Boron Neutron Capture Therapy: A Review of Clinical Applications.

Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT utilizes boronated agents to preferentially deliver boron-10 to tumors, which, after undergoing irradiation with neutrons, yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially affecting tumor tissues while sparing more distal normal tissues. To date, BNCT has been studied clinically in a variety of disease sites, including glioblastoma multiforme, meningioma, head and neck cancers, lung cancers, breast cancers, hepatocellular carcinoma, sarcomas, cutaneous malignancies, extramammary Paget's disease, recurrent cancers, pediatric cancers, and metastatic disease. We aim to provide an up-to-date and comprehensive review of the studies of each of these disease sites, as well as a review on the challenges facing adoption of BNCT.

Improving identification of candidates for lung cancer screening in a high risk population.

BACKGROUND: Low dose computerized tomography (LDCT) has been shown to reduce lung cancer specific mortality by 20 %. Despite U.S. Preventive Services Task Force (USPSTF) endorsement, screening of appropriate patients in the U.S. remains low, at 1.9 %. The goal of this study was to assess the number and type of patients that would qualify for lung cancer screening based upon recommendations by various guidelines. METHODS: We prospectively collected a patient reported questionnaire, including smoking history, family history, exposure history, and demographics, from April-October 2017 from new consults in the Department of Radiation Oncology and Otolaryngology (ORL). Patients smoking status and patient factors were collected and reported. Patients qualifying for screening by USPSTF, the National Comprehensive Cancer Network (NCCN), and Tammemagi scoring criteria were identified. Multivariate analysis assessed the factors associated with positive criteria for screening and the sensitivity of each criterion was calculated. RESULTS: There were 546 new consults during the study period and 528 successfully completed the questionnaire. A total of 104/528 (20 %) patients who completed questionnaires qualified for screening based on any guideline. After exclusion of active lung cancer (n = 19), poor prognosis (n = 24), and CT as part of surveillance (n = 16), 45 (8.5 %) patients would require LDCT. Of the entire population, 10 %, 11 % and 18 % of patients qualified based on USPSTF, NCCN, and Tammemagi, which was reduced to 4.9 %, 5.3 %, and 7.8 %, respectively after exclusions. Patients with head and neck cancer (40 %), skin cancer (27 %), and prostate cancer (11 %) accounted for the majority of patients eligible for screening after exclusions. The sensitivity of the USPSTF, NCCN, and Tammemagi criteria in patients with a diagnosis of lung cancer (n = 26) was 38.5 % (CI95 20.2 %-59.4 %), 46.2 % (CI95 26.6 %-66.6 %), and 61.5 % (CI95 40.6 %-79.8 %), respectively. CONCLUSIONS: We successfully identified 9 % of an oncology population at consultation who could benefit from lung cancer screening in survivorship. Distribution of a written or electronic questionnaire at consultation is a simple, low cost, effective method of identifying patients who would benefit from LDCT.

Atlas based segmentation in prone breast cancer radiation therapy.

The evidence supporting atlas based contour generation is growing and includes breast, prostate, central nervous system, gastrointestinal, gynecologic, and head and neck cancer patient populations. We sought to investigate atlas based segmentation (ABS) in patients with early stage breast cancer status post breast conserving surgery treated with adjuvant radiation therapy in the prone position. An initial atlas library was generated by uploading 20 previously treated patients. Subsequently, a group of 20 consecutive patients underwent treatment planning. Heart, right lung, left lung, total lungs, and breast clinical target volume (CTV) targets were manually contoured per our standard workflow. ABS was then incorporated into our radiation planning workflow and differences in contouring time were recorded, including time needed for ABS volume refinement. ABS generated volumes were compared subjectively in the unedited and edited stages by an independent radiation oncologist to reduce bias by incorporating an interobserver quality analysis. Various objective measurements were used to compare target volume quality including mean distance to agreement (MDA), Dice Coefficient (DC), logit transformation of DC (logit(DC)). The contouring physician edited 88.75% of organ at risk (OAR) volumes on average per patient, whereas the independent reviewing physician recommended revision of 27.5% OAR on average volumes per patient. CTV editing was performed in 20/20 (100%) of cases by the contouring physician, whereas CTV revision was recommended by the independent reviewing physician in 4/20 (20%) of cases. Our atlas performed well with DC values of >0.909 and logit(DC) of >2.344 across heart, lung, and breast volumes when compared to manually generated volumes. All objective measurements demonstrated improvement with physician refinement of ABS generated volumes. The largest absolute improvement was seen in the heart and breast CTV targets. There was 100% acceptance of the edited ABS generated volumes by the independent reviewing physician. The average time saved using ABS was 6.27 minutes (56.92%) per patient. This study confirms ABS offers improvements in efficiency without sacrificing contour quality in the early stage breast cancer patient population and demonstrates the functionality of ABS with prone patient positioning.

