Evolution from an antecedent chronic myeloid malignancy does not impact survival outcomes in NPM1-mutated AML.

Nucleophosmin-1 (NPM1)-mutated AML is a molecularly defined subtype typically associated with favorable treatment response and prognosis; however, its prognostic significance in AML evolving from an antecedent chronic myeloid malignancy is unknown. This study's primary objective was to determine the impact of mutated NPM1 on the prognosis of AML evolving from an antecedent chronic myeloid malignancy. We conducted a retrospective chart review including patients with NPM1-mutated de novo and sAML. sAML was defined as those with a preceding chronic-phase myeloid malignancy before diagnosis of AML. Of 575 NPM1-mutated patients eligible for inclusion in our study, 51 (8.9%) patients were considered to have sAML. The median time from diagnosis of NPM1-mutated chronic myeloid malignancy to sAML evolution was 3.6 months (0.5-79.3 months). No significant differences in leukemia-free (2-year LKFS 52.0% vs. 51.2%, p = .9922) or overall survival (2-year OS 56.3% vs. 49.4%, p = .4246) were observed between patients with NPM1-mutated de novo versus sAML. Our study suggests that evolution from a preceding myeloid malignancy is not a significant predictor of poor prognosis in the setting of an NPM1 mutation. Our study demonstrated a short time to progression to sAML in most patients, which further supports the consideration of NPM1 as an AML-defining mutation.

Upfront allogeneic transplantation versus JAK inhibitor therapy for patients with myelofibrosis: a North American collaborative study.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF) and is recommended for patients with higher risk disease. However, there is a risk of early mortality, and optimal timing is unknown. JAK inhibitor (JAKi) therapy may offer durable improvement in symptoms, splenomegaly and quality of life. The aim of this multicentre, retrospective observational study was to compare outcomes of patients aged 70 years or below with MF in chronic phase who received upfront JAKi therapy vs. upfront HCT in dynamic international prognostic scoring system (DIPSS)-stratified categories. For the whole study cohort, median overall survival (OS) was longer for patients who received a JAKi vs. upfront HCT, 69 (95% CI 57-89) vs. 42 (95% CI 20-not reached, NR) months, respectively (p = 0.01). In patients with intermediate-2 and high-risk disease, median OS was 55 (95% CI 36-73) months with JAKi vs. 36 (95% CI 20-NR) months for HCT (p = 0.27). An upfront HCT strategy was associated with early mortality and difference in median OS was not observed in any risk group by 5 years of follow-up. Within the limitations of a retrospective observational study, we did not observe any benefit of a universal upfront HCT approach for higher-risk MF.

Management of Mixed Warm/Cold Autoimmune Hemolytic Anemia: A Case Report and Review of Current Literature.

Background: Mixed warm/cold autoimmune hemolytic anemia (AIHA) is a rare diagnostic entity with limited therapeutic options. Previous literature has described the diagnostic difficulty in this pathology and the limited response rates to corticosteroids. Furthermore, there is limited evidence regarding the use of rituximab in this condition. Methods: Alongside our case report, we conducted a scoping review of case reports/case series describing mixed AIHA, their treatment, and clinical outcomes since 2000. Inclusion criteria included a confirmed diagnosis of mixed AIHA (confirmed warm antibodies and cold agglutinins based on DAT). Case Summary/Results. We present a case of mixed AIHA in an 83-year-old female presenting with extensive, bilateral pulmonary embolisms and left renal vein thrombosis. The patient underwent extensive workup with no identifiable provoking etiology. Initial treatment involved prednisone therapy was transitioned to rituximab upon diagnosis of mixed AIHA. The patient demonstrated a mixed response with stable hemoglobin and transfusion independence; however, with persistently elevated hemolytic indices following completion of rituximab treatment. Our literature review identified 16 articles; two were excluded for unavailable clinical details. The most commonly associated conditions included autoimmune conditions (n = 5, 26%) and lymphoproliferative disorders (n = 3, 12%). The most common treatment involved corticosteroids; seven studies involved the use of rituximab. Conclusion: Mixed AIHA represents a complex diagnosis and optimal management is not well established. Consistent with our case, recent literature suggests a promising response to rituximab and a limited response to steroid treatment. Given the limited literature, additional studies are required to elucidate optimal management of this unique pathology.

Silver(I)-Catalyzed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres.

Bridged or caged polycyclic hydrocarbons have rigid structures that project substituents into precise regions of 3D space, making them attractive as linking groups in materials science and as building blocks for medicinal chemistry. The efficient synthesis of new or underexplored classes of such compounds is, therefore, an important objective. Herein, we describe the silver(I)-catalyzed rearrangement of 1,4-disubstituted cubanes to cuneanes, which are strained hydrocarbons that have not received much attention since they were first described in 1970. The synthesis of 2,6-disubstituted or 1,3-disubstituted cuneanes can be achieved with high regioselectivities, with the regioselectivity being dependent on the electronic character of the cubane substituents. A preliminary assessment of cuneanes as scaffolds for medicinal chemistry suggests cuneanes could serve as isosteric replacements of trans-1,4-disubstituted cyclohexanes and 1,3-disubstituted benzenes. An analogue of the anticancer drug sonidegib was synthesized, in which the 1,2,3-trisubstituted benzene was replaced with a 1,3-disubstituted cuneane.

Advancing Traditional Prostate-specific Antigen Kinetics in the Detection of Prostate Cancer: A Machine Learning Model.

BACKGROUND: Prostate-specific antigen (PSA) kinetics, defined as the change in PSA over time, may be of use as a predictor of prostate cancer. PSA kinetics can be assessed as the PSA velocity, which is traditionally evaluated dichotomously and classified as abnormal if greater than either 0.35 or 0.75 ng/ml/yr. Machine learning models may provide additional benefit in assessing risk using PSA kinetics instead of PSA velocity. OBJECTIVE: To improve the utility of PSA kinetics by constructing a generalizable, universal machine learning model. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the PLCO and PCPT trials and from a contemporary Australian cohort. PSA data were interpolated using a modified Gaussian process. A machine learning model based on a two-headed approach was designed, in which the multivariable input was fed into a one-dimensional ResNet18 model. OUTCOME MEASURES AND STATISTICAL ANALYSIS: The model performance was assessed compared to PSA levels and PSA velocity in terms of area under the receiver operator characteristic curve (AUC). RESULTS AND LIMITATIONS: A total of 10719 patients were included in the analysis. In tests on a validation set of the complete database to diagnose grade group ≥2, the AUC was 0.886 (95% confidence interval [CI] 0.870-0.902) for the machine learning model, compared to 0.807 (95% CI 0.796-0.819) for PSA and 0.627 (95% CI 0.607-0.648) for PSA velocity. CONCLUSIONS: Machine learning models can be used to augment the diagnostic utility of PSA kinetics in the diagnosis of prostate cancer. We demonstrated significant improvements in accuracy compared to the traditional approaches of PSA velocity and PSA thresholds. PATIENT SUMMARY: Prostate cancer diagnosis is limited by the diagnostic accuracy of the prostate-specific antigen (PSA) blood test. Advances in techniques such as machine learning algorithms can greatly improve the diagnostic accuracy of prostate cancer screening without additional costs or tests.

Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study.

There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). The association of frailty with overall survival (OS) and cumulative JAK inhibitor (JAKi) therapy failure was measured using hazard ratio (HR, 95% CI). In multivariable analysis, prefrail (HR 1·7, 1·1-2·5) and frail patients (HR 2·9, 1·6-5·5), those with higher DIPSS score (HR 2·5, 1·6-3·9) and transfusion dependency (HR 1·9, 1·3-2·9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2·5, 1·1-5·7), patients with higher DIPSS score (HR 1·7, 1·0-3·1) and transfusion dependence (HR 1·7, 1·1-2·7) had higher cumulative incidence of JAKi failure. Age, comorbidities, ECOG performance status, and MPN driver mutations did not impact outcomes. Thus, higher frailty scores are associated with worse OS and increased JAKi failure in MF, and is a superior indicator of fitness in comparison to age, comorbidities, and performance status.

Association of Factors Influencing Selection of Upfront Hematopoietic Cell Transplantation versus Nontransplantation Therapies in Myelofibrosis.

