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Published in: Radiation Oncology 1/2011

Open Access 01-12-2011 | Research

The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer

Authors: Bing Xia, Gui-Yuan Chen, Xu-Wei Cai, Jian-Dong Zhao, Huan-Jun Yang, Min Fan, Kuai-Le Zhao, Xiao-Long Fu

Published in: Radiation Oncology | Issue 1/2011

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Abstract

Background

To investigate the biological radiation dose-response for patients of limited-stage small-cell lung cancer (LS-SCLC) treated with high radiation dose.

Methods

Two hundred and five patients of LS-SCLC treated with sequential chemotherapy and thoracic radiotherapy with involved-field between 1997 and 2006 were reviewed retrospectively. Biologically effective dose (BED) was calculated for dose homogenization and was corrected with the factor of overall radiation time. Patients were divided into low BED group (n = 70) and high BED group (n = 135) with a cut-off of BED 57 Gy (equivalent to 60 Gy in 30 fractions over 40 days). Outcomes of the two groups were compared.

Results

Median follow-up was 20.7 months for all analyzable patients and 50.8 months for surviving patients. Considering all patients, median survival was 22.9 months (95% confidence interval, 20.6-25.2 months); 2- and 5-year survival rates were 47.2% and 22.3%, respectively. Patients in high BED group had a significantly better local control (p = 0.024), progression-free survival (p = 0.006) and overall survival (p = 0.005), with a trend toward improved distant-metastasis free survival (p = 0.196). Multivariable Cox regression demonstrated that age (p = 0.003), KPS (p = 0.009), weight loss (p = 0.023), and BED (p = 0.004) were significant predictors of overall survival.

