In head and neck cancer, especially in elderly patients who are not candidates for concurrent chemotherapy there is renewed interest in hypofractionated radiation therapy, however there is limited data and lack of consensus to support its use. Additionally, swallowing outcomes for patients treated with radiotherapy alone are poorly described compared with those treated with chemo-radiotherapy, largely because they represent a group under-represented in clinical trials.

This multi-center retrospective observational study in UK compared long term swallowing function as well as outcomes (i.e., LRC and OS) between patients treated with curative intent mild hypofractionation (65-66 Gy in 30 fx over 6 weeks) and standard fractionation (70 Gy in 35 fx over 7 weeks) radiation alone for locally-advanced oropharyngeal squamous cell carcinoma (OPSCC). Swallowing function was assessed using MD Anderson Dysphagia Inventory (MDADI) questionnaire, which was sent to patients alive and cancer-free at a minimum of 2 years post-radiotherapy (n = 151, 65%).

LRC and OS were similar across schedules (p = 0.78 and 0.95 respectively, log-rank test). Enteral feeding rates during radiotherapy appeared higher in the 7-week group though this did not reach statistical significance (59% vs 48%, p = 0.08). Feeding rates were similar at 1 year post radiotherapy for both groups (10% vs 6%, p = 0.27). 107 patients returned MDADI questionnaires (71%); there were no differences between the 6- and 7-week groups for median global (60.0 vs 60.0, p = 0.99) and composite (65.8 vs 64.2, p = 0.44) MDADI scores.

This observational study of patients with oropharyngeal cancer who were treated with radiation therapy only, suggests that treatment outcomes and long-term swallowing function after mild hypofractionation over six weeks are comparable to standard fractionation over seven weeks

Reference (Pub-Med Link): Price, J. M., West, C. M., Dixon, L. M., et al.  (2022). Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharyngeal cancer: A multi-centre study. Radiotherapy and Oncology, 172, 111–117. https://doi.org/10.1016/j.radonc.2022.05.013

This publication reports the longer term follow-up from the previously reported 3-year follow up of this randomized phase III trial investigating induction chemotherapy with gemcitabine and cisplatin followed by chemoradiation for patients with locoregionally advanced nasopharyngeal cancer. The study involved patients treated with concurrent chemoRT alone (238 pts) versus gemcitabine and cisplatin followed by concurrent chemoRT (242 pts).

Previous 3-year overall survival was shown to be improved with induction chemotherapy followed by chemoRT (94% vs 93%) compared to chemoRT alone. This 5-year overall survival study continues to see this trend with 88% vs 79% overall survival, respectively. The authors were able to correlate tumor response with the induction chemotherapy to the overall survival. Patients who had complete response had 100% overall survival at 5 years. Patients with partial response and stable disease were less likely to survive at 5 years with 88% and 62% overall survival. The authors did a subset analysis of patients with low pre-treatment EBV and found that overall survival for this cohort of patients was not different between the induction chemo and chemoRT versus chemoRT alone (91% vs 91%).

Reference (Pub-Med Link): Zhang, Y., Chen, L., Hu, G.-Q., et al. (2022). Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction  Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial. Journal of Clinical Oncology, 40(22), 2420–2425. https://doi.org/10.1200/JCO.22.00327

Key Institution: Sun Yat-sen University Cancer Center and other hospitals in China
Keywords: H&N

In this retrospective nonrandomized study, the authors analyzed 1483 adult patients with nonmetastatic locally advanced cancers treated with concurrent chemotherapy between 2011 and 2016 at the University of Pennsylvania. 391 patients received proton therapy and 1092 received photon therapy. The main research question was whether proton therapy can reduce the risk of severe adverse events associated with unplanned hospitalizations compared to photon therapy for patients also receiving chemotherapy. The authors found that patients treated with protons tended to be older, with more medical comorbidities. Despite this, patients treated with protons had a lower risk of developing 90-day adverse events of at least grade 3, grade 2, and were less likely to have a decline in overall performance status. There was no difference in disease-free or overall survival. Although this does appear favorable for proton therapy, there are several important limitations. The study is retrospective and although the authors did use statistical techniques to try to account for potential sources of bias, there may be unmeasured differences between the groups, and randomize prospective studies are needed to confirm these results.

Reference (PubMed Link): Baumann BC, Mitra N, Harton JG, et al. Comparative effectiveness of proton vs photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer. JAMA Oncol 2019;6:237-46.

Key Institution: U Pennsylvania
Keywords: Proton therapy, photon therapy, locally advanced cancer, concurrent chemoradiation 

The purpose of this study was to compare clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) who receive ablative photon vs proton therapy.

This was a single-institution retrospective study looking at patients treated between 2008-2017 with unresectable HCC not treated with prior RT. This study looked at OS (main endpoint) as well as incidence of non-classic radiation-induced liver disease.

There were 133 patients on this study with a median follow-up of 14 months. There were 49 (37%) patients who received proton therapy. The study found that proton therapy was associated with a higher OS (HR 0.47, p=0.047). Proton therapy was also found to be associated with a lower risk of radiation-induced liver disease (OR 0.26, p=0.03). There was no difference in locoregional recurrence between the two arms.

The results showed that proton therapy was associated with improved OS compared to photon therapy, possibly owing to a reduction in the incidence of radiation-related liver disease. The findings of this retrospective study support a prospective study comparing proton and photon therapy for treatment of unresectable HCC.

Reference (PubMed Link): Sanford NN, Pursley J, Noe B, et al. Protons versus photons for unresectable hepatocellular carcinoma: Liver decompensation and overall survival. Int J Radiat Oncol Biol Phys 2019;105:64-72.

Key Institution: Harvard
Keywords: HCC, proton therapy, ablative radiation