Head and Neck Cancer Clinical Research on ClinicalTrials.gov: An Opportunity for Radiation Oncologists.

PURPOSE: Many improvements in head and neck cancer (HNC) outcomes are related to optimization of radiation therapy (RT) dose, fractionation, normal-tissue sparing, and technology. However, prior work has shown that the literature of randomized controlled trials is dominated by industry-sponsored trials that have lower rates of incorporating RT. We characterized HNC clinical trials, hypothesizing that RT-specific research questions may be relatively underrepresented among HNC randomized controlled trials. METHODS AND MATERIALS: A web query of all open interventional trials on www.ClinicalTrials.gov was performed using search terms "head and neck cancer" and specific HNC subsites. Trial details were captured including the modality used, principal investigator (PI) specialty, funding, and whether the study tested a RT-modality specific hypothesis. Chi-square testing and logistic regression were used to compare groups. RESULTS: There were 841 open HNC trials, including definitive (47.6%) and recurrent/metastatic (41.9%) populations. Most trials (71.7%) were phase I or nonrandomized phase II studies, rather than phase III or randomized phase II (28.3%). Among single-arm studies, most (79.6%) incorporated systemic therapy (ST), and fewer (25.2%) incorporated RT. Even fewer phase III and randomized phase II trials tested an RT-specific hypothesis (11.1%), compared with ST-related hypotheses (77.1%; P < .001); trials were more likely to test an RT-hypothesis if the study PI was a radiation oncologist (20.9% vs 6.0%; P < .001). Among RT trials, most early-phase studies tested novel modalities (eg, stereotactic body radiation therapy, proton therapy), whereas most later-phase studies tested dose and fractionation. RT-focused trials had low rates of federal (10.4%) or industry (2.6%) funding. CONCLUSIONS: RT-specific research hypotheses are a minority of phase II-III HNC trials, which mostly focus on incorporating ST in the definitive or recurrent/metastatic setting and have higher rates of industry funding. Radiation oncologist PI leadership and increased nonindustry funding access may ensure that RT-specific hypotheses are incorporated into trial design.

The impact of quantitative CT-based tumor volumetric features on the outcomes of patients with limited stage small cell lung cancer.

INTRODUCTION: Limited stage small cell lung cancer (LS-SCLC) has a poor prognosis. Additional prognostic markers are needed for risk-stratification and treatment intensification. This study compares quantitative CT-based volumetric tumor measurements versus International Association for the Study of Lung Cancer (IASLC) TNM staging to predict outcomes. MATERIALS & METHODS: A cohort of 105 patients diagnosed with LS-SCLC and treated with chemoradiation (CRT) from 2000 to 2013 were analyzed retrospectively. Patients were staged by the Union for International Cancer Control (UICC) TNM Classification, 8th edition. Tumor volumes and diameters were extracted from radiation planning CT imaging. Univariable and multivariable models were used to analyze relationships between CT features and overall survival (OS), locoregional recurrence (LRR), in-field LRR, any progression, and distant metastasis (DM). RESULTS: Median follow-up was 21.3 months. Two-year outcomes were as follows: 38% LRR, 31% in-field LRR, 52% DM, 62% any progression, and 47% OS (median survival 16.5 months). On univariable analysis, UICC T-stage and N-stage were not associated with any clinical outcome. UICC overall stage was only statistically associated with in-field LRR. One imaging feature (3D maximum tumor diameter) was found to be significantly associated with LRR (HR 1.10, p = 0.003), in-field LRR (HR 1.10, p = 0.007), DM (HR 1.10, p = 0.02), any progression (HR 1.10, p = 0.008), and OS (HR 1.10, p = 0.03). On multivariable analysis, this feature remained significantly associated with all outcomes. CONCLUSION: For LS-SCLC, quantitative CT-based volumetric tumor measurements were significantly associated with outcomes after CRT and may be better predictors of outcome than TNM stage.

Funding Support and Principal Investigator Leadership of Oncology Clinical Trials Using Radiation Therapy.

PURPOSE: Sources of funding and principal investigator (PI) leadership for clinical trials using radiation therapy (RT) are not well characterized but are important mediators of innovation, particularly because funding for trials from the National Institutes of Health (NIH) has decreased and industry funding has increased. We sought to determine characteristics of trials using RT that are associated with industry funding, NIH funding, and radiation oncologist (RO) PI leadership. METHODS AND MATERIALS: www.ClinicalTrials.gov was queried for all open, interventional trials that administered RT. Logistic regression was used to identify associations between trial characteristics, receipt of funding type (NIH, industry, or other), and PI leadership. RESULTS: The authors identified 1469 oncology trials, of which 41% were based in the United States, 56% were based internationally, and 3% were based in the United States and internationally. Of these, 22% were RT monotherapy, 53% were bimodality (40% RT + drug, 13% RT + surgery), and 24% were trimodality. Although ROs led 60% of all trials, industry-sponsored trials were significantly less likely to have RO PIs (35% RO vs 65% non-RO PI; adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.28-0.73), to fund trials that did not incorporate drug therapy (aOR, 0.19; 95% CI, 0.10-0.35), or to fund phase III trials (aOR, 0.25; 95% CI, 0.11-0.60) because industry-sponsored trials favored smaller phase I trials. NIH-funded trials were not associated with PI type and, although not statistically significant, favored larger phase III trials (unadjusted OR, 2.06; 95% CI, 0.99-4.29). ROs were less likely to lead trials incorporating drug therapy (aOR, 0.30; 95% CI, 0.22-0.41). CONCLUSIONS: ROs are less likely than other specialties to lead trials that use RT in combination with drug therapy or surgery and more likely to lead trials supported by nonindustry, non-NIH funding. This suggests a need for ROs to lead multimodality trials and to consider opportunities to interact with industry. As NIH resources decrease, alternative funding is needed to support innovation, particularly in in RT-alone trials.

Radiation toxicity in patients with collagen vascular disease and intrathoracic malignancy treated with modern radiation techniques.

BACKGROUND AND PURPOSE: There is concern that patients with collagen vascular disease (CVD) are at higher risk of developing radiation toxicity. We analyzed radiation toxicities in patients with intrathoracic malignancy and CVD treated using modern radiotherapy. MATERIALS AND METHODS: This single-institution retrospective study included 31 patients with CVD and 825 patients without CVD treated from 1998 to 2014. Radiation esophagitis (RE) and radiation pneumonitis (RP) were scored by RTOG scales. RE was analyzed with logistic regression and RP with Cox regression. RESULTS: CVD patients experienced similar grade ≥3 RE compared to control patients (23% vs. 19%, p = 0.64) but more grade ≥3 RP (26% vs. 10%, p = 0.01). There was no significant association between CVD subtype and toxicities. In multivariate analysis, CVD and lung V20 >30% were associated with grade ≥3 RP. We identified V20 ≤30%, V5 ≤50%, and MLD ≤18 Gy as dose thresholds in patients with CVD. CVD patients with mild severity disease and only 1 organ system involved were at low risk for RP. CONCLUSIONS: Patients with CVD may be at higher risk of RP. However, CVD patients may be offered curative thoracic RT with particular attention to risk-reduction strategies and maintaining recommended dose constraints as described in this study.