Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Omission of adjuvant radiotherapy in low-risk elderly males with breast cancer.

PURPOSE: Randomized clinical trials demonstrate that lumpectomy + hormone therapy (HT) without radiation therapy (RT) yields equivalent survival and acceptable local-regional outcomes in elderly women with early-stage, node-negative, hormone-receptor positive (HR +) breast cancer. Whether these data apply to men with the same inclusion criteria remains unknown. METHODS: The National Cancer Database was queried for male patients ≥ 65 years with pathologic T1-2N0 (≤ 3 cm) HR + breast cancer treated with breast-conserving surgery with negative margins from 2004 to 2019. Adjuvant treatment was classified as HT alone, RT alone, or HT + RT. Male patients were matched with female patients for OS comparison. Survival analysis was performed using Cox regression and Kaplan - Meier method. Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding. RESULTS: A total of 523 patients met the inclusion criteria, with 24.4% receiving HT, 16.3% receiving RT, and 59.2% receiving HT + RT. The median follow-up was 6.9 years (IQR: 5.0-9.4 years). IPTW-adjusted 5-yr OS rates in the HT, RT, and HT + RT cohorts were 84.0% (95% CI 77.1-91.5%), 81.1% (95% CI 71.1-92.5%), and 93.0% (95% CI 90.0-96.2%), respectively. On IPTW-adjusted MVA, relative to HT, receipt of HT + RT was associated with improvements in OS (HR: 0.641; p = 0.042). RT alone was not associated with improved OS (HR: 1.264; p = 0.420). CONCLUSION: Among men ≥ 65 years old with T1-2N0 HR + breast cancer, RT alone did not confer an OS benefit over HT alone. Combination of RT + HT demonstrated significant improvements in OS. De-escalation of treatment through omission of either RT or HT at this point should be done with caution.

Experience From an Early Exposure Education Program in Radiation Oncology for High School and Undergraduate Students.

Exposure to radiation oncology (RO), which is a small and highly subspecialized field of oncology, during undergraduate or medical education is often limited. Coupled with reduced elective exposures during the COVID-19 pandemic, unsubstantiated concerns regarding the RO job market have led to a noticeable decline in residency applications and medical students who express an interest in the field. Here, we describe a summer education program piloted in our RO department at a comprehensive cancer center to provide premedical school students (ranging from high school to postbaccalaureate) early exposure to the specialty through clinical shadowing, research opportunities, journal club, and formal didactic lectures. Pre- and postprogram surveys were administered to these students to evaluate the change in knowledge in RO. A total of 8 students participated in the program. We found an increase in understanding of the specialty, high levels of interest in considering RO as a career, and positive feedback regarding the program overall. This study supports the role of early exposure and education in stimulating interest in future medical students to pursue RO as a career. Future efforts are needed to further develop and evaluate these education programs as well as disseminate the program more broadly.

Perception and Utilization of Cannabinoids in Patients Undergoing Radiation Treatment: Our Patients Are Curious.

PURPOSE: Limited studies have described the utilization of cannabinoids among patients with cancer. This survey study aimed to characterize utilization patterns and perceptions of cannabinoid use for treatment-related side effects among patients receiving radiation treatment. METHODS AND MATERIALS: This was an anonymous survey study of patients who were undergoing or recently completed radiation treatment at a comprehensive cancer center. Data on cannabinoid use during cancer treatment, reasons for the use of cannabinoids, perceived effects of cannabinoids, and formulations of usage were collected and summarized using descriptive statistics. RESULTS: Of the 431 respondents, 111 (25.8%) patients reported cannabinoid use since their cancer diagnosis. Among the cannabinoid users, a majority (73.9%) experienced improvement in symptoms; 38.7% had better relief of cancer-treatment symptoms from cannabinoids in comparison to their prescription medications, and 16.2% lowered the amount of prescription pain medications needed after using cannabinoids. Cannabinoids appeared to be most effective in helping patients manage sleep (76.6%) and anxiety (72.1%). When asked about whether physicians should be discussing cannabinoid use, 45.1% of cannabinoid users wanted to speak with their doctors regarding its utilization. For patients who did not report cannabinoid use, a large majority (83.1%) never had discussions with their doctors regarding its utilization as part of their cancer care, and 34.8% wanted to learn more about cannabinoids from their doctors. CONCLUSIONS: About 1 in 4 patients with cancer reported cannabinoid use to assist in symptom control. A majority had subjective alleviation of treatment-related symptoms from cannabinoid use. Regardless of cannabinoid use, a sizable percentage of patients never had any discussions about cannabinoids with their oncologists, with some expressing interest in learning more. Guidelines are needed to assist radiation oncologists on how cannabinoids may play a role in caring for patients.

