Eastern Cooperative Oncology Group Poor Performance Status Research Articles

Clinical outcomes of ROS1-positive non-small cell lung cancer with limited access to ROS1-tyrosine kinase inhibitors (TKIs): experience from an Indian tertiary referral centre.

ROS1 as a driver mutation is observed in approximately 1%-2% of all non-small cell lung cancer (NSCLC). Given its rarity, we share our experience regarding ROS1-positive NSCLC including the access to ROS1 tyrosine kinase inhibitors (TKIs) in a low-middle income country like India. It is a retrospective analysis of ROS1-positive NSCLC patients registered between January 2015 to December 2021 for demographics, treatment patterns and outcomes i.e., overall survival (OS) and progression free survival (PFS). Baseline characteristics were available for 70 patients of 78 patients positive for ROS1 by fluorescent in situ hybridisation. Median age at presentation was 52 years, 39 (55.7%) were males, most (51, 72.86%) were non-smokers and ten patients (14.3%) had poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) i.e., PS >2 at presentation. A total of 67 patients receiving cancer directed therapy were analysed for survival. The first line (1L) therapies included - ROS1 TKIs in 38, chemotherapy in 20, epidermal growth factor receptor TKI in eight and chemotherapy-bevacizumab in one only. ROS1 TKI was provided to 20 patients as part of an assistance programme. The median OS for patients who received ROS1 TKI was not attained (95% CI 37.85-NA), while it was 8.11 (95% CI 6.31-NA) months for those who did not (HR-0.1673). The median PFS for the 1L ROS1 TKI compared to the no-TKI group was 27.07 (95% CI 24.28-NA) months versus 5.78 (95% CI 3.42-12) months (HR: 0.2047). Poor ECOG PS at presentation was the only independent prognosticator for survival. Using ROS1 TKI improves clinical outcomes in all-comers though statistically not significant. To further improve outcomes, future trials should pay special attention to patients with poor PS and find a way to increase the current limited access to TKI.

Real-world analysis of first-line afatinib in patients with EGFR-mutant non-small cell lung cancer and brain metastasis: survival and prognostic factors.

Overall survival (OS) in patients with non-small cell lung cancer (NSCLC) and brain metastases (BMs) is poor. We aimed to identify prognostic factors and ascertain treatment outcomes of first-line afatinib for patients with epidermal growth factor receptor (EGFR)-mutant NSCLC with BM in a real-world setting. This retrospective observational study reviewed electronic records of patients with EGFR-mutant NSCLC who received first-line afatinib treatment between October 2014 and October 2019 in 16 hospitals across South Korea. The Kaplan-Meier method estimated time on treatment (TOT) and OS; multivariate analyses were performed using Cox proportional hazards (PH) models. Among 703 patients who received first-line afatinib, 262 (37.3%) had baseline BM. Of 441 patients without baseline BM, 92 (20.9%) developed central nervous system (CNS) failure. Compared with patients without CNS failure, those with CNS failure during afatinib treatment were younger (P=0.012), had a higher Eastern Cooperative Oncology Group (ECOG) performance status (PS) (P<0.001), increased metastatic site involvement (P<0.001), advanced stage disease (P<0.001), with liver metastasis (P=0.008) and/or bone metastasis (P<0.001) at baseline. Cumulative incidence of CNS failure in years 1, 2 and 3 was 10.1%, 21.5% and 30.0%, respectively. In multivariate analysis, cumulative incidence was significantly higher in patients with ECOG PS ≥2 (P<0.001), uncommon EGFR mutations (P=0.001), and no baseline pleural metastasis (P=0.017). Median TOT was 16.0 months (95% CI: 14.8-17.2) and, in patients with CNS failure, without CNS failure, and with baseline BM was 12.2, 18.9, and 14.1 months, respectively (P<0.001). Median OS was 52.9 months (95% CI: 45.4-60.3) and, in patients with CNS failure, without CNS failure, and with baseline BM was 29.1, 67.3 and 48.5 months, respectively (P<0.001). First-line afatinib in the real-world setting showed clinically meaningful effectiveness in patients with EGFR-mutant NSCLC and BM. CNS failure was a poor prognostic factor for TOT and OS correlating with younger age, poor ECOG PS, higher metastatic number, advanced disease stage, uncommon EGFR mutations, and baseline liver and/or bone metastases.

Long-Term Results with Thiotepa-Containing Conditioning Regimens for Autologous Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) remains a cornerstone in the treatment of both Hodgkin lymphoma (HL) and various non-Hodgkin lymphoma (NHL) subtypes. BEAM (carmustine, etoposide, cytarabine, and melphalan) is the most frequently used conditioning regimen; however, owing due to limited availability and toxicity of carmustine, thiotepa-containing regimens have been suggested. We previously reported encouraging results in ASCT with a TECAM (thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan) conditioning regimen from 2000 to 2013. We aimed to update our experience with the TECAM regimen by adding our experience from 2013 to 2020 to the previously reported cohort. Moreover, we aimed to use the detailed data for the 2 transplant cohorts to identify improvements in ASCT outcomes in the recent era. We retrospectively analyzed all lymphoma patients who underwent ASCT at our center between January 2000 and December 2020. A total of 353 lymphoma patients were included (142 in the newer cohort added to 211 previously reported patients), all of whom were treated with our standard TECAM conditioning regimen. The cohort included 127 patients with HL, 107 with DLBCL, and 119 with other NHL subtypes. The newer cohort was characterized by significantly poorer Eastern Cooperative Oncology Group Performance Status (ECOG-PS) prior to ASCT (45.7% versus 19.3% with ECOG-PS ≥1; P < .01), whereas a higher proportion of patients entered transplantation in complete response (CR) (71.9% versus 47.8%; P < .01). The median follow-up after ASCT was 136.4 months (95% confidence interval [CI], 91.4 to 181.4 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates post-ASCT for the entire cohort were 59.8% and 79.3%, respectively. Evaluating the 303 of 353 patients (86.4%) who entered ASCT with a responsive disease-a population that represents today's approach to the selection of patients for ASCT-the 3-year PFS and OS rates were 61.5% and 81.9%, respectively. In this population, the 3-year PFS rate was 62.2% for HL, 62.6% for DLBCL, 64.3% for primary central nervous system lymphoma (PCNSL), and the 3-year OS rate were 90.1%, 75.2%, and 78.6%, respectively. OS was significantly better in the newer cohort (P < .01), but not when evaluating only patients who entered ASCT with responsive disease. Dose reductions, poor disease status, and poor ECOG-PS at ASCT entry were associated with worse outcomes across all lymphoma subtypes. In accordance with our previous report, patients entering transplantation for DLBCL with a partial response achieved similar outcomes as those with a CR. Eighteen patients died within the first 100 days, 8 due to disease progression and 10 due to transplantation-related complications (2.8%). There were no cases of interstitial pneumonitis syndrome. Twenty-two cases (6.2%) of secondary malignancies were documented. Our results confirm that TECAM is an effective and safe conditioning regimen for ASCT in patients with HL and various NHLs, including favorable results in PCNSL. Despite a higher proportion of frail patients, the newer cohort's outcomes were favorable, driven by better lymphoma control pretransplantation. In the DLBCL cohort, ECOG-PS had more prognostic value than achieving a CR pre-ASCT, a finding relevant to the optimal allocation of patients to different treatment options in the era of chimeric antigen receptor T cell availability.

Survival Analysis and Prognostic Factors for Metastatic Colorectal Cancer Patients Treated with Chemotherapy

Background: Currently, there are limited data on prognostic factors in metastatic colorectal cancer (mCRC) patients treated with chemotherapy. Prognostic factors in colorectal cancer remain varied in each situation when considering their use in different contexts. Objective: To analyze the independent prognostic factors of mCRC in patients receiving chemotherapy. Materials and Methods: Data from 156 mCRC patients completely treated by first-line chemotherapy were collected between 2013 and 2018. A retrospective observational cohort study was conducted to evaluate the survival analysis and prognostic factors. A univariate and multivariate Cox’s proportional-hazards model were used to explore and identify the independent prognostic factors for overall survival. An analysis of the restricted mean survival time (RMST) method was used to estimate the event-free time from zero to 24 months. Results: Median overall survival was 18.3 months (96% CI 15.31 to 20.95). The multivariate Cox’s proportional-hazards model revealed two rognostic factors for decreased survival, poor Eastern Cooperative Oncology Group (ECOG) performance status greater than or equal to 2 (HR 2.05, 95% CI 1.08 to 3.86; p=0.027) and hypoalbuminemia lower than 3.5 g/dL (HR 3.47, 95% CI 2.10 to 5.75, p&lt;0.001). Analysis of the RMST method was used to estimate the event-free time from zero to 24 months in the group receiving first-line oxaliplatin-based chemotherapy, secondline oxaliplatin-based chemotherapy, and second-line irinotecan-based chemotherapy. It was found that only the group receiving second-line oxaliplatin-based chemotherapy had significantly longer survival time than the comparison groups, with an adjusted mean of survival time of 21.12 months (different mean 5.99, 95% CI 3.99 to 8.00, p&lt;0.001). Conclusion: Poor ECOG performance status greater than or equal to 2, and hypoalbuminemia lower than 3.5 g/dL can be used as prognostic factors in mCRC patients receiving chemotherapy. Keywords: Survival; Prognostic factors; Metastatic colorectal cancer; Chemotherapy

Frontline immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma patients with poor performance status

BackgroundImmune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. MethodsWe performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. ResultsWe identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. ConclusionWe report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results.

