Yoo Na Lee, Min Kyu Sung, Dae Wook Hwang, Yejong Park, Bong Jun Kwak, Woohyung Lee, Ki Byung Song, Jae Hoon Lee, Changhoon Yoo, Kyu-Pyo Kim, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2024;56(4):1240-1251. Published online June 19, 2024
Purpose Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.
Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo
Cancer Res Treat. 2023;55(4):1313-1320. Published online May 4, 2023
Purpose There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.
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A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic? Purvi Jonnalagadda, Virginia Arnold, Benjamin A. Weinberg Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
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So Heun Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Sora Kang, Jae Ho Jeong, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Yejong Park, Bong Jun Kwak, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2023;55(3):956-968. Published online February 27, 2023
Purpose The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.
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The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database Hao Hu, Yang Xu, Qiang Zhang, Yuan Gao, Zhenyu Wu Expert Review of Anticancer Therapy.2024; 24(6): 467. CrossRef
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Cancer Res Treat. 2021;53(2):424-435. Published online November 9, 2020
Purpose This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.
Materials and Methods Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.
Results The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).
Conclusion AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.
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Purpose
This study was conducted to evaluate the prognostic values of the 7th and 8th American Joint Committee on Cancer (AJCC) staging systems for patients with resected perihilar cholangiocarcinoma (PHCC).
Materials and Methods
A total of 348 patients who underwent major hepatectomy for PHCC between 2008 and 2015 were identified from a single center. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index was used to evaluate the prognostic predictability of the 8th AJCC staging system compared with that of the 7th.
Results
In the 8th edition, the stratification of each group of T classification improved compared to that in the 7th, as the survival rate of T4 decreased (T2, 31.2%; T3, 13.9%; T4, 15.1%; T1- T2, p=0.260; T2-T3, p=0.001; T3-T4, p=0.996). Both editions showed significant survival differences between each N category, except between N1 and N2 (p=0.063) in 7th edition. Differences of point estimates between the 8th and 7th T and N classification and overall stages were +0.028, +0.006, and +0.039, respectively (T, p=0.005; N, p=0.115; overall stage, p=0.005). In multivariable analysis, posthepatectomy liver failure, T category, N category, distant metastasis, histologic differentiation, intraoperative transfusion, and resection margin status were associated with OS.
Conclusion
The prognostic predictability of 8th AJCC staging for PHCC improved slightly, with statistical significance, compared to the 7th edition, but its overall performance is still unsatisfactory.
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Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-hong Park, Seung-Mo Hong, Kyu-pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo
Cancer Res Treat. 2020;52(2):594-603. Published online December 18, 2019
Purpose
The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.
Materials and Methods
In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.
Results
Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).
Conclusion
Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.
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Cancer Res Treat. 2019;51(4):1639-1652. Published online April 19, 2019
Purpose
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (PNET) included several significant changes. We aim to evaluate this staging system compared to the 7th edition AJCC staging system and European Neuroendocrine Tumors Society (ENETS) system.
Materials and Methods
We used Korean nationwide surgery database (2000-2014). Of 972 patients who had undergone surgery for PNET, excluding patients diagnosed with ENETS/World Health Organization 2010 grade 3 (G3), only 472 patients with accurate stage were included.
Results
Poor discrimination in overall survival rate (OSR) was noted between AJCC 8th stage III and IV (p=0.180). The disease-free survival (DFS) curves of 8th AJCC classification were well separated between all stages. Compared with stage I, the hazard ratio of II, III, and IV was 3.808, 13.928, and 30.618, respectively (p=0.007, p < 0.001, and p < 0.001). The curves of OSR and DFS of certain prognostic group in AJCC 7th and ENETS overlapped. In ENETS staging system, no significant difference in DFS between stage IIB versus IIIA (p=0.909) and IIIA versus IIIB (p=0.291). In multivariable analysis, lymphovascular invasion (p=0.002), perineural invasion (p=0.003), and grade (p < 0.001) were identified as independent prognostic factors for DFS.
Conclusion
This is the first large-scale validation of the AJCC 8th edition staging system for PNET. The revised 8th system provides better discrimination compared to that of the 7th edition and ENETS TNM system. This supports the clinical use of the system.
Citations
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Purpose
Pancreatic cancer associated double primary tumors are rare and their clinicopathologic characteristics are not well elucidated.
Materials and Methods
Clinicopathologic factors of 1,352 primary pancreatic cancers with or without associated double primary tumors were evaluated.
Results
Of resected primary pancreatic cancers, 113 (8.4%) had associated double primary tumors, including 26 stomach, 25 colorectal, 18 lung, and 13 thyroid cancers. The median interval between the diagnoses of pancreatic cancer and associated double primary tumors was 0.5 months. Overall survival (OS) of pancreatic cancer patients with associated double primary tumors was longer than those with pancreatic cancer only (median, 23.1 months vs. 17.0 months, p=0.002). Patients whose pancreatic cancers were resected before the diagnosis of metachronous tumors had a better OS than patients whose pancreatic cancer resected after the diagnosis of metachronous tumors (48.9 months and 13.5 months, p=0.001) or those whose pancreatic cancers were resected synchronously with non-pancreas tumors (19.1 months, p=0.043). The OS of pancreatic cancer patients with stomach (33.9 months, p=0.032) and thyroid (117.8 months, p=0.049) cancers was significantly better than those with pancreas cancer only (17.0 months).
