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Preview: Japanese Journal of Clinical Oncology - current issue

Japanese Journal of Clinical Oncology Current Issue





Published: Tue, 06 Feb 2018 00:00:00 GMT

Last Build Date: Tue, 06 Feb 2018 05:45:05 GMT

 









IN THIS ISSUE

Tue, 06 Feb 2018 00:00:00 GMT







Wide-spread ignorance on the treatment of subcutaneous malignant tumors; a questionnaire-based study

Tue, 26 Dec 2017 00:00:00 GMT

Abstract
Background
Subcutaneous malignant tumors are often treated by non-specialized clinicians in musculoskeletal oncology. While the resection of subcutaneous tumors appears technically feasible, unplanned resection of malignant tumors can result in a devastating clinical outcome. The aim of this study was to evaluate the potential estrangement in the awareness of and the treatment strategy for the patients with subcutaneous soft tissue tumors between musculoskeletal oncologists and non-specialized clinicians.
Methods
A questionnaire probing the clinical assessment of subcutaneous tumors was sent to orthopedic surgeons, dermatologists, plastic surgeons, and general surgeons. Results of the questionnaire were statistically analyzed.
Results
One hundred sixteen clinicians out of 150 responded to the questionnaire; the response rate was 77.3%. Among those, 46 clinicians had treated subcutaneous tumors. Thirty-nine of these 46 clinicians (27 musculoskeletal oncologists and 12 non-specialized clinicians) preoperatively performed enhanced MRI for diagnostic evaluation. Preoperative incisional biopsy to confirm the pathological diagnosis was performed by 36 of the 46 clinicians (29 musculoskeletal oncologists and seven non-specialized clinicians). These results indicate that musculoskeletal oncologists perform preoperative enhanced MRI (P = 0.08) and biopsy (P < 0.01) more frequently than non-specialized clinicians. The recognition rate of ‘myxofibrosarcoma’ was 60.8% among clinicians with an experience with sarcoma treatment (25 musculoskeletal oncologists and three non-specialized clinicians). The recognition rate of ‘myxofibrosarcoma’ between musculoskeletal oncologists and non-specialized clinicians was statistically significant (P < 0.01).
Conclusions
Preoperative evaluations for subcutaneous tumors are more often inappropriate in non-specialized clinicians than those who are. Therefore, it will be mandatory to raise the awareness of this condition to improve the clinical outcome of patients with subcutaneous tumors.



Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells

Tue, 26 Dec 2017 00:00:00 GMT

Abstract
Background
Gliomas are highly malignant brain tumors. Aberrant activation of NF-κB plays a crucial role in tumor progression.
Method
ELISA assay was used to detect NF-κB activity in glimoas cells with different treatments. PPP3CC expression was evaluated by qRT-PCR and western blot assay. Kaplan–Meier analysis estimated the overall survival rates according to the protein level of PPP3CC. Transwell and MTS assay were performed to determine cell invasion and growth. Chromatin immunoprecipitation combined with luciferase reporter assays illustrated the transcriptional regulation of PPP3CC.
Results
We showed that PPP3CC decrease was responsible for constitutive activation of NF-κB in gliomas. Restored PPP3CC expression inhibited activation of NF-κB. PPP3CC was frequently decreased in gliomas and that repression of the expression of PPP3CC correlated glioma progression. The ectopic expression of PPP3CC inhibited the invasive potential of glioma cells, and inhibited glioma cells proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E-box-binding homeobox 1(ZEB1) was increased in gliomas and was negatively correlated with clinical outcomes of glioma patients. ZEB1 inversely correlated with the expression of PPP3CC. ZEB1 was also confirmed to physically bind to the PPP3CC promoter. ZEB1 knockdown resulted in an increase in the expression of PPP3CC and elevation of PPP3CC promoter activity in glioma cells.
Conclusion
These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-κB is a critical oncogenic event in gliomas.



Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA

Thu, 21 Dec 2017 00:00:00 GMT

Abstract
Background
To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs).
Methods
The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR.
Results
In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1–2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796.In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity.
Conclusion
Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.



