Long-term risk of carotid stenosis and cerebrovascular disease after radiation therapy for head and neck cancer.

BACKGROUND: Recipients of radiation therapy (RT) for head and neck cancer (HNC) are at significantly increased risk for carotid artery stenosis (CAS) and cerebrovascular disease (CVD). We sought to determine (1) cumulative incidences of CAS and CVD among HNC survivors after RT and (2) whether CAS is associated with a RT dose response effect. METHODS: This single-institution retrospective cohort study examined patients with nonmetastatic HNC who completed (chemo)RT from January 2000 through October 2020 and subsequently received carotid imaging surveillance ≤2 years following RT completion and, in the absence of CAS, every 3 years thereafter. Exclusion criteria included history of known CAS/CVD. Asymptomatic CAS was defined as ≥50% reduction of luminal diameter, symptomatic CAS as stroke or transient ischemic attack, and composite CAS as asymptomatic or symptomatic CAS. RESULTS: Of 628 patients undergoing curative intent RT for HNC, median follow-up was 4.8 years (interquartile range, 2.6-8.3), with 97 patients followed ≥10 years. Median age was 61 years and 69% of patients received concurrent chemotherapy and 28% were treated postoperatively. Actuarial 10-year incidences of asymptomatic, symptomatic, and composite CAS were 29.6% (95% CI, 23.9-35.5), 10.1% (95% CI, 7.0-13.9), and 27.2% (95% CI, 22.5-32.1), respectively. Multivariable Cox models significant association between asymptomatic CAS and absolute carotid artery volume receiving ≥10 Gy (per mL: hazard ratio, 1.09; 95% CI, 1.02-1.16). CONCLUSIONS: HNC survivors are at high risk for post-RT CAS. A dose response effect was observed for asymptomatic CAS at doses as low as 10 Gy. PLAIN LANGUAGE SUMMARY: Recipients of radiation therapy for head and neck cancer are at significantly increased risk for carotid artery stenosis and cerebrovascular disease. However, carotid artery screening is not routinely performed among head and neck survivors following radiation therapy. In this single-institution retrospective cohort study, patients with head and neck cancer were initially screened for carotid artery stenosis ≤2 years following radiation therapy completion, then every 3 years thereafter. The 10-year actuarial incidence of carotid artery stenosis was >25% and stroke/transient ischemic attack >10%. Multivariable analysis demonstrated significant associations between asymptomatic carotid artery stenosis and artery volumes receiving ≥10 Gy.

Rapid unpaired CBCT-based synthetic CT for CBCT-guided adaptive radiotherapy.

In this work, we demonstrate a method for rapid synthesis of high-quality CT images from unpaired, low-quality CBCT images, permitting CBCT-based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state-of-the-art.

18F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial.

BACKGROUND: Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. METHODS: In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov, NCT01666808 and is closed to new participants. FINDINGS: From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98-3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2-not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached-not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2-74·0) in the conventional imaging group versus 75·5% (95% CI 62·5-84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3-20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06-3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). INTERPRETATION: Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. FUNDING: National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Impact of Metastasectomy and Aggressive Local Therapy in Newly Diagnosed Metastatic Soft Tissue Sarcoma: An Analysis of the NCDB.

BACKGROUND: The optimal management of patients with stage IV soft tissue sarcoma of the extremity (STSE) with distant metastases at diagnosis is unclear due to limited evidence and heterogeneity of current practice patterns. National guidelines have recommended surgical management of the primary site (SP) with or without radiotherapy (R), chemotherapy (C), and metastasectomy (M). METHODS: In the National Cancer Database (NCDB), patients with initially metastatic STSE who received definitive SP from 2004 to 2014 were identified. Survival distributions were estimated and compared using the Kaplan-Meier method and log-rank tests, and covariates were compared using Chi-square tests or analysis of variance (ANOVA). Propensity score analysis using inverse probability of treatment weighting was used. RESULTS: Overall, 1124 patients were included, with a median age of 55 years (range 18-90). Utilization of SP+M increased over time from 18.8% in 2004-2006, to 33.3% in 2007-2009, to 47.9% in 2010-2014 (p = 0.024). The addition of M to SP was associated with superior 5-year overall survival (OS) at 30.8% (SP+M+/-C+/-R) compared with 18.2% for those treated with non-surgical adjuvant therapies (SP+/-C+/-R) and 12.6% for SP alone (p < 0.0001). Positive surgical margins were noted in 24.1% of patients and was associated with worse OS (hazard ratio 1.44, p < 0.001) on multivariable analysis. CONCLUSIONS: This is the first known study utilizing a large database to explore practice patterns and outcomes for patients with metastatic STSE receiving definitive SP. Utilization of metastasectomy increased in the study period and was associated with longer survival compared with SP alone. These hypothesis-generating data warrant additional study.

