Skip to main content

Advertisement

SpringerLink
Log in

Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer

  • RESEARCH
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

We analyzed the effectiveness, safety, and mid-term oncological outcomes of short-course radiotherapy (SCRT) and oxaliplatin-based consolidation chemotherapy in patients with locally advanced rectal cancer (LARC).

Methods

We retrospectively evaluated 64 patients with LARC who underwent SCRT and tegafox (tegafur–uracil/leucovorin plus oxaliplatin) or mFOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) consolidation chemotherapy before surgery between January 2015 and December 2020. Tumor response, patient compliance, toxicity, surgical outcomes, overall survival (OS), and disease-free survival (DFS) were analyzed.

Results

Sixty-four patients with a mean age of 58.67 years (44 males) were included; 48 (75%) had tumors within 5 cm of the anal verge. Additionally, 93.8% of the patients underwent at least 2 months of chemotherapy, and three required dose reduction. Grade III toxicity occurred in 2 patients, and 10 had a clinical complete response and opted for non-operative management. One patient experienced tumor progression and underwent further treatment without surgery. Among the 53 patients who underwent surgery, 51 (96.2%) had sphincter preservation, 3 had Clavien–Dindo grade III complications, and no mortality occurred. The complete response rate for the entire cohort was 23.4%. Moreover, 47 patients (74.6%) had a neoadjuvant rectal score of < 16 after treatment. After a median follow-up time of 32.01 months, 6 (9.3%) had local recurrence, and 17 (26.6%) had distant metastasis. The 3-year OS, DFS and stoma–free rates were 89.5%, 65.5%, and 78.1% respectively.

Conclusion

SCRT followed by oxaliplatin-based consolidation chemotherapy is safe and effective for tumor downstaging in LARC, further improving the sphincter preservation rate.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1 
Fig. 2 
Fig. 3 
Fig. 4 

Similar content being viewed by others

Data availability

The datasets generated and analyzed during the current study available from the corresponding author on reasonable request.

References

  1. Sung H, Ferlay J, Siegel R et al (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Sauer AG et al (2020) Colorectal cancer statistics, 2020. Ca Cancer J Clin 70:145–164. https://doi.org/10.3322/caac.21601

    Article  PubMed  Google Scholar 

  3. Keller DS, Berho M, Perez R et al (2020) The multidisciplinary management of rectal cancer. Nat Rev Gastroentero 17:414–429. https://doi.org/10.1038/s41575-020-0275-y

    Article  Google Scholar 

  4. IV AA, Koprowski MA, Nabavizadeh N, Tsikitis VL (2022) The evolution of rectal cancer treatment: the journey to total neoadjuvant therapy and organ preservation. Ann Gastroenterol 35:226–233. https://doi.org/10.20524/aog.2022.0712

  5. Guida AM, Sensi B, Formica V et al (2022) Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview. Biol Direct 17:16. https://doi.org/10.1186/s13062-022-00329-7

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kasi A, Abbasi S, Handa S et al (2020) Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer. Jama Netw Open 3:e2030097. https://doi.org/10.1001/jamanetworkopen.2020.30097

  7. Liao CK, Kuo YT, Lin YC et al (2022) Neoadjuvant short-course radiotherapy followed by consolidation chemotherapy before surgery for treating locally advanced rectal cancer: a systematic review and meta-analysis. Curr Oncol 29:3708–3727. https://doi.org/10.3390/curroncol29050297

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rödel C, Martus P, Papadoupolos T et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696. https://doi.org/10.1200/jco.2005.02.1329

  9. George TJ, Allegra CJ, Yothers G (2015) Neoadjuvant rectal (NAR) score: a new surrogate endpoint in rectal cancer clinical trials. Curr Colorectal Cancer Rep 11:275–280. https://doi.org/10.1007/s11888-015-0285-2

  10. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications. Ann Surg 240:205–213. https://doi.org/10.1097/01.sla.0000133083.54934.ae

  11. Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2006) Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Brit J Surg 93:1215–1223. https://doi.org/10.1002/bjs.5506

    Article  CAS  PubMed  Google Scholar 

  12. Ngan SY, Burmeister B, Fisher RJ et al (2012) Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with t3 rectal cancer: trans-tasman radiation oncology group trial 01.04. J Clin Oncol 30:3827–3833. https://doi.org/10.1200/jco.2012.42.9597

    Article  PubMed  Google Scholar 

  13. Pettersson D, Cedermark B, Holm T et al (2010) Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Brit J Surg 97:580–587. https://doi.org/10.1002/bjs.6914