Conclusions

Our data showed that a high BED was significantly associated with favourable outcomes in the Chinese LS-SCLC population, indicating that a positive BED-response relationship still existed even in a relatively high radiation dose range.
Appendix
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Literature
1.
go back to reference De Ruysscher D, Vansteenkiste J: Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects. Radiother Oncol 2000, 55: 1-9.CrossRefPubMed De Ruysscher D, Vansteenkiste J: Chest radiotherapy in limited-stage small cell lung cancer: facts, questions, prospects. Radiother Oncol 2000, 55: 1-9.CrossRefPubMed
2.
go back to reference Murray N, Turrisi AT: A review of first-line treatment for small-cell lung cancer. J Thorac Oncol 2006, 1: 270-278.PubMed Murray N, Turrisi AT: A review of first-line treatment for small-cell lung cancer. J Thorac Oncol 2006, 1: 270-278.PubMed
3.
go back to reference Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH: Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999, 340: 265-271. 10.1056/NEJM199901283400403CrossRefPubMed Turrisi AT, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH: Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999, 340: 265-271. 10.1056/NEJM199901283400403CrossRefPubMed
4.
go back to reference Miller KL, Marks LB, Sibley GS, Clough RW, Garst JL, Crawford J, Shafman TD: Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003, 56: 355-359. 10.1016/S0360-3016(02)04493-0CrossRefPubMed Miller KL, Marks LB, Sibley GS, Clough RW, Garst JL, Crawford J, Shafman TD: Routine use of approximately 60 Gy once-daily thoracic irradiation for patients with limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003, 56: 355-359. 10.1016/S0360-3016(02)04493-0CrossRefPubMed
5.
go back to reference Roof KS, Fidias P, Lynch TJ, Choi NC: Radiation dose escalation in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003, 57: 701-708. 10.1016/S0360-3016(03)00715-6CrossRefPubMed Roof KS, Fidias P, Lynch TJ, Choi NC: Radiation dose escalation in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2003, 57: 701-708. 10.1016/S0360-3016(03)00715-6CrossRefPubMed
6.
go back to reference Bogart JA, Herndon JE, Lyss AP, Watson D, Miller AA, Lee ME, Turrisi AT, Green MR: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys 2004, 59: 460-468. 10.1016/j.ijrobp.2003.10.021CrossRefPubMed Bogart JA, Herndon JE, Lyss AP, Watson D, Miller AA, Lee ME, Turrisi AT, Green MR: 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys 2004, 59: 460-468. 10.1016/j.ijrobp.2003.10.021CrossRefPubMed
7.
go back to reference Miller AA, Wang XF, Bogart JA, Hodgson LD, Rocha Lima CM, Radford JE, Vokes EE, Green MR: Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002. J Thorac Oncol 2007, 2: 645-651. 10.1097/JTO.0b013e318074bbf5CrossRefPubMed Miller AA, Wang XF, Bogart JA, Hodgson LD, Rocha Lima CM, Radford JE, Vokes EE, Green MR: Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002. J Thorac Oncol 2007, 2: 645-651. 10.1097/JTO.0b013e318074bbf5CrossRefPubMed
8.
go back to reference Komaki R, Swann RS, Ettinger DS, Glisson BS, Sandler AB, Movsas B, Suh J, Byhardt RW: Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: Report of Radiation Therapy Oncology Group (RTOG) protocol 97-12. Int J Radiat Oncol Biol Phys 2005, 62: 342-350. 10.1016/j.ijrobp.2004.11.030CrossRefPubMed Komaki R, Swann RS, Ettinger DS, Glisson BS, Sandler AB, Movsas B, Suh J, Byhardt RW: Phase I study of thoracic radiation dose escalation with concurrent chemotherapy for patients with limited small-cell lung cancer: Report of Radiation Therapy Oncology Group (RTOG) protocol 97-12. Int J Radiat Oncol Biol Phys 2005, 62: 342-350. 10.1016/j.ijrobp.2004.11.030CrossRefPubMed
9.