Despite the curative potential of allogeneic hematopoietic cell transplantation (HCT) for myelofibrosis (MF), a significant number of patients with MF do not undergo HCT. Factors influencing treatment preferences in these patients have not been well studied. This study was conducted to identify patient-, disease-, and donor-related factors influencing the decision regarding HCT in patients with MF. A secondary objective was to compare survival between patients who elected upfront HCT and those who opted for nontransplantation therapy. We conducted a retrospective chart review amongst patients meeting criteria for transplant indication, evaluating clinical characteristics, treatment preferences, and outcomes. Of the 183 study eligible patients age <70 years, 129 (70%) developed an HCT indication. Age >60 years was significantly associated with higher rates of HLA-typing refusal (13 of 72 versus 1 of 44; P = .02). Caucasian ethnicity was significantly associated with an increased rate of identifying well-matched donors compared with non-Caucasian ethnicity (75% versus 48%; P = .02). Of the 69 patients with well-matched donors, 34 (49%) preferred to not pursue upfront HCT despite an indication for transplantation. Patient preference for nontransplantation therapies was the most common reason for declining HCT. We did not find any difference in survival between patients pursuing upfront HCT and those opting for nontransplantation therapies, although more patients in the HCT arm were in remission at the last follow-up. Patients of Caucasian ethnicity were significantly more likely than non-Caucasian patients to identify a well-matched donor. Despite availability of a well-matched donor, a significant proportion of MF patients with an indication for transplantation do not pursue HCT. Patient age, donor type, and patient preference play major roles in the selection of upfront HCT. Although a survival difference was not observed between upfront HCT versus non-transplant therapy, more patients in the HCT arm were in remission at the last follow-up.

Internet and social media use in cancer patients: association with distress and perceived benefits and limitations.

OBJECTIVE: Cancer patients may turn to social media (SM) to cope with distress. We investigated associations between distress and internet/SM use for cancer information/support. METHODS: Adult patients at a Canadian cancer centre completed a cross-sectional survey on sociodemographics, health status, use of cancer online resources and distress (EQ5D-5L). Statistical models adjusted for relevant variables. RESULTS: Of 376 participants, median age was 52 years, time since diagnosis was 1.63 years, 272 (74%) had post-secondary education and 192 (51%) were female. For cancer information/support, 276 (73%) used internet and 147 (39%) SM. Dose response relationships were observed between distress and cancer-related internet (p = 0.02), and SM use (p < 0.001). Respondents using internet/SM for cancer information/support reported greater internet confidence (internet OR = 4.0, 95% CI: 1.9-8.3; SM OR = 4.18, 95%, CI: 1.9-11.3), higher education (internet OR = 3.0, 95% CI: 1.7-5.2; SM OR = 2.21, 95% CI: 1.2-4.1) and were more likely female (internet OR = 2.6, 95% CI 1.5-4.6; SM OR = 2.1, 95% CI: 1.3-3.4). For SM for cancer information/support, more used SM > 30 min daily (OR = 3.4; 95% CI: 2.1-5.7), and were distressed (OR = 1.67, 95% CI: 1.0-2.7). SM benefits were to learn about cancer (93; 25%), distract from cancer (85; 23%) and connect with survivors (81; 22%). SM limitations were privacy (161; 43%), quality (90; 24%) and personal applicability (85; 23%). Females used SM more to connect with survivors than males (p = 0.001). CONCLUSIONS: Greater internet confidence, higher education and being female were associated with cancer-related internet/SM use. Distressed cancer patients were also more likely to turn to SM. Privacy concerns may limit SM use for coping. Future research should determine how to optimize SM in caring for and connecting with patients and reduce cancer-related distress.

Subtypes of EGFR- and HER2-Mutant Metastatic NSCLC Influence Response to Immune Checkpoint Inhibitors.

INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICIs) is low among EGFR-mutated non-small-cell lung cancer (NSCLC), although prolonged responses have occasionally been reported. We investigated the association between mutation subtypes and ICI outcomes among HER2- and EGFR-mutated NSCLC. PATIENTS AND METHODS: This retrospective single-center study analyzed patients with EGFR- and HER2-mutated advanced NSCLC who received at least 1 cycle of ICI between 2013 and 2019. Patient characteristics, mutation subtype, and ICI outcomes. RESULTS: Among 48 patients with advanced NSCLC, 14 (29%) had HER2 mutations and 34 (71%) had EGFR mutations. EGFR mutations included 16 (47%) exon 19 deletion, 7 (21%) L858R, 5 (15%) uncommon, and 6 (18%) exon 20 insertion. Compared to EGFR-sensitizing mutations (ESMs), HER2 and EGFR exon 20 mutations were associated with a trend toward better response (respectively, ESM, HER2, and EGFR exon 20: 11%, 29%, and 50%; P = .07) and significantly better disease control rates (respectively, 18%, 57%, and 67%; P = .008). Compared to ESM, HER2 mutations (adjusted hazard ratio, 0.35; P = .02) and EGFR exon 20 mutations (adjusted hazard ratio, 0.37; P = .10 trend) were also associated with improved PFS. Programmed death ligand 1 (PD-L1) expression remained an independent predictor of PFS (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.76; P = .004). The 6-month PFS rates were 29% (HER2), 33% (EGFR exon 20), and 4% (ESM). ICIs were generally well tolerated in this population. Importantly, no immune-related toxicity was observed in 10 patients who received a tyrosine kinase inhibitor (TKI) as the immediate next line treatment after ICI. CONCLUSION: HER2 and EGFR exon 20 mutations derive greater benefit from ICIs with comparable PFS to wild-type historical second/third-line unselected cohorts. ICIs remain a treatment option for this genomic subgroup, given the absence of approved targeted therapies for these rare mutations.

Systemic Inflammatory Markers of Survival in Epidermal Growth Factor-Mutated Non-Small-Cell Lung Cancer: Single-Institution Analysis, Systematic Review, and Meta-analysis.

BACKGROUND: Systemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non-small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], lactate dehydrogenase [LDH], and lung immune prognostic index [LIPI]) were assessed as prognostic factors in NSCLC survival. PATIENTS AND METHODS: Retrospective survival analysis (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed. RESULTS: From 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, aHR = 1.53; LMR, aHR = 0.62; LDH, aHR = 2.04; and LIPI, aHR = 2.04. Similar patterns were found for PFS in early stage NLR (aHR = 1.96) and late stage NLR (aHR = 1.46), while for PFS, only late stage derived NLR (aHR = 1.34), LDH (aHR = 1.75), and LIPI (aHR = 1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH, and LIPI were all significantly associated with OS and PFS in the late stage. CONCLUSION: This primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions.

PSA-based machine learning model improves prostate cancer risk stratification in a screening population.

CONTEXT: The majority of prostate cancer diagnoses are facilitated by testing serum Prostate Specific Antigen (PSA) levels. Despite this, there are limitations to the diagnostic accuracy of PSA. Consideration of patient demographic factors and biochemical adjuncts to PSA may improve prostate cancer risk stratification. We aimed to develop a contemporary, accurate and cost-effective model based on objective measures to improve the accuracy of prostate cancer risk stratification. METHODS: Data were collated from a local institution and combined with patient data retrieved from the Prostate, Lung, Colorectal and Ovarian Cancer screening Trial (PLCO) database. Using a dataset of 4548 patients, a machine learning model was developed and trained using PSA, free-PSA, age and free-PSA to total PSA (FTR) ratio. RESULTS: The model was trained on a dataset involving 3638 patients and was then tested on a separate set of 910 patients. The model improved prediction for prostate cancer (AUC 0.72) compared to PSA alone (AUC 0.63), age (AUC 0.52), free-PSA (AUC 0.50) and FTR alone (AUC 0.65). When an operating point is chosen such that the sensitivity of the model is 80% the specificity of the model is 45.3%. The benefit in AUC secondary to the model was related to sample size, with AUC of 0.64 observed when a subset of the cohort was assessed. CONCLUSIONS: Development of a dense neural network model improved the diagnostic accuracy in screening for prostate cancer. These results demonstrate an additional utility of machine learning methods in prostate cancer risk stratification when using biochemical parameters.

Prior Coronary Artery Bypass Graft Surgery and Outcome After Percutaneous Coronary Intervention: An Observational Study From the Pan-London Percutaneous Coronary Intervention Registry.

