Clinical Trial

. 2023 Nov 3;23(1):1059.

doi: 10.1186/s12885-023-11363-7.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial)

Min Kyu Kang^#¹, Soo Yeun Park^#², Jun Seok Park², Hye Jin Kim², Jong Gwang Kim³, Byung Woog Kang³, Jin Ho Baek³, Seung Hyun Cho⁴, An Na Seo⁵, Duck-Woo Kim⁶, Jin Kim⁷, Se Jin Baek⁷, Ji Hoon Kim⁸, Ji Yeon Kim⁹, Gi Won Ha¹⁰, Eun Jung Park¹¹, In Ja Park¹², Chang Hyun Kim¹³, Hyun Kang¹⁴, Gyu-Seog Choi¹⁵

Affiliations

¹ Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
² Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukro, Buk-gu, Daegu, 41404, South Korea.
³ Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁴ Department of Radiology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁵ Department of Pathology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁶ Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.
⁷ Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, South Korea.
⁸ Division of Colorectal Surgery, Department of Surgery, Incheon St. Mary's Hospital, the Catholic University of Korea, Incheon, South Korea.
⁹ Division of Colorectal Surgery, Department of Surgery, Chungnam National University Hospital, Daejeon, South Korea.
¹⁰ Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Jeonbuk, South Korea.
¹¹ Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹² Division of Colon and Rectal Surgery, Department of surgery, , University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
¹³ Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, South Korea.
¹⁴ Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
¹⁵ Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukro, Buk-gu, Daegu, 41404, South Korea. kyuschoi@knu.ac.kr.

^# Contributed equally.

PMID: 37923987
PMCID: PMC10623855
DOI: 10.1186/s12885-023-11363-7

Clinical Trial

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial)

Min Kyu Kang et al. BMC Cancer. 2023.

. 2023 Nov 3;23(1):1059.

doi: 10.1186/s12885-023-11363-7.

Authors

Affiliations

¹ Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
² Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukro, Buk-gu, Daegu, 41404, South Korea.
³ Department of Oncology/Hematology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁴ Department of Radiology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁵ Department of Pathology, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁶ Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.
⁷ Division of Colon and Rectal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, South Korea.
⁸ Division of Colorectal Surgery, Department of Surgery, Incheon St. Mary's Hospital, the Catholic University of Korea, Incheon, South Korea.
⁹ Division of Colorectal Surgery, Department of Surgery, Chungnam National University Hospital, Daejeon, South Korea.
¹⁰ Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Jeonbuk, South Korea.
¹¹ Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
¹² Division of Colon and Rectal Surgery, Department of surgery, , University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
¹³ Department of Surgery, Chonnam National University Hwasun Hospital and Medical School, Hwasun, South Korea.
¹⁴ Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, Seoul, South Korea.
¹⁵ Colorectal Cancer Center, Kyungpook National University Chilgok Hospital, School of Medicine, Kyungpook National University, 807 Hogukro, Buk-gu, Daegu, 41404, South Korea. kyuschoi@knu.ac.kr.

^# Contributed equally.

PMID: 37923987
PMCID: PMC10623855
DOI: 10.1186/s12885-023-11363-7

Abstract

Background: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT).

Methods: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness.

Discussion: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness.

Trial registration: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Keywords: Consolidation chemotherapy; Disease-free survival; Neoadjuvant radiotherapy; Protocol; Randomized controlled phase II trial; Rectal neoplasm; Short-course radiation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Fig. 1**
Flowchart of the SOLAR trial. SCRT, short-course radiotherapy; FOLFOX, 5-fluorouracil with oxaliplatin; CRT, chemoradiotherapy; CT, computed tomography; MRI, magnetic resonance imaging; TME, total mesorectal excision

See this image and copyright information in PMC

References

1. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23. doi: 10.1056/NEJMoa060829. - DOI - PubMed
1. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the german CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. doi: 10.1200/JCO.2011.40.1836. - DOI - PubMed
1. Nilsson PJ, van Etten B, Hospers GA, Pahlman L, van de Velde CJ, Beets-Tan RG, Blomqvist L, Beukema JC, Kapiteijn E, Marijnen CA, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer–the RAPIDO trial. BMC Cancer. 2013;13:279. doi: 10.1186/1471-2407-13-279. - DOI - PMC - PubMed
1. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM-K, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29–42. doi: 10.1016/S1470-2045(20)30555-6. - DOI - PubMed
1. Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, et al. Multicenter, Randomized, Phase III Trial of short-term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in locally advanced rectal Cancer (STELLAR) J Clin Oncol. 2022;40(15):1681–92. doi: 10.1200/JCO.21.01667. - DOI - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- ClinicalTrials.gov
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial)

Affiliations

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous