肝部肿瘤三维立体定向适形放疗计划设计探讨

 目的 探讨肝部肿瘤的三维适形放射治疗计划设计。方法 对50例肝部原发及转移性肿瘤患者，根据医师要求的CTV和周围正常的敏感器官限制受量设计三维适形放射治疗计划，结合剂量-体积直方图选择最佳方案。结果 以ICRU剂量参考点（肿瘤中心点剂量）剂量归一，80 % ~ 90 %剂量线均能包绕90 %以上的PTV。90 %剂量线包绕PTV的程度和靶区的大小及所在部位有关。结论 肝部肿瘤的治疗计划设计时，对位于不同部位的病灶采用不同的设计；正常肝组织的受照体积的大小和受照剂量直接影响着患者的放射治疗反应，同时对处方剂量、剂量分割方式的选择有重要影响。     

胃肠间质瘤肝转移的临床特征及生存分析

目的 探讨胃肠间质瘤（GIST）肝转移患者的临床病理特征和预后因素。方法 回顾性分析2002年1月至2014年1月入组的复发或转移性GIST共138例患者,其中肝转移者74例。根据治疗前病灶部位将全组病例分为单纯肝转移组34例、腹盆腔转移组64例和肝腹盆腔转移组40例。均给予伊马替尼起始剂量400 mg／d口服。用Logistic回归分析近期疗效相关因素,生存分析用Kaplan-Meier法,预后多因素分析用Cox回归模型。结果 135例可评价近期疗效。74例肝转移患者中,CR 11例,PR 41例,SD 18例,PD 4例,有效率（RR）为70.3％,疾病控制率（DCR）为 94.6％。3组RR、DCR的差异均无统计学意义（P＞0.05）。Logistic回归分析显示,是否伴同时性肝转移是影响RR的独立因素。全组患者的中位无进展生存期（PFS）为52个月,中位总生存期（OS）为66个月,1、2、3和5年生存率分别为97.0％、89.6％、82.3％和60.0％。肝转移患者的中位PFS为45个月,中位OS为68个月,1、2、3和5年生存率分别为97.2％、92.5％、87.4％和59.2％。单纯肝转移组、腹盆腔转移组和肝腹盆腔转移组的中位PFS分别为61、56和30个月,中位OS分别为75、65和63个月。是否合并其他部位转移和近期疗效是影响PFS的独立因素,是否合并其他部位转移和年龄是影响其OS的独立因素。3组患者的主要不良反应为水肿、白细胞减少和腹泻,多为1～2级,3组不良反应发生率的差异均无统计学意义（P＞0.05）。结论 肝转移并未影响伊马替尼治疗晚期GIST的近期疗效,肝外病灶、年龄和近期疗效是影响GIST肝转移患者远期生存的重要因素。     

Malignant hepatic vascular tumors in adults: Characteristics,diagnostic difficulties and current management

Malignant vascular tumors of the liver include rare primary hepatic mesenchymal tumors developed in the background of a normal liver parenchyma. Most of them are detected incidentally by the increased use of performing imaging techniques. Their diagnosis is challenging, involving clinical and imaging criteria, with final confirmation by histology and immunohistochemistry. Surgery represents the mainstay of treatment. Liver transplantation (LT) has improved substantially the prognosis of hepatic epithelioid hemangioendothelioma (HEHE), with 5-year patient survival rates of up to 81%, based on the European Liver Intestine Transplantation Association-European Liver Transplant Registry study. Unfortunately, the results of surgery and LT are dismal in cases of hepatic angiosarcoma (HAS). Due to the disappointing results of very short survival periods of approximately 6-7 mo after LT, because of tumor recurrence and rapid progression of the disease, HAS is considered an absolute contraindication to LT. Recurrences after surgical resection are high in cases of HEHE and invariably present in cases of HAS. The discovery of reliable prognostic markers and the elaboration of prognostic scores following LT are needed to provide the best therapeutic choice for each patient. Studies on a few patients have demonstrated the stabilization of the disease in a proportion of patients with hepatic vascular tumors using novel targeted antiangiogenic agents, cytokines or immunotherapy. These new approaches, alone or in combination with other therapeutic modalities, such as surgery and classical chemotherapy, need further investigation to assess their role in prolonging patient survival. Personalized therapeutic algorithms according to the histopathological features, behavior, molecular biology and genetics of the tumors should be elaborated in the near future for the management of patients diagnosed with primary malignant vascular tumors of the liver.     

