From LI-RADS Classification to HCC Pathology: A Retrospective Single-Institution Analysis of Clinico-Pathological Features Affecting Oncological Outcomes after Curative Surgery

Background: The latest Liver Imaging Reporting and Data System (LI-RADS) classification by the American College of Radiology has been recently endorsed in the American Association for the Study of Liver Disease (AASLD) guidelines for Hepatocellular carcinoma (HCC) management. Although the LI-RADS protocol has been developed as a diagnostic algorithm, there is some evidence concerning a possible correlation between different LI-RADS classes and specific pathological features of HCC. We aimed to investigate such radiological/pathological correlation and the possible prognostic implication of LI-RADS on a retrospective cohort of HCC patients undergoing surgical resection. Methods: We performed a retrospective analysis of the pathological characteristics of resected HCC, exploring their distribution among different LI-RADS classes and analyzing the risk factors for recurrence-free, overall and cancer-specific survival Results: LI-RADS-5 (LR-5) nodules showed a higher prevalence of microvascular invasion (MVI), satellitosis and capsule infiltration, as well as higher median values of alpha-fetoprotein (αFP) compared to LI-RADS-3/4 (LR-3/4) nodules. MVI, αFP, satellitosis and margin-positive (R1) resection resulted as independent risk factors for recurrence-free survival, while LI-RADS class did not exert any significant impact. Focusing on overall survival, we identified patient age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Model for End Stage Liver Disease (MELD) score, αFP, MVI, satellitosis and R1 resection as independent risk factors for survival, without any impact of LI-RADS classification. Last, MELD score, log10αFP, satellitosis and R1 resection resulted as independent risk factors for cancer-specific survival, while LI-RADS class did not exert any significant impact. Conclusions: Our results suggest an association of LR-5 class with unfavorable pathological characteristics of resected HCC; tumor histology and underlying patient characteristics such as age, ECOG-PS and liver disease severity exert a significant impact on postoperative oncological outcomes.

Initial Treatment Patterns and Survival Outcomes of Mantle Cell Lymphoma Patients Managed at Chinese Academic Centers in the Rituximab Era: A Real-World Study

PurposeThe aim of the study was to delineate the disease characteristics, the initial treatment patterns, and survival in patients with mantle cell lymphoma (MCL) managed in the real world.MethodsData of 518 MCL patients from 5 major Chinese Hematology Centers in the period from 2007 to 2017 were retrospectively analyzed.ResultsThe median age was 58 years. Of the patients, 88.6% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and 80.7% had advanced-stage disease. Ki67 expression was <30% in 39.6% of the patients, and 43.2% of patients were categorized into a low-risk group based on the Mantle Cell Lymphoma International Prognostic Index (MIPI) scoring system. Overall, 73.4% of the patients received rituximab as their first-line therapy. The most commonly used chemotherapy was the CHOP-like (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) regimen (45.2%), followed by high-dose cytarabine-containing chemotherapy (31.3%) and bendamustine (3.3%). Of the patients, 13.7% (n = 71) underwent consolidative autologous stem cell transplantation (ASCT), and 19.3% (n = 100) received novel agents containing first-line regimens. With a median follow-up time of 52 months, the 3- and 5-year overall survival (OS) rates were 73.7% and 61.4%, respectively. Age ≤60 years, ECOG PS 0–1, stages I–II, normal lactate dehydrogenase (LDH), absence of bone marrow involvement, Ki67 <30%, and lower-risk IPI/MIPI scores were significantly associated with improved OS (p < 0.05). The inclusion of rituximab improved the 5-year OS, with borderline significance (62.5% vs. 55.2%, p = 0.076). High-dose cytarabine-containing chemotherapy showed significant clinical benefit in 5-year OS (72.1% vs. 55.9%, p = 0.010). Patients with ASCT had better 5-year OS in the younger (≤60 years) age group (87.2% vs. 64.8%, p = 0.002).ConclusionThis large retrospective dataset unequivocally confirmed the survival advantage afforded by cytarabine-containing regimen and ASCT in a first-line setting under real-world management in the rituximab era.

