Median On Overall Survival Research Articles

Chemotherapy effectiveness and age-group analysis of older adult patients with metastatic pancreatic cancer: A Japanese cancer registry cohort study

IntroductionAlthough older adults aged ≥75 years comprise a substantial proportion of patients diagnosed with pancreatic cancer (PC), the effectiveness of chemotherapy in older adults with PC remains to be established. Materials and MethodsThis retrospective study examined the effectiveness of chemotherapy according to age in older adult patients with metastatic PC. We used a large database that combined three data sources (the hospital-based cancer registry database, Osaka Cancer Registry, and Japan's Diagnosis Procedure Combination) and extracted data from patients pathologically diagnosed with metastatic PC between 2013 and 2015 in 31 designated cancer care hospitals in Japan. Propensity score matching (PSM) was used to identify a cohort of patients with similar backgrounds. The effect of chemotherapy on overall survival (OS) was analyzed using the log-rank test. ResultsCompared with 687 younger patients (<75 years old), 276 older adult patients had significant impairments in activities of daily living and poorer prognoses (6.8 vs. 4.1 months, p < 0.001), with a lower frequency of chemotherapy (81.5% vs. 55.1%; p < 0.001). PSM of older adult patients showed that chemotherapy significantly contributed to a better prognosis (best supportive care, 2.6 months vs. chemotherapy, 5.8 months, p < 0.001). Age group analysis with PSM of five-year age ranges revealed that the median OS was significantly longer in the chemotherapy group among older adult patients aged <85 years. DiscussionChemotherapy provides a survival benefit in older adult patients with metastatic PC, and patients aged <85 years could be promising candidates for chemotherapy.

Effects of Radiotherapy on Survival of Esophageal Cancer Patients Receiving Immunotherapy: Propensity Score Analysis and Nomogram Construction.

PurposeThe present study assessed the effects of radiotherapy on overall survival (OS) and progression-free survival time (PFS) in patients with stage II or higher esophageal cancer receiving immunotherapy; evaluated factors independently prognostic of OS and PFS in these patients; and utilized these factors to establish a prognostic nomogram.Patients and MethodsThis study enrolled 134 patients with stage II or higher esophageal cancer treated with chemotherapy (platinum-based agents plus paclitaxel or fluorouracil) and immunotherapy. These patients were divided into two groups, a radiotherapy (RT) group (n = 55) and a non-radiotherapy (non-RT) group (n = 79). Following 1:1 propensity score matching, OS and PFS were compared by the Kaplan–Meier method, and factors associated with survival were determined by univariate and multifactorial Cox regression analyses. These factors were used to construct a prognostic nomogram.ResultsAfter propensity matching, all covariates were well balanced in the two groups (all P > 0.05). After matching, both median PFS (15.70 months [95% confidence interval (CI) 8.68–22.72 months] vs 5.70 months [95% CI 3.38–8.02 months], P = 0.002) and median OS (15.72 months [95% CI 12.94–18.46 months] vs 12.06 months [95% CI 9.91–14.20 months], P = 0.036) were significantly longer in the RT than in the non-RT group. Univariate and multifactorial analyses showed that RT, neutrophil-lymphocyte ratios, and tumor differentiation were independently prognostic of OS, with all hazard ratios (HRs) <1 and all P-values <0.05. A nomogram based on these factors was constructed, and its accuracy was verified.ConclusionImmunotherapy plus RT resulted in better survival outcomes than immunotherapy alone. A nomogram based on prognostic factors can guide personalized treatment and monitor prognosis.

Real-world utilization of PD-1/PD-L1 inhibitors with palliative radiotherapy in patients with metastatic non-small cell lung cancer.

BackgroundProgrammed cell death protein 1 (PD‐1) blockade plus radiotherapy may be a promising strategy to improve the prognosis of patients with metastatic non‐small cell lung cancer (NSCLC). However, the optimum combined scheme, treatment time of radiotherapy, and irradiated lesion have not been fully determined.MethodsA total of 321 metastatic NSCLC patients treated with immunotherapy were identified. Among them, 107 patients received PD‐1/PD‐ligand 1 (PD‐L1) inhibitors with radiotherapy, while the remaining cases did not receive radiotherapy. Data on overall survival (OS), progression‐free survival (PFS), treatment response and adverse events were collected. Comparisons based on type of radiation, timing of radiotherapy and number of irradiated lesions were performed.ResultsThe median OS in PD‐1/PD‐L1 inhibitors plus radiotherapy was longer than in nonradiotherapy (22.8 vs. 16.6 months, p = 0.022). The median PFS showed a similar trend in this study (9.4 vs. 6.2 months, p = 0.042). Moreover, the combined strategy demonstrated a superior disease control rate and abscopal control rate versus without radiotherapy (both p ≤ 0.001). Further multivariate analysis in the immunotherapy and radiotherapy groups revealed that age below 65 (p = 0.004), Eastern Cooperative Oncology Group performance scores of 0–1 (p = 0.001), oligometastasis (p = 0.006), concurrent combination (p = 0.002), and treated with SRT (p = 0.013) were associated with longer OS. There was a similar incidence of adverse events between the two groups (both p ≥ 0.05).ConclusionsThe combination of PD‐1/PD‐L1 inhibitors plus palliative radiotherapy demonstrated favorable survival and good tolerability in metastatic NSCLC patients.