Tecam (Thiotepa, Etoposide, cyclophosphamide, Cytarabine and Melphalan) Is an Effective and Safe Conditioning Regimen for Autologous Transplant in Lymphoma

Background: Autologous stem cell transplant (ASCT) is still a cornerstone in the treatment armamentarium of both Hodgkin's lymphoma (HL) and various non-Hodgkin lymphoma (NHL) subtypes. BEAM (carmustine, cytarabine, etoposide and melphalan) is the most commonly used conditioning regimen; however, due to limited availability and toxicity of carmustine, thiotepa-containing regimens have been suggested. We previously reported encouraging results with TECAM conditioning regimen (thiotepa, etoposide, cyclophosphamide, cytarabine and melphalan). Objectives: We aimed to update our experience with TECAM as the conditioning regimen for ASCT in all lymphomas, by adding our experience from Oct 2013 to 2020 to the previously reported cohort of Jan 2000 - Sep 2013 (Grisariu et al 2018). Moreover, we aimed to utilize the detailed data on the two transplant cohorts, from different eras, to appreciate possible improvement in ASCT outcome in the recent era. Furthermore, we aimed to evaluate our ASCT results in different NHL subgroups. Methods: We retrospectively analyzed all lymphoma patients who underwent ASCT in our center between 2000 and 2020. Results: Three hundred and fifty-three patients were included (141 in the newer cohort added to the 212 in the cohort of 2000-2013 previously reported), all of whom were treated with TECAM, which is our standard conditioning regimen for lymphoma patients undergoing ASCT. The cohort included 126 HL patients, 108 diffuse large B-cell lymphoma (DLBCL) patients and 119 patients of other subtypes (among them 14 diagnosed with primary central nervous system lymphoma (PCNSL)). The median number of treatment lines before ASCT was 2 (range 1-7). Compared to the older cohort, the newer cohort was characterized by significantly poorer Eastern Cooperative Oncology Group performance status (ECOG-PS) prior to ASCT (45.6% vs 19.3% with ECOG-PS ≥1, p<0.001), while A Higher proportion of patients in the newer cohort were in complete remission (CR) status at transplantation (71.9% vs. 47.8%, p<0.001). The median follow-up from ASCT was 38.8 months (range: 0.03-251.6). The 3-years progression-free survival (PFS) and overall survival (OS) rates post-ASCT were 59.8% and 79.3% respectively. For HL, the 3-years PFS and OS rates were 61.1% and 89% respectively; for DLBCL 59.4% and 67.9% respectively and for PCNSL 64.3% and 78.6% respectively. Outcomes of the newer cohort were significantly favorable (3-years OS of 87.3% vs. 73.8%, p=0.015, 5-year OS of 86.6% vs 69%, p=0.008, Figure 1). Poor disease status and poor ECOG-PS at ASCT entry were associated with worse outcomes across all lymphoma subtypes. Dose reduction was associated with a shorter PFS but did not affect OS. Similar to our previous report, patients entering transplantation for DLBCL with a partial response (PR) achieved similar outcomes as those with CR. Eighteen patients died within the first 100 days, eight due to disease progression, and 10 due to transplant related causes (2.8%). There were no cases of interstitial pneumonitis syndrome (IPS). Twenty cases (5.7%) of secondary malignancies were documented. Discussion: Our results confirms that TECAM is an effective and safe conditioning regimen for ASCT in patients with HL and various NHL's, including favorable results in PCNSL. Though outcomes were compared to published experience with BEAM, we have shown similar efficacy with a favorable toxicity profile. Despite a higher proportion of frail patients, the newer cohort's outcomes were favorable, probably due to better lymphoma control at transplant entry, which can be explained by more efficacious therapies pre- and post-transplant. In the DLBCL cohort, ECOG performance status was more prognostic than achieving a CR before ASCT, a finding that is relevant to the optimal selection of patients to different second-line options in the era of chimeric antigen receptor (CAR-T) availability. Conclusion: TECAM is a safe, effective, CNS-penetrating conditioning regimen for ASCT, in HL and various NHL's. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Nutrition-inflammation marker enhances prognostic value to ECOG performance status in overweight or obese patients with cancer.

