1.Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis.
Fei SU ; Ke ZHENG ; Yiyun FU ; Qian WU ; Yuan TANG ; Weiya WANG ; Lili JIANG
Chinese Journal of Lung Cancer 2018;21(5):389-396
BACKGROUND:
Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy.
METHODS:
ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed.
RESULTS:
The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS).
CONCLUSIONS
For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.
Adenocarcinoma
;
blood
;
drug therapy
;
genetics
;
mortality
;
Adenocarcinoma of Lung
;
Adult
;
Aged
;
Aged, 80 and over
;
Cell-Free Nucleic Acids
;
blood
;
ErbB Receptors
;
genetics
;
Female
;
Humans
;
Lung Neoplasms
;
blood
;
drug therapy
;
genetics
;
mortality
;
Male
;
Middle Aged
;
Molecular Targeted Therapy
;
Mutation, Missense
;
Prognosis
2.Prognostic Factors Associated with Survival in Patients with Primary Duodenal Adenocarcinoma.
Woo Chul CHUNG ; Chang Nyol PAIK ; Sung Hoon JUNG ; Kang Moon LEE ; Sang Woo KIM ; U Im CHANG ; Jin Mo YANG
The Korean Journal of Internal Medicine 2011;26(1):34-40
BACKGROUND/AIMS: The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. METHODS: From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. RESULTS: The median survival was 5.7 months. The survival rate was 46.7% (14/30), 16.7% (5/30), 10% (3/30), and 6.7% (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-directed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). CONCLUSIONS: The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treatments improved patient survival.
Adenocarcinoma/*mortality/pathology/therapy
;
Adult
;
Aged
;
Aged, 80 and over
;
Duodenal Neoplasms/*mortality/pathology/therapy
;
Female
;
Hospice Care
;
Humans
;
Male
;
Middle Aged
;
Neoplasm Staging
;
Prognosis
3.Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma.
Jie YANG ; Keng SHEN ; Jinhui WANG ; Jiaxin YANG ; Dongyan CAO
Journal of Gynecologic Oncology 2016;27(4):e40-
OBJECTIVE: To evaluate whether adjuvant simple hysterectomy after concurrent chemoradiotherapy (CCRT) improves progression-free survival (PFS) compared with current standard care in locally advanced cervical adenocarcinoma (LACAC). METHODS: We reviewed a cohort of 55 patients with LACAC (International Federation of Gynecology and Obstetrics [FIGO] stage IB2, IIA2, IIB, III without distant metastasis) diagnosed and treated with radical CCRT at Peking Union Medical College Hospital between January 2004 and October 2014. We compared 34 patients who underwent adjuvant extrafascial hysterectomy with 21 patients with standard care after CCRT. The primary outcome was PFS. Overall survivals (OS) between the two groups were also compared. Surgery feasibility, operative complications, and pathologic features after radiation therapy were also analyzed. RESULTS: PFS was significantly improved in surgery group (log-rank p=0.0097; hazard ratio [HR], 0.3431; 95% CI, 0.152 to 0.772), as were OS (log-rank p=0.0419; HR, 0.3667; 95% CI, 0.139 to 0.964). Analysis of stage IIB demonstrates a similar result. There were no severe complications related to postradiation surgery in this series. The mean blood loss was less in laparoscopic group than those in the open group (87 mL vs. 208 mL, p=0.036, Mann-Whitney U-test). Approximately 47% patients (16/34) had pathologic residue tumor on hysterectomy specimens. About 94% patients (32/34) got complete remission after adjuvant surgery. CONCLUSION: Adjuvant hysterectomy after CCRT improves survival outcome for patients with LACAC compared with current standard care. Extrafascial hysterectomy is sufficient in tumor reduction and laparoscopic procedure may be more promising with lower blood loss and expedite recovery.
Adenocarcinoma/mortality/*therapy
;
Adult
;
*Chemoradiotherapy
;
Cohort Studies
;
Disease-Free Survival
;
Female
;
Humans
;
Hysterectomy/*methods
;
Middle Aged
;
Uterine Cervical Neoplasms/mortality/*therapy
4.Extrafascial hysterectomy after concurrent chemoradiotherapy in locally advanced cervical adenocarcinoma.
Jie YANG ; Keng SHEN ; Jinhui WANG ; Jiaxin YANG ; Dongyan CAO
Journal of Gynecologic Oncology 2016;27(4):e40-
OBJECTIVE: To evaluate whether adjuvant simple hysterectomy after concurrent chemoradiotherapy (CCRT) improves progression-free survival (PFS) compared with current standard care in locally advanced cervical adenocarcinoma (LACAC). METHODS: We reviewed a cohort of 55 patients with LACAC (International Federation of Gynecology and Obstetrics [FIGO] stage IB2, IIA2, IIB, III without distant metastasis) diagnosed and treated with radical CCRT at Peking Union Medical College Hospital between January 2004 and October 2014. We compared 34 patients who underwent adjuvant extrafascial hysterectomy with 21 patients with standard care after CCRT. The primary outcome was PFS. Overall survivals (OS) between the two groups were also compared. Surgery feasibility, operative complications, and pathologic features after radiation therapy were also analyzed. RESULTS: PFS was significantly improved in surgery group (log-rank p=0.0097; hazard ratio [HR], 0.3431; 95% CI, 0.152 to 0.772), as were OS (log-rank p=0.0419; HR, 0.3667; 95% CI, 0.139 to 0.964). Analysis of stage IIB demonstrates a similar result. There were no severe complications related to postradiation surgery in this series. The mean blood loss was less in laparoscopic group than those in the open group (87 mL vs. 208 mL, p=0.036, Mann-Whitney U-test). Approximately 47% patients (16/34) had pathologic residue tumor on hysterectomy specimens. About 94% patients (32/34) got complete remission after adjuvant surgery. CONCLUSION: Adjuvant hysterectomy after CCRT improves survival outcome for patients with LACAC compared with current standard care. Extrafascial hysterectomy is sufficient in tumor reduction and laparoscopic procedure may be more promising with lower blood loss and expedite recovery.
Adenocarcinoma/mortality/*therapy
;
Adult
;
*Chemoradiotherapy
;
Cohort Studies
;
Disease-Free Survival
;
Female
;
Humans
;
Hysterectomy/*methods
;
Middle Aged
;
Uterine Cervical Neoplasms/mortality/*therapy
5.Clinical observation of young, middle-aged and elderly women with endometrial carcinoma.
Fu-rong DAI ; Guo-qing PENG ; Yi ZHANG ; Cheng-xiang CHEN
Journal of Central South University(Medical Sciences) 2005;30(6):690-693
OBJECTIVE:
To explore the clinical features, diagnosis, treatment and prognosis of endometrial carcinoma in young, middle-aged and elderly women.
METHODS:
We retrospectively analyzed the clinical data of 82 cases of endometrial carcinoma in young, middle-aged women and 33 cases of endometrial cacinoma in elderly women.
RESULTS:
The rates of adenocarcinoma in young, middle-aged and elderly groups were 74.4% and 75.5%, respectively. The young,middle-aged and elderly patients with Stage I endometrial cancer were 64.6% and 69.7%, and those with Stage III and IV were 15.9% and 15.2%, respectively. The histological Grade 1 carcinoma of endometrium in young,middle-aged and elderly women were 70.7% and 60.6%, respectively. The young, middle-aged women without myometrial invasion were more than the elderly women (42.8% vs 15.6%, P < 0.01). The young, middle-aged women with myometrial invasion more than half of myometrial wall were less than the elderly women (10.4% vs 40.6%, P < 0.01). The rate of chemical treatment after the surgery in the elderly women was more than that of the young, middle-aged women (P < 0.05). The 5-year survival rate of the young, middle-aged women was obviously higher than that of the elderly women (92.79% vs 72.21%, P < 0.05).
