Inter-fraction robustness of intensity-modulated proton therapy in the post-operative treatment of oropharyngeal and oral cavity squamous cell carcinomas.

OBJECTIVE: To evaluate dosimetric consequences of inter-fraction setup variation and anatomical changes in patients receiving multifield optimised (MFO) intensity modulated proton therapy for post-operative oropharyngeal (OPC) and oral cavity (OCC) cancers. METHODS: Six patients receiving MFO for post-operative OPC and OCC were evaluated. Plans were robustly optimised to clinical target volumes (CTVs) using 3 mm setup and 3.5% range uncertainty. Weekly online cone beam CT (CBCT) were performed. Planning CT was deformed to the CBCT to create virtual CTs (vCTs) on which the planned dose was recalculated. vCT plan robustness was evaluated using a setup uncertainty of 1.5 mm and range uncertainty of 3.5%. Target coverage, D95%, and hotspots, D0.03cc, were evaluated for each uncertainty along with the vCT-calculated nominal plan. Mean dose to organs at risk (OARs) for the vCT-calculated nominal plan and relative % change in weight from baseline were evaluated. RESULTS: Robustly optimised plans in post-operative OPC and OCC patients are robust against inter-fraction setup variations and range uncertainty. D0.03cc in the vCT-calculated nominal plans were clinically acceptable across all plans. Across all patients D95% in the vCT-calculated nominal treatment plan was at least 100% of the prescribed dose. No patients lost ≥10% weight from baseline. Mean dose to the OARs and max dose to the spinal cord remained within tolerance. CONCLUSION: MFO plans in post-operative OPC and OCC patients are robust to inter-fraction uncertainties in setup and range when evaluated over multiple CT scans without compromising OAR mean dose. ADVANCES IN KNOWLEDGE: This is the first paper to evaluate inter-fraction MFO plan robustness in post-operative head and neck treatment.

A Phase 2 Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed After Transoral Robotic Surgery for Human Papilloma Virus-Related Squamous Cell Carcinoma of the Oropharynx.

PURPOSE: This trial tested the safety and efficacy of a novel, deintensified radiation therapy (RT) approach after initial surgical resection for patients with human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS: This single-arm phase 2 prospective clinical trial enrolled 60 patients with stage pT1-pT2 N1-3 HPV-associated OPSCC treated with transoral robotic surgery (TORS) and selective neck dissection at a single institution between May 2014 and September 2017. Patients had favorable features at the primary site (negative surgical margins ≥2 mm, no perineural invasion, and no lymphovascular invasion) but required adjuvant therapy based on lymph node involvement. Surgeries were all performed at a high-volume head and neck cancer center with expertise in TORS. Patients received postoperative RT to at-risk areas in the involved neck (60-66 Gy) and uninvolved neck (54 Gy). The resected primary site was treated as an active avoidance structure in the treatment planning of postoperative RT. Concurrent chemotherapy was administered for patients with extranodal extension. RESULTS: Median follow-up of the 60 patients enrolled was 2.4 years (range, 8.5-53.8 months). A single patient recurred at the primary site, for 2-year local control of 98.3%. One patient (1.7%) developed a regional neck recurrence, and 2 patients (3.3%) developed distant metastases. Measured 2-year local recurrence-free survival was 97.9% (95% confidence interval, 86.1%-99.7%). Overall survival was 100% at the time of analysis. The mean radiation dose to the primary site was 36.9 Gy (standard deviation, 10.3 Gy). Two patients (3.3%) experienced late soft tissue necrosis in the primary site surgical bed that resolved within 2 months. Feeding tube dependence rates were 0% during RT, 3.3% temporarily during follow-up, and 0% at last follow-up. CONCLUSIONS: Deintensified postoperative RT that avoids the resected primary tumor site and targets only the at-risk neck after TORS for selected patients with HPV-associated OPSCC may be safe and is worthy of further study.

Impact of Multi-leaf Collimator Parameters on Head and Neck Plan Quality and Delivery: A Comparison between Halcyon™ and Truebeam® Treatment Delivery Systems.

