Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Oct 3;16(19):3384.
doi: 10.3390/cancers16193384.

A Systematic Review of Phase II/III Trials of Hypofractionated versus Conventionally Fractionated Radiation Therapy in Stage III Non-Small Cell Lung Cancer Patients

May N Tsao  1 , Yee Ung  1 , Patrick Cheung  1 , Ian Poon  1 , Alexander V Louie  1
Affiliations
Review

A Systematic Review of Phase II/III Trials of Hypofractionated versus Conventionally Fractionated Radiation Therapy in Stage III Non-Small Cell Lung Cancer Patients

May N Tsao et al. Cancers (Basel). .

Abstract

Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint.

Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients.

Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months-42.5 months) and toxicities such as grade 3 or higher esophagitis (0-42%) and grade 3 or higher pneumonitis (0-18%) were reported.

Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy.

Keywords: hypofractionated; lung cancer; radiation; systematic review.

PubMed Disclaimer

Conflict of interest statement

May N. Tsao: none. Alexander V. Louie received honoraria from Astra-Zeneca for speaker’s fees and advisory board participation. Patrick Cheung: none. Ian Poon is a member of the advisory board for Sanofi Aventis and Astra-Zeneca. Yee Ung: none.

Figures

Figure 1
Figure 1
PRISMA 2020 Flow Diagram. BED10 = Biological Effective Dose α/β 10. Source: ref. [17].
Figure 2
Figure 2
Forest plot (1 year overall survival for hypofractionated radiation versus conventional radiation) [31,32,33]. Review Manager 5.4.1 (RevMan 5.4.1) [Computer program]. Version 5.4.1. Copenhagen: The Cochrane Collaboration, 2020.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Daly M.E., Singh N., Ismaila N., Antonoff M.B., Arenberg D.A., Bradley J., David E., Detterbeck F., Früh M., Gubens M.A., et al. Management of stage III non-small-cell lung cancer: ASCO guideline. J. Clin. Oncol. 2022;40:1356–1384. doi: 10.1200/JCO.21.02528. - DOI - PubMed
    1. Bezjak A., Temin S., Franklin G., Giaccone G., Govindan R., Johnson M.L., Rimner A., Schneider B.J., Strawn J., Azzoli C.G. Definitive and adjuvant radiotherapy in locally advanced non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline endorsement of the American Society for Radiation Oncology evidence-based clinical practice guideline. J. Clin. Oncol. 2015;33:2100–2105. doi: 10.1200/JCO.2014.59.2360. - DOI - PubMed
    1. Perez C.A., Pajak T.F., Rubin P., Simpson J.R., Mohiuddin M., Brady L.W., Perez-Tamayo R., Rotman M. Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Report by the Radiation Therapy Oncology Group. Cancer. 1987;59:1874–1881. doi: 10.1002/1097-0142(19870601)59:11<1874::AID-CNCR2820591106>3.0.CO;2-Z. - DOI - PubMed
    1. Perez C.A., Stanley K., Rubin P., Kramer S., Brady L., Perez-Tamayo R., Brown G.S., Concannon J., Rotman M., Seydel H.G. A prospective randomized study of various irradiation doses and fractionation schedules in the treatment of inoperable non-oat-cell carcinoma of the lung. Preliminary report by the Radiation Therapy Oncology Group. Cancer. 1980;45:2744–2753. doi: 10.1002/1097-0142(19800601)45:11<2744::AID-CNCR2820451108>3.0.CO;2-U. - DOI - PubMed
    1. Bradley J.D., Paulus R., Komaki R., Masters G., Blumenschein G., Schild S., Bogart J., Hu C., Forster K., Magliocco A., et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): A randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015;16:187–199. doi: 10.1016/S1470-2045(14)71207-0. - DOI - PMC - PubMed

LinkOut - more resources