Arteriovenous shunting in patients with colorectal liver metastases

The outlook for patients with colorectal liver metastases is poor. Microspheres have been combined with cytotoxics and administered via the hepatic artery in an attempt to improve tumour drug exposure within the liver. However, it has been suggested that arteriovenous connections might occur in association with intrahepatic tumours causing loss of regional advantage, and that the administration of microspheres further exacerbates arteriovenous shunting. In seven patients with colorectal liver metastases, base-line shunting was measured using a tracer quantity of radio-labelled albumin microspheres. The shunted fraction of a 'therapeutic quantity' of microspheres was subsequently measured in the same group of patients using albumin microspheres carrying a different radio-label. Base-line shunt for 0.5 x 10(6) microspheres was found to be 2.2 +/- 1.8% (mean +/- s.d.); the percentage shunt of a therapeutic quantity (40-80 x 10(6)) of microspheres was 3.0 +/- 0.8%. We conclude that arteriovenous shunting in patients with colorectal liver metastases is minimal, and is not significantly increased by the administration of therapeutic quantity of microspheres during regional chemotherapy.     

Clinical and imaging experience with yttrium-90 microspheres in the management of unresectable liver tumours.

INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new therapeutic modality in recent years for management of non-resectable hepatic malignancies. Our experience in clinical application of this treatment is reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours were no longer amenable for any conventional treatment with either chemotherapy or surgery were considered for yttrium-90 microspheres treatment after discussion at our multidisciplinary meeting. A pre-treatment planning was carried out with visceral angiography and technetium-99m macroaggregated albumin (MAA) for assessment of both tumour volume and extrahepatic shunting in addition to a baseline PET and CT scans, respectively. Two weeks later, a second visceral angiogram was performed to deliver the calculated dosage of microspheres into the arterial system supplying the tumour. Patients were then followed up with tumour markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter. RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years) received yttrium-90 microspheres consisting of liver metastases from colorectal primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours (n=3). One patient received 2 treatments. The mean administered activity of microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres had no immediate effect on either clinical haematology or liver function tests. At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment SUV was 9.3+/-3.7, indicating a significant improvement measured with PET activity. Only 13% showed a reduction in the size of tumour on CT scan. For patients with colorectal liver metastases, there was no significant reduction in CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4 patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and duodenal ulceration (n=1). All resolved without surgical intervention. Seven patients died at follow-up from progressive extrahepatic disease (33%). CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It has a significant effect on liver disease in the absence of extrahepatic disease. PET imaging has an integral role in the assessment of patients treated with yttrium-90 SIR-Spheres.     

High level of Nm23-H1 gene expression is associated with local colorectal cancer progression not with metastases.

This study aimed to determine the expression of Nm23-H1 in colorectal cancer and liver metastases and to correlate Nm23-H1 expression with clinicopathological variables. Specimens from 59 primary colorectal cancers and five liver metastases were studied using Northern blot hybridisation. The mean +/- s.e. of tumour/normal (T/N) ratio of Nm23-H1 RNA expression was 4.3 +/- 0.4 (P < 0.001) and 5.1 +/- 0.90 (P < 0.01) for colorectal cancer and liver metastases respectively. No significant relationship was observed between the level of Nm23-H1 RNA and the patient''s age, sex, tumour location, differentiation, presence of lymph node involvement or distant metastases. Nm23-H1 RNA level was 2.6 +/- 0.5 for tumour size less than 3.0 cm and 4.6 +/- 0.5 for those > or = 3.0 cm (P = 0.05). There appeared to be a trend between increasing relative Nm23-H1 RNA and bowel wall invasion, irrespective of metastatic status (T1 = 1.9 +/- 0.3, T2 = 4.1 +/- 0.6, T3 = 4.1 +/- 0.5 and T4 = 6.4 +/- 1.6). This difference was statistically significant when T1 was compared against > or = T2 lesions (P = 0.01). Western blot analysis reveals two Nm23H-1 bands (17.0 kDa and 18.5 kDa). In 16 colorectal patients, the T/N fold-increase in protein expression was 2.66 +/- 0.46 (P < 0.001) and 2.40 +/- 0.32 (P < 0.001) for the 17.0 and 18.5 kDa band respectively. Both Nm23-H1 RNA and protein levels in primary colorectal cancers do not appear to correlate with synchronous regional or distant metastases. Since Nm23-H1 RNA expression is associated with increasing tumour size and tumour local invasion, Nm23-H1 RNA expression may be associated with local disease progression.     

