Increase in Tumor Control and Normal Tissue Complication Probabilities in Advanced Head-and-Neck Cancer for Dose-Escalated Intensity-Modulated Photon and Proton Therapy

Abstract

Introduction: Presently used radiochemotherapy regimens result in moderate local control rates for patients with advanced head-and-neck squamous cell carcinoma (HNSCC). Dose escalation (DE) may be an option to improve patient outcome, but may also increase the risk of toxicities in healthy tissue. The presented treatment planning study evaluated the feasibility of two DE levels for advanced HNSCC patients, planned with either intensity-modulated photon therapy (IMXT) or proton therapy (IMPT).

Materials and methods: For 45 HNSCC patients, IMXT and IMPT treatment plans were created including DE via a simultaneous integrated boost (SIB) in the high-risk volume, while maintaining standard fractionation with 2 Gy per fraction in the remaining target volume. Two DE levels for the SIB were compared: 2.3 and 2.6 Gy. Treatment plan evaluation included assessment of tumor control probabilities (TCP) and normal tissue complication probabilities (NTCP).

Results: An increase of approximately 10% in TCP was estimated between the DE levels. A pronounced high-dose rim surrounding the SIB volume was identified in IMXT treatment. Compared to IMPT, this extra dose slightly increased the TCP values and to a larger extent the NTCP values. For both modalities, the higher DE level led only to a small increase in NTCP values (mean differences <2%) in all models, except for the risk of aspiration, which increased on average by 8 and 6% with IMXT and IMPT, respectively, but showed a considerable patient dependence.

Conclusion: Both DE levels appear applicable to patients with IMXT and IMPT since all calculated NTCP values, except for one, increased only little for the higher DE level. The estimated TCP increase is of relevant magnitude. The higher DE schedule needs to be investigated carefully in the setting of a prospective clinical trial, especially regarding toxicities caused by high local doses that lack a sound dose-response description, e.g., ulcers.

Keywords: head-and-neck cancer; normal tissue complication probability; photon radiotherapy; proton radiotherapy; tumor control probability.

Figure 1

Relative dose distributions. (A) Illustration of calculating the voxel-wise relative dose distribution, exemplarily for DE level of 2.3 Gy. For the high DE level, the SIB volume is normalized to 2.6 Gy in the same way. (B) Relative dose distribution in the elective target only showing high-dose areas outside ICRU constraints (>107%). All four SIB treatment plans for one patient are shown for series I treatment, illustrating the larger high-dose rim around the SIB volume for the high DE level of 2.6 Gy. PTV_elec is outlined in black, GTV_SIB-I in yellow.

Figure 2

Schematic drawing of the sub-volume TCP model approach. Empirical dose–response data from comparable patient cohorts – given as (A) dose–response curve and (B) spatial distribution of local failures (represented by the asterisks) – serve as input to generate (C) one dose–response curve for each target sub-volume. The total TCP results from the product of all sub-volume TCP. Note, all target sub-volumes have to be disjoint. Therefore, inner sub-volumes are excluded from outer encompassing structures.

Figure 3

Estimated differences between the two dose escalation levels for IMXT and IMPT: (A) ΔTCP and (B) ΔNTCP. MUC, oral mucositis; X12, xerostomia after 12 months; ASP, aspiration; DYS, physician-rated swallowing dysfunction; SWS, patient-rated problems with swallowing solids; SWL, patient-rated problems with swallowing liquids; LOE, laryngeal edema; TRI, trismus.

Figure 4

Dependence of the difference in total tumor control probability ΔTCP between the two dose escalation levels on the model input parameters (A) D₅₀ and (B) γ₅₀. Results are shown for IMXT and IMPT plans. The enlarged symbols mark the parameter values used in this study.