A digital physician peer to automatically detect erroneous prescriptions in radiotherapy.

Appropriate dosing of radiation is crucial to patient safety in radiotherapy. Current quality assurance depends heavily on a physician peer-review process, which includes a review of the treatment plan's dose and fractionation. Potentially, physicians may not identify errors during this manual peer review due to time constraints and caseload. A novel prescription anomaly detection algorithm is designed that utilizes historical data from the past to predict anomalous cases. Such a tool can serve as an electronic peer who will assist the peer-review process providing extra safety to the patients. In our primary model, we create two dissimilarity metrics, R and F. R defining how far a new patient's prescription is from historical prescriptions. F represents how far away a patient's feature set is from that of the group with an identical or similar prescription. We flag prescription if either metric is greater than specific optimized cut-off values. We use thoracic cancer patients (n = 2504) as an example and extracted seven features. Our testing set f1 score is between 73%-94% for different treatment technique groups. We also independently validate our results by conducting a mock peer review with three thoracic specialists. Our model has a lower type II error rate compared to the manual peer-review by physicians.

Association of severe lymphopenia and disease progression in unresectable locally advanced non-small cell lung cancer treated with definitive chemoradiation and immunotherapy.

BACKGROUND: Definitive chemoradiation with consolidative immunotherapy offers the best chance for cure in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC). However, treatment-related lymphopenia (TRL) may negatively impact outcomes. METHODS: Patients definitively treated with chemoradiation and immunotherapy from 2015 to 2019 at a single tertiary academic center were identified. Severe lymphopenia was defined as <0.5 × 109 cells/L. Progression-free survival (PFS) was calculated by Kaplan Meier methodology. Univariate and multivariate Cox Proportional Hazard modeling was used to correlate clinical variables with disease outcome. Immune-related adverse events (irAEs) were assessed according to CTCAE version 5.0 criteria. RESULTS: Seventy-eight patients were included in the final cohort. The median age was 66 years (IQR: 58-73), 55 % were males, and 88 % had a KPS of >70. At baseline, 90 % (n = 70/78) of patients had a normal ALC and one patient had severe lymphopenia. After chemoradiation, the median ALC decreased from 1.52 × 109cells/L (IQR: 1.23-1.98) to 0.72 × 109cells/L (IQR: 0.52-0.94) (p < 0.001), 22 % (n = 17/78) of patients had a normal ALC, and 23 % (n = 18/78) of patients developed severe lymphopenia. Patients who initiated consolidative immunotherapy with severe lymphopenia had worse PFS than those who did not (median 217 days [IQR: 120-434] vs. 570 days [IQR: 401-NR], p < 0.001). On multivariate modeling, severe lymphopenia at the time of immunotherapy initiation remained an independent predictor of worse PFS (HR 4.90, p < 0.001). CONCLUSIONS: This is the first report to associate severe TRL with disease progression in patients with locally advanced NSCLC receiving consolidative immunotherapy. Factors associated with development of lymphopenia and strategies to mitigate lymphopenic effects should be considered.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

BACKGROUND: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear. METHODS: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020. FT was measured via the validated COmprehensive Score for financial Toxicity (COST) at the time of cancer diagnosis and at 6-month follow-up (6MFU). 6MFU data were compared with corresponding baseline data. A lower COST score indicates increased financial hardship. RESULTS: At the time of analysis, 215 agreed to participate. Subsequently, 112 patients completed 6MFU. On average, slightly more FT was observed at diagnosis compared with 6MFU (median COSTbase 25 v COST6M 27; P < .001); however, individual patients experienced large changes in FT. At 6MFU, 27.7% of patients had made financial sacrifices to pay for treatment but only 4.5% refused medical care based on cost. Median reported out-of-pocket (OOP) costs for the initial 6 months of cancer treatment was $2,496 (range, $0-25,900). Risk factors for FT at diagnosis were unique from risk factors at 6MFU. Actual OOP expenses were not correlated with FT; however, inability to predict upcoming treatment expenses resulted in higher FT at 6MFU. DISCUSSION: FT is a pervasive challenge during the initiation of lung cancer treatment. Few patients are willing to sacrifice medical care regardless of the cost. Risk factors for FT evolve, resulting in unique interventional targets throughout therapy.

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram.

