Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.104
Hyun Chang, H. Hong, Yongho Kim
104 Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.
{"title":"Prognostic value of trafficking of regulatory T cells to tumors in head and neck cancer patients.","authors":"Hyun Chang, H. Hong, Yongho Kim","doi":"10.1200/jgo.2019.5.suppl.104","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.104","url":null,"abstract":"104 Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41347466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.132
K. Fukushima, H. Motoyama, A. Shimizu, T. Notake, T. Ikehara, H. Hayashi, K. Yasukawa, A. Kobayashi, Y. Soejima
132 Background: The impact of adjuvant chemotherapy for advanced biliary cancer remains controversial. We previously failed to show survival benefit of adjuvant gemcitabine chemotherapy (UMIN000014018). The aim of this study was to evaluate the safety and efficacy of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for advanced biliary cancer. Methods: Between January 2006 and May 2019, a total of 110 patients who underwent surgical resection for biliary cancer (UICC Stage II or more) were enrolled in this study. Of these, 33 patients subsequently received 12 cycles of adjuvant chemotherapy (GS group), and 77 patients underwent surgery alone (S group). A cycle of chemotherapy consisted of oral S-1 70mg/m2 for 7 consecutive days and intravenous gemcitabine 1000mg/m2 on day 7, followed by a 1-week break from chemotherapy. Clinicopathological factors and patient survival were compared between the two groups. Results: GS group had significantly younger patients ( P = 0.036) and higher UICC T factor ( P = 0.001). Surgical procedure was significantly different in the two groups (P = 0.010). Other patient demographics and tumor characteristics were similar between the two groups. The completion rate of adjuvant chemotherapy was 57.6%, and there was no treatment-related deaths. All grades and grade 3/4 adverse event were seen in 60.6% and 33.3%, respectively. Three-year recurrence-free and overall survival rates were significantly higher in GS group than S group (61.9% vs. 34.4%, P = 0.016; 77.6% vs. 39.7%, P < 0.001, respectively). Conclusions: Adjuvant chemotherapy using gemcitabine plus S-1 was well tolerated and it would be an effective treatment strategy for the patients with resected advanced biliary cancer. Based on these results, randomized controlled study should be warranted.
背景:辅助化疗对晚期胆道癌的影响仍有争议。我们之前未能显示辅助吉西他滨化疗(UMIN000014018)的生存获益。本研究的目的是评价晚期胆道癌手术切除后辅助吉西他滨加S-1化疗的安全性和有效性。方法:在2006年1月至2019年5月期间，共有110例胆道癌(UICC II期或以上)手术切除患者纳入本研究。其中，33例患者随后接受了12个周期的辅助化疗(GS组)，77例患者单独接受手术(S组)。化疗周期为连续7天口服S-1 70mg/m2，第7天静脉注射吉西他滨1000mg/m2，休息1周。比较两组患者的临床病理因素及生存率。结果:GS组患者明显年轻化(P = 0.036)， UICC T因子明显增高(P = 0.001)。两组手术方式差异有统计学意义(P = 0.010)。两组患者的其他人口统计学特征和肿瘤特征相似。辅助化疗完成率为57.6%，无治疗相关死亡。所有等级和3/4级不良事件发生率分别为60.6%和33.3%。GS组3年无复发生存率和总生存率显著高于S组(61.9% vs. 34.4%， P = 0.016;77.6% vs. 39.7%， P < 0.001)。结论:吉西他滨联合S-1辅助化疗耐受性良好，是晚期胆道癌切除患者的有效治疗策略。基于这些结果，应该进行随机对照研究。
{"title":"Impact of adjuvant chemotherapy using gemcitabine plus S-1 after surgical resection for advanced biliary cancer.","authors":"K. Fukushima, H. Motoyama, A. Shimizu, T. Notake, T. Ikehara, H. Hayashi, K. Yasukawa, A. Kobayashi, Y. Soejima","doi":"10.1200/jgo.2019.5.suppl.132","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.132","url":null,"abstract":"132 Background: The impact of adjuvant chemotherapy for advanced biliary cancer remains controversial. We previously failed to show survival benefit of adjuvant gemcitabine chemotherapy (UMIN000014018). The aim of this study was to evaluate the safety and efficacy of adjuvant gemcitabine plus S-1 chemotherapy after surgical resection for advanced biliary cancer. Methods: Between January 2006 and May 2019, a total of 110 patients who underwent surgical resection for biliary cancer (UICC Stage II or more) were enrolled in this study. Of these, 33 patients subsequently received 12 cycles of adjuvant chemotherapy (GS group), and 77 patients underwent surgery alone (S group). A cycle of chemotherapy consisted of oral S-1 70mg/m2 for 7 consecutive days and intravenous gemcitabine 1000mg/m2 on day 7, followed by a 1-week break from chemotherapy. Clinicopathological factors and patient survival were compared between the two groups. Results: GS group had significantly younger patients ( P = 0.036) and higher UICC T factor ( P = 0.001). Surgical procedure was significantly different in the two groups (P = 0.010). Other patient demographics and tumor characteristics were similar between the two groups. The completion rate of adjuvant chemotherapy was 57.6%, and there was no treatment-related deaths. All grades and grade 3/4 adverse event were seen in 60.6% and 33.3%, respectively. Three-year recurrence-free and overall survival rates were significantly higher in GS group than S group (61.9% vs. 34.4%, P = 0.016; 77.6% vs. 39.7%, P < 0.001, respectively). Conclusions: Adjuvant chemotherapy using gemcitabine plus S-1 was well tolerated and it would be an effective treatment strategy for the patients with resected advanced biliary cancer. Based on these results, randomized controlled study should be warranted.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42099433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.20
G. Bariani, Rafael Lopes Ribeiro, L. Soares, Artur Katz
20 Background: In recent years the impact of technology has marked a major transformation in the way society produces and generates services. Several initiatives have been developed in the health area to face this new reality. A major oncology center in Brazil carried out a project based on Design Thinking with the objective of understanding the current scenario and promoting innovative solutions for the care of cancer patients. Methods: Design Thinking is the set of ideas and insights to address problems related to information acquisition, knowledge analysis and proposal of solutions. This process took place in four stages designated as empathise (approach to the context of the problem and data collection), define (synthesis of collected information, and organization of insights in order to standardize and better understand the problem), ideate (stimulation of creativity and generation of solutions) and prototype (validation of the ideas). Results: A total of 130 interviews were carried out with hospital personnel and 46 with patients and caregivers, as well as workshops to develop the project activities. Twenty-six projects were generated, and the priorities differed according to personnel and patients. Among the projects are financial consultancy; predictability of the total cost of treatment; diversification of payment methods; customization of the food menu offered to patients; promotion of entertainment activities during waiting periods in the practice; increase interactivity of chemotherapy rooms; improvement of services offered to international patients; and development of digital tools that provide reliable information about cancer, promotes patient autonomy and strengthens patient’s relationship with the hospital personnel. Conclusions: There is a growing need to modernize oncology practices creating new products and services. The opinion of hospital personnel and patients diverged about priorities. The former have chosen projects to improve facilities and design new roles for the team while the latter have given their best evaluations to new systems and services. For patients using digital media is not only welcome but also necessary attributes to provide more information and increase their autonomy.
{"title":"Creating solutions through design thinking.","authors":"G. Bariani, Rafael Lopes Ribeiro, L. Soares, Artur Katz","doi":"10.1200/jgo.2019.5.suppl.20","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.20","url":null,"abstract":"20 Background: In recent years the impact of technology has marked a major transformation in the way society produces and generates services. Several initiatives have been developed in the health area to face this new reality. A major oncology center in Brazil carried out a project based on Design Thinking with the objective of understanding the current scenario and promoting innovative solutions for the care of cancer patients. Methods: Design Thinking is the set of ideas and insights to address problems related to information acquisition, knowledge analysis and proposal of solutions. This process took place in four stages designated as empathise (approach to the context of the problem and data collection), define (synthesis of collected information, and organization of insights in order to standardize and better understand the problem), ideate (stimulation of creativity and generation of solutions) and prototype (validation of the ideas). Results: A total of 130 interviews were carried out with hospital personnel and 46 with patients and caregivers, as well as workshops to develop the project activities. Twenty-six projects were generated, and the priorities differed according to personnel and patients. Among the projects are financial consultancy; predictability of the total cost of treatment; diversification of payment methods; customization of the food menu offered to patients; promotion of entertainment activities during waiting periods in the practice; increase interactivity of chemotherapy rooms; improvement of services offered to international patients; and development of digital tools that provide reliable information about cancer, promotes patient autonomy and strengthens patient’s relationship with the hospital personnel. Conclusions: There is a growing need to modernize oncology practices creating new products and services. The opinion of hospital personnel and patients diverged about priorities. The former have chosen projects to improve facilities and design new roles for the team while the latter have given their best evaluations to new systems and services. For patients using digital media is not only welcome but also necessary attributes to provide more information and increase their autonomy.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42949298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.15
S. Dawood, A. Dhar, Poonam Sharma, L. Kini
15 Background: BRCA mutations is emerging as an agnostic marker for PARPi. Accessibility to genetic counselling is limited due to shortage of manpower and access to institutions that provide it. Our aim was to look at the incidence of pathogenic germline mutations in India/UAE and develop a virtual pathway, aimed at increasing accessibility to genetic counselling. Methods: 864 patients(pts) were tested in the UAE and India for germline mutations. Based on discussion between physicians and patients, an urgent need for genetic counseling was identified. A virtual platform (telegenetics) was constructed for those who sought genetic counseling due to a personal or family history of malignancies. Referral of pts was either self-based or through a treating physician. Primary goals included 1) ease of access for pts, 2) increase comprehension of the indications, implications and consequences of genetic testing, 3) decrease physician time in the clinic. 10 questions were developed determine pt and physician satisfaction. Results: 241(28.9%)pts had a pathogenic variant in BRCA1/BRCA. 115pts were enrolled in the pilot phase of the tele genetics program; all physician referred. Counselling was by a dedicated trained genetic counsellor through voice-call(43.5%), video-conferencing(47.8%) or in person when requested (8.7%). All pts completed a satisfaction survey. Majority of pts were comfortable sharing information on a virtual platform(80%), were happy with the quality of virtual connection(85%), and felt comfortable connecting with the genetic counselor(90%). Information is currently being collected from referring physicians. Conclusions: Our ongoing pilot phase reveals improved pt satisfaction and understanding of the information provided. A mobile application has been developed to enhance pt accessibility/convenience and physician connectivity with the testing phase of the app currently on going. To our knowledge this is the first tele genetics program to target the middle east/Asia pac region that is targeted to cope with increase in pt volumes, expand appropriate referrals, starting with pts who have a personal or family history of cancers, expanding to more complex high risk diseases over time.
{"title":"Development of a telegenetics program in the Asia-Pacific/Middle East region.","authors":"S. Dawood, A. Dhar, Poonam Sharma, L. Kini","doi":"10.1200/jgo.2019.5.suppl.15","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.15","url":null,"abstract":"15 Background: BRCA mutations is emerging as an agnostic marker for PARPi. Accessibility to genetic counselling is limited due to shortage of manpower and access to institutions that provide it. Our aim was to look at the incidence of pathogenic germline mutations in India/UAE and develop a virtual pathway, aimed at increasing accessibility to genetic counselling. Methods: 864 patients(pts) were tested in the UAE and India for germline mutations. Based on discussion between physicians and patients, an urgent need for genetic counseling was identified. A virtual platform (telegenetics) was constructed for those who sought genetic counseling due to a personal or family history of malignancies. Referral of pts was either self-based or through a treating physician. Primary goals included 1) ease of access for pts, 2) increase comprehension of the indications, implications and consequences of genetic testing, 3) decrease physician time in the clinic. 10 questions were developed determine pt and physician satisfaction. Results: 241(28.9%)pts had a pathogenic variant in BRCA1/BRCA. 115pts were enrolled in the pilot phase of the tele genetics program; all physician referred. Counselling was by a dedicated trained genetic counsellor through voice-call(43.5%), video-conferencing(47.8%) or in person when requested (8.7%). All pts completed a satisfaction survey. Majority of pts were comfortable sharing information on a virtual platform(80%), were happy with the quality of virtual connection(85%), and felt comfortable connecting with the genetic counselor(90%). Information is currently being collected from referring physicians. Conclusions: Our ongoing pilot phase reveals improved pt satisfaction and understanding of the information provided. A mobile application has been developed to enhance pt accessibility/convenience and physician connectivity with the testing phase of the app currently on going. To our knowledge this is the first tele genetics program to target the middle east/Asia pac region that is targeted to cope with increase in pt volumes, expand appropriate referrals, starting with pts who have a personal or family history of cancers, expanding to more complex high risk diseases over time.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45410733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.68
A. Tateishi, H. Horinouchi, K. Masuda, H. Jo, Y. Shinno, Y. Okuma, T. Yoshida, Y. Goto, N. Yamamoto, Y. Ohe
68 Background: Previous retrospective analyses have revealed higher response rates and a trend towards longer progression-free survival (PFS) and overall survival (OS) in response to immune checkpoint inhibitors (ICIs) in overweight patients. There are few reports concerning the association between the overweight state and the efficacy of ICIs specifically in non-small cell lung cancer (NSCLC) patients. We investigated the association between the body mass index (BMI) and the efficacy of ICIs in patients with NSCLC. Methods: Patients with advanced NSCLC who received ICI therapy (nivolumab or pembrolizumab) at the National Cancer Center Hospital from January 2016 to December 2018 were included in this retrospective cohort study. Based on their BMI, the patients were categorized into the overweight (A) group (BMI ≥25) and the non-overweight (B) group (BMI < 25). The PFS was compared between the two groups as the primary outcome. Results: Data of a total of 323 patients (median age, 63 years) were analyzed; 87 (26.9%)/43 (13.3%)/193 (59.8%) patients received pembrolizumab as 1st line therapy, pembrolizumab as 2nd line therapy, and nivolumab, respectively. Tumor proportion score was ≥50% in 58.4% (139/238) patients. The ECOG-PS was ≥2 in 37 patients (11.5%). The median body weight was 58.1, and the median BMI was 21.4. Of the 323 patients, 46 (14.2%) were categorized into group A (overweight) and 277 (85.8%) into group B (non-overweight). The median PFS and OS in two groups were as follows: A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25], p = 0.38), and A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43], p = 0.64), respectively. In accordance with the ICI regimen that the patients received, the PFS was A, 7.9 m/B, 7.8 m (HR 0.86, 95%CI [0.37-2.04], p = 0.74) in the patients who received pembrolizumab as 1st line therapy, A, 7.5 m/B, 5.3 m (HR 0.60, 95% CI [0.18-2.00], p = 0.40) in the patients who received pembrolizumab as 2nd line therapy, and A, 6.5 m/B, 4.4 m (HR 0.84, 95% CI [0.52-1.36], p = 0.48) in the patients who received nivolumab. Conclusions: Overweight NSCLC patients treated with ICIs showed a trend (non-statistically significant) towards a longer PFS as compared to non-overweight patients.
68背景:以往的回顾性分析显示，超重患者对免疫检查点抑制剂(ICIs)的应答率更高，无进展生存期(PFS)和总生存期(OS)更长。关于非小细胞肺癌(NSCLC)患者超重状态与ICIs疗效之间关系的报道很少。我们研究了非小细胞肺癌患者的身体质量指数(BMI)与ICIs疗效之间的关系。方法:2016年1月至2018年12月在国家癌症中心医院接受ICI治疗(纳武单抗或派姆单抗)的晚期NSCLC患者纳入本回顾性队列研究。根据BMI将患者分为超重(A)组(BMI≥25)和非超重(B)组(BMI < 25)。将两组间的PFS作为主要终点进行比较。结果:共分析323例患者资料，中位年龄63岁;分别有87例(26.9%)/43例(13.3%)/193例(59.8%)患者接受了派姆单抗作为一线治疗、派姆单抗作为二线治疗和纳武单抗。58.4%(139/238)患者肿瘤比例评分≥50%。ECOG-PS≥2者37例(11.5%)。中位体重为58.1，中位BMI为21.4。323例患者中，A组(超重)46例(14.2%)，B组(非超重)277例(85.8%)。两组患者的中位PFS和OS分别为:A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25]， p = 0.38)， A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43]， p = 0.64)。根据患者所接受的ICI方案，接受派姆单抗一线治疗的患者PFS分别为A、7.9 m/B、7.8 m (HR 0.86, 95%CI [0.37-2.04]， p = 0.74)，接受派姆单抗二线治疗的患者PFS分别为A、7.5 m/B、5.3 m (HR 0.60, 95%CI [0.18-2.00]， p = 0.40)，接受纳武单抗的患者PFS分别为A、6.5 m/B、4.4 m (HR 0.84, 95%CI [0.52-1.36]， p = 0.48)。结论:与非超重患者相比，接受ICIs治疗的超重NSCLC患者有更长的PFS趋势(无统计学意义)。
{"title":"Body mass index in non-small cell lung cancer patients treated with anti-PD-1 immune checkpoint inhibitors.","authors":"A. Tateishi, H. Horinouchi, K. Masuda, H. Jo, Y. Shinno, Y. Okuma, T. Yoshida, Y. Goto, N. Yamamoto, Y. Ohe","doi":"10.1200/jgo.2019.5.suppl.68","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.68","url":null,"abstract":"68 Background: Previous retrospective analyses have revealed higher response rates and a trend towards longer progression-free survival (PFS) and overall survival (OS) in response to immune checkpoint inhibitors (ICIs) in overweight patients. There are few reports concerning the association between the overweight state and the efficacy of ICIs specifically in non-small cell lung cancer (NSCLC) patients. We investigated the association between the body mass index (BMI) and the efficacy of ICIs in patients with NSCLC. Methods: Patients with advanced NSCLC who received ICI therapy (nivolumab or pembrolizumab) at the National Cancer Center Hospital from January 2016 to December 2018 were included in this retrospective cohort study. Based on their BMI, the patients were categorized into the overweight (A) group (BMI ≥25) and the non-overweight (B) group (BMI < 25). The PFS was compared between the two groups as the primary outcome. Results: Data of a total of 323 patients (median age, 63 years) were analyzed; 87 (26.9%)/43 (13.3%)/193 (59.8%) patients received pembrolizumab as 1st line therapy, pembrolizumab as 2nd line therapy, and nivolumab, respectively. Tumor proportion score was ≥50% in 58.4% (139/238) patients. The ECOG-PS was ≥2 in 37 patients (11.5%). The median body weight was 58.1, and the median BMI was 21.4. Of the 323 patients, 46 (14.2%) were categorized into group A (overweight) and 277 (85.8%) into group B (non-overweight). The median PFS and OS in two groups were as follows: A, 6.9 m/B, 5.6 m (HR 0.84, 95% CI [0.57-1.25], p = 0.38), and A, 22.3 m/B, 15.4 m (HR 0.90, 95% CI [0.56-1.43], p = 0.64), respectively. In accordance with the ICI regimen that the patients received, the PFS was A, 7.9 m/B, 7.8 m (HR 0.86, 95%CI [0.37-2.04], p = 0.74) in the patients who received pembrolizumab as 1st line therapy, A, 7.5 m/B, 5.3 m (HR 0.60, 95% CI [0.18-2.00], p = 0.40) in the patients who received pembrolizumab as 2nd line therapy, and A, 6.5 m/B, 4.4 m (HR 0.84, 95% CI [0.52-1.36], p = 0.48) in the patients who received nivolumab. Conclusions: Overweight NSCLC patients treated with ICIs showed a trend (non-statistically significant) towards a longer PFS as compared to non-overweight patients.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47956407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.22
S. Kurnaz, A. Loaiza-Bonilla
22 Background: Precision oncology encompasses the implementation of high level of evidence disease-specific and biomarker-driven diagnostic and treatment recommendations for optimized cancer care. Artificial Intelligence (AI), telemedicine and value-based care may optimize clinical trial enrollment (CTE) and overall cost-benefit. This ongoing, international registry for cancer pts evaluates the feasibility and clinical utility of an AI-based precision oncology clinical trial matching tool, powered by a virtual tumor boards (VTB) program, and its clinical impact on pts with advanced cancer to facilitate CTE, as well as the financial impact, and potential outcomes of the intervention. Methods: The SYNERGY-AI Registry is an international prospective, observational cohort study of eligible adult and pediatric pts with advanced solid and hematological malignancies, for whom the decision to consider CTE has already been made by their primary providers (PP). Using a proprietary application programming interface (API) linked to existing electronic health records (EHR) platforms, individual clinical data is extracted, analyzed and matched to a parametric database of existing institutional and non-institutional CTs. Machine learning algorithms allow for dynamic matching based on CT allocation and availability for optimized matching. Patients voluntarily enroll into registry, which is non-interventional with no protocol-mandated tests/procedures—all treatment decisions are made at the discretion of PP in consultation with their pts, based on the AI CT matching report, and VTB support. CTE will be assessed on variables including biomarkers, barriers to enrollment. Study duration anticipated as ~36 mo. The impact time to initiation of CTE on PFS and OS will be estimated by Kaplan-Meier and Cox multivariable survival analysis. Enrollment is ongoing, with a target of ≥ 1500 patients. Key inclusion criteria: Pts with solid and hematological malignancies; Pts cancer-related biomarkers. Key exclusion: ECOG PS > 2; abnormal organ function; hospice. Results: To be presented. Conclusions: AI-based, patient-driven CTE is feasible, highly effective and paradigm-changing. Clinical trial information: NCT03452774.
{"title":"SYNERGY-AI: Artificial intelligence-based precision oncology clinical trial matching and registry.","authors":"S. Kurnaz, A. Loaiza-Bonilla","doi":"10.1200/jgo.2019.5.suppl.22","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.22","url":null,"abstract":"22 Background: Precision oncology encompasses the implementation of high level of evidence disease-specific and biomarker-driven diagnostic and treatment recommendations for optimized cancer care. Artificial Intelligence (AI), telemedicine and value-based care may optimize clinical trial enrollment (CTE) and overall cost-benefit. This ongoing, international registry for cancer pts evaluates the feasibility and clinical utility of an AI-based precision oncology clinical trial matching tool, powered by a virtual tumor boards (VTB) program, and its clinical impact on pts with advanced cancer to facilitate CTE, as well as the financial impact, and potential outcomes of the intervention. Methods: The SYNERGY-AI Registry is an international prospective, observational cohort study of eligible adult and pediatric pts with advanced solid and hematological malignancies, for whom the decision to consider CTE has already been made by their primary providers (PP). Using a proprietary application programming interface (API) linked to existing electronic health records (EHR) platforms, individual clinical data is extracted, analyzed and matched to a parametric database of existing institutional and non-institutional CTs. Machine learning algorithms allow for dynamic matching based on CT allocation and availability for optimized matching. Patients voluntarily enroll into registry, which is non-interventional with no protocol-mandated tests/procedures—all treatment decisions are made at the discretion of PP in consultation with their pts, based on the AI CT matching report, and VTB support. CTE will be assessed on variables including biomarkers, barriers to enrollment. Study duration anticipated as ~36 mo. The impact time to initiation of CTE on PFS and OS will be estimated by Kaplan-Meier and Cox multivariable survival analysis. Enrollment is ongoing, with a target of ≥ 1500 patients. Key inclusion criteria: Pts with solid and hematological malignancies; Pts cancer-related biomarkers. Key exclusion: ECOG PS > 2; abnormal organ function; hospice. Results: To be presented. Conclusions: AI-based, patient-driven CTE is feasible, highly effective and paradigm-changing. Clinical trial information: NCT03452774.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47717530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.48
C. Rinaldi, K. Boasman, M. Simmonds
48 Background: In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti- phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. We investigated the expression of CALR and CD47 in patients with essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). Methods: Mononuclear cells were collected from peripheral blood of 27 MPN patients (8 PV, 16 ET, 3 MF), and from 4 controls. In total 14 patients received cyto-reductive therapies (Hydroxyurea, Anagrelide and Ruxolitinib). Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples comparing with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold). CD47 showed higher expression on MPN cells membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR when patients are treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET however, CD47 expression is reduced after treatment (22% vs 16.6%), suggesting instead a pro-phagocytic effect. Conclusions: CD47, is overexpressed on the membrane of patients with MPN suggesting a role for CD47 as a strong anti-phagocytic signal responsible for immune survival in MPN. MPN patients decreased CALR expression during therapy, but we observed a significant difference in CD47 expression in different MPN types. Anti-CD47 antibodies could represent a new strategy to enhance the pro-phagocytic signal via increasing the CALR expression, and in combination with standard cyto-reduction therapy, might represent a new therapeutical strategy in MPN.
背景:在实体肿瘤中，钙网蛋白(calreticulin, CALR)的过表达产生促吞噬信号，并被伴随的抗吞噬CD47的表达抵消，反映了细胞凋亡与生存的机制。在化疗反应中，细胞膜上CALR和CD47的增加已被观察到，然而它们在髓系恶性肿瘤中的作用尚不清楚。我们研究了CALR和CD47在原发性血小板增多症(ET)、真性红细胞增多症(PV)和骨髓纤维化(MF)患者中的表达。方法:采集27例MPN患者(PV 8例，ET 16例，MF 3例)外周血单个核细胞，对照组4例。共有14例患者接受了细胞减少治疗(羟基脲、阿纳格列德和鲁索替尼)。细胞分为4个区室:膜、细胞质、胞浆和细胞核。TRIzol提取蛋白，western blotting分析CALR和CD47蛋白表达。结果:与对照组相比，MPN样品中总CALR和CD47蛋白表达增加(CALR- 7.9 vs 5.1;CD47- 2.7 vs 2.2倍)。与CALR相比，CD47在MPN细胞膜上的表达更高(22%比13.9%)。我们观察到，当患者接受细胞还原剂治疗时，CALR显著降低(ET-未治疗43.3% vs治疗2%，PV- 3.6% vs 2.2%， ET- 21% vs 11%)。有趣的是，我们观察到MF和PV治疗后CD47显著增加(MF治疗组CD47增加11.8%，vs治疗组34.3%，PV治疗组CD47增加11.4%，vs治疗组35.9%)，提示细胞毒性药物诱导的抗吞噬作用。然而，在ET中，CD47表达在治疗后降低(22% vs 16.6%)，表明其具有促吞噬作用。结论:CD47在MPN患者的膜上过表达，提示CD47作为一种强抗吞噬信号在MPN的免疫存活中起作用。MPN患者在治疗期间CALR表达降低，但我们观察到CD47在不同MPN类型中的表达有显著差异。抗cd47抗体可能代表了一种通过增加CALR表达来增强吞噬前信号的新策略，并且与标准的细胞减少治疗相结合，可能代表了一种新的治疗MPN的策略。
{"title":"Expression of CD47 and CALR in myeloproliferative neoplasms: Potential new therapeutic targets.","authors":"C. Rinaldi, K. Boasman, M. Simmonds","doi":"10.1200/jgo.2019.5.suppl.48","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.48","url":null,"abstract":"48 Background: In solid tumours, calreticulin (CALR) overexpression produces a pro-phagocytic signal and is counteracted by concomitant expression of anti- phagocytic CD47, reflecting an apoptosis vs survival mechanism. Increases of both CALR and CD47 on the cell membrane have been observed in response to chemotherapy, however their role in myeloid malignancies is poorly understood. We investigated the expression of CALR and CD47 in patients with essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). Methods: Mononuclear cells were collected from peripheral blood of 27 MPN patients (8 PV, 16 ET, 3 MF), and from 4 controls. In total 14 patients received cyto-reductive therapies (Hydroxyurea, Anagrelide and Ruxolitinib). Cells were fractionised into 4 compartments: membrane, cytoplasm, cytosol and nucleus. Proteins were extracted using TRIzol, with CALR and CD47 protein expression analysed by western blotting. Results: Total CALR and CD47 protein expression increased in MPN samples comparing with controls (CALR- 7.9 vs 5.1; CD47- 2.7 vs 2.2 fold). CD47 showed higher expression on MPN cells membranes when compared with CALR (22% vs 13.9%). We observed a significant reduction of CALR when patients are treated with cyto-reductive agents (ET- untreated 43.3% vs treated 2%, PV- 3.6% vs 2.2%, ET- 21% vs 11%). Interestingly we have observed a significant increase in CD47 after treatment in MF and PV (CD47 in MF- untreated 11.8% vs treated 34.3%, PV-11.4% vs 35.9%), suggesting an anti-phagocytic effect induced by cytotoxic drugs. In ET however, CD47 expression is reduced after treatment (22% vs 16.6%), suggesting instead a pro-phagocytic effect. Conclusions: CD47, is overexpressed on the membrane of patients with MPN suggesting a role for CD47 as a strong anti-phagocytic signal responsible for immune survival in MPN. MPN patients decreased CALR expression during therapy, but we observed a significant difference in CD47 expression in different MPN types. Anti-CD47 antibodies could represent a new strategy to enhance the pro-phagocytic signal via increasing the CALR expression, and in combination with standard cyto-reduction therapy, might represent a new therapeutical strategy in MPN.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47342551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.130
Jason Joon Bock Lee, A. Yang, J. Chang, Han Sang Kim, H. I. Yoon, S. Shin, Y. Kim, W. Koom, J. Ahn
130 Background: Somatic mutations of genes involved in DNA repair (e.g. ATM and BRCA1/2) may result in chemotherapy resistance and poor prognosis, but may confer sensitivity to radiation therapy. In this study, we aimed to the hypothesis that patients with such mutations may be more susceptible to radiotherapy. Methods: Using prospectively collected RT registry, we identified patients who underwent both RT to gross disease and NGS panel screening between 2013 and 2019 (N = 27,664). From a cohort of 134 patients, 33 patients with somatic mutation in ATM or BRCA 1/2 were identified and closely matched with 33 patients without mutation using propensity score based on radiation dose and histology. Results: Infield response rate was evaluated in 66 patients with 90 gross lesions (ATM mutation, 11 patients and BRCA 1/2 mutation, 22 patients). The median tumor size and RT dose was 24 mm (3-140) and 40 Gy (12-66), respectively. Stark differences were seen in infield complete response rate, overall response rate, and local control rate at target lesions by ATM mutation (mutation vs. no mutation; 50% vs. 8%, 61% vs. 24%, and 94% vs. 58%, P < .05). Response duration was also longer ATM mutation (median 11 vs. 3 months, P = .001). However, RT-related toxicities were not different (17% vs. 11%, P = .515) and no severe toxicity occurred. Conclusions: ATM mutations confer exceptional responses to radiation therapy, even with palliative dose, which has potential therapeutic implications.
