Clinical implementation and outcome evaluation of dihydropyrimidine dehydrogenase (DPYD) pharmacogenomic testing for fluoropyrimidine dosing in a Canadian Provincial Healthcare center.

Background: 5-Fluorouracil (5-FU) and its pro-drug, capecitabine, are widely used to treat solid tumors. Patients with dihydropyrimidine dehydrogenase (DPYD) deficiency are at increased risk for severe treatment-related toxicity. This study reported the implementation of DPYD genotyping in clinical practice and assessed the impact of genotype-guided dosing on clinical outcomes.

Dosimetric Outcomes of SBRT to Ultra-central Lung Tumors: Lessons from the SUNSET trial.

Purpose / Introduction: The BLINDED FOR REVIEW trial investigated the maximum tolerated dose for ultracentral lung tumors treated with stereotactic body radiotherapy (SBRT). Here we report a spatial and dosimetric secondary analysis of the treatment plans and assess relationships between doses to targets, organs-at-risk (OARs) and clinical outcomes.

Material And Methods: Five institutions enrolled patients with ultracentral lung cancer, cT1-3N0M0, and all received 60 Gy in 8 fractions.

Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003.

Purpose: Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity.

Methods: This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy.

"Hope" Drives Quality of Life in Patients With Brain Metastases, But, the "Hope Center" Remains Elusive: An Analysis of NRG-CC003.

Purpose: NRG-CC003 randomized 393 patients with small cell lung cancer to prophylactic cranial irradiation (PCI) with or without hippocampal avoidance (HA). "Hopefulness" is a cognitive construct with 3 components: goals, pathways, and agency. Hope is measurable with validated instruments.

Patient-Reported Outcomes During Pelvic Radiation Therapy: A Secondary Analysis on Sexual Function From NRG-RTOG 1203.

Purpose: NRG-RTOG 1203 reported that intensity-modulated radiation therapy (IMRT) reduced patient-reported GI toxicities in patients with cervical/endometrial cancer receiving postoperative RT, compared with 3-dimensional conformal radiation therapy (3DRT). We conducted a secondary analysis of patient-reported sexual function (PR-SF) among treatment groups to identify factors associated with sexual dysfunction.

Methods And Materials: Patients on NRG-RTOG 1203 were randomly assigned to 3DRT versus IMRT and completed Patient-Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) and FACT-Cx surveys at baseline, week 5 of RT, and at 4-6 weeks, 1 year, and 3 years after RT.

Toxicity in patients receiving radiotherapy for ultracentral stage I non-small cell lung cancer: A secondary analysis of the LUSTRE randomized trial.

Background And Purpose: Stereotactic body radiotherapy (SBRT) carries potentially higher risks for ultracentral (UC) NSCLC with limited prospective data to guide decision making. We conducted a secondary analysis from a randomized trial of SBRT and conventionally hypofractionated radiation (CRT) to assess these risks.

Materials And Methods: Patients (n = 233) with medically inoperable stage I NSCLC were recruited from 2014 to 2020.

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cancer.

Purpose: NRG-RTOG0617 demonstrated a detrimental effect of uniform high-dose radiation in stage III non-small cell lung cancer. NRG-RTOG1106/ECOG-ACRIN6697 (ClinicalTrials.gov identifier: NCT01507428), a randomized phase II trial, studied whether midtreatment F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can guide individualized/adaptive dose-intensified radiotherapy (RT) to improve and predict outcomes in patients with this disease.

Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial.

Importance: Stereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non-small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist.

Objective: To examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).

Design Setting And Participants: This phase 3 RCT was conducted in 16 Canadian centers.

The Story Behind the First Mini-BEAM Photon Radiation Treatment: What is the Mini-Beam and Why is it Such an Advance?

Radiation treatment has been the cornerstone in cancer management. However, long term treatment-related morbidity always accompanies tumor control which has significant impact on quality of life of the patient who has survived the cancer. Spatially fractionated radiation has the potential to achieve both cure and to avoid dreaded long term sequelae.

