Chikako Suzuki

The initial change in tumor size predicts response and survival in patients with metastatic colorectal cancer treated with combination chemotherapy

BACKGROUND To determine whether the change in tumor diameters at the first follow-up computed tomography (CT) examination after baseline examination (first change) correlates with outcome in patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy. PATIENTS AND METHODS The first change was analyzed in a multicenter randomized phase III trial (Nordic VI, N = 567) comparing first-line irinotecan with either bolus or infused 5-fluorouracil. Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses after correction for guarantee-time bias were carried out to evaluate correlations between first change, objective response according to RECIST 1.0, progression-free survival (PFS), and overall survival (OS). RESULTS The hazard ratios for PFS and OS decreased along with first change. A decrease between 10% and <30%, albeit RECIST does not regard this as a partial response, was a positive prognostic factor for PFS and OS. Patients who had new lesions or unequivocal progression of nonmeasurable lesions had a worse prognosis than those with only an increase in size of >20%. CONCLUSIONS The change in tumor size at the first follow-up CT is strongly prognostic for PFS and OS in mCRC.

Interobserver and intraobserver variability in the response evaluation of cancer therapy according to RECIST and WHO-criteria

Abstract Background. Response Evaluation Criteria In Solid Tumors (RECIST) and WHO-criteria are used to evaluate treatment effects in clinical trials. The purpose of this study was to examine interobserver and intraobserver variations in radiological response assessment using these criteria. Material and methods. Thirty-nine patients were eligible. Each patients series of CT images were reviewed. Each patient was classified into one of four categories according RECIST and WHO-criteria. To examine interobserver variation, response classifications were independently obtained by two radiologists. One radiologist repeated the procedure on two additional different occasions to examine intraobserver variation. Kappa statistics was applied to examine agreement. Results. Interobserver variation using RECIST and WHO-criteria were 0.53 (95% CI 0.33–0.72) and 0.60 (0.39–0.80), respectively. Response rates (RR) according to RECIST obtained by reader A and reader B were 33% and 21%, respectively. RR according to WHO-criteria obtained by reader A and reader B were 33% and 23% respectively. Intraobserver variation using RECIST and WHO-criteria ranged between 0.76–0.96 and 0.86–0.91, respectively. Conclusion. Radiological tumor response evaluation according to RECIST and WHO-criteria are subject to considerable inter- and intraobserver variability. Efforts are necessary to reduce inconsistencies from current response evaluation criteria.

The importance of rectal cancer MRI protocols on iInterpretation accuracy

BackgroundMagnetic resonance imaging (MRI) is used for preoperative local staging in patients with rectal cancer. Our aim was to retrospectively study the effects of the imaging protocol on the staging accuracy.Patients and methodsMR-examinations of 37 patients with locally advanced disease were divided into two groups; compliant and noncompliant, based on the imaging protocol, without knowledge of the histopathological results. A compliant rectal cancer imaging protocol was defined as including T2-weighted imaging in the sagittal and axial planes with supplementary coronal in low rectal tumors, alongside a high-resolution plane perpendicular to the rectum at the level of the primary tumor. Protocols not complying with these criteria were defined as noncompliant. Histopathological results were used as gold standard.ResultsCompliant rectal imaging protocols showed significantly better correlation with histopathological results regarding assessment of anterior organ involvement (sensitivity and specificity rates in compliant group were 86% and 94%, respectively vs. 50% and 33% in the noncompliant group). Compliant imaging protocols also used statistically significantly smaller voxel sizes and fewer number of MR sequences than the noncompliant protocolsConclusionAppropriate MR imaging protocols enable more accurate local staging of locally advanced rectal tumors with less number of sequences and without intravenous gadolinium contrast agents.

The minimum number of target lesions that need to be measured to be representative of the total number of target lesions (according to RECIST)

Response evaluation criteria in solid tumours (RECIST) were introduced as a means to classify tumour response with no definition of the minimum number of lesions. This study was conducted in order to evaluate discrepancies between full assessments based on either all target lesions or fewer lesions. RECIST evaluation was performed on separate occasions based on between one and seven of the target lesions, with simultaneous assessment of non-target lesions. 99 patients were included. 38 patients demonstrated progressive disease, in 61% of whom it was a result of the appearance of new lesions or unequivocal progress in non-target lesions. 32 patients showed stable disease, with 8 having results that differed when 1-3 target lesions were measured. 22 cases were considered as having partial regression, with only 1 case differing when performing 1-3 target lesion assessments. Seven cases demonstrated complete response. The number of discordant cases increased gradually from measuring three lesions to one target lesion. The average number of available target lesions among those with discrepancies was 7.1, which was significantly higher than those demonstrating concordance (4.1 lesions; p<0.05). In conclusion, measuring fewer than four target lesions might cause discrepancies when more than five target lesions are present.

Morphological assessment of the interface between tumor and neighboring tissues, by magnetic resonance imaging, before and after radiotherapy in patients with locally advanced rectal cancer

Background: Magnetic resonance imaging (MRI) in rectal cancer is sometimes performed after radiotherapy (MRI 2) to evaluate tumor response and to choose alternative forms of surgery. The accuracy of MRI 2 in distinguishing tumor delineation might be difficult due to fibrosis. Purpose: To evaluate the morphological changes in the interface between the tumor and neighboring organs on MRI 2 performed after radiotherapy, and to assess the accuracies of MRI before and after radiotherapy compared to histopathology after surgery. Material and Methods: Sixteen patients with locally advanced primary rectal cancer, with MRI before and after radiotherapy, were retrospectively studied, concerning the interface between the tumor and neighboring structures. The accuracies of MRI before and after radiotherapy were compared based on histopathology as a reference. Results: The accuracies of both MRI before and after radiotherapy were moderate, with no additional value of MRI after radiotherapy compared to MRI before radiotherapy. The most predictive form of interface for involvement of a neighboring organ after radiotherapy was nodular growth of the tumor into a neighboring structure. Conclusion: The morphological assessment of pelvic MRI after preoperative radiotherapy does not provide any significant new information about tumor extent in patients with locally advanced rectal cancer.

Immune gene expression and response to chemotherapy in advanced breast cancer

Background:Transcriptomic profiles have shown promise as predictors of response to neoadjuvant chemotherapy in breast cancer (BC). This study aimed to explore their predictive value in the advanced BC (ABC) setting.Methods:In a Phase 3 trial of first-line chemotherapy in ABC, a fine needle aspiration biopsy (FNAB) was obtained at baseline. Intrinsic molecular subtypes and gene modules related to immune response, proliferation, oestrogen receptor (ER) signalling and recurring genetic alterations were analysed for association with objective response to chemotherapy. Gene-set enrichment analysis (GSEA) of responders vs non-responders was performed independently. Lymphocytes were enumerated in FNAB smears and the absolute abundance of immune cell types was calculated using the Microenvironment Cell Populations counter method.Results:Gene expression data were available for 109 patients. Objective response to chemotherapy was statistically significantly associated with an immune module score (odds ratio (OR)=1.62; 95% confidence interval (CI), 1.03–2.64; P=0.04). Subgroup analysis showed that this association was restricted to patients with ER-positive or luminal tumours (OR=3.54; 95%, 1.43–10.86; P=0.012 and P for interaction=0.04). Gene-set enrichment analysis confirmed that in these subgroups, immune-related gene sets were enriched in responders.Conclusions:Immune-related transcriptional signatures may predict response to chemotherapy in ER-positive and luminal ABC.

Randomized, double-blind, multicenter trial of hydrogen water for Parkinson's disease: LETTERS: NEW OBSERVATIONS

Oxidative stress might be involved in Parkinson’s disease (PD) progression. Molecular hydrogen (H2) water has been shown to reduce oxidative stress and dopaminergic neuronal cell loss in a PD model. A previous randomized, doubleblind study showed that drinking 1,000 mL of H2 water per day for 48 weeks significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) scores of patients with PD and treated with levodopa. We conducted a longer and larger scale H2 water trial that also included patients who were not treated with levodopa. A placebo-controlled, randomized, double-blind, parallel-group (1:1) clinical trial was performed in 14 hospitals (trial registration UMIN000010014). The inclusion criteria, ethical considerations, randomization, blinding, procedures, statistical analyses, and characteristics of the 178 enrolled Japanese participants with PD (93 women and 85 men; an error in this number exists in the previous report) were described previously. At the baseline visit, the groups were well matched (Supplementary Table 1). The reasons for discontinuation of the study were disease progression, adverse events, unwillingness to proceed, and failure to comply with the protocol (Supplementary Table 2 and Supplementary Figure 1). There were no significant differences in the change in the total UPDRS score from baseline to the 72nd week between the H2-water group (1.6 ± 14.0 [mean ± standard deviation]) and the placebo water group (0.8 ± 9.6; t test, P = .939; analysis of variance, P = .538; Table 1). There were no significant differences in changes in the scores on parts II and III of the UPDRS, the individual parts of the UPDRS, the Hoehn and Yahr stage, and the Parkinson’s Disease Questionnaire-39 *Corresponding author: Dr. Asako Yoritaka, Department of Neurology, Juntendo University Koshigaya Hospital. Fukuroyama 560, Koshigayashi, Saitama, Japan, 343-0032; ayori@juntendo.ac.jp

Long-term quality of life after comprehensive surgical staging of high-risk endometrial cancer – results from the RASHEC trial

Abstract Purpose: The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT). Patients and Methods: A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis. Results: There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in ‘cognitive functioning’ albeit not statistically significant −6 (95% CI−14 to 0, p = .06). LT conferred a significantly better outcome for the ‘nausea and vomiting’ item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03). Conclusion: Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC.

Cardiophrenic lymph node resection in advanced ovarian cancer: surgical outcomes, pre- and postoperative imaging

Abstract Objective: To evaluate the accuracy of preoperative imaging in the diagnosis of cardiophrenic lymph node (CPLN) metastases and to report perioperative outcomes after resection of CPLN at the time of cytoreductive surgery for advanced epithelial ovarian cancer (EOC). Furthermore, to assess clearance of CPLN by postoperative imaging. Methods: All women with stage IIIC/IV EOC subjected to surgery at our institution from January 2014 to October 2016 were retrospectively identified from a database. Among these, women subjected to CPLN resection during surgery were identified. Pre- and postoperative computed tomography (CT) scans, pathology reports, surgical approach and outcomes were reviewed. Results: One hundred and eighty women with stage IIIC/IV EOC subjected to surgery with curative intent were identified. Twenty-four (13%) of these women underwent CPLN resection. All had CT imaging suggestive of CPLN metastases. 20/24 (83%) had confirmed metastases upon final pathology. CPLN resection was associated with longer operation time, more often advanced upper abdominal surgery and more postoperative complications but there was no difference in days from surgery to initiation of chemotherapy. Postoperative CT was still indicative of CPLN metastases in 13/22 (59%) women despite resection with confirmative pathology. Conclusions: Resection of CPLN metastases is highly feasible without considerable added morbidity. Concern regarding surgical clearance is raised since postoperative imaging was indicative of metastases in the majority of women. The prognostic significance of stage IV disease based exclusively on CPLN metastases is unclear and any survival benefit from the procedure is yet to be determined.