130背景:参与DNA修复的基因(如ATM和BRCA1/2)的体细胞突变可能导致化疗耐药和不良预后，但可能赋予放射治疗敏感性。在这项研究中，我们的目的是假设有这种突变的患者可能更容易接受放疗。方法:使用前瞻性收集的RT登记处，我们确定了2013年至2019年期间接受了总体疾病RT和NGS面板筛查的患者(N = 27,664)。从134例患者中，鉴定出33例ATM或BRCA 1/2体细胞突变患者，并使用基于辐射剂量和组织学的倾向评分与33例无突变患者密切匹配。结果:对66例90个大体病变(ATM突变11例，BRCA 1/2突变22例)的患者进行内野反应率评估。中位肿瘤大小为24 mm(3-140)，放疗剂量为40 Gy(12-66)。ATM突变在靶病变内野完全缓解率、总缓解率和局部控制率方面存在显著差异(突变vs.无突变;50%和8%、61%和24%,94%和58%,P < . 05)。ATM突变的反应持续时间也更长(中位11个月vs. 3个月，P = 0.001)。然而，rt相关的毒性没有差异(17% vs. 11%， P = .515)，没有发生严重的毒性。结论:ATM突变对放射治疗具有特殊的反应，即使是姑息性剂量，也具有潜在的治疗意义。
{"title":"Genomic analysis reveals somatic mutations of ATM gene in DNA repair confer exceptional target lesion response to radiation therapy.","authors":"Jason Joon Bock Lee, A. Yang, J. Chang, Han Sang Kim, H. I. Yoon, S. Shin, Y. Kim, W. Koom, J. Ahn","doi":"10.1200/jgo.2019.5.suppl.130","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.130","url":null,"abstract":"130 Background: Somatic mutations of genes involved in DNA repair (e.g. ATM and BRCA1/2) may result in chemotherapy resistance and poor prognosis, but may confer sensitivity to radiation therapy. In this study, we aimed to the hypothesis that patients with such mutations may be more susceptible to radiotherapy. Methods: Using prospectively collected RT registry, we identified patients who underwent both RT to gross disease and NGS panel screening between 2013 and 2019 (N = 27,664). From a cohort of 134 patients, 33 patients with somatic mutation in ATM or BRCA 1/2 were identified and closely matched with 33 patients without mutation using propensity score based on radiation dose and histology. Results: Infield response rate was evaluated in 66 patients with 90 gross lesions (ATM mutation, 11 patients and BRCA 1/2 mutation, 22 patients). The median tumor size and RT dose was 24 mm (3-140) and 40 Gy (12-66), respectively. Stark differences were seen in infield complete response rate, overall response rate, and local control rate at target lesions by ATM mutation (mutation vs. no mutation; 50% vs. 8%, 61% vs. 24%, and 94% vs. 58%, P < .05). Response duration was also longer ATM mutation (median 11 vs. 3 months, P = .001). However, RT-related toxicities were not different (17% vs. 11%, P = .515) and no severe toxicity occurred. Conclusions: ATM mutations confer exceptional responses to radiation therapy, even with palliative dose, which has potential therapeutic implications.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46127285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.18
Jun Zhang
18 Background: It is a major challenge that the hypoxia microenvironment can induce gastric cancer (GC).Understanding the underlying mechanisms and developing effective strategies against GC invasive and metastasis are highly desired in the clinic. Methods: GC cells were cultured under 1% O2 (HGC) and 20% O2 condition (NGC). NGC were co-cultured with HGC- medium. Exosomes from GC were extracted by ultracentrifugation. Electron microscopy images, western-blot and NanoSight particletracking used to analysis the size distributions and number of exosomes. Exosomal long noncoding RNA (lncRNA) profiling was performed using a lncRNA array. The “R” was used to recognize the differentially expressed lncRNAs (DELs). RNA-pulldown and mass spectrometry analysis were recruited to investigate the binding protein of target lncRNA. Results: Compared to NGC, HGC was more capable of invasion and metastasis which was evaluated by scrape and transwell. And HGC-medium induced NGC dissociation. Differential analysis revealed that lncRNA PCGEM1 was specifically expressed in HGC exosomes. PCGEM1 was up-regulated in GC cell and tissue. And the luciferase report confirmed HIF-1α, as a transcription factor, can bind to the promoter sequence of PCGEM1, promotes the overexpression of PCGEM1 in GC. Dii tracer proved that HGC-derived exosomes could be absorbed by NGC. RNA pull-down assay and mass spectrometry analysis showed that SNAI1 and USP9X with PCGEM1 directly. Conclusions: Our results suggest that the overexpressed of HIF-1α can up-regulated the expression of lncRNA PCGEM1 under hypoxia condition. And part of the overexpression PCGEM1 can be encapsulated into exosomes. These exosomes promoted invasion and metastasis of other GC cells. The mechanism was that PCGEM1 can bind both USP9X and SNAI1 at the same time, and under the effect of deubiquitination enzyme USP9X, the expression of SNAI1 increased, thus promoting EMT and thereby promoted the invasion and metastasis of GC cells.
