Outcomes of conventional transarterial chemoembolization for hepatocellular carcinoma ≥10 cm.

AIM: To retrospectively evaluate the outcomes of conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC) ≥10 cm. METHODS: Twenty-five patients with naïve HCC ≥10 cm (mean maximum tumor diameter, 130 ± 27.6 mm; single [n = 12], 2-9 [n = 6], and ≥10 [n = 7]) without extrahepatic spread treated with cTACE were eligible. Five (20%) had vascular invasion. Two to three stepwise cTACE sessions using iodized oil ≤10 mL in one cTACE session were scheduled. When the tumor recurred, additional cTACE was repeated on demand, if possible. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The prognostic factors were evaluated using uni- and multivariate analyses. RESULTS: Stepwise cTACE sessions were completed for 20 (80%) patients, but could not be completed for four (16%). In the remaining (4%) patient, the whole tumor was embolized in one session. Additional treatment, mainly cTACE, was undertaken for 19 (76%) patients. The OS rates at 1, 3, and 5 years were 68, 34.7, and 23.1%, respectively. A tumor number of three was a significant prognostic factor (P = 0.020) and the 1-, 3-, and 4-year OS rates in patients with ≤3 and ≥4 tumors were 81.3 and 33.3, 55.6 and 11.1, and 38.9% and 0%, respectively. Whole tumor embolization and the serum level of protein induced by vitamin K absence or antagonist-II were also significant prognostic factors (P < 0.001 and P = 0.042, respectively). Bile duct complications requiring additional interventions developed in two (8%) patients. CONCLUSION: Conventional TACE is safe and effective for huge HCCs, but has limited effects in cases with four or more tumors.

Intensity-modulated radiotherapy using two static ports of tomotherapy for breast cancer after conservative surgery: dosimetric comparison with other treatment methods and 3-year clinical results.

This study investigated the differences in dose-volume parameters for the breast and normal tissues during TomoDirectTM (TD) intensity-modulated radiation therapy (IMRT), TD-3D conformal radiotherapy (3DCRT) and 3DCRT plans, all using two beams, and analyzed treatment outcomes of two-beam TD-IMRT for breast cancer after breast-conserving surgery. Between August 2011 and January 2015, 152 patients were treated using two-beam TD-IMRT with 50 Gy/25 fractions. Among them, 20 patients with left-sided breast cancer were randomly chosen, and two-beam TD-IMRT, TD-3DCRT and 3DCRT plans were created for each patient. The homogeneity and conformity indices and various dose-volume parameters for the planning target volume and OARs were evaluated. Clinical outcomes were evaluated at 3 years. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. TD-IMRT and TD-3DCRT showed better whole-breast coverage than 3DCRT (P < 0.001). Most of the mean values of dosimetric endpoints for OARs were better in TD-IMRT than in TD-3DCRT and 3DCRT. Overall survival rates were 97.7% and local control rates were 99.1% at 3 years. Regional control and distant metastasis control rates at 3 years were 98.6% and 96.8%, respectively. Twenty-four of the 152 patients had Grade 2 or higher acute radiation dermatitis. Four patients (4/146 = 2.7%) had Grade 2 radiation pneumonitis. There were no late adverse events of Grade 2 or higher. Two-beam TD-IMRT appeared to yield better dose distribution for whole-breast external-beam radiation therapy than TD-3DCRT and two-beam 3DCRT. The treatment appeared to provide low skin toxicity and acceptable tumor control.

Solitary choroidal metastasis from gastric adenocarcinoma: a case report.

BACKGROUND: Metastatic choroidal carcinomas that originated from the gastrointestinal tract are extremely rare. We report a case of suspected solitary choroidal metastasis from gastric adenocarcinoma. CASE PRESENTATION: The patient was a 60-year-old man who had undergone laparoscopic distal gastrectomy with D1+ lymphadenecetomy for gastric cancer. The clinical stage was T1bN0M0 (TNM classification), but the pathological stage was T4aN0M0 beyond expectation. Adjuvant chemotherapy with oral Tegafur, Gimeracil, Oteracil potassium (TS-1®) was initiated. But he suddenly complained of decreased visual acuity in his right eye about 8 months later. This was suspected to be caused by choroidal metastasis of gastric adenocarcinoma. Chemotherapy with paclitaxel (PTX) and intensity-modulated radiotherapy (IMRT) achieved complete remission and spared the patient from going blind. CONCLUSIONS: This case demonstrates that we should be aware of the possibility of choroidal metastases, when visual symptoms arise during treatment of gastric cancer.

Analysis and Management of Rectal Gas with Kampo Formulas During Intensity-Modulated Radiotherapy of Prostate Cancer: A Case Series Study.

