Use Of External Beam Radiotherapy Research Articles

Performance evaluation of an inorganic optical fibre dosimeter for use in external beam radiotherapy with pulsed beams

Objective. Optical fibre dosimeters (OFDs) offer great promise for real-timein vivodose measurement in radiation-based treatment modalities such as radiotherapy and brachytherapy. This is attributed to their many useful qualities such as high spatial resolution and sensitivity. However, there are several requirements that an optical fibre dosimeter must meet to be acceptable for dose measurement in a specified treatment modality. In this work, the dosimetric performance of a novel optical fibre dosimeter for use in external beam radiotherapy is presented.Approach. The dosimeter was characterised for photon beam energies between 6-15 MV using a Varian TrueBeam Linac at dose rates between 100-2400 MU/min and assessed based on its repeatability, dose dependence, dose rate dependence, energy dependence and dose-per-pulse dependence.Main Results. The results demonstrated excellent short-term repeatability of 0.3%, good linearity in response (R2>0.9997), and minor dose rate dependence between 0.53%-2.49% for all beam qualities investigated. As the scintillator of the OFD is non-water equivalent, Monte-Carlo-TOPAS simulations were used to calculate the absorbed dose energy dependence. A dose-per-pulse dependence was also investigated and compared with dosimetry measurements made with an ionisation chamber and simulated from the treatment planning system. An over-response of 20%was found at the lowest investigated dose-per-pulse, and an under-response of 34%was found at the highest investigated dose-per-pulse. This is believed to be due to an intrinsic energy dependence making this type of OFD unsuitable for external beam radiotherapy dosimetry.Significance. The OFD evaluated in this work was primarily designed for high-dose-rate brachytherapy whereas this study includes the first measurements made in external beam radiotherapy and highlights the challenges of transferability of the dosimeter to a different radiation source.

How we approach conservative treatment of retinoblastoma in South America in the era of local ocular treatments: A consensus of the Grupo America Latina de Oncologia Pediatrica (GALOP).

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.

Planned organ preservation for elderly patients with rectal cancer using short course radiotherapy and a contact brachytherapy boost-an International multi-institution analysis.

The use of external beam radiotherapy (EBRT) and contact X-Ray brachytherapy (CXB) is emerging as an effective alternative in patients with early stage rectal cancer with the intent of organ preservation (OP). Short course radiotherapy (SCRT) is an alternative EBRT schedule for patients not fit for chemotherapy or for longer courses of EBRT. There are no multicentre studies that have reported on the outcomes of SCRT with a CXB boost, therefore we present these from patients from centres from the UK and Sweden. From the Guildford Colorectal Database or local databases, 258 patients who underwent SCRT and CXB with the intent of OP from five centres treated between 2007 and 2019 were identified. Response and survival data was analysed and presented. With a median age of 81, 226 patients were treated with radiotherapy alone (RTA) and 32 immediately after local excision (ILE). Median follow-up was 24 months. 70% and 97% of patients in the RTA and ILE groups respectively had a complete clinical response (cCR) after SCRT with CXB. Of those, local relapse was seen in 16% of the RTA and 3% of the ILE group. Median survival was 40 months after CXB in the RTA and 52 months in the ILE group. 94% of patients remained stoma-free to the point of latest follow-up. This data suggests that CXB when combined with SCRT, in a mainly elderly and comorbid population, provides good palliation with stoma-avoidance. Oncological outcomes compare with previously published work. A greater focus is required on quality of life outcomes after OP.

Clinical endpoints in trials of palliative radiotherapy: A systematic meta-research analysis

