Additional file 1 of Ways to unravel the clinical potential of carbon ions for head and neck cancer reirradiation: dosimetric comparison and local failure pattern analysis as part of the prospective randomized CARE trial

Additional file 1: Tab. S3. Target dose-volume comparison of reirradiation with CIRT vs. VMAT in recurrent head and neck cancer. Relative dose differences are specified in percent of 60 Gy equivalent dose in 2 Gy fractions. Tab. S4. Organs at risk dose-volume comparison of reirradiation with CIRT vs. VMAT in recurrent head and neck cancer. Relative dose differences are specified in percent of 60 Gy equivalent dose in 2 Gy fractions. Tab. S5. Clinical goals comparison of reirradiation with CIRT vs. VMAT in recurrent head and neck cancer. Fig. S5. 57-year-old male patient with recurrent nasopharyngeal cancer treated with 51 Gy (RBE) CIRT (D–F) around 0.7 years after prior radiotherapy with 74 Gy. CIRT yielded significant clinical benefits w.r.t. the spinal cord (− 29.5% Dmax) compared to VMAT (A–C). The patient developed type E local failure (> CTV + 5 mm), delineated on the planning CT (D–F), caused by aberrant areas of recurrence. Fig. S6. 72-year-old female patient with recurrent paranasal sinus cancer treated with 60 Gy VMAT (A–C) around 1 year after prior radiotherapy with 66 Gy. CIRT (D–F) yielded significant clinical benefits w.r.t. the brainstem (− 19.7% Dmax), ipsilateral eye (− 27.0% Dmean) and ipsilateral inner ear (− 13.3% Dmean). The patient developed type B and E (> CTV + 5 mm) local failure, delineated on the planning CT (A–C), caused by overgrown recurrence and aberrant areas of recurrence. Fig. S7. 54-year-old male patient with recurrent nasopharyngeal cancer treated with 60 Gy VMAT (A–C) around 4.5 years after prior radiotherapy with 64 Gy. CIRT (D–F) yielded significant clinical benefits w.r.t. the brainstem (− 37.0% Dmax), ipsilateral inner ear (− 26.8% Dmean) and contralateral inner ear (− 20.2% Dmean). The patient developed no local failure during follow-up. Fig. S8. 54-year-old male patient with recurrent paranasal sinus cancer treated with 54 Gy (RBE) CIRT (D–F) around 1.6 years after prior radiotherapy with 60 Gy. CIRT yielded significant clinical benefits w.r.t. the brainstem (− 43.5% Dmax) and the contralateral eye (− 17.7% Dmax) compared to VMAT (A–C). The patient developed type E local failure (< CTV + 5 mm), delineated on the planning CT (D–F), caused by improper risk assessment. Fig. S9. 52-year-old female patient with skull base recurrence treated with 60 Gy VMAT (A–C) around 1 year after prior radiotherapy with 70 Gy. CIRT (D–F) yielded significant clinical benefits w.r.t. the ipsilateral inner ear (− 13.8% Dmean) and the optic chiasma (− 13.5% Dmax) but not the brainstem (+ 2.2% Dmax). The patient developed type E local failure (> CTV + 5 mm), delineated on the planning CT (A–C), caused by aberrant areas of recurrence. Fig. S10. 49-year-old male patient with recurrent nasopharyngeal cancer treated with 60 Gy VMAT (A–C) around 3.3 years after prior radiotherapy with 64 Gy. CIRT (D–F) yielded significant clinical benefits w.r.t. the optic chiasma (− 50.7% Dmax), ipsilateral optic nerve (− 29.3% Dmax) and ipsilateral inner ear (− 28.0% Dmean). The patient developed type B local failure, delineated on the planning CT (A–C), caused by dosimetric failure due to direct contact of the tumor to the brainstem. CIRT was non-superior with regard to gross tumor volume coverage next to the brainstem. Fig. S11. 61-year-old male patient with hypopharyngeal recurrence treated with 51 Gy (RBE) CIRT (D–F) around 3.6 years after previous radiotherapy with 60 Gy. CIRT yielded significant clinical benefits w.r.t. the spinal cord (− 23.8% Dmax) compared to VMAT (A–C). The patient developed type A local failure in the central high-dose region of the CTV, caused by biological and/or dosimetric failure. The recurrent tumor (rGTV) and its centroid were delineated in black/red and mapped to the planning CT (D–F). Dose recalculation with the modified microdosimetric model showed no relevant changes compared to the local effect model I. Fig. S12. 50-year-old male patient with recurrent nasal cavity cancer treated with 51 Gy (RBE) CIRT (D–F) around 1.2 years after prior radiotherapy with 66 Gy. CIRT yielded significant clinical benefits w.r.t. the optic chiasma (− 25.0% Dmax), ipsilateral/contralateral optic nerve (− 41.0% Dmax) and ipsilateral eye (− 40.2% Dmean) compared to VMAT (A–C). The patient developed type B and E local failure, delineated on the planning CT (D–F), caused overgrown recurrence and aberrant areas of recurrence. Fig. S13. 69-year-old male patient with recurrent oropharyngeal cancer treated with 54 Gy (RBE) CIRT (D–F) around 17.9 years after prior radiotherapy with 66 Gy. CIRT yielded significant clinical benefits w.r.t. the spinal cord (− 25.8% Dmax) but not the mandible (+ 7.8% Dmax; − 10.2% Dmean) compared to VMAT (A–C). The patient developed no local failure during follow-up.

