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Biomedical subjects

Kazunari Yamada

Publications and source records attributed to Kazunari Yamada.

13 recordsLinked to original sources

Induction of remission of relapsed acute myeloid leukemia after unrelated donor cord blood transplantation by concomitant low-dose cytarabine and calcitriol in adults.

Low-dose cytarabine and calcitriol (LDCA + VD3) combination therapy was performed in two adult patients with acute myeloid leukemia (AML) that relapsed within 1 yr after unrelated donor cord blood transplantation (URD CBT) performed in a relapse or non-remission stage. Concomitant aclarubicin was also administered in one patient. Remission because of recovery of donor cord blood hematopoiesis was obtained in both patients. The treatment was low intensive, and neither adverse effects in terms of digestive symptoms nor hypercalcemia was observed. Activity of daily life was maintained. The patients were followed as outpatients after remission, and the remission duration was approximately 6 months in both patients. Although LDCA + VD3 therapy is minimally intensive chemotherapy, it may prolong the survival time of patients with relapsed AML after URD CBT.

Aclarubicin↗

Efficacy and feasibility of cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To investigate the efficacy and feasibility of a cisplatin-based concurrent chemoradiotherapy (CRT) protocol based on Intergroup Study 0099 for nasopharyngeal carcinoma (NPC). METHODS: Sixteen patients with stage II-IVB NPC were treated with a protocol of cisplatin-based concurrent CRT and adjuvant chemotherapy from 1998 to 2002. Three courses of cisplatin (80 mg/m2) were scheduled during 70 Gy of radiotherapy (RT), and two agents of adjuvant chemotherapy (FP regimen: cisplatin 80 mg/m2 and 5-fluorouracil 800 mg/m2/day by 4-day continuous infusion) were challenged. Overall survival (OS) and relapse-free survival (RFS) rates were calculated by the Kaplan-Meier method. RESULTS: Median follow-up duration was 45 months. Both 3-year OS and RFS rates were 81%. Proportions of patients who tolerated each scheduled treatment were 94% for RT, 63% for concurrent chemotherapy and 38% for adjuvant chemotherapy. CONCLUSIONS: Our protocol of the cisplatin-based concurrent CRT followed by adjuvant chemotherapy consisting of FP regimen was effective for Japanese patients with NPC. However, the doses and numbers of cycle of chemotherapy need to be modified because of the low compliance rate. Larger numbers of data accumulation and/or multi-institutional trials may be warranted to confirm the efficacy of this protocol.

Adolescent↗

Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma.

PURPOSE: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer. PATIENTS AND METHODS: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. RESULTS: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. CONCLUSION: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.

Aged↗

Change in dose distribution of three-dimensional conformal radiotherapy during treatment for lung tumor.

PURPOSE: We investigated the changes in dose distribution of three-dimensional conformal radiotherapy (3D CRT) during lung tumor treatment. MATERIALS AND METHODS: Ten patients with non-small cell lung cancer who had undergone planning for radical radiotherapy were selected for study. Computed tomography (CT) examination was performed at two time intervals during the course of conformal radiotherapy: t0 Gy at the time of planning and t40 Gy at 40 Gy of treatment. We transferred all the planned beam data at t0 Gy to each t40 Gy CT image. The isodose distribution was recalculated at time t40 Gy for the same beam characteristics. Variations in volumes and dose-volume histograms (DVHs) were analyzed and compared for lung, gross target volume (GTV), and planning target volumes (PTV) between t0 Gy and t40 Gy. A paired t-test was performed to compare the DVH between t0 Gy and t40 Gy. RESULTS: The mean minimum doses for t40 y GTV, and PTV were lower than t0 y. However, there was no significant difference between t0 Gy and t40 Gy (p=0.493, 0.378, respectively). There was a patient whose minimum doses of GTV and PTV were decreased and who had notable improvement of lobar atelectasis after 40 Gy of radiotherapy. Comparison of the percent volume of received dose exceeding 20 Gy (V20) and the mean dose for the total lung revealed that t40 Gy was larger than to Gy (p=0.013, 0.012). CONCLUSION: Incorporation of the time factor into 3D treatment planning is mandatory for frequent reiteration of treatment planning during treatment periods. Clearly, more work in this area should be considered.

Aged↗

Treatment results of radiotherapy for carcinoma of the cervical esophagus.

The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.

Aged↗

High-speed screening of human ATP-binding cassette transporter function and genetic polymorphisms: new strategies in pharmacogenomics.

Drug transporters represent an important mechanism in cellular uptake and efflux of drugs and their metabolites. Hitherto a variety of drug transporter genes have been cloned and classified into either solute carriers or ATP-binding cassette (ABC) transporters. Such drug transporters are expressed in various tissues such as the intestine, brain, liver, kidney, and, importantly, cancer cells, where they play critical roles in the absorption, distribution, and excretion of drugs. We developed high-speed functional screening and quantitative structure-activity relationship analysis methods to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function. These methods would provide powerful and practical tools for screening synthetic and natural compounds, and the deduced data can be applied to the molecular design of new drugs. Furthermore, we demonstrate a new "SNP array" method to detect genetic polymorphisms of ABC transporters in human samples.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

Stereotactic hypofractionated high-dose irradiation for stage I nonsmall cell lung carcinoma: clinical outcomes in 245 subjects in a Japanese multiinstitutional study.

BACKGROUND: Stereotactic irradiation (STI) has been actively performed using various methods to achieve better local control of Stage I nonsmall cell lung carcinoma (NSCLC) in Japan. The authors retrospectively evaluated results from a Japanese multiinstitutional study. METHODS: Patients with Stage I NSCLC (n = 245; median age, 76 years; T1N0M0, n = 155; T2N0M0, n = 90) were treated with hypofractionated high-dose STI in 13 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18-75 gray (Gy) at the isocenter was administered in 1-22 fractions. The median calculated biologic effective dose (BED) was 108 Gy (range, 57-180 Gy). RESULTS: During follow-up (median, 24 months; range, 7-78 months), pulmonary complications of National Cancer Institute-Common Toxicity Criteria Grade > 2 were observed in only 6 patients (2.4%). Local progression occurred in 33 patients (14.5%), and the local recurrence rate was 8.1% for BED > or = 100 Gy compared with 26.4% for < 100 Gy (P < 0.05). The 3-year overall survival rate of medically operable patients was 88.4% for BED > or = 100 Gy compared with 69.4% for < 100 Gy (P < 0.05). CONCLUSIONS: Hypofractionated high-dose STI with BED < 150 Gy was feasible and beneficial for curative treatment of patients with Stage I NSCLC. For all treatment methods and schedules, local control and survival rates were better with BED > or = 100 Gy compared with < 100 Gy. Survival rates in selected patients (medically operable, BED > or = 100 Gy) were excellent, and were potentially comparable to those of surgery.

Adult↗

[Hypothyroidism after radiotherapy to the neck].

PURPOSE: The purpose of this study was to investigate the incidence and possible predictors of hypothyroidism after radiotherapy to the neck, focusing on radiation dose-volume factors. METHODS AND MATERIALS: Thyroid function was measured in 169 patients treated with radiation ports including the thyroid, between 1989 and 2000. Hypothyroidism was determined with an endpoint of elevated serum thyroid stimulating hormone(TSH) levels > 10.0 microU/ml. In 60 patients, radiation dose-volume factors were calculated; e.g., total volume of the thyroid, mean radiation dose to the thyroid, and %-volume of the thyroid which received radiation doses of no less than 10-70 Gy(V10-V70). The evaluated risk factors for hypothyroidism included these dose-volume factors, sex, age, primary disease, combined chemotherapy, and follow-up period. RESULTS: Hypothyroidism was detected in 33 (19.5%) of the 169 patients. None of them had clinical symptoms of hypothyroidism. V10, V20, and V30 seemed to be possible predictors of hypothyroidism and had a significant impact on the peak level of serum TSH. CONCLUSION: Radiation dose-volume factors of the thyroid seemed to correlate with the incidence of hypothyroidism, and V10, V20, and V30 had a significant impact on the peak level of serum TSH.

Adolescent↗

Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma.

PURPOSE: We conducted a prospective trial of combined transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) for portal vein tumor thrombus (PVTT) in unresectable hepatocellular carcinoma (HCC). The aim of the present study was to investigate the efficacy and toxicity of this trial regime. METHODS AND MATERIALS: Patients with unresectable HCC complicated with tumor thrombus in the first branch of portal vein were selected as eligible for this study. TACE was performed using Lipiodol, epirubicin hydrochloride, and mitomycin, followed by gelatin sponge cubes. The 3D-CRT was performed targeting the clinical target volume (CTV) defined as PVTT only to a total dose of 60 Gy using 10-MV accelerator. RESULTS: A total of 19 patients were enrolled in this study. Survival rates at 1 and 2 years were 40.6% and 10.2%, respectively. The median survival time was 7.0 months. An objective response was observed in 11 of 19 cases (57.9%). Recanalization of the first portal branches was not observed; however, the protrusion of PVTT into the main portal trunk decreased in all cases. Growth of intrahepatic metastasis outside the 3D-CRT field was observed in 12 cases (63%). Deterioration of the Child-Pugh Score was observed in 5 of 6 cases with the percent volume of the total liver receiving a dose exceeding 30 Gy (V(30)) > or =40%, vs. 2 of 13 cases with a V(30) <40% (p < 0.01). CONCLUSION: This combined therapy was feasible. Our results indicate that V(30) was a predictive test for deterioration of liver function. Further investigation of treatment modalities is needed to prevent the growth of intrahepatic metastasis.

Aged↗

Three-dimensional treatment planning using electrocardiographically gated multi-detector row CT.

PURPOSE: Information concerning the amount and nature of target motion is essential for the determination of internal margin size. However, there are few published reports outlining the motion with heart and aortic pulsation. We introduce a method for three-dimensional radiation treatment planning (3D-RTP) by using electrocardiographically (ECG) gated spiral scanning with a four-section CT system. We describe a new approach to visualize internal organ motion resulting from cardiac motion with ECG gated multidetector row CT. MATERIALS AND METHODS: Five patients with lung or liver tumors were studied with a multidetector row CT system under shallow inspiration breath-holding. With retrospective ECG gating, only data acquired within a predefined interval of the cardiac cycle are used for image reconstruction. All reconstructed image data at diastolic and systolic phases of the cardiac cycle were transferred to the 3D-RTP system. The shift of the internal organs between the cardiac cycles was evaluated. RESULTS: Cardiac contraction influences anterior thorax, pulmonary peripheral vessels, and liver position, in addition to locations near the heart. Apparent movements more than 5 mm between diastolic and systolic phases were observed in the left ventricle, right atrium, and superior vena cava. Two-phase imaging was useful for showing the movement of internal organs during cardiac contraction under breath-holding. CONCLUSIONS: Spatial information using ECG-gated CT has the potential to determine the planning target volume of moving lung and liver tumors more precisely than conventional CT planning.

Computer Systems↗

[Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

Acute Disease↗

Improvement of three-dimensional treatment planning models of small lung targets using high-speed multi-slice computed tomographic imaging.

PURPOSE: To improve the reliability of the patient model and reduce treatment volume by acquiring multi-slice computed tomographic (CT) data with the patients' single holding of breath at normal inhalation and exhalation. METHODS AND MATERIALS: Seven patients with nine small peripheral lung cancer tumors underwent CT scanning under three respiration conditions using multi-slice CT: free breathing (FB), shallow inspiration (SI), and shallow expiration (SE). To compare the treatment plan created using the two-respiratory-phase images (SI + SE) with the plans created using only SE images or using only FB images, we attempted to calculate the true dosimetric characteristics for three-dimensional treatment planning taking respiratory movement into consideration. Minimum dose to the gross tumor volume (GTV) and ipsilateral lung dose-volume histogram (DVH) were calculated for the inhalation and exhalation positions of shallow breathing. RESULTS: There was no significant difference between minimum doses of the GTV in the three treatment plans when using anteroposterior/posteroanterior parallel-opposed fields. However, there was a significant difference between the minimum doses of the GTV in the two-phase treatment plan and the minimum dose in the other treatment plans when using the four-field technique, consisting of shaped anterior, posterior, right and left lateral fields (p = 0.03, 0.04). Comparison of the percent volume of ipsilateral lung receiving a dose exceeding 20 Gy (V(20)) based on inhalation and exhalation CT data revealed that the V(20) of the two-phase plan was the smallest of the three treatment planning fields (p < 0.001). CONCLUSION: Two-phase planning using multi-slice CT provides an immediate reduction in the amount of normal tissue treated and improved reliability of patient data for DVH modeling.

Humans↗

Radiotherapy for medically inoperable non-small cell lung cancer at clinical stage I and II.

We reviewed the records of 36 patients with medically inoperable stage I-II non-small cell lung carcinoma who were treated with radiotherapy. The median dose to the target was 60 Gy with conventional fractionation. Fifteen patients were treated without elective irradiation fields, while the remaining 21 were treated with extended fields including elective mediastinal regional lymph nodes. The overall survival rates at three and five years were 32.3% and 18.8%, the cause-specific survival rates were 40.9% and 27.3%, and the local control rates were 31.7% and 23.8%, respectively. In multivariate analysis the radiation dose had a marginally significant influence on the cause-specific survival, while tumor size had a significant influence on the local control rate. Only one patient had relapse in the regional mediastinal lymph nodes as the only site of metastasis. We conclude that the dose used in the present study is inadequate and recommend that further efforts be made to improve local control by dose escalation within a small target volume.

Aged↗