Resected Adenocarcinoma Research Articles

Combined analysis of a serum mRNA/miRNA marker signature and CA 19-9 for timely and accurate diagnosis of recurrence after resection of pancreatic ductal adenocarcinoma: A prospective multicenter cohort study.

Timely and accurate detection of tumor recurrence in pancreatic ductal adenocarcinoma (PDAC) patients is an urgent and unmet medical need. This study aimed to develop a noninvasive molecular diagnostic procedure for the detection of recurrence after PDAC resection based on quantification of circulating mRNA and miRNA biomarkers in serum samples. In a multicentric study, serum samples from a total of 146 patients were prospectively collected after resection. Samples were classified into a "No Evidence of Disease" and a "Recurrence" group based on clinical follow-up data. A multianalyte biomarker panel was composed of mRNAs and miRNA markers and simultaneously analyzed in serum samples using custom microfluidic qPCR arrays (TaqMan array cards). A diagnostic algorithm was developed combining a 7-gene marker signature with CA19-9 data. The best-performing marker combination achieved 90% diagnostic accuracy in predicting the presence of tumor recurrence (98% sensitivity; 84% specificity), clearly outperforming the singular CA 19-9 analysis. Moreover, time series data obtained by analyzing successively collected samples from 5 patients during extended follow-up suggested that molecular diagnosis has the potential to detect recurrence earlier than routine clinical procedures. TaqMan array card measurements were found to be biologically valid and technically reproducible. The BioPac multianalyte marker panel is capable of sensitive and accurate detection of recurrence in patients resected for PDAC using a simple blood test. This could allow a closer follow-up using shorter time intervals than currently used for imaging, thus potentially prompting an earlier work-up with additional modalities to allow for earlier therapeutic intervention. This study provides a promising approach for improved postoperative monitoring of resected PDAC patients, which is an urgent and unmet clinical need.

TRAF4 promotes lung cancer development by activating tyrosine kinase of EGFR

Objective: To explore the role of tumor necrosis factor receptor-associated factor 4 (TRAF4) in promoting the abnormal activation of epidermal growth factor receptor (EGFR) and its effect on lung cancer cell proliferation, migration and invasion. Methods: Tumor tissues from patients who underwent lung adenocarcinoma resection at The First Affiliated Hospital of Second Military Medical University, from January 2015 to May 2017 were collected, and the expressions of TRAF4 and Ki-67 in lung cancer tissues were detected by immunohistochemistry, the mRNA levels of Cyclin D and Vimentin were detected by real-time fluorescence quantitative PCR (qRT-PCR). The effect of TRAF4 on the tumor growth ability of lung cancer A549 cells was investigated by the xenograft model, the effect of TRAF4 or EGFR on the tumor proliferation ability was detected by using cell counting kit 8 (CCK8) and BrdU assay, and the migration and invasion abilities of tumor cells were detected by Transwell assay. Different structural domain deletion expression vectors of TRAF4 and EGFR were constructed to transfect cells, and the interaction mode of TRAF4 and EGFR was investigated by immunoprecipitation assay. Results: The expression of TRAF4 in non-small cell lung cancer (NSCLC) tissues was positively correlated with the expressions of Ki-67, cyclin D, and vimentin (r2: 0.438, 0.695, and 0.736, respectively, all P＜0.01). Immunohistochemical assay of tumor tissues from NSCLC patients showed that tissues with high expression of TRAF4 were also high in Ki-67. Patients with high TRAF4 expression (TRAF4 positivity >30%) had a shorter progression-free survival (PFS) time than that of patients with low TRAF4 expression (TRAF4 positivity ≤30%) (median PFS of 12 and 19 months, respectively; P=0.034). Traf4-/- cells had a weakened proliferative capacity than traf4+/+ cells and formed tumors with smaller size (P＜0.05). The expression level of Ki-67 in the tumor tissues formed by traf4-/- cells [(45.6±8.7)%] was lower than that in the tumor tissues formed by traf4+/+ cells [(62.3±10.3)%, P=0.015], the mRNA levels of cyclin D (1.01±0.15) and vimentin (1.01±0.12) in the traf4-/- cells were lower than those of the traf4+/+ cells (3.41±0.32 and 3.12±0.18, respectively, both P＜0.05).The western blot results showed that, with the elevated intracellular expression level of TRAF4, phosphorylation level of EGFR was significantly increased in both wild-type EGFR and activation mutant EGFR-expression cells. The capacities of proliferation, migration and invasion of A549 cells was weakened after EGFR knockdown (all P＜0.01). Immunoprecipitation experiments showed that TRAF4 binds to the peptide segment of the near-membrane region of EGFR through the TRAF structural domain, and the mutual binding between EGFR molecules was enhanced under TRAF4 overexpression conditions. Increasing TRAF4 expression promoted EGFR molecular phosphorylation and activation of downstream signaling. Conclusions: TRAF4 expression is elevated in NSCLC tissues and tumor cells, which promotes tumor proliferation, migration and invasion. TRAF4 directly binds to EGFR molecules, enhances its own phosphorylation and activates the downstream signaling pathway by promoting the interaction between EGFR molecules.

Assessing Influence of Mismatch Repair Mutations on Survival in Patients After Resection of Pancreatic Ductal and Periampullary Adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Previous studies have indicated that microsatellite instability and deficient mismatch repair (MMR) may be associated with improved survival in patients with pancreatic cancer. Here, we aim to investigate the impact of deficient MMR (dMMR) status on oncologic outcomes in patients after resection of PDAC and periampullary adenocarcinoma. Methods: This is a single-institution, retrospective study based on a prospectively maintained database. Pancreatic ductal adenocarcinoma (N = 342) and periampullary adenocarcinoma patients (N = 76) who underwent pancreatic resection surgery between 2016 and 2021 were included. Immunohistochemistry staining results of MMR proteins and next-generation sequencing data were recorded. Cancer-type dependent Cox regression analyses were performed to assess overall and disease-free survival, which was complemented with a 1:2 propensity-score matching for each of the cancer types in order to compare oncologic outcomes. Results: A total of 418 pancreatic cancer patients were included in the analysis. Fifteen patients (3.5%) were diagnosed as dMMR (PDAC N = 7 and periampullary adenocarcinoma N = 8). Cox regression modeling of dMMR status interaction with TNM staging and cancer type revealed that dMMR status strongly improves overall survival (p < 0.05). After propensity-score matching, Cox regression identified dMMR status as a significant marker of improved overall survival (HR = 0.27, 95%CI 0.09-0.88, p = 0.029). Conclusions: Overall, our findings suggest that dMMR status is associated with markedly improved survival outcomes in patients after resection of pancreatic and periampullary cancer. Future large-scale studies are needed to further validate this finding.

Prediction of R0 Resectability in Pancreatic Adenocarcinoma by MRI Using NCCN Criteria

Prediction of R0 Resectability in Pancreatic Adenocarcinoma by MRI Using NCCN Criteria

Prognostic value of the CRM-status in pancreatic ductal adenocarcinoma - data from a regional cancer registry

BackgroundDuctal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been established and has been incorporated into the German national S3 guideline on exocrine pancreatic cancer. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline corresponds with overall and progression free survival in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany.MethodsData from the cancer registry of the State of Baden-Württemberg, Germany, were used to assess the relationship between CRM-status and progression free survival (PFS) as well as 3-year overall survival (OS) using documented patients diagnosed with resectable ductal adenocarcinoma of the pancreas between 2015 and 2020. Patients were residents of the State of Baden-Württemberg and underwent surgery for PDAC. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is > 1 mm from the tumour, R0 narrow/CRM + when CRM is ≤ 1 mm from the tumour and R1 when tumour cells are found at the resection margin.ResultsIn total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM + resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM + and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading and tumour location.ConclusionsCRM is prognostic for patients with resectable PDAC making the pathological assessment of the R-status according to the CRM concept worthwhile.

Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma

PurposeSerum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection.MethodsConsecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS).ResultsAmong 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients.ConclusionThe FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.

Distal Pancreatectomy with and without Celiac Axis Resection for Adenocarcinoma: A Comparison in the Era of Neoadjuvant Therapy.

Distal pancreatectomy with celiac axis resection (DP-CAR) has been used for selected patients with pancreatic cancer infiltrating the celiac axis. We compared the short- and long-term outcomes between DP-CAR and distal pancreatectomy alone (DP) in patients receiving neoadjuvant therapy. Patients undergoing DP-CAR from 2013 to 2022 were retrospectively reviewed. Clinicopathologic features, post-operative morbidity, and survival outcomes were compared with patients undergoing DP after neoadjuvant chemotherapy. Twenty-two DP-CAR and thirty-four DP patients who underwent neoadjuvant chemotherapy were identified. There were no differences in comorbidities or CA19-9 levels. OR time was longer for DP-CAR (304 vs. 240 min, p = 0.007), but there was no difference in the transfusion rate (22.7% vs. 14.7%). Vascular reconstruction was more common in DP-CAR (18.2% vs. 0% arterial, p = 0.05; 40.9% vs. 12.5% venous, p = 0.04). There was no difference in morbidity or mortality between the two groups. Although there was a trend towards larger tumors in DP-CAR (5.1 cm vs. 3.8 cm, p = 0.057), the overall survival from the initiation of treatment (32 vs. 28 months, p = 0.43) and surgery (30 vs. 24 months, p = 0.43) were similar. DP-CAR is associated with similar survival and morbidity compared to DP patients requiring neoadjuvant chemotherapy and should be pursued in appropriately selected patients.

THE ROLE OF CA 19.9 IN PREDICTING THE OPERABILITY OF CARCINOMA PANCREAS

Objectives: Adenocarcinoma of the pancreas remains a relatively incurable disease despite advances in surgical care. Approximately 25% of patients will be found to have unresectable tumors during surgery even though computed tomography (CT) has demonstrated that they are resectable. There is a controversy regarding the use of cancer antigen 19-9 (CA 19-9) to decide the resectability of pancreatic adenocarcinoma [1]. Our aim is to study the use of CA 19-9 in determining the operability of carcinoma pancreas [2]. Methods: This was a prospective study which included 69 patients and the study period was from December 2021 to December 2022. Data were collected from all patients with carcinoma of the pancreas who underwent surgical management. CA 19-9 levels were measured and recorded [3]. During surgery, the operative findings on resectability were documented and tabulated against corresponding CA 19-9 levels and contrast-enhanced CT (CECT) findings. Results: Of the 69 patients who were operated on, 38 patients had resectable tumors and underwent the Whipples procedure and 31 of them had non-resectable tumors and had to undergo palliative bypass procedures. Among the 31 patients whose tumors were non-resectable, only four were diagnosed non-resectable preoperatively with CECT, and the other 27 were found to be non-resectable only during surgery. That shows the relevance of this study. Of the 31 non-resectable cases, 14 (45.2%) patients had elevated CA 19-9 values of more than 501, and the rest 17 (54.8%) patients had low CA 19-9 values. Among the 38 resectable cases, 12 patients (31.6%) had elevated CA 19-9 more than 501, and 26 patients (68.4%) had low values. In conclusion, among non-resectable cases, 45.2% had raised CA 19-9, and among operable cases, 31.6% showed raised CA 19-9. Hence, CA 19-9 seems to be an insignificant predictor of tumor resectability [4]. Conclusion: It was found that the need for a pre-operative predictor for resectability of carcinoma pancreas is relevant while considering mortality and morbidity in operating carcinoma pancreas cases. On evaluating CA 19-9 as a pre-operative predictor, we found that CA 19-9 has no significant role as an indicator of local advancement or metastasis. Hence, we cannot consider CA 19-9 as a predictor of resectability of carcinoma pancreas preoperatively [5].

Circulating tumor DNA predicts recurrence and survival in patients with resectable gastric and gastroesophageal junction cancer.

Gastric and gastroesophageal junction (GEJ) cancer represents a significant global health challenge, with high recurrence rates and poor survival outcomes. This study investigates circulating tumor DNA (ctDNA) as a biomarker for assessing recurrence risk in patients with resectable gastric and GEJ adenocarcinomas (AC). Patients with resectable gastric and GEJ AC, undergoing perioperative chemotherapy and surgery, were prospectively enrolled. Serial plasma samples were collected at baseline, after one cycle of chemotherapy, after preoperative chemotherapy, and after surgery. ctDNA was assessed by a ddPCR test (TriMeth), which targets the gastrointestinal cancer-specific methylation patterns of the genes C9orf50, KCNQ5, and CLIP4. ctDNA analysis was performed on 229 plasma samples from 86 patients. At baseline, ctDNA was detected in 56% of patients, which decreased to 37% following one cycle of chemotherapy, 25% after preoperative chemotherapy and 15% after surgical resection. The presence of ctDNA after one cycle of chemotherapy was associated with reduced recurrence-free survival (RFS) (HR = 2.54, 95% confidence interval (CI) 1.33-4.85, p = 0.005) and overall survival (OS) (HR = 2.23, 95% CI 1.07-4.62, p = 0.032). Similarly, ctDNA after surgery was associated with significantly shorter RFS (HR = 6.22, 95% CI 2.39-16.2, p < 0.001) and OS (HR = 6.37, 95% CI 2.10-19.3, p = 0.001). Multivariable regression analysis confirmed ctDNA after surgery as an independent prognostic factor (p < 0.001). ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

6857 Adrenal Incidentaloma In A Patient With Surgically Treated Lung Adenocarcinoma A Decade After Complete Remission

Abstract Disclosure: L. Kaur: None. R. Kaur: None. F. Haider: None. A. Iqbal: None. N. Patel: None. Adrenal incidentaloma is an adrenal mass &amp;gt;1 cm in size commonly discovered incidentally in up to 5-7% of patients on imaging performed for reasons other than adrenal causes. Metastasis to the adrenal glands is common due to their rich blood supply, with lung cancer being the most common primary site, followed by the stomach, esophagus and the liver. Bilateral adrenal metastasis is common, however isolated metachronous or synchronous adrenal metastasis is rare, with an incidence of 1-6%. We present a case of incidentally discovered isolated right adrenal mass ten years after curative surgical resection of right lung adenocarcinoma. A 74 year old male with history significant for adenocarcinoma of the right upper lung lobe stage 1A , negative for metastasis status post lobectomy and no adjuvant chemotherapy or radiation 10 years ago presented to the hospital for his routine follow up evaluation. His vitals were within normal limits and physical examination was unremarkable. The follow up diagnostic CT imaging was done which showed an incidental 2.1 x 1.6 x 1.2 cm right adrenal mass without any pathological lesion or lymphadenopathy. A review of CT scan done one year ago revealed no prior adrenal mass or other suspicious findings. The patient was referred to endocrinology for evaluation of the adrenal mass. He denied abdominal or right flank pain, headaches, palpitations, elevated blood pressure, sweating, muscle weakness, weight gain/loss and was healthy appearing. Lab work up including biochemical studies for hormonal over production, including aldosterone-renin ratio, adrenocorticotropic hormone, plasma catecholamines with urine metanephrines and urine cortisol were within physiological ranges. CT scan was repeated after 2 months which revealed right adrenal mass of 3.2 x 1.8 x 1.7 cm in size with heterogeneity and high pre contrast density. Given the patient's history of lung cancer, imaging characteristics and rapid interval increase in size, there was high suspicion for metastatic disease. Other differentials considered due to fast growth rate included adrenocortical carcinoma and less likely adrenal adenoma. A decision was made to proceed with right adrenalectomy for definitive resection and histological diagnosis secondary to quickly growing adrenal mass with no lymphadenopathy. The patient underwent laparoscopic adrenalectomy and the final pathological report was consistent with metastatic lung adenocarcinoma. Postoperatively the patient recovered well. At 2 week and 3 month follow up he reported no concerns. Isolated adrenal metastasis is unusual and rare but may occur in lung cancer patients years after curative resection of the primary tumor and hence long term annual follow up imaging and monitoring is recommended for prompt diagnosis and timely treatment. Presentation: 6/2/2024

Should we perform regular surveillance capsule endoscopies in patients following small-bowel adenocarcinoma resection? A case report and discussion.

Because small-bowel tumors are rare, prospective data on the utility of video capsule endoscopy (VCE) for their detection are limited. Current guidelines do not advocate for surveillance VCEs in patients following small-bowel tumor resection, which is mostly due to a lack of data. Here, we report an 81-year-old male patient who had undergone curative segmental ileal adenocarcinoma resection 15 years ago and another segmental jejunal adenocarcinoma resection (TNM-Classification: pT2 pN0 (0/2) G2M0) 7 years ago. He now presents with melena, progressive dyspnea, and decreased hemoglobin levels. VCE revealed local intestinal recurrence of the previously resected jejunal adenocarcinoma, leading to a second segmental jejunal resection (TNM-Classification: pT3 L1 pN0 (0/5) G2 M0). We believe that regular surveillance VCEs after the first jejunal adenocarcinoma resection might have facilitated earlier detection of tumor recurrence in this patient's case. Therefore, we suggest considering regular surveillance VCEs, at least in patients with recurrent small-bowel malignancies. However, future prospective studies are warranted to validate our findings.

Predicting Recurrence after Sublobar Resection in Patients with Lung Adenocarcinoma Using Preoperative Chest CT Scans.

Background Sublobar resection for lung cancer is usually guided by cutoff values for consolidation size (maximal diameter of the solid tumor component) and consolidation-to-tumor ratio (CTR). The effects of these factors as continuous variables and the reason for established cutoffs are, to the knowledge of the authors, unexplored. Purpose To quantitatively assess the predictive value of CTR and consolidation size for cancer recurrence risk after sublobar resection in clinical stage IA lung adenocarcinoma. Materials and Methods This retrospective study reviewed sublobar resection for clinical stage IA lung adenocarcinoma performed between January 2010 and December 2019. A restricted cubic spline function verified linearity by estimating recurrence probabilities using CTR and consolidation size obtained on preoperative CT scans. Statistical analyses included a Cox proportional hazards model to identify risk factors for cancer recurrence and the Cochran-Armitage trend test for the association between CTR and consolidation size. Results Of 1032 enrolled patients (age, 63.9 years ± 9.9 [SD]; 464 male patients), 523 (50.7%) and 509 (49.3%) underwent wedge resection and segmentectomy, respectively. Among patients with a CTR between 1% and 50% (n = 201), 187 (93.0%) had a consolidation size of less than or equal to 10 mm (P < .001). There was a positive association between the risk of recurrence with CTR and consolidation size (r2 = 0.727; P < .001). The recurrence rate showed the greatest increase when CTR was greater than 50% or consolidation size was greater than 10 mm. Specifically, the recurrence rate increased from 2.1% (three of 146) at 26%-50% CTR to 8.3% (nine of 108) at 51%-75% CTR, and from 4.4% (eight of 183) for 6-10-mm consolidation size to 11.9% (23 of 194) for 11-15-mm consolidation size. The probability of recurrence exhibited linearity and increased with CTR and consolidation size. Conclusion Cancer recurrence risk after sublobar resection for stage IA adenocarcinoma consistently rises with CTR and consolidation size. Current guideline cutoffs for sublobar resection remain clinically relevant given observed recurrence rates. © RSNA, 2024 Supplemental material is available for this article.

Clinicopathologic and Genomic Features Associated with Brain Metastasis After Resection of Lung Adenocarcinoma

ObjectiveTo identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis. MethodsPatients who underwent complete resection of stage I-IIIA LUAD (2011 – 2020) were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors. Fine-Gray models for the development of brain metastasis, with death without brain metastasis as a competing risk, were constructed. ResultsIn total, 2660 patients were included. Median follow-up was 71 months (95% confidence interval, 69-73 months). The cumulative incidence of brain metastasis at 10 years was 9.8%. Among patients who developed a brain metastasis, the median time from surgery to brain metastasis was 21 months (interquartile range, 10-42 months). Higher maximum standardized uptake value of the primary tumor, neoadjuvant therapy, lymphovascular invasion, and stage III disease were associated with development of a brain metastasis. Among patients who had next-generation sequencing performed, a multivariable analysis showed that neoadjuvant therapy, pathologic stage, and TP53 mutations were associated with development of brain metastasis. Median survival after brain metastasis was 18 months (95% confidence interval, 13-24 months). Better performance status, lack of extracranial metastasis, stereotactic radiosurgery, and targeted therapy were associated with better survival after brain metastasis. ConclusionsBrain metastasis is common after complete resection of LUAD and often occurs within 2 years. Markers of aggressive tumor biology, including higher maximum standardized uptake value, lymphovascular invasion, and TP53 mutations, and neoadjuvant therapy are associated with brain metastasis.

Integrating Clinical Variables, Radiomics, and Tumor-derived Cell-free DNA for Enhanced Prediction of Resectable Esophageal Adenocarcinoma Outcomes

The value of integrating clinical variables, radiomics, and tumor-derived cell-free DNA (cfDNA) for the prediction of survival and response to chemoradiation of resectable esophageal adenocarcinoma (rEAC) patients is not yet known. Our aim was to investigate if radiomics and cfDNA metrics combined with clinical variables can improve personalized predictions. A cohort of 111 rEAC patients from two centers treated with neoadjuvant chemoradiotherapy was used for exploratory retrospective analyses. Models combining the clinical variables of the SOURCE survival model with radiomic features and cfDNA, were built using elastic net regression and internally validated using 5-fold cross validation. Model performance for overall survival (OS) and time to progression (TTP) were evaluated with the C-index and the area under the curve (AUC) for pathological complete response (pCR) RESULTS: The best performing baseline models for OS and TTP were based on the combination of SOURCE-cfDNA which reached a C-index of 0.55 and 0.59 compared to 0.44-0.45 with SOURCE alone. The addition of re-staging PET radiomics to SOURCE was the most promising addition for predicting OS (C-index: 0.65) and TTP (C-index: 0.60). Baseline risk-stratification was achieved for OS and TTP by combining SOURCE with radiomics or cfDNA, log-rank p<0.01. The best performing combination model for the prediction of pCR reached an AUC of 0.61 compared to 0.47 with SOURCE variables alone. The addition of radiomics and cfDNA can improve the performance of an established survival model. External validity needs to be further assessed in future studies together with the optimization of radiomic pipelines.

EP.03B.03 Whole Genome Analysis in Resected Adenocarcinoma and Squamous Cell Carcinoma of the Lungs

EP.03B.03 Whole Genome Analysis in Resected Adenocarcinoma and Squamous Cell Carcinoma of the Lungs

S2855 A Case of Endoscopic Full-Thickness Resection for a Known Colon Adenocarcinoma in a Patient With Decompensated Cirrhosis

S2855 A Case of Endoscopic Full-Thickness Resection for a Known Colon Adenocarcinoma in a Patient With Decompensated Cirrhosis

Long-term prognostic characteristics of patients with clinical stage IA part-solid lung adenocarcinoma: a conditional survival analysis.

Despite excellent 5-year survival, there are limited data on the long-term prognostic characteristics of clinical stage IA part-solid lung adenocarcinoma. The objective was to elucidate the dynamics of prognostic characteristics through conditional survival analysis. Consecutive patients who underwent complete resection for clinical stage IA part-solid lung adenocarcinoma between 2011 and 2015 were retrospectively reviewed. Conditional survival is defined as the probability of surviving further y years, conditional on the patient has already survived x years. The conditional recurrence-free survival (CRFS) and conditional overall survival (COS) were analysed to evaluate prognosis over time, with conditional Cox regression analysis performed to identify time-dependent prognostic factors. A total of 1539 patients were included with a median follow-up duration of 98.4 months, and 80 (5.2%) patients experienced recurrence. Among them, 20 (1.3%) recurrence cases occurred after 5 years of follow-up with 100% intrathoracic recurrence. The 5-year CRFS increased from 95.8% to 97.4%, while the 5-year COS maintained stable. Multivariable Cox analysis revealed that histologic subtype was always an independent prognostic factor for CRFS even after 5 years of follow-up, while the independent prognostic value of consolidation-to-tumour ratio, visceral pleural invasion and lymph node metastasis was observed only within 5 years. Besides, age, pathologic size and lymph node metastasis maintained independent predictive value for COS during long-term follow-up, while consolidation-to-tumour ratio was predictive for COS only within 5 years of follow-up. The independent prognostic factors for clinical stage IA part-solid lung adenocarcinoma changed over time, along with gradually increasing 5-year CRFS and stable 5-year COS.

Splenic flexure adenocarcinoma: A national cohort analysis of extent of surgical resection and outcomes.

The optimal extent of resection for splenic flexure adenocarcinoma remains debated. These tumours straddle the left- and right-sided vasculature with lymphatic drainage in a watershed area; current guidelines recommend either segmental or extended colectomy. We analysed surgical management of splenic flexure tumours and compared outcomes between approaches. The Surveillance, Epidemiology and End Results database was searched for adults with Stage I-III splenic flexure adenocarcinoma, 2004-2019. Of 5238 patients, 55% underwent extended colectomy. Compared to segmental colectomy, these patients were more likely to have advanced stage. On multivariable analysis, age ≤ 65 years remained independently associated with extended colectomy. Although fewer nodes were examined in segmental colectomy (median 14 vs. 16, p < 0.001), the number of positive nodes (both, median 0 [interquartile ratio 0-2], p = 0.20) and the lymph node ratio were similar between cohorts. Surgical approach was not significantly associated with increased positive nodal yield in adjusted analyses. Five-year overall and disease-specific survival were 73% and 84% for segmental and 72% and 83% for extended colectomy (p > 0.4); these remained comparable after adjustment. Nationally, we observed similar rates of segmental and extended colectomy for splenic flexure adenocarcinoma. Extended colectomy was not more common in Stage III disease, indicating lack of stage migration, and was not associated with better oncological outcomes. These observations support current practice involving either approach, which should be tailored to patient-related factors and preferences, while considering technical aspects and quality of life.

Abstract A015: Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDA) has consistently poor outcomes, even for early-stage tumors that undergo resection (&amp;gt;70%), despite completion of prescribed perioperative systemic therapy. Mucin 5AC (MUC5AC), a heavy glycoprotein, exists in two major glycoforms: heavily glycosylated mature (MM) and less glycosylated immature (IM) forms. MM is located in the apical region and extracellular space, whereas IM is in the perinuclear region. Our previous work demonstrated the association between MM and treatment response and outcomes in resected PDA after neoadjuvant therapy (NAT). In this study, we investigate the impact of MUC5AC tissue expression in resected PDA samples on recurrence site characteristics (local (LR) vs. distant metastasis (mets) vs. both LR and mets). Resected PDA formalin-fixed paraffin-embedded tissue blocks from January 2010 to June 2021 were obtained from the Ohio State University biorepository. Immunohistochemistry was performed to study the expression for MM and IM using monoclonal antibodies 45M1 and CLH2, respectively, and H-scores (0-300) were calculated. Logistic regression was used to study this association of interest. We had 100 R-PDA (43 received NAT, and 57 had upfront surgery (UpS)) available for testing. The median age of diagnosis was 65 years, and 50% were males. Most of the patients in the NAT group received FOLFIRINOX (n=36) and received gemcitabine/nab-paclitaxel (n=5) or FOLFOX (n=2). The median number of doses received is 6 (range 2-9). The results in these groups can be summarized as follows: a) 35/43 had recurrence (LR=7, mets=21, and LR+mets=7), with the liver being the most common site of metastasis (13/28) followed by lung (5/28) and peritoneum (5/28), b) Higher IM expression (mean H-score) was significantly (p=0.0275) higher in LR+mets (H-score 196) than in LR (H-score 69) or mets (H-score 115) groups, c) Higher MM expression (mean H-score) was also significantly different among these groups (LR vs. mets vs. LR+mets = 81 vs. 120 vs. 206, p= 0.0358), e) similar trend of mean H-scores was noted in FOLFIRINOX sub-group (LR vs. mets vs. LR+mets = 205 vs. 109 vs. 60, p=0.0185 for IM and 65 vs. 116 vs. 205, p=0.0329 for MM). No significant association between recurrence patterns and tissue MUC5AC expression in the UpS group. These findings concur with our prior observations, underscoring the clinical significance of MUC5AC in resected PDA post-NAT and suggesting its potential role in facilitating pancreatic tumor cell metastasis. Although larger prospective studies are needed to confirm these results, our study highlights MUC5AC as a potential therapeutic target to prevent metastasis in early-stage PDA, potentially improving overall outcomes. Citation Format: Ashish Manne, Lianbo Yu, Ashwini Esnakula. Tissue MUC5AC expression predicts recurrence patterns following resection in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A015.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1>2cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P=0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. In pathologic stage I (>2cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.