High World Heath Organization Performance Status Is Associated With Short- and Long-term Outcomes After Colorectal Cancer Surgery: A Nationwide Population-Based Study.

BACKGROUND: The value of performance status is widely used in medical oncology, but the association with surgical outcomes in colorectal cancer has not been described. OBJECTIVE: The aim of this study was to investigate the association between World Heath Organization performance status and 90-day mortality, 30-day mortality, complications, and overall survival after elective colorectal cancer surgery. DESIGN: The study was conducted as a nationwide population-based cohort study with prospectively collected data. SETTING: Data from 2014 through 2016 were provided by the Danish nationwide colorectal cancer database (Danish Colorectal Cancer Group). PATIENTS: All patients aged ≥18, who had elective surgery for colorectal cancer were included. MAIN OUTCOME MEASURES: Multiple logistic regressions were performed to investigate 90-day mortality, 30-day mortality, and complications. One-year mortality was determined by Cox regression, and overall survival was illustrated by Kaplan-Meier curves. RESULTS: A total of 10,279 patients had elective colorectal cancer surgery during the study period (6892 colonic and 3387 rectal). Thirty-four percent of the patients with colorectal cancer had a World Heath Organization performance status ≥1. The odds ratios of postoperative 90-day mortality in colon cancer for performance status 1, 2, and 3/4 compared with performance status 0 were 2.50 (95% CI, 1.67-3.73), 5.00 (95% CI, 3.19-7.86), and 17.34 (95% CI, 10.18-29.55). The odds ratios of postoperative 90-day mortality in rectal cancer for performance status 1, 2, and 3/4 were 3.90 (95% CI, 2.23-6.85), 9.25 (95% CI, 4.75-18.02), and 10.56 (95% CI, 4.07-27.41). Performance status was also associated with 30-day mortality, overall survival, and medical complications. LIMITATIONS: Only 1 year of follow-up was possible for all patients, and cancer-specific survival was not available. CONCLUSION: One of three patients has a performance status >0 and is associated with an increased risk of death, complications, and overall survival for both colonic and rectal cancers. See Video Abstract at http://links.lww.com/DCR/B540. EL ALTO NIVEL DE DESEMPEO DE LA ORGANIZACIN MUNDIAL DE LA SALUD SE ASOCIA CON RESULTADOS A CORTO Y LARGO PLAZO DESPUS DE LA CIRUGA DEL CNCER COLORRECTAL UN ESTUDIO POBLACIONAL A NIVEL NACIONAL: ANTECEDENTES:El valor del estado funcional se usa ampliamente en oncología médica, pero no se ha descrito la asociación con los resultados quirúrgicos en el cáncer colorrectal.OBJETIVO:El objetivo fue investigar la asociación entre el estado funcional de la Organización Mundial de la Salud y la mortalidad a 90 días, la mortalidad a 30 días, las complicaciones y la supervivencia general después de la cirugía electiva del cáncer colorrectal.DISEÑO:El estudio se realizó como un estudio de cohorte poblacional a nivel nacional con datos recolectados prospectivamente.ENTORNO CLINICO:Los datos fueron proporcionados por la base de datos de cáncer colorrectal a nivel nacional danés (DCCG.dk) en un período de estudio de 2014-2016.PACIENTES:Se incluyeron todos los pacientes de ≥18 años que se sometieron a cirugía electiva por cáncer colorrectal.PRINCIPALES MEDIDAS DE VALORACION:Para investigar la mortalidad a los 90 días, la mortalidad a los 30 días y las complicaciones se realizaron regresiones logísticas múltiples. La mortalidad a un año se determinó mediante regresión de Cox y la supervivencia general se ilustra mediante curvas de Kaplan-Meier.RESULTADOS:Un total de 10 279 pacientes se sometieron a cirugía electiva de cáncer colorrectal en el período de estudio (6892 colónico y 3387 rectal). Treinta y cuatro por ciento de los pacientes con cáncer colorrectal tenían un estado funcional de la Organización Mundial de la Salud ≥1. Los ratios de probabilidades (odds ratios) de mortalidad postoperatoria a los 90 días en cáncer de colon para el estado funcional 1, 2 y 3/4 en comparación con el estado funcional 0 fueron 2,50 (IC del 95%: 1,67-3,73), 5,00 (IC del 95%: 3,19-7,86) y 17,34 (IC del 95%: 10,18-29,55), respectivamente. Los ratios de probabilidades de mortalidad postoperatoria de 90 días en cáncer de recto para el estado funcional 1, 2 y 3/4 fueron 3,90 (IC del 95%: 2,23-6,85), 9,25 (IC del 95%: 4,75-18,02) y 10,56 (IC del 95%: 2,23-6,85) % CI: 4,07-27,41). El estado funcional también se asoció con la mortalidad a los 30 días, la supervivencia general y las complicaciones médicas.LIMITACIONES:Solo fue posible un año de seguimiento para todos los pacientes y la supervivencia específica del cáncer no estaba disponible.CONCLUSIÓN:Uno de cada tres pacientes tiene un estado funcional> 0 y se asocia con un mayor riesgo de muerte, complicaciones y supervivencia general para los cánceres de colon y recto. Consulte Video Resumen en http://links.lww.com/DCR/B540.

