Real-World Treatment Patterns and Timeliness of Clinical Care Pathway for Non-Small Cell Lung Cancer Patients in Austria: The PRATER Retrospective Study.

This was a retrospective study of the profile and initial treatments of adults diagnosed with early-stage (ES) non-small cell lung cancer (NSCLC) during January 2018-December 2021 at 16 leading hospital institutions in Austria, excluding patients enrolled in clinical trials. In total, 319 patients were enrolled at a planned ~1:1:1 ratio across StI:II:III. Most tested biomarkers were programmed death ligand 1 (PD-L1; 58% expressing), Kirsten rat sarcoma virus (KRAS; 22% positive), and epidermal growth factor receptor (EGFR; 18% positive). Of 115/98/106 StI/II/III patients, 82%/85%/36% underwent surgery, followed by systemic therapy in 9%/45%/47% of those [mostly chemotherapy (ChT)]. Unresected treated StIII patients received ChT + radiotherapy [43%; followed by immune checkpoint inhibitors (ICIs) in 39% of those], ICI ± ChT (35%), and ChT-alone/radiotherapy-alone (22%). Treatment was initiated a median (interquartile range) of 24 (7-39) days after histological confirmation, and 55 (38-81) days after first medical visit. Based on exploratory analyses of all patients newly diagnosed with any stage NSCLC during 2018-2021 at 14 of the sites (N = 7846), 22%/10%/25%/43% had StI/II/III/IV. The total number was not significantly different between pre-COVID-19 (2018-2019) and study-specific COVID-19 (2020-2021) periods, while StI proportion increased (21% vs. 23%; p = 0.012). Small differences were noted in treatments. In conclusion, treatments were aligned with guideline recommendations at a time which preceded the era of ICIs and targeted therapies in the (neo)adjuvant setting.

Smoking-Associated Endotracheal Hair Growth: A Case Report on Tracheal Complications.

BACKGROUND A 52-year-old male patient presented with symptoms of chronic cough and persistent tracheal irritation 26 years after surgical closure of a tracheostoma, supported by an autologous auricular cartilage graft and cutaneous transplant. At the initial clinical presentation, the patient was an active smoker, with a cumulative dose of 31 pack years. CASE REPORT Bronchoscopy revealed endotracheal hair growth and local inflammation at the graft site. Initial anti-inflammatory, antimycotic, and antibacterial therapy was administered, followed by endoscopic structure remodeling. There were multiple recurrences with similar symptoms, showing isolated hair growth, without inflammation. Annual endoscopic restructuring sessions were indicated, and the patient experienced them as highly relieving. Recurrent hair growth was finally terminated by argon plasma laser-coagulation and after smoking cessation. We hypothesize that the onset of hair growth was triggered by the patient's cigarette smoking. CONCLUSIONS Endotracheal hair growth is a potential complication of autograft-supported tracheal restructuring. The initial administration of antimicrobial and anti-inflammatory medication, combined with endoscopic restructuring, could have contained the active inflammation; the application of argon plasma laser-coagulation finally stopped the hair growth. Smoking is associated with the upregulation of molecular signaling pathways in the respiratory epithelium, which can stimulate hair follicles, such as sonic hedgehog protein, WNT-1/ß-catenin, and epidermal growth factor receptor.

Screening for rheumatoid arthritis-associated interstitial lung disease-a Delphi-based consensus statement.

OBJECTIVE: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a major driver of premature mortality in patients with rheumatoid arthritis (RA). Detection of RA-ILD is crucial but requires awareness among the treating physicians. To date, however, there is no international recommendation concerning screening for ILD in RA patients. METHODS: After a systematic literature review, the modified Delphi technique in combination with the nominal group technique was used to provide a Delphi consensus statement elaborated by an expert panel of pneumonologists, rheumatologists, and a radiologist. Based on the available evidence, several clusters of questions were defined and discussed until consent was reached. RESULTS: A screening algorithm for ILD in patients with RA based on clinical signs, respiratory symptoms, and risk factors has been developed. Further, the recommendations address diagnostic tools for RA-ILD and the follow-up of RA patients qualifying for ILD screening.

