Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial.

Background: Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC.

Methods: In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA.

Financial Toxicity and Quality-of-Life Outcomes on a Phase 1 5-fraction Stereotactic Partial Breast Irradiation Protocol for Early-Stage Breast Cancer.

Purpose: We report the financial toxicity and quality-of-life outcomes of our prospective phase 1 dose-escalation study of 5-fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer.

Materials And Methods: Women with unifocal in situ or invasive epithelial histologies, clinical stages 0, I, or II with tumor size < 3 cm treated with lumpectomy were enrolled in our phase 1 5-fraction S-PBI dose-escalation trial. Our institutionally generated questionnaire on the "Patient Perspective Cost and Convenience of Care" and the EuroQol 5-Dimension 5-level questionnaire were administered to patients treated at follow-up.

Full Dose SBRT in Combination With Mediastinal Chemoradiation for Locally Advanced, Non-Small Cell Lung Cancer: A Practical Guide for Planning, Dosimetric Results From a Phase 2 Study, and a Treatment Planning Guide for the Phase 3 NRG Oncology LU-008 Trial.

Purpose: Stereotactic body radiation therapy (SBRT) has been used with high effectiveness in early-stage non-small cell lung cancer (NSCLC) but has not been studied extensively in locally advanced NSCLC. We conducted a phase 2 study delivering SBRT to the primary tumor followed by conventionally fractionated chemoradiation to the involved lymph nodes for patients with node-positive locally advanced NSCLC. This manuscript serves as both a guide to planning techniques used on this trial and the subsequent phase 3 study, NRG Oncology LU-008, and to report patient dosimetry and toxicity results.

Dosimetric Analysis of Intra-Fraction Motion Detected by Surface-Guided Radiation Therapy During Linac Stereotactic Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) immobilization with an open face mask is more comfortable and less invasive than frame based, but concerns about intrafraction motion must be addressed. Surface-guided radiation therapy (SGRT) is an attractive option for intrafraction patient monitoring because it is continuous, has submillimeter accuracy, and uses no ionizing radiation. The purpose of this study was to investigate the dosimetric consequences of uncorrected intrafraction patient motion detected during frameless linac-based SRS.

The utilization of immunotherapy with radiation therapy in lung cancer: a narrative review.

Despite decreasing smoking rates, lung cancer remains the leading cause of death from cancer in the United States. Radiation therapy has been established as an effective locoregional therapy for both early stage and locally advanced disease and is known to stimulate local immune response. Past treatment paradigms have established the role of combining cytotoxic chemotherapy regimens and radiation therapy to help address the local and systemic nature of lung cancer.

Volumetric Modulated Arc Therapy (VMAT) Craniospinal Irradiation (CSI) for Children and Adults: A Practical Guide for Implementation.

Purpose: Volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) has been shown to have significant dosimetric advantages compared to 3-dimensional conformal therapy but is a technically complex process. We sought to develop a guide for all aspects of the VMAT CSI process and report patient dosimetry results.

Methods And Materials: We initiated VMAT CSI in 2017 and have regularly revised our standard operating procedure for this process since then.

Accelerated Hypofractionated Image-Guided vs Conventional Radiotherapy for Patients With Stage II/III Non-Small Cell Lung Cancer and Poor Performance Status: A Randomized Clinical Trial.

Importance: A significant subset of patients with stage II/III non-small cell lung cancer (NSCLC) cannot receive standard concurrent chemoradiotherapy owing to the risk of toxic effects outweighing potential benefits. Without concurrent chemotherapy, however, the efficacy of conventional radiotherapy is reduced.

Objective: To determine whether hypofractionated image-guided radiotherapy (IGRT) would improve overall survival in patients with stage II/III NSCLC who could not receive concurrent chemoradiotherapy and therefore were traditionally relegated to receiving only conventionally fractionated radiotherapy (CFRT).

The Association Between Radiation Therapy Dose and Overall Survival in Patients With Intracranial Infiltrative Low-Grade Glioma Treated With Concurrent and/or Adjuvant Chemotherapy.

