Dusquetide: Reduction in oral mucositis associated with enduring ancillary benefits in tumor resolution and decreased mortality in head and neck cancer patients.

Innate immunity is a key component in the pathogenesis of oral mucositis, a universal toxicity of chemoradiation therapy (CRT). Dusquetide, a novel Innate Defense Regulator, has demonstrated both nonclinical and clinical efficacy in ameliorating severe oral mucositis (SOM). Long term follow-up studies from the Phase 2 clinical study evaluating dusquetide as a treatment for SOM in head and neck cancer (HNC) patients receiving CRT have now been completed. Extended analysis indicates that dusquetide therapy was well-tolerated and did not contribute to increased infection, tumor growth or mortality. Potential ancillary benefits of duquetide therapy were also identified.

Dusquetide: A novel innate defense regulator demonstrating a significant and consistent reduction in the duration of oral mucositis in preclinical data and a randomized, placebo-controlled phase 2a clinical study.

Dusquetide, a novel Innate Defense Regulator, modulates the innate immune system at a key convergence point in intracellular signaling pathways and has demonstrated activity in both reducing inflammation and increasing clearance of bacterial infection. Innate immunity has also been implicated in the pathogenesis of oral mucositis (OM), a universal toxicity of chemoradiation therapy (CRT). Testing the hypothesis that dusquetide can mitigate the development and duration of OM, preclinical studies have been completed and correlated with interim results from a Phase 2 clinical study in patients undergoing CRT for head and neck cancer. Dusquetide reduced the duration of OM in mouse and hamster models by approximately 50%, which was recapitulated by the 50% reduction of severe OM (SOM) in the Phase 2 trial. A reduction in the clinical rate of infection was also observed, consistent with previously reported preclinical studies. In aggregate, these results not only demonstrate the safety and efficacy of dusquetide in addressing this unmet medical need, but also provide proof of concept for the translation of dusquetide action between animal models and the human clinical setting, and further support the contention that innate immunity is an important driver for the initiation and continued impact of OM.

American Society for Radiation Oncology (ASTRO) 2012 Workforce Study: the radiation oncologists' and residents' perspectives.

PURPOSE: The American Society for Radiation Oncology (ASTRO) conducted the 2012 Radiation Oncology Workforce Survey to obtain an up-to-date picture of the workforce, assess its needs and concerns, and identify quality and safety improvement opportunities. The results pertaining to radiation oncologists (ROs) and residents (RORs) are presented here. METHODS: The ASTRO Workforce Subcommittee, in collaboration with allied radiation oncology professional societies, conducted a survey study in early 2012. An online survey questionnaire was sent to all segments of the radiation oncology workforce. Respondents who were actively working were included in the analysis. This manuscript describes the data for ROs and RORs. RESULTS: A total of 3618 ROs and 568 RORs were surveyed. The response rate for both groups was 29%, with 1047 RO and 165 ROR responses. Among ROs, the 2 most common racial groups were white (80%) and Asian (15%), and the male-to-female ratio was 2.85 (74% male). The median age of ROs was 51. ROs averaged 253.4 new patient consults in a year and 22.9 on-treatment patients. More than 86% of ROs reported being satisfied or very satisfied overall with their career. Close to half of ROs reported having burnout feelings. There was a trend toward more frequent burnout feelings with increasing numbers of new patient consults. ROs' top concerns were related to documentation, reimbursement, and patients' health insurance coverage. Ninety-five percent of ROs felt confident when implementing new technology. Fifty-one percent of ROs thought that the supply of ROs was balanced with demand, and 33% perceived an oversupply. CONCLUSIONS: This study provides a current snapshot of the 2012 radiation oncology physician workforce. There was a predominance of whites and men. Job satisfaction level was high. However a substantial fraction of ROs reported burnout feelings. Perceptions about supply and demand balance were mixed. ROs top concerns reflect areas of attention for the healthcare sector as a whole.

Low-lying rectal cancer with anal canal involvement: abdominoperineal or low anterior resection after neoadjuvant chemoradiotherapy.