A systematic review of craniospinal irradiation for leptomeningeal disease: past, present, and future.

PURPOSE: Leptomeningeal disease (LMD) is a rare but deadly complication of cancer in which the disease spreads to the cerebrospinal fluid and seeds the meninges of the central nervous system (CNS). Craniospinal irradiation (CSI) involves treatment of the entire CNS subarachnoid space and is occasionally used as a last-resort palliative therapy for LMD. METHODS: This review examined literature describing the role of CSI for LMD from solid and hematologic malignancies in adults. A search for studies published until September 1, 2020 was conducted using PubMed database. RESULTS: A total of 262 unique articles were identified. Thirteen studies were included for analysis in which a total of 275 patients were treated with CSI for LMD. Median age at time of irradiation was 43 years, and most patients had KPS score of 70 and higher. The most common cancers resulting in LMD were acute lymphocytic leukemia, breast cancer, and acute myelogenous leukemia. Median CSI dose was 30 Gy and 18% of patients were treated with proton radiation. 52% of patients had stable-to-improved neurologic symptoms. Median overall survival for the entire cohort was 5.3 months. Patients treated with marrow-sparing proton radiation had median OS of 8 months. The most common treatment toxicities were hematologic and gastrointestinal events. CONCLUSIONS: Despite advances in systemic and radiation therapies, LMD remains a devastating end-stage complication of some malignancies. Treatment-related toxicities can be a significant barrier to CSI delivery. In select patients with LMD, marrow-sparing proton CSI may provide safer palliation of symptoms and prolong survival.

Validation of the UK myeloma research alliance risk profile, a new clinical prediction model for outcome in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation; a population-based study from the Danish national multiple myeloma registry.

In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.

Comparison of Risk Scoring Systems in HLA-Matched Related Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study

Objective: Allogeneic hematopoietic stem cell transplantation (AHSCT) is a potentially curative treatment of choice for many hematological diseases. However, there are some transplantation-related risks. Predicting the risk-benefit ratio prior to AHSCT facilitates the choice of conditioning regimens and posttransplant follow-up. Hence, many risk models have been developed. The aim of the present study was to compare 6 different risk models that are clinically used. Materials and Methods: A total of 259 patients were enrolled in this study. The European Society for Blood and Marrow Transplantation (EBMT), Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), Age-Adjusted Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI-Age), revised Pretransplant Assessment of Mortality (rPAM), Acute Leukemia-EBMT (AL-EBMT), and Disease Risk Index (DRI) risk models were applied retrospectively. Results: The AL-EBMT, HCT-CI, and HCT-CI-Age scoring systems were found to be predictive for 2-year overall survival (OS) and 2-year non-relapse mortality (NRM) (2-year OS: AL-EBMT, reference vs. score 8.5-10, HR: 1.3, p=0.035; AL-EBMT, reference vs. score >10, HR: 3.8, p=0.001; HCT-CI: reference vs. score 1-2, HR: 1.4, p=0.018; HCT-CI: reference vs. score ≥3, HR: 2.5, p<0.001; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p<0.001; HCT-CI-Age: reference vs. score ≥3, HR: 3.2, p<0.001) (2-year NRM: AL-EBMT: reference vs. score 8.5-10, HR: 1.61, p<0.001; AL-EBMT: reference vs. score >10, HR: 3.3, p<0.001; HCT-CI: reference vs. score 1-2, HR: 1.3, p=0.028; HCT-CI: reference vs. score ≥3, HR: 2.3, p=0.011; HCT-CI-Age: reference vs. score 1-2, HR: 1.3, p=0.01; HCT-CI-Age: reference vs. score ≥3, HR: 2.4, p=0.003). In terms of the Kaplan-Meier estimates of 2-year OS and 2-year NRM, the risk scoring system with the highest predictive power was found to be AL-EBMT (2-year AUC: 0.59 and 0.60, respectively). The other scores were not found to be predictive for 2-year OS and NRM. Conclusion: In the present study at our bone marrow and stem cell transplant center, it has been demonstrated that the HCT-CI, HCT-CI-Age, and AL-EBMT are good predictors of 2-year NRM and OS.

Real-World Treatment and Outcomes of Metastatic Colorectal Cancer Patients With a Poor or Very Poor Performance Status.

BACKGROUND: The management of metastatic colorectal cancer patients with a poor performance status (PS) continues to be a clinical dilemma, with the potential activity and safety of treating this population remaining poorly understood. Few of these patients are enrolled onto clinical trials, and poor PS is often multifactorial. PATIENTS AND METHODS: We analyzed the Treatment of Recurrent and Advanced Colorectal Cancer registry to describe treatment practices and outcomes in poor (Eastern Cooperative Oncology Group [ECOG] PS 2) and very poor PS (ECOG PS > 2) patients to explore the relationship between age, tumor burden, comorbidities, and PS, and to evaluate the benefit of systemic therapy. Standard descriptive statistical methods, Kaplan-Meier analysis, and a multivariate Cox regression model were used. RESULTS: Of 2769 registry patients (diagnosed January 2009 to June 2018), 329 (12%) and 182 (7%) patients had a poor and very poor PS, respectively. Good PS patients were more likely to receive systemic therapy than poor and very poor PS patients (85%, 55%, and 21.5%, P < .0001), but clinician assessed response was observed in all subsets (53%, 41%, and 29%, P = .0003). Treatment with chemotherapy was associated with longer median overall survival across PS groups. Exploratory analysis based on comorbidity score and tumor burden subgroups demonstrated a consistently positive overall survival association with treatment. Benefit was observed where poor overall survival was attributable to medical comorbidities and to tumor burden. CONCLUSION: In routine clinical care, a substantial proportion of poor and very poor PS patients receive active treatment, which is often associated with meaningful clinical benefit.

Karnofsky Performance Scale and Neurological Assessment of Neuro-Oncology Scale as Early Predictor in Glioma.

OBJECTIVE: Glioma is one of the most frequent and disabling primary brain tumour. Patients are not only dealing with survival, but also quality of life, which remains another major concern. Karnofsky Performance Scale (KPS) is one of the most commonly used scale to assess patients' quality of life. A recent scale, known as Neurological Assessment of Neuro-Oncology Scale, has surfaced to examine neurological disability caused by brain tumour. Previous study showed this scale to be superior to KPS in predicting survival. However, these scales have never been used to foresee functional scale improvement during disease progression. We sought to determine whether initial KPS and NANO Scale can predict functional scale improvement 2 months after surgery. METHODS: Patients with glioma grade II-IV were included in the study. IDH mutation and MGMT methylation were tested. KPS and NANO scale were examined before surgery and 2 months after surgery. Favorable outcome (FO) was defined as improvement in functional scale 2 months after surgery. Patients initial functional scales were analyzed towards favorable outcome. RESULTS: Glioma WHO grade II, III and IV was found in 17 patients (36.2%), 3 patients (6.4%) and 27 patients (57.4%) respectively. Median KPS before and 2 months after surgery were 50 (30-80) and 60 (0-100), whereas median NANO scale before and 2 months after surgery were 5 (0-12) and 3 (0-12). Favorable outcome was found in 63.8% (KPS) and 78.7% (NANO Scale). Patients initial functional scales were significantly related to FO. CONCLUSION: Good initial functional scales are 4 to 5 times likely of having a favorable outcome 2 months after surgery.

High mortality rate in cancer patients with symptoms of COVID-19 with or without detectable SARS-COV-2 on RT-PCR.

