A Novel Polymer-Encapsulated Multi-Imaging Modality Fiducial Marker with Positive Signal Contrast for Image-Guided Radiation Therapy.

BACKGROUND: Current fiducial markers (FMs) in external-beam radiotherapy (EBRT) for prostate cancer (PCa) cannot be positively visualized on magnetic resonance imaging (MRI) and create dose perturbation and significant imaging artifacts on computed tomography (CT) and MRI. We report our initial experience with clinical imaging of a novel multimodality FM, NOVA. METHODS: We tested Gold Anchor [G-FM], BiomarC [carbon, C-FM], and NOVA FMs in phantoms imaged with kilovoltage (kV) X-rays, transrectal ultrasound (TRUS), CT, and MRI. Artifacts of the FMs on CT were quantified by the relative streak artifacts level (rSAL) metric. Proton dose perturbations (PDPs) were measured with Gafchromic EBT3 film, with FMs oriented either perpendicular to or parallel with the beam axis. We also tested the performance of NOVA-FMs in a patient. RESULTS: NOVA-FMs were positively visualized on all 4 imaging modalities tested. The rSAL on CT was 0.750 ± 0.335 for 2-mm reconstructed slices. In F-tests, PDP was associated with marker type and depth of measurement (p < 10-6); at 5-mm depth, PDP was significantly greater for the G-FM (12.9%, p = 10-6) and C-FM (6.0%, p = 0.011) than NOVA (4.5%). EBRT planning with MRI/CT image co-registration and daily alignments using NOVA-FMs in a patient was feasible and reproducible. CONCLUSIONS: NOVA-FMs were positively visible and produced less PDP than G-FMs or C-FMs. NOVA-FMs facilitated MRI/CT fusion and identification of regions of interest.

Proton therapy for the management of localized prostate cancer: Long-term clinical outcomes at a comprehensive cancer center.

BACKGROUND AND PURPOSE: Proton therapy (PT) has emerged as a standard-of-care treatment option for localized prostate cancer at our comprehensive cancer center. However, there are few large-scale analyses examining the long-term clinical outcomes. Therefore, this article aims to evaluate the long-term effectiveness and toxicity of PT in patients with localized prostate cancer. MATERIALS AND METHODS: Review of 2772 patients treated from May 2006 through January 2020. Disease risk was stratified according to National Comprehensive Cancer Network guidelines as low [LR, n = 640]; favorable-intermediate [F-IR, n = 850]; unfavorable-intermediate [U-IR, n = 851]; high [HR, n = 315]; or very high [VHR, n = 116]. Biochemical failure and toxicity were analyzed using Kaplan-Meier estimates and multivariate models. RESULTS: The median patient age was 66 years; the median follow-up time was 7.0 years. Pelvic lymph node irradiation was prescribed to 28 patients (1%) (2 [0.2%] U-IR, 11 [3.5%] HR, and 15 [12.9%] VHR). The median dose was 78 Gy in 1.8-2.0 Gy(RBE) fractions. Freedom from biochemical relapse (FFBR) rates at 5 years and 10 years were 98.2% and 96.8% for the LR group; 98.3% and 93.6%, F-IR; 94.2% and 90.2%, U-IR; 94.3% and 85.2%, HR; and 86.1% and 68.5%, VHR. Two patients died of prostate cancer. Overall rates of late grade ≥ 3 GU and GI toxicity were 0.87% and 1.01%. CONCLUSIONS: Proton therapy for localized prostate cancer demonstrated excellent clinical outcomes in this large cohort, even among higher-risk groups with historically poor outcomes despite aggressive therapy.

Implementation and Assessment of an Informal Virtual Elective for Medical Student Radiation Oncology Exploration During the COVID19 Pandemic: a Brief Report.

