Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study.

BACKGROUND: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. PATIENTS AND METHODS: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m2 each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. RESULTS: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade ≥3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade ≥3 or treatment-related death did not occur. CONCLUSIONS: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed.

Can a belly board reduce respiratory-induced prostate motion in the prone position?--assessed by cine-magnetic resonance imaging.

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.

SU-E-J-26: Automated Estimation Method of Patient Setup Errors Using Simulated Portal Images for Prostate Cancer Radiotherapy.

PURPOSE: We developed a novel automated estimation method for patient setup errors based on simulated and real portal images for prostate cancer radiotherapy. METHODS: The estimation of patient setup errors in this study was based on a template matching technique with a cross-correlation coefficient and Sobel filter between the real portal image and localized pelvic template of reference image, which were DRR (digitally reconstructed radiography) images and simulated portal images. The simulated portal image was derived by projecting a CT image according to an inverse exponential power law of x-ray attenuation for a water-equivalent path length of each voxel of the CT image on each ray from a source to each pixel on the EPID (electric portal imaging device). A localized pelvic template of each patient in AP (anterior-posterior) or lateral view was automatically extracted from the DRR or simulated portal images by cropping a rectangular region, which was determined by using the mean pelvic template and four anatomical feature points. We applied the proposed method to three prostate cancer cases, and evaluated it using the residual error between the patient setup error obtained by proposed method and the gold standard setup error determined by two radiation oncologists. RESULTS: The average residual errors of the patient setup error for the DRR and simulated portal images were 0.79 and 1.26 mm in the left-right (LR) direction, 3.17 and 2.05 mm in the superior-inferior (SI) direction, 1.69 and 5.82 mm in the anterior-posterior (AP) direction, 3.84 and 6.94 mm in Euclidean distance (ED), respectively. If we used the simulated portal image for LR and SI directions and the DRR image for AP direction, the Euclidean distance was 3.22 mm. CONCLUSIONS: The proposed method has a potential to correctly estimate patient setup errors for prostate cancer radiotherapy.

TU-E-BRB-01: Similar-Case-Based Optimization of Beam Arrangements in Stereotactic Body Radiation Therapy.

PURPOSE: The quality of a treatment plan for stereotactic body radiotherapy (SBRT) depends on an experience of each treatment planner. Therefore, the treatment plans are subjectively determined by comparison of several treatment plans developed by time consuming iterative manners, while considering the benefit to a tumor and the risk to the surrounding normal tissues. The aim of our study was to develop an automated optimization method for beam arrangements based on similar cases in a database including plans designed by senior experienced treatment planners. METHODS: Our proposed method consists of three steps. First, similar cases were automatically selected based on image features from the treatment planning point of view. We defined four types of image features relevant to planning target volume (PTV) location, PTV shape, lung size, and spinal cord positional features. Second, the beam angles of the similar case were registered to the objective case with respect to lung regions using a linear registration technique. Third, the beam direction of the objective case was locally optimized based on the cost function considering radiation absorption in normal tissues and organs at risk. The proposed method was evaluated with 10 test cases and a treatment planning database including 81 cases by using eight planning evaluation indices such as D95, lung V20, and maximum spinal cord dose. RESULTS: The proposed method may provide usable beam directions, which have no statistically significant differences with the original beam directions (P > 0.05) in terms of the seven planning evaluation indices. Moreover, the mean value of D95 for 10 test cases was improved with a statistically significant difference by using the proposed method, compared with the original beam directions (P = 0.03). CONCLUSIONS: The proposed method could be used as a computer-assisted treatment planning tool for determination of beam directions in SBRT.

WE-G-BRCD-04: Development of Automated Determination Method of Robust Beam Directions against Patient Setup Errors Based on Spatial Distribution of Electron Density in Particle Therapy.

PURPOSE: The three-dimensional (3D) dose distribution covering a tumor region tends to be more breakable if the beam's eye view (BEV) of the 3D electron density (ED) map in a beam direction changes more abruptly with large fluctuations. Our aim of this study was to develop an automated determination method of robust beam directions against the patient setup error based on the ED-based BEV in the beam direction in the particle therapy. METHODS: The basic idea of our proposed method was to find the robust beam directions, whose the ED-based BEV has the spatial fluctuations with low special frequency and small amplitude. For evaluation of the spatial fluctuation in the ED-based BEV in a beam direction, we obtained power spectra of the ED-based BEVs in all directions, i.e., 0 to 355 degree, with an interval of 5 degree. It was assumed that as the average spatial frequency and amplitude of the fluctuation in the ED-based BEV in a beam direction is lower and smaller, respectively, the absolute value of a gradient of the power spectrum becomes larger. Therefore the gradient of the power spectrum was calculated for determination of the robust beam direction. The ED-based BEV was produced by projecting a 3D electron density map derived from the computed tomography (CT) image from a beam source to the distal end of a planning target volume (PTV). Four cases of head and neck cancer patients were selected for evaluation of the proposed method. RESULTS: As a preliminary result, radiation oncologists agreed with most beam directions, which seem to be robust against patient setup errors, suggested by the proposed method. CONCLUSIONS: Our proposed method could be feasible to suggest the robust beam directions against patient setup errors in hadron particle therapy.

