Abstract
Purpose
The effect of neoadjuvant chemoradiotherapy (CRT) and the relationship between pathological complete response (pCR) with clinical outcomes has been evaluated in elderly locally advanced rectal cancer (LARC) patients.
Methods
We retrospectively analyzed 117 LARC patients treated with conformal RT and concomitant fluoropirimidine-based chemotherapy. A dose of 4500 cGy, on the pelvis, up to 5500 cGy on the tumor was delivered. Multidisciplinary evaluation, including geriatric assessment, was previously performed to identify frail patients unsuitable for combined treatment.
Results
The median age was 75 (range 70–88 years), and 103 (88%) patients had ECOG Performance Status (PS) = 0. All patients except one completed CRT. Ten (8.5%) patients temporarily suspended CRT for acute severe hematologic complication, diarrhea and/or proctitis and hypokalemia. Of the 103 operated patients (88%), a pCR, according to Mandard tumor regression grade (TRG) score, was obtained in 28 patients (27.2%), with TRG1-2 rate of 43.7%. The 3- and 5-year overall survival (OS) rates were 80.2% ± 4.2% and 68.0% ± 5.2%, 72.4% ± 4.5% and 57.8% ± 5.2% for disease-free survival (DFS), and 92.2% ± 2.8% and 89.5% ± 3.9% for loco-regional control. Patients with TRG1-2 had 3- and 5-year OS rates of 84.1% ± 6.6% and 84.1% ± 6.6% compared with 82.8% ± 5.5% and 67.7% ± 7.2% for patients with TRG3-5 (p = 0.012). The 3- and 5-year DFS rates for patients with TRG1-2 were 77.6% ± 7.0% and 74.2% ± 7.5% compared with 70.9% ± 6.3% and 54.7% ± 7.3% for patients with TRG3-5 (p = 0.009).
Conclusion
Our results reported good tolerability and clinical outcomes of neoadjuvant CRT, with a benefit in patients ≥ 70 years, confirming the prognostic role of pCR on clinical outcomes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Åsli LM, Johannesen TB, Myklebust TÅ, Møller B, Eriksen MT, Guren MG (2017) Preoperative chemoradiotherapy for rectal cancer and impact on outcomes—a population-based study. Radiother Oncol 123:446–453. https://doi.org/10.1016/j.radonc.2017.04.012
Balducci L (2006) Management of cancer in the elderly. Oncology (Williston Park) 20:135–143 (discussion 144, 146, 151-2, 2006)
Bergquist JR, Thiels CA, Shubert CR, Habermann EB, Hayman AV, Zielinski MD, Mathis KL (2016) Is chemotherapy or radiation therapy in addition to surgery beneficial for locally advanced rectal cancer in the elderly? A national cancer data base (NCDB) study. World J Surg 40:447–455. https://doi.org/10.1007/s00268-015-3319-7
Bhangu A, Kiran RP, Audisio R, Tekkis P (2014) Survival outcome of operated and non-operated elderly patients with rectal cancer: a surveillance, epidemiology, and end results analysis. Eur J Surg Oncol 40:1510–1516. https://doi.org/10.1016/j.ejso.2014.02.239
Cai X, Wu H, Peng J, Zhu J, Cai S, Cai G, Zhang Z (2013) Tolerability and outcomes of radiotherapy or chemoradiotherapy for rectal cancer in elderly patients aged 70 years and older. Radiat Oncol 8:86. https://doi.org/10.1186/1748-717X-8-86
Choi Y, Kim JH, Kim JW, Kim JW, Lee KW, Oh HK, Kim DW, Kang SB, Song C, Kim JS (2016) Preoperative chemoradiotherapy for elderly patients with locally advanced rectal cancer-a real-world outcome study. Jpn J ClinOncol 46:1108–1117. https://doi.org/10.1093/jjco/hyw126
Cox DR (1972) Regression models and life-tables. J R Stat Soc Ser B34:187–220
Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346. https://doi.org/10.1016/0360-3016(95)00060-C
Cancer research UK - CRUK (2020) Cancer incidence by age. Available at https://www.cancerresearchuk.org/cancerinfo/cancerstats/incidence/age/#Cancer
François E, Azria D, Gourgou-Bourgade S, Jarlier M, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Seitz JF, Conroy T, Juzyna B, Gerard JP (2014) Results in the elderly with locally advanced rectal cancer from the ACCOR12/PRODIGE 2 phase III trial: tolerance and efficacy. Radiother Oncol 110:144–149. https://doi.org/10.1016/j.radonc.2013.10.019
Guillerme F, Clavier JB, Nehme-Schuster H, Leroy V, Heitz D, Schumacher C, Abdelghani M, Brigand C, Kurtz JE, Noël G (2014) Age impacts the pattern of care for elderly patients with rectal cancer. Int J Colorectal Dis 29:157–163. https://doi.org/10.1007/s00384-013-1778-6
Jiang DM, Raissouni S, Mercer J, Kumar A, Goodwin R, Heng DY, Tang PA, Doll C, MacLean A, Powell E, Price-Hiller J, Monzon J, Cheung WY, Vickers MM (2015) Clinical outcomes of elderly patients receiving neoadjuvant chemoradiation for locally advanced rectal cancer. Ann Oncol 26:2102–2106. https://doi.org/10.1093/annonc/mdv331
Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ, Dutch Colorectal Cancer Group (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638–646. https://doi.org/10.1056/NEJMoa010580
Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RGH GH, Beets GL (2010) 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. https://doi.org/10.1016/S1470-2045(10)70172-8
Margalit DN, Mamon HJ, Ancukiewicz M, Kobayashi W, Ryan DP, Blaszkowsky LS, Clark J, Willett CG, Hong TS (2011) Tolerability of combined modality therapy for rectal cancer in elderly patients aged 75 years and older. Int J Radiat Oncol Biol Phys 81:e735–e741. https://doi.org/10.1016/j.ijrobp.2010.12.056
Martijn H, Vulto JC (2007) Should radiotherapy be avoided or delivered differently in elderly patients with rectal cancer? Eur J Cancer 43:2301–2306. https://doi.org/10.1016/j.ejca.2007.06.014
Martin ST, Heneghan HM, Winter DC (2012) Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg 99:918–928. https://doi.org/10.1002/bjs.8702
Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Köhne C-H, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M (2015) Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 26:463–476. https://doi.org/10.1093/annonc/mdu253
Pfeffer MR, Blumenfeld P (2017) The changing paradigm of radiotherapy in the elderly population. Cancer J 23:223–230. https://doi.org/10.1097/PPO.0000000000000271
Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C (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
Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study Group (2004) Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. N Engl J Med 351:1731–1740. https://doi.org/10.1056/NEJMoa040694
Scheithauer W, McKendrick J, Begbie S, Borner M, Burns WI, Burris HA, Cassidy J, Jodrell D, Koralewski P, Levine EL, Marschner N, Maroun J, Garcia-Alfonso P, Tujakowski J, Van Hazel G, Wong A, Zaluski J, Twelves C, X-ACT Study Group (2003) Oral capecitabine as an alternative to i.v. 5-fluorouracil- based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial. Ann Oncol 14:1735–1743. https://doi.org/10.1093/annonc/mdg500
Shahir MA, Lemmens VE, van de Poll-Franse LV, Voogd AC, Martijn H, Janssen-Heijnen ML (2006) Elderly patients with rectal cancer have a higher risk of treatment-related complications and a poorer prognosis than younger patients: a population-based study. Eur J Cancer 42:3015–3021. https://doi.org/10.1016/j.ejca.2005.10.032
Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30. https://doi.org/10.3322/caac.21166
Sung SY, Jang HS, Kim SH, Jeong JU, Jeong S, Song JH, Chung MJ, Cho HM, Kim HJ, Kim JG, Lee IK, Lee JH (2019) Oncologic outcome and morbidity in the elderly rectal cancer patients after preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional and case-matched control study. Ann Surg 269:108–113. https://doi.org/10.1097/SLA.0000000000002443
Teoh S, Muirhead R (2016) Rectal radiotherapy–intensity-modulated radiotherapy delivery, delineation and doses. Clin Oncol (R Coll Radiol) 28:93–102. https://doi.org/10.1016/j.clon.2015.10.012
Tougeron D, Roullet B, Paillot B, Hamidou H, Tourani JM, Bensadoun RJ, Michel P, Silvain C (2014) Safety and outcome of chemoradiotherapy in elderly patients with rectal cancer: results from two French tertiary centres. Dig Liver Dis 44:350–354. https://doi.org/10.1016/j.dld.2011.10.017
Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M, Miccichè F, Ricci R, Morganti AG, Gambacorta MA, Maurizi F, Coco C (2005) The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 62:752–760. https://doi.org/10.1016/j.ijrobp.2004.11.017
Vironen JH, Sainio P, Husa AI, Kellokumpu IH (2004) Complications and survival after surgery for rectal cancer in patients younger than and aged 75 years or older. Dis Colon Rectum 47:1225–1231. https://doi.org/10.1007/s10350-004-0557-4
Author information
Authors and Affiliations
Contributions
LC, MT, GAC and DG designed and coordinate the study and the analysis. CR, LG, FCDG, ADP and SC collected the data. MDT and LC reviewed and approved data selection. CR and LC performed main data analysis and provided pictures elaboration. MM and MDN performed statistical data analysis. CR, MDT and LC drafted the manuscript. MT, CL and DG critically revised the study and the manuscript. All authors reviewed and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
None.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rosa, C., Di Tommaso, M., Caravatta, L. et al. Clinical outcomes in elderly rectal cancer patients treated with neoadjuvant chemoradiotherapy: impact of tumor regression grade. J Cancer Res Clin Oncol 147, 1179–1188 (2021). https://doi.org/10.1007/s00432-020-03403-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-020-03403-7