Masatoshi Hasegawa

Pathological and clinical impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer

Background/purposeThe therapeutic options available as preoperative strategies for resectable pancreatic cancer have received worldwide attention. We have recently introduced neoadjuvant chemoradiotherapy (NACRT) to achieve local control and possibly complete cure. In this study, we have retrospectively evaluated its impact on pathology and the perioperative clinical course in addition to its safety.MethodsSixty-one patients who received full-dose gemcitabine (1000xa0mg/m2) preoperatively with concurrent radiation (50 or 54xa0Gy) were evaluated. Seventy-one patients who received no preoperative therapy served as controls. Perioperative outcomes, postoperative complications, immunonutritional status, and the performance of adjuvant chemotherapy were compared.ResultsFifty-nine patients (97xa0%) completed NACRT. Toxicity was acceptable and the regimen was feasible as outpatient treatment. The perioperative outcomes were closely comparable to control. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group. The rate of lymph node metastasis and stage was lower in the NACRT group. Furthermore, R0 resection could be achieved in 92xa0% of patients treated with NACRT. Nutritional status decreased after NACRT and further deteriorated during adjuvant chemotherapy. The initiation of postoperative chemotherapy was delayed in the NACRT group.ConclusionsOur current protocol of neoadjuvant chemoradiotherapy is feasible and substantially improves the pathology. However, it has some detrimental effects on postoperative nutritional status and performance of adjuvant chemotherapy. Furthermore, it should be noted that there is a possibility of arterial complications.

Preoperative concurrent chemoradiotherapy for stages II–IV oral squamous cell carcinoma: a retrospective analysis and the future possibility of this treatment strategy

This study evaluated survival in 154 patients with stages II-IV oral squamous cell carcinoma (OSCC) treated with preoperative concurrent chemoradiotherapy and assessed the future use of this treatment strategy. 14 patients exhibited advanced stage II, 73 exhibited stage III and 67 exhibited stage IV. All patients received 40Gy irradiation and concurrent cisplatin-based chemotherapy in two courses. Radical surgery was undertaken after 2-6 weeks. The clinical tumour response, histopathologic regression grade, residual tumour grade (RGrade) in the primary tumour and the level of residual pN+ were associated with prognosis. 90% of patients with complete response and 73% of patients with good partial response in the primary tumour were RGrade 0 (no residual tumour cells) or RGrade 1 (viable tumour cells remained within central superficial portion). In patients with complete response in the neck, residual pN+ was only seen in levels IB (8%) and IIA (8%); the higher the level of residual pN+, the lower the survival rate (p<0.0001). This treatment strategy was excellent for stages II-IV OSCC. It may be possible to perform minimally invasive surgery in which the extent of resection in primary tumour and neck is reduced in patients who achieve good response following preoperative chemoradiotherapy.

Bone Scan Can Be Spared in Asymptomatic Prostate Cancer Patients with PSA of ≤20 ng/ml and Gleason Score of ≤6 at the Initial Stage of Diagnosis

OBJECTIVEnAccording to several guidelines, it is acceptable to spare a bone scan in the patients who are newly diagnosed with low-risk prostate cancer. Our aim is to clarify a suitable group whereby a bone scan could be spared at the initial staging of prostate cancer.nnnMETHODSnConsecutive 857 patients who were newly diagnosed from 2004 through 2009 and received bone scans using technetium 99m methylene diphosphonate at the initial staging were enrolled. The proportion of positive bone metastases by age distribution, prostate-specific antigen level at diagnosis, Gleason score and clinical T stage were evaluated. Univariate and multivariate logistic regression analyses were performed to identify the predictors of positive bone metastases.nnnRESULTSnOf all 857 patients, 40 patients (4.7%) showed bone metastases. Patients with higher age, prostate-specific antigen level, clinical stage and Gleason score showed significantly higher rate of bone metastases (P < 0.001). In univariate logistic regression analyses, age, prostate-specific antigen level, clinical stage and Gleason score were independent predictors of bone metastasis. The multivariate analysis showed that both the prostate-specific antigen level >50 ng/ml and the Gleason score ≥4 + 3 were independent predictors of bone metastases.nnnCONCLUSIONSnThe incidences of bone metastases in patients with a prostate-specific antigen level of ≤20 ng/ml and Gleason score of ≤6 were reasonably low. Collectively, a bone scan is not necessary as a routine examination for these patients at their initial staging of prostate cancer.

Periodical assessment of genitourinary and gastrointestinal toxicity in patients who underwent prostate low-dose-rate brachytherapy.

