Poor Eastern Cooperative Oncology Group Research Articles

Outcomes to first-line pembrolizumab in patients with PD-L1-high (≥50%) non-small-cell lung cancer and a poor performance status.

9568 Background: Patients with non-small cell lung cancer (NSCLC) and a poor Eastern Cooperative Oncology Group performance status (ECOG PS) have been excluded from immunotherapy clinical trials. We sought to evaluate clinical outcomes to first-line pembrolizumab in patients with advanced NSCLC, a PD-L1 tumor proportion score (TPS) of ≥50%, and an ECOG PS of 2. Methods: We performed a multicenter retrospective analysis of patients with metastatic NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50% (negative for genomic alterations in EGFR and ALK) who received treatment with first-line commercial pembrolizumab. Clinical outcomes were compared in patients based on ECOG PS. Results: Among 234 patients, 83.3% (N = 195) had an ECOG PS of 0 or 1, and 16.7% (N = 39) had an ECOG PS of 2. The baseline clinicopathological characteristics were balanced between the ECOG PS 0-1 vs 2 groups in terms of age, sex, tobacco use, histology, KRAS mutation status, presence of other potentially targetable driver mutations ( BRAF, MET, HER2, RET), history of central nervous system (CNS) disease, and PD-L1 TPS distribution. Compared to patients with an ECOG PS of 0-1, patients with an ECOG PS of 2 had a significantly lower objective response rate (ORR 43.1% vs 25.6%; P = 0.04), a numerically shorter median progression free survival (mPFS 6.6 months vs 4.0 months; P = 0.09), and a significantly shorter median overall survival (mOS 20.3 months vs 7.4 months; P < 0.001). Upon disease progression, patients with an ECOG PS of 2 were significantly less likely to receive second-line systemic therapy compared to patients with an ECOG PS of 0-1 (55.5% vs 14.3%, P < 0.001). Conclusions: Although a subset of patients with an ECOG PS of 2 can respond first-line pembrolizumab, clinical outcomes in this population are poor, and use of second-line systemic therapy is infrequent.

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution's guidelines. Responses were assessed as per Lugano 2014 classification. Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel-treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.

Understanding the Prognostic Value of Primary Tumor Location and KRAS in Metastatic Colorectal Cancer: A Post Hoc Analysis of the OPTIMOX3 DREAM Phase III Study

IntroductionWe evaluated the prognostic value of KRAS and primary tumor location (PTL) for overall survival (OS), progression-free survival (PFS), and post-progression survival (PPS) in metastatic colorectal cancer (mCRC). Material and MethodsIndividual patient data from the DREAM phase III study were retrospectively analyzed. PTL was defined as right-sided or left-sided if tumor arising from the cecum to transverse colon or from the splenic flexure to the rectum, respectively. OS, PFS, and PPS were estimated using the Kaplan-Meier method and compared using log-rank test. ResultsAmong 700 patients included in the DREAM study, both PTL and KRAS were available for 536 (76.6%) patients. PTL showed stronger prognostic impact than KRAS status for OS (HRPTL, 1.62 vs. HRKRAS, 1.37), PFS (HRPTL, 1.27 vs. HRKRAS, 1.15) and PPS (HRPTL, 1.54 vs. HRKRAS, 1.33). Interaction between PTL and KRAS was significant (Pinteraction = .003). A negative impact of KRAS mutation was observed for OS and PPS, but not for PFS. Right-sided tumor was associated with poorer Eastern Cooperative Oncology Group performance status, anemia, and KRAS mutation, whereas left-sided KRAS wild-type tumor was associated with an increased lactate dehydrogenase. In patients with KRAS mutant mCRC, alkaline phosphatase was the main prognostic factor whatever the tumor site, whereas in those with KRAS wild-type tumors, prognostic factors varied according to PTL. The exposition to the anti-epidermal growth factor receptor (anti-EGFR) agents during and after study was similar in patients with left-sided and right-sided KRAS wild-type tumors. ConclusionOur findings suggest that a better prognosis of patients with mCRC with left-sided tumors is driven more strongly by PPS than by PFS when compared with patients with right-sided tumors, whatever the KRAS mutation status. This phenomenon was independent from the exposition to poststudy anti-EGFR monoclonal antibody.

