We evaluated the immunohistochemical (IHC) expression of cytokeratin 7 (CK7), cytokeratin 20 (CK20), CDX2, CEA, MUC2, MUC5AC and -methylacyl-CoA racemase (AMACR) in 22 POMAs and 41 metastatic colorectal adenocarcinomas (MCAOs) involving ovaries.

MCAOs, in contrast with POMAs, were almost always negative for MUC5 (97.6%), often negative for CK7 (82.9%), focal or diffuse positive for CDX2 (73.2%), diffuse positive for CK20 (65.9%), focal or diffuse positive for MUC2 (51.2%), diffuse positive for CEA (41.5%) and negative for AMACR (41.5%). We therefore considered CK7 (–), CK20 (diffuse +), CDX2 (+) and MUC2 (+) to be colonic markers and regarded cases with expression of more than two colonic markers as MCAO, those with no expression of colonic markers as POMA and those with expression of one colonic marker as indeterminate. Using CK7/CK20/CDX2/MUC2, 82.5% of the cases were correctly classified, 6.3% were misclassified and 6.3% were indeterminate.

CK7, CK20, CDX2 and MUC2 IHC staining is a useful adjunctive diagnostic tool to differentiate MCAOs from POMAs, in addition to clinical history and gross and microscopic findings.

This study included a total of 139 males with newly diagnosed GCTs of the testis or extragonadal origin who received treatment, including surgery, chemotherapy and radiation therapy, at our hospital between 1980 and 2005. We reviewed late recurrence that occurred at least 2 years after the initial disease-free status and secondary malignancies as well as oncological outcomes.

In patients with seminoma, 5-year progression-free survival and cause-specific survival rates were 87.2% and 100% for Stage I, 88.9% and 100% for Stage II, and 50.0% and 50.0% for Stage III, respectively, whereas in those with non-seminomatous GCTs, they were 79.1% and 96.3% for Stage I, 89.5% and 89.4% for Stage II, and 85.7% and 78.4% for Stage III, respectively. Late recurrence was found in five (3.6%) patients and all of them responded to salvage treatment and achieved disease-free status. Second primary hematological neoplasms occurred in three (2.2%), although they had a long-term free of the primary disease. All died of the second primary disease.

Late recurrence was successfully managed with appropriate treatments, although its incidence was not negligible. Periodic follow-up may be necessary for >5 years in patients with GCTs for early detection of late recurrence. In addition, care should be taken to watch for the development of life-threatening second primary malignant disease during long-term follow-up.

Fifty-one Japanese patients with prior nephrectomy, 25 treatment-naive patients (first-line group) and 26 cytokine-refractory patients (pretreated group) were enrolled in this phase II trial. Patients received sunitinib 50 mg orally, once daily, in repeated 6-week cycles (4 weeks on treatment, 2 weeks off). The primary endpoint was RECIST-defined objective response rate (ORR) with tumour assessments every 6 weeks via computed tomography or magnetic resonance imaging. Toxicity was assessed regularly. In the primary efficacy analysis of the intent-to-treat (ITT) population, ORR and 95% confidence interval were calculated based on independent review. Secondary time-to-event endpoints, such as progression-free survival (PFS), were estimated using the Kaplan–Meier method.

In the ITT population, ORR was 48.0% in the first-line group (after a median 4 cycles), 46.2% in the pretreated group (5 cycles) and 47.1% overall, with median times to tumour response of 7.1, 10.7 and 10.0 weeks, respectively. Median PFS was 46.0, 33.6 and 46.0 weeks, respectively. The most common treatment-related grade 3/4 adverse events and laboratory abnormalities were fatigue (20%), hand-foot syndrome (14%) and hypertension (12%), decreased platelet count (55%), decreased neutrophil count (51%), increased lipase (39%) and decreased lymphocyte count (33%).

In Japanese patients with RCC, sunitinib is consistently effective and tolerable with similar risk/benefit as that in Western patients, though there was a trend toward greater antitumour efficacy and higher incidence of haematological adverse events in Japanese patients.

In our study, the expression of carcinoembryonic antigen (CEA), p53 and intracytoplasmic keratin (AE1/AE3) using haematoxylin–eosin (HE) staining negative lymph nodes (LNs) in 28 patients with early-stage NSCLC were analysed using fluorescent quantitation reverse transcription–polymerase chain reaction (FQ–PCR) and immunohistochemistry (IHC).

