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ISSN / EISSN : 0030-2414 / 1423-0232
Published by: S. Karger AG (10.1159)
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Oskar Steinbrecher, Thomas Brodowicz, Markus Raderer, , Johannes Fabsits, Wolfgang Lamm
Published: 21 October 2022
Journal: Oncology
Abstract:
Introduction: Soft tissue sarcomas (STS) are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic Liposarcoma (LPS) patients, who have failed first line chemotherapy and has been approved for the use in patients with LPS in the United States and Europe due to its efficacy in this histological subtype in a phase III trial. We have evaluated efficacy and tolerability of eribulin in LPS and Leiomyosarcoma (LMS) patients in the routine clinical setting at our department. Methods: In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. Results: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate (ORR) was 9.4% for all patients, with one patient with LPS and two patients with leiomyosarcoma (LMS) showing a partial response (PR). Disease control rate (PR plus stable disease -SD) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression free survival (PFS) and overall survival (OS) was detected between patients with LPS and LMS (p=0.807 and p=0.519), respectively. Patients with LMS (n=2) had received fewer previous therapy lines than patients with LPS (n=14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3+4 events were rare. Conclusion: The activity and tolerability of eribulin in LPS as well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase III trials.
Norio Akuta, Hitomi Sezaki, Shunichiro Fujiyama, , , Mariko Kobayashi, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Yoshiyuki Suzuki, et al.
Published: 21 October 2022
Journal: Oncology
Abstract:
Introduction: Simple predictive markers enabling even non-specialized medical doctors, and clinicopathological features of primary liver cancer (PLC) following HCV clearance with direct-acting antivirals (DAAs) are unclear. Methods: The subjects of this retrospective study were 2 476 patients following HCV clearance with DAAs. All patients were confirmed to be PLC-free before and during DAAs. Results: PLC was diagnosed in 73 patients during the follow-up, with an incidence rate per 1 000 person years of 5.9. The annual rate of PLC during the first 6 years was 0.6%. Multivariate analysis identified gender, GGT, and FIB-4 index as the significant determinants of PLC. According to a combination of these risk factors, the cumulative PLC incidence rates were significantly different among the five subgroups based on the number of PLC risk scores. In 73 patients with PLC, the rates of abnormal AFP, PIVKAII, and serum TERT C228T positive were 37.0, 32.4, and 22.2%. PIVKAII levels in BCLC stage A and B were significantly higher than those in stage 0. In 41 patients, who underwent surgical resection for PLC, maximum tumor diameters of abnormal PIVKAII were significantly larger than those of normal PIVKAII. PLC of abnormal PIVKAII significantly indicated presence of vp more than that of normal PIVKAII, and did not contain well-differentiated HCC. Conclusions: Combination of simple markers, enabling even non-specialized medical doctors, is useful for the evaluation of PLC risk following HCV clearance with DAAs. However, imaging studies are regularly recommended for the early detection of PLC.
Victor Duque-Santana, Fernando López-Campos, Margarita Martin-Martin, Mireia Valero, , , Sonsoles Sancho
Published: 21 October 2022
Journal: Oncology
Abstract:
INTRODUCTION The standard therapy for locally advanced rectal cancer is based on neoadjuvant chemoradiotherapy (nCRT) with fluoropyrimidines. There are different biomarkers used as prognostic factors in these tumors. Some studies advocate the use of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in this clinical scenario. The aim of the study is to evaluate NLR and PLR as prognostic factors of disease-free survival (DFS) and overall survival (OS) and as predictive factors of pathological complete response (pCR) using Ryan tumor regression scoring system on surgical specimens, in patients with locally advanced rectal adenocarcinoma who received nCRT and radical surgery. METHODS We retrospectively evaluated patients with locally advanced rectal adenocarcinoma (T3-T4, N1-N3, M0 according to the TNM classification, AJCC 8th edition) who received neoadjuvant chemoradiotherapy based on fluoropyrimidines and radical surgery. Complete blood cell count before nCRT were obtained to calculate NLR and PLR. We made subgroups of patients according to NLR and PLR. We obtained the cut-off point for these ratios based on receiver operating characteristic analysis. We analyzed OS and DFS using the Kaplan-Meier method and Cox proportional hazard models. The relationships between NLR/PLR and pCR, along with other clinical-pathological characteristics were evaluated by Pearson´s χ2 or Fisher´s exact test as appropriate. Multivariate analyses were performed using Cox proportional hazard regression models. RESULTS Between February 2012 and February 2017, 100 consecutive patients were treated according to the reported schedules. Median age was 76 years (68-83). All patients received radiotherapy up to 50,4 Gy and 5-FU-based chemotherapy. 100% completed nCRT and surgery. 38% had elevated basal NLR (cut-off >1,95), 50% had elevated basal PLR (cut-off >133). After a median follow-up of 72 months (55-88), a lower DFS was obtained in the high NLR subgroup (Long Rank, Mantel-Cox 5,165, p=0,023) and in the high PLR subgroup (Long Rank, Mantel-Cox 13,971, p=0,001). Multivariate analysis showed that PLR (p=0,006) was a strong significant predictor of DFS. A lower overall survival was observed in the high NLR and PLR subgroup without significant differences (Long Rank, Mantel-Cox 1,245, p= 0,265; 0,578, p=0,447). No significant differences were obtained in any of the subgroups analysis regarding pCR rates. CONCLUSION In light of our results, both NLR and PLR could be considered prognostic factors for DFS in patients with LARC that receive treatment with nCRT followed by surgery.