    Article  CAS  PubMed  Google Scholar 

  14. Pettersson D, Lörinc E, Holm T et al (2015) Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg 102:972–978. https://doi.org/10.1002/bjs.9811

    Article  CAS  PubMed  Google Scholar 

  15. Erlandsson J, Holm T, Pettersson D et al (2017) Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol 18:336–346. https://doi.org/10.1016/s1470-2045(17)30086-4

    Article  PubMed  Google Scholar 

  16. van der Valk MJM, Marijnen CAM, van Etten B et al (2020) Compliance and tolerability of short-course radiotherapy followed by preoperative chemotherapy and surgery for high-risk rectal cancer - Results of the international randomized RAPIDO-trial. Radiother Oncol 147:75–83. https://doi.org/10.1016/j.radonc.2020.03.011

    Article  CAS  PubMed  Google Scholar 

  17. Jin J, Tang Y, Hu C et al (2022) Multicenter, randomized, Phase III Trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). J Clin Oncol JCO2101667. https://doi.org/10.1200/jco.21.01667

  18. Thavaneswaran S, Kok PS, Price T (2017) Evaluating the addition of oxaliplatin to single agent fluoropyrimidine in the treatment of locally advanced rectal cancer: a systematic review and meta-analysis. Expert Rev Anticanc 17:965–979. https://doi.org/10.1080/14737140.2017.1369881

    Article  CAS  Google Scholar 

  19. Bahadoer RR, Dijkstra EA, van Etten B et al (2021) 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 22:29–42. https://doi.org/10.1016/s1470-2045(20)30555-6

    Article  CAS  PubMed  Google Scholar 

  20. Chakrabarti D, Rajan S, Akhtar N et al (2021) Short-course radiotherapy with consolidation chemotherapy versus conventionally fractionated long-course chemoradiotherapy for locally advanced rectal cancer: randomized clinical trial. Brit J Surg 108:znab020. https://doi.org/10.1093/bjs/znab020

  21. Markovina S, Youssef F, Roy A et al (2017) Improved metastasis- and disease-free survival with preoperative sequential short-course radiation therapy and FOLFOX chemotherapy for rectal cancer compared with neoadjuvant long-course chemoradiotherapy: results of a matched pair analysis. Int J Radiat Oncol Biology Phys 99:417–426. https://doi.org/10.1016/j.ijrobp.2017.05.048

    Article  Google Scholar 

  22. Ciseł B, Pietrzak L, Michalski W et al (2019) Long-course preoperative chemoradiation vs. 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: Long-term results of the randomized Polish II study. Ann Oncol 30:1298–1303. https://doi.org/10.1093/annonc/mdz186

    Article  PubMed  Google Scholar 

  23. Chapman WC, Kim H, Bauer P et al (2022) Total neoadjuvant therapy with short-course radiation: us experience of a neoadjuvant rectal cancer therapy. Dis Colon Rectum 65:198–206. https://doi.org/10.1097/dcr.0000000000001997

    Article  PubMed  Google Scholar 

  24. Garcia-Aguilar J, Patil S, Gollub MJ et al (2022) Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol 40:2546–2556. https://doi.org/10.1200/jco.22.00032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chin R-I, Roy A, Pedersen KS et al (2022) Clinical complete response in patients with rectal adenocarcinoma treated with short-course radiation therapy and non-operative management. Int J Radiat Oncol Biology Phys 112:715–725. https://doi.org/10.1016/j.ijrobp.2021.10.004

    Article  Google Scholar 

  26. Bahadoer R, Dijkstra E (2022) Patterns of locoregional failure and distant metastases in patients treated for locally advanced rectal cancer in the RAPIDO trial. Eur J Surg Oncol 48:e34. https://doi.org/10.1016/j.ejso.2021.12.439

  27. Conroy T, Bosset JF, Etienne PL et al (2021) Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 22:702–715. https://doi.org/10.1016/s1470-2045(21)00079-6

    Article  CAS  PubMed  Google Scholar 

  28. Fokas E, Schlenska-Lange A, Polat B et al (2022) Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for patients with locally advanced rectal cancer. Jama Oncol 8:e215445. https://doi.org/10.1001/jamaoncol.2021.5445

  29. ClinicalTrials.Gov. Available online: https://clinicaltrials.gov/ct2/show/NCT05253846. Accessed on 6 Jan 2023

  30. ClinicalTrials.Gov. Available online: https://clinicaltrials.gov/ct2/show/NCT04246684. Accessed on 6 Jan 2023

  31. Fokas E, Fietkau R, Hartmann A et al (2018) Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial. Ann Oncol 29:1521–1527. https://doi.org/10.1093/annonc/mdy143

