Cost-Effectiveness of Tumor Genomic Profiling to Guide First-Line Targeted Therapy Selection in Patients With Metastatic Lung Adenocarcinoma.

OBJECTIVES: A cost-effectiveness analysis comparing comprehensive genomic profiling (CGP) of 10 oncogenes, targeted gene panel testing (TGPT) of 4 oncogenes, and no tumor profiling over the lifetime for patients with metastatic lung adenocarcinoma from the Centers for Medicare and Medicaid Services' perspective was conducted. METHODS: A decision analytic model used 10 000 hypothetical Medicare beneficiaries with metastatic lung adenocarcinoma to simulate outcomes associated with CGP (ALK, BRAF, EGFR, ERBB2, MET, NTRK1, NTRK2, NTRK3, RET, ROS1), TGPT (ALK, BRAF, EGFR, ROS1), and no tumor profiling (no genes tested). First-line targeted cancer-directed therapies were assigned if actionable gene variants were detected; otherwise, nontargeted cancer-directed therapies were assigned. Model inputs were derived from randomized trials (progression-free survival, adverse events), the Veterans Health Administration and Medicare (drug costs), published studies (nondrug cancer-related management costs, health state utilities), and published databases (actionable variant prevalences). Costs (2019 US$) and quality-adjusted life-years (QALYs) were discounted at 3% per year. Probabilistic sensitivity analyses used 1000 Monte Carlo simulations. RESULTS: No tumor profiling was the least costly/person ($122 613 vs $184 063 for TGPT and $188 425 for CGP) and yielded the least QALYs/person (0.53 vs 0.73 for TGPT and 0.74 for CGP). The costs per QALY gained and corresponding 95% confidence interval were $310 735 ($278 323-$347 952) for TGPT vs no tumor profiling and $445 545 ($322 297-$572 084) for CGP vs TGPT. All probabilistic sensitivity analysis simulations for both comparisons surpassed the willingness-to-pay threshold ($150 000 per QALY gained). CONCLUSION: Compared with no tumor profiling in patients with metastatic lung adenocarcinoma, tumor profiling (TGPT, CGP) improves quality-adjusted survival but is not cost-effective.

Evaluation of delays during diagnosis and management of lung cancer in India: A prospective observational study.

OBJECTIVE: The majority of lung cancers are diagnosed at an advanced stage; the reasons for which are variable and unclear. METHODS: Lung cancer patients were evaluated prospectively to quantify various timelines and establish reasons for delays. Timelines were defined as time intervals between symptom onset, first physician visit, first specialist visit, date of diagnosis and treatment. RESULTS: A total 410 patients were included, majority having advanced disease. The median period for a first visit to a physician was 30 days (interquartile range [IQR] 20-90), 50 days (IQR 20-110) for referral to our centre, 23 days (IQR 14-33) to reach diagnosis, and 24 days (IQR 14.5-34) to initiate treatment. Administration ofanti-tuberculosis treatment further delayed referral to specialist centre. Treatment delays were related to performance status, disease stage and treatment type. On multivariate analysis, education and histology affected diagnosis delay and treatment delay. Treatment delay was less in those who received targeted therapy compared to chemotherapy. Various time delays did not affect the overall survival. CONCLUSION: Poor education status and inappropriate anti-tubercular treatment were primary factors associated with longer diagnostic delays. Creating disease awareness and high clinical suspicion are essential to overcome these lacunae in lung cancer care.

Light guiding, bending, and splitting via local modification of interfaces of a photonic waveguide.

A general approach to the surface control of the localization, guiding, and redirecting of volume-mode light in photonic waveguides via tailoring their interfaces (surfaces) is proposed. The approach is demonstrated for dielectric rod-type photonic crystal slabs, whose regular and defect parts are distinguished by whether the nanocylinders are covered by metal caps. Thus, the rod-array part of the structure is not changed, while the local modifications are only applied to the interfaces. The basic functionalities, i.e., localized volume wave guiding, bending, and splitting are achievable. Selective dual-mode operation is possible due to the co-existence of a defect mode and a chainlike mode in one structure.

Liquid-crystal tunable color filters based on aluminum metasurfaces.

