The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer research.At the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and beyond.Although CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of cancer.Looking back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be developed.The quantity and quality of these samples will be compatible with omics analyses.All biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

Precision medicine is a growing field worldwide.Despite its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical practice.The main obstacles are associated with the quality of samples used for genomic analysis。

Application of Survival Quilts for prognosis prediction of gastrectomy patients based on the Surveillance,Epidemiology,and End Results database and China National Cancer Center Gastric Cancer database

Objective:Accurate prognosis prediction is critical for individualized-therapy making of gastric cancer patients.We aimed to develop and test 6-month,1-,2-,3-,5-,and 10-year overall survival(OS)and cancer-specific survival(CSS)prediction models for gastric cancer patients following gastrectomy.Methods:We derived and tested Survival Quilts,a machine learning-based model,to develop 6-month,1-,2-,3-,5-,and 10-year OS and CSS prediction models.Gastrectomy patients in the development set(n=20,583)and the internal validation set(n=5,106)were recruited from the Surveillance,Epidemiology,and End Re-sults(SEER)database,while those in the external validation set(n=6,352)were recruited from the China National Cancer Center Gastric Cancer(NCCGC)database.Furthermore,we selected gastrectomy patients with-out neoadjuvant therapy as a subgroup to train and test the prognostic models in order to keep the accuracy of tumor-node-metastasis(TNM)stage.Prognostic performances of these OS and CSS models were assessed using the Concordance Index(C-index)and area under the curve(AUC)values.Results:The machine learning model had a consistently high accuracy in predicting 6-month,1-,2-,3-,5-,and 10-year OS in the SEER development set(C-index=0.861,0.832,0.789,0.766,0.740,and 0.709;AUC=0.784,0.828,0.840,0.849,0.869,and 0.902,respectively),SEER validation set(C-index=0.782,0.739,0.712,0.698,0.681,and 0.660;AUC=0.751,0.772,0.767,0.762,0.766,and 0.787,respectively),and NCCGC set(C-index=0.691,0.756,0.751,0.737,0.722,and 0.701;AUC=0.769,0.788,0.790,0.790,0.787,and 0.788,respectively).The model was able to predict 6-month,1-,2-,3-,5-,and 10-year CSS in the SEER development set(C-index=0.879,0.858,0.820,0.802,0.784,and 0.774;AUC=0.756,0.827,0.852,0.863,0.874,and 0.884,respectively)and SEER validation set(C-index=0.790,0.763,0.741,0.729,0.718,and 0.708;AUC=0.706,0.758,0.767,0.766,0.766,and 0.764,respectively).In multivariate analysis,the high-risk group with risk score output by 5-year OS model was proved to be a strong survival predictor both in the SEER development set(hazard ratio[HR]=14.59,95%confidence interval[CI]:1.872-2.774,P<0.001),SEER validation set(HR=2.28,95%CI:13.089-16.293,P<0.001),and NCCGC set(HR=1.98,95%CI:1.617-2.437,P<0.001).We further explored the prognostic value of risk score resulted 5-year CSS model of gastrectomy patients,and found that high-risk group remained as an independent CSS factor in the SEER development set(HR=12.81,95%CI:11.568-14.194,P<0.001)and SEER validation set(HR=1.61,95%CI:1.338-1.935,P<0.001).Conclusion:Survival Quilts could allow accurate prediction of 6-month,1-,2-,3-,5-,and 10-year OS and CSS in gastric cancer patients following gastrectomy.

Survival of patients with gastric cancer surgically treated at the National Cancer Center of China from 2011 to 2018 according to stage at diagnosis

Objective:The postoperative survival rates of patients with gastric cancer at different stages treated at the National Cancer Center(NCC)of China have not been reported.Therefore,we evaluated the survival of patients with gastric cancer who underwent surgery at the NCC from 2011 to 2018 to provide baseline information for further studies.Methods:We identified 7,301 patients with primary gastric carcinoma who underwent surgery at the NCC be-tween January 2011 and May 2018;among these,5,008 patients were enrolled in this study.Follow up was completed on April 30,2020.We analyzed the 5-year survival according to the stage,sex,age,and other clini-copathological features.Results:Five-year survival rates of patients with pTNM stages ⅠA,ⅠB,ⅡA,ⅡB,ⅢA,ⅢB,ⅢC,and Ⅳ treated at the NCC were 94.9%,91.8%,86.5%,76.1%,61.1%,44.2%,29.7%,and 8.1%,respectively,which were similar to those reported in Japan during the same period.Five-year survival rates of patients with ypTNM stages I,II,III,and IV were 93.1%,63.2%,27.2%,and 0.0%,respectively.In multivariable analysis,age,signet ring cell carcinoma,adjuvant chemotherapy,and degree of differentiation were revealed as important prognostic factors.Conclusion:The survival rates of patients with gastric cancer treated at the NCC have been significantly improved,reaching the levels of Japan in the same period.

Prognostic role of the ABO blood types in Chinese patients with curatively resected non-small cell lung cancer:a retrospective analysis of 1601 cases at a single cancer center

Background:A positive association between the ABO blood types and survival has been suggested in several malignancies.The aim of this study was to assess the role of the ABO blood types in predicting the prognosis of Chinese patients with curatively resected non-small cell lung cancer(NSCLC).Methods:We retrospectively analyzed 1601 consecutive Chinese patients who underwent curative surgery for NSCLC between January 1,2005 and December 31,2009.The relationship between the ABO blood types and survival was investigated.In addition,univariate and multivariate analyses were performed.Results:Group 1(patients with the blood type O or B) had significantly prolonged overall survival(OS) compared with group 2(patients with the blood type A or AB),with a median OS of 74.9 months versus 61.5 months[hazard ratio(HR) 0.83;95%confidence interval(CI) 0.72-0.96;P = 0.015].Additionally,group 1 had significantly longer disease-free survival(DFS;HR 0.86;95%CI 0.76-0.98;P = 0.022) and locoregional relapse-free survival(LRFS;HR 0.79;95%CI 0.64-0.98;P = 0.024) than group 2.The association was not significantly modified by other risk factors for NSCLC,including smoking status,pathologic tumor-node-metastasis stage,pT category,pN category,and chemotherapy.Conclusions:There is an association between the ABO blood types and the survival of Chinese patients with resected NSCLC.Patients with the blood type O or B had significantly prolonged OS,DFS,and LRFS compared with those with the blood type A or AB.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer:10 years'experience of National Cancer Center in China

Objective： The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. Methods： The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics （FIGO） Ib-[Ia cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. Results： Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival （DFS） of 92.1% and 5-year overall survival （OS） of 95.0%. In multivariate analysis, differentiation of G3 （P〈0.05）, lymph node metastasis （LNM, P〈0.05） and lymphovascular space invasion （LVSI, P〈0.05） were independent predictors for OS, while LNM （P〈0.05）, deep stroma invasion （DSI, P〈0.05） and LVSI （P〈0.05） were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma （SCC） was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamons carcinoma （AC/ASC）, differentiation was the independent predictor of OS （P〈0.05）; and LVSI of DFS （P〈0.05）. Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy （CCRT, n=195）, radiotherapy （RT, n=24）, and chemotherapy （CT, n=17）. Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT （P=0.118）, with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. Conclusions： LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT＋CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.

