Jinming Yu

A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.

Background:Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC). Methods and Materials:A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. Results:Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048). Conclusion:IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

Value of PET/CT versus enhanced CT for locoregional lymph nodes in non-small cell lung cancer ☆

PURPOSE To compare the diagnostic efficacies of integrated (18)F FDG PET/CT images and contrast-enhanced helical CT images in locoregional lymph node metastasis in the patients with non-small cell lung cancer (NSCLC). METHODS From June 2005 to June 2007, 122 potentially operable patients with proven or suspected non-small cell lung cancer underwent integrated PET/CT and contrast-enhanced CT scans followed by surgical nodal staging. The results of reviewing PET/CT and enhanced CT images for the locoregional lymph node metastasis were compared in relation to pathologic findings. RESULTS Preoperative nodal staging was compared with postoperative histopathological staging, 80% (98 of 122) of patients correctly staged, 13% (16 of 122) of patients were overstaged, and 7% (8 of 122) were understaged by PET/CT, while those values for CT were 56% (68 of 122), 26% (32 of 122), and 18% (22 of 122), respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for lymph nodes were 86%, 85%, 85%, 64%, 95%, respectively; compared with 69%, 71%, 70%, 43%, 88% for CT (P=0.000, 0.000, 0.000, 0.001, 0.001, respectively). 81% false-negative interpretations and 72% false-positive interpretations on CT were corrected by PET/CT. 57% false-negative interpretations and 45% false-positive interpretations on PET/CT were corrected by CT. 6 % (9 of 153) positive lymph nodes and 8% (40 of 486) negative nodes at pathology were incorrectly diagnosed both by PET/CT and CT. CONCLUSION Integrated PET/CT improves the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value than enhanced CT in the assessment of locoregional lymph nodes, and provides more efficient and accurate data of nodal staging, with a better effect on diagnosis and therapy in non-small cell lung cancer.

Study of local three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for patients with stage III hepatocellular carcinoma.

The purpose of this study was to evaluate treatment-related toxicity, outcome, patterns of failure, and prognostic factors for patients with stage III unresectable hepatocellular carcinoma (HCC) treated with a combination of local 3-dimensional conformal radiotherapy (3D-CRT) and transcatheter arterial chemoembolization (TACE) under the support of G-CSF. From October 1997 to August 2001, 45 patients with stage III unresectable hepatocellular carcinoma underwent transcatheter arterial chemoembolization with local 3D-CRT. Twenty-seven patients were classified as having stage IIIA disease according to the American Joint Committee on Cancer (AJCC) staging system and 18 were classified as stage IIIB. The mean diameter of the treated hepatic tumor was 8.5 cm. Before 3D-CRT, 2 cycles of transcatheter arterial chemoembolization were prescribed. Forty-eight hours later, the G-CSF was prescribed for 5 days after the completion of every TACE. With the interval of 10 to 14 days after the second cycle of TACE, 3D-CRT was prescribed to all patients with a total dose of 50.4 Gy at 1.8 Gy per fraction 5 days per week. After the completion of 3D-CRT, the additional 2 cycles of TACE were given. All patients were monitored for treatment-related toxicity, outcome, patterns of failure, causes of death, and prognostic factors. Forty-two of 45 patients were treated smoothly with the primary schedule. In a median follow-up period of 27 months, 22 patients were alive and 23 were dead. Progressive disease occurred in 28 patients, including local recurrence alone (4 patients), distant metastases with local recurrence (8 patients), and distant metastases alone (16 patients). Nine patients developed radiation-induced liver disease (RILD). Three patients had treatment-related gastrointestinal bleeding. There were 2 treatment-related deaths, including 1 from RILD and 1 from gastrointestinal bleeding. Complete regression (CR) was observed in 6 patients, partial regression (PR) in 35 patients, and stable disease (SD) in 4 patients. The median overall survival duration from treatment was 23.5 months with a 1-year overall survival rate of 68.5%, a 2-year survival rate of 48.3%, and a 3-year survival rate of 22.6%. The median freedom from progressive disease survival duration from treatment was 25 months with 1-year, 2-year, and 3-year progression-free survival rates of 76.2%, 56.8%, and 42.4%, respectively. The stage of HCC, regional lymph node status, portal vein thrombosis, pretreatment &agr;-fetoprotein level (AFP), and tumor size affected the treatment outcomes significantly. Therefore, for patients with stage III unresectable hepatocellular carcinoma, combined local 3D conformal radiotherapy with transcatheter arterial chemoembolization under the support of G-CSF is an effective treatment protocol. Further research is required to decrease distant metastases and to determine the safe irradiation dose-volume.