Overweight or obese cancer patients are more likely to develop a proinflammatory status. The aim of this study was to investigate whether the nutrition-inflammation marker can provide additional prognostic information on top of well-established Eastern Cooperative Oncology Group performance status (ECOG-PS) in overweight or obese patients with cancer. A total of 1667 overweight or obese cancer patients were enrolled in this study. We assessed the prediction accuracy of 10 nutrition-inflammation markers by time-dependent receiver operating characteristic (ROC) and elucidated their association with overall survival by the Kaplan-Meier method and a Cox model. In this analysis, the majority of patients had a good performance status (ECOG-PS score ≤1; 88.3%). Both the area under ROC curves and the C-index of the lymphocyte-C-reactive protein ratio (LCR) demonstrated that LCR was the most significant nutrition-inflammation marker correlated with survival. In patients with good ECOG-PS, a low LCR was significantly associated with poorer prognosisand enhanced the predictive ability of one-year mortality. For specific tumor types, a low LCR was an independent prognostic factor for lung cancer, upper gastrointestinal cancer, and colorectal cancer, and it tended to be a significant predictor for breast cancer. In addition, those patients with a combined low LCR and poorer ECOG-PS (ECOG-PS score >1) showed the worst prognosis. The LCR is more strongly associated with overall survival than other nutrition-inflammation markers, and it is able to further detect patients with worse prognosis on top of ECOG-PS in overweight or obese patients with cancer.

Systematic performance status assessment by primary care providers in patients with advanced cancer and its impact on referral to palliative care and cost in a value-based practice.

6595 Background: Value Based (VB) Care model has been growing in the primary care (PrC) Medicare population, its role in oncology and integration with VB PrC has not been well defined. Key initiatives in VB include reducing hospitalizations by multidisciplinary management of chronic conditions. Earlier Palliative Care (PaC) has shown to favorably impact outcomes. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) is a validated tool used for decision making. Poor PS is associated with worse outcomes and futile end of life care; Guidelines recommend using ECOG-PS to decide on involvement of PaC in patients (pts) with metastatic cancer (mCa). ECOG-PS is subject to significant variability among oncologists and rarely used by PrC providers (PCPs). We created a standardized system for ECOG-PS documentation and monitoring by PCPs in a VB model in a large Medicare Advantage (MA) population with the goal of increasing earlier PaC referrals. Methods: Pts with mCa managed by PCPs in a multi-state MA practice were identified via EMR from February 2021 to September 2021. At every visit, an automated alert asked PCPs to determine pts’ ECOG-PS and for those ≥ 2, recommendation to refer to PaC. PCPs were trained on use of the tool and were given a script to discuss with pts the role of PaC. Hospital admissions as well as total cost of care was measured in pts comanaged by PCP’s &amp; PaC versus those managed by PCPs &amp;Oncology without PaC. Statistical analysis between the groups was done using Pearson's Chi-squared test with Yates' continuity correction. Results: An ECOG-PS was measured in a total of 565 pts with mCa during the study period. Median age was 73 years, 40% were ≥75 yrs. 55% were female. Breast, Prostate, Lung, Colorectal and Gyn ca accounted for 75% cases. ECOG was documented in 97% of patients; 250 (44%) had ECOG ≥ 2, 124 (22%) had ECOG ≥ 3. Of those PaC referral was done by the PCP in 70%, in total 69 patients were comanaged by PC vs 181 who did not. Pts that had PaC involvement were 43% less likely (RR 0.57 [95%CI 0.33,0.98 p = 0.043]) to be admitted compared to patients without PC. Pts without PaC that were admitted had 238% higher admission days per 1,000 pts compared to pts comanaged by PaC. Total medical costs of pts comanaged by PaC was 86% lower after PaC involvement $18,541 3-months prior vs $2,742 3-months after PaC involvemen, driven by lower part A and part B costs (p=0.001) Conclusions: ECOG PS monitoring of pts with mCa by PCPs was very successful, easy to perform and implement in a PrC. Poor PS is common in this medicare advantage population. PaC involvement in pts with poor ECOG-PS was associated with lower admission rates at the end of life, and significantly lower total medical costs. [Table: see text]

Sarcopenia are Associated with Poor Performance Status in Indonesian Patients with Hepatocellular Carcinoma

Background: Sarcopenia affects hepatocellular carcinoma (HCC) prognosis. Sarcopenia can be assessed by using skeletal muscle index (SMI), measured on transverse CT images at the third lumbar vertebra (L3). HCC staging consists of liver function assessment and Eastern Cooperative Oncology Group performance status (ECOG-PS). ECOG-PS can reflect physical function. This study was aimed to describe the proportion of sarcopenia among adults, using Japan Society of Hepatology criteria and explore association between sarcopenia and poor performance status.Method: The study was conducted in a tertiary hospital during January – October 2021. SMI were evaluated using computed tomography images of L3 in 85 HCC patients. Clinical, laboratory and body composition data were analyzed using bivariate analysis. Logistic regression was performed to obtain an independent association between ECOG-PS and sarcopenic status of HCC patients.Results: Eighty-five HCC patients (median age, 52 years) were analyzed. Sarcopenia was observed in 49,4% of HCC patients. On multivariate binary regression analysis, a poor ECOG-PS remained independently associated with sarcopenia in HCC (adjusted OR = 4.169 (CI 95% = 1.504-11,555), p 0,006).Conclusion: Sarcopenia has high proportion in HCC patients. There were strong association between ECOG-PS and sarcopenia in HC.

