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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 2/2017

01-02-2017 | Research Article

Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer

Authors: F. Alongi, S. Fersino, R. Mazzola, A. Fiorentino, N. Giaj-Levra, F. Ricchetti, R. Ruggieri, G. Di Paola, M. Cirillo, S. Gori, M. Salgarello, G. Zamboni, G. Ruffo

Published in: Clinical and Translational Oncology | Issue 2/2017

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Abstract

Background

To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer.

Methods

A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0–1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week.

Results

Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5–51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8–12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78–0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55–0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05).

Conclusion

Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary.
Literature
1.
Trial Swedish Rectal Cancer. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336(14):980–7.CrossRef
2.
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):1926–33.CrossRefPubMed
3.
Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–20.CrossRefPubMedPubMedCentral
4.
Tural D, Selcukbiricik F, Yıldız Ö, Elcin O, Erdamar S, Güney S, et al. Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer. Int J Clin Oncol. 2014;19(5):889–96.CrossRefPubMed
5.
Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99(7):918–28.CrossRefPubMed
6.
Mazzola R, Ferrera G, Cucchiara T, Figlia V, Gueci M, Sciumè F, et al. Sequential boost in neoadjuvant irradiation for T3N0-1 rectal cancer: long term results from a mono-institutional experience. Tumori Journal. 2016;. doi:10.​5301/​tj.​5000481.
7.
Jakobsen A, Ploen J, Vuong T, Appelt A, Lindebjerg J, Rafaelsen SR. Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses. Int J Radiat Oncol Biol Phys. 2012;84(4):949–54.CrossRefPubMed
8.
Myerson RJ, Valentini V, Birnbaum EH, Cellini N, Coco C, Fleshman JW, et al. A phase I/II trial of three dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma. Int J Radiat Oncol Biol Phys. 2001;50:1299–308.CrossRefPubMed
9.
Hernando-Requejo O, Lopez M, Cubillo A, Rodriguez A, Ciervide R, Valero J, et al. Complete pathological responses in locally advanced rectal cancer after preoperative IMRT and integrated-boost chemoradiation. Strahlenther Onkol. 2014;190(6):515–20.CrossRefPubMed
10.
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):1981–7.CrossRefPubMed
11.
Taylor FG, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease free survival and local recurrence: 5 years follow up results of the Mercury study. J Clin Oncol. 2014;32(1):34–43.CrossRefPubMed
12.
Perez RO, Habr-Gama A, Gama-Rodrigues J, Proscurshim I, Julião GP, Lynn P, et al. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683). Cancer. 2012;118(14):3501–11.CrossRefPubMed
13.
Ueno M, Oya M, Azekura K, Yamaguchi T, Muto T. Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer. Br J Surg. 2005;92:756–63.CrossRefPubMed
14.
Sato H, Maeda K, Masumori K, Koide Y. Who can get the beneficial effect from lateral lymph node dissection for Duke C rectal carcinoma below the peritoneal reflection? Dis Colon Rectum. 2006;49:S3–12.CrossRefPubMed
15.
Erdi YE, Mawlawi O, Larson SM, Imbriaco M, Yeung H, Finn R, Humm JL. Segmentation of lung lesion volume by adaptive positron emission tomography image thresholding. Cancer. 1997;80(12 Suppl):2505–9.CrossRefPubMed
16.
Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88(4):822–8.CrossRefPubMed
17.
Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JC, et al. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015;16(8):919–27.CrossRefPubMed
18.
Burbach JP, den Harder AM, Intven M, van Vulpen M, Verkooijen HM, Reerink O. Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis. Radiother Oncol. 2014;113(1):1–9.CrossRefPubMed
19.
Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516.CrossRefPubMed
20.
Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93:1215–23.CrossRefPubMed
21.
Wagman R, Minsky BD, Cohen AM, Guillem JG, Paty PP. Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up. Int J Radiat Oncol Biol Phys 1998; 42(1):51–7.
22.
Lefevre JH, Parc Y, Tiret E, French Research Group of Rectal Cancer Surgery (GRECCAR). Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer. Ann Surg. 2015;262(6):e116.CrossRefPubMed
23.
Petrelli F, Sgroi G, Sarti E, Barni S. Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer a meta-analysis of published studies. Ann Surg. 2016;263(3):458–64.CrossRefPubMed
24.
Avallone A, Aloj L, Caracò C, Delrio P, Pecori B, Tatangelo F, et al. Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome. Eur J Nucl Med Mol Imaging. 2012;39(12):1848–57.CrossRefPubMed
25.
Leccisotti L, Gambacorta MA, de Waure C, Stefanelli A, Barbaro B, Vecchio FM, et al. The predictive value of 18F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy. Eur J Nucl Med Mol Imaging. 2015;42(5):657–66.CrossRefPubMed
26.
Jo HJ, Kim SJ, Lee HY, Kim IJ. Prediction of survival and cancer recurrence using metabolic volumetric parameters measured by 18F-FDG PET/CT in patients with surgically resected rectal cancer. Clin Nucl Med. 2014;39(6):493–7.PubMed
27.
Alongi F, Mazzola R, Ricchetti F, Fersino S, Levra NG, Fiorentino A, et al. Volumetric-modulated arc therapy with vaginal cuff simultaneous integrated boost as an alternative to brachytherapy in adjuvant irradiation for endometrial cancer: a prospective study. Anticancer Res. 2015;35(4):2149–55.PubMed
28.
Alongi F, Fogliata A, Navarria P, Tozzi A, Mancosu P, Lobefalo F, et al. Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy (RapidArc) for prostate cancer. Report of feasibility and acute toxicity. Strahlenther Onkol. 2012;188(11):990–6.CrossRefPubMed
29.
Mazzola R, Fersino S, Fiorentino A, Ricchetti F, Giaj Levra N, Di Paola G, et al. The impact of prostate gland dimension in genitourinary toxicity after definitive prostate cancer treatment with moderate hypofractionation and volumetric modulated arc radiation therapy. Clin Transl Oncol. 2016;18(3):317–21.CrossRefPubMed
30.
Otto K. Volumetric modulated arc therapy: IMRT in a single gantry arc. Med Phys. 2008;35(1):310–7.CrossRefPubMed
31.
Stanic S, Mayadev JS. Tolerance of the small bowel to therapeutic irradiation: a focus on late toxicity in patients receiving para-aortic nodal irradiation for gynecologic malignancies. Int J Gynecol Cancer. 2013;23(4):592–7.CrossRefPubMed
32.
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;351:1731–40.CrossRefPubMed
33.
Gerard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.CrossRefPubMed
Metadata
Title
Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer
Authors
F. Alongi
S. Fersino
R. Mazzola
A. Fiorentino
N. Giaj-Levra
F. Ricchetti
R. Ruggieri
G. Di Paola
M. Cirillo
S. Gori
M. Salgarello
G. Zamboni
G. Ruffo
Publication date
01-02-2017
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 2/2017
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-016-1522-0

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