Outcomes of Minimally Invasive Thyroid Surgery - A Systematic Review and Meta-Analysis.

Purpose: Conventional thyroidectomy has been standard of care for surgical thyroid nodules. For cosmetic purposes different minimally invasive and remote-access surgical approaches have been developed. At present, the most used robotic and endoscopic thyroidectomy approaches are minimally invasive video assisted thyroidectomy (MIVAT), bilateral axillo-breast approach endoscopic thyroidectomy (BABA-ET), bilateral axillo-breast approach robotic thyroidectomy (BABA-RT), transoral endoscopic thyroidectomy via vestibular approach (TOETVA), retro-auricular endoscopic thyroidectomy (RA-ET), retro-auricular robotic thyroidectomy (RA-RT), gasless transaxillary endoscopic thyroidectomy (GTET) and robot assisted transaxillary surgery (RATS). The purpose of this systematic review was to evaluate whether minimally invasive techniques are not inferior to conventional thyroidectomy. Methods: A systematic search was conducted in Medline, Embase and Web of Science to identify original articles investigating operating time, length of hospital stay and complication rates regarding recurrent laryngeal nerve injury and hypocalcemia, of the different minimally invasive techniques. Results: Out of 569 identified manuscripts, 98 studies met the inclusion criteria. Most studies were retrospective in nature. The results of the systematic review varied. Thirty-one articles were included in the meta-analysis. Compared to the standard of care, the meta-analysis showed no significant difference in length of hospital stay, except a longer stay after BABA-ET. No significant difference in incidence of recurrent laryngeal nerve injury and hypocalcemia was seen. As expected, operating time was significantly longer for most minimally invasive techniques. Conclusions: This is the first comprehensive systematic review and meta-analysis comparing the eight most commonly used minimally invasive thyroid surgeries individually with standard of care. It can be concluded that minimally invasive techniques do not lead to more complications or longer hospital stay and are, therefore, not inferior to conventional thyroidectomy.

Improved survival with enasidenib versus standard of care in relapsed/refractory acute myeloid leukemia associated with IDH2 mutations using historical data and propensity score matching analysis.

BACKGROUND: The present study evaluated the relative survival benefits associated with enasidenib and current standard of care (SoC) therapies for patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and an isocitrate dehydrogenase 2 (IDH2) mutation who are ineligible for hematopoietic stem cell transplantation (HSCT). METHODS: Propensity score matching (PSM) analysis compared survival outcomes observed with enasidenib 100 mg daily in the phase I/II AG221-C-001 trial and SoC outcomes obtained from a real-world chart review of patients in France. RESULTS: Before matching, enasidenib (n = 195) was associated with numerically improved overall survival (OS) relative to SoC (n = 80; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.61-1.11). After matching and adjusting for covariates (n = 78 per group), mortality risk was significantly lower with enasidenib than with SoC (HR, 0.67; 95% CI, 0.47-0.97). The median OS was 9.26 months for enasidenib (95% CI, 7.72-13.24) and 4.76 months for SoC (95% CI, 3.81-8.21). Results remained robust across all sensitivity analyses conducted. CONCLUSIONS: PSM analyses indicate that enasidenib significantly prolongs survival relative to SoC among patients with R/R AML and an IDH2 mutation who are ineligible for HSCT. Future prospective studies are needed to validate these findings using other data sources and to assess the comparative efficacy of enasidenib for other treatment outcomes.

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer.

BACKGROUND: The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. METHODS: We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. RESULTS: Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70-0.79] and [HR = 0.82; 95% CI, 0.75-0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. CONCLUSION: ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

Do standards of care and early outcomes of periprosthetic fractures change during the COVID-19 pandemic? A multicentre study.