Designing color pixels using plasmonic nanostructures and metasurfaces has become a luring area of research in recent years. Here, we experimentally demonstrated the voltage tunability of a dynamic plasmonic color filter by using an aluminum grating integrated with the nematic liquid crystal (LC). Along with a typical substrate coated with rubbed polyimide film, the aluminum grating itself serves as a molecular alignment layer to form a twisted LC cell. This hybrid structure allows electrically controlled transmission color by applying the voltage. A significant spectral tunability of such a device has been demonstrated by applying the small voltage from 0 to 4 Vrms.

Current and recent clinical trials for perioperative systemic therapy for muscle invasive bladder cancer: a systematic review.

BACKGROUND: Although Muscle Invasive Bladder Cancer (MIBC) is increasing in incidence, treatment has largely remained limited to radical cystectomy with or without cisplatin-based neoadjuvant and/or adjuvant chemotherapy. We reviewed the current and recent clinical trials evaluating perioperative chemotherapy, targeted therapy, and novel therapeutic regimens for MIBC patients undergoing radical cystectomy. METHODS: An overview of perioperative MIBC management was conducted initially using MEDLINE. The Clinical Trials Registry and MEDLINE were further searched specifically for perioperative MIBC chemotherapy, targeted therapy, and other novel therapeutic approaches. Trials involving non-perioperative management, operative management other than radical cystectomy, multiple tumors, or purely superficial or metastatic disease were excluded from selection. These criteria were not specifically fulfilled for mTOR inhibitor and immune therapy trials. Only phase III chemotherapy and phase II targeted therapy trials found in the Clinical Trials Registry were selected. MEDLINE searches of specific treatments were limited to January 2009 to January 2014 whereas the Clinical Trials Registry search had no timeline. Systematic MEDLINE searches had no phase restrictions. Trials known by the authors to fulfill search criteria but were not found via searches were also selected. RESULTS: Twenty-five trials were selected from the Clinical Trials Registry including 7 phase III chemotherapy trials, 11 Phase II targeted therapy trials, 3 immune therapy trials, 1 mammalian target of rapamycin (mTOR) inhibitor trial, and 3 gene and vaccine therapy trials. Nine trials have been completed and 5 have been terminated early or withdrawn. Nine trials have data available when individually searched using MEDLINE and/or Google. Systematic searches of MEDLINE separately found 12 trials in the past 5 years. Two phase III chemotherapy trials were selected based on knowledge by the authors. No phase III trials of targeted therapy have been registered or published. CONCLUSIONS: New trials are currently being conducted that may revolutionize MIBC treatment preceding or following cystectomy. Head-to-head phase III trials of perioperative chemotherapy and further phase II and phase III trials of targeted therapy and other therapeutic approaches are necessary before the current cisplatin-based perioperative chemotherapy paradigm is altered.

EBER-Negative, Double-Hit High-Grade B-Cell Lymphoma Responding to Methotrexate Discontinuation.

Background: First classified in 2016, high-grade B-cell lymphoma (HGBCL) is a lymphoid neoplasm that is typically seen as an aggressive lymphoproliferative disorder (LPD). In most patients with HGBCL, various oncogene rearrangements present with advanced clinical features, such as central nervous system involvement. Patients with underlying autoimmune and rheumatologic conditions, such as rheumatoid arthritis, are at higher risk for developing LPDs, including highly aggressive subtypes of non-Hodgkin lymphomas such as HGBCL. Case Presentation: We present a case of stage IV double-hit HGBCL with the presence of MYC and BCL6 gene rearrangements in an older veteran with rheumatoid arthritis treated with methotrexate. An excellent sustained response was observed for the patient's disease within 4 weeks of methotrexate discontinuation. To our knowledge, this is the first reported response to methotrexate discontinuation for a patient with HGBCL. Conclusions: Reducing immunosuppression should be considered in all patients with LPDs associated with autoimmune conditions or immunosuppressive medications, regardless of additional multiagent systemic therapy administration.

