Despite some clinical guidelines for incorporating integrated psychosocial care (combining psychological screening and psychological intervention, including adequate collaboration with mental health specialists) into routine oncology practice, definitive empirical evidence regarding the effectiveness of such care remains unavailable. Here the findings of recent experimental studies are reviewed to provide guidance regarding this issue.

Comparative studies examining integrated psychosocial care were reviewed.

Studies examining interventions that include both screening and psychological care have produced contradictory results regarding effectiveness, but all the studies that have examined the effect of psychological care after the identification of distress using systematic screening have shown positive results.

Integrated psychosocial care may affect patients with significant distress, but the adequacy of introducing such care into routine oncology practice remains debatable.

Ofatumumab is a human IgG1 monoclonal antibody that targets a membrane proximal epitope encompassing the small and large loops of CD20. This Phase I study evaluated the safety, tolerability, efficacy and pharmacokinetics of ofatumumab monotherapy in Japanese patients with relapsed/refractory B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma.

Ofatumumab was administered intravenously weekly for a total of eight doses (dose escalation: 500 and 1000 mg). Six patients (two chronic lymphocytic leukemia and four small lymphocytic lymphoma) were enrolled into two dose cohorts (500 mg, three patients; 1000 mg, three patients). All six patients received 300 mg ofatumumab at the first infusion and either 500 or 1000 mg at seven subsequent weekly infusions.

No dose-limiting toxicities or serious adverse events were observed. Grade 3–4 adverse events observed were grade 3 lymphocytopenia (n = 1) and neutropenia (n = 1). Grade 1–2 infusion-related adverse events leading to temporary interruption of ofatumumab infusion were observed in all six patients on the first infusion day, and all patients completed the planned eight infusions. The overall response rate was 50% (3/6).

Ofatumumab was well tolerated at doses up to 1000 mg and showed preliminary evidence of activity in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, warranting further investigations. This study was registered at ClinicalTrials.gov (NCT00742144).

We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck.

Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m² initial dose then 250 mg/m² weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2–7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule).

Twenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85–100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60–95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each).

Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck.

This analysis was conducted to clarify risk factors for severe adverse effects and treatment-related deaths reported during a postmarketing survey of irinotecan.

The survey covered all patients treated with irinotecan in Japan between April 1995 and January 2000. The patient background data and adverse drug reactions were collected through case report forms. Univariate and multivariate logistic regression analyses including 14 explanatory variables were performed to determine the risk factors for grade 3–4 leukopenia, thrombocytopenia and diarrhea for all patients and subgroups with five major cancers. Treatment-related deaths were also analyzed.

Case report forms of 13 935 patients (94.1% of 14 802 patients registered) treated with irinotecan-based chemotherapy were collected. Major grade 3–4 adverse drug reactions were leukopenia (34.8%), thrombocytopenia (12.4%) and diarrhea (10.1%). Multivariate analysis revealed that the risk factors (odds ratio ≥1.5) common for all these three adverse drug reactions were performance status (≥3), infection and renal dysfunction before starting irinotecan therapy. Additionally, the risk factors for leukopenia were being female and prior radiotherapy, those for thrombocytopenia were age (≥65 years), while those for diarrhea were pleural effusion and watery stool. The risk factors in each cancer were also identified. The incidence of treatment-related death was 1.3% (176). Myelosuppression-related deaths accounted for 70% and interstitial lung disease for 11% of all treatment-related deaths. Being male, age, performance status ≥3, massive ascites and infection and renal dysfunction were identified as risk factors for treatment-related death.

To ensure the safety of irinotecan therapy, it is important to select appropriate patients by considering the risk factors.

The analysis of cancer trends in Japan has only been sporadically reported. We present a comprehensive report on the trends in cancer incidence and mortality in Japan using the most recent population-based data.

National cancer mortality data between 1958 and 2011 were obtained from published vital statistics. Cancer incidence data between 1985 and 2007 were obtained from high-quality population-based cancer registries of four prefectures (Miyagi, Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality.