P506: ACHIEVEMENT OF MEASURABLE RESIDUAL DISEASE CLEARANCE IS A STRONGER PREDICTOR OF PATIENT OUTCOME THAN TREATMENT INTENSITY IN NEWLY DIAGNOSED PATIENTS WITH ACUTE MYELOID LEUKEMIA

Background: Modern therapy for acute myeloid leukemia (AML) can consist of either intensive or low-intensity regimens selected based on patient (pt) age/comorbidities. Measurable residual disease (MRD) has emerged as a strong independent prognostic factor in AML. It is unknown whether pts who achieve similar levels of MRD clearance experience comparable outcomes irrespective of treatment intensity. Aims: To establish the relative prognostic contribution of treatment intensity and MRD status on overall survival (OS) and relapse-free survival (RFS) in newly diagnosed AML pts who have achieved a first response. Methods: We conducted a retrospective chart review to identify non-CBF, non-APL AML pts treated at our institution between 2010 and 2021 with intensive (IA; int/high-dose cytarabine + anthracycline-based, without venetoclax) or low-intensity (Lo + VEN; low-dose cytarabine/hypomethylating agent-based, with venetoclax) regimens who had achieved CR/CRi/MLFS and undergone MRD testing by multiparameter flow cytometry at time of first response. Differences in baseline pt characteristics were evaluated using the Chi-square or Wilcoxon-Mann-Whitney tests for categorical and continuous variables, respectively. The Kaplan-Meier method was used to estimate median OS and RFS, with pts censored at the time of stem cell transplantation (SCT). Multivariate analysis was performed using a Cox proportional hazards model. Results: We identified 635 pts meeting inclusion criteria. Baseline characteristics are shown in Table 1. Compared to the IA-treated pts (n=385), pts treated with Lo + VEN (n=250) were significantly older, more likely to be male, less likely to achieve MRD clearance, and more likely to be classified as adverse risk by ELN 2017. The SCT rate in the Lo + VEN cohort was half that of the IA cohort (25% vs 50%). Median OS was 51m, 24.6m, 15m, and 9.9m in the IA MRD(-), Lo + VEN MRD(-), IA MRD(+), and Lo + VEN MRD(+) groups, respectively. Median RFS was 27.8m, 15.4m, 7.3m, and 5.2m in the IA MRD(-), Lo + VEN MRD(-), IA MRD(+), and Lo + VEN MRD(+) groups, respectively. Pts within the same MRD category (+ or -) had significantly higher OS and numerically higher RFS if treated with IA versus Lo + VEN. When the analysis was restricted to pts aged ≥ 60 years (n=56 in IA, n=239 in Lo + VEN; Fig. A-B), the differences within MRD categories did not reach statistical significance (median OS NR in IA MRD(-) vs 24.6m in Lo + VEN MRD(-), p=0.08; median OS 13m in IA MRD(+) vs 10.6m in Lo + VEN MRD(+), p=0.50; median RFS NR in IA MRD (-) vs 15.4m in Lo + VEN MRD(-), p=0.07; median RFS 25.1m in IA MRD(+) vs 5.3m in Lo + VEN MRD(+), p=0.24). The SCT rate was 29% (87/295) in the age ≥ 60 cohort. Given the confounding effect of unbalanced pt characteristics between the IA and Lo + VEN cohorts, we performed a multivariate analysis on the full population (n=635) taking into consideration the effects of age, treatment intensity, MRD status, and ELN category on OS and RFS (all significant by univariate analysis). In the multivariate analysis for OS, ELN adverse risk was the strongest predictor (HR 2.09, p<0.001), followed by MRD(+) status (HR 1.68, p<0.001), while treatment intensity and age were not significantly predictive. For RFS, ELN adverse risk (HR 2.31, p<0.001) and MRD(+) status (HR 1.98, p<0.001) were also the only two significant predictors. Image:Summary/Conclusion: In newly diagnosed AML patients, MRD status at time of first response and ELN risk are stronger predictors of pt outcome than intensity of therapy received.

P578: GILTERITINIB FOR RELAPSED/REFRACTORY FLT3 MUTATED ACUTE MYELOID LEUKEMIA A REAL-WORLD, MULTI-CENTER, MATCHED ANALYSIS

Background: Patients with FLT3-mutated relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis. Gilteritinib is a FLT3 tyrosine kinase inhibitor (TKI) recently approved for patients with R/R AML. Aims: We aimed to characterize real-world data regarding gilteritinib treatment in FLT3-mutated R/R AML and to compare outcomes with matched FLT3-mutated R/R AML patients treated with chemotherapy-based salvage regimens. Methods: Survival analysis was performed by Kaplan Meyer with log rank test to compare between subgroups. Cox proportional hazards regression models were fitted to predict effect of covariates on overall survival (OS) and event free survival (EFS). All statistical analyses used 2-sided p value with a threshold of 0.05. Results: Twenty-five patients from six academic centers were treated with gilteritinib for FLT3-mutated R/R AML. The median age was 58 (IQR1-3 47-73) years, 80% (n=20) were treated with a prior intensive induction regimen and 40% of them received prior TKI therapy. After a median time of seven months post gilteritinib initiation (range 1-34), 12 patients (48%) achieved complete response (CR) with gilteritinib (figure 1A). The estimated median overall survival (OS) of the entire cohort was eight (CI 95% 0-16.2) months and was significantly higher in patients who achieved CR compared to those who did not (16.3 months, CI 95% 0-36.2 vs. 2.6 months, CI 95% 1.47-3.7; p value=0.046, figure 1B). In a multivariate cox regression analysis, achievement of CR was the only predictor for longer OS (HR 0.33 95% CI 0.11-0.97, p=0.044). Prior TKI exposure did not affect OS but was associated with better event-free survival (HR 0.15 95% CI 0.03-0.71, p=0.016). An age and ELN-risk matched comparison between patients treated with gilteritinib and intensive salvage revealed similar response rates (50% in both groups); median OS was 9.6 months (CI 95% 2.3-16,8) vs. 7 months (CI 95% 5.1-8.9) in gilteritinib and matched controls, respectively (p = 0.869, figure 1C). Image:Summary/Conclusion: In the real-world setting gilteritinib is effective, including in heavily pre-treated, TKI exposed patients.

P1323: PREDICTION OF NON-RELAPSE MORTALITY BY EASIX AND HCT-CI SCORES IN PATIENTS WITH CHRONIC MYELOMONOCYTIC LEUKEMIA UNDERGOING ALLOGENEIC STEM CELL TRANSPLANT

Background: The endothelial activation and stress index (EASIX) score has been shown as a predictor of non-relapse morality (NRM) after allogeneic stem cell transplantation (alloSCT) [Luft, et al. Bone Marrow Transplant. 2020;55(3):553–561]. However, data in patients with chronic myelomonocytic leukemia (CMML) is limited. Aims: Our goal was to study the risk of NRM and the impact on overall survival (OS) by EASIX and HCT-CI scores in patients with CMML undergoing alloSCT. Methods: We retrospectively evaluated patients with CMML who underwent alloSCT. We reviewed patient demographics, disease characteristics, and post-transplant outcomes. EASIX score was calculated using the formula: LDH (U/L) × Creatinine (mg/dL) / platelet count (10^9/L) and analyzed based on log2 transformed values. EASIX score was calculated within 45 days of alloSCT, but prior to starting conditioning therapy. The optimal log2 EASIX score cutoff was determined using maximally selected log-rank statistics. Patients with an HCT-CI score ≥ 3 were considered to have a high HCT-CI score. Results: Between, January 1992 to February 2019, a total of 70 CMML patients underwent alloSCT, 13 patients were excluded due to incomplete records and 57 patients (39 males and 18 females) were evaluated for the purposes of the study. CMML-0 was the most common subtype (21 patients, 36.8%), followed by CMML-2 (19 patients, 33.3%)) and CMML-1 (17 patients, 29.8%). Seventeen (29.8%) patients had progressed to CMML blast phase before alloSCT. Of the entire cohort, 18 (31.6%) patients were in complete remission at the time of alloSCT. Median age at transplant for the entire cohort was 58 years (range: 18 – 73 years). Median time of follow-up was 2 years (range: 11 days – 16 years). Median OS was 2 years, with a 3-year OS rate of 49.1%. Eighteen (31.6%) patients were alive at last follow-up. The median log2 EASIX score was 0.88 (range -2.29 to 5.91). The optimal log2 EASIX score cutoff using the maximally selected LogRank statistics was found to be 2.33. Patients with log2 EASIX score > 2.33 were considered to have a high EASIX score. Thirteen (22.8%) patients had a high EASIX score and 44 (77.2%) had a low EASIX score. The cumulative incidence of NRM among patients with high EASIX score was significantly higher compared to those with low EASIX score at 100 days (30.8% vs 0%, p < 0.001), at 1-year (46.2% vs 9.1%, p = 0.002) and at 3-years (53.8% vs 15.9%, p = 0.003) after alloSCT (Figure 1A). A total of 55 patients were evaluated for HCT-CI score, of whom 30 (54.54%) were found to have a low HCT-CI score, i.e., HCT-CI < 3, and 25 (45.45%) were found to have a high HCT-CI score. The median HCT-CI score was 2 (range: 0-7). NRM after alloSCT among patients with high HCT-CI score was not significantly different compared to those with low HCT-CI scores at 100 days (8% vs 6.7%, p = 0.85), at 1 year (24% vs 13.3%, p = 0.33), and at 3 years (24% vs 26.7%, p = 0.92) after alloSCT (Figure 1B). In multivariate competing risk regression analysis, a high EASIX score significantly increased NRM at 3 year (HR 4.14, 95% CI: 1.42 – 12.01, p = 0.009). Patients with a high log2 EASIX score had significantly worse OS at 3 years (median 8 months vs. NA, p = 0.007). OS at 3 years did not differ among patients with high vs. low HCT-CI scores (median 1.02 years vs. NA, p = 0.38). Image:Summary/Conclusion: In CMML, EASIX predicted NRM following alloSCT. EASIX was a better predictor of NRM compared to HCT-CI in this patient population. Larger patient cohort is required to confirm our findings.

P917: HOW COMORBID ARE OUR MYELOMA PATIENTS AND HOW MANY MAKE IT TO THE SECOND-LINE TREATMENT: REAL-WORLD DATA OF 251 MYELOMA PATIENTS TREATED IN THE HEMATOLOGICAL NETWORK OF THE OEGK