Association between Patient-Reported Outcomes and Survival in Patients with Advanced Urothelial Carcinoma Treated with Atezolizumab

BACKGROUND: Atezolizumab is an immune checkpoint inhibitor (ICI) and a frontline treatment of patients with cisplatin-ineligible advanced urothelial carcinoma (UC). There is limited evidence on the prognostic value of patient reported outcomes (PROs) in advanced UC treatment, particularly in the context of ICI therapy. OBJECTIVE: To investigate the prognostic association of PROs with survival in patients with advanced UC treated with atezolizumab. METHODS: This study used data from 467 patients with advanced UC initiating atezolizumab in the IMvigor211 trial. Pre-treatment PROs association with overall survival (OS) and progression free survival (PFS) was assessed using Cox proportional hazard analysis. PROs were recorded via the European Organisation for Research and Treatment of Cancer QLQ-C30. Discrimination performance was assessed via the C-statistic (c). RESULTS: Patient reported physical function, pain, appetite loss, global health, fatigue, role function, constipation, nausea and vomiting, dyspnoea, and insomnia were significantly associated with OS and PFS on univariable and adjusted analysis (P < 0.05). Physical function (c = 0.63), pain (c = 0.63), appetite loss (c = 0.62), global health status (c = 0.62), and fatigue (c = 0.62), were the most prognostic factors of OS. The OS discrimination performance of physical function (c = 0.61) was superior to ECOG PS (c = 0.58). Of patients assessed by investigators as having no performance restrictions (ECOG PS of 0), 38 (18%) and 91 (42%) self-reported low and intermediate physical function scores, respectively. CONCLUSION: Pre-treatment PROs were identified as independent prognostic factors of OS and PFS. Patient-reported physical function was more prognostic of OS than ECOG PS. This highlights a potential for PROs to enable improved patient stratification in ICI trials.

Prognostic Impact of the SARC-F Score in Gastrointestinal Advanced Cancers

We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0–2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.

Pre-Treatment Neutrophil-to-Lymphocyte Ratio (NLR) as a Predictive Marker of Pazopanib Treatment for Soft-Tissue Sarcoma

Pazopanib with trabectedin and eribulin is widely used to treat soft-tissue sarcoma (STS). We have shown that baseline neutrophil-to-lymphocyte ratio (NLR) may predict the efficacy and patient prognosis of eribulin. Changes in NLR, but not baseline NLR, can predict patient prognosis of trabectedin. However, prognostic factors of pazopanib for STS have not been identified. We present a retrospective analysis of 141 patients treated with pazopanib for recurrent or metastatic non-round cell STS. Univariate and multivariate analyses were performed to determine the predictive factors of durable clinical benefit (DCB), overall survival (OS), and progression-free survival. L-sarcoma histology (odds ratio [OR] = 0.31, 95% CI = 0.12–0.79; p = 0.014) and pre-treatment NLR < 3.0 (OR = 2.03, 95% CI = 1.02–6.67; p = 0.045) were independent predictive factors of DCB. Pre-treatment NLR < 3.0 (hazard ratio [HR] = 0.55, 95% CI = 0.36–0.84; p = 0.0057), liposarcoma histology (HR = 1.78, 95% CI = 1.09–2.91; p = 0.022), primary extremity site (HR = 0.48, 95% CI = 0.31–0.75; p = 0.0010), ECOG PS ≥ 1 (HR = 1.62, 95% CI = 1.08–2.42; p = 0.019), and CRP < 0.3 (HR = 0.52, 95% CI = 0.33–0.82; p = 0.0050) were independent predictive factors of OS. These findings indicate that baseline NLR predicts the efficacy and patient prognosis of pazopanib for STS.

Combination of CD47 Expression and SIRI as a Prognostic Factor in Nasopharyngeal Carcinoma Patients

Aim: The present study aimed to investigate the prognostic value of the combination of CD47 expression and SIRI level in nasopharyngeal carcinoma (NPC) patients.Materials & Methods: NPC patients who received radical chemoradiation therapy between January 2012 and December 2016 at the Second Xiangya Hospital were retrospectively reviewed. The clinical and laboratory data was collected from the electro-history system. The expression of CD47 was detected by immunohistochemical (IHC) method. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using Kaplan-Meier method, and Cox proportional hazard model was used to identify prognostic factors.Results: A cohort of 183 NPC patients were enrolled. CD47 was highly expressed in 36.1% (66/183) patients at a cut-off value of 35%. And SIRI was elevated in 35.0% (64/183) patients at a cut-off value of 0.94. CD47 expression had no significant correlation with NPC patients’ age, gender, ECOG status, clinical stage, smoking history or chemo-agent. While SIRI level was significantly higher in male patients and patients who has smoking history. Univariate analyzes shown that younger age, better ECOG PS, earlier clinical stage, and low expression of CD47 and SIRI level predicts better PFS, while better ECOG PS, earlier clinical stage, and low expression of CD47 and SIRI level predicts longer OS. Further multivariate Cos regression model showed that aside from ECOG PS and clinical stage, CD47 and SIRI statue was an independent prognostic factor for PFS and OS.Conclusion: Our findings indicate that the combination of CD47 expression and SIRI level might be a promising prognostic predictor for the NPC patients.

