title: Interfraction interval does not affect survival of patients with non-small cell lung cancer treated with chemotherapy and/or hyperfractionated radiotherapy: a multivariate analysis of 1076 RTOG patients.
abstract: OBJECTIVE
  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
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University and Kimmel Cancer Center, Philadelphia, PA 19107-5097, USA.
authors.forename: M
authors.initials: M
authors.lastname: Werner-Wasik
authors.forename: C
authors.initials: C
authors.lastname: Scott
authors.forename: M L
authors.initials: ML
authors.lastname: Graham
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: R W
authors.initials: RW
authors.lastname: Byhardt
authors.forename: M
authors.initials: M
authors.lastname: Roach
authors.forename: E J
authors.initials: EJ
authors.lastname: Andras
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004941:Esophagitis / Q000453:epidemiology / Q000209:etiology; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012189:Retrospective Studies; D016019:Survival Analysis; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014747:Vinblastine; D005047:Etoposide; D002945:Cisplatin