Three-dimensional conformal radiotherapy for portal vein thrombosis of hepatocellular carcinoma

BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with advanced-stage hepatocellular carcinoma (HCC). The authors evaluated the impact of radiotherapy (RT) for PVT of HCC and analyzed the dose-response relation between RT and PVT. METHODS: Between March 1995 and December 2003, 59 patients diagnosed as HCC with PVT were included. The inclusion criteria were unresectable tumor with thrombosis in the main or first branch of the portal vein, liver function of Child-Pugh Class A or B, and an Eastern Cooperative Oncology Group performance status score of 0-2. The median age of the patients was 57 years (range, 36-78 years). A daily dose ranging from 2 to 3 gray (Gy) was administered using 6 or 10-megavolt (MV) X-rays, at 5 fractions a week, to deliver a total dose range of 30-54 Gy, which was a biologic effective dose of 39-70.2 Gy(10) with an alpha/beta ratio of 10. RESULTS: Follow-up computed tomography scans showed a complete response (CR) in 4 of 59 patients (6.8%), a partial response (PR) in 23 patients (39.0%), no response (NR) in 28 patients (47.5%), and progressive disease (PD) in 4 patients (6.8%). The mean RT doses in the responders (CR and PR) and nonresponders (NR and PD) were 59.6 +/- 5.6 Gy(10) and 54.9 +/- 8.5 Gy(10), respectively (P = 0.036). The response rates in patients receiving < 58 Gy(10) and > or = 58 Gy(10) were 20% and 54.6%, respectively (P = 0.034). The median survival duration and the 1-year and 2-year survival rates in the responders were 10.7 months, 40.7%, and 20.7%, respectively, and were 5.3 months, 25.0%, and 4.7%, respectively, in the nonresponders (P = 0.050). CONCLUSIONS: RT induced a 45.8% objective response rate for PVT in patients with HCC. A dose-response relation was found to exist between the RT dose and PVT response. These results suggested that RT may be a treatment option for PVT in patients with HCC and that an RT dose > or = 58 Gy(10) should be recommended.     

Local radiotherapy for patients with unresectable hepatocellular carcinoma

PURPOSE: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. METHODS AND MATERIALS: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy(10) using the alpha/beta ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. RESULTS: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy(10) had a significant response; CR or PR was 72.8% with >50 Gy(10) and 46.7% with < or =50 Gy(10) (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. CONCLUSIONS: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC.     

Glass yttrium-90 microspheres for patients with colorectal liver metastases.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).     

MR加速器在肝脏肿瘤放疗中的临床应用北大核心CSCD

目的初步探讨MR加速器在肝脏肿瘤中的应用流程、疗效及安全性。方法回顾性分析2019—2021年15例采用MR加速器治疗的肝脏肿瘤患者的临床数据, 探讨肝脏肿瘤采用MR加速器治疗的流程, 分析患者肿瘤的图像识别率、疗效及不良反应。结果全组15例患者中肝细胞癌6例、结直肠癌肝转移8例、乳腺癌肝转移1例;肝内1个病灶10例、2个病灶4例、3个病灶1例;中位肿瘤最长径2.4 cm (0.8~9.8 cm)。MR加速器大体肿瘤体积(GTV)识别率达13/15, 2例患者GTV显示不清, 采用肿瘤周边大血管或胆管识别辅助仍可达精准配准。全组患者均接受体部立体定向放疗。肝细胞癌患者中位分割次数9次(5~10次), GTV或计划靶体积(PGTV)中位单次剂量6 Gy (5~10 Gy), 中位总剂量52 Gy (50~54 Gy), α/β=10的中位2 Gy等效剂量(EQD2Gy)为72 Gy (62.5~83.3 Gy)。肝转移瘤患者中位分割次数10次(5~10次), GTV或PGTV的中位单次剂量5 Gy (5~10 Gy), 中位总剂量50 Gy (40~50 Gy), α/β=5的中位EQD2Gy为71.4 Gy (71.4~107.1 Gy)。放疗后1个月野内总有效率8/13, 疾病控制率13/13, 放疗后3~6个月野内总有效率6/6。全组患者中位随访4.0个月(0.3~11.6个月), 4个月局部无进展生存、无进展生存和总生存分别为15/15、11/15和15/15。放疗不良反应轻微, 未见≥3级不良反应。结论 MR加速器对肝内肿瘤显示率高, 且可通过周边大血管或胆管的显示辅助精准配准, 在肝脏肿瘤的精准治疗上初步展现优势, 局部疗效肯定, 耐受性好。     