One hundred and ninety-three LNs were analysed. Two patients staged as I up-staged to II, and six patients staged as II up-staged to III. About 32, 19 and 36 LNs were positive, respectively, for CEA mRNA (32/193, 16.6%), p53 (19/193, 9.84%) and AE1/AE3 (36/193, 18.65%) compared with control LNs. Only FQ–PCR test for CEA mRNA could detect micrometastases in stage I NSCLC patients with N0 LNs (2/13, 15.4%). Disease-free time in patients with CEA mRNA (P = 0.000), p53 protein (P = 0.013) and AE1/AE3 (P = 0.003) positive were significantly inferior to those with micrometastases negative. Moreover, the results demonstrated that the positive LNs for CEA mRNA (P = 0.028), p53 protein (P = 0.048) and AE1/AE3 (P = 0.007) were associated with the relapse time, respectively. However, Cox proportional hazards test showed that only clinical stage was the independent risk factor of relapse, and denied the correlation between micrometastases in LNs and recurrence.

Detection of CEA mRNA, p53, AE1/AE3 in HE-negative LNs may improve veracity of N staging and predict its prognosis in patients with early-stage NSCLC. Furthermore, micrometastases in stage I may be performed by FQ–PCR more sensitive than IHC.

Cases with osteosarcoma of the flat bone were compared with those of the extremity in order to evaluate their clinicopathologic characteristics. And the influences of heterogeneous treatment modalities on outcome were analyzed.

Tumors of the flat bone comprised 91 (11.3%) of 806 osteosarcoma cases. Eight cases were secondary osteosarcoma associated with previous radiotherapy. Patients with a flat bone tumor were significantly older and more likely to present with metastases at diagnosis than extremity tumor. The proportions of female sex and chondroblastic subtype were higher among flat bone tumors than among extremity tumors. The 5-year overall survival and event-free survival rates were 35.2 ± 5.4% and 24.7 ± 5.5%, respectively. Although age and histologic response to pre-operative chemotherapy were not related to outcome of flat bone tumors, treatment modality influenced the survival. Patients treated surgically had better outcomes than those treated by another means. Radiation therapy did not appear to be an effective local control measure as surgery.

Treatment outcome of the tumor of the flat bone was worse than extremity tumors. Further studies are needed to identify effective local control measures that can substitute for surgery and to determine the biologic characteristics of osteosarcoma of the flat bone.

We identified consecutive data on 169 patients who underwent RC for bladder cancer. The mean follow-up was 64 months (range: 1–253 months). Node-positive status (pN(+)) was seen in 16 patients and 91 were diagnosed as node-negative (pN(–)). The lymph node status of the remaining 62 patients was unclear (pN(x)). We analysed the association between lymph node status and cancer-specific survival (CSS), and examined the role of the number of retrieved lymph nodes, particularly in pN(–).

The median number of retrieved nodes was 12.9 and 10.2 for stage pN(+) and stage pN(–), respectively. In 91 patients with pN(–), multivariate analysis revealed that pathological T3-4 (P = 0.0276) and less than nine retrieved lymph nodes (P = 0.0108) were independent risk factors for CSS. In a subgroup of 83 patients with pT3-4, Kaplan–Meier curves showed that the 5-year CSS rate in pN(–) patients with less than nine retrieved lymph nodes was 38.8%, which was extremely similar to the 40.8% in pN(+) and 45.1% in pN(x).

Our results demonstrate that at least nine lymph nodes should be removed to improve the survival of pN(–) patients at RC and lymphadenectomy, and would provide information not only on prognosis but also on the therapeutic impact on pT3-4 invasive bladder cancer.

Subjects comprised 84 patients with histologically confirmed advanced or metastatic breast cancer and at least one measurable metastatic lesion. We evaluated time to disease progression (TTP), response rate (RR) and clinical benefit rate (CBR) for 1st (n = 17), 2nd (n = 28), 3rd (n = 23) and ≥4th (n = 16) line setting treatments of capecitabine monotherapy.

Median number of cycles of capecitabine monotherapy was 12 cycles in 1st line, 11 cycles in 2nd line, 9 cycles in 3rd line and 11 cycles in ≥4th line. RR and CBR were 23.5% and 58.8% in 1st line, 21.4% and 53.6% in 2nd line, 21.7% and 52.2% in 3rd line, and 18.8% and 50.0% in ≥4th line, respectively. No significant differences in TTP were seen between each line setting (P = 0.843).

