Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Evaluating Directional Dependency of Selective Laser Sintered Patient Specific Biodegradable Devices to Improve Predictive Modeling and Design Verification.

Additive manufacturing, or 3D printing, of the bioresorbable polymer [Formula: see text]-polycaprolactone (PCL) is an emerging tissue engineering solution addressing patient specific anatomies. Predictively modeling the mechanical behavior of 3D printed parts comprised of PCL improves the ability to develop patient specific devices that meet design requirements while reducing the testing of extraneous design variants and development time for emergency devices. Predicting mechanical behavior of 3D-printed devices is limited by the variability of effective material moduli that are determined in part by the 3D printing manufacturing process. Powder fusion methods, specifically laser sintering, are known to produce parts with internal porosity ultimately impacting the mechanical performance of printed devices. This study investigates the role of print direction and part size on the material and structural properties of laser sintered PCL parts. Solid PCL cylinders were printed in the XY (perpendicular to laser) and Z direction (parallel to laser), scanned using microcomputed tomography, and mechanically tested under compression. Compositional, structural, and functional properties of the printed parts were evaluated with differential scanning calorimetry, gel permeation chromatography, microcomputed tomography, and mechanical testing. Computational models of printed and scanned cylinders were fit to experimental data to derive effective moduli. Effective moduli were used to predict the mechanical behavior of splints used for emergency repair of severe tracheobronchomalacia. Laser sintering did not cause significant differences in polymer material properties compared to unmanufactured powder. Effective moduli (Eeff) were greater for larger part sizes (p < 0.01) and for parts oriented in the XY direction compared to the Z direction (p < 0.001). These dependencies were congruent with the differences in void volumes associated with the print direction (p < 0.01) and part size (p < 0.01). Finite element models of splint parallel compression tests utilizing the Eeff dependent on print direction and size agreed with experimental closed compression tests of splints. Evaluating the microstructural properties of printed parts and selecting effective moduli for finite element models based on manufacturing parameters allows accurate prediction of device performance. These findings allow testing of a greater number of device design variants in silico to accomodate patient specific anatomies towards providing higher quality parts while lowering overall time and costs of manufacturing and testing.