BACKGROUND: Periprosthetic fractures (PPFs) are a growing matter for orthopaedic surgeons, and patients with PPFs may represent a frail target in the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of this study is to investigate whether hospital reorganisations during the most severe phase of the SARS-CoV-2 pandemic affected standards of care and early outcomes of patients treated for PPFs in Northern Italy. MATERIALS AND METHODS: Data were retrieved from a multicentre retrospective orthopaedics and traumatology database, including 14 hospitals. The following parameters were studied: demographics, results of nasopharyngeal swabs, prevalence of coronavirus disease 2019 (COVID-19), comorbidities, general health status (EQ-5D-5L Score), frailty (Clinical Frailty Scale, CFS), pain (visual analogue scale, VAS), anaesthesiologic risk (American Society of Anaesthesiology Score, ASA Score), classification (unified classification system, UCS), type of operation and anaesthesia, in-hospital and early complications (Clavien-Dindo Classification, CDC), and length of stay (LOS). Data were analysed by means of descriptive statistics. Out of 1390 patients treated for any reason, 38 PPFs were included. RESULTS: Median age was 81 years (range 70-96 years). Twenty-three patients (60.5%) were swabbed on admission, and two of them (5.3%) tested positive; in three patients (7.9%), the diagnosis of COVID-19 was established on a clinical and radiological basis. Two more patients tested positive post-operatively, and one of them died due to COVID-19. Thirty-three patients (86.8%) presented a proximal femoral PPF. Median ASA Score was 3 (range, 1-4), median VAS score on admission was 3 (range, 0-6), median CFS was 4 (range, 1-8), median EQ-5D-5L Score was 3 in each one of the categories (range, 1-5). Twenty-three patients (60.5%) developed post-operative complications, and median CDC grade was 3 (range, 1-5). The median LOS was 12.8 days (range 2-36 days), and 21 patients (55.3%) were discharged home. CONCLUSIONS: The incidence of PPFs did not seem to change during the lockdown. Patients were mainly elderly with comorbidities, and complications were frequently recorded post-operatively. Despite the difficult period for the healthcare system, hospitals were able to provide effective conventional surgical treatments for PPFs, which were not negatively influenced by the reorganisation. Continued efforts are required to optimise the treatment of these frail patients in the period of the pandemic, minimising the risk of contamination, and to limit the incidence of PPFs in the future. LEVEL OF EVIDENCE: IV.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

OBJECTIVES: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital. DESIGN: We applied our hospital-adopted guidelines, which defined severe and major chronic conditions as those associated with a greater than 50% likelihood of 1- and 5-year mortality, respectively, to a critically ill patient population. We investigated mortality for the same intervals. SETTING: An urban safety-net hospital ICU. PATIENTS: All adults hospitalized during April of 2015 and April 2019 identified through a clinical database search. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 365 admitted patients, 15.89% had one or more defined chronic life-limiting conditions. These patients had higher 1-year (46.55% vs 13.68%; p < 0.01) and 5-year (50.00% vs 17.22%; p < 0.01) mortality rates than those without underlying conditions. Irrespective of classification of disease severity, patients with metastatic cancer, congestive heart failure, end-stage renal disease, and neurodegenerative disease had greater than 50% 1-year mortality, whereas patients with chronic lung disease and cirrhosis had less than 50% 1-year mortality. Observed 1- and 5-year mortality for cirrhosis, heart failure, and metastatic cancer were more variable when subdivided into severe and major categories. CONCLUSIONS: Patients with major and severe chronic medical conditions overall had 46.55% and 50.00% mortality at 1 and 5 years, respectively. However, mortality varied between conditions. Our findings appear to support a crisis standards protocol which focuses on acute illness severity and only considers underlying conditions carrying a greater than 50% predicted likelihood of 1-year mortality. Modifications to the chronic lung disease, congestive heart failure, and cirrhosis criteria should be refined if they are to be included in future models.

Cost-effectiveness of single-use negative-pressure therapy compared with standard care for prevention of reconstruction failure in prepectoral breast reconstruction.