Serum tumor markers for response prediction and monitoring of advanced lung cancer: A review focusing on immunotherapy and targeted therapies.

BACKGROUND: The value of serum tumor markers (STMs) in the current therapeutic landscape of lung cancer is unclear. OBJECTIVE: This scoping review gathered evidence of the predictive, prognostic, and monitoring value of STMs for patients with advanced lung cancer receiving immunotherapy (IT) or targeted therapy (TT). METHODS: Literature searches were conducted (cut-off: May 2022) using PubMed and Cochrane CENTRAL databases. Medical professionals advised on the search strategies. RESULTS: Study heterogeneity limited the evidence and inferences from the 36 publications reviewed. While increased baseline levels of serum cytokeratin 19 fragment antigen (CYFRA21-1) and carcinoembryonic antigen (CEA) may predict IT response, results for TT were less clear. For monitoring IT-treated patients, STM panels (including CYFRA21-1, CEA, and neuron-specific enolase) may surpass the power of single analyses to predict non-response. CYFRA21-1 measurement could aid in monitoring TT-treated patients, but the value of CEA in this context requires further investigation. Overall, baseline and dynamic changes in individual or combined STM levels have potential utility to predict treatment outcome and for monitoring of patients with advanced lung cancer. CONCLUSIONS: In advanced lung cancer, STMs provide additional relevant clinical information by predicting treatment outcome, but further standardization and validation is warranted.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Review of evidence supporting the use of nasal corticosteroid irrigation for chronic rhinosinusitis.

OBJECTIVE: To analyze published reports on the efficacy and safety of CSI in CRS and evaluate the clinical implications of current gaps in evidence. Corticosteroid irrigation (CSI) is commonly used for management of chronic rhinosinusitis (CRS) with nasal polyps; however, such use is not approved by the US Food and Drug Administration (FDA). DATA SOURCES: Publications were obtained through PubMed searches through January 2022. STUDY SELECTION: Searches were conducted using 2 terms: "chronic rhinosinusitis" or "nasal polyps" as the first term and "corticosteroid irrigation," "steroid nasal lavage," or "sinus rinse" as the second term. We reviewed relevant, peer-reviewed literature (19 original research [9 controlled, 10 uncontrolled trials], 7 reviews, and 1 meta-analysis) reporting safety and efficacy of CSI in patients with CRS. RESULTS: Studies were difficult to compare because they used a variety of solution volumes (60 mL to 125 mL per nostril), corticosteroid agents (budesonide, betamethasone, mometasone, or fluticasone), corticosteroid doses, preparation protocols (by compounding pharmacy or by patient), and administration (frequency, time of day, body positioning). It is difficult to determine which parameters might substantially influence clinical effects because studies were generally small, showed marginal benefits, and rarely assessed safety. To date, no studies evaluating CSI have shown statistically significant differences in a type-I error-controlled primary end point over any comparator, possibly owing to small sample sizes. CONCLUSION: Designing more robust clinical trials may help determine whether CSI is a valid treatment option. Until more evidence supporting CSI use exists, health care professionals should strongly consider choosing FDA-approved therapies for the treatment of CRS.

Incidental Pathogenic Fibrin-Associated Diffuse Large B-cell Lymphoma Found During Aorto-Biiliac Bypass.

Fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL) is in and of itself a rare entity and is a subset of the Epstein-Barr virus (EBV)-associated lymphoma. Due to its indolent course, FA-DLBCL is generally an incidental finding on histopathological examinations. We present the first reported case of FA-DLBCL found within a native aortic thrombus during an aorto-biiliac bypass. This is a 77-year-old male who was taken to the operative theater for open aorto-biiliac bypass secondary to aortooclusive disease resulting in intermittent claudication and gangrene of the right lower extremity digits. Intraoperatively, suspicious inflammatory changes were noted around the aorta. Pathological evaluation of the thrombus within the aorta noted cells of B-cell lineage with BCL2 and MYC positivity in addition to CD30 and EBV positivity. Postoperatively, the patient's course was complicated by acute tubular necrosis, uremia, dialysis dependence, intubation, and cardiac arrhythmias including cardiac arrest. He was able to recover from these complications, however, he ultimately chose to self-enroll in hospice care. An extensive literature review of over 128 mentions of FA-DLBCL noted a complete paucity of reported cases of FA-DLBCL within a native aorta. The patient's clinical presentation and histopathology without mass-forming lesions lead to the diagnosis of FA-DLBCL. FA-DLBCL is an extremely rare EBV+ lymphoproliferative disorder associated with chronic inflammation (DLBCL-CI). FA-DLBCL is a rare condition without defined uniform treatment. This article serves to highlight the first reported case of FA-DLBCL found within an abdominal aortic thrombus in a native aorta. Given the paucity of literature on this condition, postoperative treatment and long-term outcomes should be the focus of this condition.

Workers' compensation prescription medication patterns and associated outcomes.

BACKGROUND: Opioid use in the treatment of musculoskeletal injuries is a complex decision where benefits must be balanced with risk. Previous research has shown an association between higher opioid doses and adverse health effects. The study's objective was to investigate whether opioid prescriptions are associated with increased costs and deaths through an injury mechanism or as a direct result of the opioid prescription. METHODS: Data for 144,553 deidentified Ohio Bureau of Workers' Compensation claims from 2010 to 2014 with shoulder, knee, and low back injuries were obtained and followed until 2016. Each claim had associated prescription information. Injury claims were further classified using the allowed diagnoses by single or multiple body areas affected and injury severity ("simple" or "complex"). The outcome variables were medical and indemnity costs, lost days, MaxMED (maximum claim-prescribed daily morphine equivalent dose), and death status. Association between maximum opioid dose with deaths was determined by logistic regression analysis. RESULTS: Several outcome variables, including claim medical and indemnity costs, and the likelihood of claimant death, showed significant associations with the MaxMED. In the analysis of claim deaths, these associations held for all claim types (except complex), even after adjusting for age, gender, surgery, and lost time. CONCLUSION: The association between increasing opioid doses and deaths for low-severity diagnoses was disturbing given the lack of demonstrated efficacy of opioids for treatment of minor injuries. A focus on provider education, increased utilization of non-opioids, and early intervention for minor soft-tissue injuries could reduce claims costs, disability, and future deaths.

First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes.

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such, data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n = 70) or as monotherapy (n = 15). Maximum and mean standardized uptake value, total metabolic tumor volume (MTV), total lesion glycolysis, bone marrow-/and spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Median follow-up was 12 months (M; 95% confidence interval 10-14). Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p < 0.001). Median PFS/OS were significantly longer in patients with MTV ≤ 70 mL vs. >70 mL (PFS: 10 M (4-16) vs. 4 M (3-5), p = 0.001; OS: not reached vs. 10 M (5-15), p = 0.004). Disease control rate was 81% vs. 53% for MTV ≤/> 70 mL (p = 0.007). BLR ≤ 1.06 vs. >1.06 was associated with better outcomes (PFS: 8 M (4-13) vs. 4 M (3-6), p = 0.034; OS: 19 M (12-/) vs. 6 M (4-12), p = 0.005). In patients with MTV > 70 mL, concomitant BLR ≤ 1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI-treated NSCLC, with BLR allowing additional risk stratification.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy-A Retrospective Bi-Centric Cohort Study.

Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan-Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10-3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00-1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32-3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03-1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41-11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88-16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06-1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04-3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02-1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03-1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.

