Outcomes of neoadjuvant chemoradiotherapy for locally advanced rectal cancer under non‑smoking conditions confirmed by measuring expiratory CO levels: An observational study

Inoue,Akira; Kagawa,Yoshinori; Nishizawa,Yujiro; Komori,Takamichi; Hashimoto,Masahiro; Ozato,Yuki; Morimoto,Yoshihiro; Shimamoto,Shigetoshi; Miyazaki,Yasuhiro; Tomokuni,Akira; Motoori,Masaaki; Fujitani,Kazumasa

doi:10.3892/ol.2025.15012

Outcomes of neoadjuvant chemoradiotherapy for locally advanced rectal cancer under non‑smoking conditions confirmed by measuring expiratory CO levels: An observational study

Authors:
- Akira Inoue
- Yoshinori Kagawa
- Yujiro Nishizawa
- Takamichi Komori
- Masahiro Hashimoto
- Yuki Ozato
- Yoshihiro Morimoto
- Shigetoshi Shimamoto
- Yasuhiro Miyazaki
- Akira Tomokuni
- Masaaki Motoori
- Kazumasa Fujitani
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Affiliations: Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Osaka 558‑8558, Japan, Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo 662‑0918, Japan, Department of Radiation Oncology, Osaka General Medical Center, Osaka, Osaka 558‑8558, Japan
Published online on: April 2, 2025 https://doi.org/10.3892/ol.2025.15012
Article Number: 266
Copyright: © Inoue et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The outcomes of neoadjuvant chemoradiotherapy (CRT) under non‑smoking conditions in patients with locally advanced rectal cancer (LARC) remain unclear. The aim of the present study was to evaluate the outcomes in patients with LARC who underwent neoadjuvant CRT under non‑smoking conditions, followed by total mesorectal excision (TME). To this end, the medical records of 28 patients treated with CRT and surgery for LARC between January 2014 and December 2019 were retrospectively analyzed. Smoking cessation was monitored by measuring carbon monoxide (CO) levels using a Smokerlyzer. Survival outcomes and clinicopathological factors associated with pathological complete response (pCR) were investigated. The median age was 66 (45‑89) years, and 20 (71.4%) patients were male. A total of 16 (57.1%) patients were diagnosed with clinical stage III LARC. Seven patients smoked at diagnosis, with an average expiratory CO level of 8 (8‑30) ppm. These patients ceased smoking and maintained exhaled CO levels <3 ppm before treatment. All patients successfully underwent CRT and TME. No major postoperative complications occurred. pCR was achieved in 8/28 patients (28.6%) and the 5‑year recurrence‑free and overall survival rates were 78.0% [95% confidence interval (CI), 57.4‑89.5] and 85.7% (95% CI, 66.3‑94.4), respectively. The median follow‑up period was 60.1 (range, 5.6‑114.6) months. Survival did not significantly differ between smokers and non‑smokers at diagnosis. Clinically negative N stage (hazard ratio: 18.9; 95% CI, 1.63‑218; P=0.0187) was significantly associated with pCR. In conclusion, neoadjuvant CRT under non‑smoking conditions, as confirmed by measuring expiratory CO levels, followed by TME yields favorable pCR rates and survival outcomes in patients with LARC.