BACKGROUND: Cancer patients presenting with COVID-19 have a high risk of death. In this work, predictive factors for survival in cancer patients with suspected SARS-COV-2 infection were investigated. METHODS: PRE-COVID-19 is a retrospective study of all 302 cancer patients presenting to this institute with a suspicion of COVID-19 from March 1st to April 25th 2020. Data were collected using a web-based tool within electronic patient record approved by the Institutional Review Board. Patient characteristics symptoms and survival were collected and compared in SARS-COV-2 real-time or reverse-transcriptase PCR (RT-PCR)-positive and RT-PCR-negative patients. RESULTS: Fifty-five of the 302 (18.2%) patients with suspected COVID-19 had detectable SARS-COV-2 with RT-PCR in nasopharyngeal samples. RT-PCR-positive patients were older, had more frequently haematological malignancies, respiratory symptoms and suspected COVID-19 pneumonia of computed tomography (CT) scan. However, respectively, 38% and 20% of SARS-COV-2 RT-PCR-negative patients presented similar respiratory symptoms and CT scan images. Thirty of the 302 (9.9%) patients died during the observation period, including 24 (80%) with advanced disease. At the median follow-up of 25 days after the first symptoms, the death rate in RT-PCR-positive and RT-PCR-negative patients were 21% and 10%, respectively. In both groups, independent risk factors for death were male gender, Karnofsky performance status <60, cancer in relapse and respiratory symptoms. Detection of SARS-COV-2 on RT-PCR was not associated with an increased death rate (p = 0.10). None of the treatment given in the previous month (including cytotoxics, PD1 Ab, anti-CD20, VEGFR2…) correlated with survival. The survival of RT-PCR-positive and -negative patients with respiratory symptoms and/or COVID-19 type pneumonia on CT scan was similar with a 18.4% and 19.7% death rate at day 25. Most (22/30, 73%) cancer patients dying during this period were RT-PCR negative. CONCLUSION: The 30-day death rate of cancer patients with or without documented SARS-COV-2 infection is poor, but the majority of deaths occur in RT-PCR-negative patients.

Development and Validation of a Prognostic Survival Model With Patient-Reported Outcomes for Patients With Cancer.

Importance: Existing prognostic cancer tools include biological and laboratory variables. However, patients often do not know this information, preventing them from using the tools and understanding their prognosis. Objective: To develop and validate a prognostic survival model for all cancer types that incorporates information on symptoms and performance status over time. Design, Setting, and Participants: This is a retrospective, population-based, prognostic study of data from patients diagnosed with cancer from January 1, 2008, to December 31, 2015, in Ontario, Canada. Patients were randomly selected for model derivation (60%) and validation (40%). The derivation cohort was used to develop a multivariable Cox proportional hazards regression model with baseline characteristics under a backward stepwise variable selection process to predict the risk of mortality as a function of time. Covariates included demographic characteristics, clinical information, symptoms and performance status, and health care use. Model performance was assessed on the validation cohort by C statistics and calibration plots. Data analysis was performed from February 6, 2018, to November 6, 2019. Main Outcomes and Measures: Time to death from diagnosis (year 0) recalculated at each of 4 annual survivor marks after diagnosis (up to year 4). Results: A total of 255 494 patients diagnosed with cancer were identified (135 699 [53.1%] female; median age, 65 years [interquartile range, 55-73 years]). The cohort decreased to 217 055, 184 822, 143 649, and 109 569 patients for each of the 4 years after diagnosis. In the derivation cohort year 0, and the most common cancers were breast (30 855 [20.1%]), lung (19 111 [12.5%]), and prostate (18 404 [12.0%]). A total of 47 614 (31.1%) had stage III or IV disease. The mean (SD) time to death in year 0 was 567 (715) days. After backward stepwise selection in year 0, the following factors were associated with increased risk of death by more than 10%: being hospitalized; having congestive heart failure, chronic obstructive pulmonary disease, or dementia; having moderate to high pain; having worse well-being; having functional status in the transitional or end-of-life phase; having any problems with appetite; receiving end-of-life home care; and living in a nursing home. Model discrimination was high for all models (C statistic: 0.902 [year 0], 0.912 [year 1], 0.912 [year 2], 0.909 [year 3], and 0.908 [year 4]). Conclusions and Relevance: The model accurately predicted changing cancer survival risk over time using clinical, symptom, and performance status data and appears to have the potential to be a useful prognostic tool that can be completed by patients. This knowledge may support earlier integration of palliative care.

Functional status and survival in patients ≥85 years of age who have keratinocyte carcinoma: A retrospective cohort study.

