Repeat 18F-FDG PET for monitoring neoadjuvant chemotherapy in patients with stage III non-small cell lung cancer

PURPOSE: The relevance of (18)F-FDG PET for staging non-small cell lung cancer (NSCLC), in particular for the detection of lymph node or distant metastases, has been shown in several studies. The value of FDG-PET for therapy monitoring in NSCLC, in contrast, has not yet been sufficiently analysed. Aim of this study was to evaluate FDG-PET for monitoring treatment response during and after neoadjuvant radiochemotherapy (NARCT) in advanced NSCLC. METHODS: Sixty-five patients with histologically proven NSCLC stage III initially underwent three FDG-PET investigations, during NARCT prior to initiating radiation, and post-NARCT. Changes of FDG-uptake in the primary tumour at two time-points during NARCT were analysed concerning their impact on long-term survival. RESULTS: The mean maximum FDG uptake (standardized uptake value, SUVmax) of the whole group decreased significantly during NARCT (SUVmax PET 1: 14.9+/-4.0, SUVmax PET 3: 5.5+/-2.4, p=0.004). The difference between initial FDG uptake (PET 1) and uptake after induction chemotherapy (PET 2) was found to be highly predictive for long-term survival patients which had a greater than 60% decreases in their SUV change had a significantly longer survival than those below this threshold (5-year-survival 60% versus 15%, p=0.0007). Patients who had a lower than 25% decrease in their SUV change had a 5-years-survival lower than 5%. Furthermore, the difference between initial FDG uptake (PET 1) and uptake after completion of the whole NARCT (PET 3) was predictive for survival when 75% was applied as cut-off (p=0.02). However, the level of significance was considerably lower. CONCLUSION: FDG-PET is suitable for therapy monitoring in patients with stage III NSCLC. The decrease of FDG uptake during induction chemotherapy is highly predictive for patient outcome.     

Correlation of early PET findings with tumor response to molecular targeted agents in patients with advanced driver-mutated non-small cell lung cancer

Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST. FDG uptake was evaluated as the maximum standardized uptake value (SUVmax) of each targeted lesion. SUVmax decreased in all lesions after therapy (mean SUVmax 8.3 ± 3.4 before to 3.7 ± 1.8 after therapy, p < 0.05). The % decrease in SUVmax of each lesion was significantly correlated with the % tumor size reduction (r = 0.44). In addition, the reduction rate of SUVmax in metastatic bone lesions after initiation of molecular targeted therapy was significantly lower than that in targeted organs (27.1 ± 27.5 vs. 51.2 ± 21.3%, respectively, p < 0.05). Early reduction in FDG-PET uptake after initiation of molecular targeted agents was able to predict subsequent tumor reduction in patients harboring EGFR-mutated or ALK-positive NSCLC. In addition, nontargeted bone metastasis may have different glucose metabolism after TKI treatment compared with other involved organs.     

Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization

BACKGROUND: This study was designed to investigate the fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging characteristics of triple-negative (estrogen receptor-negative [ER-]/progesterone receptor-negative [PR-]/HER2-negative [HER2-]) breast carcinoma and compare the results with characteristics of ER+/PR+/HER2- breast carcinomas, which usually carry a favorable prognosis. METHODS: Patients with newly diagnosed breast carcinoma who had undergone dual-time-point FDG-PET before any therapeutic intervention and were identified as either ER-/PR-/HER2- or ER+/PR+/HER2- (the control group) on histopathology of the surgical specimen, were considered candidates for inclusion in this analysis. These patients underwent FDG-PET as a component of a prospective study that evaluated the role of multimodality imaging for characterizing primary breast lesions and locoregional staging. Breast cancer lesions were imaged twice at approximately 63 minutes and 101 minutes after the administration of FDG. Maximum standardized uptake values (SUVmax) were measured at both time points (SUVmax1 and SUVmax2) to analyze the data generated. After FDG-PET imaging, the patients underwent either breast-conserving surgery or mastectomy, and histopathology reports were used to provide the definitive diagnosis against which the PET study results were compared. RESULTS: In total, 88 patients with breast cancer (29 patients with 'triple-negative' breast cancer and 59 patients with ER+/PR+/HER2- breast malignancies) were selected among 206 individuals who were enrolled in the study protocol. The 'triple-negative' group comprised 14.08% of the total study population. The age of the patients with this subtype of tumor ranged from 33 years to 75 years (mean age+/-standard deviation, 51.6 +/- 10.1 years), and tumors in this subgroup ranged in size from 0.9 cm to 6 cm (mean size, 1.99 cm). Among the histopathologic subtypes, 25 tumors were infiltrating ductal carcinoma (86%), and 1 tumor each (3.5% each subtype) was lobular, mixed ductal-lobular, medullary, and tubular. For the calculation of FDG-PET parameters in this group, only patients who had undergone FDG-PET studies before any intervention were considered, and 18 patients in the triple-negative group met this criterion. According to same criterion, a control group of 59 patients with ER+/PR+/HER2- cancer who had focal FDG uptake were selected for comparison with the triple-negative population. The breast cancer lesions were observed as areas with focally enhanced uptake of FDG in all patients (sensitivity, 100%) in the triple-negative group. The mean (+/-standard deviation) SUVmax1 of the primary lesion for the triple-negative group was 7.27 +/- 5.6, the mean SUVmax2 was 8.29 +/- 6.4, and the percentage change in SUVmax (%DeltaSUVmax) was 14.3 +/- 15.8%. In the control group of 59 patients with ER+/PR+/HER2- breast carcinoma, the mean values for SUVmax1, SUVmax2, and %DeltaSUVmax were 2.68 +/- 1.9, 2.84 +/- 2.2, and 3.7 +/- 13.0%, respectively. The mean values for SUVmax1, SUVmax2, and %Dgr;SUVmax in the triple-negative group were significantly higher compared with the values in the nontriple-negative control group (P = .0032, P = .002, and P = .017, respectively). When the 2 subgroups were compared according to tumor size, grade, and stage, the SUVmax1 was significantly higher in the triple-negative group for both size categories (5.4 vs 1.9, P = .006; and 9.2 vs 3.5, P = .04) and for grade 3 tumors (9.1 vs 3.9, P = .022). The %DeltaSUVmax values for patients in the triple-negative group who had tumors that measured < or =2 cm and > 2 cm were 14.8 and 13.8, respectively; and the corresponding values for patients in the control group were 0.6 and 6.7, respectively. Although the mean %DeltaSUVmax clearly was higher in the triple-negative group for both tumor size categories, comparison between the 2 groups demonstrated a statistically significant difference in tumors that measured < or =2 cm (P = .016). The authors also observed that, in the triple-negative group, tumor grades were correlated significantly with the magnitude of SUVmax1 and SUVmax2 (P = .012 and P = .01, respectively). Stage for stage, tumors from the triple-negative group appeared to have a higher mean SUVmax1 compared with tumors from nontriple-negative control group. However, the trend reached statistical significance in patients with stage II disease. CONCLUSIONS: Triple-negative breast tumors were associated with enhanced FDG uptake commensurate with their aggressive biology and were detected with very high sensitivity by using FDG-PET imaging.     

加速康复外科理念在行腹腔镜膀胱根治性切除术患者围术期中应用的临床观察#br#

目的探讨加速康复外科（ERAS）理念在腹腔镜膀胱根治性切除中应用的有效性和安全性。 方法收集2015年6月至2017年6月潍坊市人民医院收治的58例膀胱癌患者,分为传统组（n=28）和ERAS组（n=30）。比较两组患者的手术时间、手术出血量、术后排气时间、术后重度疼痛的发生数、麻醉苏醒时间、盆腔引流时间、术后住院天数以及术后并发症的发生情况。 结果ERAS组和传统组手术时间分别为（1722±379）min和（1873±218）min;术中出血量分别为（1597±465）ml 和（1771±469）ml,差异均无统计学意义（P＞005）。ERAS组和传统组麻醉苏醒时间分别为（254±54）min和（417±98）min;术后排气时间分别为（16±07）d和（22±07）d;盆腔引流时间分别为（25±11）d和（50±16）d;术后住院天数分比为（76±14）d和（110±18）d;术后疼痛VAS评分＞7分发生率分别为100％（3／30）和429％（12／28）;两组差异均有统计学意义（P＜005）。ERAS组1例刀口液化,1例发生肾结石;传统组2例肠梗阻,1例发生坠积性肺炎,1例发生肾结石。两组患者中均无尿瘘患者。 结论加速康复外科理念在腹腔镜下膀胱根治性切除术患者中的临床应用是安全、有效的,可加速患者的术后康复,值得临床推广应用。     

Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB-IV non-small cell lung carcinoma: a prospective randomized study

