Real-time electromagnetic tracking–based treatment platform for high-dose-rate prostate brachytherapy: Clinical workflows and end-to-end validation

PurposeNew technologies were integrated into a novel treatment platform combining electromagnetically (EM) tracked catheters, a 3D ultrasound (3DUS) imaging device, and a new treatment planning system to provide a real-time prostate high-dose-rate (HDR) brachytherapy treatment system. This work defines workflows for offline CT and online 3DUS planning scenarios and preclinical end-to-end validation of the platform.Methods and MaterialsThe platform is composed of an EM-tracked stylet, a EM-tracked 3DUS probe, and an EM-tracked template guide, all used with the NDI Aurora field generator (NDI, Ontario, Canada). The treatment planning system performs continuous position and angular readings from all three EM sensors into a streamlined environment that allows for (1) contouring; (2) planning; (3) catheter insertion guidance and reconstruction; (4) QA of catheter path and tip position; and (5) exporting to an afterloader. Data were gathered on the times required for the various key steps of the 3DUS-based workflow.ResultsThe complete 3DUS-based workflow on 16-catheter implant phantoms took approximately 15 min. This time is expected to increase for actual patients. Plan generation is fast (7.6 ± 2.5s) and the initial catheter reconstruction with updated dose distribution is obtained at no (time) cost as part of the insertion process. Subsequent catheter reconstruction takes on average 10.5 ± 3.1s per catheter, representing less than 3 min for a 16-catheter implant.ConclusionsThis preclinical study suggests that EM technology could help to significantly streamline real-time US-based high-dose-rate prostate brachytherapy.     

Quantifying institutional resource utilization of adjuvant brachytherapy and intensity-modulated radiation therapy for endometrial cancer via time-driven activity-based costing

PurposeThe purpose of this study was to quantify the cost of resources required to deliver adjuvant radiation therapy (RT) for high- to intermediate-risk endometrial cancer using time-driven activity-based costing (TDABC).Methods and MaterialsComparisons were made for three and five fractions of vaginal cuff brachytherapy (VCB), 28 fractions of intensity-modulated radiation therapy (IMRT), and combined modality RT (25-fraction IMRT followed by 2-fraction VCB). Process maps were developed representing each phase of care. Salary and equipment costs were obtained to derive capacity cost rates, which were multiplied by process times and summed to calculate total costs. Costs were compared with 2018 Medicare physician fee schedule reimbursement.ResultsFull cycle costs for 5-fraction VCB, IMRT, and combined modality RT were 42%, 61%, and 93% higher, respectively, than for 3-fraction VCB. Differences were attributable to course duration and number of fractions/visits. Accumulation of cost throughout the cycle was steeper for VCB, rising rapidly within a shorter time frame. Personnel cost was the greatest driver for all modalities, constituting 76% and 71% of costs for IMRT and VCB, respectively, with VCB requiring 74% more physicist time. Total reimbursement for 5-fraction VCB was 40% higher than for 3-fractions. Professional reimbursement for IMRT was 31% higher than for 5-fraction VCB, vs. IMRT requiring 43% more physician TDABC than 5-fraction VCB.ConclusionsTDABC is a feasible methodology to quantify the cost of resources required for delivery of adjuvant IMRT and brachytherapy and produces directionally accurate costing data as compared with reimbursement calculations. Such data can inform institution-specific financial analyses, resource allocation, and operational workflows.     