{"title":"Exosome-transmitted lncRNA PCGEM1 as a \"scaffold\" for invasion and metastasis in gastric cancer.","authors":"Jun Zhang","doi":"10.1200/jgo.2019.5.suppl.18","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.18","url":null,"abstract":"18 Background: It is a major challenge that the hypoxia microenvironment can induce gastric cancer (GC).Understanding the underlying mechanisms and developing effective strategies against GC invasive and metastasis are highly desired in the clinic. Methods: GC cells were cultured under 1% O2 (HGC) and 20% O2 condition (NGC). NGC were co-cultured with HGC- medium. Exosomes from GC were extracted by ultracentrifugation. Electron microscopy images, western-blot and NanoSight particletracking used to analysis the size distributions and number of exosomes. Exosomal long noncoding RNA (lncRNA) profiling was performed using a lncRNA array. The “R” was used to recognize the differentially expressed lncRNAs (DELs). RNA-pulldown and mass spectrometry analysis were recruited to investigate the binding protein of target lncRNA. Results: Compared to NGC, HGC was more capable of invasion and metastasis which was evaluated by scrape and transwell. And HGC-medium induced NGC dissociation. Differential analysis revealed that lncRNA PCGEM1 was specifically expressed in HGC exosomes. PCGEM1 was up-regulated in GC cell and tissue. And the luciferase report confirmed HIF-1α, as a transcription factor, can bind to the promoter sequence of PCGEM1, promotes the overexpression of PCGEM1 in GC. Dii tracer proved that HGC-derived exosomes could be absorbed by NGC. RNA pull-down assay and mass spectrometry analysis showed that SNAI1 and USP9X with PCGEM1 directly. Conclusions: Our results suggest that the overexpressed of HIF-1α can up-regulated the expression of lncRNA PCGEM1 under hypoxia condition. And part of the overexpression PCGEM1 can be encapsulated into exosomes. These exosomes promoted invasion and metastasis of other GC cells. The mechanism was that PCGEM1 can bind both USP9X and SNAI1 at the same time, and under the effect of deubiquitination enzyme USP9X, the expression of SNAI1 increased, thus promoting EMT and thereby promoted the invasion and metastasis of GC cells.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46315544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-10-07DOI: 10.1200/jgo.2019.5.suppl.58
Huy P. Do, T. Nguyen, U. Tran, Thanh-Truong Tran, A. Dang, V. Nguyen, C. Nguyen, H. N. Do, M. Phan, L. S. Tran, H. Nguyen, H. Giang
58 Background: Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Genotype-directed therapy becomes a promising method for cancer treatment beside surgery and chemo-radiotherapy. Liquid biopsy using massive parallel sequencing has emerged as a non-invasive alternative procedure in profiling cancer driver mutations. In this study, we report the spectrum of clinically actionable mutations in plasma circulating tumor DNA of 299 non-small cell lung cancer patients using ultra-deep massive parallel sequencing with unique identifier tagging. Methods: Plasma circulating tumor DNA was extracted, ligated with unique identifier (Swift Bioscience), enriched of the target coding regions of EGFR, KRAS, NRAS, BRAF and the breakpoints of ALK, ROS1 (IDT) and sequenced using NextSeq 550 (Illumina) at mean coverage depth of 20,000X. Results: Out of 299 patients tested, 128 (42,8%) carried driver mutations. Genetic alterations were identified in EGFR (79 samples, 26,4%), KRAS (30 samples, 10%), ALK (7 samples, 2,34%), ROS1 (6 samples, 2%), BRAF (3 samples, 1%). There was no sample with NRAS mutation. In 79 EGFR-cases, there were 23 carry two pathogenic variants. 28 mutation types of EGFR were found including 19 indels and 9 missense variants L858R and T790M were the major ones. One case was found with concomitant EGFR and BRAF. Our study showed the spectrum and frequency of the cancer driver mutations detected in liquid biopsy was correlated to those detected in tissue biopsy samples. Conclusions: For the first time the spectrum of mutation types in liquid biopsy of Vietnamese NSCLC patients were investigated and showed the correlation with those detected in tissue biopsy samples.
{"title":"Plasma circulating tumor DNA-based genetic profiling of lung cancer patients in Vietnam using ultra-deep massive parallel sequencing with unique identifier tagging.","authors":"Huy P. Do, T. Nguyen, U. Tran, Thanh-Truong Tran, A. Dang, V. Nguyen, C. Nguyen, H. N. Do, M. Phan, L. S. Tran, H. Nguyen, H. Giang","doi":"10.1200/jgo.2019.5.suppl.58","DOIUrl":"https://doi.org/10.1200/jgo.2019.5.suppl.58","url":null,"abstract":"58 Background: Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Genotype-directed therapy becomes a promising method for cancer treatment beside surgery and chemo-radiotherapy. Liquid biopsy using massive parallel sequencing has emerged as a non-invasive alternative procedure in profiling cancer driver mutations. In this study, we report the spectrum of clinically actionable mutations in plasma circulating tumor DNA of 299 non-small cell lung cancer patients using ultra-deep massive parallel sequencing with unique identifier tagging. Methods: Plasma circulating tumor DNA was extracted, ligated with unique identifier (Swift Bioscience), enriched of the target coding regions of EGFR, KRAS, NRAS, BRAF and the breakpoints of ALK, ROS1 (IDT) and sequenced using NextSeq 550 (Illumina) at mean coverage depth of 20,000X. Results: Out of 299 patients tested, 128 (42,8%) carried driver mutations. Genetic alterations were identified in EGFR (79 samples, 26,4%), KRAS (30 samples, 10%), ALK (7 samples, 2,34%), ROS1 (6 samples, 2%), BRAF (3 samples, 1%). There was no sample with NRAS mutation. In 79 EGFR-cases, there were 23 carry two pathogenic variants. 28 mutation types of EGFR were found including 19 indels and 9 missense variants L858R and T790M were the major ones. One case was found with concomitant EGFR and BRAF. Our study showed the spectrum and frequency of the cancer driver mutations detected in liquid biopsy was correlated to those detected in tissue biopsy samples. Conclusions: For the first time the spectrum of mutation types in liquid biopsy of Vietnamese NSCLC patients were investigated and showed the correlation with those detected in tissue biopsy samples.","PeriodicalId":15862,"journal":{"name":"Journal of global oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46318627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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