Eastern Cooperative Oncology Group PS Research Articles

First-line FOLFOX therapy for advanced esophageal squamous cell carcinoma: Multicenter prospective study in Japan.

280 Background: Cisplatin (CDDP) plus fluoropyrimidine was the standard first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). FOLFOX is promising option especially in patients with ESCC intolerant to CDDP but there were limited data on efficacy and safety of FOLFOX. We conducted a multicenter prospective observational study of FOLFOX for Japanese patients with ESCC intolerant to CDDP. Methods: Eligible participants had clinical stage IVB ESCC, with measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, intolerant to CDDP, but tolerant to FOLFOX. FOLFOX (oxaliplatin 85 mg/m², leucovorin 200 mg/m², bolus fluorouracil 400 mg/m², and infusional fluorouracil 2400 mg/m²) was administered every 14 days. The primary endpoint was the response rate (RR) by RECIST v1.1 and the null hypothesis of RR was 10%. Based on the assumption of performing a one-sided test with an α of 0.10, 29 patients were needed to ensure the statistical power of 90% assuming RR of 30%. Results: In this study, 31 patients were enrolled from 14 hospitals between Apr. 2021, and Jul. 2022 and 30 patients received FOLFOX. The patient characteristics were: median age, 77 (range 66–89); male/female, 30/1; ECOG PS 0/1/2, 16/12/3; median creatinine clearance, 49.9 ml/min (33.4–80.2); median G8 score, 12 (range 7–17); and median CARG score, 8 (range 6–13). As the data cutoff of Jul 2023, all 30 patients discontinued FOLFOX. The reason for treatment discontinuation was disease progression, 86.7%; adverse events, 13.3%. Median follow-up time (interquartile range: IQR) was 20.2 (IQR 13.7–23.1) months. Median number of cycles administered were 5 (range 1–24). The RR was 22.6% (80%CI 0.13–0.35; p = 0.031) and disease control rate was 42.0%. Median progression-free survival was 3.9 months (95% CI 2.3–6.1). Median overall survival was 13.3 months (95% CI 9.5–not reached). The incidence of grade 3 or higher adverse events was 40% (neutropenia 26.7%, anemia 3.3%, nausea 6.7%, anorexia 6.7%, infection 6.7%, peripheral sensory neuropathy 3.3%). There was no treatment related death. Twenty-three patients (76.7%) received subsequent therapies, such as nivolumab (70%). Conclusions: First-line FOLFOX showed an acceptable safety profile and the prespecified statistical efficacy target was achieved. FOLFOX might be a treatment option for advanced ESCC patients who are intolerant to CDDP. Clinical trial information: UMIN000044485 .

A MULTI‐CENTER RETROSPECTIVE STUDY OF PEMBROLIZUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY EXTRANODAL NK/T‐CELL LYMPHOMA

Background: Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. PD-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) ENKTL in case series. Real-world data about the efficacy of pembrolizumab in R/R ENKTL patients are limited. Methods: We performed a multicenter retrospective study to evaluate pembrolizumab efficacy and safety in patients with R/R ENKTL from 10 academic centers in South Korea. Pembrolizumab 100 mg was administered intravenously every 3 weeks. Results: A total of 24 patients were enrolled. The median age was 67 years old (range, 36–87) and 29.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater. Pembrolizumab was administered as 2nd-, 3rd- and 4th or greater line chemotherapy in 9 (37.5%), 9 (37.5%), and 6 (25.0%) patients, respectively, and median 3 cycles (range 1–21) of pembrolizumab were given. In response evaluation, complete remission (CR) and partial response (PR) was achieved in 6 (25.0%) and 3 (12.5%), respectively. The median progression-free survival and overall survival were 2.0 months (95% CI, 0.9–3.0) and 8.0 months (95% CI, 0.0–22.4), respectively. Multivariate analysis indicated that ECOG PS was the only significant predictor of PFS after pembrolizumab treatment (hazard ratio, 5.33; 95% confidence interval, 1.09–26.1; P = .039) Overall, 14 (58.3%) patients experienced adverse events (AEs), with fatigue (n = 7, 29.1%) being the most common Eight patients (33.3%) developed G3-4 AEs, the most frequent of which was neutropenia (4,16.7%) Conclusion: Pembrolizumab could be a therapeutic approach for the control of R/R ENKTL. Keyword: Aggressive T-cell non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Five-Year Outcome and Safety in Patients Treated With Immune Checkpoint Blockade Therapies for Urothelial Carcinoma: Experience From Real-World Clinical Practice.

