Metastatic Subgroup Research Articles

Nomograms to predict lung metastasis in malignant primary osseous spinal neoplasms and cancer-specific survival in lung metastasis subgroup.

To construct and validate nomograms for predicting lung metastasis probability in patients with malignant primary osseous spinal neoplasms (MPOSN) at initial diagnosis and predicting cancer-specific survival (CSS) in the lung metastasis subgroup. A total of 1,298 patients with spinal primary osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma were retrospectively collected. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic analysis were used to identify the predictors for lung metastasis. LASSO and multivariate Cox analysis were used to identify the prognostic factors for 3- and 5-year CSS in the lung metastasis subgroup. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analyses (DCA) were used to estimate the accuracy and net benefits of nomograms. Histologic type, grade, lymph node involvement, tumor size, tumor extension, and other site metastasis were identified as predictors for lung metastasis. The area under the curve (AUC) for the training and validating cohorts were 0.825 and 0.827, respectively. Age, histologic type, surgery at primary site, and grade were identified as the prognostic factors for the CSS. The AUC for the 3- and 5-year CSS were 0.790 and 0.740, respectively. Calibration curves revealed good agreements, and the Hosmer and Lemeshow test identified the models to be well fitted. DCA curves demonstrated that nomograms were clinically useful. The nomograms constructed and validated by us could provide clinicians with a rapid and user-friendly tool to predict lung metastasis probability in patients with MPOSN at initial diagnosis and make a personalized CSS evaluation for the lung metastasis subgroup.

Ewing sarcoma among children 5years of age or younger: Is it a different disease?

Children ≤5years of age with Ewing's sarcoma (ES) possibly have a distinct disease biology, data on which are scarce. We evaluated clinical features, outcomes, and prognostic factors of ES among children with age ≤5years. Children with ES registered between 2003 and 2019 were included. Baseline clinical and treatment details were retrieved from medical records. Prognostic factors were identified using multivariable Cox regression. Clinical features and outcomes of children ≤5years were compared with those greater than 5years by chi-square and log-rank tests. Propensity score-matched (PSM) analysis was done to evaluate the impact of age on survival in the metastatic and localized subgroups. Out of the 859 patients, 86 (10%) were ≤5years of age (median age 4years, 60 males [69.8%]). The most common location was the extremities (37.2%), followed by thorax (27.9%) and head and neck (H&N) (22.1%); baseline metastases were seen in 25 patients (29.8%). The median event-free-survival (EFS) and overall survival (OS) were 25.6 and 68.7months, respectively. Metastatic disease predicted inferior OS (hazard ratio [HR]=2.54, p=.018) and EFS (HR=2.47, p=.007], symptom duration ≤3months predicted an inferior OS (HR=2.17, p=.048). Compared to age greater than 5years, younger children had more H&N and less pelvic primaries (p<.001) and lesser baseline metastases (p=.037). PSM analysis did not reveal any significant impact of age on OS in the metastatic (HR=1.59, p=.29) or localized cohort (HR=1.77, p=.09). Children with ES ≤5years of age have a distinct favorable clinical presentation. However, age is not an independent prognostic factor for survival outcomes when adjusted for confounders.

Residual biliary intraepithelial neoplasia without malignant transformation at resection margin for perihilar cholangiocarcinoma does not require expanded resection: a dual center retrospective study

BackgroundAdditional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN).MethodConsecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics.Results306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup.ConclusionFor pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.

MDB-44. MIR-106B-5P DEPLETION IN GROUP 4 METASTATIC MEDULLOBLASTOMA SEVS FINE-TUNES MMP-2 ACTIVATION VIA DIFFERENTIAL TIMP-2 PROTEIN ABUNDANCE

Abstract BACKGROUND Small Extracellular Vesicles (sEVs) are major intercellular communicators, with growing evidence of a role in establishing favourable metastatic niches during cancer progression. We have shown that, relative to their paired primary counterpart, Group 4 (Grp4) metastatic Medulloblastoma (MB) cell-lines release significantly more sEVs with increased functionally active MMP-2 on their surface, resulting in enhanced extracellular matrix degradation and subsequently increased cell invasiveness. METHODS Transcriptomic analysis of sEV microRNA cargoes derived from metastatic/recurrent and primary cell-line and patient CSF samples, followed by microRNA target prediction of differentially abundant microRNAs using TargetScan and miRDB was conducted. Patient dataset analysis was used to confirm microRNA target mRNA expression levels. Finally, microRNA inhibition followed by RT-qPCR or invasion assays were used to quantify changes at the gene and functional level. RESULTS Transcriptomic analysis demonstrated &amp;gt;75% miR-106b-5p depletion in Grp4 MB metastatic sEVs compared to their primary sEV counterparts derived from cell-line and patient CSF samples. This microRNA is predicted to target TIMP-2, which plays a crucial role in MMP-2 activation. We confirmed TIMP-2 to be upregulated in paired metastatic Grp4 tumours relative to their primary counterpart using a publicly available patient dataset. Following miR-106b-5p inhibition in the primary cell-line, RT-qPCR analysis and invasion assays determined the existence of a complex functional response, with increasing TIMP-2 gene expression leading to decreasing invasiveness. This suggests a delicately balanced process where TIMP-2 overabundance can ultimately impede MMP-2 activation. In support of this, analysis of patient datasets showed intermediate TIMP-2 gene expression amongst Grp3/4 patients compared to less frequently metastatic subgroups. CONCLUSIONS Our data support the hypothesis that sEV-derived miR-106b-5p regulates enhanced ECM degradation through fine-tuning MMP-2 activation via differential TIMP-2 abundance. Future work will quantify changes in cell/sEV surface-bound TIMP-2 and MMP-2 alongside MMP-2 activation via flow cytometry and gelatin zymography respectively.

Outcome of prostate cancer with CNS metastasis: An analysis of SEER database (2010-2020).

e17037 Background: Brain metastasis from prostate cancer is rare, with an estimated incidence of &lt;1%, and its characteristics and outcomes are poorly understood. We report a contemporary analysis of outcomes in patients with CNS metastasis from prostate cancer in association with clinicopathological variables by utilizing the Survival, Epidemiology, and End Result (SEER) database with data from 2010 to 2020. Methods: From the SEER database, we identified histologically confirmed primary prostate cancers with any distant metastasis. Data for survival as well as multiple clinicopathological variables including age, race, prostate-specific antigen (PSA) level, Gleason score, prior radiotherapy, histology, and specific metastatic sites were extracted. Statistical analysis included chi-square. ANOVA, and Kaplan-Meier analysis for overall survival (OS) and disease-specific survival. Results: SEER database (2010-2020) identified 27,501 patients with metastatic prostate cancer, of which 27,118 (98.6%) were adenocarcinoma and 383 (1.4%) were prostate cancer with neuroendocrine features. Brain metastasis was seen in 282 (1.04%) and 15 (5.32%) patients in these histologic groups, respectively. Brain metastases were associated with worse prognosis with median OS of 14 months compared to bone-dominant and non-regional lymph node only diseases that showed median OS of 31 months and not reached, respectively (P &lt; 0.01). Within the population with brain metastases, outcome comparison based on age (&lt;65 vs. ≥65 years), ethnicity (Caucasian vs. African American vs. Hispanic), PSA (&lt;98 vs. ≥98 ng/ml), and Gleason score (&lt;9 vs. ≥9) showed no statistically significant difference (table). Presence of metastasis to other solid organs showed numerically worse outcome without statistical significance (OS: 26 months vs. 13 months, p=0.09). Significant OS difference was observed between the adenocarcinoma and neuroendocrine tumor within the brain metastasis subgroup (OS: 14 months vs. 6 months, p=0.03). Conclusions: CNS metastasis with prostate cancer carries worse prognosis in comparison to metastases to bone or distant lymph-nodes. Neuroendocrine tumor has higher risk of CNS metastasis although most of such cases are from adenocarcinoma due to its higher prevalence. OS analysis confirms worse outcome with neuroendocrine features compared to adenocarcinoma in CNS metastatic settings. [Table: see text]

Survival by depth of response and efficacy by International Metastatic Renal Cell Carcinoma Database Consortium Subgroup with lenvatinib plus pembrolizumab versus sunitinib in advanced renal cell carcinoma: analysis of the phase 3 randomized CLEAR study