A Prospective Phase II Study of Simultaneous Modulated Accelerated Radiotherapy Concurrently With CDDP/S1 for Esophageal Squamous Cell Carcinoma in the Elderly

BackgroundTo explore the efficacy and toxicity of simultaneous modulated accelerated radiotherapy (SMART) concurrently with cisplatin (CDDP) and S1 (tegafur/gimeracil/oteracil) in elderly patients with esophageal squamous cell carcinoma (ESCC).MethodsThis single-arm, phase II study enrolled pathologically confirmed, stage II–IVa ESCC of 70–80 years old and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients received SMART (64 Gy to gross tumor volume and 48 Gy to clinical target volume in 30 fractions) with concurrent CDDP (day 1 of each week) and S1 (days 1–14, 22–35). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicities.ResultsThirty-seven eligible patients were analyzed with median follow-up of 25.7 months for all and 46.1 months for survivors. The ORR was 88.9%. Patients with baseline weight loss &lt;5% (p=0.050) and nutritional risk index (NRI) ≥105.2 (p=0.023) had better tumor response. Median PFS was 13.8 months with 2-year PFS of 37.5%. Median OS was 27.7 months with 2-year OS of 57.5%. OS was significantly associated with ECOG PS (p=0.005), stage (p=0.014), gross tumor volume (p=0.004), baseline NRI (p=0.036), baseline C-reactive protein (CRP) level (p=0.003) and tumor response (p=0.000). CRP level (p=0.016) and tumor response (p=0.021) were independently prognostic of OS. ≥grade 3 anemia, neutropenia and thrombocytopenia occurred in 2.7%, 10.8% and 13.5% of patients; ≥grade 3 esophagitis and pneumonitis occurred in 18.9% and 2.7% of patient, respectively.ConclusionSMART concurrently with CDDP/S1 yielded satisfactory response rate, survival outcome and tolerable treatment-related toxicities in elderly patients with ESCC. Further studies are warranted to validate the results.

The impact of muscle mass loss and deteriorating physical function on prognosis in patients receiving hemodialysis

Muscle mass loss and worsening physical function are crucial issues in patients receiving hemodialysis (HD). However, few studies have investigated the association between temporal changes in muscle mass and physical function in a large number of HD patients. We examined 286 patients receiving HD (males, 58%; age, 66.8 ± 13.0 years) at a single center, and calculated the percent changes in psoas muscle mass index (%PMI) using computed tomography over two screenings, once per year (July 2011–June 2013). Physical function was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (range 0–4). The observation period was from July 2012 to June 2021. The median %PMI was -9.5%, and those with the lowest quartile of %PMI (< −20.5%) showed a significantly poor prognosis compared with other patients (p < 0.001). Multivariable logistic regression analysis revealed that these patients tended to have decreased physical function (ECOG-PS 2–4) [odds ratio (OR): 2.46, p < 0.001] and albumin levels (OR: 0.22, p = 0.007). Multiple-factor-adjusted Cox regression analyses showed that %PMI (hazard ratio: 0.99, p = 0.004) and each ECOG-PS stage (1–4 vs. 0) (p < 0.01) were associated with mortality. Augmenting physical activities in daily life and serum albumin levels should be considered to maintain muscle mass and improve the prognosis of patients receiving HD.

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study

Background We have previously reported the effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) in real-world clinical practice in Japan. Here, we report long-term outcomes from this study in the overall population and subgroups stratified by subsequent chemotherapy. Methods In this multicenter, retrospective observational study, Japanese patients with recurrent or metastatic (R/M) HNC receiving nivolumab were followed up for 2 years. Effectiveness endpoints included overall survival (OS), OS rate, progression-free survival (PFS), and PFS rate. Safety endpoints included the incidence of immune-related adverse events (irAEs). Results Overall, 256 patients received a median of 6.0 doses (range: 1–52) of nivolumab over a median duration of 72.5 days (range: 1–736). Median OS was 9.5 months [95% confidence interval (CI) 8.2–12.0] and median PFS was 2.1 months (95% CI 1.8–2.7). A significant difference between 2-year survivors (n = 62) and non-2-year survivors was observed by median age (P = 0.0227) and ECOG PS (P = 0.0001). Of 95 patients who received subsequent chemotherapy, 54.7% received paclitaxel ± cetuximab. The median OS and PFS from the start of paclitaxel ± cetuximab were 6.9 months (95% CI 5.9–11.9) and 3.5 months (95% CI 2.3–5.5), respectively. IrAEs were reported in 17.2% of patients. Endocrine (7.0%) and lung (4.3%) disorders were the most common irAEs; kidney disorder (n = 1) was newly identified in this follow-up analysis. Conclusions Results demonstrated the long-term effectiveness of nivolumab and potential effectiveness of subsequent chemotherapy in patients with R/M HNC in the real-world setting. Safety was consistent with that over the 1-year follow-up.