BACKGROUND: Functional status assessment may help estimate which patients ≥85 years of age will benefit from surgical treatment for keratinocyte carcinoma (KC), but predictive value for short-term survival in this population has not been determined. OBJECTIVE: We sought to assess the predictive value of functional status for short-term survival in patients ≥85 years of age who have KC. METHODS: This was a retrospective cohort review of 238 patients ≥85 years of age who presented for the management of KC between 2010 and 2015. Functional status was assessed with the Karnofsky Performance Scale (KPS) and Katz Activities of Daily Living (ADL) index. Overall survival was determined. RESULTS: Lower functional status scores of KPS ≤40 and Katz ADL ≤4 were associated with 37% and 53% survival at 2 years, respectively. LIMITATIONS: Retrospective design and single-center study. CONCLUSION: In this study, KPS and Katz ADL predicted short-term survival. Patients with low functional status scores had significantly decreased survival at 2 years, with double the death rate of patients with high functional status. Functional status should be considered during shared decision-making for elderly individuals who are seeking treatment for KC.

Characterization and management of elderly and very elderly patients with non-small cell lung cancer.

OBJECTIVES: Despite non-small cell lung cancer (NSCLC) high prevalence and increasing incidence, evidence specific to the elderly and very elderly is sparse. To retrospectively compare characterization and approach of NSCLC patients (pts) aged 70-79 and ≥80 years. METHODS: We performed a retrospective analysis of 297 adult NSCLC pts who registered and initiated NSCLC management in our Pulmonology Oncology Unit from January 2013 to December 2016 corresponding to 38.2% of all NSCLC patients (n = 778). Demographic data and lung cancer management were analysed. RESULTS: Pts were categorized as elderly (n = 211, 71.0%) and very elderly (n = 86, 29.0%). Very elderly pts had worse Eastern Cooperative Oncology Group performance status (P = 0.047), higher Charlson age comorbidity index (P < 0.001) and the majority had stage IV cancer (66.3%, P = 0.04). The first management option in very elderly pts was chemotherapy (CTX) (30.2%, P = 0.37) and in elderly pts was multimodal therapy (30.3%, P ≤ 0.001). Support therapy and first-line targeted (EGFR or ALK-positive) were more common in the very elderly (23.6%, P = 0.01; 17.4% P = 0.002, respectively). Curative radiation or surgery rates did not differ between groups. Reasons for premature first-line CTX stop, toxicity and hospitalization did not differ. Death rate (69.7% vs 63.5% for very elderly and elderly, respectively) and mean survival since diagnosis (11.5 vs 11.6 months for very elderly and elderly, respectively) did not differ. CONCLUSIONS: There were significant differences in pts characteristics having the very elderly more multimorbidity and advanced state of disease. First management options were significantly different with respect to multimodal, targeted and support therapy.

Inter-rater reliability in performance status assessment among healthcare professionals: an updated systematic review and meta-analysis.

INTRODUCTION: Survival prediction for patients with incurable malignancies is invaluable information during end-of-life discussions, as it helps the healthcare team to appropriately recommend treatment options and consider hospice enrolment. Assessment of performance status may differ between different healthcare professionals (HCPs), which could have implications in predicting prognosis. The aim of this systematic review and meta-analysis is to update a prior systematic review with recent articles, as well as conduct a meta-analysis to quantitatively compare performance status scores. METHODS: A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, from the earliest date until the first week of August 2019. Studies were included if they reported on (1) Karnofsky Performance Status (KPS), Eastern Cooperative Oncology Group (ECOG) Performance Status, and/or Palliative Performance Scale (PPS) and (2) assessment of performance status by multiple HCPs for the same patient sets. The concordance statistics (Kappa, Krippendorff's alpha, Kendall correlation, Spearman rank correlation, Pearson correlation) were extracted into a summary table for narrative review, and Pearson correlation coefficients were calculated for each study and meta-analyzed with a random effects analysis model. Analyses were conducted using Comprehensive Meta-Analysis (Version 3) by Biostat. RESULTS: Fourteen articles were included, with a cumulative sample size of 2808 patients. The Pearson correlation coefficient was 0.787 (95% CI: 0.661, 0.870) for KPS, 0.749 (95% CI: 0.716, 0.779) for PPS, and 0.705 (95% CI: 0.536, 0.819) for ECOG. Four studies compared different tools head-to-head; KPS was favored in three studies. The quality of evidence was moderate, as determined by the GRADE tool. CONCLUSIONS: The meta-analysis's Pearson correlation coefficient ranged from 0.705 to 0.787; there is notable correlation of performance status scores, with no one tool statistically superior to others. KPS is, however, descriptively better and favored in head-to-head trials. Future studies could now examine the accuracy of KPS assessment in prognostication and focus on model-building around KPS.