In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n=21), 22.4% (n=45), and 32.4% (n=66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients.

Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids

Study aimTo investigate the efficacy of PD-1-directed antibody-based therapy in patients with symptomatic melanoma brain metastases (MBM) and concurrent treatment with corticosteroids. MethodsThis retrospective cohort study included patients with cutaneous melanoma with symptomatic MBM and concurrent treatment with corticosteroids who received PD-1-directed antibody-based treatment at the Royal Marsden Hospital London between 2016 and 2021. The primary outcome was overall survival (OS), secondary outcomes were intracranial response rate (ORR) and duration of response (DOR). We used the Kaplan-Meier method to describe survival. ResultsBetween 2016 and 2021, 256 patients presented with metastatic melanoma, of whom 29 were eligible with symptomatic MBM requiring corticosteroids and receiving ipilimumab plus nivolumab. Median age was 54 (interquartile range 44, 66). Median OS was 5.45months (95% confidence interval (CI) 2.89, 29.40), with 21% of patients (95% CI 9%, 47%) alive after 3years. ORR was 28% (8/29) and DOR was 7.85months (95% CI 7.85, not estimably [NE]). Responding patients had a median OS of 56.4months (95% CI 46.03, NE). Elevated lactate dehydrogenase and Eastern Cooperative Oncology Group PS> 2 were associated with poorer outcomes (median OS 29.4 versus 3.12months and 6.44 versus 5.13months), no such association was observed for corticosteroid dose, number of lesions, or line of treatment. ConclusionPatients with symptomatic MBM derive only modest benefit from combination immunotherapy treatment. Nevertheless, those with disease response have the potential to derive long-term benefit, justifying ipilimumab plus nivolumab in this group in the absence of other more effective treatment options.

Enrolment of older adults with advanced or metastatic non-small cell lung cancer in first-line clinical trials in the multicentre ESME cohort

IntroductionThere is a great need for data based on clinical trials for the older population in order to improve treatment. Historically, the inclusion rate of older adults in clinical trials has been low, but the rate specific to lung cancer is unknown, as are the factors associated with enrolment. Materials and MethodsWe used the national Epidemio-Strategy and Medical Economics Advanced or Metastatic Lung Cancer (AMLC) Data Platform, a multicentre real-life database. Inclusion criteria were patients with advanced or metastatic non-small cell lung cancer (AMNSCLC) aged 70 years or older, with at least one line of systemic treatment from 01 January 2015 to 31 December 2018. The primary objective was to evaluate the proportion of older adults enrolled in clinical trials. Secondary objectives were to identify factors associated with enrolment in clinical trials for older patients and to compare the overall survival of older adults included in trials versus those not included. ResultsThere were 3488 patients aged ≥70 years (median age at AMNSCLC 75 years). Among older patients, 234 (6.7%) were enrolled in a clinical trial in the first-line setting. Significant factors associated with enrolment in the multivariable analysis in older patients were: good Eastern Cooperative Oncology Group (ECOG) Performance Status (PS 0) (p < 0.001), de novo versus recurrent presentation at diagnosis (p < 0.001), and non-central nervous system (CNS) metastases versus advanced setting or CNS metastases (p < 0.001). Medical history was associated with fewer inclusions (odds ratio [OR] = 0.74, 95% confidence interval [CI] [0.56; 0.99]). Among older patients, being enrolled in a trial in the first-line setting was not associated with better overall survival (OS) (hazard ratio [HR] = 1.03; 95%CI 0.86–1.22) in the multivariable analysis. DiscussionIn this large database, few older AMNSCLC patients were enrolled in a trial. Factors associated with enrolment were: good ECOG PS, absence of medical history, de novo AMNSCLC, and presentation with non-CNS metastases.

