JSCO2016: International Session 7 Central Nervous System Tumor

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The 54th Annual Meeting of Japan Society of Clinical Oncology (JSCO2016)

"Renovation of Cancer Medicine in the Mature Society"



International Session 1: Lung Cancer
International Session 2: Colorectal Cancer
International Session 3: Gastric Cancer
International Session 4: Urological Cancer (Prostate and Renal Cancer)
International Session 5: Supportive Care for Adverse Events
International Session 6: Gynecological Cancer (Uterine Body Cancer and Ovarian Cancer)
International Session 7: Central Nervous System Tumor
International Session 8: New Development of Particle Beam Therapy for Cancer
International Session 9: International Cooperation in Radiation Medicine
International Session 10: Recent Advances In Cancer Immunotherapy
International Session 11: Breast Cancer
International Session 12: Pharmacology of Antitumor Agents: New Drug Application (NDA)
International Session 13: Malignant Lymphoma
International Session 14: Palliative Care
International Session 15: Radiation Therapy
International Session 16: Head and Neck Cancer
International Session 17: Skin Cancer (Malignant Melanoma)
International Session 18: Hepato-Biliary and Pancreas Cancers
International Session 19: Leukemia
International Session 20: Ethics for Clinical Research
International Session 21: Esophageal Cancer
International Session 22: Bone and Soft Tissue Tumor
FACO/JSCO Joint Symposium

Abstract Archives (in Japanese)


International Session 7: Central Nervous System Tumor


Brain tumor practice guidelines in Japan
Yoko Nakasu (Division of Neurosurgery, Shizuoka Cancer Center)
Guidelines have become relevant for the treatment of brain tumors, due to the importance of the multidisciplinary coordination of care with medical and neuro-oncology, radiation oncology and neurosurgery. They provide a starting point where a systematic review leads to practice recommendations formulated by a panel of specialty experts.
The Japan Neurosurgical Society recommended the development of practice parameters to treat patients with brain tumor, and requested it of the Japan Society for Neuro-Oncology Guidelines Committee. Three tumors were selected initially because of their multidisciplinary nature of therapies and challenging outcomes: Glioblastoma, primary central nervous system lymphoma and brain metastasis.
These guidelines adhere to a two-tired methodology whereby levels of recommendation are directly linked to levels of evidence with detailed evidentiary tables. The committee members met regularly to assess and screen literature search results. The data from the publications were classified as for evidence level: Class I evidence was defined that provided by one or more randomized controlled clinical trials, Class II as well-designed clinical studies, Class III as cohort studies, or case controlled studies, Class IV as case reports and case series, Class V as expert opinions.
With the evidence data classified, the information was summarized as recommendation grades: Grade A was defined as a standard with strong scientific evidences, Grade B as a standard with scientific background, Grade C as practice options or advisories without scientific evidences, Grade D as a prohibited practice with scientific evidences of harm or no effect.
Brain tumor guidelines have sought to reduce unexplained variability in care while not restricting the ability of providers to deliver individualized care for patients. The guidelines provide benchmarking knowledge and show realistic evidence gaps to introduce need of future basic and clinical research.


Health-Related Quality of Life as outcome measure for brain tumor patients
Martin J.B. Taphoorn (Leiden University Medical Center, and Medical Center Haaglanden The Hague, The Netherlands)
Traditionally, treatment efficacy in brain tumor trials is measured with (progression-free) survival as outcome, or imaging changes as a surrogate outcome for survival. Quality of survival is increasingly being recognized as important next to duration of survival, especially in patients that either cannot be cured and have a dismal progression, or have a relatively long survival and run the risk of serious late adverse treatment effects. The multidimensional concept of Health-Related Quality of Life (HRQoL), covering physical, psychological and social functioning, as well as symptoms induced by the disease and its treatment, encompasses all three WHO levels of functioning: impairment, activity limitations and participation restrictions.
In clinical trials HRQoL can be used as primary or secondary outcome measure, which in combination with survival rates can be used to measure the net clinical benefit of different treatment modalities. By definition, HRQoL is a patient-reported outcome (PRO). Treatment either improves, or reduces, the duration and quality of (progression-free) survival, but the effect on both is not necessarily the same. When duration and quality of life are affected in opposite manners, a trade-off discussion arises. In clinical practice, HRQoL can be used as a facilitating tool for patient-doctor communication, for monitoring patients' problems and functioning during the disease trajectory and as quality indicator of healthcare.
Logistic as well as methodologic barriers may hamper the interpretation of HRQoL data, thereby seriously limiting its usefulness. Also, which holds specifically true for brain tumor patients, cognitive decline occurring over time may impact the patient's ability to rate his HRQoL. Despite these barriers and limitations, PRO's, such as HRQoL, have in the last decade provided important insight in the net clinical benefit of (new) treatment options for brain tumor patients.


A mutation and prognostic biomarker study in grade Ⅱ and Ⅲ gliomas utilizing a combined cohort of NRG oncology/RTOG 9802 and NRG oncology/RTOG 9813
Arnab Chakravarti (The Ohio State University, USA)
BACKGROUND: This study examined the prognostic significance of mutations within IDH1/2, ATRX, CIC, FUBP1, and the TERT promoter using a combined cohort of two prospective phase III studies of high-risk grade II and III gliomas using multivariate analyses (MVAs).
METHODS: IDH mutation status was determined by immunohistochemistry and/or next-generation sequencing. A custom Ion AmpliSeq™ DNA panel was used for mutation analysis; TERT promoter mutations were detected by Sanger sequencing. Overall survival (OS) was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated and tested using the Cox proportional hazard model and the log-rank test. MVAs were performed incorporating clinical variables.
RESULTS: Mutations were found within IDH1/2 in 65% (142/219), ATRX in 34% (44/128), the TERT promoter in 32% (43/135), CIC in 18% (23/130), and FUBP1 in 6% (8/130) of analyzed cases. In the univariate analyses on OS, IDH1/2 mutations (HR=0.38; p<0.001) and CIC mutations (HR= 0.48; p=0.04) significantly associated with better OS. Upon MVA, IDH1/2 mutations were significantly associated with OS (HR=0.50; p<0.001), whereas CIC mutations trended toward significance for OS (HR=0.47; p=0.073).
CONCLUSIONS: This study highlights the prognostic value of IDH mutations independent of age, treatment, surgery, histology, and performance status. In addition, this study provides evidence that CIC may provide prognostic information independent of grade/histology. Most importantly, this is the first study to examine the prognostic effects of these mutations using rigorous MVA in a combined cohort of grade II and III gliomas with prospectively-collected, well-annotated clinical data.
FUNDING: U10CA21661, U10CA180868, U10CA180822, U10CA37422 (NCI), Bristol Myers Squibb and Merck &Co. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).


Clinical problems associated with glioblastoma and the future direction of its treatment
Yoshitaka Narita (Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital)
Glioblastoma has one of the worst prognoses among cancers, although temozolomide improved the 5 year overall survival rate of glioblastomas from 10% (Brain tumor registry of Japan 2001-2005) to 16% (2005-2008). One of the biggest reasons for the poor prognosis of glioblastoma is that more than half of patients have a Karnofsky performance status score of 70 or less. Other reasons are as follows: 2) most patients are aged ≥60 years; 3) the tumor grows immediately[A1] and invades the surrounding brain regions; 4) only 50-60% patients are eligible for gross total tumor resection; 5) local tumor control is poor and most patients develop recurrence about 10 months after initial treatment; 6) there are many complications associated with glioblastoma; 7) limited number of effective drugs; 8) treatment does not readily improve the quality of life in patients; 9) only 30-40% of patients are positive for biomarkers indicating a good prognosis; 10) many patients do not undergo treatment in a centralized hospital.
A combination of temozolomide and bevacizumab did not improve the overall survival of glioblastoma patients, although bevacizumab improved the performance status in some patients. One of the answers to solve these problems is an earlier diagnosis and initiation of treatment for glioblastoma patients. In this session, the current problems associated with treating glioblastoma and the future direction of its treatment are discussed.


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