Median Overall Survival Values Research Articles

Peripheral Eosinophil Count May Be the Prognostic Factor for Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Treatment

(1) Background: The importance of total eosinophil count in peripheral blood (EOS) as a type 2 inflammation marker is known to be fundamental in asthma, chronic sinusitis, and vasculitis. In cancer, despite their questionable antiproliferative effect, their role remains unclear. Our purpose was to describe the relationship between baseline blood EOS and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC) patients. (2) Methods: We retrospectively analyzed data from 137 adult patients who underwent surgical treatment for pancreatic ductal adenocarcinoma (PDAC) between the years 2012 and 2019. Patients with no recent history of systemic steroid use and without intraoperative metastases were included. Patients were categorized into two groups based on EOS (≥0.1 G/l and <0.1 G/l). Survival outcomes were analyzed using Cox proportional hazards regression models. (3) Results: According to EOS and PDAC stage, median OS values were as follows: in stage I–III, EOS ≥ 0.1 G/l group: 14.5 months, in stage I–III, EOS < 0.1 G/l group: 8.0 months, in stage IV, EOS ≥ 0.1 G/l group: 7.0 months, and in stage IV, EOS < 0.1 G/l group: 5.0 months. EOS < 0.1 G/l (vs. ≥0.1 G/l) was an independent prognostic factor for OS in both the uni- and multivariate Cox regression, respectively (HR = 1.48, p = 0.035 and HR = 1.57, p = 0.021). (4) Conclusions: Peripheral eosinophilia seems to be a potential independent prognostic factor. Further studies are necessary to confirm this hypothesis, since our findings suggest that type 2 inflammation may be the factor directly or indirectly lengthening the survival of patients with PDAC.

A Clinico-Genetic Score Incorporating Disease-Free Intervals and Chromosome 8q Copy Numbers: A Novel Prognostic Marker for Recurrence and Survival Following Liver Resection in Patients with Liver Metastases of Uveal Melanoma

Surgical treatment of liver metastases of uveal melanoma (LMUM) could be proposed for selected patients. This retrospective study examined the prognostic significance of the genetic profiles of liver metastases after LMUM resection. A total of 86 patients treated with resection for LMUM, who underwent genetic analysis of liver metastasis, were included. A multivariable Cox model identified the independent predictors of recurrence-free survival (RFS) and overall survival (OS). The disease-free interval (DFI) and a chromosome 8q surgain (>3 copies) were independent predictors and categorized patients into three risk groups with distinct postoperative prognoses. For the low-, intermediate-, and high-risk scores of recurrence, the median RFS values were 15 months (95% CI: 10–22), 6 months (95% CI: 4–11), and 4 months (95% CI: 2–7), and the median OS values were 86 months (95% CI: 55-NR), 25 months (95% CI: 17–48), and 19 months (95% CI: 12–22), respectively. The predictive accuracy of this scoring system was demonstrated by a mean area under the curve (AUC(t)) of 0.77 (95% CI: 0.65–0.90) for RFS and 0.81 (95% CI: 0.70–0.92) for OS. This novel score, based on a DFI of ≤24 months combined with a chromosome 8q surgain, identifies patients at a high risk of early recurrence and could help clinicians to propose perioperative treatment.

Real-world clinical outcomes and economic burden of early discontinuation of taxane therapy among patients with metastatic castration-resistant prostate cancer.