Intracranial motion during frameless Gamma-Knife stereotactic radiosurgery.

PURPOSE/OBJECTIVES: The Gamma-Knife radiosurgery (GKRS) (Elekta AB, Stockholm) platform delivers highly conformal and precise radiation; however, intracranial displacement during treatment allows for the potential of a marginal target-miss. Frameless (mask-based) GKRS using the Gamma Knife Icon system monitors nasal tip motion as a surrogate for intracranial motion by tracking an infrared marker using a high-definition motion management (HDMM) system. To date, there is limited data available regarding the incidence and severity of motion and factors that impact intrafraction motion when treating with frameless GKRS. MATERIALS/METHODS: A retrospective study was performed to evaluate patients with brain tumors who were treated with frameless GKRS using the Gamma Knife Icon between May and December 2018. All patients underwent mask-based immobilization using a thermoplastic mask. Data on patient demographics, mask type, use of bite block, and number of treatments received, use of anxiolytics, treatment time, and whether a physics clearance check was performed prior to treatment were collected. For each treatment session, average displacement (mm), maximum displacement (mm) and total treatment time (min) were recorded and logistic regression analyses were performed. RESULTS: Data was collected for 89 consecutive treatments (38 patients). Of these, an anxiolytic was used in 61 treatments and a physics clearance check was performed for 45 treatments. The median average and maximum displacement was 0.60 mm and 1.22 mm, respectively. An average displacement greater than 0.60 mm was seen with Eastern Cooperative Oncology Group performance status (ECOG) > 1, male gender, and malignant tumors (p < 0.05). Anxiolytic use prior to treatment was associated with a significant reduction in average displacement (p < 0.05). Significantly greater odds of observing a maximum displacement over 1.22 mm was seen with patients with ECOG > 1, male gender, and increased treatment time (p < 0.05). Age > 65 and anxiolytic use were associated with a significant reduction in maximum displacement (p < 0.05). Performance of clearance checks and use of bite block use did not impact average or maximum patient displacement. CONCLUSIONS: This is the first study to evaluate patient and treatment-related factors that influence intrafraction motion during GKRS with mask-based immobilization through HDMM tracking. Increased intracranial displacement during frameless GKRS was associated with higher ECOG, male gender, increased treatment time and malignant tumors, while anxiolytics were shown to mitigate excessive motion. Radiosurgery teams should consider these patient factors when treating patients with mask immobilization.

Public interest in stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) in the United States.

Stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery have become widely used in both palliative and curative treatments for variety of primary and secondary malignancies. Although the indications and use of stereotactic techniques have increased substantially in the past decades, there been no studies to date analyzing public interest in these techniques. Using Google Trends (Google LLC, Mountain View, CA), four search terms ("SBRT," "stereotactic radiosurgery," "Gamma Knife" and "Cyberknife") were analyzed in the U.S. from January 2004 to June 2019. Each term was assigned a relative interest score based on frequency of searches. "SBRT" is becoming an increasingly popular search term, reaching peak interest in October 2018. Conversely, "stereotactic radiosurgery" and "Gamma Knife" radiosurgery initially had high interest, before declining over the past decade. "Cyberknife" was most popular in the mid-2000s but decreased steadily since that time. These trends were subsequently compared against PubMed publication data over the same time.

Proton beam therapy utilization in adults with primary brain tumors in the United States.

