[Show abstract][Hide abstract] ABSTRACT: We investigated the rectal dose-sparing effect and tumor control of a point A dose-reduced plan in patients with Stage I-II cervical cancer (≤4 cm) arising from a small-sized uterus. Between October 2008 and August 2011, 19 patients with Stage I-II cervical cancer (≤4 cm) were treated with external beam radiotherapy (EBRT) for the pelvis and CT-guided brachytherapy. Seven patients were treated with brachytherapy with standard loading of source-dwell positions and a fraction dose of 6 Gy at point A (conventional brachy-plan). The other 12 patients with a small uterus close to the rectum or small intestine were treated with brachytherapy with a point A dose-reduction to match D2cc of the rectum and <6 Gy as the dose constraint ('point A dose-reduced plan') instead of the 6-Gy plan at point A ('tentative 6-Gy plan'). The total doses from EBRT and brachytherapy were added up and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2). The median doses to the high-risk clinical target volume (HR-CTV) D90 in the conventional brachy-plan, tentative 6-Gy plan and point A dose-reduced plan were 62 GyEQD2, 80 GyEQD2 and 64 GyEQD2, respectively. The median doses of rectal D2cc in the corresponding three plans were 42 GyEQD2, 62 GyEQD2 and 51 GyEQD2, respectively. With a median follow-up period of 35 months, three patients developed Grade-1 late rectal complications and no patients developed local recurrence. Our preliminary results suggested that CT-guided brachytherapy using an individualized point A dose-reduced plan might be useful for reducing late rectal complications while maintaining primary tumor control.
Journal of Radiation Research 02/2014; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm(3) (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0-19.7 cm(3). There were 16 lesions with a V14 of ≥7.0 cm(3), and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm(3) exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.
Journal of Radiation Research 11/2013; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To prospectively investigate the changes in bone mineral density (BMD) after pelvic radiation therapy in patients with uterine cervical cancer.
Of 52 cervical cancer patients who received pelvic RT in our university hospital between 2009 and 2011, 46 patients without recurrence and who were followed up for more than 12 months were included in the study. The BMD of the irradiated region and nonirradiated regions, serum estradiol, tartrate-resistant acid phosphatase-5b, and N-terminal cross-linking telopeptide of collagen 1 were measured before, at 3 months after, and at 12 months after RT. The patient cohort was divided into 2 groups according to estradiol level before RT, and the groups were defined as postmenopausal (<40 pg/mL) and premenopausal (≥40 pg/mL).
The mean BMDs within the irradiation field (lumbar vertebra 5) in the postmenopausal and the premenopausal groups were 0.825 and 0.910 g/cm(2) before RT and 0.746 and 0.841 g/cm(2) 12 months after RT, respectively. Significant decreases were observed in both groups (P<.05 and P<.01, respectively). In addition, in the premenopausal group the mean BMDs of the nonirradiated regions at thoracic vertebrae 9-12 and lumbar vertebrae 2-4 were 0.753 and 0.958 g/cm(2) before RT and were significantly decreased to 0.706 and 0.921 g/cm(2) 12 months after RT (P<.01 and P<.05, respectively). Estradiol significantly decreased 3 months after RT, whereas tartrate-resistant acid phosphatase-5b and N-terminal cross-linking telopeptide of collagen 1 continued to increase over time in the premenopausal group.
A decrease in BMD in the irradiated region after RT was observed within 1 year, regardless of menopausal status. Furthermore, in premenopausal patients, pelvic RT caused a decrease in systemic BMD.
International journal of radiation oncology, biology, physics 10/2013; · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm(3) were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6-31.5 cm(3). There were 35 lesions with a V14 of 7 cm(3) or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm(3) exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.
Journal of Radiation Research 02/2013; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).
Methods and materials
S-1 (50 mg/m2) was administered orally twice daily for 14 days, with cisplatin (40 mg/m2) on days 1 and 8 of each cycle every 3 weeks, for 2–4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.
Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8–97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.
The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.
Lung Cancer 01/2013; 82(3):449–454. · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to compare the size and clearness of gross tumor volumes (GTVs) of metastatic brain tumors on T1-weighted magnetic resonance images between a single dose contrast administration protocol and a double dose contrast administration protocol to determine the optimum dose of contrast-enhancement for clear delineation of GTV in stereotactic radiotherapy (SRT). A total of 28 small metastatic brain tumors were evaluated in 13 patients by intra-individual comparison of GTV measurements using single dose and double dose contrast-enhanced thin-slice (1-mm) magnetic resonance imaging (MRI). All patients had confirmed histological types of primary tumors and had undergone hypo-fractionated SRT for metastatic brain tumors. The mean tumor diameter with single dose and double dose contrast-enhancement was 12.0 ± 1.1 mm and 13.2 ± 1.1 mm respectively (P < 0.001). The mean incremental ratio (MIR) obtained by comparing mean tumor diameters was 11.2 ± 0.02 %. The mean volume of GTV-1 (single dose contrast-enhancement) and GTV-2 (double dose contrast-enhancement) was 1.38 ± 0.41 ml and 1.59 ± 0.45 ml respectively (P < 0.01). The MIR by comparing mean tumor volumes was 32.3 ± 0.4 %. The MIR of GTV-1 with < 1ml volume and GTV-1 with > 1ml volume was 41.8 ± 0.05 % and 12.4 ± 0.03 % respectively (P < 0.001). We conclude that double dose contrast-enhanced thin-slice MRI is a more useful technique than single dose contrast-enhanced thin-slice MRI, especially for clear delineation of GTVs of small metastatic brain tumors in treatment planning of highly precise SRT.
Journal of Radiation Research 07/2012; · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Radiotherapy plays an important role in the treatment for thoracic cancers. Accurate diagnosis is essential to correctly perform curative radiotherapy. Tumor delineation is also important to prevent geographic misses in radiotherapy planning. Currently, planning is based on computed tomography (CT) imaging when radiation oncologists manually contour the tumor, and this practice often induces interobserver variability. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been reported to enable accurate staging and detect tumor extension in several thoracic cancers, such as lung cancer and esophageal cancer. FDG-PET imaging has many potential advantages in radiotherapy planning for these cancers, because it can add biological information to conventional anatomical images and decrease the inter-observer variability. FDG-PET improves radiotherapy volume and enables dose escalation without causing severe side effects, especially in lung cancer patients. The main advantage of FDG-PET for esophageal cancer patients is the detection of unrecognized lymph node or distal metastases. However, automatic delineation by FDG-PET is still controversial in these tumors, despite the initial expectations. We will review the role of FDG-PET in radiotherapy for thoracic cancers, including lung cancer and esophageal cancer.
International journal of molecular imaging. 01/2012; 2012:609545.
[Show abstract][Hide abstract] ABSTRACT: Recently, it has become clear that acute hypoxia affecting radioresistance exists widely in tumor tissues. Concurrently, hypoxia-inducible factor-1α (HIF-1α) is recognized as an essential transcriptional factor, enabling cells to survive through hypoxia. However, it is unclear as to whether HIF-1α plays a direct role in the radioresistance caused by acute hypoxia. Therefore, in this study, we investigated the in vitro response of the human lung adenocarcinoma cell line, A549, to ionizing radiation in an experimental model that imitates acute hypoxia in the presence and absence of HIF-1α expression, using the HIF-1α inhibitor 5-[1-(phenylmethyl)-1H-indazol-3-yl]-2-furanmethanol (YC-1). Cells were treated with or without 10 μM YC-1 for 2 h. Cells were exposed to either 95% N(2) and 5% CO(2) (hypoxic condition of <0.1 mmHg) or atmospheric air (normoxic condition) for 1 h, and irradiated with 2, 5 and 10 Gy. Western blot analysis revealed that, without YC-1, cells exposed to hypoxic conditions expressed increased levels of HIF-1α compared with those exposed to normoxic conditions. Under hypoxic conditions, HIF-1α expression was suppressed by YC-1 to the same extent as that observed in cells exposed to normoxic conditions without YC-1. Clonogenic survival assay revealed that under hypoxic conditions there was no significant difference between the surviving fraction of cells treated with YC-1 and without YC-1 at any dose point examined. The oxygen enhancement ratio at 10% surviving fraction was calculated as 2.7 and 2.6 in the presence and the absence of YC-1, respectively. These results indicate that HIF-1α itself is not an immediate cause of acute hypoxia-induced radioresistance in A549 cells.
Experimental and therapeutic medicine 01/2012; 3(1):141-145. · 0.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the clinical applicability of a protocol evaluated in a previously reported phase II study of concurrent chemoradiotherapy followed by consolidation chemotherapy with bi-weekly docetaxel and carboplatin in patients with stage III, unresectable, non-small-cell lung cancer (NSCLC).
