Rapidly progressive Kaposi's Sarcoma in an Iraqi boy received Valproic acid: a case report and review of literature.

BACKGROUND: Kaposi's sarcoma (KS), an endothelial neoplasm, is associated with human herpes virus (HHV) -8 infection. KS has four clinical sub-types: Mediterranean/classic, African/endemic, human immunodeficiency virus (HIV) -associated/epidemic, and transplantation-related/iatrogenic. Immunosuppression is an important cofactor in KS process. Classic KS (CKS) is exceedingly rare in children and when occurs, it is much more disseminated than adults. The epidemic, HIV-associated and the iatrogenic forms of childhood KS are a result of a profound and acquired T-cell deficiency. To our knowledge, this is the first paediatric KS case report from Iraq. Our patient was showing an unusual aggressive course of the disease while receiving Valproic acid (VPA) of the potential immune-suppressive effect. CASE PRESENTATION: A six-year-old Iraqi boy, who had cerebral palsy (CP) and epilepsy since the age of 9-months, had received VPA to control his seizures. He developed skin discoloration followed by nodules that disseminated proximally from the lower extremities to the groin, face, ears and oral cavity, and then he died from severe respiratory distress after 110 days from the disease evolution. KS diagnosis was proved by a skin biopsy. As the patient was of Arab-Asian ethnicity and was HIV-seronegative status, accordingly, his condition best fitted the classic form of KS. However, recent studies showed the link of VPA with the reactivation of HHV-8. Moreover, accumulated experimental and clinical data elucidated that VPA induces T-cell suppression. Given that there was a lack of facilities to perform the laboratory immunological diagnostic tests in Iraq, the VPA-induced effect on immunity in our case (iatrogenic KS) could not be evaluated. CONCLUSIONS: Our report demonstrates a rare, rapidly progressing paediatric KS case and highlights the possible role of the 5-years' administration of VPA and its challenging effect on cellular immunity based on recent studies. Thus, VPA could have promoted the development of the KS in our patient. This report also recalls the need of paediatricians to consider KS especially when the skin lesion appears at the child's foot even in countries outside the geographical map of the disease.

Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.

BACKGROUND: KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). METHODS: Diagnostic samples of 485 patients (<18 years) with acute leukemia from Iraq and Jordan were obtained, using Flinders Technology Associates filter papers. Polymerase chain reaction and direct sequencing were performed in Japan. RESULTS: RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. CONCLUSION: The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.

Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.

BACKGROUND: RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan. PROCEDURE: Bone marrow and/or peripheral blood samples were collected from 178 patients of Arab Asian ethnicity (aged ≤17 years) newly diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA sequencing was performed on six genes including RUNX1 gene (exons 3-8). RESULTS: RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients with RUNX1 mutations were significantly older than those with wild-type of the gene. Additionally, AML M0 subtype was more frequently found in patients with RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of 10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand, 36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations died of hematological relapse. CONCLUSION: The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.

Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.

Background: Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Methods: Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Results: Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Conclusions: Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.

Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards.

BACKGROUND: Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood. PATIENTS AND METHODS: The diagnosis of ALL was made according to standard French-American-British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription-polymerase chain reaction was adopted for the analysis. RESULTS: TEL-AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A-PBX1 mRNA, MLL-AF4 mRNA, and BCR-ABL mRNA, respectively. One patient had both TEL-AML1 and E2A-PBX1 fusion genes. The incidence of TEL-AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A-PBX1 or BCR-ABL were comparable to the data reported elsewhere. CONCLUSION: International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low-income and underdeveloped countries.

[A new attempt to promote home medical care in Kashiwa city-usefulness of information and communication technology with seamless multidisciplinary cooperation].

Due to the rapidly increasing super-aging society, medical policy in Japan should be redefined. Therefore, the medical and nursing home care system should now be revised greatly. We need to change the current principle that is based on cure only. The patients should receive hospitable care closely connected with their life in their home-town(region)throughout their lifetime. This is termed as "home medical care system". Here, we promote patient-centered medical home care, which implements the chronic and/or End-Of-Life care models, in Kashiwa city, Chiba prefecture. This system is a promising framework for primary care transformation. There is a need for a multidisciplinary team-based care system using information and communication technology(ICT)with smooth and seamless cooperation. However, increased awareness among the workers engaged in home medical care is first required.

Eliciting a User's Preferences by the Self-Disclosure of Socially Assistive Robots in Local Households of Older Adults to Facilitate Verbal Human-Robot Interaction.

To realize a society in which older adults can live independently in their homes and familiar environments for as long as possible, their lives can be supported by providing appropriate technology. In this case, a new intervention for older people using socially assistive robots (SARs) is proposed; however, previous research has demonstrated that individual differences exist in the use and response to SAR interventions, and it has also been reported that SARs are not used by users in some cases. Therefore, in this study, we developed a self-disclosure function to promote continuous interaction with robots, using a Japanese corpus and self-disclosure items. In this study, we defined the specific requirements and functions of self-disclosure in SARs and developed ten non-arbitrary speech scripts from the field of social psychology using a Japanese corpus and self-disclosure items. To evaluate the effect of self-disclosure in SARs, an SAR was introduced to each household for 20 days, with the consent of seven community-dwelling older adults. Based on the recorded voice interaction data, we analyzed how the number, total time, and quality of verbal interactions changed with the SAR's self-disclosure. Furthermore, we conducted group interviews with the participants and received positive comments regarding the robot's self-disclosure. Some participants considered the specific personality of the SAR by accumulating its behavioral characteristics. As a consequence, these results indicate that the robot's self-disclosure feature is effective in significantly increasing the quantity and quality of verbal interactions with older adults.

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study.

PURPOSE: The objective of the present prospective study was to compare the safety and efficacy of a 12-h method to a 6-h method in chronic cancer pain management. MATERIALS AND METHODS: Randomized, prospective clinical trial was conducted between December 2007 and June 2009, enrolling 90 patients with chronic cancer pain. Patients with chronic cancer pain were randomly assigned to the conversion from continuous intravenous infusion to transdermal fentanyl using two-step taper of the continuous intravenous infusion in 12 h (12-h method) or the conversion in 6 h (6-h method). The parameters assessed in the present study included pain intensity (on a scale of 0 to 10) and bolus use frequency, and the adverse effects were assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: Pain intensity and the number of boluses during conversion remained stable in both arms. The incidence of adverse events was 25.6% in the 12-h method group and 2.3% in the 6-h method group (95% confidence interval, 0.01-0.55; p = 0.002). Adverse events occurred in four patients at 6-12 h, five patients at 12-18 h, two patients at 18-24 h, and one patient at 24-48 h after application. CONCLUSIONS: Excellent safety profile and sustained efficacy are shown for the 6-h conversion method.

[Automated Driving Cuts the Future].

There are strong expectations for automated driving. Whether the purpose is accident prevention or driver shortage, it is technically difficult to move fully automatically anywhere, and it is also difficult to establish business potential and merchantability through reasonable cost. In this paper, to properly understand automated driving, I will explain the current conditions and prospects.

A Study on Evaluations of Living Spaces by Caregivers for Elderly People.

Caregivers who provide nursing-care visits to the elderly learn to notice changes in the physical and mental functions of residents by looking for signs of disorder in living spaces and changes in the orderliness of living spaces. In this research, to understand what draws caregiver attention and how they evaluate them, 15 caregivers are interviewed and asked to evaluate images of 33 living spaces. The results show variances in evaluations concerning the degree of clutter of living spaces even among experienced caregivers, but that it is possible to classify the degree of clutter using a two-axis scale.

Design of a Behavior of Robot That Attracts the Interest of the Mildly Demented Elderly.

In this study, using the unexpected intervention overturning the interaction amount of the field and the mental model, an interaction of a robot system that enables sustained nonverbal communication with the mildly demented elderly was proposed and its effectiveness was shown in the group home of the mildly demented elderly.

Single-institute phase I/II trial of alternating chemoradiotherapy with 5-FU and nedaplatin for esophageal carcinoma.

AIM: To assess the efficacy and feasibility of alternating chemoradiotherapy for esophageal cancer. MATERIALS AND METHODS: Patients, with previously untreated esophageal cancer, Eastern Cooperative Oncology Group performance status of 0 to 2, age 20 to 75 years and sufficient organ function, were eligible for this study. Three cycles of systemic chemotherapy with the continuous infusion of 3500 mg/m2 of 5-fluorouracil (5-FU: days 1-5) and a 6-h infusion of nedaplatin (NDP; day 6: 120-140 mg/m2), were accompanied by thoracic irradiation of 63 Gy in 35 fractions over 7 weeks. Radiation therapy was stopped during systemic chemotherapy (alternating setting). In the phase I part, the dose of nedaplatin was increased to define dose-limiting toxicities. For the phase II part, patients with distant metastasis were excluded. RESULTS: From 1998 through 2002, 40 patients were recruited for this protocol study. The median patient age was 54 years (range, 49-65 years) for the phase I and 58 years (range, 44-73 years) for the phase II trials. There were 35 men and 5 women in this study. For the phase I part (n = 15), the maximal tolerated dose of NDP was 140 mg/m2; thus, the recommended dose was 130 mg/m2. Twenty-five patients were treated with the recommended doses in the phase II part of the study. Ten patients had T4 disease and 14 patients had stage IV disease in the phase II part of the study. The overall survival rates at 1 and 2 years were 58.9% and 45.9%, respectively. The most frequent toxicities were leukopenia (grade 3 or greater: 80%), followed by thrombocytopenia (56%), granulocytopenia (56%) and anemia (28%). Radiation esophagitis of grade 3 or greater developed in 6 patients (24%). Two patients died of radiation pneumonitis. The actual dose intensities of NDP and 5-FU were 68.8% and 73.3%, respectively. CONCLUSION: This intensive treatment for esophageal cancer was feasible and effective; however, moderate-to-severe toxicity occurred. This protocol warrants further clinical evaluation in a multi-institutional prospective study.

[Radiotherapy for bone metastases from hepatocellular carcinoma and pancreas cancer].

There are few reports on the treatment for bone metastases from hepatocellular carcinoma (HCC) and pancreas cancer. We evaluated the therapeutic effects of radiotherapy (RT) in patients with bone metastases from these cancers. Bone metastases from HCC are typically lytic and expansive. We evaluated 13 patients with 16 bone metastases from HCC undergoing RT (30-40 Gy, median 39 Gy) in our department from September 2002 to December 2004. Tumor regression was evaluated by CT or MRI. More than 50% tumor regression was achieved in 4 of 16 lesions (25%). Pain relief was achieved in 12/13 (92%). The median survival was 7 months (95% confidence interval [CI], 4-10 months), and the 6-month and 12-month local control rates were 81% and 67%, respectively. For patients with a limited life expectancy, standard dose RT is appropriate, however,with more than one year life expectancy, investigation employing dose escalation or combination with surgery or TAE is needed. Thirteen patients with 18 bone metastases from pancreas cancer received RT (20-30 Gy, median 30 Gy) from September 2002 to March 2005. The median survival was 3 months (95% CI, 1-6 months). Pain relief was achieved in 12/13 (92%). The prognosis of patients with bone metastases from pancreas cancer is still very poor, and a single fraction or short fraction schedule RT is appropriate.

[Case series of localized nasal NK/T-cell lymphoma treated with preceding intensified local radiation therapy before systemic chemotherapy].

Nasal NK/T-cell lymphoma is EB virus-associated aggressive lymphoma, which is more prevalent in Asia. Previously, this lymphoma which was recognized as lethal midline granuloma, commonly presents with midline facial destructive lesions. In early stage I/II disease, radiation therapy exerts a powerful treatment outcome, however, toxic adverse events are indispensable and the tolerability of radiation therapy with chemotherapy has not been fully studied. It is imperative to offer an appropriate treatment for cure of this disease. We report consecutive 4 cases of nasal NK/T-cell lymphoma, which was treated with 56 Gy intensified local radiation therapy followed by systemic chemotherapy. Two cases complicated with grade 3 stomatitis during the treatment course and 3 cases were hospitalized due to the decrease of oral intake. The scheduled radiation chemotherapy was completed and resulted in complete response of disease in all cases. High intensified radiation therapy followed by chemotherapy may be effective for localized nasal NK/T-cell lymphoma.

Evaluation of anatomy-based dwell position and inverse optimization in high-dose-rate brachytherapy of prostate cancer: a dosimetric comparison to a conventional cylindrical dwell position, geometric optimization, and dose-point optimization.

BACKGROUND AND PURPOSE: To compare treatment planning methods in high-dose-rate (HDR) brachytherapy of prostate cancer. In particular, to assess quantitatively the dosimetric superiority, if any, of the anatomy-based dwell position (ABDP) and inverse optimization (IO) over the conventional cylindrical dwell position (CDP), geometric optimization (GO), and dose-point optimization (DO) in terms of the determination of dwell positions and dwell times. PATIENTS AND METHODS: Between September 2002 and April 2003, 10 cases of treatment-planning CT images were taken for external radiotherapy for prostate cancer. Treatment planning computer software and the CT data were used to create hypothetical HDR brachytherapy applicator needles, which were properly implanted in the prostate. Six different plans including IO with ABDP (IO(ABDP)), IO with CDP (IO(CDP)), GO with ABDP (GO(ABDP)), GO with CDP (GO(CDP)), DO with ABDP (DO(ABDP)), and DO with CDP (DO(CDP)) were made for each case, that is, 60 plans in total. All plans were normalized so that the D(95) should be equal to 100% of the prescribed dose. Dose-volume histograms from all 60 plans were analyzed, and multiple implant quality indices, including CI, EI, DNR, %V(R 75), %V(B 75), and %V(U 150) for each plan, were extracted and compared. Then, the best settings for IO(ABDP) regarding dwell position and dose limit were sought for. RESULTS: ABDP showed a statistically significantly lower EI (P<0.001), %V(R 75) (P=0.002), and %V(B 75) (P=0.015) than CDP. IO showed a statistically significantly lower %V(U 150) than GO (P=0.009), or than DO (P<0.001). Given a definition that a figure exceeding three-fold of the minimum figure of the index is clinically unacceptable, only in IO(ABDP) all index figures were clinically acceptable, while in the other five plans at least one index figure was unacceptable. CONCLUSIONS: In the CT-based treatment planning for prostate HDR brachytherapy, ABDP is useful to achieve a high conformity, which leads to a reduction of the doses to the bladder, rectum, and surrounding normal tissue. IO is useful to lower the urethral dose without sacrificing conformity. IO(ABDP) is recommended on the basis of the current study. However, this conclusion has been drawn from the idealized hypothetical settings, and some possibility remains that this conclusion is not always applicable to the real implants.

Treatment results of stage I oral tongue cancer with definitive radiotherapy.

The medical records of 133 patients with Stage I tongue cancer treated by definitive radiotherapy between 1966 and 2001 were reviewed. Overall survival rate (OS), progression free survival rate (PFS), and survival rate after recurrence were calculated according to the Kaplan-Meier method. We investigated prognostic factors for local control and risk factors of late neck LN metastasis. The 5-year OS was 81.8% and the 5-year PFS was 67.2%. The 5-year OS after local recurrence was 100% by salvage operation, and that after neck LN metastasis was 40.7% despite radical neck dissection. Tumor thickness over 5 mm and treatment without interstitial irradiation were prognostic factors for local control. Tumor diameter over 15 mm and tumor thickness over 5 mm were risk factors of late neck LN metastasis. We should consider prophylactic treatment for neck LN for high risk patients with Stage I tongue cancer in order to improve treatment results further.

Clinical assessment by MRI for patients with stage II cervical carcinoma treated by radiation alone in multicenter analysis: are all patients with stage II disease suitable candidates for chemoradiotherapy?

PURPOSE: From recent randomized trials, patients with Stage II cervical carcinoma are thought to be candidates for chemoradiotherapy. To refine the strategy for Stage II patients, we performed a retrospective multi-institutional analysis using MRI. METHODS AND MATERIALS: From three institutions, 84 patients with Stage II cancer diagnosed by MRI were entered into the study. All patients received intracavitary brachytherapy with (n = 83) or without (n = 1) external beam radiotherapy. Uni- and multivariate analyses were performed to identify the prognostic factors for overall survival (OAS), disease-free survival (DFS), pelvic control (PC), and distant metastasis-free survival (DMFS). RESULTS: The 5-year DFS rate of patients with maximal tumor size (D(max)) > or =50 mm (46.2%) was significantly lower than that for patients with D(max) <50 mm (88.0%; p <0.0001). Large size or volume and lymph node swelling were also significant prognostic factors of OAS, DFS, PC, and DMFS. In the multivariate model, size or volume was a significant prognostic factor of OAS, DFS, PC, and DMFS, and lymph node swelling was a prognostic factor for DFS, PC, and DMFS. Using these two prognostic factors, patients were divided into 3 subgroups. The 5-year DFS rate of patients with risk 0 (D(max) <50 mm and negative lymph node swelling), 1 (D(max) > or =50 mm or positive lymph node swelling), and 2 (D(max) > or =50 mm and positive lymph nodes) was 93.2%, 53.3%, and 25.0%, respectively (p <0.0001). CONCLUSION: In this stage-limiting analysis, we clarified the stratification according to clinical risk with the aid of MRI. For patients with low-risk factors, especially for elderly patients, radiation alone would probability be a feasible option. In the future, a randomized trial using criteria with MRI would help to identify the optimal strategy for patients with Stage II disease.

Phase I study of combination chemotherapy with 5-fluorouracil (5-FU) and nedaplatin (NDP): adverse effects and eecommended dose of NDP administered after 5-FU.

When nedaplatin (NDP) was used as a single agent in the phase I study, the dose-limiting toxicity (DLT) was thrombocytopenia and the recommended dose (RD) was 100 mg/m2. However, the DLT, maximum tolerated dose (MTD) and RD of NDP used in combination with 5-fluorouracil remained unknown. Therefore, we performed this study to assess the DLT and RD of NDP administered after 5-fluorouracil (5-FU). In this study, 5-FU was administered to 38 patients at a fixed dose (700 mg/m2/d on days 1-5) and NDP administered on day 6 at an initial dose of 80 mg/m2, which was subsequently increased to 100, 120, 130, 140, 150, and 160 mg/m2. The DLT of NDP was leukopenia and its MTD and RD were 160 and 150 mg/m2, respectively. Concerning impairment of renal function, only two patients had a grade I increase in serum creatinine. There were 19 responders (50%, 19/38) achieving partial response or complete response in the evaluation of antitumor effect. The result of this study is notable in that administration of 5-FU before NDP allows the dose of NDP to be substantially increased.

Single institute experience of chemotherapy and adjuvant radiotherapy for localized aggressive non-Hodgkin's lymphoma: retrospective analysis of the clinical efficacy of radiation therapy.

We retrospectively analyzed the clinical outcome of localized aggressive lymphoma treated with chemotherapy and adjuvant radiotherapy. Between 1982 and 1998, 77 patients who were diagnosed as having aggressive lymphoma stage I-II were treated with chemotherapy followed by radiation therapy. The median radiation dose was 44.4 Gy (range, 30-64 Gy). Some patients who achieved complete response after chemotherapy received limited-field radiation to reduce toxicity. Several prognostic factors were analyzed in the overall (OAS) and relapse-free survival (RFS) by both uni- and multivariate analysis. The 5-year rates of OAS and RFS were 74.6% and 70.8%, respectively. Patient age (p = 0.016), radiation dose (p = 0.043), and prognostic score proposed by the Japan Lymphoma Radiation Therapy Group (JLRTG; p = 0.0073) were significant predictive factors for OAS. As for RFS, predictive factors were patient age (p = 0.042), elevated level of serum lactic dehydrogenase (p = 0.046), and JLRTG score (p = 0.05). At the multivariate level, only patient age greater than 60 years was a significantly adverse variable for both OAS (p = 0.0079) and RFS (p = 0.0198). Our treatment strategy was thought to be acceptable with satisfactory outcomes. Limited-field radiation may have possible advantages in toxicity if it does not lead to worsening of the outcome, although a conclusive result could not be obtained by the current analysis.