Treatment Outcome of Cervical Cancer Patients in the Elderly Population Aged 80 Years and Above: A Single Institution Study

Introduction: Age-related deficits such as malnutrition, functional reliance, and cognitive decline also occur in older women, as they are typically weaker and have many co-morbid conditions like diabetes or cardiac illness. These prognostic factors might predict overall survival and progression-free survival. Aim: To analyse the management outcomes of elderly patients with cervical carcinoma treated with radiotherapy and brachytherapy. Materials and Methods: A retrospective observational study was conducted in the Department of Radiation Oncology at Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India. Medical records were collected from 876 patients with cervical cancer who had been treated with radiotherapy or combined radiotherapy and chemotherapy from January 2009 to December 2021. A total of 876 patients presented with cervical cancer in the Outpatient Department (OPD), and 20 patients meeting the inclusion criteria were selected. Patients diagnosed with cervical cancer, Federation International Federation of Gynaecology and Obstetrics (FIGO) stage IB to IVA, aged equal to or greater than 80 years old, and Eastern Cooperative Oncology Group (ECOG) performance status I to III were considered for inclusion. Categorical variables were expressed as counts and percentages. The following clinicopathological characteristics of the study population were examined: FIGO staging, including stage IB to stage IVA, histopathological features of adenocarcinoma, squamous carcinoma, or adenosquamous carcinoma, doses of radiotherapy and brachytherapy, overall survival, disease-free survival, and the patient’s current status (alive or dead) was determined. If death occurred, the cause of death was determined. The Kaplan-Meier approach was used to analyse overall survival and disease-free survival in the study population using XLSTAT statistical software. Results: The study population was age standardised, with 18 patients (90%) falling between the ages of 80 and 85, and 2 patients (10%) falling between the ages of 86 and 90. A total of 12 patients (60%) belonged to ECOG PS II. A total of 19 (95%) patients had histologically confirmed squamous cell carcinoma. 75% of the population was in a locally advanced stage (stage III-IVA). The overall survival (in months) was 65.58 months, which was statistically significant (p&lt;0.0083). Similarly, the average disease-free interval was 38.73 months, which was also significant (p&lt;0.0062). Conclusion: According to the findings of the study, age may not be an independent risk factor for determining the outcome of cervical cancer patients in the Indian scenario. Even though elderly females may present with multiple co-morbidities, the standard treatment protocol must be radical.

Duration of frontline therapy and impact on clinical outcomes in newly diagnosed multiple myeloma patients not receiving frontline stem cell transplant.

Extended first-line therapy (1LT) has improved clinical outcomes in newly diagnosed multiple myeloma (NDMM). This retrospective study of NDMM patients evaluated the relationship between dose-attenuation of 1LT and duration of therapy (DOT) and DOT on outcomes. Adults with NDMM not undergoing stem cell transplant (SCT) from January 1, 2012 toMarch 31, 2018 from the Integrated Oncology Network were included; 300 were randomly selected for chart review. 1LT DOT, time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis. Marginal structural models evaluated relationships between DOT and TTNT, PFS, and OS at 2 years accounting for confounders and survival bias from the time-dependent nature of DOT. Of 300 chart-reviewed patients, 93 were excluded for incomplete data or meeting exclusion criteria. Among 207 NDMM patients, median age was 74 years; 146 (70.5%) did not receive dose-attenuation during 1LT. Patients with short DOT were older, frailer, with a higher comorbidity burden, and a significantly lower proportion had an Eastern Cooperative Oncology Group PS=0. As DOT increased, more patients underwent dose-attenuation (p< 0.0001). The median 1LT DOT was 20.9 (95% confidence interval [CI]: 13.9, 26.4) versus 4.2months (95% CI: 3.2, 4.9) for patients receiving versus not receiving dose-attenuation, respectively (p< 0.0001). After accounting for survival bias, confounder-adjusted TTNT was prolonged with each additional month of 1LT (odds ratio [OR]: 0.76 [95% CI: 0.75, 0.78]); likelihoods of risks of disease progression (OR: 0.87 [95% CI: 0.86, 0.88]) and death at 2 years (OR: 0.72 [95% CI: 0.70, 0.74]) were reduced with each month of 1LT (p< 0.0001 for all outcomes). Dose-attenuated 1LT was associated with longer DOT among patients with non-SCT NDMM. Each additional month of 1LT was associated with a reduced adjusted likelihood of disease progression and death at 2 years. Dose-attenuation of 1LT can extend DOT; longer DOT may improve clinical outcomes.