Background: Comorbid conditions have a negative impact on overall survival (OS) in multiple myeloma (MM) patients. Furthermore, a European multi-center study reported that only 61% of patients proceed to second-line treatment. Aims: The objective of this study was to determine the prevalence of common comorbidities and their impact on OS. Furthermore, we examined the mortality during first-line treatment and the percentage of patients proceeding to second-line treatment. Methods: This retrospective study was conducted in the hematology care network “Hämatologieverbund der Österreichischen Gesundheitskasse (OEGK)”, consisting of the Hanusch hospital and three outpatient centers, in Vienna, Austria. We included all patients who were observed and/or treated for multiple myeloma between 2012 and 2018 within the hematology care network. Follow-up was conducted until March 2021. Results: We analyzed 251 patients (median age 69 years). Prevalent concomitant conditions at diagnosis were hypertension (67.4%), further cardiovascular diseases excluding hypertension (23.1%), obesity (15.2%), diabetes (13.8%) and chronic lung disease (9.2%). For the evaluation of renal impairment, we used the CCI, which defines kidney disease as a creatinine >3mg/dl or the need for dialysis, as well as the chronic kidney disease (CKD) classification system. While 7.8% of patients fulfilled the CCI criteria for kidney disease, 39.5% had a CKD stage ≥3A. Comorbidity in general, as well as specific comorbid conditions had a negative effect on overall survival. Patients with a CCI score of 0 points at diagnosis showed a median OS of 8.7 years compared to 3.8 years and 2.6 years for patients with a score of 1 point and ≥2 points, respectively (p <0.001). We also observed a reduced OS of 4.9 years in patients with at least one creatinine clearance (CrCl) value <60 ml/min throughout the observation period compared to 16.4 years in patients with a CrCl consistently ≥60 ml/min (p <0.001). In total, 232 patients received a first-line treatment. During the observation period after first-line therapy, 146 patients proceeded to second-line treatment due to progress, 30 showed no sign of progress so far and 12 had an ongoing first-line maintenance therapy. 21 patients were referred from other centers for a second opinion and/or ASCT. These patients were still alive at the end of the observation period, but data about further treatment lines were missing. One patient eligible for second-line treatment refused further therapeutic measures. Furthermore, 22 patients died during first-line treatment or the subsequent treatment-free interval. Of these 22 patients, 11 died during active first-line treatment due to progression of myeloma or treatment-related toxicity. The other 11 patients died after completion of first-line treatment during the observation period due to secondary neoplasms (4) and infection (2). For the remaining five patients the cause of death was unknown. In total, 90.5% of patients who had received a first-line treatment were or still are eligible for second-line treatment. Summary/Conclusion: Comorbid conditions were prevalent in our population and exerted a major impact on mortality. In comparison to the CCI, the chronic kidney disease classification system showed superior sensitivity for detection of renal impairment, which is a good predictor of survival. In contrast to previously published data, a high proportion of patients were eligible for second-line treatment. Disease-specific mortality prevented only a small number of patients from receiving second-line treatment.

Value of routine intraoperative frozen sections of proximal bile duct margins in perihilar cholangiocarcinoma, a retrospective multicenter and matched case-control study

BackgroundCurrently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. Materials and methodsA retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved ‘additional’ R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. ResultsForty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as “true” R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5–36.5) compared to 30 months (95%CI:24.4–35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7–59.3) after initial R0 (P = 0.348). ConclusionThere were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.

Prognostic impact of obesity in newly-diagnosed glioblastoma: a secondary analysis of CeTeG/NOA-09 and GLARIUS

PurposeThe role of obesity in glioblastoma remains unclear, as previous analyses have reported contradicting results. Here, we evaluate the prognostic impact of obesity in two trial populations; CeTeG/NOA-09 (n = 129) for MGMT methylated glioblastoma patients comparing temozolomide (TMZ) to lomustine/TMZ, and GLARIUS (n = 170) for MGMT unmethylated glioblastoma patients comparing TMZ to bevacizumab/irinotecan, both in addition to surgery and radiotherapy.MethodsThe impact of obesity (BMI ≥ 30 kg/m2) on overall survival (OS) and progression-free survival (PFS) was investigated with Kaplan–Meier analysis and log-rank tests. A multivariable Cox regression analysis was performed including known prognostic factors as covariables.ResultsOverall, 22.6% of patients (67 of 297) were obese. Obesity was associated with shorter survival in patients with MGMT methylated glioblastoma (median OS 22.9 (95% CI 17.7–30.8) vs. 43.2 (32.5–54.4) months for obese and non-obese patients respectively, p = 0.001), but not in MGMT unmethylated glioblastoma (median OS 17.1 (15.8–18.9) vs 17.6 (14.7–20.8) months, p = 0.26). The prognostic impact of obesity in MGMT methylated glioblastoma was confirmed in a multivariable Cox regression (adjusted odds ratio: 2.57 (95% CI 1.53–4.31), p < 0.001) adjusted for age, sex, extent of resection, baseline steroids, Karnofsky performance score, and treatment arm.ConclusionObesity was associated with shorter survival in MGMT methylated, but not in MGMT unmethylated glioblastoma patients.

Abstract 4097: Clinicopathologic descriptors of subcutaneous panniculitis-like T-cell lymphoma (SPTCL): Analysis of a pooled database of a rare entity

Abstract Introduction: SPTCL is a rare primary cutaneous T-cell lymphoma. SPTCL was initially described as an aggressive cutaneous T-cell lymphoma frequently associated with hemophagocytic syndrome (HPS) and requiring aggressive multiagent chemotherapy. In 2005, this entity was restricted to SPTCL with αβ phenotype, a less aggressive entity compared to its γδ counterpart, currently known as primary cutaneous γδ T-cell lymphoma. We conducted this analysis to explore the clinicopathologic characteristics of this little-known primary cutaneous T-cell entity. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 214 cases. Descriptive statistics were calculated. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 214 patients with confirmed SPTCL diagnosis were identified. The median age was 34 years with a peak incidence between ages 13 and 26. There was a female predominance with F:M ratio of 1.7. Upon presentation, 12% had lymphadenopathy, 12% had hepatosplenomegaly, and 27% had bone marrow involvement. No extra-nodal or extra-cutaneous involvement were reported. Cases expressed CD2 (8%), CD3 (85%), CD4(10%), CD5(10%), CD7 (9%), CD8 (77%), CD56 (6%), Granzyme-B (33%), and TIA-1 (34%). None of the cases expressed CD30. The most common clinical presentations were nodular skin changes (87%) followed by constitutional symptoms (57%). Fifteen and ten percent of SPTCL patients had history of immune-deregulatory disorders and immunosuppressive therapies, respectively. HPS occurred in 24% of the cases. Karyorrhexis, fat necrosis, and dermal involvement were noted in 15%, 9%, and 17%. The median duration of symptoms prior to diagnosis was 4 months. Median OS of the whole group was not reached while the mean OS was 73 months. OS was not impacted by sex, constitutional symptoms, immunocompromising factors, presence of lymphadenopathy, hepatosplenomegaly, or bone marrow involvement. OS was not impacted by histological or immunohistochemical features either. While older age and the occurrence of HPS negatively impacted OS, attaining complete remission positively impacted OS. Conclusions: This study presents a comprehensive clinicopathologic data from a pooled cohort of patients with SPTCL. It describes the clinicopathologic features of SPTCL and identifies major determinants of OS in this rare disease. Citation Format: Philip A. Haddad, Nowell Ganey. Clinicopathologic descriptors of subcutaneous panniculitis-like T-cell lymphoma (SPTCL): Analysis of a pooled database of a rare entity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4097.

