We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis.

There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (≥1 mg/dl) was the only independent predictor of recurrence in N0M0 patients.

Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. N0M0 patients whose RCC has worst-grade components but whose CRP levels are <1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

Patients with Stage I (T1N0M0) ESCC, aged 20–75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m² (day 1) and 5-FU 700 mg/m²/day (days 1–4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1–21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence.

From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6–94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3–89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3–78.8) (mucosal recurrence removed by endoscopy was not counted as an event).

High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

Patients with advanced or metastatic colorectal cancer (CRC) received: UFT 300 mg/m², LV 75 mg/body and CPT-11 150 mg/m² (UFT and LV given on days 1–14, and CPT-11 on day 1, every 3 weeks). Eligibility: ECOG performance status (PS) 0–1, adequate bone marrow/liver function and serum creatinine level less than institutional normal value.

Eighteen patients enrolled, 17 evaluable for toxicity and response and 1 patients recalled chemotherapy upon registration. Characteristics: 61% male, median age 63.5 years (51–71). Seventy-two per cent PS 0, 50% first line. One hundred and eighty-six cycles have been delivered. The common Grade 3–4 toxicities were neutropenia (35.3%), leukopenia (29.4%), diarrhea (5.9%), anorexia (5.9%), vomiting (5.9%) and dizziness (5.9%). There was no episode of febrile neutropenia. No death occurred on treatment: Overall RR was 41.2% [7/17: 1 complete response (CR) + 6 partial response (PR)]. Progression-free survival (PFS) is 6.9 months, median survival time (MST) is 25.1 months and 1-year survival rate is 70.6%, whereas PFS 15.0 months, MST 43.6+ months and 1-year survival rate 100% in cases with CR or PR.

Approved dose of CPT-11 is 150 mg/m² in Japan. As is lower dose with CPT-11, TEGAFIRI for patients with advanced or metastatic CRC in Japan seems to have the similar effect with that reported in aboard and indicates prolonged PFS and MST in cases with CR or PR.

An immunohistochemical approach was used to detect VEGF-R1, -R2 and -R3 expression in 91 CRC patients who underwent surgery and received chemotherapy at the National Cancer Center Hospital. Statistical analysis was performed to determine the prognostic significance of these biomarkers.

Immunoreactivity for VEGF-R2 and -R3 was localized in microvessels and that for VEGF-R1 in cancer cells and stromal microvessels. VEGF-R1 staining in cancer cells (>10% staining) was found in 84 patients (92%) and in stromal vessels in 75 patients (82%). VEGF-R2 staining in tumor vessels (>10% staining) was found in 84 patients (92%), whereas VEGF-R3 staining was found in 85 patients (93%). Strong positive staining (>60% staining) of VEGF-R1 in tumor cells, and VEGF-R1, -R2 and -R3 in vessels was identified in 58 (64%), 33 (36%), 52 (57%) and 60 (66%) patients, respectively. Univariate analysis revealed that VEGF-R1 strong positive staining correlated with shorter post-operative survival in patients with Stage II/III disease (P = 0.01), but neither VEGF-R2 nor R3 expression correlated with survival.

VEGF-R1, -R2 and -R3 were highly expressed in CRC cells and stromal vessels. VEGF-R1 strong positive staining correlated with shorter survival after CRC surgery.

We provided home care to 580 patients from 1 January through 31 October 2007. Patients with hematologic malignancies were selected from these 580 patients; subsequently, by reviewing their medical records.

The main clinical condition in 15 (2.6%) of 580 patients was hematologic malignancies. The median age of the patients was 78 years (range, 64–92). Of the 15 patients, 12 showed a performance status (PS) of 3–4, and the condition of 6 patients was complicated with dementia. Food intake via the oral route was possible in 14 patients. These patients were administered palliative care. Among the seven patients who required pain control, four had been opioid users; however, none had used anticancer drugs for pain relief. Furthermore, three patients received blood transfusion. Although three patients developed severe complications (acute appendicitis, pneumonia and hyperglycemia), we were able to treat all cases adequately. Eight patients died at home due to aggravation of the primary diseases. The remaining seven patients were transferred to other hospitals for the treatment of complications or for the convenience of their respective families.

