Skip to main content
Top
Published in: Radiation Oncology 1/2018

Open Access 01-12-2018 | Research

Comparing simultaneous integrated boost vs sequential boost in anal cancer patients: results of a retrospective observational study

Authors: Pierfrancesco Franco, Berardino De Bari, Francesca Arcadipane, Alexis Lepinoy, Manuela Ceccarelli, Gabriella Furfaro, Massimiliano Mistrangelo, Paola Cassoni, Martina Valgiusti, Alessandro Passardi, Andrea Casadei Gardini, Elisabetta Trino, Stefania Martini, Giuseppe Carlo Iorio, Andrea Evangelista, Umberto Ricardi, Gilles Créhange

Published in: Radiation Oncology | Issue 1/2018

Login to get access

Abstract

Background

To evaluate clinical outcomes of simultaneous integrated boost (SIB) - intensity modulated radiotherapy (RT) in patients with non metastatic anal cancer compared to those of a set of patients treated with 3-dimensional conformal RT and sequential boost (SeqB).

Methods

A retrospective cohort of 190 anal cancer patients treated at 3 academic centers with concurrent chemo-RT employing either SIB or SeqB was analysed. The SIB-group consisted of 87 patients, treated with 2 cycles of Mitomycin (MMC) and 5-Fluorouracil (5FU) using SIB-IMRT delivering 42-45Gy/28–30 fractions to the elective pelvic lymph nodes and 50.4-54Gy/28-30fractions to the primary tumor and involved nodes, based on pre-treatment staging. The SeqB group comprised 103 patients, treated with MMC associated to either 5FU or Capecitabine concurrent to RT with 36 Gy/20 fractions to a single volume including gross tumor, clinical nodes and elective nodal volumes and a SeqB to primary tumor and involved nodes of 23.4 Gy/13 fractions. We compared colostomy-free survival (CFS), overall survival (OS) and the cumulative incidence of colostomy for each radiation modality. Cox proportional-hazards model addressed factors influencing OS and CFS.

Results

Median follow up was 34 (range 9–102) and 31 months (range 2–101) in the SIB and SeqB groups. The 1- and 2-year cumulative incidences of colostomy were 8.2% (95%CI:3.6–15.2) and 15.0% (95%CI:8.1–23.9) in the SIB group and 13.9% (95%CI: 7.8–21.8) and 18.1% (95%CI:10.8–27.0) in the SeqB group. Two-year CFS and OS were 78.1% (95%CI:67.0–85.8) and 87.5% (95%CI:77.3–93.3) in the SIB group and 73.5% (95%CI:62.6–81.7) and 85.4% (95%CI:75.5–91.6) in the SeqB, respectively. A Cox proportional hazards regression model highlighted an adjusted hazard ratio (AdjHR) of 1.18 (95%CI: 0.67–2.09;p = 0.560), although AdjHR for the first 24 months was 0.95 (95%CI: 0.49–1.84;p = 0.877) for the SIB approach.