Toshiyasu Ojima, Keiji Hayata, Junya Kitadani, Akihiro Takeuchi, Hiroki Yamaue
Published: 21 October 2022
Journal: Oncology
Oncology, Volume 100, pp 583-590; https://doi.org/10.1159/000526920

Abstract:
Introduction: Robotic surgery is regarded as an evolved type of laparoscopic surgery. Few studies have undertaken detailed analysis of complications following robotic gastrectomy for gastric cancer. Methods: This is a single-center retrospective study of 149 consecutive patients with gastric cancer who underwent robotic gastrectomy. It examines in detail the postoperative complications in robotic gastrectomy for gastric cancer, focusing on intra-abdominal infectious complications including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess. We also aim to identify the related risk factors. Results: The median operation time was 299 min and the median bleeding was 25 mL. The incidence of overall complications higher than grade II was 8.7%. Clinically serious complications higher than grade IIIa occurred in 6.7% of cases. The incidence of intra-abdominal infectious complications that were higher than grade II was 4.0%. Mortality in our consecutive series was zero. Multivariate logistic regression analysis indicated that postoperative intra-abdominal infectious complications were significantly associated with history of abdominal surgery (p = 0.043), with odds ratios of 17.890 (95% confidence interval 1.092–293.150) and with non-curative resection (p = 0.025), with odds ratios of 58.629 (95% confidence interval 1.687–2,037.450). Discussion/Conclusion: Robotic gastrectomy was shown to be a safe and effective treatment for gastric cancer when performed by experienced surgeons. Attention should be paid to the risk of developing postoperative complications when performing robotic gastrectomy in gastric cancer patients with a history of abdominal surgery and in patients with advanced gastric cancer in whom there is expected to be difficulty in curative resection.
Yoshihito Ohhara, Ichiro Kinoshita, Akira Suzuki, Makoto Imagawa, Jun Taguchi, Takuro Noguchi, Satoshi Takeuchi, Yasushi Shimizu, Hideyuki Seki, Junichi Suzuki, et al.
Published: 21 October 2022
Journal: Oncology
Abstract:
Introduction: Karyopherin alfa 2 (KPNA2) and karyopherin beta 1 (KPNB1), constitute nuclear transport protein complexes involved in nuclear import, and are significant in tumor progression. Although high KPNA2 expression was associated with poor prognosis in solid tumors, the relationship between KPNA2 and KPNB1 expression and their prognostic role in gastric cancer (GC) remains unclear. Methods: Immunohistochemistry was used to correlate the expression of KPNA2 and KPNB1 with various features, including clinicopathologic characteristics in 130 patients with GC and survival in 94 patients with invasive lesions extending to the submucosa or deeper. Results: High expression of KPNA2 and KPNB1 was found in 25% and 36% of the patients, respectively. Both were significantly related to tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, and Ki-67 expression. KPNA2 expression was significantly related to that of KPNB1 (P < 0.001). Patients with high KPNB1 expression had poorer prognosis than those with low expression (P = 0.027), as was also observed in case of KPNA2 (P < 0.001). Patients with high expression of both KPNA2 and KPNB1 accounted for 18% and had a poorer prognosis than those with high expression of either and those with low expression of both (P = 0.001). Multivariate analysis revealed that high expression of both KPNA2 and KPNB1 was an independent prognostic factor in patients with GC (HR 3.46, 95% CI 1.64–2.73, P = 0.001). Conclusion: KPNA2 expression was correlated with KPNB1 expression, and high co-expression of KPNA2 and KPNB1 may represent a strong prognostic biomarker in GC.