Prognostic features and comprehensive genomic analysis of NF1 mutations in EGFR mutant lung cancer patients.

NF1 is a tumor suppressor gene that encodes the neurofibromin protein and negatively regulates Ras signaling. This study was aimed to investigate the molecular, clinical characteristics, and prognostic features of NF1 gene in EGFR mutant lung cancer patients. The next-generation sequencing (NGS) was used to analyze the data from lung cancer patients in the Guangdong Lung Cancer Institute (GLCI) from June 2016 to December 2020. Somatic NF1 mutations were present in 4.2% (135/3220) of Chinese lung cancer patients. NF1 mutations where clearly enriched in older (p < 0.001), male (p < 0.001), and smoking (p < 0.001) patients. Patients with NF1 mutations were more likely to have TP53 (p=0.003), BRAF (p =0.001) and RASA1 (p=0.026) mutations and mutually exclusive with EGFR mutations (p=0.006). TP53 mutation had worsen prognosis in cases of NF1 mutant (p=0.026) or EGFR/NF1 co-mutant (p=0.031) lung adenocarcinomas (LUAD) patients. There was no effect on overall survival (OS) in LUAD patients with and without NF1 mutations, even in LUAD driver-gene negative patients. NF1/EGFR co-mutation patients had a longer OS than a single mutation of either the EGFR gene (median OS: 47.7m vs. 30.2 m, hazard ratio [95% CI], 0.47 [0.30-0.74], p=0.004) or NF1 gene (47.7m vs. 19.0 m, 0.44 [0.27-0.73], p=0.003). Furthermore, NF1 mutations significantly prolonged OS in EGFR mutant/TP53 wild-type LUAD patients (106.5m vs. 25.5 m, 0.28 [0.13-0.59], p=0.003) but not in patients with EGFR/TP53 co-mutations (36.8m vs. 30.2 m, 0.70 [0.39-1.26], p=0.280). Our results indicated NF1 mutations served as a good prognostic factor in EGFR mutant/TP53 wild-type lung cancer patients in this single-center study. TP53 mutation was obviously enriched in NF1 mutant patients and had shorter OS.

Machine Learning of Dose-Volume Histogram Parameters Predicting Overall Survival in Patients with Cervical Cancer Treated with Definitive Radiotherapy.

Purpose To analyze the effects of dosimetric parameters and clinical characteristics on overall survival (OS) by machine learning algorithms. Methods and Materials 128 patients with cervical cancer were treated with definitive pelvic radiotherapy with or without chemotherapy followed by image-guided brachytherapy. The elastic-net models with integrating DVH parameters and baseline clinical factors, only DVH parameters and only baseline clinical factors were constructed in 5-folds cross-validations for 100 iteration bootstrapping, and then were compared using concordance index (C-index) criteria. Finally, the selected important factors were used to build multivariable Cox-pH models for OS and also shown in nomograms for clinical usage. Results The median OS occurred was 25.78 months with 25 (19.53%) deaths. The elastic-net models integrating clinical and DVH factors had the best prediction performances (C-index 0.76 in the train set and C-index 0.74 in the test set). Three important factors were selected, including baseline hemoglobin level as the protective factor, primary tumor volume (GTV_P) volume, and body V5 as the risk factors. The final multivariable Cox-pH models were constructed using these important factors and had prediction performance (C-index: 0.78, 95%CI: 0.73–0.81). Conclusions This is the first attempt to establish elastic-net models to study the contributions of DVH parameters for predicting OS in patients with cervical cancer. These results can facilitate individualized tailoring of radiation treatment in cervical cancer patients.

P-17 Real-life use and long-term effectiveness results from CIREL – the multi-centre, observational study on irinotecan-eluting transarterial chemoembolization in CRLM

Transarterial chemoembolization (TACE) using irinotecan-eluting beads as a treatment approach for patients with unresectable colorectal cancer liver metastases (CRLM) is finding use beyond treatment guidelines but real-life data from multi-centre studies are lacking. The CIrse REgistry for LifePearl microspheres (CIREL, NCT03086096) is a prospective, Europe-wide, multi-centre, observational study on the real-life clinical outcomes of LifePearlTM microspheres TACE (LP-irinotecan TACE). The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Eligible patients were adults with CRLM treated with LP-irinotecan TACE and were enrolled between February 2018 and August 2020. Baseline characteristics and treatment-related data were collected. The median follow-up inclusion according to reverse Kaplan-Meier was 19 months (95% CI: 17-23) during which data on overall survival (OS), progression-free survival (PFS), hepatic progression free survival (hPFS) and adverse events (AEs) graded according to CTCAE 4.03 were collected. 152 patients were enrolled in the study. Median age was 66 years and 39% were female. Eastern Cooperative Oncology Group was 0 in 59%; 1 in 34%; and ≥2 7%; liver involvement was 50% in 7% of patients. 84% had progressive disease at baseline. 42% received 1 line, 40% 2 or more lines and 18% no line of previous systemic therapy. 91 (60%) patients experienced 266 adverse events within 24 hours after a TACE session, of which 19 (7%) were grade 3 or higher in 12 (8%) patients. The complete treatment plan was administered in 80% of patients and no treatment-related deaths were reported. The median OS for the whole cohort was 13.0 months (95% CI 10.5-15.0), median hPFS was 6.2 months (95% CI 5.1-6.9) (hPFS rate at 9 months: 29%) and median PFS was 4.7 months (95% CI 3.8-5.3) (PFS rate at 9 months: 13%). We could observe statistically significant differences (p=0.005) in OS for different treatment strategies. When LP-irinotecan TACE was used as a first-line treatment or as consolidation after response to first-line treatment (41, 27%), the median OS was 17 months (95% CI 12.7-23.1). When it was used in combination with ablation (with curative intent) (19, 13%), the median OS was 17.1 (95% CI 10.5-NA). When chemo-refractory patients still eligible for further systemic treatment were treated with LP-irinotecan TACE (41, 27%), the median OS was 10.3 months (95% CI 7.5-14.0). Salvage treatment of chemo-refractory patients not eligible for further systemic treatment (46, 30%) resulted in the smallest median OS of 9.0 months (95% CI 6.8-13.0). For 5 (3%) patients LP-irinotecan TACE was used after response to second-line treatment. The results from this large prospective multi-centre observational study show that in a real-world context, LP-irinotecan TACE is well tolerated with low occurrences of severe adverse events and patients with CRLM receiving LP-irinotecan have a median overall survival comparable to gold-standard systemic treatment for later lines.

Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis.

e16142 Background: Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Methods: Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs &gt; 65 years); baseline ECOG PS (0 vs ³ 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. Results: From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was ³ 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP-based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Conclusions: Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ-based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

P-155 Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis

Ampullary adenocarcinoma (AA) is a rare tumor. Radical surgery is the only curative treatment for localized AA. The role of AT is not clearly defined and previous evidence in literature is poor and controversial. Hence, we retrospectively analyzed radically resected AA pts at our Institution, investigating the impact of AT on survival and the role of possible prognostic and/or predictive factors. Radically resected AA pts were retrospectively included in the analysis, divided into two groups: pts receiving AT and pts undergoing only postoperative observation (PO). The following variables were collected: gender; age (≤ 65 vs > 65 years); baseline ECOG PS (0 vs 3 1); histologic subtype (pancreatobiliary vs intestinal); tumor stage (T1-2 vs T3-4); nodal status (N0 vs N+), margin status (R0 vs R+); radiotherapy (yes vs no), AT regimen [Gemcitabine (GMZ)-based vs fluoropyrimidine (FP)-based treatment)]. The objective of the analysis was to evaluate the impact of AT on overall survival (OS). Univariate and multivariate analyses were performed. From 2007 to 2021, a total of 69 pts with radically resected AA were identified: 41 (59%) pts received AT, 28 (41%) PO. The median age was 65 years (41-81), 42 (61%) were males, ECOG PS was 3 1 in 45 (65%) pts. Tumor characteristics were: 31 (45%) pancreatobiliary, 26 (38%) intestinal, 9 (13%) mixed subtype and 3 (4%) not available; 41 (59%) pts had T3-T4 stage tumor; 34 (49%) were N+. Out of 41 pts receiving AT, 27 (66%) pts were treated with FP- based AT, 14 (34%) with GMZ-based AT; 16 (23%) pts received also RT. In the overall population, median OS was 59.8 months. At the univariate analysis, there was a statistically significant association of T status with OS (p 0.03), confirmed at multivariate analysis (p 0.03). Further variables (ECOG PS, AT, nodal status and histologic subtype) were not associated with survival. Among the 41 pts receiving AT, median OS was 58.7 months. At the univariate analysis, AT regimen was significantly associated with OS (p 0.02), and it was confirmed at the multivariate analysis. In particular, median OS was 59.8 and 28.3 months in pts receiving FP- and GMZ-based AT, respectively [HR 0.26, (95% CI: 0.09-0.78), p = 0.001]. Among pts with radically resected AA, AT, compared with PO, was not associated with a significant survival benefit. However, among pts receiving AT, FP-based regimen seems to significantly improve OS in comparison to GMZ- based regimen, independently of histologic subtype. Our findings, from a retrospective and limited case series, add to controversial literature data and miss to clarify the real impact of AT in radically resected AA pts. A randomized trial of AT vs PO would provide further information in this setting.

Association of comprehensive molecular genotyping and overall survival in patients with advanced non-squamous non-small cell lung cancer.

9022 Background: Current guidelines recommend comprehensive molecular genotyping for newly diagnosed patients (pts) with metastatic non-squamous (non-Sq) NSCLC. We have previously demonstrated that concurrent plasma (P) and tissue (T) based next-generation sequencing (NGS) improves detection of clinically actionable mutations in pts with advanced NSCLC. We analyzed the impact of concurrent T+P NGS on comprehensiveness of molecular genotyping and on overall survival (OS). Methods: A retrospective cohort study of pts with newly diagnosed stage IV non-Sq NSCLC who received therapy at our institution between 01/2019 and 12/2020 was performed. Categories of NCCN guideline testing were defined, i) comprehensive: EGFR, ALK, BRAF, ROS1, MET, RET, and NTRK testing, ii) incomplete: 2-6 genes tested, and iii) no testing performed. The proportion of pts with comprehensive molecular testing performed, prior to 1st-line therapy and by detection modality (T NGS vs. T+P NGS), were compared using Fisher’s exact test. Median OS was estimated using Kaplan-Meier methodology from diagnosis to death or censored at most recent follow-up. Results: 335 patients were included in this analysis, 98.5% (330/335) underwent molecular testing: either comprehensive: n = 291 (86.9%), incomplete testing: n = 39 (11.6%); or no testing n = 5 (1.5%). Testing with T NGS was completed in 32.7% (108/330); 67.2% (222/330) underwent concurrent T+P NGS. These groups were well balanced for baseline characteristics, with the exception of a higher number of never smokers in T+P vs. T NGS (30.2% vs. 14.8%, p &lt; 0.0001). Proportion of pts with comprehensive molecular testing was higher among pts with T+P NGS: 99.5% (221/222) vs. T NGS: 64.8% (70/108), p &lt; 0.0001. All pts with T+P NGS testing had results available prior to 1st line therapy; 100% (204/204) compared to 60.7% (51/84) for T NGS, p &lt; 0.0001. With median follow up of 20.5 months (mos, range 0.3 - 33.1), median OS was 18.6 mos. Median OS for pts tested with T+P NGS vs T alone was numerically longer at 23.2 vs. 14.1 mos, but not statistically significant (p = 0.078). However, regardless of testing modality, patients with comprehensive molecular genotyping had superior OS compared to those with incomplete or no testing (22.1 mos vs. 11.6 mos, p = 0.017). The institution of oral targeted therapy had no bearing on this difference in OS (test for interaction, p = 0.6509). Conclusions: Performance of concurrent T+P NGS testing was associated with a higher likelihood of comprehensive molecular genotyping, as well as improved availability of results, including prior to first line therapy. Patients with comprehensive genotyping have improved OS compared to patients with incomplete or no testing. These results support implementation of a concurrent T+P NGS approach upon initial diagnosis of metastatic non-Sq NSCLC.