Prevalence of highly actionable mutations among Indian patients with advanced non-small cell lung cancer: A systematic review and meta-analysis.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality in India. To clarify rates of actionable mutations, and thereby identify opportunities to improve the delivery of best available care for a large volume of patients, a comprehensive review of available data is warranted. METHODS: Studies that reported prevalence of any actionable gene variant among adult Indian patients with advanced NSCLC were selected from three databases (PubMed, EMBASE, and Cochrane Library). Ranges in actionable variant prevalence were reported. Meta-analysis of proportions was completed among studies specifically evaluating mutational prevalence within ALK or EGFR. Sensitivity analyses were undertaken among populations sharing high heterogeneity. RESULTS: Twenty-six studies were selected. Ranges in actionable mutational prevalence among NSCLC patients were as follows: ALK: 4.1-21.4%, BRAF: 1.5-3.5%, EGFR: 11.9-51.8%, HER2: 0-1.5%, KRAS: 4.5-6.4%, NTRK: 0-.7%, and ROS-1: 3.5-4.1%. Following sensitivity analysis, pooled ALK mutational prevalence rates were 8.3% (95% CIs: 6.6-10.4%) and 4.01% (95% CIs: 2.3-7.0) for adenocarcinoma and NSCLC patients, respectively. Pooled EGFR mutational prevalence rates were 28.7% (95% CIs: 23.5-34.6%) and 24.2% (95% CIs: 19.9-29.1%) for adenocarcinoma and NSCLC patients, respectively. CONCLUSIONS: Nearly 40% of Indian patients with advanced adenocarcinoma and 30% with NSCLC share an actionable mutation in ALK or EGFR. Approximately one-half of adenocarcinoma patients have an actionable variant. Efforts should be directed toward efficiently identifying candidates for targeted agents and delivering such treatments.

Real-world Experience With Neurotrophic Tyrosine Receptor Kinase Fusion-positive Tumors and Tropomyosin Receptor Kinase Inhibitors in Veterans.

PURPOSE: Neurotrophic tyrosine receptor kinase 1-3 (NTRK1-3) gene fusions are found in a broad range of tumor types. Clinical trials demonstrated high response rates to tropomyosin receptor kinase (TRK) inhibitors in NTRK fusion-positive cancers, but few reports have described real-world experience with these targeted agents. We evaluated the prevalence of NTRK fusions and the outcomes with TRK inhibitor therapy in a real-world population of patients in the Veterans Health Administration. METHODS: Patients with NTRK fusions or rearrangements were identified from the Veterans Affairs (VA) National Precision Oncology Program (NPOP), and patients who were prescribed TRK inhibitors were identified from the Corporate Data Warehouse. Baseline data and clinical outcomes were obtained by retrospective review of medical records. RESULTS: A total of 33 patients with NTRK fusions or rearrangements were identified, including 25 patients comprising 0.12% of all patients with solid tumors sequenced through VA NPOP. Twelve patients with NTRK fusions or rearrangements were treated with TRK inhibitors, none of whom had objective responses. Eight patients experienced toxicities leading to drug interruption, dose reduction, or discontinuation. CONCLUSION: In this retrospective study of VA patients, NTRK fusions and rearrangements were less common than in previous studies, and objective responses to TRK inhibitors were not observed. Real-world experience with TRK inhibitors differs markedly from clinical trial findings, possibly due to differences in patient demographics, tumor types, and sequencing methods. Our findings highlight the need to study TRK inhibitors in the real-world setting and in populations underrepresented in clinical trials.

Health outcomes and healthcare resource utilization among Veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy.

BACKGROUND: Until recently, multi-agent chemotherapy (CT) was the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Clinical trials have confirmed benefits in overall survival (OS) and progression-free survival with immunotherapy (IO) compared to CT. This study compares real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC. MATERIALS AND METHODS: This retrospective study included patients in the United States Department of Veterans Affairs healthcare system diagnosed with stage IV NSCLC during 2012-2017 and receiving IO or CT in the 2L. Patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) were compared between treatment groups. Logistic regression was used to examine differences in baseline characteristics between groups, and inverse probability weighting multivariable Cox proportional hazard regression was used to analyze OS. RESULTS: Among 4,609 Veterans who received first-line (1L) therapy for stage IV NSCLC, 96% received 1L CT alone. A total of 1,630 (35%) were administered 2L systemic therapy, with 695 (43%) receiving IO and 935 (57%) receiving CT. Median age was 67 years (IO group) and 65 years (CT group); most patients were male (97%) and white (76-77%). Patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). 2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75-0.94). IO was more frequently prescribed during the study period (p < 0.0001). No difference in rate of hospitalizations was observed between the two groups. CONCLUSIONS: Overall, the proportion of advanced NSCLC patients receiving 2L systemic therapy is low. Among patients treated with 1L CT and without IO contraindications, 2L IO should be considered, as this supports potential benefit of IO for advanced NSCLC. The increasing availability and indications for IO will likely increase the administration of 2L therapy to NSCLC patients.

