Cobalt compensator-based IMRT device: A treatment planning study of head and neck cases.

PURPOSE: Our goal is to develop a novel cobalt-compensator-based IMRT device for low- and middle-income countries that is reliable and cost-effective while delivering treatment plans of equal quality to those from linac-MLC devices. The present study examines the quality of treatment plans using this device. METHODS: A commercial treatment planning system (TPS; RayStation v.8B) was commissioned for this device using Monte Carlo simulations from the Geant4 toolkit. Patient-specific compensators were created as regions-of-interest. Thirty clinical head & neck cases were planned and compared to clinical plans with a 6MV linac using IMRT. The mock head and neck plan from TG-119 was used for further validation. RESULTS: PTV objectives were achieved in all 30 plans with PTV V95% >95 %. OAR sparing was similar to clinical plans. There were 14 cases where OAR dose limits exceeded the recommended QUANTEC limits in the clinical plan in order to achieve target coverage. OAR sparing was better in the cobalt compensator plan in 8 cases and worse in 3 cases, in the latter cases exceeding the clinical plan doses by an average of 8.22 % (0.0 %-13.5 %). Average field-by-field gamma pass-rate were 93.7 % (2 %/2mm). Estimated treatment times using the Co-60 compensator device were 1 min 27 s vs 1 min 2 s for the clinical system. CONCLUSION: This system is the first of its kind to allow for IMRT with a Co-60 device. Data here suggests that the delivery meets plan quality criteria while maintaining short treatment times which may offer a sustainable and cost-low option for IMRT on the global scale.

Performance of multiparametric prostate magnetic resonance imaging validated by targeted and systematic transperineal biopsies.

Objective: To measure the performance of multiparametric (mp) magnetic resonance imaging (MRI) to identify intraprostatic tumour deposits using a systematic and targeted MR-guided transperineal prostate biopsy technique. Materials and Methods: Patients underwent a combined systematic and targeted MR-guided transperineal biopsy procedure in the dorsal lithotomy position under general anaesthesia. Systematic biopsies were spaced 10 mm or less apart and additional biopsies targeted any Prostate Imaging-Reporting and Data System (PI-RADS) 3, 4 or 5 lesions identified on mpMRI. Cancer detection rates were calculated on a per patient and per lesion basis. Results: A total of 125 patients underwent the biopsy procedure. The positive predictive value (PPV) of mpMRI per patient was 59% for any cancer and 49% for Gleason score (GS) ≥ 7 cancer. The negative predictive value (NPV) of mpMRI per patient was 67% for any cancer and 88% for GS ≥ 7 cancer. On a per lesion basis, the PPV of PI-RADS 3 lesions for any and GS ≥ 7 cancer was 24% and 10%. For PI-RADS 4 lesions it was 42% and 32%. For PI-RADS 5 lesions, it was 76% and 70%. MpMRI failed to identify GS ≥ 7 cancer found on systematic biopsy in 22% of patients. Conclusion: Based on a combination of systematic and targeted transperineal prostate biopsies, mpMRI showed a high NPV and low PPV for GS ≥ 7 cancer on a per patient basis. The PPV of mpMRI on a per lesion basis increased with increasing PI-RADS score. However, there were a significant number of both false positive as well as false negative (mpMRI invisible) areas within the prostate that contained GS ≥ 7 cancer. Therefore, pathologic confirmation using both targeted and systematic mapping biopsy is necessary to accurately identify all intraprostatic tumour deposits.

Management of locally advanced mesonephric carcinoma of the cervix in the setting of Mullerian Duct anomaly spectrum and unilateral renal agenesis: A case report and review of the literature.

Cervical mesonephric adenocarcinoma is a rare histologic cervical carcinoma variant arising from remnants of the mesonephric duct. Few clinical cases have been reported in the literature, and given the low rate of occurrence, the optimal management strategy is unknown. Most reported cases involve patients with either early stage (FIGO I) or metastatic disease. Herein, we report the only known case of locally advanced, node-positive cervical mesonephric carcinoma in a 55-year old woman with Mullerian duct anomaly of the uterus, obstructed hemivagina, and ipsilateral renal agenesis. To our knowledge, this would be the first case report with the concurrence of both rare entities. We review the treatment paradigm in this patient, and the literature, including radiotherapy and brachytherapy techniques.

Executive Summary of the American Radium Society Appropriate Use Criteria for Radiation Treatment of Node-Negative Muscle Invasive Bladder Cancer.