CK+/CD45+ (dual-positive) circulating cells are associated with prognosis in patients with advanced breast cancer.

1093 Background: Circulating tumor cells (CTCs) expressing epithelial markers (EPCAM, cytokeratin (CK)) and lacking CD45 (a leukocyte marker) have been associated with poor outcome in many cancer types. Nonetheless, the presence of cells expressing both CK and CD45 (CK+/CD45+), circulating in the blood of cancer patients (pts) have also been reported, but not widely investigated. Early evidence indicates that circulating dual-positive cells (DPcells) are hybrids deriving from the fusion of tumor cells and macrophages. We previously reported that it is possible to detect DPcells in the blood of pts with metastatic breast cancer (BC) and that they are associated with shorter progression-free survival (PFS), in pts with &lt;5 CK+/CD45- CTCs. Here, we investigated the impact of DPcells on overall survival (OS) in pts with advanced BC (aBC). Methods: Blood samples (7.5 ml) were collected from aBC pts before starting a new therapy and processed with the FDA-approved CellSearch platform for CTCs and DPcells enumeration. The prognostic role of CTCs and DPcells was assessed through the Kaplan-Meier method using the log-rank test. Single DPcells were isolated using the DEPArray platform and underwent whole genome amplification and lowpass whole genome sequencing (Ampli1 WGA and Ampli1 Lowpass kits). Results: Blood samples from 341 pts with luminal (n=168), HER2+ (n=76) and triple negative (n=88) BC were analyzed. Of these, 131 samples (38.4%) contained ≥5 CTCs (CTCpos), whereas DPcell were detected in 152 samples (44.6%, range 0-53), of which 66 (43.4%) were CTCpos and 86 (56.6%) CTCneg. Overall, DPcells were associated with a shorter OS: median OS 24.5 vs 35.0 months, p=0.046. However, when analyzing CTCpos and CTCneg separately, only the latter group showed a difference in OS according to DPcells presence. In particular, among CTCneg pts, those with ≥4 DPcells showed a 2.3-fold shorter OS (26.7 vs 60.6 months, p=0.025). Moreover, pts with ≥4 DPcells were less likely to experience a 6-months PFS clinical benefit (p=0.015). Interestingly, in the analysis by BC subtype, DPcells were confirmed to be associated with worse OS only in pts with triple negative BC (median OS 11.5 vs 16.9, p=0.048). To explore the exiology of DPcells, 2 out of 3 cells analyzed after single-cell isolation from 1 patient were confirmed to have copy number alterations (CNA) consistent with malignant cells. CNA and mutational profiling of additional single DPcells and CTCs are ongoing. Conclusions: DPcells are associated with worse OS in aBC pts, with the prognostic impact primarily in pts with &lt;5 CTCs and triple negative BC. This suggests that DPcells might be an alternative way of tumor dissemination in specific pts, in which CK+/CD45- CTCs are less prevalent. More studies are needed to better elucidate DPcell clinical significance in BC, and to confirm their fusion-hybrid origin.

Prognostic value of hematologic parameters in patients with muscle invasive bladder cancer.

e16502 Background: Muscle invasive bladder cancers (MIBC) tend to have an increased risk of progression and recurrence despite optimal management. Since various blood cells affect tumor microenvironments, modulate tumor growth and treatment responses, we examined the impact of Platelet/Lymphocyte ratio (PLR) and systemic inflammation response index [(SIRI) = N×M/L), N- Neutrophil, M-monocyte, and L-Lymphocyte] at diagnosis of MIBC patients on overall prognosis. Methods: We performed a retrospective analysis of all muscle invasive bladder cancer patients treated at our institute from January 2015 to December 2020. Patients with Stage I and IV disease were excluded. Descriptive statistics were obtained for entire cohort. The optimal cutoff points for PLR and SIRI were accessed by the receiver operating characteristic curve (ROC) based on overall survival (OS) and Progression free survival (PFS). Kaplan-Meier curve was used to compare the OS and the PFS between the groups. Univariate and multivariate Cox regression analyses were used to evaluate the impact of PLR and SIRI on the OS. Results: In our cohort of 112 patients, median age at diagnosis was 65 years (95% CI: 62-68). Patients were predominantly males (74.1%), Caucasians (88.3%), smokers (71.4%), and 59.8% had a BMI above 24.9. The median duration of follow up was 18.7 months (mo). The median OS was 28.5 mo (95% CI: 19.8-55.4) and median PFS was 16.7 mo (95% CI: 11.7-30.0). 50 patients (44.6%) were stage II and 62 patients (55.4%) were Stage III. 34 patients (30.4%) received chemotherapy in neoadjuvant or adjuvant setting, 6 patients (5.4%) received radiotherapy, and majority of patients (total 75; 67.0%) were treated with surgical intervention. The optimal cutoff points on OS for PLR and SIRI were 304.04 and 1.83 respectively. On univariate analysis, SIRI did not affect OS (HR: 1.26, 95% CI: 0.73-2.19, p = 0.406). Patients with high PLR had worse OS on both univariate (HR: 1.003, 95% CI: 1.001-1.005, p = 0.003) and multivariate (HR: 1.002, 95% CI: 1.000-1.004, p = 0.028) analyses. Nodal staging, radiation treatment, and baseline hemoglobin level were other statistically significant factors associated with OS. Conclusions: Although the standard TNM staging system is helpful in predicting tumor behavior, there is marked heterogeneity in responses to treatment for MIBC. Our study suggests that PLR at diagnosis can be a novel prognostic marker for patients with MIBC.

