Biological Therapy ; Carcinoma, Hepatocellular ; drug therapy ; radiotherapy ; therapy ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; therapy ; Radiography, Interventional ; Ultrasonic Therapy

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. With frequent association of viral liver disease, HCC is highly complex, harboring both cancer and chronic liver disease. The tumor stage and underlying liver function are both major determinants of the treatment selection as well as prognosis in HCC patients, thus allowing no more than a 20% chance for potentially curative therapies. Radiotherapy technology has been evolved remarkably during the past decade, and radiation can be precisely delivered, thereby permitting higher doses to the tumour and reduced doses to surrounding normal tissues. There has been increasing interest in the merits of radiotherapy in HCC over the past few years, as indicated by a Pub Med search. Radiotherapy has been used as the definitive therapy with curative intent in early stage tumours. It has been used also in combination with TACE for intermediate stage tumours. In locally advanced tumours, radiotherapy has been combined with systemic agents. Despite its efficacy, radiotherapy has not yet been incorporated into the standard management guidelines of HCC. The lack of high evidence level data, especially randomized controlled trials, has posed an obstacle in including radiotherapy into the routine treatment schema of HCC. Therefore, well-designed prospective studies are strongly recommended using developing technology for radiotherapy alone or combination therapies. Also, many issues such as the optimal dose-fractionation, intra- or extrahepatic metastasis after radiotherapy, and radiation-induced hepatic dysfunction remain to be solved. In this review, current status of radiotherapy for HCC will be discussed with regard to technical consideration and combination strategy. The limitation and future perspectives will also be discussed.
Carcinoma, Hepatocellular/drug therapy/radiography/*radiotherapy ; Humans ; Liver/radiation effects ; Liver Neoplasms/drug therapy/radiography/*radiotherapy ; Neoplasm Metastasis ; Radiation Dosage ; Radiotherapy, Adjuvant/adverse effects/methods ; Treatment Outcome

Several anticancer chemotherapeutic agents (5-fluorouracil, adriamycin and cisplatinum) and desferrioxamine, an iron chelator, were tested with regard to cytotoxicity and to the combined effect on radiation induced cell killing using two human hepatoma cell lines (HepG2 and PLC/PRF/5). Survival fractions were measured by quantitative colorimetric assay (MTT assay) and dose-response curves were plotted. MTT assay could be successfully used in the assessment of radiosensitivity in addition to chemosensitivity, because a good linear relationship between optical densities and cell numbers was observed and cells approached exponential growth for the first 7 days of culture when 5 x 10(3) or less cells were inoculated per well in our study. Steepness of the final slope (D0), width of the shoulder (D0) and the extrapolation number (n) of radiation survival curves were 1061.72 rad, 226.43 rad and 1.25 respectively in HepG2 and 1091.38 rad, 268.42 rad and 1.29 respectively in PLC/PRF/5. After combining anticancer chemotherapeutic agents and desferrioxamine with radiation, the widths of the shoulders were decreased whereas sensitizer enhancement ratios were increased as the concentration of drugs increased in both cell lines. These results suggest that neither anticancer chemotherapeutic agents nor desferrioxamine enhance cell killing induced by radiation alone, but suggested the possibility that they inhibit the repair of radiation damage.
Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/*drug therapy/*radiotherapy ; Deferoxamine/*pharmacology ; Human ; Liver Neoplasms/*drug therapy/*radiotherapy ; Support, Non-U.S. Gov't ; Tumor Cells, Cultured/drug effects/radiation effects

PURPOSE: To evaluate the effectiveness of external radiation therapy and the prognostic factors, we retrospectively analyzed therapeutic results of malignant extrahepatic biliary obstruction (EHBO). METHODS AND MATERIALS: We analyzed the results of the external radiation therapy in 59 patients of inoperable malignant EHBO who had been treated with more than 10 Gy of external radiation therapy from April 1984 to December 1996. There were 21 stomach cancer (35.6%), 12 pancreas cancer (20.3%), 15 extrahepatic biliary cancer (18.6%) and 11 another cancer (18.6%). Their pathologies were confirmed in 31 patients (52.5%). They divided into 27 adenocarcinoma and 4 nonadenocarcinoma. Their chief complaints were jaundice in 47 patients (79.7%) and abdominal pain in 15 patients (49.2%). Twelve patients had slightly increased bilirubin level in liver function test without jaundice. We treated twenty four patients (40.6%) with percutaneous transhepatic biliary drainage (PTBD) and 32 patients (54%) with systemic chemotherapy (CT). We performed external radiation therapy (ERT) upto 10.8~55.8 Gy (median 37.8 Gy) with palliative aim. RESULTS: Overall median survival duration was 7.80+/-1.15 months. The response rates of jaundice were 81.8% in PTBD group and 66.7% in non-PTBD group without statistical significance. The improving rate of jaundice was not significantly different in decreased ratio of total bilirubin level. But abdominal pain was more decreased in CT group than non-CT group (P<0.05). The significant prognostic factors were high performance status (Karnofski Performance Status >70), total radiation dose more than 35 Gy and good response of pain after therapy. There were increased in bacterial cholagitis in PTBD group and gastrointestinal complications in CT group. CONCLUSION: External radiotheapy could improve jaundice and abdominal pain in malignant EHBO patients. Overall survival duration was prolonged in patients with higher performance status and patients who had been treated with more than 35 Gy of total radiation dose. In the future, we expect not only better palliative role but also the prolongation of survival of using the ERT combined with other treatment method. But to achieve certain conclusion, we need futher study consisted with many kinds of treatment methods including new technologies in RT.
Abdominal Pain ; Adenocarcinoma ; Bilirubin ; Drainage ; Drug Therapy ; Humans ; Jaundice ; Liver Function Tests ; Pancreatic Neoplasms ; Pathology ; Radiotherapy ; Retrospective Studies ; Stomach Neoplasms

PURPOSE: This study was designed to analyze the clinical characteristics of patients with immediate distant metastasis after preoperative chemoradiotherapy for locally advanced rectal cancer and to help select patients for preoperative chemoradiotherapy. METHODS: Two hundred eight patients, who underwent preoperative chemoradiotherapy for locally advanced rectal cancer, were included. Patients were excluded from the study if they had tumor types other than an adenocarcinoma, prior chemotherapy, radiotherapy, or hereditary nonpolyposis colorectal cancer. The clinicopathological characteristics of patients with distant metastasis immediately after preoperative chemoradioterapy were compared with those of patients without distant metastasis. RESULTS: Distant metastases immediately after preoperative chemoradiotherapy were identified in 15 patients (7.2%). The liver was the most common site of metastasis (8/15), followed by peritoneal seeding (4), the lung (2), bone (1), and the aortocaval lymph node (1). Age, sex, chemotherapy regimen used, and primary tumor response for patients with distant metastases were similar to those for patients without distant metastasis. In patients with immediate distant metastasis, pre-chemoradiotherapy CEA was significantly higher (11.1 vs. 7.4 ng/ml; P= 0.003). CONCLUSIONS: Immediate distant metastasis after preoperative chemoradiotherapy is associated with pre-chemoradiotherapy CEA level. A careful work-up is necessary when pre-chemoradiotherapy CEA is higher than the normal range.
Adenocarcinoma ; Chemoradiotherapy* ; Colorectal Neoplasms, Hereditary Nonpolyposis ; Drug Therapy ; Humans ; Liver ; Lung ; Lymph Nodes ; Neoplasm Metastasis* ; Radiotherapy ; Rectal Neoplasms* ; Reference Values

OBJECTIVETo investigate the time of whole brain irradiation and the prognostic factors for non-small lung cancer patients with brain metastasis.

METHODSFrom August 1996 to December 2003, 147 patients with brain metastasis from non-small cell lung cancer received whole brain irradiation. The patients were divided into two groups: with or without symptoms caused by brain metastasis, each group was then divided into two sub-groups, early whole brain irradiation group (the interval between the diagnosis of brain metastasis and the brain irradiation < or = one month) and late group ( the interval > one month ). Univariate and multivariate analysis (Cox regression) as well as Kaplan-Meier method in SPSS software package 11.5 was used to analyze the data of the 147 patients including 72 with brain metastasis symptom and 75 without.

RESULTSThe median survival time (MS) of patients with or without extracranial metastasis was 9.9 months and 11.3 months (P = 0.0002). Multivariate analysis indicated that extracranial metastasis was an independent prognostic factor (P = 0.0004). For 72 patients with brain metastasis symptom, the MS of the patients with and without extracranial metastasis was 9.3 months and 11.3 months (P = 0.0036). The MS of patients with early and late whole brain irradiation was 11.4 months and 9.2 months (P = 0.001). Multivariate analysis showed that extracranial metastasis, the interval between the diagnosis of brain metastasis and the whole brain irradiation were independent prognostic factors. However, for 75 patients without brain metastasis symptom, the MS difference of those with early or late whole brain irradiation was not statistically significant (P = 0.1643).

CONCLUSIONThe extracranial metastasis in non-small cell lung cancer patients with brain metastasis is an independent prognostic factors. Early whole brain irradiation may improve the survival for those with brain metastasis symptoms.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; radiotherapy ; secondary ; Brain Neoplasms ; drug therapy ; radiotherapy ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; secondary ; Combined Modality Therapy ; Cranial Irradiation ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; secondary ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Radiotherapy, High-Energy ; Retrospective Studies ; Survival Rate ; Time

PURPOSE: Breast conserving surgery is increasingly performed in early stage breast cancer patients. A certain propotion of these patients are at substantial risk for systemic metastasis. However, there is no valid consensus about optimal sequencing of chemotherapy and radiation therapy. METHODS: We conducted a randomized prospective study to investigate whether concurrent chemotherapy and radiation therapy after breast conserving surgery are associated with increased toxicity. Fifty-seven patients with stage I or II breast cancer were randomly assigned to receive CMF chemotherpy either simultaneously with (n=37) or before (n=20) radiation therapy. RESULTS: Moist desquamation was the most common adverse effect which occurred in 46% (16/37) of the patients treated with concurrent chemotherapy and radiation therapy and 40% (8/20) of those treated with the sequential regimen. This difference between two groups was not statistically significant. Also the incidence of severe neutropenia (WBC<1,800) or abnormal elevation of liver enzymes was not influenced by the sequencing of the adjuvant therapies. Arm edema was observed in 2 patients of the concurrent group and in 2 patients of the sequential regimen. Two patients treated with the concurrent regimen did not complete 6 cycles of chemotherapy while only one patient treated with sequential regimen did not. The incidence of toxicity during chemotherapy was not altered by the timing of radiation therapy. CONCLUSION: Chemotherapy and radiation therapy can be given concurrently after breast conserving surgery in stage I or II breast cancer patients without increase in serious toxicity.
Arm ; Breast Neoplasms* ; Breast* ; Consensus ; Drug Therapy* ; Edema ; Humans ; Incidence ; Liver ; Mastectomy, Segmental ; Neoplasm Metastasis ; Neutropenia ; Prospective Studies ; Radiotherapy*

Hepatocellular carcinoma (HCC) involving the inferior vena cava (IVC) and/or right atrium (RA) is a rare and intractable disease. A standard treatment has not been established yet, owing to the rarity of disease and difficulties in the therapeutic treatment. Herein, we report the case of a patient who had recurrent HCC (after a prior lobectomy) involving both IVC and RA and underwent multimodality treatments including external beam radiotherapy and transarterial chemotherapy, followed by sorafenib treatment. The disease was well controlled with local treatments and sustained for 7 years until last follow-up after the systemic treatments. Our case shows a possibility of long-term survival for patients affected by HCC involving IVC and/or RA, after a rigorous multimodality treatment strategy.
Carcinoma, Hepatocellular ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Heart Atria ; Humans ; Liver Neoplasms ; Radiotherapy ; Vena Cava, Inferior

OBJECTIVETo investigate the time to progression (TTP) and overall survival in patients with previously untreated metastatic or relapsed esophageal squamous cell carcinoma treated with chemotherapy (paclitaxel plus cisplatin) combined with radiotherapy versus chemotherapy alone, and also to evaluate the efficacy and toxicity of the regimen.

METHODSIn this prospective and non-randomized study, 47 patients with definite measurable lesion and having no previous chemotherapy were enrolled. All patients were treated with paclitaxel 175 mg/m2 by 2-hour iv infusion on d1 and cisplatin 75 mg/m2 by iv infusion on d1, which were repeated every 21 days. After 2-6 cycles of chemotherapy, those who gained CR, PR or SD were non-randomly assinged into radiotherapy group (group A) or non-radiotherapy group (group B).

RESULTSTotally, 47 patients were enrolled into this study, and all of them were valuable for response. One patient achieved complete response (CR), 19 partial response (PR), 24 stable disease (SD), and 3 were found to have disease progression (PD). The overall response rate of chemotherapy was 42.6% (95% CI, 0.28-0.58). Twenty-one of these 47 patients were sequentially treated with radiotherapy. The median survival and TTP was 13 months and 10 months in the group A , versus 11 months and 5 months in the group B (P < 0.024, P < 0.015), respectively. The most common toxicities were neutropenia and alopecia. There were no grade 4 clinical toxicity and treatment-related death in this series. Systemic adverse effects frequently occurred during radiotherapy were esophagitis and fatigue, which were tolerable.

CONCLUSIONThe combined therapy using chemotherapy (paclitaxel + cisplatin) followed by radiotherapy is effective, tolerable, and statistically superior to chemotherapy alone in patients with metastatic or relapsed esophageal squamous cell carcinoma.

Adolescent ; Adult ; Aged ; Alopecia ; etiology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; secondary ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Esophageal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Fatigue ; etiology ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; secondary ; Lung Neoplasms ; drug therapy ; radiotherapy ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; etiology ; Paclitaxel ; administration & dosage ; Prospective Studies ; Radiotherapy ; adverse effects ; methods ; Radiotherapy, High-Energy ; adverse effects ; Survival Analysis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma (NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P < 0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival (OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio (HR) = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment (HR = 0.4, P = 0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (HR = 2.3, P < 0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; drug therapy ; radiotherapy ; secondary ; surgery ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; drug therapy ; radiotherapy ; secondary ; surgery ; Lung Neoplasms ; drug therapy ; radiotherapy ; secondary ; surgery ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Palliative Care ; Radiotherapy, Intensity-Modulated ; Retrospective Studies ; Survival Rate ; Young Adult