This study was performed to investigate the utility of FDG-PET for: (1) initial staging, and (2) restaging of the primary and mediastinal nodal lesions 2 weeks after the completion of preoperative chemoradiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Twenty-six patients with histologically confirmed stage III NSCLC were accrued to this study from April 1993 to July 1998. They included 21 with stage IIIA (N2) NSCLC who were enrolled into an institutional phase II study, and 5 patients with a highly selected subset of stage IIIB disease characterized by the presence of microscopic metastatic disease in contralateral mediastinal lymph nodes who were also treated with preoperative chemoradiotherapy; N3 lesions (n=3) and minimal T4 lesions. Demographic characteristics included median age 62 years (a range from 47 to 73) and gender ratio of male 15 to female 11. Histologic types of tumor consisted of squamous cell carcinoma 6, adenocarcinoma 11, large cell carcinoma 5, and non-small cell carcinoma 4. All patients had FDG-PET imaging of the chest before the initiation and 2 weeks after completion of preoperative therapy. The FDG-PET images were evaluated qualitatively for uptake at the primary tumor sites and mediastinal lymph nodes. Standard uptake values (SUVs) were also calculated for the primary tumors and all PET findings were correlated with surgical histopathologic data. Preoperative chemoradiotherapy resulted in complete pathologic response in 8 of 26 primary lesions. By qualitative analysis, 96% of these tumors showed level 3 or 4 uptake before preoperative chemoradiotherapy. After chemoradiotherapy, 57% (15/26) of patients showed at least a one level decrease in uptake, and the sensitivity and specificity of FDG-PET for differentiating residual tumor from pathologic complete response were 67% (12/18) and 63% (5/8). Mean SUV was 14.87+/-7.11 at baseline and decreased to 5.72+/-3.35 after chemoradiotherapy (n=21, P<0.00001). When a value of 3.0 was used as the SUV cut-off, sensitivity and specificity were 88 and 67%, respectively. The mean values of visual intensity were 3.87+/-0.35 and 3.8+/-0.51 for patients who achieved pathologic complete response (n=8) and for those who showed residual cancer after the preoperative therapy (n=18), respectively. The mean SUVs were 16.97+/-8.52 and 14.03+/-6.61 for patients who achieved pathologic complete response (n=6) and for those who showed residual cancer (n=15) after the preoperative therapy, respectively. Therefore, the degree of FDG uptake before preoperative chemoradiotherapy did not provide predictive value for subsequent tumor response. For mediastinal initial staging, the sensitivity and specificity of FDG-PET were 75 and 90.5%. The sensitivity and specificity of FDG-PET for mediastinal restaging were 58.0 and 93.0%. These results indicate that FDG-PET is useful for monitoring the therapeutic effect of neoadjuvant chemoradiotherapy in patients with stage III NSCLC. For the primary lesions, SUV based analysis has high sensitivity but limited specificity for detecting residual tumor. In contrast, for restaging of mediastinal lymph nodes, FDG-PET is highly specific, but has limited sensitivity.     

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.

PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.     

Use of positron emission tomography in localized extremity soft tissue sarcoma treated with neoadjuvant chemotherapy

BACKGROUND: Patients with high-grade soft tissue sarcomas are at high risk of developing local disease recurrence and metastatic disease. [F-18]-fluorodeoxy-D-glucose (FDG) positron emission tomography (PET) scans are hypothesized to detect histopathologic response to therapy and to predict risk of tumor progression in patients with various malignancies. Serial FDG-PET scans were taken to determine the correlation between FDG uptake and patient outcomes in patients receiving multimodality treatment of extremity sarcomas. METHODS: Forty-six patients with high-grade localized sarcomas were studied. The maximum standardized uptake values (SUVmax) of tumors were measured before receipt of neoadjuvant chemotherapy and again before surgery. Resected specimens were examined for residual viable tumor. Patients were followed up at least annually for evidence of local and distant recurrence of disease and survival. RESULTS: Patients with a baseline tumor SUVmax >/= 6 and < 40% decrease in FDG uptake were at high risk of systemic disease recurrence estimated to be 90% at 4 years from the time of initial diagnosis. Patients whose tumors had a >/= 40% decline in the SUVmax in response to chemotherapy were at a significantly lower risk of recurrent disease and death after complete resection and adjuvant radiotherapy. CONCLUSIONS: The FDG-PET scan was found to be a useful method with which to predict the outcomes of patients with high-grade extremity soft tissue sarcomas treated with chemotherapy. The pretreatment tumor SUVmax and change in SUVmax after neoadjuvant chemotherapy independently identified patients at high risk of tumor recurrence. The FDG-PET scan showed promise as a tool to identify the patients with sarcoma who are most likely to benefit from chemotherapy.     