    Article  CAS  PubMed  Google Scholar 

  32. Huang WS, Kuan FC, Lin MH et al (2020) Prognostic significance of neoadjuvant rectal scores in preoperative short-course radiotherapy and long-course concurrent chemoradiotherapy for patients with locally advanced rectal cancer. Ann Surg Oncol 27:4309–4318. https://doi.org/10.1245/s10434-020-09018-z

    Article  PubMed  Google Scholar 

  33. Lim YJ, Song C, Jeon SH et al (2021) Risk stratification using neoadjuvant rectal score in the era of neoadjuvant chemoradiotherapy: validation with long-term outcome data. Dis Colon Rectum 64:60–70. https://doi.org/10.1097/dcr.0000000000001777

    Article  PubMed  Google Scholar 

  34. Dijkstra EA, Nilsson PJ, Hospers GAP et al (2023) Locoregional Failure During and After Short-course Radiotherapy followed by Chemotherapy and Surgery Compared to Long-course Chemoradiotherapy and Surgery - A Five-year Follow-up of the RAPIDO Trial [published online ahead of print, 2023 Jan 20]. Ann Surg. https://doi.org/10.1097/SLA.0000000000005799

  35. Romesser PB, Park BK, Nemirovsky D et al (2023) Organ preservation and total neoadjuvant therapy for rectal cancer: Investigating long-course chemoradiation versus short-course radiation therapy. J Clin Oncol 41:10–10. https://doi.org/10.1200/jco.2023.41.4_suppl.10

    Article  Google Scholar 

  36. Glynne-Jones R, Hollingshead J (2023) TNT and local recurrence in the RAPIDO trial — untangling the puzzle. Nat Rev Clin Oncol 1–2. https://doi.org/10.1038/s41571-023-00751-4

Download references

Acknowledgements

The authors would like to thank the medical team at Chang Gung Memorial Hospital including the colorectal departments and the surgeons, nurses and specialized nurses, oncologists, radiologists, radio-oncologists, and pathologists.

Author information

Authors and Affiliations

  1. Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou, No. 5, Fuxing St., Guishan Dist., Taoyuan, 333, Taiwan

    Chun-Kai Liao, Ya-Ting Kuo, Yu-Jen Hsu, Yih-Jong Chern, Yueh-Chen Lin, Pao-Shiu Hsieh, Jy-Ming Chiang, Chien‐Yuh Yeh & Jeng-Fu You

  2. School of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan, 333, Taiwan

    Chun-Kai Liao, Yu-Jen Hsu, Pao-Shiu Hsieh, Jy-Ming Chiang, Chien‐Yuh Yeh & Jeng-Fu You

  3. Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital, Keelung Branch, No. 222, Maijin Rd., Anle Dist., Keelung City, 204, Taiwan

    Yen-Lin Yu

Authors
  1. Chun-Kai Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ya-Ting Kuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yu-Jen Hsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yih-Jong Chern
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yen-Lin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yueh-Chen Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pao-Shiu Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jy-Ming Chiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chien‐Yuh Yeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeng-Fu You
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Chun-Kai Liao conceived the study design. Ya-Ting Kuo, Yih-Jong Chern, Yu-Jen Hsu, Yueh-Chen Lin, and Yen-lin Yu acquired the data for the study. Chun-Kai Liao, Pao-Shiu Hsieh, and Jy-Ming Chiang analysed and interpreted the data. Chun-Kai Liao drafted the manuscript. Chien‐Yuh Yeh and Jeng-Fu You revised the manuscript critically. All authors have read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Jeng-Fu You.

Ethics declarations

Ethics approval

This study was approved by the Human Investigation Committee of Chang Gung Memorial Hospital (approval number: 202101444B0).

Consent to participate

The requirement for informed consent was waived owing to the study's retrospective nature.

Competing interest

The authors have no competing interests to declare that are relevant to the content of this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (TIFF 93 KB)

Supplementary file2 (DOCX 19 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liao, CK., Kuo, YT., Hsu, YJ. et al. Effect of short-course radiotherapy followed by oxaliplatin-based consolidation chemotherapy on organ preservation in locally advanced rectal cancer. Int J Colorectal Dis 38, 92 (2023). https://doi.org/10.1007/s00384-023-04388-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00384-023-04388-8

Keynotes

Search

Navigation