Palliation of colorectal cancer

Patients with advanced incurable colorectal cancer (CRC) face a grim prognosis. The goal of palliative intervention is directed at alleviating disease-related symptoms and improving quality of life. The provision of optimal palliative care for these patients is a compound and demanding process. This dilemma becomes more challenging when patients with advanced metastatic colorectal disease present with an incurable and asymptomatic primary lesion. Treatment options are numerous and include a variety of surgical and nonsurgical interventions. Most data regarding the role of surgery in palliation of CRC are from retrospective, nonrandomized case series. Surgical resection may provide good palliation of symptoms and prevent future tumor-related complications. Metal stents are also able to provide good palliative relief of obstruction and should be used when appropriate. The best palliative care will often require a multidisciplinary approach that involves input from surgical and nonsurgical teams, where treatment plans will be made in accordance with the wishes of the patient and family with a goal of decreasing morbidity and a focus on quality of life.     

18F-FDG PET/CT显像在肝脏恶性肿瘤的初步应用

目的：评价^18F-FDGPET／CT对于肝脏恶性肿瘤的诊断、分期及疗效评判的价值。方法：对55例肝脏恶性肿瘤患者的PET／CT检查资料进行回顾性分析。原发性肝细胞性肝癌（PHC）11例,胆管细胞性肝癌1例,转移性肝癌40例,白血病肝浸润1例,淋巴瘤肝浸润2例。其中原发性肝癌经手术或穿刺证实,继发性肝脏恶性肿瘤均有明确肿瘤病史或临床检查随访证实。所有患者均行双时相全身PET／CT显像检查。结果：低分化PHC4例及胆管细胞癌1例,^18F—FDG异常高摄取,延迟后大部分病灶^18F—FDG摄取SUVmax上升;高分化原发性肝癌7例,其中^18F-FDG等摄取5例,相对肝本底为略低摄取2例;9例PHC及1例胆管细胞癌CT表现为低密度灶,2例PHC为等密度,7例患者有肝炎肝硬化基础,另外同时发现肝外病灶6例。继发性肝脏恶性肿瘤43例（含淋巴瘤、白血病肝浸润）中PET／CT上共发现109个病灶;其中99个肝内病灶表现为^18F-FDG高摄取,31个病灶CT未显示,另外有2例患者有4个病灶经手术证实有肝内微小病灶而PET／CT未检出;而淋巴瘤、白血病肝浸润表现为大片状或弥漫性^18F—FDG明显异常高摄取;大部分患者改变了原有的治疗方案。结论：^18F-FDGPET／CT在肝脏恶性肿瘤诊断、分期、评价分化程度及治疗方案的选择有较好的临床价值,PET／CT诊断肝脏恶性肿瘤明显优于单纯PET。充分认识PET／CT在肝脏恶性肿瘤中的应用价值及局限性,有利于临床对肝脏恶性肿瘤的诊治。     

Shades of Gray: A Personal View of Palliation by Radiotherapy*

Palliation is a significant part of the work of a radiation oncologist and yet is discussed infrequently. All too often it is considered simple when in many cases the contrary is the case. The philosophy of palliation is discussed and is defined as non-curative treatment. Further sub-division into symptom control, growth restraint/local control is helpful. The aim of palliation must be clearly defined if it is to be achieved_? taking into account not only the lesion causing the problem but also many other factors including the patient's general condition, the clinical evolution of the tumour, previous treatment and social factors. The aim should be communicated to the patient and relatives. Doses for effective palliation vary from low to high and require different fractionation regimens. Examples are given from clinical practice with emphasis on difficult and controversial areas. There are as many diseases as patients and the need to individualise treatment is stressed.     