The utilization of proton beam therapy (PBT) as the primary treatment of adults with primary brain tumors (APBT) was evaluated through query of the National Cancer Database (NCDB) between the years 2004 and 2015. International Classification of Diseases for Oncology code for each patient was stratified into six histology categories; high-grade gliomas, medulloblastomas, ependymomas, other gliomas, other malignant tumors, or other benign intracranial tumors. Demographics of the treatment population were also analyzed. A total of 1,296 patients received PBT during the 11-year interval for treatment of their primary brain tumor. High-grade glioma, medulloblastoma, ependymoma, other glioma, other malignant, and other benign intracranial histologies made up 39%, 20%, 13%, 12%, 13%, and 2% of the cohort, respectively. The number of patients treated per year increased from 34 to 300 in years 2004 to 2015. Histologies treated with PBT varied over the 11-year interval with high-grade gliomas comprising 75% and 45% at years 2004 and 2015, respectively. The majority of the patient population was 18-29 years of age (59%), Caucasian race (73%), had median reported income of over $63,000 (46%), were privately insured (68%), and were treated at an academic institution (70%). This study characterizes trends of malignant and benign APBT histologies treated with PBT. Our data from 2004 through 2015 illustrates a marked increase in the utilization of PBT in the treatment of APBT and shows variability in the tumor histology treated over this time.

Impact of Patient Stage and Disease Characteristics on the proposed Radiation Oncology Alternative Payment Model (RO-APM).

PURPOSE: The proposed Radiation Oncology Alternative Payment Model (RO-APM) released on July 10, 2019, represents a dramatic shift from fee-for-service (FFS) reimbursement in radiation therapy (RT). This study compares historical revenue at Mayo Clinic to the RO-APM and quantifies the effect that disease characteristics may have on reimbursement. METHODS AND MATERIALS: FFS Medicare reimbursements were determined for patients undergoing RT at Mayo Clinic from 2015 to 2016. Disease categories and payment episodes were defined as per the RO-APM. Average RT episode reimbursements were reported for each disease site, except for lymphoma and metastases, and stratified by stage and disease subcategory. Comparisons with RO-APM reimbursements were made via descriptive statistics. RESULTS: A total of 2098 patients were identified, of whom 1866 (89%) were categorized per the RO-APM; 840 (45%) of those were aged >65 years. Breast (33%), head and neck (HN) (14%), and prostate (11%) cancer were most common. RO-APM base rate reimbursements and sensitivity analysis range were lower than historical reimbursement for bladder (-40%), cervical (-34%), lung (-28%), uterine (-26%), colorectal (-24%), upper gastrointestinal (-24%), HN (-23%), pancreatic (-20%), prostate (-16%), central nervous system (-13%), and anal (-10%) and higher for liver (+24%) and breast (+36%). Historical reimbursement varied with stage (stage III vs stage I) for breast (+57%, P < .01), uterine (+53%, P = .01), lung (+50%, P < .01), HN (+24%, P = .01), and prostate (+13%, P = .01). Overall, for patients older than 65 years of age, the RO-APM resulted in a -9% reduction in total RT reimbursement compared with historical FFS (-2%, -15%, and -27% for high, mid, and low adjusted RO-APM rates). CONCLUSIONS: Our findings indicate that the RO-APM will result in significant reductions in reimbursement at our center, particularly for cancers more common in underserved populations. Practices that care for socioeconomically disadvantaged populations may face significant reductions in revenue, which could further reduce access for this vulnerable population.

Current use of stereotactic body radiation therapy for low and intermediate risk prostate cancer: A National Cancer Database Analysis.