e17043 Background: Despite comprising an important part of the treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) for over a decade, real-world use of taxanes is hindered by adverse events (AEs). AEs may lead to early treatment discontinuation, which may adversely affect outcomes. The two goals of this study were to determine the proportion of mCRPC patients who discontinue taxanes early (defining the early discontinuation threshold relative to efficacy results associated with androgen receptor pathway inhibitors [ARPIs]) and to evaluate the impact of early discontinuation on clinical outcomes, AEs, and healthcare costs. Methods: This was a retrospective, observational study of adult men with mCRPC treated with an ARPI as their first-line (1L) therapy and who initiated second-line (2L) therapy with another ARPI or a taxane. The Flatiron Health electronic health record database (07/01/2012–06/30/2020) was used to estimate Kaplan-Meier overall survival (OS) curves for the taxane cohort by the number of cycles received; these were compared with patients who received ARPI at 2L. Cox regression modeling and median PFS and OS values were used to identify the number of taxane cycles needed to achieve comparable OS to ARPI. The number of taxane cycles with similar OS outcomes to ARPI was then considered the threshold for early discontinuation. In addition, the IQVIA PharMetrics Plus claims database (01/01/2013–08/31/2021) was used to estimate taxane-related AEs (based on product information) and associated healthcare costs among patients who did and did not discontinue taxanes early. Results: From Flatiron, 473 2L ARPI patients and 214 2L taxane patients were included. Similar clinical characteristics – e.g., prostate-specific antigen level, ECOG performance status, and Gleason score – were observed between the two cohorts. Overall, 2L ARPI was associated with longer median OS (15.4 vs. 13.6 months) than 2L taxane. The number of taxane cycles needed to reach comparable OS to ARPI was determined to be 8. Patients receiving >8 cycles (n=48; 22%) compared to those receiving ≤8 cycles (n=166; 78%) had longer median OS (18.4 vs. 11.9 months, respectively) and PFS (9.0 vs. 4.3 months, respectively). From PharMetrics, 158 2L taxane patients were included. Patients receiving >8 cycles (n=20; 13%) were more likely to experience an AE (95% vs. 88%) than those receiving ≤8 cycles (n=138; 87%) but had lower mean AE-related total healthcare costs per patient per month ($3,429 vs. $6,334). Conclusions: These results suggest that mCRPC patients need to receive >8 cycles of taxane at 2L to receive more clinical benefit than 2L ARPI. However, the vast majority of patients in the study discontinued taxane early, resulting in shorter survival outcomes compared to ARPI.

Anti-PD-L1 antibody TQB2450 combined with tyrosine kinase receptor inhibitor AL2846 for immunotherapy-refractory advanced hepatocellular carcinoma and esophageal squamous cell carcinoma: A prospective phase 1b cohort study.

Effective systemic therapy remains limited for advanced esophageal squamous cell carcinoma (ESCC) and hepatocellular carcinoma (HCC), particularly after prior failed treatment with immune checkpoint inhibitors (ICIs). Theoretically, a combination of tyrosine kinase inhibitors (TKIs) with ICIs may restore immunotherapy sensitivity. In this phase 1b study, patients received AL2846, an antiangiogenic TKI with multiple targets (c-MET, VEGFR1, c-KIT, Axl, RET, KDR, and VEGFR3), in combination with an anti-PD-L1 antibody (TQB2450) until disease progression, intolerable toxicity, death, or discontinuation for any cause. The primary end points included overall response rate (ORR) and safety, with secondary end points encompassing progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response. Between November 2021 and September 2022, 18 patients with ESCC and 15 patients with HCC, whose ORR was 11.1% (95% confidence interval [CI], 3.1%-32.8%) and 0%, respectively, were enrolled. Adverse events (AEs) of any grade and treatment-related AEs were documented in 32 patients (97.0%) and 31 patients (93.9%), respectively. Grade 3 or higher AEs were observed in 10 patients (30.3%), with vomiting (6.1%) and infectious pneumonia (9.1%) being the most prevalent. Median PFS and OS values were 3.22 months (95% CI, 1.35-5.68 months) and 5.98 months (95% CI, 3.71-8.87 months), respectively, in patients with ESCC, and 5.55 months (95% CI, 2.66 months to not evaluable [NE]) and 16.72 months (95% CI, 4.86 months to NE), respectively, in patients with HCC. The DCRs were 66.7% (95% CI, 43.75%-83.72%) in patients with ESCC and 73.3% (95% CI, 48.05%-89.10%) in patients with HCC. Combined TQB2450 and AL2846 therapy exhibited a favorable safety profile in immunotherapy-refractory patients with advanced ESCC and HCC.

Chinese collaborative study of survival analysis in 980 patients with AL amyloidosis

AbstractBackgroundThe prognosis of patients with light‐chain amyloidosis (AL) has improved markedly in the past decade in China; whether the current staging systems are suitable to predict the overall survival (OS) of the patients remains undetermined.MethodsBased on 980 biopsy‐proved AL patients with 5‐year follow‐up from China Registration Network for Light‐chain Amyloidosis, we evaluated the efficacy of existing staging systems and developed a new stratification model. This involved analyzing parameters such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) thresholds and estimated glomerular filtration rate (eGFR).ResultsWe found that 30% patients were classified as stage I, 25% as stage II, 26% as stage III, and 19% as stage IV disease using the Mayo 2012 staging system, with varying median OS values. However, the observed median OS values were notably higher than previously reported. By incorporating NT‐proBNP thresholds and eGFR values, we developed a four‐stage score system. With this new model, 41.6% patients were reclassified to stage I, 34.3% to stage II, 17.8% to stage III, and 6.3% to stage IV disease, with adjusted median OS values.ConclusionThe new stratification model exhibited improved consistency compared to traditional staging systems. It effectively identified patients with the best and worst prognoses, even among those receiving comprehensive treatment. Specifically, NT‐proBNP levels exceeding 9000 pg/mL combined with an eGFR less than 60 mL/min/1.73 m2 proved superior in prognosticating patient outcomes. Overall, the median OS of AL amyloidosis patients in China has significantly improved, underscoring the need for tailored prognostic models in clinical practice.