Between January 2000 and March 2006, 116 previously untreated patients with histologically proven, stage III NSCLC were treated with concurrent chemoradiotherapy. Radiation therapy was administered in 2-Gy daily fractions to a total dose of 60 Gy in combination with docetaxel, 30 mg/m(2), and carboplatin at an area under the curve value of 3 every 2 weeks during and after radiation therapy.
The median survival time for the entire group was 25.5 months. The actuarial 2-year and 5-year overall survival rates were 53% and 31%, respectively. The 3-year cause-specific survival rate was 60% in patients with stage IIIA disease, whereas it was 35% in patients with stage IIIB disease (p = 0.007). The actuarial 2-year and 5-year local control rates were 62% and 55%, respectively. Acute hematologic toxicities of Grade ≥3 severity were observed in 20.7% of patients, while radiation pneumonitis and esophagitis of Grade ≥3 severity were observed in 2.6% and 1.7% of patients, respectively.
The feasibility of the protocol used in the previous phase II study was reconfirmed in this series, and excellent treatment results were achieved.
International journal of radiation oncology, biology, physics 05/2011; 82(5):1791-6. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aims of this study were to carry out a dose volume analysis of high-dose-rate interstitial brachytherapy with computed tomography-based treatment planning and to investigate the treatment outcome of patients with locally advanced bulky and/or irregularly shaped uterine cervical carcinoma. Between July 2003 and December 2007, 15 patients were treated with external beam radiation therapy and high-dose-rate interstitial brachytherapy with or without intracavitary brachytherapy. Seven patients were treated with interstitial brachytherapy alone, and 8 were treated with combined use of intracavitary and interstitial brachytherapy. A comparison of the volume and dose parameters with intracavitary and interstitial brachytherapy in patients who received both treatments showed that the median D90 of the high-risk clinical target volume per fraction was 4.4 Gy with intracavitary brachytherapy and 5.6 Gy with interstitial brachytherapy, and the median V100 was 66% with intracavitary brachytherapy and 85% with interstitial brachytherapy. The median D2cc of the bladder with intracavitary and interstitial brachytherapy per fraction was 5.5 Gy and 4.7 Gy, respectively, and the median D2cc of the rectum with intracavitary and interstitial brachytherapy was 5.9 Gy and 4.1 Gy, respectively. The median follow-up time was 37 months, and the overall and progression-free survival rates for all patients at 3 years were 78% and 51%, respectively. The actuarial 2-year and 3-year locoregional control rates were 80% and 71%, respectively. Dose distribution was improved with image-based interstitial brachytherapy, and satisfactory local control was achieved for patients with locally advanced uterine cervical carcinoma in which intracavitary brachytherapy may result in a suboptimal dose distribution.
Journal of Radiation Research 01/2011; 52(4):490-5. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypoxia-inducible factor 1α (HIF-1α) is an intrinsic marker of tumor hypoxia. It has been considered that hypoxic conditions reduce radiosensitivity, but the role of HIF-1α in patients treated with preoperative therapy for rectal cancer is still unclear. The aim of this study was to evaluate the predictive value of tumor response to preoperative hyperthermo-chemoradiotherapy (HCRT) and the prognostic significance of HIF-1α expression in patients with locally advanced rectal cancer. Between 2003 and 2006, 50 patients with histologically proven rectal adenocarcinoma who underwent HCRT followed by surgery were investigated. HIF-1α expression was immunohistochemically evaluated using pre-treatment biopsies. The total radiation dose was 40-50 Gy and chemotherapy consisted of 5-FU and LV administered by continuous infusion on Day 1-5, Day 15-19, and Day 29-33 during radiotherapy. Hyperthermia treatment was performed for once a week for 2-5 sessions. The surgical operation was performed 8 weeks after HCRT and each resected specimen was graded by histological criteria of the Japanese Classification of Colorectal Carcinoma. The effects of HIF-1α on clinical outcomes were analyzed by univariate and multivariate analysis. Positive HIF-1α expression was recognized in 42.0% of samples (21/50). Resected specimens that showed pathological grades 1, 2, and 3 numbered 17, 24, and 9 cases, respectively. There were no significant differences between the HIF-1α-positive group and HIF-1α-negative group for pathological grading and pCR. Overall survival (OS) rate at 3 years in the HIF-1α-negative group was 85.2%, which was significantly better than the 60.6% in the HIF-1α-positive group. Recurrence-free survival (RFS) rate at 3 years in the HIF-1α-negative group was 82.8%, being significantly better than 47.6% in the HIF-1α-positive group. In addition, elevated HIF-1α expression was significantly correlated with recurrence-free survival and metastasis-free survival rate in multivariate analysis. HIF-1α expression might be predictive of recurrence-free survival and metastasis-free survival rate for rectal cancer patients treated with HCRT.
Journal of Radiation Research 01/2011; 52(6):821-7. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a new technique of brachytherapy consisting of intracavitary combined with computed tomography (CT)-guided interstitial brachytherapy for locally advanced cervical cancer. A Fletcher-Suit applicator and trocar point needles were used for performing high-dose rate brachytherapy under in-room CT guidance. First, a tandem and ovoids were implanted into the patient's vagina and uterus by conventional brachytherapy method. Based on clinical examination and MRI/CT imaging, operating radiation oncologists decided the positions of insertion in the tumor and the depth of the needles from the upper surface of the ovoid. Insertion of the needle applicator was performed from the vaginal vault inside the ovoid within the tumor under CT guidance. In treatment planning, dwell positions and time adaptations within the tandem and ovoids were performed first for optimization based on the Manchester system, and then stepwise addition of dwell positions within the needle was continued. Finally, dwell positions and dwell weights were manually modified until dose-volume constraints were optimally matched. In our pilot case, the dose of D90 to high-risk clinical target volume was improved from 3.5 Gy to 6.1 Gy by using our hybrid method on the dose-volume histogram. D1cc of the rectum, bladder and sigmoid colon by our hybrid method was 4.8 Gy, 6.4 Gy and 3.5 Gy, respectively. This method consists of advanced image-guided brachytherapy that can be performed safely and accurately. This approach has the potential of increasing target coverage, treated volume, and total dose without increasing the dose to organs at risk.
Journal of Radiation Research 01/2011; 52(1):54-8. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to compare dose reduction to the small bowel and sacral bone by two-field and four-field techniques when the common iliac lymph node region is excluded from the radiation field in external beam radiotherapy of uterine cervical cancer. Thirteen patients with cervical cancer were entered into the study. Conventional treatment plans based on bony landmarks were made with parallel-opposed two-field technique (C2F) and four-field box technique (C4F). Modified C2F (M2F) and C4F (M4F) plans of excluding the common iliac lymph node region from the conventional radiation fields were created in reference to the bifurcations of pelvic arteries in computed tomography images. For each patient, the dose volume histograms for the small bowel and sacral bone resulting from the C2F, C4F, M2F, and M4F plans were compared. The volumes were obtained at 10 levels of prescribed dose, at increments of 10%, from 5 Gy to 50 Gy. By sparing both small bowel and sacral bone, the M2F and M4F plans were significantly better than the C2F and C4F plans at any dose level (p < 0.05), respectively. In addition, the M4F plan was significantly better than the M2F plan in sparing both small bowel at 10-50% of the prescribed dose (p < 0.05) and sacral bone at 40-100% of the prescribed dose (p < 0.05). The present study suggests that modified treatment planning could be useful for selected patients for reducing small bowel complications and insufficiency fracture after radiotherapy.
Journal of Radiation Research 10/2010; 51(6):715-21. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of metastatic angiosarcoma of the lung with alveolar hemorrhage was experienced. A 76-year-old woman was diagnosed as stage IIb uterine cervical cancer. The cancer disappeared after radiotherapy. Five years later, she was readmitted because of severe pain around the right hip joint. Fracture of the neck of the right femur was found on roentgenogram. On chest CT and roentgenogram, spotted or restiform shadows with uncertain margins were found in the peripheral regions of the bilateral lung field. The lesions reached just underneath the pleura, and interstitial shadows such as ground-glass-like shadows and thickening of the interlobular walls were also found. These lesions were rapidly aggravated in the course of 1-2 weeks. She died after a short period of hospitalization (2 months) with pathological fracture. In autopsy, metastases of the tumor were found to bones, lungs, heart, and other organs that mainly occurred hematogenously. No recurrence of the uterine cervical cancer was detected. Tumor cells were polymorphic or ovoid, and occurred scattered individually or showed growth-forming small aggregates. By immunohistochemical staining, CD31, CD34 and Factor VIII were found to be positive, and the tumor was diagnosed as epithelioid angiosarcoma. The main findings in the lungs were intraalveolar hemorrhage consequent to tumor embolization.
Japanese journal of radiology 11/2009; 27(9):381-4. · 0.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the efficacy of hypofractionated linac-based stereotactic radiotherapy with a micro-multileaf collimator (mMLC) in lung cancer patients with brain metastases.
Seventy-eight lesions of brain metastases in 49 lung cancer patients treated by stereotactic radiotherapy between September 2003 and December 2006 were analyzed. In the treatment planning, the planning target volume (PTV) was defined as an enhanced lesion plus 3 mm margin. A total dose of 39-42 Gy in three fractions was delivered to the isocenters of the PTV.
The median survival time after stereotactic radiotherapy was 17.4 months. The 1- and 2-year survival rates were 61% and 32%, respectively. The presence of extracranial tumors, the pre-treatment performance status, and the Radiation Therapy Oncology Group recursive partitioning analysis class were significant prognostic factors. The 1- and 2-year local recurrence rates were 14% and 17%, respectively, with no serious acute toxic effect. Injuries involving brain necrosis were observed in six patients. New brain metastases or meningeal carcinomatosis was seen in more than half of the patients following treatment with stereotactic radiotherapy.
Hypofactionated stereotactic radiotherapy with mMLC is considered to be an effective and safe modality for the treatment of brain metastases in lung cancer patients.
Japanese Journal of Clinical Oncology 10/2009; 40(2):119-24. · 1.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is currently unclear which patients with breast cancer with sentinel lymph node (SLN) metastases do not need axillary lymph node dissection (ALND).
A cohort of 1,132 women who had unilateral invasive breast cancer with clinically negative nodes or nodes suspicious for metastasis, were intraoperatively diagnosed as having negative SLNs, and did not undergo an immediate ALND. Our intraoperative histological investigation uses H&E staining of a frozen section from a maximum cut surface of each SLN. Of these 1,132 women, 132 (11.7%) were postoperatively diagnosed as having positive SLNs, which classifies them as having an intraoperative, false-negative SLN biopsy (SLNB). Patient and tumor characteristics, treatment methods, and the prognoses of these patients were investigated and compared with the remaining 1,000 patients who were negative for SLNB.
Of the 132 patients with intraoperative, false-negative SLNB, none underwent a further ALND. With a median follow-up period of 58.1 months, none of these patients exhibited recurrence in the axillary nodes. Their recurrence-free survival rates were not statistically different from those of patients with negative SLNB.
ALND can be avoided in most patients with breast cancer with intraoperative, false-negative SLNB.
Breast Cancer 08/2009; 17(1):9-16. · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several investigations have revealed that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy.
Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the alpha/beta ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on computed tomography images. The number of patients in each fractionation group was as follows: 13 in the 5-Gy group; 19 in the 7-Gy group, and 38 in the 9-Gy group. The tumor stage was T1 in 10 patients, T2 in 36 patients, and T3 in 24 patients. The Gleason score was 2-6 in 11 patients, 7 in 34 patients, and 8-10 in 25 patients. Androgen ablation was performed in all the patients. The median follow-up duration was 14 months (range 3-42 months). The toxicities were graded based on the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria.
The main symptoms of acute GU toxicity were dysuria and increase in urinary frequency or nocturia. The grade distribution of acute GU toxicity in the patients was as follows: Grade 0-1, 39 patients (56%), and Grade 2-4, 31 patients (44%). One patient who developed acute urinary obstruction was classified as having Grade 4 toxicity. Comparison of the distribution of the grade of acute GU toxicity among the different fractionation groups revealed no statistically significant differences among the groups. The urethral dose in HDR brachytherapy was evaluated using the following DVH parameters: V30 (percentage of the urethral volume receiving 30% of the prescribed radiation dose), V80, V90, V100, V110, V120, V130, and V150. The V30-110 values in the patients with Grade 2-4 acute GU toxicity were significantly higher than those in patients with Grade 0-1 toxicity. On the other hand, there were no significant differences in the V120-150 values between patients with Grade 0-1 and Grade 2-4 toxicity. Regarding the influence of the number of needles implanted for the radiation therapy, patients with 11 needles or less showed a significantly higher incidence of Grade 2-4 acute GU toxicity compared with those with 12 needles or more (p < 0.05).
It was concluded that HDR brachytherapy combined with hypofractionated EBRT is feasible for localized prostate cancer when considered from the viewpoint of acute toxicity. Increase in the fraction dose or reduction in the number of fractions in HDR brachytherapy did not affect the severity of acute GU toxicity, and the volume of urethra receiving an equal or lower radiation dose than the prescribed dose was more closely associated with the grade severity of acute GU toxicity than that receiving a higher than the prescribed dose.
International Journal of Radiation OncologyBiologyPhysics 10/2005; 63(2):463-71. · 4.52 Impact Factor