Prediction of survival in non-Hodgkin lymphoma based on markers of systemic inflammation, anemia, hypercoagulability, dyslipidemia, and Eastern Cooperative Oncology Group performance status

AbstractBackgroundThe International Prognostic Index and its modifications are used to estimate prognosis in non-Hodgkin lymphoma. However, the outcome is often different in patients with similar index scores.AimThe aim of this study was to elaborate a prognostic model for patients with mature B-cell non-Hodgkin lymphoma using a combination of predictive markers.Material and methodsThe study included 45 patients with mature B-cell non-Hodgkin lymphoma. Before the administration of treatment, clinical and laboratory parameters were measured. After the 35-month follow-up period, overall survival was studied in relation to the data obtained at initial examination.ResultsWe revealed nine adverse predictive markers for overall survival of enrolled patients: Eastern Cooperative Oncology Group (ECOG) performance status >1; erythrocyte sedimentation rate >30 mm/h; levels of hemoglobin <120 g/L, fibrinogen ≥6 g/L, interleukin-6 ≥2 pg/mL, tumor necrosis factor ≥1.45 pg/mL, soluble fibrin monomer complexes >4 mg/dL, high-density lipoprotein cholesterol <1.03 mmol/L in men, and <1.29 mmol/L in women; and short activated partial thromboplastin time. A prognostic model for the estimation of the risk of death within the ensuing 1.5–2 years in patients with non-Hodgkin lymphoma was constructed.ConclusionMarkers of inflammation, anemia, hypercoagulability, dyslipidemia, and poor ECOG status are associated with worse survival in patients with mature B-cell non-Hodgkin lymphoma.

Effect of Hospitalization During First Chemotherapy and Performance Status on Small-cell Lung Cancer Outcomes

IntroductionSmall-cell lung cancer (SCLC) is highly responsive to chemotherapy (CT) and one of the few malignancies treated in hospitalized patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS). Because of the little current information available on the outcomes experienced by hospitalized patients with SCLC receiving CT, we explored the outcomes for these patients to improve the evidence base for practice. Materials and MethodsWe conducted a retrospective cohort study to evaluate patients with a diagnosis of SCLC and treated with CT during a 10-year period. Progression-free survival (PFS) and overall survival (OS) were evaluated according to site of first CT (inpatient vs. outpatient) and PS. Multivariable analysis was completed to assess for independent survival predictors. ResultsA total of 530 patients with SCLC were treated, with 82 (15%) receiving their first CT in hospital. Inpatients had a greater burden of disease and poorer PS. Neutropenia, thrombocytopenia, nephrotoxicity, and fatigue were all experienced less often by the inpatient cohort (P < .001, P < .001, P < .001, and P = .007, respectively). For inpatients and outpatients, the OS rate at 12, 24, and 60 months was 22%, 9%, and 7% and 43%, 20%, and 9%, respectively (P < .001 for all). The median PFS and OS were longer for outpatients and highly functional patients. On multivariable analysis, ECOG PS was an independent predictor of the outcome and the site of first CT was not (P = .04 and P = .49, respectively). ConclusionPatients with SCLC initially treated as inpatients and those with poor functional status had shorter PFS and OS; however, some experienced long-term survival, including 5-year survival of 7% for the inpatient cohort and 5% for the ECOG PS 3-4 cohort. CT toxicities were less common in the inpatient cohort, validating that administration of CT in hospital should be considered for these patients because they could experience a meaningful long-term response to therapy.

Local and systemic morbidities of de novo metastatic prostate cancer in Singapore: insight from 685 consecutive patients from a large prospective Uro-oncology registry

ObjectiveTo evaluate the incidence and management of local and systemic complications afflicting patients with de novo metastatic prostate cancer (mPCa) in Singapore.DesignRetrospective analysis of a large prospective Uro-oncology registry of...