Molecular-Guided Off-Label Targeted Therapy in a Large-Scale Precision Oncology Program.

PURPOSE: Increasing utilization of comprehensive genomic profiling (CGP) and a growing number of targeted agents (TAs) have led to substantial improvements in outcomes among patients with cancer with actionable mutations. We sought to evaluate real-world experience with off-label TAs among Veterans who underwent CGP. METHODS: The National Precision Oncology Program database and VA Corporate Data Warehouse were queried to identify patients who underwent CGP between February 2019 and December 2021 and were prescribed 1 of 73 TAs for malignancy. OncoKB annotations were used to select patients who received off-label TAs based upon CGP results. Chart abstraction was performed to review response, toxicities, and time to progression. RESULTS: Of 18,686 patients who underwent CGP, 2,107 (11%) were prescribed a TA and 169 (0.9%) were prescribed a total of 183 regimens containing off-label TAs for variants in 31 genes. Median age was 68 years and 83% had prior systemic therapy, with 28% receiving three or more lines. Frequency of off-label TA prescriptions was highest for patients undergoing CGP for thyroid (8.6%) and breast (7.6%) cancers. Most patients harbored alterations in BRCA1/BRCA2/ATM (22.5%), ERBB2 (19.5%), and BRAF (19.5%). Among the 160 regimens prescribed > 4 weeks, 43 (27%) led to response. Median progression-free survival and overall survival were 5.3 (4.2-6.5) and 9.7 (7.5-11.9) months, respectively. Patients with OncoKB level 2/3A/3B annotations had longer median progression-free survival (5.8 [4.5-7] months v 3.7 [1.6-7.7] months; hazard ratio, 0.45; 95% CI, 0.24 to 0.82; P = .01) compared with those receiving level 4 treatments. CONCLUSION: Although administration of off-label TAs is infrequent after CGP, more than one quarter of treatment regimens led to response. TAs associated with level 4 annotations lead to worse outcomes than TAs bearing higher levels of evidence.

A Case Series of Rare Immune-Mediated Adverse Reactions at the New Mexico Veterans Affairs Medical Center.

Background: Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several solid tumors. The use of ICIs is expected to rise as a growing number of indications are approved for their use by the US Food and Drug Administration and with the increasing number of patients with cancer. Unfortunately, ICIs are associated with the development of immune-mediated adverse reactions (IMARs). About 5% to 10% of patients developing severe toxicities requiring treatment postponement or discontinuation. IMARs can affect any organ, but most frequently the skin and endocrine glands are involved. Case Presentation: We present a case series of IMARs observed at the New Mexico Veterans Affairs Medical Center. First, we present a case of grade 4 myocarditis in an 84-year-old man receiving chemoimmunotherapy for lung adenocarcinoma to demonstrate the rapid progression of this rare condition. Second, we present a case of uveitis in a 70-year-old man with superficial bladder cancer undergoing treatment with pembrolizumab. Finally, we present a case of a 63-year-old man with pleuritis and organizing pneumonia secondary to dual ICI treatment (nivolumab and ipilimumab) for mesothelioma. A discussion regarding the epidemiology of these IMARs, expected course, and optimal management follows each rare toxicity described. Conclusions: Though these toxicities are uncommon, they serve as a reminder to clinicians across specialties that IMARs can drive the acute deterioration of any organ, and consideration of toxicities secondary to ICIs should be considered for any atypical presentation of unclear etiology.

Mutational profiles of head and neck squamous cell carcinomas based upon human papillomavirus status in the Veterans Affairs National Precision Oncology Program.