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy.

BACKGROUND: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. METHODS: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). RESULTS: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. CONCLUSIONS: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.

Role of adjuvant therapy in resected stage IA subcentimeter (T1a/T1b) pancreatic cancer.

BACKGROUND: The standard of care for patients with resected stage I to stage III pancreatic ductal adenocarcinoma (PDAC) is adjuvant gemcitabine-based chemotherapy. The role of adjuvant treatment in patients with subcentimeter, stage IA PDAC is unknown. The current study evaluated the effect of adjuvant treatment on survival outcomes among patients with American Joint Committee on Cancer/International Union Against Cancer stage IA (T1N0) resected PDAC using the National Cancer Data Base (NCDB). METHODS: A retrospective review of the NCDB was conducted for patients diagnosed with T1 (tumor limited to the pancreas and measuring ≤2 cm in greatest dimension), lymph node-negative (N0), resected PDAC between 2004 and 2013. Patient demographics, histology, adjuvant treatment, and survival trends were examined. Kaplan-Meier analysis and log-rank tests were performed to determine the unadjusted association between overall survival (OS), tumor size, and treatment. RESULTS: A total of 876 patients met the inclusion criteria. The patients had a mean age of 66.2 years (range, 32-90 years); approximately 83.3% were white (730 patients) and 53.1% were female (465 patients). Approximately 45.9% of the patients had moderately differentiated tumor histology (402 patients); 70.0% (613 patients) had tumors measuring 1 to 2 cm (T1c) and 30.0% (263 patients) had tumors measuring <1 cm (T1a/T1b). Approximately 94.2% of patients had negative surgical margins (815 patients) and 46.9% (410 patients) received adjuvant therapy. The median OS was significantly different for patients who received adjuvant therapy compared with patients who did not (70.7 months vs 46.9 months; P = .0001). For patients with tumors measuring <1 cm, survival was not found to be significantly different between patients who received adjuvant treatment compared with those who did not (not reached vs 85.3 months; P = .54). In the multivariable analysis, none of the covariates (treatment group, Charlson-Deyo Score, age, insurance, and facility status) demonstrated significant differences for patients with tumors measuring <1 cm. CONCLUSIONS: The current study is the first to demonstrate no survival benefit for adjuvant therapy in patients with resected subcentimeter PDAC.

Targeted sequencing and intracranial outcomes of patients with lung adenocarcinoma brain metastases treated with radiotherapy.

BACKGROUND: Treatment for advanced lung adenocarcinoma (AC) has become increasingly personalized based on molecular results. However, for patients with AC brain metastases (BMs), intracranial outcomes based on molecular subtype and the frequency of molecular aberrations are less well defined. This study sought to report targeted next-generation sequencing results and investigate molecularly based outcomes for patients with AC-BMs treated with radiotherapy. METHODS: The records of 132 patients with AC-BMs treated at Emory University from September 2008 to August 2016 with successful next-generation sequencing were reviewed. Rates of local disease recurrence, distant brain failure (DBF), and salvage whole-brain radiotherapy (WBRT) were estimated using cumulative incidence with competing risk analysis. Univariate and multivariate analyses were performed. RESULTS: The most common aberrations included tumor protein 53 (TP53) (60%), KRAS (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of patients (62%) were treated with stereotactic radiosurgery alone. In these patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and having ≥ 6 BMs were associated with an increased risk of salvage WBRT (P < .05). KRAS mutation remained significant for an increased risk of salvage WBRT when compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P < .05), despite a similar risk of DBF. PTEN loss was associated with increased risk of DBF (P < .05), whereas EGFR and ALK aberrations were associated with a decreased risk of local disease recurrence (P < .05). CONCLUSIONS: The results of the current study quantified the frequency of genetic aberrations in patients with AC-BMs and demonstrated their association with intracranial outcomes. In particular, a cohort of patients with KRAS mutations and ≥6 BMs were identified to be at high risk of requiring salvage WBRT after undergoing upfront stereotactic radiosurgery.

