From Bragg Peaks to Adaptive Fields-The Need for Evidence-Based Adoption of New Technologies in Radiotherapy.

This Viewpoint discusses the need for multi-institutional prospective randomized trials of new technologies in radiotherapy to improve the therapeutic ratio and safety of radiotherapy treatments.

Radiation Oncology Resident Quality by National Resident Matching Program Metrics From 2007 to 2018.

PURPOSE: To quantify how the quality of US medical students accepted to radiation oncology (RO) training programs, as defined by National Resident Matching Program (NRMP) metrics, has changed over time. METHODS AND MATERIALS: We examined NRMP data of senior US medical students matched into RO training programs from 2007 to 2018. Metrics include United States Medical Licensing Exam (USMLE) Step 1 and 2-Clinical Knowledge scores, research output, percentage with PhD, and percentage in Alpha Omega Alpha (AOA), among others. Linear regression analysis assessed the statistical significance of changes in available metrics of matched RO residents over time. The Student t test and χ2 test compared quality metrics between matched students in RO versus all other specialties. RESULTS: From 2007 to 2018, the mean USMLE Step 1 and 2-Clinical Knowledge for RO residents significantly increased from 235 to 247 (1.0 point/year; 95% confidence interval [CI], 0.70-1.52; P = .002) and from 237 to 253 (1.3 points/year; 95% CI, 1.27-1.62; P <.001), respectively. The mean number of research experiences and abstracts/presentations/publications increased from 3.7 to 6.1 (0.2/year; 95% CI, 0.12-0.29; P = .003) and from 6.3 to 15.6 (0.78/year; 95% CI, 0.60-1.04; P <.001), respectively. The percentage of RO residents inducted into AOA increased from 24.2% to 35.2%, whereas those with a PhD remained stable (∼21%). Matched RO residents had statistically superior metrics versus all other specialties for USMLE Step 1 scores (mean +13.5 points; 95% CI, 7.26-19.67; P <.001), research experience (mean +2.04; 95% CI, 1.11-2.97; P <.001), abstracts/presentations/publications (mean +6.80; 95% CI, 3.38-10.22; P = .001), percentage with a PhD (22.2% vs 4.1%; P <.001), and percentage in AOA (29.5% vs 15.8%; P <.001). CONCLUSIONS: RO resident quality, defined by routinely reported NRMP metrics, increased from 2007 to 2018. Furthermore, RO resident quality is significantly higher than in all other specialties combined for most metrics. Whether the recent decline in medical student interest in RO will correlate with reduced NRMP quality metrics is unknown.

A service line approach: Using whiteboard analytics to improve time efficiency in radiation oncology.

The purpose of this study was to develop and implement a custom-designed electronic workflow management tool created by Medlever, Inc, in order to improve efficiency, leverage interoperability and maximize overall labor resources. Administrators and clinicians from five Banner MD Anderson Cancer Center, Department of Radiation Oncology clinics utilized Medlever, Inc. to track and analyze clinical workflow. Real-time data were collected for the duration of 3 months. Time and process data were compared month-to-month from each of the five Banner MD Anderson facilities. The data were quantified based on efficiency scores, where efficiency score was defined by measured timelines for work completion, which was defined by average measured times to complete clinical process steps. The overall average efficiency score for the clinical process steps were as follows: simulation - 66%, define target volume - 69%, creating a treatment plan - 71%, plan review - 76%, finalizing plan - 81%, physics review - 73%, IMRT QA - 72%, approving treatment plan - 69%, and therapy chart check - 66%. The combined average efficiency scores for facility A through E were approximately 72%, 77%, 82%, 66%, and 60%, respectively. Overall, the average sum of all clinical efficiency scores for the radiation oncology service line for all five facilities was approximately 73%. The results set the base line for efficiency and can be evaluated in future studies. In conclusion, a workflow management tool is an effective system to provide results for real-time data tracking, opportunities of improved efficiency, and evidence-based approaches to workflow decision making.

Adjuvant stereotactic body radiotherapy for resected pancreatic adenocarcinoma with close or positive margins.