Capecitabine monotherapy is effective and well tolerated in all line settings of chemotherapy in patients with metastatic or advanced breast cancer, and is suitable for outpatient therapy.

We retrospectively analyzed MBC patients treated at Seoul National University Hospital between 1996 and 2006. The medical records were reviewed.

Fifty-one patients were identified. At a median follow-up of 40.8 months, the 3-year disease-free survival (DFS) and overall survival (OS) rates were 75.5% and 86.3%, respectively. Non-triple negativity (P = 0.012) correlated significantly with OS in multivariate analysis. Of the 51 patients, 41 (80.4%) had TNMC and 10 (19.6%) had NTNMC. The two groups did not differ significantly by age, tumor size or nodal status. In patients with NTNMC, the positivity rates for estrogen receptor, progesterone receptor and HER2 were 20.0%, 30.0% and 80.0% in NTNMC. The 3-year OS rates in patients with TNMC and NTNMC were 93.4% and 58.2%, respectively (P = 0.007). With respect to DFS, there was no statistically significant difference between patients with TNMC and those with NTNMC (P = 0.149).

In MBC, the non-triple-negative group had a poor prognosis compared with the triple-negative group, which is contrary to what has been reported in patients with invasive ductal carcinoma of breast. Further research exploring the mechanism underlying this result is needed.

Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m², ranging from 70 to 88 mg/m².

Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C_max and AUC_{0–48 h} values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.

We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.

Sixty patients with an unsatisfactory colposcopy during the period of September 2007–November 2008 were recruited and randomly allocated to receive either two tablets of 200 µg misoprostol (400 µg) or two tablets of similar-looking placebo vaginally. Colposcopic re-examination was performed ~6 h later. The results and side effects before and 2 weeks after the colposcopic re-examination were recorded.

Six out of 30 patients in the misoprostol group (20.0%) had a satisfactory colposcopic re-examination compared with 2 out of 27 patients (7.4%) in the placebo group without statistically significant difference (P = 0.172). Three patients in the placebo group dropped out due to not present at the appointment time. Six out of 30 patients (20.0%) and 1 out of 30 patients (3.3%) in the misoprostol group had side effects before and 2 weeks after the colposcopic re-examination orderly. Twenty-seven patients in the placebo group did not have any side effects before and 2 weeks after the colposcopic re-examination. All side effects occurred were minimal and well tolerated.

Four hundred micrograms of vaginal misoprostol were not proved to be effective in converting an unsatisfactory to a satisfactory colposcopy.

Twenty patients with hormone refractory prostate cancer (HRPC) were administered a treatment regimen consisting of docetaxel 75 mg/m² once every 3 or 4 weeks and prednisolone 5 mg twice daily at our institution between 2006 and 2008.

The patients received a median of 5.5 cycles of treatment (range, 2–11 cycles). Nine of the 20 patients (45%) had a ≥50% decrease in serum prostate-specific antigen (PSA). The median duration of response was 4 months (range, 1–12 months). The number of cycles performed, the presence of bone metastasis and the extent of disease had statistically significant associations with the response. Three patients had a transient PSA rise among the patients who ultimately had a response. Grade 3/4 leukopenia and neutropenia occurred in 80.0% and 85.0% of the patients, respectively. Interstitial pneumonia occurred in only one patient; however, the patient recovered. Finally, no treatment-related deaths were seen during the observation period.

The combination of docetaxel 75 mg/m² every 3 weeks and prednisolone 10 mg daily was effective and well tolerated in Japanese patients with HRPC. The results of this study suggest that a decision concerning discontinuation of this treatment should be carefully considered because a transient PSA rise was observed. Although interstitial pneumonia was rare, the potential risk of its development should be taken into consideration.

Between 2000 and 2007, 35 patients with Stage I–IVB NPC treated by IMRT were included. For all patients, treatment-planning computed tomography was done twice before and during IMRT to a total dose of 60–70 Gy/28–35 fractions (median 68 Gy). Chemotherapy (cisplatin 80 mg/m²/3 weeks x 1–3 courses) was given concurrently with IMRT for 31 patients.