Is ICI-based therapy better than chemotherapy for metastatic NSCLC patients who develop EGFR-TKI resistance? A real-world investigation

PurposeTo evaluate the outcomes of immune checkpoint inhibitor (ICI)-based treatments versus classical chemotherapy for metastatic non-small cell lung cancer (NSCLC) patients who develop epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance and to explore the population that may benefit from ICI-based therapy.Materials and methodsAll patients who had previously received EGFR-TKI therapy at two cancer centers in China and developed resistance to targeted therapies were included. Progression-free survival (PFS) and overall survival (OS) were utilized to evaluate the outcomes of the study cohort.ResultsA total of 132 patients were included. The median follow-up time for this cohort was 21.7 months (IQR, 14.8–28.8 months), calculated from the date of EGFR-TKI resistance. The median PFS and OS were 4.9 months (IQR, 2.8–9.2) and 13.5 months (IQR, 6.6–26.5 months), respectively. Multivariate analysis showed that ICI-based therapy could significantly improve OS when compared to the classic chemotherapy (hazard ratio [HR], 0.55; 95% CI, 0.34–0.88; P = 0.01) after adjusting for variables such as gender, age, mutation status, and brain or liver metastasis status. The combined modality of ICI plus chemotherapy could offer a long-term OS benefit in most subgroups, such as young (<65 years) patients, and those without secondary T790M mutations or absence of liver and brain metastases, and the populations with good Eastern Cooperative Oncology Group (ECOG) scores.ConclusionFor patients presenting with EGFR-TKI resistance, ICI-based therapy could offer a more favorable survival than classical chemotherapy. The combination of ICI with chemotherapy may be the optimal modality for those with good ECOG PS scores.

Impact of performance status on survival outcomes and health care utilization in patients with advanced non–small cell lung cancer treated with immune checkpoint inhibitors.

9053 Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the high prevalence of patients with poor Eastern Cooperative Oncology Group (ECOG) performance status (PS ≥2) in real-world practice, landmark studies have typically excluded this patient group from enrolment. The primary objective of this study was to evaluate the impact of ECOG PS on clinical outcomes and health care utilization in a large cohort of NSCLC patients treated with ICI in real-world practice. Methods: Using the Alberta Immunotherapy Database, we identified consecutive patients who received at least one dose of Pembrolizumab or Nivolumab for the treatment of advanced NSCLC between 1/1/2010 and 12/30/2019. The data cut-off date was 10/1/2020. Baseline clinical, pathological, and laboratory-based data were collected retrospectively. The primary outcome was median overall survival (mOS), as stratified by ECOG PS. The secondary outcomes were median time-to-treatment failure (mTTF) and metrics of health care utilization, including emergency department (ED) visits, hospitalizations, and death in hospital. Kaplan-Meier survival curves were used to determine survival outcomes, and compared with the log-rank test. The association between ECOG PS and healthcare utilization were represented with risk ratios and evaluated using chi-square tests. Results: A total of 790 patients were included. Median follow-up time was 20.6 months. 29.2% (n = 231) had PS ≥2 at the time of ICI initiation. As compared with the favorable PS group (PS &lt; 2), patients with PS ≥2 had significantly lower mOS - 3.3 months (95% CI 2.5-4.0) versus 13.4 months (95% CI 11.7-16.0) (HR, 3.0; 95% CI 2.5-3.6, p &lt; 0.0001), and mTTF – 1.4 months (95% CI 0.9-1.8) versus 4.9 months (95% CI 4.4-5.6) (HR, 2.2; 95% CI 1.9-2.6, p &lt; 0.0001). 3- and 12-month survival rates were also significantly lower in the PS ≥2 group as compared with the PS &lt; 2 group (52.8% versus 86.4% and 13.4% versus 41.0%, p &lt; 0.0001 for both comparisons). Patients with PS ≥2 were also significantly more likely to present to the ED (RR 1.6; 95% CI, 1.3-2.0, p &lt; 0.001) and be admitted to hospital (RR 2.3; 95% CI 1.7-3.0, p &lt; 0.0001) within the first month after treatment initiation. These patients were also significantly more likely to die in hospital during their first admission (RR 2.7; 95% CI 1.8-4.1, p &lt; 0.0001), as well as at any point during treatment (RR 2.2; 95% CI 1.60-3.0, p &lt; 0.0001). Conclusions: NSCLC patients with poor ECOG PS at the time of ICI initiation had significantly worse survival outcomes and were significantly more likely to utilize health care services than those with favorable ECOG PS. The large proportion of patients with poor ECOG PS further justifies the urgent need for randomized trials evaluating the efficacy of ICI in this high-risk population.