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry

IntroductionPatients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far. MethodsCapitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics. ResultsAs of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group—performance status (ECOG-PS) (OR = 2.47, 1.87–3.26), neutrophil count (OR = 2.46, 1.76–3.44), serum procalcitonin (OR = 2.37, 1.64–3.43), development of pneumonia (OR = 1.95, 1.48–2.58), C-reactive protein (OR = 1.90, 1.43–2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46–2.66), and age (OR = 1.71, 1.29–2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75–0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis. ConclusionsFrom 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.

Real-World Outcomes Among Crizotinib-Treated Patients with ROS1-Positive Advanced Non-Small-Cell Lung Cancer: A Community Oncology-Based Observational Study.

BackgroundCrizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited.ObjectiveThis study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting.Patients and MethodsWe conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan–Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS). A Cox proportional hazards model was conducted to determine factors associated with OS.ResultsThe study cohort included 38 ROS1-positive patients treated with crizotinib. The median age was 68 years (interquartile range 60.0–73.0) and 65.8% were female. Over 50% were current/former smokers, and 18.4% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2. Overall, 21 (55.3%) patients remained on crizotinib, 10 (26.3%) had evidence of subsequent treatment, and 16 (42.1%) died. The median TTD, TTNT, and OS were 25.2 months [95% confidence interval (CI): 5.2–not reached (NR)], 25.0 months (95% CI 5.2–61.0), and 36.2 months (95% CI 15.9–NR), respectively. In a multivariate Cox regression model, ECOG performance status of 2 was associated with a 4.9-fold higher risk of death (hazard ratio = 4.9; 95% CI 1.1–21.4) compared to ECOG performance status of 0 or 1.ConclusionsThis ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11523-021-00860-z.

Hypomethylating Agents Versus Intensive Chemotherapy in Elderly Patients (Age ≥ 70) with Acute Myeloid Leukemia with High White Blood Cell Count