Epidemiologic characteristics of oral cancer:single-center analysis of 4097 patients from the Sun Yat-sen University Cancer Center

Background:Oral cancer is a common type of head and neck cancers.Knowing its epidemiologic characteristics is crucial to preventing,diagnosing,and treating this cancer.This study aimed to explore the epidemiologic characteristics of oral cancer in South China.Methods:We retrospectively analyzed data from 4097 oral cancer patients treated at the Sun Yat-sen University Cancer Center between 1960 and 2013.We compared the age of onset,sex ratio,pathologic type,and primary tumor location among three subcultural areas(Guangfu,Hakka,and Chaoshan) and between an economically developed region and a less-developed one in Guangdong.Results:Overall,oral cancer had a male-to-female ratio of approximately 2:1,and this ratio decreased over time.Oral cancer occurred mostly in patients of 45-64 years old(54.5%),and the percentage of older patients gradually increased over time.The most common tumor location was the tongue.Squamous cell carcinoma was the predominant pathologic type.The percentage of blood type O in oral cancer patients was lower than that in the healthy population.The male-to-female ratio in the Chaoshan area was higher than that in the Guangfu and Hakka areas,whereas the age of disease onset in Guangfu was higher than that in Hakka and Chaoshan.The male-to-female ratio was lower and the age of disease onset was higher in the economically developed region than in the less-developed region.Conclusion:The incidence of oral cancer in South China presents typical characteristics to which doctors should pay attention when diagnosing and treating oral cancer patients.

Proposal of new expanded selection criteria using total tumor size and ^(18)F-fluorodeoxyglucose- positron emission tomography/computed tomography for living donor liver transplantation in patients with hepatocellular carcinoma:The National Cancer Center K

AIM: To expand the living donor liver transplantation(LT) pool of eligible patients with hepatocellular carcinoma(HCC) using new morphological and biological criteria.METHODS: Patients with HCC who underwent living donor LT(LDLT) from March 2005 to May 2013 at the National Cancer Center Korea(NCCK) were enrolled. We performed the 18F-fluorodeoxyglucose positron emission tomography/computed tomography(PET/CT)before LDLT. Overall and disease-free survival analysis was done in patients to evaluate the usefulness of new NCCK criteria using PET/CT and total tumor size(10 cm).RESULTS: We enrolled a total of 280 patients who pathologically confirmed to have HCC and performed the PET/CT before transplantation. Among them, 164(58.6%) patients fulfilled the NCCK criteria and 132 patients(47.1%) met the Milan criteria. Five-year overall and disease-free survival rates for patients who fulfilled the NCCK criteria showed 85.2% and 84.0%, respectively, and were significantly higher than those beyond the NCCK criteria(60.2% and 44.4%, respectively; P < 0.001). The correlation analysis between preoperative imaging tests and pathologic reports using Cohen's Kappa demonstrated the better results in the NCCK criteria than those in the Milan criteria(0.850 vs 0.583). The comparison of diseasefree analysis among the NCCK, Milan, and University of California, San Francisco(UCSF) criteria using the receiver operating characteristics curves revealed the similar area under the curve value criteria(NCCK vs Milan, P = 0.484; NCCK vs UCSF, P = 0.189 at 5-years).CONCLUSION: The NCCK criteria using hybrid concept of both morphological and biological parameters showed an excellent agreement between preoperative imaging and pathological results, and favorable survival outcomes. These new criteria might select the optimal patients with HCC waiting LDLT and expand the selection pool.

Impact of body mass index on complications following pancreatectomy:Ten-year experience at National Cancer Center in China

AIM: To examine the impact of body mass index(BMI)on outcomes following pancreatic resection in the Chinese population.METHODS: A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Individuals who underwent pancreatic resection between January2004 and December 2013 were identified and included in the study. Persons were classified as having a normal weight if their BMI was < 24 kg/m2 and overweight/obese if their BMI was ≥ 24 kg/m2 as defined by the International Life Sciences Institute Focal Point in China. A χ 2 test(for categorical variables) or a t test(for continuous variables) was used to examine the differences in patients' characteristics between normal weight and overweight/obese groups. Multiple logistic regression models were used to assess the associationsof postoperative complications, operative difficulty,length of hospital stay, and cost with BMI, adjusting for age, sex, and type of surgery procedures.RESULTS: A total of 362 consecutive patients with data available for BMI calculation underwent pancreatic resection for benign or malignant disease from January1, 2004 to December 31, 2013. Of the 362 patients,156 were overweight or obese and 206 were of normal weight. One or more postoperative complications occurred in 35.4% of the patients following pancreatic resection. Among patients who were overweight or obese, 42.9% experienced one or more complications,significantly higher than normal weight(29.6%)individuals(P = 0.0086). Compared with individuals who had normal weight, those with a BMI ≥ 24.0kg/m2 had higher delayed gastric emptying(19.9% vs5.8%, P < 0.0001) and bile leak(7.7% vs 1.9%, P =0.0068). There were no significant differences seen in pancreatic fistula, gastrointestinal hemorrhage, reoperation,readmission, or other complications. BMI did not show a significant association with intraoperative blood loss, operative time, length of hospital stay, or cost.CONCLUSION: Higher BMI increases the risk for postoperative complications after pancreatectomy in the Chinese population. The findings require replication in future studies with larger sample sizes.