The diagnostic performance of the Mindray system in detecting CA125 and HE4 for patients with ovarian cancer.

Background: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings. Methods: Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system. Conclusions: The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation.

Current Status and Future Directions of Image-Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer.

PURPOSE: The standard of care for patients with locally advanced cervical cancer is definitive chemoradiation followed by a brachytherapy boost. This review describes the current status and future directions of image-guided adaptive brachytherapy for locally advanced cervical cancer. METHODS: A systematic search of the PubMed and Clinicaltrials.gov databases was performed, focusing on studies published within the last 10 years. The search queried "cervical cancer [AND] image-guided brachytherapy [OR] magnetic resonance imaging (MRI) [OR] adaptive brachytherapy". DISCUSSION: The retroEMBRACE and EMBRACE-I trials have established the use of MRI as the standard imaging modality for brachytherapy application and planning. Quantitative imaging and radiomics have the potential to improve outcomes, with three ongoing prospective studies examining the use of radiomics to further risk-stratify patients and personalize brachytherapy. Another active area of investigation includes utilizing the superior soft tissue contrast provided by MRI to increase the dose per fraction and decrease the number of fractions needed for brachytherapy, with several retrospective studies demonstrating the safety and feasibility of three-fraction courses. For developing countries with limited access to MRI, trans-rectal ultrasound (TRUS) appears to be an effective alternative, with several retrospective studies demonstrating improved target delineation with the use of TRUS in conjunction with CT guidance. CONCLUSIONS: Further investigation is needed to continue improving outcomes for patients with locally advanced cervical cancer treated with image-guided brachytherapy.

CT-Guided Online Adaptive Hypofractionated Radiotherapy for Primary Bladder Cancer: A Report of Two Cases.

Trimodality treatment for bladder cancer, consisting of maximal transurethral resection of the tumor followed by concurrent chemoradiotherapy, is an attractive management option with curative and organ-sparing intent. However, such treatment can be associated with acute toxicities related to the large treatment margins required due to daily variation in bladder filling, with resultant bladder, bowel, and rectal toxicity. Adaptive radiation, which accounts for inter-fraction variations in bladder size, allows the confident delivery of radiation to bladder cancer with smaller margins, with the potential to reduce toxicities without the associated risk of compromising the target coverage. Herein, we present a case series of two patients with primary bladder cancer who were treated with computed tomography (CT)-based online adaptive hypofractionated radiotherapy using the Ethos system (Varian Medical Systems, Palo Alto, CA, USA). The first is an 83-year-old male with a remote history of prostate cancer treated with radiotherapy, who received adaptive radiotherapy as a means of decreasing the required margin size and optimizing planning based on adjacent bowel to reduce the risk of re-irradiation. The second patient is a 78-year-old male with node-positive bladder cancer, which necessitated whole pelvis radiotherapy, who underwent adaptive treatment (25 fractions) as a means of sparing cumulative dose to the bowel while ensuring suitable target coverage. In both cases, the clinical target volume consisted of the entire bladder (± nodes) with a planning target volume expansion of 7 mm. During treatment, daily cone-beam CT scans were acquired and used to generate adapted plans. These plans were compared to the original plans, with attention to target coverage and dose to organs at risk. For all 45 fractions, the adaptive plan was selected, primarily as a means of improving target coverage. This case series demonstrates that the adaptive Ethos system effectively delivers treatment for primary bladder cancer. Further data are needed for clinical toxicity outcomes and the efficacy of this approach.

