Correlation between Biological Effective Dose and Radiation-induced Liver Disease from Hypofractionated Radiotherapy.

BACKGROUND: The prevention of radiation-induced liver disease (RILD) is very significant in ensuring a safe radiation treatment and high quality of life. AIMS AND OBJECTIVES: The purpose of this study is to investigate the correlation of physical and biological effective dose (BED) metrics with liver toxicity from hypo-fractionated liver radiotherapy. MATERIALS AND METHODS: 41 hypo-fractionated patients in 2 groups were evaluated for classic radiation-induced liver disease (RILD) and chronic RILD, respectively. Patients were graded for effective toxicity (post-treatment minus pre-treatment) using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Physical dose (PD) distributions were converted to BED. The V10Gy, V15Gy, V20Gy, V25Gy and V30Gy physical dose-volume metrics were used in the analysis together with their respective BED-converted metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3. All levels were normalized to their respective patient normal liver volumes (NLV) and evaluated for correlation to RILD. Results were measured quantitatively using R2 regression analysis. RESULTS: The classic RILD group had median follow-up time of 1.9 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD yielding R2 correlations of 0.84, 0.72, 0.73, 0.65 and 0.70, respectively while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.84, 0.74, 0.66, 0.78 and 0.74, respectively. BED compared to PD showed a statistically significant (p=.03) increase in R2 for the classic RILD group. Chronic RILD group had median follow-up time of 12.3 months and the average PD-NLV normalized V10Gy, V15Gy, V20Gy, V25Gy and V30Gy metrics per grade were plotted against RILD grade yielding R2 correlations of 0.48, 0.92, 0.88, 0.90 and 0.99 while the BED-volume metrics of V16.7Gy3, V30Gy3, V46.7Gy3, V66.7Gy3 and V90Gy3 resulted in correlation values of 0.43, 0.94, 0.99, 0.21 and 0.00, respectively. CONCLUSION: The strong correlations of the V10Gy and V15Gy PD-volume metrics as well as the V16.7Gy3 (BED of V10Gy) to both classic and chronic RILD imply the appropriateness of the current 15Gy evaluation level for liver toxicity with hypo-fractionated treatments.

Clinical Outcomes of Spatially Fractionated GRID Radiotherapy in the Treatment of Bulky Tumors of the Head and Neck.

Objectives The clinical outcomes of patients treated with spatially fractionated GRID radiotherapy (SFGRT) for bulky tumors of the head and neck at a single institution were evaluated retrospectively. Endpoints of interest included tumor response, symptom improvement, treatment tolerance, and adverse events. Methods Institutional review board approval was obtained prior to study initiation. The institutional database was queried for patients with tumors of the head and neck treated with SFGRT between August 2007 and April 2015. Medical records of identified patients were reviewed for treatment details and clinical endpoints of interest. SFGRT was delivered in one fraction of 15 gray (Gy) or 20 Gy; 6 megavolt (MV) or 18 MV photon beams were passed through a multileaf collimator (MLC)-based or brass GRID template. All patients had a planned course of conventionally-fractionated external beam radiotherapy (EBRT) to begin on the day following SFGRT delivery. Results Twenty-one consecutive patients meeting study criteria were identified. The most common tumor histology was squamous cell carcinoma. Median patient age was 59 years (range 13 - 83 years); median maximum tumor dimension was 9.5 centimeters (cm) (range 5.0 - 25.0 cm). Fifteen patients (71.4%) completed their full course of EBRT. Twelve patients were treated with palliative intent for local tumor symptoms, of which 54.5% experienced some degree of symptom improvement. Of nine patients treated with curative intent, 44.4% achieved a clinical complete response (CR). Concurrent chemotherapy was administered in 12 patients, with all patients being treated having definitively received chemotherapy. Radiation Therapy Oncology Group (RTOG) grade three or higher skin toxicity occurred in five patients; no grade five events were reported. Conclusions Our institutional experience suggests that SFGRT is a feasible treatment option for the palliative or definitive management of large tumors of the head and neck. In combination with EBRT, SFGRT can provide timely symptom management and improve patient quality of life in the palliative setting. In the definitive setting, the addition of chemotherapy to SFGRT and EBRT can result in an excellent clinical response. Treatment toxicity was found to be within an acceptable range. When considering SFGRT for patients with these challenging presentations, careful patient selection is needed to identify those who will likely tolerate a full course of EBRT following SFGRT, as these patients are most likely to receive maximal benefit from SFGRT treatment. More data on the feasibility and efficacy of this radiation modality will be helpful for continued optimization of SFGRT delivery and patient selection.

Quantitatively and qualitatively augmenting medical student knowledge of oncology and radiation oncology: an update on the impact of the oncology education initiative.

PURPOSE: The Oncology Education Initiative was established in 2007 in an effort to advance oncology and radiation oncology education at the undergraduate level. As a continuation of the initiative, the aim of this study was to determine whether these structured didactics would continue to increase overall medical student knowledge about oncologic topics. METHODS: Preclerkship and postclerkship tests examining concepts in general oncology, radiation oncology, breast cancer, and prostate cancer were administered. The 21-question, multiple-choice examination was administered at the beginning and end of the radiology clerkship, during which a 1.5-hour didactic session was given by an attending radiation oncologist. Changes in individual question responses, student responses, and overall categorical responses were analyzed. All hypothesis tests were two tailed with a significance level of .05. RESULTS: In the 2009-2010 academic year, 155 third-year and fourth-year students had average examination score improvements from 62% to 68.9% (P < .0001). Every topic (100%) showed improvement in scores, with the largest absolute improvement seen in the radiation oncology category, which increased from 56.5% to 71.8% (P < .0001). As the year proceeded, average examination scores increased among third-year students and decreased among fourth-year students. CONCLUSIONS: In the successive years since its inception, the Oncology Education Initiative continues to show a significant improvement in medical students' knowledge of cancer. The initiative has also succeeded in providing radiation oncology education to all graduating medical students at the authors' institution. Dedicated oncology education in the undergraduate medical curriculum provides students with a better understanding of multidisciplinary oncology management.

Variation in the presence of neuraminidase genes among Streptococcus pneumoniae isolates with identical sequence types.

Streptococcus pneumoniae frequently colonizes the upper respiratory tract of young children and is an important cause of otitis media and invasive disease. Carriage is more common than disease, yet the genetic factors that predispose a given clone for disease are not known. The relationship between capsule type, genetic background, and virulence is complex, and important questions remain regarding how pneumococcal clones differ in their ability to cause disease. Pneumococcal neuraminidase cleaves sialic acid-containing substrates and is thought to be important for pneumococcal virulence. We describe the distribution of multilocus sequence types (ST), capsule type, and neuraminidase genes among 342 carriage, middle ear, blood, and cerebrospinal fluid (CSF) pneumococcal strains from young children. We found 149 STs among our S. pneumoniae isolates. nanA was present in all strains, while nanB and nanC were present in 96% and 51% of isolates, respectively. The distribution of nanC varied among the strain collections from different tissue sources (P = 0.03). The prevalence of nanC was 1.41 (95% confidence interval, 1.11, 1.79) times higher among CSF isolates than among carriage isolates. We identified isolates of the same ST that differed in the presence of nanB and nanC. These studies demonstrate that virulence determinants, other than capsule loci, vary among strains of identical ST. Our studies suggest that the presence of nanC may be important for tissue-specific virulence. Studies that both incorporate MLST and take into account additional virulence determinants will provide a greater understanding of the pneumococcal virulence potential.