▪BackgroundAcute myeloid leukemia (AML) is primarily a disease of older adults, with 40-50% of patients ≥ 70 years old at diagnosis. Optimal frontline therapy for elderly AML patients remains controversial. Intensive chemotherapy (IC) is often favored in those AML patients who present with leukocytosis (P-AML), yet the evidence to support this practice as opposed to lower intensity therapy is scarce. We aimed to investigate the outcomes of older patients with P-AML based on treatment choice of intensive chemotherapy (IC) vs hypomethylating agents (HMA).MethodsWe retrospectively analyzed 983 elderly AML patients (age ≥ 70 years) treated at Moffitt Cancer Center between 1995 and 2016. Patients with prior exposure to HMA for non-AML diagnoses were excluded. We focused on P-AML patients, defined as baseline WBC ≥ 10x109/L, who received initial therapy with either: intensive chemotherapy (IC) (defined as daunorubicin/cytarabine or equivalent) or hypomethylating agents (HMA) (azacitidine (AZA) or decitabine (DEC)). Age, type of AML, history of antecedent hematologic disease, cytogenetics (per European LeukemiaNet (ELN) criteria), Eastern Cooperative Oncology Group (ECOG) performance status, Charlson comorbidity Index (CCI), complete blood counts and myeloblast percentage at time of diagnosis were obtained for each patient. Kaplan-Meier analysis was performed to calculate overall survival (OS) and the log-rank test was used to determine significance where a p-value of 0.05 was defined as significant. Fisher's exact t-test, hazard ratios (HR) and confidence interval (CI) were calculated using GraphPad Prism v7.03. Univariate and multivariate analysis for the baseline characteristics and type of therapy were performed using SPSS v24.0 to determine prognostic impact.ResultsWithin the entire cohort of older AML patients, we identified 156 who were treated with either HMA (n=41) or IC (n=115). Baseline characteristics of these patients are described in Figure 1A. Significant baseline differences in age, hemoglobin, WBC, ELN cytogenetic category, marrow blast %, and CCI score were observed between the HMA and IC groups. Most notably, the HMA group were older (median age 77 yrs vs 74 yrs, p=0.0037), had a higher incidence of poor-risk cytogenetics (36.6% vs 7%), and were more likely to have CCI score ≥ 3 (29.3% vs 8.7%).Median time of initial treatment was 4.3 months (range: 0.10-70.0 months) in the HMA group compared to 0.5 months (range: 0.33-1.90months) in the IC group. Median OS of the entire group was 7.85 mo. Median OS in the HMA-treated patients was superior to IC treated patients (13.7 mo vs. 5.1 mo, HR 0.63, 95% CI 0.443 - 0.886, p=0.0082) (Figure 1B). The 12 month survival rate was 55.0% in the HMA group and 31.0% in the IC group (p=0.0082). Fifty-two (33%) patients achieved CR/CRi. There was no difference in CR/CRi rates between HMA or IC treated cohorts (30.0% vs. 34.8%, p=0.6983). Rate of relapse upon achievement of CR/CRi was not statistically significant between HMA and IC cohort (41.7% vs. 62.5%, p=0.3181). The 30-day mortality rate was lower in the HMA group compared to the IC group (7.3% vs 24.4%, p=0.0217).Univariate analysis identified treatment type (p<0.0001), cytogenetic risk category (p <0.0001), and ECOG performance status (p<0.0001) as significant prognostic factors for OS. Multivariate analysis identified IC treatment (HR 2.01, 95% CI 1.24-3.26, p=0.005) and poor ECOG performance status (HR 4.30, 95% CI 1.182-15.659, p=0.027) as independent negative predictors of OS.ConclusionsElderly patients (age ≥ 70) with proliferative AML appear to achieve a survival advantage with HMA-based frontline therapy compared to IC, despite a disproportionately higher incidence of traditionally adverse prognostic features (poor-risk cytogenetics, high CCI score) in the HMA group. The reasons for this observation are unclear, but could relate to a higher early death rate with IC or biologic/molecular features that induce greater sensitivity to HMAs, which should be studied in future analyses. Although this study was limited by small size and retrospective nature, our findings cast doubt on the notion that intensive therapy should be the standard frontline approach in elderly patients proliferative/high WBC AML. [Display omitted] DisclosuresSallman:Celgene: Research Funding. Padron:Incyte: Honoraria, Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria. Lancet:Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy; Pfizer: Other: Institutional research funding.

The Importance of a Detailed Geriatric Functional Assessment of Older Patients with Cancer

Background: For older patients with cancer, maintaining or regaining their ability to care of themselves is of major interest. Which tools are appropriate to measure this? Different tools to assess functional status (FS) are established in geriatric and oncological care, but they have been compared poorly in the past. Patients and Methods: Within a prospective cohort trial, we included 483 patients: 198 older patients with cancer, 156 younger patients with cancer, and 129 older patients with benign disease. FS was assessed as Eastern Cooperative Oncology Group performance status (ECOG-PS), activities of daily living (ADL), and instrumental activities of daily living (IADL). Results were compared for their differences in identifying patients as functionally compromised. Summary: The relative frequency of cancer patients with limitations in ECOG-PS, ADL, and IADL, respectively, increased from 25.7, 13.5, and 17.9% in those <60 years of age to 50.0, 47.1, and 66.7% in those ≥80 years. Results in older patients with cancer were comparable to older patients with benign disease. In older patients with cancer, 20.7 and 21.6% with a good ECOG-PS had limitations in ADL and IADL, respectively; of those without limitations in ADL and IADL, 34.7 and 26.0%, respectively, had a poor ECOG-PS. Treatment approach (curative vs. palliative) was found to be significantly associated with functional limitations. Key Messages: Geriatric and oncological measure of FS report differences in functional impairment. Geriatric functional measures are more sensitive to age-related changes and should be included as patient-reported outcomes in clinical trials and care.

High D-dimer is a predictor for short-term mortality in patients with active cancer and acute pulmonary embolism

Objectives: Acute pulmonary embolism (PE) is the main cause of death in cancer patients, but there are limited prognostic tools for the patients with active cancer and acute PE. We aimed to identify prognostic factors of 30-day mortality in patients with active cancer and acute PE. Methods: This retrospective observational study included all adult patients aged ≥18 years with active cancer and acute PE from February 2017 to February 2019 at the emergency department in tertiary care hospital, Seoul, Korea. The primary outcome is 30-day mortality. Results: A total of 178 patients were included with a mean age of 63.9 years (SD 10.4) and males of 52.8%. The overall 30-day mortality rate was 30.9%. In a multivariable logistic analysis, high D-dimer, defined as ≥median value of 14.7 µg/mL, with odds ratio (OR) 2.47 (95% confidence interval [CI], 1.15–5.33), high Pulmonary Embolism Severity Index (PESI) scores with OR 2.95 (95% CI, 1.21–7.75) for class IV and OR 2.90 (95% CI, 1.06–7.90) for class V, and Eastern Cooperative Oncology Group (ECOG) performance status 3/4 with OR 3.22 (95% CI, 1.18–8.76) were independent predictors of 30-day mortality. Conclusion: High D-dimer values, high PESI scores, and poor ECOG performance status may be reliable predictors of mortality in patients with active cancer and acute PE.