Combined Regional Approach of Talimogene laherparepvec and Radiotherapy in the Treatment of Advanced Melanoma.

Talimogene laherparepvec (TVEC) is a genetically modified oncolytic herpes simplex virus (HSV-1) that is used for the intralesional treatment of advanced or metastatic melanoma. Given that TVEC produces the granulocyte-macrophage colony-stimulating factor (GM-CSF), recent reports have suggested that radiation treatment (RT) given in conjunction with TVEC may provide synergistic immune activation at the site, and possibly systemically. However, studies on combining RT with TVEC remain limited. We conducted a retrospective review of melanoma patients from a single cancer center who received TVEC and RT in the same region of the body and compared them to patients who received TVEC with RT at another site (other than the site of TVEC injection). Between January 2015 and September 2022, we identified twenty patients who were treated with TVEC and RT; fourteen patients received TVEC and RT in the same region, and six had treatments in separate regions. Regions were determined at the time of analysis and were based on anatomic sites (such as arm, leg, torso, etc.). Kaplan-Meier analysis of progression-free survival (PFS), analyses of time to distant metastasis (DM), overall survival (OS), and locoregional control (LRC), and the corresponding log-rank test were performed. With a median follow-up of 10.5 months [mos] (range 1.0-58.7 mos), we found an improvement in PFS with TVEC and RT in the same region compared to different regions, which were 6.4 mos (95% CI, 2.4-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively; p = 0.005. There was also a significant improvement in DM when TVEC and RT were used in the same region compared to different regions: 13.8 mos (95% CI, 4.6-NR mos) and 2.8 mos (95% CI, 0.7-4.4 mos), respectively (p = 0.001). However, we found no difference in overall survival (OS) between patients who had TVEC and RT in the same region (19.0 mos, 95% confidence interval [CI], 4.1-not reached [NR] mos) and those who received treatments in different regions (18.5 mos, 95% CI, 1.0-NR mos); p = 0.366. There was no statistically significant improvement in locoregional control (LRC) in patients who had TVEC and RT in the same region was 26.0 mos (95% CI, 6.4-26.0 mos) compared to patients who received TVEC and RT in different regions (4.4 mos) (95% CI, 0.7-NR mos) (p = 0.115). No grade 3 or higher toxicities were documented in either group. Overall, there were improvements in PFS and DM when TVEC and RT were delivered to the same region of the body compared to when they were used in different regions. However, we did not find a significant difference in locoregional recurrence or OS. Future studies are needed to assess the sequence and timing of combining RT and TVEC to potentially enhance the immune response both locally and distantly.

The impact of pretreatment symptom burden on long-term quality of life following head and neck radiation: A prospective longitudinal study.

BACKGROUND: This study characterized the impact of baseline symptom burden on long-term quality-of-life in patients receiving head and neck radiation therapy (RT). METHODS: The Vanderbilt Head and Neck Symptom Survey was collected prior to head and neck RT and at follow-up visits. Responses were divided into symptom clusters of toxicities and scored from 0 (asymptomatic) to 10 (severe). Patients with responses at baseline and 1-year or 2-year follow-up were stratified by scores ≤1 or >1 and compared using the Mann-Whitney U-test. RESULTS: At 1-year follow-up (n = 75), patients with higher baseline scores had greater symptom burden for every cluster except in taste/smell. At 2-year follow-up (n = 47), patients with higher baseline scores had greater symptom burden for every cluster except in nutrition, dry mouth, trismus, neck tightness, and hearing. CONCLUSION: The Vanderbilt Head and Neck Symptom Survey demonstrated a relationship between baseline symptom burden and long-term quality-of-life and might be useful as a screening tool.

Explainable artificial intelligence analysis of brachytherapy boost receipt in cervical cancer during the COVID-19 era.