SU-E-J-117: Computer-Assisted Verification of Accumulated Dose Distribution during the Treatment Time Based on Estimation of Four-Dimensional Dose Distribution Using an Electronic Portal Imaging Device.

PURPOSE: The accumulated dose distributions during the course of radiation treatment are substantially important for verifying whether treatment dose distributions are produced according to planned dose distributions. The purpose of this study was to develop a computer-assisted verification method of accumulated dose distribution during the irradiation of a tumor based on estimation of four-dimensional (4D) dose distribution using an electronic portal imaging device (EPID). METHODS: The 4D 'treatment' computed tomography (CT) images during the irradiation were estimated based on affine transformations including respiratory motions, which were derived by registration between a planning portal dose image and treatment portal dose dynamic image. Planning portal dose images were calculated from planning CT images and an algorithm for calculation of dose spatial distribution. Treatment portal dose images were estimated from EPID dynamic images obtained during a treatment time. The planning portal dose images were registered to the treatment portal dose images to obtain the affine transformation, which could include respiratory motion in a patient body. The CT images at a treatment time were determined by deforming the planning CT images using the affine transformation matrix. 4D dose distributions during a treatment delivery were obtained by applying a dose calculation algorithm to the 4D treatment CT images. Finally, accumulated dose distributions during the course of radiation treatment were verified with planned dose distributions. RESULTS: We applied the proposed method to EPID dynamic images of 2 lung cancer patients, and evaluated the difference in accumulated dose distribution between the plan and treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases was 78.2%. CONCLUSIONS: The proposed method can be used for adaptively modifying the plan based on the dose discrepancy between the plan and treatment. This work was partially supported by Grant-in-Aid for Scientific Research (C) (22611011) and Okawa Foundation for Information and Telecommunications.

Apparent diffusion coefficient calculated with relatively high b-values correlates with local failure of head and neck squamous cell carcinoma treated with radiotherapy.

BACKGROUND AND PURPOSE: Few studies have investigated the relationship between ADC and clinical outcome in HNSCC. Our hypothesis has that relatively high pretreatment ADC would correlate with local failure of HNSCC treated with radiation therapy. MATERIALS AND METHODS: This includes prospective and validation studies. Seventeen patients treated with radiation therapy for primary HNSCC completed the prospective study. Variables considered to affect local failure including MR imaging-related parameters such as ADC and its change ratio were compared between patients with local failure and controls, and those showing difference or association with local failure were further tested by survival analysis. Furthermore, variables were analyzed in 40 patients enrolled in the validation study. RESULTS: Relatively high ADC calculated with b-values (300, 500, 750, and 1000 s/mm(2)) before treatment, high ADC increase ratio, and treatment method (chemoradiotherapy versus radiation therapy alone) revealed significant difference between patients with local failure and controls or association with local failure. In Cox proportional hazard testing, high ADC before treatment alone showed significant association with local failure (P = .0186). In the validation study, tumor volume before treatment, high ADC before treatment, T stage (T12 versus T34), and treatment method showed significance. Tumor volume before treatment (P = .0217) and high ADC before treatment (P = .0001) revealed significant association with local failure in Cox proportional hazard testing. High ADC before treatment was superior to tumor volume before treatment regarding association with local failure. CONCLUSIONS: These results suggest pretreatment ADC obtained at high b-values as well as tumor volume correlate with local failure of HNSCC treated with radiation therapy.

Phase I/II clinical study of percutaneous vertebroplasty (PVP) as palliation for painful malignant vertebral compression fractures (PMVCF): JIVROSG-0202.

BACKGROUND: The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Usefulness of mini-tracheostomy and torque controlled insertion of applicator in fractionated endobronchial brachytherapy.

Endobronchial brachytherapy was developed as effective treatment of endobronchial cancer and fractionated schedule is applied to decrease late toxicity. However, repeated bronchofiberscopy is onerous to the patient and restricts the treatment schedule itself. We applied mini-tracheostomy for a ready access route, and a torque controlled technique for easy insertion of the endobronchial applicator. Eight patients with tracheobronchial cancer invasion were treated with endobronchial brachytherapy of 18-30 Gy/3-5 fractions/1.5-2.5 weeks (median 24 Gy/4 fractions/2 weeks) at reference points of 5 mm from the bronchial surface. The averaged individual irradiation and single session times were 4 min and 24 min, respectively. There were no procedure-related complications. These technical improvements may facilitate flexible fractionated dose prescriptions.

Gluteal muscular and sciatic nerve metastases in advanced urinary bladder carcinoma: case report.

We present a case of gluteal muscular and sciatic nerve metastases from urinary bladder carcinoma. T2-weighted magnetic resonance images demonstrated diffuse swelling and an increase in the signal of the right gluteus maximus muscle without destruction of the original arrangement of muscular fibers. Further, remarkable thickening of the right sciatic nerve showing a relatively hypointense signal was detected. Postcontrast T1-weighted images showed strong enhancement of these structures. Fine-needle aspiration biopsy with ultrasonographic guidance confirmed metastatic carcinoma cells in the right gluteal muscle and the sciatic nerve. These radiologic findings may represent a rare pattern of metastasis from urinary bladder carcinoma.

Use of small pelvic field instead of whole pelvic field in postoperative radiotherapy for node-negative, high-risk stages I and II cervical squamous cell carcinoma.

We investigated whether a small pelvic (SP) field that covers primarily the pericervical regions in postoperative radiotherapy for cervical squamous cell carcinoma is adequate for a subgroup of node-negative patients. Of 84 patients with stage I-II disease treated with postoperative radiotherapy due to pathologic risk factors, 42 node-negative patients received SP-field radiotherapy, whereas remaining 42 node-positive patients were treated with a conventional whole pelvic (WP) field that also covered pelvic lymph nodes, both with 50.0-50.4 Gy/25-28 fractions. The pathologic risk factors included positive nodes, deep stromal invasion (>/=2 /3 thickness), parametrial extension, and positive or close surgical margin. Recurrence was identified for 20 patients: three in the SP group and 17 in the WP group. Intrapelvic recurrence accounted for all three recurrences in the SP group and for four in the WP group; 5-year pelvic-control rate did not differ significantly between the SP (93%) and WP (90%) groups. Extrapelvic recurrence (n = 11) was identified exclusively in the WP group. Patterns of recurrence indicate that use of an SP field instead of a WP field may be adequate in postoperative radiotherapy for a subgroup of node-negative, high-risk patients.

Comparison between pancreatoduodenectomy and hepatopancreatoduodenectomy for bile duct cancer.

BACKGROUND/AIMS: Pancreatoduodenectomy has been accepted as a standard operative procedure for distal bile duct cancer with low operative mortality. However, hepatopancreatoduodenectomy has not been accepted as a standard treatment modality for diffuse bile duct cancer. METHODOLOGY: From December 12, 1992 to December 15, 2000, 37 patients with the diagnosis of extrahepatic bile duct adenocarcinoma (cholangiocarcinoma) underwent pancreatoduodenectomy or hepatopancreatoduodenectomy, at the department of surgery, Ibaraki Prefectural Central Hospital and the Cancer Center. The differences in indications and results of both operative procedures were investigated retrospectively. RESULTS: Thirty-day operative mortality was 0% after either pancreatoduodenectomy or hepatopancreatoduodenectomy. One- to 5-year cumulative survival rates for the 24 patients after pancreatoduodenectomy were 76.3%, 41.5%, 41.5%, 41.5%, 41.5%, respectively. One- to 4-year cumulative survival rates for the 13 patients after hepatopancreatoduodenectomy were 48.0%, 32.0%, 32.0%, 16.0%, respectively. There were no statistically significant differences between cumulative survival rates after pancreatoduodenectomy and hepatopancreatoduodenectomy either in all the patients or in patients with UICC stage IV. CONCLUSIONS: Hepatopancreatoduodenectomy should be tried for patients with diffuse bile duct cancer, because only hepatopancreatoduodenectomy has the possibility of a cure at this time.

Self-expandable metallic stents for patients with recurrent esophageal carcinoma after failure of primary chemoradiotherapy.