CONCLUSION
Adenocarcinoma and well-differentiated cells are the main pathological characteristics of endometrial carcinoma both in the young, middle-aged and the elderly women. Most young, middle-aged and el-derly patients can be diagnosed and treated in the early stage. Early diagnosis and reasonable treatment can improve the prognosis. The prognosis of the young, middle-aged patients is obviously better than that of the elderly patients, and the myometrial invasion depth may be the main difference.
Adenocarcinoma
;
diagnosis
;
mortality
;
therapy
;
Age Factors
;
Aged
;
Endometrial Neoplasms
;
diagnosis
;
mortality
;
therapy
;
Female
;
Humans
;
Middle Aged
;
Prognosis
;
Retrospective Studies
;
Survival Rate
6.Effect of neoadjuvant chemotherapy on cervical carcinoma.
Lanqin CAO ; Xin LI ; Xinguo LI ; Yi ZHANG
Journal of Central South University(Medical Sciences) 2009;34(6):527-530
OBJECTIVE:
To investigate the effect of neoadjuvant chemotherapy on cervical carcinoma and its association with clinical data.
METHODS:
A total of 97 patients with stage Ib2 approximately IIIa of cervical cancinoma were treated with neoadjuvant chemotherapy. The effect of chemotherapy, factors associated with outcome of chemotherapy, and histology were analyzed.
RESULTS:
Effective rate of chemotherapy was 86.6% which was associated with clinical stage and histology. Eight-four patients received radical hysterectomy. The histological grade of 17 patients was lowered, lymph nodes in 19 patients were positive, and 6 patients had parametrium invasion. One patient died within 1 year after the operation, and 5 patients recurred.
CONCLUSION
The effect of neoadjuvant chemotherapy for locally advanced cervical cancinoma is good. Surgery after chemotherapy can improve the prognosis and 5-year survival rate.
Adenocarcinoma
;
drug therapy
;
mortality
;
surgery
;
Adult
;
Carcinoma, Squamous Cell
;
drug therapy
;
mortality
;
surgery
;
Female
;
Humans
;
Middle Aged
;
Neoadjuvant Therapy
;
methods
;
Prognosis
;
Survival Rate
;
Uterine Cervical Neoplasms
;
drug therapy
;
mortality
;
surgery
7.Endoscopic Resection for Synchronous Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma in Early Stage Is a Possible Alternative to Surgery.
Se Jeong PARK ; Ji Yong AHN ; Hwoon Yong JUNG ; Shin NA ; So Eun PARK ; Mi Young KIM ; Kwi Sook CHOI ; Jeong Hoon LEE ; Do Hoon KIM ; Kee Don CHOI ; Ho June SONG ; Gin Hyug LEE ; Jin Ho KIM ; Seungbong HAN
Gut and Liver 2015;9(1):59-65
BACKGROUND/AIMS: We investigated the clinical outcomes according to the method of treatment in synchronous esophageal and gastric cancer. METHODS: Synchronous esophageal squamous cell carcinoma and gastric adenocarcinoma were diagnosed in 79 patients between 1996 and 2010. We divided the patients into four groups according to treatment; Group 1 received surgical resection for both cancers or surgery for gastric cancer with chemoradiotherapy for esophageal cancer (n=27); Group 2 was treated by endoscopic resection with or without additional treatment (n=14); Group 3 received chemoradiotherapy only (n=18); and Group 4 received supportive care only (n=20). RESULTS: The median survival times in groups 1 and 2 were 86 and 60 months, respectively. The recurrence rate and mortality were 23% and 48%, respectively, in group 1 and 21% and 4%, respectively, in group 2. The median survival time was 12 months in group 3 and 9 months in group 4. Multivariate analysis showed that age (p<0.001) and treatment group (p=0.019) were significantly associated with death. Compared with group 1, treatment in the intensive care unit (p=0.003), loss of body weight (p=0.042), and decrease in hemoglobin (p=0.033) were worse in group 1. CONCLUSIONS: Endoscopic resection for synchronous esophageal and gastric cancer could be considered as a possible alternative to surgery for early-stage cancer.