BACKGROUND: Patients with advanced head and neck squamous cell carcinoma (HNSCC) associated with human papillomavirus (HPV) demonstrate favorable clinical outcomes compared to patients bearing HPV-negative HNSCC. We sought to characterize the association between HPV status and mutational profiles among patients served by the Veterans Health Administration (VHA). METHODS: We performed a retrospective analysis of all Veterans with primary HNSCC tumors who underwent next-generation sequencing (NGS) through the VHA's National Precision Oncology Program between July 2016 and February 2019. HPV status was determined by clinical pathology reports of p16 immunohistochemical staining; gene variant pathogenicity was classified using OncoKB, an online precision oncology knowledge database, and mutation frequencies were compared using Fisher's exact test. RESULTS: A total of 79 patients met inclusion criteria, of which 48 (60.8%) had p16-positive tumors. Patients with p16-negative HNSCC were more likely to have mutations in TP53 (p < 0.0001), and a trend towards increased mutation frequency was observed within NOTCH1 (p = 0.032) and within the composite CDK/Rb pathway (p = 0.065). Mutations in KRAS, NRAS, HRAS, and FBXW7 were exclusively identified within p16-positive tumors, and a trend towards increased frequency was observed within the PI3K pathway (p = 0.051). No difference in overall mutational burden was observed between the two groups. CONCLUSIONS: In accordance with the previous studies, no clear molecular basis for improved prognosis among patients harboring HPV-positive disease has been elucidated. Though no targeted therapies are approved based upon HPV-status, current efforts to trial PI3K inhibitors and mTOR inhibitors across patients with HPV-positive disease bear genomic rationale based upon the current findings.

The Accuracy of Physical Examination to Diagnose Anemia Among Patients Five Years or Older: A Systematic Review.

Anemia remains a significant public health challenge, disproportionately impacting lower-income patients residing in areas of lesser healthcare resources. We sought to evaluate the accuracy of physical exam techniques to diagnose anemia among patients 5 years of age or older. A systematic review of 5 databases (MEDLINE via OVID, EMBASE, Scopus, Global Health and Global Health Archives, and WHO Global Index Medicus) was conducted. Studies that (1) compared non-invasive physical exam techniques with anemia diagnoses using standard laboratory measurements and (2) solely assessed or separately reported the diagnostic accuracy of physical exam techniques for patients 5 years or older were considered for inclusion. The diagnostic accuracies of individual and combinatorial physical exam techniques todiagnose anemia were documented. This systematic review was registered with PROSPERO. The systemic literature search yielded 6,457 unique studies after removal of duplicates. Fourteen studies were ultimately selected for inclusion. Eight studies solely assessed pregnant females, 4 solely assessed hospitalized patients, and 2 evaluated the general population. The diagnostic accuracy ranged widely for pallor assessments of conjunctivae (sensitivity: 19-97%, specificity: 65-100%), nailbed (sensitivity: 41-65%, specificity: 58-93%), and palms (sensitivity: 33-91%, specificity: 54-93%). Examining 9 or more sites leads to higher sensitivity (73.8-82.9%) and specificity (76.0-90.9%). No individual examination technique is superior to others for diagnosing anemia. Combinatorial approachs are associated with more acceptable accuracy measures, but improvements need to be balanced with time available for examination. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01543-z.

Lung cancer in Asian Indian females: Identification of disease-specific characteristics and outcome measures over a 12-year period.

