HIGH TOTAL DOSE RADIATION IMPROVES SURVIVAL OF PATIENTS WITH LOCALLY ADVANCED SMALL CELL LUNG CANCER: RESULTS OF SINGLE-CENTRAL RETROSPECTIVE ANALYSIS
Abstract
The overall survival of patients with locally advanced small cell lung cancer who received at least 2 courses of chemotherapy and external beam radiation therapy at a total dose >50 Gy delivered to the primary tumor was retrospectively studied. Patients were divided
into 2 groups. Patients in the standard treatment group (n=71) were treated to 50–58 Gy total dose. The dose escalation group (n=69) was treated to 60–74 Gy. Accelerated fractionation regimen in radiotherapy was more frequently given in dose escalation treatment group. The 1-, 3- and 5-year survival rates in the dose escalated and standard dose groups were respectively 54 % (95 % CI 42–65 %) and 32 % (95 % CI 23–44 %), р=0,11; 25 % (95 % CI 16–36 %) and 1 % (95% CI 0–8 %), р=0,0003; 17 % (95 % CI 10–28 %) and 0 % (95 % CI 0–5 %) (р=0.0007). The median survival was 14 months (95 % CI 10–17 months) in the dose escalated treatment group and 9 months (95 % CI 8–11
months) in patients of the standard treatment group (χ2=16,8, р<0,0001). Multifactorial analysis showed that a total dose of ≥60 Gy resulted in reduction in risk of death (RR 0,57 (CI 0,37–0,88), р=0,012). Radiation dose escalation can result in improvement of local control for patients with locally advanced small cell lung cancer. Prospective randomized studies are required to finally confirm this hypothesis.
into 2 groups. Patients in the standard treatment group (n=71) were treated to 50–58 Gy total dose. The dose escalation group (n=69) was treated to 60–74 Gy. Accelerated fractionation regimen in radiotherapy was more frequently given in dose escalation treatment group. The 1-, 3- and 5-year survival rates in the dose escalated and standard dose groups were respectively 54 % (95 % CI 42–65 %) and 32 % (95 % CI 23–44 %), р=0,11; 25 % (95 % CI 16–36 %) and 1 % (95% CI 0–8 %), р=0,0003; 17 % (95 % CI 10–28 %) and 0 % (95 % CI 0–5 %) (р=0.0007). The median survival was 14 months (95 % CI 10–17 months) in the dose escalated treatment group and 9 months (95 % CI 8–11
months) in patients of the standard treatment group (χ2=16,8, р<0,0001). Multifactorial analysis showed that a total dose of ≥60 Gy resulted in reduction in risk of death (RR 0,57 (CI 0,37–0,88), р=0,012). Radiation dose escalation can result in improvement of local control for patients with locally advanced small cell lung cancer. Prospective randomized studies are required to finally confirm this hypothesis.
About the Authors
Yu. V. Skripchak
Northern State Medical University
Russian Federation
Russian Federation
G. V. Kononova
Northern State Medical University
Russian Federation
Russian Federation
S. M. Asakhin
Northern State Medical University, Arkhangelsk.
Arkhangelsk Clinical Cancer Center
Russian Federation
Russian Federation
M. L. Levit
Northern State Medical University, Arkhangelsk.
Arkhangelsk Clinical Cancer Center
Russian Federation
Russian Federation
T. Yu. Gagarina
Northern State Medical University, Arkhangelsk.
Arkhangelsk Clinical Cancer Center
Russian Federation
Russian Federation
I. K. Pushkareva
Arkhangelsk Clinical Cancer Center
Russian Federation
Russian Federation
M. Yu Valkov
Northern State Medical University, Arkhangelsk.
Arkhangelsk Clinical Cancer Center
Russian Federation
Russian Federation
References
1. Давыдов М.И.,Аксель Е.М. Заболеваемость злокачественными новообразованиями населения России и стран СНГ в 2007 г. // Вестник РОНЦ им. Н.Н. Блохина РАМН. 2009. № 20 (3s). C. 52–90.
2. Кононова Г.В., Вальков М.Ю., Пушкарева И.К. Химиолучевое лечение локализованных форм мелкоклеточного рака легкого: отдаленные результаты // Материалы XI Российского онкологического конгресса. М., 2007. С. 19.
3. Минимальные клинические рекомендации Европейского общества медицинской онкологии (ESMO). М.: Издательская группа РОНЦ им. Н.Н. Блохина РАМН, 2009. С. 13–15.