Central nervous system metastases of lung adenocarcinoma harboring EGFR-activating mutations: survival results from a multidisciplinary approach, including EGFR-TKIs

OBJECTIVES: Central nervous system (CNS) metastases are frequent in advanced lung adenocarcinomas harboring EGFR-activating mutations. However, the best treatment approach must be defined. We aimed to evaluate the effectiveness of a multidisciplinary approach for CNS metastases in patients previously untreated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). METHODS: We performed a retrospective analysis of EGFR-TKI naïve patients with CNS metastases from lung adenocarcinomas harboring EGFR-activating mutations treated in a Brazilian academic cancer center. Data were collected from electronic records. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method and compared by logrank test. Cox model was used to evaluate prognostic factors. RESULTS: 35 consecutive patients were included. Treatment included an EGFR-TKI (erlotinib or gefitinib) for all patients, whole brain radiation therapy for 26 patients, stereotactic radiosurgery for 2 patients, and surgery for 8 patients. Median PFS and OS were 8.2 and 11.9 months, respectively. In a multivariable analysis, poor Eastern Cooperative Oncology Group performance status (3-4 vs 0-2) was associated with inferior OS (HR 2.86; 95% CI 1.12-6.74; p=0.016), while radiation therapy to treat brain lesions (yes vs no) showed a trend towards improved OS (HR 0.40; 95% CI 0.15-1.06; p=0.066). No difference was seen between upfront and salvage radiation therapy to the brain. CONCLUSIONS: A multidisciplinary treatment approach, including an EGFR-TKI, allowed promising outcomes for patients with CNS metastases of lung adenocarcinoma harboring EGFR-activating mutations, but the small number of patients here studied precludes definitive conclusions. Although radiation therapy to treat brain metastases has an important role, the best treatment sequence remains unclear. Currently, the approach must be individualized, considering patient characteristics, tumor biology and healthcare resources availability.

Radiotherapy Dose and Induction Chemotherapy Cycles Are Associated With Prognosis and Toxicity Risk: A Retrospective Study of 227 Patients With Unresectable Stage III Non-Small-Cell Lung Cancer

Objective:Concurrent chemoradiation (cCHRT) has been confirmed as the standard treatment for local advanced non-small-cell lung cancer (NSCLC). This study is to assess the appropriate timing of radiotherapy and cycles of induction chemotherapy for those patients.Methods:227 inoperable stage III NSCLC patients were selected, we analyzed the potential prognostic factors and the influence of induction chemotherapy was evaluated.Results:The median survival time was 20.7 months; only 25 patients chose chemotherapy alone (11.0%), 137 patients underwent sequential chemoradiation (sCHRT, 60.4%), and 65 patients received cCHRT (28.6%). Multivariate analyses showed radiation therapy (P = 0.001), the Eastern Cooperative Oncology Group (ECOG) score (P = 0.000) and the lymph node stage (P = 0.001) were independent prognostic factors. cCHRT was not found to be superior (P = 0.330). We selected patients received 60-66 Gy and found the cCHRT groups achieved a relatively better outcome, with a median Overall Survival (OS) of 25.2 months vs 20.1 months in the sCHRT group (P = 0.019). We also found cycles of induction chemotherapy did not compromise survival; however, ≥3 cycles resulted in more grade 3-4 hematology toxicities, with a proportion of 18/99 compared with 53/103 among patients who underwent ≤3 cycles. In addition, higher grade hematology toxicities and poor ECOG were also the most common reasons for abandoning cCHRT.Conclusions:For inoperable stage III NSCLC, cCHRT showed its superiority only when the radiotherapy dose was 60-66 Gy. Cycles of induction chemotherapy did not interfere with survival; however, ≥3 cycles resulted in more grade 3-4 hematology toxicities, leading to the cessation of cCHRT.

Abstract B35: Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging

Abstract Background: Objective responses to first-line systemic chemotherapy in patients (pts) with metastatic pancreatic cancer (mPC) are seen in less than one third of cases. While disease stabilization is achievable for a significant percentage, many of these pts will have radiographic evidence of disease progression (PD) on their first restaging imaging. With patients’ short life expectancy in the metastatic setting, limited systemic treatment options, and significant toxicities associated with multidrug chemotherapy, it is crucial for clinicians to be prudent when deciding whom and when to treat. The purpose of our study was to evaluate outcomes of pts who progressed on their first restaging imaging while on first-line therapy. Methods: We retrospectively analyzed mPC pts treated at MD Anderson since 2011 whose first restaging imaging on first-line therapy demonstrated PD. Data collected included patient demographics, choice of first-line therapy, and whether they received second-line therapy. Primary outcome was overall survival (OS) from date of metastatic diagnosis to death or last follow-up. Results: A total of 121 pts were included in the analysis. Seventy-two received second-line therapy, and 49 did not pursue second-line therapy. The median ages for pts who did and did not receive second-line therapy were 61 and 67, respectively (p=0.001). More pts had a poor Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 2-3) at the time of initial diagnosis in the non-second-line therapy group (31% vs. 6.9%, p=0.003). Forty-two pts (34.7%) received combination 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) first-line, while 72 pts (59.5%) received gemcitabine + nab-paclitaxel (GnP). Thirty-four pts (80%) who received FOLFIRINOX first-line did proceed with second-line therapy, and 29 pts (40%) who received GnP proceeded with second-line therapy. Median OS for those receiving second-line therapy was 8.28 months compared to 2.73 months for those not receiving second-line therapy (p&amp;lt;0.001). Conclusions: Although likely biased due to better performance status and younger age, our mPC pts who progressed rapidly on first-line therapy showed an OS benefit if they received second-line therapy. These results suggest that pts maintaining a good performance status after immediate progression on first-line therapy should be offered second-line therapy. Citation Format: Jonathan D. Mizrahi, Jane E. Rogers, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Gauri R. Varadhachary, Milind M. Javle, Rachna T. Shroff, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Shubham Pant. Outcomes of patients with metastatic pancreatic cancer who progress on first restaging imaging [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B35.

Impact of performance status on treatment outcomes: A real-world study of advanced urothelial cancer treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs. In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS≥2 at ICI initiation. The association between a new ICI in the last 30 and 90days of life (DOL) and death location was also tested. Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS≥2. OS was higher in those with a PS of 0 to 1 than those with a PS≥2 who were treated in the first line (median, 15.2 vs 7.2months; hazard ratio [HR], 0.62; P=.01) but not in subsequent lines (median, 9.8 vs 8.2months; HR, 0.78; P=.27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS≥2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P=.04). Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.

The efficacy of immune checkpoint inhibitors in advanced non-small-cell lung cancer with liver metastases

Although liver metastasis has been known to be associated with poor prognosis, only a few studies have shown an association between liver metastasis and treatment outcomes with immune checkpoint inhibitors (ICI). Furthermore, factors associated with prognosis have remained unclear. The present study therefore evaluates the efficacy of nivolumab, pembrolizumab, and atezolizumab among patients with non-small cell lung cancer (NSCLC) who had liver metastasis and identifies factors correlated with prognosis. A total of 215 patients with advanced and recurrent NSCLC who received ICI therapy at a single center were retrospectively reviewed. A total of 41 patients (19.1%) had liver metastasis upon initiation of ICI therapy. Overall, 125, 64, and 26 patients were treated with nivolumab, pembrolizumab, and atezolizumab, respectively. Among the included patients, those with liver metastasis had shorter overall survival (OS) [hazard ratio (HR), 2.04; 95% CI 1.33-3.13] and progression-free survival (PFS) (HR, 1.89; 95% CI 1.29-1.71) compared to those without the same. Patients with liver metastasis had a response rate (RR) of 22.5%. Among patients with liver metastasis, inferior OS was associated with low albumin, poor Eastern Cooperative Oncology Group performance status, driver mutation, and number of liver metastasis (≥ 5). Moreover, patients with liver metastasis who had good Royal Marsden Hospital (0-1) and Gustave Roussy Immune (0-1) scores showed significantly longer OS and PFS. Despite the poor outcomes with ICI treatment in patients with advanced and recurrent NSCLC who had liver metastasis, some characteristics among patients with liver metastasis may be associated with prognosis.