PurposeUp to 50% of radiotherapy courses are delivered in palliative intent for various indications. Despite the large number of treated patients, we know little about the choice of endpoints in trials of palliative radiotherapy. Our primary aim was, therefore, to analyze primary endpoints in trials of palliative radiotherapy. MethodsWe conducted a pre-registered (https://doi.org/10.17605/OSF.IO/GMCAF) meta-research analysis searching Pubmed/MEDLINE, EMBASE, CENTRAL, and “ClinicalTrials.gov” for clinical trials of palliative radiotherapy published 1990–2020. Endpoints were categorized in “patient-centered endpoints”, including overall survival and patient-reported outcomes, and “tumor-centered endpoints” such as local control. The remainder were “other endpoints” including toxicity or observer-rated symptoms. We applied descriptive statistics to summarize data and logistic regression to assess if year of publication predicted the choice of primary endpoints. ResultsOf 7379 records screened, 292 were eligible. Trials were characterized by small sample sizes and use of external beam radiotherapy for metastases or thoracic primaries. Median patient age was 64 and median ECOG was 1. Only 64.4%(145/225) of published trials clearly stated their primary endpoint. Published trials employed a “patient-centered primary endpoint” in 45.5%(66/145) and a “tumor-centered primary endpoint” in 17.3%(25/145) of the cases. There was no statistically significant trend in time for the use of “patient-centered primary endpoints”. Registered ongoing trials used a “patient-centered primary endpoint” in 32.8%(22/67) and a “tumor-centered primary endpoint” in 26.9%(18/67) of the cases. ConclusionAlthough “patient-centered primary endpoints” appear relatively prevalent in published trials of palliative radiotherapy, their use is still suboptimal and appears to be lower in currently ongoing trials.

Radiotherapy and cancer status in Latin America: economic analysis of investment opportunities up to 2030

Timely access to radiotherapy treatments for cancer in Latin America is hindered by substantial delays in investment. We herein report on the current incidence of the ten most frequent malignancies and on radiotherapy-related logistics across Latin America with the objective of identifying resource gaps and facilitate the planning of health-care investments up to 2030. Data were collected from the International Atomic Energy Agency's (IAEA) Directory of Radiotherapy Centers and matched to open-source databases and individual surveys sent to national scientific societies in participant countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Paraguay, Peru, Uruguay, and Venezuela). Demographic, economic, and epidemiological data were gathered from the World Bank and the Global Cancer Observatory registries. The incidence rates of the ten most common cancers treated with radiotherapy in each country were multiplied by the respective radiotherapy use rate according to the IAEA's Time-Driven Activity-Based-Costing model. Country-specific adjustments were made and the following assumptions were factored for the analysis: 240 working days, 60 patients treated per teletherapy unit per day, and 25 external beam radiotherapy fractions required per diagnosis at a cost of US$ 1703·75 or equivalent per full treatment, and four brachytherapy fractions for cervical (75% of total) and endometrial (27%) cancer and one boost fraction for prostate cancer (5%) diagnosis, at a cost of US$ 1426·40 per treatment. These values were adopted from India (for cervix cancer data) and Spain (endometrial cancer data), which are countries with a cancer incidence profile similar to that of Latin America. The prostate brachytherapy use rate was adopted from recently published US data. Human resource requirements were estimated according with the observed annual cancer incidence, keeping with IAEA's recommendations. 10-year incidence and costs projections were calculated according to the estimated demography dynamics and time value of money equation for each country for the period 2020-30. Current and projected cancer incidences and radiotherapy, personnel, and logistic requirements are reported through absolute numeric differences and mean values. Potentially saved lives (equivalent to 50% of newly included patients after increasing radiotherapy capacities to recommended levels) and monetary return, assumed as a mean regional monthly wage multiplied by the rescued life-years, are also reported. Information concerning the 11 most populous countries in Latin America was obtained. As of 2020, a population of 557 213 447 individuals was recorded, accounting for 85% of the Latin American inhabitants and projected to increase to 772 038 620 (an increase of 214 825 173) by 2030. The 2020 overall cancer incidence was 1 055 892 cases and the mean 2020 incidence per country was 95 990 (SD 135 013). The 10-year projection was of 1 460 154 new cases with a mean of 132 741 (SD 188 832) per country, highlighting the high variability in needs across the region. Overall external beam radiotherapy use rate was estimated for 663 236 annual new cases in 2020, versus 916 592 annual new cases by 2030, and overall brachytherapy use was estimated for 90 428 annual new cases in 2020 and 125 152 annual new cases by 2030. The 2020 regional availability of treatment fractions was 11 822 400 for external beam radiotherapy and 216 960 for brachytherapy. Conversely, the 2020 required number of fractions was 13 241 088 (+12·2%) for external beam radiotherapy and 361 672 (+66·7%) for brachytherapy; and the projected required number of fractions in 2030 is 18 324 720 (+55·0%) for external beam radiotherapy and 500 744 (+130·8%) for brachytherapy. If the projected demand was to be covered, an additional 181 622 lives could potentially be saved by 2030, accounting for a 2-year total financial return of US$ 1 963 776 038·20, assuming 50% of additionally treated patients will be reincorporated to the economically active population. Bridging the gap in radiotherapy up to 2030 will save lives and reduce the financial toxicity of cancer management in Latin America. Governmental and private investment in radiotherapy is urgently required to shorten access disparities and reach these goals. None.