Serum Tumor Marker Dynamics as Predictive Biomarkers in NSCLC Chemo-Immunotherapy and Mono-Immunotherapy Maintenance: A Registry-Based Descriptive Study.

OBJECTIVE: To evaluate serum tumor markers (STM) as predictive biomarkers in advanced non-small cell lung cancer (NSCLC) treated with chemo-immunotherapy. METHODS: Patients having received platinum-based chemo-(CHT) and PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) combination therapy were retrospectively followed. Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis. The marker with the highest relative elevation was defined "leading STM", its change was assessed between CHT-ICI as well as mono-ICI maintenance initiation and the respective subsequent restaging. Corresponding computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST). For CHT-ICI combination and subsequent mono-ICI-maintenance therapy, leading STM and RECIST response were evaluated regarding progression-free (PFS) and overall survival (OS) in Kaplan-Meier analyses. RESULTS: Among 80 CHT-ICI patients (41% women, mean age 63 years), median PFS was 5 months (M;4,9), median OS was 15M (10,/). PFS was significantly (p=0.042) longer, when the leading STM had decreased at first restaging under CHT-ICI combination therapy (9M (5,12; n=41) vs 5M (3,6; n=16)). In the 54 (67.5%) patients who received subsequent mono-ICI maintenance therapy, STM decrease was similarly associated with significantly (p<0.001) longer PFS (16M (7,/; n=16) vs 3.5M (2,6; n=22)). Patients with radiologically stable or progressive disease and concomitant leading STM decrease had similar PFS in the CHT-ICI combination phase (4M (3,7; n=16) vs 4.5M (2,6; n=14)), but longer PFS in the mono-ICI maintenance setting (13M (7,16; n=10) vs 3M (2,4; n=17)). Median OS was not reached in most subgroups. CONCLUSION: Leading STM dynamics provide predictive biomarker information additional to radiological response evaluation patients receiving CHT-ICI combination therapy, especially in the mono-ICI maintenance setting.

Impact of PET/CT for Assessing Response to Immunotherapy-A Clinical Perspective.

Cancer immunotherapy using immune-checkpoint inhibitors (ICI) has revolutionized the therapeutic landscape of various malignancies like non-small-cell lung cancer or melanoma. Pre-therapy response prediction and assessment during ICI treatment is challenging due to the lack of reliable biomarkers and the possibility of atypical radiological response patterns. Positron emission tomography/computed tomography (PET/CT) enables the visualization and quantification of metabolic lesion activity additional to conventional CT imaging. Various biomarkers derived from PET/CT have been reported as predictors for response to ICI and may aid to overcome the challenges clinicians currently face in the management of ICI-treated patients. In this narrative review, experts in nuclear medicine, thoracic oncology, dermatooncology, hemato- and internal oncology, urological and head/neck tumors performed literature reviews in their respective field and a joint discussion on the use of PET/CT in the context of ICI treatment. The aims were to give a clinical overview on present standards and evidence, to identify current challenges and fields of research and to enable an outlook to future developments and their possible implications. Multiple promising studies concerning ICI response assessment or prediction using biomarkers derived from PET/CT alone or as composite biomarkers have been identified for various malignancies and disease stages. Of interest, additional major incentives in the field may evolve from novel tracers specifically targeting immune-checkpoint molecules which could allow not only response assessment and prognosis, but also visualization of histological tumor cell properties like programmed death-ligand (PD-L1) expression in vivo. Despite the broad range of existing literature on PET/CT-derived biomarkers in ICI therapy, implications for daily clinical practice remain elusive. High-quality prospective data are urgently warranted to determine whether patients benefit from the application of PET/CT in terms of prognosis. At the moment, the lack of such evidence as well as the absence of standardized imaging methods and biomarkers still precludes PET/CT imaging to be included in the relevant clinical practice guidelines.

Suspected food allergies in a septuagenarian with recurrent anaphylaxis.