Indirect Treatment Comparisons of the Effect of Fedratinib Versus Navitoclax Plus Ruxolitinib on Spleen Volume and Symptoms in Patients with Myelofibrosis and Prior Ruxolitinib Treatment

Introduction: Myelofibrosis (MF) is a serious and life-threatening myeloproliferative neoplasm that is characterized by stem cell-derived clonal myeloproliferation, bone marrow fibrosis, anemia and splenomegaly. The Janus kinase (JAK) pathway is the critical pathway in its pathogenesis. Ruxolitinib, a JAK1/2 inhibitor, was the first US Food and Drug Administration (FDA)-approved therapy for intermediate- and high-risk MF. However, there remains a high unmet need for alternative treatment options for patients who discontinue (41.1%-60.9% of patients discontinue after 3 months and 48.4%-73.0% after 6 months) (Fonseca E, et al. Blood 2013;122. Abstract 2833) or are no longer responding to ruxolitinib therapy (Bose P, Verstovsek S. Leuk Lymphoma 2020;61:1797-1809). The efficacy and safety of fedratinib, a JAK2 inhibitor approved by the FDA in 2019, was investigated post ruxolitinib in the single-arm trial JAKARTA-2 (NCT01523171) (Harrison CN, et al. Lancet Haematol 2017;4:e317-324; Harrison CN, et al. Am J Hematol 2020;95:594-603). New clinical evidence for treating a similar population with navitoclax plus ruxolitinib was presented at the American Society of Hematology Annual Meeting in 2020 (Pemmaraju N, et al. Blood 2020;136(suppl 1):49-50). The efficacy of fedratinib relative to navitoclax plus ruxolitinib in patients with MF previously treated with ruxolitinib has not yet been evaluated. Objective: To explore the comparative efficacy of fedratinib versus navitoclax plus ruxolitinib in patients with MF previously treated with ruxolitinib for the 2 binary endpoints of ≥ 35% spleen volume reduction (SVR) from baseline to the end of cycle 6 (EOC6; 24 weeks) and ≥ 50% reduction in total symptom score (TSS) from baseline to the EOC6. Methods: Evidence for fedratinib was informed by JAKARTA-2 patient-level data, and evidence for navitoclax plus ruxolitinib was informed by known reported evidence from the REFINE study (NCT03222609) (Pemmaraju N, et al. Blood 2020;136(suppl 1):49-50; Harrison CN, et al. J Clin Oncol 2019;37 (suppl 15). Abstract 7057). The suitability of these studies for indirect treatment comparison (ITC) was assessed by considering the comparability of study design, population, intervention, and outcomes. Given the lack of a common comparator in the identified studies, unanchored ITCs were performed for SVR using matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) methods. Univariable and multivariable regression models were used to identify potential prognostic factors to adjust for in the ITCs. Additionally, all reported Dynamic International Prognostic Scoring System (DIPSS)-Plus criteria were considered. Where sample size was too small, response rates (number of responders divided by total number of patients) were compared naively. Results: A subgroup of 58 JAKARTA-2 patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1 and intermediate-2 or high-risk disease most closely aligned with the REFINE population was used in the analyses. Baseline mean platelet count was similar between subgroups. Across the analyses performed, results suggested fedratinib consistently increased the odds/risk of a spleen response compared with navitoclax plus ruxolitinib (Table). The MAIC, matching on ECOG PS, suggested that the odds of having an SVR for patients in the fedratinib group was 2.19 times (95% confidence interval [CI], 1.26 to 3.66) that of the navitoclax plus ruxolitinib group, and the risk of having an SVR for patients in the fedratinib group was 17.59% higher (95% CI, −2.14 to 36.97). The results from the MAIC that additionally matched on all possible DIPSS-Plus criteria (age, hemoglobin, and platelet count) were consistent. Results from the 2 methods (MAIC and STC) were also consistent. For TSS reduction, the sample size (N = 20) in REFINE was considered too small to perform a meaningful ITC; however, the absolute response rates for TSS reduction were similar across the 2 groups (29% [16/56] in the fedratinib group and 30% [6/20] in the navitoclax plus ruxolitinib group). Conclusion: In the population of patients with MF previously treated with ruxolitinib, these analyses suggest treatment with fedratinib was associated with a greater proportion of patients achieving a spleen response compared with navitoclax plus ruxolitinib. Limited data were available for comparison of TSS. Figure 1 Figure 1. Disclosures Abraham: Bristol Myers Squibb: Current Employment. Liao: BMS: Consultancy. Chevli: Bristol-Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Smith: Sarah Smith is an employee of BresMed. BresMed received consultancy fees from BMS/Celgene for the reasearch in this abstract. She did not receive direct payment as a result of this work outside of her normal salary payments.: Consultancy.