Purpose: It was observed by Jeremic et al. that a shorter interfraction interval (IFI) was associated with an improved survival in patients (pts) with locally advanced non-small cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (HFX-RT), with or without chemotherapy (CT). Our analysis was undertaken to verify this hypothesis.
Methods and materials: Records of patients treated on 5 Radiation Therapy Oncology Group (RTOG) studies were reviewed, and an actual IFI, defined as a mean of all daily IFIs, was calculated. RT dose was 1.2 Gy BID to 69.6 Gy. The relationship between the length of IFI and the median survival time and incidence of esophagitis was investigated.
Results: In 682 pts eligible for this analysis, a full dose of RT was delivered and at least 90% of all daily IFIs were available. The actual mean IFI was as follows: 4-4.9 h in 51% of pts; 5-5.9 h in 17%; 6-6.9 h in 28% and 7-8 h in 4%. In multivariate analysis, only lack of weight loss, use of CT, low nodal stage and good KPS, but not IFI (4-6 h vs. 6-8 h) were associated with an improved survival for all pts (p values: <0.0001; <0.0001; 0.006; 0.006, and 0.73, respectively), as well as for HFX-RT only pts. For the CT-HFX-RT pts, not enough data points are available for a meaningful analysis. Length of IFI did not influence the incidence of Grade 3 or higher esophagitis (p = 0.82), but use of CT was associated with a 12-fold greater risk of developing severe esophagitis (p < 0.0001).
Conclusion: Length of IFI (4-6 h vs. 6-8 h) did not influence survival and acute complications incidence in pts with NSCLC treated in RTOG studies with HFX-RT to 69.6 Gy. Previously identified factors, such as use of CT, minimal weight loss, good KPS and low nodal stage, were confirmed again to be associated with a favorable prognosis in a multivariate analysis. Use of CT was associated with a 12-fold greater risk of developing severe esophagitis than HFX-RT alone. It appears that an IFI of 4-8 hr is acceptable in clinical practice for pts with NSCLC, treated with HFX-RT.