The 3- and 5-year overall survival rates for the 31 patients treated with concurrent chemotherapy were 88% and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31 patients were 93% and 87%, respectively. Planning target volume delineation for the primary site or involved nodes was insufficient for three early cases, resulting in marginal recurrence in the three patients (9%). Except for one patient with early death, xerostomia scores at 1–2 years were: Grade 0, 11; Grade 1, 17; Grade 2, 5; Grade 3, 1.

Excellent overall survival and loco-regional control rates were obtained by a two-step IMRT method with concurrent chemotherapy for NPC, although marginal recurrence was noted in some early cases.

We retrospectively reviewed 48 patients with primary T1G3 bladder cancer in which a muscle layer in the TUR specimens was confirmed between 1990 and 2006 in our institute. We investigated recurrence and progression in 45 patients, excluding 3 who were immediately treated with radical cystectomy. Fifteen and 12 patients received intravesical treatment with bacillus Calmette–Guérin (BCG) and anticancer agents just after TUR, respectively. The remaining 18 did not have any such treatment.

Recurrence and progression were observed in 21 (47%) and 3 patients (6.7%), respectively, during a median follow-up period of 42.1 months. The 3-year recurrence-free and progression-free survival rates were 54% and 91%, respectively. No significant differences were observed in the rates between the patients with and without BCG treatment in the study.

There is a possibility that the progression rate in patients with T1G3 bladder cancer is not as high as previously reported when only patients whose muscle layer was histologically confirmed were analyzed. An adequate technique for TUR that unmistakably collects the muscle layer may be important to predict the outcome accurately.

The records of elderly (≥70 years of age) patients with LD-SCLC who had been treated with etoposide and cisplatin chemotherapy with early concurrent twice-daily thoracic radiotherapy (TRT) were reviewed retrospectively.

Of the 25 elderly patients with LD-SCLC identified, 12 (48%) individuals received etoposide–cisplatin chemotherapy with early concurrent twice-daily TRT. The main toxicities of this treatment regimen were hematologic, with neutropenia of Grade 4 being observed in all patients and febrile neutropenia of Grade 3 in eight patients during the first cycle of chemoradiotherapy. The toxicity of TRT was acceptable, with all patients completing the planned radiotherapy within a median of 29 days (range, 19–33). No treatment-related deaths were observed. The median progression-free survival and overall survival times were 14.2 months (95% confidence interval, 4.3–18.2) and 24.1 months (95% confidence interval, 11.3–27.2), respectively.

Etoposide–cisplatin chemotherapy with early concurrent twice-daily TRT was highly myelotoxic in elderly patients with LD-SCLC, although no treatment-related deaths were observed in our cohort. Prospective studies are required to establish the optimal schedule and dose of chemotherapy and TRT in such patients.

In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined.

In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11.

Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.

Between 2006 and 2008, 12 metastatic lung tumors (colorectal cancer, 7; others, 5) in 10 patients and 56 lesions of Stage I primary lung cancer (T1, 43; T2, 13) in 52 patients were treated with SBRT of 48 Gy in four fractions at the isocenter.

Two-year overall survival rates were 86% for patients with metastatic lung tumors and 96% for patients with Stage I primary lung cancer (P = 0.4773). One- and 2-year local control rates were 48% and 25% for metastatic lung tumors, and 91% and 88% for Stage I primary lung cancer, respectively (P < 0.0001).

The local control rates after SBRT of 48 Gy in four fractions were significantly worse in metastatic lung tumors compared with Stage I primary lung cancer. In SBRT, metastatic lung tumors should be clearly differentiated from primary lung cancer and should be given higher doses.

Seventy-eight lesions of brain metastases in 49 lung cancer patients treated by stereotactic radiotherapy between September 2003 and December 2006 were analyzed. In the treatment planning, the planning target volume (PTV) was defined as an enhanced lesion plus 3 mm margin. A total dose of 39–42 Gy in three fractions was delivered to the isocenters of the PTV.

The median survival time after stereotactic radiotherapy was 17.4 months. The 1- and 2-year survival rates were 61% and 32%, respectively. The presence of extracranial tumors, the pre-treatment performance status, and the Radiation Therapy Oncology Group recursive partitioning analysis class were significant prognostic factors. The 1- and 2-year local recurrence rates were 14% and 17%, respectively, with no serious acute toxic effect. Injuries involving brain necrosis were observed in six patients. New brain metastases or meningeal carcinomatosis was seen in more than half of the patients following treatment with stereotactic radiotherapy.