PURPOSE: Definitive radiation therapy (RT), with or without concurrent chemotherapy, is an alternative to radical cystectomy for patients with localized, muscle-invasive bladder cancer (MIBC) who are either not surgical candidates or prefer organ preservation. We aim to synthesize an evidence-based guideline regarding the appropriate use of RT. METHODS AND MATERIALS: We performed a Preferred Reporting Items for Systematic Reviews and Meta-analyses literature review using the PubMed and Embase databases. Based on the literature review, critical management topics were identified and reformulated into consensus questions. An expert panel was assembled to address key areas of both consensus and controversy using the modified Delphi framework. RESULTS: A total of 761 articles were screened, of which 61 were published between 1975 and 2019 and included for full review. There were 7 well-designed studies, 20 good quality studies, 28 quality studies with design limitations, and 6 references not suited as primary evidence. Adjuvant radiation therapy after cystectomy was not included owing to lack of high-quality data or clinical use. An expert panel consisting of 14 radiation oncologists, 1 medical oncologist, and 1 urologist was assembled. We identified 4 clinical variants of MIBC: surgically fit patients who wish to pursue organ preservation, patients surgically unfit for cystectomy, patients medically unfit for cisplatin-based chemotherapy, and borderline cystectomy candidates based on age with unilateral hydronephrosis and normal renal function. We identified key areas of controversy, including use of definitive radiation therapy for patients with negative prognostic factors, appropriate radiation therapy dose, fractionation, fields and technique when used, and chemotherapy sequencing and choice of agent. CONCLUSIONS: There is limited level-one evidence to guide appropriate treatment of MIBC. Studies vary significantly with regards to patient selection, chemotherapy use, and radiation therapy technique. A consensus guideline on the appropriateness of RT for MIBC may aid practicing oncologists in bridging the gap between data and clinical practice.

National Quality Improvement Participation Among US Radiation Oncology Facilities: Compliance with Guideline-Concordant Palliative Radiation Therapy for Bone Metastases.

PURPOSE: To characterize the participation of radiation oncology (RO) in reporting quality metrics through the Centers for Medicare and Medicaid Services' (CMS) Hospital Compare database and to describe the association of hospital characteristics with RO-specific quality metrics. METHODS AND MATERIALS: Data from the CMS Hospital Compare, International Atomic Energy Agency's Directory of Radiotherapy Centre, 2010 US Census, and CMS Inpatient Prospective Payment System were linked to create an integrated data set of geographic information, facility characteristics, and quality measures, focusing on the use of external beam radiation therapy (EBRT) for bony metastases. RESULTS: Of 4829 hospitals in the Hospital Compare database, 2030 had access to radiation therapy. Among these, 814 (40%) reported on the rate of guideline-concordant EBRT for bony metastases, a RO-specific quality measure. A total of 33,614 eligible cases of bony metastases treated with EBRT were sampled. Participation in quality reporting varied significantly by geography, population type, teaching status, hospital ownership, hospital type, and hospital size. The median rate of guideline-concordant palliative EBRT utilization was 89%. Nine percent of 814 centers had a compliance rate of less than 50%. On multivariable analysis, increasing number of cases sampled (odds ratio 0.93, P = .028), increasing hospital star-rating, and above-average patient experience rating (odds ratio 0.58, P = .024) remained significantly associated with decreased odds of falling into the lowest quartile of guideline-concordant EBRT utilization. CONCLUSIONS: RO participation in a large, national quality improvement effort is nascent and reveals potential quality gaps between hospitals offering palliative EBRT for bone metastases. More robust RO-specific quality measures are needed.

Rectal Hydrogel Spacer Improves Late Gastrointestinal Toxicity Compared to Rectal Balloon Immobilization After Proton Beam Radiation Therapy for Localized Prostate Cancer: A Retrospective Observational Study.

PURPOSE: Our purpose was to compare dosimetric parameters and late gastrointestinal outcomes between patients treated with proton beam therapy (PBT) for localized prostate cancer with rectal balloon immobilization versus a hydrogel rectal spacer. METHODS AND MATERIALS: Patients with localized, clinical stage T1-4 prostate adenocarcinoma were treated at a single institution using conventionally fractionated, dose-escalated PBT from 2013 to 2018. Patient-reported gastrointestinal toxicity was prospectively collected, and the incidence of rectal bleeding was retrospectively reviewed from patient records. RESULTS: One hundred ninety-two patients were treated with rectal balloon immobilization, and 75 were treated with a rectal spacer. Rectal hydrogel spacer significantly improved rectal dosimetry while maintaining excellent target coverage. The 2-year actuarial rate of grade 2+ late rectal bleeding was 19% and 3% in the rectal balloon and hydrogel spacer groups, respectively (P = .003). In univariable analysis, the probability of grade 2+ rectal bleeding was significantly correlated with increasing rectal dose. In multivariable analysis, only receipt of spacer hydrogel (hazard ratio, 0.145; P = .010) and anticoagulation use (hazard ratio, 5.019; P < .001) were significantly associated with grade 2+ bleeding. At 2-year follow-up, patient-reported Expanded Prostate Cancer Index Composite bowel quality of life composite scores were less diminished in the hydrogel spacer group (absolute mean difference, 5.5; P = .030). CONCLUSIONS: Use of rectal hydrogel spacer for prostate PBT is associated with a significantly lower incidence of clinically relevant, late rectal bleeding and lower decrement in long-term, patient-reported bowel quality of life compared with rectal balloon immobilization. Our results suggest that hydrogel spacer may improve rectal sparing compared with rectal balloon immobilization during PBT for prostate cancer.

A Case of Rectal Ulcer during Intensity Modulated Radiotherapy for Prostate Cancer Using Hydrogel Spacer.