All-cancer mortality decreased from the mid-1990s, with an annual percent change of –1.3% (95% confidence interval: –1.4, –1.3), while all-cancer incidence continually increased from 1985, with an annual percent change of 0.7% (95% confidence interval: 0.6, 0.8). Major cancer sites, particularly the liver, colorectum and lung (males), showed a pattern of increasing incidence and mortality rates until the mid-1990s, stabilizing or decreasing thereafter. Stomach cancer showed a long-term decreasing trend for both incidence and mortality, while female breast cancer showed a continuously increasing trend. The incidence of prostate cancer, particularly at the localized stage, increased rapidly between 2000 and 2003, while that of mortality decreased from 2004. No changes were detected in the incidence or mortality for colorectal, female breast or cervical cancers after the establishment of national screening programs for these cancers.

The analysis of cancer trends in Japan revealed a recent decrease in mortality and a continuous increase in incidence, which are considered to reflect changes in the underlying risk factors such as tobacco smoking and infection, and are partially explained by early detection and improved treatment.

Lack of agreement and inconsistency in capturing late bowel toxicity may be a source of error while reporting trials with toxicity endpoints. Documenting baseline inconsistency while scoring toxicity questionnaires (RTOG/EORTC and CTCAE) may be worthwhile. The present study was conducted as a quality assurance measure prior to initiating a randomized trial (PARCER; NCT01279135) that evaluates the impact of image-guided radiation on bowel toxicity.

From August 2010 to July 2011, patients with cervical cancer who underwent pelvic chemoradiation >6 months ago, with controlled disease and any bowel symptom at follow-up, were included. RTOG and CTCAE questionnaires were filled by two blinded observers. Interscale (RTOG vs CTCAE) and interobserver (observer A and B) agreement were evaluated with Spearman's correlation and kappa statistic.

Fifty-five patients were included. Twelve patients with symptoms could not be graded by the RTOG scale. Of those graded as asymptomatic on RTOG, distension, vomiting, pain and nausea were identified as the most common symptoms. Amongst these, grade 1, 2 and 3 toxicity was observed in 6, 5 and 1 patient, respectively. The interscale correlation was moderate (Spearman's correlation = 0.56; P = 0.001). High interobserver agreement (92%) was observed within the RTOG scale [kappa () –0.94; 95% CI 0.77–1]. All disagreements were observed while scoring grade 1–2 toxicity. Among CTCAE, agreement was lower with modules such as distension, anorexia, nausea and constipation.

High interobserver agreement was observed for both RTOG and most CTCAE subscales; most disagreements were for grade 1–2. Interscale agreement (RTOG and CTCAE) was moderate. Detailed patient interrogation or use of patient-reported-outcome scores while documenting the aforesaid subscales may be worthwhile.

Risk-reducing salpingo-oophorectomy is currently regarded as the most certain primary method for preventing ovarian cancer among BRCA1/2 mutation carriers with hereditary breast and ovarian cancer syndrome. However, risk-reducing salpingo-oophorectomy has rarely been performed in Japan.

We developed the first system in Japan for performing risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers at our university hospital in 2008.

The indication for risk-reducing salpingo-oophorectomy for patients with hereditary breast/ovarian cancer syndrome is currently limited in Japan. This situation may be because of the limited number of genetic counseling units, the limited number of facilities that can perform BRCA1/2 genetic testing and the fact that prophylactic surgery is not covered by health insurance in Japan.

Recent treatment guidelines for breast cancer in Japan recommended risk-reducing salpingo-oophorectomy for BRCA1/2 mutation carriers. Risk-reducing salpingo-oophorectomy should be performed in the framework of the standard therapeutic modality for BRCA1/2 mutation carriers in the near future.

This study was conducted to assess local recurrence and clinical prognosis in patients diagnosed as having a positive margin in the epithelial layer after a partial glossectomy treated by close observation.

A total of 365 cases of squamous cell carcinoma of the tongue diagnosed as clinical Stage I or II, treated by partial glossectomy in the National Cancer Center Hospital East between 1992 and 2006, were studied retrospectively.