Purpose A new dual-layer multi-leaf collimator (MLC) system with several improved characteristics was introduced with the Varian Halcyon™ treatment platform. This study evaluated this new MLC's impact on head and neck plan quality and delivery efficiency. Methods Nine patients were retrospectively studied with Institutional Review Board (IRB) approval. To compare plan quality between the Halcyon dual-layer MLC and Truebeam® MLC, all patients were replanned with the same prescription and target coverage following the institutional clinical protocol for both platforms and using both intensity modulated radiation therapy (IMRT) or volumetrically modulated arc therapy (VMAT) techniques. Organs-at-risk (OAR) dose-volume histogram (DVH) statistics were compared along with total plan monitor units (MU). To evaluate delivery efficiency, actual beam-on time for five patients' plans were recorded and compared. To evaluate the impact of MLC performance parameters on plan quality, virtual MLC models were generated by matching Truebeam MLC's parameters to those of the Halcyon dual-layer MLC both individually and combined. OAR doses were then compared between these virtual MLCs, the Truebeam MLC, and the actual Halcyon MLC. Results Overall the Halcyon dual-layer MLC provided similar plan quality compared to Truebeam MLC for VMAT plans, and improved sparing for majority of the OARs when using IMRT. Paired comparison showed median dose differences in mean doses to the parotids, cochlea, esophagus, and larynx ranged from -0.83 Gy to 0.37 Gy for VMAT, and from -4.79 Gy to -0.04 Gy for IMRT, with negative values indicating improved performance by Halcyon. Despite a slight increase in plan MU, the Halcyon reduced the total beam-on time by 42.8 ± 8.5%. Virtual MLC simulations demonstrated that matching MLC transmission accounted for nearly half of the total dose difference between Halcyon and Truebeam IMRT plans. Conclusion When compared to the Truebeam, the Halcyon's dual-layer MLC achieved similar plan quality using VMAT, and improved OAR sparing using IMRT, while providing nearly twice as fast treatment delivery. Reduction in MLC transmission is the dominating factor contributing to dosimetric differences in OAR sparing.

Long non-coding RNA urothelial carcinoma associated 1 (UCA1) mediates radiation response in prostate cancer.

Radioresistance remains a significant obstacle in the treatment of Prostate Cancer (PCa). To simulate the clinical scenario of irradiation resistance (IRR), we created DU145-IRR PCa cell lines by treatment with 2 Gy daily IR for 59 fractions. DU145-IRR cells acquired an aggressive phenotype as evidenced by increased clonogenic survival, tumorigenic potential and invasiveness. We performed transcriptome profiling to discover dysregulated genes in DU145-IRR cells and identified the long non-coding RNA (lncRNA), Urothelial carcinoma-associated 1 (UCA1). We first investigated the role of UCA1 in radiation response and found that UCA1 abundance was significantly higher in DU145-IRR cells compared to control cells. UCA1 siRNA-knockdown reversed the aggressive phenotype and significantly increased sensitivity to IR. UCA1 depletion inhibited growth, induced cell cycle arrest at the G2/M transition and decreased activation of the pro-survival Akt pathway. We then studied the clinical significance of UCA1 expression in two independent cohorts of PCa patients: MSKCC (130 patients) and CPC-GENE (209 patients). UCA1 over-expression was associated with decreased 5-year disease-free survival in MSKCC patients (HR = 2.9; p = 0.007) and a trend toward lower biochemical recurrence-free survival in CPC-GENE patients (HR = 2.7; p = 0.05). We showed for the first time that UCA1 depletion induces radiosensitivity, decreases proliferative capacity and disrupts cell cycle progression, which may occur through altered Akt signaling and induced cell cycle arrest at the G2/M transition. Our results indicate that UCA1 might have prognostic value in PCa and be a potential therapeutic target.

Role of palliative radiotherapy in the management of mural cardiac metastases: who, when and how to treat? A case series of 10 patients.

Cardiac metastases (CM), although a rare manifestation of metastatic cancer, are increasing in incidence with the improved prognosis and increased longevity of many patients with cancer. This condition may be life-threatening, especially for bulky rapidly growing tumors. Such cancer presentations may be amenable to palliative radiotherapy to improve symptoms and to prevent further cardiac function decline. Here, we report on our experience with 10 patients with mural CM who received radiotherapy (RT) to the heart with palliative intent. The radiation treatment was given in different clinical situations using different dose and fractionation, and with a variety of outcomes. Palliative RT was a reasonably effective treatment, leading to good radiographic response in five patients who were evaluable for radiologic response. The mean duration of response in responding patients was 6.3 months (range: 3-11 months). This report describing clinical dilemmas around CM radiation therapy summarizes the previous experiences with radiation in treatment of CM and may assist in the considerations of palliative treatment for these patients.

Seroprevalence of human herpes simplex, hepatitis B and epstein-barr viruses in children with acute lymphoblastic leukemia in southern iran.

To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age-sex matched healthy participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA) were measured by enzyme-linked immunosorbent assay (ELISA). There were 54 (60%) male and 36 (40%) female in both study groups with mean age of 8.47 ± 3.61 and 8.61 ± 2.84 years in case and control group respectively (P = 0.812). The prevalence of antibodies against HBsAg (P = 0.002), HSV1 (P < 0.0001), VCA (P = 0.021) and EA (P < 0.0001) antigens of EBV were significantly higher in ALL patients. With the results of this study, we could not exclude a connection between these viral infections and later leukemogenesis in childhood ALL, although nor latent infection nor congenital infection cannot be excluded by this method.