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.

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.