BACKGROUND: Single-use negative-pressure wound therapy (sNPWT) has been reported to reduce the incidence of reconstruction failure in prepectoral breast reconstruction compared with standard surgical dressings. The aim of this economic evaluation was to investigate the cost-effectiveness of sNPWT compared with standard care for the prevention of reconstruction failure in prepectoral breast reconstruction in the UK. METHOD: A decision tree model was used to estimate the expected cost and effectiveness per patient. Effectiveness was measured both by the number of reconstruction failures avoided and the gain in quality-adjusted life-years (QALYs). The baseline incidence of reconstruction failure (8.6 per cent) was taken from a recently published study of 2655 mastectomies in the UK. The effectiveness of sNPWT used results from a clinical study comparing sNPWT with standard dressings. Previously published utility weights were applied. The cost of reconstruction failure was estimated from detailed resource data from patients with reconstruction failure, applying National Health Service reference costs. One-way, probabilistic, scenario and threshold analyses were conducted. RESULTS: The undiscounted cost per patient associated with reconstruction failure was estimated to be £23 628 (£22 431 discounted). The use of sNPWT was associated with an expected cost saving of £1706 per patient, an expected increase in QALYs of 0.0187 and an expected 0.0834 reconstruction failures avoided. Cost-effectiveness acceptability analysis demonstrated that, at a threshold of £20 000 per QALY, 99.94 per cent of the simulations showed sNPWT to be more cost-effective than standard care. CONCLUSION: Among patients undergoing immediate prepectoral breast reconstruction, the use of sNPWT is more cost-effective than standard dressings.

Anti-PD1/PD-L1 monotherapy vs standard of care in patients with recurrent or metastatic head and neck squamous cell carcinoma: A meta-analysis of randomized controlled trials.

BACKGROUND: In recent years, a number of clinical trials for antibody drugs targeting programmed cell death protein 1 (PD1)/programmed cell death 1 ligand 1 (PD-L1) have been carried out on recurrent or metastatic head and neck squamous cell carcinoma (R/M SCCHN) and reported promising prospects. To further evaluate and understand the effects and risk of anti-PD1/PD-L1 monotherapy vs standard of care (SoC) in R/M SCCHN, we conducted this meta-analysis of published randomized controlled trials. METHOD: The potential eligible trials were searched from Cochrane library and Pubmed and Embase databases. Randomized controlled trials evaluating the effects and risk of anti-PD1/PD-L1 monotherapy vs SoC in platinum refractory R/M SCCHN were selected. The outcomes, including objective response rate, disease control rate, progression-free survival, overall survival, and treatment-related adverse events, were extracted and pooled. RESULTS: 1345 patients with R/M SCCHN from three randomized controlled trials were enrolled in this analysis. Compared with SoC, anti-PD1/PD-L1 monotherapy could provide statistically significant overall survival benefit, hazard ratio (95% confidence interval ) = 0.79 [0.70-0.90]. However, we observed no significant difference between 2 treatments in progression-free survival (hazard ratio [95% confidence interval] = 0.96 [0.85-1.09]). Furthermore, anti-PD1/PD-L1 monotherapy caused less treatment-related adverse events than standard of care. CONCLUSION: Anti-PD1/PD-L1 monotherapy could indeed reduce the risk of death in R/M SCCHN patients, and provide higher safety vs SoC. Expression level of PD-L1 may be a useful biomarker for selecting patients with better response to anti-PD1/PD-L1 monotherapy.

Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study.

PURPOSE: BEACON CRC evaluated encorafenib plus cetuximab with or without binimetinib versus investigators' choice of irinotecan or FOLFIRI plus cetuximab in patients with BRAFV600E-mutant metastatic colorectal cancer (mCRC), after progression on 1-2 prior regimens. In the previously reported primary analysis, encorafenib, binimetinib plus cetuximab (ENCO/BINI/CETUX; triplet) and encorafenib plus cetuximab (ENCO/CETUX; doublet) regimens improved overall survival (OS) and objective response rate (ORR; by blinded central review) versus standard of care. The purpose of this analysis was to report updated efficacy and safety data. METHODS: In this open-label, phase III trial, 665 patients with BRAF V600E-mutant mCRC were randomly assigned 1:1:1 to receive triplet, doublet, or control. Primary end points were OS and independently reviewed ORR comparing triplet to control. OS for doublet versus control was a key secondary end point. Updated analyses include 6 months of additional follow-up and ORR for all randomized patients. RESULTS: Patients received triplet (n = 224), doublet (n = 220), or control (n = 221). Median OS was 9.3 months (95% CI, 8.2 to 10.8) for triplet and 5.9 months (95% CI, 5.1 to 7.1) for control (hazard ratio [HR], 0.60 [95% CI, 0.47 to 0.75]). Median OS for doublet was 9.3 months (95% CI, 8.0 to 11.3) (HR v control, 0.61 [95% CI, 0.48 to 0.77]). Confirmed ORR was 26.8% (95% CI, 21.1% to 33.1%) for triplet, 19.5% (95% CI, 14.5% to 25.4%) for doublet, and 1.8% (95% CI, 0.5% to 4.6%) for control. Adverse events were consistent with the prior primary analysis, with grade ≥ 3 adverse events in 65.8%, 57.4%, and 64.2% for triplet, doublet, and control, respectively. CONCLUSION: In the BEACON CRC study, encorafenib plus cetuximab improved OS, ORR, and progression-free survival in previously treated patients in the metastatic setting compared with standard chemotherapy. Based on the primary and updated analyses, encorafenib plus cetuximab is a new standard care regimen for previously treated patients with BRAF V600E mCRC.

