Jian-Ying Zhang

Radiotherapy may improve overall survival of patients with T3/T4 transitional cell carcinoma of the renal pelvis or ureter and delay bladder tumour relapse

BackgroundSince transitional cell carcinoma (TCC) of the upper urinary tract is a relatively uncommon malignancy, the role of adjuvant radiotherapy is unknown.MethodsWe treated 133 patients with TCC of the renal pelvis or ureter at our institution between 1998 and 2008. The 67 patients who received external beam radiotherapy (EBRT) following surgery were assigned to the radiation group (RT). The clinical target volume included the renal fossa, the course of the ureter to the entire bladder, and the paracaval and para-aortic lymph nodes, which were at risk of harbouring metastatic disease in 53 patients. The tumour bed or residual tumour was targeted in 14 patients. The median radiation dose administered was 50 Gy. The 66 patients who received intravesical chemotherapy were assigned to the non-radiation group (non-RT).ResultsThe overall survival rates for the RT and non-RT groups were not significantly different (p = 0.198). However, there was a significant difference between the survival rates for these groups based on patients with T3/T4 stage cancer. A significant difference was observed in the bladder tumour relapse rate between the irradiated and non-irradiated bladder groups (p = 0.004). Multivariate analysis indicated that improved overall survival was associated with age < 60 years, T1 or T2 stage, absence of synchronous LN metastases, and EBRT. Acute gastrointestinal and bladder reactions were the most common symptoms, but mild non-severe (> grade 3) hematologic symptoms also occurred.ConclusionEBRT may improve overall survival for patients with T3/T4 cancer of the renal pelvis or ureter and delay bladder tumour recurrence in all patients.

Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

PURPOSE The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. METHODS AND MATERIALS We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. RESULTS The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher α-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). CONCLUSIONS In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

Consideration of the Role of Radiotherapy for Abdominal Lymph Node Metastases in Patients With Recurrent Gastric Cancer

PURPOSE To evaluate the outcome of external beam radiotherapy for abdominal lymph node (LN) metastases in patients with recurrent gastric cancer. METHODS AND MATERIALS The clinical data of 79 patients with abdominal LN metastases developing after curative resection of gastric tumor were retrospectively analyzed. Of the 79 patients, 37 received radiation (40-60 Gy in fractions of 2.0 Gy daily, five times weekly; termed the radiation group), and 42 received chemotherapy or supportive care (the nonradiation group). The Kaplan-Meier method was used to evaluate survival, and a Cox regression model was used to identify predictors of prognosis. RESULTS After radiation, complete response and partial response were observed in 29.7% and 54.1% of patients, respectively. Clinical symptoms were relieved in 19 of 21 patients (90.5%) after completing radiation. Median survival time was 11.4 months in the radiation group and 4.8 months in the nonradiation group. Overall survival for patients with and without radiation was 43.2% and 19.0% at 1 year and 27.6% and 4.1% at 2 years, respectively (p = 0.002). Multivariate analysis showed that the relative risk of death in the radiation group from the time of diagnosis of LN metastases was 0.253 (p < 0.001). The most common adverse effect of radiation was gastrointestinal toxicity, but it was mild in most patients. CONCLUSIONS Abdominal LN metastases from gastric cancer are sensitive to radiation. Delivery of 50 Gy is effective as palliative treatment and may prolong overall survival.

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

BackgroundLittle is known about the clinical features and prognostic factors of bone metastases of hepatocellular carcinoma (HCC) following liver transplantation (LT).MethodsAll 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).ResultsThe 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.ConclusionThe 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.

Feasibility and efficacy of helical intensity-modulated radiotherapy for stage III non-small cell lung cancer in comparison with conventionally fractionated 3D-CRT

BACKGROUND The standard treatment for stage III non-small-cell lung cancer (NSCLC) is still 60 Gy in conventional fractions combined with concurrent chemotherapy; however, the resulting local controls are disappointing. The aim of this study was to compare and assess the feasibility and efficacy of hypofractionated chemoradiotherapy using helical tomotherapy (HT) with conventional fractionation as opposed to using three-dimensional conformal radiotherapy (3D-CRT) for stage III NSCLC. METHODS Sixty-nine patients with stage III (AJCC 7th edition) NSCLC who underwent definitive radiation treatment at our institution between July 2011 and November 2013 were reviewed and analyzed retrospectively. A dose of 60 Gy in 20 fractions was delivered in the HT group (n=34), whereas 60 Gy in 30 fractions in the 3D-CRT group (n=35). Primary endpoints were toxicity, overall response rate, overall survival (OS) and progression-free survival (PFS). RESULTS The median follow-up period was 26.4 months. V20 (P=0.005), V30 (P=0.001), V40 (P=0.004), mean lung dose (P=0.000) and max dose of spinal cord (P=0.005) were significantly lower in the HT group than in the 3D-CRT group. There was no significant difference in the incidences of acute radiation pneumonitis (RP) ≥ grade 2 between the two groups, whereas the incidences of acute radiation esophagitis ≥ grade 2 were significantly lower in the HT group than in the 3D-CRT group (P=0.027). Two-year overall response rate was significantly higher in the HT group than in the 3D-CRT group (P=0.015). One- and 2-year OS rates were significantly higher in the HT group (95.0% and 68.7%, respectively) than in the 3D-CRT group (85.5% and 47.6%, respectively; P=0.0236). One- and 2-year PFS rates were significantly higher in the HT group (57.8% and 26.3%, respectively) than in the 3D-CRT group (32.7% and 11.4%, respectively; P=0.0351). Univariate analysis indicated that performance status (PS), T stage and radiotherapy technique were significant prognostic factors for both OS and PFS. Multivariate analysis indicated that PS and radiotherapy technique were independent prognostic factors of OS and PS was independent prognostic factor of PFS. CONCLUSIONS Hypofractionated chemoradiotherapy via HT can shorten the radiotherapy time without increasing treatment-related toxicity. The preliminary findings are that OS and PFS can be improved by hypofractionated chemoradiotherapy via HT for patients with stage III NSCLC.

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.

Consensus on Stereotactic Body Radiation Therapy for Small-Sized Hepatocellular Carcinoma at the 7th Asia-Pacific Primary Liver Cancer Expert Meeting

Background: Stereotactic body radiation therapy (SBRT) is an advanced technique of external beam radiation therapy that delivers large ablative doses of radiation. In the past decade, many cancer centers have adopted SBRT as one mode of radically treating small-sized hepatocellular carcinoma (HCC), based on encouraging clinical outcomes. SBRT thus seems reasonable as first-line treatment of inoperable HCC confined to the liver. However, most of the clinical studies to date have been retrospective in nature, with key issues still under investigation. Summary: The above-mentioned publications were subjected to scrutiny, fueling discussions at the 7th Asia-Pacific Primary Liver Cancer Expert (APPLE 2016) Meeting on various clinical variables, such as indications for SBRT, therapeutic outcomes, treatment-related toxicities, doses prescribed, and specific techniques. The consensus reached should be of interest to all professionals active in the treatment of HCC, especially radiation oncologists. Key Messages: SBRT is a safe and effective therapeutic option for patients with small-sized HCC, offering substantial local control, improved overall survival, and low toxicity.

Toll‑like receptor 4 and its associated proteins as prognostic factors for HCC treated by post‑radiotherapy surgery

Locally advanced hepatocellular carcinoma (HCC) treated by radiotherapy (RT) may be suited for further treatment with surgery. As a critical mediator of the post-RT immune response, Toll-like receptor 4 (TLR4) and its associated proteins may serve as prognostic factors for patients with HCC treated by post-RT surgery. In the present study, a total of 20 patients with HCC treated by post-RT surgery were enrolled. Resected tumor and peritumoral liver tissues were used to construct tissue microarrays that were assessed with immunohistochemical staining for the expression levels of TLR4, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and vascular endothelial growth factor receptor 2 (VEGFR2). The overall (OS) and disease-free (DFS) survival outcomes for each patient were assessed, and the severity of radiation-induced liver diseases (RILDs) was detected. The patients with low TLR4 or TRAIL expression exhibited significantly better OS times than those with high TLR4 (P=0.003) or TRAIL (P=0.007) expression, whereas the median DFS times for patients with low VEGFR2 or TRAIL were significantly longer than those with high VEGFR2 (P=0.003) or TRAIL (P=0.008) expression. No significant differences in OS or DFS times were identified according to the expression of TLR4, VEGFR2 or TRAIL in peritumoral liver tissue, although more severe RILDs were identified in patients with the high expression of these factors in the peritumoral liver tissue post-RT (P<0.05). Therefore, the expression levels of TLR4 and its associated proteins in HCC tumors may be suitable as prognostic factors for patients with HCC treated by post-RT surgery. The inhibition of TLR4, VEGFR2 and TRAIL expression in HCC and non-tumor liver tissue may lessen the severity of RILDs and improve survival outcomes in the future.