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.     

Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?

BACKGROUND: The aim of this study was to evaluate the accuracy of computed tomography (CT) and [(18)F]fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients after completion of therapy. PATIENTS AND METHODS: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44 aggressive NHL patients (29 women, 72 men; aged 41+/-14 years) in a median of 2 months after therapy. Progression-free survival was evaluated using the Kaplan-Meier method. Independent prognostic factors were identified by means of Cox proportional hazards model. RESULTS: CT imaging results were progressive disease (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24 patients. Three-year progression-free survival rates after exclusion of five PD patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21% (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and bulky disease (P <0.05) were identified as independent prognostic variables. CONCLUSIONS: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated those destined to progress into a low risk of < or =20% and a high risk for recurrence of > or =80%.     

Phase II study of nedaplatin and irinotecan followed by gefitinib for elderly patients with unresectable non-small cell lung cancer

PURPOSE: We conducted a phase II study of combination chemotherapy with nedaplatin (NP) and irinotecan (CPT) followed by gefitinib to determine the effects and toxicities in patients 70 years or older with unresectable non-small cell lung cancer (NSCLC). METHODS: Eligible patients were entered to receive 3 courses of 50 mg/m(2) NP and 60 mg/m(2) CPT on days 1 and 8 every 4 weeks and sequential gefitinib 250 mg po once a day was followed until tumor progression. RESULTS: Twenty-eight patients received NP and CPT combination chemotherapy. One patient achieved CR, 10 PR, 14 SD and 3 PD, and the response rate was 39.3%. Twenty-one patients received gefitinib 250 mg per day until tumor progression after completion of the NP and CPT chemotherapy. Two patients with SD after NP and CPT chemotherapy achieved PR. For the 3-drug combination, there were 13 responders and the overall response rate was 42.9%. Of the toxicities associated with NP and CPT chemotherapy, grade 4 neutropenia, and grade 3 febrile neutropenia were observed in 24 (33.8%) and 3 (4.2%) courses, respectively. Of the toxicities associated with gefitinib treatment, grade 3 anemia, and SGOT and SGPT elevation were observed in one patient (4.8%) each, respectively. The median survival time was 8.7 months, and the 1- and 2-year survival rates were 42.9 and 32.1%, respectively. CONCLUSION: NP and CPT followed by gefitinib is feasible for elderly patients with unresectable NSCLC.     

Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET

Purpose: To evaluate the use of positron emission tomography using ¹⁸F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. Material and methods: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with ≤2?cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n?=?26) and 2 weeks after initiation of therapy (n?=?17). FDG uptake was quantitatively assessed by standardized uptake values. Results: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median ?44% (?75 to 2); in non-responders, it decreased by a median of ?15% (?46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. Conclusion: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.     

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.     

Metabolic flare: indicator of hormone responsiveness in advanced breast cancer.

PURPOSE: The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [(18)F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[(18)F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS: Forty women with biopsy-proved advanced ER-positive (ER(+)) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS: In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% +/- 23.3% (mean +/- SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% +/- 16.2%; P =.0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 +/- 2.4) than those of nonresponders (SUV, 1.8 +/- 1.3; P =.0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% +/- 14.2%) than in the nonresponders (mean percentage decrease, 19.4% +/- 17.3%; P =.0003). CONCLUSION: The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER(+) breast cancer.     

吉非替尼治疗晚期复治性非小细胞肺癌的临床研究

目的探讨应用吉非替尼(IRESSA)治疗晚期非小细胞肺癌(NSCLC)患者的疗效及其对生活质量的影响。方法既往化疗失败的Ⅲb-Ⅳ期NSCLC患者41例,其中二线化疗失败者占85.4%(35/41)。IRESSA 250 mg口服,每日1次,服药至病情进展或出现不能耐受的不良反应。患者分别在治疗后1个月、2个月和以后每3个月复查。结果本组41例患者均可评价疗效,其中PR 18例,SD 14例,PD 9例,有效率为43.9%(18/41),疾病控制率(PR SD)为78.0%(32/41)。男性患者和女性患者的有效率分别为42.1%和45.5%(P>0.05)。至随访结束,41例患者中,有22例(53.7%)存活,其中位生存时间(MST)为10.1个月;19例死亡患者的疾病进展时间(TTP)为2.7个月,MST为5.0个月;PR患者的MST为13.3个月。全组患者症状改善率为78.0%。服药28 d,KPS评分提高20±5分,无Ⅲ-Ⅳ度毒性反应。结论IRESSA单药对化疗失败的晚期NSCLC疗效确切,并可用于一般状况评分较差的患者,其不良反应轻,是二三线用药的良好选择。     