Health care disparities among octogenarians and nonagenarians with stage III lung cancer.

BACKGROUND: To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used. RESULTS: A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72). CONCLUSIONS: In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018;124:775-84. © 2018 American Cancer Society.

Chemotherapy with or Without Definitive Radiation Therapy in Inoperable Pancreatic Cancer.

BACKGROUND: The LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. METHODS: Using the NCDB, patients with American Joint Committee on Cancer (AJCC) clinical stage T2-4, N0-1, M0 adenocarcinoma of the pancreas from 2004 to 2014 were analyzed. Patients were stratified into chemotherapy only (CT) and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as at least 20 fractions or ≥ 5 Gy per fraction [i.e., stereotactic body radiation therapy (SBRT)] were included in the CRT cohort. Propensity-score matching (PSM) and landmark analysis were used to address selection bias and lead-time bias, respectively. RESULTS: 13,004 patients met inclusion criteria, of whom 7034 (54%) received CT and 5970 (46%) received CRT. After PSM, 5215 patients remained in each cohort. The CRT cohort demonstrated better overall survival (OS) compared with CT alone, with median and 1-year OS of 12 versus 10 months, and 50% and 41%, respectively (p < 0.001). On multivariable analysis, CRT was associated with superior OS with hazard ratio of 0.79 (95% confidence interval 0.76-0.83) compared with CT alone. CONCLUSIONS: In our series, addition of definitive radiotherapy to CT was associated with better OS when compared with CT alone in LAPC. Definitive radiotherapy should remain a treatment option for LAPC, but optimal selection criteria remain unclear.

Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation.

BACKGROUND: As systemic therapy has improved for locally advanced pancreatic cancer (LAPC), efforts to improve local control with optimal radiotherapy may be critical. Although conventionally fractionated radiation therapy (CFRT) has more recently shown a limited role in LAPC, stereotactic body radiation therapy (SBRT) is an emerging approach with promising results. With no studies to date comparing SBRT with CFRT for LAPC, this study used the National Cancer Data Base (NCDB) to evaluate these 2 modalities. METHODS: With the NCDB, patients with American Joint Committee on Cancer cT2-4/N0-1/M0 adenocarcinoma of the pancreas diagnosed from 2004 to 2013 were analyzed. Radiation therapy delivered at ≤2 Gy was deemed CFRT, and radiation therapy delivered at ≥4 Gy per fraction was considered SBRT. Kaplan-Meier analysis, log-rank testing, and multivariate Cox proportional hazards regression were performed with overall survival (OS) as the primary outcome. Propensity score matching was used. RESULTS: Among 8450 patients, 7819 (92.5%) were treated with CFRT, and 631 (7.5%) underwent SBRT. Receipt of SBRT was associated with superior OS in the multivariate analysis (hazard ratio, 0.84; 95% confidence interval, 0.75-0.93; P < .001). With propensity score matching, 988 patients in all were matched, with 494 patients in each cohort. Within the propensity-matched cohorts, the median OS (13.9 vs 11.6 months) and the 2-year OS rate (21.7% vs 16.5%) were significantly higher with SBRT versus CFRT (P = .0014). CONCLUSIONS: In this retrospective review using a large national database, SBRT was associated with superior OS in comparison with CFRT for LAPC, and these findings remained significant in a propensity-matched analysis. Further prospective studies investigating these hypothesis-generating results are warranted. Cancer 2017;123:3486-93. © 2017 American Cancer Society.

Next-generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy.