Adenocarcinoma/mortality/*surgery/therapy
;
Aged
;
Carcinoma, Squamous Cell/mortality/*surgery/therapy
;
Combined Modality Therapy
;
Endoscopy, Gastrointestinal/*methods
;
Esophageal Neoplasms/mortality/*surgery/therapy
;
Female
;
Humans
;
Male
;
Middle Aged
;
Neoplasms, Multiple Primary/mortality/*surgery/therapy
;
Nutritional Status
;
Risk Factors
;
Stomach Neoplasms/mortality/*surgery/therapy
;
Survival Analysis
8.Third-line docetaxel chemotherapy for recurrent and metastatic gastric cancer.
Ji Hyun LEE ; Sung Hyun KIM ; Sung Yong OH ; Suee LEE ; Hojin LEE ; Hye Jung LEE ; Hyo Jin KIM
The Korean Journal of Internal Medicine 2013;28(3):314-321
BACKGROUND/AIMS: To determine the efficacy and toxicity of docetaxel as a third-line therapy for patients with relapsed gastric cancer who have undergone modified oxaliplatin-fluorouracil (m-FOLFOX)-4 and modified irinotecan-fluorouracil (m-FOLFIRI) regimens. METHODS: We analyzed 33 patients who had been histologically diagnosed with adenocarcinoma of the stomach and who had progressed after m-FOLFOX-4 and m-FOLFIRI regimens. Patients were treated with cycles of 75 mg/m2 docetaxel on day 1 every 3 weeks. RESULTS: The median age of the patients was 56.0 years (range, 31.0 to 74.0), and 73% of the patients (24/33) had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients were evaluated in terms of tumor response: five (15%), nine (27%), and 19 (58%) patients experienced a partial response, stable disease, and progressive disease, respectively. The median time to progression was 2.1 months (95% confidence interval [CI], 1.63 to 2.58), and overall survival was 4.7 months (95% CI, 3.20 to 6.20), from the start of the docetaxel regimen. Assessing patients' toxicity profiles, the median number of cycles was 2.0 (range, 1.0 to 12.0). The major hematologic toxicities included grade 3 to 4 neutropenia (19/33, 58%), grade 3 to 4 thrombocytopenia (2/33, 6%), and grade 3 to 4 anemia (5/33, 15%). Neutropenic fever developed in three patients (3/33, 9%). The nonhematological toxicities were nausea and vomiting (10/33, 30%), abdominal pain (4/33, 12%), skin rash (1/33, 3%), and fluid retention (3/33, 9%). CONCLUSIONS: Docetaxel is a feasible third-line therapy regimen for patients with advanced gastric cancer after m-FOLFIRI and m-FOLFOX-4 regimens.
Adenocarcinoma/*drug therapy/mortality
;
Adult
;
Aged
;
Antineoplastic Agents/adverse effects/*therapeutic use
;
Antineoplastic Protocols
;
Female
;
Humans
;
Male
;
Middle Aged
;
Neoplasm Recurrence, Local/*drug therapy
;
Republic of Korea/epidemiology
;
Salvage Therapy
;
Stomach Neoplasms/*drug therapy/mortality
;
Taxoids/adverse effects/*therapeutic use
9.Efficacy of Low-dose Paclitaxel and Cisplatin in Patients with Advanced Non-Small Cell Lung Cancer.