The administration of gefitinib in patients with advanced non-small-cell lung cancer after the failure of erlotinib

Purpose

Recent studies have demonstrated that erlotinib therapy may be considered an option for patients with advanced non-small-cell lung cancer who experienced disease progression after treatment with gefitinib, particularly in patients in whom the disease had been stabilized for a long time prior to gefitinib therapy. The aim of this study was to evaluate the disease control rate and toxicity of gefitinib in patients whose disease progressed after erlotinib therapy.

Methods

From May 2005 to August 2006, 15 patients received a 250?mg/day dosage of gefitinib after having disease progression while taking erlotinib at a dose of 150?mg/day.

Results

Among patients who received erlotinib, 1 (7%) achieved a partial response (PR), and 5 (33%) achieved stable disease (SD). Among patients who received gefitinib, none achieved a PR, and 6 achieved SD (40%). Five out of 6 patients who achieved PR/SD with erlotinib also achieved SD with gefitinib; 8 out of 9 patients who achieved a progressive disease (PD) with erlotinib also achieved a PD with gefitinib. The median time to progression (TTP) and overall survival (OS) were 2.3 and 3.5?months, respectively. The TTP and OS in SD patients were 3.7 and 7.4?months, respectively. The most common toxicities of gefitinib were dry skin (grade 1–2) in 27% of patients and acneiform rashes and rashes/desquamation in 20% of patients. Diarrhea (grade 1–2) occurred in 7% of patients.

Conclusions

Our data suggest that patients who achieved PR/SD with erlotinib also benefit from taking gefitinib. Conversely, gefitinib is not recommended in patients whose disease progressed after taking erlotinib.     

FDG PET-CT标准摄取值用于非小细胞肺癌复发的预测价值

目的 探讨非小细胞肺癌(NSCLC)患者治疗前后FDG PET-CT的标准摄取值(SUV)及其变化在预测复发和转移中的作用.方法 48例Ⅲ期NSCLC患者治疗前后均行全身PET-CT检查,并计算出肺部肿瘤病灶感兴趣区的最高标准摄取值(SUVmax),治疗前后SUVmax的变化用ASUV来衡量.结果 最后入组45例,中位随访22.5个月,24例出现局部或区域复发、转移,21例无复发、转移.出现局部或区域复发、转移组治疗前和后SUVmax分别为12.30±3.17和5.35±2.29,无复发、转移组治疗前和后的分别为8.46±3.00和2.82±0.63,前者的SUVmax均高于后者(t前=4.15,P前＜0.01;t后=4.88,P后＜＜0.01).治疗前后SUVmax变化百分率两组间差异无统计学意义(t=1.99,P＞0.05).治疗前SUVmax=9.0时,对复发和转移预测的敏感性、特异性、阳性预测值、阴性预测值分别为92%、62%、73%、87%;治疗后SUVmax=4.3时,对复发和转移的分别为71%、100%、100%、72%.结论 治疗前后SUVmax高者近期出现复发和转移的可能性较大,可较早预测NSCLC复发的高危人群.NSCLC患者治疗前后SUV值可能是与生存相关的重要预后因素.     

18FDG-PET评价局部晚期和晚期非小细胞肺癌化疗的客观疗效

 目的 前瞻性地探索18-氟脱氧葡萄糖-正电子发射计算机断层扫描（18FDG-PET）的SUV值标准与实体瘤疗效评价标准（RECIST）标准评价非小细胞肺癌（NSCLC）化疗的客观疗效是否具有一致性。方法 初治不可切除的局部晚期和晚期NSCLC患者前瞻性入组，行两周期含铂双药方案全身化疗。按RECIST标准和SUV值标准（2个周期化疗后SUV值下降大于30 %）互为盲法分别评价肿瘤客观疗效。用配对计数资料的χ2检验和κ系数检验比较18FDG-PET代谢缓解与RECIST标准的客观疗效是否具有一致性（SPSS13.0）。结果 不可切除的局部晚期8例，晚期35例。18FDG-PET代谢缓解与按RECIST标准评价的疗效具有明显的一致性（P＜0.001）。18FDG-PET评价NSCLC化疗客观疗效的敏感性、特异性、准确性、阳性预测值和阴性预测值分别是94 %、70 %、80 %、67 %和95 %。结论 18FDG-PET可以评价局部晚期和晚期NSCLC化疗的客观疗效。     

FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer.

