Long-term results of randomized studies on the use of a gentamicin-collagen sponge in rectal cancer – depending on the length of time between the completion of radiotherapy and the surgery
Abstract
Introduction. Two randomized studies on the use of a gentamicin-collagen sponge (GRM01/1997 and GRM02/2007) in rectal cancer surgery showed a statistically significant decrease in the rate of distant metastases in the experimental group and a similar rate of local recurrences. The objective of the presented study was a retrospective evaluation of the effect of the GRM use on the observed rate of generalized recurrences, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) – depending on the length of the interval between radiotherapy and surgery.
Materials and methods. The study comprised 239 patients, included previously into randomized studies, in whom the 5 x 5 Gy radiotherapy was used. In 204 people, the surgery was made within 7 days of the completion of radiotherapy (group A). The remaining group of 35 patients were operated on after 4–8 weeks (group B). The follow-up period was 5 years. The statistical analysis was made with the Kaplan-Meier test. The value of α = 0.05 was degfined as the threshold of statistical significance.
Results. In both groups, there were no statistical differences between the patients operated on with the use of GRM and those operated on without the use of GRM. The analysis took into consideration the most significant parameters, which could affect the oncological results, (ypTNM, lympho-vascular invasion (LVI), blood vessel invasion (BVI). In group A, the use of GRM was connected with a lower rate of metachronic distant metastases (p = 0.002; RR 0.41; 95% CI [0.24–0.72]), the prolongation of DFS (p = 0.008; HR 2.16; 95% CI [1.20–3.83]) and of CSS (p = 0.010; HR 2.37; 95% CI [1.20–4. 67]). No such relationships were observed in group B.
Conclusions. The use of GRM decreases the risk of distant metastases and has an influence on the prolongation of recurrence free survival, but only when surgery is carried out within 7 days of the completion of irradiation.
Keywords: rectal cancerradiotherapygentamicin-collagen sponge
References
- Nowacki MP, Rutkowski A, Oledzki J, et al. Prospective, randomized trial examining the role of gentamycin-containing collagen sponge in the reduction of postoperative morbidity in rectal cancer patients: early results and surprising outcome at 3-year follow-up. Int J Colorectal Dis. 2005; 20(2): 114–120.
- Rutkowski A, Pietrzak L, Kryński J, et al. The gentamicin-collagen implant and the risk of distant metastases of rectal cancer following short-course radiotherapy and curative resection: the long-term outcomes of a randomized study. Int J Colorectal Dis. 2018; 33(8): 1087–1096.
- Hanna GG, Coyle VM, Prise KM. Immune modulation in advanced radiotherapies: Targeting out-of-field effects. Cancer Lett. 2015; 368(2): 246–251.
- Grass GD, Krishna N, Kim S. The immune mechanisms of abscopal effect in radiation therapy. Curr Probl Cancer. 2016; 40(1): 10–24.
- Peeters KC, Marijnen CAM, Nagtegaal ID, et al. Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007; 246(5): 693–701.
- Kaytan-Saglam E, Balik E, Saglam S, et al. Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer. J Cancer Res Clin Oncol. 2017; 143(8): 1597–1603.
- Erlandsson J, Holm T, Pettersson D, et al. 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. 2017; 18(3): 336–346.
- Pettersson D, Lörinc E, Holm T, et al. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015; 102(8): 972–8; discussion 978.
- Napolitano M, D'Alterio C, Cardone E, et al. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients. Oncotarget. 2015; 6(10): 8261–8270.
- Habets TH, Oth T, Houben AW, et al. Fractionated Radiotherapy with 3 x 8 Gy Induces Systemic Anti-Tumour Responses and Abscopal Tumour Inhibition without Modulating the Humoral Anti-Tumour Response. PLoS One. 2016; 11(7): e0159515.
- Golden EB, Chhabra A, Chachoua A, et al. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol. 2015; 16(7): 795–803.
- Guipaud O, Jaillet C, Clément-Colmou K, et al. The importance of the vascular endothelial barrier in the immune-inflammatory response induced by radiotherapy. Br J Radiol. 2018; 91(1089): 20170762.
- Jarosz-Biej M, Smolarczyk R, Cichoń T, et al. Tumor Microenvironment as A "Game Changer" in Cancer Radiotherapy. Int J Mol Sci. 2019; 20(13).
- Siva S, MacManus MP, Martin RF, et al. Abscopal effects of radiation therapy: a clinical review for the radiobiologist. Cancer Lett. 2015; 356(1): 82–90.
- Park B, Yee C, Lee KM. The effect of radiation on the immune response to cancers. Int J Mol Sci. 2014; 15(1): 927–943.