Decision-making factors for best supportive care alone and prognostic factors after best supportive care in non-small cell lung cancer patients

Among patients with non-small cell lung cancer (NSCLC), best supportive care (BSC) is well-known to improve patient’s quality of life and prolong survival. This study aimed to clarify (1) the decision-making factors of BSC alone and (2) the prognostic factors after selection of no further anticancer therapies. We retrospectively reviewed the clinical data of patients with NSCLC between November 2004 and February 2014, who received BSC as only therapy and BSC after completion of anticancer therapies. One hundred eighteen patients received BSC alone. Among 860 patients treated with anticancer therapies, 236 were selected as control group, 160 of whom received BSC after anticancer therapy. The significant reasons for receiving BSC alone were: comorbidities of dementia, poor Eastern Cooperative Oncology Group performance status (ECOG-PS), patients’ wishes, pulmonary comorbidities, wild type epidermal growth factor receptor (EGFR), relevant social background and psychiatric comorbidities. Poor prognostic factors at the start of BSC were poor ECOG-PS, presence of disseminated intravascular coagulation (DIC), and history of anticancer therapy. NSCLC patients with comorbidities, wild type EGFR, and relevant social background factors tended to receive BSC alone. Post-cancer therapy NSCLC patients and those with DIC and declining ECOG-PS have a shorter survival period from the start of BSC.

Risk factors for postoperative pneumonia after general and digestive surgery: a retrospective single-center study.

Pneumonia is the second-most common complication in postoperative patients and is associated with significant morbidity and high costs of care. We aimed to determine the risk factors for pneumonia after general and digestive surgery. The medical records of 1,016 patients who underwent general and digestive surgery between January 2016 and March 2019 in our hospital were reviewed. Of the 1,016 patients, 67 (6.6%) developed postoperative pneumonia. The multivariate analysis showed that significant predictors of postoperative pneumonia were a poor Eastern Cooperative Oncology Group performance status (ECOG-PS), low forced vital capacity and low forced expiratory volume in one second in the spirometry test, malnutrition (low serum albumin levels and low controlling nutritional status scores and prognostic nutritional index [PNI] values), esophagectomy, upper gastrointestinal surgery, and nonlaparoscopic surgery. Of these factors, the combination of PNI and ECOG-PS clearly stratified patients into low-, intermediate-, and high-risk groups with respect to developing postoperative pneumonia (area under the curve: 0.709). Although postoperative pneumonia is associated with many clinical variables, active medical intervention for the prevention of pneumonia in patients with multiple risk factors can improve the postoperative course. In particular, perioperative nutritional care may prevent postoperative pneumonia in patients with malnutrition and a poor PS.

Impact of Preoperative Skeletal Muscle Quality Measurement on Long-Term Survival After Curative Gastrectomy for Locally Advanced Gastric Cancer.

Skeletal muscle quality is a prognostic factor in various cancers. However, similar studies on curatively resected gastric cancer are lacking. We evaluated skeletal muscle quality using intramuscular adipose tissue content (IMAC) to clarify its impact on survival in patients with locally advanced gastric cancer. We reviewed 370 patients who underwent curative resection for stage II/III gastric cancer. IMAC was calculated using preoperative computed tomography images. IMAC cutoff values were determined for each sex and were set at the 75th percentile. The patients were classified into normal and high IMAC groups according to the cutoff values. Clinicopathological factors and survival outcomes were compared between the two groups. Multivariate Cox regression analysis was used to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). In all, 277 patients were classified into the normal IMAC group and 93 were classified into the high IMAC group. The patients in the high IMAC group were older, more obese, and had more comorbidities and poor Eastern Cooperative Oncology Group performance status than those in the normal IMAC group. Although no significant differences were observed in the pathological findings between the two groups, a high IMAC was significantly associated with poor OS and CSS. Multivariate analysis identified high IMAC as an independent prognostic factor for both OS and CSS (p = 0.046 and p = 0.035, respectively). High IMAC was significantly associated with poor survival, suggesting that skeletal muscle quality has oncological implications in patients with locally advanced gastric cancer.

