5-year Survival Outcomes Research Articles

Continuous dosing of AUM001 with cyclical gemcitabine/nab-paclitaxel to maintain the tumor growth kinetics in KPC xenograft model.

e15112 Background: PDAC is a highly desmoplastic and aggressive disease with limited therapeutic options and poor 5-year survival outcome. Gemcitabine (GEM) plus nab-paclitaxel (nPTX) is widely used as a first line treatment for PDAC but advancement for greater improvement on efficacy is still warranted. Dysregulated mRNA translation of pro-tumorigenic genes has contributed to the proliferative and metastatic nature of PDAC. Targeting oncogenic mRNA translation via MNK-coupled phosphorylation of eIF4E could serve as a target for inhibition to synergize chemotherapy. AUM001 is a novel MNK1/MNK2 inhibitor undergoing clinical trials in various solid tumors. We hypothesize that combination of AUM001 with GEM-nPTX would have synergistic effect in modulating the tumor growth kinetics and maintaining the tumor in a stable state. Methods: PDAC KPC cells were subcutaneously implanted into BL6 mice and randomized into five treatment groups once tumor volumes of 60-80mm3 were reached. Saline (control), GEM-nPTX were administered intraperitoneally on days 1, 4 and 8 while AUM001 was given orally on a daily basis for 8 days. The combination of GEM-nPTX and AUM001 were administered at similar doses and frequency. AUM001 was given for another 3 weeks in the continuous dosing group. Body weight and tumor volume were measured thrice weekly. Immunohistochemistry staining was performed on FFPE sections for Ki67, angiogenesis and stromal markers. Apoptosis was analyzed by Annexin V-propidium iodide flow cytometric assay. P < 0.05 was considered as statistically significant. Results: GEM-nPTX and AUM001 (GPA) or GEM-nPTX (GP) alone resulted in approximately 30% reduction in relative tumor volume. The continuous dosing of AUM001 (GPAc) after the cessation of chemotherapy showed a marked 55% decline in relative tumor volume ( P= 0.0079) compared to GPA. The phosphorylation of EIF4E (target of MNK1/2) and Myc expression were significantly inhibited in GPAc vs GPA groups at end of observation (EOO) (P < 0.05). VEGFA expression at EOO was found to be suppressed in GPAc compared to GPA group ( P= 0.0159) with no difference in MVD ( P> 0.05). Greater fraction of apoptotic cells was detected in GPAc at EOO ( P= 0.055) than GPA ( P> 0.999) when referenced to GP group. Conclusions: This study demonstrated that continuous dosing of AUM001 with cyclical GEM-nPTX is well-tolerated and confers good anti-tumor effect. Pharmacodynamic analysis also suggests that AUM001 may potentiate the reduction in pro-tumorigenic protein expression. This is the first study depicting the continuous dosing of AUM001 after cessation of chemotherapy could help to maintain the tumor state, facilitating its possible use in clinics as maintenance therapy in PDAC.

Five-year long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer: a large single-center cohort study.

Robotic gastrectomy (RG) has been reported to be technically feasible and safe for patients with gastric cancer. However, 5-year long-term survival and recurrence outcomes for advanced gastric cancer have rarely been reported. This study aimed to compare the long-term oncologic outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer. The general clinicopathological data of 1905 consecutive patients who underwent RG and LG were retrospectively collected at the Chinese People's Liberation Army General Hospital between November 2011 and October 2017. Propensity score matching (PSM) was used to match groups. The primary endpoints were 5-year disease-free survival (DFS) and overall survival (OS). After PSM, a well-balanced cohort of 283 patients in the RG group and 701 patients in the LG group were included in the analysis. The 5-year cumulative DFS rates were 67.28% in the robotic group and 70.41% in the laparoscopic group. The 5-year OS rate was 69.01% in the robotic group and 69.58% in the laparoscopic group. No significant differences in Kaplan-Meier survival curves for DFS (HR = 1.08, 95% CI 0.83-1.39, Log-rank P = 0.557) and OS (HR = 1.02, 95% CI 0.78-1.34, Log-rank P = 0.850) were observed between the 2 groups. In the subgroup analyses for potential confounding variables, there were no significant differences in 5-year DFS and 5-year OS survival between the 2 groups (P > 0.05), except for patients with pathological stage III and pathological stage N3 (P < 0.05). For patients with early gastric cancer, robotic and laparoscopic approaches have similar long-term survival. For patients with advanced gastric cancer, further studies need to be conducted to assess the long-term survival outcomes of RG.

O141 The patterns of metastatic disease and survival in patients with pancreatic neuroendocrine tumours: a retrospective observational study

Abstract Background The 5-year survival of patients with pancreatic neuroendocrine tumours (pNET) without metastatic spread can be as high as 93% and as low as 24% in cases with distant metastases, influenced by the resectability of the tumour and adjuvant therapies. This study examined the patterns of metastasis and survival outcomes of patients with pNET. Methods This retrospective observational study at a regional hepatopancreaticobiliary centre, used electronic healthcare records to identify all patients with confirmed pNET referred to the multidisciplinary team between 2010 and 2019. Demographic characteristics of the patients were compared using chi-squared testing, and the patterns of metastatic disease defined on radiological imaging. The 5-year survival outcomes were determined using Kaplan-Meier survival estimates, stratified by the presence (and location) or absence of metastatic disease. Results In total 96 [50 (52.1%) female] patients with pNET were identified. Of the female patients, 46% were older than 70-years compared with 24% of the males (p=0.016). Metastatic disease was present in 48% of patients at presentation. The commonest sites of metastases was the liver (50%) distant lymph node metastases (32%) and multisite metastases (13%). The corresponding 5-year survivals were 58%, 50% and 39%. Conclusion pNET is a unique type of pancreatic cancer with better overall survival compared with other pancreatic cancers. Survival is influenced by the patterns of metastatic disease with worse overall survival in those with multisite metastases.

O147 The incidence and impact of pattern of metastases on treatment strategy and outcomes for patients with pancreatic cancer

Abstract Background Pancreatic cancer is a major cause of cancer mortality with dismal survival outcomes. At the time of diagnosis, 15% of patients with pancreatic cancer have resectable disease, 35% present with locally advanced pancreatic cancer and 50% of patients present with metastatic disease. This study aimed to determine the pattern of metastatic disease in patients with pancreatic cancer and evaluate their influence on survival outcomes. Methods Electronic healthcare records were retrospectively reviewed at a regional hepatopancreaticobiliary centre to identify patients diagnosed with pancreatic cancer between 2010-2019 inclusive. Patient demographics, tumour characteristics, metastatic pattern and management were recorded and compared. Kaplan Meier survival analysis were used to assess survival outcomes stratified by sex, metastatic pattern, and treatment strategy. Results Of the 1293 patients who met the inclusion criteria, metastatic disease was present in 863 (69.1%) at diagnosis. The commonest site of metastases was liver only [25.6% (221/863], followed by disseminated metastases [24.1% (208/863)] and regional lymph nodes [22.9% (198/863)]. Only 3.7% (32/863) of patients with metastases had lung-only metastases. Detection of lung metastases synchronous with intra-abdominal metastases did not alter management. The surgical resection rate was only 15% and the 5-year survival for those who underwent surgery was 9.8% compared with 0.8% for those with unresectable disease (p&amp;lt;0.0001). Conclusion A large proportion of patients with pancreatic cancer were diagnosed with metastatic disease with the liver being the commonest site. Metastases reduce resectability rates and consequently lead to poor 5-year survival outcomes.

Impact of Race and Age and their Interaction on Survival Outcomes in Patients With Diffuse Large B-Cell Lymphoma.

Advances in treatment for patients with Diffuse Large B-Cell Lymphoma (DLBCL) have led to improved patient outcomes but the magnitude of these disparities remains understudied with regards to improved survival outcomes. We sought to describe changes in DLBCL survival trends over time and explore potential differential survival patterns by patients' race/ethnicity and age. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with DLBCL from 1980 to 009 and determined 5-year survival outcomes for all patients, categorizing patients by year of diagnosis. We used descriptive statistics and logistic regression, adjusting for stage and year of diagnosis, to describe changes in 5-year survival rates over time by race/ethnicity and age. We identified 43,564 patients with DLBCL eligible for this study. Median age was 67 years (ages: 18-64=44.2%, 65-79=37.1%, 80+= 18.7%). Most patients were male (53.4%) and had advanced stage III/IV disease (40.0%). Most patients were White race (81.4%), followed by Asian/Pacific Islander (API) (6.3%), Black (6.3%), Hispanic (5.4%), and American Indian/Alaska Native (AIAN) (0.05%). Overall, the 5-year survival rate improved from 35.1% in 1980 to 52.4% in 2009 across all races and age groups (odds ratio [OR] for 5-year survival with increasing year of diagnosis=1.05, P < .001). Patients in racial/ethnic minority groups (API: OR=0.86, P < .0001; Black: OR=0.57, P < .0001; AIAN: OR=0.51, P=.008; Hispanic: 0.76, P=0.291) and older adults (ages 65-79: OR=0.43, P < .0001; ages 80+: OR=0.13, P < .0001) had lower 5-year survival rates after adjusting for race, age, stage, and diagnosis year. We found consistent improvement in the odds of 5-year survival for year of diagnosis across all race and ethnicity groups (White: OR=1.05, P < .001; API: OR=1.04, P < .001; Black: OR=1.06, p<.001; AIAN: OR=1.05, P < .001; Hispanic: OR=1.05, P < .005) and age groups (ages 18-64: OR=1.06, P < .001; ages 65-79: OR=1.04, P < .001; ages 80+: OR=1.04, P < .001). Patients with DLBCL experienced improvements in 5-year survival rates from 1980 to 2009, despite persistently lower survival among patients in racial/ethnic minority groups and older adults.

Long-term Outcomes After Lamellar Endothelial Keratoplasty Compared With Penetrating Keratoplasty for Corneal Endothelial Dysfunction: A Systematic Review.

The purpose of this study is to evaluate long-term outcomes of endothelial keratoplasty (EK) compared with penetrating keratoplasty (PK) for corneal endothelial dysfunction [Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK)]. In this systematic review, we searched PubMed, the Cochrane Library, and Embase up to May 2022 and considered all types of studies addressing our objective. Graft survival at 5, 10, and 15 years was the main outcome. Fifty cohort studies were included. At 5 years, in FECD and BK, graft survival seemed higher after EK than PK. Two comparative studies showed either a higher 5-year graft survival after EK than PK or no significant differences. Including noncomparative studies, in FECD, the 5-year graft survival ranged from 0.69 to 0.98 for PK, from 0.93 to 1.00 for DSEK, and from 0.93 to 0.99 for Descemet membrane endothelial keratoplasty (DMEK). In BK, the 5-year graft survival ranged from 0.39 to 0.91 for PK, from 0.65 to 0.89 for DSEK, and from 0.84 to 0.95 for DMEK. The 10-year graft survival ranged from 0.20 to 0.90 for PK and from 0.62 to 0.92 for EK. The mean 5-year best spectacle-corrected visual acuity ranged from 0.73 to 0.43 LogMAR for PK, from 0.61 to 0.09 for DSEK, and from 0.31 to 0.05 for DMEK. The 5-year rejection rate ranged from 11.0% to 28.7% for PK, from 5.0% to 7.9% for DSEK, and from 1.7% to 2.6% for DMEK. These results suggest a higher 5-year graft survival and better secondary outcomes after EK. Nevertheless, the level of evidence was low. CRD42021260614.

Characterization of the m6A regulator-mediated methylation modification patterns in oral squamous cell carcinoma

N6-methyladenosine (m6A) is a form of posttranscriptional modification that plays important roles in cancer including oral squamous cell carcinoma (OSCC). Most studies to date have focused on a limited number of regulators and oncogenic pathways, thus failing to provide comprehensive insight into the dynamic effects of m6A modification. In addition, the role of m6A modification in shaping immune cell infiltration in OSCC has yet to be clarified. This study was designed to assess m6A modification dynamics in OSCC and to understand how such modifications influence clinical immunotherapeutic treatment outcomes. m6A modification patterns linked with 23 m6A regulators were analyzed in 437 OSCC patients from TCGA and GEO cohorts. These patterns were then quantified through m6A score based on algorithms derived from a principal component analysis (PCA) approach. The m6A modification patterns of OSCC samples were grouped into two clusters based on the m6A regulators expression, and immune cell infiltration was linked with the 5-year survival outcomes of patients in these clusters. 1575 genes associated with OSCC patient prognosis were identified and used to re-cluster these samples into two groups. Patients in clusters exhibiting higher levels of m6A regulator expression exhibited poorer overall survival (OS), whereas patients with high m6A scores survived for longer (p < 0.001). The overall mortality rates in the groups of patients with low and high m6A scores were 55% and 40%, respectively, and the m6A score distributions in clusters of patients grouped by m6A modification patterns and gene expression further supported the link between a high m6A score and better prognostic outcomes. Immunophenoscore (IPS) values for patients in different m6A score groups suggested that the use of PD-1-specific antibodies or CTLA-4 inhibitors alone or in combination would yield superior treatment outcomes in patients in the high-m6A score group relative to the low-m6A score group. m6A modification patterns are relevant to heterogeneity in OSCC. Detailed analyses of m6A modification patterns may thus offer novel insight regarding immune cell infiltration within the OSCC tumor microenvironment, guiding novel efforts to provide patients with more effective immunotherapeutic interventions.

Efficacy of Pemetrexed or Gemcitabine Combined with Cis-platinum on Patients with Advanced Non-small-cell Lung Carcinoma and Its Effect on Serum miR-365

Objective: To determine the efficacy of pemetrexed or gemcitabine combined with cis-platinum on patients with advanced non-small-cell lung carcinoma (NSCLC) and its effect on serum miR-365. Methods: A total of 183 patients with NSCLC were enrolled and assigned to a pemetrexed + cis-platinum group (PC group) and a gemcitabine + cis-platinum group (GC group) according to their chemotherapy regimens. The two groups were compared in general data, therapeutic effect, drug-associated toxicity, life quality, 3-year survival outcome, and serum miR-365. Results: There was no significant difference between the two groups in remission rate and disease control rate, and the PC group experienced notably less hematological events including thrombocytopenia than the GC group, but had no significant difference with the latter in nausea, vomiting, constipation, abnormal liver function, esophageal injury and peripheral neurotoxicity. Additionally, there was no significant difference between the two groups in the improvement rate of Karnofsky performance scale, increased appetite, body mass gain, 3-year overall survival and progression-free survival, while the PC group showed better grade 3-4 toxicity-free survival outcome than the GC group. Moreover, serum miR-365 was up-regulated in cases with NSCLC, and decreased in both groups after treatment, while it was lower in the PC group than in the GC group over the same period after treatment. Conclusion: Both pemetrexed or gemcitabine combined with cis-platinum can strongly mitigate advanced NSCLC and suppress serum miR-365, but the former is safer.

Five-Year Survival of Patients Treated with Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) Compared with the General Swiss Population.

To evaluate the midterm follow-up and 5-year survival outcome of the minimally invasive direct coronary artery bypass (MIDCAB) procedure compared with the survival of the general Swiss population. Retrospective study on preoperative data, intraoperative data, and postoperative outcome of patients who underwent MIDCAB surgery between June 2010 and February 2019. To assess validity of this surgical therapy, outcomes were compared with survival data of a gender- and age-matched cohort of the general Swiss population taken from the database of the Swiss Federal Statistical Office. A total of 88 patients were included. Median (interquartile range [IQR[) age was 66 (56-75) years, and 27% (n = 24) were female. The median (IQR) length of the in-hospital stay was 7 (6-8) days. No postoperative stroke occurred. The 30-day mortality was 1.1% (n = 1). Reintervention for failed left internal mammary artery was needed in 1.1% (n = 1). The median (IQR) ejection fraction was 58% (47-60) preoperatively and remained stable during follow-up. The median (IQR) follow-up period was 3 (1.1-5.2) years. Five years postoperatively, 83% (confidence interval, 69-91) of the patients were alive, showing an overlap with the range of survival of the matched subcohort of the general Swiss population (range, 84-100%). Though suffering from coronary heart disease, patients after MIDCAB show almost equal survival rates as an equivalent subcohort corresponding to the general Swiss population matched on age and gender. Thus, our data show this treatment to be safe and beneficial.

Abstract 134: Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer

Abstract Backgrounds: Gastric cancer (GC) ranked 5th and 8th on the list of cancer related deaths worldwide and in Taiwan, respectively. Due to its high frequency of lymph node spread, lymph node dissection has become a standard procedure in surgical treatment. A randomized trial showed that patients who underwent D2 lymphadenectomy had a better 5-year survival outcome than ones who had D1 dissection in advanced gastric cancer, implying the D2 lymph node might serve as an outpost before tumor cells spread to distant organs. This clinical observation raises a possibility that the regional lymphatic spread could be under strict selection but not a passive process. Materials and Methods: To understand the evolutionary relationship between primary tumors, perigastric lymph nodes, and second tier of lymph nodes in the extra-perigastric area, we reconstruct their phylogeny using genetic variants in hypermutable DNA regions where the mutation rate is 102~104-fold than unique sequence. We have assembled a cohort of 10 gastric cancer patients, including intestinal-, diffuse- and mixed type GC. For each case, we collected all workable lymph node metastases and intensely sampled primary tumors. On average, we have over fifteen samples per case on the phylogenetic tree. Results: Preliminary data of the first two patients show high heterogeneity within primary tumors as well as between different lesions of lymph nodes or peritoneal metastases in gastric cancer. Interestingly, in stark contrast to all other lymph node metastases which intermingle with primary tumors, a clade consisting of one proximal and one distal lymph node with a bootstrap value above 90% is observed in each phylogeny, and it is worth noting that samples on these clades are from intestinal type tumor. Conclusion: Our results indicate that most tumor cells arrive both regional and distal lymph nodes passively via lymphatic drainage in GC while a selective process also exists which coincides with clinical observation. Whether the existence of tumor cells under a relatively stricter selection process would lead to different clinical outcomes is under investigation. Citation Format: Pei-Chi Cheng, Wei-Ting Hung, Yung-Ming Jeng, I-Rue Lai. Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 134.

Five-Year Survival Outcomes of Laparoscopy-Assisted vs Open Distal Gastrectomy for Advanced Gastric Cancer

Evidence of implementation of laparoscopic gastrectomy for locally advanced gastric cancer is currently insufficient, as the primary end point in previous prospective studies was evaluated at a median follow-up time of 3 years. More robust evidence is necessary to verify noninferiority of laparoscopic gastrectomy. To compare 5-year survival outcomes between laparoscopy-assisted distal gastrectomy (LADG) and open distal gastrectomy (ODG) with D2 lymph node dissection for locally advanced gastric cancer. This was a multicenter, open-label, noninferiority, prospective randomized clinical trial. Between November 26, 2009, and July 29, 2016, eligible patients with histologically proven gastric carcinoma from 37 institutes in Japan were enrolled. Two interim analyses and final analysis were performed in October 2014, May 2018, and November 2021, respectively. Patients were randomly assigned (1:1) to either the ODG or LADG group. The procedures were performed exclusively by qualified surgeons. The primary end point was 5-year relapse-free survival, and the noninferiority margin for the hazard ratio (HR) was set at 1.31. The secondary end points were 5-year overall survival and safety. A total of 502 patients were included in the full-analysis set: 254 (50.6%) in the ODG group and 248 (49.4%) in the LADG group. Patients in the ODG group had a median (IQR) age of 67 (33-80) years and included 168 males (66.1%). Patients in the LADG group had a median (IQR) age of 64 (34-80) years and included 169 males (68.1%). No significant differences were observed in severe postoperative complications between the 2 groups in the safety analysis (ODG, 4.7% [11 of 233] vs LADG, 3.5% [8 of 227]; P = .64). The median (IQR) follow-up for all patients after randomization was 67.9 (60.3-92.0) months. The 5-year relapse-free survival was 73.9% (95% CI, 68.7%-79.5%) and 75.7% (95% CI, 70.5%-81.2%) for the ODG and LADG groups, respectively, and the HR was 0.96 (90% CI, 0.72-1.26; noninferiority 1-sided P = .03). Further, no significant difference was observed in overall survival time between the 2 groups, and the HR was 0.83 (95% CI, 0.57-1.21; P = .34). The pattern of recurrence was similar between the 2 groups. Results of this study show that on the basis of 5-year follow-up data, LADG with D2 lymph node dissection for locally advanced gastric cancer, when performed by qualified surgeons, was proved noninferior to ODG. This laparoscopic approach could become a standard treatment for locally advanced gastric cancer. UMIN Clinical Trial Registry: UMIN000003420.

Abstract P5-01-06: Single cell profile of tumor and immune cells in primary triple-negative breast cancer and different sites in the axillary lymph nodes

Abstract Purpose: Little is known about the host-tumor interaction in the lymph node basin at a single cell level. This study examines single cell sequences in breast cancer nodal metastasis of a patient with triple negative breast cancer. Methods: The primary breast tumor, sentinel lymph node, an adjacent lymph node with metastatic involvement and a clinically normal-appearing lymph node were collected during operation. Single-cell sequencing was performed on all specimens. Results: 14,016 cells were clustered as 6 cell populations. Cancer cells demonstrated the molecular characteristics of TNBC basal B subtype and highly expressed genes in the MAPK signaling cascade. Tumor associated macrophages regulated antigen processing and presentation and other immune-related pathways to promote tumor invasion. CD8+ and CD4+ T lymphocytes concentrated more in sentinel lymph node and mainly stratified as two transcriptional states. The immune cell amount variation among primary tumor, sentinel and normal lymph nodes showed the similar tendency between the scRNA-seq profile of TNBC samples and a previous reported bulk RNA-seq profile of a breast cancer cohort including all four breast cancer subtype samples. Discussion: Single-cell sequencing analysis suggested that the sentinel lymph node was the initial meeting site of tumor infiltration and immune response, where partial T lymphocytes perform anti-tumor activity while other T cells exhibit an exhaustion state. We proposed a molecular explanation to the well-established clinical principle that the 5-year and 10-year survival outcomes were noninferior between SLND and ALND. Citation Format: Ning Liao, Cheukfai Li, Li Cao, Yanhua Chen, Chongyang Ren, Xiaoqing Chen, Hsiaopei Mok, Lingzhu Wen, Kai Li, Yulei Wang, Yuchen Zhang, Yingzi Li, Jiaoyi Lv, Fangrong Cao, Yuting Luo, Hongrui Li, Wendy Wu, Charles M. Balch, Armando E. Giuliano. Single cell profile of tumor and immune cells in primary triple-negative breast cancer and different sites in the axillary lymph nodes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-06.

Abstract PD18-01: Adjuvant Trastuzumab Emtansine Versus Paclitaxel plus Trastuzumab for Stage I HER2+ Breast Cancer: 5-year results and correlative analyses from ATEMPT (TBCRC033)

Abstract Background: The ATEMPT trial primary analysis found that one year of adjuvant trastuzumab emtansine (T-DM1) achieved a 3-year iDFS of 97.8% for patients with stage I HER2+ breast cancer, but was not associated with fewer clinically relevant toxicities (CRTs) compared with paclitaxel and trastuzumab (TH). In this end-of-study analysis, we report 5-year survival outcomes and correlative analyses from the trial. Methods: Patients with stage I centrally confirmed HER2+ breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for one year or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or paclitaxel 80 mg/m2 IV with weekly trastuzumab IV followed by trastuzumab for 9 months. The co-primary objectives were to compare the incidence of CRTs between the 2 arms and to evaluate iDFS in patients receiving T-DM1. To investigate proteomic correlates of recurrence, spatial proteomic analyses were performed on samples from 13 patients experiencing iDFS events (cases) and 24 matched controls using the NanoString GeoMx Digital Spatial Profiler. The impact of HER2 heterogeneity on outcomes was investigated among 17 cases and 51 matched controls by fluorescence in-situ hybridization (FISH). HER2 genetic heterogeneity was assessed by scrutinizing the whole tumor area and defined as the occurrence of HER2 gene amplification in &amp;gt;5% but &amp;lt; 50% invasive tumor cells. The risk of recurrence was evaluated centrally with the HER2DX genomic assay from 225 primary tumor samples. Germline whole genome sequencing (WGS) was conducted among 55 patients experiencing T-DM1-induced thrombocytopenia and/or bleeding and 55 matched controls to identify genomic correlates for this side effect. Results: A total of 497 patients who initiated protocol therapy were included in this analysis (383 T-DM1 and 114 TH). After a median follow up 5.8 years, among patients receiving T-DM1 there were a total of 11 iDFS events, with 3 distant recurrences. The 5-year iDFS for T-DM1 was 97.0% (95% CI, 95.3-98.8%), the 5-year recurrence-free interval (RFI) was 98.6% (95% CI: 97.4-99.8%) and the 5-year overall survival (OS) for T-DM1 was 97.8 % (95% CI, 96.3-99.3%). Although the study was not powered to evaluate the efficacy of TH, among the 114 patients receiving TH, a total of 9 iDFS events were observed, including 2 distant events; the 5-year iDFS with TH was 91.3% (95% CI: 86.0-96.9%), 5-year RFI was 93.3% (95% CI: 88.6-98.2%) and 5-year OS was 97.9% (95% CI: 95.2-100%). A total of 56 samples were evaluable for heterogeneity analyses, among which 14% (n=8) harbored HER2 genetic heterogeneity. Spatial proteomic analyses found that NF1 (adjusted p=0.72 × 10-6) and CTLA-4 (adjusted p=0.15 × 10-3) were significantly upregulated in primary samples from cases, while cleaved caspase 9, CD25, GITR, ICOS, p53 and PD-L2 were significantly upregulated in controls (all with adjusted p&amp;lt; 0.05). Germline WGS found that the top gene associations with thrombocytopenia and thrombocytopenia or bleeding were ALMS1 (p=0,19 × 10-3) and APBA3 (p=0,23 × 10-3), respectively, although none reaching the threshold for genome wide significance. rs62143195 and rs114169776 were the top single nucleotide polymorphisms associated with thrombocytopenia and thrombocytopenia or bleeding, respectively. Data on the impact of HER2 heterogeneity and of HER2DX score on survival outcomes will be presented. Conclusion: With longer follow-up, adjuvant T-DM1 confirmed outstanding long-term outcomes among patients with stage I HER2+ breast cancer, demonstrating a 5-year RFI of 98.6%. Spatial proteomic analyses identified a potential association between NF1 and CTLA-4 expression with recurrence. Details on the impact of HER2 heterogeneity and HER2DX assay on prognosis will be presented. Citation Format: Paolo Tarantino, Nabihah Tayob, Chau T Dang, Denise Yardley, Steven J. Isakoff, Vicente Valero, Meredith Faggen, Therese Mulvey, Ron Bose, Douglas Weckstein, Antonio C. Wolff, Katherine Reeder-Hayes, Hope Rugo, Bhuvaneswari Ramaswamy, Dan Zuckerman, Lowell Hart, Vijayakrishna K. Gadi, Michael Constantine, Kit Cheng, Audrey Merrill Garrett, Paul K. Marcom, Kathy S. Albain, Patricia DeFusco, Nadine Tung, Blair Ardman, Rita Nanda, Rachel C. Jankowitz, Mothaffar Rimawi, Vandana Abramson, Paula R. Pohlmann, Catherine Van Poznak, Andres Forero-Torres, Minetta C. Liu, Kathryn Ruddy, Yue Zheng, Romualdo Barroso-Sousa, Adrienne Waks, Michelle K. DeMeo, Molly K. DiLullo, Giuseppe Curigliano, Harold Burstein, Ann Partridge, Eric Winer, Giuseppe Viale, Winnie Hui, Elizabeth A. Mittendorf, Bryan P. Schneider, Aleix Prat, Ian Krop, Sara Tolaney. Adjuvant Trastuzumab Emtansine Versus Paclitaxel plus Trastuzumab for Stage I HER2+ Breast Cancer: 5-year results and correlative analyses from ATEMPT (TBCRC033) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-01.

Abstract No. 94 Extended 5-Year Amputation and Survival Outcomes from SINGAPACLI: A Randomized Clinical Trial Comparing Drug-Coated Balloon to Conventional Balloon Angioplasty for Below-the-Knee Arteries in Critical Limb Ischemia

Abstract No. 94 Extended 5-Year Amputation and Survival Outcomes from SINGAPACLI: A Randomized Clinical Trial Comparing Drug-Coated Balloon to Conventional Balloon Angioplasty for Below-the-Knee Arteries in Critical Limb Ischemia

17P Impact of adjuvant chemoradiotherapy on survival outcome compared to other treatment modalities for cervical cancer stage IIIc

Cervical cancer is very common among females. Surgery, chemotherapy and radiotherapy are different treatment options for cervical cancer. In 2018, the FIGO staging system has implemented lymph node status in the staging criteria but didn’t consider the number of positive lymph nodes. The current guidelines recommends primary chemoradiotherapy to treat the advanced stages but combined treatment regimens for node positive cervical cancer remains controversial, so this study aims to evaluate the survival outcome of different treatment modalities with further stratification by the positive lymph node number. We used Surveillance, Epidemiology, and End Results (SEER) database to extract the data of 3146 patients with node positive cervical cancer diagnosed from 2000 to 2018, they were treated with different approaches: adjuvant chemoradiotherapy, adjuvant radiotherapy, surgery without systemic treatment, adjuvant chemotherapy and primary chemoradiotherapy. We divided patients into four groups according to the number of involved lymph nodes: one node, two to three nodes, four to 10 nodes, more than 10 nodes. We used SPSS for data analysis. The overall 5-year survival outcome was higher for adjuvant chemoradiotherapy compared to adjuvant radiotherapy, surgery, primary chemoradiotherapy and adjuvant chemotherapy (68.7%, 63.4%, 59.1%, 47.5%, 40.7% ; P-value >0.00). Out of adjuvant chemoradiotherapy showed better 5-year overall survival outcome in patients with one lymph node involvement 73.1% and in patients with 2-3 positive lymph nodes 63.9%. These results highlighted adjuvant chemo-radiotherapy as the treatment of choice for node cervical cancer stage IIIc, surgery and adjuvant chemoradiotherapy has have qiuet similar survival outcome. We also recommend the number of positive lymph nodes to be implemented in the upcoming FIGO system as a predictor for survival outcome and a factor for the treatment plan. Further evaluation is necessary to weigh the benefit versus side effects of the best regimen for each patient.

10-year survival outcome after clinically suspected acute myocarditis in adults: A nationwide study in the pre-COVID-19 era.

Clinical courses of acute myocarditis are heterogeneous in populations and geographic regions. There is a dearth of long-term outcomes data for acute myocarditis prior to the coronavirus disease pandemic, particularly in the older and female population. This study aimed to provide the nationwide epidemiologic approximates of clinically suspected acute myocarditis across adults of all ages over the long term. From the nationwide governmental health insurance database, a retrospective cohort comprised all patients aged 20-79 who were hospitalized for clinically suspected acute myocarditis without underlying cardiac diseases from 2006 to 2018. The complicated phenotype was defined as requiring hemodynamic or major organ support. Over 10 years, all-cause mortality and index event-driven excess mortality were evaluated according to young-adult (20-39 years), mid-life (40-59 years), and older-adult (60-79 years) age groups. Among 2,988 patients (51.0±16.9 years, 46.2% women), 362 (12.1%) were of complicated phenotype. Of these, 163 (45.0%) had died within 1 month. All-cause death at 30 days occurred in 40 (4.7%), 52 (4.8%), and 105 (10.0%) patients in the young-adult, mid-life, and older-adult groups, respectively. For 10 years of follow-up, all-cause death occurred in 762 (25.5%). Even in young adult patients with non-complicated phenotypes, excess mortality remained higher compared to the general population. In hospitalized patients with clinically suspected acute myocarditis, short-term mortality is high both in young and older adults, particularly those with comorbidities and severe clinical presentation. Furthermore, excess mortality remains high for at least 10 years after index hospitalization in young adults.

PP01.24 5-Year Survival Outcomes of Lung Cancer Treated with Surgery: A Single Institution Experience

PP01.24 5-Year Survival Outcomes of Lung Cancer Treated with Surgery: A Single Institution Experience

Retracted: Comparison of 10-Year Survival Outcomes for Early Single Hepatocellular Carcinoma following Different Treatments.

[This retracts the article DOI: 10.1155/2021/6638117.].

Five-year survival outcomes in oropharyngeal squamous cell carcinoma following transoral laser microsurgery.

To determine the 5-year survival outcomes of patients with oropharyngeal cancer treated with transoral laser microsurgery at our institution. A prospective longitudinal cohort study of all cases of oropharyngeal squamous cell cancer or clinically unknown primaries diagnosed at our institution between September 1, 2014, to December 31, 2019, treated with primary transoral laser microsurgery were analyzed. Patients with a previous history of head and neck radiation were excluded from analysis. Kaplan-Meier survival curves were used to estimate 5-year overall survival, disease-specific survival, local control, and recurrence free survival rates in oropharyngeal squamous cell carcinoma. Of 142 patients identified, 135 met criteria and were included in the survival analysis. Five-year local control rates in p16 positive and negative disease were 99.2% and 100%, respectively, with one locoregional failure in the p16 positive cohort. Five-year overall survival, disease-specific survival, and recurrence free survival in p16 positive disease were 91%, 95.2%, and 87% respectively (n= 124). Five-year overall survival, disease-specific survival, and recurrence free survival in p16 negative disease were 39.8%, 58.3%, and 60%, respectively (n= 11). The permanent gastrostomy tube rate was 1.5% and zero patients received a tracheostomy at the time of surgery. One patient (0.74%) required a return to the OR for a post-operative pharyngeal bleed. Transoral laser microsurgery is a safe primary treatment option for oropharyngeal squamous cell carcinoma with high 5-year survival outcomes, notably in p16 positive disease. More randomized trials are needed to compare survival outcomes and associated morbidity in transoral laser microsurgery compared to treatment with primary chemoradiation. 3.

Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer.

Gallbladder cancer (GBC) is one of the leading and aggressive cancers in this region of India. It is very difficult to diagnose in the early stage, as it lacks typical early signs and symptoms; thus, the diagnosis is often in the advanced stage, which ultimately leads to a poor 5-year survival outcome. Tumor markers including carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), CA 125, CA 242, and alpha fetoprotein are used as indicators in the diagnosis and prognosis of GBC. To compare tumor marker levels between GBC and benign GB diseases (GBDs) and to assess the combined use of tumor markers to increase the diagnostic accuracy for GBC. Patients of either sex aged ≥ 18 years, with suspected GBC (GB polyp, irregular thick GB wall, GB mass, porcelain GB) on the basis of radiological imaging were included in this study. GB wall thickness using ultrasonography and tumor markers CEA, CA 125, CA 19-9, and CA 242 in all patients were recorded. All cases after surgical intervention were divided into two groups, GBC and benign GBD, according to histopathological examination findings. The cases were followed up and clinical findings, radiological findings, and levels of tumor markers were assessed. A total of 200 patients were included in this study, of whom 80 patients had GBC and 120 patients had benign GBD. The median (interquartile range) age was 52.0 (41.0-60.0) years and the majority of patients (132, 66.0%) were women. Tumor markers including CA 19-9, CA 125, CEA, and CA 242 were significantly elevated in patients with GBC (P < 0.001). There was a significant reduction in tumor markers at 3 and 6 mo from baseline (P < 0.001). The mean survival of patients with normal and elevated levels of tumor markers CA 125, CA 19-9, and CEA was comparable; however lymph node metastasis and CA 242 expression level were independent prognostic factors. Serum levels of tumor markers including CA 19-9, CA 125, CEA, and CA 242 were significantly associated with GBC. However, no significant association was observed between the presence of elevated levels of any tumor marker with respect to survival. Tumor marker assessment during follow-up may represent a treatment response.