BACKGROUND: Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined. PATIENTS AND METHODS: Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified. Univariable Cox proportional-hazards model was used to compare outcomes with demographic and clinical characteristics. A predictive nomogram model for selection of patients most likely to benefit from cRT was constructed. RESULTS: There were 91 patients identified with a total of 114 metastases treated. Median PFS from the start of cRT was 10.9 months (95% confidence interval [CI], 8.1-16.6), while the median survival time was 37.0 months (95% CI, 31.3-NR). On univariable modeling, patients with squamous histology (hazard ratio, 4.16; 95% CI, 1.99-8.71; P < .001) and those treated with non-stereotactic body radiotherapy hypofractionated therapy (hazard ratio, 5.43; 95% CI, 2.10-14.01; P < .001) had worse overall survival, while patients with targetable mutations (hazard ratio, 0.49; 95% CI, 0.25-0.98; P = .04) had a longer survival. Using a predictive nomogram model, patients with a solitary site of metastasis, targetable mutations, intracranial disease, and metachronous timing of oligometastases had a larger PFS benefit from cRT. CONCLUSION: cRT is associated with favorable outcomes in PFS and overall survival. These results may aid in patient counseling, selection for aggressive local therapy, and stratification in future prospective clinical trials.

Lung cancer and family-centered concerns.

BACKGROUND: Genetic and environmental interactions predispose certain groups to lung cancer, including families. Families or caregiving units experience the disease interdependently. We have previously evaluated the concerns and preferences of patients in addressing the lung cancer experience and cancer risks in their families. This qualitative study evaluates the concerns and preferences of family members and caregivers of patients with lung cancer in the lung cancer experience and familial cancer risks. METHODS: We held focus groups to discuss the format and timing of addressing these preferences and concerns. Qualitative data generated was analyzed using a grounded theory approach. RESULTS: Five focus groups totaling 19 participants were conducted. Seven themes were identified: (1) journey to lung cancer diagnosis has core dimensions for patient and family, (2) importance of communication between patients, families, and providers, (3) challenges for caregivers and family, (4) mixed perceptions of lung cancer causation among relatives, (5) discussion of cancer risk with relatives has complex dynamics, (6) impact of diagnosis on family health behaviors and screening, (7) role of genetic counseling. CONCLUSIONS: Family members of patients with lung cancer are interested in discussing risk factors, prevention, and diagnoses and also would like access to other supportive services do learn about and cope with some of the stresses and barriers they experience in the family lung cancer journey. The diagnosis represents a potential teachable moment with the opportunity to reduce the risk of LC development or improve early detection in LC patient's family members.

Practical data collection and extraction for big data applications in radiotherapy.

The capture of high-quality treatment data and outcomes is necessary in order to learn from our clinical experiences with big data analytics. In radiotherapy, there are several practical challenges to overcome. Practical aspects of data collection are discussed pointing to a need for a culture change in clinical practice to one that captures structured patient-related data in routine care in a prospective manner. Radiation dosimetry and the contoured anatomy must also be captured routinely to represent the best estimate of delivered radiation. The quality and integrity present in the data are critical which poses opportunities to introduce electronic validity checking to improve them. Similarly, data completeness and methods and technology to improve the efficiency and sufficiency of data capture can be introduced. In the manuscript, the types of clinical data are discussed including patient reports, images, biospecimens, treatments, and symptom management. With a data-driven culture, the realization of a learning health system is possible unlocking the potential of big data and its influence on clinical decision-making and hypothesis generation.

Modulation of the anti-cancer efficacy of microtubule-targeting agents by cellular growth conditions.

Mitotic spindle-disrupting agents target and disrupt microtubule dynamics. These agents include clinically important chemotherapies, including taxanes (paclitaxel (Taxol), docetaxel (Taxotere)) and vinca alkaloids (vincristine (Oncovin), vinblastine). Taxanes are a standard component of treatment for many malignancies, often in conjunction with other cytotoxic agents. However, the optimal sequencing of these treatments and whether efficacy may be influenced by in vitro cellular growth conditions remain incompletely investigated. Yet such preclinical investigations may guide clinical decision making. We therefore studied the effect of cell density on rapid killing by paclitaxel and vincristine. Breast, ovarian and prostate cancer cells were sensitive to rapid killing by either agent when grown at low density, but were markedly resistant when grown at high density, i.e. nearly confluent. The resistance of densely growing cells to rapid killing by these drugs translated to increased clonogenic survival. Pretreatment of densely growing cancer cells with cisplatin followed by paclitaxel, partially reversed the treatment resistance. Gene ontology associations from microarray analyses of cells grown at low and high density, suggested roles for membrane signal transduction and adhesion, but potentially also DNA damage repair and metabolism. Taken together, the treatment resistance at higher cell density may be associated with a lower proportion of active cycling in cells growing at high density as well as transduction of survival signals induced by increased cell-cell adhesion. Collectively these findings suggest mechanisms by which growth conditions may contribute to resistance to rapid killing by microtubule-disrupting drugs.