Yong Hoon Lee, Sook Kyung Do, Shin Yup Lee, Hyo-Gyoung Kang, Jin Eun Choi, Mi Jeong Hong, Jang Hyuck Lee, Sunwoong Lee, Won Kee Lee, Ji Yun Jeong, et al.
Published: 18 October 2022
Journal: Oncology
Abstract:
Objective This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. Methods Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. Results Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ration [aOR] = 0.59, 95% CI = 0.36-0.97, P = 0.04; adjusted hazard ratio [aHR] = 1.44, 95% CI = 1.09-1.91, P = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. Conclusion This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
, Jin Young Kim, Keon Uk Park
Published: 18 October 2022
Journal: Oncology
Abstract:
Introduction: Current standard chemotherapy for biliary tract cancer (BTC) has limited survival benefits, and the need for targeted therapies is increasing. This study investigated the genetic profiles and clinical implications of BRCA mutations in patients with advanced BTC. Methods: Targeted high-throughput sequencing was performed on samples obtained from 25 patients with advanced BTC who had received palliative first-line platinum-based chemotherapy. Results: Of the 25 patients, 16 (64.0%) were younger than 65 years of age and 16 (64.0%) were male. The BTC cases consisted of intrahepatic cholangiocarcinoma (9, 36.0%), extrahepatic cholangiocarcinoma (5, 20.0%), and gallbladder cancer (11, 44.0%). The median overall survival (OS) and progression-free survival (PFS) of all patients were 11.9 months (95% confidence interval [CI] 9.233–14.567) and 5.6 months (95% CI 3.812–7.321), respectively. Genomic alterations in TP53 (52.0%), BRCA (36.0%), ATM (32.0%), ERBB2 (24.0%), NOTCH1 (20.0%), and FGFR3 (20.0%) were frequently reported. TP53 and ATM mutations were associated with OS (TP53: hazard ratio [HR] 2.719, 95% CI 1.074–6.881, p = 0.035; ATM: HR 2.780, 95% CI 1.091–7.082, p = 0.032). Patients with BRCA mutations had a slightly improved PFS compared to those with intact BRCA (6.7 months [range, 2.674–10.660 months] vs. 5.3 months [range, 3.601–6.999 months], p = 0.090). However, there was no significant difference in OS between groups (BRCA mutant vs. intact: 10.6 months [range, 3.588–17.612 months] vs. 11.9 months [range, 7.499–16.301 months], p = 0.252). BRCA mutations were significantly associated with PFS in the multivariate analysis (HR 0.150, 95% CI 0.034–0.655, p = 0.012). Conclusion: This study demonstrated that BRCA mutations might have a role as predictive biomarkers for palliative first-line platinum-based chemotherapy in patients with advanced BTC.
, , Shigenobu Emoto, Koji Murono, Kazuhito Sasaki,
Published: 17 October 2022
Journal: Oncology
Abstract:
Introduction: Adjuvant chemotherapy improves the prognosis of patients with colorectal cancer (CRC) following radical resection. However, the safety and efficacy of oxaliplatin-based chemotherapeutic regimens for elderly patients remains to be elucidated. The aim of the present study was to examine the tolerability and efficacy of adjuvant CAPOX (capecitabine and oxaliplatin) therapy for elderly patients in comparison with young patients. Methods: We examined 138 Japanese patients who received adjuvant CAPOX therapy for high-risk stage II or III CRC between July 2010 and June 2021 at our hospital. Patients were divided according to an age of 70 years. Treatment details of CAPOX therapy were analyzed in association with age. Moreover, prognosis of stage III CRC was compared between the patient groups. Results: Twenty-three patients (17%) were ≥70 years old. Male patients were predominant in the ≥70 years group (p = 0.006). Patients ≥70 years old had more comorbidities (diabetes, p = 0.014; cardiovascular disease, p < 0.001; renal disease, p = 0.042) than patients <70 years old. There were no age-dependent differences in dose intensity, the number of cycles, or DLTs of CAPOX therapy. CSS and RFS were also similar between the ≥70 and <70 years old patients with stage III CRC. Conclusions: Adjuvant CAPOX therapy was tolerable in elderly Japanese patients. The prognosis of elderly patients with stage III CRC was similar to that of their younger counterparts. Advanced age itself may not be a contraindication for adjuvant chemotherapy in CRC. Future studies with a larger patient cohort are required to confirm the present results.
