Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with decreased QoL in several domains, and these factors may identify patients who can benefit most from early multidisciplinary care, including financial counseling and additional psychosocial support.

PDF file, 138K, High-throughput profiling of survival following exposure to -radiation.

STEAM cocktail staining specifically identifies GBM cells.

PDF file, 20K, High-throughput profiling of lung cancer cell lines.

PDF file, 282K, Clonogenic survival following exposure to -radiation.

Purpose The quality of life (QoL) impact of multidisciplinary treatment for patients with nonfunctioning pituitary macroadenomas (NFPMA) is unclear. We sought to investigate associations between patient factors, clinical data, and patient-reported QoL in patients with NFPMA. Methods Patients with treated NFPMA and > 1 year of follow up after transsphenoidal surgery (TSS) and with no evidence of progressive disease were evaluated utilizing the following patient-reported outcome measures: RAND-36-Item Health Survey, Multidimensional Fatigue Inventory, Cognitive Failures Questionnaire. Results 229 eligible patients completed QoL questionnaires a median of 7.7 years after initial transsphenoidal surgery (TSS). 25% of participants received radiation therapy (RT) a median of 2.0 years (0.1–22.5) after initial TSS. Patients who received RT were younger (median age 46 v 58, p < 0.0001), had larger tumors (28 mm v 22 mm, p < 0.0001), were more likely to have visual symptoms (65% v 34%, p = 0.0002), and were more likely to have hypopituitarism (93% v 62%, p < 0.0001). Patients with hypopituitarism reported worse energy and fatigue and cognitive function (p < 0.03). Patients who received RT reported significantly worse general health, physical health, physical fatigue and cognitive functioning (p < 0.05). The largest QoL differences were in patients who experienced a financial stressor, independent of treatment type. Conclusion Hypopituitarism, radiation therapy after TSS, and financial stressors are associated with more impaired QoL in patients with NFPMA. Awareness of these factors can better guide use and timing of radiation therapy in addition to identifying patients who can benefit from multidisciplinary surveillance.

PDF file, 103K, NFE2L2 is frequently activated in human cancers.

PDF file, 42K, TP53 is frequently altered in lung SqCC lines and its activation correlates with radiation resistance.

Unsupervised hierarchical clustering analysis of patient and xenograft single cell qRT-PCR expression data.

PDF file, 86K, ssGSEA identifies gene sets that correlate with radiation resistance (left) and sensitivity (right). Top 15 gene sets are listed.

PDF file, 86K, ssGSEA identifies gene sets that correlate with radiation resistance (left) and sensitivity (right). Top 15 gene sets are listed.

PDF file, 42K, TP53 is frequently altered in lung SqCC lines and its activation correlates with radiation resistance.

Clinical trials generate the highest level of scientific evidence to advance clinical practice by identifying interventions that are safe and effective in human subjects. Interventions include diagnostic tests, medicines, therapies, and procedures. The phases of clinical trials, Phase 0 to Phase IV, highlight the stepwise evaluation of an intervention's safety and efficacy in a controlled environment. Phase 0 trials determine initial pharmacologic activity. Phase I trials establish safety and Phase II trials assess efficacy in addition to safety. Phase III trials compare interventions with current the standard of care. Phase IV trials implement post-marketing surveillance of long-term benefits and toxicities.

DNA-FISH analysis of non-EGFR-amplified GBM CTCs.

Clinical association of CTC frequency

PDF file, 109K, Clonogenic survival of lung SqCC after radiation (S1); High-throughput profiling of lung SqCC after radiation (S2); Mutations in NFE2L2 and KEAP1 in lung SqCC cell lines (S3); MSigDB Gene Sets from Fig S5 (S4); TP53 alterations, LOH, and mRNA levels in lung SqCC cell lines (S5).

AbstractPurpose: Perineural invasion (PNI) is associated with aggressive tumor behavior, recurrence, and metastasis, and can influence the administration of adjuvant treatment. However, standard histopathologic examination has limited sensitivity in detecting PNI and does not provide insights into its mechanistic underpinnings. Experimental Design: A multivariate Cox regression was performed to validate associations between PNI and survival in 2,029 patients across 12 cancer types. Differential expression and gene set enrichment analysis were used to learn PNI-associated programs. Machine learning models were applied to build a PNI gene expression classifier. A blinded re-review of hematoxylin and eosin (H&E) slides by a board-certified pathologist helped determine whether the classifier could improve occult histopathologic detection of PNI. Results: PNI associated with both poor overall survival [HR, 1.73; 95% confidence interval (CI), 1.27–2.36; P < 0.001] and disease-free survival (HR, 1.79; 95% CI, 1.38–2.32; P < 0.001). Neural-like, prosurvival, and invasive programs were enriched in PNI-positive tumors (Padj < 0.001). Although PNI-associated features likely reflect in part the increased presence of nerves, many differentially expressed genes mapped specifically to malignant cells from single-cell atlases. A PNI gene expression classifier was derived using random forest and evaluated as a tool for occult histopathologic detection. On a blinded H&E re-review of sections initially described as PNI negative, more specimens were reannotated as PNI positive in the high classifier score cohort compared with the low-scoring cohort (P = 0.03, Fisher exact test). Conclusions: This study provides salient biological insights regarding PNI and demonstrates a role for gene expression classifiers to augment detection of histopathologic features.