Oncology

Oncologic and reproductive outcomes of cystectomy as a fertility-sparing treatment for early-stage epithelial ovarian cancer Abstract Background Fertility-sparing surgery (FSS) has mainly been chosen for young women with ovarian-confined/well-differentiated epithelial ovarian cancer (EOC). In general, FSS consists of at least conservation of contralateral ovary and the uterus with a staging surgery. However, information on the clinical outcome in women who underwent cystectomy as a fertility-preserving option is lacking. Methods After a central pathological review and search of the medical records from multiple institutions between 1987 and 2015, a total of eight early-stage EOC patients treated with cystectomy as FSS were retrospectively evaluated. Diagnosis and staging were based on International Federation of Gynecology and Obstetrics criteria (2014). Surgery consisted of uni- or bilateral cystectomy. The oncologic and reproductive outcomes were assessed. Results The median age was 29 years (range 26–38 years). The median follow-up time was 103.6 months (range 42.2–218.3 months). The stage was IA in 3, IC1 in 4, and IC3 in one patient. Five patients received adjuvant chemotherapy. After cystectomy, two patients experienced recurrence in the pelvic cavity and bilateral ovaries, respectively. The former patient died of the disease 42 months after cystectomy, and conversely, the latter one was rescued by subsequent radical surgery. Four full-term childbirths were observed in three patients. Conclusions Although oophorectomy is considered as an appropriate fertility-preserving operation, cystectomy may be an unavoidable option when it is the only surgical procedure available. It is desirable to verify the utility by accumulating larger numbers of patients through a future registry system.

Biweekly S-1 plus oxaliplatin (SOX) reintroduction in previously treated metastatic colorectal cancer patients (ORION 2 study): a phase II study to evaluate the efficacy and safety Abstract Background The reintroduction of oxaliplatin as a third-or-later-line regimen has been a promising option for patients with metastatic colorectal cancer (mCRC) who previously received chemotherapy including oxaliplatin. In this single-arm phase II study, we evaluated the efficacy of biweekly SOX, which is the combination of oxaliplatin reintroduction and S-1, as a third-or-later-line treatment. Methods Patients with mCRC who had previously received prior chemotherapy including oxaliplatin and irinotecan and were planned to receive the reintroduction of oxaliplatin were enrolled. Oxaliplatin (85 mg/m2) with/without bevacizumab (5 mg/kg) was given intravenously on day 1. Oral S-1 was administered on day 2–8 at a dose of 40–60 mg (calculated according to the body surface area) twice a day. Cycles were repeated every 2 weeks. The primary endpoint was the progression-free survival (PFS); our hypothesis was that the median PFS would be 3.5 months with a minimum threshold above 2.0 months. The secondary endpoints included the adverse events (AEs), response rate and overall survival (OS). Results A total of 41 patients from 12 institutes were enrolled. The median PFS and OS survival were 3.3 months (95% confidence interval [CI] 2.7–4.2) and 10.1 months (8.3–14.6), and response rate and disease control rate were 10.0% and 65.0%, respectively. Grade 3 AEs included thrombocytopenia (5.0%), anorexia (5.0%), pneumonia (5.0%) and fatigue (5.0%). There were no cases of grade 4 AEs or treatment-related death. Conclusion Biweekly SOX regimen with reintroduction of oxaliplatin could be exploitable as the third- and/or later-line treatments for patients with mCRC.

Inflammation–nutrition score predicts prognosis of patients with resectable hepatocellular carcinoma Abstract Background Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC). Methods Data were collected retrospectively from 674 HCC patients who underwent curative resection. The correlation between INS (inflammation–nutrition score), BCLC (Barcelona Clinic Liver Cancer) stage and inflammatory indices and overall survival (OS) and disease free survival (DFS) was examined. Results An elevated INS was associated with both tumor and host clinical characteristics. The combination of INS and BCLC stage stratifies OS and DFS from 80% and 65% (INS = 0, stage A) to 0% (INS = 2, stage C). Univariate and multivariate analyses revealed that the INS was an independent predictor for OS and DFS, and was superior to inflammation-based scores. In addition, INS was demonstrated to be a prognostic factor for patients with early stage and had a higher AUC value in comparison with inflammation scores. Conclusion This study demonstrates that the INS is an independent marker of poor prognosis in patients with resectable HCC, especially for those with early stage, and it provides complimentary prognostic information to BCLC stage, and may aid in treatment strategy.

Discrimination between breast invasive ductal carcinomas and benign lesions by optimizing quantitative parameters derived from dynamic contrast-enhanced MRI using a semi-automatic method Abstract Background To propose a semi-automatic method for distinguishing invasive ductal carcinomas from benign lesions on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods 142 cases were included. In the conventional method, the region of interest for a breast lesion was drawn manually and the corresponding mean time–signal intensity curve (TIC) was qualitatively categorized. Only one quantitative parameter was obtained: the maximum slope of increase (MSI). By contrast, the proposed method extracted the suspicious breast lesion semi-automatically. Besides MSI, more quantitative parameters reflecting perfusion information were derived from the mean TIC and lesion region, including the signal intensity slope (SIslope), initial percentage of enhancement, percentage of peak enhancement, early signal enhancement ratio, and second enhancement percentage. The mean TIC was categorized quantitatively according to the value of SIslope. Regression models were established. The diagnostic performance differed between the new and conventional methods according to the Wilcoxon rank-sum test and receiver operating characteristic analysis. Results According to the TIC categorization results, the accuracies of the traditional and the new method were 59.16% and 76.05%, respectively (P < 0.05). The accuracy was 63.35% for MSI, which was derived from the manual method. For the semi-automatic method, the accuracies were 81.0% and 78.9% for the lesion region and the corresponding mean TIC regression models, respectively. Conclusions The results demonstrate that our proposed semi-automatic method is beneficial for discriminating breast IDCs and benign lesions based on DCE-MRI, and this method should be considered as a supplementary tool for subjective diagnosis by clinical radiologists.

Analysis of major BCR-ABL1 mRNA by digital polymerase chain reaction is useful for prediction of international scale Abstract Background Major BCR-ABL1 mRNA in patients with chronic myeloid leukemia (CML) has generally been analysed by real-time polymerase chain reaction (PCR). Application of the international scale (IS) for the quantification of major BCR-ABL1 mRNA has been recommended in several sets of guidelines, including those of the European LeukemiaNet. The aim of this study was to clarify the efficacy of digital PCR technology for the IS of BCR-ABL1 mRNA in the patients with CML by comparing with real-time PCR. Methods The analysis of BCR-ABL1 mRNA was carried out by the Ipsogen® BCR-ABL1 Mbcr IS-MMR DX Kit (Qiagen), and the QuantStudio 3D Digital PCR System (Thermo Fisher Scientific‎) using 20 peripheral blood samples obtained from the 9 patients with CML at Sapporo Medical University Hospital. Results The correlation between the data obtained by digital PCR and by real-time PCR was really high at R = 0.96. The detection limit of digital PCR was up to 0.003% and was equal to IS with 0.01% or less in comparison with real-time PCR. Conclusions Digital PCR technology is promising for predicting the IS value with similar efficacy to real-time PCR and should be useful for simple monitoring of the effects of tyrosine kinase inhibitor (TKI) treatments.

Comparative assessment of prognostic outcomes between first-generation antiandrogens and novel androgen-receptor-axis-targeted agents in patients with non-metastatic castration-resistant prostate cancer Abstract Background To compare the prognostic outcomes between first-generation antiandrogen (FGA) and novel androgen-receptor-axis-targeted agent (ARATA) as first-line therapy in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Methods This study retrospectively included a total of 103 consecutive nmCRPC patients consisting of 47 (45.6%) and 56 (54.4%) who received FGA (bicalutamide or flutamide) and ARATA (abiraterone acetate or enzalutamide), respectively, as the first-line agent after the failure of primary androgen deprivation therapy (ADT). Results There were no significant differences in the major clinicopathological parameters and previous therapeutic histories between the FGA and ARATA groups. During the observation period, 31 (66.0%) and 29 (51.8%) discontinued first-line therapy in the FGA and ARATA groups, respectively, and of these, 27 (87.1%) and 23 (79.3%) in the FGA and ARATA groups, respectively, were subsequently treated with approved agents as second-line therapy. The prostate-specific antigen (PSA) response rate in the FGA group was significantly lower than that in the ARATA group. Although no significant difference in overall survival was noted between the FGA and ARATA groups, there were significant differences in the PSA progression-free survival on first-line therapy and metastasis-free survival between the two groups, favoring the ARATA group compared with FGA group. Conclusions Collectively, these findings suggest that among nmCRPC patients who progressed following treatment with the primary ADT, the introduction of ARATA may result in the delay of disease progression compared with FGA.