Oligorecurrent prostate cancer treated with metastases-directed therapy or standard of care: a single-center experience.

BACKGROUND: The optimal treatment for oligorecurrent prostate cancer (PCa) is a matter of debate. We aimed to assess oncologic outcomes of patients treated with metastasis-directed therapy (MDT) vs. androgen deprivation therapy (ADT) for oligorecurrent PCa. METHODS: We analyzed data from patients with oligorecurrent PCa treated with ADT (n = 121), salvage lymph node dissection (sLND) (n = 191) or external beam RT (EBRT) (n = 178). Radiological recurrence (RAR) was defined as a positive positron emission tomography imaging after MDT or ADT. Second-line systemic therapies (SST) were defined as any systemic therapy administered for progression. Oncologic outcomes were evaluated separately for patients with node-only or bone metastases. Kaplan-Meier method was used to assess time to RAR, SST, and cancer-specific mortality (CSM). Predictors of RAR, SST, and castration-resistant PCa (CRPCa) were assessed with Cox regression analyses. RESULTS: Overall, 74 (22.6%), 63 (19.2%), and 191 (58.2%) patients were treated with ADT, EBRT, and sLND for lymph node-only recurrence. Both sLND (HR 0.56, 95% CI 0.33-0.94) and EBRT (HR 0.46, 95% CI 0.25-0.85) were associated with better RAR than ADT. Similarly, sLND (HR 0.25, 95% CI 0.13-0.50) and EBRT (HR 0.41, 95% CI 0.19-0.87) were associated with longer SST, as compared with ADT. Similar results were found for CRPCa status. Oncologic outcomes were similar between sLND and EBRT. MDT was not associated with survival benefit in patients with bone metastases as compared with ADT. CONCLUSIONS: sLND and EBRT were associated with better RAR, SST, and CRPCa-free survival as compared with ADT in patients with oligometastatic PCa nodal recurrence. No difference in survival outcomes was observed between sLND and EBRT. MDT was not associated with survival benefit in patients with bone metastases, as compared with ADT.

Patient-Reported Outcome Measures Used in Routine Care Predict for Survival at Disease Progression in Patients With Advanced Lung Cancer.

BACKGROUND: Patient-reported outcome (PRO) measures have been increasingly implemented in routine care to aid in clinical decision-making. However, the prognostic value of PRO measures as a tool for decision making is not easily interpreted by clinicians. Our aims were to explore the prognostic value of PRO measures at disease progression and the changes in PRO measures between treatment start (baseline) and disease progression. PATIENTS AND METHODS: Since 2014, patients with lung cancer have completed an electronic version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 and LC-13 before every outpatient visit at the Department of Oncology, Hospital Unit West, Jutland, Denmark. The patients' responses were used in routine care. Patients receiving palliative antineoplastic treatment were eligible for analysis if the questionnaire had been completed at the initiation of first-line treatment and at disease progression. The prognostic value of the scores was evaluated using a Cox proportional hazard model. A P value < .01 was considered statistically significant. RESULTS: A total of 94 screened patients were included. At disease progression, survival could be predicted from the absolute score of the global health scale, 3 functional scales (physical, role, emotional), and 7 symptom scales (fatigue, pain, dyspnea, hemoptysis, lung cancer dyspnea, chest pain). In addition, changes in hemoptysis, dysphagia, dyspnea, and chest pain predicted for survival at progression. CONCLUSION: PRO measures used in routine care can provide clinicians with relevant prognostic information about patients with lung cancer at disease progression. These results show the potential value of PRO measures when used in clinical decision-making.

