Table 3

Competing Risks and Cox Regression Analyses for Major Adverse Cardiac Events and All-Cause Mortality

NMajor Adverse Cardiac EventsAll-Cause Mortality
No. MACEUnivariableMultivariableNo. of ACDUnivariableMultivariable
HR (95% CI)p ValueAHR (95% CI)p ValueHR (95% CI)p ValueAHR (95% CI)p Value
Lung cancer factors
 Age, yrs748771.03 (1.01–1.05)0.0071.01 (0.99–1.04)0.305331.02 (1.01–1.03)<0.0011.00 (0.99–1.01)0.41
 Sex
  Female368381.00 (Referent)2511.00 (Referent)1.00 (Referent)
  Male380391.00 (0.64–1.56)1.002821.20 (1.01–1.43)0.0341.14 (0.95–1.36)0.16
 ECOG PS
  0–1660681.00 (Referent)4581.00 (Referent)1.00 (Referent)
  2–48890.98 (0.49–1.96)0.96751.63 (1.28–2.09)<0.0011.57 (1.21–2.03)0.001
 Smoking
  Never6051.00 (Referent)401.00 (Referent)
  Ever688721.27 (0.51–3.16)0.614931.30 (0.94–1.80)0.11
 Weight loss
  No511591.00 (Referent)3601.00 (Referent)1.00 (Referent)
  Yes237180.67 (0.40–1.13)0.131731.33 (1.10–1.59)0.0021.23 (1.01–1.49)0.037
 Stage
  II79111.00 (Referent)531.00 (Referent)
  III669660.71 (0.38–1.33)0.284801.18 (0.89–1.57)0.25
 Tumor laterality
  Right417361.00 (Referent)3001.00 (Referent)
  Left281351.51 (0.95–2.41)0.0802000.97 (0.81–1.16)0.71
 Histology
  Adeno331331.00 (Referent)2321.00 (Referent)
  Nonadeno417441.09 (0.70–1.71)0.703011.17 (0.99–1.40)0.07
Baseline cardiac factors
 CHD
  No480271.00 (Referent)1.00 (Referent)3241.00 (Referent)1.00 (Referent)
  Yes268503.58 (2.25–5.71)<0.0017.00 (3.20–15.31)<0.0012091.31 (1.10–1.56)0.0031.37 (0.99–1.89)0.054
 Arrhythmia
  No645591.00 (Referent)1.00 (Referent)4531.00 (Referent)1.00 (Referent)
  Yes103182.07 (1.21–3.54)0.0081.55 (0.85–2.81)0.15801.36 (1.08–1.73)0.0111.26 (0.98–1.62)0.075
Treatment factors
 RT/surgery sequence
  Definitive RT/CRT489511.00 (Referent)3981.00 (Referent)1.00 (Referent)
  Neoadjuvant/adjuvant RT/CRT259260.97 (0.60–1.55)0.891350.40 (0.33–0.48)<0.0010.41 (0.33–0.51)<0.001
 Chemo (any)
  No4241.00 (Referent)321.00 (Referent)
  Yes706731.04 (0.38–2.86)0.945010.75 (0.52–1.07)0.11
RT technique
 3D-CRT584691.00 (Referent)1.00 (Referent)4231.00 (Referent)
 IMRT16480.43 (0.21–0.89)0.0230.39 (0.18–0.84)0.0171101.14 (0.9–1.41)0.23
RT year
 <2008273281.00 (Referent)2351.00 (Referent)1.00 (Referent)
 ≥2008475491.14 (0.72–1.80)0.572980.83 (0.70–0.99)0.0420.79 (0.66–0.95)0.013
 Mean heart dose, Gy701701.02 (1.00–1.04)0.0901.05 (1.02–1.08)<0.0014901.01 (1.00–1.02)0.0151.02 (1.01–1.03)0.003
 Interaction
  Cardiac dose × CHD701700.95 (0.92–0.99)0.0080.95 (0.91–0.99)0.0074900.98 (0.96–1.00)0.0490.98 (0.96–1.00)0.030

ACD = all-cause death; adeno = adenocarcinoma; AHR = adjusted hazard ratio; chemo = chemotherapy; ECOG = Eastern Cooperative Oncology Group; HR = hazard ratio; other abbreviations as in Tables 1 and 2.

  • Both a lung cancer and cardiac prognostic factor.

  • Interaction term between heart dose (continuous variable) and pre-existing CHD (categorical variable).