Circulating tumor DNA methylation: a promising clinical tool for cancer diagnosis and management.

Cancer continues to pose significant challenges to the medical community. Early detection, accurate molecular profiling, and adequate assessment of treatment response are critical factors in improving the quality of life and survival of cancer patients. Accumulating evidence shows that circulating tumor DNA (ctDNA) shed by tumors into the peripheral blood preserves the genetic and epigenetic information of primary tumors. Notably, DNA methylation, an essential and stable epigenetic modification, exhibits both cancer- and tissue-specific patterns. As a result, ctDNA methylation has emerged as a promising molecular marker for noninvasive testing in cancer clinics. In this review, we summarize the existing techniques for ctDNA methylation detection, describe the current research status of ctDNA methylation, and present the potential applications of ctDNA-based assays in the clinic. The insights presented in this article could serve as a roadmap for future research and clinical applications of ctDNA methylation.

Case report: Pathological complete response to perioperative treatment of radiotherapy combined with angiogenesis inhibitor in a patient with pleomorphic liposarcoma.

Background: Liposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment. Case presentation: A 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1-14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months. Conclusion: This case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.

Clinical Efficacy and Safety Analysis of PD-1/PD-L1 Inhibitor vs. Chemotherapy in the Treatment of Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Objective: To systematically evaluate the efficacy and safety of pembrolizumab (PD-1/PD-L inhibitor) and adjuvant chemotherapy to treat NSCLC and provide evidence-based reference for clinical use. Methods: By searching the Cochrane Library, EMBASE, PubMed, and Web of Science, according to the inclusion criteria, literature selection, data extraction, and quality evaluation were carried out for the included literature. The I 2 test was used to evaluate heterogeneity between studies, and the meta-analysis was performed using RevMan 5.3 software provided by Cochrane. Results: Finally, 14 relevant documents meeting the standards were included. It is a statistical difference in one-year survival rate [OR = 1.50, 95% CI (1.28, 1.76), P < 0.00001, I 2 = 0%, Z = 4.99]; overall response rate[OR =1.57, 95% CI (1.29, 1.90), P < 0.00001, I 2 = 0%, Z = 4.58]; progression-free survival [OR = 2.99, 95% CI (2.29, 3.91), P < 0.00001, I 2 = 26%, Z = 8.00]; and overall survival [OR = 1.38, 95% CI (1.07, 1.78), P = 0.01, I 2 = 46%, Z = 2.50] and reduces the incidence of adverse drug reactions [OR = 2.54, 95% CI (1.99, 3.25), P < 0.00001, I 2 = 69%, Z = 7.43]. Conclusion: Pembrolizumab adjuvant chemotherapy is effective in the treatment of advanced NSCLC, but attention should be paid to the occurrence of adverse reactions in clinical. Due to the limitations of the methodology included in the study, this conclusion required more validation of large-sample RCT.

ETV4 mediated lncRNA C2CD4D-AS1 overexpression contributes to the malignant phenotype of lung adenocarcinoma cells via miR-3681-3p/NEK2 axis.

Lung adenocarcinoma (LUAD) is originated from the mucus-producing glands of the lungs. The involvement of long noncoding RNAs (lncRNAs) has been discovered in multiple diseases. In the present research, we aimed to unmask the role of C2CD4D and THEM5 antisense RNA 1 (C2CD4D-AS1) in LUAD. RT-qPCR or western blot analysis was respectively applied in the detection of RNA or protein expressions. The function of C2CD4D-AS1 in LUAD was assessed by functional assays. Through ChIP, RNA pull down, DNA pull down, RIP and luciferase reporter assays, the in-depth regulatory mechanism of C2CD4D-AS1 in LUAD was explored. C2CD4D-AS1 was dramatically overexpressed in LUAD tissues and cell lines. As a result, depletion of C2CD4D-AS1 significantly repressed cell proliferation, migration, invasion and stimulated cell apoptosis in LUAD. Mechanistically, ETS variant transcription factor 4 (ETV4) activated the transcription of C2CD4D-AS1 and stimulated its up-regulation in LUAD cells, thus affecting LUAD cell biological functions. Furthermore, C2CD4D-AS1 sponged microRNA-3681-3p (miR-3681-3p) and regulated NIMA-related kinase 2 (NEK2), thus participating in modulating LUAD cell biological behaviors. To conclude, C2CD4D-AS1 up-regulation induced by ETV4 enhanced NEK2 expression by sequestering miR-3681-3p to contribute to the malignant behaviors of LUAD cells.

