Effects of proton versus photon irradiation on (lymph)angiogenic, inflammatory, proliferative and anti-tumor immune responses in head and neck squamous cell carcinoma
Abstract:The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological … Show more
“…Bulky tumors (prevailed in our cohort) or CTV>50 cm3 are shown to be associated with higher toxicity and poor outcomes [11,23]. Though, the lower toxicity rate of protons is usually being accounted for in its dose distribution, recent experimental studies reported lower expression of factors involved in lymph-and angiogenesis, in ammation, and immune tolerance [27].…”
Purpose: This study presents a retrospective analysis (efficacy and toxicity) of outcomes in patients with unresectable recurrence of previously irradiated head and neck cancers, treated with proton therapy.Methods: From November 2015 to January 2020, 30 patients with in-field recurrence of head and neck cancer, who were not suitable for surgery, due to medical contraindications, tumor localization or extent, received re-irradiation with intensity-modulated proton therapy (IMPT). Sites of retreatment included the aerodigestive tract (60%) and base of the skull (40%). The median total dose of prior radiotherapy was 55.0 Gy. The median time to the second course was 38 months. The median re-irradiated tumor volume was 158.1 cm3. Patients were treated with 2.0, 2.4 and 3.0 GyRBE per fraction, with a median EQD2 of 57.6 Gy (α/β=10). Radiation-induced toxicity was recorded according to the RTOG/EORTC criteria.Results: The 1- and 2-years LC, RFS, and OS were 52.6/21.0, 21.9/10.9 and 73.4/8.4%, respectively, with a median follow-up time of 21 months. The median overall survival was 16 months. Acute grade 3 toxicity was observed in 1 patient (3.3%). There were 5 late severe side effects (16.6%), with one death associated with re-irradiation.Conclusion: Re-irradiation with a proton beam can be considered a safe and efficient treatment even for a group of patients with unresectable recurrent H&N cancers.
“…Bulky tumors (prevailed in our cohort) or CTV>50 cm3 are shown to be associated with higher toxicity and poor outcomes [11,23]. Though, the lower toxicity rate of protons is usually being accounted for in its dose distribution, recent experimental studies reported lower expression of factors involved in lymph-and angiogenesis, in ammation, and immune tolerance [27].…”
Purpose: This study presents a retrospective analysis (efficacy and toxicity) of outcomes in patients with unresectable recurrence of previously irradiated head and neck cancers, treated with proton therapy.Methods: From November 2015 to January 2020, 30 patients with in-field recurrence of head and neck cancer, who were not suitable for surgery, due to medical contraindications, tumor localization or extent, received re-irradiation with intensity-modulated proton therapy (IMPT). Sites of retreatment included the aerodigestive tract (60%) and base of the skull (40%). The median total dose of prior radiotherapy was 55.0 Gy. The median time to the second course was 38 months. The median re-irradiated tumor volume was 158.1 cm3. Patients were treated with 2.0, 2.4 and 3.0 GyRBE per fraction, with a median EQD2 of 57.6 Gy (α/β=10). Radiation-induced toxicity was recorded according to the RTOG/EORTC criteria.Results: The 1- and 2-years LC, RFS, and OS were 52.6/21.0, 21.9/10.9 and 73.4/8.4%, respectively, with a median follow-up time of 21 months. The median overall survival was 16 months. Acute grade 3 toxicity was observed in 1 patient (3.3%). There were 5 late severe side effects (16.6%), with one death associated with re-irradiation.Conclusion: Re-irradiation with a proton beam can be considered a safe and efficient treatment even for a group of patients with unresectable recurrent H&N cancers.
“…Lupu‐Plesu et al . recently published results of an in vitro study in head and neck squamous cell carcinoma cells examining the biological effects of proton versus photon RT for genes involved in anti‐tumor autoimmunity, namely PD‐L1, and found that both proton and photon RT augment PD‐L1 mRNA expression in a dose‐dependent manner . Given our limited cohort size, this question should be addressed in future larger studies since no conclusion can be drawn at this time.…”
Background
Radiation‐induced tumor immunity (RITI) influences primary tumor growth and development of metastases in preclinical cancer models with conventional radiotherapy. Antigen‐specific immune responses have also been shown for prostate cancer treated with radiotherapy. We examined whether RITI can be induced in patients with non‐small cell lung cancer (NSCLC) following proton radiotherapy.
Methods
Pre‐ and post‐radiotherapy plasma samples from 26 patients with nonmetastatic NSCLC who received radiotherapy between 2010 and 2012 were evaluated by western blotting for IgG and IgM bands to assess RITI response to tumor antigens from lung cancer cell lines. Statistical analysis was used to evaluate any correlation among IgG or IgM and clinical outcomes.
Results
Twenty‐one patients received proton therapy at 2 GyRBE/fraction (n = 17) or 6–12 Gy/fraction (n = 4); five received photon therapy at 2–2.5 GyRBE/fraction. Compared with the pretreatment baseline, new IgG or IgM binding was detected in 27% and 50% of patients, respectively. New IgG bands were detected in the 25–37 kD, 50–75 kD, and 75–100 kD ranges. New IgM bands were detected in the 20–25 kD, 25–37 kD, 37–50 kD, 50–75 kD, and 75–100 kD ranges. There was no difference in IgG and/or IgM RITI response in patients treated with photons versus protons, or in patients who received SBRT compared to standard fractionation (P > 0.05). There was no difference in overall survival, metastasis‐free survival, or local control based on IgG and/or IgM RITI response (P > 0.05).
Conclusion
RITI can be induced in patients with NSCLC through upregulated IgG and/or IgM. RITI response was not associated with proton versus photon therapy or with clinical outcomes in this small cohort and should be examined in a larger cohort in future studies.
“…Further work is needed to implement proton therapy in combination with anti‐angiogenic or anti‐immune checkpoint drugs. It is not clear whether the theoretical benefits of proton beam therapy could be translated into clinically meaningful improvement for prostate cancer patients, so any progress implies an urgent need for prospective randomized clinical trials to measure the toxicity and disease control …”
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