A prognostic parameter in advanced non-small cell lung cancer: the ratio of hemoglobin-to-red cell distribution width Abstract Background This study aims to investigate the prognostic value of the ratio of hemoglobin–RDW (HRR) at diagnosis, in terms of overall survival (OS) and progression-free survival in patients with advanced non-small cell lung cancer (NSCLC). Methods Patients with metastatic NCCLC who attended two separate medical oncology clinics between April 2013 and December 2017 were retrospectively screened. HRR was calculated as Hgb (g/dL) divided by the RDW (%). Patients were assigned to either the low HRR group or high HRR group. Results A total of 153 patients were included in the study. The cuff-value for HRR was taken as 0.88. Among the low and high HRR groups, Glasgow prognostic scores (GPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and weight loss were statistically significantly different (p < 0.05). OS was found to be 5.6 months in the low HRR group and 13.9 months in the high HRR group (p < 0.001) while PFS was 5.1 months and 8.6 months in these two groups, respectively (p < 0.001). Univariate and multivariate analyses revealed that low HRR was an independent factor, predictive of both OS (p = 0.03, Hazard Ratio (HR) = 1.607, 95% CI = 1.041–2.480) and PFS (p < 0.001, HR = 2.635, 95% CI = 1.667–4.166) in advanced NSCLC. Conclusion This is the first study to show that low HRR is associated with poor OS and PFS in patients with advanced NSCLC. Thus, hemoglobin and RDW which can be easily measured in routine practice may be used as a prognostic tool in these patients.

The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV Abstract According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Long-term outcomes and prognostic factors of pulmonary metastasectomy for osteosarcoma and soft tissue sarcoma Abstract Background The prognostic factors of pulmonary metastasectomy in patients with osteosarcoma and soft tissue sarcoma remain controversial. The purpose of our analysis was to explore the prognostic factors and outcomes of patients with osteosarcoma and soft tissue sarcoma who underwent pulmonary metastasectomy at our institution. Methods We reviewed the data of 44 patients who underwent resection of pulmonary metastases from 1996 to 2016 at our institution. The Kaplan–Meier method, log-rank test and multivariate Cox hazard model were used for comparison and survival analyses. Results There was no perioperative mortality. The median post-metastasectomy overall survival was 24.8 months, and the 5-year overall survival rate of all patients was 43.5%. The 5-year survival rate of the patients who underwent repeat thoracotomies was 60.0%. Incomplete resection, a largest tumor size > 2 cm and a disease-free interval < 12 months were associated with poor survival in multivariate analyses. Among eight patients, who underwent repeat pulmonary resection, two remain alive with no evidence of disease. These patients had the longest DFI and DFI-2 (time from first pulmonary metastasectomy to the diagnosis of recurrent pulmonary metastasis), respectively. Conclusion The survival of patients with a relatively long disease-free interval, small tumor size and complete resection was favorable following the treatment of osteosarcoma and soft tissue sarcoma with pulmonary metastasectomy. Repeat pulmonary metastasectomies also provide favorable prognosis in select patients.

Molecular carcinogenesis of gastric cancer: Lauren classification, mucin phenotype expression, and cancer stem cells Abstract Gastric cancer (GC), one of the most common human cancers, is a heterogeneous disease with different phenotypes, prognoses, and responses to treatment. Understanding the pathogenesis of GC at the molecular level is important for prognosis prediction and determining treatments. Microsatellite instability (MSI), silencing of MLH1, MGMT, and CDKN2A genes by DNA hypermethylation, KRAS mutation, APC mutation, and ERBB2amplification are frequently found in intestinal type GC. Inactivation of CDH1 and RARB by DNA hypermethylation, and amplification of FGFR and MET, are frequently detected in diffuse type GC. In addition, BST2 and PCDHB9 genes are overexpressed in intestinal type GC. Both genes are associated with GC progression. GC can be divided into gastric/intestinal mucin phenotypes according to mucin expression. MSI, alterations of TP73, CDH1 mutation, and DNA methylation of MLH are detected frequently in the gastric mucin phenotype. TP53 mutation, deletion of APC, and DNA methylation of MGMT are detected frequently in the intestinal mucin phenotype. FKTN is overexpressed in the intestinal mucin phenotype, and IQGAP3 is overexpressed in the gastric mucin phenotype. These genes are involved in GC progression. To characterize cancer stem cells, a useful method is spheroid colony formation. KIFC1 and KIF11 genes show more than twofold higher expression in spheroid-forming cells than that in parental cells. Both KIF genes are overexpressed in GC, and knockdown of these genes inhibits spheroid formation. Alterations of these molecules may be useful to understand gastric carcinogenesis. Specific inhibitors of these molecules may also be promising anticancer drugs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com