Aim: Globally, the incidence of lung cancer amongst women appears to be increasing. We aimed to compare the socio-epidemiological and clinical characteristics of lung cancer amongst men and women from a large cohort at a tertiary care hospital in Northern India. Methods: Records of patients diagnosed with lung cancer between January 2008 and March 2020 were reviewed. Baseline epidemiological data, clinical characteristics, histologic profiles, treatment administered, and survival were compared between males and females. Results: A total of 2054 male and 438 female patients were included in analysis. Compared to males, female patients were younger [median age, 56 vs. 60 years, P < 0.001)], less likely to be working, less educated beyond secondary level and less likely to be smokers (29.1% vs. 84.9%, P < 0.0001). No difference in baseline performance status was observed. Females were more frequently diagnosed with adenocarcinoma (54.2% vs. 30.2%, P = <0.0001), stage IV disease (70.8% vs. 63%, P = 0.001), and had higher rate of EGFR mutation (37.2% vs. 21.5%, P < 0.0001). There was no difference in the proportion of females receiving cancer-specific therapy. Multivariate Cox proportional hazards model revealed higher progression-free survival [median 9.17 vs. 7.23 months; P = 0.007] and overall survival [median 13.80 vs. 9.10 months respectively, P = 0.001] amongst females compared to males. Conclusion: Amongst a large cohort of lung cancer, females demonstrated several distinct and characteristic demographics as well as disease-related features, especially better survival outcomes.

Homologous Recombination Repair Gene Variants and Outcomes Among Patients With Prostate Cancer Treated With Poly (ADP-ribose) Polymerase Inhibitors.

PURPOSE: Poly ADP-ribose polymerase inhibitors (PARPi) are used for patients with advanced prostate cancer bearing alterations in homologous recombination repair (HRR) genes. We sought to characterize HRR gene variants and describe real-world outcomes for patients on PARPi. METHODS: The US Department of Veterans Affairs' National Precision Oncology Program's database was reviewed to identify patients who underwent somatic DNA sequencing and were prescribed a PARPi before May 15, 2020. Somatic and germline variants within HRR genes were reported, and pathogenicity was reviewed via OncoKB. In patients treated with PARPi for > 4 weeks, the rate of those achieving a 30% decrease in prostate-specific antigen (PSA30) and composite progression-free survival (PFS) were compared between patients bearing pathogenic variants of BRCA2 and patients without these variants using Mann-Whitney and log-rank tests, respectively. RESULTS: Forty-eight patients bearing 67 total HRR gene variants were prescribed PARPi for prostate cancer. Twenty-one patients (43.8%) were found to have at least one pathogenic HRR gene variant. Eight (16.6%) were referred to genetic counseling, and five (10.4%) were ultimately confirmed with germline variants. The median PFS was 4.0 months, and PSA30 was 25.6% (11 of 43) for all 43 evaluable patients. Patients with pathogenic BRCA2 variants (n = 13) had higher PSA30 (69.2% v 4.0%; P < .001) and longer PFS (7.2 v 2.8 months; P = .0291) than those without. CONCLUSION: In a real-world setting, heavily pretreated patients with prostate cancer and pathogenic BRCA2 variants have a significant PSA response rate and a PFS > 7 months with PARPi. This work emphasizes the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions and highlights the need for provider education and other decision support tools.

Prognostic factors for treatment response and survival outcomes after first-line management of Stage 4 non-small cell lung cancer: A real-world Indian perspective.

Background: Indian data on treatment outcomes and survival in advanced non-small cell lung cancer (NSCLC) remain scarce. Materials and Methods: A retrospective review of 537 advanced NSCLC patients treated at a tertiary care facility in North India from January 2008 to March 2018 was done to assess treatment response and survival in terms of objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Median age of enrolled patients was 60 years (range: 26-89 years). The majority were males (78.2%) and smokers (66.5%). Adenocarcinoma (51.2%) was the most common pathological type. Most patients had good performance status (PS) (the Eastern Cooperative Oncology Group [ECOG] 0 or 1 in 55.7%) and received conventional chemotherapy (86.6%). ORR and DCR after 3-4 months of first-line treatment were 55.2% and 71.75%, respectively (n = 223). Never smokers had better ORR as well as DCR compared to chronic smokers whereas treatment with tyrosine kinase inhibitors achieved significantly better ORR, and patients with good PS had better DCR compared to those with poor PS. Median PFS (n = 455) was 7.0 months (95% confidence interval [CI]: 3.7-14.0) and median OS was 11.7 months (95% CI: 5.5-29.9 months). Good PS and nonsmoking status were independent predictors of better PFS on multivariate analysis. For OS, good PS, nonsmoking behavior, and treatment with epidermal growth factor receptor inhibitors were independent predictors. Conclusion: In advanced NSCLC, never-smokers, and patients with good baseline ECOG have favorable treatment and survival outcomes. Treatment with targeted therapy results in better ORR and OS but did not affect PFS.

