Long-term results of concurrent chemoradiotherapy with daily-low-dose continuous infusion of 5-fluorouracil and cisplatin (LDFP) for Stage I-II esophageal carcinoma.

We investigated long-term treatment outcomes and the feasibility of chemoradiotherapy consisting of daily-low-dose 5-fluorouracil and cisplatin (LDFP) chemotherapy plus radiotherapy for Stage I-II squamous cell esophageal cancer. Treatment records from the 2000 through 2008 period were reviewed retrospectively. Fractionated radiotherapy was performed with a total dose of 60 Gy delivered in 2 Gy per fraction. LDFP chemotherapy, as continuous infusion of 200 mg/m2 5-fluorouracil combined with one hour infusion of 4 mg/m2 cisplatin, was administered on the same days as radiotherapy. Survival was calculated by the Kaplan-Meier method. Survival, responses, failure patterns, and toxicities were evaluated. Seventy-six (47 stage I and 29 stage II) patients were analyzed with a median follow-up of 93.6 months. The 8-year overall survival (OS), progression-free survival (PFS) and cause-specific survival (CSS) rates were 63.4%, 49.8%, and 76.7%, respectively. The 8-year OS, PFS, and CSS for stage I and stage II patients were 71.0%/56.1%/82.9% and 45.2%/40.2%/66.6%, respectively. Sixty-eight patients (89.5%) completed the treatment regimen. A complete response (CR) was achieved in 68 patients (89.5%). Twenty-five patients (36.8%) experienced recurrence after CR. The failure patterns were (overlap included): local failure (n = 12), nodal metastasis (n = 12), distant metastasis (n = 3), details unknown (n = 2). Salvage therapy was performed for local failure; endoscopic therapy (n = 7) or surgery (n = 2). Six patients remain alive without relapse after salvage endoscopic therapy. Major Grade 3 or higher acute adverse events were leukopenia (22%), anorexia (17%), and esophagitis (11%). Major late toxicities (Grade 3 or 4) involved pericardial effusion (12%), pleural effusion (4%), and esophageal stenosis (3%). Chemoradiotherapy with LDFP provided favorable long-term survival with acceptable toxicity for Stage I-II squamous cell esophageal cancer. The tumor response was excellent, but close endoscopic follow-up is essential for detecting and treating local recurrence.

Enhancement of radiosensitivity by a unique novel NF-κB inhibitor, DHMEQ, in prostate cancer.

BACKGROUND: Inducible activation of nuclear factor (NF)-κB is one of the principal mechanisms through which resistant prostate cancer cells are protected from radiotherapy. We hypothesised that inactivation of inducible NF-κB with a novel NF-κB inhibitor, DHMEQ, would increase the therapeutic effects of radiotherapy. METHODS: PC-3 and LNCaP cells were exposed to irradiation and/or DHMEQ. Cell viability, cell cycle analysis, western blotting assay, and NF-κB activity were measured. The antitumour effect of irradiation combined with DHMEQ in vivo was also assessed. RESULTS: The combination of DHMEQ with irradiation resulted in cell growth inhibition and G2/M arrest relative to treatment with irradiation alone. Inducible NF-κB activity by irradiation was inhibited by DHMEQ treatment. The expression of p53 and p21 in LNCaP, and of 14-3-3σ in PC-3 cells, was increased in the combination treatment. In the in vivo study, 64 days after the start of treatment, tumour size was 85.1%, 77.1%, and 64.7% smaller in the combination treatment group than that of the untreated control, DHMEQ-treated alone, and irradiation alone groups, respectively. CONCLUSION: Blockade of NF-κB activity induced by radiation with DHMEQ could overcome radio-resistant responses and may become a new therapeutic modality for treating prostate cancer.

Comparison of clinical, tumour-related and dosimetric factors in grade 0-1, grade 2 and grade 3 radiation pneumonitis after stereotactic body radiotherapy for lung tumours.

