POSTOPERATIVE ADJUVANT INTENSITY-MODULATED RADIOTHERAPY FOR RADICALLY RESECTED RECTAL ADENOCARCINOMA: DATA FROM EVERYDAY PRACTICE

Authors

  • Nenad Mitreski University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Snezana Smichkoska University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Biljana Grozdanovska University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Igor Stojkovski University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Violeta Klisarovska University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Emilija Lazarova University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Aleksandar Atevik University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Biljana Mitreska University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia
  • Marina Iljovska University Clinic for Radiotherapy and Oncology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Republic of North Macedonia

Keywords:

rectal adenocarcinoma, adjuvant treatment, Intensity-modulated radiotherapy, acute side effects

Abstract

Introduction: Adjuvant radiochemotherapy is a standard treatment in patients with surgically treated stage II or III rectal adenocarcinoma who did not undergo neoadjuvant radiotherapy. Intensity-modulated radiation therapy (IMRT) was only marginally investigated in postoperative setting.

Material and methods: A longitudinal observational analysis was conducted in patients with radically resected stage II or III rectal adenocarcinoma treated with IMRT at the University Clinic for Radiotherapy and Oncology as part of the adjuvant postoperative treatment. The dose-volume parameters of the radiotherapy plans, as well as acute side effects of 40 patients were analyzed.

Results: The average dose received by the target volume was 49.95 Gy (range 27-54 Gy). The mean volume of peritoneal cavity receiving 45 Gy (V45) was 102.73 cm3 (±52.10), V30 for pelvic bones was 38.3% (±5.48), V40 for bladder 52.48% (±10.9). The most frequent acute side effects were diarrhea in 17 (42.5%), lymphopenia in 34 (85%) and thrombocytopenia in 26 patients (65%). Most of the side effects were self-limiting and caused disruption of the radiation treatment only in 3 patients (7.5%).

Conclusion: Integrating IMRT in the adjuvant treatment of locally advanced rectal cancer provides a good dose distribution and organs at risk sparing. The treatment is well tolerated, the side effects are mainly of lesser degrees and easily managed. A prospective trial comparing IMRT with 3-dimensional conformal radiotherapy is needed to assess whether IMRT offers a better perspective for adjuvant treatment.

References

Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Lawrence Wickerham D, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988; 80(1): 21-29. doi: 10.1093/jnci/80.1.21. PMID: 3276900.

O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994; 331(8): 502-507. doi: 10.1056/NEJM199408253310803. PMID: 8041415.

Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, 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): 1926-1933. doi: 10.1200/JCO.2011.40.1836. Epub 2012 Apr 23. PMID: 22529255.

Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 2009; 27(31): 5124-5130. doi: 10.1200/JCO.2009.22.0467. Epub 2009 Sep 21. PMID: 19770376; PMCID: PMC2773471.

Al‐Sukhni E, Milot L, Fruitman M, Beyene J, Victor JC, Schmocker Set, et al. Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta‐analysis. Ann Surg Oncol 2012; 19(7): 2212‐2223. doi: 10.1245/s10434-011-2210-5. Epub 2012 Jan 20. PMID: 22271205.

Brouwer NPM, Stijns RCH, Lemmens V, Nagtegaal ID, Beets-Tan RGH, Fütterer JJ, et al. Clinical lymph node staging in colorectal cancer; a flip of the coin? Eur J Surg Oncol 2018; 44(8): 1241‐1246. doi: 10.1016/j.ejso.2018.04.008. Epub 2018 Apr 17. PMID: 29739638.

Guerrero Urbano MT, Henrys AJ, Adams EJ, Norman AR, Bedford JL, Harrington KJ, et al. Intensity-modulated radiotherapy in patients with locally advanced rectal cancer reduces volume of bowel treated to high dose levels. Int J Radiat Oncol Biol Phys 2006; 65(3): 907-916. doi: 10.1016/j.ijrobp.2005.12.056. PMID: 16751073.

Mok H, Crane CH, Palmer MB, Briere TM, Beddar S, Delclos ME, et al. Intensity modulated radiation therapy (IMRT): differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma. Radiat Oncol 2011; 6(1): 63. doi: 10.1186/1748-717X-6-63. PMID: 21651775; PMCID: PMC3121606.

Parekh A, Truong MT, Pashtan I, Qureshi MM, Martin NE, Nawaz O, et al. Acute gastrointestinal toxicity and tumor response with preoperative intensity modulated radiation therapy for rectal cancer. Gastrointest Cancer Res 2013; 6(5-6): 137-143. PMID: 24312687; PMCID: PMC3849901.

Jabbour SK, Patel S, Herman JM, Wild A, Nagda SN, Altoos T, et al. Intensity-modulated radiation therapy for rectal carcinoma can reduce treatment breaks and emergency department visits. Int J Surg Oncol 2012; 2012: 891067. doi: 10.1155/2012/ 891067. Epub 2012 Aug 13. PMID: 22934164; PMCID: PMC3425793.

Samuelian JM, Callister MD, Ashman JB, Young-Fadok TM, Borad MJ, Gunderson LL. Reduced acute bowel toxicity in patients treated with intensity-modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012; 82(5): 1981-1987. doi: 10.1016/j.ijrobp.2011.01.051. Epub 2011 Apr 7. PMID: 21477938.

LoIudice T, Baxter D, Balint J. Effects of abdominal surgery on the development of radiation enteropathy. Gastroenterology 1977; 73(5): 1093-1097. PMID: 908489.

