Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis.
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ABSTRACT:
SUBMITTER: Ohba K
PROVIDER: S-EPMC1727260 | biostudies-other | 1998 Oct
REPOSITORIES: biostudies-other
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Project description:Background/aimIn the era of immunotherapy, treatment-related lymphopenia (TRL) is gaining attention. In this study, TRL was investigated in patients with bone metastasis from hepatocellular carcinoma (HCC) treated with radiotherapy (RT).MethodsClinical data of 302 patients receiving RT for 511 bone metastases from HCC between 2005 and 2018 were reviewed. Data on absolute lymphocyte count (ALC) from pre-RT to 12 months post-RT were collected. Severe TRL was defined as ALC <500 cells/mm3 and evaluated using ALC 2 months after initiating RT. Factors associated with TRL were analyzed, which include the amount of active bone marrow within the RT field. The amount of active bone marrow included in the RT field was calculated as the product of the percentage of the bone compartment included in the RT field and the active bone marrow percentage of the bone compartment.ResultsOverall, 33.4% of patients developed TRL 2 months after initiating RT. The mean ALC decreased after initiating RT and remained persistently low during 12 months of observation. Overall survival (OS) was significantly worse in patients with TRL than in those without (median OS: 3.7 vs. 6.5 months, p < 0.001). In the prognostic factor analysis, TRL was an independent prognostic factor of OS (p = 0.036), along with known prognostic factors of HCC. The percentage of active bone marrow within the RT field was the only significant factor associated with TRL (p < 0.001).ConclusionTRL was observed in patients receiving RT for bone metastasis from HCC, and it was associated with poor survival. The percentage of active bone marrow within the RT field significantly affected TRL development. The results suggest that a new strategy is required to prevent TRL.
| S-EPMC6883451 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) most commonly develops in patients who have a viral infection, especially in the case of hepatitis B virus (HBV), and in patients with a chronic liver disease. HCC patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. Identification of patients who are at high risk for BM after undergoing potentially curative treatment for HCC remains challenging. Here, we aimed to identify HCC BM-related genes and proteins to establish prediction biomarkers.MethodsRNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded tissue from HCC patients with and without BM. A cDNA-mediated annealing, selection, extension and ligation assay containing 502 cancer-related genes was used to identify novel BM-associated genes. An additional independent study with 350 HCC patients who had undergone hepatectomy was conducted to evaluate the expression of candidate genes at the protein level using immunohistochemistry on tissue microarrays (TMAs). Of the 350 patients, 273 (78.0%) were infected with HBV.ResultsSeven intratumoral genes and 17 peritumoral genes were overexpressed in patients with BM, whereas 15 intratumoral genes and 28 peritumoral genes were underexpressed in patients with BM. We selected the following four genes for further analysis because they were differentially expressed in the cancer gene-specific microarray and were previously reported to be associated with BM: connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1), transforming growth factor β1 (TGF-β1), and interleukin-11 (IL-11). We assessed the protein expression of these selected genes using immunohistochemistry on TMAs including 350 HCC patient specimens. We determined that expression of intratumoral CTGF, intratumoral IL-11, and peritumoral MMP-1 were independent prognostic factors for developing BM in HCC patients. Combining intratumoral CTGF and IL-11 expression was also an independent risk factor for BM development.ConclusionsSixty-seven genes were differentially expressed in HCC patients with and without BM. High intratumoral CTGF, positive IL-11, and high peritumoral MMP-1 expression were associated with BM after hepatectomy. Intratumoral CTGF expression combined with IL-11 expression may serve as a useful predictive biomarker for HCC BM.