Background: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival.Objective: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups.Design, setting, and participants: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC.Intervention: Patients were randomized 1:1:1 to lenvatinib 20mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment.Outcome measurements and statistical analysis: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1.Results and limitations: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or &gt;75 % target-lesion reduction by 6 mo had a 24-mo OS probability of 91.7 %. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4 % vs 28.8 %) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified.Conclusions: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS.Patient summary: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a ‘‘complete response’’ or had their tumors shrunk by &gt;75 % within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

Detection of metastatic lymph node and sentinel lymph node mapping ​using mannose receptor targeting in in vivo mouse footpad tumor models and rabbit uterine cancer models.

This study aimed to evaluate the effectiveness of neo-mannosyl human serum albumin-indocyanine green (MSA-ICG) for detecting metastatic lymph node (LN) and mapping sentinel lymph node (SLN) using mouse footpad uterine tumor models. Additionally, the authors assessed the feasibility of MSA-ICG in SLN mapping in rabbit uterine cancer models. The authors compared the LN targeting ability of MSA-ICG with ICG. Six mouse footpad tumor models and two normal mice were each assigned to MSA-ICG and ICG, respectively. After the assigned tracers were injected, fluorescence images were taken, and the authors compared the signal-to-background ratio (SBR) of the tracers. A SLN biopsy was performed to confirm LN metastasis status and CD206 expression level. Finally, an intraoperative SLN biopsy was performed in rabbit uterine cancer models using MSA-ICG. The authors detected 14 groin LNs out of 16 in the MSA-ICG and ICG groups. The SBR of the MSA-ICG group was significantly higher than that of the ICG group. The metastatic LN subgroup of MSA-ICG showed a significantly higher SBR than that of ICG. CD206 was expressed at a high level in metastatic LN, and the signal intensity difference increased as the CD206 expression level increased. SLN mapping was successfully performed in two of the three rabbit uterine cancer models. MSA-ICG was able to distinguish metastatic LN for an extended period due to its specific tumor-associated macrophage-targeting property. Therefore, it may be a more distinguishable tracer for identifying metastatic LNs and SLNs during uterine cancer surgery. Further research is needed to confirm these results.

Dielectrophoretic and electrochemical impedance mapping of metastatic potential in MDA-MB-231 breast cancer cells using inkjet-printed castellated microarray.

The spread of metastatic cancer cells poses a significant challenge in cancer treatment, making innovative approaches for early detection and diagnosis essential. Dielectrophoretic impedance spectroscopy (DEPIS), a powerful tool for cell analysis, combines dielectrophoresis (DEP) and impedance spectroscopy (IS) to separate, sort, cells and analyze their dielectric properties. In this study, we developed and built out-of-plane inkjet-printed castellated arrays to map the dielectric properties of MDA-MB-231 breast cancer cell subtypes across their metastatic potential. This was realized via modulating the expression of connexin 43 (Cx43), a marker associated with poor breast cancer prognosis and increased metastasis. We employed DEP-based trapping, followed by EIS measurements on bulk cell population, for rapid capture and differentiation of the cancer cells according to their metastatic state. Our results revealed a significant correlation between the various MDA-MB-231 metastatic subtypes and their respective dielectrophoretic and dielectric properties. Notably, cells with the highest metastatic potential exhibited the highest membrane capacitance 16.88 ± 3.24 mF m-2, followed by the less metastatic cell subtypes with membrane capacitances below 14.3 ± 2.54 mF m-2. In addition, highly metastatic cells exhibited lower crossover frequency (25 ± 1 kHz) compared to the less metastatic subtypes (≥27 ± 1 kHz), an important characteristic for cell sorting. Finally, EIS measurements showed distinct double layer capacitance (CDL) values at 1 kHz between the metastatic subgroups, confirming unique dielectric and dielectrophoretic properties correlated with the metastatic state of the cell. Our findings underscore the potential of DEPIS as a non-invasive and rapid analytical tool, offering insights into cancer biology and facilitating the development of personalized therapeutic interventions tailored to distinct metastatic stages.

Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer.

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in tumor tissues of several malignancies, including pancreatic cancer. Because of its role in tumor progression, IGFBP2 has been investigated as a tumor biomarker. However, little is known about its utility in pancreatic cancer. Plasma IGFBP2 levels were determined using enzyme-linked immunosorbent assay in 75 patients with pancreatic ductal adenocarcinoma (PDAC), 73 matched healthy controls, and 17 chronic pancreatitis patients. Our results showed that the plasma IGFPB2 level was significantly higher in PDAC patients than in patients with chronic pancreatitis and healthy controls. At a cut-off value of 333.9 ng/mL, the specificity and sensitivity were 78.08 and 65.33%, respectively. IGFBP2 level alone did not outperform carbohydrate antigen 19-9 (CA19-9) in diagnostic accuracy, but it successfully identified 9 out of 24 PDAC patients who were misidentified by CA19-9. The combination of IGFBP2 and CA19-9 was more accurate in the detection of PDAC than CA19-9 alone. IGFBP2 was more accurate than the other in discriminating between chronic pancreatitis and PDAC. Plasma IGFBP2, rather than CA19-9, was higher in the new-onset diabetes, lymph node involvement, and distant metastasis subgroups. IGFBP2 level was notably higher in stage IV cases than in stage I/II or stage III disease. However, CA19-9 did not show a difference between stages. After adjusting for lymph node involvement and distant metastasis, plasma IGFBP2 was identified as an independent prognostic marker for PDAC. The median survival time for patients with an IGFBP2 level ≥333.9 ng/mL was significantly shorter than that for patients with an IGFBP2 level <333.9 ng/mL. Marked elevation of plasma IGFBP2 in PDAC is associated with poorer survival. IGFBP2 may be considered as a supplementary biomarker for the diagnosis and prognostic prediction in Chinese pancreatic cancer patients.

The Probability of Metastases Within Different Prostate-specific Antigen Ranges Using Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer

Background and objectivesThe association between prostate-specific antigen (PSA) level and probability of metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has not yet been established in patients with newly diagnosed prostate cancer (PCa). Our objective was to assess the probability of metastatic disease within different PSA ranges using PSMA PET/CT for initial staging of PCa, and to identify both the anatomical distribution and the predictors of metastases on PSMA PET/CT. MethodsIn total, 2193 patients with newly diagnosed PCa were retrospectively studied. PSMA PET/CT was performed for staging purposes between January 2017 and May 2022. The proportion of patients with PSMA-avid metastases, stratified by PSA level, was studied. A vast majority of patients in whom at least one high-risk prognostic factor was present underwent PSMA PET/CT. A multivariable logistic regression analysis was performed to identify the predictors of metastases on PSMA PET/CT using clinical, biochemical, radiological, and pathological variables. Key findings and limitationsThe median PSA level at PSMA PET/CT was 14.1 ng/ml. Any metastatic disease (miN1-M1a-c) was observed in 34.7% (763/2193) of all patients and distant metastases (miM1a-c) in 25.4% (557/2193) of patients. The presence of any metastatic disease increased with PSA levels, being 15.4% in men with PSA levels <10 ng/ml and 87.5% in men with PSA levels >100 ng/ml. The multivariable logistic regression analysis found significant associations between the presence of any metastatic disease and PSA subgroups, clinical tumor stage ≥T2, grade group >3, and radiological tumor stage ≥T3b. Conclusions and clinical implicationsThis is the first large epidemiological study in patients with PCa demonstrating the association between PSA subgroups and metastatic disease on modern imaging PSMA PET/CT. Data from this study can be used to counsel patients on the probability of metastatic disease at the time of PSA screening and to provide guidance on existing guidelines. Patient summaryThe prostate-specific antigen level could be used to assess the risk of metastases on prostate-specific membrane antigen positron (PSMA) emission tomography/computed tomography (PET/CT). This knowledge is valuable for selecting patients who will benefit most from metastatic screening with PSMA PET/CT.

A review on calcinosis cutis

Calcinosis, marked by hydroxyapatite, calcium, and phosphate deposits in skin and subcutaneous tissues, is common in individuals with various physiological conditions, soft tissue ailments, and autoimmune disorders. Researchers categorize and analyze these occurrences, shedding light on their pathophysiology. They also review scientific evidence regarding non- pharmacologic and pharmacodynamic treatments. Calcinosis cutis involves the accumulation of insoluble calcium ions in the epidermis and subcutaneous tissue, classified into dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis subgroups. Dysplastic deposits result from cellular damage, while metastatic calcification stems from irregular potassium and phosphorous metabolism. Undiagnosed calcification occurs independently of tissue destruction or underlying disease. Autoimmune syndrome-induced epidermal calcification is a rare therapy-related effect. Calciphylaxis, primarily affecting the vascular system, is introduced, with disturbances in calcium and phosphorus biotransformation and congenital hypothyroidism as contributing factors.

Clinical feasibility of a commercially available MRI-only method for radiotherapy treatment planning of the brain.

Advancements in deep-learning based synthetic computed tomography (sCT) image conversion methods have enabled the development of magnetic resonance imaging (MRI)-only based radiotherapy treatment planning (RTP) of the brain. This study evaluates the clinical feasibility of a commercial, deep-learning based MRI-only RTP method with respect to dose calculation and patient positioning verification performance in RTP of the brain. Clinical validation of dose calculation accuracy was performed by a retrospective evaluation for 25 glioma and 25 brain metastasis patients. Dosimetric and image quality of the studied MRI-only RTP method was evaluated by a direct comparison of the sCT-based and computed tomography (CT)-based external beam radiation therapy (EBRT) images and treatment plans. Patient positioning verification accuracy of sCT images was evaluated retrospectively for 10 glioma and 10 brain metastasis patients based on clinical cone-beam computed tomography (CBCT) imaging. An average mean dose difference of Dmean = 0.1% for planning target volume (PTV) and 0.6% for normal tissue (NT) structures were obtained for glioma patients. Respective results for brain metastasis patients were Dmean = 0.5% for PTVs and Dmean =1.0% for NTs. Global three-dimensional (3D) gamma pass rates using 2%/2 mm dose difference and distance-to-agreement (DTA) criterion were 98.0% for the glioma subgroup, and 95.2% for the brain metastasis subgroup using 1%/1 mm criterion. Mean distance differences of <1.0 mm were observed in all Cartesian directions between CT-based and sCT-based CBCT patient positioning in both subgroups. In terms of dose calculation and patient positioning accuracy, the studied MRI-only method demonstrated its clinical feasibility for RTP of the brain. The results encourage the use of the studied method as part of a routine clinical workflow.

Efficacy and safety of first-line treatments for patients with advanced hepatocellular carcinoma: A systematic review and network meta-analysis.

4094 Background: In recent years, the first-line treatment options for advanced HCC has been increasingly abundant, including transarterial therapies, combination of the immune checkpoint inhibitors (ICIs) and the anti-vascular endothelial growth factor (VEGF) inhibitor, ICIs combined with ICIs, and tyrosine kinase inhibitors. However, it remains to be confusing which treatment pattern would benefit people most, especially for different subgroups. Methods: A systematic literature search was conducted on PubMed, Embase, Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology and European Society of Medical Oncology meeting proceedings for III phase randomized clinical trials (RCTs) investigating first-line treatments for HCC compared with sorafenib. The survival outcomes and toxic effects of RCTs should be reported, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of grade 3 or higher. This systematic review was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. The random-effects model was used to calculate the summary hazard ratios (HRs) of OS and PFS. The likelihood of ORR, and AEs of grade 3 or higher was performed by odds ratios (ORs) using a random-effects model. Results: A total of 13 phase III RCTs involving 8505 patients were included in this study. Hepatic arterial infusion of oxaliplatin combined with fluorouracil (FOHAIC-1) showed OS, PFS, and ORR benefit over all other first-line therapies, except for the regimen of sorafenib plus HAIC of FOLFOX (OS: HR, 0.88; 95% CI, 0.37-2.09; ORR: OR, 1.53; 95% CI, 0.29-8.13). More importantly, we found that sorafenib combined with FOLFOX was superior to other regimens in patients with HBV infection regarding OS except FOHAIC-1 (HR, 0.57; 95%CI, 0.21-1.52) and tremelimumab-durvalumab (HR, 0.42; 95%CI, 0.16-1.11). While in HCV-infected subgroup, ICIs combined with anti-VEGF inhibitor improved OS benefit compared with tremelimumab-durvalumab (HR, 0.31; 95% CI, 0.11-0.84) and sorafenib (HR, 0.38; 95% CI, 0.16-0.88). HAIC-FO also showed significant OS benefits to other therapies in patients with portal invasion or extrahepatic metastasis. The probability of adverse events of grade 3 or higher was significantly lower with HAIC-FO than with others except for nivolumab (RR, 0.96; 95%CI, 0.51-1.82) and tislelizumab (RR, 0.57; 95%CI, 0.30-1.08). Conclusions: This network meta-analysis supports arterial infusion as the first-line treatment for patients with HCC. In portal invasion and extrahepatic metastasis subgroups, HAIC-FO may be a preferred option, with sorafenib combined with FOLFOX as an additional option in those with HBV infection. Besides, novel combination therapy should be focused on in patients with certain subgroups.

Efficacy of bi-weekly docetaxel in hormone-sensitive metastatic prostate cancer (mHSPC).

e17070 Background: In pts with mHSPC, docetaxel in a three-week schedule is associated with better overall survival (OS) vs androgen suppression alone, principally in pts with high tumor volume(HV). In pts with mCRPC stage, biweekly docetaxel demonstrated greater efficacy and a better toxicity profile. There are few published data about the use of bi-weekly docetaxel in pts with mHSPC. Methods: Pts with mHSPC and treated with bi-weekly docetaxel from January 2014 to December 2020 at The Comprehensive Cancer Center Clinica de Occidente in Cali-Colombia, were retrospectively identified. We collected relevant variables from electronic medical records. Our primary objective was to determine the efficacy in OS and the incidence of febrile neutropenia (FN). We performed Kaplan Meier, and cox regression analysis with relevant variables. Results: 69 pts were included, with a mean follow-up time of 45 months. Median age was 72y, 82% had ECOG PS 0/1, 74% grade group 4-5, 23% visceral metastases, and 93% de novo metastatic disease. The median OS was 51 months, and 39% at 5 years. In HV and de novo metastatic pts, the median OS was 49 months. The median time to development of mCRPC was 34 months. 35% of the patients had a PSA &lt; 0.2ng/mL at month 6. In the univariate analysis, pts with HV (HR 10.49 95% CI 1.43-76.50, P = 0.0005), PSA &gt; 0.2ng/mL (HR 4.43 95% CI 2.09-9.41, P = 0.0000), imagen objective response rate (ORR) (HR 1.47 95% CI 1.09-1.95, P = 0.0156) and PS ECOG &gt; 0, (HR 3.3 CI95% 1.31-8.45, P = 0.003) had worse OS. Neither histologic grade 5 (HR 1.07, P = 0.8), visceral metastases (HR 1.2, P = 0.57), or de novo metastatic disease (HR 0.84, P = 0.74) were significantly associated. In the multivariate analysis, only PSA of &gt; 0.2ng/mL at 6 months remained significantly [Table 1]. FN was detected in 3.2% of patients. Conclusions: We report the study with the largest number of patients and follow-up time (median 42.5 months) in patients with mCSPC who used biweekly docetaxel in addition to standard androgen suppression. The outcomes are similar, indirectly compared, to those reported in the CHAARTED study in OS, specifically in the de novo high-volume metastatic subgroup (CHAARTED 48 months, current study 49 months), better time to CRPC (20 months CHAARTED, 34 months current study), and with a lower incidence of FN (6% CHAARTED, 2% current study). None of the pts used primary granulocyte colony-stimulating factor prophylaxis. The use of biweekly docetaxel in this scenario offers high efficacy with less toxicity. Randomized studies are strongly recommended to confirm these results. [Table: see text]

Integrating patient-reported-outcomes into prognostication in gastroesophageal cancer: Results of a population-based retrospective cohort analysis.

320 Background: Patient reported outcomes (PRO) measures are accurate self-reflections of an individual’s physical functioning and emotional well-being. The prognostic value is unknown in gastroesophageal (GE) cancer patients (pts). The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated 10-item PRO tool which uses a 0 to 10 rating of ten common symptoms (total rating 0-100). In this study, we examined the association between the ESAS score and overall survival (OS) in pts with localized and metastatic GE adenocarcinoma (GEA). Methods: This study is based on the retrospective cohort database of pts with localized (stage I-III) and metastatic GEA. We included pts who were diagnosed with GEA between 2011 and 2021 and completed at least 1 baseline ESAS prior to the treatment. Pts were grouped into 3 cohorts based as follows: High symptom burden (SB) ESAS score ≥ 26, Moderate SB (11-25) or low SB (0-10). OS was defined as time from the first visit date to death. OS was assessed using the Kaplan-Meier method and significance was set at 2-sided P &lt; 0.05. Univariate statistical analyses were used to examine the relationships between OS and multiple variables in the presentation. Results: 233 pts met the inclusion criteria: median age was 60.8y [51.4, 69.4]; 58% of pts were ECOG PS 1; 81% were non-Asian and 18.9% Asian; 67.4% of pts were male and 32.6% female. In terms of tumor location, gastric represented 47.2% of pts, GEJ 40.8% and esophageal 12.0% primaries; 43.7% pts were stage I-III, while 56.3% were de-novo metastatic pts. Median OS in Low, Mod, High SB pts cohorts were 22.7m, 17.6mm, &amp; 14.6m, respectively (p &lt; 0.036). Although worse OS and worse ESAS levels were not statistically significant in the localized pts (p, 505) and metastatic subgroup (p 0,092), there was a numerical tendency, especially in the metastatic pts. In the univariate analysis, there was a significant association between OS and high-symptom burden (Hazard ratio [HR] = 1.64 (95% CI, 1.12-2.38; p = 0.0104), ECOG ≥2 (HR= 2.79 (95% CI, 1.62-4.79; p = 0.0002) and metastatic pts (HR= 3.50 (95% CI, 2.51-4.86, p&lt;0.0001). Conclusions: Higher SB based on ESAS was associated with poorer OS among GEA pts. ESAS is a reliable tool that carries a prognostic significance that could be used in practice.[Table: see text]

Survival by Depth of Response and Efficacy by International Metastatic Renal Cell Carcinoma Database Consortium Subgroup with Lenvatinib Plus Pembrolizumab Versus Sunitinib in Advanced Renal Cell Carcinoma: Analysis of the Phase 3 Randomized CLEAR Study

BackgroundThe extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival. ObjectiveTo perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups. Design, setting, and participantsCLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC. InterventionPatients were randomized 1:1:1 to lenvatinib 20 mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment. Outcome measurements and statistical analysisLandmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1. Results and limitationsLandmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75% target-lesion reduction by 6 mo had a 24-mo OS probability of ≥91.7%. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4% vs 28.8%) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified. ConclusionsLenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS. Patient summaryIn this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a “complete response” or had their tumors shrunk by >75% within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution

BackgroundColorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood.MethodsWe evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures.ResultsWe detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis.ConclusionThese findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO.

Pure abdominal laparoscopic approach versus thoraco-abdominal laparoscopic approach: What is the best technique for liver resection in segment 7 and segment 8? An answer from the Institut Mutualiste Montsouris experience with short- and long-term outcome evaluation

BackgroundLesions in segments 7 and 8 are a challenge during standard laparoscopic liver resection. The addition of transthoracic trocars could be useful in the standard abdominal approach for laparoscopic liver resection. We report our experience with a thoraco-abdominal laparoscopic combined approach for liver resection with the aim of comparing short- and long-term outcomes. MethodsWe reviewed 1,003 laparoscopic liver resections in a prospectively maintained, single-institution database. We compared patient outcomes intraoperatively and postoperatively. We analyzed the long-term outcomes of the colorectal liver metastasis subgroup. Propensity score matching 1:1 was performed based on the following variables: age, American Society of Anesthesiologists, body mass index, previous abdominal surgery, multiple or single liver resection, lesion >50 mm or <50 mm, presence of solitary or multiple lesions, T stage, and N stage. ResultsThe standard abdominal approach was used in 110 laparoscopic liver resections, and the thoraco-abdominal laparoscopic combined approach was used in 62 laparoscopic liver resections. The thoraco-abdominal laparoscopic combined approach was associated with better intraoperative results (less blood loss and no need for conversion to open surgery). The R1s rate for segmentectomy 7 and 8 was lower in the thoraco-abdominal laparoscopic combined approach in the entire group and in the colorectal liver metastasis subgroup. In the colorectal liver metastasis subgroup, the 3- and 5-year overall survival was 90% and 80% in the thoraco-abdominal laparoscopic combined approach group and 76% and 52% in the standard abdominal approach group, respectively (P = .02). In univariate and multivariate analysis, the thoraco-abdominal laparoscopic combined approach was a significant factor that positively affected disease-free survival and overall survival. ConclusionThe thoraco-abdominal laparoscopic combined approach in laparoscopic liver resection in segments 7 and 8 is safe and feasible, and it has demonstrated better oncologic outcomes than the pure abdominal approach, especially in segmentectomy.

CT-Based Radiomic Score: A Risk Stratifier in Far-Advanced Gastric Cancer Patients

To prolong the survival, the value of a computed tomography-based radiomic score (RS) in stratifying survival and guiding personalized chemotherapy strategies in far-advanced gastric cancer (FGC) was investigated. This retrospective multicenter study enrolled 283 FGC patients (cT4a/bNxM0-1) from three centers. Patients from one center were randomly divided into the training (n=166) and internal validation (n=83) cohorts, whereas the external validation cohort (n=34) consisted of patients from the two other centers. The RS was calculated for each patient to predict progression-free survival (PFS). Features from the primary tumor and main metastasis (peritoneum, liver, and lymph node) were integrated in the training cohort and then validated for its ability to stratify PFS and overall survival (OS) in the validation cohort. The association between the RS and efficacy of neoadjuvant intraperitoneal and systemic (NIPS) therapy was also explored. The RS demonstrated a favorable prognostic ability to predict PFS in all cohorts (training: C-index 0.83, 95% confidence interval [CI]: 0.788-0.872; internal validation: C-index 0.75, 95% CI: 0.682-0.818; external validation: C-index 0.76, 95% CI: 0.669-0.851; all p < 0.05), as well as an excellent ability to stratify the PFS and OS in both the whole population and metastatic subgroups (p < 0.05). Patients with a low score were more likely to undergo surgery after perioperative chemotherapy (p < 0.05). Furthermore, only high-scoring patients with peritoneal metastasis benefited from NIPS. The RS may be an effective risk stratifier for the outcomes of FGC patients and may be used to select patients who can benefit from NIPS therapy.

Thoracic para-aortic lymph node recurrence in patients with esophageal squamous cell carcinoma: A propensity score-matching analysis.

Thoracic para-aortic lymph node (TPLN) recurrence in esophageal squamous cell carcinoma (ESCC) is rare and its impact on survival is unknown. We studied survival in patients with ESCC who developed TPLN recurrence. To study the survival in patients with ESCC who developed TPLNs recurrence. Data were collected retrospectively for 219 patients who had undergone curative surgery for ESCC during January 2012 to November 2017 and who developed recurrences (36.29% of 604 patients who had undergone curative surgeries for ESCC). The patients were classified into positive (+) and negative (-) TPLN metastasis subgroups. We also investigated TPLN recurrence in 223 patients with ESCC following definitive chemoradiotherapy during 2012-2013. Following propensity score matching (PSM) and survival estimation, factors predictive of overall survival (OS) were explored using a Cox proportional hazards model. Among the patients with confirmed recurrence, 18 were TPLN (+) and 13 developed synchronous distant metastases. Before PSM, TPLN (+) was associated with worse recurrence-free (P = 0.00049) and OS [vs TPLN (-); P = 0.0027], whereas only the intergroup difference in recurrence-free survival remained significant after PSM (P = 0.013). The Cox analysis yielded similar results. Among the patients who had received definitive chemoradiotherapy, 3 (1.35%) had preoperative TPLN enlargement and none had developed recurrences. TPLN metastasis is rare but may be associated with poor survival.