Image-guided intensity-modulated radiotherapy improves short-term survival for abdominal lymph node metastases from hepatocellular carcinoma.

BACKGROUND: Radiotherapy (RT) is an effective treatment for hepatocellular carcinoma (HCC) patients with lymph node metastasis (LNM), which is a rare clinical situation with a poor prognosis. We evaluated the responses and toxicities in HCC patients with abdominal LNM treated with either image-guided intensity-modulated radiotherapy (IG-IMRT) or non-IG-IMRT. METHODS: Retrospective review of the records of HCC patients with regional LNM treated with IG-IMRT (n=43) or non-IG-IMRT (n=42). The tumor responses, local control rates (LCRs), overall survival (OS) rates, and toxicities were evaluated. RESULTS: The mean biological effective dose with α/ß =10 Gy (BED10) delivered to IG-IMRT group was 67.23±8.48 vs. 63.43±5.01 Gy delivered to non-IG-IMRT group (P=0.008). OS in IG-IMRT group vs. non-IG-IMRT group was 15.3 vs. 9.7 months (P=0.098). The one-year survival of IG-IMRT group was superior (69% vs. 38.1% for non-IG-IMRT, P=0.006). Whereas two-year survival was not significantly different. Negative independent prognostic factors included ≥2 positive lymph nodes and previous treatment without surgery, while BED10 ≥65 Gy was a protective factor. Toxicities were mild for both groups, while IG-IMRT group showed less late hepatotoxicity. CONCLUSIONS: The therapeutic dose delivered by IG-IMRT is slightly higher than non-IG-IMRT which was more effective and showed superior short-term survival and local control in HCC patients with LNM.

Analysis of the role of DAMTC in lung adenocarcinoma cells based on the DNA microarrays.

The present study aimed to investigate the effect of 7, 8-diacetoxy-4-methylcoumarin (DAMTC) on lung adenocarcinoma cells (A549) and analyze the molecular mechanism underlying DAMTC-treated lung adenocarcinoma. Gene expression profile GSE29698 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in 3 DAMTC-treated A549 samples were analyzed and compared with 3 DAMTC-untreated samples using the limma package. Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by the functional annotation and protein-protein interaction (PPI) network construction. Finally, pathway crosstalk analysis was conducted. A total of 500 upregulated and 389 downregulated DEGs were identified. The upregulated and downregulated DEGs were enriched in different GO terms and pathways, including metabolic process, p53 signaling pathway and metabolic pathways. A total of 9 DEGs were determined to have node degrees >16 in the PPI network, including interleukin 6 (IL6), MDM2 oncogene, E3 ubiquitin protein ligase (MDM2), cell division cycle 42 (CDC42) and MYC associated factor X (MAX). Furthermore, numerous DEGs were identified to function as transcription factors and tumor suppressor genes, including histone deacetylase 3 and MAX. Additionally, apoptosis, tight junction, and endocytosis pathway were determined to cross-talk with small cell and non-small cell lung cancer. The DEGs (IL6, MDM2, CDC42 and MAX) involved in different pathways, including the p53 signaling pathway and endocytosis, may be the potential targets for DAMTC in lung adenocarcinoma. The elucidation of the underlying mechanism of the DAMTC effect may make it a potential drug.

A novel long noncoding RNA PILRLS promote proliferation through TCL1A by activing MDM2 in Retroperitoneal liposarcoma.

It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in retroperitoneal liposarcoma have never been reported. In our study, we found a novel lncRNA PILRLS (Proliferation Interacting LncRNA in Retroperitoneal Liposarcoma), which as an oncogene significantly overexpressed in retroperitoneal liposarcoma. Functions of PILRLS on tumor progression both in vitro and in vivo have verified in this study which PILRLS knockdown significantly inhibited cell proliferation and colony formation. RNA pull-down assay found PILRLS can specific binding with TCL1A which also regulate the expression level of TCL1A. Our work for the first time demonstrated PILRLS can activating the MDM2 by binding with TCL1A which suppress the P53 pathway to promote the unlimited growth of retroperitoneal Liposarcoma cells. It suggests that PILRLS may be an important targets for retroperitoneal liposarcoma therapy.