BackgroundTo compare the periodical incidence rates of genitourinary (GU) and gastrointestinal (GI) toxicity in patients who underwent prostate low-dose-rate brachytherapy between the monotherapy group (seed implantation alone) and the boost group (in combination with external beam radiation therapy (EBRT)).MethodsA total of 218 patients with a median follow-up of 42.5u2009months were enrolled. The patients were divided into 2 groups by treatment modality, namely, the monotherapy group (155 patients) and the boost group (63 patients). The periodical incidence rates of GU and GI toxicity were separately evaluated and compared between the monotherapy group and the boost group using the National Cancer Institute - Common Terminology Criteria for Adverse Events, version 3.0. To elucidate an independent factor among clinical and postdosimetric parameters to predict grade 2 or higher GU and GI toxicity in the acute and late phases, univariate and multivariate logistic regression analyses were carried out.ResultsOf all patients, 78.0% showed acute GU toxicity, and 7.8% showed acute GI toxicity, while 63.8% showed late GU toxicity, and 21.1% showed late GI toxicity. The incidence rates of late GU and GI toxicity were significantly higher in the boost group. Multivariate analysis showed that the International Prostate Symptom Score (IPSS) before seed implantation was a significant parameter to predict acute GU toxicity, while there were no significant predictive parameters for acute GI toxicity. On the other hand, combination with EBRT was a significant predictive parameter for late GU toxicity, and rectal volume (mL) receiving 100% of the prescribed dose (R100) was a significant predictive parameter for late GI toxicity.ConclusionsThe boost group showed higher incidence rates of both GU and GI toxicity. Higher IPSS before seed implantation, combination with EBRT and a higher R100 were significant predictors for acute GU, late GU and late GI toxicity.

Minimal percentage of dose received by 90% of the urethra (%UD90) is the most significant predictor of PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer

BackgroundTo clarify the significant clinicopathological and postdosimetric parameters to predict PSA bounce in patients who underwent low-dose-rate brachytherapy (LDR-brachytherapy) for prostate cancer.MethodsWe studied 200 consecutive patients who received LDR-brachytherapy between July 2004 and November 2008. Of them, 137 patients did not receive neoadjuvant or adjuvant androgen deprivation therapy. One hundred and forty-two patients were treated with LDR-brachytherapy alone, and 58 were treated with LDR-brachytherapy in combination with external beam radiation therapy. The cut-off value of PSA bounce was 0.1u2009ng/mL. The incidence, time, height, and duration of PSA bounce were investigated. Clinicopathological and postdosimetric parameters were evaluated to elucidate independent factors to predict PSA bounce in hormone-naïve patients who underwent LDR-brachytherapy alone.ResultsFifty patients (25%) showed PSA bounce and 10 patients (5%) showed PSA failure. The median time, height, and duration of PSA bounce were 17u2009months, 0.29u2009ng/mL, and 7.0u2009months, respectively. In 103 hormone-naïve patients treated with LDR-brachytherapy alone, and univariate Cox proportional regression hazard model indicated that age and minimal percentage of the dose received by 30% and 90% of the urethra were independent predictors of PSA bounce. With a multivariate Cox proportional regression hazard model, minimal percentage of the dose received by 90% of the urethra was the most significant parameter of PSA bounce.ConclusionsMinimal percentage of the dose received by 90% of the urethra was the most significant predictor of PSA bounce in hormone-naïve patients treated with LDR-brachytherapy alone.

The biochemical recurrence-free rate in patients who underwent prostate low-dose-rate brachytherapy, using two different definitions

BackgroundTo assess the biochemical recurrence (BCR)-free rate in patients who underwent prostate low-dose-rate brachytherapy (LDR-brachytherapy), using two different definitions (Phoenix definition and PSAu2009≥u20090.2xa0ng/mL).MethodsTwo hundreds and three patients who were clinically diagnosed with localized prostate cancer (cT1c-2cN0M0) and underwent LDR-brachytherapy between July 2004 and September 2008 were enrolled. The median follow-up period was 72xa0months. We evaluated the BCR-free rate using the Phoenix definition and the PSA cut-off value of 0.2xa0ng/mL, as in the definition for radical prostatectomy. To evaluate an independent variable that can predict BCR, Cox’s proportional hazard regression analysis was carried out.ResultsThe BCR-free rate in patients using the Phoenix definition was acceptable (5-year: 92.8%). The 5- year BCR-free rate using the strict definition (PSAu2009≥u20090.2xa0ng/mL) was 74.1%. Cox’s proportional hazard regression analysis showed that a higher biological effective dose (BED) of ≥180 Gy2 was the only independent variable that could predict BCR (HR: 0.570, 95% C.I.: 0.327-0.994, pu2009=u20090.048). Patients with a higher BED (≥180 Gy2) had a significantly higher BCR-free rate than those with a lower BED (<180 Gy2) (5-year BCR-free rate: 80.5% vs. 67.4%).ConclusionsA higher BED ≥180 Gy2 promises a favorable BCR-free rate, even if the strict definition is adopted.

Axillary lymph node accumulation on FDG-PET/CT after influenza vaccination

Objective2-[18F]fluoro-2-deoxy-d-glucose (FDG) is known to accumulate in benign conditions such as infection and inflammation as well as in malignancy. Vaccination may cause transient inflammation of lymph nodes, which may induce false-positive findings on FDG-positron emission tomography (PET) imaging. This study investigated the influence of influenza vaccination on FDG-PET/CT imaging in normal subjects.MethodsBetween November 2008 and March 2009, a total of 172 examinees underwent FDG-PET/CT during an annual cancer-screening program at our hospital, 83 of whom had a history of recent non-adjuvanted seasonal influenza vaccination. They were asked the date and injection site of the vaccination. Examinees were divided into 2 groups based on the interval after vaccination using a cutoff value of 7xa0days (1xa0week). Two double board-certified nuclear medicine physicians and radiologists visually interpreted the FDG-PET/CT images with reference to PET/CT fusion and CT images and checked the location and the number of abnormal accumulations by consensus reading.ResultsIntervals between vaccination and FDG-PET were less than 7xa0days in 5 examinees, and 7xa0days or more in 78 examinees. Unexpected accumulations were visualized in 4 examinees in the axilla and medial upper arm, and all of them belonged to the group who underwent vaccination less than 7xa0days previously. In the second group there was no abnormal FDG accumulation.ConclusionsRecent influenza vaccination before FDG-PET/CT examination may cause ipsilateral axillary lymph node accumulations, especially within several days after vaccination. Questionnaires about vaccination can help to avoid false interpretation of FDG avid axillary lymph nodes.

A comparison of surgery and radiation therapy for cT1 esophageal squamous cell carcinoma

Surgery and radiation therapy have been used to treat esophageal squamous cell carcinoma. However, treatment outcomes have not yet been extensively investigated. The aim of this study was to compare surgery and radiation therapy for clinical T1 esophageal squamous cell carcinoma. A total of 67 clinical T1 esophageal squamous cell carcinoma patients were treated between January 1997 and December 2005; 29 had undergone radical esophagectomy (surgery group) and 38 were treated with definitive radiation therapy (radiation group). The mean patient age was lower in the surgery group than in the radiation group. In surgery group, respiratory complications, anastomotic leaks, recurrent nerve palsies, and anastomotic stenosis occurred in 7, 8, 6, and 5 patients, respectively. In radiation group, leucopenia, esophagitis, pericarditis were observed in 15, 3, and 3 patients, respectively. The 5-year overall survival rate for the surgery group was 68.9%, and 74.3% for the radiation group. There were no significant difference between groups (P= 0.3780). The 5-year relapse-free survival rate in the surgery group was 61.8% and 38.8% in the radiation group. The relapse-free survival rate was significantly higher in the surgery group than in the radiation group (P= 0.0051). The 5-year overall and relapse-free survival rates for tumors invaded into but not through the muscularis mucosa were 83.3% and 75.0%, respectively, in the surgery group and 78.8% and 33.3%, respectively, in the radiation group. There were no significant differences. The 5-year overall survival rates for patients with tumors that invaded the submucosal layer was 64.9% in the surgery group and 66.5% in the radiation group. This difference was not significant (P= 0.8712). The 5-year relapse-free survival rate in the surgery group (56.0%) was significantly higher than that in the radiation group (41.8%; P= 0.0219). In conclusion, surgery may become a standard treatment for cT1 esophageal cancer that can offer longer relapse-free survival, particularly for patients with tumors that invade the submucosa.

Efficacy of FDG-PET for defining gross tumor volume of head and neck cancer.

We analyzed the data for 53 patients with histologically proven primary squamous cell carcinoma of the head and neck treated with radiotherapy between February 2006 and August 2009. All patients underwent contrast-enhanced (CE)-CT and 18F-fluorodeoxyglucose (FDG)-PET before radiation therapy planning (RTP) to define the gross tumor volume (GTV). The PET-based GTV (PET-GTV) for RTP was defined using both CE-CT images and FDG-PET images. The CE-CT tumor volume corresponding to a FDG-PET image was regarded as the PET-GTV. The CE-CT-based GTV (CT-GTV) for RTP was defined using CE-CT images alone. Additionally, CT-GTV delineation and PET-GTV delineation were performed by four radiation oncologists independently in 19 cases. All four oncologists did both methods. Of these, PET-GTV delineation was successfully performed in all 19 cases, but CT-GTV delineation was not performed in 4 cases. In the other 15 cases, the mean CT-GTV was larger than the PET-GTV in 10 cases, and the standard deviation of the CT-GTV was larger than that of the PET-GTV in 10 cases. Sensitivity of PET-GTV for identifying the primary tumor was 96%, but that of CT-GTV was 81% (P < 0.01). In patients with oropharyngeal cancer and tongue cancer, the sensitivity of CT-GTV was 63% and 71%, respectively. When both the primary lesions and the lymph nodes were evaluated for RTP, PET-GTV differed from CT-GTV in 19 cases (36%). These results suggested that FDG-PET is effective for defining GTV in RTP for squamous cell carcinoma of the head and neck, and PET-GTV evaluated by both CE-CT and FDG-PET images is preferable to CT-GTV by CE-CT alone.