BACKGROUND: Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard-of-care therapy for patients with nonoperable, early-stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population. METHODS: Under an Institutional Review Board-approved protocol, the records of 242 consecutive patients with early-stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next-generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes. RESULTS: LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48-60 grays) over a median of 5 fractions (range, 3-8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P<.05). MET amplification was associated with worse regional (OR, 4.64; P<.05) and distant (OR, 3.73; P<.05) disease control. CONCLUSIONS: To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early-stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017;123:3681-3690. © 2017 American Cancer Society.

Effect of culture intensity and probiotics application on microbiological and environmental parameters in Litopenaeus vannamei culture ponds.

The present study examined the complex interaction among stocking density and extent of probiotic use with production and environmental parameters in Litopenaeus vannamei culture ponds to suggest suitable management strategies. The study was conducted inL. vannamei culture ponds with stocking density of 35 nos sq m(-1) (Group I) and 56 nos sq m(-1) (Group II) and probiotic application @16.5 kg ha(-1) and 157 kg ha(-1), respectively. There was no significant difference noted between the two groups of ponds in respect to ammonia oxidizing bacteria (AOB) in sediment and nitrite oxidizing bacteria (NOB) in water samples, whereas significantly higher levels of AOB in water samples of high intensity culture ponds (Group II) and NOB in sediment samples of Group I were observed. The levels of sulphur oxidizing bacteria (SOB) and sulphur reducing bacteria (SRB) in Group I pond water and in Group II sediment were significantly higher than their corresponding levels in the other group. In both the groups, ammonia, nitrite and sulphide concentrations were below toxic limits prescribed for shrimp farming. Comparing the production parameters at harvest revealed that low intensity culture ponds (Group I) had higher growth rate, average body weight and significantly lower FCR and higher survival rate than high intensity culture ponds (Group II). The results indicated that application of microbial products in higher quantities did not benefit significantly, and there is a need to regulate quantum and schedule of biological product usage for economically sustainable shrimp culture.

Statin use is associated with decreased prostate cancer recurrence in men treated with brachytherapy.

PURPOSE/OBJECTIVE(S): Recent in vitro and in vivo evidence has suggested that statin medications may have anticancer activity. We sought to determine whether statin use was associated with improved clinical outcome in men treated with brachytherapy for prostate cancer. MATERIALS/METHODS: A database of men with prostate cancer treated with permanent Iodine-125 brachytherapy between January 1999 and February 2009 was retrospectively analyzed. Standard guidelines (i.e., American Brachytherapy Society selection criteria) were used for selecting patients for brachytherapy. Biochemical failure was defined using the Phoenix definition. RESULTS: From a total of 247 men with prostate adenocarcinoma treated with brachytherapy, 174 patients (70 %) were identified as using statin medications, either during initial visit or during follow-up. Median PSA follow-up was 51 months after date of implant (range 9.4-140.35). Overall biochemical failure rate was 7.3 % (18 patients). On univariate analysis, statin use was associated with significantly improved freedom from biochemical failure [hazard ratio (HR) 0.28; 95 % CI 0.10-0.72; p < 0.01 by log-rank test]. In multivariate Cox analysis performed with the variables statin use, pretreatment PSA, clinical T stage, Gleason score, and D90 or V100, statin use remained significantly associated with improved freedom from biochemical failure (HR 0.288; 95 % CI 0.086-0.886; p = 0.0299). CONCLUSIONS: Statin use was associated with a significant improvement in freedom from biochemical failure in this cohort of men treated with brachytherapy for prostate cancer. Further investigation into the favorable effect of statin use on brachytherapy and radiation therapy in general is warranted, including prospective trials.

Stereotactic body radiotherapy: a critical review for nonradiation oncologists.

Stereotactic body radiotherapy (SBRT) involves the treatment of extracranial primary tumors or metastases with a few, high doses of ionizing radiation. In SBRT, tumor kill is maximized and dose to surrounding tissue is minimized, by precise and accurate delivery of multiple radiation beams to the target. This is particularly challenging, because extracranial lesions often move with respiration and are irregular in shape, requiring careful treatment planning and continual management of this motion and patient position during irradiation. This review presents the rationale, process workflow, and technology for the safe and effective administration of SBRT, as well as the indications, outcome, and limitations for this technique in the treatment of lung cancer, liver cancer, and metastatic disease.