Estimating median overall survival of apalutamide compared to placebo in metastatic hormone-sensitive prostate cancer (mHSPC) populations: Statistical extrapolations of the TITAN study.

223 Background: Apalutamide plus ADT (APA) demonstrated significantly improved overall survival (OS) compared to placebo plus ADT (PBO) for patients with mHSPC in the TITAN study (HR, 0.65; 95% CI, 0.53 to 0.79; P < .0001). At the time of final analysis, the median OS was not reached in the APA arm or subgroups after a median follow up of 44 months. This work aimed to estimate OS medians for APA and PBO arms beyond the TITAN follow-up by fitting validated survival models. Methods: OS was predicted for the overall population treated with APA or PBO, with or without Inverse probability of censoring weighting (IPCW) crossover adjustment, and for the low and high-volume (LVD, HVD), HVD synchronous and HVD metachronous subgroups. General population mortality adjusted TITAN patient-level data was fitted to six parametric models (Weibull, exponential, log-normal, log-logistic, generalized gamma, and Gompertz) using the individual fits approach. Best fit was determined by statistical and visual fits, along with the Akaike Information Criterion (AIC)/Bayesian Information Criterion (BIC) ranking, according to the recommendations of the National Institute for Health and Care Excellence Decision Support Unit 14. Results: Best fit extrapolation estimated median OS of 71.8 months for the overall mHSPC population treated with APA (Table), leading to an estimated median improvement of up to 32 months versus PBO. Median OS values predicted by the other five models ranged from 62.4 to 78.1 months. Across subgroups, best fit models estimated median OS of 113.7 months for APA in LVD and a consistent median OS of 52 months for HVD subgroups. Conclusions: While results of this extrapolation study should not be equated to those of a clinical trial, this analysis meets an evidence gap by predicting median OS in the APA arm of the TITAN study for the overall mHSPC population as well as for various subgroups of this heterogeneous population, strengthening the evidence supporting early treatment with APA across the broad mHSPC population. [Table: see text]

Real-World Treatment Patterns and Outcomes of Solitary Plasmacytoma in the United States: A National Cancer Database (NCDB) Analysis of Years 2004-2020