Subspecialty exposure during medical school can be limited. Moreover, the COVID19 pandemic prevented most onsite elective medical student (MS) rotations during 2020. Therefore, we sought to create and assess the efficacy of an informal virtual elective (IVE) for MSs to explore radiation oncology (RO) at our institution. We created IVE activities including invitations to resident didactics, a faculty lecture series, and interactive virtual events with residents and faculty. MSs were offered RO resident and faculty mentors and the opportunity to deliver a lecture. Pre- and post-IVE evaluation surveys were sent to 27 4th year MSs. Surveys utilized importance ordering (1=most important; reported as median (interquartile range), free response, and Likert-type questions (5 = extremely, 1=not at all). Our IVE, held from July to October 2020, had a median of 11 students (range 7-18) attend each activity. Pre- and post-IVE surveys were completed by 22/27 (81%) and 20/27 (74%) MSs, respectively. In pre-IVE, MSs reported participating in the IVE for faculty/resident interaction (1.5 [1, 2]), networking (3 [2, 3]), and learning (4 [3-5]). In post-IVE, MSs reported benefit from faculty mentors (5 [4, 5]), delivering a presentation (5 [3-5]), and faculty lectures (4.5 [4, 5]). In post-IVE, MSs preferred a full onsite away elective (16, 80%) over an official virtual elective (1, 5%) or IVE (3, 15%). Overall, MSs reported that the IVE provided an adequate introduction to RO at our institution (4 [4, 5]). Alternative virtual elective experiences allow MSs to informally evaluate medical subspecialties and could be offered even if formal elective opportunities are available.

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy.

PURPOSE: Magnetic resonance (MR)-guided radiation therapy (MRgRT) is a new technique for treatment of localized prostate cancer (PCa). We report the 12-month outcomes for the first PCa patients treated within an international consortium (the MOMENTUM study) on a 1.5T MR-Linac system with ultrahypofractionated radiation therapy. METHODS AND MATERIALS: Patients treated with 5 × 7.25 Gy were identified. Prostate specific antigen-level, physician-reported toxicity (Common Terminology Criteria for Adverse Events [CTCAE]), and patient-reported outcomes (Quality of Life Questionnaire PR25 and Quality of Life Questionnaire C30 questionnaires) were recorded at baseline and at 3, 6, and 12 months of follow-up (FU). Pairwise comparative statistics were conducted to compare outcomes between baseline and FU. RESULTS: The study included 425 patients with localized PCa (11.4% low, 82.0% intermediate, and 6.6% high-risk), and 365, 313, and 186 patients reached 3-, 6-, and 12-months FU, respectively. Median prostate specific antigen level declined significantly to 1.2 ng/mL and 0.1 ng/mL at 12 months FU for the nonandrogen deprivation therapy (ADT) and ADT group, respectively. The peak of genitourinary and gastrointestinal CTCAE toxicity was reported at 3 months FU, with 18.7% and 1.7% grade ≥2, respectively. The QLQ-PR25 questionnaire outcomes showed significant deterioration in urinary domain score at all FU moments, from 8.3 (interquartile range [IQR], 4.1-16.6) at baseline to 12.4 (IQR, 8.3-24.8; P = .005) at 3 months, 12.4 (IQR, 8.3-20.8; P = .018;) at 6 months, and 12.4 (IQR, 8.3-20.8; P = .001) at 12 months. For the non-ADT group, physician- and patient-reported erectile function worsened significantly between baseline and 12 months FU. CONCLUSIONS: Ultrahypofractionated MR-guided radiation therapy for localized PCa using a 1.5T MR-Linac is effective and safe. The peak of CTCAE genitourinary and gastrointestinal toxicity was reported at 3 months FU. Furthermore, for patients without ADT, a significant increase in CTCAE erectile dysfunction was reported at 12 months FU. These data are useful for educating patients on expected outcomes and informing study design of future comparative-effectiveness studies.

Comparative Toxicities and Cost of Intensity-Modulated Radiotherapy, Proton Radiation, and Stereotactic Body Radiotherapy Among Younger Men With Prostate Cancer.

Purpose To compare the toxicities and cost of proton radiation and stereotactic body radiotherapy (SBRT) with intensity-modulated radiotherapy (IMRT) for prostate cancer among men younger than 65 years of age with private insurance. Methods Using the MarketScan Commercial Claims and Encounters database, we identified men who received radiation for prostate cancer between 2008 and 2015. Patients undergoing proton therapy and SBRT were propensity score-matched to IMRT patients on the basis of clinical and sociodemographic factors. Proportional hazards models compared the cumulative incidence of urinary, bowel, and erectile dysfunction toxicities by treatment. Cost from a payer's perspective was calculated from claims and adjusted to 2015 dollars. Results A total of 693 proton therapy patients were matched to 3,465 IMRT patients. Proton therapy patients had a lower risk of composite urinary toxicity (33% v 42% at 2 years; P < .001) and erectile dysfunction (21% v 28% at 2 years; P < .001), but a higher risk of bowel toxicity (20% v 15% at 2 years; P = .02). Mean radiation cost was $115,501 for proton therapy patients and $59,012 for IMRT patients ( P < .001). A total of 310 SBRT patients were matched to 3,100 IMRT patients. There were no significant differences in composite urinary, bowel, or erectile dysfunction toxicities between SBRT and IMRT patients ( P > .05), although a higher risk of urinary fistula was noted with SBRT (1% v 0.1% at 2 years; P = .009). Mean radiation cost for SBRT was $49,504 and $57,244 for IMRT ( P < .001). Conclusion Among younger men with prostate cancer, proton radiation was associated with significant reductions in urinary toxicity but increased bowel toxicity at nearly twice the cost of IMRT. SBRT and IMRT were associated with similar toxicity profiles; SBRT was modestly less expensive than IMRT.