Lung Cancer Survival in Patients With Autoimmune Disease.

Importance: Patients with autoimmune disease and lung cancer pose a multidisciplinary treatment challenge, particularly with the advent of immunotherapy. However, the association between autoimmune disease and lung cancer survival is largely unknown. Objective: To determine the association between autoimmune disease and lung cancer survival. Design, Setting, and Participants: Retrospective cohort study between 2003 and 2019 at a single academic medical center (Northwestern University). A query of the Northwestern Medicine Enterprise Data Warehouse identified 349 patients with lung cancer and several autoimmune diseases. Types of lung cancers included small cell, adenocarcinoma, squamous cell carcinoma, non-small cell not otherwise specified, and large cell carcinoma. Autoimmune diseases included rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, myositis, and Sjögren syndrome. Inclusion criteria were biopsy-confirmed lung cancer, autoimmune diagnosis confirmed by a rheumatologist, and death or an encounter listed in the electronic medical record within 2 years of study end. A control group of patients with biopsy-proven lung cancer but without autoimmune disease was identified. Data analysis was conducted from March to July 2020. Exposure: Presence of autoimmune disease. Main Outcomes and Measures: Overall survival and progression-free survival in patients with autoimmune disease. The hypothesis was that patients with autoimmune disease would have worse progression-free survival and overall survival compared with patients in the control group. Results: Of the original 349 patients, 177 met inclusion criteria. Mean (SD) age at lung cancer diagnosis was 67.0 (10.0) years and 136 (76.8%) were women. Most common autoimmune diseases were rheumatoid arthritis (97 [54.8%]), systemic sclerosis (43 [24.3%]), and systemic lupus erythematous (15 [8.5%]). Most common lung cancers were adenocarcinoma (99 [55.9%]), squamous cell carcinoma (29 [16.4%]), and small cell lung cancer (17 [9.6%]). A total of 219 patients (mean [SD] age at diagnosis, 65.9 [4.1] years; 173 [79.0%]) were identified as having lung cancer without autoimmune disease and included in the control cohort. Compared with patients in the control group, patients with autoimmune disease experienced no difference in overall survival (log-rank P = .69). A total of 126 patients (69.5%) with autoimmune disease received standard of care vs 213 patients (97.3%) in the control group (P < .001). No individual autoimmune disease was associated with worse prognosis, even among patients with underlying interstitial lung disease. Conclusions and Relevance: Compared with institutional controls, patients with autoimmune disease experienced no difference in survival despite the fact that fewer patients in this group received standard-of-care treatment. No individual autoimmune disease was associated with worse prognosis. Future multicenter prospective trials are needed to further evaluate autoimmune disease and lung cancer survival.

Cost-effectiveness of surveillance with CT colonography after resection of colorectal cancer.

OBJECTIVE: Surveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test. DESIGN: We developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year. RESULTS: For persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression. CONCLUSION: In a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

Complete response to immune checkpoint inhibitors-based therapy in advanced renal cell carcinoma patients. A meta-analysis of randomized clinical trials.