Differences in radiotherapy application according to regional disease characteristics of hepatocellular carcinoma.

There are differences in opinion regarding the application of external beam radiotherapy in the treatment of hepatocellular carcinoma. Some major guidelines state that external beam radiotherapy is yet to attain a sufficient level of evidence. However, caution should be exercised when attempting to understand the clinical need for external beam radiotherapy solely based on the level of evidence. Previously, external beam radiotherapy had low applicability in the treatment of hepatocellular carcinoma before computed tomography-based planning was popularized. Modern external beam radiotherapy can selectively target tumor cells while sparing normal liver tissues. Recent technologies such as stereotactic body radiotherapy have enabled more precise treatment. The characteristics of hepatocellular carcinoma differ significantly according to the regional etiology. The main cause of hepatocellular carcinoma is the hepatitis B virus. It is commonly diagnosed as a locally advanced tumor but with relatively preserved hepatic function. The majority of these hepatocellular carcinoma cases are found in the East Asian population. Hepatocellular carcinoma caused by hepatitis C virus or other benign hepatitis tends to be diagnosed as a less locally aggressive tumor but with deteriorated liver function. The western world and Japan tend to have patients with such causes. External beam radiotherapy has been more commonly performed for the former, although the use of external beam radiotherapy in the latter might have more concerns with regard to hepatic toxicity. This review discusses the above subjects along with perspectives regarding external beam radiotherapy in recent guidelines.

Artificial intelligence in brachytherapy: a summary of recent developments.

Artificial intelligence (AI) applications, in the form of machine learning and deep learning, are being incorporated into practice in various aspects of medicine, including radiation oncology. Ample evidence from recent publications explores its utility and future use in external beam radiotherapy. However, the discussion on its role in brachytherapy is sparse. This article summarizes available current literature and discusses potential uses of AI in brachytherapy, including future directions. AI has been applied for brachytherapy procedures during almost all steps, starting from decision-making till treatment completion. AI use has led to improvement in efficiency and accuracy by reducing the human errors and saving time in certain aspects. Apart from direct use in brachytherapy, AI also contributes to contemporary advancements in radiology and associated sciences that can affect brachytherapy decisions and treatment. There is a renewal of interest in brachytherapy as a technique in recent years, contributed largely by the understanding that contemporary advances such as intensity modulated radiotherapy and stereotactic external beam radiotherapy cannot match the geometric gains and conformality of brachytherapy, and the integrated efforts of international brachytherapy societies to promote brachytherapy training and awareness. Use of AI technologies may consolidate it further by reducing human effort and time. Prospective validation over larger studies and incorporation of AI technologies for a larger patient population would help improve the efficiency and acceptance of brachytherapy. The enthusiasm favoring AI needs to be balanced against the short duration and quantum of experience with AI in limited patient subsets, need for constant learning and re-learning to train the AI algorithms, and the inevitability of humans having to take responsibility for the correctness and safety of treatments.

High dose rate intra-cavitary brachytherapy with cobalt 60 source for locally advanced cervical cancer: the Zimbabwean experience