Intratumoral heterogeneity and chemoresistance in nonseminomatous germ cell tumor of the testis.

BACKGROUND: Nonseminomatous germ cell tumor of the testis (NSGCT) is largely curable. However, a small group of patients develop refractory disease. We investigated the hypothesis that intratumoral heterogeneity contributes to the emergence of chemoresistance and the development of refractory tumor subtypes. RESULTS: Our institution's records for January 2000 through December 2010 included 275 patients whose primary tumor showed pure embryonal carcinoma (pure E); mixed embryonal carcinoma, yolk sac tumor, and teratoma (EYT); or mixed embryonal carcinoma, yolk sac tumor, seminoma, and teratoma (EYST). Patients with EYST had the highest cancer-specific mortality rate (P = .001). They tended to undergo somatic transformation (P = .0007). Two of 5 patients with clinical stage I EYST who had developed recurrence during active surveillance died of their disease. MATERIALS AND METHODS: In this retrospective study, we evaluated consecutive patients who had been diagnosed with the three most common histological phenotypes of NSGCT. Chemoresistance was defined as the presence of teratoma, viable germ cell tumor, or somatic transformation in the residual tumor or the development of progressive or relapsed disease after chemotherapy. In a separate prospective study, we performed next-generation sequencing on tumor samples from 39 patients to identify any actionable genetic mutations. CONCLUSIONS: Our data suggest that patients with EYST in their primary tumor may harbor a potentially refractory NSGCT phenotype and are at increased risk of dying from disease. Despite intratumoral heterogeneity, improved patient selection and personalized care of distinct tumor subtypes may optimize the clinical outcome of patients with NSGCT.

Assessing the Quality of a Radiation Oncology Case-Based, Peer-Review Program in an Integrated Academic and Community Cancer Center Network.

PURPOSE: Academic centers increasingly find a need to define a comprehensive peer-review program that can translate high-quality radiation therapy (RT) to community network sites. In this study, we describe the initial results of a quarterly quality audit program that aims to improve RT peer-review and provider educational processes across community sites. MATERIALS AND METHODS: An electronic tool was used by community-based certified member (CM) sites to enter clinical treatment information about patients undergoing peer review. At least 10% of the patient load for each CM physician was selected for audit on a quarterly basis by expert academic faculty. Quality metrics included the review of the management plan, technical plan, and other indicators. RT was scored as being concordant or nonconcordant with institutional guidelines, national standards, or expert judgment. RESULTS: A total of 719 patients were entered into the peer-review database by the first four CM sites. Of 14% of patients audited, 17% (18 of 104) were deemed nonconcordant. Nonconcordance rates were lowest in prevalent disease sites, such as breast (16%), colorectal (14%), and lung (12%), whereas rates were highest in lymphoma (50%), brain (44%), and gynecology (27%). Deficiencies included incomplete staging work-up, incorrect target and normal tissue delineation, and nonadherence to accepted dose-volume constraints. CONCLUSION: Given the high rate of nonconcordance, we recommend prospective, pre-RT peer review of all patients, and, in particular, expert review of patients that are from low-volume or complex disease sites. An integrated approach to peer review holds a promise of improving the quality, safety, and value of cancer therapy in the community setting.

PSA response to neoadjuvant androgen deprivation therapy is a strong independent predictor of survival in high-risk prostate cancer in the dose-escalated radiation therapy era.

PURPOSE: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. METHODS AND MATERIALS: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. RESULTS: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs ≥0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. CONCLUSIONS: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level≥0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level≥0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.