PURPOSE: Brachytherapy is a critical component of the standard-of-care curative radiotherapy regimen for women with locally advanced cervical cancer (LACC). However, existing literature suggests that many patients will not receive the brachytherapy boost. We used machine learning (ML) and explainable artificial intelligence to characterize this disparity. MATERIALS AND METHODS: Patients with LACC diagnosed from 2004 to 2020 who received definitive radiation were identified in the National Cancer Database. Five ML models were trained to predict if a patient received a brachytherapy boost. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To identify trends that may be attributable to the coronavirus disease 2019 (COVID-19) pandemic, the previous analysis was repeated and limited to 2019 to 2020. RESULTS: A total of 37,564 patients with LACC were identified; 5799 were diagnosed from 2019 to 2020 (COVID cohort). Of these patients, 59.3% received a brachytherapy boost, with 76.4% of patients diagnosed in 2019 to 2020 receiving a boost. The random forest model achieved the best performance for both the overall and COVID cohorts. In the overall cohort, the most important predictive features were the year of diagnosis, stage, age, and insurance status. In the COVID cohort, the most important predictive features were FIGO stage, age, insurance status, and hospital type. Of the 26 patients who tested positive for COVID-19 during their course of radiotherapy, 19 (73.1%) received a brachytherapy boost. CONCLUSIONS: A gradual increase in brachytherapy boost utilization has been noted, which did not seem to be significantly impacted by the onset of the COVID-19 pandemic. ML could be considered to identify patient populations where brachytherapy is underutilized, which can provide actionable feedback for improving access.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases.

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Use of Personalized Ultra-Fractionated Stereotactic Adaptive Radiotherapy for Oligometastatic Lung Adenocarcinoma: Leveraging CT-Guided Online Adaptive Radiotherapy.

Management of oligometastatic non-small cell lung cancer (OM-NSCLC) has changed considerably in recent years, as these patients were found to have better survival with systemic therapy followed by consolidative radiation. Stereotactic body radiotherapy (SBRT), characterized by high doses of radiation delivered in a limited number of fractions, has been shown to have improved local control compared to conventionally fractionated radiation in early-stage lung cancer, but its use in large tumors, ultra-central tumors, or mediastinal nodal regions is limited due to concerns of toxicity to nearby serial mediastinal structures. Recent improvements in image guidance and fast replanning allow adaptive radiotherapy to be used to personalize treatment to the patient's daily anatomy and ensure accurate dose delivery to the tumor while minimizing dose and toxicity to normal. Adaptive SBRT can expand its use into ultra-central tumors that otherwise may not be amenable to SBRT or enable alternative fractionation schedules such as personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) with one-month intervals between fractions. In this case, we report a patient initially presenting with bulky OM-NSCLC of the left lung and mediastinum with an isolated left femur metastasis who was referred for consolidative radiotherapy after systemic therapy. We demonstrate how CT-guided online adaptive radiotherapy to the lung and mediastinum can be used despite the long time interval between treatments. In addition, adaptive plans lead to a substantial decrease in the heart dose, with moderate decreases in other organs compared to non-adaptive plans. This case demonstrates the feasibility of using adaptive radiotherapy for PULSAR of ultra-central OM-NSCLC.

CT-Guided Online Adaptive Radiotherapy Delivered via Personalized Ultrafractionated Stereotactic Adaptive Radiotherapy (PULSAR) for a Bulky Thoracic and Abdominal Mass in Oligometastatic Renal Cell Carcinoma.

