Forty-seven patients with head and neck cancers who underwent definitive chemoradiotherapy from December 1998 to March 2006 were reviewed retrospectively. Median age was 63 years (range, 16–81). The locations of the primary lesion were as follows: larynx in 18 patients, oropharynx in 11, nasopharynx in 7, hypopharynx in 7 and others in 4. Clinical stages were as follows: Stage II in 20 and Stages III–IV in 27. Almost all patients underwent platinum-based concomitant chemoradiotherapy. The median cumulative dose of cisplatin was 100 mg/m² (range, 80–300) and median radiation dose was 70 Gy (range, 50–70).

Severe dysphagia (Grade 3–4) was observed in 22 patients (47%) as an acute toxic event. One patient required tube feeding even at 12-month follow-up. In univariate analysis, clinical stage (III–IV) (P = 0.017), primary site (oro-hypopharynx) (P = 0.041) and radiation portal size (>11 cm) (P < 0.001) were found to be associated with severe dysphagia. In multivariate analysis, only radiation portal size was found to have a significant relationship with severe dysphagia (P = 0.048).

Larger radiation portal field was associated with severe dysphagia induced by chemoradiotherapy.

Tumor specimens from 23 patients with previously untreated NK/T-cell lymphoma initially treated with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) or CHOP-based chemotherapy were examined by immunohistochemistry for three NF-B subunits (p65, p50 and p52), which are involved in either the canonical or alternative pathway.

None of the cases could be detected with p65 or p50 nuclear staining. On the other hand, 15 (65.2%) cases had p52 nuclear staining, suggesting NF-B activation through the alternative pathway. All major clinical characteristics were balanced between NF-B p52-positive and -negative patients. The objective response rate achieved in NF-B-positive patients was significantly lower than that in negative patients (33.3% vs. 87.5%, P = 0.027). At a median follow-up of 25 months, 8 (53.3%) of 15 NF-B-positive patients had died compared with none of 8 NF-B-negative patients (P = 0.041). In a multivariate analysis, NF-B status and stage were identified to be independent prognostic factors.

Our results suggest that NF-B activation through the alternative pathway is frequently observed in NK/T-cell lymphoma and associated with chemoresistance and poor survival.

Eighteen Japanese lung cancer patients who had experienced severe neutropenia (absolute neutrophil counts <0.5 x 10⁹ cells/l) were enrolled. Six patients were sequentially enrolled in each pegfilgrastim dose cohort (dose levels of 30, 60 or 100 µg/kg). Patients received the same chemotherapy regimen as in their previous cycle and pegfilgrastim was injected subcutaneously the day after chemotherapy ended in each treatment cycle. Pharmacokinetic, pharmacodynamic and safety analyses were performed.

Dose-limiting toxicity and serious adverse events related to pegfilgrastim were not observed in any patients. Pegfilgrastim antibodies were not detected. Maximum serum concentrations and area under the serum concentration–time curves of pegfilgrastim were dependent on the pegfilgrastim dose in a non-linear manner. Of the 18 patients, severe neutropenia occurred in 4 (22.2%), and, of these, 1 patient (5.5%) required rescue treatment by filgrastim.

A single dose of pegfilgrastim increases the serum concentration of pegfilgrastim for several days in a dose-dependent manner and is not associated with significant toxicity. Good efficacy of pegfilgrastim for the prevention of severe neutropenia was observed at all dose levels. Based on these data, further studies are warranted to determine the recommended dose of pegfilgrastim for Japanese patients with chemotherapy-induced neutropenia.

From 2004 through 2006, 78 patients with metastases of the thoracic and/or the cervical spine were treated with radiation therapy (RT). Of these, 86 irradiated lesions in 73 patients were evaluable by magnetic resonance imaging and/or computed tomography at the initiation of RT and were reviewed retrospectively in this study. Twenty-eight patients (38%) had motor deficits at the initiation of RT. Assessed factors were age, sex, primary disease (lung, breast, digestive system and other cancer), lamina involvement, main level of tumor location and vertebral-body involvement.

Incidence of motor deficits at the initiation of RT was 55% for lesions with lamina involvement and 5% for lesions without lamina involvement (P < 0.0001). Incidence of motor deficits was 15% for lesions located mainly in the cervical spine and/or the upper thoracic spine (Th1–4), 54% for lesions located mainly in the middle thoracic spine (MTS) (Th5–8) and 30% for lesions located mainly in the lower thoracic spine (Th9–12) (P = 0.0095). Age, sex, primary disease and vertebral-body involvement were not statistically significant factors for incidence of motor deficits due to MSCC (P > 0.9999, P = 0.7798, P = 0.1702 and P = 0.366, respectively).

Vertebral metastases with lamina involvement tended to cause symptomatic MSCC. Latent development of MSCC occurred more frequently in the MTS compared with other levels of the thoracic and the cervical spine.

Patients over 40 years who were referred for initial colonoscopy at six institutes were selected. They were classified into four groups based on the initial colonoscopy: A, patients without any adenoma; B, with adenomas of <6 mm only; C, with adenomas of ≥6 mm; D, with any intramucosal cancer. The index lesion (IL) at follow-up colonoscopy was defined as large adenoma ≥10 mm, intramucosal/invasive cancer.

A total of 5309 patients were enrolled in this study. Overall, median follow-up period was 5.1 years. The numbers of eligible patients in the various subgroups were A, 2006; B, 1655; C, 1123; D, 525. A total of 379 ILs were newly diagnosed during follow-up colonoscopy. The cumulative incidence of ILs in each group was A, 2.6%; B, 6.7%; C, 13.4%; and D, 12.6%.

Patients with any adenomas >6 mm or intramucosal cancer at the initial colonoscopy have a higher risk of advanced neoplasia during follow-up colonoscopy.

Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this single-blind randomized controlled study. Patients were randomly assigned to receive GRN at a single dose of 1 or 3 mg. The primary endpoint was the rate of complete protection from emetic events (no vomiting, no retching and no need for rescue medication) during the first 24 h following the initiation of chemotherapy.

There were 89 patients in the 1 mg group and 90 patients in the 3 mg group. Complete protection was achieved in 70 patients (78.7%) in the 1 mg group and 73 (81.1%) patients in the 3 mg group. The one-sided test did not reveal non-inferiority of either dose of GRN to the other at a 5% significance level.

Our data failed to show the non-inferiority of 1 mg of GRN to 3 mg of GRN administered as a single dose. However, the rate of complete protection from nausea and vomiting was similar in the two groups. Given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of GRN at 1 mg may be an appropriate, alternative treatment for acute CINV in cancer patients.

We performed a retrospective analysis of 69 patients with MM who received bortezomib-containing regimens (n = 30) or VAD (n = 39) before collection of peripheral blood stem cells and ASCT.

Objective response rate (at least a partial response) prior to ASCT was documented in 27 (90%) of 30 and 31 (81.6%) of evaluable 38 patients with bortezomib-containing regimens and VAD, respectively. The difference between the two groups was not significant (P = 0.494). However, the high-quality response rate with VGPR or more in the bortezomib group was significantly higher compared with the VAD group (66.7% vs. 34.2%, respectively, P = 0.006). The superiority of bortezomib-containing regimens in the high-quality response rate remained significant for only the newly diagnosed patients (n = 16, P = 0.008). The engraftment data as well as stem cell harvesting were comparable between the two groups. The major bortezomib-related toxicities were thrombocytopenias and peripheral neuropathies; toxicities of VAD were hematologic and infectious. After ASCT, the difference between the two groups did not reach the level of statistical significance with respect to progression-free survival and overall survival (P = 0.498 and 0.835, respectively).

The results of this retrospective comparison of bortezomib-containing regimens with the VAD as induction treatment prior to ASCT for MM provided a demonstration of the superiority of bortezomib therapy in terms of achieving a high-quality response. However, survivals following ASCT did not differ according to the induction regimens.

Two authors independently searched PubMed and EMBASE for studies regarding the association of flavonoids intake with lung cancer risk. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated by using random-effects model.

Eight prospective studies and four case–control studies involving 5073 lung cancer cases and 237 981 non-cases were included in this meta-analysis. The combined results indicated a statistically significant association between highest flavonoids intake and reduced risk of developing lung cancer (RR = 0.76, 95% CI = 0.63–0.92). Furthermore, an increase in flavonoids intake of 20 mg/day was associated with a 10% decreased risk of developing lung cancer (RR = 0.90, 95% CI = 0.83–0.97). In stratified analyses, the highest flavonoids intake was significantly associated with decreased lung cancer risk in prospective studies, studies conducted in Finnish population, studies without adjustment for fruits and vegetables or vitamins, males, smokers and studies using dietary history interview for flavonoids intake estimation. Most subclasses of flavonoids were inversely associated with lung cancer except for hesperetin.

Our data indicate that high or an increased intake of flavonoids is associated with reduced risk of lung cancer in some population but not in other population.

A total of 64 patients aged 75 or older were retrospectively reviewed; 40 were treated with surgery and 24 with CRT. The CRT group included eight patients with unresectable disease and four patients medically unfit for surgery. Surgery included esophagectomy with lymphadenectomy and CRT consisted of 60–70 Gy of radiation concurrent with 5-fluorouracil alone or combined with cisplatin. Short- and long-term outcomes and survival of each modality were assessed.

In the surgery group, 33 patients (82.5%) had co-morbid conditions. Complete resection rate was 90.0%. An overall post-operative complication rate was 65.0% and in-hospital mortality was seen in three patients (7.5%). In the CRT group, complete response rate was 41.7%. Leukopenia was most common Grade 3 hematological toxicity. Treatment-related deaths caused by acute toxicities occurred in three patients (12.5%), whereas those caused by late toxicities in four (16.7%). For cStage I disease in the surgery group, the overall 1-, 3- and 5-year survival rate were 90.9%, 63.6% and 54.5%, respectively, with a median survival time of 78.7 months. For cStages II–IV, the median survival time of the surgery and the CRT group was 18.7 and 12.8 months, respectively.

The short- and long-term outcomes of surgery for the elderly seemed acceptable; however, definitive CRT may be a promising treatment modality. Further investigation may alter the sphere of influence in the field of esophageal cancer treatment in the elderly.

The data source for this study was the IMS Health, Oncology Analyzer^TM. We utilized data on the use of anticancer drugs and follow-up information for patients with CRC from April 2006 to March 2007, collected from the USA, the EU (G5: France, Germany, Italy, Spain and the UK) and Japan. A total of 102 502 patients were enrolled.

Wide differences were found in the actual regimens adopted by each region and nation. In other words, the concept of oncologist-related variability in chemotherapy for CRC was clearly seen. Factors such as a nation's historical characteristics and the healthcare policies of respective governments, including drug approval and cost-effectiveness, also appeared to have roles. However, comparisons of 5-year relative survival rates from population-based cancer registries in the USA, the EU and Japan showed that survival rates for CRC in the three regions did not differ widely, despite differences in the actual use of medical therapy. This may suggest that regional usage trends for anticancer regimens were optimal, although the application of chemotherapy was not the intentional standardization.

Global information exchanges regarding oncologist-related factors along with global evidence could result in patient survival being prolonged by the establishment of intentional standardized treatments suited for regional characteristics.

Fifty patients with Stages I–III cervical cancer, treated with vessel-contouring-based three-dimensional radiotherapy since August 2002, were entered into the study (median age: 54, 47 received concurrent daily cisplatin). All patients were treated with external beam radiotherapy using a four-field box technique with or without brachytherapy. Pelvic blood vessels were identified and contoured on computed tomography simulation images. A generous margin was set outside these vessels outlined on digitally reconstructed radiograph accounting for normal size lymph nodes, patient’s motion and set-up uncertainty. Multi-leaf collimator (MLC) was inserted and adjusted manually. Patterns of recurrence were clinically evaluated.

Distance between major vessels and MLC edges varied inter- and intra-individually. Median distance in the mid-iliosacral joint level was 25 mm (left) and 24 mm (right). The maximum and the minimum distances ranged from 25 to 45 mm (median, 32) and 9 to 27 mm (median, 15) for left side and 24 to 41 mm (median, 30) and 7 to 28 mm (median, 15) for right side, respectively. With a median follow-up of 43 months, 10 patients developed recurrence. However, no marginal recurrence was occurred just lateral to the contoured vessels. All three patients who developed regional recurrence had recurred at the internal iliac node or the obturator node medial to contoured vessels.

Contoured vessels can be used as surrogate markers for location of the pelvic lymph nodes.

Between January 1992 and December 2006, 94 patients with confirmed muscle invasion were treated with intra-arterial chemotherapy and concurrent radiotherapy after an initial complete transurethral resection. Intra-arterial chemotherapy consisted of cisplatin (Days 1–3) and pirarubicin (Days 8–10), and radiation was administered with the chemotherapy (2 Gy/session) with a total dosage of 44 Gy. The median age was 67.0 years. There were 60 patients in T2, 19 patients in T3 and 15 patients in T4. The median follow-up period was 72.9 months in the survivors.

Among these patients, 84 patients (89.4%) obtained a complete response (CR) and 10 patients did not achieve a CR. Between the CR and non-CR patients, the clinical stage and the existence of hydronephrosis were significantly different. The cause-specific survival rates at 5 and 10 years were 76.2% and 67.5%, respectively. The overall survival rates at 5 and 10 years were 66.6% and 47.4%, respectively. A Cox proportional hazard model showed that only the cause-specific survival rate was associated with a CR after treatment. The bladder preservation rates were 89.7% at 5 years and 87.6% at 10 years. Myelosuppression was the major adverse event but it was manageable. Non-hematological sever adverse events were rare.

Bladder preservation therapy shows good survival and good bladder preservation rates. Clinical stage T2 and the absence of hydronephrosis are favorable factors.

A consecutive 77 Japanese patients with Gleason score 8–10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan–Meier method and the difference between groups was assessed with log-rank test. Cox's proportional hazards model was used to elucidate predictors of PSA failure.

During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups.

Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

The subjects of this study were 311 patients who underwent elastography during prostate needle biopsy at Hitachi General Hospital. Strain images obtained during compression of the prostate tissue were displayed on a monitor and recorded on the computer. The elastographic moving images (EMI) were evaluated retrospectively. The evaluable images and biopsy results were compared in terms of the feasibility and accuracy.

The median patient age was 67 years (range 50–85 years), the median serum level of prostate-specific antigen was 8.4 ng/ml (range 0.3–82.5 ng/ml) and the median prostate volume was 42.6 ml (range 12–150 ml). Among the 311 patients, prostate cancer was detected in 95 patients (30%) by biopsy. The diagnostic sensitivity was 37.9% for digital rectal examination (DRE) and 59.0% for transrectal ultrasonography (TRUS), whereas it was 72.6% for elastography and 89.5% for the combination of TRUS and elastography. Elastography-positive EMIs with negative biopsies were eventually determined to be due to benign prostatic hyperplasia.

Elastography has a significantly higher sensitivity for the detection of prostate cancer than the conventionally used examinations including DRE and TRUS. It is a useful real-time diagnostic method because it is not invasive, and simultaneous evaluation is possible while performing TRUS.

Fifteen children (median age: 3 years) with a large OPHA were treated. All of them presented with progressive disease, and the tumor size was larger than 34 mm. Pilocytic astrocytoma was confirmed histologically in 10 patients. Eleven patients had visual disturbance, six had diencephalic syndrome and four had hydrocephalus.

The children received six to eight cycles of cisplatin (20 mg/m²: days 1–5) and vincristine (1.4 mg/m²: days 1, 8, 15), every 4 weeks. Objective response was obtained in 11 patients (73%); one complete response, eight partial responses and two minor responses. Although the remaining four cases were evaluated as stable disease, all tumors decreased in volume. All children tolerated the chemotherapy well under careful audiological monitoring.