Background and purposeCervical cancer is the fourth commonest cancer in women in the world with the highest regional incidence and mortality seen in Southern, Eastern and Western Africa. It is the commonest cause of cancer morbidity and mortality among Zimbabwean women. Most patients present with locally advanced disease that is no longer amenable to surgery. Definitive concurrent chemoradiation (CCRT), which is the use of external beam radiotherapy (EBRT) and weekly cisplatin, includes use of intracavitary brachytherapy, as the standard treatment. In the setting of this study, cobalt-60 (Co60)-based high dose rate brachytherapy (HDR-BT) has been in use since 2013. This study sought to review practices pertaining to use of brachytherapy in Zimbabwe, including timing with external beam radiotherapy, adverse effects and patient outcomes.MethodsA retrospective analysis of data from records of patients with histologically confirmed cervical cancer treated with HDR-BT at the main radiotherapy centre in Zimbabwe from January 2013 to December 2014 was done. Outcome measures were local control, overall survival as well as gastro-intestinal and genito-urinary toxicity.ResultsA total of 226 patients were treated with HDR-BT during the study period, with a 97% treatment completion rate. All patients received between 45-50Gy of pelvic EBRT. Seventy-four percent received concurrent platinum-based chemotherapy. In 52% of the patients, HDR-BT was started when they were still receiving EBRT. The commonest fractionation schedule used was the 7Gy × 3 fractions, once a week (87%). Clinical complete tumour response was achieved in 75% at 6 weeks post treatment, 23% had partial response. Follow-up rates at 1 year and 2 years were 40 and 19% respectively. Disease free survival at 1 year and 2 years was 94 and 95% respectively. Vaginal stenosis was the commonest toxicity recorded, high incidence noted with increasing age. Four patients developed vesico-vaginal fistulae and two patients had rectovaginal fistulae.ConclusionOne hundred and seventeen patients patients started HDR-BT during EBRT course, with a treatment completion rate of 97%. The overall treatment duration was within 56 days in the majority of patients. Early local tumour control was similar for all the HDR-BT fractionation regimes used in the study, with a high rate (75%) of complete clinical response at 6 weeks post-treatment. Prospective studies to evaluate early and long-term outcomes of HDR-BT in our setting are recommended.

Effect of adding androgen deprivation therapy to permanent iodine-125 implantation with or without external beam radiation therapy on the outcomes in patients with intermediate-risk prostate cancer: A propensity score–matched analysis

PurposeThe purpose of the study was to evaluate the effect of adding androgen deprivation therapy (ADT) to brachytherapy with or without external beam radiation therapy on oncological outcomes in prostate cancer. Methods and MaterialsOverall, 1,171 patients with intermediate-risk prostate cancer treated with brachytherapy with or without external beam radiation therapy with or without ADT between 2003 and 2013 were identified. Propensity score matching was used to counter biases between the ADT and non-ADT groups. The biochemical failure-free rate (bFFR), local recurrence-free rate, and overall survival rate were evaluated using Kaplan–Meier curves, and predictors were identified using Cox proportional hazards regression models. ResultsAfter propensity score matching, 405 patients were included in each group. The median followup duration was 9.1 years; the median ADT duration was 6 months. In the ADT versus non-ADT groups, the 9-year bFFR, local recurrence-free rate, and overall survival rate were 93.4% versus 87.8% (p = 0.016), 96.9% versus 98.1% (p = 0.481), and 88.1% versus 90.4% (p = 0.969), respectively. On multivariate analyses, Gleason score (hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 1.58–4.03) and ADT use (HR: 0.55, 95% CI: 0.34–0.89) were associated with biochemical failure. Supplemental external beam radiation therapy use (HR: 0.38, 95% CI: 0.16–0.91) was associated with lower local recurrence rates. Age (HR: 1.12, 95% CI: 1.08–1.16) and comorbidities (HR: 1.56, 95% CI: 1.04–2.34) were associated with all-cause mortality. ConclusionsA risk-benefit assessment between bFFR improvement and the potential side effects of adding ADT to brachytherapy-based radiotherapy is warranted before incorporating ADT as routine practice.

The Use and Benefit of Adjuvant Radiotherapy in Parathyroid Carcinoma: A National Cancer Database Analysis

BackgroundThe routine use of external beam radiotherapy (EBRT) is not recommended for parathyroid carcinoma (PC). However, case series have demonstrated a potential benefit in preventing local recurrence with EBRT. We aimed to characterize the patient population treated with EBRT and identify any impact of EBRT on overall survival (OS) in parathyroid carcinoma.MethodsPatients who underwent surgery for PC from 2004 to 2016 were identified from the National Cancer Database. Clinicopathologic variables and OS were compared between patients based on treatment with EBRT. Multivariable logistic and Cox regression models were performed with propensity scores and inverse-probability-weighting (IPW) adjustment to reduce treatment-selection bias in the OS analysis.ResultsA total of 885 patients met the inclusion criteria, with 126 (14.2%) undergoing EBRT. Demographics were similar between the two cohorts (EBRT vs. no EBRT). However, patients treated with EBRT had a higher frequency of regionally extensive disease, nodal metastases, and residual microscopic disease (all p < 0.05). On multivariable analysis, Black race, regional tumor extension, nodal metastasis, and treatment at an urban facility were independently associated with EBRT. The 5-year OS was 85.3% with a median follow-up of 60.8 months. EBRT was not associated with a difference in OS in crude, multivariable, or IPW models. More importantly, 10.5% of patients with completely resected localized disease (M0, N0 or Nx) underwent EBRT without a benefit in OS (p = 0.183).ConclusionsEBRT is not associated with any survival benefit in the treatment of PC. Therefore, it may be overutilized, particularly in patients with localized disease and complete surgical resection.

