Impact of RBE variations on risk estimates of temporal lobe necrosis in patients treated with intensity-modulated proton therapy for head and neck cancer

Figures & data

Table 1. NTCP model predictors and dose constraints from the literature.

NTCP model predictor variables	Reference
DMax	Kong et al. [16]
D0.5 cc	Wen et al. [25]
D1.0 cc	Kong et al. [16]
D2.0 cc	Feng et al. [37]
V60.0	The European Particle Therapy Network consensus [38]
V65.0	International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma [18]
Dose constraints
DMax ≤ 72.0 Gy*	Quantitative Analysis of Normal Tissue Effects in the Clinic [17]
D0.5 cc ≤ 65.05 Gy	Wen et al. [25]
D1.0 cc ≤ 62.4 Gy	Kong et al. [16]
D2.0 cc ≤ 60.3 Gy	Feng et al. [37]
V60.0 ≤ 3.0 cc*	The European Particle Therapy Network consensus [38]
V65.0 ≤ 0.03 cc	International Guideline on Dose Prioritization and Acceptance Criteria in Radiation Therapy Planning for Nasopharyngeal Carcinoma [18]
V70.0 ≤ 0.03 cc**

All the NTCP model predictors were photon-derived based on analysis of associations between TLN and temporal lobe dose distributions in patients treated with IMRT for nasopharyngeal cancer.

*Brain dose constraints in original publications, ** recommended for T3-T4 tumors nasopharyngeal cancers.

Table 2. Patient characteristics for those with (n = 13) and without (n = 32) image changes on the follow-up MRIs.

	No TLIC (n = 32)	TLIC (n = 13)	Total
Parameter	n (%)	n (% )	n (%)	p Value
Age, median (range)	44 (18–82)	54 (32–71)	46 (18–82)	ns
Sex				ns
Male	13 (40.6)	5 (38.5)	18 (40)
Female	19 (59.4)	8 (61.5)	27 (60)
Site				ns
Nasopharynx	11 (34.4)	8 (61.5)	19 (42.2)
Sinonasal	8 (25.5)	4 (30.8)	12 (26.7)
Parotid	8 (25.5)	–	8(17.8)
Other	5 (15.6)	1 (7.7)	6 (13.3)
T-category				ns
T1–T2	9 (28.1)	2 (15.4)	11 (24.4)
T3–T4	14 (43.8)	10 (76.9)	24 (53.3)
Recurrence	7 (21.9)	1 (7.7)	8 (17.8)
NA	2 (6.3)	–	2 (4.4)
Surgery				ns
No	12 (37.5)	9 (69.2)	21 (46.7)
Yes	20 (62.5)	4 (30.8)	35 (77.8)
Chemotherapy				<0.05
No	10 (31.0)	–	10 (22.2)
Yes	22 (68.8)	13 (100)	35 (77.8)
Intracranial involvement				<0.01
No	23 (71.9)	3 (23.1)	26 (57.8)
Yes	9 (28.1)	10 (76.9)	19 (42.2)
Dose, median (range)	66 (60–70)	70 (60–70)	68 (60–70)	<0.05
Follow-up time, median (range)	60.0 (37–100)	49 (24–105)	59 (24–105)	ns
Latency time, median (range)	–	19 (9–33)	–
CTCAE 4.03 grading
Grade 1	–	11 (57.6%)	–
Grade 3	–	2 (15.4%)	–

Other site: Skin, Base of Skull. Follow-up time: from end of treatment to last available MRI. Latency time: from end of treatment to first MRI with image change. Significant tests: Chi-Square/Fisher exact test for categorical variables, Mann–Whitney for continuous variables.

Figure 1. (a) Example of fixed and variable RBE weighted dose distributions. Note the high dose area in the contoured image change (red line) in the RWD_Var dose distributions. (b–c) boxplots of selected dose volume indices for the temporal lobes. RWD_Fix: dose distribution calculated using a constant RBE of 1.1, RWD_McN: dose distribution calculated using the RBE model from McNamara et al. [6], RWD_Wed: dose distribution calculated using the RBE model from Wedenberg et al. [7]. CTV 70: prescribed dose 70 GyRBE (RBE = 1.1).

Figure 2. Scatter plot showing the difference in estimated probabilities between RWD_Fix and RWD_Var.

Figure 3. (a) Evaluation of the different dose constraints according to RWD_Fix, RWD_McN and RWD_Wed. Barplot of observed proportion of TLIC when the different dose constraints were met. *Dose constraint only evaluated for patients with T3–T4 disease and with skull base/intra cranial involvement. The dotted horizontal line represents the 5% level of observed TLIC in the data set. Dose and volumes in GyRBE and cc, respectively.

Kong C, Zhu XZ, Lee TF, et al. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma. Sci Rep. 2016;6:26378.

 PubMed Web of Science ®Google Scholar

Wen D-W, Lin L, Mao Y-P, et al. Normal tissue complication probability (NTCP) models for predicting temporal lobe injury after intensity-modulated radiotherapy in nasopharyngeal carcinoma: a large registry-based retrospective study from China. Radiother Oncol. 2021;157:99–105.

 PubMed Web of Science ®Google Scholar

Feng M, Huang Y, Fan X, et al. Prognostic variables for temporal lobe injury after intensity modulated-radiotherapy of nasopharyngeal carcinoma. Cancer Med. 2018;7(3):557–564.

 PubMed Web of Science ®Google Scholar

Lambrecht M, Eekers DBP, Alapetite C, work package 1 of the taskforce “European Particle Therapy Network” of ESTRO, et al. Radiation dose constraints for organs at risk in neuro-oncology; the european particle therapy network consensus. Radiother Oncol. 2018;128(1):26–36.

 PubMed Web of Science ®Google Scholar

Lee AW, Ng WT, Pan JJ, et al. International guideline on dose prioritization and acceptance criteria in radiation therapy planning for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2019;105(3):567–580.

 PubMed Web of Science ®Google Scholar

Lawrence YR, Li XA, el Naqa I, et al. Radiation dose-volume effects in the brain. Int J Radiat Oncol Biol Phys. 2010;76(3):S20–S27.

 PubMed Web of Science ®Google Scholar

McNamara AL, Schuemann J, Paganetti H. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Phys Med Biol. 2015;60(21):8399–8416.

 PubMed Web of Science ®Google Scholar

Wedenberg M, Lind BK, Hardemark B. A model for the relative biological effectiveness of protons: the tissue specific parameter alpha/beta of photons is a predictor for the sensitivity to LET changes. Acta Oncol. 2013;52(3):580–588.

 PubMed Web of Science ®Google Scholar