We report a case of a severely symptomatic rectal ulcer, a CTCAE (Common Terminology Criteria for Adverse Events) grade 3 complication, after intensity modulated radiotherapy for prostate cancer using the SpaceOAR® hydrogel spacer.

Durable Improvement in Patient Safety Culture Over 5 Years With Use of High-volume Incident Learning System.

PURPOSE: Incident learning systems (ILSs) require substantial time and effort to maintain, risking staff burnout and ILS disuse. Herein, we assess the durability of ILS-associated safety culture improvements and ILS engagement at 5 years. METHODS AND MATERIALS: A validated survey assessing safety culture was administered to all staff of an academic radiation oncology department before starting ILS and annually thereafter for 5 years. The survey consists of 70 questions assessing key cultural domains, overall patient safety grade, and barriers to incident reporting. A χ2 test was used to compare baseline scores before starting the ILS (pre-ILS) with the aggregate 5 years during which ILS was in use (with ILS). ILS engagement was measured by the self-reported number of ILS entries submitted in the previous 12 months. RESULTS: The survey response rate was ≥68% each year (range, 68%-80%). High-volume event reporting was sustained (4673 reports; average of 0.9 ILS entries per treatment course). ILS engagement increased, with 43% of respondents submitting reports during the 12 months pre-ILS compared with 64% with ILS in use (P < .001). Significant improvements (pre- vs. with-ILS) were observed in the cultural domains of patient safety perceptions (25% vs 39%; P < .03), and responsibility and self-efficacy (43% vs 60%; P < .01). The overall patient safety grade of very good or excellent significantly increased (69% vs 85%; P < .01). Significant reductions were seen in the following barriers to error reporting: embarrassment in front of colleagues, getting colleagues into trouble, and effect on department reputation. CONCLUSIONS: Comprehensive incident learning was sustained over 5 years and is associated with significant durable improvements in metrics of patient safety culture.

NF-κB inhibition by dimethylaminoparthenolide radiosensitizes non-small-cell lung carcinoma by blocking DNA double-strand break repair.

Despite optimal chemotherapy, radiotherapy (RT), and/or surgery, non-small-cell lung carcinoma (NSCLC) remains the leading cause of cancer-related death in the US and worldwide. Thoracic RT, a mainstay in the treatment of locally advanced NSCLC, is often restricted in efficacy by a therapeutic index limited by sensitivity of tissues surrounding the malignancy. Therefore, radiosensitizers that can improve the therapeutic index are a vital unmet need. Inhibition of the NF-κB pathway is a proposed mechanism of radiosensitization. Here we demonstrate that inhibition of the canonical NF-κB pathway by dimethylaminoparthenolide (DMAPT) radiosensitizes NSCLC by blocking DNA double-strand break (DSB) repair. NF-κB inhibition results in significant impairment of both homologous recombination (HR) and non-homologous end joining (NHEJ), as well as reductions in ionizing radiation (IR)-induced DNA repair biomarkers. NF-κB inhibition by DMAPT shows preclinical potential for further investigation as a NSCLC radiosensitizer.

Circulating miR-29a and miR-150 correlate with delivered dose during thoracic radiation therapy for non-small cell lung cancer.

BACKGROUND: Risk of normal tissue toxicity limits the amount of thoracic radiation therapy (RT) that can be routinely prescribed to treat non-small cell lung cancer (NSCLC). An early biomarker of response to thoracic RT may provide a way to predict eventual toxicities-such as radiation pneumonitis-during treatment, thereby enabling dose adjustment before the symptomatic onset of late effects. MicroRNAs (miRNAs) were studied as potential serological biomarkers for thoracic RT. As a first step, we sought to identify miRNAs that correlate with delivered dose and standard dosimetric factors. METHODS: We performed miRNA profiling of plasma samples obtained from five patients with Stage IIIA NSCLC at five dose-points each during radical thoracic RT. Candidate miRNAs were then assessed in samples from a separate cohort of 21 NSCLC patients receiving radical thoracic RT. To identify a cellular source of circulating miRNAs, we quantified in vitro miRNA expression intracellularly and within secreted exosomes in five NSCLC and stromal cell lines. RESULTS: miRNA profiling of the discovery cohort identified ten circulating miRNAs that correlated with delivered RT dose as well as other dosimetric parameters such as lung V20. In the validation cohort, miR-29a-3p and miR-150-5p were reproducibly shown to decrease with increasing radiation dose. Expression of miR-29a-3p and miR-150-5p in secreted exosomes decreased with radiation. This was concomitant with an increase in intracellular levels, suggesting that exosomal export of these miRNAs may be downregulated in both NSCLC and stromal cells in response to radiation. CONCLUSIONS: miR-29a-3p and miR-150-5p were identified as circulating biomarkers that correlated with delivered RT dose. miR-150 has been reported to decrease in the circulation of mammals exposed to radiation while miR-29a has been associated with fibrosis in the human heart, lungs, and kidneys. One may therefore hypothesize that outlier levels of circulating miR-29a-3p and miR-150-5p may eventually help predict unexpected responses to radiation therapy, such as toxicity.