Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors

Figures & data

Figure 1. Fit of the TCP-model parameters $c\mathrm{}$ (red, dotted line), $\alpha ,\mathrm{}\beta$ ($\alpha /\beta$-ratio, solid black line), $\mathrm{\gamma }$ (blue, dashed line) in Equation 2 for different values of A (x-axis). Green line denotes the residual sum of squares from the fit. In (a) the p16-cohort of 433 patients and in (b) the corresponding p16-negative cohort of 90 patients (with a fixed $\alpha /\beta$-ratio).

Table 1. Fitted parameters in Equation 2.

parameter	estimate	95% ci	P
$\alpha$	$\text{0.130}$	$\text{0.038}\text{- 0.206}$	<.001
$\beta$	$\text{0.0134}$	$\text{-0.037}\text{- 0.089}$	0.94
$\alpha /\beta$	9.7	−2.3 − 21.6^*
$c_{p16+}$	1.44	1.06 − 1.91	<.001
${\gamma }_{p16+}$	0.048	−0.026 − 0.145	0.35
$A_{p16+}$	6.08	3.7-8.4
$c_{p16-}$	0.90	0.54 − 1.32	<.001
${\gamma }_{p16-}$	0.048	0.011 − 0.076	0.06
$A_{p16-}$	86.3	48.2 − 124.4

* estimated according to $\pm 1.96\times SE,$ with $SE\left(\raisebox{1ex}{$\alpha $}\!\left/ \!\raisebox{-1ex}{$\beta $}\right.\right)=(\frac{1}{\beta })\sqrt{{SE(\alpha )}^2+\frac{\alpha }{\beta }{SE(\beta )}^2}$

Figure 2. Estimated probability of local failure using the TCP-model in Equation 2, incorporating primary tumor volume (x-axis), fractionation schedule (black, red and blue) and overall treatment time for the individual patients. Model predictions for p16-negative (darkgreen dotted lines) and p16-positive (dashed line) tumors treated with 68.0 Gy/34 fractions over 47 days are shown, as well as outcome for the actual patients (p16-positive tumor without failure (+), p16-positive tumor with failure (triangles), p16-negative tumor without failure (empty circles), p16-negative tumor with failure (filled circles)). horizontal bars denote the proportion of patients with failure, grouped per 20 cm3, with 95% confidence interval (vertical lines) for p16-positive (black, longer bars, filled error lines) and p16-negative (darkgreen, shorter bars, dot-dashed lines).

Table 2. Multivariable Cox-Regression for patients with p16-positive and p16-negative tumors. Primary tumor volume (GTV-T) was log2-transformed and included as continuous parameter.

	p16-positive			p16-negative
	Estimates	CI	p	Estimates	CI	p
Primary tumor volume (per log2)	2.37	1.72 – 3.28	<0.001	1.83	1.28 – 2.62	0.001
Performance status WHO ≥1/Karnofsky ≤80 vs. better [ref]	1.49	0.57 – 3.92	0.42	1.72	0.56 – 3.23	0.51
Smoker Current/previous vs. no smokers [ref]	1.64	0.81 – 3.32	0.17	6.41	0.85–48.2	0.07
Patients (events)	406 (34)			77 (23)