A population perspective on the use of external beam radiotherapy in Catalonia, Spain.

To assess the use of external beam radiotherapy in Catalonia (Spain), overall and by health management area. We assessed radiotherapy treatments in a cohort of patients diagnosed with cancer from 2009 to 2011, using the population-based cancer registries in Girona and Tarragona. Participants had to have a minimum follow-up of 5years from the time the cancer registry database was linked to the catalan health service database for financing radiation oncology. Outcomes included the proportion of patients receiving radiotherapy within 1 and 5years of diagnosis. A log-binomial model was used to assess age-related trends in the use of radiotherapy by tumour site. Finally, we calculated the standardized utilization rate and 95% confidence intervals by health management area covered by the radiation oncology services, using indirect methods. At 1 and 5years from diagnosis, 21.4 and 24.4% of patients, respectively, had received external beam radiotherapy. Patients aged 40-64years had the most indications for the treatment, and there was a negative correlation between the patients' age and the use of radiotherapy for most tumour sites (exceptions were cervical, thyroid, and uterine cancers). There were no statistically significant differences in the use of radiotherapy according to th health management area. Population-based data show that external beam radiotherapy is underutilized in Catalonia. This situation requires a careful analysis to understand the causes, as well as an improvement of the available resources, oriented toward achieving realistic targets for the optimal use of external beam radiotherapy in our country.

Impact of vaginal brachytherapy on survival in stage I endometrioid endometrial carcinoma

ObjectiveTo evaluate trends in use of radiation therapy and its impact on overall survival in low- and high-grade stage I endometrioid endometrial carcinoma.MethodsPatients with stage I endometrial cancer who underwent...

Design and verification of an external radiobiological beam port on a 16.5 MeV GE PETtrace proton cyclotron.

Protons and heavy ions are considered to be ideal particles for use in external beam radiotherapy due to the superior properties of the dose distribution. While a photon (x-ray) beam delivers considerable dose to healthy tissues around the tumor, a proton beam that is delivered with sufficient energies has: a low entrance dose (the dose in front of the tumor); a high-dose region within the tumor, known as the Bragg peak; and, no exit dose beyond the tumor. Proton therapy is the next major step in advancing radiotherapy treatment. The purpose of this project was to adapt an existing radioisotope production cyclotron, a General Electric (GE) PETtrace, to enable radiobiological studies using proton beams. During routine use the PETtrace delivers 16.5MeV protons to target with beam currents in the range of 10-100µA resulting in dose rates in the order of kGy/s. To achieve the aim of the project the dose rate had to be reduced to the Gy/min range, without attenuating the proton energy below 5MeV. This paper covers the design, construction and validation of the beam port. Monte Carlo simulations were performed, using GEANT4, SRIM and PACE4 to design the beam port and optimize its components. Once the beam port was fabricated, validation experiments were performed using EBT3 and HD-V2 Gafchromic™ films, and a Keithley 6485 picoampere meter. The external beam port was successfully modeled, designed and fabricated. By using a 0.25mm thick gold foil and a brass pin-hole collimator the beam was spread from a narrow full beam diameter of 10mm to a wide beam with a 5% flatness area in the center of the beam that had a diameter of ~20mm. In using this system the dose rate was reduced from kGy/s to ~30Gy/min.

Next-Generation Technologies and Strategies for the Management of Retinoblastoma

Retinoblastoma (RB) is an inherited retinal disorder (IRD) caused by the mutation in the RB1 gene or, rarely, by alterations in the MYCN gene. In recent years, new treatment advances have increased ocular and visual preservation in the developed world. The management of RB has improved significantly in recent decades, from the use of external beam radiation to recently, more localized treatments. Determining the underlying genetic cause of RB is critical for timely management decisions. The advent of next-generation sequencing technologies have assisted in understanding the molecular pathology of RB. Liquid biopsy of the aqueous humor has also had significant potential implications for tumor management. Currently, patients’ genotypic information, along with RB phenotypic presentation, are considered carefully when making treatment decisions aimed at globe preservation. Advances in molecular testing that improve our understanding of the molecular pathology of RB, together with multiple directed treatment options, are critical for developing precision medicine strategies to treat this disease.

