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Japanese Journal of Clinical Oncology

Japanese Journal of Clinical Oncology - RSS feed of current issue

Radiotherapy plays an essential role in the management of head and neck squamous cell carcinoma. Radiotherapy has a distinct advantage over surgical procedures in that it could achieve organ and function preservation with an efficacy similar to that of surgical series. To improve the clinical outcomes achievable by radiotherapy, altered fractionated radiotherapy has been prospectively tested for early and intermediate risk diseases, and was previously shown to be beneficial for local control and survival. Radiotherapy alone is insufficient for locally advanced disease; therefore, concurrent chemoradiotherapy is typically performed and plays an important role. A meta-analysis (Level Ia) revealed that the concurrent use of platinum agents appeared to improve tumor control and survival; however, this was accompanied by increases in the rates of both acute and late toxicities. Regarding radiation techniques, intensity modulated radiotherapy evolved in the 1990s, and has been globally used to treat head and neck squamous cell carcinoma patients. Intensity modulated radiotherapy reduces the exposure of normal tissue to radiation while preserving excellent dose coverage to the target volume; therefore, the rate of late toxicities especially xerostomia is minimized. Small size randomized studies and a meta-analysis have provided evidence to support the benefits of intensity modulated radiotherapy over two-dimensional or three-dimensional radiation therapy. Intensity modulated radiotherapy can also preserve quality of life following definitive chemoradiotherapy. Further improvements using intensity modulated proton therapy are warranted.


Since the publication of Intergroup Study 0099, representing a superiority of concurrent chemoradiotherapy with cisplatin followed by adjuvant chemotherapy to radiotherapy alone for the treatment of locoregionally advanced nasopharyngeal carcinoma, an efficacy of concurrent setting of cisplatin-based chemotherapy with radiotherapy has been repeatedly validated. In meanwhile, the role of adjuvant part of the protocol has been controversial. There is an increasing evidence for the positive role of neoadjuvant chemotherapy with following concurrent chemoradiotherapy whereas favorable contribution was not proven in the last century. This article reviews the role of chemotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma.


Objective

This retrospective study analyzed the oncological and treatment outcomes of the patients with T1–T2N0 glottic cancer, who were treated with radiotherapy as initial treatment and salvaged by conservative surgery for radiation failure.

Methods

Between May 1999 and December 2010, 115 patients with glottic laryngeal cancer were treated at Kobe University Hospital. At presentation, 54 patients had stage T1a disease, 26 had stage T1b disease and 35 had stage T2 disease. Seventy-nine patients were treated with conventional radiotherapy and 36 patients were treated with hyperfractionated radiotherapy as initial treatment.

Results

Median duration of follow-up was 61 months. Five-year local control rates of radiotherapy were 92% in T1a, 83% in T1b and 86% in T2. Of 12 patients who developed local recurrence, larynx was successfully preserved in 3 patients by laryngomicrosurgery, 7 patients by vertical partial laryngectomy and one patient by subtotal laryngectomy. Ultimate 5-year laryngeal preservation rate and local control rate of all cases were 99 and 100%, respectively.

Conclusions

Present results suggest that initial treatment with radiotherapy salvaged by organ preservation surgery is an effective strategy for laryngeal preservation in the treatment of T1–T2N0 glottic laryngeal cancer.


Background

Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known.

Methods

We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0–2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated.

Results

Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)].

Conclusions

Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted.


Objective

The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning.

Methods

We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C–D, the duration from the last day of chemotherapy to death and D–D, that from the day of confirmed do-not-attempt-resuscitation order to death.

Results

The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on ‘incurable disease before first-line chemotherapy’, 69 (50%) were informed about ‘supportive care before first-line chemotherapy’, whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C–D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C–D in multivariate analysis. The median D–D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D–D in multivariate analysis.

Conclusions

Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care.


Objective

Parathyroid hormone-like related protein was a prognostic factor for non-small-cell lung cancer, but the results were conflicting. The present study was to examine the role of cytoplasmic and nuclear parathyroid hormone-like related protein in patients with non-small-cell lung cancer who have undergone surgical therapy.

Methods

The expression of parathyroid hormone-like related protein was examined by immunohistochemical staining in 56 patients with resectable non-small-cell lung cancer. The impact of parathyroid hormone-like related protein expression on cancer recurrence and survival was assessed in combination with clinicopathologic features.