BACKGROUND: A major breakthrough with immunotherapy is its potential to achieve complete responses (CR) in a subset of advanced renal cell carcinoma (RCC) patients. We aim at evaluating the incidence and relative risk (RR) of CR in RCC patients treated with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. The proportion of patients with CR events and the derived 95% confidence intervals (CIs) were calculated for each study. Combined relative risks (RRs) and 95% CIs were calculated using fixed- or random-effects methods. The analysis was performed in the intention to treat population, in the PD-L1 expressing (≥1%) RCC tumors and in patients treated with the combination of ICIs and anti-VEGFR tyrosine kinase inhibitors. RESULTS: Six articles were considered for final analysis (total of 4.531 patients). The incidence of CR was 6.2% with ICIs and 2.6% with SOC. Treatment with ICIs significantly increased the risk of achieving CR compared to SOC (RR = 2.40; P = 0.001). This data was confirmed for patients treated with the combination of ICIs plus anti-VEGFR tyrosine kinase inhibitors (RR = 2.50; P = 0.002). In PD-L1 positive tumors, the incidence of CR was 10.0% with ICIs and 4.0% in the SOC arm (RR = 2.49; P < 0.0001). CONCLUSIONS: ICIs provide higher rates of CR compared to SOC, even higher in patients with PD-L1 positive tumors.

Identifying risk factors and optimizing standard of care for patients with acquired haemophilia A: Results from a Czech patient cohort.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare autoimmune disorder, characterized by bleeds of varying severity caused by autoantibodies against factor VIII (FVIII). AIM: Identify risk factors associated with AHA-related deaths/relapses and assess the effect of increased corticosteroid doses. METHODS: AHA patients treated across two specialist centres in the Czech Republic, generally receiving first-line haemostatic therapy with rFVIIa and immunosuppression with corticosteroids/cyclophosphamide, were included. We analysed the association between early death (within 8 weeks of diagnosis [considered disease-related]) and age, malignancy, FVIII levels and bleeding severity. Risk factors associated with reduced 2-year survival and relapse incidence, and the effect of increased corticosteroid doses on early death and remission were also assessed. RESULTS: The demographics of the described cohort (n = 66) were similar to other AHA registries. Early death occurred in 20% of cases. Unlike age and malignancy, FVIII levels <1% and severe bleeding were associated significantly with early death (P = .010 and P = .046, respectively). Patients with underlying malignancy or requiring continued haemostatic therapy exhibited significantly decreased 2-year survival compared with those without these risk factors (P = .007 and P = .006, respectively). Patients with an underlying autoimmune disease relapsed significantly more than those without (P = .015). Higher corticosteroid doses were associated with a significantly increased incidence of early deaths (P < .001), but also with early remission (P < .001). CONCLUSION: Based on this rather large patient cohort, we were able to evaluate the significance of several risk factors associated with treatment outcomes in AHA and the effect of initial treatment with corticosteroids on survival and time to remission.

Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness.

INTRODUCTION: There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES: To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES: To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS: We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION: This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42019130504.

Real-world treatment patterns, healthcare resource use and clinical outcomes of patients receiving second line therapy for advanced or metastatic gastric cancer.

BACKGROUND: Second-line (2 L) chemotherapies for advanced or metastatic gastric cancer have shown improved survival but there is no commonly accepted standard of care. This study examines real-world patient characteristics, treatment patterns, healthcare resource use (HCRU) and clinical outcomes in this setting. METHODS: Retrospective chart reviews were performed at participating institutions from Australia, Canada, Italy and UK for adult patients receiving 2 L treatment for advanced/metastatic disease from January 2013 to July 2015. Data were collected for 12 months or until death. RESULTS: Two hundred eighty patients were included, mean age was 60.9 years and 68.9% were male. Half (51.8%) received monotherapy in 2 L, of whom 69.0% received taxanes. Irinotecan monotherapy was common in Australia (30.0% of monotherapy patients) and Canada (43.8%), but infrequent in Italy and UK. Doublet chemotherapy was used in 36.4% of 2 L patients, most commonly fluoropyrimidine + irinotecan. Use of targeted therapies (trastuzumab, ramucirumab) was infrequent except in Italy. Estimated median real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) from the time of 2 L treatment initiation was 3.09 (95% CI: 2.76-3.68) and 6.54 (5.29-7.76) months, respectively, and estimated 12-month rwPFS and rwOS rate was 8 and 26%, respectively. Only a minority (26.8%) of patients were hospitalized during the follow-up period, with the lowest hospitalization in Italy (16.7%). Laboratory and imaging tests were performed for 93.2 and 70.4%, respectively. CONCLUSIONS: About half of patients received monotherapy as 2 L chemotherapy for advanced/metastatic gastric cancer and a third received doublets. Real-world clinical outcomes for 2 L treatment are poor and HCRU is considerable.