Impact of decompressive laminectomy on the functional outcome of patients with metastatic spinal cord compression and neurological impairment.

Metastatic spinal cord compression (MSCC) is a frequent phenomenon in advanced tumor diseases with often severe neurological impairments. Affected patients are often treated by decompressive laminectomy. To assess the impact of this procedure on Karnofsky Performance Index (KPI) and Frankel Grade (FG) at discharge, a single center retrospective cohort study of neurologically impaired MSCC-patients treated with decompressive laminectomy between 2004 and 2014 was performed. 101 patients (27 female/74 male; age 66.1 ± 11.5 years) were identified. Prostate was the most common primary tumor site (40%) and progressive disease was present in 74%. At admission, 80% of patients were non-ambulatory (FG A-C). Imaging revealed prevalently thoracic MSCC (78%). Emergency surgery (< 24 h) was performed in 71% and rates of complications and revision surgery were 6% and 4%, respectively. At discharge, FG had improved in 61% of cases, and 51% of patients had regained ambulation. Univariate predictors for not regaining the ability to walk were bowl dysfunction (p = 0.0015), KPI < 50% (p = 0.048) and FG < C (p = 0.001) prior to surgery. In conclusion, decompressive laminectomy showed beneficial effects on the functional outcome at discharge. A good neurological status prior to surgery was key predictor for a good functional outcome.

Nab-paclitaxel plus gemcitabine in patients with locally advanced pancreatic cancer (LAPACT): a multicentre, open-label phase 2 study.

BACKGROUND: Treatment options for patients with unresectable locally advanced pancreatic cancer are scarce. Results from a subanalysis of the phase 3 MPACT trial in metastatic pancreatic cancer suggested potential activity of nab-paclitaxel plus gemcitabine against locally advanced pancreatic cancer. The objective of this phase 2 trial was to evaluate safety and efficacy of nab-paclitaxel plus gemcitabine in previously untreated locally advanced pancreatic cancer. METHODS: This international, open-label, multicentre, phase 2 trial (LAPACT) took place at 35 sites in five countries (USA, France, Spain, Canada, and Italy). Patients with Eastern Cooperative Oncology Group performance status of up to 1 underwent six cycles of induction with nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (days 1, 8, and 15 of each 28-day cycle). After induction, patients without progressive disease or unacceptable adverse events were eligible to receive continued therapy per investigator's choice: continued nab-paclitaxel plus gemcitabine, chemoradiation, or surgery. The primary endpoint was time to treatment failure; secondary endpoints were disease control rate, overall response rate, progression-free survival, overall survival, safety, and quality of life. The reported efficacy outcomes were analysed in the intention-to-treat population, and safety outcomes were analysed in the treated population. This trial is registered with ClinicalTrials.gov, NCT02301143, and EudraCT, 2014-001408-23 and is complete. FINDINGS: Between April 21, 2015, and April 26, 2018, 107 patients were enrolled in the study. 106 received the study treatment; one patient enrolled but did not receive treatment. 44 (41%) of 107 enrolled patients discontinued induction; the most common reason for discontinuing induction was adverse events (22 [21%] patients). 62 (58%) of 107 enrolled patients completed induction treatment and 47 (44%) patients subsequently received continued treatment per investigator's choice: 12 (11%) continued nab-paclitaxel plus gemcitabine, 18 (17%) received chemoradiation, and 17 (16%) underwent surgery (seven had R0 resection status, nine had R1). 15 (14%) patients completed induction treatment but did not receive continued treatment. Median time to treatment failure was 9·0 months (90% CI 7·3-10·1); median progression-free survival was 10·9 months (90% CI 9·3-11·6), and median overall survival was 18·8 months (90% CI 15·0-24·0). During induction, 83 patients achieved disease control and the disease control rate was 77·6% (90% CI 70·3-83·5). 36 patients had a best response of partial response; the overall response rate during induction was 33·6% (90% CI 26·6-41·5). The most common treatment-emergent adverse events that were grade 3 or higher in the treated population during induction were neutropenia (35 [33%] of 106 patients), anaemia (12 [11%]), and fatigue (11 [10%]). The most common treatment-emergent serious adverse events during induction were pneumonia (five [5%] patients), pyrexia (five [5%]), and febrile neutropenia (three [3%]). No deaths were caused by treatment-related adverse events during the induction phase, and global quality of life was maintained in most patients. INTERPRETATION: The data from this trial support the tolerability and activity of nab-paclitaxel plus gemcitabine for locally advanced pancreatic cancer, and a potential to convert unresectable, locally advanced disease to surgically resectable disease. The safety profile was generally consistent with previous findings. FUNDING: Celgene.

