肝癌肝移植术后骨转移的放射治疗及其对预后的影响

目的通过回顾性分析肝细胞肝癌(以下简称肝癌)肝移植后骨转移患者的临床特征、放疗疗效及预后因素,探讨其有效治疗方法。方法 随访853例肝癌患者。其中30例在肝移植后出现骨转移,接受针对骨转移部位放疗,剂量范围8～60 Gy(中位剂量为40 Gy)。用Kaplan-Meier法进行生存分析,单因素分析用Log-rank方法,多因素分析采用Cox回归模型Backward-Wald法。结果 30例患者肝移植后出现骨转移,1年、2年生存率分别为39.7%、24.4%,中位生存时间8.6月。96.7%的患者接受放疗后疼痛缓解(29/30)。放疗剂量在30～60 Gy之间对疼痛的缓解在剂量效应关系上无相关性(P=0.670)。结论 放疗可以缓解肝细胞癌患者肝移植后骨转移的疼痛,从而提高患者的生存质量。     

Radiotherapy for bone metastases of hepatocellular carcinoma.

Radiotherapeutic effects of 42 bone metastases in 26 hepatocellular carcinoma patients were retrospectively analyzed. Pain relief was observed in 79% of 37 bone metastases treated (29/37). Antitumor effects and improvement of paralysis were also observed in 88% (8/9) and 17% (1/6), respectively. The toxicities experienced were tolerable. Radiotherapy was an effective means of palliation in the treatment of hepatocellular carcinoma bone metastases.     

Radiotherapy for bone metastases from hepatocellular carcinoma and pancreas cancer

There are few reports on the treatment for bone metastases from hepatocellular carcinoma (HCC) and pancreas cancer. We evaluated the therapeutic effects of radiotherapy (RT) in patients with bone metastases from these cancers. Bone metastases from HCC are typically lytic and expansive. We evaluated 13 patients with 16 bone metastases from HCC undergoing RT (30-40 Gy, median 39 Gy) in our department from September 2002 to December 2004. Tumor regression was evaluated by CT or MRI. More than 50% tumor regression was achieved in 4 of 16 lesions (25%). Pain relief was achieved in 12/13 (92%). The median survival was 7 months (95% confidence interval [CI], 4-10 months), and the 6-month and 12-month local control rates were 81% and 67%, respectively. For patients with a limited life expectancy, standard dose RT is appropriate, however,with more than one year life expectancy, investigation employing dose escalation or combination with surgery or TAE is needed. Thirteen patients with 18 bone metastases from pancreas cancer received RT (20-30 Gy, median 30 Gy) from September 2002 to March 2005. The median survival was 3 months (95% CI, 1-6 months). Pain relief was achieved in 12/13 (92%). The prognosis of patients with bone metastases from pancreas cancer is still very poor, and a single fraction or short fraction schedule RT is appropriate.     

Prostaglandin-E-producing hepatocellular carcinoma with hypercalcemia

An autopsy case of prostaglandin E-producing hepatocellular carcinoma with hypercalcemia is presented in this article. A 72-year-old man showed high serum calcium levels (14.2 to 17.3 mg/100 ml) and hypophosphatemia. The plasma level of immunoreactive parathyroid hormone was below the normal range. Administration of oral indomethacin 50 mg daily was effective in decreasing the serum calcium concentration. However, this effect lasted only 5 days, after which it returned to pretreatment levels. The patient died in a hypercalcemic coma. By an autopsy, hepatocellular carcinoma was found in the right lobe of the liver. However, no obvious bone metastases nor abnormalities in the parathyroid glands were detected. The immunoreactive prostaglandin E level assayed in the neoplastic tissue (2278 ng/g) was significantly high when compared with level in the nonneoplastic liver tissue (194 ng/g). The production of prostaglandin E by the tumor itself appears to be the most likely mechanism for the hypercalcemia in this patient.     

Significance of reduction surgery for giant hepatocellular carcinoma with diffuse lung metastases and multiple intrahepatic metastases

Continuous systemic infusion of low-dose cisplatin (CDDP) (10 mg/body/day) and 5-fluorouracil (5-FU) (500 mg/body/day) was performed for advanced hepatocellular carcinoma (HCC) after hepatectomy with diffuse lung metastases and multiple intrahepatic metastases. This infusion chemotherapy, cisplatin was continued for five days, and discontinued for two days, whereas 5-fluorouracil was administered every day and repeated four weeks as one course basally. Remnant metastases had almost disappeared after systemic chemotherapy for 10 weeks. In our experience, the response rate in 13 patients who underwent reduction surgery for multiple HCC was 84.6%. Continuous infusion of low-dose CDDP/5-FU may be effective in patients having absolute non-curative resection.     