Survival of Critically Ill Oncologic Patients Requiring Invasive Ventilatory Support: A Prospective Comparative Cohort Study With Nononcologic Patients.

PURPOSECancer is in the process of changing to become a chronic disease; therefore, an increasing number of oncologic patients (OPs) are being admitted to intensive care units (ICUs) for supportive care of disease or therapy-related complications. We compare the short- and long-term outcomes of critically ill mechanically ventilated OPs with those of their nononcologic counterparts.PATIENTS AND METHODSWe performed a prospective study of patients admitted to our ICU between October 2017 and February 2019. Demographic, physiologic, laboratory, clinical, and treatment data were obtained. The primary outcome was survival at 28 days and at the end of the follow-up period. Secondary outcomes were survival according to acute severity scoring (Acute Physiology and Chronic Health Evaluation II score), Eastern Cooperative Oncology Group (ECOG) performance status, and Charlson comorbidity index.RESULTSA total of 1,490 patients were admitted during the study period; 358 patients (24%) were OPs, and 100 of these OPs were supported with mechanical ventilation. Seventy-three percent of OPs had an ECOG performances status of 0 or 1, and 90% had solid tumors. Reason for admission to the ICU was postoperative admission in 44 patients and neutropenic infection in 10 patients. The follow-up period was 148 days (range, 42 to 363 days). Survival at 28 days was similar between OPs and nononcologic patients and associated with the Acute Physiology and Chronic Health Evaluation II score. However, long-term survival was lower in OPs compared with nononcologic patients (52% v 76%, respectively; P < .001) and associated with poor ECOG performance status.CONCLUSIONShort-term survival of critically ill, mechanically ventilated OPs is similar to that of their nononcologic counterparts and is determined by the severity of the critical illness.

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer. Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group. In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P=.0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P=.007]) and whites (323 individuals; 77% [P=.002]), and patients reported higher scores regarding depression (P=.0001), anxiety (P≤.0001), drowsiness (P=.048), and worst feeling of well-being (P=.001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5mg/day [interquartile range (IQR), 30-135mg/day] vs 60mg/day [IQR, 30-105mg/day]; P=.034). Multivariate analysis demonstrated that anxiety (P≤.0001), white race (P=.0092), and poor Eastern Cooperative Oncology Group performance status (P=.0017) were significantly associated with concurrent use. The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

Ambulation Recovery After Surgery for Metastases to the Femur.

BackgroundPostoperative ambulation recovery after surgery for femur metastases has significant implications for not only the patient's quality of life but also administration of further cancer treatment. Thus, identification of preoperative predictors of ambulation recovery is necessary to set appropriate expectations and guide treatment. This study aimed to assess ambulation recovery rate and identify predictors of ambulation recovery in patients undergoing surgery for femur metastases.Materials and MethodsA total of 244 patients who underwent surgery for femur metastases at our institution were reviewed. Patients were considered ambulatory if they were able to walk independently or walk with aids and nonambulatory if they were wheelchair bound or bedridden. The following potential clinicopathologic factors that might predict postoperative ambulation recovery were evaluated: premorbid general status, cancer burden, and local factors.ResultsA total of 165 patients (68%) regained ambulatory status postoperatively. A multivariate analysis revealed poor Eastern Cooperative Oncology Group (ECOG) performance status (odds ratio [OR], 5.327; p < .001) and nonambulatory premorbid ambulatory status (OR, 7.459; p < .001) as independent predictors of poor ambulation recovery after surgery for femur metastases. Postoperative ambulatory status was significantly associated with postoperative survival time (p < .001).ConclusionPostoperative ambulation recovery rate in our cohort was 68%. Premorbid ambulatory status and ECOG performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases.Implications for PracticePostoperative ambulation recovery rate in this cohort was 68%. Premorbid ambulatory status and Eastern Cooperative Oncology Group performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases.