BACKGROUND: Recent studies have demonstrated both safety and efficacy of stereotactic body radiation therapy (SBRT) as monotherapy in the treatment of low and intermediate risk prostate cancer. Our study aims to provide an update analyzing the use of SBRT compared with conventional and hypofractionated regimens in the United States from 2004 to 2015. METHODS: This retrospective review was conducted using the National Cancer Database. We identified 114,931 patients with sufficient diagnostic and treatment information treated with definitive radiation therapy in the United States from 2004 to 2015. The relative utilization of conventional fractionation (defined as 180-200 cGy per fraction and >5 fractions), moderate hypofractionation (defined as >200 cGy per fraction and >5 fractions), and SBRT (defined as >200 cGy per fraction and 5 fractions or less) were compared over the same time period. Logistic regression models were used to estimate trends. Demographic factors were collected and analyzed using chi-squared tests and independent t-tests. RESULTS: The proportion of prostate cancer patients receiving SBRT increased substantially from 0.9% in 2004 to 19.5% in 2015. Moderate hypofractionation exhibited some growth, increasing from 2.7% of patients to 4.7% in 2015. Conventional fractionation use declined significantly from 96.3% in 2004 to 75.8% in 2015. Notably, there was a sharp decline in the absolute number of patients receiving conventional fractionation in 2011, from 14,699 patients treated in 2009 to 1492 in 2011. Patients treated with SBRT were more likely to be treated in academic centers, younger, and have higher income than other fractionation groups. The most frequently used fractionation schedule was 3625 cGy in five fractions. CONCLUSIONS: The use of SBRT for low and intermediate risk prostate cancer has increased significantly from 2004 to 2015, coinciding with recently published data supporting the efficacy and favorable toxicity profile of this technique.

Idiopathic mast cell activation syndrome and radiation therapy: a case study, literature review, and discussion of mast cell disorders and radiotherapy.

BACKGROUND: Mast Cell Activation Syndrome (MCAS) is classified as an idiopathic mast cell disorder where inconsistent or unknown triggers release inflammatory mediators and cause a constellation of symptoms. Studies demonstrate mast cells increase histamine, tryptase, and inflammatory cytokine expression following ionizing radiation. Additionally, there are cases of cutaneous mastocytosis developing within the initial radiation field suggesting mast cells play a role in local tissue reactions. Literature is sparse on radiation induced toxicity in patients with mast cell disorders. CASE PRESENTATION: A 62 year old female patient with a history of MCAS received breast conservation therapy for invasive lobular carcinoma of the left breast initially AJCC 7th Stage IIB, pT3 pN0 M0. The patient underwent external beam radiotherapy (EBRT) and received 4500 cGy to the left whole breast, followed by a 1000 cGy boost to the lumpectomy cavity. She developed grade 1 radiation dermatitis. Two years later she progressed distantly and received stereotactic body radiation therapy to a lumbar vertebrae lesion to a dose of 2400 cGy in a single fraction. She developed no in-field dermatologic or systemic flare in her MCAS symptoms during radiation therapy. CONCLUSIONS: To our knowledge there are no reported cases in the literature of patients diagnosed with MCAS or other idiopathic mast cell disorders undergoing radiation therapy. Idiopathic mast cell disorders such as MCAS and primary mast cell disorders alike should not be considered a contraindication to treatment with EBRT. This patient population appears to tolerate treatment without systemic flares in symptoms.

Google Search Trends in Oncology and the Impact of Celebrity Cancer Awareness.

Introduction There is widespread public interest when celebrities are diagnosed with cancer. We sought to assess how this interest impacts awareness of prevalent cancers. Methods We reviewed common cancer-related search terms using Google Trends (Google LLC, Mountain View, CA) between the years 2004 and 2017 and retrospectively correlated these findings with media or celebrity-related events. The Google Trends application was used to obtain the "search volume index" (SVI), defined as the number of searches for a specific term standardized to the total number of searches over that time period. Data were presented in a graphical format. Isolated peaks of greater than 25% from the baseline SVI were identified. Using the date of the peaks, a further search was performed to determine if any event in the media triggered the peak. Results "Lung Cancer," "Pancreas Cancer," "Endometrial Cancer," "Cervical Cancer," "Brain Cancer," and "Glioblastoma" each had the highest peak correspond with a celebrity-related event covered in the media. These search terms displayed several additional isolated peaks, the majority of which could all be correlated with a significant media event (%). The search term "Breast Cancer" consistently had a peaked interest during October (breast cancer awareness month). Breast cancer events relating to public figures had little to no relative impact on search volume during this period. None of the other cancer search terms displayed the same cyclical pattern during their respective awareness months. Colon, rectal, and prostate cancer demonstrated stable search volumes over time, without an isolated peak. Conclusion Internet search activity among English speakers of most general cancer terms exhibit peaks coinciding with events that occur to celebrity figures or advances in medicines that are substantially covered in the media. In all cases but "breast cancer," these events lend to higher search activity as compared to campaigns and awareness months. Our study suggests that media coverage of public figures with cancer may trigger substantial Internet interest in non-breast cancers, more so than traditional efforts to raise awareness.

