Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal adenocarcinoma on computed tomography scans indicate response to cytotoxic therapy.

BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to therapy remains challenging. The objective of this study was to investigate whether changes in the tumor/parenchyma interface are associated with response. METHODS: Computed tomography (CT) scans before and after therapy were reviewed in 4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients with stage I/II PDAC who received neoadjuvant chemoradiation and were prospectively followed in a registry). The tumor/parenchyma interface was visually classified as either a type I response (the interface remained or became well defined) or a type II response (the interface became poorly defined) after therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was performed. Changes in enhancement at the interface were quantified using a proprietary platform. RESULTS: In cohort 1, type I responders had a greater probability of achieving a complete or near-complete pathologic response (21% vs 0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer disease-free and overall survival, independent of traditional covariates of outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4, 2 senior radiologists achieved a κ value of 0.8, and the interface score was associated with overall survival. The quantitative method revealed high specificity and sensitivity in classifying patients as type I or type II responders (with an area under the receiver operating curve of 0.92 in cohort 1, 0.96 in cohort 2, and 0.89 in cohort 3). CONCLUSIONS: Changes at the PDAC/parenchyma interface may serve as an early predictor of response to therapy. Cancer 2018;124:1701-9. © 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

A prospective parallel design study testing non-inferiority of customized oral stents made using 3D printing or manually fabricated methods.

BACKGROUND AND PURPOSE: Customized mouth-opening-tongue-depressing-stents (MOTDs) may reduce toxicity in patients with head and neck cancers (HNC) receiving radiotherapy (RT). However, making MOTDs requires substantial resources, which limits their utilization. Previously, we described a workflow for fabricating customized 3D-printed MOTDs. This study reports the results of a prospective trial testing the non-inferiority of 3D-printed to standard and commercially-available (TruGuard) MOTDs as measured by patient reported outcomes (PROs). MATERIALS AND METHODS: PROs were collected at 3 time points: (t1) simulation, (t2) prior to RT, (t3) between fractions 15-25 of RT. Study participants received a 3D-printed MOTDs (t1, t2, t3), a wax-pattern (t1), an acrylic-MOTDs (t2, t3) and an optional TruGuard (t1, t2, t3). Patients inserted the stents for 5-10 min and completed a PRO-questionnaire covering ease-of-insertion and removal, gagging, jaw-pain, roughness and stability. Inter-incisal opening and tongue-displacement were recorded. With 39 patients, we estimated 90% power to detect a non-inferiority margin of 2 at a significance level of 0.025. Matched pairs and t-test were used for statistics. RESULTS: 41 patients were evaluable. The 3D-printed MOTDs achieved a significantly better overall PRO score compared to the wax-stent (p = 0.0007) and standard-stent (p = 0.0002), but was not significantly different from the TruGuard (p = 0.41). There was no difference between 3D-printed and standard MOTDs in terms of inter-incisal opening (p = 0.4) and position reproducibility (p = 0.98). The average 3D-printed MOTDs turn-around time was 8 vs 48 h for the standard-stent. CONCLUSIONS: 3D-printed stents demonstrated non-inferior PROs compared to TruGuard and standard-stents. Our 3D-printing process may expand utilization of MOTDs.

Malignant paraganglioma presenting as a mandibular metastasis.

BACKGROUND: Metastatic paragangliomas are rare neuroendocrine tumors. Bony metastases most commonly occur in the ribs, vertebrae, and pelvis. Few cases of mandibular metastases have been reported. METHODS: A 75-year-old female presented with a 6-month history of an enlarging mandibular mass. A biopsy was consistent with a paraganglioma. RESULTS: Staging workup with 18 F-fluorodeoxyglucose positron emission tomography demonstrated 2 hypermetabolic intra-abdominal lesions adjacent to the inferior vena cava. These were confirmed as paraganglioma by biopsy and presumed as the primary lesions. The patient underwent left segmental mandibulectomy and neck dissection with osteocutaneous fibula free tissue reconstruction. CONCLUSION: A rare case of malignant paraganglioma presenting as a mandibular metastasis is described. Nuclear medicine studies for paraganglioma are reviewed.

Novel design and development of a 3D-printed conformal superficial brachytherapy device for the treatment of non-melanoma skin cancer and keloids.

BACKGROUND: Skin tumors are the most predominant form of cancer in the United States. Radiation therapy, particularly high dose-rate (HDR) brachytherapy, provides an effective form of cancer control when surgery is not possible or when surgical margins are incomplete. The treatment of superficial skin cancers on irregular surfaces, such as the nose, lips or ears, present challenges for treatment. To address this issue, we designed and constructed a novel conformal superficial brachytherapy (CSBT) device prototype to improve patient-specific treatment for complex sites. The device is mounted on an automated remote after-loader, providing limited radiation exposure to operating personnel, is inexpensive to construct, and offers a unique method of conformal surface radiation therapy. RESULTS: A prototype of the CSBT device was successfully manufactured. A computed tomography (CT) scan of a Rando phantom was used to plan the target treatment area. The CSBT device has a hexagonal lattice array of retractable rods with radioactive seeds placed at the tip of each rod. A 3D-printed conformal shape insert with a hexagonal array of cylindrical projections of varying length is driven into the rods by a single linear actuator. The rods are displaced to conform to the patient's skin. This elegant device design permits the delivery of radiation to complex targets using readily available beta-emitting radionuclides, such as Yttrium-90 (Y-90) or Strontium-90 (Sr-90). CONCLUSION: A working prototype of a novel CSBT device was built using 3D-printing technology that provides a safe and economically attractive means of improving radiation delivery to complex treatment sites.