Background Limited information exists regarding procedural success and clinical outcomes in patients with previous coronary artery bypass grafting (CABG) undergoing percutaneous coronary intervention (PCI). We sought to compare outcomes in patients undergoing PCI with or without CABG. Methods and Results This was an observational cohort study of 123 780 consecutive PCI procedures from the Pan-London (UK) PCI registry from 2005 to 2015. The primary end point was all-cause mortality at a median follow-up of 3.0 years (interquartile range, 1.2-4.6 years). A total of 12 641(10.2%) patients had a history of previous CABG, of whom 29.3% (n=3703) underwent PCI to native vessels and 70.7% (n=8938) to bypass grafts. There were significant differences in the demographic, clinical, and procedural characteristics of these groups. The risk of mortality during follow-up was significantly higher in patients with prior CABG (23.2%; P=0.0005) compared with patients with no prior CABG (12.1%) and was seen for patients who underwent either native vessel (20.1%) or bypass graft PCI (24.2%; P<0.0001). However, after adjustment for baseline characteristics, there was no significant difference in outcomes seen between the groups when PCI was performed in native vessels in patients with previous CABG (hazard ratio [HR],1.02; 95%CI, 0.77-1.34; P=0.89), but a significantly higher mortality was seen among patients with PCI to bypass grafts (HR,1.33; 95% CI, 1.03-1.71; P=0.026). This was seen after multivariate adjustment and propensity matching. Conclusions Patients with prior CABG were older with greater comorbidities and more complex procedural characteristics, but after adjustment for these differences, the clinical outcomes were similar to the patients undergoing PCI without prior CABG. In these patients, native-vessel PCI was associated with better outcomes compared with the treatment of vein grafts.

Salvage open radical prostatectomy for recurrent prostate cancer following MRI-guided transurethral ultrasound ablation (TULSA) of the prostate: feasibility and efficacy.

Introduction: MRI-guided transurethral ultrasound ablation (TULSA) is a novel modality for minimally invasive ablation in patients with localised prostate cancer (PCa). A multi-national Phase 1 (30 patients) and subsequent Phase 2 (115 patients) study showed TULSA to be feasible, safe and well tolerated. However, technical viability and safety of salvage prostatectomy for those who failed TULSA is unclear. Herein, we report the feasibility and morbidity of salvage radical prostatectomy (sRP) post-TULSA.Methods: Four patients with biopsy-proven residual cancer following TULSA underwent open retropubic sRP within 39 months of TULSA. Peri-and post-operative morbidity were reported. Detailed histopathologic assessment is reported.Results: Median follow-up was 43 months after sRP. Mean operating times, blood loss, and length of stay were 210 min, 866 ml, and 3.5 days, respectively. Intraoperative finding of some fibrotic reaction of endopelvic and Denonvilliers fascia was characteristic. There were no perioperative complications. Whole-mount pathology sections showed one pT2b and three pT3a, suggesting under-staging pre-TULSA. Location of disease was compatible with persistent cancer mostly in the untreated peripheral safety region. One man received an artificial urinary sphincter. All men experienced erectile dysfunction responsive to treatment. Two patients with positive surgical margins had PSA progression requiring salvage radiation, with one requiring long-term androgen deprivation therapy.Conclusions: RP is a viable and safe salvage option if TULSA fails. Technical difficulty and perioperative morbidity were negligible and attributable to minimal peri-prostatic reaction from TULSA.

Age differences in patterns and confidence of using internet and social media for cancer-care among cancer survivors.

OBJECTIVES: The internet and social media provide information and support to cancer survivors, and adolescent and young adults (AYA, age < 40 years), adults, and older (age 65+ years) cancer survivors may have different needs. We evaluated the impact of age on cancer-related internet and social media use and confidence in evaluating online information for cancer-care decision making. MATERIALS AND METHODS: Cancer survivors completed a convenience cross-sectional survey evaluating their cancer-related internet and social media use and their confidence in using these resources for decision making. Multivariable regression models evaluated the impact of age on usage patterns and confidence. RESULTS: Among 371 cancer survivors, 58 were older adults and 138 were AYA; 74% used the internet and 39% social media for cancer care; 48% felt confident in using online information for cancer-care decisions. Compared to adult survivors, there was a non-significant trend for older survivors to be less likely to use the internet for cancer-care information(aOR = 0.49, 95% CI[0.23-1.03], P = .06), while AYA were more likely to use social media for cancer-care (aOR = 1.79[1.08-2.99], P = .03). Although confidence at using online information for cancer-care decision making did not differ between age groups, increasing age had a non-significant trend towards reduced confidence (aOR = 0.99 per year [0.97-1.00], P = .09). Most commonly researched and desired online information were causes/risk factors/symptoms, treatment options, and prognosis/outcomes. CONCLUSIONS: Age may influence the use of internet and social media for cancer-care, and older cancer survivors may be less confident at evaluating online information for cancer-care decision making. Future research should explore other strategies at meeting the informational needs of older cancer survivors.