4. Birch R., Omura G.A., Greco F.A., Perez C.A. Patterns of failure in combined chemotherapy and radiotherapy for limited small cell lung cancer: Southeastern Cancer Study Group experience // NCI Monogr. 1988. № 6. P. 265–270.
5. Bonner J.A., Sloan J.A., Shanahan T.G. et al. Phase III comparison of twice-daily split-course irradiation versus once-daily irradiation for patients with limited stage small-cell lung carcinoma // J. Clin. Oncol. 1999. Vol. 17. Р. 2681–2685.
6. Choi N.C., Carey R.W. 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. Vol. 17 (2). P. 307–310.
7. Choi N.C., Herndon J.E. II, Rosenman J. et al. Phase I study to determine the maximum-tolerated dose of radiation in standard daily and hyperfractionated-accelerated twice-daily radiation schedules with concurrent chemotherapy for limited-stage small-cell lung cancer // J. Clin. Oncol. 1988. Vol. 16. P. 3528–3536.
8. Coy P., Hodson I., Payne D.G. et al. 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. Vol. 14 (2). P. 219–226.
9. De Ruysscher D., Pijls-Johannesma M., Bentzen S.M. et al. 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. Vol. 24. P. 1057–1063.
10. Faivre-Finn C., Blackhall F., Snee M. et al. Improving survival with thoracic radiotherapy in patients with small cell lung cancer. The CONVERT and the REST trials // Clin. Oncology. 2010. Vol. 22. P. 547–549. 11. Fowler J.F. Practical time-dose evaluations, or how to stop worrying and learn to love linear quadratics / Technical basis of radiation therapy / Eds. S.H. Levitt, J.A. Purdy, C.A.Perez, P. Poortmans. Springer, 2012. P. 8–46.
11. Gregor A., Drings P., Burghouts J. et al. Randomized trial of alternating versus sequential radiotherapy/chemotherapy in limited-disease patients with small-cell lung cancer: a European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group Study // J. Clin. Oncol.1997. Vol. 15. P. 2840–2849.
12. Jemal A., Siegel R., Xu J. et al. Global cancer statistics // CA Cancer J. Clin. 2011. Vol. 61 (2). P. 69–90.
13. Osterlind K., Hansen H.H., Hansen H.S. et al. Chemotherapy versus chemotherapy plus irradiation in limited small cell lung cancer. Results of a controlled trial with 5 years follow-up // Br. J. Cancer. 1986. Vol. 54 (1). P. 7–17.
14. Papac R.J., Son Y., Bien R. et al. Improved local control of thoracic disease in small cell lung cancer with higher dose thoracic irradiation and cyclic chemotherapy // Int. J. Radiat. Oncol. Biol. Phys. 1987. Vol. 13 (7). Р. 993–998.
15. Pignon J.P., Arriagada R., Ihde D.C. et al. A meta-analysis of thoracic radiotherapy for small cell lung cancer // N. Engl. J. Med. 1992. Vol. 327. P. 1618–1624.
16. Roof K.S., Fidias P., Lynch T.J. et al. Radiation dose escalation in limited-stage small-cell lung cancer // Int. J. Radiat. Oncol. Biol. Phys. 2003. Vol. 57 (3). P. 701–708.
17. Sculier J.P., Lafitte J.J., Efremidis A. et al. A phase III randomized study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer // Ann. Oncol. 2008. Vol. 19(10). P. 1691-1697.
18. Skarlos D.V., Samantas E., Briassoulis E. et al. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG) // Ann. Oncol. 2001. Vol. 12 (9). P. 1231–1238.
19. Takada M., Fukuoka M., Kawahara M. et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104 // J. Clin. Oncol. 2002. Vol. 20 (14). P. 3054–3060.
20. Tomita N., Kodaira T., Hida T. et al. The impact of radiation dose and fractionation on outcomes for limited-stage small-cell lung cancer // Int. J. Radiat. Oncol. Biol. Phys. 2010. Vol. 76 (4). P. 1121–1126. 22. Turrisi A.T., Kim K., Blum R. et al. 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. Vol. 340. Р. 265–271.
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For citations:
Skripchak Yu.V., Kononova G.V., Asakhin S.M., Levit M.L., Gagarina T.Yu., Pushkareva I.K., Valkov M.Yu. HIGH TOTAL DOSE RADIATION IMPROVES SURVIVAL OF PATIENTS WITH LOCALLY ADVANCED SMALL CELL LUNG CANCER: RESULTS OF SINGLE-CENTRAL RETROSPECTIVE ANALYSIS. Siberian journal of oncology. 2013;(1):5-11. (In Russ.)
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