补充材料1：表S3 复发性头颈部癌碳离子放疗（CIRT, Carbon Ion Radiotherapy）与容积调强放疗（VMAT, Volume-Modulated Arc Therapy）再程放疗的靶区剂量体积对比。相对剂量差异以60 Gy等效2 Gy分次剂量的百分比表示。表S4 复发性头颈部癌CIRT与VMAT再程放疗的危及器官剂量体积对比。相对剂量差异以60 Gy等效2 Gy分次剂量的百分比表示。表S5 复发性头颈部癌CIRT与VMAT再程放疗的临床目标对比。

图S5 1例57岁男性复发性鼻咽癌患者，于接受74 Gy常规放疗后约0.7年，采用51 Gy（相对生物效应RBE, Relative Biological Effectiveness）CIRT治疗（D-F组）。与VMAT治疗（A-C组）相比，CIRT在脊髓剂量方面具有显著临床获益（最大剂量Dmax降低29.5%）。该患者出现E型局部失败（>临床靶区CTV+5mm范围），于计划CT（D-F）上勾画，由复发异常区域导致。

图S6 1例72岁女性复发性鼻窦癌患者，于接受66 Gy常规放疗后约1年，采用60 Gy VMAT治疗（A-C组）。CIRT治疗（D-F组）在脑干（最大剂量Dmax降低19.7%）、同侧眼球（平均剂量Dmean降低27.0%）及同侧内耳（平均剂量Dmean降低13.3%）方面具有显著临床获益。该患者出现B型和E型局部失败（>CTV+5mm范围），于计划CT（A-C）上勾画，由过度生长的复发灶及复发异常区域导致。

图S7 1例54岁男性复发性鼻咽癌患者，于接受64 Gy常规放疗后约4.5年，采用60 Gy VMAT治疗（A-C组）。CIRT治疗（D-F组）在脑干（最大剂量Dmax降低37.0%）、同侧内耳（平均剂量Dmean降低26.8%）及对侧内耳（平均剂量Dmean降低20.2%）方面具有显著临床获益。该患者随访期间未出现局部失败。

图S8 1例54岁男性复发性鼻窦癌患者，于接受60 Gy常规放疗后约1.6年，采用54 Gy（RBE）CIRT治疗（D-F组）。与VMAT治疗（A-C组）相比，CIRT在脑干（最大剂量Dmax降低43.5%）及对侧眼球（最大剂量Dmax降低17.7%）方面具有显著临床获益。该患者出现E型局部失败（<CTV+5mm范围），于计划CT（D-F）上勾画，由风险评估不当导致。

图S9 1例52岁女性颅底复发癌患者，于接受70 Gy常规放疗后约1年，采用60 Gy VMAT治疗（A-C组）。CIRT治疗（D-F组）在同侧内耳（平均剂量Dmean降低13.8%）及视交叉（最大剂量Dmax降低13.5%）方面具有显著临床获益，但对脑干无显著获益（最大剂量Dmax升高2.2%）。该患者出现E型局部失败（>CTV+5mm范围），于计划CT（A-C）上勾画，由复发异常区域导致。

图S10 1例49岁男性复发性鼻咽癌患者，于接受64 Gy常规放疗后约3.3年，采用60 Gy VMAT治疗（A-C组）。CIRT治疗（D-F组）在视交叉（最大剂量Dmax降低50.7%）、同侧视神经（最大剂量Dmax降低29.3%）及同侧内耳（平均剂量Dmean降低28.0%）方面具有显著临床获益。该患者出现B型局部失败，于计划CT（A-C）上勾画，由肿瘤与脑干直接接触导致的剂量学失败所致。CIRT在脑干旁大体肿瘤体积覆盖方面未体现优势。

图S11 1例61岁男性下咽癌复发患者，于接受60 Gy常规放疗后约3.6年，采用51 Gy（RBE）CIRT治疗（D-F组）。与VMAT治疗（A-C组）相比，CIRT在脊髓剂量方面具有显著临床获益（最大剂量Dmax降低23.8%）。该患者在CTV中央高剂量区出现A型局部失败，由生物学和/或剂量学失败导致。复发肿瘤（rGTV, recurrent gross tumor volume）及其质心以黑/红色勾画并匹配至计划CT（D-F）。采用改进型微剂量学模型进行剂量再计算，与局部效应模型I相比无显著变化。

图S12 1例50岁男性复发性鼻腔癌患者，于接受66 Gy常规放疗后约1.2年，采用51 Gy（RBE）CIRT治疗（D-F组）。与VMAT治疗（A-C组）相比，CIRT在视交叉（最大剂量Dmax降低25.0%）、同侧/对侧视神经（最大剂量Dmax降低41.0%）及同侧眼球（平均剂量Dmean降低40.2%）方面具有显著临床获益。该患者出现B型和E型局部失败，于计划CT（D-F）上勾画，由复发灶过度生长及复发异常区域导致。

图S13 1例69岁男性复发性口咽癌患者，于接受66 Gy常规放疗后约17.9年，采用54 Gy（RBE）CIRT治疗（D-F组）。与VMAT治疗（A-C组）相比，CIRT在脊髓剂量方面具有显著临床获益（最大剂量Dmax降低25.8%），但对下颌骨无显著获益（最大剂量Dmax升高7.8%，平均剂量Dmean降低10.2%）。该患者随访期间未出现局部失败。