Hypofactionated stereotactic radiotherapy with mMLC is considered to be an effective and safe modality for the treatment of brain metastases in lung cancer patients.

From January 1986 through December 2000, we performed treatment in the setting of upfront PDS in 128 patients with Stage III/IV epithelial ovarian cancer. Sixty-six patients with residual disease (RD) at PDS underwent interval surgery (IS) such as ILS or IDS; 4 patients after two cycles of chemotherapy and 62 after three or more cycles. We investigated how disease status at the end of IS was associated with overall survival (OS).

The 5-year OS rates for no, minimal and gross RD were not available (n = 0), 67% (n = 3) and 0% (n = 1) after two cycles, and 47% (n = 42), 0% (n = 18) and 0% (n = 2) after three or more cycles, respectively. No visible tumors at the end of IS after three or more cycles of chemotherapy were necessary for 5-year survival.

If the optimal goal of IDS is defined as the surgery that is expected to result in long-term survival in the NAC setting treatment, our data on the assessment of peritoneal findings during the upfront PDS setting treatment suggest that only complete resection with no RD could be the optimal goal of IDS in the NAC setting treatment.

The reactivity of the monoclonal antibody against pfetin was examined by western blotting and immunohistochemistry.

Western blotting demonstrated that the monoclonal antibody was specific to pfetin. The immunohistochemical study demonstrated that the 5-year disease-free survival rate was 93.2% and 94.5% for GIST patients with pfetin-positive tumors and 70.0% and 80.7% for those with pfetin-negative tumors in the 159 cases from the National Cancer Center Hospital (P < 0.0001) and in the 100 cases from Niigata University Medical and Dental Hospital (P < 0.0001), respectively. Uni- and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinico-pathological parameters examined.

These results establish pfetin as a practical prognostic marker for GIST patients after surgery. Pfetin may also present a novel therapeutic target to prevent recurrence of GIST.

Individual case reviews (ICRs) were performed on all 60 study participants. Radiotherapy data were submitted to the quality assurance (QA) committee, which performed ICRs on 16 QA items according to previously selected criteria. The items focused on quality of external beam radiotherapy (EBRT), HDR-ICBT and both. Each item was determined to be either acceptable or a deviation. The QA committee performed ICR three times as planned, two during the patient accrual and the final one just after the final patient accrued. The QA results of the first and second reviews were reported back to the investigators after each ICR.

In 40 cases (67%), all 16 QA items were classified as acceptable. One deviation was found in 16 cases, two deviations were identified in 3 cases and three deviations were noted in 1 case. The most frequently observed deviation was missing the rules for determining point A (10 cases). The items described by quantitative values, such as prescribed doses, certain time intervals and overall treatment time, were well followed. The proportion of deviations gradually decreased during the ICR process.

The present ICR demonstrated the favorable radiotherapy compliance with the JAROG0401/JROSG04-2 protocol. The QA process using ICRs can potentially be used to improve the quality of radiotherapy, including HDR-ICBT in the multi-institutional prospective studies for cervical cancer.

Twenty patients with advanced oral squamous cell carcinomas, who were treated with preoperative chemo-RT, underwent morphological assessment with CT or MRI and functional assessment with the Saxon test. For the Saxon test, saliva production was measured by weighing a gauze pad before and 2 min after chewing without swallowing; the low-normal value is 2 g. Saliva production and parotid volumes before and 2 weeks after RT were compared with the paired t-test, the Spearman rank correlation test and the Fisher exact test.

After 30 Gy irradiation, mean saliva production was decreased from 4.2 to 1.0 g (P < 0.01); the reduction in saliva production ranged from 1.7 to 5.4 g (mean 3.2 g). The mean parotid volume was decreased from 68.2 to 47.9 cm³ (P < 0.01); the post-RT:pre-RT parotid volume ratio ranged from 54% to 85% (mean 71%). Although the initial parotid volume was correlated with initial saliva production (r = 0.47, P = 0.04), no significant correlation was noted after RT (r = 0.08, P = 0.71), and there were considerable individual variations. The parotid volume ratio was inversely correlated with the saliva-reduction amount (r = – 0.79, P < 0.01).

There was a correlation between decreased parotid gland volume and decreased saliva production in patients with head-and-neck cancer undergoing RT. Parotid volume reduction may predict parotid gland function.