Anaphylaxis is an acute, life-threatening reaction that can occur due to a variety of triggers. It is often associated with allergen exposure, such as food, venom, or medications; however, there are other less-common causes, and many patients are ultimately classified as idiopathic. In this report, we described a patient with recurrent reactions attributed to food exposure. Further evaluation revealed an alternative, less common diagnosis.

Consensus report from the Food Allergy Research & Education (FARE) 2019 Oral Immunotherapy for Food Allergy Summit.

Food allergy is a major health problem affecting 5% to 10% of the population in developed nations, including an estimated 32 million Americans. Despite the large number of patients suffering from food allergies, up until the end of January 2020, no treatment for food allergies had been approved by the US Food and Drug Administration. The only options were avoidance of food allergen triggers and acute management of allergic reactions. A considerable body of data exists supporting oral immunotherapy (OIT) as a promising, novel treatment option, including that for the now Food and Drug Administration-approved peanut OIT product Palforzia (Aimmune Therapeutics, Brisbane, Calif). However, data for long-term quality-of-life improvement with OIT varies, depending on the measures used for analysis. Like many therapies, OIT is not without potential harms, and burdens, and the evaluation of patient-specific risk-benefit ratio of food OIT produces challenges for clinicians and patients alike, with many unanswered questions. Food Allergy Research & Education organized the Oral Immunotherapy for Food Allergy Summit on November 6, 2019, modeled after the PRACTALL sessions between the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology to address these critical issues. Health care providers, patient representatives, researchers, regulators, and food allergy advocates came together to discuss OIT and identify areas of common ground as well as gaps in existing research and areas of uncertainty and disagreement. The purpose of this article was to summarize that discussion and facilitate collaboration among clinicians and patients to help them make better-informed decisions about offering and accepting OIT, respectively, as a therapeutic option.

Therapy Line and Associated Predictors of Response to PD-1/PD-L1-Inhibitor Monotherapy in Advanced Non-small-Cell Lung Cancer: A Retrospective Bi-centric Cohort Study.

BACKGROUND: Evidence on PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy for advanced non-small-cell lung cancer (NSCLC) is mainly based on clinical trials in first- or second-line settings. OBJECTIVE: We aimed to investigate response and prognostic factors with special regard to third- or later-line therapy. PATIENTS AND METHODS: We retrospectively analyzed all patients who had received ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab for advanced NSCLC. Computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST, version 1.1). Kaplan-Meier analyses were conducted to calculate progression-free (PFS) and overall (OS) survival; the impact of influencing variables was evaluated using uni- and multivariate Cox-regression analyses. RESULTS: Among 153 patients (59% men, mean age 66 years), median PFS was 4 months [mo; 95% confidence interval (95% CI) 3-5], OS was 13 mo (10-17), and objective response rate (ORR) was 22%. Therapy line ≥ 3 was associated with significantly inferior PFS (p = 0.003) and OS (p = 0.001). In first-line therapy PFS, OS, and ORR were 7 mo (3-11), 17 mo [9-not evaluable (n.e.)], and 36%; in second-line 4 mo (3-7), 18 mo (13-n.e.) and 19%, and in ≥ third-line 2 mo (1-3), 9 mo (4-12), and 13%. PFS was significantly influenced by PD-L1 expression in first-line therapy (p = 0.006). In ≥ third-line patients, Eastern Cooperative Oncology Group (ECOG) performance status significantly affected PFS and OS (both p < 0.001). CONCLUSIONS: Third- or later-line single-agent anti-PD-1/PD-L1 therapy is less efficacious as compared to first- and second-line treatment. In that setting, ECOG performance status predominates known predictors like PD-L1 expression or presence of an alteration in EGFR or ALK.

Penicillin allergy skin testing as an antibiotic stewardship intervention reduces alternative antibiotic exposures in hematopoietic stem cell transplant recipients.

BACKGROUND: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-ß-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. METHODS: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. RESULTS: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported ß-lactam allergy (136/844 [16%] pre- and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients pre- and post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). CONCLUSION: Penicillin allergy skin testing adjudicates reported ß-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study.