PLA as a suitable 3D printing thermoplastic for use in external beam radiotherapy.

The purpose of this paper is to investigate the tissue equivalence and radiological properties of Polylactic Acid (PLA) to determine if this material is suitable for use as a 3D printing thermoplastic for radiotherapy applications. Profiles and percentage depth-dose measurements (PDDs) were analysed for photon and electron modalities with PLA samples (~ 1.25g/cm3) to determine material dosimeteric characteristics. Beam profiles and PDDs from treatment planning system (TPS) simulations, water tank measurements and radiochromic film measurements were compared. Tissue equivalence was determined through CT scanning several PLA samples and measuring the Hounsfield units (HUs) to determine relative electron density (RED), mass density and mass attenuation, these results were compared to several commercial tissue phantoms with varying properties. Geometric accuracy was tested by comparing digitally planned dimensions to physical and CT image measurements. Finally, resistance to radiation damage was tested by exposing PLA samples to several thousand monitor units (MUs) over several weeks and inspecting for damage. It was determined that PLA is a safe and effective thermoplastic for use as a patient specific bolus for both electron and photon treatment modalities. The material properties have been characterised and can be accurately modelled in the MONACO TPS.

A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy

IntroductionThere is evidence to support use of external beam radiotherapy (EBRT) in combination with both low dose rate brachytherapy (LDR–EBRT) and high dose rate brachytherapy (HDR–EBRT) to treat intermediate and high risk prostate cancer. MethodsMen with intermediate and high risk prostate cancer treated using LDR–EBRT (treated between 1996 and 2007) and HDR–EBRT (treated between 2007 and 2012) were identified from an institutional database. Multivariable analysis was performed to evaluate the relationship between patient, disease and treatment factors with biochemical progression free survival (bPFS). Results116 men were treated with LDR-EBRT and 171 were treated with HDR–EBRT. At 5 years, bPFS was estimated to be 90.5% for the LDR–EBRT cohort and 77.6% for the HDR–EBRT cohort. On multivariable analysis, patients treated with HDR–EBRT were more than twice as likely to experience biochemical progression compared with LDR–EBRT (HR 2.33, 95% CI 1.12–4.07). Patients with Gleason ≥8 disease were more than five times more likely to experience biochemical progression compared with Gleason 6 disease (HR 5.47, 95% CI 1.26–23.64). Cumulative incidence of ≥grade 3 genitourinary and gastrointestinal toxicities for the LDR–EBRT and HDR–EBRT cohorts were 8% versus 4% and 5% versus 1% respectively, although these differences did not reach statistical significance. ConclusionLDR–EBRT may provide more effective PSA control at 5 years compared with HDR–EBRT. Direct comparison of these treatments through randomised trials are recommended to investigate this hypothesis further.

VCAM-1 targeted alpha-particle therapy for early brain metastases.

BackgroundBrain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1).MethodsHuman breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT.Results 212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed.ConclusionsThe present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.

What Is the Optimal Radiotherapy Utilization Rate for Lung Cancer? a Systematic Review