Patients received capecitabine 1000 mg/m² b.i.d. on days 1–14 followed by a 7-day rest period, and irinotecan 100 mg/m² was administered through a 90 min intravenous infusion on days 1 and 8, based on a 3-week cycle.

Forty-six (95.8%) of the 48 patients were assessable for response. Thirteen cases of partial response were confirmed, response rate of 27.1% (95% CI, 14.5–39.7%). The median follow-up period was 25.2 months. The median time to progression and overall survival for all patients were 4.1 months (95% CI, 3.4–4.8 months) and 7.6 months (95% CI, 5.1–10.1 months). Grade 3 diarrhea and hand-foot syndrome occurred in eight (17.4%) and two (4.3%) patients, respectively. The most common Grade 3/4 hematological adverse event was neutropenia in four (8.7%) patients. There were no treatment-related deaths during this study.

Irinotecan plus capecitabine was a relatively active and tolerable regimen as a second-line chemotherapy for AGC. Further investigation of this regimen is warranted, including the addition of new biological agents such as bevacizumab or cetuximab to improve the salvage regimen.

The Patterns of Care Study conducted a random survey of 61 institutions nationwide. Detailed information was collected on prostate cancer patients without distant metastases who were irradiated during the periods 2003–05. Radiation treatment planning and delivery were evaluated in 397 patients who were treated radically with external photon beam radiotherapy.

Computed tomography data were used for planning in ~90% of the patients. Contrast was rarely used for treatment planning. Simulations and treatments were performed in the supine position in almost all patients. Immobilization devices were used in only 15% of the patients. Verification of the treatment fields using portal films or electric portal imaging devices was performed in most of the patients. However, regular or multiple verifications in addition to initial treatment and/or portal volume changes were performed in only 30% of the patients. Typical beam arrangements for treatment of the prostate consisted of a four-field box. Three-dimensional conformal techniques were applied less frequently in non-academic hospitals than in academic ones. Modernized multileaf collimators with leaf widths ≤10 mm were used in about two-thirds of the patients. Although the total doses given to the prostate were affected by the leaf widths, there were no significant differences between leaf widths of 5 and 10 mm.

The results of the survey identified certain patterns in the current treatment planning and delivery processes for localized prostate cancer in Japan.

We evaluated several immunological parameters in patients with advanced pancreatic cancer who received a conventional dose of gemcitabine for 2 months. Twenty-eight patients with metastasis or locally advanced tumor, including 18 gemcitabine-naïve and 10 with a history of preceding gemcitabine treatment, were enrolled in this study. The patients received gemcitabine 1000 mg/m² for 3 weeks, followed by 1 week of rest. We monitored the kinetics of lymphocytes, natural killer cells, monocytes, dendritic cells (DC), human leukocyte antigen (HLA)-multimer conjugated with CMV or WT1 peptide, and intracellular cytokine production of interferon- and interleukin-4 by flow cytometry. The T cell receptor (TCR) repertoire was also analyzed.

The absolute number and percentage of CD14⁺ monocytes and CD11c⁺ (myeloid) DC increased with gemcitabine treatment (P = 0.033 and P = 0.021). The percentage of CD123⁺ (plasmacytoid) DC also increased (P = 0.034), whereas no significant change was observed in other immune parameters, including multimer, intracellular cytokine production and TCR repertoire.

Our finding that gemcitabine treatment induced the proliferation of CD14⁺ monocytes and CD11c⁺ DC could support combination therapy with gemcitabine and specific immunotherapy such as peptide vaccination against pancreatic cancers.

An open-label, non-randomized, dose-escalation Phase I study of RAD001 administered continuously once daily in a 28-day cycle was performed. The study had a ‘3 + 3’ design, with three patients recruited to each of three successive cohorts treated with RAD001 at 2.5, 5.0 or 10.0 mg/day.

The pharmacokinetics of RAD001 in Japanese patients were similar to those previously determined in Caucasians. The drug safety profile was consistent with that of a mammalian target of rapamycin inhibitor. No dose-limiting toxicities were observed. One patient with esophageal cancer and one with gastric cancer treated with RAD001 at 10 mg/day showed marked tumor responses.

Treatment of Japanese cancer patients with RAD001 may be undertaken with the expectation that previously determined pharmacokinetic and safety profiles apply. The drug may hold promise for treatment of esophageal and gastric cancer.