AIMS: FDG uptake in NSCLC is related to glucose transporter type 1 (Glut-1) expression. Here, we investigated the direct causal relationship between FDG uptake and Glut-1 expression to determine the role of Glut-1 in FDG uptake by malignant and benign lymph nodes (LNs). METHODS: Fifty-five curative lung resections in 53 NSCLC patients (male:female=36:17, age=62.0+/-11.8 years) were included. Maximum standardized uptake values (maxSUVs) of LNs in preoperative whole body FDG-PET and Glut-1 immunostaining results were compared. RESULTS: Of 316 pathologically confirmed LNs, 12.3% (39/316) were malignant, and in malignant LNs, FDG positive LNs were no different from FDG negative LNs in terms of size (15.0+/-6.7 mm vs 10.0+/-6.1mm, p>0.05), or in terms of the proportion of LNs occupied by tumor (60.0+/-28.8% vs 39.2+/-38.4%, p>0.05), but had greater percentages of Glut-1 positive cells in tumors (74.1+/-31.8% vs 22.7+/-18.7%, p<0.01), and Glut-1 staining intensities (3.4+/-0.9 vs 1.8+/-1.3, p<0.01). FDG negative malignant LNs featured cytoplasmic Glut-1 expression and adenocarcinoma. Glut-1 staining intensities were found to be significantly correlated with the maxSUVs of malignant LNs (rho=0.516, p<0.05), but the percentages of Glut-1 positive cells in tumors were not (r=0.2072, p>0.05). Analysis of FDG positive benign LNs showed that maxSUV was not correlated with degree of follicular hyperplasia, or Glut-1 expression (p>0.05). CONCLUSIONS: Intense Glut-1 immunoreactivity was found to be proportionally related to the degree of FDG uptake by malignant LNs in NSCLC. However, the finding that Glut-1 expression in lymphoid hyperplasia showed no correlation with FDG uptake in benign LNs requires further investigation.     

吉非替尼治疗晚期非小细胞肺癌临床研究

目的观察吉非替尼治疗晚期非小细胞肺癌的疗效及毒副反应。方法30例经放、化疗治疗失败的非小细胞肺癌患者,其中5例肿瘤局限于胸腔内,25例已有远处转移。吉非替尼剂量为250 mg/d,口服,每天1次,全组用药的中位时间为4个月。结果30例患者中,完全缓解1例,部分缓解8例,稳定10例,进展11例。全组有效率30.0%,疾病控制率为63.3%,中位生存期5.3个月（1～18个月）,1年生存率为43.3%。主要毒副作用是皮疹,共发生11例,占36.7%;其他毒副作用为腹泻,转氨酶升高。结论吉非替尼对放、化疗失败的晚期非小细胞肺癌有较好的治疗效果,且毒副反应轻。     

细支气管肺泡癌的FDG-PET影像特点

目的研究细支气管肺泡癌对~(18)氟脱氧葡萄糖(FDG)的摄取特点。方法 1998年12月～2004年10月间,35例细支气管肺泡癌患者术前行FDG-正电子发射体层显像(PET)检查。PET结果用目测法与半定量分析方法判读。半定量分析方法中计算标准摄取值(SUV)。结果所有肿瘤都被FDG-PET探测到,目测法相应部位FDG不同程度浓聚。半定量分析细支气管肺泡癌组织的FDG摄取(SUVmax and SUVmean)高于相应的正常肺组织(SUVlung)(P＜0.001),SUVmax、SUVmean和SUVlung分别为3.14±1.65、2.40±1.34 和0.38±0.08。细支气管肺泡癌SUV与肿瘤大小正相关(P＜0.05)。21例(21／35,60.0％)SUVmean与15例(15／35,42.9％)SU Vmax低于2.5。这21例肿瘤全部被目测法与半定量分析判断为良性。结论 (1)细支气管肺泡癌组织的FDG摄取高于正常肺组织。(2)肿瘤FDG摄取与肿瘤大小有关。(3)很多细支气管肺泡癌病例 FDG-PET检查可呈现假阴性。