In the context of oligometastatic renal cell carcinoma (RCC), local treatment with stereotactic body radiotherapy (SBRT) may improve oncologic outcomes. However, the location and size can often pose a technical challenge in standard SBRT delivery, and the dose is potentially limited by nearby organs at risk (OARs). Online adaptive radiotherapy (oART) improves radiation delivery by personalizing high-dose fractions to account for daily stochastic variations in patient anatomy or setup. The oART process aims to maximize tumor control and enhances precision by tailoring to a more accurate representation of a patient in near-real time. The proceeding re-optimization can mitigate the uncertainty inherent in the traditional radiation delivery workflow and precludes the need for larger margins that account for anatomical variations and setup errors. Here, we describe a case of oligometastatic RCC with a bulky (>300 cm3) pleural-based left lower lobe mass extending into the upper abdomen treated via personalized ultrafractionated stereotactic adaptive radiotherapy (PULSAR). Three fractions were delivered four weeks apart allowing for tumor shrinkage of these bulky lesions, and oART permitted on-table adaptation of the plan without traditional re-simulation and re-planning required during off-line adaptive radiotherapy. The plan was designed for the Ethos linear accelerator (Varian Medical Systems, Inc., Palo Alto, CA, USA). The prescription dose was 36 Gray (Gy) in three fractions, and the adapted plan was selected in each treatment over the scheduled plan due to better target coverage and reversal of OAR dose violations. The adapted plan met all OAR dose constraints, and it achieved higher target coverage in the first two PULSAR fractions compared to the scheduled plan. In the third fraction, the cumulative point dose was approaching the maximum heart tolerance, and target coverage was accordingly compromised based on clinical judgment. There was evidence of tumor regression throughout the course of treatment, and the patient did not develop any significant radiation-related toxicities. Follow-up imaging has demonstrated the overall stable size of her lesion without any evidence of disease progression. Our case reflects the benefit of adaptive SBRT delivery to a bulky mass near multiple OARs in the setting of oligometastatic RCC. The adapted plan allowed for prioritization of critical structures on a fraction-by-fraction basis while preserving the therapeutic intent of SBRT. Further integration of advanced imaging techniques, optimal disease-specific systemic immunotherapies or targeted therapies, and refinement of patient selection will be crucial in identifying which patients would most benefit from an adaptive approach.

Phase 1 Study of Bortezomib, Fludarabine, and Melphalan, With or Without Total Marrow Irradiation, as Allogeneic Hematopoietic Stem Cell Transplant Conditioning for High-risk or Relapsed/Refractory Multiple Myeloma.

OBJECTIVE: We conducted a phase 1 study of a conditioning regimen with or without total marrow irradiation (TMI) before allogeneic hematopoietic stem cell transplantation for patients with high-risk or refractory multiple myeloma. METHODS: Eighteen patients were enrolled on one of 2 strata. Patients with no prior radiation received TMI (900 cGy), fludarabine (FLU), and melphalan (MEL) conditioning, with bortezomib added in the second cohort (stratum I). Patients with prior radiation received FLU, MEL, and bortezomib, without TMI (stratum II). RESULTS: Eight patients were enrolled in the TMI arm (stratum I). One of 3 patients in cohort 1 experienced dose-limiting toxicity (DLT), which led to the expansion to 3 more patients with no DLT. Cohort 2 enrolled only 2 patients due to low accrual, with bortezomib, added at 0.5 mg/m 2 ; neither experienced DLT. Nine patients were enrolled in the non-TMI arm (stratum II). Three patients were enrolled in cohort 1 (bortezomib 0.5 mg/m 2 ) and none experienced DLT. Three were enrolled in cohort 2 (bortezomib 0.7 mg/m 2 ), and 1 experienced DLT; therefore, the cohort expanded to 3 more patients. One more patient experienced DLT. Median overall survival on strata I and II was 44.5 months (95% CI: 1.73-not reached) and 21.6 months (95% CI: 4.1-72.7), respectively. Median progression-free survival on strata I and II was 18.1 months (95% CI: 1.73-not reached) and 8.9 months (95% CI: 2.7-24.4), respectively. CONCLUSION: TMI 900 cGy, FLU, and MEL are considered feasible as conditioning for allogeneic stem cell transplantation and may warrant further investigation due to favorable response rates and survival.

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

Modern Radiation for Hematologic Stem Cell Transplantation: Total Marrow and Lymphoid Irradiation or Intensity-Modulated Radiation Therapy Total Body Irradiation.

The development of large-field intensity-modulated radiation therapy (IMRT) has enabled the implementation of total marrow irradiation (TMI), total marrow and lymphoid irradiation (TMLI), and IMRT total body irradiation (TBI). IMRT TBI limits doses to organs at risk, primarily the lungs and in some cases the kidneys and lenses, which may mitigate complications. TMI/TMLI allows for dose escalation above TBI radiation therapy doses to malignant sites while still sparing organs at risk. Although still sparingly used, these techniques have established feasibility and demonstrated promise in reducing the adverse effects of TBI while maintaining and potentially improving survival outcomes.