Forty-six cases of nasopharyngeal carcinoma treated with 50 Gy radiotherapy plus hematoporphyrin derivative:20 years of follow-up and outcomes from the Sun Yat-sen University Cancer Center

Background:With the improved overall survival(OS) of nasopharyngeal carcinoma(NPC) patients,the importance of quality of life(Qo L) is increasingly being recognized.For some radiosensitive NPC patients,whether low?dose radio?therapy can improve the Qo L without affecting clinical efficacy is unknown.This study aimed to assess the survival rates and Qo L of NPC patients treated with 50 Gy radiotherapy plus hematoporphyrin derivative(HPD).Methods:Forty?six newly diagnosed NPC patients treated with 50 Gy radiotherapy plus HPD between June 1988 and July 1992 were analyzed.All patients were restaged according to the 7th edition of the American Joint Commit?tee on Cancer staging system.The radiotherapy plan was designed on the basis of pretreatment computed tomog?raphy.The OS,local recurrence?free survival(LRFS),distant metastasis?free survival(DMFS),and disease?free survival(DFS) rates were estimated using the Kaplan–Meier method.Qo L was assessed using the Late Radiation Morbidity Scoring Criteria of the Radiation Therapy Oncology Group.Results:The 5?year OS,LRFS,DMFS,and DFS rates were 74.3%,72.6%,82.1%,and 61.2%,respectively.The corre?sponding 10?year rates were 38.4%,62.9%,78.5%,and 49.8%,respectively,and the 20?year rates were 27.7%,51.4%,78.5%,and 40.7%,respectively.None of the patients developed severe radiation?related complications,such as radiation?induced temporal lobe necrosis,hearing loss,trismus,and dysphagia.Conclusion:Some NPC patients were sensitive to 50 Gy radiotherapy plus HPD,and this sensitivity was characterized by long?term survival without significant late treatment morbidities.

“Day Ward” and “Consultation Center of Intractable Pain Cases”——New services of Wuhan Tongji Cancer Center benefit patients

Recently, two new services - ＂Day Ward＂ and ＂Consultation Center of Intractable Pain Cases＂ - were launched in Wuhan Tongji Cancer Center, in order to simplify diagnosis and treatment process, and improve patients＇ quality life,

Tongji Cancer Center(Wuhan, China) held 2014 Multidisciplinary Symposium for The Consultation Center of Intractable Pain Cases

The 2014 Multidisciplinary Symposium for The Consultation Center of Intractable Pain Cases was held on April 21th, 2014. Fourteen departments took part in the symposium.

Bring health,bring happiness and bring hope The series of activities of the 17th National Tumor Prophylaxis and Treatment Week in Tongji Cancer Center, Tongji Hospital, Wuhan,china

The 17th National Tumor Prophylaxis and Treatment Week, with the theme of "fight cancer scientifically and care life", kicked off in Wuhan, China. As one of the most important social works all over the year, the Week was broadened into a series of activities, lasting for one month, in Tongji Cancer Center, Tongji Hospital, Wu-han, China.