Nomograms for predicting disease progression in patients of Stage I non-small cell lung cancer treated with stereotactic body radiotherapy

Fri, 15 Dec 2017 00:00:00 GMT

Abstract
Objective
Non-local progression is a major concern in non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Herein we aimed to create a pre-treatment prognostic nomogram for patients with Stage I NSCLC receiving SBRT.
Methods
We retrospectively studied 182 eligible patients. Patients were randomly divided into a model (70%) group and a validation (30%) group. In the model group, thirteen parameters consisting of patient, treatment, and tumor factors were studied and multivariate Cox proportional hazards regression was performed to identify independent predictors for survival outcome, based on which we developed clinical nomogram. The nomogram was externally validated in the validation group.
Results
Multivariate analysis showed that tumor size (P = 0.011) was the only factor correlated with 2-year overall survival, whereas 2-year locoregional control (LRC) was significantly related to tumor size (P = 0.024) and the maximum standardized uptake value (SUVmax) (P = 0.044), so does 2-year progression-free survival (PFS) (tumor size: P = 0.026; SUVmax: P = 0.038). Nomogram for 2-year LRC and 2-year PFS were created based on aforementioned results. The C-indexes for the nomograms to predict 2-year LRC and PFS were 0.816 and 0.804, respectively, in model group, and were 0.729 and 0.731, respectively, in the validation group. Calibration plots also showed that the model performed well.
Conclusions
Tumor of larger size and higher SUVmax predisposed patients to early onset of locoregional and distant progression. The nomogram developed in our study would be helpful in clinical decision-making and selection of patients who may benefit from more rigorous follow-up and aggressive systemic treatment plan.



Chemotherapy for hepatocellular carcinoma: current status and future perspectives

Fri, 15 Dec 2017 00:00:00 GMT

Abstract
Chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC). On the basis of the results of two pivotal Phase III placebo-controlled studies, sorafenib is currently acknowledged worldwide as the standard therapeutic agent for advanced HCC. Following the introduction of sorafenib for the treatment of HCC, Phase III trials of numerous other agents as first-line or second-line chemotherapy have been conducted to determine if any of these agents might offer superior survival benefit to sorafenib. In 2016, a clear survival benefit of regorafenib over placebo was demonstrated in HCC patients showing disease progression after sorafenib treatment. A year later, in 2017, lenvatinib has been shown to be non-inferior to sorafenib, in terms of the overall survival, in chemo-naïve patients with advanced HCC. More recently, promising outcomes have also been reported with new agents, such as nivolumab and cabozantinib. At present, various novel combination regimens including these agents are currently under development. Hepatic arterial infusion chemotherapy (HAIC) is frequently adopted for the treatment of locally advanced HCC in Japan, based on reports of high response rates and favorable long-term outcomes. Although some randomized controlled trials of HAIC plus sorafenib vs. sorafenib alone as first-line therapy have been conducted in patients with advanced HCC, no firm evidence of the superiority of one over the other has been established yet. In the future, demonstration of the survival advantage of HAIC and the recognition of HAIC as one of the standard treatments for patients with advanced HCC are expected.



Risk and prognostic factors for multiple primary carcinomas in patients with head and neck cancer

Wed, 13 Dec 2017 00:00:00 GMT

Abstract
Background
Unexpected multiple primary carcinomas (MPCs) that develop in patients with head and neck carcinomas complicate approaches to their management. We therefore investigated the clinical factors associated with survival outcomes after the treatment of MPCs.
Methods
We performed a retrospective review of records of 1104 patients who underwent treatment for primary head and neck carcinoma at Hamamatsu University Hospital. We evaluated clinical staging, age, sex, smoking, alcohol consumption, the primary tumor site (particularly the involvement of the mucosal epithelial lining of the aerodigestive tract), and overall survival (OS) as determined by Kaplan–Meier analysis. Information on patients’ survival status was obtained after a mean follow-up period of 43.8 months (range, 1–144 months).
Results
Among 566 patients with mucosa-associated carcinoma arising in the epithelial lining, the 5- and 10-year OS rates (68.49% and 58.96%, respectively) were significantly shorter than those of patients with mucosa non-associated carcinoma (74.22%, and 66.76%, respectively) (log-rank P = 0.0219). Older age (P = 0.016) and male sex (P < 0.001) were likely independent risk factors for developing MPCs; smoking (P < 0.001) and alcohol consumption (P < 0.001) were also significant risk factors.
Conclusion
Mucosa-associated carcinomas arising in the epithelial lining of the aerodigestive tract in the head and neck are a significant risk factor for developing MPC and are a poor prognostic factor. Careful follow-up and more frequent examinations of the aerodigestive tracts of these patients are recommended.