Lazarus type response to immunotherapy in three patients with poor performance status and locally advanced NSCLC: a case series and literature review.

Immune checkpoint inhibitors (ICIs) have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the safety and efficacy of ICIs in severe advanced NSCLC patients with poor performance status (PS) are still unclear. In the current study, we report a retrospective case series of three critically ill NSCLC patients with poor PS treated with immunotherapy in our hospital, and discussed these cases with reference to the existing literature and guidelines. Before treatment, the Eastern Cooperative Oncology Group (ECOG) PS scores of all three patients were 4, while programmed cell death protein ligand-1 (PD-L1) was strongly expressed (over 50%). After initiating anti-programmed cell death 1 (PD-1)/PD-L1 agents, the PS score of the three patients improved rapidly to 0-1 in a short time. A Lazarus type response was observed in all patients. There were no grade 3-4 immune-related adverse events (irAEs) in any of the patients, and only one patient developed rash (grade 2 irAE) and hypothyroidism (grade 2 irAE). The best response across all three patients was partial response (PR). As of the latest follow-up date on June 10, 2020, two patients are still alive, with the other having died on January 14, 2020, whose progression-free survival (PFS) and overall survival (OS) were 11 and 16 months, respectively. Immunotherapy is still an effective and low-toxicity option for severe advanced NSCLC patients with poor PS. Lazarus type response may occur, especially in patients whose PD-L1 is strongly expressed (≥50%). However, a greater amount of real-world data or randomized clinical trials are needed in this setting.

Hospitalizations and Clinical Outcome in Metastatic Colorectal Cancer During Regorafenib or TAS-102 Therapy.

Simple SummaryRegorafenib and TAS-102 showed a survival benefit against placebo, and both drugs are approved for the treatment of metastatic colorectal cancer (mCRC) beyond second-line. The highly differential toxicity profile of both substances has led to a potentially biased perception of drug tolerability and complications—such as hospitalization—in the oncologic community. The aim of this retrospective analysis was to investigate hospitalization frequency during regorafenib and TAS-102 treatment and the impact of hospitalizations on survival. Treatment with regorafenib as well as a low Eastern Cooperative Oncology Group (ECOG) performance status turned out to be independent risk factors for hospitalization. Hospitalizations due to gastrointestinal toxicity were only seen with regorafenib. However, hospitalizations during regorafenib or TAS-102 treatment did not impact survival. In light of increased gastrointestinal toxicity leading to hospitalization during regorafenib treatment, we call for increased awareness to drug-specific toxicities, in order to prevent unnecessary complications by the early detection of adverse events and prompt counteraction.Current National Comprehensive Cancer Network (NCCN) and European Society of Medical Oncology (ESMO) guidelines recommend regorafenib or trifluridine/tipiracil (TAS-102) for the third-line therapy of metastatic colorectal cancer (mCRC). In this analysis, we evaluated hospitalizations during regorafenib or TAS-102 treatment and the impact of hospitalizations on overall survival (OS). This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 at the tertiary cancer centers in Salzburg and Wels-Grieskirchen, Austria. Between January 2013 and May 2019, 93 patients started third- or fourth-line therapy with regorafenib or TAS-102. Tumor therapy (regorafenib versus TAS-102, HR: 1.95 [95% CI: 1.07–3.54], p = 0.03) and the Eastern Cooperative Oncology Group (ECOG) performance status (2–3 versus 0–1, HR: 4.04 [95% CI: 2.11–7.71], p < 0.001) showed a statistically significant association with hospitalization risk in multivariate analysis. The corresponding hospitalization probability from initiation of third- or fourth-line was 30% with regorafenib versus 18% with TAS-102 at five weeks and 41% versus 28% at ten weeks, respectively. Hospitalizations irrespective of cause during regorafenib or TAS-102 therapy did neither impact median survival in patients undergoing only third-line therapy (never-hospitalized: 5.7 months [95% CI: 3.9–10.5] versus hospitalized: 5.4 months [95% CI: 2.8–9.6], p = 0.45), nor in patients receiving third- and fourth-line therapy (12.2 months [95% CI: 10.6–28.8] versus 18.6 months [95% CI: 6.3-not reached], p = 0.90). In conclusion, apart from poor ECOG performance status, regorafenib therapy was associated with an increased hospitalization probability during palliative systemic third- and fourth-line therapy in mCRC. However, hospitalizations during regorafenib or TAS-102 therapy did not impact OS beyond second-line therapy.