Pattern of lymph node metastases and its implication in radiotherapeutic clinical target volume in patients with thoracic esophageal squamous cell carcinoma: A report of 1077 cases

PURPOSE To study the pattern of lymph node metastases after esophagectomy and clarify the clinical target volume (CTV) delineation of thoracic esophageal squamous cell carcinoma (ESCC). METHODS AND MATERIALS Total 1077 thoracic ESCC patients who had undergone esophagectomy and lymphadenectomy were retrospectively examined. The clinicopathologic factors related to lymph node metastasis were analyzed using logistic regression analysis. RESULTS The rates of lymph node metastases in patients with upper thoracic tumors were 16.7% (9/54) cervical, 38.9% (18/54) upper mediastinal, 11.1% (6/54) middle mediastinal, 5.6% (3/54) lower mediastinal, and 5.6% (3/54) abdominal, respectively. The rates of lymph node metastases in patients with middle thoracic tumors were 4.0% (27/680), 3.8% (26/680), 32.9% (224/680), 7.1% (48/680), and 17.1% (116/680), respectively. The rates of lymph node metastases in patients with lower thoracic tumors were 1.0% (5/343), 3.0% (10/343), 22.7% (78/343), 37.0% (127/343), and 33.2% (114/343), respectively. T stage, the length of tumor and the histological differentiation emerged as statistically significant risk factors of lymph node metastases of thoracic ESCC (P < 0.001). CONCLUSIONS T stage, the length of tumor and the histologic differentiation influence the pattern of lymph node metastases in thoracic ESCC. These factors should be considered comprehensively to design the CTV for radiotherapy (RT) of thoracic ESCC. Selective regional irradiation including the correlated lymphatic drainage regions should be performed as well.

Mediastinal lymph nodes staging by 18F-FDG PET/CT for early stage non-small cell lung cancer: A multicenter study

PURPOSE Accurate staging of mediastinal lymph nodes metastases is critical for determining the application of stereotactic body radiation therapy (SBRT) for patients with early stage non-small cell lung cancer (NSCLC). In this multicenter study the accuracy of (18)F-FDG PET/CT to detect lymph node metastases was evaluated for early stage NSCLC. MATERIALS AND METHODS The data from the patients with stage1 NSCLC who received preoperative (18)F-FDG PET/CT staging and radical surgery was retrospectively reviewed of five centers from February 2004 to August 2010. The lymph node metastases were confirmed histopathologically after radical surgery. And the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for PET/CT staging. RESULTS Two hundred patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for lymph node metastases on PET/CT were 44%, 83%, 78%, 29% and 91%, respectively. There were eight and 19 cases positive for lymph node metastases with central (n=62) and peripheral (n=138) NSCLC (P>0.05), respectively. CONCLUSION (18)F-FDG PET/CT was specific in N(0) staging for T(1-2) NSCLC. The NPV was about 91% in clinical N(0) patients, suggested that (18)F-FDG PET/CT may help to accurately stage N(0) patients and thus identify patients for SBRT.

Prognostic value of serial [18F]fluorodeoxyglucose PET-CT uptake in stage III patients with non-small cell lung cancer treated by concurrent chemoradiotherapy.