go back to reference Komaki R, Paulus R, Ettinger DS, Videtic GM, Bradley JD, Glisson BS, Choy H: A phase II study of accelerated high-dose thoracic radiation therapy (AHTRT) with concurrent chemotherapy for limited small cell lung cancer: RTOG 0239[abstract]. J Clin Oncol 2009, 27: s388. Komaki R, Paulus R, Ettinger DS, Videtic GM, Bradley JD, Glisson BS, Choy H: A phase II study of accelerated high-dose thoracic radiation therapy (AHTRT) with concurrent chemotherapy for limited small cell lung cancer: RTOG 0239[abstract]. J Clin Oncol 2009, 27: s388.
10.
go back to reference Tada T, Minakuchi K, Koda M, Masuda N, Matsui K, Kawase I, Nakajima T, Nishioka M, Fukuoka M, Kozuka T: Limited-stage small cell lung cancer: local failure after chemotherapy and radiation therapy. Radiology 1998, 208: 511-515.CrossRefPubMed Tada T, Minakuchi K, Koda M, Masuda N, Matsui K, Kawase I, Nakajima T, Nishioka M, Fukuoka M, Kozuka T: Limited-stage small cell lung cancer: local failure after chemotherapy and radiation therapy. Radiology 1998, 208: 511-515.CrossRefPubMed
11.
go back to reference Choi NC, Carey RW: Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: an update. Int J Radiat Oncol Biol Phys 1989, 17: 307-310. 10.1016/0360-3016(89)90444-6CrossRefPubMed Choi NC, Carey RW: Importance of radiation dose in achieving improved loco-regional tumor control in limited stage small-cell lung carcinoma: an update. Int J Radiat Oncol Biol Phys 1989, 17: 307-310. 10.1016/0360-3016(89)90444-6CrossRefPubMed
12.
go back to reference Coy P, Hodson I, Payne DG, Evans WK, Feld R, MacDonald AS, Osoba D, Pater JL: The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial. Int J Radiat Oncol Biol Phys 1988, 14: 219-226. 10.1016/0360-3016(88)90424-5CrossRefPubMed Coy P, Hodson I, Payne DG, Evans WK, Feld R, MacDonald AS, Osoba D, Pater JL: The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a Canadian Multicenter Randomized Trial. Int J Radiat Oncol Biol Phys 1988, 14: 219-226. 10.1016/0360-3016(88)90424-5CrossRefPubMed
13.
go back to reference Chen GY, Jiang GL, Wang LJ, Qian H, Fu XL, Yang H, Wu KL, Zhao S: Cisplatin/etoposide chemotherapy combined with twice daily thoracic radiotherapy for limited small-cell lung cancer: a clinical phase II trial. Int J Radiat Oncol Biol Phys 2005, 61: 70-75. 10.1016/j.ijrobp.2004.04.058CrossRefPubMed Chen GY, Jiang GL, Wang LJ, Qian H, Fu XL, Yang H, Wu KL, Zhao S: Cisplatin/etoposide chemotherapy combined with twice daily thoracic radiotherapy for limited small-cell lung cancer: a clinical phase II trial. Int J Radiat Oncol Biol Phys 2005, 61: 70-75. 10.1016/j.ijrobp.2004.04.058CrossRefPubMed
14.
go back to reference Fowler JF: The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989, 62: 679-694. 10.1259/0007-1285-62-740-679CrossRefPubMed Fowler JF: The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989, 62: 679-694. 10.1259/0007-1285-62-740-679CrossRefPubMed
15.
go back to reference Bepler G, Jaques G, Neumann K, Aumüller G, Gropp C, Havemann K: Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol 1987, 113: 31-40. 10.1007/BF00389964CrossRefPubMed Bepler G, Jaques G, Neumann K, Aumüller G, Gropp C, Havemann K: Establishment, growth properties, and morphological characteristics of permanent human small cell lung cancer cell lines. J Cancer Res Clin Oncol 1987, 113: 31-40. 10.1007/BF00389964CrossRefPubMed
17.
go back to reference Tomita N, Kodaira T, Hida T, Tachibana H, Nakamura T, Nakahara R, Inokuchi H: The impact of radiation dose and fractionation on outcomes for limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2010, 76: 1121-1126. 10.1016/j.ijrobp.2009.03.069CrossRefPubMed Tomita N, Kodaira T, Hida T, Tachibana H, Nakamura T, Nakahara R, Inokuchi H: The impact of radiation dose and fractionation on outcomes for limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2010, 76: 1121-1126. 10.1016/j.ijrobp.2009.03.069CrossRefPubMed
18.