Conclusions

SIB-based RT provides similar clinical outcomes compared to SeqB-based in the treatment of patients affected with non metastatic anal cancer.
Literature
1.
go back to reference Franco P, Mistrangelo M, Arcadipane F, Munoz F, Sciacero P, Spadi R, et al. Intensity-modulated radiation therapy with simultaneous integrated boost combined with concurrent chemotherapy for the treatment of anal cancer patients: 4-year results of a consecutive case series. Cancer Investig. 2015;33(6):259–66.CrossRef Franco P, Mistrangelo M, Arcadipane F, Munoz F, Sciacero P, Spadi R, et al. Intensity-modulated radiation therapy with simultaneous integrated boost combined with concurrent chemotherapy for the treatment of anal cancer patients: 4-year results of a consecutive case series. Cancer Investig. 2015;33(6):259–66.CrossRef
2.
go back to reference James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. 2013;14(6):516–24.CrossRefPubMed James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol. 2013;14(6):516–24.CrossRefPubMed
3.
go back to reference Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Rondi N, et al. Early-stage node negative (T1-T2N0) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):1943–8.PubMed Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Rondi N, et al. Early-stage node negative (T1-T2N0) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):1943–8.PubMed
4.
go back to reference Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Rondi N, et al. Locally advanced (T3-T4 or N+) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):2027–32.PubMed Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Rondi N, et al. Locally advanced (T3-T4 or N+) anal cancer treated with simultaneous integrated boost radiotherapy and concurrent chemotherapy. Anticancer Res. 2016;36(4):2027–32.PubMed
5.
go back to reference Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(6):1914–21.CrossRefPubMed Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA. 2008;299(6):1914–21.CrossRefPubMed
6.
go back to reference Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33.CrossRefPubMed Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J, et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin C for the reduction of acute morbidity in carcinoma of the anal canal. Int J Radiat Oncol Biol Phys. 2013;86(1):27–33.CrossRefPubMed
7.
go back to reference Weber D, Kurthz JM, Allal AS. The impact of gap duration on local control of anal cancer treated by split-course radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys. 2001;50(3):675–80.CrossRefPubMed Weber D, Kurthz JM, Allal AS. The impact of gap duration on local control of anal cancer treated by split-course radiotherapy and concomitant chemotherapy. Int J Radiat Oncol Biol Phys. 2001;50(3):675–80.CrossRefPubMed
8.
go back to reference Franco P, Ragona R, Arcadipane F, Mistrangelo M, Cassoni P, Rondi N, et al. Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer. Clin Transl Oncol. 2017;19(1):67–75.CrossRefPubMed Franco P, Ragona R, Arcadipane F, Mistrangelo M, Cassoni P, Rondi N, et al. Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer. Clin Transl Oncol. 2017;19(1):67–75.CrossRefPubMed
9.
go back to reference Call J, Prendergast BM, Jensen LG, Ord CB, Goodman KA, Jacob R, et al. Intensity-modulated radiation therapy for anal cancer. Results from multi-institutional retrospective cohort study. Am J Clin Oncol. 2016;39(1):8–12.CrossRefPubMed Call J, Prendergast BM, Jensen LG, Ord CB, Goodman KA, Jacob R, et al. Intensity-modulated radiation therapy for anal cancer. Results from multi-institutional retrospective cohort study. Am J Clin Oncol. 2016;39(1):8–12.CrossRefPubMed
10.
go back to reference Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Munoz F, et al. Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients. Br J Radiol. 2016;89(1060):2015832.CrossRef Franco P, Arcadipane F, Ragona R, Mistrangelo M, Cassoni P, Munoz F, et al. Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients. Br J Radiol. 2016;89(1060):2015832.CrossRef
11.
go back to reference Glynne-Jones R, Tan D, Hughes R, Hoskin P. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment. Nat Rev Clin Oncol. 2016;13(7):447–59.CrossRefPubMed Glynne-Jones R, Tan D, Hughes R, Hoskin P. Squamous-cell carcinoma of the anus: progress in radiotherapy treatment. Nat Rev Clin Oncol. 2016;13(7):447–59.CrossRefPubMed
12.
go back to reference Lepinoy A, Lescut N, Puyraveau M, Caubet M, Boustani J, Lakkis Z, et al. Evaluation of a 36 Gy elective node irradiation dose in anal cancer. Radiother Oncol. 2015;116(2):197–201.CrossRefPubMed Lepinoy A, Lescut N, Puyraveau M, Caubet M, Boustani J, Lakkis Z, et al. Evaluation of a 36 Gy elective node irradiation dose in anal cancer. Radiother Oncol. 2015;116(2):197–201.CrossRefPubMed
13.
go back to reference De Bari B, Jumeau R, Bouchaab H, Vallet V, Matzinger O, Troussier I, et al. Efficacy and safety of helical tomotherapy with daily image guidance in anal cancer patients. Acta Oncol. 2016;55(6):767–73.CrossRefPubMed De Bari B, Jumeau R, Bouchaab H, Vallet V, Matzinger O, Troussier I, et al. Efficacy and safety of helical tomotherapy with daily image guidance in anal cancer patients. Acta Oncol. 2016;55(6):767–73.CrossRefPubMed
14.
go back to reference Graf R, Wust P, Hildebrandt B, Gögler H, Ullrich R, Herrmann R, et al. Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology. 2003;65(1):14–22.CrossRefPubMed Graf R, Wust P, Hildebrandt B, Gögler H, Ullrich R, Herrmann R, et al. Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology. 2003;65(1):14–22.CrossRefPubMed
15.
go back to reference Franco P, Arcadipane F, Ragona R, et al. Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients. Med Oncol. 2016;33(7):72.CrossRefPubMed Franco P, Arcadipane F, Ragona R, et al. Dose to specific subregions of pelvic bone marrow defined with FDG-PET as a predictor of hematologic nadirs during concomitant chemoradiation in anal cancer patients. Med Oncol. 2016;33(7):72.CrossRefPubMed
16.