OBJECTIVE To evaluate (18)FDG PET-CT for the assessment of therapy response and prediction of patient outcome after concurrent chemoradiotherapy (CCRT) for non-small cell lung cancer (NSCLC). METHODS Forty-six patients with pathologically proven stage III NSCLC had 2 serial FDG PET-CT scans, before and during CCRT. The maximum standardized uptake value (SUV(max)) of the primary lung lesion was calculated. The value changes of SUV(max) before and during treatment were calculated according to the following equation: SUV=(SUV(before)-SUV(during))100%/SUV(before). The relationship between changes of the SUV(max) and the therapy response as well as long-term survival was studied in the responsive and non-responsive groups after CCRT. RESULTS Of the 46 enrolled patients, after a medicine follow-up of 2 years, the initial SUV(max) in the responsive and non-responsive groups was 7.59±3.14 and 14.72±4.67, respectively. The SUV(max) during treatment in the two groups was 2.89±1.39 and 9.82±3.31, respectively. Significant difference (P=0.001; P=0.001) in SUV(max) was observed either before or during treatment. Furthermore, the percent change of SUV(max) before and during treatment was 61.91±86.69 and 33.56±90.37, respectively. There was significant difference between these two groups (P=0.007). In addition, the 1-year survival rate in the responsive and non-responsive group was 73% and 69%, respectively. The 2-year survival rate in the two groups was 40% and 37%, respectively. There was significant difference between these two groups (P=0.001). CONCLUSIONS (18)FDG PET-CT is an effective method in the prediction of therapy response in patients with stage III NSCLC. The analysis of percent change of SUV(max) provides additional value in early prediction of therapy response and patient outcome.

Bone metastasis in patients with non-small cell lung cancer: The diagnostic role of F-18 FDG PET/CT

PURPOSE To evaluate the performance of F-18 FDG PET/CT in the detection of bone metastasis in non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS Three hundred and sixty-two consecutive NSCLC patients who underwent F-18 FDG PET/CT scanning were retrospectively analyzed. Each image of PET/CT, combined CT, and PET was performed at 10 separate areas and interpreted blindly and separately. The sensitivity, specificity and accuracy of F-18 FDG PET/CT, combined CT and F-18 FDG PET were calculated and the results were statistically analyzed. RESULTS Bone metastasis was confirmed in 82 patients with 331 positive segments based on the image findings and clinical follow-up. On patient-based analysis, the sensitivity of F-18 FDG PET/CT (93.9%) was significantly higher than those of combined CT (74.4%) and F-18 FDG PET (84.1%), respectively (p<0.05). The overall specificity and accuracy of combined CT, F-18 FDG PET, and F-18 FDG PET/CT were 90.7%, 93.2%, 98.9% and 87.0%, 91.2%, and 97.8%, respectively (compared with PET/CT, p<0.05). On segment-based analysis, the sensitivity of the three modalities were 79.5%, 94.3%, and 98.8%, respectively (compared with PET/CT, p<0.05). The overall specificity and accuracy of the three modalities were 87.9%, 89.2%, 98.6% and 84.5%, 91.2%, 98.7%, respectively (compared with PET/CT, p<0.05). CONCLUSION F-18 FDG PET/CT is superior to F-18 FDG PET or combined CT in detecting bone metastasis of NSCLC patients because of the complementation of CT and PET. It is worth noting that the added value of F-18 FDG PET/CT may beneficially impact the clinical management of NSCLC.

Serial hypoxia imaging with 99mTc-HL91 SPECT to predict radiotherapy response in nonsmall cell lung cancer.

