Destruction of hypoxic regions within tumors, virtually inaccessible to cancer therapies, may well prevent malignant progression. The tumor's recruitment of monocytes into these regions may be exploited for nanoparticle-based delivery. Monocytes containing therapeutic nanoparticles could serve as "Trojan Horses" for nanoparticle transport into these tumor regions. Here we report the demonstration of several key steps toward this therapeutic strategy: phagocytosis of Au nanoshells, and photoinduced cell death of monocytes/macrophages as isolates and within tumor spheroids.
Purpose There has been much recent interest in promoting gender equality in academic medicine. This study aims to analyze gender differences in rank, career duration, publication productivity and research funding among radiation oncologists at U.S. academic institutions. Methods For 82 domestic academic radiation oncology departments, the authors identified current faculty and recorded their academic rank, degree and gender. The authors recorded bibliographic metrics for physician faculty from a commercially available database (SCOPUS, Elsevier BV, Amsterdam, NL), including numbers of publications and h-indices. The authors then concatenated this data with National Institute of Health funding for each individual per Research Portfolio Online Reporting Tools (REPORTer). The authors performed descriptive and correlative analyses, stratifying by gender and rank. Results Of 1031 faculty, 293 (28%) women and 738 (72%) men, men had a higher median h-index (8 (0-59) versus 5 (0-39); P<.05) and publication number (26 (0-591) versus 13 (0-306); P<.05) overall, and were more likely to be senior faculty and receive NIH funding. However, after stratifying for rank, these differences were largely non-significant. On multivariate analysis, there were significant correlations between gender, career duration and academic position, and h-index (P<.01). Conclusions The determinants of a successful career in academic medicine are certainly multi-factorial, particularly in traditionally male-dominated fields. However, data from radiation oncologists show a systematic gender association withfewer women achieving senior faculty rank. However, women who achieve senior status have productivity metrics comparable to their male counterparts. This suggests early career development and mentorship of female faculty may narrow productivity disparities.
A B S T R A C T PurposeColon cancer overall survival (OS) is usually computed from the time of diagnosis. Survival gives the initial prognosis but does not reflect how prognosis changes with changing hazard rates over time. Conditional survival (probability of surviving y additional years given they have survived x years [CS or OS͉OS]) is an alternative measure that accounts for elapsed time since diagnosis, providing more relevant prognostic information. We extend the concept of CS to condition on the set of patients alive, recurrence-free, and second primary cancer-free (disease-free survival [OS͉DFS]). Patients and MethodsUsing data from National Surgical Adjuvant Breast and Bowel Project trials C-03 through C-07, 5-year OS͉DFS was calculated on patients who were disease free up to 5 years after diagnosis, stratified by age, stage, nodal status, and performance status (PS). ResultsFor stage II, OS͉DFS improved from 87% to 92% at 5 years. For stage III, OS͉DFS improved from 69% to 88%. Patients younger than 50 years showed OS͉DFS improvement from 79% to 95%; those older than 70 years showed no sustained increase in OS͉DFS. Node-negative patients with Ն 12 nodes resected showed little change (89% to 94%); those with more than four positive nodes showed an improvement (57% to 86%). Patients with a PS of 0 or 1 demonstrated a small improvement; those with a PS of 2 did not (64% to 58%). ConclusionPrognosis improves over time for almost all groups of patients with colon cancer, especially those with positive nodes. OS͉DFS is a more relevant measure of prognosis for those who have already survived disease free a period of time after diagnosis.
Objective: To develop decision trees predicting for tumor volume reduction in patients with head and neck (H&N) cancer using pretreatment clinical and pathological parameters. Methods: Forty-eight patients treated with definitive concurrent chemoradiotherapy for squamous cell carcinoma of the nasopharynx, oropharynx, oral cavity, or hypopharynx were retrospectively analyzed. These patients were rescanned at a median dose of 37.8 Gy and replanned to account for anatomical changes. The percentages of gross tumor volume (GTV) change from initial to rescan computed tomography (CT; %GTVD) were calculated. Two decision trees were generated to correlate %GTVD in primary and nodal volumes with 14 characteristics including age, gender, Karnofsky performance status (KPS), site, human papilloma virus (HPV) status, tumor grade, primary tumor growth pattern (endophytic/exophytic), tumor/nodal/group stages, chemotherapy regimen, and primary, nodal, and total GTV volumes in the initial CT scan. The C4.5 Decision Tree induction algorithm was implemented. Results: The median %GTVD for primary, nodal, and total GTVs was 26.8%, 43.0%, and 31.2%, respectively. Type of chemotherapy, age, primary tumor growth pattern, site, KPS, and HPV status were the most predictive parameters for primary %GTVD decision tree, whereas for nodal %GTVD, KPS, site, age, primary tumor growth pattern, initial primary GTV, and total GTV volumes were predictive. Both decision trees had an accuracy of 88%. Conclusions: There can be significant changes in primary and nodal tumor volumes during the course of H&N chemoradiotherapy. Considering the proposed decision trees, radiation oncologists can select patients predicted to have high %GTVD, who would theoretically gain the most benefit from adaptive radiotherapy, in order to better use limited clinical resources.
Objective: To investigate the effects of adaptive radiotherapy on dosimetric, clinical, and toxicity outcomes for patients with head and neck cancer undergoing chemoradiotherapy with intensity-modulated radiotherapy. Methods: Fifty-one patients with advanced head and neck cancer underwent definitive chemoradiotherapy with the original plan optimized to deliver 70.2 Gy. All patients were resimulated at a median dose of 37.8 Gy (range, 27.0-48.6 Gy) due to changes in tumor volume and/or patient weight loss (>15% from baseline). Thirty-four patients underwent adaptive replanning for their boost planning (21.6 Gy). The dosimetric effects of the adaptive plan were compared to the original plan and the original plan copied on rescan computed tomography. Acute and late toxicities and tumor local control were assessed. Gross tumor volume reduction rate was calculated. Results: With adaptive replanning, the maximum dose to the spinal cord, brain stem, mean ipsilateral, and contralateral parotid had a median reduction of À4.5%, À3.0%, À6.2%, and À2.5%, respectively (median of 34 patients). Median gross tumor volume and boost planning target volume coverage improved by 0.8% and 0.5%, respectively. With a median follow-up time of 17.6 months, median disease-free survival and overall survival was 14.8 and 21.1 months, respectively. Median tumor volume reduction rate was 35.2%. For patients with tumor volume reduction rate 35.2%, median disease-free survival was 8.7 months, whereas it was 16.9 months for tumor volume reduction rate >35.2%. Four patients had residual disease after chemoradiotherapy, whereas 64.7% (20 of 34) of patients achieved locoregional control. Conclusion: Implementation of adaptive radiotherapy in head and neck cancer offers benefits including improvement in tumor coverage and decrease in dose to organs at risk. The tumor volume reduction rate during treatment was significantly correlated with disease-free survival and overall survival.
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