Results

Patients with a high expression of cytoplasmic parathyroid hormone-like related protein had a significantly unfavorable prognosis in both disease-free survival (median 16.7 vs. 58.0 months, P = 0.029) and overall survival (median 31.6 months vs. not reached, P = 0.046). In contrast, the patients with high expression of nuclear parathyroid hormone-like related protein had favorable disease-free survival (median 35.1 vs. 19.9 months, P = 0.069) and a significantly better overall survival (median not reached vs. 36.9 months, P = 0.033). There was no correlation between the expression of cytoplasmic and nuclear parathyroid hormone-like related protein (P = 1.00). Furthermore, multivariate analysis using a Cox regression model confirmed that high expression of cytoplasmic parathyroid hormone-like related protein (disease-free survival, hazard ratio: 1.973, P = 0.079; overall survival, hazard ratio: 2.461, P = 0.067) and nuclear parathyroid hormone-like related protein (disease-free survival, hazard ratio: 0.436, P = 0.029; overall survival, hazard ratio: 0.375, P = 0.018) were independently prognostic factors for disease-free survival and overall survival.

Conclusion

Cytoplasmic and nuclear parathyroid hormone-like related protein play opposing prognostic roles for the disease-free survival and overall survival of patients with early non-small-cell lung cancer who have undergone curative resection.


Objective

Result of clinical trial for registration purpose is often difficult to generalize because of its limited population in number and inclusion criteria.

Methods

To understand the efficacy of sorafenib under daily medical practice, we retrospectively investigated therapeutic outcomes of 175 Japanese patients with advanced renal cell carcinoma treated with sorafenib at 15 centers.

Results

The objective response rate and disease control rate were 15.4 and 77.1%, respectively, being similar to those in the Phase II study in Japanese patients (19.4 and 73.6 months). Any tumor shrinkage was observed with 53% of patients, while tumor control without growth was in 61%. Lung lesions were more sensitive to sorafenib than other lesions, in terms of any tumor shrinkage (54%) and the extent of maximal shrinkage, while tumor control was better in lymph node metastases (77%) than in lung (69%). Liver was worse in any tumor shrinkage (35%), tumor control (55%) and the extent of tumor growth. Slightly, shorter median overall survival of 21.1 months compared with Phase II clinical trial (25.3 months) is likely to be attributable to different patient population, because median overall survival was improved to 26.4 months when the population was matched to that in Phase II trial. Univariate and multivariate analyses identified prognostic factors for worse overall survival, including intermediate and poor Memorial Sloan-Kettering Cancer Center risk, Eastern Cooperative Oncology Group performance status ≥1, the presence of non-clear cell component and the presence of liver metastasis.

Conclusions

In conclusion, the present study confirmed the efficacy of sorafenib in the real-world setting on advanced renal cell carcinoma.


Objective

The aim of this study was to evaluate the efficacy and toxicity of the combination of docetaxel, ifosfamide and cisplatin as salvage chemotherapy after failure of standard cisplatin-based regimens for metastatic urothelial carcinoma.

Methods

We prospectively administered docetaxel, ifosfamide and cisplatin chemotherapy to patients with metastatic urothelial carcinoma refractory to standard cisplatin-based regimens from 2003 to 2013. Patients who had received only adjuvant and/or neoadjuvant chemotherapy were excluded. Eligible patients received every 28 days docetaxel 60 mg/m2 on Day 1, ifosfamide 1.0 g/m2 on Days 2–6 and cisplatin 20 mg/m2 on Days 2–6. The primary endpoints were progression-free survival and overall survival, calculated from the start of docetaxel, ifosfamide and cisplatin chemotherapy. Secondary endpoints included objective response and related toxicity.

Results

Twenty-six cases received a median of 3.0 cycles of docetaxel, ifosfamide and cisplatin chemotherapy (interquartile range: 2–5), resulting in a median progression-free survival of 3 months (interquartile range: 2–9.5 months) and median overall survival of 8.5 months (interquartile range: 6.5–18.75 months), respectively. Of 26 patients, seven (27%) achieved major treatment responses, with one complete response (4%) and six partial responses (23%). Most of Grade 3/4 toxicities were hematologic events, including leukopenia (77%), anemia (54%) and thrombocytopenia (46%). No death from toxicity was observed.

Conclusions

Our results indicate that docetaxel, ifosfamide and cisplatin chemotherapy is a tolerable and moderately active regimen for metastatic urothelial carcinoma after failure of standard cisplatin-based regimens.


Recently, bevacizumab has become a key drug for treatment of metastatic colorectal cancer. Molecularly targeted agents such as bevacizumab can cause life-threatening adverse effects, though they are generally considered less toxic than cytotoxic drugs. Here, we review the case of a 76-year-old male rectal cancer patient with liver metastasis who suffered extensive bowel necrosis after administration of 5-fluorouracil-based chemotherapy with bevacizumab, and required a subtotal colectomy and end-ileostomy. Microscopic findings revealed extensive mucosal necrosis in the resected colon specimen and necrosis at the muscularis propria of the descending colon. Pathological findings suggested that the mucosal damage induced by chemotherapy may be exacerbated by treatment with bevacizumab, resulting in extensive necrosis.


Cancer registration provides core information for cancer surveillance and control. The population-based Taiwan Cancer Registry was implemented in 1979. After the Cancer Control Act was promulgated in 2003, the completeness (97%) and data quality of cancer registry database has achieved at an excellent level. Hospitals with 50 or more beds, which provide outpatient and hospitalized cancer care, are recruited to report 20 items of information on all newly diagnosed cancers to the central registry office (called short-form database). The Taiwan Cancer Registry is organized and funded by the Ministry of Health and Welfare. The National Taiwan University has been contracted to operate the registry and organized an advisory board to standardize definitions of terminology, coding and procedures of the registry's reporting system since 1996. To monitor the cancer care patterns and evaluate the cancer treatment outcomes, central cancer registry has been reformed since 2002 to include detail items of the stage at diagnosis and the first course of treatment (called long-form database). There are 80 hospitals, which count for >90% of total cancer cases, involved in the long-form registration. The Taiwan Cancer Registry has run smoothly for >30 years, which provides essential foundation for academic research and cancer control policy in Taiwan.


Objective

In cancer screening programs, performing appropriate further work-up is essential. In order to elucidate whether the further work-up for the subjects with positive screening results by sputum cytology was performed appropriately, the present study was conducted as the first large-scale thorough survey in Japan.

Methods

All of the lung cancer screening records from 2007 to 2012 in Ishikawa Prefecture were reviewed. Additional investigations about the further work-up were performed.

Results

In total, 2 234 984 people were invited to undergo lung cancer screening, and 494 424 people participated in the screening. Of these, 25 264 people underwent sputum cytology, and 68 positive cases were identified. Three of these 68 cases did not undergo further work-up, and another three cases had already been diagnosed to have lung cancer. Forty-five of the remaining 62 cases did not have suspicious chest shadows, and bronchoscopic examinations were performed in 36 cases. Seventeen of these 36 cases were diagnosed as having cancer, whereas none of the nine cases who did not receive the examination was diagnosed (P = 0.038). A bronchoscopic examination was not performed due to other medical conditions in three cases, due to the patient's refusal in another three cases and in the remaining three cases, the reasons were unknown.

Conclusion

The participation rate for further work-up was very high. However, there are some issues to be resolved regarding the transmission of information. With our new registered hospital system, the quality assurance of our screening program will be improved.


Paclitaxel is an agent widely used in second-line chemotherapy for advanced gastric cancer. The aim of this trial is to evaluate the efficacy and safety of 3-weekly or weekly doses of nanoparticle albumin-bound-paclitaxel compared with weekly doses of Cremophor-based paclitaxel in patients with unresectable or recurrent gastric cancer refractory to first-line chemotherapy comprising fluoropyrimidines. A total of 730 patients will be enrolled from 72 institutions. The primary endpoint is the overall survival, and the secondary endpoints are progression-free survival, time to treatment failure, overall response rate, disease control rate, quality of life (by using the EQ-5D system) and safety.


The positive correlation between smoking and cancer risk is well estimated in sporadic colorectal cancer, whereas little is known with regard to Lynch syndrome-associated colorectal cancer. A total of 118 familial colorectal cancer patients from the Hereditary Nonpolyposis Colorectal Cancer Registry and Genetic Testing Project of the Japanese Society for Cancer of the Colon and Rectum, were assessed to determine whether smoking alters the incidence of multiple colorectal cancers. In male patients with Lynch syndrome (n = 29), the incidence of multiple colorectal cancers in patients who had ever smoked (smoking duration: median of 19 years) was higher than that in those who never smoked (58.8% vs. 10.0%, P = 0.02). The cumulative risk for metachronous colorectal cancer was significantly higher in male Lynch syndrome patients who had previously smoked than in those who had never smoked (P = 0.03). Our data suggest that long-term cigarette smoking might be a strong risk factor for the development of multiple colorectal cancers in male Lynch syndrome patients.