Erythropoietin/Erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors

Background To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors.Methods To induce hepatic tumors and cirrhosis, diaminobenzidine was administered to Wistar rats for 5 months. In total, 30 hepatic tumors of greater than 3mm in diameter were induced in 12 rats. The 30 hepatic tumors were resected with the surrounding hepatic tissues. The Epo content was measured by a radioimmunoassay (RIA) method. The number of tumor vessels in a definite area was counted in 100 areas of each tumor. To demonstrate the expression of Epo-R in tumors or surrounding liver tissues, immunohistochemial staining for Epo-R was performed.Results The Epo content of tumors ranged from 6.1 to 97.8mU/ml, with a median of 21.8mU/ml, which was significantly higher than that of the cirrhotic tissues adjacent to the tumors. Epo was not detectable in the normal or cirrhotic liver tissues without tumors. A significant correlation between Epo content and vascular density was noted in the 30 hepatic tumors (correlation coefficient, 0.480; P = 0.01). Immunoreactive Epo-R was detectable in the endothelium of intervening vessels of all hepatic tumors examined.Conclusion The Epo/Epo-R system is related to the angiogenesis of murine hepatic tumors.     

Yttrium-90 internal radiation therapy for hepatic malignancy

Surgical resection is the only potentially curative strategy in the treatment of patients with hepatic malignancy. Unfortunately, due to advanced stage, underlying liver disease, or medical comorbidities, most patients are inoperable at the time of presentation. As a result, various locoregional therapies have emerged for otherwise unresectable hepatic tumors. One such modality is Yttrium-90 (Y(90)) internal radiation therapy. Numerous studies demonstrate the safety and potential survival benefit of intra-arterial Y(90) for primary and metastatic liver tumors. However, more data is needed in order to understand the exact role of Y(90) in the algorithm of hepatic tumor management. This review presents the available literature on Y(90) with the aim of defining the current status of Y(90) in the armamentarium of therapeutic strategies for hepatic malignancy.     

Radioembolization of hepatic tumors

Unresectable primary and metastatic liver tumors are a leading cause of cancer mortality and morbidity. This remains a challenging and key task for every oncologist despite significant advances that have been made with selective targeted systemic agents and in technology advances with radiotherapy delivery. Radioembolization (RE) is a technique of permanently implanting microspheres containing Yttrium-90 (⁹⁰Y), a beta-emitting isotope with a treatment range of 2 mm, into hepatic tumors. This form of brachytherapy utilizes the unique dual vascular anatomy of the liver to preferentially deliver radioactive particles via the hepatic artery to tumor, sparing normal liver parenchyma. The main treatment inclusion criteria are patients with solid tumors, compensated liver functions, life expectancy of at least three months, and ECOG performance status 0-2. Benefit of RE has been proven in patients that have low-to-moderate extrahepatic disease burden, prior liver radiotherapy, heavy prior chemotherapy and biologic agent exposure, and history of hepatic surgery or ablation. Most of the clinical evidence is reported in metastatic colorectal, and neuroendocrine tumors (NET), and primary hepatocellular cancer. A growing body of data supports the use of RE in hepatic metastatic breast cancer, intrahepatic cholangiocarinoma, and many other metastatic tumor types. Side effects are typically mild constitutional and GI issues limited to the first 7-14 days post treatment, with only 6% grade 3 toxicity reported in large series. Potentially serious or fatal radiation induced liver disease is extremely rare, reported in only 1% or fewer in major series of both metastatic and primary tumors treated with RE. Currently, high priority prospective clinical trials are testing RE combined with chemotherapy in first line therapy for colorectal hepatic metastases, and combined with sorafenib for hepatocellular carcinomas (HCCs). Fortunately, this beneficial and now widely available therapy is being increasingly incorporated into the standard therapy algorithms of multidisciplinary GI cancer teams worldwide. This form of radiotherapy differs significantly from daily external beam radiotherapy in many ways, particularly in dose rate, dosimetric coverage and duration of radiation delivery, side effects, and patient selection factors. A wealth of experience using RE in solid tumors exists and ongoing major prospective clinical trials will soon clarify the role of RE in the management of metastatic colorectal liver metastases.     

Palliation of hepatic metastasis.

Between 1971 and 1975, 55 patients underwent palliative radiation therapy for symptomatic hepatic metastasis. Most patients received 2400 rad in 300 rad fractions to the entire liver. There were 31 patients who received concomitant chemotherapy, and 14 who were prior chemotherapy failures. Ninety percent of the patients with symptomatic pain and liver enlargement and significant palliation of their symptoms. The median survival of the entire group was 4.5 months, while those patients experiencing an excellent response (21) had a median survival of 9 months. The median survival of patients having an excellent response to radiation is comparable to that of patients having regional arterial chemotherapy while incuring fewer complications. The overall complication rate of those patients completing therapy (50) was 12%.     

Isolated hepatic perfusion chemotherapy for unresectable malignant hepatic tumors

Treatment failure with conventional approaches, including systemic and regional chemotherapy, for refractory advanced primary or metastatic hepatic cancers has evoked periodic waves of enthusiasm for isolated hepatic perfusion (IHP) over the past 50 years. With technical refinements of the procedure and the introduction of a novel biochemical regimen combining tumor necrosis factor and melphalan, several hepatobiliary-oncological centers initiated clinical trials of IHP in the 1990s. In parallel, a percutaneous technique of IHP has been developed in this era as a minimally invasive, simple form of IHP, and phase I and II studies have been done in some specialized centers. This study attempts to review past and current techniques of IHP, and to outline their possible role in the treatment of unresectable hepatic tumors, with special reference to hepatocellular carcinoma and colorectal hepatic metastases. Received: January 10, 2002     

Surgery for hepatic neuroendocrine tumors: a single institutional experience in Japan

BACKGROUND: Surgical resection has been advocated as an effective treatment for hepatic neuroendocrine tumors (HNETs) in Western countries, but few data are available to define its indications. We evaluated the results of Japanese patients to determine the prognostic factors and the feasibility of our aggressive surgical approach. METHODS: The records of all consecutive patients who underwent surgical resection for HNETs at our institution were retrospectively reviewed. Patients were selected for surgery if all tumors were deemed resectable, regardless of their extent. RESULTS: A total of 21 patients were identified. Bilobar disease was present in 13 patients (62%). Eleven patients (52%) underwent major hepatectomy, which included right trisectionectomy, extended right or left hepatectomy and right hepatectomy. No in-hospital death occurred. The overall 1-, 3- and 5-year survival rates were 95, 68 and 41%, respectively, with a median follow-up of 34 months. Metastatic HNETs from bronchopulmonary primaries exhibited significantly poor outcome compared with other primary sites (P = 0.04). Patients who underwent curative resection had an improved overall 5-year survival rate of 73% compared with palliative resection (0%, P = 0.01). The longest survival in the latter group was 57 months. Complete symptom resolution rate was 92%. CONCLUSIONS: This is the first study from Asia demonstrating the safety of aggressive hepatic resection for HNETs. Significant symptom relief and long-term survival were achieved irrespective of the extent of disease or the magnitude of operation. Metastatic HNETs from bronchopulmonary primaries may represent a more lethal subset of tumors.     

胃肠道间质瘤肝转移治疗进展

胃肠道问质瘤(GIST)常见的转移器官是肝脏。GIST肝转移以外科治疗为主,术后3年、5年生存率分别可达58%和30%以上。生物靶向制剂治疗以伊马替尼为代表,但有部分患者耐药。其他靶向治疗药物如SU11248、RAD001、AMG706正在临床试验中,以解决伊马替尼耐药问题。伊马替尼新辅助和辅助治疗试验仍在进行中。介入治疗对GIST肝转移为有效的姑息疗法,肝移植也有一定效果。总之,外科联合生物治疗有望成为GIST肝转移个体化治疗的突破。     

胃肠道间质瘤肝转移治疗进展

胃肠道间质瘤（GIST）常见的转移器官是肝脏。GIST肝转移以外科治疗为主,术后3年、5年生存率分别可达58％和30％以上。生物靶向制剂治疗以伊马替尼为代表,但有部分患者耐药。其他靶向治疗药物如SU11248、RAD001、AMGT06正在临床试验中,以解决伊马替尼耐药问题。伊马替尼新辅助和辅助治疗试验仍在进行中。介入治疗对GIST肝转移为有效的姑息疗法,肝移植也有一定效果。总之,外科联合生物治疗有望成为GIST肝转移个体化治疗的突破。     

Short-Course External Beam Radiotherapy Versus Brachytherapy for Palliation of Dysphagia in Esophageal Cancer: A Matched Comparison of Two Prospective Trials

IntroductionShort-course external beam radiotherapy (EBRT) and intraluminal brachytherapy are both accepted treatments for the palliation of dysphagia in patients with incurable esophageal cancer. We compared the effects of both treatments from two prospective studies.MethodsWe performed a multicenter prospective cohort study of patients with metastasized or otherwise incurable esophageal cancer requiring palliation of dysphagia from September 2016 to March 2019. Patients were treated with EBRT in five fractions of 4 Gy. Data were compared with all patients treated with a single brachytherapy dose of 12 Gy in the SIREC (Stent or Intraluminal Radiotherapy for inoperable Esophageal Cancer) trial, both between the original cohorts and between 1:1 propensity score–matched cohorts. The primary end point was an improvement of dysphagia at 3 months without reintervention. The secondary end points included toxicity and time-to-effect.ResultsA total of 115 patients treated with EBRT and 93 patients who underwent brachytherapy were eligible for analysis. In the original cohorts, dysphagia improved after EBRT in 79% of patients compared with 64% after brachytherapy (p = 0.058). Propensity score matching resulted in 69 patients in each cohort well-balanced at baseline. Improvement of dysphagia was observed in 83% after EBRT versus 64% after brachytherapy (p = 0.048). In responding patients, improvement of dysphagia at 2 weeks was observed in 67% after EBRT compared with 35% after brachytherapy, and the maximum effect was reached after 4 weeks in 55% and 33%, respectively. Severe toxicity occurred in 3% of patients after EBRT compared with 13% after brachytherapy.ConclusionsShort-course EBRT appears at least as effective as brachytherapy in the palliation of dysphagia in patients with esophageal cancer.     

肝脏转移性间质瘤的MSCT诊断分析

目的 探讨MSCT对肝脏转移性间质瘤的诊断价值.方法 回顾性分析18例经临床及病理证实的肝脏转移性间质瘤的MSCT资料.结果 18例中,原发灶位于食管下段1例,胃8例,小肠7例,肠系膜1例,腹膜后1例;其中多发16例,单发2例;15例为囊实性,壁厚薄不均,3例为实性;肿瘤呈圆形或类圆形,最大径8～150mm;平扫17例呈不均匀较低密度,边界相对较清晰,1例出现不均匀钙化;增强强化不均匀,9例明显强化,7例中等强化,2例轻度强化;15例囊实性肿瘤中央可见未强化坏死区.结论 肝脏转移性间质瘤常多发,大小不等,边界相对清晰,少有钙化;多数肿瘤内部可见低密度坏死囊变区,增强以明显强化或中等强化多见,MSCT对其诊断具有重要价值.     

Effects of Dexamethasone and Placebo on Symptom Clusters in Advanced Cancer Patients: A Preliminary Report

Objective.

Advanced cancer patients frequently experience debilitating symptoms that occur in clusters, but few pharmacological studies have targeted symptom clusters. Our objective was to examine the effects of dexamethasone on symptom clusters in patients with advanced cancer.

Methods.

We reviewed the data from a previous randomized clinical trial to determine the effects of dexamethasone on cancer symptoms. Symptom clusters were identified according to baseline symptoms by using principal component analysis. Correlations and change in the severity of symptom clusters were analyzed after study treatment.

Results.

A total of 114 participants were included in this study. Three clusters were identified: fatigue/anorexia-cachexia/depression (FAD), sleep/anxiety/drowsiness (SAD), and pain/dyspnea (PD). Changes in severity of FAD and PD significantly correlated over time (at baseline, day 8, and day 15). The FAD cluster was associated with significant improvement in severity at day 8 and day 15, whereas no significant change was observed with the SAD cluster or PD cluster after dexamethasone treatment.

Conclusion.

The results of this preliminary study suggest significant correlation over time and improvement in the FAD cluster at day 8 and day 15 after treatment with dexamethasone. These findings suggest that fatigue, anorexia-cachexia, and depression may share a common pathophysiologic basis. Further studies are needed to investigate this cluster and target anti-inflammatory therapies.

Implications for Practice:

Results of this preliminary study suggest that fatigue-anorexia/cachexia/depression cluster scores significantly improved in the dexamethasone treatment group as compared with placebo. These findings indicate that symptoms in the fatigue/anorexia-cachexia/depression cluster might share a common causative mechanism. Further studies are needed to validate these findings.