Stereotactic Radiation for Ultra-Central Non-Small Cell Lung Cancer: A Safety and Efficacy Trial (SUNSET).

Purpose: The use of stereotactic body radiation therapy for tumors in close proximity to the central mediastinal structures has been associated with a high risk of toxicity. This study (NCT03306680) aimed to determine the maximally tolerated dose of stereotactic body radiation therapy for ultracentral non-small cell lung carcinoma, using a time-to-event continual reassessment methodology.

Methods And Materials: Patients with T1-3N0M0 (≤6 cm) non-small cell lung carcinoma were eligible.

Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203.

Introduction: NRG/RTOG 1203 compared 3-D conformal radiotherapy (3D CRT) to intensity-modulated radiotherapy (IMRT) in patients with endometrial or cervical cancer requiring post-operative radiotherapy after hysterectomy. The purpose of this study was to report the first quality-adjusted survival analysis comparing the two treatments.

Methods: NRG/RTOG 1203 randomized patients having undergone hysterectomy to either 3DCRT or IMRT.

Association of Pretreatment Hippocampal Volume With Neurocognitive Function in Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology/RTOG 0933.

Purpose: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933.

Methods And Materials: Hippocampal volume and total brain volume were calculated from the radiation therapy plan.

Lung SBRT credentialing in the Canadian OCOG-LUSTRE randomized trial.

Purpose: To report on the Stereotactic Body Radiation Therapy (SBRT) credentialing experience during the Phase III Ontario Clinical Oncology Group (OCOG) LUSTRE trial for stage I non-small cell lung cancer.

Methods: Three credentialing requirements were required in this process: (a) An institutional technical survey; (b) IROC (Imaging and Radiation Oncology Core) thoracic phantom end-to-end test; and (c) Contouring and completion of standardized test cases using SBRT for one central and one peripheral lung cancer, compared against the host institution as the standard. The main hypotheses were that unacceptable variation would exist particularly in OAR definition across all centres, and that institutions with limited experience in SBRT would be more likely to violate per-protocol guidelines.

Intensity-Modulated Radiation Therapy Reduces Patient-Reported Chronic Toxicity Compared With Conventional Pelvic Radiation Therapy: Updated Results of a Phase III Trial.

JCO The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General.

Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

Purpose: In oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).

Patients And Methods: Patients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT).

Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001.

Purpose: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition.

Methods: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine.

Pretreatment Volume of MRI-Determined White Matter Injury Predicts Neurocognitive Decline After Hippocampal Avoidant Whole-Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology Radiation Therapy Oncology Group 0933.

Purpose: NRG Oncology's RTOG 0933 demonstrated benefits to memory preservation after hippocampal avoidant whole-brain radiation therapy (HA-WBRT), the avoidance of radiation dose to the hippocampus (using intensity modulated radiation planning and delivery techniques) during WBRT, supporting the hypothesis of hippocampal radiosensitivity and associated memory specificity. However, some patients demonstrated cognitive decline, suggesting mechanisms outside hippocampal radiosensitivity play a role. White matter injury (WMI) has been implicated in radiation therapy-induced neurocognitive decline.

Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy.

Objective: Women with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT.

Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC).

Canadian Phase III Randomized Trial of Stereotactic Body Radiotherapy Versus Conventionally Hypofractionated Radiotherapy for Stage I, Medically Inoperable Non-Small-Cell Lung Cancer - Rationale and Protocol Design for the Ontario Clinical Oncology Group (OCOG)-LUSTRE Trial.

We describe a Canadian phase III randomized controlled trial of stereotactic body radiotherapy (SBRT) versus conventionally hypofractionated radiotherapy (CRT) for the treatment of stage I medically inoperable non-small-cell lung cancer (OCOG-LUSTRE Trial). Eligible patients are randomized in a 2:1 fashion to either SBRT (48 Gy in 4 fractions for peripherally located lesions; 60 Gy in 8 fractions for centrally located lesions) or CRT (60 Gy in 15 fractions). The primary outcome of the study is 3-year local control, which we hypothesize will improve from 75% with CRT to 87.

CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials.

Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation.

Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients.