Shigeru Nawano

Phase I/II Study of Concurrent Chemoradiotherapy for Localized Nasal Natural Killer/T-Cell Lymphoma: Japan Clinical Oncology Group Study JCOG0211

PURPOSE To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy. PATIENTS AND METHODS Treatments comprised concurrent radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose. RESULTS Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male:female, 17:10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed. CONCLUSION Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.

Computerized detection of malignant tumors on digital mammograms

This paper presents a tumor detection system for fully digital mammography. The processing scheme adopted in the proposed system focuses on the solution of two problems. One is how to detect tumors as suspicious regions with a very weak contrast to their background and another is how to extract features which characterize malignant tumors. For the first problem, a unique adaptive filter called the iris filter is proposed. It is very effective in enhancing approximately rounded opacities no matter what their contrasts might be. Clues for differentiation between malignant tumors and other tumors are believed to be mostly in their border areas. This paper proposes typical parameters which reflect boundary characteristics. To confirm the system performance for unknown samples, large scale experiments using 1212 CR images were performed. The results showed that the sensitivity of the proposed system was 90.5% and the average number of false positives per image was found to be only 1.3. These results show the effectiveness of the proposed system.

Segmentation of multiple organs in non-contrast 3D abdominal CT images

ObjectiveWe propose a simultaneous extraction method for 12 organs from non-contrast three-dimensional abdominal CT images.Materials and methodsThe proposed method uses an abdominal cavity standardization process and atlas guided segmentation incorporating parameter estimation with the EM algorithm to deal with the large fluctuations in the feature distribution parameters between subjects. Segmentation is then performed using multiple level sets, which minimize the energy function that considers the hierarchy and exclusiveness between organs as well as uniformity of grey values in organs. To assess the performance of the proposed method, ten non-contrast 3D CT volumes were used.ResultsThe accuracy of the feature distribution parameter estimation was slightly improved using the proposed EM method, resulting in better performance of the segmentation process. Nine organs out of twelve were statistically improved compared with the results without the proposed parameter estimation process. The proposed multiple level sets also boosted the performance of the segmentation by 7.2 points on average compared with the atlas guided segmentation. Nine out of twelve organs were confirmed to be statistically improved compared with the atlas guided method.ConclusionThe proposed method was statistically proved to have better performance in the segmentation of 3D CT volumes.

Medical image analysis of 3D CT images based on extension of Haralick texture features

PURPOSE A new approach to the segmentation of 3D CT images is proposed in an attempt to provide texture-based segmentation of organs or disease diagnosis. 3D extension of Haralick texture features was studied calculating co-occurrences of all voxels in a small cubic region around the voxel. RESULTS For verification, the proposed method was tested on a set of abdominal 3D volumes of patients. Statistically, the improvement in segmentation was significant for most of the organs considered herein. CONCLUSIONS The proposed method has potential application in medical image segmentation, including diagnosis of diseases.

Automated pancreas segmentation from three-dimensional contrast-enhanced computed tomography

PurposeWe propose an automated pancreas segmentation algorithm from contrast-enhanced multiphase computed tomography (CT) and verify its effectiveness in segmentation.MethodsThe algorithm is characterized by three unique ideas. First, a two-stage segmentation strategy with spatial standardization of pancreas was employed to reduce variations in the pancreas shape and location. Second, patient- specific probabilistic atlas guided segmentation was developed to cope with the remaining variability in shape and location. Finally, a classifier ensemble was incorporated to refine the rough segmentation results.ResultsThe effectiveness of the proposed algorithm was validated with 20 unknown CT volumes, as well as three on-site CT volumes distributed in a competition of pancreas segmentation algorithms. The experimental results indicated that the segmentation performance was enhanced by the proposed algorithm, and the Jaccard index between an extracted pancreas and a true one was 57.9%.ConclusionsThis study verified the effectiveness of two-stage segmentation with spatial standardization of pancreas in delineating the pancreas region, patient-specific probabilistic atlas guided segmentation in reducing false negatives, and a classifier ensemble in boosting segmentation performance.

Phase II/III Study of R-CHOP-21 Versus R-CHOP-14 for Untreated Indolent B-Cell Non-Hodgkin's Lymphoma: JCOG 0203 Trial

PURPOSE Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat indolent B-cell lymphoma. Granulocyte colony-stimulating factor (G-CSF), which potentiates antibody-dependent rituximab cytotoxicity, is used to shorten CHOP intervals. To improve progression-free survival (PFS) in patients treated with R-CHOP as the primary end point, we conducted a phase III study. PATIENTS AND METHODS Patients with untreated stages III to IV indolent B-cell lymphoma were randomly assigned to six cycles of R-CHOP every 3 weeks (R-CHOP-21) or every 2 weeks (R-CHOP-14) with G-CSF. Maintenance rituximab was not allowed. RESULTS Three hundred patients were enrolled. At the median follow-up time of 5.2 years, there was no significant difference in PFS between arms for the 299 eligible patients; the median was 3.7 (R-CHOP-21) v 4.7 (R-CHOP-14) years, 57% v 58% at 3 years, and 41% v 43% at 6 years, respectively (hazard ratio [HR], 0.92; 95% CI, 0.68 to 1.25; one-sided P = .30). The median overall survival (OS) time was not reached in either arm, and there was no significant difference (6-year OS: 87% [R-CHOP-21] v 88% [R-CHOP-14]; HR, 1.15; 95% CI, 0.57 to 2.30; one-sided P = .65). Although grade 4 neutropenia and grade 3 infections were more frequent in the R-CHOP-21 group, R-CHOP was feasible in both arms. CONCLUSION The R-CHOP dose-dense strategy failed to improve PFS of patients with untreated indolent B-cell lymphoma. Further improvement of first-line treatment or investigations on postremission therapy following R-CHOP should be explored.

A conditional statistical shape model with integrated error estimation of the conditions; Application to liver segmentation in non-contrast CT images

This paper presents a novel conditional statistical shape model in which the condition can be relaxed instead of being treated as a hard constraint. The major contribution of this paper is the integration of an error model that estimates the reliability of the observed conditional features and subsequently relaxes the conditional statistical shape model accordingly. A three-step pipeline consisting of (1) conditional feature extraction from a maximum a posteriori estimation, (2) shape prior estimation through the novel level set based conditional statistical shape model with integrated error model and (3) subsequent graph cuts segmentation based on the estimated shape prior is applied to automatic liver segmentation from non-contrast abdominal CT volumes. Comparison with three other state of the art methods shows the superior performance of the proposed algorithm.

Computer-aided diagnosis in full digital mammography

RATIONALE AND OBJECTIVES The authors clarify the detection rates for breast cancerous tumors and clustered microcalcifications with computer-aided diagnosis (CAD) based on Fuji Computed Radiography. The authors also determine whether mammographic reading with CAD contributes to the discovery of breast cancer. METHODS Data acquired by Fuji Computed Radiography 9000, which consisted of 4148 digital mammograms including 267 cases of breast cancer, was transferred directly to an analysis workstation where an original software program determined extraction rates for breast tumors and clustered microcalcifications. Furthermore, using another 344 mammograms from 86 women, observer performance studies were conducted on five doctors for receiver operating characteristic (ROC) analysis. RESULTS Sensitivity to breast cancerous tumors and clustered microcalcifications were 89.9% and 92.8%, respectively false-positive rates were 1.35 and 0.40 per image, respectively. The observer performance studies indicate that an average Az value for the five doctors was greater with the CAD system than with a film-only reading without CAD, and that a reading with CAD was significantly superior at P < 0.022. CONCLUSIONS It has been shown that CAD based on Fuji Computed Radiography offers good detection rates for both breast cancerous tumors and clustered microcalcifications, and that the reading of mammograms with this CAD system would provide potential improvement in diagnostic accuracy for breast cancer.

Phase II Study of Oral Fludarabine Phosphate in Relapsed Indolent B-Cell Non-Hodgkin's Lymphoma

PURPOSE Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkins lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. PATIENTS AND METHODS Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). RESULTS Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. CONCLUSION Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

Japanese phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma

There is no data about the efficacy and safety of radioimmunotherapy with 90Y‐ibritumomab tiuxetan in patients with relapsed or refractory indolent B‐cell lymphoma pretreated with rituximab‐containing chemotherapy. We focused on this in a Japanese phase II study. Radioimmunotherapy with 90Y‐ibritumomab tiuxetan (11.1 and 14.8 MBq) was evaluated in patients with 100–149 × 109 and >150 × 109 platelets/L, respectively. The primary endpoint was the overall response rate. Forty patients were treated with 90Y‐ibritumomab tiuxetan (18 with 11.1 MBq/kg and 22 with 14.8 MBq/kg). Thirty‐five patients (88%) had been pretreated with rituximab, including 27 (68%) pretreated with rituximab‐containing chemotherapy. The overall response rate was 83% (33/40; 95% confidence interval, 67–93%), and the complete response rate was 68% (27/40; 95% confidence interval, 51–81%). The overall response rates in patients pretreated with rituximab‐containing chemotherapy and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) were 83% (19/23) and 94% (17/18), respectively. The median progression‐free survival time of the 40 patients who received 90Y‐ibritumomab tiuxetan was 9.6 months. Toxicity was primarily hematological and mostly transient. No grade 4 non‐hematological toxicity was observed. In conclusion, radioimmunotherapy with 90Y‐ibritumomab tiuxetan is safe and highly effective in patients with relapsed or refractory indolent B‐cell lymphoma, including those pretreated with rituximab‐containing chemotherapy. (ClinicalTrials.gov number NCT00220285) (Cancer Sci 2009; 100: 158–164)