Although the present series was small, this chemotherapy is a useful regimen for induction therapy in children with an aggressive deep-seated pilocytic astrocytoma.

This study involved 108 breast cancer patients with non-palpable ALNs. All patients had PET-CT, breast sonography and mammography imaging before sentinel lymph node (SLN) biopsy. After SLN biopsy, all patients underwent complete ALN dissection. ALNs were evaluated by standard hematoxylin and eosin staining techniques. The findings of PET-CT, breast sonography and mammography imaging of 108 patients were compared with pathologic findings after surgery. Sensitivity, specificity and accuracy of individual diagnostic modalities were compared. Diagnostic accuracy was evaluated applying receiver operating characteristic (ROC) curve areas.

The sensitivity, specificity and accuracy of PET-CT imaging were 48.5%, 84% and 73.2%, respectively. The sensitivity, specificity and accuracy of breast sonography were 51.5%, 89.3% and 77.8%, respectively. The sensitivity, specificity and accuracy of mammography were 33.3%, 96% and 76.9%, respectively. For involvement of ALNs, PET-CT imaging, breast sonography and mammography had areas under the ROC curve of 0.662, 0.704 and 0.647, respectively.

Compared with the combination of breast sonography and mammography, PET-CT was less sensitive and had less accuracy in detecting ALN metastasis. Consequently, PET-CT is not a reliable non-invasive modality for assessing ALN involvement that can replace ALN dissection or SLN biopsy before decisions are made on appropriate systemic interventions.

We performed immunohistochemical staining for survivin, p53 and Bax in formalin-fixed, paraffin-embedded blocks from 157 surgically resected Stage III gastric cancer tissues. To determine the association with clinical course, we reviewed the patients' clinical records.

Of the 157 gastric cancer tissues, 63 (40.1%) cases showed positive expression for survivin protein. There was no significant association between survivin expression and p53 or Bax. For clinicopathologic parameters, large tumor size was closely related to survivin expression (P < 0.05). The 5-year survival rate of patients with positive survivin expression was significantly lower compared with that for survivin-negative cancer patients (P < 0.05). Survivin and p53 were independent prognostic factors in Stage III gastric cancer.

Survivin protein is an important predictive and prognostic parameter of poor outcome in gastric carcinoma.

We performed a retrospective review of 92 consecutive patients who underwent PET [either integrated PET/computed tomography (CT) or manual fusion of dedicated PET and CT] scans for post-treatment surveillance of gastric cancer between June 2006 and December 2007. Of these patients, 46 patients were suspected of recurrence by other imaging modalities (Group A), 19 patients were suspected of recurrence by tumor markers without definite findings (Group B) and the remaining 27 patients underwent a PET scan without evidence of recurrence (Group C). The diagnostic performance and prevalence of the clinical impact of FDG-PET were analyzed.

Recurrence of gastric cancer was confirmed in 31 patients (67%) in Group A, in 11 patients (58%) in Group B and in 2 patients (7%) in Group C. In addition, colon cancer (n = 3), lung cancer (n = 1) and pulmonary carcinoid (n = 1) were identified in five patients (5%). In patient-basis, the sensitivity, specificity and diagnostic accuracy of PET for recurrence were 81%, 87% and 83%, respectively, in Group A, 73%, 88% and 79%, respectively, in Group B and 50%, 88% and 85%, respectively, in Group C. Therapeutic management was influenced by PET results in 22 patients (48%) in Group A, in 8 patients (42%) in Group B and in 2 patients (7%) in Group C, including cases in which PET was helpful for detecting second primary cancer.

PET with FDG yielded useful information in patients with suspected recurrent gastric cancer, especially when recurrence was suspected in the clinical setting.