Computed tomography cardiac angiography for planning invasive angiographic procedures in patients with previous coronary artery bypass grafting.

AIMS: Invasive coronary angiography (ICA) is more complex and challenging in patients with previous coronary artery bypass grafts (CABG). Computed tomography coronary angiography (CTCA) may provide useful information prior to ICA to improve these procedures. This study aimed to see if upfront CTCA prior to coronary angiography can reduce contrast load, procedural duration, and procedural complications compared to ICA alone. METHODS AND RESULTS: This single-centre observational study included 835 patients with prior CABG undergoing invasive coronary angiography. One hundred and six patients underwent CTCA prior to ICA and were compared to 729 patients undergoing conventional coronary angiography alone (control group). No significant differences were seen between the two groups in patient demographics and procedural characteristics (number of bypass grafts), and interventional cardiologists' experience. The CTCA group had lower contrast volumes (171.3 vs 287.4 ml, p<0.0001), radiation doses (effective dose 4.6 vs 10.5 mSv, p<0.0001) and procedure times (fluorosocopy time 9.5 vs 12.6 min, p<0.0001) at the time of ICA compared to patients who did not have prior CTCA. Combined radiation doses (ICA+CTCA) versus ICA alone were similar (p=0.867) with significant reductions in overall contrast used seen in the CTCA group (p=0.005). Complete diagnostic studies were performed in all patients with prior CTCA (106 patients, 100%) compared to 543 patients (74.64%, p=<0.0001) without previous CTCA. As a result, 34 patients (4.4%) went on to have CTCA post angiography due to missed grafts. Of these, four needed further invasive angiographic assessment and subsequent coronary intervention following the CTCA scan. CONCLUSIONS: Prior CTCA improves graft detection at the time of coronary angiography and reduces the time necessary to localise graft ostium, the total procedure time, and volume of contrast media used.

Real-world health utility scores and toxicities to tyrosine kinase inhibitors in epidermal growth factor receptor mutated advanced non-small cell lung cancer.

BACKGROUND: As the treatment landscape in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFRm) continues to evolve, real-world health utility scores (HUS) become increasingly important for economic analyses. METHODS: In an observational cohort study, questionnaires were completed in EGFRm NSCLC outpatients, to include demographics, EQ-5D-based HUS and patient-reported toxicity and symptoms. Clinical and radiologic characteristics together with outcomes were extracted from chart review. The impact of health states, treatment type, toxicities, and clinical variables on HUS were evaluated. RESULTS: Between 2014 and 2018, a total of 260 patients completed 994 encounters. Across treatment groups, patients with disease progression had lower HUS compared to controlled disease (0.771 vs 0.803; P = .01). Patients predominantly received gefitinib as the first-line EGFR tyrosine kinase inhibitor (TKI) (n = 157, mean-HUS = 0.798), whereas osimertinib (n = 62, mean-HUS = 0.806) and chemotherapy (n = 38, mean-HUS = 0.721) were more likely used in subsequent treatment lines. In longitudinal analysis, TKIs retained high HUS (>0.78) compared to chemotherapy (HUS < 0.74). There were no differences between the frequency or severity of toxicity scores in patients receiving gefitinib compared to osimertinib; however, TKI therapy resulted in fewer toxicities than chemotherapy (P < .05), with the exception of worse diarrhea and skin rash (P < .001). Severity in toxicities inversely correlated with HUS (P < .001). Clinico-demographic factors significantly affecting HUS included age, Eastern Cooperative Oncology Group Performance Score (ECOG PS), disease state, treatment group, and metastatic burden. CONCLUSIONS: In a real-world EGFRm population, patients treated with gefitinib or osimertinib had similar HUS and toxicities, scores which were superior to chemotherapy. Health utility scores inversely correlated with patient-reported toxicity scores. In the era of targeted therapies, future economic analyses should incorporate real-world HUS.