Background: Solitary plasmacytoma, whether it affects the bone (P-Bone) or occurs as an extramedullary disease (P-EM), is typically treated with radiation therapy. Surgery, either combined with radiation or as a standalone option, is also recognized as a curative option, especially for P-EM. Prognosis depends on treatment and disease location. In this IRB approved retrospective analysis, the National Cancer Database (NCDB) was utilized to assess treatment patterns and overall survival (OS) among plasmacytoma patients treated at Commission on Cancer (CoC) accredited facilities across the USA. Methods: N=9,427 plasmacytoma patients from 2004 to 2020 were identified using the NCDB, excluding multiple myeloma patients. Descriptive statistics examined data and differences in primary site, radiation dosage, and treatment patterns. OS tables and Kaplan-Meier curves compared primary sites, radiation dose, and treatment outcomes. Multivariate Cox regression analysis identified independent survival factors. SAS version 9.4 was used to analyze the data. Results: P-Bone accounted for 73% while P-EM represented 27% of cases. Patients' characteristics are presented in Table 1. The median OS was significantly longer in P-EM patients with OS of 146 months compared to 106 months in P-Bone patients (p<0.0001). Radiation therapy alone was the most utilized modality in both P-Bone (58%) and P-EM (36%), followed by combination of radiation and surgery in 20% and 27% of cases, respectively. Notably, a small proportion of patients received surgery alone (8% in P-Bone and 23% in P-EM). Patients who underwent combined surgery and radiation exhibited the longest median OS of 181 months, compared to 137 months for surgery alone and 116 months for radiation alone (p<0.0001)(Fig 1). Median OS also varied significantly (p<0.0001) based on the radiation dose: <35Gy (46.62 months), 35-39.9Gy (80.66 months), 40-44.9Gy (125.31 months), 45-49.9Gy (151.52 months), and ≥50Gy (176.36 months). Primary P-Bone sites were categorized as follows: limb bones (n=932), skull and mandible (n=571), vertebral column (n=2,729), ribs/sternum/clavicle (n=861), and pelvis (n=991). The median OS varied significantly (p<0.0001) across the bone sites, with the longest median OS of 122.25 months observed in cases involving the skull and mandible (95% CI: 102.34-181.29) followed by vertebral column with OS of 110.88 months (95% CI: 102.87-120.90). Pelvis, ribs/sternum/clavicle, limb bones, and other bones demonstrated median OS values of 108.75 months (95% CI: 88.51-122.71), 105.49 months (95% CI: 88.87-124.42), 96.43 months (95% CI: 79.61-122.68), and 72.18 (95% CI: 60.65-93.01) respectively (p<0.0001). In most bone sites, the predominant radiation dose fell within the range of 45-49.9 Gy (21.67% for limb bones, 26.78% for skull and mandible, 32.28% for vertebral column). However, the ribs/sternum/clavicle and pelvis categories stood out, with the predominant radiation dose being equal to or exceeding 50 Gy (32.96% for ribs/sternum/clavicle, 29.9% for pelvis). Furthermore, radiation therapy alone emerged as the predominant treatment modality across all bone sites. Conclusion: This 16-year study to 2020 is the largest database to date in the USA that analyzes the real-world treatment patterns and OS of P-bone and P-EM. Long term median survival of greater than 9 years was observed for solitary plasmacytoma. Combined surgery and radiation therapy showed improved survival outcomes in solitary plasmacytoma, emphasizing the role for combined modality in selected sites, but optimal radiation dose is unclear. P-Bone, given the locations, are generally treated with radiation only. Therefore, evaluation of the radiation dose for curative modality is pertinent for management. This study suggests 45-50 Gy may confer better survival than lower dosage. Guidelines for radiation dose vary. Our study provides an additional 7-year data to a published database to 2013 (Ghiassi-Nejad et al.) with similar OS. We further stratified the outcome of P-bone, the bulk of solitary plasmacytoma by site of disease and radiation dose along with patient characteristics. Although higher doses have benefit for survival, modern techniques will hopefully decrease comorbidities that can occur locally and longitudinally. Our large dataset can provide reference to develop better guidelines for management of solitary plasmacytoma, especially P-bone.

Survival analysis and prognostic factors in posterior fossa ependymomas in children and adolescents.

In this study, the authors aimed to analyze the overall survival (OS) and progression-free survival (PFS) of patients younger than 18 years of age who were diagnosed with posterior fossa ependymomas, and to identify prognostic factors such as the degree of resection, tumor topography, and involvement of the lesion in the hindbrain. The authors performed a retrospective cohort study of patients younger than 18 years of age, treated beginning in 2000, with a diagnosis of posterior fossa ependymoma. Ependymomas were separated into three groups: tumors restricted to the fourth ventricle, tumors inside the fourth ventricle and exiting from the foramen of Luschka, and tumors inside the fourth ventricle and completely surrounding the hindbrain. Furthermore, the tumors were classified by molecular group using the staining method for H3K27me3. Statistical analysis was performed using Kaplan-Meier survival curves, with p < 0.05 considered statistically significant. Of 1693 patients who underwent surgical treatment between January 2000 and May 2021, 55 patients who met the inclusion criteria were included. The median age at diagnosis was 2.98 years. The median OS was 44 months, and the survival rates at 1, 5, and 10 years were 92.5%, 49.1%, and 38.3%, respectively. The cases were assigned to two posterior fossa ependymoma molecular groups: 35 (63.6%) cases to group A and 8 (14.5%) to group B. The median ages in groups A and B were 2.94 and 2.85 years and the median OS values were 44 and 38 months, respectively (p = 0.9245). Statistical analysis was performed on multiple variables, including age, sex, histological grade, Ki-67 expression, tumor volume, extent of resection, and adjuvant therapies. The median PFS of patients with dorsal-only involvement was 28 months; for dorsolateral involvement, it was 15 months; and for total involvement, it was 9.5 months (p = 0.0464). No statistically significant difference was found for OS. There was a statistically significant difference between the proportion of patients in whom gross-total resection was achieved in the dorsal-only involvement group (73.1%, 19/26) and those in the total involvement group (0%, 0/6) (p = 0.0019). This study confirmed that the extent of resection has an impact on OS and PFS. The authors found that adjuvant radiotherapy resulted in a higher OS but did not prevent progression, that the pattern of involvement of the brainstem in the tumor at diagnosis could elicit important information regarding the patient's prognosis regarding PFS, and that the total involvement of the rhombencephalon impaired the gross-total resection of these tumors.

