Towards individualized dose constraints: Adjusting the QUANTEC radiation pneumonitis model for clinical risk factors

Figures & data

Table I. Odds ratios for the effects of clinical risk factors.

Clinical risk factor	OR [95% CI]	p-value
Pre-existing pulmonary co-morbidity^a	2.27 [1.25, 4.13]	0.007
Mid or inferior tumor location	1.87 [1.26, 2.79]	0.002
Current smoker	0.62 [0.43, 0.88]	0.008
Former smoker	0.69 [0.47, 1.01]	0.06
Old age^b	1.66 [1.29, 2.13]	< 0.0001
Sequential chemotherapy^c	1.60 [1.11, 2.32]	0.01

Data from [4]. CI, Confidence interval; OR, Odds ratio for the development of radiation pneumonitis.

^aDefined as chronic obstructive pulmonary disorder or general pre-existing lung disease; ^bAverage cut point used: 63 years; ^cAs opposed to concomitant chemotherapy.

Table II. Summary of prevalence of clinical risk factors in the QUANTEC analysis.

	Pulmonary co-morbidity	Lower or middle lobe	Current smokers	Former smokers	Mean age [years]	Sequential chemo
Prevalence	0.258	0.444	0.283	0.663	65.4	0.258
No. of studies reporting	4	4	3	2	8	8

The overall prevalence was calculated as the weighted averages of the prevalence in studies reporting the number of patients with/without the specified factors present. See Appendix A (available online at http://informahealthcare.com/doi/abs/10.3109/0284186X.2013.820341) for full details of the data used.

Figure 1. Relationships between the mean dose to the lungs and the risk of radiation pneumonitis. Solid line: Dose-response reported in the QUANTEC study [1]. Dashed line: Estimated dose-response for a patient currently smoking, with no risk factors (no pulmonary co-morbidities, no lower/middle tumor, below 63 years old, and no sequential chemotherapy). Dotted line: Estimated dose-response for patients with highest risk (pulmonary co-morbidities, middle or lower tumor location, no history of smoking, above 63 years of age, and sequential chemotherapy). Appropriate constraints on the mean lung dose in order to ensure a < 20% complication rate are marked on the primary axis.

Figure 2. Cumulative incidence functions for competing outcomes for patients in the validation cohort. Solid line: Radiation pneumonitis CTCAE v. 3.0 grade 3 or above. Dashed line: Local progression of lung cancer. Dotted line: Death from lung cancer. Dot-dashed line: Death from other (or unknown) cause.

Table III. Patient characteristics in validation cohort.

Patient characteristics	Total no. of patients: 103
Pre-existing pulmonary co-morbidity:	20 / 103 (19%)
Current smokers:	34 / 103 (33%)
Former smokers:	65 / 103 (63%)
Median age:	66 years (range: 43–81)
Sequential chemotherapy:	77 / 103 (75%)

No data available on the tumor location (upper, middle or lower tumor).

Table IV. Crude incidence of radiation pneumonitis (as first event) in validation cohort.

Grade RP (CTCAE v 3.0)	No. of patients	Median time to RP [months]
0	30	–
1	37	4.3
2	20	4.3
3	14	3.1
4	0	–
5	2	1.6

RP, radiation pneumonitis.

Figure 3. Cumulative incidence of radiation pneumonitis for high/low risk patients in the validation cohort: Subdistribution cumulative incidence functions for radiation pneumonitis CTCEA v. 3.0 grade 3 or above. Solid line: Patients with predicted normal tissue toxicity (NTCP) below or equal to the group median (low-risk patients). Dashed line: Patients with NTCP above the group median (high-risk patients). Shaded areas: 95% confidence intervals. a) NTCP calculated using the dose-only relationship from the QUANTEC analysis [1]. Group median: 17.0%. b) NTCP calculated using the individualized risk estimate, with the QUANTEC model adjusted for the effects of clinical risk factors. Group median: 13.4%.

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