OBJECTIVES: During intensity-modulated radiation therapy (IMRT) for prostate cancer, the target, bladder, and rectum positions should be kept constant to reduce adverse events, such as radiation proctitis, and to increase local tumor control. For this purpose, decreasing the rectal contents as much as possible is important. Daisaikoto (DST) and bukuryoingohangekobokuto (BIHKT) are traditional Japanese herbal (Kampo) formulas that have been used to treat patients with abdominal bloating or constipation. MATERIALS AND METHODS: This study investigated the effect of DST and BIHKT on the rectal gas volume during prostate IMRT according to Kampo diagnosis. Five patients were treated with DST or BIHKT at a dose of 5.0 or 7.5 g/d. The volume of rectal gas in 189 megavoltage computed tomographic images taken before each treatment session and the frequency of rectal gas drainage were evaluated before and after DST or BIHKT administration. RESULTS: After DST or BIHKT treatment, the mean volume of rectal gas was reduced from 6.4 to 2.1 mL, and the mean frequency of gas drainage decreased from 43% to 9%. CONCLUSIONS: DST and BIHKT appear to be useful in reducing rectal gas, which would help prevent radiation proctitis and improve the local control of prostate cancer with IMRT.

Safety and efficacy of intensity-modulated stereotactic body radiotherapy using helical tomotherapy for lung cancer and lung metastasis.

Stereotactic body radiotherapy (SBRT) proved to be an effective treatment with acceptable toxicity for lung tumors. However, the use of helical intensity-modulated (IM) SBRT is controversial. We investigated the outcome of lung tumor patients treated by IMSBRT using helical tomotherapy with a Japanese standard fractionation schedule of 48 Gy in 4 fractions (n = 37) or modified protocols of 50-60 Gy in 5-8 fractions (n = 35). Median patient's age was 76 years and median follow-up period for living patients was 20 months (range, 6-46). The median PTV was 6.9 cc in the 4-fraction group and 14 cc in the 5- to 8-fraction group (P = 0.001). Grade 2 radiation pneumonitis was seen in 2 of 37 patients in the 4-fraction group and in 2 of 35 patients in the 5- to 8-fraction group (log-rank P = 0.92). Other major complications were not observed. The LC rates at 2 years were 87% in the 4-fraction group and 83% in the 5- to 8-fraction group. Helical IMSBRT for lung tumors is safe and effective. Patients with a high risk of developing severe complications may also be safely treated using 5-8 fractions. The results of the current study warrant further studies of helical IMSBRT.

Treatment of single or multiple brain metastases by hypofractionated stereotactic radiotherapy using helical tomotherapy.

This study investigated the clinical outcomes of a 4-fraction stereotactic radiotherapy (SRT) study using helical tomotherapy for brain metastases. Between August 2009 and June 2013, 54 patients with a total of 128 brain metastases underwent SRT using tomotherapy. A total dose of 28 or 28.8 Gy at 80% isodose was administered in 4 fractions for all tumors. The mean gross tumor volume (GTV) was 1.9 cc. Local control (LC) rates at 6, 12, and 18 months were 96%, 91%, and 88%, respectively. The 12-month LC rates for tumors with GTV ≤0.25, >0.25 and ≤1, and >1 cc were 98%, 82%, and 93%, respectively; the rates were 92% for tumors >3 cc and 100% for >10 cc. The 6-month rates for freedom from distant brain failure were 57%, 71%, and 55% for patients with 1, 2, and >3 brain metastases, respectively. No differences were significant. No major complications were observed. The 4-fraction SRT protocol provided excellent tumor control with minimal toxicity. Distant brain failure was not so frequent, even in patients with multiple tumors. The results of the current study warrant a prospective randomized study comparing single-fraction stereotactic radiosurgery (SRS) with SRT in this patient population.

Usefulness of C-arm CT during superselective infusion chemotherapy for advanced head and neck carcinoma.

PURPOSE OF THE STUDY: To evaluate the usefulness of C-arm computed tomography (CT) during superselective intra-arterial infusion chemotherapy for advanced head and neck carcinoma. METHODS: C-arm CT was performed during superselective intra-arterial infusion chemotherapy for 11 patients with advanced head and neck carcinoma located in the hypopharynx (n = 3), maxillary sinus (n = 3), oropharynx (n = 1), larynx (n = 1), extra-auditory canal (n = 1), tonsil (n = 1) and tongue (n = 1). The usefulness of C-arm CT during superselective catheterisation was evaluated. RESULTS: On arteriography, nine tumours showed tumour stains and two in the oropharynx or tonsil showed no obvious tumour stains. C-arm CT was performed one to four times (mean ± standard deviation, 2.5 ± 0.8) in each patient during a single procedure. C-arm CT clearly showed not only the vascular territory of the selected branch but also the tumour itself in all patients. Intra-arterial infusion chemotherapy was performed through one to three branches (mean, 1.7 ± 0.9) according to C-arm CT findings without any complications. CONCLUSION: C-arm CT during superselective intra-arterial infusion chemotherapy was useful to determine the arterial supply of head and neck carcinoma. C-arm CT may replace conventional CT during superselective arteriography in this procedure.

[Evaluation of a method for correcting systematic setup error in external-beam radiation therapy].

BACKGROUND AND PURPOSE: We verified the propriety of our systematic error reduction strategy by means of a computer simulation based on our data of position error with a prone fixation device for prostate IMRT. MATERIALS AND METHODS: Computer simulations of the off-line correction method for systematic setup errors based on the portal imaging taken on the first several days of the treatment session were performed. Using the computer simulations, an optimal number of portal images were evaluated for the SD value, from 0.5 mm to 1.5 mm at a 0.25 mm interval, and the respective required setup margins were calculated. RESULTS: The value of systematic error was reduced as the frequency of data obtained increased. Moreover, the reduction rate was so remarkable that random error was large.

[Usefulness of the classification technique of cerebral artery for 2D/3D registration.].

Several papers have proposed 2D/3D registration methods of the cerebral artery using magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). Since differences between vessels in a DSA image and MRA volume data cause registration failure, we previously proposed a method to extract vessels from MRA volume data using a technique based on classification of the cerebral artery. In this paper, we evaluated the usefulness of this classification technique by evaluating the reliability of this 2D/3D registration method. This classification method divides the cerebral artery in MRA volume data into 12 segments. According to the results of the classification, structures corresponding to vessels on a DSA image can then be extracted. We applied the 2D/ 3D registration with /without classification to 16 pairs of MRA volume data and DSA images obtained from six patients. The registration results were scored into four levels (Excellent, Good, Fair and Poor). The rates of successful registration (> fair) were 37.5% for registration without classification and 81.3% for that with classification. These findings suggested that there was a low percentage of incorrectly extracted voxels and we could facilitate reliable registration. Thus, the classification technique was shown to be useful for feature-based 2D/ 3D registration.

Analysis of the effective point of measurement of a thimble chamber dosimeter set parallel to the X-ray beam axis.

To measure the narrow beam used in stereotactic irradiation, installation of the ionization chamber parallel to the X-ray beam axis has been used instead of perpendicular installation. However, the definition of the effective point is a major problem in the parallel installation. In this study, we analyzed the effective point in parallel installation, and considered the prediction and evaluation of measurement point displacement. Relative dosimetry was carried out by installing the thimble ionization chamber in both perpendicular and parallel configurations. We then searched for the measurement point that coincided with the PDD of the perpendicular installation by using the displacement of the measurement point of the parallel installation. We found that the effective point of measurement for relative photon beam dosimetry depends on every detail of the chamber design, including the cavity length and the cavity radius. Moreover, the effective point of measurement also depends on the beam quality and the field size. The amount of effective point displacement for the parallel installation was quantified with the linear expression of TPR(20,10). Our results showed that the amount of effective point displacement can be estimated by the ionization volume of the dosimeter and the energy used.

Haplotype-based analysis of genes associated with risk of adverse skin reactions after radiotherapy in breast cancer patients.

PURPOSE: To identify haplotypes of single nucleotide polymorphism markers associated with the risk of early adverse skin reactions (EASRs) after radiotherapy in breast cancer patients. METHODS AND MATERIALS: DNA was sampled from 399 Japanese breast cancer patients who qualified for breast-conserving radiotherapy. Using the National Cancer Institute-Common Toxicity Criteria scoring system, version 2, the patients were grouped according to EASRs, defined as those occurring within 3 months of starting radiotherapy (Grade 1 or less, n = 290; Grade 2 or greater, n = 109). A total of 999 single nucleotide polymorphisms from 137 candidate genes for radiation susceptibility were genotyped, and the haplotype associations between groups were assessed. RESULTS: The global haplotype association analysis (p < 0.05 and false discovery rate < 0.05) indicated that estimated haplotypes in six loci were associated with EASR risk. A comparison of the risk haplotype with the most frequent haplotype in each locus showed haplotype GGTT in CD44 (odds ratio [OR] = 2.17; 95% confidence interval [CI], 1.07-4.43) resulted in a significantly greater EASR risk. Five haplotypes, CG in MAD2L2 (OR = 0.55; 95% CI, 0.35-0.87), GTTG in PTTG1 (OR = 0.48; 95% CI, 0.24-0.96), TCC (OR = 0.48; 95% CI, 0.26-0.89) and CCG (OR = 0.50; 95% CI, 0.27-0.92) in RAD9A, and GCT in LIG3 (OR = 0.46; 95% CI, 0.22-0.93) were associated with a reduced EASR risk. No significant risk haplotype was observed in REV3L. CONCLUSION: Individual radiosensitivity can be partly determined by these haplotypes in multiple loci. Our findings may lead to a better understanding of the mechanisms underlying the genetic variation in radiation sensitivity and resistance among breast cancer patients.

Randomized phase II study of immunomodulator Z-100 in patients with stage IIIB cervical cancer with radiation therapy.

OBJECTIVE: To find the optimal dose of immunomodulator Z-100 in patients with stage IIIB squamous cell carcinoma of the cervix in combination with radiation therapy. METHODS: The patients were randomly assigned to the dosage levels of 2, 20 or 40 mug of Z-100. Z-100 was subcutaneously injected twice a week during radiotherapy and once in two weeks during the maintenance period. The response rate after radiotherapy was evaluated, and the optimal clinical dosage was then determined. Safety of Z-100 was evaluated during the radiation therapy and maintenance therapy. Survival was also evaluated. RESULTS: A total of 116 patients were entered. The adverse reactions were not dose-dependent and no serious toxicities were observed. The response rates were 72.2% (26/36) in the 2 microg group, 84.6% (33/39) in the 20 microg group and 94.3% (33/35) in the 40 microg group (P = 0.006). However, the survival was not significantly different. CONCLUSIONS: The optimal dose of Z-100 was determined to be 40 mug in combination with radiation therapy for stage IIIB cervical cancer. However, impact of Z-100 on survival must be determined by the placebo controlled randomized trial, because survival benefit was not observed in this small population study.

Elective neck irradiation on ipsilateral side in patients with early tongue cancer for high-risk group with late cervical lymph node metastasis.

A prospective study was performed to assess the efficacy of elective neck irradiation (ENI) on the ipsilateral side in patients with early tongue cancer among a high-risk group with late cervical lymph node metastasis. Patients in the high-risk group had T2-tumors, excluding superficials or T1-tumors > or =19 mm in maximal diameter with invasion or ulcer. Between February 1989 and October 1997, 70 patients with tongue cancer of Stages I and II were enrolled in the present study (ENI group: 31, non-ENI group: 39). In a combination therapy of external beam irradiation and brachytherapy, the standard dose of interstitial brachytherapy for primary tumors was approximately 60 Gy. Irradiation was initiated with a 9-MeV electron beam at a dose of 50 Gy on the ipsilateral side of the neck only when the day of brachytherapy approached. Three patients (9.7%) in the ENI group had neck lymph node metastasis as did 5 (12.8%) in the non-ENI group (p= 0.684). In patients with ulceration, the incidence of subsequent lymph node metastasis was significantly higher (p=0.029). Neck lymph node metastasis occurred in 2 (16.7%) of 12 patients with ulcers in the ENI group and in 2 (66.7%) of 3 with ulcers in the non-ENI group. Although we could not demonstrate the significant efficacy of ENI in the high-risk group in this study, ENI decreased the neck lymph node metastasis. In addition, our results suggested that ENI particularly inhibits cervical lymph node metastasis in tongue tumor patients with ulcers.

Phase III double-blind randomized trial of radiation therapy for stage IIIb cervical cancer in combination with low- or high-dose Z-100: treatment with immunomodulator, more is not better.

BACKGROUND: To evaluate the efficacy of low or high-dose immunomodulator, Z-100, in combination with radiotherapy for cervical cancer. METHODS: Between 1995 and 1999, 221 patients with stage IIIb squamous cell carcinoma of the cervix were randomly assigned to treatment with Z-100 either at 0.2 microg or 40 microg in a double-blind manner in combination with radiotherapy. RESULTS: The 5-year survival of patients with high-dose and low-dose Z-100 was 41.5% (95% CI: 31.7-51.3%) and 58.2% (95% CI: 48.7-67.7%), respectively, showing a 30% reduction in the death rate (hazard ratio: 0.670 [95% CI: 0.458-0.980], P = 0.039). Survival of high-dose group was equivalent to the 4-year survival of the radiotherapy plus hydroxyurea arm (49.7%) of GOG120 study, and that of low-dose group was similar to the survival of the cisplatin-based chemoradiation arm. The progression-free survival was also significantly improved in favor of low-dose group (hazard ratio: 0.667 [95% CI: 0.447-0.997], P = 0.048). The survival of low-dose group was similar to the survival of the cisplatin-based chemoradiation arms of the GOG120 study. CONCLUSIONS: Unexpectedly, the survival of patients with advanced cervical cancer treated by lower dose of Z-100 in combination with radiotherapy was significantly better than those treated with higher dose Z-100, which was equivalent to the survival with radiotherapy alone. The hypothesis that lower dose of Z-100 enhances the efficacy of radiation therapy is now being tested by placebo-controlled randomized trial.

Development of a semi-automated superimposing image verification system using a template matching algorithm in radiotherapy.

To analyze shifts in the isocenter of images, we developed a semi-automated superimposing image-verification system that is capable of automatically quantifying shifts in the isocenter through image analysis with a personal computer (PC). The accuracy and usefulness of this software were examined through a comparison of nine portal images with a simulation image and by comparing nine portal images with a DRR image, using a human pelvic phantom. The difference between the known magnitude of shift and the magnitude of shift detected with this method was analyzed as detection error. When the portal images were compared with the simulation image, the 95% confidence interval (95% CI) of detection errors (mean+/-SD) was 0.57+/-0.36 mm (95% CI: 0.49-0.65 mm). When the portal images were compared with the DRR image, the respective figures were 0.68+/-0.38 mm (95% CI: 0.59-0.77 mm). No significant difference was noted between these two categories of comparison (N.S). The absolute detection error (mean+/-SD) in all directions was 0.34+/-0.34 mm for the comparison of portal images with the simulation image and 0.41+/-0.36 mm for the comparison of portal images with the DRR image. This system seems to be appropriate for verification of the treatment field by improving the accuracy of radiotherapy as a method of computer-assisted landmark recognition during image comparison.

Development of computerized patient setup verification and correction system in radiotherapy.

Visual comparison of a reference image with a verification image is commonly used for setup verification in external beam radiation therapy. However, it sometimes lacks reproducibility and provides insufficient quantitative evidence. The present study was performed to develop computerized methods for determining landmarks to verify a portal image with digital reconstruction radiograph (DRR), and to investigate the clinical effectiveness of our method. Our computer algorithm consisted of three main procedures--preprocessing, determination of landmarks, and verification--none of which required manual operation. Finally, our system indicated the distance for setup correction. We evaluated the accuracy of our system using pelvic phantom images, and the maximum magnitude of error was shown to be 1.12 (n=9). The results indicated that the error range of our system was sufficiently small to examine patient positioning error, which should be less than 5 mm, as described in AAPM report TG40. Our system will aid operators in positioning patients accurately for external radiation therapy.

[Online-conference using JGN.].

Telemedicine and online conference systems have some benefits so that equalizing medical level, improving efficiency of medical care and improving service for patients. It is possible to give advice and to support its medical projects stationed in other facility and to provide the same quality treatments for patients. In this paper, we set up an experimental network system to teleconference using JGN (Japan Gigabit Network) and tried to discussion alternatively for case study between Kanazawa university and Fukui red cross hospital, 70 km away. The JGN used in this study is an ultra-high-speed network for the purpose of research and development. Kanazawa university, and Fukui red cross hospital are connected by a 10 Mbps communication link of the JGN. We tried online conference on the experimental network using video chat system. In result, using video chat system, the average transmission rate of MRI images (256 X 256pixel, 16bit) is 0.2 s/frame.

[Study of optimal imaging parameters for digitally reconstructed radiographs (DRR) in radiotherapy treatment planning using single-slice helical CT].

In recent years, by making digitally reconstructed radiographs (DRR) from helical CT images in the position check of an irradiation field, the verification performed by DRR, lineacgraphy (LG), or an electronic portal imaging device (EPID) has become possible. We examined the optimal parameters of single-slice helical scanning in DRR image construction and the usefulness of DRR replaced with the simulation film. We performed a section sensitivity profile at the Z-axis (SSPz) as evaluation of a physical characteristic of helical CT equipment and the form of image of DRR, fixed quantity evaluation of imaging distortion, and visual verification of images. It was determined that DRR was influenced by the partial volume effect depending on slice thickness and pitch, such that this influence occurred when slice thickness and pitch were large. Between a simulation film and DRR reconstructed using imaging parameters with a slice thickness of 3 mm, pitch of 1.0, and reconstruction slice thickness of 3 mm, coincidence was not complete. However, the distortion of DRR was small and the difference was not statistically; thus it was considered to be useful. In conclusion, we consider that DRR reconstructed using the parameters of single-slice helical scanning is useful for clinical evaluation in radiotherapy planning.