BACKGROUND: Rectal cancer with anal involvement is typically treated with abdominoperineal resection (APR). However, patients treated with neoadjuvant chemoradiotherapy with good clinical response and tumor regression from the anus present a controversial management dilemma. This is a report of patients treated with low anterior resection (LAR) versus APR. METHODS: Patients with T2-3N0-2M0 (IIA-IIIC) rectal cancer with anal canal involvement were eligible. Anal canal involvement was determined by sigmoidoscopy/colonoscopy or endoscopic ultrasound. Patients were treated in the prone position with the three-field technique to 45-50.4 Gy at 1.8 Gy/fraction given concurrently with 5-fluorouracil. Patients then underwent APR/LAR via total mesorectal excision 4-6 weeks after chemoradiotherapy. LAR was performed in patients with good sphincter function at presentation, in those with sufficient tumor regression away from anal canal to permit LAR, and in those compliant with close follow-up. RESULTS: A total of 32 patients with rectal cancer with anal canal involvement were treated with neoadjuvant chemoradiotherapy. Local control was 85% and 89% for patients treated with APR and LAR, respectively. Overall survival was 76% and 86% in patients treated with APR and LAR, respectively. Pathologic complete response was seen in 24% of patients who underwent APR and 27% of patients who underwent LAR. CONCLUSION: Rectal cancers with anal involvement with good clinical response after neoadjuvant chemoradiotherapy are typically treated with APR. However, LAR may be a feasible alternative, particularly in those with excellent clinical response to neoadjuvant treatment with sufficient tumor regression away from the anal canal. In these patients close follow-up is necessary, and APR may be reserved as salvage when needed.

Prognostic significance of bone or cartilage invasion of locally advanced head and neck cancers.

PURPOSE/OBJECTIVE(S): Locally advanced squamous cell cancers of the head and neck with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with radiotherapy or less commonly definitive chemoradiotherapy (CRT). However, it is unclear whether bone or cartilage invasion confers a worse prognosis in comparison with each other. MATERIALS/METHODS: T4N0-3M0 squamous cell cancers of the head and neck patients underwent CRT or radical resection followed up with postoperative CRT. Oral cavity, oropharynx, laryngeal and hypopharyngeal squamous cell cancers were included. Radiotherapy ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based. RESULTS: Forty-six patients with BCI were treated. When treated with CRT, 5-year local control was 55% and 43% for BCI, respectively (P = 0.23). Five-year overall survival for these patients was 54% and 29% for BCI, respectively (P = 0.99). When treated with upfront resection, 5-year local control was not significantly different (P = 0.60) nor was 5-year overall survival (P = 0.15). CONCLUSIONS: This study suggests similar outcomes between patients with bone or cartilage invasion treated with upfront CRT or resection followed by CRT. Concurrent CRT may be viable alternative to resection in patients with either bone or cartilage invasion.

Treatment outcomes of T4 locally advanced head and neck cancers with soft tissue invasion or bone and cartilage invasion.

PURPOSE/OBJECTIVE(S): T4 locally advanced squamous cell cancers of the head and neck (SCCHN) with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with chemoradiotherapy (CRT). Because the organ preservation trials, more patients with BCI, as well as those with soft tissue invasion (STI), have been treated with definitive CRT. This is a review of our experience. MATERIALS/METHODS: We performed a retrospective review of patients who underwent definitive CRT or radical resection followed up with postoperative CRT for T4N0-3M0 locally advanced SCCHN. We analyzed outcomes based on STI/BCI and types of treatment. Radiotherapy doses ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based in all CRT patients. RESULTS: From 1995 to 2006, 101 patients with locally advanced SCCHN were treated definitively. Of these, 51 had STI and 50 had BCI. Of the 51 patients with STI, 42 were treated with CRT, 5 patients were treated with resection followed by CRT, and 4 patients were treated with radiotherapy alone. Of the 50 patients with BCI, 26 patients were treated with CRT, 20 patients were treated with radical resection followed by radiotherapy or CRT, and 4 patients were treated with radiotherapy alone. Five-year local-regional control was 51% and 43% for STI and BCI patients treated with CRT, respectively, and 44% for BCI treated with radical resection. Five-year overall survival was 23%, 51%, and 28% for STI treated with CRT, BCI treated with CRT, and BCI treated with radical resection. Outcomes were not statistically different between these groups. CONCLUSIONS: This study suggests similar outcomes for CRT or resection followed up with chemoradiotherapy for patients with locally advanced SCCHN with BCI. Concurrent CRT may be viable alternative to upfront resection in these patients. Further studies should be performed to validate these provocative findings.