go back to reference Arcadipane F, Franco P, Ceccarelli M, Furfaro G, Rondi N, Trino E, et al. Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer. Asia Pac J Clin Oncol. 2018;14(3):217–23.CrossRefPubMed Arcadipane F, Franco P, Ceccarelli M, Furfaro G, Rondi N, Trino E, et al. Image-guided IMRT with simultaneous integrated boost as per RTOG 0529 for the treatment of anal cancer. Asia Pac J Clin Oncol. 2018;14(3):217–23.CrossRefPubMed
17.
go back to reference Grambsch PM, Therneau TM. Proportional hazards test and diagnostic based on weights residuals. Biometrika. 1994;3:515–26.CrossRef Grambsch PM, Therneau TM. Proportional hazards test and diagnostic based on weights residuals. Biometrika. 1994;3:515–26.CrossRef
18.
go back to reference Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statist Med. 1999;18:695–706.CrossRef Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Statist Med. 1999;18:695–706.CrossRef
19.
go back to reference Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–7.CrossRef Fine J, Gray R. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–7.CrossRef
20.
go back to reference Papillon J, Montbarbon JF. Epidermoid carcinoma of the anal canal. A series of 276 cases. Dis Colon Rectum. 1987;30(5):324–33.CrossRefPubMed Papillon J, Montbarbon JF. Epidermoid carcinoma of the anal canal. A series of 276 cases. Dis Colon Rectum. 1987;30(5):324–33.CrossRefPubMed
21.
go back to reference Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer radiotherapy and gastrointestinal cooperative group. J Clin Oncol. 1997;15(5):2040–9.CrossRefPubMed Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer radiotherapy and gastrointestinal cooperative group. J Clin Oncol. 1997;15(5):2040–9.CrossRefPubMed
22.
go back to reference UKCCCR Anal cancer Trial Working Party. UK co-ordination committee on Cancer research: epidermoid anal cancer: results from the UKCCCR randomized trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348(9034):1049–54.CrossRef UKCCCR Anal cancer Trial Working Party. UK co-ordination committee on Cancer research: epidermoid anal cancer: results from the UKCCCR randomized trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. Lancet. 1996;348(9034):1049–54.CrossRef
23.
go back to reference Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, et al. Role of mytomicin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14(9):2527–39.CrossRefPubMed Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, et al. Role of mytomicin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14(9):2527–39.CrossRefPubMed
24.
go back to reference Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5(7):516–25.CrossRefPubMed Kim JJ, Tannock IF. Repopulation of cancer cells during therapy: an important cause of treatment failure. Nat Rev Cancer. 2005;5(7):516–25.CrossRefPubMed
25.
go back to reference Bosset JF, Roelofsen F, Morgan DAL, Budach V, Coucke P, Jager JJ, et al. Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and gastrointestinal cooperative groups. Eur J Cancer. 2003;39(1):45–51.CrossRefPubMed Bosset JF, Roelofsen F, Morgan DAL, Budach V, Coucke P, Jager JJ, et al. Shortened irradiation scheme, continuous infusion of 5-fluorouracil and fractionation of mitomycin C in locally advanced anal carcinomas. Results of a phase II study of the European Organization for Research and Treatment of Cancer. Radiotherapy and gastrointestinal cooperative groups. Eur J Cancer. 2003;39(1):45–51.CrossRefPubMed
26.
go back to reference Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock JD, et al. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of radiation therapy oncology groups trials 87-04 and 98.11. J Clin Oncol. 2010;28(34):5061–6.CrossRefPubMedPubMedCentral Ben-Josef E, Moughan J, Ajani JA, Flam M, Gunderson L, Pollock JD, et al. Impact of overall treatment time on survival and local control in patients with anal cancer: a pooled data analysis of radiation therapy oncology groups trials 87-04 and 98.11. J Clin Oncol. 2010;28(34):5061–6.CrossRefPubMedPubMedCentral
27.
go back to reference John M, Pajak T, Flam M, Hoffman J, Markoe A, Wolkov H, et al. Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08. Cancer J Sci Am. 1996;2(4):205–11.PubMed John M, Pajak T, Flam M, Hoffman J, Markoe A, Wolkov H, et al. Dose escalation in chemoradiation for anal cancer: preliminary results of RTOG 92-08. Cancer J Sci Am. 1996;2(4):205–11.PubMed
28.
go back to reference Konski A, Garcia M Jr, Madhu J, Krieg R, Pinover W, Myerson R, et al. Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08. Int J Radiation Oncol Biol Phys. 2008;72(1):114–8.CrossRef Konski A, Garcia M Jr, Madhu J, Krieg R, Pinover W, Myerson R, et al. Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08. Int J Radiation Oncol Biol Phys. 2008;72(1):114–8.CrossRef
29.
go back to reference Glynne-Jones R, Sebag-Montefiore D, Adams R, McDonald A, Gollins S, James R, et al. “Mind the gap” – The impact of variations in the duration of the treatment gap and overall treatment time in the first UK anal cancer trial (ACT I). Int J Radiation Oncol Biol Phys. 2011;81(5):1488–94.CrossRef Glynne-Jones R, Sebag-Montefiore D, Adams R, McDonald A, Gollins S, James R, et al. “Mind the gap” – The impact of variations in the duration of the treatment gap and overall treatment time in the first UK anal cancer trial (ACT I). Int J Radiation Oncol Biol Phys. 2011;81(5):1488–94.CrossRef
Metadata
Title
Comparing simultaneous integrated boost vs sequential boost in anal cancer patients: results of a retrospective observational study
Authors
Pierfrancesco Franco
Berardino De Bari
Francesca Arcadipane
Alexis Lepinoy
Manuela Ceccarelli
Gabriella Furfaro
Massimiliano Mistrangelo
Paola Cassoni
Martina Valgiusti
Alessandro Passardi
Andrea Casadei Gardini
Elisabetta Trino
Stefania Martini
Giuseppe Carlo Iorio
Andrea Evangelista
Umberto Ricardi
Gilles Créhange
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2018
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-018-1124-9

Other articles of this Issue 1/2018

Radiation Oncology 1/2018 Go to the issue