Hepatic artery infusion chemotherapy (HAIC) combined with sintilimab and bevacizumab biosimilar (IBI305) for initial unresectable hepatocellular carcinoma (HCC): A prospective, single-arm phase II trial.

4073 Background: Sintilimab plus IBI305, a bevacizumab biosimilar, showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for patients with unresectable hepatocellular carcinoma. Hepatic arterial infusion chemotherapy is an intraarterial procedure that has been widely used in Asia, with high response rate. This trial was designed to assess the feasibility and efficacy of HAIC combined with sintilimab and IBI305 in advanced unresectable hepatocellular carcinoma. Methods: This is a prospective, single-arm phase II study. Patients with histologically or cytologically diagnosed or clinically confirmed hepatocellular carcinoma, China liver cancer staging (CNLC) stage IIb-IIIb, no previous systemic treatment, Child-Pugh classification A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. Patients received FOLOFOX-HAIC, followed by intravenous sintilimab (200 mg every 3 weeks, four cycles) and intravenous IBI305 (7.5 mg/kg every 3 weeks, three cycles). The primary endpoint was objective response rate (ORR) per mRECIST. Secondary endpoint were surgical conversion rate, pCR rate and R0 resection rate. The study is registered with Clinicaltrials.gov: NCT05029973. Results: Between May, 2021 to Sep, 2021, a total of 30 eligible patients were enrolled: median age 54.5 years (range 37-73); M:F 27:3; CNLC stage IIb/IIIa/IIIb: 3/16/11; Child-Pugh class A/B: 28/2; ECOG PS 0/1: 26/4. There were 23(76.7%) patients with hepatitis B and 5(16.7%) with hepatitis C. The median tumor size was 8.75 cm (interquartile range [IQR], 4.9-10.5), 60.0% pts present vascular invasion, and 36.7% had extrahepatic metastasis. Of 30 pts evaluable for response, 20 (66.7%; 95% CI: 47.2%-82.7%) achieved confirmed partial response, and became eligible for surgical resection. Finally, 14 of them received surgical resection and all (100%) achieved R0 resection, 3 pts completed radiofrequency ablation (RAF), 3 pts refused resection or RFA. The pCR rate in the patients completed pathological examination was 52.6% (95% CI: 28.9%-75.6%). The most common TRAEs included hypertension (23.3%), rash (16.7%), and abnormal liver function (10.0%). No grade 3-4 TRAEs were observed. Of note, in patients received surgery, 1 developed grade 1 biliary fistula, 1 developed hepatic failure and finally lead to death Conclusions: HAIC Combined With sintilimab and IBI305 resulted in a promising ORR, R0 surgical conversion rate and pCR rate with a manageable safety for initial unresectable advanced hepatocellular carcinoma. Further follow-up is ongoing. Clinical trial information: NCT05029973.

An exploratory clinical trial of apatinib combined with intensity-modulated radiation therapy for patients with unresectable hepatocellular carcinoma.

To evaluate the clinical efficacy and safety of apatinib combined with intensity-modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC). Open-label, single-arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18-75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46-60 Gy) and continuous apatinib (250-500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR-OPC-17011890. A total of 33 patients have taken part in the study. The median age was 58 years old (range 32-77), 27 (81.9%) patients were ECOG PS 0-1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B-C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first-line and second or later-line therapy, respectively. The average follow-up was 11.4months, the median PFS was 7.8months (95% confidence interval: 3.9-11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment-related adverse events in Grades 3-4 (12.1%). No radiation-induced liver disease and Grade 5 toxicity were recorded. Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti-tumor activity in patients with uHCC.

Use of a Chemotherapy Toxicity Prediction Tool to Decrease Risks for Hospitalization in Older Patients.