PURPOSE: The aim of this study was to evaluate the role of stereotactic body radiotherapy (SBRT) as adjuvant therapy for resected pancreatic adenocarcinoma with close or positive margins. METHODS: Between September 2006 and January 2010, 24 patients were treated with adjuvant SBRT following surgical resection. Eight (33.3%) patients had close margins of 1-2.5 mm to the retroperitoneal, vascular structures, and periduodenal adipose tissue. Sixteen (66.7%) patients had positive margins at retroperitoneal margin and vascular structures. Twenty-three patients received 24 Gy (20-24 Gy) in one fraction, and one had 30 Gy in three fractions. The median target volume was 11 cc (4.5-30 cc). Eighteen patients were treated with the Cyberknife® Robotic Radiosurgery System and six patients were treated with Trilogy™ intensity-modulated radiosurgery. Kaplan-Meier survival analyses were used to estimate freedom-from-local-progression (FFLP), and overall survival (OS) rates. PET/CT or CT was used to monitor disease recurrence following SBRT. RESULTS: The median follow-up for all patients was 12.5 months (1.4-39.5 months), and among surviving patients it was 16.3 months (2-39.5 months). The FFLP rates at 6 months, 1 and 2 years were 94.7%, 66%, and 44%, respectively. Overall, FFLP was achieved in seven (87.5%) patients with close margins, and 10 (62.5%) with positive margins. After SBRT, 19 patients resumed or started a 6-month course of gemcitabine-based chemotherapy at a median interval of 18 days (range, 9-31 days) post-SBRT. The median OS was 26.7 months and the 1- and 2-year OS rates were 80.4% and 57.2%, respectively. Of the 24 patients, 12 (50%) developed distant metastases of whom two (25%) had close margins and 10 (62.5%) had positive margins. Ten patients (41.7%) were free of progression at last follow-up (range, 3-39.5 months). Three patients (12.5%) had grade 1-2 acute GI toxicities, and two patients (8.3%) had grade 1 and 2 late toxicities. No patients experienced grade 3 or 4 toxicity, including bowel perforation, secondary to SBRT. CONCLUSIONS: Our data suggest that adjuvant SBRT for resected pancreatic cancer can be achieved with minimal toxicity. This shorter treatment course allowed initiation of systemic chemotherapy shortly after the completion of SBRT.

Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas.

OBJECTIVES: The aim of the study was to assess the feasibility and safety of stereotactic body radiotherapy (SBRT) in patients with advanced pancreatic adenocarcinoma. METHODS: We reviewed outcomes of 71 patients treated with SBRT for pancreatic cancer between July 2004 and January 2009. Forty patients (56%) had locally unresectable disease, 11 patients (16%) had local recurrence following surgical resection, 8 patients (11%) had metastatic disease, and 12 patients (17%) received adjuvant SBRT for positive margins. The median dose was 24 Gy (18-25 Gy), given in a single-fraction SBRT (n = 67) or fractionated SBRT (n = 4). Kaplan-Meyer survival analyses were used to estimate freedom from local progression (FFLP) and overall survival (OS) rates. RESULTS: The median follow-up among surviving patients was 12.7 months (4-26 months). The median tumor volume was 17 mL (5.1-249 mL). The overall FFLP rates at 6 months/1 year were 71.7%/48.5%, respectively. Among those with macroscopic disease, FFLP was achieved in 77.3% of patients with tumor size <15 mL (n = 22), and 59.5% for ≥15 mL (n = 37) (P = 0.02). FFLP was achieved in 73% following 24 to 25 Gy, and 45% with 18 to 22 Gy (P = 0.004). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%, respectively. Grade 1-2 acute and late GI toxicity were seen in 39.5% of patients. Three patients experienced acute grade 3 toxicities. CONCLUSIONS: SBRT is feasible, with minimal grade ≥3 toxicity. The overall FFLP rate for all patients was 64.8%, comparable to rates with external beam radiotherapy. This shorter treatment course can be delivered without delay in adjuvant systemic therapy.

Elimination of human lung cancer stem cells through targeting of the stem cell factor-c-kit autocrine signaling loop.

Cancer stem cells (CSC) are thought to be responsible for tumor initiation and tumor regeneration after chemotherapy. Previously, we showed that chemotherapy of non-small cell lung cancer (NSCLC) cells lines can select for outgrowth of highly tumorigenic and metastatic CSCs. The high malignancy of lung CSCs was associated with an efficient cytokine network. In this study, we provide evidence that blocking stem cell factor (SCF)-c-kit signaling is sufficient to inhibit CSC proliferation and survival promoted by chemotherapy. CSCs were isolated from NSCLC cell lines as tumor spheres under CSC-selective conditions and their stem properties were confirmed. In contrast to other tumor cells, CSCs expressed c-kit receptors and produced SCF. Proliferation of CSCs was inhibited by SCF-neutralizing antibodies or by imatinib (Gleevec), an inhibitor of c-kit. Although cisplatin treatment eliminated the majority of tumor cells, it did not eliminate CSCs, whereas imatinib or anti-SCF antibody destroyed CSCs. Significantly, combining cisplatin with imatinib or anti-SCF antibody prevented the growth of both tumor cell subpopulations. Our findings reveal an important role for the SCF-c-kit signaling axis in self-renewal and proliferation of lung CSCs, and they suggest that SCF-c-kit signaling blockade could improve the antitumor efficacy of chemotherapy of human NSCLC.

Fractionated radiosurgical management of intramedullary spinal cord metastasis: A case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Intramedullary spinal cord metastasis (ISCM) comprises 8.5% of central nervous system metastases and confers significant morbidity. Radioresistant histologies such renal cell carcinoma and melanoma are not generally amenable to long-term palliation with conventional radiotherapy while surgery has often been found to be technically challenging and frequently morbid. In this report, we present a patient with a C5 ISCM from renal cell carcinoma treated with fractionated stereotactic radiosurgery. CLINICAL PRESENTATION: A 50-year-old gentleman with metastatic renal cell carcinoma presented with profound bilateral shoulder pain and upper extremity paresthesias. Magnetic resonance imaging revealed an intramedullary lesion at the level of fifth cervical vertebra (C5). Medical management and chiropractic manipulation proved to be ineffective. The patient was then treated with external beam radiation therapy, but continued to experience severe pain, paresthesias, and progressive, profound neurologic symptoms. INTERVENTION: The patient was referred to radiation oncology and neurosurgery for evaluation. Consideration was given to cordotomy and resection but the location and procedure was deemed to be high-risk and therefore was deferred. The decision was made to treat with fractionated stereotactic radiosurgery. A dose of 15Gy was successfully delivered in 3 fractions to the 80% isodose line without complication or adverse effects. Twenty-six months following treatment, the patient was still alive, fully functional, and reported no pain and rare of paresthesias. CONCLUSION: Fractionated stereotactic radiosurgery is a feasible, safe, and effective modality for the treatment of ICSM and should be carefully considered in the management of this difficult to treat condition.

Analysis of influence of age on acute and chronic radiotherapy toxicity in treatment of prostate cancer.

OBJECTIVES: To provide a single-institution analysis of the influence of age on acute and late genitourinary (GU) and gastrointestinal (GI) toxicity after radiotherapy (RT) administered in different prostate cancer scenarios. Improved understanding of the influence of age on toxicity outcome after RT for prostate cancer can assist in treatment decision-making. METHODS: The records of 527 consecutive nonmetastatic patients receiving RT at a single institution and for whom demographic, disease, treatment, and follow-up information were available were reviewed. The cohort was divided into four major categories as a function of age: younger than 60 years, 60 to 69 years, 70 to 74 years, and 75 years and older. The toxicity rates in each of these categories were tabulated according to the Radiation Therapy Oncology Group toxicity scales and compared using the chi-square test. Additionally, an ordered logit regression analysis was performed for each of these categories using all major patient, disease, and treatment factors. RESULTS: The toxicity rates were not significantly different as a function of age for either acute GU (P = 0.10) or acute GI (P = 0.19) toxicity or for either late GU (P = 0.22) or late GI (P = 0.09) toxicity. The ordered logit regression analysis showed that age was not a factor that correlated with toxicity in any setting (acute GU, P = 0.44; acute GI, P = 0.55; late GU, P = 0.65; late GI, P = 0.14). CONCLUSIONS: Patient age did not independently influence GI or GU toxicity after RT for nonmetastatic prostate cancer and should not be used as an independent factor in treatment decision-making or in patient counseling with regard to GI and GU toxicity outcomes after RT.