Bone metastases of hepatocellular carcinoma after liver resection.

Between January 1985 and July 1990, 323 cases of hepatocellular carcinoma underwent liver resection in our department. Bone metastases were found in 12 of these cases (3.7%). Bone metastases were mainly found in vertebral bone (58.3%) and pelvic bone (41.7%). The time interval to the development of bone metastasis after liver resection was closely related to the presence of intrahepatic metastasis and the stage at operation. In all cases, the initial clinical symptom was pain and/or motor disturbance. Radiotherapy was performed in 10 cases and transcatheter arterial embolization or surgery was performed in 4 cases. The pain or neurological symptoms improved with these therapies in all cases. Cumulative survival was 1 year in 74%, 2 years in 34%, and 3 years in 17%, respectively.     

肝细胞癌骨转移的临床特征及预后因素

目的 分析原发性肝细胞癌(以下简称肝癌)骨转移患者的临床特征及预后因素,以期为临床制定合适的放疗策略提供依据.方法 收集接受外照射治疗的肝癌骨转移患者205例,对其一般资料、实验室指标、肿瘤特性(原发灶及骨转移灶)及治疗措施进行回顾性分析.放射剂量范围为32 ～ 60 Gy,中位剂量50 Gy,照射区为骨转移灶区域.用Kaplan-Meier法进行生存分析,单因素分析用Log-rank方法,多因素分析采用Cox回归模型Backward-Wald法.结果 205例肝癌骨转移患者中位生存时间为7.4月,有80例(39.0％)骨转移灶周围伴有软组织肿块.发现在照射剂量32 -66 Gy范围内,其剂量与效应之间并不呈正相关.单因素分析发现较短的生存率和以下几方面有关:较低的Karnofsky评分、白蛋白水平,较高的骨转移时ALP水平、γ-GT水平、AFP水平、肝内肿瘤＞5 cm、肝内原发灶未控、多发骨转移灶等.多因素分析发现,较低的Kamofsky评分、骨转移时较高的AFP水平、AST水平、血小板计数、肝内原发灶未控制、前5年的治疗诸因素均为独立预后因子(P值均＜0.05).结论 本研究提供了有关肝癌骨转移患者的临床特征、生存结果、预后因素,这些预后因素将有助于制定合适的针对这类患者的放疗策略.     

Radiofrequency ablation for hepatocellular carcinoma and liver metastases

We evaluated the efficacy of radiofrequency ablation (RFA) therapy for 29 patients with 36 hepatocellular carcinoma (HCC) nodules and 16 patients with 38 metastatic hepatic nodules. The mean tumor size was 26.4 mm. The primary lesions of patients with metastatic liver tumors were 9 colon cancer, 2 rectal cancer, 2 breast cancer, 2 gastric cancer, and 1 esophageal cancer. All nodules were treated using a Cool-tip RFA system. US-guided RFA was performed for 44 nodules, CT-guided RFA for 24 nodules, and intra-operative US-guided RFA for 6 nodules. In a mean observation period of 13.5 months, the mean complete ablation rate and the mean distant recurrence rate were 83.3% and 30.6% for HCC and 65.8% and 31.6% for metastatic nodules, respectively. The mean complete ablation rate of HCC was significantly higher than that of metastatic nodules (p < 0.05). The mean complete ablation rates of both HCC and metastatic hepatic nodules 3 cm or smaller in diameter were significantly higher than those of both tumors larger than 3 cm in diameter (p < 0.05). The mean distant recurrence rate of HCC in patients who have multiple nodules was 62.5% and it was significantly higher than that in patients who have a single nodule (28.6%) (p < 0.05). The mean complete ablation rate of metastatic nodules by intra-operative US guided RFA was 100% and it was statistically higher than that by other image guided RFA (p < 0.05).     

PTHrP and breast cancer: more than hypercalcemia and bone metastases

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in cancer patients. PTHrP is required for normal breast development and has been shown to promote bone metastases from breast cancers. However, whether the protein also contributes to the formation of primary tumors has been unclear. Two recent papers suggest it may. First, a report in Nature Genetics identified the PTHrP locus as a new breast cancer susceptibility gene. Second, a paper in Journal of Clinical Investigation demonstrated that PTHrP promotes tumor growth and metastases in MMTV-PyMT mice. These studies implicate PTHrP in the development and growth of primary breast tumors and underscore the need for further research.     

A retrospective study of radiotherapy for spinal bone metastases from hepatocellular carcinoma (HCC)

OBJECTIVE: To evaluate the therapeutic effects of radiotherapy on spinal bone metastases from hepatocellular carcinoma (HCC). METHODS: A retrospective review was conducted on 24 ambulatory patients with spinal bone metastases from HCC treated by radiotherapy from 1995 to 2004. Ambulatory rate and local progression-free rate after radiotherapy were analyzed. Eight (33%) of 24 patients had radiographic spinal cord compression from the spinal bone metastases before the treatment. Two (8.3%) of the 24 patients had some spinal deficits before the treatment. Biological equivalent dose (BED) with alpha/beta ratios of 10 ranged from 39 to 50.7 Gy (median 44.8 Gy). RESULTS: The median observation period was 5.1 months ranging from 0.9 to 36.0 months. Among the 24 patients, five (21%) underwent salvage therapies, while of the remaining 19 patients four (21%) became nonambulatory by the last follow-up. The ambulatory rates at 3 months and 6 months were 85 and 63%, respectively. The local progression-free rates at 3 months and 6 months were 53 and 47%, respectively. CONCLUSIONS: Radiotherapy with a BED of 39-50.7 Gy (median 44.8 Gy) is not sufficiently effective for the patients with spinal bone metastases from HCC to prevent paralysis. Dose escalation with a highly precise radiation technique will need to be evaluated.     

8例肝癌脑转移病例分析

目的探讨肝癌脑转移病例的临床特点和治疗方法。方法回顾性分析1994年1月一2008年6月我院收治原发性肝癌发生脑转移患者的临床特点、治疗方法及生存期。结果本组共8例肝癌脑转移病例,其中7例为男性,中位发病年龄为50．0岁。5例患者有慢性乙型肝炎、肝硬化病史。患者血中甲胎蛋白含量7例〉1000ng／ml,并且2例〉10000ng／ml。头痛是最常见的首发症状（4／8）,3例患者出现头晕、轻偏瘫、感觉障碍,2例出现复视、意识障碍,1例出现构音障碍,6例患者同时伴有至少2种症状,5例患者同时伴有肺转移,4例患者在2个月内死亡。结论肝癌脑转移患者预后很差,其治疗模式有待积极探索。     

Radiotherapy for adrenal gland metastases from hepatocellular carcinoma

Background

Several studies have found benefits of radiotherapy for adrenal metastasis from hepatocellular carcinoma (HCC). However, the efficacy, safety and outcome issues have not yet been fully addressed. Therefore, we performed this study to further elucidate the feasibility and outcome of radiotherapy in treating adrenal metastasis from HCC.

Methods

We retrospectively analyzed 81 patients with adrenal metastasis from HCC between 2001 and 2015. Eighteen patients received helical tomotherapy and 63 patients received conventional radiotherapy, including two-dimensional (2-D) or three-dimensional conformal radiotherapy (3-D CRT). The median radiation dose was 50 Gy (range 26–64 Gy) with median fraction size of 2.0 Gy (range 2.0–5.0 Gy). Tumor responses, adverse effects, patient outcomes and prognostic factors were analyzed.

Results

An objective response (complete and partial response) was achieved in 55.6% patients. The helical tomotherapy group showed higher objective response rate than the conventional radiotherapy group (P = 0.031). The major adverse effects were anorexia (51.8%), nausea (41.9%), and fatigue (35.8%). Similar toxicity profile occurred in the 2-D, 3-D CRT and helical tomotherapy groups. The overall survival (OS) rate at 1, 2 and 5 years was 59.9, 35.0, and 12.9%, respectively, with a median survival of 15 months. Patients who received helical tomotherapy achieved a better OS compared to the conventional radiotherapy group (P = 0.047). However, multivariate analysis indicated that radiotherapy technique was not an independent prognostic factor for patient outcome.

Conclusion

These results suggest that radiotherapy offers a noninvasive approach in controlling adrenal metastasis from HCC with promising local control and acceptable tolerability.

     

Stereotactic radiosurgery for brain metastases from hepatocellular carcinoma

The purpose of this study is to investigate the possible role of stereotactic radiosurgery (SRS) in the management of patients with brain metastases from hepatocellular carcinoma (HCC). Thirty-two consecutive patients with 80 brain metastases from HCC were treated with SRS. Twenty-eight (87.5 %) patients were male, and the mean age of the patients was 54 ± 12 years (range 22–73). Twenty-seven (84.4 %) patients were classified as RTOG RPA Class 2. The mean tumor volume was 6.14 ± 11.3 cm³ (range 0.01–67.3). The mean marginal dose prescribed was 20.1 ± 3.6 Gy (range 10.0–25.0). The median overall survival time after SRS was 11.3 ± 5.8 weeks (95 % CI 0–22.7). A greater total volume of brain metastases (>14 cm³) was the only independent prognostic factor (HR = 2.419; 95 % CI 1.040–5.624; p = 0.040). The actuarial control rate of brain metastases was 51.3 % at 4 months after SRS. The prescribed marginal dose (>18 Gy) was significantly related with the actuarial tumor control (HR = 0.254; 95 % CI 0.089–0.725; p = 0.010). The prognosis of patients with brain metastases from HCC is dismal even with the modern technology of radiosurgery. The marginal dose prescribed should be reevaluated to improve upon the current poor local control rates.     

Regional treatment of hepatic metastases and hepatocellular carcinoma

Hepatic metastases represent a common site of dissemination for a number of primary malignancies related in part to the dual blood supply, large blood flow, and receptive environment of the hepatic parenchyma. Although this review focuses on regional therapy, we have included sections on systemic therapy to better interpret the results with intrahepatic therapy. We will also discuss the efficiency of hepatic arterial ligation, embolization, and radiotherapy of hepatic metastases. Primary gastrointestinal neoplasms are particularly prone to produce hepatic metastases. Because colorectal carcinoma metastasizes to the liver in up to 70% of patients with advanced disease, the treatment of hepatic metastases is a relevant topic. We will discuss the systemic and regional therapy of colorectal, gastric, and gallbladder cancers. Breast carcinoma and malignant melanoma frequently metastasize to the liver, and we have described systemic and regional treatments of these diseases. Because sarcomas are often treated by regional therapy, we have included a section on the treatment of hepatic sarcomas. Neuroendocrine tumors (carcinoid and islet cell), although often slow growing, frequently metastasize to the liver and then cause symptomatic problems. Much of the work done with embolization and hepatic ligation in the treatment of hepatic metastases has been performed in neuroendocrine tumors, and these studies, as well as the systemic and regional chemotherapy of hepatic metastases, will be described. The last section concerns the treatment of hepatocellular carcinoma. We have outlined the staging systems used. We then detail the results of systemic and intrahepatic therapy, embolization, and hepatic ligation in the treatment of hepatocellular carcinoma. Because hepatic metastases are a frequent problem, many patients are available for clinical investigation. It is hoped that newer strategies for the treatment of liver metastases will lead to higher response rates and perhaps control of local disease. These therapeutic approaches may also give us leads to the treatment of systemic disease.     

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.     

肝细胞肝癌肾上腺转移的放射治疗

目的探讨肝癌肾上腺转移的放射治疗效果.方法回顾性总结本院22例肝癌肾上腺转移病人,用6MX或15MV光子,进行肾上腺病灶外照射,剂量36～54Gy,中位剂量50Gy.结果14例肾上腺转移病人出现疼痛症状,外放疗后11例(78.6%)疼痛得到完全缓解;2例(14.3%)得到明显缓解,但仍需要止痛药治疗;73%(15/22)病例的肿瘤明显缩小;全部病例中位生存期为10个月;未出现因肾上腺转移灶致死病例;副作用轻微.结论肝细胞肝癌肾上腺转移对放射治疗敏感,50Gy的放疗剂量是比较安全的姑息性治疗.     

Radiation therapy for bone metastasis of hepatocellular carcinoma

Background The efficacy of radiation therapy for bone metastasis of hepatocellular carcinoma was examined retrospectively. Methods The effect of radiation therapy for pain and paresis was evaluated in 38 patients who received planned radiation therapy with the total dose ranging from 26 to 60 Gy. The percentage regression of 14 metastatic bone lesions was calculated by using computed tomography: percentage regression=[(pre-radiation therapy tumor volume—postradiation therapy tumor volume)/pre-radiation therapy tumor volume]×100. Results The 1-, 2-, and 5-year survival rates of the 38 patients from the start of the radiation therapy were 30% 18%, and 9.0% respectively. The median survival period was 172 days. Pain relief was obtained in 91% of 44 painful bone metastases. No correlation was observed between the percentage regression and the tumor size. Complete regression of bone metastasis was noted in 6 of 14 patients who could be evaluated with computed tomography. Three of the 6 paiients with complete response have survived for more than 6 years after radiation therapy. Conclusion Radiation therapy is an effective method for palliation of bone metastasis. Although the prognosis of most patients with bone metastasis from hepatocellular carcinoma is poor, some attain longterm survival after treatment.