Treatment-interval associated effect of irradiation on locoregionally-relapsed ovarian cancer.

Recurrent ovarian cancer following chemotherapy is usually incurable, particularly when the tumor acquires a drug resistance. The present study aimed to define the effect of irradiation on locoregional recurrences and the impact of the factors on the efficacy. The study retrospectively reviewed the clinical records of 61 patients with epithelial ovarian cancer who received irradiation following repeated chemotherapy between 1997 and 2006. A positive-irradiation response was designated as complete response, partial response, minor response or no change (NC). Due to the possible synergistic effect of chemotherapy and irradiation, and the cross-resistance to chemotherapeutic drugs and radiation, the focus was on the treatment break between chemotherapy and radiation, and patients were classified into 3 categories: Category I, ≤1 month; II, 1-6 months; and III, >6 months. The effect of irradiation was analyzed in association with histology, treatment break, recurrent site, irradiation dose and chemosensitivity. The post-irradiation survival time was analyzed by the irradiation response and treatment category. The median biological-effective dose was 60.0 Gy (range, 15.6-72.0 Gy). The sites irradiated included nodal recurrence (36), abdominal (six) and pelvic cavity (five cases). Histologically, serous adenocarcinoma was the most common type of the disease (23 cases) compared to mucinous (four), endometrioid (three), and clear-cell types (six cases). The median survival times were 4.5 months in the radiation responders (13 cases) and 15.3 months in the non-responders (37) (P=0.004). The positive-irradiation response was significantly associated with the treatment break (P=0.026) and chemosensitivity (P=0.007). In conclusion, irradiation for recurrent ovarian cancer produced an improved survival benefit when applied to chemoresponsive, locoregional-recurrent tumors immediately following chemotherapy.

Pulmonary metastases after low-dose-rate brachytherapy for localized prostate cancer.

PURPOSE: To analyze unusual events and focus discussion on pulmonary metastasis in particular after low-dose-rate brachytherapy (LDR-BT) for prostate cancer (PCa). MATERIALS AND METHODS: A total of 616 consecutive patients who had undergone LDR-BT for clinically localized PCa at Jikei University Hospital between October 2003 and April 2010 were enrolled in this study. Follow-up information was summarized, and patterns of biochemical recurrence and clinical outcome were investigated. RESULTS: Disease risk was stratified as low-risk in 231 patients, intermediate-risk in 365, and high-risk in 20, respectively. Of these patients, 269 (43.7%) had received hormonal therapy (HT) in combination with LDR-BT, and 80 (13.0%) had received external beam radiotherapy (EBRT). Average dosimetric parameter values with and without EBRT were 95.3% and 94.2% for V100, 132.8 Gy and 164.2 Gy for D90, and 180.6 Gy2 and 173.7 Gy2 for the biologically effective dose. Biochemical recurrence was noted in 14 patients (6.1%) in the low-risk group, 25 patients (6.8%) in the intermediate-risk group, and 6 patients (30.0%) in the high-risk group, respectively. In these cases of biochemical recurrence, 9 (64.3%), 13 (52.0%), and 4 patients (66.7%) in each respective risk group showed signs of clinical recurrence. Five patients (19.2%) with clinical recurrence developed pulmonary metastases, of which 4 were isolated lesions. All tumors responded favorably to subsequent HT. CONCLUSIONS: LDR-BT for biologically aggressive PCa may be linked to possible pulmonary metastasis owing to tumor dissemination during seed implantation. This information is important in planning adequate treatment for these patients.

Analysis of prognostic factors in localized high-risk prostate cancer patients treated with HDR brachytherapy, hypofractionated 3D-CRT and neoadjuvant/adjuvant androgen deprivation therapy (trimodality therapy).

Trimodality therapy consisting of high dose rate (HDR) brachytherapy combined with external beam radiation therapy (EBRT), neoadjuvant hormonal therapy (NHT) and adjuvant hormonal therapy (AHT) has been used to treat localized high-risk prostate cancer. In this study, an analysis of patients receiving the trimodality therapy was performed to identify prognostic factors of biochemical relapse-free survival (bRFS). Between May 2005 and November 2008, 123 high-risk prostate cancer patients (D'Amico classification) were treated with NHT prior to HDR brachytherapy combined with hypofractionated EBRT. Among these patients, 121 had completed AHT. The patients were assigned by time to be treated with a low-dose or high-dose arm of HDR brachytherapy with subsequent hypofractionated 3D conformal radiation therapy (3D-CRT). Multivariate analysis was used to determine prognostic factors for bRFS. With a median follow-up of 60 months, the 5-year bRFS for all patients was 84.3% (high-dose arm, 92.9%; low-dose arm, 72.4%, P = 0.047). bRFS in the pre-HDR PSA ≤ 0.1 ng/ml subgroup was significantly improved compared with that in the pre-HDR PSA > 0.1 ng/ml subgroup (88.3% vs 68.2%, P = 0.034). On multivariate analysis, dose of HDR (P = 0.045, HR = 0.25, 95% CI = 0.038-0.97) and pre-HDR PSA level (P = 0.02 HR = 3.2, 95% CI = 1.18-10.16) were significant prognostic factors predicting bRFS. In high-risk prostate cancer patients treated with the trimodality therapy, the dose of HDR and pre-HDR PSA were significant prognostic factors. The pre-HDR PSA ≤ 0.1 subgroup had significantly improved bRFS. Further studies are needed to confirm the relevance of pre-HDR PSA in trimodality therapy.

Possible clinical cure of metastatic breast cancer: lessons from our 30-year experience with oligometastatic breast cancer patients and literature review.

BACKGROUND: Metastatic breast cancer (MBC) is generally incurable. However, 10-20-year relapse-free survival of MBC is approximately 2%, implying that at least a small subset of MBC patients achieve prolonged survival. We therefore analyzed long-term outcome in a particular subset, i.e., oligometastatic breast cancer (OMBC). METHODS: Data of OMBC subjects (N = 75) treated in our institution from April 1980 to March 2010 were retrospectively analyzed. OMBC was identified as: one or 2 organs involved with metastatic lesions (excluding the primary lesion resectable by surgery), fewer than 5 lesions per metastasized organ, and lesion diameter less than 5 cm. Patients were generally treated with systemic chemotherapy first, and those who achieved complete response (CR) or partial response (PR) were further treated, if applicable, with local therapy (surgical or radiation therapy) to maintain CR or to induce no evidence of clinical disease (NED), with additional systemic therapy. RESULTS: Median follow-up duration was 103 (6-329) months. Single or 2 organs were involved in, respectively, 44 (59%) and 31 (41%) cases with metastatic lesions, 48% of which were visceral. In cases where effects of systemic therapy, possibly in combination with other treatments, were evaluated (N = 68), CR or PR was achieved in 33 (48.5%) or 32 (47.1%), respectively, with overall response rate (ORR: CR + PR) of 95.6% (N = 65). In cases receiving multidisciplinary treatment (N = 75), CR or NED (CR/NED), or PR was induced in 48 (64.0%) or 23 (30.7%) cases, respectively, with ORR (CR/NED + PR) of 94.7% (N = 71). CR rates (60.5%) with systemic therapy and CR/NED rates (79.5%) with multidisciplinary treatment were significantly better in subjects with a single involved organ than in those with two involved organs (P = 0.047 and 0.002, systemic only or multidisciplinary treatments, respectively). Medians estimated by Kaplan-Meier method were: overall survival (OS) of 185.0 months and relapse-free interval (RFI) of 48.0 months. Estimated outcomes were: OS rates (OSR) of 59.2% at 10 years and 34.1% at 20 years, and relapse-free rates (RFR) of 27.4% at 10 years and 20 years. No disease progression was observed after 101.0 months as RFR. Cases with single organ involvement (N = 44) showed significantly better outcomes (OSR of 73% at 10 years and 52% at 20 years, RFR of 42% at 10 years and 20 years). Those who received local therapies (N = 35) also showed better prognosis: OSR of 82% at 10 years and 53% at 20 years, RFR of 38% at 10 years and 20 years. Three cases (4%) survived for their lifetime without relapse after achieving CR or NED, our definition of clinical cure. Multivariate analysis revealed factors favoring better prognosis as: none for OS, and single organ involvement with metastasis, administration of local treatment, and shorter disease-free interval (DFI) (P = 0.030, 0.039, and 0.042, respectively) for RFR. Outcomes in OMBC in literature were OSR of 35-73% at 10 years and 26-52% at 20 years, and RFR of 27-42% at 10 years and 26-42% at 20 years. CONCLUSIONS: The present analyses clearly indicate that OMBC is a distinct subgroup with long-term prognosis superior to MBC, with reasonable provability for clinical cure. Further prospective studies to better characterize OMBC are warranted to improve prognosis in MBC.

Radiographic and CT features of radiation-induced organizing pneumonia syndrome after breast-conserving therapy.

PURPOSE: To investigate radiographic and computed tomography features of radiation-induced organizing pneumonia syndrome after breast-conserving surgery. MATERIALS AND METHODS: The appearances and distribution of lung parenchymal abnormalities were retrospectively analyzed on chest radiographs (n = 12) and computed tomography scan images (n = 10) of 12 women (range 37-78 years, mean 55.8 years) with radiation-induced organizing pneumonia syndrome after breast-conserving surgery. RESULTS: The principal radiographic feature was an airspace filling pattern in all patients that involved the middle and lower lung zones in 10 of the 12 patients. Multi-focal lesions manifesting airspace consolidation surrounded by ground-glass opacities were the predominant CT finding in all 10 of these patients. The main lesion was predominantly located in the lung periphery in nine patients and contiguously extended to the central portion of the lung in seven patients. Frequent ancillary findings were airway dilation within the consolidation and lobar volume loss in nine and eight patients, respectively. All had solitary (6/10) or multifocal (4/10) distant lung opacities, mostly consistent with the finding of ground-glass opacities (9/10). Migration of the lung disease was observed in ten patients on subsequent radiographs. CONCLUSION: The cardinal radiologic feature of this syndrome is airspace consolidation surrounded by ground-glass opacification with airway dilation and volume loss, involving primarily the irradiated, subpleural area, along with distant opacities.

Intravitreal bevacizumab for delayed radiation maculopathy and papillopathy after irradiation for maxillary sinus cancer.

BACKGROUND: The evaluation of intravitreal bevacizumab treatment for delayed radiation maculopathy and papillopathy after irradiation for maxillary sinus cancer. CASE REPORT: A patient with radiation maculopathy and papillopathy was treated with intravitreal bevacizumab (1.25 mg). Main outcome measures included fundus photography, angiography, and optical coherence tomography (OCT). Two weeks after intravitreal bevacizumab, visual acuity improved from 0.4 to 1.2. Fundus examination revealed decreased disc swelling, peripapillary hemorrhage, and macular edema. OCT demonstrated complete resolution of serous retinal detachment. At the 12-month follow-up, there was no exudation recurrence. No ocular or systemic side effects were observed. CONCLUSION: Intravitreal bevacizumab can be used to treat radiation maculopathy and papillopathy. Antivascular endothelial growth factor therapy may decrease tissue injury associated with radiation vasculopathy.

Evaluation of rectal bleeding factors associated with prostate brachytherapy.

PURPOSE: To analyze rectal bleeding prognostic factors associated with prostate brachytherapy (PB) or in combination with external-beam radiation therapy (EBRT) and to examine dosimetric indications associated with rectal bleeding. MATERIALS AND METHODS: The study included 296 patients followed up for >36 months (median, 48 months). PB was performed alone in 252 patients and in combination with EBRT in 44 patients. PB combined with EBRT is indicated for patients with a Gleason score >6. The prescribed dose was 144 Gy for monotherapy and 110 Gy for PB + EBRT (44-46 Gy). RESULTS: Although 9.1% who received monotherapy had 2.3% grade 2 rectal bleeding, 36.3% who received combined therapy had 15.9% grade 2 rectal bleeding. Combined therapy was associated with higher incidence of rectal bleeding (P = 0.0049) and higher percentage of grade 2 bleeding (P = 0.0005). Multivariate analysis revealed that R-150 was the only significant factor for rectal bleeding, and modified Radiation Therapy Oncology Group (RTOG) grade in monotherapy and biologically equivalent dose (BED) were significant for combined therapy. Moreover, grade 2 rectal bleeding increased significantly at D90 > 130 Gy. CONCLUSION: Although R-150 was the significant prognostic factor for rectal bleeding and modified RTOG rectal toxicity grade, BED was the significant prognostic factor for modified RTOG rectal toxicity grade.

[Changes of edema associated with I-125 prostate brachytherapy].

We have been performing TRUS-guided transperineal prostate brachytherapy with I-125 for prostate-confined adenocarcinoma since October 2003. We examined prostate volume using CT scanning on Day 1, Day 15, and Day 30 in the initial 15 patients, and investigated time-dependent changes of edema associated with I-125 prostate brachytherapy. Prostate volume had increased to 173% of the average on the first day after implantation. Improvements in the swelling of the prostate showed decreases in 30% in the first 2 weeks (Days 1-15) and 12% in the second 2 weeks (Days 15-30). V100 and D 90% showed statistically significant increases of 5.5% and 8.4% in the first 2 weeks after implantation and 2.3% and 5.2% in the second 2 weeks (Days 15-30). We considered one month a suitable time at which to calculate post-planning because V100 and D 90% changed little statistically.

[Transcatheter arterial embolization of unresectable hepatocellular carcinoma: does selective treatment improve outcome?].

PURPOSE: To evaluate whether selective transcatheter arterial embolization (TAE) contributes to preservation of liver function and improves local control and survival in patients with hepatocellular carcinoma. MATERIALS AND METHODS: One hundred patients with hepatocellular carcinoma who underwent single or multiple TAE were retrospectively analyzed. The incidence of deterioration of liver function caused by TAE was compared between patients with Child class A disease and those having Child B/C disease. The correlation between extent of embolization and incidence of deterioration of liver function was analyzed. In addition, factors affecting deterioration of liver function after TAE were determined. Recurrence-free and overall survival rate were calculated using the Kaplan-Meier method. A Cox proportional hazard model was used to analyze prognostic factors affecting recurrence-free and overall survival. RESULTS: The incidence of deterioration of liver function in the Child B/C group (47%) was significantly higher than that in the Child A group (21%). Pretreatment Child-Pugh classification and extent of embolization were significant factors in the deterioration of liver function after TAE. Recurrence-free survival rates at 1, 2, and 3 years were 38%, 19%, and 8%, respectively. Overall survival rates at 1, 3, 5, and 7 years were 89%, 59%, 22%, and 22%, respectively. Findings of multivariate analyses of prognostic factors showed that tumor size and selectivity of TAE were significant for recurrence-free survival and the initial Child-Pugh classification was the most important factor for overall survival. CONCLUSION: Selective TAE improves local control and avoids damage to nontumorous liver tissue. The selective technique appears to be associated with a favorable outcome.

Long-term, irradiation-induced effects on thermoregulation in the skin after thermal stimulation.

PURPOSE: The morphological effect of radiation on the skin has been adequately analyzed, but the functional effect has received little attention. The purpose of this study was to examine the long-term effects of radiation on the skin from the viewpoint of function. MATERIALS AND METHODS: Physiological changes in the irradiated skin of patients who had undergone breast-conserving therapy for the treatment of breast cancer were examined throughout the follow-up period. Thermal stimulation was applied to both breasts, and changes in skin temperature and sweating reactivity of irradiated and non-irradiated skin were measured. RESULTS: From three weeks to the end of radiotherapy, the resting skin temperature of the irradiated region was significantly elevated, while the rate of sweating was lower. More than two years after radiotherapy, the elevated resting skin temperature of the irradiated region had returned to within the range observed for non-irradiated skin, although an abnormally high increase in skin temperature after thermal stimulation continued to be observed for more than two years after radiotherapy. At the same time, sweating after thermal stimulation continued to be suppressed. CONCLUSION: Present observations suggest that functional effects, such as the skin temperature and sweating ability of irradiated skin, persist longer than readily visible morphological changes.

Enhanced four-detector row computed tomography imaging of laryngeal and hypopharyngeal cancers.

PURPOSE: Four-detector row computed tomography (4D CT) enables imaging of the larynx and hypopharynx with high temporal resolution and rapid reformatting of coronal planes. The aim of our study was to assess the usefulness of postcontrast biphasic 4D CT in diagnosing tumor extent. METHODS: Forty-seven patients with laryngeal or hypopharyngeal cancer were investigated using 4D CT. Two radiologists retrospectively evaluated transverse and reformatted coronal images in both the early and late phases. RESULTS: Images in the late phase were superior to those in the early phase in the conspicuity of the depicted lesions. The coronal images facilitated assessment of the craniocaudal extension of tumors and obliteration of the paraglottic space. The maximal diameter of tumors tended to be larger on the coronal image than on the transverse image. CONCLUSIONS: Images in the late phase were more informative than images in the early phase to demonstrate tumor extension. Reformatted coronal imaging was useful in evaluating craniocaudal extension.