PURPOSE: To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation. METHODS AND MATERIALS: Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases. RESULTS: Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire. CONCLUSIONS: The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial.

Purpose

To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation.

Methods and materials

Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases.

Results

Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions' plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire.

Conclusions

The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial.

Purpose

Stereotactic body radiation therapy (SBRT) has become the standard of care for inoperable early-stage non-small cell lung cancer and is often used for recurrent lung cancer and pulmonary metastases. Radiation-induced lung toxicity (RILT), including radiation pneumonitis and pulmonary fibrosis, is a major concern for which it is important to understand dosimetric and clinical predictors.

Methods and materials

This study was undertaken through the American Association of Physicists in Medicine's Working Group on Biological Effects of Stereotactic Body Radiotherapy. Data from studies of lung SBRT published through the summer of 2016 that provided detailed information about RILT were analyzed.

Results

Ninety-seven studies were ultimately considered. Definitions of the risk organ and complication endpoints as well as dose-volume information presented varied among studies. The risk of RILT, including radiation pneumonitis and pulmonary fibrosis, was reported to be associated with the size and location of the tumor. Patients with interstitial lung disease appear to be especially susceptible to severe RILT. A variety of dosimetric parameters were reported to be associated with RILT. There was no apparent threshold "tolerance dose-volume" level. However, most studies noted safe treatment with a rate of symptomatic RILT of <10% to 15% after lung SBRT with a mean lung dose (MLD) of the combined lungs ≤8 Gy in 3 to 5 fractions and the percent of total lung volume receiving more than 20 Gy (V₂₀) <10% to 15%.

Conclusions

To allow more rigorous analysis of this complication, future studies should standardize reporting by including standardized endpoint and volume definitions and providing dose-volume information for all patients, with and without RILT.

Background

Cancer is the leading cause of death among Asian Americans, who often face barriers to cancer care. Cancer supportive care needs among Asian Americans remain understudied.

Aims

We examined cancer supportive care needs and participant factors correlated with these needs, identified profiles of supportive care needs, and examined whether needs profiles are associated with quality of life among Asian American adults.

Methods and results

We recruited 47 Asian American adults with colorectal, liver, or lung cancer who spoke Chinese, English, or Vietnamese, and were starting or undergoing cancer treatment. We assessed cancer supportive care needs in four domains: cancer information, daily living, behavioral health, and language assistance. Hierarchical cluster analysis was used to identify clusters of participants based on their supportive need profiles to further examine the association between need profiles and quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy. Participants (mean age = 57.6) included 72% males and 62% spoke English less than very well. Older participants (age ≥ 65) and those with annual income <$50K reported higher daily living needs. Men and younger participants (age < 50) reported higher behavioral health needs. We found three clusters displaying distinct cancer supportive need profiles: Cluster 1 (28% of the sample) displayed high needs across all domains; Cluster 2 (51%) had low needs across all domains; and Cluster 3 (21%) had high needs for cancer information and daily living. Cluster 1 participants reported the lowest QoL.

Conclusion

Cancer supportive care needs among Asian American patients with colorectal, liver, and lung cancer were associated with patient characteristics and QoL. Understanding cancer supportive care needs will inform future interventions to improve care and QoL for Asian American patients with cancer.

Clinicaltrials

gov Identifier: NCT03867916.

Purpose

Cancer is the leading cause of death for Asian Americans. However, few studies have documented supportive care needs from the perspective of Asian American cancer patients. This study describes the needs reported by Asian American patients with colorectal, liver, or lung cancer over a 6-month period during their treatment.

Methods

Participants were recruited through the Greater Bay Area Cancer Registry and from cancer care providers in San Francisco. Participants self-identified as Asian or Asian American; were age 21 or older; spoke English, Chinese, or Vietnamese; and had stage I-III colon, rectum, liver, or lung cancer. Participants were matched with a language concordant patient navigator who provided support during a 6-month period. Needs were assessed by surveys at baseline, 3, and 6 months.

Results

Among 24 participants, 58% were 65 years or older, 42% did not complete high school, and 75% had limited English proficiency (LEP). At baseline, the most prevalent needs were cancer information (79%), nutrition and physical activity (67%), language assistance (54%), and daily living (50%). At the 3- and 6-month follow-up surveys, there was a higher reported need for mental health resources and healthcare access among participants.

Conclusion

In this pilot study of Asian American cancer patients who predominantly had LEP, participants reported many needs, with cancer information and language assistance as the most prominent. The findings highlight the importance of culturally and linguistically appropriate patient navigators in addressing supportive care needs among cancer patients with LEP.

Trial registration

ClinicalTrials.gov identifier: NCT03867916.

Reactive oxygen species (ROS) are unstable reactive molecules that are toxic to cells. Regulation of ROS homeostasis is crucial to protect cells from dysfunction, senescence, and death. In plant leaves, ROS are mainly generated from chloroplasts and are tightly temporally restricted by the circadian clock. However, little is known about how ROS homeostasis is regulated in nonphotosynthetic organs, such as petals. Here, we showed that hydrogen peroxide (H2O2) levels exhibit typical circadian rhythmicity in rose (Rosa hybrida) petals, consistent with the measured respiratory rate. RNA-seq and functional screening identified a B-box gene, RhBBX28, whose expression was associated with H2O2 rhythms. Silencing RhBBX28 accelerated flower senescence and promoted H2O2 accumulation at night in petals, while overexpression of RhBBX28 had the opposite effects. RhBBX28 influenced the expression of various genes related to respiratory metabolism, including the TCA cycle and glycolysis, and directly repressed the expression of SUCCINATE DEHYDROGENASE 1, which plays a central role in mitochondrial ROS (mtROS) homeostasis. We also found that PHYTOCHROME-INTERACTING FACTOR8 (RhPIF8) could activate RhBBX28 expression to control H2O2 levels in petals and thus flower senescence. Our results indicate that the circadian-controlled RhPIF8-RhBBX28 module is a critical player that controls flower senescence by governing mtROS homeostasis in rose.

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5'-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.