Population-level planning for radiotherapy services requires estimates for optimal radiotherapy utilization rates (RTU) and epidemiological data on incidence and stage of each cancer type. Lung cancer is a common indication for palliative radiotherapy (RT), and is increasingly treated using RT for curative intent. This project aimed to review the literature to determine actual and estimated optimal RTU for non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). A systematic review of PubMed/MEDLINE database for articles from January 2009 to January 2019 was performed. A search strategy was performed using keywords related to the terms utilization, underutilization, demand, epidemiologic, benchmark, radiotherapy and cancer. Abstracts were reviewed independently by two investigators, with discrepancies settled by consensus. Data abstracted included: cancer registry used, diagnosis, stage, time of diagnosis, time of RT, intent of RT, treatment sites, radiotherapy utilization rates, estimated optimal utilization rates, and methods used for estimating optimal rate. Included studies provided RTU or estimated optimal RTU for patients with lung cancer, SCLC, or NSCLC, based on cancer registry data from 2009 or later, with greater than 1000 patients. The initial search strategy yielded 1627 unique abstracts. After review, 94 articles were determined appropriate for a full-text review. From these, a final set of 17 articles met all inclusion criteria. Thirteen papers provided data on lung cancer, inclusive of SCLC and NSCLC. RTU within 9 months to 1 year of diagnosis ranged from 39% to 46%. Lifetime RTU ranged from less than 25% in Poland to an estimated 52% in Canada. Palliative intent RTU ranged from 12% in Poland to 46% in Canada. In 8 papers, optimal RTU was estimated using the evidence-based guideline model, Malthus model, or criterion-based benchmarking (CBB) model. The majority (n=6) of estimates used the evidence-based guideline model. Estimated lifetime RTU ranged from 61% with the Malthus model to 82% with the evidence-based guideline model. Three papers presented data specific to SCLC. RTU increased overall for stage 1 SCLC from 2009 to 2013. SBRT use increased from 3% to 6%, and conventional fractionation external beam RT use decreased from 34% to 30%. Optimal RTU for SCLC was 59% using the evidence-based guideline method. There is wide geographical variation in RTU for lung cancer. RTU for SCLC and NSCLC increased between 2009 and 2019. Optimal RTU for lung cancer ranged from 61% to 82%, and was higher than all observed RTU.

Evaluating vandetanib in the treatment of medullary thyroid cancer: patient-reported outcomes.

Medullary thyroid cancers (MTCs) are neuroendocrine tumors, which secrete calcitonin and carcinoembryonic antigen, both of which can serve as tumor markers. Extensive and accurate surgical resection is the primary treatment for MTC, whereas the use of external beam radiotherapy is limited. Moreover, since MTC is derived from thyroid parafollicular cells or C cells, it is not responsive to either radioiodine or thyroid-stimulating hormone suppression, and therefore, they cannot be considered as treatment strategies. Traditional therapies for advanced or metastatic progressive medullary thyroid cancer (pMTC) are poorly effective. Among the new approaches tested in clinical trials, targeted chemotherapies with tyrosine kinase inhibitors (TKIs) are now available and they represent effective interventions for progressive disease, with additional investigational options emerging. This paper reviews the efficacy and safety of vandetanib in patients with a pMTC, as it has been shown to improve progression-free survival (30.5 vs 19.3 months in controls). Vandetanib is approved by the FDA and EMA for symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease in adults, adolescents, and children older than 5 years. The most common adverse events in vandetanib-treated patients are diarrhea, rash, folliculitis, nausea, QTc prolongation, hypertension, and fatigue. More data are required to deepen our knowledge on molecular biology of tumor and host defense, with the aim to achieve better prognosis and higher quality of life for affected patients.

Detection of air gaps around the cylinder by postinsertion computed tomography in vaginal cuff brachytherapy: A prospective series, systematic review, and meta-analysis

PurposePostinsertion computed tomography (CT) can identify air gaps (AGs) around the cylinder in vaginal cuff brachytherapy (VCB). This study investigates the incidence and location of AGs. Methods and MaterialsPlanning CTs of 22 prospectively recruited patients (NCT02091050) treated with 2.6 cm (n = 8) and 3.0 cm (n = 14) cylinders were evaluated. In addition, a systematic literature review and meta-analysis was performed (PubMed and EMBASE). The pooled incidence of AGs was calculated by using the random-effects model weighted by inverse variance. ResultsIn 18 cases (82%), a total of 45 AGs were found: 26 within the 2 cm cranial length and 19 between 2 and 4 cm of the cylinder. The mean AG diameter was 3.7 mm (range: 1.3–11.8). Cylinder diameter, primary tumor site, and use of external beam radiotherapy were not associated with AG incidence. Systematic literature review revealed nine additional relevant studies, totaling 657 patients. The pooled incidence of patients with ≥1 AG was 67% (95% confidence interval: 50–83). AGs were located at the apex in 43.4%–94.4% of cases. In patients with ≥1 AG (n = 244), the pooled mean number of AGs was 2.18 per patient. The mean dose reduction varied from 9.6% to 29.3%. ConclusionMore than two-thirds of VCB cases present with AGs, which are most commonly at the apex and can potentially reduce mucosal dose. By identifying AGs, postinsertion CT can facilitate selection of optimal cylinder size in VCB.