Previously untreated patients with Stage IIIB/IV NSCLC were given gemcitabine (1000 mg/m²) and split-dose cisplatin (40 mg/m²) on days 1 and 8 at 3-week intervals for four cycles. Gemcitabine was administered over the course of 30 min, and cisplatin was over the course of 60 min on the same days on an outpatient basis.

Forty-five patients were enrolled, and all of them were assessable for response and toxicity. None had a complete response and 17 had a partial response (37.8%), for an overall response rate of 37.8% (95% confidence interval, 25.1–52.4%). The survival rate was 56.5% at 1 year and 38.9% at 2 years, with a median survival time of 15.7 months. Leukopenia, neutropenia, anemia and thrombocytopenia were the most common toxic reactions, with Grade ≥ 3 reactions occurring at rates of 35%, 51%, 31% and 13%, respectively.

Weekly gemcitabine and split-dose cisplatin is active and well tolerated in patients with Stage IIIB/IV NSCLC, administered on an outpatient basis without requiring prolonged hydration or hospitalization.

Ninety-five consecutive males with advanced GCTs of the testis or extragonadal origin who received chemotherapy between 1980 and 2006 were enrolled. All patients underwent induction chemotherapy including cisplatin.

The median follow-up period was 36.1 months (0 – 288.5) for all patients and 52.6 months (2.2 – 288.5) for the 73 current survivors. Totally, 75 patients (78.9%) achieved complete remission (CR). CR was achieved in 61.1%, 37.9% and 75.0% of the patients after induction therapy, second-line therapy and third-line or more, respectively. As salvage therapy, high-dose chemotherapy was performed in 11 patients (11.7%) and regimens with novel anticancer agents such as paclitaxel and irinotecan were employed for 8 patients (8.5%) from 2003 and later. The era of the treatment, extrapulmonary metastasis and serum -fetoprotein were independent prognostic factors for patients. The 5-year overall survival of patients after 1992 was 83.0%, which was significantly higher than that of those before 1992 (56.3%). CR was never achieved in 20 patients and most of them met the criteria of the poor-prognosis group. Disease recurrence after CR was found in nine patients who were initially classified into the good- or intermediate-prognosis group.

Improvement of medical management during chemotherapy and the development of several regimens for salvage chemotherapy seemed to contribute to improving outcomes of patients with advanced testicular cancer. Newly established chemotherapy regimens are needed for improvement of survival of patients in the poor-prognosis group.

Patients received irinotecan (240 mg/m²) as a 30 min intravenous infusion on day 1 and capecitabine (1000 mg/m²) orally bid for 14 days beginning on day 2. Treatment was repeated every 3 weeks. The protocol encouraged two to four cycles of irinotecan/capecitabine after recovery from surgery.

Between May 2004 and February 2007, 48 patients entered in the study. Forty-seven (97.9%) of the 48 patients were assessable for response. The overall response rate before surgery was 56.3% (95% CI, 42.3–70.3%) in the treated population, including 2 non-confirmed complete response (CR), 18 partial responses (PR) and 7 non-confirmed PR. Twenty-three (47.9%) of 29 patients with tumor shrinkage proceeded to surgical intervention. Twenty of the 23 patients had a complete resection (S-CR). With a median follow-up time of 32 months (range, 24–38 months), the overall median time to progression and overall survival for all patients were 16.7 months (95% CI, 10.0–23.4 months) and 27.5 months (95% CI, 23.6–31.4 months) for all patients. The 1- 2- and 3-year overall survival estimates were 79.2% (95% CI, 67.7–90.7%), 60.4% (95% CI, 46.6–74.3%) and 29.2% (95% CI, 16.3–42.0%), respectively. Grade 3 diarrhea occurred in eight (17.0%) patients. The most common Grade 3/4 hematological adverse event was neutropenia in 8.5% of the patients. There were no treatment-related deaths during this study.

Irinotecan/capecitabine appears to be a safe and very effective regimen in selected patients with unresectable liver metastases from CRC, but who are treated with a curative intent.