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1	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
2	Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, et al: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 351:1731–1740. 2004. View Article : Google Scholar : PubMed/NCBI
3	Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Garrido-Laguna I, et al: NCCN guidelines insights: Rectal cancer, version 6.2020. J Natl Compr Canc Netw. 18:806–815. 2020. View Article : Google Scholar : PubMed/NCBI
4	Rallis KS, Lai Yau TH and Sideris M: Chemoradiotherapy in cancer treatment: Rationale and clinical applications. Anticancer Res. 41:1–7. 2021. View Article : Google Scholar : PubMed/NCBI
5	Tatekawa S, Shimamoto S, Miyata Y, Yoshino Y, Hirata T, Tamari K, Seo Y, Isohashi F, Yamamoto Y, Uno A, et al: Monitoring expiratory carbon monoxide to study the effect of complete smoking cessation on definitive radiation therapy for early stage glottic carcinoma. Acta Oncol. 60:582–588. 2021. View Article : Google Scholar : PubMed/NCBI
6	Lerman J, Hennequin C, Etienney I, Abramowitz L, Goujon G, Gornet JM, Guillerm S, Aparicio T, Valverde A, Cattan P and Quéro L: Impact of tobacco smoking on the patient's outcome after (chemo)radiotherapy for anal cancer. Eur J Cancer. 141:143–151. 2020. View Article : Google Scholar : PubMed/NCBI
7	Japanese Society for Cancer of the Colon and Rectum, . Japanese classification of colorectal, appendiceal, and anal carcinoma: The 3d English edition [secondary publication]. J Anus Rectum Colon. 3:175–195. 2019. View Article : Google Scholar : PubMed/NCBI
8	Deveci SE, Deveci F, Açik Y and Ozan AT: The measurement of exhaled carbon monoxide in healthy smokers and non-smokers. Respir Med. 98:551–556. 2004. View Article : Google Scholar : PubMed/NCBI
9	Nordsmark M and Overgaard J: Tumor hypoxia is independent of hemoglobin and prognostic for loco-regional tumor control after primary radiotherapy in advanced head and neck cancer. Acta Oncol. 43:396–403. 2004. View Article : Google Scholar : PubMed/NCBI
10	Browman GP, Wong G, Hodson I, Sathya J, Russell R, McAlpine L, Skingley P and Levine MN: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med. 328:159–163. 1993. View Article : Google Scholar : PubMed/NCBI
11	Akagi T, Inomata M, Fujishima H, Fukuda M, Konishi T, Tsukamoto S, Teraishi F, Ozawa H, Tanaka K, Hida K, et al: Preoperative chemoradiotherapy versus surgery alone for advanced low rectal cancer: A large multicenter cohort study in Japan. Surg Today. 50:1507–1514. 2020. View Article : Google Scholar : PubMed/NCBI
12	Huh JW, Kim HR and Kim YJ: Clinical prediction of pathological complete response after preoperative chemoradiotherapy for rectal cancer. Dis Colon Rectum. 56:698–703. 2013. View Article : Google Scholar : PubMed/NCBI
13	Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, et al: Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: A pooled analysis of individual patient data. Lancet Oncol. 11:835–844. 2010. View Article : Google Scholar : PubMed/NCBI
14	Sadahiro S, Suzuki T, Tanaka A, Okada K, Saito G, Kamijo A, Akiba T and Kawada S: Phase II study of preoperative concurrent chemoradiotherapy with S-1 plus bevacizumab for locally advanced resectable rectal adenocarcinoma. Oncology. 88:49–56. 2015. View Article : Google Scholar : PubMed/NCBI
15	Tomono A, Yamashita K, Kanemitsu K, Sumi Y, Yamamoto M, Kanaji S, Imanishi T, Nakamura T, Suzuki S, Tanaka K and Kakeji Y: Prognostic significance of pathological response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Int J Clin Oncol. 21:344–349. 2016. View Article : Google Scholar : PubMed/NCBI
16	Garland ML, Vather R, Bunkley N, Pearse M and Bissett IP: Clinical tumour size and nodal status predict pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis. 29:301–307. 2014. View Article : Google Scholar : PubMed/NCBI
17	Huang CM, Huang CW, Ma CJ, Yeh YS, Su WC, Chang TK, Tsai HL, Juo SH, Huang MY and Wang JY: Predictive value of FOLFOX-based regimen, long interval, hemoglobin levels and clinical negative nodal status, and postchemoradiotherapy CEA levels for pathological complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy. J Oncol. 2020:94376842020. View Article : Google Scholar : PubMed/NCBI
18	Al-Sukhni E, Attwood K, Mattson DM, Gabriel E and Nurkin SJ: Predictors of pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Ann Surg Oncol. 23:1177–1186. 2016. View Article : Google Scholar : PubMed/NCBI
19	Berardi R, Braconi C, Mantello G, Scartozzi M, Del Prete S, Luppi G, Martinelli R, Fumagalli M, Valeri G, Bearzi I, et al: Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. Ann Oncol. 17:1661–1664. 2006. View Article : Google Scholar : PubMed/NCBI
20	Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, et al: 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. 2021. View Article : Google Scholar : PubMed/NCBI
21	Asoglu O, Bulut A, Aliyev V, Piozzi GN, Guven K, Bakır B and Goksel S: Chemoradiation and consolidation chemotherapy for rectal cancer provides a high rate of organ preservation with a very good long-term oncological outcome: A single-center cohort series. World J Surg Oncol. 20:3582022. View Article : Google Scholar : PubMed/NCBI
22	Asoglu O, Goksoy B, Aliyev V, Mustafayev TZ, Atalar B, Bakir B, Guven K, Demir G and Goksel S: Watch and wait strategy for rectal cancer: How long should we wait for a clinical complete response? Surg Technol Int. 40:130–139. 2022. View Article : Google Scholar : PubMed/NCBI
23	Aliyev V, Goksel S, Bakir B, Guven K and Asoglu O: Sphincter-saving robotic total mesorectal excision provides better mesorectal specimen and good oncological local control compared with laparoscopic total mesorectal excision in male patients with mid-low rectal cancer. Surg Technol Int. 38:160–166. 2021.PubMed/NCBI
24	Aliyev V, Piozzi GN, Shadmanov N, Guven K, Bakır B, Goksel S and Asoglu O: Robotic and laparoscopic sphincter-saving resections have similar peri-operative, oncological and functional outcomes in female patients with rectal cancer. Updates Surg. 75:2201–2209. 2023. View Article : Google Scholar : PubMed/NCBI
25	Aliyev V, Piozzi GN, Huseynov E, Mustafayev TZ, Kayku V, Goksel S and Asoglu O: Robotic male and laparoscopic female sphincter-preserving total mesorectal excision of mid-low rectal cancer share similar specimen quality, complication rates and long-term oncological outcomes. J Robot Surg. 17:1637–1644. 2023. View Article : Google Scholar : PubMed/NCBI