Even patients with hematologic malignancies could be candidates for home care if their underlying diseases are slowly progressive, and they can sustain themselves by oral intakes. Dementia and poor PS are not contraindicated to it.

Forty-seven cases of TNBC were included. Immunohistochemical stains for androgen receptor (AR), p53, CD10, c-kit, CK5/6, vimentin, bcl-2, E-cadherin, Ki-67 and epidermal growth factor receptor were performed. In vitro ATP-CRA was used to analyze chemosensitivity for 5-fluorouracil (5-FU), docetaxel, doxorubicin, epirubicin, vinorelbine, gemcitabine, methotrexate (MTX), oxaliplatin and paclitaxel.

The results showed that all cytotoxic agents demonstrated the trend that E-cadherin-expressing cases had a higher cell death rate than E-cadherin-negative cases. Particularly, vinorelbine showed statistical significance (P = 0.004). Cases with AR expression showed higher cell death rates than those without in 5-FU and MTX (P = 0.012 and 0.014, respectively).

E-cadherin and AR could be candidate predictive factors for chemotherapy response in TNBC. Further in vivo study is required to clarify their roles.

From June 1989 to January 2008, 202 patients (128 males and 74 females) with high-grade osteosarcoma of the extremities were treated at our institution. Patients were divided into three groups depending on the time of identification of pulmonary metastasis: group A, identified with primary tumor diagnosis; group B, during whole treatment course; and group C, after completion of treatment. Long-term survival was calculated and factors related to metastases were analyzed.

Ninety-one patients developed pulmonary metastases; 21 in group A, 18 in group B and 52 in group C. The mean period from initial diagnosis to lung metastases in groups B and C was 22.2 months (±20.6). Five-year survival rates were 82.0% and 38.3% in the non-metastasis group and metastasis group, respectively (P < 0.001). The 5-year survival rate was significantly worse in group A than in group B or C (0%, 7.4%, 59.5%, P < 0.001), in patient with more than one lobe involved (27.0%, P = 0.006) and more than three pulmonary nodule metastases (21.3%, P = 0.002). Factors related to the pulmonary metastasis were: old age (65.5% in older than 27.5 years old and 41.6% in younger, P = 0.017), large tumor volume (54.4% in larger than 202.5 ml and 33.7% in smaller, P = 0.005) and elevated lactodehydrogenase (LDH; 55.1% vs.31.0% in normal, P = 0.001).

The prognosis of osteosarcoma with pulmonary metastases is dismal, especially for patients who have primary pulmonary metastases, more than three pulmonary metastatic nodules or involvement of more than one lobe. Factors such as older age, larger tumor volume and elevated LDH may reflect high metastatic rate.

Chemotherapy-naïve NSCLC patients with PS 2 were enrolled. Chemotherapy consisted of an escalated dose of GEM on days 1 and 8 and CBDCA on day 1 every 3 weeks. Patients were scheduled to receive GEM (mg/m²)/CBDCA (area under the curve: AUC) at four dose levels: 800/4 (level 1), 1000/4 (level 2), 1000/4.5 (level 3) and 1000/5 (level 4), respectively.

Between February 2004 and August 2006, 13 patients were enrolled in this study. Dose-limiting toxicities (DLTs) were thrombocytopenia, febrile neutropenia and hyponatremia. DLTs were observed in two of six patients at dose level 1 and in three of six patients at dose level 2. Dose level 2 was thus determined to be the MTD. Among 12 evaluable patients, 7 patients had stable diseases and 5 patients had progressive diseases, and the median survival time was 3.8 months.

The MTD and the recommended dose for Phase II studies of this regimen were determined to be GEM 1000 mg/m² and CBDCA AUC of 4. Additional objective measures are needed to evaluate patients’ risk and benefit in future clinical trials for PS 2 patients.

One hundred patients who had previously undergone BC surgery and were alive without recurrence for >5 years were asked to answer the patient-administered questionnaires to assess their QOL (Functional Assessment of Cancer Therapy scale-Breast: FACT-B) and psychological distress (Hospital Anxiety and Depression Scale: HADS). Of them, 93 responded to the questionnaires affirmatively.

Although none of the QOL scores were related to the surgical procedures, statistically significant relationships were found between age and the scores of FACT-General and social/family well-being (SWB), and between the educational status and scores of SWB in univariate analyses. There was no statistically significant relationship between psychological distress and each factor examined. In multivariate analyses, significant correlations were established between scores of the FACT-BC subscale (FACT-BCS) and the type of surgery and between those on the FACT SWB subscale and age at study or educational status. Namely, patients who had undergone BCT, younger patients and patients with higher educational background scored higher QOL.

Among the BC survivors, those who underwent BCT experienced significantly but slightly better QOL than those who received mastectomy in FACT-BCS assessments. Younger patients and patients with higher educational backgrounds experienced significantly better SWB.

Twenty patients with inoperable NSCLC received weekly carboplatin at area under the curve (AUC) = 2 mg/ml min and paclitaxel. Paclitaxel was escalated if MTD was not reached. Three patients each were entered at levels 1 and 2 (level 1, paclitaxel 50 mg/m² and carboplatin AUC = 2 mg/ml min; level 2, 60/2), six at level 3 (70/2), five at level 4 (80/2) and three at level 5 (90/2).

One patient had grade 4 (G4) neutropenia at level 2, one had G3 hepatic toxicity at level 3 and one had G3 cardiac toxicity at level 4. MTD was not reached for all dose levels. Response rate (RR) was 35% (7/20) and median survival was 11.1 months. Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C_max) and the duration of plasma concentration >50 ng/ml of paclitaxel.

Weekly combined paclitaxel (up to 90 mg/m²) and carboplatin (AUC = 2 mg/ml min) was well tolerated. A higher dose intensity of paclitaxel can be given, and RR and survival are not less than the every-3-week protocol. The weekly regimen is an alternative for untreated inoperable NSCLC patients.

Patients with advanced esophageal cancer received 175 mg/m² of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m² in a 1 h infusion on day 1 every 3 weeks until the documented disease progression, unacceptable toxicity or patient's refusal.

Between March 2005 and December 2007, 48 patients entered in the study. Forty-six (95.8%) of the 48 patients were assessable for response. The overall response rate was 41.7% (95% CI, 27.8–55.7%) with 2 complete responses and 18 partial responses. The median follow-up period was 20.5 months (range, 12.5–27.2 months). The median overall time to progression and overall survival (OS) were 6.1 months (95% CI, 4.8–7.4 months) and 11.5 months (95% CI, 9.1–13.9 months), respectively. The estimate of OS at 12 and 24 months was 43.8% (95% CI, 29.7–77.8%) and 10.4% (95% CI, 1.8–19.1%), respectively. Most patients experienced anemia, during their course of therapy with 6 (13.0%) patients for grade 3/4 anemia, and grade 1 or 2 anemia was detected in 23 (50%) patients. Grade 3 leucopenia, neutropenia and thrombocytopenia were documented in 8 (17.4%), 9 (17.4%) and 2 (4.3%) patients, respectively. Grade 3 nausea and vomiting were detected in 3 (6.5%) and 2 (4.3%) patients, respectively. Two patients (4.3%) were hospitalized because of treatment-related complications. The treatment was well tolerated and no toxic death occurred.

Combination of paclitaxel and nedaplatin is a tolerated treatment modality with promising activity in previously untreated advanced esophageal cancer.

Four hundred and seventy two consecutive patients with curatively resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and the –94 insertion/deletion ATTG polymorphism of NFKB1 determined using a polymerase chain reaction–restriction fragment length polymorphism assay.

The NFKB1 promoter gene polymorphism was successfully amplified in 97.8% of the cases. There were no sexual differences in relation to the genotype and allele. No correlation was observed between the frequency of the genotype or allele and the T, N or M stage. The multivariate survival analysis showed no association between the NFKB1 –94 insertion/deletion promoter polymorphism and the disease-free survival or overall survival of the patients with gastric cancer.

The functional NFKB1 promoter polymorphism was not found to be a prognostic marker for Korean patients with surgically resected gastric adenocarcinoma.