Nonadherence to Standard of Care for Locally Advanced Colon Cancer as a Contributory Factor for High Mortality Rates in Kentucky.

BACKGROUND: Kentucky has one of the highest mortality rates for colon cancer, despite dramatic improvements in screening. The National Comprehensive Cancer Network (NCCN) guidelines recommend operation and adjuvant chemotherapy for locally advanced (stage IIb/c and stage III) colon cancer (LACC). The purpose of this study was to determine the rate of nonadherence with current standard of care (SOC) and associated factors as possible contributors to mortality. METHODS: The Kentucky Cancer Registry database linked with administrative health claims was queried for individuals (20 years and older) diagnosed with LACC from 2007 to 2012. Bivariate and logistic regression of nonadherence was performed. Survival analysis was performed with Cox regression and Kaplan-Meier plots. RESULTS: A total of 1,404 patients with LACC were included. Approximately 42% of patients with LACC were noted to be nonadherent to SOC, with nearly all (95.7%) failing to receive adjuvant chemotherapy. After adjusting for all significant factors, we found the factors associated with nonadherence included the following: age older than 75 years, stage III colon cancer, high Charlson Comorbidity Index (3+), low poverty level, Medicaid coverage, and disability. Adherence to SOC is associated with a significant improvement in the 5-year survival rate compared with nonadherence (63.0% and 27.4%, respectively; p < 0.0001). CONCLUSIONS: Our study identified multiple factors associated with the failure of patients with LACC to receive SOC, particularly adjuvant chemotherapy, suggesting the need to focus on improving adjuvant chemotherapy compliance in specific populations. Nonadherence to LACC SOC is likely a major contributor to the persistently high mortality rates in Kentucky.

Impact of Patients' Gender on Efficacy of Immunotherapy in Patients With Metastatic Kidney Cancer: A Systematic Review and Meta-analysis.

Recent meta-analyses on checkpoint inhibitors in cancer report conflicting data regarding the association of patient gender with inhibitor efficacy. In advanced kidney cancer, checkpoint inhibitors have shown improved outcomes in first- and second-line settings compared with standard of care, but the role of patient gender on treatment outcome is unclear. We aimed to assess the efficacy of immunotherapy according to patient gender in advanced kidney cancer. We performed a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search was performed using PubMed, Scopus, Web of Science, and The Cochrane Library to identify eligible studies published through February 16, 2019. Studies were included if they reported on the differential outcomes of male and female patients with metastatic kidney cancer receiving immunotherapy. Our outcomes of interest were overall survival (OS) or progression-free survival (PFS). Four randomized controlled trials comprising a total of 3664 patients (2715 males and 949 females) met our inclusion criteria. Both men and women with metastatic kidney cancer had an OS and PFS advantage with immunotherapy compared with standard-of-care, but no statistically significant difference between the genders was observed (OS hazard ratio [HR] for men, 0.69; 95% confidence interval [CI], 0.59-0.8; P = .40; HR for women, 0.62; 95% CI, 0.48-0.81; P = .13; PFS HR for men, 0.7; 95% CI, 0.59-0.82; P = .24; HR for women, 0.68; 95% CI, 0.52-0.90; P = .105). In patients with advanced kidney cancer receiving checkpoint inhibitors, there seems to be no association of patient gender with treatment outcome.

Utilization of palliative care consultations in pediatric oncology phase I clinical trials.

Pediatric phase I clinical oncology trials represent a unique cohort of patients who have not responded to standard therapies and remain highly vulnerable to treatment toxicity and/or disease burden. Incorporating a palliative care consultation into the care plan for those with relapsed/refractory cancer where chance of cure is limited is generally recommended. A retrospective chart review of pediatric phase I trials revealed that palliative care was consulted in <20% of patients, most often for symptom management. Efforts to increase the use of palliative services in this population may enhance quality of life for children and families enrolled in phase I studies.