| S-EPMC3228144 | biostudies-literature
Project description:BACKGROUND:Bone metastasis (BM) is one of the common sites of hepatocellular carcinoma (HCC), and the prognosis of BM patients is worse than patients without it. Our study aimed to identify predictors and prognostic factors of BM in HCC patients and develop two nomograms to quantify the risk of BM and the prognosis of HCC patients with BM. METHODS:We retrospectively reviewed the data of patients who were diagnosed as HCC between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors for BM from HCC patients were determined by the univariate and multivariate logistic regression analysis. Independent prognostic factors for HCC patients with BM were identified by univariate and multivariate Cox regression analysis. Two nomograms were established and evaluated by calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). RESULTS:Nine thousand and forty-seven patients were included. The independent risk factors of BM in newly diagnosed HCC patients are sex, grade, T stage, and N stage. The independent prognostic factors for HCC patients with BM are radiotherapy, chemotherapy, and lung metastasis. The AUC of diagnostic nomogram were 0.726 in the training set and 0.629 in the testing set. For the prognostic nomogram, the AUCs of 6-, 9-, and 12-months were 0.753, 0.799, and 0.732 in the training set and 0.698, 0.770, and 0.823 in the validation set. The calibration curve and DCA indicated the good performance of the nomogram. CONCLUSIONS:Two nomograms were established to predict the incidence of BM in HCC patients and the prognosis of HCC patients with BM, respectively. Both nomograms have satisfactory accuracy, and clinical utility may benefit for clinical decision-making.
| S-EPMC7268752 | biostudies-literature
Project description:RNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded (FFPE) tissue from hepatocellular carcinoma (HCC) patients with and without bone metastases (BM). The Human Cancer Panel DASL Assay containing 502 cancer-related genes was used to identify novel BM-associated genes. A cDNA-mediated annealing, selection, extension, and ligation assay was performed with an array of 502 known cancer-related genes to identify differentially expressed genes in 96 RNA samples. Total RNA was purified from the tissue specimens using the High Pure RNA Paraffin Kit according to the manufacturer’s protocol. DASL experiments were performed to identify genes that were differentially expressed between the BM and NBM groups of matched intratumoral and peritumoral tissues by using A cDNA-mediated annealing, selection, extension, and ligation assay.
2011-10-27 | E-GEOD-27635 | biostudies-arrayexpress
Project description:PurposeTo study tumor regression and failure patterns in T1-T2 non-metastatic nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).MethodsA retrospective analysis of 139 nasopharyngeal carcinoma patients treated with IMRT between January 2005 and December 2010 in our center was performed. According to the AJCC staging system, all primary lesions were attributed to T1 and T2. The prescription doses were 66 Gy at 30 fractions to gross tumor volume of the nasopharynx and the positive neck nodes, 60 Gy to high-risk clinical target volume and 54 Gy to low-risk clinical target volume. Patients staged III, IV A/B or II (lymph node measured 4 cm or more in diameter) received platinum-based chemotherapy.ResultsBy the end of radiotherapy, 7.2% (10/139), 23.7% (33/139), and 9.4% (13/139) of patients had residual lesions in the nasopharynx, cervical lymph nodes and retropharyngeal lymph nodes, respectively. The majority of patients had complete remission within 6 months of radiotherapy completion. Five months after IMRT, three patients with residual tumors in the cervical lymph nodes underwent surgery. Among these patients, two patients had positive pathological findings, and one patient had negative findings. With a median follow-up of 59 months, the 5-year overall survival, local control, regional control and distant metastasis-free rates were 87.8%, 96.7%, 94.9% and 89.1%, respectively. Fifteen patients developed distant metastases, representing the primary failure pattern.ConclusionsMost residual lesions that persisted after IMRT vanished completely in six months. Considering the potential damage to normal structures, clinicians should be cautious when considering the use of boost irradiation after radiotherapy. Distant metastasis was the primary cause of treatment failure, which was significantly higher in N2-3 patients than in N0-1. Additional studies to better understand distant metastases are needed.
| S-EPMC4847870 | biostudies-literature
Project description:BackgroundRecently, radiotherapy has been used in the treatment of hepatocellular carcinoma (HCC). However, there is no study analyzing the efficacy of radiotherapy in cases of advanced HCC. The objective of this investigation was to determine the efficacy of radiotherapy in patients with HCC invading distant organs.MethodsThe data of 2342 patients diagnosed between 2010 and 2015 with HCC invading distant organs were extracted from the SEER database. Propensity score matching (PSM) was used to reduce selection bias.ResultsBefore PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group (mOS = 5 months, 95% CI: 4.5-5.5; mCSS = 5 months, 95% CI: 4.4-5.6) were longer than those in the nonradiotherapy group (mOS = 3 months, 95% CI: 2.8-3.2; mCSS = 3 months, 95% CI: 2.8-3.2; both P < 0.001). After PSM, mOS in the radiotherapy group (5 months, 95% CI: 4.5-5.5) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6-3.4; P < 0.001), and the mCSS in the radiotherapy group (5 months, 95% CI: 4.4-5.6) was longer than that in the nonradiotherapy group (3 months, 95% CI: 2.6-3.4; P < 0.001). Before PSM, the multivariate analysis showed that all-cause and cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group. The adjusted Cox regression analysis for subgroups showed that, in the nonradiotherapy group, patients with bone metastases and multiorgan metastases had a worse survival than those in the radiotherapy group.ConclusionHCC patients with metastases to distant organs obtain survival benefit from radiotherapy, particularly patients with bone metastases and multiorgan metastases.
| S-EPMC8612773 | biostudies-literature
Project description:RNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded (FFPE) tissue from hepatocellular carcinoma (HCC) patients with and without bone metastases (BM). The Human Cancer Panel DASL Assay containing 502 cancer-related genes was used to identify novel BM-associated genes. A cDNA-mediated annealing, selection, extension, and ligation assay was performed with an array of 502 known cancer-related genes to identify differentially expressed genes in 96 RNA samples.
2011-10-28 | GSE27635 | GEO
Project description:The incidence of hepatocellular carcinoma (HCC) continues to increase world-wide. Many patients present with advanced disease with extensive local tumor or vascular invasion and are not candidates for traditionally curative therapies such as orthotopic liver transplantation (OLT) or resection. Radiotherapy (RT) was historically limited by its inability to deliver a tumoricidal dose; however, modern RT techniques have prompted renewed interest in the use of liver-directed RT to treat patients with primary hepatic malignancies.The aim of this review was to discuss the use of external beam RT in the treatment of HCC, with particular focus on the use of stereotactic body radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and delivery. Liver-directed RT involves accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. We also summarize the published data on liver-directed RT, and demonstrate that it is associated with excellent local control and survival rates, particularly in patients who are not candidates for OLT or resection.Modern liver-directed RT is safe and effective for the treatment of HCC, particularly in patients who are not candidates for OLT or resection. Liver-directed RT, including SBRT, depends on accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. Further prospective studies are needed to fully delineate the role of liver-directed RT in the treatment of HCC.
| S-EPMC4960357 | biostudies-other
Project description:Although the adrenal glands are not common sites of metastasis from hepatocellular carcinoma (HCC), this metastasis can be met in patients with advanced HCC in some clinical settings. However, the effectiveness of radiotherapy against such metastases is unclear. Therefore, we performed the present multi-institutional study to investigate tumor response, overall survival (OS), treatment-related toxicity, and prognostic factors after radiotherapy. We retrospectively reviewed 134 patients who completed a planned radiotherapy for their adrenal metastases. Complete response was noted in 6 (4.3%), partial response in 48 (34.0%), and stable disease in 78 patients (55.3%). The median OS was 12.8 months, and the 1-, 2-, and 5-year OS rates were 53.1%, 23.9%, and 9.3%, respectively. Grade 3 anorexia occurred in 2 patients, grade 3 diarrhea in 1, and grade 3 fatigue in 1. Multivariate analyses revealed that the following factors had significant effects on OS: controlled intrahepatic tumor; controlled extrahepatic metastasis; and Child-Pugh class A. Although patients with adrenal metastasis from HCC had poor OS, radiotherapy provided an objective response rate of 38.3% and disease stability of 93.6%, with minimal adverse events. Therefore, radiotherapy for these patients could represent a good treatment modality, especially for patients with controlled intrahepatic tumors, controlled extrahepatic metastasis, and good hepatic function.
| S-EPMC4811532 | biostudies-literature
Project description:BACKGROUND: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC. PATIENTS AND METHODS: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed. RESULTS: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001). CONCLUSIONS: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.
| S-EPMC4149423 | biostudies-other