We performed DNA sequencing of the JAK2 exon 12 after TA-cloning in JAK2-V617F-negative and JAK2-V617F-positive PV patients.

We found clonal mutations (i.e. H538-K539delinsL and D544G) in 3 of 7 JAK2-V617F-negative PV patients, however, unlike JAK2-V617F, allele burden of JAK2 exon 12 mutation was low. Since allele-specific PCR is able to amplify only the limited region which contains known mutations with gain-of-function, we need to clarify the biological implications of unknown single nucleotide substitution of the JAK2 exon 12 with low clonal burden in erythrocytosis patients.

The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008. As post-operative adjuvant chemotherapy, four cycles of TC (DTX 75 mg/m² + CPA 600 mg/m²) were administered at 3-week intervals. Adverse events were evaluated based on National Cancer Institute—Common Terminology Criteria for Adverse Events ver. 3.0. The safety and completion rate were evaluated as the primary and secondary endpoints, respectively.

Regarding hematological toxicity, Grade (G) 4 neutropenia occurred in 71.7% and G3 in 26.4%. G3–4 leukopenia developed in 32.1% and 56.6%, respectively, G4 anemia in 1.9% and G1–2 anemia in 26.4%. Regarding non-hematological toxicity, systemic malaise, skin eruption, edema, myalgia, arthralgia and nausea were noted in most patients. The completion rate was 94.3%, dose reduction was necessary in 7.5% and granulocyte colony-stimulating factor (G-CSF) support was required in 17.0%. On comparison between patients aged 65 years or older and younger than 65 years, the completion rate, dose reduction and incidence of febrile neutropenia (FN) were higher in the elderly patients. G-CSF support was more often needed in this subgroup.

TC therapy is tolerable for Japanese patients, but attention should be paid to the development of FN and neutropenia. The completion rate was lower in the elderly patients, showing that tolerability was not necessarily favorable.

Between October 2005 and June 2007, 96 patients were treated by an RRP and 88 patients were treated by a PPB. A HRQOL survey was completed at baseline, and at 1, 3, 6 and 12 months after treatment, prospectively.

The general HRQOL in the RRP and PPB groups was not different after 3 months. However, at baseline and 1 month after treatment, the mental component summary was significantly better in the PPB group than in the RRP group. Moreover, the disease-specific HRQOL was worse regarding urinary and sexual functions in the RRP group. Urinary irritative/obstructive was worse in the PPB group, but urinary incontinence was worse in the RRP group and had not recovered to baseline after 12 months. The bowel function and bother were worse in the PPB group than in the RRP group after 3 months. In the RRP group, the patients with nerve sparing demonstrated the same scores in sexual function as the PPB group.

This prospective study revealed the differences in the HRQOL after an RRP and PPB. Disease-specific HRQOL is clarified by using EPIC survey. These results will be helpful for making treatment decisions.

A retrospective analysis of 125 HER2-positive breast cancer patients treated by NAC using an anthracycline plus taxane with (HCN group, n = 54) or without trastuzumab (non-HCN group, n = 71) was performed. The clinical parameters, including the pathological complete remission (pCR) rate, disease-free survival (DFS) and organ-specific recurrence-free survival, were measured.

According to the results of the univariate analyses, age, clinical stage, pCR and axillary lymph node status were the factors significantly associated with the DFS. The inclusion of trastuzumab in the NAC regimen did not yield a significant difference in the DFS. Only the axillary lymph node status and age were found to be the significant factors affecting the DFS in a multivariate model. There were no significant differences in the patient/tumor characteristics between the HCN and non-HCN groups except for the pCR rate (50% in the HCN group vs. 24% in the non-HCN group) and the median follow-up time (738 days in the HCN group vs. 1579 days in the non-HCN group). Within the first 2 years from the initiation of NAC treatment, the central nervous system (CNS) was the most common site of first recurrence in the HCN group, whereas no cases of CNS metastasis were observed in the non-HCN group.

The pathological axillary node status and age were found to be the significant prognostic factors in HER2-positive breast cancer patients who received NAC. The pattern of recurrence may be different between HCN-treated and non-HCN-treated patients.