Using Modularized Pin Ridge Filter in Proton FLASH Planning for Liver Stereotactic Ablative Body Radiotherapy.

We previously developed a FLASH planning framework for streamlined pin-ridge-filter (pin-RF) design, demonstrating its feasibility for single-energy proton FLASH planning. In this study, we refined the pin-RF design for easy assembly using reusable modules, focusing on its application in liver SABR. This framework generates an intermediate IMPT plan and translates it into step widths and thicknesses of pin-RFs for a single-energy FLASH plan. Parameters like energy spacing, monitor unit limit, and spot quantity were adjusted during IMPT planning, resulting in pin-RFs assembled using predefined modules with widths from 1 to 6 mm, each with a WET of 5 mm. This approach was validated on three liver SABR cases. FLASH doses, quantified using the FLASH effectiveness model at 1 to 5 Gy thresholds, were compared to conventional IMPT (IMPT-CONV) doses to assess clinical benefits. The highest demand for 6 mm width modules, moderate for 2-4 mm, and minimal for 1- and 5-mm modules were shown across all cases. At lower dose thresholds, the two-beam case showed significant dose reductions (>23%), while the other two three-beam cases showed moderate reductions (up to 14.7%), indicating the need for higher fractional beam doses for an enhanced FLASH effect. Positive clinical benefits were seen only in the two-beam case at the 5 Gy threshold. At the 1 Gy threshold, the FLASH plan of the two-beam case outperformed its IMPT-CONV plan, reducing dose indicators by up to 28.3%. However, the three-beam cases showed negative clinical benefits at the 1 Gy threshold, with some dose indicators increasing by up to 16% due to lower fractional beam doses and closer beam arrangements. This study evaluated the feasibility of modularizing streamlined pin-RFs in single-energy proton FLASH planning for liver SABR, offering guidance on optimal module composition and strategies to enhance FLASH planning.

Deep learning-based synthetic dose-weighted LET map generation for intensity modulated proton therapy.

The advantage of proton therapy as compared to photon therapy stems from the Bragg peak effect, which allows protons to deposit most of their energy directly at the tumor while sparing healthy tissue. However, even with such benefits, proton therapy does present certain challenges. The biological effectiveness differences between protons and photons are not fully incorporated into clinical treatment planning processes. In current clinical practice, the relative biological effectiveness (RBE) between protons and photons is set as constant 1.1. Numerous studies have suggested that the RBE of protons can exhibit significant variability. Given these findings, there is a substantial interest in refining proton therapy treatment planning to better account for the variable RBE. Dose-average linear energy transfer (LETd) is a key physical parameter for evaluating the RBE of proton therapy and aids in optimizing proton treatment plans. Calculating precise LETddistributions necessitates the use of intricate physical models and the execution of specialized Monte-Carlo simulation software, which is a computationally intensive and time-consuming progress. In response to these challenges, we propose a deep learning based framework designed to predict the LETddistribution map using the dose distribution map. This approach aims to simplify the process and increase the speed of LETdmap generation in clinical settings. The proposed CycleGAN model has demonstrated superior performance over other GAN-based models. The mean absolute error (MAE), peak signal-to-noise ratio and normalized cross correlation of the LETdmaps generated by the proposed method are 0.096 ± 0.019 keVµm-1, 24.203 ± 2.683 dB, and 0.997 ± 0.002, respectively. The MAE of the proposed method in the clinical target volume, bladder, and rectum are 0.193 ± 0.103, 0.277 ± 0.112, and 0.211 ± 0.086 keVµm-1, respectively. The proposed framework has demonstrated the feasibility of generating synthetic LETdmaps from dose maps and has the potential to improve proton therapy planning by providing accurate LETdinformation.

Integration of Radiation Oncology Into the Preclinical Curriculum Through Problem-Based Learning.

