Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment.

A Prospective Study on Deep Inspiration Breath Hold Thoracic Radiation Therapy Guided by Bronchoscopically Implanted Electromagnetic Transponders.

Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study.

Methods: We enrolled patients with primary lung cancer or lung metastases.

Improving Pediatric Normal Tissue Radiation Dose-Response Modeling in Children With Cancer: A PENTEC Initiative.

The development of normal tissue radiation dose-response models for children with cancer has been challenged by many factors, including small sample sizes; the long length of follow-up needed to observe some toxicities; the continuing occurrence of events beyond the time of assessment; the often complex relationship between age at treatment, normal tissue developmental dynamics, and age at assessment; and the need to use retrospective dosimetry. Meta-analyses of published pediatric outcome studies face additional obstacles of incomplete reporting of critical dosimetric, clinical, and statistical information. This report describes general methods used to address some of the pediatric modeling issues.

Stereotactic Body Radiation Therapy for Stage IIA to IIIA Inoperable Non-Small Cell Lung Cancer: A Phase 1 Dose-Escalation Trial.

Purpose: Larger tumors are underrepresented in most prospective trials on stereotactic body radiation therapy (SBRT) for inoperable non-small cell lung cancer (NSCLC). We performed this phase 1 trial to specifically study the maximum tolerated dose (MTD) of SBRT for NSCLC >3 cm.

Methods And Materials: A 3 + 3 dose-escalation design (cohort A) with an expansion cohort at the MTD (cohort B) was used.

Comparison of Risks of Late Effects From Radiation Therapy in Children Versus Adults: Insights From the QUANTEC, HyTEC, and PENTEC Efforts.

Pediatric Normal Tissue Effects in the Clinic (PENTEC) seeks to refine quantitative radiation dose-volume relationships for normal-tissue complication probabilities (NTCPs) in survivors of pediatric cancer. This article summarizes the evolution of PENTEC and compares it with similar adult-focused efforts (eg, Quantitative Analysis of Normal Tissue Effects in the Clinic [QUANTEC] and Hypofractionated Treatment Effects in the Clinic [HyTEC]) with respect to content, oversight, support, scope, and methodology of literature review. It then summarizes key organ-specific findings from PENTEC in an attempt to compare NTCP estimates in children versus adults.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation.

Purpose: Disease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20-40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression.

Materials/methods: Published CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122).

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer.

Purpose: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC.

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma.

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown.

Four-Dimensional Computed Tomography-Based Correlation of Respiratory Motion of Lung Tumors With Implanted Fiducials and an External Surrogate.

Purpose: Our purpose was to assess the suitability of airway-implanted internal fiducial markers and an external surrogate of respiratory motion for motion management during radiation therapy of lung tumors.

Methods And Materials: We analyzed 4-dimensional computed tomography scans acquired during radiation therapy simulation for 28 patients with lung tumors who had anchored fiducial markers bronchoscopically implanted inside small airways in or near the tumor in a prospective trial. We used a linear mixed model to build population-based correlative models of tumor and surrogate motion.

Modeling of Tumor Control Probability in Stereotactic Body Radiation Therapy for Adrenal Tumors.

Purpose: Stereotactic body radiation therapy (SBRT) in the management of adrenal metastases is emerging as a well-tolerated, effective method of treatment for patients with limited metastatic disease. SBRT planning and treatment utilization are widely variable, and publications report heterogeneous radiation dose fractionation schemes and treatment outcomes. The objective of this analysis was to review the current literature on SBRT for adrenal metastases and to develop treatment guidelines and a model for tumor control probability of SBRT for adrenal metastases based on these publications.

Primary Hypothyroidism in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

Purpose: From the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative, a systematic review and meta-analysis of publications reporting on radiation dose-volume effects for risk of primary hypothyroidism after radiation therapy for pediatric malignancies was performed.

Methods And Materials: All studies included childhood cancer survivors, diagnosed at age <21 years, whose radiation therapy fields exposed the thyroid gland and who were followed for primary hypothyroidism. Children who received pituitary-hypothalamic or total-body irradiation were excluded.

Association of Ablative Radiation Therapy With Survival Among Patients With Inoperable Pancreatic Cancer.

Importance: Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease.

Treatment planning and outcomes effects of reducing the preferred mean esophagus dose for conventionally fractionated non-small cell lung cancer radiotherapy.

Based on an analysis of published literature, our department recently lowered the preferred mean esophagus dose (MED) constraint for conventionally fractionated (2 Gy/fraction in approximately 30 fractions) treatment of locally advanced non-small cell lung cancer (LA-NSCLC) with the goal of reducing the incidence of symptomatic acute esophagitis (AE). The goal of the change was to encourage treatment planners to achieve a MED close to 21 Gy while still permitting MED to go up to the previous guideline of 34 Gy in difficult cases. We compared all our suitable LA-NSCLC patients treated with plans from one year before through one year after the constraint change.

Early Prediction of Acute Esophagitis for Adaptive Radiation Therapy.

Purpose: Acute esophagitis (AE) is a common dose-limiting toxicity in radiation therapy of locally advanced non-small cell lung cancer (LA-NSCLC). We developed an early AE prediction model from weekly accumulated esophagus dose and its associated local volumetric change.

Methods And Materials: Fifty-one patients with LA-NSCLC underwent treatment with intensity modulated radiation therapy to 60 Gy in 2-Gy fractions with concurrent chemotherapy and weekly cone beam computed tomography (CBCT).

Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy.

Purpose: Radiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era.

Predictive Modeling of Thoracic Radiotherapy Toxicity and the Potential Role of Serum Alpha-2-Macroglobulin.

To investigate the impact of alpha-2-macroglobulin (A2M), a suspected intrinsic radioprotectant, on radiation pneumonitis and esophagitis using multifactorial predictive models. Baseline A2M levels were obtained for 258 patients prior to thoracic radiotherapy (RT). Dose-volume characteristics were extracted from treatment plans.

Radiation pneumonitis in lung cancer patients treated with chemoradiation plus durvalumab.

Introduction: Durvalumab after concurrent chemoradiation (cCRT) is now standard of care for unresected stage III non-small cell lung cancer (NSCLC). However, there is limited data on radiation pneumonitis (RP) with this regimen. Therefore, we assessed RP and evaluated previously validated toxicity models in predicting for RP in patients treated with cCRT and durvalumab.

AAPM task group 224: Comprehensive proton therapy machine quality assurance.

Purpose:  Task Group (TG) 224 was established by the American Association of Physicists in Medicine's Science Council under the Radiation Therapy Committee and Work Group on Particle Beams. The group was charged with developing comprehensive quality assurance (QA) guidelines and recommendations for the three commonly employed proton therapy techniques for beam delivery: scattering, uniform scanning, and pencil beam scanning. This report supplements established QA guidelines for therapy machine performance for other widely used modalities, such as photons and electrons (TG 142, TG 40, TG 24, TG 22, TG 179, and Medical Physics Practice Guideline 2a) and shares their aims of ensuring the safe, accurate, and consistent delivery of radiation therapy dose distributions to patients.

Intrafraction tumor motion during deep inspiration breath hold pancreatic cancer treatment.

Purpose: Beam gating with deep inspiration breath hold (DIBH) has been widely used for motion management in radiotherapy. Normally it relies on some external surrogate for estimating the internal target motion, while the exact internal motion is unknown. In this study, we used the intrafraction motion review (IMR) application to directly track an internal target and characterized the residual motion during DIBH treatment for pancreatic cancer patients through their full treatment courses.

Stereotactic body radiation therapy (SBRT) improves local control and overall survival compared to conventionally fractionated radiation for stage I non-small cell lung cancer (NSCLC).

Background: Stereotactic body radiotherapy (SBRT) has been adopted as the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), with local control rates consistently >90%. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking.

Material And Methods: Between 1990 and 2013, 497 patients (525 lesions) with early-stage NSCLC (T1-T2N0M0) were treated with CONV (n = 127) or SBRT (n = 398).

Evaluation of respiratory motion-corrected cone-beam CT at end expiration in abdominal radiotherapy sites: a prospective study.

Background: Cone beam computed tomography (CBCT) for radiotherapy image guidance suffers from respiratory motion artifacts. This limits soft tissue visualization and localization accuracy, particularly in abdominal sites. We report on a prospective study of respiratory motion-corrected (RMC)-CBCT to evaluate its efficacy in localizing abdominal organs and improving soft tissue visibility at end expiration.

Heart Dosimetry is Correlated With Risk of Radiation Pneumonitis After Lung-Sparing Hemithoracic Pleural Intensity Modulated Radiation Therapy for Malignant Pleural Mesothelioma.

Purpose: To determine clinically helpful dose-volume and clinical metrics correlating with symptomatic radiation pneumonitis (RP) in malignant pleural mesothelioma (MPM) patients with 2 lungs treated with hemithoracic intensity modulated pleural radiation therapy (IMPRINT).

Methods And Materials: Treatment plans and resulting normal organ dose-volume histograms of 103 consecutive MPM patients treated with IMPRINT (February 2005 to January 2015) to the highest dose ≤50.4 Gy satisfying departmental normal tissue constraints were uniformly recalculated.

Identifying the Optimal Radiation Dose in Locally Advanced Non-Small-cell Lung Cancer Treated With Definitive Radiotherapy Without Concurrent Chemotherapy.

Introduction: The optimal radiation dose for locally advanced non-small-cell lung cancer (NSCLC) is not known for patients who receive sequential chemoradiation (CRT) or definitive radiotherapy (RT) only. Our objective was to determine whether a benefit exists for radiation dose escalation for these patients.

Materials And Methods: The patients included in our retrospective analysis had undergone RT for NSCLC from 2004 to 2013, had not undergone surgery, and received a dose ≥ 50.

Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma.

Introduction: Higher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicity. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) with previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D).

Methods: We analyzed 209 patients who underwent P/D and adjuvant RT (131 who received CONV and 78 who received IMPRINT) for MPM between 1974 and 2015.