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Figure S1B- Higher magnification showing the skin of the mini-pig 15 and 32 weeks post radiotherapy (RT). At 15 weeks, skin area irradiated with 31Gy-FLASH-RT shows hair regrowth but not with 31Gy-Conv-RT. At 32 weeks, skin area irradiated with 34Gy-FLASH-RT is healthy whereas contractile skin fibrosis is observed with 34 Gy-Conv-RT.

Supplementary Data Table S1: WHO staging system (TNM Classification of Tumors in Domestic Animals. Geneva: World Health Organization; 1980) Table S2: Cat patient and treatment characteristics

Purpose:Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals.Experimental Design:Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT.Results:Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%.Conclusions:Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients.See related commentary by Harrington, p. 3

Figure S1: A- Serial pictures showing evolution of the mini-pig's skin over time post FLASH and Conv-RT. Three doses are shown (28-34Gy) 24h to 32 weeks post-RT.

Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3

Lumbo-sacral chordoma is a rare, slow-growing tumor, arising from embryonic nothocordal remnants. Wide en bloc excision with clear margins remains mandatory to achieve satisfactory recurrence rates and disease-free survival. No chemotherapy has been demonstrated to be effective and radiotherapy is only marginally effective. Tyrosine kinase receptor inhibitors have showed encouraging results in locally advanced and metastatic chordoma. Reconstructive surgery may become very complex. Multidisciplinary approach in tertiary hospitals is always necessary.

Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC.L’immunothérapie, en particulier les inhibiteurs de points de contrôles immunitaires (checkpoints) tels que les anticorps anti-PD1 et anti-PDL1, a déjà modifié la prise en charge standard et le pronostic du mélanome, mais également du cancer pulmonaire, rénal et du lymphome de Hodgkin. Les résultats des études préliminaires sont aussi prometteurs dans le traitement des carcinomes épidermoïdes ORL, ainsi que pour des cancers plus rares de la sphère tête et cou, comme les carcinomes nasopharyngés et les carcinomes de haut grade des glandes salivaires. Le traitement anti-PD1 par nivolumab a récemment démontré un bénéfice de survie globale chez les patients présentant un carcinome épidermoïde ORL récidivant et/ou métastatique résistant aux platines dans une étude de phase 3.

We investigated in a prospective cohort of patients treated with trans-oral robotic surgery (TORS) for oropharyngeal cancer (OPC), who were selected for the absence of radiographic extra-capsular extension (ECS) and surgically revised for inadequate margins, the possibility of reducing adjuvant radiation (RT)/chemo-radiation therapy (CRT) without jeopardizing tumor control and functional outcome.We conducted a prospective observational cohort of patients treated with TORS for oropharyngeal cancer.Twenty-nine patients with T1/2N0 to N2B stage cancers were treated with TORS. Forty-five percent of them were treated for secondary primaries. Nine of 29 patients (31%) were revised for close/positive margins. Adjuvant RT was prescribed for 2 of 19 patients with early squamous cell carcinoma (SCCs) and CRT for 1 of 10 patients with advanced oropharyngeal SCCs. Overall survival (OS), disease-specific survival (DSS), and locoregional control at 2 years were 85%, 96%, and 93%, respectively. Posttreatment Functional Outcome Swallowing Scale (FOSS) scores worsened with prior or adjuvant RT, local recurrence, site, and revision for margins.Patients with early and moderately advanced oropharyngeal SCC selected for radiographic ECS and revised for inadequate margins have excellent tumor control and favorable functional recovery. © 2017 Wiley Periodicals, Inc. Head Neck 39: 965-973, 2017.

Lumbo-sacral chordoma is a rare, slow-growing tumor, arising from embryonic nothocordal remnants. Wide en bloc excision with clear margins remains mandatory to achieve satisfactory recurrence rates and disease-free survival. No chemotherapy has been demonstrated to be effective and radiotherapy is only marginally effective. Tyrosine kinase receptor inhibitors have showed encouraging results in locally advanced and metastatic chordoma. Reconstructive surgery may become very complex. Multidisciplinary approach in tertiary hospitals is always necessary.