PURPOSE: Early exposure to oncology care during the preclinical years of medical school may translate to increased student interest in oncology-related fields and improved understanding of oncologic treatment modalities, including radiation oncology. Many schools incorporate problem-based learning (PBL) into the medical school curriculum; this is an opportunity to immerse students in oncologic case management. We describe the effective incorporation of one course into the medical school curriculum that may be replicated at other institutions. METHODS AND MATERIALS: A PBL case regarding pancreatic cancer was created by a radiation oncology resident and faculty member in collaboration with the gastrointestinal course director for first-year medical students at a single institution. Pancreatic cancer was chosen based on curricular needs. Learning objectives were discussed to guide the creation of the case. RESULTS: All 140 first-year medical students participated in the 1-hour small group case focused on oncologic work up, multidisciplinary care, and radiation therapy concepts. Students were provided with a case prompt and resources to review prior to the PBL session. Volunteer radiation oncology facilitators attended a 30-minute educational meeting and were provided a detailed case guide 1 week before the PBL session. During the PBL case, facilitators guided students to achieve desired learning objectives. Among the 76 (54%) medical students who completed an optional post-PBL survey, the majority reported that the case motivated them to learn more about oncology (89%) and radiation oncology (82%). There was an increase in the number of subscribers to the Oncology Interest Group (43% increase from previous year) and preclinical students shadowing in the radiation oncology department. The PBL case was continued in future years for all first-year students and extended to 2 hours to promote additional discussion in response to student and facilitator feedback. CONCLUSIONS: A cancer-specific PBL case facilitated by radiation oncology educators is an effective avenue to integrate radiation oncology into the preclinical curriculum and stimulate interest in oncology among first-year medical students.

Streamlined pin-ridge-filter design for single-energy proton FLASH planning.

BACKGROUND: FLASH radiotherapy (FLASH-RT) with ultra-high dose rate has yielded promising results in reducing normal tissue toxicity while maintaining tumor control. Planning with single-energy proton beams modulated by ridge filters (RFs) has been demonstrated feasible for FLASH-RT. PURPOSE: This study explored the feasibility of a streamlined pin-shaped RF (pin-RF) design, characterized by coarse resolution and sparsely distributed ridge pins, for single-energy proton FLASH planning. METHODS: An inverse planning framework integrated within a treatment planning system was established to design streamlined pin RFs for single-energy FLASH planning. The framework involves generating a multi-energy proton beam plan using intensity-modulated proton therapy (IMPT) planning based on downstream energy modulation strategy (IMPT-DS), followed by a nested pencil-beam-direction-based (PBD-based) spot reduction process to iteratively reduce the total number of PBDs and energy layers along each PBD for the IMPT-DS plan. The IMPT-DS plan is then translated into the pin-RFs and the single-energy beam configurations for IMPT planning with pin-RFs (IMPT-RF). This framework was validated on three lung cases, quantifying the FLASH dose of the IMPT-RF plan using the FLASH effectiveness model. The FLASH dose was then compared to the reference dose of a conventional IMPT plan to measure the clinical benefit of the FLASH planning technique. RESULTS: The IMPT-RF plans closely matched the corresponding IMPT-DS plans in high dose conformity (conformity index of <1.2), with minimal changes in V7Gy and V7.4 Gy for the lung (<3%) and small increases in maximum doses (Dmax) for other normal structures (<3.4 Gy). Comparing the FLASH doses to the doses of corresponding IMPT-RF plans, drastic reductions of up to nearly 33% were observed in Dmax for the normal structures situated in the high-to-moderate-dose regions, while negligible changes were found in Dmax for normal structures in low-dose regions. Positive clinical benefits were seen in comparing the FLASH doses to the reference doses, with notable reductions of 21.4%-33.0% in Dmax for healthy tissues in the high-dose regions. However, in the moderate-to-low-dose regions, only marginal positive or even negative clinical benefit for normal tissues were observed, such as increased lung V7Gy and V7.4 Gy (up to 17.6%). CONCLUSIONS: A streamlined pin-RF design was developed and its effectiveness for single-energy proton FLASH planning was validated, revealing positive clinical benefits for the normal tissues in the high dose regions. The coarsened design of the pin-RF demonstrates potential advantages, including cost efficiency and ease of adjustability, making it a promising option for efficient production.