Biology-Guided Radiation Therapy: An Evolving Treatment Paradigm.

Biology-guided radiation therapy is an emerging field whereby delivery of external beam radiotherapy incorporates biological/molecular imaging to inform radiation treatment. At present, there is evidence for the use of functional imaging such as PET to evaluate treatment response in patients both during and after radiation treatment as well as to provide a method of adapting or selecting patient-specific treatments. Examples in thoracic, gastrointestinal, and hematologic malignancies are provided. Improvements in PET metrics, thresholds, and novel radiotracers will further move this novel field forward.

Thoracic Radiation in Limited Stage Small Cell Lung Cancer: Trends in Radiation Fractionation.

INTRODUCTION: Thoracic radiotherapy (TRT) is standard of care for limited-stage small cell lung cancer (LS-SCLC). Although initial data supported the use of twice-daily (BID) radiation to a dose of 45 Gy, recent trials have suggested similar efficacy with daily fractionation (QD) to a dose of 60 to 70 Gy. This study evaluates trends in treatment regimen in patients treated with TRT for LS-SCLC. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried for patients with LS-SCLC treated with TRT between 2004 to 2017 grouped by RT fractionation QD vs. BID. Exclusion criteria were unknown stage, and unknown RT dose. Multivariable (MVA) analyses using logistic regression were performed to investigate factors associated with receipt of a specific fractionation schedule. RESULTS: A total of 17,453 patients met inclusion criteria, with 4,996 receiving BID treatment and 12,457 receiving QD treatment. The most common QD dose was 60 Gy (48.9%). Overall, QD fractionation has increased (1.3%/year). In 2004, 45 Gy BID treatment (41.4%) was the dominant fractionation. By 2017, 60 Gy QD (45.2%) increased (1.9%/y) to be the dominant fractionation, while 45 Gy BID (24.8%) decreased (-1.4%/y) to be the second most common fractionation. On MVA, factors that affect 1 treatment over the other were further stratified. CONCLUSION: Since 2004, QD fractionation has been the preferred TRT regimen for patients with LS-SCLC compared to BID fractionation, with the proportion of patients getting QD treatment continuing to increase. The choice of treatment regimen appears to be influenced by both patient and facility characteristics.

Clinical Applications of Magnetic Resonance-Guided Radiotherapy: A Narrative Review.

Magnetic resonance-guided radiotherapy (MRgRT) represents a promising new image guidance technology for radiation treatment delivery combining an onboard MRI scanner with radiation delivery technology. By enabling real-time low-field or high-field MRI acquisition, it facilitates improved soft tissue delineation, adaptive treatment, and motion management. Now that MRgRT has been available for nearly a decade, research has shown the technology can be used to effectively shrink treatment margins to either decrease toxicity (in breast, prostate cancer, and pancreatic cancer) or facilitate dose-escalation and improved oncologic outcomes (in pancreatic and liver cancer), as well as enabling indications that require clear soft tissue delineation and gating (lung and cardiac ablation). In doing so, the use of MRgRT has the potential to significantly improve the outcomes and quality of life of the patients it treats. The present narrative review aims to describe the rationale for MRgRT, the current and forthcoming state of technology, existing studies, and future directions for the advancement of MRgRT, including associated challenges.

Assessment of Barriers and Challenges to Screening, Diagnosis, and Biomarker Testing in Early-Stage Lung Cancer.

Management of lung cancer has transformed over the past decade and is no longer considered a singular disease as it now has multiple sub-classifications based on molecular markers. The current treatment paradigm requires a multidisciplinary approach. One of the most important facets of lung cancer outcomes however relies on early detection. Early detection has become crucial, and recent effects have shown success in lung cancer screening programs and early detection. In this narrative review, we evaluate low-dose computed tomography (LDCT) screening and how this screening modality may be underutilized. The barriers to broader implementation of LDCT screening is also explored as well as approaches to address these barriers. Current developments in diagnosis, biomarkers, and molecular testing in early-stage lung cancer are evaluated as well. Improving approaches to screening and early detection can ultimately lead to improved outcomes for patients with lung cancer.