiation (CRT) can reduce the local recurrence rates and has subsequently moved to the neoadjuvant setting from the adjuvant setting. Pathological complete response (pCR) rates have also [...] Read more.
Local and metastatic recurrence are primary concerns following the treatment of locally advanced rectal cancer (LARC). Chemoradiation (CRT) can reduce the local recurrence rates and has subsequently moved to the neoadjuvant setting from the adjuvant setting. Pathological complete response (pCR) rates have also been noted to be greater in patients treated with neoadjuvant CRT prior to surgery. The standard approach to treating LARC would often involve CRT followed by surgery and optional adjuvant chemotherapy and remained the treatment paradigm for almost two decades. However, patients were often unable to complete adjuvant chemotherapy due to a decreased tolerance of chemotherapy following surgery, which led to upfront treatment with both CRT and chemotherapy, and total neoadjuvant therapy, or TNT, was created. The efficacy outcomes of local recurrence, disease-free survival, and pCR have improved in patients receiving TNT compared to the standard approach. Additionally, more recent data suggest a possible improvement in overall survival as well. Patients with a complete clinical response following TNT have the opportunity for watch-and-wait surveillance, allowing some patients to undergo organ preservation. Here, we discuss the clinical trials and studies that led to the adoption of TNT as the standard of care for LARC, with the possibility of watch-and-wait surveillance for patients achieving complete responses. We also review the possibility of overtreating some patients with LARC. Full article
(This article belongs to the Special Issue Total Neoadjuvant Therapy for Rectal Cancer)
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