Cancer, did you know?——Tongji Cancer Center held World Cancer Day 2013 in China

On February 2nd, World Cancer Day 2013 in China hosted by China Anti-Cancer Association （CACA）, and jointly undertaken by Cancer Rehabilitation and Palliative Care Committee, China （CRPC）, a branch of CACA,

Dosimetric Comparison: Volumetric Modulated Arc Therapy (VMAT) and 3D Conformal Radiotherapy (3D-CRT) in High Grade Glioma Cancer—Experience of Casablanca Cancer Center at the Cheikh Khalifa International University Hospital

Background: Intensity Modulated Radiation Therapy (IMRT) is currently employed as a major arm of treatment in multiforme glioblastoma (GBM). The present study aimed to compare 3D-CRT with IMRT to assess tumor volume coverage and OAR sparing for the treatment of malignant gliomas. Materials and methods: We assessed 22 anonymized patients datasets with High Grade Glioblastoma who had undergone post-operative Intensity Modulated Radiotherapy (IMRT) and 3D Conformal Radiotherapy (3D-CRT), This study will compare and contrast treatment plans Rapidarc and 3D-CRT to determine which technology improves significantly dosimetric parameters. Results: Plans will be assessed by reviewing the coverage of the PTV using mean, maximum and minimum doses while the OAR doses will be compared using the maximal doses for each, as set out in the QUANTEC dose limits. Conclusion: The use of IMRT seems a superior technique as compared to 3D-CRT for the treatment of malignant gliomas having the potential to increase the dose to the PTV while sparing OARs optimally.

Tongji cancer center held the 3rd session of PICC concern group

The 3rd Session of PICC Concern Group in Tongji Cancer Center was held in the classroom of Tongji Cancer Center on April 17th, 2013. PICC （peripherally inserted central catheter） is a new technique which is widely adopted in Chinese hospitals soon after it was invented. The technique need smooth cooperation of medical staff and patients.

Tongji Cancer Center(Wuhan, China) held the 5th "Heart Warming" & National Tumor Prophylaxis and Treatment Week Party

On April 12th, the 5th ＂Heart Warming＂ ＆ National Tumor Prophylaxis and Treatment Week Party was held in the classroom of Tongji Cancer Center by Tongji Cancer Center and ＂Sunshine Medical Students＂ group of Tongji Young Volunteers Association. More than 100 patients and their care-givers enjoyed themselves in the party.

Synergetic role of integrating the departments of cancer registry and clinical research at an academic comprehensive cancer center

Integration of the cancer registry and clinical research departments can have a significant impact on the accreditation process of a Commission on Cancer(Co C) Program.Here in we demonstrate that the integration of both departments will benefit as there is increased knowledge, manpower and crossover in job responsibilities in our Co C-accredited Academic Comprehensive Cancer Center.In our model this integration has led to a more successful cooperative interaction among departments, which has in turn created an enhanced combined effect on overall output and productivity.More manpower for the cancer registry has led to increased caseloads, decreased time from date of first contact to abstraction, quality of data submissions, and timely follow-up of all patients from our reference date for accurate survival analysis along with completeness of data.In 2016, our Annual Facility report showed an additional 163 cases over prediction by the state of Maryland Cancer Registry and a 39% increase in case completeness.As proof of the synergetic effectiveness of our model within one year of its implementation, the cancer center was able to apply for, and was awarded membership from Alliance for Clinical Trials in Oncology, Central IRB, and in turn led to increased clinical trial accrual from 2.8% in 2014 compared to 13.2% currently.Our cancer registry in year one submitted over 150 more cases than predicted, improved quality outcome measures displayed by our Cancer Program Practice Profile reports and had more timely and complete data submissions to national and state registries.This synergetic integration has led to a better understanding, utilization and analysis of data by an integrated team with Clinical Research expertise.

Erratum to‘Evolution and genotypic characteristics of small cell lung cancer transformation in non-small cell lung carcinomas’[Journal of the National Cancer Center,1(2021),4:153-162]

The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.