The distress and benefit to bereaved family members of participating in a post-bereavement survey

Wed, 13 Dec 2017 00:00:00 GMT

Abstract
Background
Few studies have simultaneously collected quantitative data regarding the positive and negative effects of participating in post-bereavement surveys.
Methods
We conducted a cross-sectional postal questionnaire survey in October 2013. Potential participants were caregivers for family members who had died in four inpatient palliative care units, two home hospices, and a general hospital. We collected opinions regarding the distress and benefit of completing a post-bereavement survey. After collecting data, we provided feedback to participating institutions in the form of study results and de-identified open-ended comments.
Results
Of 692 potential participants, 596 were sent questionnaires; 393 returned questionnaires were valid and analyzed. Of the respondents, 62% reported being distressed by completing the questionnaire. Female participants and those who were mentally ill during the caregiving period reported more distress. However, 86% of respondents reported they found the questionnaire beneficial. Better quality of end-of-life care and respondent depression were associated with more benefit. Major benefits were: contributing to the development of end-of-life care as a family (63%); expressing gratitude to the hospital and medical staff (60%); and looking back and reflecting on the end-of-life period (40%). Feeling benefit was not correlated with feeling distressed (P = −0.02).
Conclusion
In this large-scale study on the effects of post-bereavement surveys in Japan, many bereaved family members reported that completing the survey was beneficial. In addition to possibly having feelings of distress, post-bereavement surveys might also be beneficial to end-of-life care facilities.



External validation of two web-based postoperative nomograms predicting the probability of early biochemical recurrence after radical prostatectomy: a retrospective cohort study

Fri, 08 Dec 2017 00:00:00 GMT

Abstract
The present study aimed to validate and compare the predictive accuracies of the Memorial Sloan Kettering Cancer Center (MSKCC) and Johns Hopkins University (JHU) web-based postoperative nomograms for predicting early biochemical recurrence (BCR) after radical prostatectomy (RP) and to analyze clinicopathological factors to predict early BCR after RP using our dataset. The c-index was 0.72 (95% confidence (CI): 0.61–0.83) for the MSKCC nomogram and 0.71 (95% CI: 0.61–0.81) for the and JHU nomogram, demonstrating fair performance in the Japanese population. Furthermore, we statistically analyzed our 174 patients to elucidate prognostic factors for early BCR within 2 years. Lymphovascular invasion (LVI) including lymphatic vessel invasion (ly) was a significant predictor of early BCR in addition to common variables (pT stage, extraprostatic extension, positive surgical margin and seminal vesicle invasion). LVI, particularly ly, may provide a good predictor of early BCR after RP and improve the accuracy of the nomograms.



Correlation of biologically effective dose and the tumor control in Stage I (<5 cm) non-small cell lung cancer with stereotactic ablative radiotherapy: a single institutional cohort study

Wed, 29 Nov 2017 00:00:00 GMT

Abstract
Backgrounds
Stereotactic ablative radiotherapy (SABR) is one of the newly developed innovative radiotherapy and of which optimal dose prescription needs to be standardized. We aimed to investigate the dose–response relationship for patients with SABR.
Methods
Fifty-three patients with Stage I non-small cell lung cancer patients, who underwent SABR between November 2006 and January 2015, were evaluated retrospectively. Thirteen patients (24.5%), who refused the surgery were included and 40 patients (75.5%) were medically inoperable at diagnosis. The median age was 74 years. The median SABR dose was 50 Gy in 3–8 fractions and the median biologically effective dose (BED;α/β = 10) was 105.6 Gy (range: 60–160.53 Gy).
Results
The median follow-up was 37.1 months. The 1 and 3 year local control rates were 91.7% and 85.1%. The 3 year overall and progression-free survival rate were 63.3% and 47.5%, respectively, and freedom from progression was 62.2%. Local control rate and 3-year overall survival according to tumor size was 100% and 79.4% in T1 tumors in a while 61.8% and 45% in T2a tumors. The 3-year local and regional control by BED10 was 79.4% and 69.4% in ≤100 Gy vs. 89.1% and 100% in >100 Gy (P = 0.526, 0.004). Dyspnea more than Grade 3 was reported in six (11.3%) patients and Grade 1 chest pain was shown in five (9.4%) patients.
Conclusions
The excellent regional control was conferred with a prescription of more than BED10 of 100 Gy, which also might be needed to achieve better local tumor control in T2a patients with tolerable lung function.