Comparison of the prognostic value of MUST, ECOG-PS, mGPS and CT derived body composition analysis in patients with advanced lung cancer

Assessment of malnutrition, performance status and systemic inflammation are routine aspects of clinical assessment in patients with advanced cancer. There is increasing evidence that body composition measurements from routine staging CT also have prognostic value. To date the relative prognostic value of Malnutrition Universal Screening Tool (MUST), Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic score (mGPS) and CT derived body composition analysis in patients with advanced lung cancer has not been examined. The aim of the present study was to examine this relationship. Clinicopathological characteristics including MUST, ECOG-PS, mGPS and body composition data were collected pre-radiotherapy from a prospectively maintained database of patients with advanced lung cancer (n=643). Using the MUST score, patients were classified into low (MUST=0, n=189), medium (MUST=1, n=341) and high (MUST≥2, n=113) malnutrition risk and their relationship to systemic inflammatory response (SIR) and body composition with clinical outcomes were examined using univariate and multivariate analyses. Primary outcome of the study was overall survival. Compared with the patients at low nutrition risk (MUST=0), patients at moderate to high risk (MUST 1-≥2) had poorer ECOG-PS>1 (p<0.01), elevated modified frailty index (mFI) (p<0.001), elevated mGPS (p<0.001), lower skeletal muscle index (SMI, p<0.01) but not lower skeletal muscle density (SMD, p=0.115). MUST was an important prognostic marker of 12 months overall survival (p=0.001). On multivariate analysis, higher MUST (HR 1.16, 95% CI 1.03-1.31, p<0.05), ECOG-PS>1 (HR 1.23, 95% CI 1.10-1.39, p<0.001), elevated mGPS (HR 1.20, 95% CI 1.09-1.33, p<0.001) were independently associated with overall survival. A large proportion of patients (71%) with advanced lung cancer were at moderate to high nutrition risk. Higher malnutrition risk and elevated inflammatory status were independently associated with poor overall survival. MUST, ECOG-PS and mGPS all had independent prognostic value and may form an important prognostic framework in treatment decision making and resource utilization.

Efficacy and Safety of Immune Checkpoint Inhibitors in Patients with Microsatellite Instability-High End-Stage Cancers and Poor Performance Status Related to High Disease Burden.

Few real-world series on the efficacy and safety of anti-programmed cell death protein-1(PD-1)/programmed death ligand-1(PD-L1)-based therapy are available in molecularly unselected patients with poor performance status (PS) and specific types of advanced cancers, because such populations are typically excluded from clinical trials due to poor life expectancy and risk of toxicity. This multicenter retrospective case series included patients with microsatellite instability (MSI)-high metastatic cancers with Eastern Cooperative Oncology Group (ECOG) PS of 2 or 3 not related to comorbidities receiving anti-PD-1 with or without anti-CTLA-4 therapy after failure of at least one prior treatment line. We included 27 patients with six diverse tumor types: colorectal (n = 18), gastric (n = 5), biliary tract, pancreatic, small bowel, and endometrial cancers (n = 1 each). Baseline ECOG PS was 2 (74%) or 3 (26%). Overall response rate was 33%, with six partial and three complete responses. Median time to response was 3.1, months and median duration of response was 16.9 months. Median progression-free survival was 3.4 months (95% CI: 2.3 to not evaluable), and 18-month overall survival was 50.8% (95% confidence interval, 32.7-78.8). Baseline variables were not associated with survival outcomes. ECOG PS 1 was reached by 52% of patients in a median time of 6 weeks, and ECOG PS 0 was reached by 30% of patients in a median time of 10 weeks. In a high proportion of patients with MSI-high cancers and poor performance status related to end-stage disease, salvage immunotherapy can induce potentially long-lasting "Lazarus responses". Immunotherapy decisions near the end-of-life should be carefully integrated with predictive biomarkers and with palliative care measures in the real-world setting. In this retrospective cohort study of 27 pretreated patients with microsatellite instability (MSI)-high cancers and Eastern Cooperative Oncology Group performance status of 2 or 3 not related to comorbidities, PD-1/PD-L1-based therapy induced a RECIST response in 33% of patients, with a median duration of 16.9 months, and an improvement of performance status in 52% of patients. MSI-high status can be used in clinical practice as a tumor-agnostic predictive biomarker to select critically ill patients with end-stage cancers for salvage immunotherapy.

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.

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.