Prognostic implications of morphological subtypes in a surgical cohort of perihilar cholangiocarcinoma: the overriding impact of nodal status.

Circulating tumor cells (CTCs), CTC heterogeneity and distinct morphological CTC subtypes predict worse survival in metastatic breast cancer (MBC)BackgroundThe presence of CTCs has been shown to be a poor prognostic factor in patients with MBC. Studies in prostate cancer have shown patients with distinct morphological subtypes of CTCs have worse outcomes than high CTC burden alone and could have treatment implications. In this study, we report a comprehensive analysis of CTC phenotypes in MBC and their impact on survival.MethodsA total of 148 blood samples from 90 patients with MBC whose disease was progressing on therapy were enrolled for CTC analysis. Blood was sent overnight to Epic Sciences, processed onto glass slides and biobanked. Replicate slides were stained with antibodies targeting the androgen receptor (AR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2) in addition to cytokeratin, CD45, and DAPI. Total CTCs were quantified per sample from approximately 3 mL of blood. A threshold defining positive AR, ER, and HER2 protein expression was set using cultured cancer cell lines expressing the individual proteins. CTC morphology subtypes (heterogeneity [Scher et al Cancer Res 2017], small cell/neuroendocrine-like [SC/NE; Brown et al CCR 2021] and chromosomal instability [CIN+; Schonhoft et al Cancer Res 2020]) were quantified as previously described. High heterogeneity samples (Het+) were defined as having a Shannon Index (SI; a measure of morphologic diversity) of ≥1. CIN positivity was defined as having ≥0.7 CIN+ CTC/mL. Association with these CTC subtypes and survival were evaluated with a univariate COX proportional hazard model. ResultsOver 90% of samples and patients had CTCs (Table 1). The percentage of patients with the CTC subtypes evaluated are below. Table 1. Percentage of blood samples with CTCs and CTC subtypes in MBC patients, by MBC subtype The presence of CTCs was associated with worse survival, with a median survival of 15.3 months (mos) vs 24.0 mos with no CTCs (p=0.028). The presence of AR+ or HER2+ CTCs was not associated with survival. Analysis of ER is ongoing and will be presented. High morphologic heterogeneity or the presence of the SC/NE or CIN+ CTC subtypes, predicted for a worse survival outcome (Table 2). Table 2. Overall survival of patients with and without distinct CTC subtypes CTC morphological subtypes did not correlate with each other, except CTC heterogeneity by SI which correlated weakly with SC/NE and CIN+. HER2+ CTCs strongly correlated with a higher SI while AR+ CTCs did not. AR and HER2 expression did not associate with the CIN+ or SC/NE subtypes. ConclusionsDigital pathology analysis of CTCs identifies distinct CTC morphological subtypes that predict for worse prognosis in MBC patients. To our knowledge, this is the first report of SC/NE CTCs in MBC patients and that MBC patients with SC/NE and CIN+ CTCs have worse outcomes. Longitudinal characterization of CTC subtypes across the MBC continuum could potentially identify effective therapies against these more lethal cancers. Citation Format: Joyce A O'Shaughnessy, Maren K Levin, Esther San Roman Rodriguez, James Lu, Joshua T Jones, Amanda KL Anderson, Alisa Tubbs, Joseph D Schonhoft, Rick Wenstrup. Circulating tumor cells (CTCs), CTC heterogeneity and distinct morphological CTC subtypes predict worse survival in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-02-03.

Safety and Efficacy of Endoscopic Ampullectomy in Tumors with and Without Intraductal Growth and Predictive Factors of Success: A Prospective Trial

Intrahepatic cholangiocellular carcinoma (ICC) presenting intraductal growth (IG) has distinct clinicopathological features with a favorable prognosis. The mass-forming (MF) plus IG type of ICC has not been previously investigated. One hundred forty-four patients with ICC underwent surgical resections and were classified according to the macroscopic type. The clinicopathological features of the IG type (n = 7) and MF plus IG type (n = 14) were retrospectively analyzed. The clinicopathological differences between the MF plus IG type and MF plus periductal infiltrating (PI) type (n = 37) were compared. All of the patients with the IG type had no sign of recurrence and survived. The 5-year overall survival rates was significantly better in the MF plus IG type than in the MF plus PI type (41.3% vs. 13.3%, P = 0.034). Significant differences were recognized between the MF plus IG type and MF plus PI type, in terms of vascular resection (P = 0.030), mucosal extension (P = 0.006), and postoperative recurrence (P = 0.004). The MF plus IG type had significantly better prognosis than the MF plus PI type. The IG type and MF plus IG type should be distinguished from other types even if hepatic hilar confluence is involved, because of the favorable outcome after surgery.

Improved Survival Outcomes in Non-small Cell Lung Cancer Patients With Incidental Concurrent Use of Beta-Blockers and Definitive Radiation Therapy

MP50-02 HOW IMPORTANT ARE MORPHOLOGIC SUBTYPES ON THE PROGNOSIS OF SURGICALLY TREATED NON-METASTATIC PAPILLARY RENAL CELL CARCINOMA? AN ANALYSIS FROM A CONTEMPORARY MULTI-INSTITUTIONAL DATABASE

The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Background: This systematic review examines the efficacy of multiorgan resection (MOR) in treating locally advanced gastric cancer (LAGC), focusing on survival outcomes, postoperative morbidity, and mortality. Methods: We conducted a comprehensive search of studies in PubMed, Scopus, and Embase up to November 2023, based on the PRISMA guidelines. The inclusion criteria focused on clinical trials, observational studies, case-control studies, and qualitative research, involving patients of any age and gender diagnosed with LAGC undergoing MOR aimed at R0 resection, with secondary outcomes focusing on survival rates, postoperative outcomes, and the effects of adjuvant and neoadjuvant therapies. Exclusion criteria ruled out non-human studies, research not specifically focused on LAGC patients undergoing MOR, and studies lacking clear, quantifiable outcomes. The quality assessment was performed using the Newcastle-Ottawa Scale. The final analysis included twenty studies, involving a total of 2489 patients across a time span from 2001 to 2023. Results highlighted a significant variation in median survival times ranging from 10 to 27 months and R0 resection rates from 32.1% to 94.3%. Survival rates one-year post-R0 resection varied between 46.7% and 84.8%, with an adjusted weighted mean of 66.95%. Key predictors of reduced survival included esophageal invasion and peritoneal dissemination, the presence of more than six lymph nodes, and tumor sizes over 10 cm. Nevertheless, the meta-analysis revealed a significant heterogeneity (I2 = 87%), indicating substantial variability across studies, that might be caused by differences in surgical techniques, patient demographics, and treatment settings which influence survival outcomes. Results: The review underlines the important role of achieving R0 resection status in improving survival outcomes, despite the high risks associated with MOR. Variability across studies suggests that local practice patterns and patient demographics significantly influence results. Conclusions: The findings emphasize the need for aggressive surgical strategies to improve survival in LAGC treatment, highlighting the importance of achieving curative resection despite inherent challenges.

High expression of tumor necrosis factor receptor 2 in tissue is associated with progression and prognosis of esophageal squamous cell carcinoma

Background/Objectives: This study aimed to investigate the impact of preoperative weight loss on long-term postoperative survival and the significance of preoperative nutrition on perioperative weight change in patients with pancreatic cancer. Methods: Overall, 125 patients who underwent radical resection for invasive pancreatic ductal carcinoma were retrospectively analyzed. The preoperative weight loss rate (pre-%WL) from the initial visit to immediately before surgery was calculated. Patients were classified by pre-%WL into the weight-loss (≥6% loss) and weight-maintenance (<6% loss) groups. The association of pre-%WL with postoperative outcomes and long-term survival was assessed. We evaluated preoperative nutrition's effect on perioperative weight change. Results: The study cohort included 91 (73%) and 34 (27%) patients with weight maintenance and weight loss, respectively. Specifically, the weight-loss group had a longer operative time (p = 0.025) and greater blood loss (p = 0.018) than the weight-maintenance group. Patients with weight loss had significantly poorer recurrence-free survival (RFS; 8.7 vs. 17.8 months, p = 0.004) and overall survival (OS; 18.1 vs. 45.2 months, p = 0.002) than those with weight maintenance. Multivariate analysis revealed weight loss as an independent prognostic indicator of poor RFS (hazard ratio = 2.07; p = 0.003) and OS (hazard ratio = 2.55; p = 0.0008). The presence or absence of preoperative nutritional therapy was not correlated with the pre-%WL but was associated with postoperative (by the time of discharge) weight loss rate (median weight change rate: -2.9% vs. -5.6%, p = 0.001). Conclusions: Preoperative weight loss ≥ 6% was associated with poor RFS and OS in patients with pancreatic cancer. Although preoperative nutritional therapy did not suppress preoperative weight loss, it suppressed postoperative weight loss.

Morphological subtypes of intraductal papillary mucinous neoplasm (IPMN) have been established. Invasive IPMNs include colloid carcinoma and tubular carcinoma. Few studies have explored the association between the morphological and invasive subtypes in a large population. Clinical relevance of the morphological subtypes remains unclear. One hundred sixty-nine consecutive patients who underwent curative resection of IPMN were enrolled. The intraductal components were classified into four distinct epithelial subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. The invasive components were classified as colloid or tubular. The numbers of patients with gastric, intestinal, pancreatobiliary, and oncocytic subtypes were 123, 42, 3, and 1, respectively. Fifty-six patients had invasive cancer (tubular type, 42; colloid type, 14). The proportions of gastric type IPMN within each histological grade were 88 % among adenomas, 43 % among noninvasive carcinomas, 41 % among minimally invasive carcinomas, and 74 % among invasive carcinomas. Gastric subtype was more commonly associated with branch duct type and intestinal subtype with main duct type, and these tendencies were statistically significant (P = 0.0131). Furthermore, there was a strong correlation between gastric and tubular types and between intestinal and colloid types (P < 0.0001). The 5-year survival rate among the 56 invasive cancers was 52.7 % for gastric type and 89.7 % for intestinal type, which was statistically significant (P = 0.030). Gastric type IPMN is mostly derived from branch duct IPMN and often demonstrates benign behavior, as seen with adenomas. However, once gastric type IPMN develops into invasive carcinoma, the survival rate is significantly lower than other types.

To evaluate the treatment tolerance and clinical outcomes in patients aged 70 years and older with locally advanced oropharyngeal cancer treated by definitive intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 15 consecutive elderly patients, with histologically-proven squamous cell carcinoma of the oropharynx, staged T3-4 with or without involved lymph nodes at diagnosis, who received definitive sequential IMRT (70 Gy; 2 Gy/fraction). Adult Comorbidity Evaluation-27 (ACE-27) score was calculated and its influence on treatment tolerance and clinical outcomes was analyzed. A total of 15 patients were included with a median age of 77 years (range=70-88 years). At baseline, 8 patients (53.3%) had an ACE-27 score of 1, and the remainder (n=7, 46.7%) had a comorbidity index of 0. All patients completed programmed IMRT treatment, without any reduction of total dose. Oral pain and mucositis were the most common acute side-effects, classified as grade 3 in 6 patients (40%) only. Xerostomia was reported in 13 patients (86.7%), without severe manifestation. There was no hematological toxicity. ACE-27 score was not related to higher severe acute toxicity. No patients experienced grade 3 or more late toxicity. Five-year overall survival and disease-free survival rates were 63.6% (95% confidence interval=32.7-83.3%) and 55% (95% confidence interval=24.4-77.6%), respectively. Comorbidity score did not influence survival outcomes, both overall survival (p=0.46) and disease-free survival (p=0.55). Treatment tolerance, as well as survival outcomes were good in elderly oropharyngeal cancer patients treated with definitive sequential IMRT. Due to age and comorbidity, no dose or volume reduction for IMRT should be considered in this setting of patients. A prospective randomized trial with a large sample size should be conducted to confirm our results.

ObjectiveA novel classification system of high-grade serous ovarian carcinoma based on gross morphology observed at pre-treatment laparoscopy was recently defined. The purpose of this study was to identify radiographic features...

Extracapsular tumor spread does not influence survival outcomes in resected N1-patients with intrahepatic cholangiocarcinoma- a retrospectively controlled cohort study.

Current guidelines for gallbladder cancer (GBC) contain controversies and some reported no survival improvement in GBC during 20years. This study was designed to explore the chronologic change of survival outcomes in GBC and prognostic factors. Clinicopathologic features and survival outcomes were analyzed in 692 consecutive GBC patients who underwent surgery between 1987 and 2014, including 255 treated in Period (P) 1 (1987-2000) and 437 in P2 (2001-2014). The mean age was 63.3 years. Curative resection rate was 59.2% and 5-year survival rate (5-YSR) after curative resection was 67.1%. Comparisons between P1 and P2 showed that mean age, asymptomatic presentation, extended cholecystectomy, curative resection, adjuvant chemotherapy, and tumor ≤ T2 were significantly higher during P2. The overall 5-YSR after curative surgery was significantly lower in P1. In patients who underwent curative resection, poor prognostic factors included symptomatic presentation, CA 19-9 >37 IU/ml, poor differentiation, tumor ≥ T3, and lymph nodal involvement. In patients who received non-curative surgery, well- or moderately differentiated tumor and adjuvant chemotherapy provide survival benefit. Detection of GBC at an early stage and optimal curative surgery may improve survival outcomes in GBC. Chemotherapy provides survival benefit in palliative setting.

Development and Validation of a Novel Model to Predict Lymph Node Metastasis among Patients with Intrahepatic Cholangiocarcinoma