Twenty-one patients with advanced or metastatic biliary tree cancers with no prior chemotherapy were enrolled in this Phase II trial. Patients were treated on 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m² on days 1, 8 and 15, and 5-FU at 150 mg/m² and CDDP at 3 mg/m² on days 1–5, 8–12 and 15–19. After two cycles, a 4-week outpatient treatment of gemcitabine (1000 mg/m²) on days 1 and 15 combined with 5-FU (500 mg/m²) and CDDP (7 mg/m²) on days 1 and 15 was commenced. Treatment was repeated until tumor progression or remission allowing curative operation, or unacceptable toxicity occurred.

Of these 21 patients, no complete responses were observed, but 7 patients (33.3%) demonstrated partial responses (PRs) with an additional 12 patients (57.2%) having stable diseases, as assessed by RECIST. Three patients with PRs were treated by curative operation after GFP chemotherapy, and all of them survived with no recurrence for over 3 years. The median overall survival time was 18.8 months, and median time to progression was 13.4 months. Grade 3 side effects such as leukopenia, thrombocytopenia and anemia were found in six patients (28.6%), but no patients dropped out because of toxicity.

This GFP chemotherapy has promising anti-tumor activity and is well tolerated in patients with advanced biliary tree cancers.

RCC patients aged 50 years or over, refractory to therapy, were eligible for the study. HSCT was performed after reduced-intensity conditioning. Primary endpoint was defined as the survival at day 100 after HSCT with complete donor chimerism, and secondary endpoint was the effectiveness of HSCT.

Seven patients, provided with written informed consent, were enrolled in the study. Six of the seven patients achieved complete donor chimera at day 30 after HSCT, but one patient received second HSCT because of graft rejection. Four patients achieved a partial response (PR) and stable disease was observed in another patient, but these responses were temporary. The disease of the other two patients became progressive. Autopsy findings revealed an accumulation of CD8⁺ lymphocytes and degenerative changes in the local RCC lesion in three of six patients who responded clinically. An autopsy of a patient who had obtained a PR revealed lymphocyte involvement with a cytotoxic T cell (CTL) phenotype in the metastasis of RCC.

Our results demonstrate the efficacy of HSCT for RCC and suggest that the graft-versus-tumor effect elicited by CTLs is induced in vivo. HSCT should be further explored as a potential curative treatment for RCC.

This Phase II study was designed to determine the toxicity and efficacy of two courses of chemotherapy (CDDP 80 mg/m² on day 1 and irinotecan 60 mg/m² on days 1 and 8) followed by accelerated hyperfractionated thoracic radiotherapy (60 Gy/40 fractions in 4 weeks) combined with daily carboplatin (CBDCA) administration. CBDCA was administered at a target area under the plasma level–time curve of 0.4 x (24 h creatinine clearance + 25), according to Calvert's formula.

Twenty-six patients were enrolled in the study. The patients' median age was 63 years (range 40–74 years) and included 22 males and 4 females. Seven patients were Stage IIIA and 19 were Stage IIIB. Twenty had a performance status (PS) of 1 versus six with a PS of 0. There was one treatment-related death due to sepsis and pneumonia associated with Grade 4 neutropenia and diarrhea during chemotherapy. Grade 3 or 4 neutropenia and diarrhea were observed in 14 and 5 patients, respectively. Toxicity of the radiotherapy was mild. There were 0 complete response and 13 partial responses, giving a response rate of 50.0%. Median survival time and 2-year survival were 16.4 months and 21.5%, respectively. This study was designed with Simon's two-stage design, and the response rate did not meet the criteria to proceed to the second stage and the study was terminated early.

This regimen might be inactive for patients with unresectable Stage III NSCLC.

Five patients with penile cancer, receiving at least two courses of IA chemotherapy, were analyzed from January 2005 to January 2009. These patients all refused surgery initially. The drug combinations were as follows: methotrexate, mitomycin C, bleomycin, cisplatin and 5-fluorouracil. Carboplatin was used instead of cisplatin for one patient with renal insufficiency.

The overall response rate (complete or partial) was 100%. One case achieved complete remission and four cases achieved partial remission. Among the partial responders, three cases underwent subsequent partial penectomy to preserve partial appearance. Mild (Grades I–II) anorexia is the most common adverse effect of IA chemotherapy. Hematological toxicity included two episodes of Grade III anemia and one episode of Grade III febrile neutropenia.

Organ- and function-sparing approaches are proposed using combination therapies, especially for those with huge tumor burden. Our preliminary data indicated that a combination of IA neoadjuvant chemotherapy and surgery may have the potential to achieve the goal in the treatment of penile cancer with negative lymph node.