Creating customized oral stents for head and neck radiotherapy using 3D scanning and printing.

BACKGROUND: To evaluate and establish a digital workflow for the custom designing and 3D printing of mouth opening tongue-depressing (MOTD) stents for patients receiving radiotherapy for head and neck cancer. METHODS: We retrospectively identified 3 patients who received radiation therapy (RT) for primary head and neck cancers with MOTD stents. We compared two methods for obtaining the digital impressions of patients' teeth. The first method involved segmentation from computed tomography (CT) scans, as previously established by our group, and the second method used 3D scanning of the patients' articulated stone models that were made during the conventional stent fabrication process. Three independent observers repeated the process to obtain digital impressions which provided data to design customized MOTD stents. For each method, we evaluated the time efficiency, dice similarity coefficient (DSC) for reproducibility, and the 3D printed stents' accuracy. For the 3D scanning method, we evaluated the registration process using manual and automatic approaches. RESULTS: For all patients, the 3D scanning method demonstrated a significant advantage over the CT scanning method in terms of time efficiency with over 60% reduction in time consumed (p < 0.0001) and reproducibility with significantly higher DSC (p < 0.001). The printed stents were tested over the articulated dental stone models, and the trueness of fit and accuracy of dental anatomy was found to be significantly better for MOTD stents made using the 3D scanning method. The automated registration showed higher accuracy with errors < 0.001 mm compared to manual registration. CONCLUSIONS: We developed an efficient workflow for custom designing and 3D-printing MOTD radiation stents. This workflow represents a considerable improvement over the CT-derived segmentation method. The application of this rapid and efficient digital workflow into radiation oncology practices can expand the use of these toxicity sparing devices to practices that do not currently have the support to make them.

Consolidative Radiotherapy After Autologous Stem Cell Transplantation for Relapsed or Refractory Diffuse Large B-cell Lymphoma.

INTRODUCTION: We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: We reviewed the medical records of 72 consecutive patients who had undergone ASCT for relapsed or refractory DLBCL at our institution from 2006 to 2014. Pretransplant conditioning consisted of HDC and total body irradiation. Of the 72 patients, 13 received post-transplant consolidative RT at the discretion of the consulted radiation oncologist. RESULTS: Consolidative RT was associated with significantly improved 2-year locoregional control (LRC) (92% vs. 68%; P = .04). However, no difference was seen in either the 2-year progression-free survival (PFS) (69% vs. 54%; P = .25) or overall survival (OS) (85% vs. 59%; P = .44). Analysis of the subgroup of 19 patients with persistent residual masses ≥ 2 cm on post-transplant imaging demonstrated a significant improvement in LRC (100% vs. 36%; P < .01), PFS (88% vs. 27%; P = .01), and OS (100% vs. 45%; P = .02) with consolidative RT. CONCLUSION: The use of consolidative RT after HDC and ASCT for relapsed or refractory DLBCL appears to significantly improve LRC. For patients with masses ≥ 2 cm after ASCT, improved 2-year PFS and OS were seen. Prospective trials are needed to further identify the patients who would derive the most benefit from consolidative RT in the ASCT setting.

Design and fabrication of a 3D-printed oral stent for head and neck radiotherapy from routine diagnostic imaging.

BACKGROUND: Oral stents have been shown to reduce the deleterious effects of head and neck radiotherapy through the displacement of normal tissues away from the areas of high dose irradiation. While these stents are commonly used in the treatment of patients with head and neck cancer at many large academic cancer centers, their use is much more limited outside of these institutions due to the time and expertise required for their fabrication. RESULTS: In the study, we describe a novel method to design and manufacture oral stents from routine computed tomography (CT) imaging studies through the use of 3D printing technologies. CONCLUSION: Our proposed method may help to greatly expand access to these beneficial devices for patients undergoing radiation treatment at centers without access to dental and oral/maxillofacial specialists.

Peripheral dose heterogeneity due to the thread effect in total marrow irradiation with helical tomotherapy.

PURPOSE: To report potential dose heterogeneity leading to underdosing at different skeletal sites in total marrow irradiation (TMI) with helical tomotherapy due to the thread effect and provide possible solutions to reduce this effect. METHODS AND MATERIALS: Nine cases were divided into 2 groups based on patient size, defined as maximum left-to-right arm distance (mLRD): small mLRD (≤47 cm) and large mLRD (>47 cm). TMI treatment planning was conducted by varying the pitch and modulation factor while a jaw size (5 cm) was kept fixed. Ripple amplitude, defined as the peak-to-trough dose relative to the average dose due to the thread effect, and the dose-volume histogram (DVH) parameters for 9 cases with various mLRD was analyzed in different skeletal regions at off-axis (eg, bones of the arm or femur), at the central axis (eg, vertebrae), and planning target volume (PTV), defined as the entire skeleton plus 1-cm margin. RESULTS: Average ripple amplitude for a pitch of 0.430, known as one of the magic pitches that reduce thread effect, was 9.2% at 20 cm off-axis. No significant differences in DVH parameters of PTV, vertebrae, or femur were observed between small and large mLRD groups for a pitch of ≤0.287. Conversely, in the bones of the arm, average differences in the volume receiving 95% and 107% dose (V95 and V107, respectively) between large and small mLRD groups were 4.2% (P=.016) and 16% (P=.016), respectively. Strong correlations were found between mLRD and ripple amplitude (rs=.965), mLRD and V95 (rs=-.742), and mLRD and V107 (rs=.870) of bones of the arm. CONCLUSIONS: Thread effect significantly influences DVH parameters in the bones of the arm for large mLRD patients. By implementing a favorable pitch value and adjusting arm position, peripheral dose heterogeneity could be reduced.