P-90 First-line anti-EGFR agents (panitumumab or cetuximab) plus chemotherapy in patients with metastatic colorectal cancer: Onco-colon Turkey study subgroup analysis

The guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab or cetuximab for the treatment of metastatic colorectal cancer (mCRC) on significant clinical benefits in patients with wild-type RAS. We assessed the efficacy and toxicity of panitumumab versus cetuximab in Onco-Colon Turkey registry patients. Patients with wild-type RAS mCRC treated with fluorouracil-oxaliplatin- and irinotecan-based chemotherapies in first-line setting were evaluated to either panitumumab or cetuximab including combinations. The efficacy of cetuximab vs panitumumab on overall survival (OS) and progression-free survival (PFS) and safety profile when combined with chemotherapy regimen was compared retrospectively. From January 2016 to March 2019, 1065 patients were recorded in Onco-Colon Turkey Registry, and 316 (47.4%) and 351(52.6%) patients were received the panitumumab and cetuximab as anti-EGFR treatment in first-line setting, respectively. The panitumumab was used more commonly with a combination regimen containing oxaliplatin (74.9%), while the cetuximab was used more in contingency with a combination regimen containing irinotecan (50.4%) (p=0.000). The median PFS was 11.6 months in the panitumumab arm and 11.0 months in the cetuximab arm, (p=0.270), and median OS was 26.5 and 27.6 months (p = 0.726), respectively. The overall response rate was 58.4% in panitumumab arm and 51.4% in cetuximab arm (p=0.138). The incidence of acneiform rash and thrombocytopenia was higher in the panitumumab arm (p=0.011 and 0.045) and the incidence of nausea/vomiting was higher in the cetuximab arm (p=0.013). Our findings show that panitumumab is similar to cetuximab and that these agents provide equal progression-free and overall survival benefit in this population of patients with wild-type RAS. Both agents had toxicity profiles that were to be expected.

Effect of immunotherapy and time-of-day infusion chronomodulation on survival in advanced cancers.

1588 Background: Emerging clinical studies report correlation of time-of-day infusion (TOI) to immunotherapy outcomes and the intricate interplay of the human circadian rhythm and cancer and immunotherapy exposure. Preclinical and clinical studies have shown cancer chronotherapy to play important role in transcriptional rhythmicity of oncogenic process. We evaluated the association of TOI and immunotherapy outcomes in a large cohort to determine impact of TOI on overall survival (OS) and progression free survival (PFS). Methods: We reviewed charts of patients with solid tumors who received immunotherapy, specifically anti programmed cell death protein 1 (PD1) and anti-programmed death-ligand 1 (PD-L1) agents at MD Anderson Cancer Center. Infusion times were divided into two hours cohorts from 8am-8pm and one overnight cohort from 8pm-8am. Accelerated failure time models were used to model OS (log-normal distribution) and PFS (Weibull distribution) with relation to TOI after adjusting for factors such as age, gender, tumor type and prednisone &gt; 10mg daily use within 1 month of immunotherapy initiation to minimize confounding factors. Results: Of 6151 patients with advanced tumors, 4441 patients received immunotherapy therapy after adjusting for minimum 140 patients in each tumor cohort from 10/15/2016 until 10/15/2021. Tumor types included advanced lung cancer (31.4%), melanoma (28.7%), renal (14.4%), breast (7.6%), colon (6.2%), liver cancer (3.9%) and head and neck (H&amp;N) cancers (2.8%). Median age was 63 (15-99) with 58% males and 42% female. 1894 (43%) patients received investigational agents and 2547 (57%) received standard of care therapies. Mechanism of action of various agents: anti PD1, anti-PDL1, TGF-βRII and anti-PDL1, anti-PD-1 with OX40+ T Cell activation, PD-1 / PD-L1 bispecific antibody, PD-L1 dependent 4-1BB agonist and anti PD-1 and CTLA-4 activity. Among all patients, median OS was 26.4 months while median PFS was 4.8 months. Preponderance of immunotherapy TOI occurred between 12-2pm and 2-4pm in all patients. Patients receiving overnight TOI with lung, renal and breast cancer demonstrated significantly (p &lt; 0.05) poorer OS compared to TOI (10am-4pm) whereas in melanoma, significantly lower OS was seen with overnight, 8-10am and 6-8pm compared to 10am-4pm TOIs. Among H&amp;N cancer patients, early TOI (8-10am) was associated with significantly lower OS compared to afternoon TOI (12pm-4pm). PFS trends were less distinct than for OS but showed a slighted inverted tendency towards lower PFS following daytime TOI. Conclusions: In this large cohort of patients treated with immunotherapy, clinically significant association of TOI with overall survival is seen. These intriguing findings warrant prospective validation in a future randomized trial to harness the role of chronomodulation of cancer therapies for improving outcomes.