Immune Checkpoint Inhibitor Use Near the End of Life Is Associated With Poor Performance Status, Lower Hospice Enrollment, and Dying in the Hospital.

BACKGROUND: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. METHODS: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. RESULTS: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. CONCLUSION: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.

Inter-rater reliability in performance status assessment between clinicians and patients: a systematic review and meta-analysis.

INTRODUCTION: Performance status is an essential consideration for clinical practice and for patient eligibility for clinical trials in oncology. Assessment of performance status is traditionally done by clinicians, but there is an increasing interest in patient-completed assessment. The aim of this systematic review and meta-analysis was to summarise inter-rater concordance between patient and clinician ratings of performance status. METHODS: A search strategy was developed and executed in the databases of Ovid MEDLINE, Embase and Cochrane Central Register of Controlled Trials, from inception until 15 August 2019. Articles were eligible for inclusion if there was mention of both (1) use of performance status tool Karnofsky Performance Status (KPS) or Eastern Cooperative Oncology Group Performance Status (ECOG), and (2) assessment of performance status by both clinicians and patients. Pearson correlation coefficients were calculated for each study and were meta-analysed according to a random-effect analysis model. Analyses were conducted using Comprehensive Meta-Analysis (V.3) by Biostat. RESULTS: Sixteen articles were included in our review, reporting on a cumulative sample size of 6619 patients. The quality of evidence was moderate, as determined by the GRADE tool.Concordance ranged from fair to moderate for both the KPS and ECOG tools. The Pearson correlation coefficient was 0.449 for KPS and 0.584 for ECOG. CONCLUSIONS: There is fair to moderate concordance of patient and clinician performance status ratings. Future studies should examine the reasoning behind clinician and patient ratings to better understand discrepancies between ratings.

A high C-reactive protein level and poor performance status are associated with delayed sputum conversion in elderly patients with pulmonary tuberculosis in Japan.

INTRODUCTION: Although the aging population had been increasing in many countries, the factors associated with sputum conversion in elderly patients with pulmonary tuberculosis have not been fully elucidated. OBJECTIVES: We aimed to identify the predictors of delayed sputum conversion and to assess the impact of non-conversion on mortality during tuberculosis treatment in elderly patients. METHODS: Elderly patients (>65 years) admitted at our hospital in Japan for sputum smear-positive pulmonary tuberculosis were included. The risk factors for sputum non-conversion after 2 months of treatment were determined using multiple logistic regression. Cox hazard regression was used to assess the influence of non-conversion on mortality. RESULTS: We included 185 patients, with median age of 82 years (IQR, 79-88 years). The median time to conversion was 47 (95% CI 43-51) days, and 62 (34%) were identified as non-converters. Multivariate analysis showed that high pretreatment smear grade, high C-reactive protein level and poor performance status were associated with non-conversion. Non-conversion did not contribute to death during treatment. CONCLUSIONS: In elderly patients, inflammation level and physical activity level, along with initial smear grade may have a significant impact on delayed sputum conversion. Non-conversion after two months of treatment might not be related with mortality.

Patients with Alcoholic Liver Disease Have Worse Functional Status at Time of Liver Transplant Registration and Greater Waitlist and Post-transplant Mortality Which Is Compounded by Older Age.

BACKGROUND: Worse functional status correlates with increased mortality on the liver transplant (LT) waitlist. Whether functional status affects LT outcomes equally across cirrhosis etiologies is unclear. AIMS: We evaluate the impact of functional status on waitlist and post-LT mortality stratified by etiology and age. METHODS: Functional status among US adults from 2005 to 2017 United Network for Organ Sharing LT registry data was retrospectively evaluated using Karnofsky Performance Status Score (KPS-1 = functional status 80-100%, KPS-2 = 60-70%, KPS-3 = 40-50%, KPS-4 = 10-30%). Waitlist and post-LT survival were stratified by KPS and cirrhosis etiology, including alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C (HCV), and HCV/ALD, and evaluated using Kaplan-Meier and multivariate Cox proportional hazard models. RESULTS: Among 94,201 waitlist registrants (69.4% men, 39.5% HCV, 26.7% ALD, 23.2% NASH), ALD patients had worse functional status compared to HCV (KPS-4: 17.2% vs. 8.3%, p < 0.001). Worse functional status at time of waitlist registration was associated with higher 90-day waitlist mortality with the greatest effect in ALD (KPS-4 vs. KPS-1: ALD HR 2.16, 95% CI 1.83-2.55; HCV HR 2.17, 95% CI 1.87-2.51). Similar trends occurred in 5-year post-LT survival with ALD patients the most harmed. Compared to patients < 50 years, patients ≥ 65 years had increased waitlist mortality at 90-days if they had HCV or HCV/ALD, and 5-year post-LT mortality regardless of cirrhosis etiology with ALD patients most severely affected. CONCLUSIONS: In a retrospective cohort study of patients, US ALD patients had disparately worse functional status at time of LT waitlist registration. Worse functional status correlated with higher risk of waitlist and post-LT mortality, affecting ALD and HCV patients the most.

Risk factors for the development of cutaneous melanoma after allogeneic hematopoietic cell transplantation.

BACKGROUND: Melanoma risk is increased after allogeneic hematopoietic cell transplantation (HCT), but specific risk factors are unknown. OBJECTIVE: Investigate risk factors for melanoma after allogeneic hematopoietic cell transplantation. METHODS: We conducted a nested case-control study of 140 melanoma cases and 557 controls (matched by age at HCT, sex, primary disease, survival time) through the Center for International Blood and Marrow Transplant Research. RESULTS: Melanoma risk was significantly increased among HCT survivors who received total body irradiation-based myeloablative conditioning (multivariable adjusted odds ratio [OR] = 1.77; 95% confidence interval [CI] = 1.00-3.15) or reduced-intensity conditioning containing melphalan (OR = 2.60; 95% CI = 1.13-6.02) or fludarabine (OR = 2.72; 95% CI = 1.02-7.30) versus busulfan-based myeloablative regimens; were diagnosed with acute graft-versus-host disease (GVHD) with stage 2+ skin involvement (OR = 1.92; 95% CI = 1.19-3.10), chronic GvHD without skin involvement (OR = 1.91; 95% CI = 1.03-3.57), or keratinocytic carcinoma (OR = 2.37; 95% CI = 1.16-4.83); and resided in areas with higher ambient ultraviolet radiation (ORtertile3 = 1.64; 95% CI = 1.01-2.67). LIMITATIONS: Data on individual-level ultraviolet radiation exposure and clinical data on melanoma characteristics were lacking. Additionally, misclassification of melanoma is possible as not all pathology reports were available for review. CONCLUSION: These results emphasize the importance of adherence to current surveillance guidelines (routine skin examination, photoprotection recommendations), particularly for HCT survivors at highest risk.

Predicting Survival for Patients With Metastatic Disease.

PURPOSE: This prospective study aimed to determine the accuracy of radiation oncologists in predicting the survival of patients with metastatic disease receiving radiation therapy and to understand factors associated with their accuracy. METHODS AND MATERIALS: This single-institution study surveyed 22 attending radiation oncologists to estimate patient survival. Survival predictions were defined as accurate if the observed survival (OS) was within the correct survival prediction category (0-6 months, >6-12 months, >12-24 months, and >24 months). The physicians made survival estimates for each course of radiation, yielding 877 analyzable predictions for 689 unique patients. Data analysis included Stuart's Tau C, logistic regression models, ordinal logistic regression models, and stepwise selection to examine variable interactions. RESULTS: Of the 877 radiation oncologists' predictions, 39.7% were accurate, 26.5% were underestimations, and 33.9% were overestimations. Stuart's Tau C showed low correlation between OS and survival estimates (0.3499), consistent with the inaccuracy reported in the literature. However, results showed less systematic overprediction than reported in the literature. Karnofsky performance status was the most significant predictor of accuracy, with greater accuracy for patients with shorter OS. Estimates were also more accurate for patients with lower Karnofsky performance status. Accuracy by patient age varied by primary site and race. Physician years of experience did not correlate with accuracy. CONCLUSIONS: The sampled radiation oncologists have a 40% accuracy in predicting patient survival. Future investigation should explore how survival estimates influence treatment decisions and how to improve survival prediction accuracy.