Supratotal Resection of Glioblastoma: Better Survival Outcome than Gross Total Resection

Supratotal resection (SupTR) of glioblastoma allows for a superior long-term disease control and increases overall survival. On the other hand, aggressive conventional approaches, including gross total resections (GTR), are limited by the impairment risk of adjacent eloquent areas, which may cause severe postoperative functional morbidity. This study aimed to analyze institutional cases with respect to the potential survival benefits of additional resection, including lobectomy, as a paradigm for SupTR in patients of glioblastoma. Between 2014 and 2018, 15 patients with glioblastoma underwent SupTR (GTR and additional lobectomy) at the authors' institution. The postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS) were analyzed for the patients. Patients with SupTR showed significantly prolonged PFS and OS. The median PFS and OS values for the entire study group were 33.5 months (95% confidence intervals (CI): 18.5-57.3 months) and 49.1 months (95% CI: 24.7-86.6 months), respectively. Multivariate analysis revealed that the O6-DNA-methylguanine methyltransferase (MGMT) promoter methylation status was the only predictor for both superior PFS (p = 0.03, OR 5.7, 95% CI 1.0-49.8) and OS (p = 0.04, OR 6.5, 95% CI 1.1-40.2). There was no significant difference between the pre- and postoperative KPS scores. Our results suggest that SupTR with lobectomy allows for a superior PFS and OS without negatively affecting patient performance. However, due to the small number of patients, further studies that include more patients are needed.

An elevated systemic inflammation index is related to an inferior response to pomalidomide and dexamethasone treatment in patients with relapsed and refractory multiple myeloma.

The systemic inflammation index (SII) might serve as an indicator of the equilibrium between the inflammatory and immune responses. The aim of the study was to determine the clinical value and prognostic significance of SII in the cohort of multiple myeloma (MM) patients treated with a regimen of pomalidomide and dexamethasone (Pd). This retrospective, real-life study included patients who received a Pd regimen in our centre between November 2018 and July 2022. The systemic inflammation index was calculated from peripheral blood counts of platelets, neutrophils, and lymphocytes collected shortly before commencement of Pd treatment using the equation: SII = N × P/L, where N, P, and L are the respective counts per litre of peripheral blood for neutrophils, platelets, and lymphocytes. The study group consisted of 54 patients. Most patients received Pd as the third (38.9%) or fourth (37.0%) line of treatment. The median number of completed treatment cycles was 5 (IQR: 1-12). The median progression-free survival (PFS) was 6.8 months and overall survival (OS) 14.8 months. High SII (> 374) was an independent prognostic factor for PFS (HR = 3.0, 95% CI: 1.4-6.3, p < 0.01) and OS (HR = 2.2, 95% CI: 1.0-4.6, p = 0.04). In the low SII group, the respective median PFS and OS values were 9.6 and 21.7 months, compared to 2.6 (p = 0.018) and 5.5 months (p = 0.035) in the high SII group. The systemic inflammation index has prognostic significance in MM patients treated with Pd. A high SII predicts a poorer outcome in pretreated MM patients undergoing Pd treatment evaluation. As such, it may well be a key factor for guiding subsequent treatment decisions.

Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis.

KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P < 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742-0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P < 0.001). mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.

Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine, Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma

PurposeTo determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA). Materials and MethodsData of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured. ResultsCalculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%–95.9%) and 2-year OS of 52.9% (95% CI, 20.3%–77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy. ConclusionsFirst-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy.

Nivolumab improves overall survival (OS) in patients with advanced gastric cancer (AGC) refractory to at least two previous chemotherapy regimens. We investigated whether changes in body weight and nutrition from first-line chemotherapy to nivolumab affected its efficacy. The correlation between weight change and nutritional status up to the start of nivolumab treatment and OS and progression-free survival (PFS) after starting nivolumab treatment was determined. Nutritional status was examined using the C-reactive protein/albumin ratio (CAR). A loss in body weight (LBW) from the onset of the first treatment of <4.5% led to OS prolongation and improved PFS outcomes. The median OS values in the LBW < 4.5% and ≥4.5% groups were 11.4 and 3.6 months, respectively. Similarly, changes in CAR from first-line chemotherapy (ΔCAR) affected OS; the ΔCAR < 0.01 group had a better prognosis than the ΔCAR ≥ 0.01 group. The median OS values in the ΔCAR < 0.01 and ≥0.01 groups were 9.4 and 4.5 months, respectively. The median OS in the group with LBW < 4.5% and ΔCAR < 0.01 was 12.9 months. LBW and deterioration of nutritional status following first-line chemotherapy are poor prognostic factors in AGC patients who received nivolumab as third- or later-line therapy. Early intervention to maintain body weight and nutritional status may improve the efficacy of immune checkpoint inhibitors.

Molecular-targeted Therapy for Metastatic Renal Cell Carcinoma As First-line Therapy: A Single Institution 13-year Experience.

We aimed to identify the role of first-line monotherapy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in patients with metastatic RCC. Eligible patients were categorized into three groups (favorable, intermediate, and poor risk) according to the International Metastatic RCC Database Consortium risk criteria. Overall survival (OS) was the primary endpoint. Survival was compared using the log-rank test. A total of 108 patients were retrospectively analyzed. The numbers of patients in the favorable-, intermediate-, and poor-risk groups were 32 (30%), 66 (61%), and 10 (9%), repestively. The median OS values in the entire cohort was 36 months (95% confidence interval [CI] 29-53). The median OS in the favorable, intermediate, and poor risk groups were 94 months (95% CI: 43-Not reached), 30 months (95% CI: 20-38), and 8 months (95% CI: 0-Not reached), respectively (p<0.05). Prior nephrectomy, clear cell histology, clinical T stage ≤2, no metastasis at the time of diagnosis, nivolumab beyond first-line therapy, and objective response to VEGFR-TKIs were factors significantly prolonging OS on univariate analysis. VEGFR-TKI monotherapy as first-line therapy was an effective treatment option for patients with metastatic clear cell RCC with favorable risk.

Targeting HER2 mutation–positive advanced biliary tract cancers with neratinib: Final results from the phase 2 SUMMIT basket trial.

4079 Background: HER2 mutations are infrequent genomic events in biliary tract cancers (BTCs) and are associated with poor overall survival (OS) in patients with metastatic disease. HER2 overexpression is associated with an increased risk of disease recurrence in patients with resected BTC. There is limited data on targeting HER2 in BTC harboring activating somatic HER2 mutations. Neratinib, an irreversible, pan-HER, oral tyrosine kinase inhibitor, interferes with constitutive receptor kinase activation and has demonstrated activity in several HER2-mutant solid tumors. Methods: SUMMIT is an open-label, single-arm, multi-cohort, phase 2, ‘basket’ trial of neratinib in patients with solid tumors harboring oncogenic HER2 somatic mutations. The primary objective of the BTC cohort was to estimate objective response rate (ORR). Secondary objectives were clinical benefit rate (CBR), progression-free survival (PFS), OS, response duration, safety, and tolerability. Retrospective central confirmation of locally reported HER2 mutation (next-generation sequencing on archival or fresh tumor tissue using MSK-IMPACT or in cfDNA extracted from plasma by MSK-ACCESS) and association with outcome was an exploratory endpoint. This trial is registered with ClinicalTrials.gov (NCT01953926). Results: 25 treatment-refractory patients with metastatic BTC were enrolled (11 cholangiocarcinoma, 10 gallbladder, 4 ampullary cancers). ORR was 16% (95% CI 4.5–36.1%) and CBR was 28% (95% CI 12.1–49.4%). Median PFS and OS were 2.8 (95% CI 1.1–3.7) and 5.4 (95% CI 3.7–11.7) months, respectively. Median PFS for the gallbladder, cholangiocarcinoma and ampulla cohorts was 3.7 (95% CI 0.8–6.4), 1.4 (95% CI 0.5–9.1), and 1.1 (95% CI 1.1–3.8) months, respectively. Corresponding median OS values in these cohorts were 9.8 (95% CI 2.4–NE), 5.4 (95% CI 0.8–16.2), and 5.0 (95% CI 3.7–10.2) months, respectively. Central mutation confirmation was feasible for 23 of 25 patients; 22 were concordant with enrolment assays. The most common HER2 mutations were S310F (n = 11; 48%) and V777L (n = 4; 17%). Exploratory analyses suggested worse outcomes for HER2-mutant tumors with co-occurring oncogenic TP53 and CDKN2A alterations. Loss of amplified HER2 S310F and acquisition of multiple previously undetected oncogenic co-mutations were identified at progression in one of four responders. Diarrhea (56% any grade) was the most common toxicity. Conclusions: Neratinib is tolerable with modest antitumor activity in patients with BTC harboring HER2 mutations. Although the primary endpoint was met, future studies should evaluate rational combinations to augment and/or prolong responses. Clinical trial information: NCT01953926.

Proton Pump Inhibitors Ameliorate Capecitabine-induced Hand-Foot Syndrome in Patients With Breast Cancer: A Retrospective Study

Hand-foot syndrome (HFS) is the most common adverse event associated with capecitabine, and its pathogenesis is known to be associated with inflammation. Proton pump inhibitors (PPIs) reportedly exert anti-inflammatory effects; however, the impact of PPIs on capecitabine-induced HFS needs to be clarified in the clinical setting. In the present study, we retrospectively investigated the efficacy and safety of PPIs in patients with breast cancer receiving capecitabine. We analyzed the effects of PPIs on the development of severe HFS (grade ≥2), progression-free survival (PFS), and overall survival (OS) in 195 patients who received capecitabine chemotherapy for breast cancer. In total, 50 patients (26%) were treated with PPIs, while 145 patients (74%) did not receive PPIs. The incidence of severe HFS was significantly lower in patients who received PPIs (18%) than in patients who did not receive PPIs (43%, p=0.001), and the discontinuation rate of capecitabine therapy due to HFS was also lower in patients receiving PPIs than in those who did not receive PPIs (p=0.003). Multivariate analysis revealed that concomitant PPIs use was an independent factor that significantly contributed to the prevention of severe HFS (odds ratio (OR)=0.265, p=0.003). Meanwhile, no significant difference in median PFS and OS values was observed between patients treated with and without PPIs. Concomitant use of PPIs could ameliorate capecitabine-induced HFS in patients with breast cancer.

Real-World Metastatic Renal Cell Carcinoma Treatment Patterns and Clinical Outcomes in The Netherlands.

The number of treatment options for patients with metastatic renal cell carcinoma (mRCC) has significantly grown in the last 15 years. Although randomized controlled trials are fundamental in investigating mRCC treatment efficacy, their external validity can be limited. Therefore, the efficacy of the different treatment options should also be evaluated in clinical practice. We performed a chart review of electronic health records using text mining software to study the current treatment patterns and outcomes. mRCC patients from two large hospitals in the Netherlands, starting treatment between January 2015 and May 2020, were included. Data were collected from electronic health records using a validated text mining tool. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan–Meier method. Most frequent first-line treatments were pazopanib (n = 70), sunitinib (n = 34), and nivolumab with ipilimumab (n = 28). The overall median PFS values for first-line treatment were 15.7 months (95% confidence interval [95%CI], 8.8–20.7), 16.3 months (95%CI, 9.3–not estimable [NE]) for pazopanib, and 6.9 months (95% CI, 4.4–NE) for sunitinib. The overall median OS values were 33.4 months (95%CI, 28.1–50.9 months), 39.3 months (95%CI, 29.5–NE) for pazopanib, and 28.1 months (95%CI, 7.0–NE) for sunitinib. For nivolumab with ipilimumab, median PFS and median OS were not reached. Of the patients who finished first- and second-line treatments, 64 and 62% received follow-up treatments, respectively. With most patients starting on pazopanib and sunitinib, these real-world treatment outcomes were most likely better than in pivotal trials, which may be due to extensive follow-up treatments.

Prognostic Nutritional Index Predicts Early Mortality in Diffuse Large B-cell Lymphoma

Objective:The international prognostic index (IPI) and the revised IPI (R-IPI) are used to determine the prognosis in diffuse large B-cell lymphoma (DLBCL). However, these scoring systems are insufficient to identify very high-risk patients. Recently, the prognostic nutritional index (PNI) -calculated with lymphocyte count and albumin- has been used to determine the prognosis in DLBCL. This study aimed to evaluate the effect of PNI score on prognosis and survival in patients with high-risk DLBCL.Methods:Patients diagnosed with DLBCL and treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone were included. Pre-treatment IPI, R-IPI, and PNI scores and progression-free survival (PFS) and overall survival (OS) times were calculated. The cutoff value for PNI according to OS was determined by using the X-Tile program.Results:One hundred and ten patients were included, the median age was 63 years and the median follow-up period was 25 months. According to R-IPI, the median OS could not be reached for the very good risk group, and the median OS values were 83 and 17 months in the good and poor-risk groups, respectively (p=0.001). The cohort was divided into three groups according to the cut-off value for the PNI: patients with PNI <33 were classified as high-risk, 33-42 intermediate-risk, and ≥42 as low-risk. According to PNI, the median durations of PFS and OS were 2 months and 3 months in the high-risk group, 9 months and 19 months in the intermediate-risk group respectively, and in the low-risk group the median duration for PFS and OS could not be reached (p=0.001).Conclusions:The R-IPI is widely used to estimate the prognosis in DLBCL. But in our cohort, in the poor-risk patient group, the OS was 17 months according to R-IPI, while this period was 3 months according to PNI. This finding demonstrated that PNI might predict early mortality in DLBCL.

An Observational Study on Treatment Outcomes in Patients With Stage III NSCLC in Taiwan: The KINDLE Study

IntroductionPatients with stage III NSCLC represent a very heterogenous group that requires different treatment strategies, especially in patients with N2 (2 nearby lymph nodes having cancer)-positive NSCLC and unresectable EGFR-mutant NSCLC. This real-world study may provide more insights into treatment decisions. MethodsThe KINDLE study is a large, multinational real-world observational study that assessed different treatment strategies in patients with stage III NSCLC. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using Kaplan-Meier and log-rank testing. Patients were classified on the basis of disease stage, resectability, and treatment modalities. ResultsThe Taiwan subgroup enrolled 200 patients. The median PFS and OS values were similar among patients with stage IIIA and stage IIIB disease, but were significantly better in patients who were deemed as a resectable disease than in those who were deemed as an unresectable disease. In patients with N2-positive NSCLC, patients who underwent surgery had better PFS, but not OS, than patients administered with chemoradiotherapy (CRT) (PFS 13.4 vs. 7.3 mo, hazard ratio [HR] = 0.18, p < 0.001; OS 32.4 vs. 22.0 mo, HR = 0.64, p = 0.215). Among patients with unresectable EGFR-mutant NSCLC, OS was significantly poorer after upfront EGFR–tyrosine kinase inhibitors (TKI) than after upfront CRT with sequential EGFR-TKI (27.4 vs. 49.0 mo, HR = 3.09, p = 0.03). ConclusionsOur study suggests that surgery could be added as part of therapy for patients with stage III N2-positive NSCLC. Moreover, upfront CRT with sequential EGFR-TKI seems to be appropriate for stage III unresectable EGFR-mutant NSCLC. Further randomized studies are needed to validate these results.

Chemoradiotherapy with temozolomide vs. radiotherapy alone in patients with IDH wild-type and TERT promoter mutation WHO grade II/III gliomas: A prospective randomized study

PurposePatients with grade II/III diffuse glioma (lower grade glioma, LGG) with isocitrate dehydrogenase wild-type (IDH-wt) and telomerase reverse-transcriptase promoter mutation (TERTp-mut) experience shorter overall survival (OS) time than IDH mutant patients. The optimal treatment strategy for these patients is unclear. We compared the effects of radiotherapy (RT) alone vs. RT concurrent with temozolomide (TMZ) followed by adjuvant TMZ in these LGG patients. Patients and methodsThirty-seven LGG patients with IDH-wt and TERTp-mut were randomly allocated to either RT alone treatment (RT group, n = 18; 60 Gy in 30 daily fractions) or RT concurrent with TMZ (75 mg/m2/d, 7 d/week) followed by adjuvant TMZ (CRT group, n = 19). The median follow-up duration was 17 months. Log-rank test was used for OS and PFS comparisons. ResultsThe 1-year OS rate was 94.1% [95% confidence interval (CI) 82.9–100] in the CRT group and 74.6% (95% CI, 52.9–96.4) in the RT group. The median OS values in the CRT and RT groups were statistically different [25 vs. 17 months, respectively; hazard ratio (HR) 0.271; 95% CI, 0.092–0.793; P = 0.017], while PFS values were not (16 vs. 7 months, respectively; HR, 0.917; 95% CI, 0.397–2.120; P = 0.840). Multivariate analysis indicated that CRT treatment and female sex were associated with significantly longer OS (P = 0.001, P = 0.016, respectively). ConclusionCRT treatment for IDH-wt/TERTp-mut grade II/III gliomas resulted in significantly longer OS than RT alone. Female sex was a significant favorable prognostic factor.