A randomized Phase III trial of lobe-specific vs. systematic nodal dissection for clinical Stage I–II non-small cell lung cancer (JCOG1413)

Tue, 21 Nov 2017 00:00:00 GMT

Abstract
In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group commenced a randomized Phase III trial to confirm the clinical benefit of lobe-specific nodal dissection for clinical Stage I–II non-small cell lung cancer. The primary endpoint is overall survival, and the main objective is to confirm the non-inferiority of lobe-specific in comparison to systematic nodal dissection with regard to lobectomy. The secondary endpoints are relapse-free survival, %local recurrence, %regional lymph node recurrence, operation time, blood loss, length of hospitalization, duration of chest tube placement and adverse events. A total of 1700 patients will be accrued from 44 Japanese institutions within 5 years. This study is the first and large prospective trial to evaluate whether the difference in the area of nodal dissection affects the overall survival of patients with relatively early-stage non-small cell lung cancer. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025530.



Significance of preoperative butyrylcholinesterase level as an independent predictor of survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy

Tue, 21 Nov 2017 00:00:00 GMT

Abstract
Objectives
Butyrylcholinesterase (BChE) is an alpha-glycoprotein synthesized in the liver. Its serum levels are reportedly correlated with disease activity in patients with cancer. The aim of this study was to estimate the potential prognostic significance of preoperative serum BChE levels in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU).
Methods
Of the 220 patients with UTUC who underwent RNU between 1995 and 2016 at Hirosaki University Hospital, 149 patients with available laboratory data were included for analysis. Covariates included age, sex, preoperative laboratory data, clinical T and N grades, tumor grade, tumor location and preoperative chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analysis was performed using the Kaplan–Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model.
Results
The median BChE level was 276 U/l and the optimal cut-off point for the serum BChE level was determined to be 218 IU/ml. The 5-year OS and DFS rates were 81.0% and 73.7%, respectively. The 5-year OS and DFS rates were significantly greater in the BChE ≥ 218 than <218 U/l groups (86.6% vs. 53.7%, P < 0.001 and 76.4% vs. 58.3%, P = 0.049, respectively). In multivariate analysis, BChE levels were most significantly associated with OS, whereas BChE level and tumor grade were significantly associated with DFS.
Conclusions
This study validated preoperative serum BChE levels as an independent prognostic factor for UTUC after RNU.



Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer

Fri, 10 Nov 2017 00:00:00 GMT

Abstract
Background
We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease.
Methods
Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings.
Results
Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P < 0.01). Two types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08–3.54 and odds ratio 2.85, 95% confidence interval 1.12–7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P < 0.01). One serious urological complication (intraperitoneal rupture of the bladder) occurred among women who underwent pelvic radiotherapy (0.6% vs. 0%).
Conclusions
Surgeons should be aware that eGFR is reduced after platinum-based chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up.



Does fluid collection impact radiotherapy outcomes after wide excision of lower extremity soft tissue sarcoma?

Thu, 09 Nov 2017 00:00:00 GMT

Abstract
Background
Fluid collection (FC) of lymph or blood may accumulate at the site of excision after surgery for soft tissue sarcoma, with reported incidence rates from 10% to 36%. The purpose of this study is to analyze the impact of FC on local recurrence (LR) and wound complication rates after adjuvant postoperative radiotherapy (PORT) in lower extremity soft tissue sarcoma (LE-STS).
Methods
Eighty-eight patients diagnosed with LE-STS were curatively treated with wide excision and PORT. FC developed in 51.1% of patients. Full FC volumes were included in the irradiation field throughout the full course of PORT for 36 patients (80.0%). A median of 61.2 and 63 Gy was prescribed for patients with and without FC, respectively.
Results
After a median follow-up of 4.3 years, patients with and without FC had 5-year local control rates of 77.7% and 90.8% (P = 0.105). Eight patients with FC had LR, of which six patients had recurrent tumors at or within 4 cm of the FC wall and three of these patients had out-of-field LR. Wound complication occurred after RT in 3 (6.7%) of 45 patients with FC and 1 (2.3%) of 43 patients without FC.
Conclusions
FC presents a potential risk for increased LR, particularly near the FC wall. Based on reasonable wound complication rates, we suggest the need and feasibility of fully including FC volumes in the irradiation field.