OBJECTIVES: To evaluate serum tumor markers (STM) as biomarkers for treatment monitoring and prognosis in advanced non-small cell lung cancer (NSCLC) treated with single-agent PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis, initially elevated markers were used for follow-up. Leading STM change between ICI initiation and first subsequent restaging as well as corresponding computed tomography evaluations according to response evaluation criteria in solid tumors (RECIST) were retrospectively analyzed regarding progression-free (PFS) and overall survival (OS). In uni- and multivariate stepwise Cox-regression analyses, STM and RECIST response were analyzed for their impact on PFS and OS together with other known prognostic patient and tumor characteristics. RESULTS: Among 84 patients (61% men, mean age 68 years), median PFS was significantly (p < 0.001) longer, when STM decreased (11 M (7,19) N = 37) than in case of increases (<2-fold: 6 M (3,8) N = 31; ≥2-fold: 2 M (1,2) N = 16). Patients with initial STM decrease had longer (p < 0.001) median OS (not reached) than with STM increase (<2-fold: 14 M (12,26); ≥2-fold: 4 M (3,7)). Patients with stable or progressive disease by RECIST and concomitant STM decrease had longer (p < 0.001) PFS and OS (8 M (4,14) and 18 M (10,n.e.) N = 24) than upon STM increase (PFS: 2 M (2,4); OS: 10 M (6,13) N = 42). Significant impact on PFS was shown for STM response (p < 0.001), RECIST response (p = 0.003) and PD-L1 status (p = 0.003). For OS, STM response (p < 0.001), presence of cerebral metastases (p = 0.036) and therapy line ≥3 (p = 0.001) were identified. CONCLUSION: Decreasing leading STM at first restaging predict longer PFS and OS and identify patients with favorable outcomes among initial radiological non-responders in ICI treated NSCLC patients.

Baseline Absolute Lymphocyte Count and ECOG Performance Score Are Associated with Survival in Advanced Non-Small Cell Lung Cancer Undergoing PD-1/PD-L1 Blockade.

Immune-checkpoint blockade in front-line or second-line treatment improves survival in advanced non-small cell lung cancer (aNSCLC) when compared with chemotherapy alone. However, easily applicable predictive parameters are necessary to guide immune-checkpoint inhibition in clinical practice. In this retrospective bi-centric analysis, we investigated the impact of baseline patient and tumor characteristics on clinical outcome in aNSCLC patients treated with programmed cell death protein 1(PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors. Between May 2015 and January 2018, 142 unselected consecutive NSCLC patients received PD-1/PD-L1 inhibitors during the course of disease. In multivariate analysis, we identified the Eastern Cooperative Oncology Group (ECOG) performance status (ECOG > 1 versus ECOG ≤ 1, HR: 3.23, 95%CI: 1.58-6.60, P = 0.001), baseline absolute lymphocyte count (ALC; high: >0.93 × 109/L versus low: ≤ 0.93 × 109/L, HR: 0.38, 95%CI: 0.23-0.62, P < 0.001), prior or concomitant anti-vascular endothelial growth factor (VEGF) targeting therapy (yes versus no, HR: 2.18, 95%CI: 1.15-4.14, P = 0.017) and TNM stage (IV versus III, HR: 4.18, 95%CI: 1.01-17.36, P = 0.049) as the most relevant parameters for survival. Neither antibiotic exposure (antibiotic-positive versus antibiotic-negative, HR: 0.90, 95%CI: 0.56-1.45, P = 0.675), nor PD-L1 expression on tumor cells (≥1% versus <1%, HR: 0.68, 95%CI: 0.41-1.13, P = 0.140) was associated with survival. Baseline ECOG performance status and ALC were associated with survival in aNSCLC patients treated with PD-1/PD-L1 inhibitors and assessment of these parameters could be suitable in clinical practice.