Dose-response relationship for radiation therapy of recurrent, residual, and primarily inoperable colorectal cancer

One hundred and thirteen patients with advanced locoregional recurrent (77), residual (18) or primarily inoperable (18) colorectal carcinoma were treated with radiotherapy. Eighty-five patients had locoregional disease only and 28 had both local disease and distant metastases. The treatment was given with varying dose levels (23-73 Gy) in daily fractions of approximately 2 Gy in 3-8 weeks. This dose variation allowed an evaluation of the dose-response relationship for radiation treatment of this tumour. A good subjective response was obtained in 63%. This effect showed no dose-response relationship except for doses greater than or equal to 56 Gy, where all patients received relief of symptoms. Eighty-two per cent of evaluable patients achieved an objective response (PR 53%, CR 29%). The frequency and duration of the complete responses showed a marked dose-response relationship. Thus, at doses greater than or equal to 56 Gy, a 2-year actuarial complete response rate of 40% was found compared with 7, 4 and 0% at doses of 46-55 Gy, 36-45 Gy and less than or equal to 35 Gy, respectively. The dose-response relationship for local control also influenced the survival rate, although a number of patients died from distant metastases even when local control was obtained. However, with regard to locoregional disease, the 2-year survival was 53% for patients with complete tumour regression but only 8% for patients without complete tumour regression.     

Increased endothelin-1 in colorectal cancer and reduction of tumour growth by ET(A) receptor antagonism.

Endothelin-1 (ET-1) is a vasoconstrictor peptide which stimulates proliferation in vitro in different cell types, including colorectal cancer cells. Raised ET-1 levels have been detected both on tissue specimens and in the plasma of patients with cancers. To investigate the role of ET-1 in colorectal cancer: (i) ET-1 plasma levels in patients with colorectal cancer were measured by radioimmunoassay: group 1 = controls (n = 22), group 2 = primary colorectal cancer only (n = 39), group 3 = liver metastases only (n = 26); (ii) ET-1 expression in primary colorectal cancer specimens (n =10) was determined immunohistochemically and (iii) the effect of intraportally infused antagonists to the two ET-1 receptors, ET(A) and ET(B), on the growth of liver metastases in a rat model was assessed. ET-1 plasma levels were significantly increased in both patients with primary tumour and patients with metastases, compared to controls (P < 0.01, 3.9 +/- 1.4, 4.5 +/- 1.5, vs. 2.75 +/- 1.37 pg/ml, respectively). Immunohistochemically, strong expression of ET-1 was found in the cytoplasm, stroma and blood vessels of cancers, unlike the normal colon where only the apical layer of the epithelium, vascular endothelial cells and surrounding stroma were positively stained. In the rat model, there was significant reduction in liver tumour weights compared to controls, following treatment with the ET(A) antagonist (BQ123) 30 min after the intraportal inoculation of tumour cells (P < 0.05). These results suggest ET-1 is produced by colorectal cancers and may play a role in the growth of colorectal cancer acting through ET(A) receptors. ET(A) antagonists are indicated as potential anti-cancer agents.     

三维适形放疗结合TACE在结直肠癌患者根治术后肝转移的临床应用

目的：探讨对于不宜或不能手术治疗的结直肠癌肝转移灶行TACE后根治性三维适形放射治疗的可行性,不良反应及疗效。方法：对20例结直肠癌根治术后出现肝转移灶的病人,行TACE（ADM＋碘油）后3周内,针对其肝转移灶行三维适形放疗,常规分割2Gy,总剂量60—66Gy。结果：4例（20％）患者出现Ⅲ度恶心呕吐,3例（15％）出现Ⅲ度中性粒细胞减少,1例（5％）出现Ⅲ度血小板减少,4例（20％）出现Ⅲ度肝功能异常。治疗结束后,4例（20％）CR,11例（55％）PR,5例（25％）SD,无1例进展,有效率为75％。结论：对于结直肠癌根治术后出现不宜或不能手术的肝转移癌,应用三维适形放疗结合TACE的治疗模式,是可行的,无严重不良反应,近期疗效显著。     

