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Japanese Journal of Clinical Oncology

Japanese Journal of Clinical Oncology - RSS feed of current issue

Objective

Although pre-operative chemoradiation therapy for advanced lower rectal cancer is a controversial treatment modality, it is increasingly used in combination with surgery. Few studies have considered the combination of chemoradiation therapy followed by laparoscopic surgery for locally advanced lower rectal cancer; therefore, this study aimed to assess the usefulness of this therapeutic combination.

Methods

We retrospectively reviewed the medical records of patients with locally advanced lower rectal cancer treated by pre-operative chemoradiation therapy and surgery from February 2002 to November 2012 at Oita University. We divided patients into an open surgery group and a laparoscopic surgery group and evaluated various parameters by univariate and multivariate analyses.

Results

In total, 33 patients were enrolled (open surgery group, n = 14; laparoscopic surgery group, n = 19). Univariate analysis revealed that compared with the open surgery group, operative time was significantly longer, whereas intra-­operative blood loss and intra-operative blood transfusion requirements were significantly less in the laparoscopic surgery group. There were no significant differences in post-operative complication and recurrence rates between the two groups. According to multivariate analysis, operative time and intra-operative blood loss were significant predictors of outcome in the laparoscopic surgery group.

Conclusions

This study suggests that laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is a safe procedure. Further prospective investigation of the long-term oncological outcomes of laparoscopic surgery after chemoradiation therapy for locally advanced lower rectal cancer is required to confirm the advantages of laparoscopic surgery over open surgery.


Objective

Emotional distress is considered to be higher in patients with head and neck cancer than other types of cancer. The present study aimed to identify predictors of the postoperative levels of depression in patients with head and neck cancer who have undergone surgery.

Methods

Postoperative levels of depression were assessed at 3, 6 and 12 months after surgery. The preoperative factors that were significant predictors of the postoperative level of depression at each time point were extracted using multiple regression analyses.

Results

The preoperative level of depression was a significant predictor of the postoperative level of depression at the 3rd, 6th and 12th postoperative months. At the sixth postoperative month, negative adjustment to cancer at baseline was also a significant predictor of the postoperative level of depression.

Conclusion

Evaluating the level of depression and negative adjustment before surgery is considered to be effective for identifying patients who will develop depression after surgery.


Objective

Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan.

Methods

We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010.

Results

The median follow-up period was 20.0 months (range 0.5–92.7 months). Six (18.2%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8%, with a complete response rate of 72.7%. The two-year overall survival rate was 68.1%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n = 20) and without rituximab (n = 13) (P = 0.49). The two-year overall survival rate was 66.7% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P = 0.72). There was one treatment-related death.

Conclusions

Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.


Objective

Ampullary adenocarcinoma is a rare disease entity and little information regarding these tumors is available. The aim of the present study was to clarify the treatment outcome of systemic chemotherapy in patients with advanced ampullary adenocarcinoma.

Methods

This study consisted of a retrospective review of data obtained from patients diagnosed as having advanced ampullary adenocarcinoma who received non-surgical treatment at a single institution between 1997 and 2010.

Results

We identified 26 patients (15 men, 11 women; median age, 62.0 years) who received treatment for advanced ampullary adenocarcinoma. Twelve patients had Stage IV disease and 14 had recurrences. The chemotherapy regimens consisted of 5-fluorouracil-based regimens (5-fluorouracil + cisplatin, n = 3; tegafur-uracil + doxorubicin, n = 5 and tegafur, gimeracil and oteracil potassium, n = 3) and gemcitabine-based regimens (gemcitabine, n = 10 and gemcitabine + cisplatin, n = 5). The overall response rate was 7.7%. The median progression-free survival period was 3.2 months (2.5 months in the 5-fluorouracil group vs. 3.5 months in the gemcitabine group), and the median overall survival time was 9.1 months (8.0 months in the 5-fluorouracil group vs. 12.3 months in the gemcitabine group). The median overall survival was significantly longer in stage IV disease than in recurrent disease. The histological phenotype was determined in 10 of the 26 patients. Eight patients had intestinal-type adenocarcinomas and remaining two patients had pancreatobiliary-type adenocarcinomas.

Conclusions

The treatment outcome of patients with advanced ampullary adenocarcinoma was poor. Further development of novel treatments is necessary to improve the prognosis.


Objective

To investigate predictors affecting the development of hypothyroidism after radiotherapy for head and neck cancer, focusing on radiation dose-volumetric parameters, and to determine the appropriate radiation dose-volumetric threshold of radiation-induced hypothyroidism.

Methods

A total of 114 patients with head and neck cancer whose radiotherapy fields included the thyroid gland were analysed. The purpose of the radiotherapy was either definitive (n = 81) or post-operative (n = 33). Thyroid function was monitored before starting radiotherapy and after completion of radiotherapy at 1 month, 6 months, 1 year and 2 years. A diagnosis of hypothyroidism was based on a thyroid stimulating hormone value greater than the maximum value of laboratory range, regardless of symptoms. In all patients, dose volumetric parameters were analysed.

Results

Median follow-up duration was 25 months (range; 6–38). Forty-six percent of the patients were diagnosed as hypothyroidism after a median time of 8 months (range; 1–24). There were no significant differences in the distribution of age, gender, surgery, radiotherapy technique and chemotherapy between the euthyroid group and the hypothyroid group. In univariate analysis, the mean dose and V35–V50 results were significantly associated with hypothyroidism. The V45 is the only variable that independently contributes to the prediction of hypothyroidism in multivariate analysis and V45 of 50% was a threshold value. If V45 was <50%, the cumulative incidence of hypothyroidism at 1 year was 22.8%, whereas the incidence was 56.1% if V45 was ≥50% (P = 0.034).

Conclusions

The V45 may predict risk of developing hypothyroidism after radiotherapy for head and neck cancer, and a V45 of 50% can be a useful dose-volumetric threshold of radiation-induced hypothyroidism.


Objective

The primary objective of this study was to re-evaluate the feasibility of docetaxel at doses of up to 75 mg/m2 in Japanese patients with previously treated non-small cell lung cancer.

Methods

Patients received escalated doses of docetaxel at 70 mg/m2 (level 1) or 75 mg/m2 (level 2) every 3 weeks until disease progression or unacceptable toxicities. Dose escalation was decided on the basis of dose-limiting toxicity in the first cycle of chemotherapy.

Results

At dose level 1, dose-limiting toxicity—Grade 3 febrile neutropenia—was observed in one of the six patients and at dose level 2, it was seen in one of the first six patients. Therefore, an additional 14 patients were enrolled at dose level 2, as originally planned. Among the total of 20 patients at dose level 2, 6 (<33%) developed dose-limiting toxicity in the first cycle: febrile neutropenia in 5 and pneumonia in 1. Finally, 10 (50%) of the 20 patients experienced toxicities that met the dose-limiting toxicity criteria, including 8 with febrile neutropenia throughout the treatment period, but this was manageable with dose reduction or appropriate supportive care. Other observed toxicities were predictable from the safety profile of decetaxel and were also well managed. Four partial responses were observed, giving an overall response rate of 15.4%. The median progression-free survival period of the patients overall was 4.0 months (95% confidence interval 1.4–6.6 months).

Conclusions

Although docetaxel administration at an initial dose of 75 mg/m2 requires careful attention because of the high incidence of febrile neutropenia, this dose is considered feasible according to the protocol definition in Japanese patients with previously treated non-small cell lung cancer.


Objective

Magnesium supplementation has been reported to have a nephroprotective effect on cisplatin-induced renal dysfunction, but little evidence exists regarding the effect of magnesium preloading before cisplatin administration. We started to include magnesium preloading (8 mEq) in cisplatin-containing treatment regimens in January 2011. The aim of the present study was to evaluate whether magnesium preloading reduces cisplatin-induced nephrotoxicity.

Methods

We retrospectively reviewed 496 thoracic malignancy patients treated with cisplatin (≥60 mg/m2)-containing regimens as a first-time chemotherapy between January 2009 and December 2011. We compared the incidence of Grade ≥2 serum creatinine elevation according to the Common Terminology Criteria for Adverse Events, version 4.0, between magnesium preloading group (n = 161 [32%]) and non-magnesium preloading group (n = 335 [68%]) during the first cycle and all cycles.

Results

The median number of administered cycles was four in both groups. The incidence of Grade ≥2 serum creatinine elevation in magnesium preloading group was significantly lower during both the first cycle and all cycles than in the non-magnesium preloading group (4.9 versus 19.1% during the first cycle, and 14.2 versus 39.7% during all the cycles). A multivariate analysis indicated that magnesium preloading significantly reduced cisplatin-induced nephrotoxicity throughout the entire period from after the first administration (odds ratio: 0.262, 95% confidence interval: 0.106–0.596 during the first cycle, and odds ratio: 0.234, 95% confidence interval: 0.129–0.414 during all cycles).

Conclusions

Magnesium preloading before cisplatin administration significantly reduced cisplatin-induced nephrotoxicity.


Objective

To elucidate the patterns and risk factors for loss to follow-up during active surveillance for Stage I seminoma.

Methods

A total of 425 cases with Stage I seminoma underwent radical orchiectomy from 1985 to 2006 at 25 Japanese institutions, including 22 community hospitals and 3 university hospitals. The post-orchiectomy management selected was active surveillance for 186 patients, adjuvant radiotherapy for 182 patients and chemotherapy for 57 patients. The Kaplan–Meier method was used to estimate the recurrence-free survival and loss to follow-up rate. The risk factors for loss to follow-up were examined using Cox's proportional hazards model with multiple variables.

Results

The 2-, 5- and 10-year loss to follow-up rates in the active surveillance group were 14.2, 37.8 and 71.3%, respectively, which were not significantly different in comparison with those in the active surveillance and adjuvant radiotherapy or chemotherapy groups. With regard to the active surveillance group, the multivariate analysis demonstrated that patients younger than 36 years at diagnosis, patients diagnosed since 2000 and patients treated at hospitals that enrolled more than 10 cases had a significant risk for loss to follow-up. No significant correlation between the loss to follow-up rate and pathological risk factors such as tumor size (≤4 versus >4 cm) and rete testis invasion (presence versus absence) was shown.

Conclusions

The loss to follow-up rates beyond 5 years were unsatisfactorily high during active surveillance. Further approaches to improve the quality of active surveillance are needed, especially for high-risk patients such as those of younger age.


Background

A novel risk assessment method, Japan Cancer of the Prostate Risk Assessment, has been developed based on database of patients receiving primary androgen deprivation therapy. To investigate the usefulness of Japan Cancer of the Prostate Risk Assessment for non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy.

Methods

Patients with non-metastatic, high-risk prostate cancer (T3, initial prostate specific antigen level ≥20 ng/ml, and/or Gleason score ≥8) were included. The patients were treated with carbon ion radiotherapy (the total dose from 57.6 Gy (relative biological effectiveness)/16 fractions to 66.0 Gy(relative biological effectiveness)/20 fractions), and neoadjuvant as well as adjuvant androgen deprivation therapy for at least 24 months.

Results

Four hundred and twenty-six patients were included with the median follow-up of 68.1 months. Of 426, 210 (49.3%), 270 (63.4%) and 251 (58.9%) had Gleason 8–10, prostate specific antigen ≥20 ng/ml and T3, respectively. The 10-year progression-free and cause-specific survival rates in Japan Cancer of the Prostate Risk Assessment 1–2 group (76.5 and 98.9%) were significantly better than those in Japan Cancer of the Prostate Risk Assessment 3–6 group (52.6 and 93.1%), (P < 0.001 and P = 0.044, respectively). The median progression-free survivals in the Japan Cancer of the Prostate Risk Assessment 1–2 and 3–6 groups were 158.9 months and 125.9 months (95% confidence interval: 108.6–143.2 months), respectively.

Conclusions

For non-metastatic, high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy, Japan Cancer of the Prostate Risk Assessment score was useful for predicting the progression-free and cause-specific survivals.


A 44-year-old woman was admitted to the hospital for asymptomatic gross hematuria. At the age of 28, she underwent transplantation of a kidney from her father for end-stage renal disease secondary to rapidly progressive glomerulonephritis. She resumed peritoneal dialysis when the allograft kidney stopped functioning at the age of 42. Dialysis was continued for the next 2 years, when the hematuria occurred and she was readmitted. Radiologic evaluation and transurethral resection of the bladder tumor revealed a tumor of the renal pelvis of the allograft kidney (cT3N0M0) and multiple bladder tumors (cT1N0M0). Total cystectomy and allograft nephroureterectomy were performed. Histopathological examinations revealed high grade urothelial carcinoma in the renal pelvis of the allograft kidney (pT3) and native bladder (pT1). Fluorescence in situ hybridization of both specimens demonstrated that the renal pelvic tumors and bladder cancer possessed XY karyotypes. These results indicated that the urothelial carcinoma developed de novo in the renal pelvis of the allograft kidney and was implanted into the recipient's native bladder.


The authors present the first case report of pre-surgical axitinib treatment on primary renal tumor and vena cava thrombus. We report the case of a 78-year-old woman with renal cell carcinoma and inferior vena cava tumor thrombus, successfully downstaged with pre-surgical therapy with axitinib. A significant objective response was observed for tumor size and thrombus. After initiation of axitinib therapy, computed tomography showed a decrease, from 57 to 51 mm, in the maximal renal tumor diameter. The tumor thrombus had shortened to 42 mm and had moved to the inferior hepatic vein (Levels 4–3), thereby obviating the need for thoracotomy. The patient finally accepted surgical treatment. Our case was enabled to perform less surgery for advanced renal cell carcinoma with tumor thrombus using axitinib as a pre-surgical therapy.


A 72-year-old male visited a local hospital on presentation of melena. Colonoscopy revealed a protruded lesion in the ascending colon, and computed tomography revealed a 20 cm retroperitoneal tumor. Biopsy failed to provide a definitive diagnosis of the colonic lesion. He was diagnosed as having a retroperitoneal liposarcoma and an ascending colon tumor using computed tomography, and referred to our hospital. Biopsy of the ascending colon lesion showed spindle cells with fibrosis. On immunohistochemical staining, tumor cells were positive for cyclin-dependent kinase 4 and murine double minute 2, and the lesion was diagnosed as a well-differentiated or dedifferentiated liposarcoma. The retroperitoneal liposarcoma, which had infiltrated the ascending colon, was resected along with the right colon and the right kidney. Macroscopically, the tumor had infiltrated the ascending colon, forming a multinodular solid mass in the lumen and the right kidney. Microscopic finding of the main tumor revealed a well-differentiated liposarcoma, and that of the colonic lesion revealed a dedifferentiated liposarcoma with nuclei of different sizes and shapes and increased spindle cell morphology. The right kidney and ureter were surrounded by tumor cells but were not infiltrated, and there was no lymph node involvement. The diagnosis of retroperitoneal liposarcoma is often difficult because symptoms appear only after the tumor becomes very large. Some retroperitoneal liposarcomas are found on computed tomography by chance. The clinical course of this case was very rare because of the presentation of melena as the first symptom and the detection of an invasive mass in the ascending colon using colonoscopy.


A randomized Phase III trial commenced in Japan in March 2013. Post-operative adjuvant chemotherapy with etoposide plus cisplatin is the current standard treatment for resected pulmonary high-grade neuroendocrine carcinoma including small cell lung cancer and large cell neuroendocrine carcinoma. The purpose of this study is to confirm the superiority of irinotecan plus cisplatin in terms of overall survival over etoposide plus cisplatin as post-operative adjuvant chemotherapy for pathological Stage I–IIIA completely resected pulmonary high-grade neuroendocrine carcinoma patients. A total of 220 patients will be accrued from 54 Japanese institutions within 6 years. The primary endpoint is overall survival and the secondary endpoints are relapse-free survival, proportion of treatment completion, adverse events, serious adverse events and second malignancy. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000010298 [http://www.umin.ac.jp/ctr/index.htm].


We have planned a multicentre prospective study to examine the relative impact of the efficacy and adverse events of cetuximab plus first-line chemotherapy on the quality of life in Japanese patients with KRAS wild-type unresectable colorectal cancer. The Dermatology Life Quality Index and the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core 30 will be used to assess dermatology-specific and health-related quality of life. The severity of adverse events will be assessed by using the National Cancer Institute Common Terminology Criteria for adverse Events ver. 4.0. The endpoints will be the following associations: adverse events, including skin toxicity and quality of life; efficacy and skin toxicity; efficacy and quality of life; and skin-related quality of life and health-related quality of life. A total of 140 patients are considered to be appropriate for inclusion in this study. The results of this study will provide more information to both patients and physicians regarding the practical use of cetuximab and its impact on quality of life in patients with unresectable colorectal cancer in Japan. This study was registered at the University Hospital Medical Information Network Clinical Trial Registry as UMIN000010985.


The Japan Cancer Surveillance Research Group aimed to estimate the cancer incidence in Japan in 2008 based on data collected from 25 of 34 population-based cancer registries, as part of the Monitoring of Cancer Incidence in Japan project. The incidence in Japan for 2008 was estimated to be 749 767 (C00–C96). Stomach cancer and breast cancer were the leading types of cancer in males and females, respectively.