ObjectivesPerformance status (PS) scales such as the Eastern Cooperative Oncology Group (ECOG) PS and the Karnofsky Performance Index have limited utility in selecting therapies and predicting related adverse events in older patients with cancer. In July 2016, medical oncologists at our institution adopted the Cancer and Aging Research Group toxicity prediction score (CARG), a toxicity prediction tool, to identify patients who are “fit” for chemotherapy versus those who are “frail” and may experience severe complications.MethodsOur retrospective review included referrals of beneficiaries 75 years of age and older who received standard systemic therapy and patients of the same age whose treatment was modified due to CARG. We compared the score’s utilization six months before and after its incorporation and then assessed how its application impacted admissions, emergency department (ED) visits, and medical management.ResultsThirty-eight patients with a mean age of 81 years met the inclusion criteria. Their diagnoses included gastrointestinal (37%), lung (21%), hematologic (18%), breast (10.5%), genitourinary (3%), and other (10.5%) malignancies. CARG was documented for 12.5% of systemic therapy recipients before its adoption and 41% of recipients after adoption. Its use was limited by the reliance on physicians to perform scoring during time-constrained patient encounters. Patients had fewer mean inpatient admissions (0.7 versus 2.3), admission days (4.3 versus 8), and ED visits (1.1 versus 2.5) when management was modified based on the score.ConclusionCARG assessment may facilitate a safer and more tailored approach to cancer care in older patients than conventional PS scales alone. Its integration into patient screening would increase its application and better define its potential predictive capacity to decrease risks for hospitalization.

Impact of Body Composition on Prognosis and Dose-Limiting Toxicities on Metastatic Colorectal Cancer.

Sarcopenia is a progressive skeletal muscle disease, often present in oncological patients, that is associated with multiple adverse events such as worse prognosis, physical performance, and quality of life. Body composition evaluation by CT cross-section at the L3 vertebrae region appears to be a precise method to quantify skeletal muscle. The optimal cut-off for the definition of sarcopenia is not yet established, therefore the incidence of sarcopenia varies according to different studies. The main goal was to evaluate the presence of sarcopenia in patients with metastatic colorectal cancer (mCRC) and its impact on overall survival (OS) and dose-limiting toxicities (DLT). A retrospective cohort study of 178 patients with mCRC under first-line chemotherapy (ChT) in association with target therapy, in two hospital units, between January 2015 and December 2018. Skeletal mass area (SMA) was quantified with the NIH ImageJ software in CT cross-sectional images at the L3 vertebrae region. Statistical analysis was performed with IBM SPSS v25 software https://www.ibm.com/analytics/spss-statistics-software. The median age was 62 (SD ± 11) years old, 65% were men and 62.9% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. The cut-off value was established based on ROC analysis, with sarcopenia defined as SMI < 49.12 cm2/m2 for men and < 35.85 cm2/m2 for women. Despite the mean body mass index (BMI) of 25.71 (± 4.71) kg/m2, half of the patients presented sarcopenia. In a multivariate analysis using a Cox regression model, an association was observed between OS and higher ECOG PS (p = 0.014; HR 5.46, CI 95% [1.42–21.10]), neutrophil-to-lymphocyte ratio (NLR) >2.80 (p = 0.038; HR 2.20, CI 95% [1,05–4.62]), and sarcopenia (p = 0.01; HR 4.73, CI 95% [1.85–12.09]). Additionally, in a logistic regression model, age (p = 0.014; OR 1.09, IC 95% [1.02–1.16]) and sarcopenia (p= 0.030, OR 4.13, IC 95% [1.15-14.8]) were associated with higher incidence of DLT. The CT evaluation of the body composition at the L3 region allows for the quantification of sarcopenia, providing prognostic information and predictive value of DLT in patients with mCRC, although the establishment of optimal cut-off values are required for implementation in clinical practice. A multimodal strategy to delay muscle waste should be considered in these patients.

Time interval from last visit to imaging diagnosis influences outcome in pancreatic adenocarcinoma: A regional population-based study on linked medico-administrative and clinical data.