Byung Su KIM ; Do Youn OH ; Yo Han JOH ; Do Yeun KIM ; Jee Hyun KIM ; Se Hoon LEE ; Dae Ho LEE ; Tae You KIM ; Dae Seog HEO ; Yung Jue BANG ; Noe Kyeong KIM
Cancer Research and Treatment 2001;33(6):469-473
PURPOSE: To evaluate the efficacy and toxicity of combination chemotherapy with low-dose paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. MATERIALS AND METHODS: Chemotherapy-naive patients with unresectable, pathologically proven non-small cell lung cancer were eligible for inclusion in the study. Patients received paclitaxel (145 mg/m2 iv 3 hour D1) and cisplatin (60 mg/m2 iv D1) every 3 weeks. RESULTS: Forty-two patients were enrolled between February 2000 and February 2001. The median age was 53.5 years. Patients with adenocarcinoma numbered 29, squamous cell carcinoma 7, large cell carcinoma 3, and undifferentiated carcinoma 3. Seventeen patients had stage IIIB, 19 had stage IV disease and the remaining 6 displayed recurred disease after previous surgical resection. Four patients terminated treatment early because of hypersensitivity (1) and severe emesis (3). Of the 38 evaluable patients, 14 had PR and the response rate was 36.8%. Among partial responders, 6 patients received additional chest radiation. The median duration of response was 47.9 weeks and the median overall survival was 54.0 weeks. Of the total 176 courses, 14 were delayed, 22 required dose reduction, and grade 3~4 neutropenia occurred in 5.6% of courses. Only one episode of neutropenic fever developed and there were no treatment- related mortalities. Other toxicities were generally mild. CONCLUSION: The combination chemotherapy with low-dose paclitaxel and cisplatin was effective and tolerable in patients with advanced non-small cell lung cancer.
Adenocarcinoma
;
Carcinoma
;
Carcinoma, Large Cell
;
Carcinoma, Non-Small-Cell Lung*
;
Carcinoma, Squamous Cell
;
Cisplatin*
;
Drug Therapy
;
Drug Therapy, Combination
;
Fever
;
Humans
;
Hypersensitivity
;
Mortality
;
Neutropenia
;
Paclitaxel*
;
Thorax
;
Vomiting
10.Clinical features and treatment of 49 patients with anal canal adenocarcinoma.
Li-ren LI ; De-sen WAN ; Zhi-zhong PAN ; Zhi-wei ZHOU ; Gong CHEN ; Xiao-jun WU ; Zhen-hai LU ; Pei-rong DING
Chinese Journal of Gastrointestinal Surgery 2006;9(5):402-404
OBJECTIVETo investigate the clinical features and treatment of anal canal adenocarcinoma.
METHODSClinical data of 49 patients with anal canal adenocarcinoma treated in our hospital from January 1965 to March 2002 were analyzed retrospectively.
RESULTSThe ratio of male to female was 1.3. The median age was 56 years old. Anal bleeding, tapering stool and anal lump were the most common symptoms. Chronic perianal diseases were complicated in 36.7% of the cases. The median follow-up was 66 months. Local recurrence and inguinal lymph node metastasis were found in 7 cases respectively, lung metastasis in 2, supraclavicular and mediastinal metastasis in 1 respectively. The 3-year survival rates in the patients with resection alone, radiochemotherapy alone, resection combined with radiochemotherapy, and without any treatment were 41.3%, 20.0%, 56.3% and 15.0%, respectively, and the 5-year survival rates were 34.4%, 0, 37.5%, 0, respectively.
CONCLUSIONSAnal canal adenocarcinoma is a rare and fatal malignancy. Abdomino-perineal resection combined with postoperative radiochemotherapy is the principal treatment.
Adenocarcinoma ; diagnosis ; mortality ; pathology ; therapy ; Adult ; Aged ; Aged, 80 and over ; Anal Canal ; pathology ; Anus Neoplasms ; diagnosis ; mortality ; pathology ; therapy ; Combined Modality Therapy ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Survival Rate ; Young Adult