Postoperative Imaging and Tumor Marker Surveillance in Resected Pancreatic Cancer.

Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.

Impact of clinical features on the efficacy of osimertinib therapy in patients with T790M-positive non-small cell lung cancer and acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors.

Osimertinib exhibits good efficacy in patients with T790M-positive non-small cell lung cancer (NSCLC) and acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Compared with the clinical trials, in real-world clinical practice, osimertinib must be administered to older patients and those with poor Eastern Cooperative Oncology Group performance status (ECOG-PS). Therefore, we investigated the association between osimertinib efficacy/safety and PS score, age, and other clinical features in patients with T790M-positive NSCLC. We reviewed all patients with T790M-positive NSCLC and acquired resistance to initial EGFR-TKIs who were administered osimertinib between March 2016 and January 2018 at the Tokyo Metropolitan Cancer and Infectious Diseases Center in Komagome Hospital, Japan. In total, 31 patients, including 8 young (<65 years) and 23 elderly (≥65 years) patients, were included in the study. Of these, 10 (32.3%) patients had poor PS scores. The progression-free survival (PFS) was significantly shorter in young patients was than elderly patients [3.5 vs. 6.4 months, P=0.041; hazard ratio (HR), 2.41]. The overall survival (OS) of the young patients tended to be shorter than that of the elderly patients (5.3 vs. 19.4 months, P=0.067; HR, 2.58). The PFS (9.1 vs. 5.5 months; P=0.071; HR, 0.38) and the OS (not reached vs. 6.6 months, P=0.061; HR, 0.39) were shorter in patients with poor ECOG-PS than those with good ECOG-PS. The toxic effects of osimertinib were manageable. By multivariate analysis, both age and ECOG-PS were independent predictors of osimertinib efficacy. Poor ECOG-PS and younger age were associated with lower efficacy of osimertinib in T790M-positive NSCLC.

Pembrolizumab for advanced nonsmall cell lung cancer: Efficacy and safety in everyday clinical practice

ObjectivesWhile pembrolizumab improves overall survival (OS) in a subset of advanced nonsmall cell lung cancer (aNSCLC) patients (pts) in clinical trials, individuals with poor Eastern Cooperative Oncology Group performance status (ECOG PS) were excluded. Furthermore, some studies have identified a potential link between improved pt outcomes and development of immune related adverse events (irAE.) In a large provincial cohort, we studied the efficacy and safety of pembrolizumab for poor ECOG PS pts and whether irAE correlate with improved OS. Materials and methodsaNSCLC pts treated with pembrolizumab between 06/2015 and 08/2018 at BC Cancer were retrospectively identified. Kaplan-Meier curves of OS from initiation of pembrolizumab were plotted. 3-, 6-, and 9- month landmark Kaplan-Meier analysis was performed and log-rank tests used to determine an association of irAE subtypes with OS. Multivariable logistic regression identified variables associated with grade ≥3 irAE within 3 months of pembrolizumab initiation. ResultsOf 190 pts, 74.2% were treatment naïve and 92.6% had PD-L1 expression ≥ 50%. Median OS in the 1st line and ≥2nd line settings were 24.3 months (95% CI, 9.7-not reached, NR) and 13.4 months (95% CI, 8.1-NR), respectively. Pts with ECOG PS 2/3 had lower median OS than if ECOG PS 0/1 (5.8 months vs. 16.7 months, p < 0.0001). In multivariable analysis, the odds of grade ≥ 3 irAE within 3 months was 6.3 fold higher if ECOG PS 2/3 versus 0/1 (p = 0.05). Development of pneumonitis at the 9 month landmark weakly correlated with decreased OS (p = 0.09). ConclusionIn the studied cohort, ECOG PS 2/3 pts had a significantly lower OS and greater odds of experiencing high-grade irAE than if ECOG PS 0/1. Development of irAE did not result in improved OS. Randomized trials to determine benefit of pembrolizumab for poor ECOG PS pts are needed.