ABSTRACT
BACKGROUND: Understanding the basis of clinical radiosensitivity is a key goal of radiation research. In this study, we used the limiting dilution assay (LDA) to analyze in vitro radiosensitivity of cell lines from individuals with breast and other cancers, who had been treated with ionizing radiation, and who either had a non-radiosensitive (RS) radiation response or who were clinically RS. METHODS: Lymphoblastoid cell lines (LCLs) were created from 29 cancer patients including 19 RS patients, 10 controls who had not developed severe normal tissue reactions, and 1 ataxia telangiectasia RS control cell line. The clinically RS patients had grade 3 or grade 4 reactions; one had a grade 2 reaction. All cells were exposed to graded doses of gamma-radiation in vitro and cell survival assessed via LDA. Cell survival was expressed on non-linear regression analysis-fitted survival curves and also as the surviving fraction at 2 Gray (Gy) (SF2). RESULTS: Our LDA analysis yielded two notable positive results. Firstly, it could distinguish control cells from cells from pooled breast cancer cases with severe reactions of all types (acute reactors, consequential late reactors and late reactors). Secondly, two radiosensitivity outliers were detected on the fitted curves, corresponding clinically to grade 3 and 4 late radiation reactions in breast and head and neck cancer cases respectively. The assay showed considerable cell survival heterogeneity. CONCLUSIONS: The LDA as used here may provide unique clinical utility in detecting potential RS breast cancer patients prior to radiotherapy (RT), a form of personalized medicine. The assay may be especially useful in situations where its results can be temporally available prior to therapy initiation (e.g., those patients not undergoing RT until some months after surgery, typically those having adjuvant chemotherapy prior to RT). Two LCLs from RS outliers could potentially yield insight into the cellular and/or genetic basis of radiosensitivity, for example by undertaking genomic analyses on these cell lines.
ABSTRACT
INTRODUCTION: Oropharyngeal squamous cell carcinoma (OPSCC) incidence has increased over the past two decades largely because of an increase in human papilloma virus (HPV)-related OPSCC. We report here outcomes of definitive radiation therapy for OPSCC with simultaneous integrated boost intensity-modulated radiotherapy (IMRT) in a regional Australian cancer centre. METHODS: We retrospectively reviewed electronic medical records (EMR) of all patients treated with IMRT for head and neck cancer. We included patients who received a curative intent IMRT for OPSCC (2010-2014). RESULTS: Of 61 patients, 80% were men, and the median age was 57 years. Ninety percent of our patients received concurrent systemic therapy, and 68% were p16 positive. The median radiotherapy dose received was 70 Gy in 35 fractions. The median follow up for surviving patients was 22 months. Twenty-four month actuarial data show that the loco-regional recurrence free, metastasis-free MFS, cancer-specific (CaSS) and overall survival percentages were 98.3%, 92.6%, 91% and 90.3%, respectively. We did not observe grades 4 or 5 acute or late toxicities, and 10 patients (16.2%) exhibited persistent grade 3 toxicity 6 months after completing the treatment. CONCLUSION: The results from curative IMRTs for OPSCC delivered in a regional cancer centre are comparable with results published by tertiary referral centres. A long-term follow up of this patient cohort will continue for further analyses and comparisons with tertiary centres.