Purpose: Previous trials have shown no benefit for radiation therapy (RT) dose escalation when RT is given as adjuvant monotherapy for infiltrative low-grade glioma (LGG). However, the current standard of care for high-risk LGG is RT with concurrent and/or adjuvant chemotherapy. The effect of RT dose escalation on overall survival (OS) in the setting of concurrent and/or adjuvant chemotherapy is not well established.

The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma.

Background: Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined.

Methods: We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post-subtotal resection only, (4) and grade 3 only.

Use of surface-guided radiation therapy in combination with IGRT for setup and intrafraction motion monitoring during stereotactic body radiation therapy treatments of the lung and abdomen.

Background And Purpose: Multiple techniques can be used to assist with more accurate patient setup and monitoring during Stereotactic body radiation therapy (SBRT) treatment. This study analyzes the accuracy of 3D surface mapping with Surface-guided radiation therapy (SGRT) in detecting interfraction setup error and intrafraction motion during SBRT treatments of the lung and abdomen.

Materials And Methods: Seventy-one patients with 85 malignant thoracic or abdominal tumors treated with SBRT were analyzed.

Preoperative stereotactic radiosurgery before planned resection of brain metastases: updated analysis of efficacy and toxicity of a novel treatment paradigm.

Objective: Preoperative stereotactic radiosurgery (SRS) is a feasible alternative to postoperative SRS and may lower the risk of radiation necrosis (RN) and leptomeningeal disease (LMD) recurrence. The study goal was to report the efficacy and toxicity of preoperative SRS in an expanded patient cohort with longer follow-up period relative to prior reports.

Methods: The records for patients with brain metastases treated with preoperative SRS and planned resection were reviewed.

Single-Fraction Stereotactic Radiosurgery (SRS) Alone Versus Surgical Resection and SRS for Large Brain Metastases: A Multi-institutional Analysis.

Purpose: Stereotactic radiosurgery (SRS) dose is limited by brain metastasis (BM) size. The study goal was to retrospectively determine whether there is a benefit for intracranial outcomes and overall survival (OS) for gross total resection with single-fraction SRS versus SRS alone for patients with large BMs.

Methods And Materials: A large BM was defined as ≥4 cm (2 cm in diameter) prior to the study.

Stereotactic body radiation therapy for early-stage non-small cell lung cancer: Executive Summary of an ASTRO Evidence-Based Guideline.

Purpose: This guideline presents evidence-based recommendations for stereotactic body radiation therapy (SBRT) in challenging clinical scenarios in early-stage non-small cell lung cancer (NSCLC).

Methods And Materials: The American Society for Radiation Oncology convened a task force to perform a systematic literature review on 4 key questions addressing: (1) application of SBRT to operable patients; (2) appropriate use of SBRT in tumors that are centrally located, large, multifocal, or unbiopsied; (3) individual tailoring of SBRT in "high-risk" clinical scenarios; and (4) SBRT as salvage therapy after recurrence. Guideline recommendations were created using a predefined consensus-building methodology supported by American Society for Radiation Oncology-approved tools for grading evidence quality and recommendation strength.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose.

Methods And Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires.

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

Background: A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3 cm, with each factor assigned 1 point.

Novel radiotherapy approaches for lung cancer: combining radiation therapy with targeted and immunotherapies.

Targeted therapies and immunotherapies have quickly become fixtures in the treatment armamentarium for metastatic non-small cell lung cancer (NSCLC). Targeted therapies directed against epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) translocations, and ROS-1 rearrangements have demonstrated improved progression free survival (PFS) and, in selected populations, improved overall survival (OS) compared with cytotoxic chemotherapy. Immunotherapies, including checkpoint inhibitor monoclonal antibodies against programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), have now also demonstrated improved survival compared with chemotherapy.

Optimization of normalized prescription isodose selection for stereotactic body radiation therapy: conventional vs robotic linac.