Hiroaki Tanioka, Yoshiko Mori, Takehiro Tanaka, Kazuya Yasui, Keisuke Kimura, , , Akihiro Nyuya, Shuya Yano,
Published: 14 October 2022
Journal: Oncology
Abstract:
Introduction Gastric cancer is divided into four subtypes by their molecular features linked with genetic alterations, e.g., Epstein-Barr virus (EBV), microsatellite instability-high (MSI-high), chromosomal instability (CIN), and genomically stable (GS), called as TCGA classification. In this study, we tried to clarify the epigenetic features of the four GC subtypes according to aberrant methylation status in 23 loci. Methods A total of 98 gastric cancers and their normal gastric mucosa samples were included in this study. We divided gastric cancers into TCGA subtypes which were determined in line with MSI-high, EBV, CIN, to GS by their molecular features. The 13 loci of polymorphic microsatellite sequences were used to determine loss of heterogeneity (LOH) for the detection of CIN. The MSI status was determined by three mononucleotide repeat markers. Infection of EBV was determined by recovering EBV BNRF1 sequence from genomic DNA collected from gastric cancers. Methylation status of 23 loci was investigated by the combined bisulfite restriction analysis (COBRA). Status of other findings, e.g., KRAS mutations, HER2 expression status and infection of helicobacter pylori were confirmed. Results Gastric cancers were divided into MSI (13%), EBV (7%), CIN (53%), and GS (27%). By histological classification, poorly differentiated adenocarcinoma (por) was more in tumors categorized in MSI-high, and GS and signet-ring cell carcinoma (sig) was more in GS. Among the 23 loci investigated their methylation status, 18 loci were significantly hypermethylated in caner tissues. A unsupervised clustering divided gastric cancers into two clusters, and revealed that most GS tumors clustered together in a cluster that exhibited lower methylation levels, distinct from the other subtypes. The inter-variable clustering revealed that a cluster contained the three loci (SFRP2-region 1/2 and APC) belonging to the Wnt signal cascade (Wnt-associated loci). The mean methylation score of Wnt-associated loci was the lowest in GS tumors (MSI-high: 2.7 [95% confidence interval (CI), 2.3-2.9]; EBV:2.1[1.2-3.1]; CIN: 2.4 [2.2-2.7]; GS: 1.3 [0.8-0.7]). In contrast, the mean methylation score of the other 15 loci was significantly higher in MSI-high, while that in GS was as same as that in EBV or CIN (MSI- high: 10.4 [8.3-12.4]; EBV:5.7 [1.7-9.7]; CIN: 4.4 [3.6-5.1]; GS: 3.4 [2.2-4.6]). Additionally, the lower methylation score of Wnt-associated loci was observed only in sig tumors. Conclusions GS subtype tumors have the potential to possess distinct signatures in DNA hypomethylation profiles in Wnt signaling pathway, especially in signet-ring cell carcinoma.
Yutaka Suehiro, Shigeyuki Suenaga, Yuki Kunimune, Shoko Yada, Kaori Hamamoto, Takanori Tsuyama, Shogo Amano, Hiroto Matsui, Shingo Higaki, Ikuei Fujii, et al.
Published: 14 October 2022
Journal: Oncology
Abstract:
Introduction: We previously developed a novel methylation assay, the combined restriction digital PCR (CORD) assay, consisting of treatment of DNA with methylation-sensitive restriction enzymes and droplet digital PCR. Methods: In this study, we assessed the diagnostic performance of serum methylated Homeobox A1 (mHOXA1) and methylated somatostatin (mSST) using the CORD assay in combination with CA19-9 for pancreatic cancer using serum samples from 82 healthy individuals, 13 patients with benign pancreatic disease, 3 patients with branched-duct intraductal papillary mucinous neoplasm, and 91 patients with pancreatic cancer. Results: For the single marker tests, sensitivity for all stages of pancreatic cancer, stage I cancer, and specificity were, respectively, 71.4%, 50.0%, and 94.9% for CA19-9; 51.6%, 68.8%, and 90.8% for mHOXA1; and 50.1%, 68.8%, and 94.9% for mSST. Those for the combined marker tests were, respectively, 86.8%, 81.3%, and 85.7% for combined mHOXA1 and CA19-9; 86.8%, 87.5%, and 89.8% for combined mSST and CA19-9; and 89.0%, 87.5%, and 85.7% for all three markers combined. Conclusion: The combination of mHOXA1 and mSST with CA19-9 appears to be useful to detect pancreatic cancer even at an early stage.
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