Novel intraoperative radiotherapy utilizing prefabricated custom three-dimensionally printed high-dose-rate applicators

BackgroundIntraoperative radiotherapy (IORT) is an effective strategy for the delivery of high doses of radiotherapy to a residual tumor or resection cavity with relative sparing of nearby healthy tissues. This strategy is an important component of the multimodality management of pediatric soft tissue sarcomas, particularly in cases where patients have received prior courses of external beam radiotherapy.PurposeTumor beds with significant topographic irregularity remain a therapeutic challenge because existing IORT technologies are typically most reliable with flat surfaces. To address this limitation, we have developed a novel strategy to create custom, prefabricated high-dose-rate (HDR)-IORT applicators designed to match the shape of an anticipated surgical cavity.Methods and MaterialsSilastic applicators are constructed using three-dimensional (3D) printing and are derived from volumetric segmentation of preoperative imaging.ResultsHDR preplanning with the applicators improves dosimetric accuracy and minimizes incremental operative time. In this report, we describe the fabrication process for the 3D-printed applicators and detail our experience utilizing this strategy in two pediatric patients who underwent HDR-IORT as part of complex base of skull sarcoma resections.ConclusionsEarly experience suggests that usage of the custom applicators is feasible, versatile for a variety of clinical situations, and enables the uniform delivery of high superficial doses of radiotherapy to irregularly shaped surgical cavities.     

The roles and applications of autoantibodies in progression,diagnosis, treatment and prognosis of human malignant tumours

The existence of autoantibodies towards an individual's own proteins or nucleic acids has been established for more than 100 years, and for a long period, these autoantibodies have been believed to be closely associated with autoimmune diseases. However, in recent years, researchers have become more interested in the role and application of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Over the past few decades, numerous epidemiological studies have shown that the risk of certain cancers is significantly altered (increased or decreased) in patients with autoimmune diseases, which suggests that autoantibodies may play either promoting or suppressing roles in cancer progression. The idea that autoantibodies are directly involved in tumour progression gains special support by the findings that some antibodies secreted by a variety of cancer cells can promote their proliferation and metastasis. Because the cancer cells generate cell antigenic changes (neoantigens), which trigger the immune system to produce autoantibodies, serum autoantibodies against tumour-associated antigens have been established as a novel type of cancer biomarkers and have been extensively studied in different types of cancer. The autoantibodies as biomarkers in cancer diagnosis are not only more sensitive and specific than antigens, but also could appear before clinical evidences of the tumours, thus disclosing them. The observations that cancer risk is lower in patients with some autoimmune diseases suggest that certain autoantibodies may be protective from certain cancers. Moreover, the presence of autoantibodies in healthy individuals implies that it could be safe to employ autoantibodies to treat cancer. Of note, an autoantibodies derived from lupus murine model received much attention due to their selective cytotoxicity for malignant tumour cell without harming normal ones. These studies showed the therapeutic value of autoantibodies in cancer. In this review, we revisited the pathological or protective role of autoantibodies in cancer progression, summarize the application of autoantibodies in cancer diagnosis and prognosis, and discuss the value of autoantibodies in cancer therapy. The studies established to date suggest that autoantibodies not only regulate cancer progression but also promise to be valuable instruments in oncological diagnosis and therapy.     

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria

Purpose

For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy.

Materials and methods

Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix ± parametria treated with neoadjuvant external beam radiotherapy (45–50.4 Gy in 25–28 fractions) and image-based HDR brachytherapy (5–5.5 Gy times 3–4 fractions) ± chemotherapy followed by extrafascial hysterectomy performed at a median of 6 weeks after radiotherapy.

Results

All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20 months (range: 0–153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4 + toxicity.

Conclusions

Neoadjuvant radiation therapy ± chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5–5.5 Gy times 3–4 fractions, for a cumulative EQD₂ of 60–70 Gy, is well tolerated with high rates of clinical and pathological response.     

The First Turkish Case of Hypoparathyroidism,Deafness and Renal Dysplasia (HDR) Syndrome

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is an autosomal dominant genetic disorder characterized by hypoparathyroidism, sensorineural deafness and renal dysplasia. We herein present the first Turkish patient with HDR syndrome, who has a p.R367X mutation. This report indicates that p.R367X is not a mutation specific for the Far Eastern populations and also that urological findings in infants with hypoparathyroidism should be carefully examined because clinical findings relating to the p.R367X mutation may show a variable age of onset.