OBJECTIVE: The aim of this study was to investigate significant clinical, tumour-related and dosimetric factors among patients with grade 0-1, grade 2 and grade 3 radiation pneumonitis (RP) after stereotactic body radiotherapy (SBRT) for lung tumours. METHODS: Patients (n=128) with a total of 133 lung tumours treated with SBRT of 50 Gy in 5 fractions were analysed. RP was graded according to the Common Terminology Criteria for Adverse Events v.3.0. Significant factors were identified by univariate and multivariate analyses. Threshold dose-volume histograms (DVHs) were constructed to identify the incidence of RP. RESULTS: The median follow-up period was 12 months (range, 6-45 months). In univariate analyses, gender, operability, forced expiratory volume in 1 s (FEV1), internal target volume, lung volumes treated with doses >5-30 Gy (V5-30) and mean lung dose were significant factors differentiating between grade 0-1 and grade 2 RP, and V15-30 were significant factors differentiating between grade 2 and grade 3. However, no factors were significant between grade 0-1 and grade 3 RP. Multivariate analysis showed that female gender, high FEV1 and high V15 were significant factors differentiating between grade 0-1 and grade 2 RP. Threshold DVH curves were created based on ≤5% and ≤15% risk of grade 2 RP among patients with grade 0-2 RP. CONCLUSIONS: Grade 0-2 RP was dose-volume dependent, and female gender and high FEV1 were significant predictive clinical factors for grade 2 RP among patients with grade 0-2 RP. However, incidences of V15-30 in grade 3 RP were significantly lower than those in grade 2 RP, and no significant clinical or tumour-related factors were found. Further studies are needed to identify the mechanism underlying the development of grade 3 RP after SBRT for lung tumours.

CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function.

This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC.

Non-sentinel lymph node status and prognosis of breast cancer patients with micrometastatic sentinel lymph nodes.

BACKGROUND: The prognostic significance of sentinel lymph node (SLN) micrometastases and the need for axillary lymph node dissection (ALND) on patients with micrometastases in SLNs remain controversial. METHODS: A prospective database of 657 breast cancer patients who underwent SLN biopsy (SLNB) was analyzed. SLNs were detected using a combined method of isosulfan blue dye and small-sized technetium-99m-labeled tin colloid. RESULTS: Micrometastases in SLNs were found in 50 (7.6%) of 657 patients. Twenty-nine (58.0%) of 50 patients with micrometastatic SLNs underwent ALND and no further metastases were found in non-sentinel lymph nodes. Among 21 patients (42.0%) with micrometastatic SLNs who decided to forego ALND, no axillary lymph node recurrence has been observed during a median follow-up time of 47 months. There is no significant difference in recurrence-free survival between the patients with micrometastatic and negative SLNs (p = 0.90). CONCLUSIONS: These data suggest that it may not be necessary to perform ALND on patients with micrometastases in SLNs and that the presence of micrometastases in SLNs may not be associated with prognosis.

Superiority of radioisotope over blue dye for sentinel lymph node detection in breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly performed using radioisotopes and/or blue dye. However, it is still undefined which reagent is more suitable for identifying sentinel lymph nodes (SLN). PATIENTS AND METHODS: A consecutive series of 640 breast cancer patients who had undergone SLNB at the Keio University Hospital from 2001 to 2006 was analyzed. The SLN was identified by a combination of technetium-99m tin colloid and isosulfan blue dye. The correlation between clinicopathological factors and the distribution of radioisotopes and blue dye was analyzed. The single metastatic lymph node revealed by axillary lymph node dissection (ALND) is the 'true SLN', and the distribution of radioisotopes and blue dye to the 'true SLN' was also analyzed. RESULTS: Blue-dye- and radioisotope-positive SLN were identified in 79.6 and 94.7% of the patients, respectively. Taken together, SLN were identified in 625 patients (97.7%) by radioisotope and/or blue dye. No significant correlation was observed between clinicopathological features and the distribution of the reagents. ALND found 73 patients with single lymph node metastasis, and 73 'true SLN' were identified by blue dye in 65.7% (48/73), and by radioisotope in 95.9% (70/73) of the cases. CONCLUSION: These data suggest that radioisotopes are superior to blue dye in detecting SLN in breast cancer.

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation.

This study aimed to retrospectively evaluate the incidence of kerato-conjunctivitis in patients receiving TBI followed by high-dose cytarabine, and to clarify how effectively topical corticosteroid eye drops prevent kerato-conjunctivitis in these patients. Fifty-three patients who received cytarabine at a dose of 3 g/m2 every 12 h for 4 days after receiving TBI (12 Gy) as a conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated. For the prophylaxis of kerato-conjunctivitis, all patients received betamethasone sodium phosphate eye drops every 6 h, starting 1 day before the first dose of cytarabine and continuing until 1 day after the last dose of cytarabine or the complete resolution of ocular symptoms. For grading of kerato-conjuncitivitis, the National Cancer Institute-Common Toxicity Criteria were used. Among the 53 patients, the grades of kerato-conjunctivitis were grade 0 in 13 patients, grade 1 in 6 patients (11.3%), grade 2 in 10 patients (18.9%) and grade 3 in 25 patients (47.2%). These results strongly suggest that topical corticosteroid eye drops could not effectively prevent the development of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI. Further investigation into a more effective prophylaxis for cytarabine-induced kerato-conjunctivitis in this setting is required.

Adjuvant pelvic irradiation in patients with pathologic T2b carcinoma of the uterine cervix.

Patients with cervical cancer are subject to postoperative adjuvant therapy if the histopathologic examination reveals parametrial involvement. This study evaluated the patterns of failure in patients with pathologic parametrial invasion (pT2b) treated with adjuvant pelvic irradiation. Between April 1985 and March 1997, 45 patients with pT2b cervical cancer were treated with postoperative pelvic irradiation. The median age was 52 years. Preoperative clinical stages were stage Ib in 8 patients, IIa in 4, and IIb in 33. Twenty-three patients had lymph node metastasis. The median total dose of whole pelvic radiation therapy was 50 Gy. Occurrence of pelvic failure or distant metastasis according to the nodal status was examined. None of the 22 patients without lymph node metastasis developed distant metastasis. Among the 23 node-positive patients, 6 developed distant metastasis as an initial failure site. The 5-year overall survival of the entire group was 78%. The actuarial distant metastasis-free rates at 5 years were 73% and 100% for those with and without pelvic lymph node metastasis, respectively (P = 0.016). Results support previous evidence for chemoradiation in patients with pelvic lymph node metastasis. However, it appears that the role of systemic chemotherapy for node-negative pT2b patients is yet to be established.

Clinical role of Tc-99m-MIBI scintigraphy in non-Hodgkin's lymphoma.

This study was designed to investigate the relationship between Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy and outcome of treatment in patients with non-Hodgkin's lymphoma (NHL). Forty-five patients with NHL were studied with Tc-99m-MIBI before any treatment. Images of the lesions were obtained at 20 min and 2 h after radionuclide administration. Visual semi-quantitative interpretation was performed for Tc-99m-MIBI (grade 0-4) scintigraphy. Patients underwent 3-5 cycles of CHOP chemotherapy with/without involved field radiotherapy for large tumors. Their responses to treatment were evaluated at the end of chemotherapy and during the follow-up period. Forty of 45 patients (89%) showed abnormal uptake of Tc-99m-MIBI. There was no correlation between intensity of MIBI accumulation and response to chemotherapy. However, patients with negative or decreased MIBI activity 2 h after radionuclide administration showed worse response to chemotherapy compared to those with continued MIBI activity. MIBI activity could not predict the development of relapse in the follow-up study. In this study, the number of patients was small and we could not reach definite conclusions. However, we think that MIBI scintigraphy is not valuable for predicting the chemotherapy outcome in patients with NHL.

Breast-conserving therapy for ductal carcinoma in situ.

This retrospective analysis evaluates the treatment results and prognostic factors of 114 patients with ductal carcinoma in situ (DCIS) undergoing breast conserving therapy (BCT) at Keio University Hospital Department of Radiology, between 1988 and 1997. A total of 132 patients with DCIS of the breast came to our hospital between 1988 and 1997, and 114 cases were suitable candidates for BCT. All of the patients were female and ranged in age from 26 to 81 years (median 46). Ninety-one patients were premenopausal, and 23 were postmenopausal. Median clinical tumor size was 2.0 cm (0-8.0 cm). Postoperatively 48 cases received 50 Gy/25 fractions of external irradiation to the whole breast via tangential ports. The follow-up period after treatment ranged from 11 to 162 months (median 46.7). The local relapse-free rate and overall survival rate of the 114 patients were 89.5% and 100%, respectively. Local failure and regional nodal failure occurred in 12 and 1 patient, respectively. Radiotherapy was a significant risk factor for local failure (p=0.05). No postmenopausal patients developed local failure, but the difference did not reach statistical significance (p=0.103). The 12 recurrent cases underwent additional surgery and all remain alive without recurrence, to date, i.e., at least 16 months. Breast-conserving surgery plus irradiation is appropriate treatment for DCIS patients.

Effect of combined treatment with radiation and low dose etoposide on cell survival.

BACKGROUND: To improve the radiotherapy results, we evaluated etoposide as an effective radiosensitizer by using cultured cell-lines. MATERIALS AND METHODS: Four cell lines having different doubling times (DT) were used: V79 (Chinese hamster fibroblasts, DT = 9 hours), (1), T24 (human bladder cancer, DT = 19 hours) (2), MDA-MB231 (human breast cancer, DT = 25-30 hours) (3) and RMG1 (human ovarian cancer, DT = 50 hours) (4). Cell survival was determined by colony assay and cell cycle analysis was performed by flow-cytometry. RESULTS: The survival curves showed RMG1 to be the most radiosensitive, followed by MDA-MB231, T24, and V79. V79 was most chemosensitive to etoposide, followed by T24, MDA-MB231 and RMG1. Neither 24-hours exposure to etoposide (< or = 0.05 microgram/ml) or 0.5-h exposure (< or = 1.0 microgram/ml) had any cell killing effect on any of the cell lines used. When the cells were irradiated after exposure to 1 microgram/ml of etoposide for 0.5 hours, no radiosensitization was observed in any of the cell lines except V79. Enhanced radiosensitivity was observed in V79 and T24 cells (which have a relatively short DT) when they were incubated with 0.05 microgram/ml etoposide for 24 hours but no enhanced effect was seen in MDA-MB231 or RMG1 cells (which have a relatively long DT). CONCLUSION: It is suggested that a combination of radiation and etoposide may be useful in the treatment of rapidly growing cancer.

Cell killing and mutation induction by heavy ion beams.

Carbon beam radiotherapy for cancer patients was initiated in Japan in June 1994. This study attempts to clarify the radiobiological effects of heavy ion beams. In this study, human cancer cell lines (RMG-1, MDA-MB231) and V79 cells were used. The cell killing was determined by colony forming assay, and mutation induction was determined by counting the number of 6-thioguanine resistant colonies (hprt locus mutation assay). The cell lines were irradiated with carbon (20 or 80 keV/microm) or neon beams (80 keV/microm). Carbon ions with a higher LET value (80 keV/microm) had an enhanced cytotoxic effect compared to those with a lower LET value (20 keV/microm). Carbon beams produced a slightly stronger cytotoxic effect than neon beams when irradiated at the same LET level (80 keV/microm), but the difference was not remarkable. The mutant fraction was significantly higher in all cell lines when they were irradiated with heavy ion beams, compared to the results for X-ray irradiation. The mutant fraction increased when the LET of the carbon beams increased. At equivalent LET values, the mutant fraction was lower for neon beams than for carbon beams. Fractionation of carbon beam irradiation had no effect on survival, but reduced the mutant fraction. Neon beams might be more appropriate for heavy ion therapy, especially when higher doses are being used. In addition, the fractionation of heavy ion beam administration might be appropriate for reducing the mutant fraction.

Indications of stereotactic irradiation for brain lesions.

Stereotactic radiosurgery (SRS: single-fraction stereotactic irradiation) was originally developed to treat benign lesions in the brain, and has been adopted for the treatment of small primary or metastatic brain tumours. It has recently been recommended that stereotactic radiotherapy (SRT: fractionated stereotactic irradiation) be applied to the treatment of brain tumours; however, it requires much more time and work than SRS, and sufficient radiobiological evaluations of these techniques have never been carried out. Biologically effective doses were calculated to determine the indications for SRS and SRT, and to decide on an effective SRT schedule, incorporating the factors of 'repair' and 'cell proliferation'. The results suggest that SRS would be recommended for arteriovenous malformations and benign tumours that have distinct margins separating them from surrounding normal tissue and SRT would be recommended for benign or malignant brain tumours without clearly defined boundaries. The recommended SRT schedules would be 7 Gy x 7 fractions every other day for malignant tumours and 3.5 Gy x 12 fractions every other day for benign tumours. However, clinically, these schedules should be modified according to many other factors in individual cases.

Postoperative radiation therapy for pituitary adenoma.

BACKGROUND: We evaluated the efficacy of postoperative radiation therapy (RT), prognostic factors for local control probability, dose response relationship and treatment sequelae in 75 patients with pituitary adenoma. MATERIALS AND METHODS: A total dose of 48-60 Gy (median: 50 Gy) was delivered with a conventional fractionation schedule after surgery. Of 75 patients, 55 (73%) were followed for more than 5 years and 27 (36%) were followed for more than 10 years with a median of 95 months. RESULTS: Five- and 10-year local control probabilities were 87.1% and 85.0%, respectively. Univariate analysis revealed that age (p = 0.007), tumor volume smaller than 30 cm3 (p = 0.018) and the absence of prolactin secretion (p = 0.003) were significantly favorable prognostic factors for local control probability. After multivariate analysis combining these 3 factors, tumor volume smaller than 30 cm3 (p = 0.017) and age (p = 0.039) were statistically significant. Patients with prolactinoma greater than 30 cm3 showed particularly poor local control rates. No significant improvement of the local control rate was detected with increasing total irradiation doses between 48 and 60 Gy (p = 0.29). The most common side effect was hypopituitarism, and there were no severe sequelae such as optic neuropathy or brain necrosis. CONCLUSION: Except with prolactinoma, the dose of postoperative RT for pituitary adenoma should not exceed 50 Gy. Large prolactinoma, however, was very difficult to control with the irradiation doses between 50 and 60 Gy, and would be good candidates for stereotactic radiosurgery or stereotactic radiation therapy.

Low-dose induction radiotherapy for stomach conservation in patients with massive gastric lymphoma.

Low-dose induction radiotherapy was performed in 4 patients with massive gastric lymphoma in order to treat the disease without gastrectomy. Following the radiotherapy, gastric lesions had shrunk considerably without any complications. Standard chemotherapy and/or radiotherapy could then be performed safely, and stomach conservation could be achieved in all 4 patients.

Postoperative radiation therapy for stage IB-IIB carcinoma of the cervix with poor prognostic factors.

BACKGROUND: To investigate failure pattern and to evaluate the prognostic impact of lymph node metastasis in patients with cervical cancer treated with postoperative adjuvant pelvic irradiation. MATERIALS AND METHODS: Ninety-eight patients with FIGO IB to IIB cervical cancer were treated with radical hysterectomy, bilateral pelvic lymphadenectomy and postoperative radiation therapy. All the patients had at least one of the following pathologic risk factors for pelvic recurrence; 1) positive margins, 2) positive pelvic lymph nodes other than common iliac node, 3) deep stromal invasion more than 50% or parametrial invasion. RESULTS: The 5-year overall survival (OAS) rate for the entire patient group was 82%. Causes of the first failure were pelvic recurrence in 5 cases and distant metastasis in 15 cases. Fifteen of the 47 patients with positive pelvic lymph nodes developed distant metastasis, whereas distant metastasis was noted in only 1 of 51 patients without lymph node metastasis. The 5-year OAS rates for patients with and without pelvic lymph node metastasis were 76% and 89%, respectively (p = 0.018). CONCLUSION: Despite receiving postoperative pelvic irradiation, apparently lower survival was observed for node positive patients.

Structures of five components of the actinomycin Z complex from Streptomyces fradiae, two of which contain 4-chlorothreonine.

Structure elucidation of five components of the actinomycin Z complex (Z(1)-Z(5)) isolated from Streptomyces fradiae is described. The components were separated by Si gel column chromatography and TLC/PLC and analyzed by ESIMS, FABMS, LC-MS of derivatized hydrolysates, and 2D NMR techniques. This permitted determination of the complete structures of actinomycins Z(1)-Z(5). In Z(3) and Z(5,) site 1 of the beta-depsipeptide is occupied by the rare 4-chloro-L-threonine, an amino acid not previously found in an actinomycin. The structural variants of the actinomycin Z complex have the molecular architecture typical of other actinomycins but possess greater structural diversity resulting from the presence of several highly unusual amino acids. Actinomycins Z(3) and Z(5,) but not Z(1), were more potent than actinomycin D in cytotoxicity assays against three tumor cell lines.

The modified tangential irradiation technique for breast cancer: how to cover the entire axillary region.

PURPOSE: The two-portal tangential irradiation technique has usually been applied to breast cancer patients after breast-conserving surgery (1, 2) and is expected to irradiate the axillary lymph node region to some extent (3). We investigated the range of the axillary region covered by this technique and tried to devise an optimal irradiation technique (modified tangential irradiation) that would cover the axillary lymph node region properly. METHODS AND MATERIALS: We checked the status of the surgical clips left at axillary lymph node sites by reviewing the simulator films and planning CT scans of 63 patients who underwent axillary dissection of level I, I-II, or I-III lymph nodes. Then we created the modified tangential irradiation technique and applied this technique to 16 patients and checked the irradiation volume by CT scans. RESULTS: We found that all of the surgical clips on lateral-view simulator films were on the ventral side of the dorsal edge line of the humeral head. All but one clip were on the caudal side of the caudal edge line of the humeral head. Accordingly, it is possible to irradiate almost all axillary lymph node regions by setting the dorsal edge of the irradiation field on lateral-view simulator films at the dorsal edge of the humeral head and the cranial edge at the caudal edge of the humeral head. CONCLUSIONS: All breast tissue and the entire axillary lymph node region can be covered by the modified tangential irradiation technique without increasing the lung volume irradiated.

Radiotherapy for large hepatocellular carcinoma combined with transcatheter arterial embolization and percutaneous ethanol injection therapy.

This study was performed to determine the effect of radiotherapy (RT) combined with transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) on large HCC. Between 1988 and 1996, 102 patients with unresectable, biopsy proven HCC underwent uniform pretreatment assessment followed by TAE and PEI. Of the 102 patients, 68 (67%) had more than 2 lesions in the liver, and the largest tumor sizes in each patient ranged from 3 to 8 cm in diameter. Immediately after TAE and PEI, external beam RT (36 to 70 Gy) was administered to the largest tumors only in 44 patients. The cause-specific 5-year survival rate for all patients was 39.9%. The 3-year survival rate of the RT group was better than that of the no RT group (81.1% vs. 54.6%). The cumulative local control rates of the largest treated tumors were 53.2% in the RT group and 32.7% in the no RT, respectively (p=0.006). When the survival rate was compared between patients with and without local control in the RT group, that of patients with local control was significantly better than that with local recurrences (p=0.048). No deaths or major treatment related complications occurred. RT combined with TAE and PEI did not clearly show improvement of the survival, however, it effectively controlled large HCC, and demonstrated minimal toxicity. This treatment may represent therapeutic option for some patients with unresectable large HCC.

Late retinal complications of radiation therapy for nasal and paranasal malignancies: relationship between irradiated-dose area and severity.

PURPOSE: Radiation-induced cataract, once a notorious ocular complication of radiation therapy, is no longer considered a severe complication, because visual acuity can be restored by surgical treatment without significant complications. Late retinal complications of retinopathy and glaucoma, for which there is no effective method of treatment, have become serious complications of radiotherapy of the head and neck. We retrospectively investigated the risk of late retinal complications of radiotherapy for nasal and paranasal malignancies according to the radiation dose and area of the retina irradiated. METHODS AND MATERIALS: Between October 1982 and May 1996, 43 eyes of 25 patients were exposed to fractionated external-beam irradiation for treatment of advanced nasal and paranasal cancer. None of the patients had tumor invasion into the eyes. The patients were followed ophthalmologically for a minimum of 2 years (range 2.0-11, mean 4.5, median 3.3). The radiation dose and area of the retina irradiated were estimated from the dose distribution figures calculated using the portal films and CT scan. RESULTS: Major late adverse effects of radiotherapy were observed in the retina in 9 of 43 eyes (in 8/25 patients). Radiation retinopathy was observed in 7 eyes, and the cumulative incidence was 25%. The median interval before the onset of symptoms attributable to retinopathy was 32 months (range 16-60). Neovascular glaucoma developed in 3 of the 43 eyes, with a cumulative incidence of 7%. The median period to the onset of symptoms attributable to glaucoma was 22 months (range 16-26). Obstruction of the central retinal artery was observed in 1 eye. The irradiation doses to the retinas that developed late complications ranged between 54-75 Gy (mean 61, median 61). No patients who received less than 50 Gy developed retinal complications. The retina in 21 eyes was exposed to a dose of 50 Gy or more. In 13 of the 21 eyes, 60% or more of the retina was irradiated, and 8 of the eyes (62%) in this group (> or = 50 Gy, > or = 60%) developed severe retinal complications, whereas such complications only developed in 1 of the 8 eyes (13%) in the other group (> or = 50 Gy, > or = 60%). The results suggest that the radiation dose and area irradiated are the most important factors in the development of severe complications. CONCLUSION: Radiation-induced retinopathy and glaucoma are more serious late complications than cataracts, which are easily treated with surgery. We investigated the risk of late retinal complications of radiotherapy, and our findings suggested that the radiation dose and area irradiated are the most important factors in the development of severe complications. We recommend that the radiation dose and area of the retina irradiated be minimized in patients at risk of eye complications, and the patients should be closely followed by periodic ophthalmologic testing after treatment.