X. Meng

Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of central nerve system metastases from non-small cell lung cancer.

Brain metastases (BM) are common and disastrous occurrence in patients with non-small cell lung cancer (NSCLC). Currently increasing studies suggest remarkable efficacy and mild toxicity of the epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) in these patients, making targeted therapy an attractive option to BM from NSCLC. We here present a review about the use of EGFR-TKIs in this context and the following questions would be discussed: Are TKIs capable of permeating across brain-blood barrier (BBB)? How to boost exposure of EGFR TKI in cerebrospinal fluid to overcome the resistance of refractory metastases? Would the combination with other treatment like radiotherapy bring about advanced effect? And which patients with BM is the fittest population to EGFR-TKI treatment? In fact, though the administration of EGFR TKI only could achieve certain effect with limited penetration across BBB, increasing dose and combined radiotherapy would carry out better outcome. Unsurprisingly EGFR mutations were still the most important predictor of the sensitivity.

Cetuximab in combination with chemoradiotherapy in Chinese patients with non-resectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trail

BACKGROUND AND PURPOSE This multicenter phase II trial investigated cetuximab combined with chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS Eligible patients with non-resectable, locally-advanced ESCC received cetuximab 400mg/m(2) loading dose on day 1; and on day 1 of the 2nd-7th weeks: cetuximab 250mg/m(2), paclitaxel 45mg/m(2), and cisplatin 20mg/m(2), concurrent with 59.4Gy/33 fractions of radiation therapy. Primary endpoint was clinical response rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and KRAS status. RESULTS Of 55 patients enrolled, 45 completed therapy. Forty-four patients had a clinical response: 29 complete response and 15 partial response. One-year PFS and OS of 45 evaluable patients were 84.23% and 93.33%, respectively, and 2-year PFS and OS were 74.87% and 80.00%, respectively. Non-hematologic adverse events were generally grade 1 or 2; primarily rash (92.7%), mucositis (45.5%), fatigue (41.8%), and nausea (38.2%). Grade 3 hematologic adverse events included neutropenia (32.7%) and anemia (1.8%). No KRAS mutations were identified in 50 evaluated samples. CONCLUSIONS Cetuximab can be safely administered with chemoradiotherapy to patients with locally-advanced ESCC and may improve clinical response rate.

Involved field irradiation for the treatment of esophageal cancer: Is it better than elective nodal irradiation?

Esophageal cancer (EC) is an extremely aggressive and lethal malignancy with an increasing incidence worldwide. Currently, the combination of radiotherapy and concurrent chemotherapy is performed for nonsurgical EC. However, there is no clear consensus on the accurate definition of the clinical target volume. Still, elective nodal irradiation (ENI) is the conventional remedy adopted for EC patients, while severe radiotherapy-related toxicities would occur in at least half of patients. Involved field irradiation (IFI) is a selective way to decrease the irradiation volume and thereby to decline toxicities. This review centers on the modality of IFI and compares the treatment efficacy between IFI and ENI.

Early detection of radiation-induced heart disease using 99mTc-MIBI SPECT gated myocardial perfusion imaging in patients with oesophageal cancer during radiotherapy

BACKGROUND AND PURPOSE The primary aim of this prospective study was to investigate the value of (99m)Tc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) gated myocardial perfusion imaging (GMPI) in the detection of radiation-induced heart disease (RIHD) as early as during radiotherapy (RT) for oesophageal cancer (EC). The second aim was to analyse the correlation between cardiac toxicity and the dose-volume factors. MATERIALS AND METHODS The (99m)Tc-MIBI SPECT GMPI was performed both pre-RT and during RT (40Gray). The results of the SPECT were quantitatively analysed with QGS/QPS software and read by two experienced nuclear medicine physicians. The correlation between the changes in the SPECT parameters and the RT dosimetric data was analysed. RESULTS Eighteen patients with locally advanced EC were enrolled in the study. Compared with the baseline, the imaging during RT showed not only significant decreases in the wall motion (WM) (1/20 segments), wall thickening (WT) (2/20 segments), end-diastolic perfusion (EDP) (5/20 segments) and end-systolic perfusion (ESP) (8/20 segments) (p<0.05) but also a significant increase in the heart rate (74.63±7.79 vs 81.49±9.90, p=0.036). New myocardial perfusion defects were observed in 8 of the 18 patients. The V37-V40 was significantly higher (p<0.05) in the patients with the new perfusion defects during RT than in the patients who did not exhibit these defects. CONCLUSIONS Radiotherapy for EC induces cardiac damage from an early stage. (99m)Tc-MIBI SPECT GMPI can detect the occurrence of cardiac impairment during RT. The WM, WT, EDP and ESP may be valuable as early indicators of RIHD. The percentage of the heart volume that receives a high dose is an important factor that is correlated with RIHD.

Exploring Spatial Overlap of High-Uptake Regions Derived From Dual Tracer PET/CT Imaging Using 18F-FDG and 18F-FLT in Non–Small Cell Lung Cancer Patients: A Prospective Pilot Study

restored electronic radiation plans and patient charts were retrospectively reviewed through an IRB approved study. Analysis was restricted to patients with available DVH data. Fisher’s exact test was used to assess associations between patient/treatment characteristics and post-treatment pulmonary toxicity. Actuarial overall survival (OS), progression-free survival (PFS), and local control (LC) were determined by the Kaplan-Meier method. Results: All patients (nZ42) received neoadjuvant chemoradiation with intensity modulated radiation (median 50.4 Gy, range 45-70) and concurrent platinum doublet chemotherapy. The median age was 68.9 (range 49.8-84.5), and the median follow-up time was 1.9 years (range, 0.5-8.4). Of the patients, 76.2% were former/current smokers, and 40.5% had underlying lung conditions. Median baseline FEV1 was 85.5% predicted (range, 52.9-132.2); median baseline DLCO was 88.2% predicted (range, 43.9-160.1). 23.8% (nZ10) patients developed grade 2 or higher pulmonary complications. These consisted of pneumonitis (nZ3), respiratory failure (nZ5), and pleural effusion (nZ6). Fifty percent (nZ21) developed pulmonary complications of any grade. Pneumonectomy/bi-lobectomy was associated with pulmonary toxicity (P Z 0.013). Patients were categorized as having received a high or low mean lung dose (MLD) to the contralateral lung based on the median value within our study population (less or more than 5.6 Gy). For patients who received contralateral MLD <5.6 Gy, 14.3% developed grade 2 or higher lung complications (nZ3) while 33.3% of patients who received contralateral MLD > 5.6 Gy developed grade 2 or higher lung complications (nZ7). Three-year OS was 65.8%. Three-year PFS was 60.2%. Three-year LC was 81.2%. 14.3% of patients had pathologic complete response. Conclusion: Our descriptive analysis demonstrates that patients who received a higher radiation dose to the contralateral uninvolved lung had a higher incidence of post-operative pulmonary toxicity. Dosimetric consideration of radiation fall-off dose to the uninvolved lung may be an important consideration in limiting post-operative toxicity in patients who undergo trimodality therapy. However, further analysis in a larger study population is needed to clarify associations. Author Disclosure: W. Guo: None. X. Hui: None. S. Alfaifi: None. S.P. Robertson: None. L. Anderson: None. R.K. Hales: None. C. Hu: None. T.R. McNutt: None. S. Broderick: None. R. Voong: None.

Validation of 18F-FLT PET as an Imaging Surrogate of Tumor Reproliferation During Fractionated Radiation Therapy: Spatial Coincidence of 8F-FLT Uptake and Immunohistochemistry Ki-67

minimally invasive thoracic surgical patients has not been previously described. Therefore, we report our initial experience using the fentanyl ITS system in minimally invasive thoracic surgical patients. Materials/Methods: We performed a retrospective review of patients that underwent minimally invasive thoracic surgical procedures at a single institution. Charts were reviewed for type of intravenous pain medications utilized, pain rating, and the amount of oral narcotics utilized. These data were compared to available historic data on patients who underwent robotic thoracic wedge resections and used IV PCA narcotic. Results: Fifteen patientsmet the criteria to be included in the review. Themean age was 57.9 years (range 35-68), with 40% female. Twelve patients (75%) underwent robotic-assisted lung wedge resection, 2 patients (13%) underwent robotic-assisted lobectomy, and 1 patient underwent diagnostic thoracoscopy with biopsy and open reduction/internal fixation of rib fractures. The average pain rating score was 3.1 in the ITS group, compared to 2.9 in the PCA group (PZ.76). The amount of oral narcotics used was 17.3mg per day per patient in the ITS group compared to 17.8mg per day per patient in the PCA group (PZ.95). The median time (in minutes) of IV narcotic bolus for breakthrough pain from end of surgery to last dose was 45 minutes (range 0-271 minutes). Conclusion: The use of ITS in minimally invasive thoracic surgical patients is a good alternative to using IV PCA narcotics. ITS allows greater freedom to ambulate, which can decrease pulmonary complications associated with thoracic surgical procedures. Author Disclosure: P. Baik: None.

Prediction of Early Response to Chemoradiation Therapy in Non-Small Cell Lung Cancer by Using Cone Beam Computed Tomography-Based Tumor Volume and Density Changes.

Prediction of Early Response to Chemoradiation Therapy in NoneSmall Cell Lung Cancer by Using Cone Beam Computed TomographyeBased Tumor Volume and Density Changes Q. Wen, X. Meng, J. Yue, C. Ma, M. Hu, X. Sun, and J. Yu; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, China, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China