Erin McSpadden

Multi-institutional phase I study of low-dose ultra-fractionated radiotherapy as a chemosensitizer for gemcitabine and erlotinib in patients with locally advanced or limited metastatic pancreatic cancer

PURPOSE Gemcitabine (G) has been shown to sensitize pancreatic cancer to radiotherapy but requires lower doses of G and thus delays aggressive systemic treatment, potentially leading to distant failure. We initiated a phase I trial combining ultra-fractionated low-dose radiotherapy with full dose G and erlotinib in the treatment of patients with advanced pancreatic cancer. METHODS Patients with locally advanced or metastatic pancreatic cancer confined to the abdomen and an ECOG performance status (PS) of 0-1 who had received 0-1 prior regimens (without G or E) and no prior radiotherapy were eligible. Patients were treated in 21 day cycles with G IV days 1 & 8, E once PO QD, and twice daily RT fractions separated by at least 4h on days 1, 2, 8, and 9. Whole abdominal RT fields were used. Primary endpoint was to define dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). RESULTS 27 patients (median age 64 years and 15 male) were enrolled between 11/24/08 and 4/12/12. 1 patient withdrew consent prior to receiving any protocol therapy. 17 patients had a PS of 1. The majority of patients were stage IV. One DLT was noted out of 7 patients at dose level (DL) 1. Subsequently no DLTs were noted in 3 patients each enrolled at DL2-4 or 11 patients in the expansion cohort. The majority of grade 3 toxicities were hematologic with 1 grade 5 bowel perforation in dose level 1 in cycle 4. Best response in 24 evaluable patients: PR (8), stable (15), PD 1. Median survival for the entire group was 9.1 months. CONCLUSION This phase I study combining low-dose ultra-fractionated RT as a sensitizer to full dose G plus E was well tolerated with encouraging efficacy. This represents a novel strategy worthy of further investigation in advanced pancreatic cancer patients.

Target Volume Heterogeneity Index, a Potentially Valuable Metric in IMRT Prostate Cancer Treatment Planning

Abstract Purpose/Objectives: Heterogeneity index (HI) has been described in the literature as a tool for evaluating dose gradients within a planning target volume (PTV). HI may be expressed as D1/D95 where D1 and D95 equal the dose encompassing 1% and 95% of the target volume. The purpose of this study is to evaluate the effect of target volume dose heterogeneity on dose received by local organs at risk in the treatment of low and intermediate risk prostate cancer. Materials/Methods: Treatment plans were reviewed for 157 patients with low or intermediate risk prostate cancer treated with dose-escalated radiation therapy between 6/2007 and 2/2012. Patients treated in the post-operative setting or receiving pelvic nodal irradiation were excluded. Patients were treated with either standard intensity modulation (IMRT) using 7 or 8 fields or 2-arc volumetric modulated arc therapy (VMAT). All patients had daily image-guidance. PTV HI (D1/D95) and dose-volume histogram (DVH) data at 8 dose levels for rectum and bladder were recorded. Patients were categorized into two groups (low HI or high HI) with respect to median index score. A two-tailed t-test was used to test for differences in dose received by rectum and bladder for the two groups. Results: For the 157 plans evaluated, mean PTV volume was 164cc and mean prescription dose was 7833cGy. Median HI was 1.04 (range 1.0-1.08). Low HI (≤1.04) was found to correlate with significantly lower rectal V50 (p=0.02), V55 (p=0.01), V60 (p=0.01), V65 (p=0.01), and V70 (p=0.01). There was no significant correlation with dose received by bladder at any dose level. HI was similar for patients treated with standard IMRT and VMAT (p=0.85). Conclusions: Target volume HI ≤1.04 is associated with more favorable rectal doses at clinically relevant dose-levels. We believe HI may serve as a valuable metric in prostate cancer treatment planning. Further work is needed to correlate these dosimetric findings with clinical outcomes.

Correlation of admissions statistics to graduate student success in medical physics

The purpose of this work is to develop metrics for evaluation of medical physics graduate student performance, assess relationships between success and other quantifiable factors, and determine whether graduate student performance can be accurately predicted by admissions statistics. A cohort of 108 medical physics graduate students from a single institution were rated for performance after matriculation based on final scores in specific courses, first year graduate Grade Point Average (GPA), performance on the program exit exam, performance in oral review sessions, and faculty rating. Admissions statistics including matriculating program (MS vs. PhD); undergraduate degree type, GPA, and country; graduate degree; general and subject GRE scores; traditional vs. nontraditional status; and ranking by admissions committee were evaluated for potential correlation with the performance metrics. GRE verbal and quantitative scores were correlated with higher scores in the most difficult courses in the program and with the program exit exam; however, the GRE section most correlated with overall faculty rating was the analytical writing section. Students with undergraduate degrees in engineering had a higher faculty rating than those from other disciplines and faculty rating was strongly correlated with undergraduate country. Undergraduate GPA was not statistically correlated with any success metrics investigated in this study. However, the high degree of selection on GPA and quantitative GRE scores during the admissions process results in relatively narrow ranges for these quantities. As such, these results do not necessarily imply that one should not strongly consider traditional metrics, such as undergraduate GPA and quantitative GRE score, during the admissions process. They suggest that once applicants have been initially filtered by these metrics, additional selection should be performed via the other metrics shown here to be correlated with success. The parameters used to make admissions decisions for our program are accurate in predicting student success, as illustrated by the very strong statistical correlation between admissions rank and course average, first year graduate GPA, and faculty rating (p<0.002). Overall, this study indicates that an undergraduate degree in physics should not be considered a fundamental requirement for entry into our program and that within the relatively narrow range of undergraduate GPA and quantitative GRE scores of those admitted into our program, additional variations in these metrics are not important predictors of success. While the high degree of selection on particular statistics involved in the admissions process, along with the relatively small sample size, makes it difficult to draw concrete conclusions about the meaning of correlations here, these results suggest that success in medical physics is based on more than quantitative capabilities. Specifically, they indicate that analytical and communication skills play a major role in student success in our program, as well as predicted future success by program faculty members. Finally, this study confirms that our current admissions process is effective in identifying candidates who will be successful in our program and are expected to be successful after graduation, and provides additional insight useful in improving our admissions selection process. PACS number: 01.40.‐d

Women at increased risk for cardiac toxicity following chemoradiation therapy for esophageal carcinoma

PURPOSE The purpose of this study was to identify factors associated with cardiac toxicity in patients treated with chemoradiation therapy (CRT) for esophageal carcinoma. METHODS AND MATERIALS One hundred twenty-seven patients with adenocarcinoma or squamous cell carcinoma of the esophagus treated from July 2002 to June 2011 at 2 academic institutions with preoperative or definitive CRT were retrospectively reviewed. Association of cardiac toxicity with a number of variables was investigated, including heart disease, cardiac bypass and angioplasty, diabetes, insulin use, smoking, chemotherapy regimen, and tumor location. T test assessed risk of cardiac toxicity secondary to age. Dose volume histograms (DVH) were evaluated for percentage of heart volume receiving >20, 30, 40, and 50 Gy (V20-V50). The Fisher exact test analyzed for an association between dose volume parameters and cardiac toxicity. RESULTS Patient population included 100 men and 27 women with a mean age of 64 years. Median follow-up was 12.7 months (range, 0.3-99.6 months). Any cardiac toxicity occurred in 28 patients, the majority of which were pericardial effusion (23/28). Odds ratio for toxicity in women was 4.15 (95% confidence interval [CI], 1.63-10.50; P = .0017) and time to cardiac toxicity by sex was significant (P = .0003). Patients above the median cutoff for V20, V30, and V40 had increased odds of developing cardiac toxicity (P = .03, .008, .002). There was 4.0 increased odds of developing cardiac toxicity with V40 >57% (95% CI, 1.5-10.3, P = .002). On multivariable logistic regression analysis, sex was the only variable associated with any cardiac toxicity and pericardial effusion (P = .0016, P = .0038). None of the other investigated variables were associated with increased risk of cardiac toxicity. CONCLUSIONS Female patients and dose greater than the median for V20-V40 were associated with the development of cardiac toxicity, specifically pericardial effusion. These data suggest exercising increased care when designing radiation fields in women undergoing CRT for esophageal carcinoma, as pericardial effusion may be a long-term complication.

Limitations of the bowel bag contouring technique in the definitive treatment of cervical cancer

PURPOSE Incidence of acute grade 3 and 4 small bowel toxicity in the definitive treatment of cervical cancer is approximately 15%. Given uncertainties in position of the bowel at time of treatment, techniques including the contouring of a bowel bag have been suggested. The purpose of this study is to describe interfraction variability in bowel location for the female pelvis with intact reproductive organs and to characterize the ability of the bowel bag technique, as described in the Radiation Therapy Oncology Group pelvic normal tissue contouring guidelines, to account for organ motion in this specific clinical setting. METHODS AND MATERIALS Bowel position was assessed for 45 computed tomographic scans used in treatment planning for 9 consecutive cervical cancer patients. After a single operator contoured bowel loops, most superior, anterior, posterior, and inferior positions of bowel were recorded. Mixed effects models were used to assess significance of interfraction variability. Frequency of bowel loop migration outside of the bowel bag was then considered for each patient given all potential bowel bag volumes. Standardized scoring was used to determine additional margins that would be required to account for 95%, 90%, and 85% of significant bowel motion. RESULTS Interfraction variability in the inferior-most bowel position was significant (P = .002). Median maximum variation in the inferior bowel position was 2.1 cm (range, 0.9 cm-4.8 cm). When applying the bowel bag technique, 100% of bowel motion was accounted for as the bowel translated laterally, anteriorly, posteriorly, and superiorly, though accounted for just 70.3% of motion in the inferior direction. A 4-cm inferior margin was required to account for 90% of motion in the inferior direction. CONCLUSIONS In the intact female pelvis, the bowel bag technique is successful in accounting for most interfraction variability in bowel position but underestimates inferior motion. Until an improved approach to predicting small bowel motion can be routinely implemented, a focus on decreasing dose to potential bowel space should be emphasized.

OC-0258: Dosimetric modeling of cardiac toxicity in patients with esophageal cancer receiving radiotherapy

285 EXPERIMENTAL QUALIFICATION OF THE THERANEAN ACCELERATOR-DRIVEN NEUTRON ACTIVATOR FOR THE PRODUCTION OF ACTIVATED NANOPARTICLES FOR CANCER TREATMENT L. Maciocco, S.Avila, S. Buono, N. Burgio, F. Haddad, K. Abbas Advanced Accelerator Applications, St Genis Pouilly, France UTFISSM-PRONOC, ENEA Casaccia, Italy ARRONAX, Nantes, France Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Ispra (VA), Italy