We established the subcutaneous tumor model by inoculating wild-type Renca cells into the backs of BALB/c mice, the pulmonary metastatic tumor model by an intravenous injection of luciferase-expressing Renca cells into the tail vain and the orthotopic tumor model by injecting luciferase-expressing Renca cells into the renal subcapsule. These tumor-bearing mice were treated intra-peritoneally with rhIL-2 and/or per os with sorafenib. The antitumor efficacy was evaluated by measuring the tumor size of the subcutaneous tumor or photon intensity of the pulmonary metastatic tumor and the orthotopic tumor.

When rhIL-2 was combined with sorafenib, the antitumor efficacy was significantly augmented in comparison with either rhIL-2 or sorafenib alone in all the models. Sorafenib did not inhibit rhIL-2-induced natural killer cell expansion and rhIL-2 had no effect on the anti-angiogenic activity of sorafenib.

The results suggest that the combination of rhIL-2 and sorafenib may offer significant potential as a novel therapeutic approach for patients with RCC.

We evaluated the effect of adjuvant therapy in 508 patients with RCC following curative surgery. Patients were classified into one of the two categories based on the duration and the total dose of IFN- treatment.

Median follow-up time was 65.5 months. Overall survival rates at 5, 10, 15 and 20 years were 88.8%, 80.5%, 69.6% and 54.1%, respectively. Cause-specific survival rates at 5, 10, 15 and 20 years were 95.0%, 89.1%, 83.0% and 83.0%, respectively. Cox’s proportional hazard model revealed that C-reactive protein, T classification, histological grade and age were significantly independent factors indicative of a poor prognosis. Our examination of the 253 patients diagnosed as pT1-2N0M0 who underwent adjuvant IFN- therapy following surgery found that the therapy was not significantly associated with either cause-specific or disease-free survival. With regard to effects of duration of therapy and total dose of IFN-, patients with a total IFN- exposure of ≥180 x 10⁶ international units (IU) had a better prognosis than those exposed to <180 x 10⁶ IU.

Adjuvant therapy using large doses of IFN- may improve the prognosis of patients with RCC following curative resection, and the new possibility of IFN- therapy merits further investigation.

The subjects of this study comprised two cohorts; the first was 27 patients with MCRC who had failed with 5-FU and CPT-11 before approval of l-OHP in Japan (cohort 1), and the second was 23 patients who had failed with 5-FU, CPT-11 and l-OHP (cohort 2). S-1 was given orally twice daily (80 mg m²/day) for 28 days followed by a 14-day rest.

In cohorts 1 and 2, the response rates were 7% and 0%, and the median progression-free survivals were 2.8 and 2.7 months, and overall survivals after initiation of S-1 were 10.5 and 4.7 months, respectively. The common grade 3 and 4 adverse events in cohorts 1 and 2 were diarrhea 15% and 13%, anorexia 11% and 17% and anemia 26% and 30%, respectively.

S-1 monotherapy did not show promising activity against MCRC after the failures with 5-FU, CPT-11 and l-OHP.

Eligible patients had histologically proven colorectal adenocarcinoma and EGFR tumor expression in ≥1% of tumor cells by immunohistochemistry. Patients received panitumumab 6 mg/kg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) by independent central review. Secondary endpoints included progression-free survival (PFS), overall survival (OS), pharmacokinetic parameters and incidence of adverse events.

Fifty-two patients received at least one dose of panitumumab. Seven patients had partial responses for a confirmed ORR of 13.5% (95% CI: 5.6, 25.8). Median PFS was 8.0 weeks (95% CI: 7.4, 11.4) and median OS was 9.3 months (95% CI: 7.1, 12.8). Panitumumab pharmacokinetics were consistent with prior studies in Japanese and non-Japanese patients. The most common treatment-related adverse events (all, worst grade 3) were acne (81%, 2%), dry skin (62%, 0%), rash (46%, 2%), paronychia (33%, 2%), pruritus (33%, 0%) and hypomagnesemia (33%, 0%). No adverse event of infusion reaction was reported by the investigators.

Panitumumab monotherapy was active in Japanese patients with chemotherapy-refractory mCRC, with pharmacokinetic and safety profiles similar to those seen in prior studies.