Precision treatment for metastatic non-small cell lung cancer: A conceptual overview.

Recent developments in precision oncology have increased the complexity of diagnostic and therapeutic decisions. Here, we broadly review the field of precision oncology and discuss common mutational drivers in non-small cell lung cancer (NSCLC) that directly relate to the diagnosis, evaluation, and treatment of patients with metastatic disease.

Sequential Targeted Treatment for a Geriatric Patient with Acute Myeloid Leukemia with Concurrent FLT3-TKD and IDH1 Mutations.

Targeting and monitoring several acute myeloid leukemia mutations sequentially provides insights into optimal treatment plans.

A comprehensive comparison between young and older-age non-small cell lung cancer patients at a public referral centre in Delhi, India.

PURPOSE: Given the increasing number of non-small cell lung cancer (NSCLC) patients in India, a comparative analysis between patients under 40 years and those of older age at a major public referral centre would provide insight into the phenotypic patterns of this group. METHODS: NSCLC patients who were accessioned within the lung cancer clinic database of the Pulmonary Medicine Department at the all India institute of medical sciences - Delhi between 2008 and 2019 were reviewed. Patients 40 years or younger and 60 years or older were selected and categorised as young and older patients, respectively. Baseline clinical characteristics, histologic profiles, treatments administered and survival outcomes were compared between both groups. RESULTS: Following the database review, 154 young and 1,058 older patients were selected for inclusion. Clinically, young patients were more often female (26.0% versus 14.5%, p < 0.001), retained a more independent performance status (64.1% versus 45.5%; p < 0.001) and never smoked (63.7 % versus 18.8%, p < 0.001). Regarding disease profiles, young patients were more frequently diagnosed with adenocarcinoma (p < 0.001) and 12 young patients had adenoid cystic carcinoma. Rates of stage IV disease at presentation were higher among young patients (78.0% versus 63.0%, p < 0.001). Regarding treatment, no differences in systemic therapies administered or survival were identified. CONCLUSION: In India, young NSCLC patients are frequently non-smokers and diagnosed with advanced disease. Despite better performance status, young patients do not share better outcomes. Efforts should be directed towards optimising intensive treatment for young patients.

Barriers to Prescribing Targeted Therapies for Patients With NSCLC With Highly Actionable Gene Variants in the Veterans Affairs National Precision Oncology Program.

PURPOSE: Next-generation sequencing (NGS) gene panels are frequently completed for patients with advanced non-small-cell lung cancer (NSCLC). Patients with highly actionable gene variants have improved outcomes and reduced toxicities with the use of corresponding targeted agents. We sought to identify barriers to targeted agent use within the Veterans Health Affairs' National Precision Oncology Program (NPOP). METHODS: A retrospective evaluation of patients with NSCLC who underwent NGS multigene panels through NPOP between July 2015 and February 2019 was conducted. Patients who were assigned level 1 or 2A evidence for oncogenic gene variants by an artificial intelligence offering (IBM Watson for Genomics [WfG]) and NPOP staff were selected. Antineoplastic drug prescriptions and provider notes were reviewed. Reasons for withholding targeted treatments were categorized. RESULTS: Of 1,749 patients with NSCLC who successfully underwent NGS gene panel testing, 112 (6.4%) patients were assigned level 1 and/or 2A evidence for available targeted treatments by WfG and NPOP staff. All highly actionable gene variants were within ALK, BRAF, EGFR, ERBB2, MET, RET, and ROS1. Of these, 36 (32.1%) patients were not prescribed targeted agents. The three most common reasons were (1) patient did not carry a diagnosis of metastatic disease (33.3%), (2) treating provider did not comment on the NGS results (25.0%), and (3) provider felt that patient could not tolerate therapy (19.4%). No patients were denied access to level 1 or 2A targeted drugs because of rejection of a nonformulary drug request. CONCLUSION: A substantial minority of patients with NSCLC bearing highly actionable gene variants are not prescribed targeted agents. Further provider- and pathologist-directed educational efforts and implementation of health informatics systems to provide real-time decision support for test ordering and interpretation are needed.