Pathological findings showed that 13 cases had positive margins in the epithelial layer, 4 (30.8%) of whom showed up with local recurrence in 4.4 years (3.0–5.0) on average. Lymph node recurrence was not observed and the 5-year overall survival rate was 76.2% in those 13 cases. The treatment for the recurrent cases was an additional partial glossectomy without neck dissection, which resulted in no recurrence and a survival rate of 100% after an average follow-up of 6.7 years.

We suggest careful observation as one option for cases diagnosed with epithelial positive margin.

To assess the efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

In this open-label, single-arm, multicenter, Phase II study conducted in Japan, patients with confirmed recurrent and/or metastatic squamous cell carcinoma of the head and neck received weekly cetuximab (week 1, 400 mg/m²; subsequent weeks, 250 mg/m²) plus a maximum of six three-weekly cycles of cisplatin (100 mg/m², day 1) and 5-fluorouracil (1000 mg/m²/day, 24-h infusion, days 1–4). The primary endpoint was the best overall response assessed by an independent review committee according to the modified World Health Organization criteria.

In total, 33 patients received treatment. The most frequent primary tumor site was the hypopharynx (42%), and most patients had metastatic disease (85%). The best overall response rate as assessed by the independent review committee was 36% (95% confidence interval: 20, 55) and was significantly greater (P = 0.002) than the protocol-specified threshold of 15% at the one-sided 5% level. The disease control rate was 88%. The median progression-free survival and overall survival were 4.1 and 14.1 months, respectively. There were no unexpected safety concerns. Grade 3 or 4 adverse events were experienced by nearly all patients (32, 97%). No adverse events were fatal.

The demonstrated efficacy and safety of cetuximab in combination with cisplatin and 5-fluorouracil for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck justify the further use of this combination treatment in this patient population (ClinicalTrials.gov number, NCT00971932).

Carotid blowout syndrome is a severe complication of head and neck cancer. High mortality and major neurologic morbidity are associated with carotid blowout syndrome with massive bleeding. Prediction of outcomes for carotid blowout syndrome patients is important for clinicians, especially for patients with the risk of massive bleeding.

Between 1 January 2001 and 31 December 2011, 103 patients with carotid blowout syndrome were enrolled in this study. The patients were divided into groups with and without massive bleeding. Prognostic factors were analysed with proportional hazard (Cox) regressions for carotid blowout syndrome-related prognoses. Survival analyses were based on the time from diagnosis of carotid blowout syndrome to massive bleeding and death.

Patients with massive bleeding were more likely to have hypoalbuminemia (albumin <3.5 g/dl; P = 0.023). Univariate analysis of carotid blowout syndrome-related massive bleeding showed that treatment for carotid blowout syndrome (best supportive care, P = 0.000; embolization, P = 0.000), monocytosis (monocytes >1000 cells/μl, P = 0.041) and hypoalbuminemia (P = 0.010) were important to prognosis. Concurrent chemoradiotherapy (P = 0.007), elevated lactate dehydrogenase (>250 U/l; P = 0.050), local recurrence (P = 0.022) and hypoalbuminemia (P = 0.038) were related to poor prognosis in carotid blowout syndrome-related death. In multivariate analysis, best supportive care and hypoalbuminemia were independent factors for both carotid blowout syndrome-related massive bleeding (P = 0.000) and carotid blowout syndrome-related death (P = 0.013), respectively.

Best supportive care and serum albumin are important prognostic factors in carotid blowout syndrome. It helps clinicians to evaluate and provide better supportive care for these patients.

This study aimed to verify the prognostic impact of pleural invasion according to the revised TNM classification, seventh edition.

The study consisted of 1488 patients with surgically resected non-small cell carcinoma. The degree (pl0–3) and location of pleural invasion were examined using hematoxylin and eosin- and elastica van Gieson-stained slides, and outcome was compared with stratification by several clinicopathological factors.

The 5-year overall survival rates of 1008, 260, 85 and 135 patients with pl0, pl1, pl2 and pl3 tumours were 80, 60, 55 and 52%, respectively. Overall survival differed significantly between patients with pl0 tumours and those with pl1 tumours (P < 0.0001). The difference was significant for patients with 1<≤ 2 cm (P = 0.004), 2<≤ 3 cm (P = 0.003) and 3<≤ 5 cm (P = 0.02) tumours. The overall survival of pl0 patients was also significantly better in patients with adenocarcinoma (P < 0.0001) than squamous cell carcinoma (P = 0.043). The overall survival of pl0 patients was significantly better in patients without lymph node metastasis (P < 0.0001) than in those with lymph node metastasis. The 5-year overall survival rates of patients with interlobar, lateral, mediastinal and diaphragmatic pl3 tumours were 65, 51, 51 and 40%, respectively. Overall survival did not differ significantly among these four groups.

Outcome differs between patients with pl0 tumours and those with pl1–3 tumours, particularly among patients with 1<≤ 2 cm, 2 <≤ 3 cm and 3<≤ 5 cm tumours, adenocarcinoma histology and no lymph node metastasis. The location of pl3 pleural invasion did not affect outcome significantly.

The current study was designed to evaluate the clinical outcomes of curative intent radiation therapy for young patients with invasive uterine cervical carcinoma in Japan.

One hundred and eighteen patients aged ≤40 were registered in the multi-institutional study of the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) from 26 major institutions in Japan. The age range was 24–39 years and the maximum tumor diameter was 2.0–9.2 cm. The International Federation of Gynecology and Obstetrics clinical stages were Ib, IIa, IIb, IIIa, IIIb and IVa in 17, 6, 40, 2, 50 and 3, respectively. Curative intent radiation therapy consisted of the combination of external beam radiation therapy and high-dose rate intra-cavitary brachytherapy. The total dose of external beam radiation therapy ranged between 44 and 68 Gy. Both the median and mode of total high-dose-rate intra-cavitary brachytherapy dose to point A were 24 Gy in four fractions. Ninety-six patients (58%) received chemotherapy.

The 5-year overall survival rate and local control rate of all patients were 61 and 65%, respectively. The 5-year overall survival rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 88, 100, 75, 100, 37 and 0%, respectively. The 5-year local control rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 82, 75, 75, 100, 51 and 0%, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity.

The 5-year overall survival rate of young patients with Stage IIIb was comparatively low at 37%.

We compared the pathologic outcomes of prostate cancer patients who did not qualify for active surveillance  according to the tumor visibility on multiparametric magnetic resonance imaging.

We retrospectively analyzed 464 prostate cancer patients who underwent multiparametric magnetic resonance imaging before radical prostatectomy between 2006 and 2012. All the patients had clinically localized prostate cancer with Gleason score ≤6 and prostate-specific antigen ≤10 ng/ml. Of these patients, 238 were eligible for active surveillance (group A) and 226 were not. We divided these 226 patients into two groups according to the result of multiparametric magnetic resonance imaging: 59 (26.1%) patients without visible tumor (group B) and 167 (73.9%) patients with visible tumor (group C). We evaluated the pathologic outcomes of organ-confined Gleason ≤6 disease and unfavorable disease in each group.

The proportions of organ-confined Gleason ≤6 disease and unfavorable disease were 63.9 and 11.3% in group A, 59.3 and 10.2% in group B, and 38.9 and 22.8% in Group C. Comparing group A and B, these proportions were not statistically different (P = 0.549 and P = 1.000, respectively). However, comparing group A and C, those were significantly different (P < 0.001 and P = 0.002, respectively). In multivariate logistic regression analysis, no visible tumor on multiparametric magnetic resonance imaging was an independent predictor of organ-confined Gleason score 6 disease (odds ratio 0.426, P = 0.007) but there was no statistically independent predictor for unfavorable disease.

The tumor visibility on multiparametric magnetic resonance imaging could be a predictor of favorable disease for the prostate cancer patients who did not meet active surveillance criteria. Multiparametric magnetic resonance imaging could help to determine treatment modality for the low-risk prostate cancer patients who consider active surveillance even if they did not meet active surveillance criteria.