The Degree of Lipiodol Accumulation Can Be an Indicator of Successful Treatment for Unresectable Hepatocellular Carcinoma (HCC) Patients - in the Case of Transcatheter Arterial Chemoembolization (TACE) and External Beam Radiotherapy (EBRT).

PURPOSE: Transcatheter arterial chemoembolization (TACE) in combination with external beam radiotherapy (EBRT) results in improved survival due to better local control in patients with unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate lipiodol accumulation, as it reflects tumor burden and is a potential prognostic factor, in HCC patients treated with TACE/EBRT. METHODS AND MATERIALS: We retrospectively studied 147 patients with unresectable HCC treated with TACE and EBRT. Clinical features, adverse reactions, and prognostic factors were analyzed. All patients were treated with TACE 1-6 times in combination with EBRT (44-66 Gy) in dose of 2 Gy/fraction given once a day five times a week. Tumor status and laboratory findings were followed. The degree of lipiodol accumulation was assessed by computed tomography before EBRT, and was categorized as either complete/intense or low/moderate. RESULTS: The response rate of tumor size after EBRT was 68.2%, median survival was 23.1 months, and overall survival rates were 86.6%, 49.2%, and 28.2% at 1, 2, and 3 years, respectively. Univariate analysis showed that lower hemoglobin levels, higher alkaline phosphatase levels, Child-Pugh B, negative alpha-fetoprotein (AFP) response after EBRT, poor treatment response after EBRT, tumor diameter >10 cm, and poor lipiodol accumulation were unfavorable prognostic factors. On multivariate analysis, higher hemoglobin levels, Child-Pugh A, decreased AFP levels after treatment, Helical Tomotherapy (HT) and intense lipiodol accumulation after TACE were significant favorable predictors. CONCLUSIONS: The degree of lipiodol accumulation before EBRT is a prognostic factor in patients with unresectable HCC. Increased AFP levels after EBRT are always associated with poor survival. HT is recommended as a potentially better EBRT modality than three-dimensional conformal radiation therapy (3D-CRT).

High dose radiotherapy with image-guided hypo-IMRT for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombi is more feasible and efficacious than conventional 3D-CRT.

OBJECTIVE: To compare the efficacies of conventional three-dimensional conformal radiotherapy and image-guided hypofractionated intensity-modulated radiotherapy treatments in advanced hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi. METHODS: A total of 118 hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi who received external beam radiation therapy focused on tumor thrombi and intrahepatic tumors were retrospectively reviewed. During the three-dimensional conformal radiotherapy treatments, a median total dose of 54 Gy with a conventional fraction (1.8-2.0 Gy/fx) was delivered. During the image-guided hypofractionated intensity-modulated radiotherapy treatments, a median total dose of 60 Gy with fractions of 2.5-4.0 Gy/fx was delivered. RESULTS: The median follow-up time was 11.8 months (range, 1.7-43.7 months). Higher radiation doses were delivered by image-guided hypofractionated intensity-modulated radiotherapy than by three-dimensional conformal radiotherapy (average dose 57.86 ± 7.03 versus 50.88 ± 6.60 Gy, P ≤ 0.001; average biological effective dose 72.35 ± 9.62 versus 61.45 ± 6.64 Gy, P < 0.001). A longer median survival was found with image-guided hypofractionated intensity-modulated radiotherapy than with three-dimensional conformal radiotherapy (15.47 versus 10.46 months, P = 0.005). Multivariate analysis showed that image-guided hypofractionated intensity-modulated radiotherapy is a significant prognostic factor for overall survival. Toxicity was mild for both image-guided hypofractionated intensity-modulated radiotherapy and three-dimensional conformal radiotherapy. CONCLUSIONS: High dose radiotherapy delivered by image-guided hypofractionated intensity-modulated radiotherapy appears to be an effective treatment that provides a survival benefit without increasing severe toxicity in hepatocellular carcinoma patients with portal vein and/or inferior vena cava tumor thrombi.

The combined effects of UV-C radiation and H2O2 on Microcystis aeruginosa, a bloom-forming cyanobacterium.

In order to get insight into the impacts of UVC/H2O2 on Microcystis aeruginosa, physiological and morphological changes as well as toxicity were detected under different UVC/H2O2 treatments. In the presence of sole UVC or H2O2, the net oxygen evolution rate decreased significantly (p<0.05) since activity of photosystem II (PSII) was inhibited. Meanwhile, increase of intracellular reactive oxygen species (ROS), degradation of microcystin (MC) and ultrastructure destructions were observed. Under sole UVC treatment, no changes happened in the activity of photosystem I (PSI), but the degradation of D1 protein was observed. Under sole H2O2 treatment, an increase of malondialdehyde, aggregation of D1 protein and deformation of the thylakoid membrane were observed. ROS content under H2O2 treatment was about 5 times than that under UVC treatment. Combined use of UVC and H2O2, as well as 20mJcm(-2) UVC and 60µM H2O2, showed high synergetic effects. Obvious damage to membrane systems, the marked degradation of MC and inhibition of the photosystems were observed. It could be deduced that UVC worked on intracellular membrane components directly and the damaged oxygen-evolving complex, which was followed by the D1 protein degradation. H2O2 oxidised the membrane lipids via an ROS-mediated process, with thylakoid injury and the aggregation of D1 protein being the lethal mechanisms, and both PSII and PSI being the attacking targets. With regard towards the effective inactivation of M. aeruginosa and high removal of MC, UVC/H2O2 proposed a novel practical method in controlling cyanobacterial blooms.

The therapeutic and adverse effects of modified radiation fields for patients with rectal cancer.

PURPOSE: To compare the therapeutic effect and complications of modified radiation fields (MRFs) with those of conventional pelvic radiation fields (CPRFs) for rectal cancer. METHODS AND MATERIALS: From December 1996 to October 2009, a total of 160 patients with rectal carcinoma who received total mesorectal excision and postoperative radiotherapy were examined. Ninety-four patients were in the CPRFs group, and 66 were in the MRFs group. The dose was 50 Gy per 25 fractions in the initial plan. RESULTS: The treatment volume and the volume of small bowel that received more than 15 Gy of the MRFs was smaller than that of the CPRFs (P < .001). The rates of local recurrence, overall survival, and disease-free survival were not statistically significant between the MRFs and CPRFs groups (P > .05). There was a statistical difference (P < .05) in the incidence of acute toxicity, which included serious complications in the lower digestive tract (grade ≥3). The completion rate for the initial radiotherapy plan was higher in the MRFs group than in the CPRFs group (P = .027). CONCLUSIONS: Compared with CPRFs, MRFs manifested a lower incidence of complications and the same therapeutic effects. This finding will facilitate the clinical application of MRFs for patients with rectal cancer.

Clinical features and prognostic factors in patients with bone metastases from hepatocellular carcinoma after liver transplantation.

BACKGROUND: Little is known about the clinical features and prognostic factors of bone metastases of hepatocellular carcinoma (HCC) following liver transplantation (LT). METHODS: All adult patients undergoing LT from 2001 to 2010 were reviewed. Patients with HCC bone metastases after LT received external beam radiotherapy(EBRT) during this period. Demographic variables, laboratory values, and tumor characteristics were determined before LT and EBRT. Total radiation dose ranged from 8 to 60 Gy(median dose 40.0 Gy). RESULTS: The trunk was the most common site of bone metastases with finding of expansile soft-tissue masses in 23.3% of patients. Overall pain relief from EBRT occurred in 96.7% (29/30). No consistent dose-response relationship was found for palliation of with doses between 30 and 56 Gy (P = 0.670). The median survivals from the time of bone metastases was 8.6 months. On univariate and multivariate analyses, better survival was significantly associated with a better Karnofsky performance status (KPS) and well-controlled intrahepatic tumor, but not with lower alpha-fetoprotein levels. The median time from LT to bone metastases was 7.1 months. Patients exceeding the Shanghai criteria presented with bone metastases earlier than those within the Fudan criteria. Patients with soft-tissue extension always had later bone metastases. The majority of deaths were caused by liver failure due to hepatic decompensation or tumor progression. CONCLUSION: The prognostic factors of bone metastases of HCC following LT are KPS and well-controlled intrahepatic. Even though survival is shorter for these patients, EBRT provides effective palliation of pain.

Prognostic factors for patients with hepatocellular carcinoma with macroscopic portal vein or inferior vena cava tumor thrombi receiving external-beam radiation therapy.

Prognostic factors in patients with hepatocellular carcinoma (HCC) with tumor thrombosis are not well established, especially for those given external-beam radiation therapy (EBRT). Patients (n = 136) with HCC who had portal vein (PV) or inferior vena cava (IVC) tumor thrombus received EBRT between January 1998 and October 2007. Demographic variables, laboratory values, tumor characteristics, and treatment modalities were determined at diagnosis and before EBRT. The total radiation dose ranged from 30 to 60 Gy (median, 50 Gy) and was focused on the tumor thrombi. Predictors of survival were identified using the univariate and multivariate analysis. Of the 136 patients, the tumor thrombus completely disappeared in 41 patients (30.1%), 36 patients (26.5%) had a partial response, 49 patients (36%) had stable disease, and 10 patients (7.4%) had progressive disease. On multivariate analysis, pretreatment unfavorable predictors were associated with lower albumin, higher gamma-glutamyltransferase and alpha-fetoprotein levels, poorer Child-Pugh classification, intrahepatic multifocality, lymph node metastases, poorer response to EBRT, and 2-dimension EBRT technique. Survival rates at 1, 2, and 3 years were 31.8%, 17.5%, and 8.8% for patients with PV tumor thrombi; 66.3%, 21.1%, and 15.8% for IVC tumor thrombi; and 25%, 8.3%, and 0% for PV plus IVC tumor thrombi, respectively. Overall median survival was 9.7 months. This study provides detailed information about the survival outcomes and prognostic factors of HCC with tumor thrombi in a relatively large cohort of patients treated with radiation, and the results will help in understanding the potential factors that influence survival for patients with HCC after EBRT.

Consideration of the role of radiotherapy for unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 75 patients.

UNLABELLED: The role of radiotherapy in the treatment of intrahepatic cholangiocarcinoma is controversial. We undertook this study to determine if radiotherapy is appropriate for patients with unresectable or lymph node metastatic intrahepatic cholangiocarcinoma. METHODS AND MATERIALS: The records of 75 patients with intrahepatic cholangiocarcinoma were reviewed and analyzed by Kaplan-Meier method and Cox proportional hazards analysis. Thirty-eight patients who received limited local external-beam radiotherapy were classified as the radiotherapy group. This group included nine patients with resected intrahepatic cholangiocarcinoma with macroscopic residual lymph nodes receiving postoperative external-beam radiotherapy, seven patients with postoperative recurrences in lymph nodes receiving external-beam radiotherapy for salvage failure after treatment with surgery alone, and 22 patients with unresectable intrahepatic cholangiocarcinoma. The median total dose was 50 Gy (range, 30-60 Gy) in daily doses of 2 Gy/fraction, five times a week. Thirty-seven patients with intrahepatic cholangiocarcinoma (including 14 with resectable disease and synchronous or asynchronous lymph node metastases, and 23 with unresectable disease) who did not receive external-beam radiotherapy were selected from hospitalized patients in the same period and were classified as the nonexternal-beam radiotherapy group. Parameters observed included survival rates and tumor response to external-beam radiotherapy demonstrated both by clinical symptoms and by computed tomography scan/magnetic resonance image. RESULTS: Objective responses to external-beam radiotherapy were 36.4% for intrahepatic tumors in 22 patients with unresectable intrahepatic cholangiocarcinoma, and 52% for lymph node metastases in 25 patients with resectable or unresectable intrahepatic cholangiocarcinoma. Pain was relieved in 90% of the patients who received external-beam radiotherapy. The survival rates at 1 and 2 years for patients with unresectable intrahepatic cholangiocarcinoma treated with external-beam radiotherapy (n = 22) compared with those who did not receive external-beam radiotherapy (n = 23) were 36.1% versus 19.0% and 5.2% versus 4.7%, respectively (log-rank P = 0.021). The survival experience of the 16 patients with lymph node metastases (synchronous or asynchronous) who underwent hepatectomy combined with external-beam radiotherapy was superior to that of the group (n = 14) who did not receive external-beam radiotherapy (median survival, 468 and 211 days, respectively; log-rank P = 0.075). These results show that external-beam radiotherapy influenced the survival in the patients with unresectable intrahepatic cholangiocarcinoma or lymph node metastases. The most common reason for death was liver failure caused by uncontrolled intrahepatic disease. Grade 3 toxicity in the external-beam radiotherapy group was infrequent. CONCLUSION: External-beam radiotherapy seems to improve the prognosis of patients with unresectable intrahepatic cholangiocarcinoma and deserves further study.

Consideration of role of radiotherapy for lymph node metastases in patients with HCC: retrospective analysis for prognostic factors from 125 patients.

OBJECTIVES: To evaluate the role of radiotherapy (RT) for hepatocellular carcinoma (HCC) patients with abdominal lymph node (LN) metastasis at our institution in the past 7 years. METHODS AND MATERIALS: We identified 125 patients with HCC metastasis to regional LNs treated with or without external beam RT (EBRT) between 1998 and 2004. Clinical characteristics collected included alpha-fetoprotein status, gamma-glutamyltransferase, status of intrahepatic tumors (size and number), previous therapy for intrahepatic tumors, metastatic LN status (location, number, and size), tumor thrombi, and Child-Pugh classification. Of the 125 patients, 62 received local limited EBRT and were classified as the EBRT group. They received locoregional LN irradiation. The tumor dose ranged from 40 to 60 Gy in daily 2.0-Gy fractions, 5 times weekly. Another 63 patients, who did not receive EBRT, were selected from hospitalized patients in the same period and were classified as the non-EBRT group. The parameters studied included survival rates and tumor response to EBRT both as demonstrated by clinical symptoms and as seen on CT. The Kaplan-Meier method was used to evaluate the survival rates, and the Cox regression model was used to identify predictors of outcome. RESULTS: After EBRT, partial responses and complete responses were observed in 37.1% and 59.7% of patients, respectively. The median survival was 9.4 months (95% confidence interval 5.8-13.0) for the EBRT group and 3.3 months (95% confidence interval, 2.7-3.9) for the non-EBRT group (p < 0.001). Multivariate analysis showed that multiple intrahepatic primary tumors, occurrence of tumor thrombi, no therapy for intrahepatic tumors, and greater Child-Pugh classification were related to a poorer prognosis in all patients. In the EBRT group, the survival periods decreased as the distance of LN involvement from the liver increased (following the natural flow of lymph) and was also associated with the intrahepatic primary tumor size. The incidence of death resulting from LN-related complications was lower in the EBRT group. CONCLUSION: Lymph node metastasis from HCC is sensitive to EBRT. EBRT with 25 fractions of 2 Gy is an effective palliative treatment for patients with LN metastases from HCC presenting with good performance status and may prolong overall survival.

Radiation therapy for adrenal gland metastases from hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from hepatocellular carcinoma. However, it has been the subject of few studies, and the optimal treatment remains unclear. Methods previously tried for the management of adrenal gland metastasis of hepatocellular carcinoma included surgical resection, transarterial chemoembolization or percutaneous ethanol injection, on the basis of case reports. External beam radiation therapy has seldom been applied for patients with adrenal gland metastases. METHODS: We retrospectively studied 22 patients with adrenal metastases from hepatocellular carcinoma who were treated with limited-field external beam radiation therapy. The radiation dose to the adrenal lesion ranged from 36 to 54 (median 50) Gy, while the intrahepatic lesions were treated with either surgical resection or transarterial chemoembolization. RESULTS: Among the 14 patients who had pain related to adrenal metastases, 11 (78.6%) had complete pain relief without medication that lasted until death. Two (14.3%) patients had marked pain relief, but still required analgesics. Partial responses were observed in 73% of the patients. The median survival period for all patients was 10 months. No patient died from complications related to adrenal metastasis. Adverse effects were mild. CONCLUSION: Adrenal metastases from hepatocellular carcinoma are sensitive to radiation treatment. Radiation therapy with 50 Gy for adrenal gland metastases is a good palliative therapy with reasonable safety.

A comparison of treatment combinations with and without radiotherapy for hepatocellular carcinoma with portal vein and/or inferior vena cava tumor thrombus.

PURPOSE: To evaluate the potential role of external beam radiation therapy (EBRT) in the treatment of patients with hepatocellular carcinoma (HCC) who have portal vein (PV) and/or inferior vena cava (IVC) tumor thrombi. METHODS AND MATERIALS: One hundred fifty-eight patients with HCC who had PV and/or IVC tumor thrombus were reviewed and analyzed by Kaplan-Meier and Cox regression analysis. Forty-four patients with HCC who received local limited EBRT (in addition to other treatment modalities) were classified as the EBRT group. The total radiation dose was 36-60 Gy (median, 50 Gy) and was focused on the tumor thrombi. One hundred fourteen patients with HCC who did not receive EBRT were selected from hospitalized patients with HCC who had PV and/or IVC thrombi during the same period; these were classified as the non-EBRT group, and their intrahepatic tumors were treated with transarterial chemoembolization or resection, on the basis of the patients' status. Parameters observed included survival rates and the tumor thrombus response to EBRT as seen on CT scan or MRI. RESULTS: Of the 44 patients who received EBRT, 15 (34.1%) showed complete disappearance of tumor thrombi, 5 (11.4%) were in partial remission, 23 (52.3%) were stable in their tumor thrombi, and 1 (2.3%) showed disease progression at the end of the study period. The median survival was 8 months, and the 1-year survival rate was 34.8% in the EBRT group. In the non-EBRT group, the median survival and 1-year survival rates were 4 months and 11.4%, respectively. In stepwise multivariate analysis, EBRT showed a strongly protective value (relative risk = 0.324, p < 0.001). Survival was not related to intrahepatic tumor status in the non-EBRT patients. However, in the EBRT group, poorer prognosis was significantly related to intrahepatic multifocal or diffusion lesions, and the most common reason for death was liver failure caused by uncontrolled intrahepatic disease. CONCLUSION: Although EBRT is palliative in intent, it is preferred for prolonging survival in the treatment of tumor thrombi.

A comparison of chemoembolization combination with and without radiotherapy for unresectable hepatocellular carcinoma.

PURPOSE: This study evaluated the effect of transcatheter arterial chem-oembolization combined with external beam radiotherapy on the response rates and sur vival of patients with unresectable hepato-cellular carcinoma. Transcatheter arterial chemoembolization is frequently used for the treatment of this cancer, but complete or massive necrosis is seldom observed. Historically, radiotherapy for hepatocellular carcinoma has yielded poor long-term survival. Multimodality therapy has been initiated in an effort to improve survival statistics. PATIENTS AND METHODS: We retrospectively studied 203 patients with unresectable hepa-tocellular carcinoma, who were free of tumor thrombus, lymph node involvement, or extrahepatic metastasis based on computed tomography scans of the chest and abdomen. Among the 203 patients who received transcatheter ar terial chemoembolization as initial therapy, 54 also received combination therapy with external beam radiotherapy. Tumor response rate, survival, and failure patterns were analyzed and compared between the two groups. RESULTS: Objective responses (complete and partial responses) on computed tomography study were obser ved in 31% and 76% of patients in the non-radiotherapy and radiotherapy groups, respectively. Overall survival rates in the patients in the radiotherapy group were 71.5%, 42.3%, and 24.0% at 1, 2, and 3 years, respectively, improved over the non-radiotherapy group rates of 59.6%, 26.5%, and 11.1% at 1, 2, and 3 years, respectively. Intrahepatic failure was lower in the radiotherapy group than in the non-radiotherapy group, but the difference was not significant. Side effects from radiotherapy were common, but rarely severe. CONCLUSIONS: This retrospective study suggests that the outcome of unresectable hepatocellular carcinoma can be influenced by radiation therapy, but a prospective randomized trial would be necessary to draw definitive conclusions.