Identifying the Most Costly Patients in Radiation Oncology and Predicting the Top Spenders.

PURPOSE: Quality payment programs aim to adjust payments on the basis of quality and cost; however, few quality metrics exist in radiation oncology. This study evaluates and predicts the top spenders (TS) after radiation therapy (RT). MATERIALS AND METHODS: Patient characteristics, cancer details, treatments, toxicity, and survival data were collected for patients treated with RT at Mayo Clinic from 2007 to 2016. Standardized costs were obtained and adjusted for inflation. TSs were identified as those with greater than 93rd percentile costs (≥ $120,812). Prediction models were developed to predict TSs using training and validation sets using information available at consultation, after RT, and at last follow-up. RESULTS: A total of 15,131 patients were included and 1,065 TSs identified. Mean cost overall was $55,290 (median, $39,996) for all patients. Prediction models 1, 2, and 3 had concordance statistics of 0.83 to 0.83, 0.85 to 0.85, and 0.87 to 0.88, respectively in training and validation, indicating excellent prediction of TSs. Factors that were most predictive of TSs included stage N/A and stage 4 (v stage 0; odds ratio [OR], 18.23 and 8.44, respectively; P < .001); hematologic, upper GI, skin and lung cancers (v breast; OR, 11.45, 7.69, 3.81, and 2.43, respectively; P < .01); immunotherapy, surgery, and chemotherapy use (OR, 4.36, 2.51, and 1.61, respectively; P < .01); hospitalizations within 90 days of RT (OR, 2.26; P < .01); or death during the episode (OR, 1.56; P < .01). CONCLUSION: This is the first study of its kind to predict with high accuracy the highest spenders in radiation oncology. These patients may benefit from pre-emptive management to mitigate costs, or may require exclusion or adjustment from quality payment programs.

Primary histiocytic sarcoma of the central nervous system: a case report with platelet derived growth factor receptor mutation and PD-L1/PD-L2 expression and literature review.

BACKGROUND: Histiocytic sarcoma (HS) is an aggressive malignant neoplasm. HS in the central nervous system is exceptionally rare and associated with a poor prognosis. This report documents a case of primary HS of the central nervous system with treatment including surgery, radiotherapy, and chemotherapy. CASE PRESENTATION: Our patient was a 47 year old female presenting with progressive ataxia, headaches, imbalance, nausea, vomiting, and diplopia. MRI showed a heterogeneously enhancing lesion approximately 2.9 × 3.0 × 2.3 cm centered upon the cerebellar vermis with mild surrounding vasogenic edema and abnormal enhancement of multiple cranial nerves. The patient underwent surgical debulking, which revealed histiocytic sarcoma with grossly purulent drainage. Staging revealed diffuse leptomeningeal involvement, primarily involving the brain and lower thoracic and lumbar spine. She underwent adjuvant radiotherapy to the brain and lower spine and was started on high dose methotrexate. However, she experienced progressive disease in the cervical and thoracic spine as well as pulmonary involvement. Genomic sequencing of her tumor showed a mutation in the platelet-derived growth factor receptor A (p.V0681) which could be targeted with Dasatinib. However, she did not tolerate Dasatinib and she succumbed to progressive disseminated disease eight months from original diagnosis. Our pathologic evaluation also revealed expression of PD-L1 and PD-L2 by tumor cells raising the potential therapeutic role for immune checkpoint inhibition. CONCLUSIONS: This case provides an example of effective CNS control with resection and moderate doses of radiation therapy. A review of the literature confirms aggressive multidisciplinary treatment is the most effective treatment against this disease. In addition, genomic sequencing may play an important role in determining new therapeutic options. However, CNS histiocytic sarcoma remains an aggressive disease with a propensity for early widespread dissemination and few long term survivors.