Jincheng Shen

Tumor-Absorbed Dose Predicts Progression-Free Survival Following 131I-Tositumomab Radioimmunotherapy

The study aimed at identifying patient-specific dosimetric and nondosimetric factors predicting outcome of non-Hodgkin lymphoma patients after 131I-tositumomab radioimmunotherapy for potential use in treatment planning. Methods: Tumor-absorbed dose measures were estimated for 130 tumors in 39 relapsed or refractory non-Hodgkin lymphoma patients by coupling SPECT/CT imaging with the Dose Planning Method (DPM) Monte Carlo code. Equivalent biologic effect was calculated to assess the biologic effects of nonuniform absorbed dose including the effects of the unlabeled antibody. Evaluated nondosimetric covariates included histology, presence of bulky disease, and prior treatment history. Tumor level outcome was based on volume shrinkage assessed on follow-up CT. Patient level outcome measures were overall response (OR), complete response (CR), and progression-free survival (PFS), determined from clinical assessments that included PET/CT. Results: The estimated mean tumor-absorbed dose had a median value of 275 cGy (range, 94–711 cGy). A high correlation was observed between tracer-predicted and therapy-delivered mean tumor-absorbed doses (P < 0.001; r = 0.85). In univariate tumor-level analysis, tumor shrinkage correlated significantly with almost all of the evaluated dosimetric factors, including equivalent biologic effect. Regression analysis showed that OR, CR, and PFS were associated with the dosimetric factors and equivalent biologic effect. Both mean tumor-absorbed dose (P = 0.025) and equivalent biologic effect (P = 0.035) were significant predictors of PFS whereas none of the nondosimetric covariates were found to be statistically significant factors affecting PFS. The most important finding of the study was that in Kaplan–Meier curves stratified by mean dose, longer PFS was observed in patients receiving mean tumor-absorbed doses greater than 200 cGy than in those receiving 200 cGy or less (median PFS, 13.6 vs. 1.9 mo for the 2 dose groups; log-rank P < 0.0001). Conclusion: A higher mean tumor-absorbed dose was significantly predictive of improved PFS after 131I-tositumomab radioimmunotherapy. Hence tumor-absorbed dose, which can be estimated before therapy, can potentially be used to design radioimmunotherapy protocols to improve efficacy.

Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma.

Proinflammatory cytokine levels may be associated with cancer stage, recurrence, and survival. The objective of this study was to determine whether cytokine levels were associated with dietary patterns and fat‐soluble micronutrients in patients with previously untreated head and neck squamous cell carcinoma (HNSCC).

Comparison of methods for estimating the effect of salvage therapy in prostate cancer when treatment is given by indication

For patients who were previously treated for prostate cancer, salvage hormone therapy is frequently given when the longitudinal marker prostate-specific antigen begins to rise during follow-up. Because the treatment is given by indication, estimating the effect of the hormone therapy is challenging. In a previous paper we described two methods for estimating the treatment effect, called two-stage and sequential stratification. The two-stage method involved modeling the longitudinal and survival data. The sequential stratification method involves contrasts within matched sets of people, where each matched set includes people who did and did not receive hormone therapy. In this paper, we evaluate the properties of these two methods and compare and contrast them with the marginal structural model methodology. The marginal structural model methodology involves a weighted survival analysis, where the weights are derived from models for the time of hormone therapy. We highlight the different conditional and marginal interpretations of the quantities being estimated by the three methods. Using simulations that mimic the prostate cancer setting, we evaluate bias, efficiency, and accuracy of estimated standard errors and robustness to modeling assumptions. The results show differences between the methods in terms of the quantities being estimated and in efficiency. We also demonstrate how the results of a randomized trial of salvage hormone therapy are strongly influenced by the design of the study and discuss how the findings from using the three methodologies can be used to infer the results of a trial.

Evaluation of dual energy quantitative CT for determining the spatial distributions of red marrow and bone for dosimetry in internal emitter radiation therapy