BACKGROUND: Recent advances in chemoradiotherapy for esophageal carcinoma have resulted in improved survival rates. However, there are few options for recurrent dysphagia due to refractory carcinoma after failure of primary chemoradiotherapy. The aim of this study was to evaluate the safety and efficacy of self-expandable metallic stent placement for patients with recurrent esophageal carcinoma where definitive chemoradiotherapy has failed. METHODS: Thirteen consecutive patients with recurrent squamous cell carcinoma of the esophagus, in whom self-expandable metallic stents were placed after failure of primary chemoradiotherapy, were studied retrospectively. All patients had esophageal obstruction or malignant fistula. RESULTS: The oral alimentation status of nine of 13 patients (69%) improved after successful placement of the stent. Following placement of the stent, fever (>38 degrees C) and severe chest pain occurred in 85% (11/13) of the patients. In all patients examined, C-reactive protein was elevated within 1 week of the operation. Esophageal perforation occurred in three patients. Stent-related mediastinitis and pneumonia developed in six (46%) and three (23%) patients, respectively. Seven of the 13 patients (54%) died of stent-related pulmonary complications. CONCLUSION: Although the placement of a self-expandable metallic stent for patients with recurrent esophageal carcinoma after failure of chemoradiotherapy improved their oral alimentation status, we found that this treatment increases the risk of life-threatening pulmonary complications.

Peripancreatic arteries in thin-section multislice helical CT.

BACKGROUND: The normal and pathologic anatomies of the peripancreatic arteries were demonstrated using thin-section multislice computed tomography (CT). METHODS: Triple-phase dynamic CT was performed in 304 consecutive patients without pancreatic pathology and in 22 patients with pancreatic carcinoma. CT angiographies images (2.5-mm collimation, multihelical pitch 3, HQ mode) and a 1.25-mm reconstruction interval were obtained with a GE Lightspeed Qx/i at 25, 40, and 80 s after bolus injection of 130-150 mL of iodinated contrast medium at a rate of 3-5 mL/s. The images were assessed mainly by the manual cine paging method. RESULTS: The anterior and posterior arcades and the dorsal pancreatic artery were frequently visualized. However, small-caliber arteries smaller than 1.5 mm in diameter, such as the pancreaticomagna, caudal pancreatic, and transverse pancreatic arteries, were infrequently visualized. In some cases, the peripancreatic arteries were very useful for differentiating the origin of tumors. CONCLUSION: Multislice helical CT enables the recognition of small peripancreatic arteries, and evaluation of these arteries should be considered when assessing tumors in the pancreaticoduodenal region.

[Visualization of abdominal arteries by super-high-flow venous injection using multidetector helical CT].

The purpose in this study was to compare the ratio of visualization of upper abdominal arteries using MDHCT between the super-high-flow injection method (Group A) and the conventional injection method (Group B). The subjects ects were 200 patients who were randomly divided into Group A (100 patients) and Group B (100 patients). In Group A, visualization of the large arteries, including the CE, SMA, HA and LGA, was possible at a rate exceeding 96%, and that of the small arteries, including the DPA, SPDA, RGA and Cyst A, was more than 79%. Visualization of upper abdominal arteries was markedly improved by the super high flow injection technique.

Different mutation frequencies and spectra among organs by N-methyl-N-nitrosourea in rpsL (strA) transgenic mice.

The frequencies and spectra of N-methyl-N-nitrosourea (MNU)-induced in vivo somatic mutations were determined in rpsL (strA) transgenic mice. The wild-type rpsL gene, which exhibits a streptomycin-sensitive (Sm(S)) phenotype, was used as the rescue marker gene. Studies of mutation spectra among different organs and tissues were simplified using this system because of the short coding sequence (375 bp) of the rpsL gene. MNU administration to transgenic mice significantly elevated the mutation frequencies in various adult organs. Two distinctive patterns of mutation spectrum were observed, depending on the organs tested. Mutations derived from labile organs (spleen and thymus) were predominantly G:C to A:T transitions, as expected for MNU mutagenesis. Stable organs like the liver and brain, however, carried many fewer G:C to A:T transitions but significantly more single base deletions, of which the spectrum was very similar to that of background mutations in the rpsL transgenic mice. This spectrum difference among more and less proliferating organs was confirmed by the predominant occurrence of G:C to A:T transitions in fetal liver cells exposed to transplacental MNU treatment. In addition, most (approximately 90%) of the G:C to A:T transitions induced by MNU were detected in the first nucleotide of some 5'-G-(C or G)-3' sequences, many of which corresponded to the middle guanine residue of 5'-purine-G-(C or G)-3' sequences. It is thus suggested that at particular sites, the neighboring bases in both the 5' side and 3' side seem to influence either the susceptibility to DNA damage or the ability to repair MNU-induced lesions.