Background:Excessive waiting time intervals for the diagnosis and treatment of patients with pancreatic cancer can influence their prognosis but they remain unclear. The objective was to describe time intervals from the medical visit to diagnostic imaging and to treatment and their prognostic impact in pancreatic cancer in one French region.Methods:This retrospective observational multicentre study included all patients with pancreatic cancer seen for the first time in 2017 in multidisciplinary team meetings (MTMs), where clinical data were collected. A probabilistic matching with the medico-administrative data from the French national healthcare database (Système National des Données de Santé) was performed to define the care pathway from clinical presentation to the beginning of treatment. Median key time intervals were estimated for both resected and unresected tumours. Factors associated with 1-year survival were studied using Cox model.Results:A total of 324 patients (88% of total patients with MTM presentation) were matched and included: male 54%, mean age 72 years ±9.2, Eastern Cooperative Oncology Group (ECOG) PS > 1 19.5%, metastatic disease at diagnosis 47.4%, tumour resection 16%. At 1 year, 57% had died (65% in the unresected group and 17% in the resected group). The median time interval from the medical visit to diagnostic imaging was 15 days [Q1–Q3: 8–44]. After imaging, median time intervals to definite diagnosis and to first treatment were 11 and 20 days, respectively. Significant prognostic factors associated with the risk of death at 1 year were ECOG PS > 1 (hazard ratio (HR) 2.1 [1.4–3.0]), metastasis (HR 2.7 [1.9–3.9]), no tumour resection (HR 2.7 [1.3–5.6]) and time interval between the medical visit and diagnostic imaging ⩾25 days (HR 1.7 [1.2–2.3]).Conclusion:Delay in access to diagnostic imaging impacted survival in patients with pancreatic cancer, regardless of whether tumour resection had been performed.

Addition of metoclopramide to triple antiemetic therapy towards prevention of anthracycline-based chemotherapy-induced nausea and vomiting in breast cancer patients

Objective: The aim of this study was to evaluate if addition of metoclopramide to the triplet antiemetic therapy is superior to the triplet antiemetic therapy for prevention of delayed chemotherapy-induced nausea and vomiting. Materials and Methods: A randomized single-blind trial was performed on 200 chemotherapy-naïve breast cancer patients who have to receive anthracycline-based highly emetogenic chemotherapy (HEC). The patients were randomized to study arm (n = 100) and control arm (n = 100). Triplet antiemetic therapy (fosaprepitant on day 1, 5-HT3 antagonist on day 1, and dexamethasone for days 1–4) was used in both the arms and metoclopramide (day 1–5) was added to the study arm. Response to antiemetic prophylaxis was assessed in terms of “complete response (CR),” “only nausea,” and “both nausea and vomiting.” CR is defined as no nausea, no vomiting, and no rescue medication during the overall phase (days 1–5). Nausea/vomiting was detected by using the Visual Analog Scale and its impact on quality of life was determined by using the Functional Living Index Emesis (FLIE) score. Results: The demographical and clinical features were similar in both the groups. Majority of patients in both the arms presented with Eastern Cooperative Oncology Group PS 0, Stage III, and positive hormone receptor status. CR was observed more in the study arm than that of the control arm (51% vs. 37%; P = 0.046). The mean total FLIE score was 29.23 in the study arm and 31.16 in the control arm (P = 0.036). Conclusion: This study resulted in a significant CR and clinically relevant improvement in FLIE score for addition of metoclopramide to triple antiemetic prophylaxis. Therefore, a quadruple antiemetic combination including metoclopramide might be an antiemetic prophylaxis option for breast cancer patients receiving anthracycline-based HEC for better compliance to treatment.

Differences between Hyperprogressive Disease and Progressive Disease in Patients Receiving Immunotherapy

Objectives: Although immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment. In this group, a few of the patients with a hyperprogressive disease (HPD) have shorter overall survival (OS) compared with those having a progressive disease (PD). Therefore, biomarkers are needed to differentiate HPD and PD. Methods: Ninety-five patients treated with ICIs with progression according to response evaluation criteria ın solid tumors criteria in the first control imaging were included. HPD was defined according to Russo's work. The PILE scoring system, which includes pan-immune-inflammation value, lactate dehydrogenase, and Eastern Cooperative Oncology Group PS, was followed. The relationship between PILE score and HPD was analyzed. Results: The median OS of all cohorts was 11.18 months. The patients in the HPD group had decreased OS (4.77 vs. 13.94 months, p<0.001) and progression-free survival (PFS) (1.89 vs. 3.16 months, p<0.001) compared with those in the PD group. The risk of HPD was higher than the risk of PD in patients with a high PILE score (p=0.001). Conclusion: In this study, we showed that patients treated with ICI with a higher PILE score are at greater risk for HPD. The PILE score may be a biomarker to differentiate HPD from PD. Keywords: Hyperprogressive disease, immun checkpoint inhibitors, immunotherapy, PILE score

Risk factors for immune-related adverse events from anti-PD-1 or anti-PD-L1 treatment in an Asian cohort of nonsmall cell lung cancer patients.