Purpose: Although modern technology has allowed for target dose escalation by minimizing normal tissue dose, the dose delivered to a tumor and surrounding tissues still depends largely on the inherent characteristics of the radiation delivery platform. This work aims to determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic body radiation therapy (SBRT) for a conventional linear accelerator and a robotic delivery platform.

Methods: Spherical targets with diameters of 10, 20, and 30 mm were constructed in the lungs and liver of a computer based digital torso phantom which simulates respiratory and cardiac motion.

Dosimetric and motion analysis of margin-intensive therapy by stereotactic ablative radiotherapy for resectable pancreatic cancer.

Background: The retroperitoneal margin is a common site of positive surgical margins in patients with resectable pancreatic cancer. Preoperative margin-intensive therapy (MIT) involves delivery of a single high dose of ablative radiotherapy (30 Gy) focused on this surgically inaccessible margin, utilizing stereotactic techniques in an effort to reduce local failure following surgery. In this study, we investigated the motion of regional organs at risk (OAR) utilizing 4DCT, evaluated the dosimetric effects of abdominal compression (AC) to reduce regional motion, and compared various planning techniques to optimize MIT.

Stereotactic body radiation therapy for thoracic cancers: recommendations for patient selection, setup and therapy.

Advanced technologies have facilitated the development of stereotactic body radiation therapy (SBRT) programs capable of delivering ablative radiation doses for the control of lung cancers. To date, experience with these programs has been highly favorable, as reflected in the results of careful clinical trials. The medically inoperable lung cancer patient, lacking more effective options, has served as the initial clinical base to test SBRT; the therapeutic outcomes have confirmed a significant role for this approach.

Stereotactic ablative radiation therapy for primary lung tumors.

Stereotactic ablative radiotherapy, also known as stereotactic body radiation therapy, has been developed as an innovative therapy for stage I non-small cell lung cancer and has now emerged as a standard treatment option for medically inoperable patients through careful analysis utilizing prospective, multi-institutional trials. This article reviews and updates the evidence for use of stereotactic ablative radiotherapy in medically inoperable patients with stage I lung cancer, its extension of use to medically operable patients, and the toxicities associated with this emerging technique.

Stereotactic body radiation therapy: evaluation of setup accuracy and targeting methods for a new couch integrated immobilization system.

A new stereotactic frame system was designed at Indiana University to utilize the precision motion control of newer accelerator couches and treat obese patients previously untreatable in other frame systems during stereotactic body radiation therapy (SBRT). The repositioning accuracy and target reproducibility of this frame was evaluated in the treatment of both lung and liver tumors. The external coordinate system on the new frame was validated using a phantom system.

Four-dimensional computed tomography scan analysis of tumor and organ motion at varying levels of abdominal compression during stereotactic treatment of lung and liver.

Purpose: To investigate the effectiveness of different abdominal compression levels on tumor and organ motion during stereotactic body radiotherapy of lower lobe lung and liver tumors using four-dimensional (4D)-CT scan analysis.

Methods And Materials: Three 4D-CT scans were acquired for 10 patients first using with no compression and then compared with two different levels of abdominal compression. The position of the tumor and various organs were defined at the peak inspiratory and expiratory phases and compared to determine the maximum motion.

Predictors of early mortality in veteran patients with pancreatic cancer.

Background: Identification of predictors of outcome may assist in guiding treatment options for patients with pancreatic cancer. The aim of the current study was to determine clinical factors and laboratory values that predicted mortality of less than 6 months in a male population of the same age and body mass index at the time of diagnosis of pancreatic cancer who died as a result of their disease.

Methods: Only patients with proven diagnosis of pancreatic cancer (n = 69) were included in the study.

Modification of gene products involved in resistance to apoptosis in metastatic colon cancer cells: roles of Fas, Apaf-1, NFkappaB, IAPs, Smac/DIABLO, and AIF.

Background: Colon cancer becomes resistant to apoptosis as it acquires metastatic potential. SW480 and SW620 colon cancer cells were established from the same patient at different stages of tumor progression. The stage III colorectal cancer cell line (SW620) is more resistant to apoptosis.