go back to reference Schild SE, Bonner JA, Hillman S, Kozelsky TF, Vigliotti AP, Marks RS, Graham DL, Soori GS, Kugler JW, Tenglin RC, Wender DB, Adjei A: Results of a phase II study of high-dose thoracic radiation therapy with concurrent cisplatin and etoposide in limited-stage small-cell lung cancer (NCCTG 95-20-53). J Clin Oncol 2007, 25: 3124-3129. 10.1200/JCO.2006.09.9606CrossRefPubMed Schild SE, Bonner JA, Hillman S, Kozelsky TF, Vigliotti AP, Marks RS, Graham DL, Soori GS, Kugler JW, Tenglin RC, Wender DB, Adjei A: Results of a phase II study of high-dose thoracic radiation therapy with concurrent cisplatin and etoposide in limited-stage small-cell lung cancer (NCCTG 95-20-53). J Clin Oncol 2007, 25: 3124-3129. 10.1200/JCO.2006.09.9606CrossRefPubMed
19.
go back to reference Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, Bentzen J, Bastholt L, Hansen O, Johansen J, Andersen L, Evensen JF: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 2003, 362: 933-940. 10.1016/S0140-6736(03)14361-9CrossRefPubMed Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, Andersen E, Bentzen J, Bastholt L, Hansen O, Johansen J, Andersen L, Evensen JF: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 2003, 362: 933-940. 10.1016/S0140-6736(03)14361-9CrossRefPubMed
20.
go back to reference Bese NS, Hendry J, Jeremic B: Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys 2007, 68: 654-661. 10.1016/j.ijrobp.2007.03.010CrossRefPubMed Bese NS, Hendry J, Jeremic B: Effects of prolongation of overall treatment time due to unplanned interruptions during radiotherapy of different tumor sites and practical methods for compensation. Int J Radiat Oncol Biol Phys 2007, 68: 654-661. 10.1016/j.ijrobp.2007.03.010CrossRefPubMed
21.
go back to reference Koukourakis M, Hlouverakis G, Kosma L, Skarlatos J, Damilakis J, Giatromanolaki A, Yannakakis D: The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys 1996, 34: 315-322. 10.1016/0360-3016(95)02102-7CrossRefPubMed Koukourakis M, Hlouverakis G, Kosma L, Skarlatos J, Damilakis J, Giatromanolaki A, Yannakakis D: The impact of overall treatment time on the results of radiotherapy for nonsmall cell lung carcinoma. Int J Radiat Oncol Biol Phys 1996, 34: 315-322. 10.1016/0360-3016(95)02102-7CrossRefPubMed
22.
go back to reference Chen M, Jiang GL, Fu XL, Wang LJ, Qian H, Chen GY, Zhao S, Liu TF: The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Lung Cancer 2000, 28: 11-19. 10.1016/S0169-5002(99)00113-0CrossRefPubMed Chen M, Jiang GL, Fu XL, Wang LJ, Qian H, Chen GY, Zhao S, Liu TF: The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer. Lung Cancer 2000, 28: 11-19. 10.1016/S0169-5002(99)00113-0CrossRefPubMed
23.
go back to reference Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR: Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004, 59: 943-951. 10.1016/j.ijrobp.2004.01.055CrossRefPubMed Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR: Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys 2004, 59: 943-951. 10.1016/j.ijrobp.2004.01.055CrossRefPubMed
24.
go back to reference De Ruysscher D, Pijls-Johannesma M, Bentzen SM, Minken A, Wanders R, Lutgens L, Hochstenbag M, Boersma L, Wouters B, Lammering G, Vansteenkiste J, Lambin P: Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 2006, 24: 1057-1063. 10.1200/JCO.2005.02.9793CrossRefPubMed De Ruysscher D, Pijls-Johannesma M, Bentzen SM, Minken A, Wanders R, Lutgens L, Hochstenbag M, Boersma L, Wouters B, Lammering G, Vansteenkiste J, Lambin P: Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer. J Clin Oncol 2006, 24: 1057-1063. 10.1200/JCO.2005.02.9793CrossRefPubMed
25.
go back to reference Videtic GM, Fung K, Tomiak AT, Stitt LW, Dar AR, Truong PT, Yu EW, Vincent MD, Kocha WI: Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control. Lung Cancer 2001, 33: 249-258. 10.1016/S0169-5002(00)00240-3CrossRefPubMed Videtic GM, Fung K, Tomiak AT, Stitt LW, Dar AR, Truong PT, Yu EW, Vincent MD, Kocha WI: Using treatment interruptions to palliate the toxicity from concurrent chemoradiation for limited small cell lung cancer decreases survival and disease control. Lung Cancer 2001, 33: 249-258. 10.1016/S0169-5002(00)00240-3CrossRefPubMed
28.
go back to reference Kepka L, Danilova V, Saghatelyan T, Bajcsay A, Utehina O, Stojanovic S, Yalman D, Demiral A, Bondaruk O, Kuddu M, Jeremic B, International Atomic Energy Agency (IAEA): Resources and management strategies for the use of radiotherapy in the treatment of lung cancer in Central and Eastern European countries: results of an International Atomic Energy Agency (IAEA) survey. Lung Cancer 2007, 56: 235-245. 10.1016/j.lungcan.2006.12.011CrossRefPubMed Kepka L, Danilova V, Saghatelyan T, Bajcsay A, Utehina O, Stojanovic S, Yalman D, Demiral A, Bondaruk O, Kuddu M, Jeremic B, International Atomic Energy Agency (IAEA): Resources and management strategies for the use of radiotherapy in the treatment of lung cancer in Central and Eastern European countries: results of an International Atomic Energy Agency (IAEA) survey. Lung Cancer 2007, 56: 235-245. 10.1016/j.lungcan.2006.12.011CrossRefPubMed
29.
go back to reference Fried DB, Morris DE, Poole C, Rosenman JG, Halle JS, Detterbeck FC, Hensing TA, Socinski MA: Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004, 22: 4837-4845. 10.1200/JCO.2004.01.178CrossRefPubMed Fried DB, Morris DE, Poole C, Rosenman JG, Halle JS, Detterbeck FC, Hensing TA, Socinski MA: Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004, 22: 4837-4845. 10.1200/JCO.2004.01.178CrossRefPubMed
30.
go back to reference De Ruysscher D, Pijls-Johannesma M, Vansteenkiste J, Kester A, Rutten I, Lambin P: Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer. Ann Oncol 2006, 17: 543-552. 10.1093/annonc/mdj094CrossRefPubMed De Ruysscher D, Pijls-Johannesma M, Vansteenkiste J, Kester A, Rutten I, Lambin P: Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer. Ann Oncol 2006, 17: 543-552. 10.1093/annonc/mdj094CrossRefPubMed
31.
go back to reference Videtic GM, Truong PT, Dar AR, Yu EW, Stitt LW: Shifting from hypofractionated to "conventionally" fractionated thoracic radiotherapy: a single institution's 10-year experience in the management of limited-stage small-cell lung cancer using concurrent chemoradiation. Int J Radiat Oncol Biol Phys 2003, 57: 709-716. 10.1016/S0360-3016(03)00635-7CrossRefPubMed Videtic GM, Truong PT, Dar AR, Yu EW, Stitt LW: Shifting from hypofractionated to "conventionally" fractionated thoracic radiotherapy: a single institution's 10-year experience in the management of limited-stage small-cell lung cancer using concurrent chemoradiation. Int J Radiat Oncol Biol Phys 2003, 57: 709-716. 10.1016/S0360-3016(03)00635-7CrossRefPubMed
32.
go back to reference Videtic GM, Belderbos JS, Spring Kong FM, Kepka L, Martel MK, Jeremic B: Report from the International Atomic Energy Agency (IAEA) consultants' meeting on elective nodal irradiation in lung cancer: small-cell lung cancer (SCLC). Int J Radiat Oncol Biol Phys 2008, 72: 327-334. 10.1016/j.ijrobp.2008.03.075CrossRefPubMed Videtic GM, Belderbos JS, Spring Kong FM, Kepka L, Martel MK, Jeremic B: Report from the International Atomic Energy Agency (IAEA) consultants' meeting on elective nodal irradiation in lung cancer: small-cell lung cancer (SCLC). Int J Radiat Oncol Biol Phys 2008, 72: 327-334. 10.1016/j.ijrobp.2008.03.075CrossRefPubMed
33.
go back to reference Roof KS, Fidias P, Lynch TJ, Choi NC: Radiation dose intensification in limited-stage small-cell lung cancer. Clin Lung Cancer 2003, 4: 339-346. 10.3816/CLC.2003.n.013CrossRefPubMed Roof KS, Fidias P, Lynch TJ, Choi NC: Radiation dose intensification in limited-stage small-cell lung cancer. Clin Lung Cancer 2003, 4: 339-346. 10.3816/CLC.2003.n.013CrossRefPubMed
Metadata
Title
The effect of bioequivalent radiation dose on survival of patients with limited-stage small-cell lung cancer
Authors
Bing Xia
Gui-Yuan Chen
Xu-Wei Cai
Jian-Dong Zhao
Huan-Jun Yang
Min Fan
Kuai-Le Zhao
Xiao-Long Fu
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2011
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-6-50

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