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Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies

  • Xiao Hu
  • Bing Xia
  • Yong Bao
  • Yu-jin Xu
  • Jin Wang
  • Hong-lian Ma
  • Fang Peng
  • Ying Jin
  • Min Fang
  • Hua-rong Tang
  • Meng-yuan Chen
  • Bai-qiang Dong
  • Jia-nan Jin
  • Xiao-long FuEmail author
  • Ming ChenEmail author
Original Article

Abstract

Purpose

The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT.

Methods

Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model.

Results

Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1‑ and 2‑year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4–40.1) and 22.0 (95% CI 16.4–27.5), while the 1‑year, 3‑year, and 5‑year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20–0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32–0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29–0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003).

Conclusion

Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

Keywords

Lung cancer, small cell Limited stage Thoracic radiotherapy Radiation dose Prognosis 

Der Zeitpunkt der thorakalen Strahlentherapie ist wichtiger als die Dosisintensivierung bei Patienten mit limitiertem Stadium des kleinzelligen Lungenkarzinoms: Ein paralleler Vergleich von zwei prospektiven Studien

Zusammenfassung

Zielsetzung

Die optimale Dosis für die Radiotherapie des kleinzelligen Lungenkrebses (SCLC) im begrenzten Stadium ist nicht genau definiert. Hier sollen die Wirksamkeit der hyperfraktionierten Thoraxradiotherapie (TRT; 1,5 Gy zweimal pro Tag [bid] in 30 Fraktionen) mit der hypofraktionierten TRT (2,5 Gy einmal pro Tag [qd] in 22 Fraktionen) verglichen und prognostische Faktoren, wie der Zeitpunkt der TRT, untersucht werden.

Methoden

Die Daten von Patienten, die an zwei unabhängigen prospektiven Studien teilnahmen, wurden gepoolt analysiert. Der primäre Endpunkt war die lokoregionäre Kontrolle (LRC). Prognosefaktoren wurden mit dem Cox-proportional-hazards-Modell analysiert.

Ergebnisse

Es wurden 92 und 96 Patienten mit hyperfraktionierter TRT bzw. mit hypofraktionierter TRT behandelt. Die 1‑Jahres-, 2‑Jahres-LRC-Raten der zwei Arme betrugen jeweils 82,1 und 60,7 % sowie 84,9 und 68,8 % (P = 0,27). Das mediane Gesamtüberleben („overall survival“, OS; in Monaten) betrug 28,3 (95 %-Konfidenzintervall [KI] 16,4–40,1) und 22,0 (95 %-KI 16,4–27,5), während die 1‑Jahres-, 3‑Jahres- und 5‑Jahres-OS-Raten jeweils bei 85,2, 40,8, 27,1 % und 76,9, 34,3, 26,8 % lagen (P = 0,37). Mithilfe einer multivariaten Cox-Regressionsuntersuchung wurde erkannt, dass die Zeit (in Tagen) vom Beginn der Chemotherapie bis zur TRT (TCT) ≤43 mit einem verbesserten LRC assoziiert war (Hazard Ratio [HR] 0,39; 95 %-KI 0,20–0,76; P = 0,005). Die Zeit (in Tagen) vom Beginn der Chemotherapie bis zum Ende der TRT (SER) ≤63 (HR 0,50; 95 %-KI 0,32–0,80; P = 0,003) und bis zur prophylaktischen Schädelbestrahlung (HR 0,43; 95 %-KI 0,29–0,63; P = 0,000) standen in Korrelation mit dem OS. Eine akute Strahlenösophagitis vom Grad 2/3 wurde mit 37,0 % bei Patienten im hyperfraktionierten und mit 17,7 % im hypofraktionierten Arm beobachtet (P = 0,003).

Schlussfolgerung

In dieser Untersuchung erzielten die hyperfraktionierte sowie die hypofraktionierte TRT beide eine gute LRC und OS bei Patienten mit SCLC im beschränkten Stadium. Die Einhaltung von TCT ≤43 und SER ≤63 führten zu einer besseren Prognose. Das Auftreten einer akuten Ösophagitis war im hyperfraktionierten Arm signifikant häufiger.

Schlüsselwörter

Kleinzelliger Lungenkrebs Limitiertes Stadium Thorax-Strahlentherapie Strahlendosis Zeitpunkt der Strahlentherapie 

Notes

Funding

This study was funded by the National Natural Science Foundation of China (grant numbers 81402540 and 81672972), the National Health Commission scientific research funds—Zhejiang province major science and technology project on medicine (grant number WKJ-ZJ-1701), co-cultivation project of National Health Commission of the People’s Republic of China and Zhejiang province (grant number 2014PYA003), and Zhejiang Science and Technology Plan on Medicine and Health (grant number 2019KY046).

Conflict of interest

X. Hu, B. Xia, Y. Bao, Y.-j. Xu, J. Wang, H.-l. Ma, F. Peng, Y. Jin, M. Fang, H.-r. Tang, M.-y Chen, B.-q. Dong, J.-n. Jin, X.-l. Fu, and M. Chen declare that they have no competing interests.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xiao Hu
    • 1
  • Bing Xia
    • 1
    • 2
    • 3
  • Yong Bao
    • 4
  • Yu-jin Xu
    • 1
  • Jin Wang
    • 1
  • Hong-lian Ma
    • 1
  • Fang Peng
    • 4
  • Ying Jin
    • 5
  • Min Fang
    • 1
  • Hua-rong Tang
    • 1
  • Meng-yuan Chen
    • 1
  • Bai-qiang Dong
    • 1
  • Jia-nan Jin
    • 1
  • Xiao-long Fu
    • 3
    • 6
    Email author
  • Ming Chen
    • 1
    Email author
  1. 1.Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang Provincial Key Laboratory of Radiation OncologyInstitute of Cancer Research and Basic Medical Sciences, Chinese Academy of SciencesHangzhouChina
  2. 2.Department of Radiation OncologyHangzhou Cancer HospitalHangzhouChina
  3. 3.Department of Radiation OncologyCancer Hospital of Fudan UniversityShanghaiChina
  4. 4.Department of Radiation OncologyThe First affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina
  5. 5.Department of Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Department of Medical Oncology, Zhejiang Cancer HospitalInstitute of Cancer Research and Basic Medical Sciences, Chinese Academy of SciencesHangzhouChina
  6. 6.Department of Radiation OncologyShanghai Jiao Tong University Affiliated Chest HospitalShanghaiChina

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