Conclusion
About 8% of resected pancreatic cancers had associated double primary tumors, and those from the colorectum, stomach, lung, and thyroid were common. Patients whose pancreatic cancer was resected before the diagnosis of metachronous tumors had better OS than those resected after the diagnosis of metachronous tumors or those resected synchronously.
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A retrospective study of 797 cases of early gastric cancer(EGC) operated from 1981 to 199l at Seoul National University Hospital was performed to evaluate its prognostic factors for 9 clinicopathologic factors(sex, age, tumor location, gross type, histology, depth of invasion, lymph node metastasis, resection type). The incidence of EGC in gastric cancer was 20.l% and overall 5 year survival rate was 93%. In univariate and multivariate analysis af the above mentioned 9 factors, stastically significant prognostic factor was only regional lymph node metastasis(P<0.05). In addition, signet ring cell carcinoma was more prevalent in EGC(2.9 times) than in AGC and had a good prognosis than other histalogic type. In conclusion, extensive lymphadenectomy(R2 or R2+a) is needed only in AGC but also in EGC. And more extensive study on the prognostic factors of the signet ring cell carcinoma that has been considered as a poor prognostic type is further necessory to clarify the good effect in EGC and bad effect in AGC.
Gastric cardia cancers comprise gastric cancers which involve stomach of distal 2cm from gastroesophageal junction. It has been reported that cardia cancer has relatively poorer prog- nosis than gastric cancer of the other sites. To evaluate clinicopathological characteristics of gastric cardia cancer and to determine prognostic factors, we analyzed retrospectively 198 pa- tients who underwent operations for gastric cardia cancers between 1970 and l991 and had the following results. Gasric resection was performed in 176 patients. The ratio of gastric cardia cancer to gastric cancers of the other sites was slightly decreased in 1980s than in l970s (over- all 3.8% of gastric cancers). Gastric cardia cancer had poorer 5-year survival rate than those of gastric cancers of other sites (34.2% for cardia, 38.5% for fundus, 54.1% for body, 48.9% for an- trum). In cardia cancer, 2.5% was early gastric cancer, 89.3% had more than serosal invasion, 66. 5% had positive lymph node involvement and 75.2% were in stage III 4 IV. There was esophageal involvement in 33.5%; despite clear proximal resection mergin on frozen biopsies, there were positive resection margin of 21.4% (3/14) in cases with resection margin of less than 2 cm and 3.7% (6/162) in cases with resection margin of 2cm or more than 2cm (p<0.05, Fisher's exact test). These results suggest that the length of proximal resection margin should be at least 2 cm to get a cancer-free proximal resection margin in gastric cardia cancer. Multivariate analysis revealed that depth of invasion, length of proximal resection margin and lymph node metastasis were significant prognostic factors. We conclude that poorer prognosis of gastric cardia cancer is due to more advanced stage at the time of diagnosis. Therefore, to improve the survival of gastric cardia cancer, better means of early diagnosis should be developed.
A statistical analysis of 741 cases of stage IV gastric cancer patients diagnosed between 1987 and 1991 at Seoul National University Hospital was done to evaluate the clinicopathological features and to find a proper management of stage IV gastric cancer. Peritoneal metastais (PM) was present in 227 patients (31%), liver metastasis (LM) in 198 patients (29%), direct invasion to adjacent organ (DI) in 148 patients (20%), and synchronous peritoneal and liver metast sis in 62 patients (8%). Patients with peritoneal metastasis were younger, and have Borrmann type IV and signet rinacell type lesion more frequently. Patients with liver metastasis were loder, and have Borrman type I and II and moderately-differentiated, highly-located lesion more frequently. Two-year survival rate for patients with direct invasion (DI) group was 20.4%, 17.7% for patients with liver metastasis (LM), 6.9% for patients with pritoneal meatstasis (PM), and 4.2% for patients with synchronous liver and peritoneal metastasis. In the group of patients with direct invasion (DI), patients who received gastric resection have better survival time than the patients who recieved bypass procedure (450 days vs 202 days in median survival, P<0.05), althrough resected group shows less invasive than bypass group. There was significant survival gain in resected group when comparision was done in T4NZMO homogenized group. But there was no significant survival gain by resection in liver or peritoneal metastasis (P > 0.05). Two year survival rate of the patients who recieved gastrectomy was 34.0% in immunochemotherapy group (n=23), 23.4% in chemotheraPy group (n=33), and 13.5% in operation ony group (n=22)(P<0.05), where prognostic parameters of these aroups were relatively comparable. We conclude that in stage IV gastric cancer there were different clinicopathologic features according to the metastatic patterns and gastric resection has significant survival gain than bypass procedure in direct invasion group, although not in liver or peritoneal metastasis. This retrospective analysis suggested the possibility that postoperative immunochemotherapy or chemotherapy may have some role in treatment of stage IV gastric cancer.