Search

Background: Many individuals with cancer have survived a prior cancer and for this reason may have been excluded from clinical trials. Recent NCI guidance recommends including these individuals, especially when the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low. Using breast cancer as an example, we determined the potential effect this policy change may have on clinical trial accrual. Patients and Methods: We reviewed protocols of NCI-sponsored breast cancer clinical trials activated in 1991 through 2016. We quantified prevalence of prior cancer-related exclusion criteria and assessed the association with trial characteristics using Fisher’s exact tests. Using SEER data, we estimated the prevalence and timing of prior primary (nonbreast) cancer diagnoses among patients with breast cancer. Results: Among 87 clinical trials (total target enrollment, 137,253 patients), 77% excluded individuals with prior cancer, most commonly (79%) within the preceding 5 years. Among trials with radiographic response or toxicity endpoints, 69% excluded prior cancer. In SEER data, the prevalence of a prior (nonbreast) cancer diagnosis ranged from 5.7% to 7.7%, depending on breast cancer stage, of which 39% occurred within 5 years of the incident breast cancer. For trials excluding prior cancer, the estimated proportion of patients excluded for this reason ranged from 1.3% to 5.8%, with the estimated number of excluded patients ranging from 1 to 288. Conclusions: More than three-fourths of NCI-sponsored breast cancer clinical trials exclude patients with prior cancer, including almost 70% of trials with response or toxicity endpoints. Given that >5% of patients with breast cancer have a history of prior cancer, in large phase III trials this practice may exclude hundreds of patients. Following recent NCI eligibility guidance, the inclusion of patients with prior cancer on breast cancer trials may have a meaningful impact on accrual.

Background Recently developed stereotactic partial breast irradiation (S-PBI) allows delivery of a high biologically potent dose to the target while sparing adjacent critical organs and normal tissue. With S-PBI tumoricidal doses, accurate and precise dose delivery is critical to achieve high treatment quality. This study is to investigate both rigid and non-rigid components of target geometric error and their corresponding margins in S-PBI and identify correlated clinical factors. Methods Forty-three early-stage breast cancer patients with implanted gold fiducial markers were enrolled in the study. Fiducial positions recorded on the orthogonal kV images on a Cyberknife system during treatment were used to estimate intra-fraction errors and composite errors (including intra-fraction errors and residual errors after patient setup). Both rigid and non-rigid components of intra-fraction and composite errors were analyzed and used to estimate rigid and non-rigid margins, respectively. Univariate and multivariate linear regressions were conducted to evaluate correlations between clinical factors and errors. Results For the study group, the intra-fraction rigid and non-rigid errors are 2.0 ± 0.6 mm and 0.3 ± 0.2 mm, respectively. The composite rigid and non-rigid errors are 2.3 ± 0.5 mm and 1.3 ± 0.8 mm, respectively. The rigid margins in the left-right, anterior-posterior, and superior-inferior directions are estimated as 2.1, 2.4, and 2.3 mm, respectively. The estimated non-rigid margin, assumed to be isotropic, is 1.7 mm. The outer breast quadrants are more susceptible to composite errors occurrence than the inner breast quadrants. The target to chest wall distance is the clinical factor correlated with target geometric errors. Conclusions This is the first comprehensive analysis of breast target geometric rigid and non-rigid errors in S-PBI. Upon the estimation, the non-rigid margin is comparable to rigid margin, and therefore should be included in planning target volume as it cannot be accounted for by the Cyberknife system. Treatment margins selection also need to consider the impact of relevant clinical factor. Electronic supplementary material The online version of this article (10.1186/s13014-017-0889-6) contains supplementary material, which is available to authorized users.

We evaluated a panel of 8 immunohistochemical biomarkers as predictors of clinical response to definitive intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma (OPSCC). 106 patients with OPSCC were treated to a total dose of 66–70 Gy and retrospectively analyzed for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). All tumors had p16 immunohistochemical staining, and 101 tumors also had epidermal growth factor receptor (EGFR) staining. 53% of the patients had sufficient archived pathologic specimens for incorporation into a tissue microarray for immunohistochemical analysis for cyclophilin B, cyclin D1, p21, hypoxia-inducible factor-1α(HIF-1α), carbonic anhydrase, and major vault protein. Median followup was 27.2 months. 66% of the tumors were p16 positive, and 34% were p16 negative. On univariate analysis, the following correlations were statistically significant: p16 positive staining with higher LRC (P=0.005) and longer DFS (P<0.001); cyclin D1 positive staining with lower LRC (P=0.033) and shorter DFS (P=0.002); HIF-1αpositive staining with shorter DFS (P=0.039). On multivariate analysis, p16 was the only significant independent predictor of DFS (P=0.023). After immunohistochemical examination of a panel of 8 biomarkers, our study could only verify p16 as an independent prognostic factor in OPSCC.