Objective:To evaluate the relationship between 99mTc-HL91 (99mTc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) SPECT (single photon emission computed tomography) hypoxia imaging and the treatment outcome and also to assess changes in tumor oxygenation during the course of radiotherapy. Methods:There were 32 patients enrolled in the study with pathologically proven nonsmall cell lung cancer that received 3-dimensional conformal radiotherapy. A 99mTc-HL91 SPECT scan was performed in all patients 1 or 2 days before radiotherapy and repeated during and after radiotherapy completion in 18 patients. The radioactivity ratios of tumor to normal tissue (T/N) were calculated. Results:The relationship between T/N ratios at 4 hours images after injection that was shown as the best of 3 acquired images before radiotherapy and tumor response and over survival were analyzed for all 32 patients. The results of 99mTc-HL91 imaging of 32 patients correlate well with tumor response (P = 0.002) and also patient survival (P = 0.043). The T/N ratios of 18 patients were decreased before, during and after radiotherapy and there was significant statistic difference (P = 0.000...). Conclusions:HL91 SPECT imaging identified the hypoxia status and changes during radiotherapy in lung cancer. It was confirmed that hypoxia imaging with HL91 SPECT before radiotherapy may predict tumor response and patient survival.

Imaging proliferation of 18F-FLT PET/CT correlated with the expression of microvessel density of tumour tissue in non-small-cell lung cancer

PurposeThe aim of this study was to analyse the correlation between 18F-labelled 3′-deoxy-3′-fluorothymidine (18F-FLT) PET/CT proliferation images and tumour angiogenesis as reflected by intratumoral microvessel density (MVD) in non-small-cell lung cancer (NSCLC) to provide a noninvasive method to predict the response to antiangiogenic therapy.MethodsA total of 68 patients with proven or suspected NSCLC underwent FLT PET/CT scans followed by surgery. PET/CT images were compared with pathology. Tumour proliferation was evaluated in terms of a Ki-67 labelling index (Ki-67 LI). MVD was determined using an anti-CD31 mAb (CD31-MVD), anti-CD34 mAb (CD34-MVD) and an anti-CD105 mAb (CD105-MVD) for each resected tumour.ResultsTumour FLT maximum standardized uptake values (SUVmax) were significantly correlated with the Ki-67 LI and CD105-MVD (r = 0.550 and 0.633, P = 0.000 and 0.000, respectively), but were only marginally correlated with the CD31-MVD and CD34-MVD (r = 0.228 and 0.235, P = 0.062 and 0.054, respectively). The FLT PET false-negative patients had a longer median survival time than the FLT PET true-positive patients (log rank test, P = 0.012). The patients with a lower CD105-MVD had a longer median survival time than those with a higher CD105-MVD (P = 0.046), while patients with a lower CD31-MVD and CD34-MVD did not have a longer median survival time than those with a higher value (P = 0.438 and 0.187, respectively).ConclusionFLT PET/CT imaging correlated with tumour angiogenesis as reflected by CD105-MVD and prognosis, and may be helpful in assessing antiangiogenic therapy of NSCLC.

The prognostic value of 18F-fluorodeoxyglucose uptake by using serial positron emission tomography and computed tomography in patients with stage III nonsmall cell lung cancer.

Objectives:To determine the prognostic value of standardized uptake value (SUV) of 18F-fluorodeoxyglucose by serial positron emission tomography and computed tomography (PET/CT) in nonsmall cell lung cancer (NSCLC). Methods:Forty-seven patients (37 male, 10 female) with NSCLC in stage III were enrolled. All patients had at least 2 serial 18F-fluorodeoxyglucose PET/CT scans, both before and after therapy, and the maximum standardized uptake value (SUVmax) of the primary lung lesion was calculated. The value changes of SUVmax before and after treatment were calculated according to the following equation: &Dgr;SUV = (SUVbefore − SUVafter) × 100%/SUVbefore. Results:Of the 47 eligible patients, after a median follow-up of 23.5 months (range, 13–34 months), 26 patients had local and regional recurrence or metastasis and 21 remained disease-free. Significant differences in SUVmax were observed either before (P1 = 0.003) or after (P2 = 0.002) treatment between the 2 groups. However, the percent change of SUVmax before and after therapy were not significantly different (P = 0.054). Conclusions:SUV from 2 serial PET/CT scans, before and after concurrent chemoradiotherapy were significant predictors for local and regional recurrence or metastasis. SUV is a significant predictor for local and regional recurrence or metastasis in patients of NSCLC.