Evaluation of a National Comprehensive Cancer Network Guidelines-Based Decision Support Tool in Patients With Non-Small Cell Lung Cancer: A Nonrandomized Clinical Trial.

Importance: The association of guideline-based decision support with the quality of care in patients with non-small cell lung cancer (NSCLC) is not known. Objective: To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients' decisional conflict. Design, Setting, and Participants: A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions: An online tool customizing the NCCN guidelines to patients' clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures: Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients' decisional conflict. Results: Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P < .001) and less adjuvant chemotherapy (0 of 7 vs 7 of 11 [63.6%]; P = .012). There was no significant change in mutation testing of non-squamous cell stage IV disease (20 of 20 [100%] vs 48 of 57 [84.2%]; P = .10). There was no significant change in pathologic mediastinal staging or initial chemoradiotherapy for patients with stage III disease. After consultation with the tool, decisional conflict scores improved by a median of 20 points (IQR, 3-34; P < .001). Conclusions and Relevance: The findings of this study suggest that exposure to the NCCN guidelines is associated with increased guideline-concordant care for 2 of 6 preselected recommendations and improvement in decisional conflict. Trial Registration: ClinicalTrials.gov Identifier: NCT03982459.

Genomic Risk Predicts Molecular Imaging-detected Metastatic Nodal Disease in Prostate Cancer.

BACKGROUND: The Decipher genomic classifier (GC) is increasingly being used to determine metastasis risk in men with localized prostate cancer (PCa). Whether GCs predict for the presence of occult metastatic disease at presentation or subsequent metastatic progression is unknown. OBJECTIVE: To determine if GC scores predict extraprostatic 68Ga prostate-specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET) positivity at presentation. DESIGN, SETTING, AND PARTICIPANTS: Between December 2015 and September 2018, 91 PCa patients with both GC scores and pretreatment 68Ga-PSMA-11 PET scans were identified. Risk stratification was performed using the National Comprehensive Cancer Network (NCCN), Cancer of the Prostate Risk Assessment (CAPRA), and GC scores. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression was used to identify factors correlated with PSMA-positive disease. RESULTS AND LIMITATIONS: The NCCN criteria identified 23 (25.3%) and 68 patients (74.7%) as intermediate and high risk, while CAPRA scores revealed 28 (30.8%) and 63 (69.2%) as low/intermediate and high risk, respectively. By contrast, only 45 patients (49.4%) had high-risk GC scores. PSMA-avid pelvic nodal involvement was identified in 27 patients (29.7%). Higher GC score was significantly associated with pelvic nodal involvement (odds ratio [OR] 1.38 per 0.1 units; p=0.009) and any PSMA-avid nodal involvement (pelvic or distant; OR 1.40 per 0.1 units; p=0.007). However, higher GC score was not significantly associated with PSMA-avid osseous metastases (OR 1.11 per 0.1 units; p=0.50). Limitations include selection bias for patients able to receive both tests and the sample size. CONCLUSIONS: Each 0.1-unit increase in GC score was associated with an approximate 40% increase in the odds of PSMA-avid lymph node involvement. These data suggest that patients with GC high risk might benefit from more nodal imaging and treatment intensification, potentially via pelvic nodal dissection, pelvic nodal irradiation, and/or the addition of chemohormonal agents. PATIENT SUMMARY: Patients with higher genomic classifier scores were found to have more metastatic lymph node involvement on prostate-specific membrane antigen imaging.

Location of Recurrence by Gallium-68 PSMA-11 PET Scan in Prostate Cancer Patients Eligible for Salvage Radiotherapy.

OBJECTIVE: To identify locations of recurrence after radical prostatectomy (RP) with prostate-specific antigen (PSA) <2 by Gallium-68 prostate-specific membrane antigen (PSMA)-11 Positron Emission Tomography (PET) imaging, and to determine whether standard nodal radiation fields would cover the location of prostate cancer recurrence. MATERIALS AND METHODS: We performed a retrospective review of patients with PSMA-PET imaging for biochemical recurrence following RP with PSA ≤2.0 ng/mL and assessed if the recurrent disease was within standard radiation target volumes. We compared patient and clinical variables between men with recurrences covered by standard salvage radiation fields and those with recurrences outside of standard fields. RESULTS: We identified 125 patients for study inclusion. The median PSA at imaging was 0.40 ng/mL (interquartile range 0.28-0.63). PSMA-avid disease was found in 66 patients (53%). Of these, 25 patients (38%) had PSMA-avid lesions found outside of the pelvis, 33 (50%) had lesions confined to the pelvic lymph nodes and prostate bed, and 8 (12%) men had PSMA-avid recurrence only in the prostate bed. Salvage radiation including standard Intensity Modulated Radiation Therapy (IMRT) pelvic nodal volumes would not cover PSMA-avid nodal disease in 38 men (30%). PSA at the time of imaging was statistically associated with having PSMA-avid disease outside of standard nodal fields (P <.01). CONCLUSION: The 68Ga-PSMA-11 PET detects disease in a majority of patients with PSA ≤2.0 following RP. Nearly one-third of men had PSMA-avid disease that would be missed by standard radiation fields. This imaging modality may dramatically impact the design and use of post-RP salvage radiotherapy.

Metabolic syndrome is a sequela of radiation exposure in hypothalamic obesity among survivors of childhood brain tumors.

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (>1 Gray (Gy)) to HPA. The second subgroup of 82 subjects had surgery only and were not exposed to radiation. Both subgroups had survived for approximately 5 years at the time of study. All had clinical evaluation, vital signs, anthropometry, measurement of body composition by dual X-ray absorptiometry and fasting laboratory assays (metabolic panel, insulin, C-peptide, insulin-like growth factor-1, leptin and adiponectin). Body composition data for both subgroups was compared with the National Health and Nutrition Survey (NHANES) subgroup of similar age, gender and body mass index. Cranial surgery was associated with obesity of similar severity in both subgroups. However, survivors exposed to radiation to the HPA also had increased visceral fat mass and high prevalence of growth hormone deficiency and metabolic syndrome. Fat mass alone did not explain the prevalence of the metabolic syndrome in radiation exposure subgroup. Other factors such as growth hormone deficiency may have contributed to metabolic risk. We conclude that prevalence of metabolic syndrome among subjects exposed to hypothalamic radiation was higher than expected from hypothalamic obesity alone. Radiation exposure may exert untoward endocrinopathies due to HPA exposure that worsens metabolic risk. Early screening for metabolic syndrome in this population is indicated.

Impact of Staging 68Ga-PSMA-11 PET Scans on Radiation Treatment Plansin Patients With Prostate Cancer.

OBJECTIVE: To evaluate the impact of staging 68Ga-PSMA-11 PET imaging on radiotherapy (RT) dose and volumes in patients with prostate cancer. METHODS: Forty-five patients (89% high or very high risk by NCCN criteria) who underwent 68Ga-PSMA-11 PET imaging prior to definitive treatment for prostate cancer between December 2015 and December 2016 were included. Locations of 68Ga-PSMA-11-avid lesions were compared to Radiation Therapy Oncology Group consensus pelvic nodal volumes (clinical target volume [CTV]); coverage of lesions outside the consensus CTV was considered a major change, while dose-escalation to lesions within the consensus CTV was considered a minor change. RESULTS: All patients had 68Ga-PSMA-11 PET uptake in the prostate. Twenty-five patients (56%) had N1/M1a disease on 68Ga-PSMA-11 PET scan, of whom 21 (47%) were previously N0. Six patients (13%) had bone metastases on 68Ga-PSMA-11 PET scan, of whom 4 had prior negative bone scans. Eight patients (18%) had lymph node metastases outside the consensus CTV. Twelve patients (27%) received a RT boost to nodes within the consensus CTV. Six patients (13%) had limited bone metastases treated with focal RT. Overall PSMA PET imaging resulted in major and/or minor changes to RT plans in 24 patients (53%). CONCLUSION: 68Ga-PSMA-11 PET imaging resulted in RT changes in 53% of patients. Prospective investigation is needed to evaluate the clinical benefit of RT changes based on staging 68Ga-PSMA-11 PET imaging.