PURPOSE To evaluate a three-equation three-unknown dual-energy quantitative CT (DEQCT) technique for determining region specific variations in bone spongiosa composition for improved red marrow dose estimation in radionuclide therapy. METHODS The DEQCT method was applied to 80/140 kVp images of patient-simulating lumbar sectional body phantoms of three sizes (small, medium, and large). External calibration rods of bone, red marrow, and fat-simulating materials were placed beneath the body phantoms. Similar internal calibration inserts were placed at vertebral locations within the body phantoms. Six test inserts of known volume fractions of bone, fat, and red marrow were also scanned. External-to-internal calibration correction factors were derived. The effects of body phantom size, radiation dose, spongiosa region segmentation granularity [single (∼17 × 17 mm) region of interest (ROI), 2 × 2, and 3 × 3 segmentation of that single ROI], and calibration method on the accuracy of the calculated volume fractions of red marrow (cellularity) and trabecular bone were evaluated. RESULTS For standard low dose DEQCT x-ray technique factors and the internal calibration method, the RMS errors of the estimated volume fractions of red marrow of the test inserts were 1.2-1.3 times greater in the medium body than in the small body phantom and 1.3-1.5 times greater in the large body than in the small body phantom. RMS errors of the calculated volume fractions of red marrow within 2 × 2 segmented subregions of the ROIs were 1.6-1.9 times greater than for no segmentation, and RMS errors for 3 × 3 segmented subregions were 2.3-2.7 times greater than those for no segmentation. Increasing the dose by a factor of 2 reduced the RMS errors of all constituent volume fractions by an average factor of 1.40 ± 0.29 for all segmentation schemes and body phantom sizes; increasing the dose by a factor of 4 reduced those RMS errors by an average factor of 1.71 ± 0.25. Results for external calibrations exhibited much larger RMS errors than size matched internal calibration. Use of an average body size external-to-internal calibration correction factor reduced the errors to closer to those for internal calibration. RMS errors of less than 30% or about 0.01 for the bone and 0.1 for the red marrow volume fractions would likely be satisfactory for human studies. Such accuracies were achieved for 3 × 3 segmentation of 5 mm slice images for: (a) internal calibration with 4 times dose for all size body phantoms, (b) internal calibration with 2 times dose for the small and medium size body phantoms, and (c) corrected external calibration with 4 times dose and all size body phantoms. CONCLUSIONS Phantom studies are promising and demonstrate the potential to use dual energy quantitative CT to estimate the spatial distributions of red marrow and bone within the vertebral spongiosa.

Definitive Chemoradiation with Full-dose Gemcitabine for Unresectable Pancreatic Cancer: Efficacy of Involved-Field Radiotherapy

Objectives: Definitive chemoradiotherapy for unresectable pancreatic cancer has traditionally involved 5-fluorouracil-based chemotherapy. Our institution has a long history of combining gemcitabine and radiotherapy (RT), and performed a retrospective review of all patients treated in this manner. Materials and Methods: We reviewed the records of 180 patients treated from 1999 to 2012. Mean RT dose was 40.9 Gy in 2.2-Gy fractions, and targeted only radiographically apparent disease. Ninety-six percent of patients received full-dose gemcitabine-based chemotherapy with RT. Kaplan-Meier was used to analyze time-to-event endpoints, and Cox regression models were used to assess significant prognostic variables. Results: Eighty-nine percent of patients completed RT without a toxicity-related treatment break. Median follow-up was 10.2 months. Twenty-nine percent of patients had a radiographic decrease in primary tumor size following treatment. Median overall survival was 11.8 months, time to distant metastasis (TDM) was 6.7 months, and time to local recurrence (TLR) was 8.3 months. On multivariate analysis, male sex, lower performance status, and higher posttreatment CA 19-9 level predicted for worse overall survival. Posttreatment, CA 19-9 was also associated with TDM and TLR, and radiographic tumor response was associated with better TLR. Conclusion: Definitive chemoradiation using full-dose gemcitabine is well tolerated and achieves survival outcomes comparable to reported trials in the literature.

TH‐A‐103‐01: Investigation of Factors Affecting the Accuracy of a Dual Energy Quantitative CT Method for Estimating Regional Bone Marrow Cellularity

PURPOSE To evaluate a 3-equation 3-unknown Dual Energy Quantitative CT technique for determining region specific variations in bone marrow cellularity for improved red marrow dose estimation in radionuclide therapy. METHODS The DEQCT method was applied to 80/140kVp images of patient simulating lumbar phantoms of three different sizes (small, medium, large). External calibration rods of bone, marrow and fat simulating material were placed beneath the phantoms. Similar internal calibration inserts were placed at a vertebral location within the phantoms. Six test inserts of known volume fractions of bone, fat and red marrow (Red marrow range:0.15-0.74) were also scanned. External to internal calibration correction factors were derived. The effects of phantom size, slice thickness, dose, spongiosa region segmentation(1,4(2×2),9(3×3)) and calibration method on the accuracy of the calculated red marrow volume fractions (cellularity) were evaluated. The method was also applied to six patients. RESULTS For both the small and medium sized phantoms using internal calibration, RMS errors(RMSEs) in the estimated volume fractions of red marrow were 0.03, 0.04 and 0.05 for partitioning of a 23.4mmx23.4mm ROI into 1 region, 4 regions and 9 regions, respectively. Corresponding results for a large sized body phantom were significantly poorer (0.06,0.09,0.10). Reducing slice thickness to 2.5mm(vs. 5mm) increased RMSEs of the marrow volume fractions by 0.01 to 0.06. Similar increases in RMSEs were obtained for reduction in dose(mAs). Results for external calibrations exhibited large errors that were reduced to those of internal calibration by application of external to internal correction factors. Application of these factors to the 6 patient lumbar vertebrae yielded cellularity values that differed by 29% on average from biopsy values at the iliac crest, potentially due to regional variability. CONCLUSION Phantom studies were promising, but show poorer results for large bodies, thinner slices, lower doses and smaller sub-regions. Future validation studies in human cadaver vertebrae are needed. National Institutes of Health (NIH) under Grant 2RO1 EB001994.