Lee CY, Chang CC, Yang HY, Chiang PY, Tsang YW. Intensity modulated radiotherapy delivers competitive local control rate with limited acute toxicity in the adjuvant treatment of rectal cancer. Jpn J Clin Oncol 2018; 48(7): 653-660. doi: 10.1093/jjco/hyy075. PMID: 29868768.

Liu WY, Dinapoli N, Wang X, Meldolesi E, Gambacorta MA, Chiloiro G, et al. Possible contribution of IMRT in postoperative radiochemotherapy for rectal cancer: analysis on 1798 patients by prediction model. Oncotarget 2016; 7(29): 46536-46544. PMID: 27340785; PMCID: PMC5216815.

Mavroidis P, Giantsoudis D, Awan MJ, Nijkamp J, Rasch CR, Duppen JC, et al. Consequences of anorectal cancer atlas implementation in the cooperative group setting: radiobiologic analysis of a prospective randomized in silico target delineation study. Radiother Oncol 2014; 112(3): 418-424. doi: 10.1016/j.radonc.2014.05.011. Epub 2014 Jul 1. PMID: 24996454; PMCID: PMC4258107.

Myerson RJ, Garofalo MC, El Naqa I, Abrams RA, Apte A, Bosch WR, et al. Elective clinical target volumes for conformal therapy in anorectal cancer: a radiation therapy oncology group consensus panel contouring atlas. Int J Radiat Oncol Biol Phys 2009; 74(3): 824-830. doi: 10.1016/j.ijrobp.2008.08.070. Epub 2008 Dec 29. PMID: 19117696; PMCID: PMC2709288.

Taylor A, Rockall AG, Reznek RH, Powell ME. Mapping pelvic lymph nodes: guidelines for delineation in intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2005; 63(5): 1604-1612. doi: 10.1016/j.ijrobp.2005.05.062. Epub 2005 Sep 29. PMID: 16198509.

Gay HA, Barthold HJ, O’Meara E, Bosch WR, El Naqa I, Al-Lozi R, et al. Pelvic normal tissue contouring guidelines for radiation therapy: a Radiation Therapy Oncology Group consensus panel atlas. Int J Radioat Oncol Biol Phys 2012; 83(3): e353-e362. doi: 10.1016/j.ijrobp.2012.01.023. Epub 2012 Apr 6. Erratum in: Int J Radiat Oncol Biol Phys 2012 Sep 1; 84(1): 7. PMID: 22483697; PMCID: PMC3904368.

Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010; 76(3 Suppl): S10-S19. doi: 10.1016/j.ijrobp.2009.07.1754. PMID: 20171502; PMCID: PMC4041542.

Robertson JM, Lockman D, Yan D, Wallace M. The dose-volume relationship of small bowel irradiation and acute grade 3 diarrhea during chemoradiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2008; 70(2): 413-418. doi: 10.1016/j. ijrobp.2007.06.066. Epub 2007 Sep 27. PMID: 17904305.

Baglan KL, Frazier RC, Yan D, Huang RR, Martinez AA, Robertson JM. The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys 2002; 52(1): 176-183. doi: 10.1016/s0360-3016(01)01820-x. PMID: 11777636.

Mell LK, Schomas DA, Salama JK, Devisetty K, Aydogan B, Miller RC, et al. Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2008; 70: 1431-1437. doi: 10.1016/j.ijrobp.2007.08.074.

Brixey CJ, Roeske JC, Lujan AE, Yamada SD, Rotmensch J, Mundt AJ. Impact of intensity modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies. Int J Radiat Oncol Biol Phys 2002; 54(5): 1388-1396. doi: 10.1016/s0360-3016(02)03801-4. PMID: 12459361.

National Cancer Institute (U.S.). Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Bethesda, Md: U.S. Department of Health and Human services, National Institutes of Health, National Cancer Institute; 2009.

Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351(17): 1731-1740. doi: 10.1056/NEJMoa040694. PMID: 15496622.

Ng SY, Colborn KL, Cambridge L, Hajj C, Yang TJ, Wu AJ, et al. Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer. Radiother Oncol 2016; 121(2): 252-257. doi: 10.1056/NEJMoa040694. PMID: 15496622.

Kim TH, Chie EK, Kim DY, Park SY, Cho KH, Jung KH, et al. Comparison of the belly board device method and the distended bladder method for reducing irradiated small bowel volumes in preoperative radiotherapy of rectal cancer patients. Int J Radiat Oncol Biol Phys 2005; 62(3): 769-775. doi: 10.1016/j.ijrobp.2004.11.015. PMID: 15936558.

Kim JY, Kim DY, Kim TH, Park SY, Lee SB, Shin KH, et al. Intensity-modulated radiotherapy with a belly board for rectal cancer. Int J Colorectal Dis 2007; 22: 373-379. doi: 10.1007/s00384-006-0166-x. Epub 2006 Jun 27. PMID: 16802067.

Beriwal S, Jain SK, Heron DE, de Andrade RS, Lin CJ, Kim H, et al. Dosimetric and toxicity comparison between prone and supine position IMRT for endometrial cancer. Int J Radiat Oncol Biol Phys 2007; 67(2): 485-489. doi: 10.1016/j.ijrobp.2006.08.067. Epub 2006 Nov 2. PMID: 17084548.

Downloads

Published

2022-06-15

Issue

Section

Original Articles