Immune-related adverse events (IrAEs) of immune checkpoint inhibitors (ICIs) can be serious and unpredictable. We examine the incidence rate and risk factors for IrAEs in an Asian cohort of nonsmall cell lung cancer (NSCLC) patients treated with immunotherapy. Between June 2014 and August 2020, we retrospectively analysed IrAEs in NSCLC patients treated with anti-PD-1 or anti-PD-L1 inhibitors at the National University Cancer Institute, Singapore. A Poisson regression model was used to estimate the effect of risk factors on incidence rate of any grade IrAEs. One hundred and forty-one patients were enrolled. Median age was 63. Majority were male (67%) with Eastern Cooperative Oncology Group (ECOG) PS 0-1 (77%). More than half (56%) received pembrolizumab. Eleven percent harboured epidermal growth factor receptor (EGFR) mutation. Eighteen percent received concomitant chemotherapy. Median number of cycles was 4, and median duration of treatment was 2.1months. IrAEs were seen in 71 (50.4%) patients, with an incidence rate of 99 events per 1000 person-months. Fatigue (25%), rash (10.5%) and pneumonitis (7.9%) were the most common IrAEs. Twenty out of 152 IrAEs (13.2%) were Grade 3 or higher in severity: most common being pneumonitis (5.3%), fatigue (3.3%) and transaminitis (1.3%). Multivariable analysis demonstrated that concomitant chemotherapy use, higher BMI and presence of EGFR mutation are significant predictors for IrAEs (P < .0001; P=.016; P=.007). Our findings can help guide risk stratification and monitoring of IrAEs among NSCLC patients on immunotherapy.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. The median follow-up duration was 23.5months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p &lt;0.001). In addition, Patients with clinical benefit from first-line chemotherapy (HR= 0.39; 95% CI 0.24-0.65; p &lt;0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factor on OS in patients' use of atezolizumab as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Prognostički faktori kod starijih bolesnika sa akutnom mijeloidnom leukemijom

Introduction: Acute myeloid leukemia (AML) is characterized by pathological proliferation of myeloid lineages. It predominantly occurs in patients over 60 years of age, whose outcome is considerably worse, as compared to younger patients. Aim: The aim of the study was the analysis of the clinical characteristics of older patients with AML and their impact on the following: achieving complete remission (CR), overall survival (OS), early mortality (EM), and relapse. Materials and methods: This retrospective study included 94 patients with AML, treated with chemotherapy and palliative treatment, whose information was taken from their medical histories, upon treatment. The following clinical features were analyzed as risk factors for OS, CR, relapse and EM: leukocytes, the level of serum lactate dehydrogenase (LDH), performance status on the ECOG (Eastern Cooperative Oncology Group) scale, the European LeukemiaNet cytoplasmic risk group, the HCT-CI (hematopoietic cell transplantation - comorbidity index) and the NPM1/ FLT3-ITD (nucleophosmin 1/FLT3-internal tandem mutation) molecular status. For the identification of prognostic factors, the Cox regression analysis was used. Results: The average age of the patients was 69 years (range: 65 - 87). CR was achieved in 23 (46%) of the 50 patients (53.2%) who received intensive chemotherapy, with relapse occurring in 17/23 patients (73.9%). EM was reported in 17 patients (18.1%). Patients with ECOG PS &gt; 2 had a statistically significantly lower OS than patients with ECOG PS &lt; 2 (p = 0.030). Patients with HCT-CI &gt; 3 had a poorer OS than patients with HCT-CI &lt; 3 (p = 0.040). Serum LDH &gt; 450 U/I was found to be a factor, i.e., marker of unfavorable prognosis for the OS, as compared to LDH &lt; 450U/I (p = 0.044). Conclusion: The conclusion is that older AML patients with poorer ECOG PS, high HCT-CI, increased LDH levels have a poorer OS.