A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases

PURPOSE: To determine the maximum tolerated dose (MTD) of stereotactic body radiation therapy (SBRT) for liver metastases. METHODS AND MATERIALS: A multicenter Phase I clinical trial was conducted. Eligible patients had one to three liver metastases, tumor diameter <6 cm, and adequate liver function. The first cohort received 36 Gy to the planning target volume (PTV) in three fractions (F). Subsequent cohorts received higher doses up to a chosen maximum of 60 Gy/3F. At least 700 mL of normal liver had to receive a total dose <15 Gy. Dose-limiting toxicity (DLT) included acute Grade 3 liver or intestinal toxicity or any acute Grade 4 toxicity. The MTD was exceeded if 2/6 patients in a cohort experienced DLT. RESULTS: Eighteen patients were enrolled (10 male, 8 female): median age, 55 years (range, 26-83 years); most common primary site, colorectal (6 patients); median aggregate gross tumor volume, 18 ml (range, 3-98 ml). Four patients had multiple tumors. No patient experienced a DLT, and dose was escalated to 60 Gy/3F without reaching MTD. CONCLUSIONS: Biologically potent doses of SBRT are well tolerated in patients with limited liver metastases. Results of this study form the basis for an ongoing Phase II SBRT study of 60 Gy over three fractions for liver metastases.     

Whole-liver Radiotherapy Concurrent with Chemotherapy as a Palliative Treatment for Colorectal Patients with Massive and Multiple Liver Metastases: a Retrospective Study

The purpose of this study was to investigate whether whole-liver radiotherapy plus a tumor-boost dose withconcurrent chemotherapy is beneficial for colorectal cancer patients with massive and multiple liver metastases.From January 2007 to December 2012, 19 patients who exhibited massive (with a longest diameter > 5 cm) andinvasive liver metastases and multiple metastases were treated with radiotherapy and concurrent chemotherapy.The total radiation dose was 53.4 Gy (range 38.8 Gy-66.3 Gy). All of the patients received a continuous intravenousdose of 5 fluorouracil (5-FU) 225 mg/m2 concurrently with radiation. The median survival time was 19 months.The 1- and 2- year overall survival rates were 78.3% and 14.3%, respectively. Of all of the patients who presentedwith abdominal pain, 100% experienced a decrease in pain. Decreases in the rates of ascites and jaundice wereconfirmed by ultrasound and bilirubin levels. No cases of Grade 4 or 5 acute or late toxicity were recorded.There were only two cases of Grade 3 toxicity (elevated bilirubin). These data provide evidence that whole-liverradiotherapy plus a tumor-boost dose with concurrent chemotherapy is beneficial for colorectal cancer patientswith massive and multiple liver metastases.     

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。     

The 5-fluorouracil hepato-arterial infusion with oral UFT therapy for the hepatic and extra hepatic metastases of colorectal cancer

BACKGROUND: The 5 fluorouracil hepato-arterial infusion (5-FU HAI) therapy has a good effect on the liver metastases of colorectal cancer. To gain the antitumor effect of the extra-hepatic lesion, an oral UFT was combined with 5-FU HAI (pharmacokinetic modulating chemotherapy, PMC) to enhance the plasma 5-FU concentration. METHODS: UFT (200-400 mg/day) was orally administered daily and a continuous infusion of 5-FU (1,000-1,500 mg/5 h) was given once a week. Eight patients were treated with this regimen. Five of the eight have extra-hepatic lesions with liver metastases when this treatment was started. The response, time to progression, survival, and toxicity were detected. RESULTS: Four of the five patients with extra-hepatic lesion were evaluated. The response rate was 50% (1 CR, 1 PR, and 2 SD). For the liver metastases, the response rate was 62.5% (1 CR, 4 PR, 2 SD, and 1 PD). Grade 2 leukopenia was found in 1 patient. CONCLUSIONS: The 5-FU HAI with an oral UFT therapy had a good effect on the extra-hepatic lesions as well as hepatic metastases of colorectal cancer.     

体部大分割放射治疗肝转移癌疗效及安全性

目的 分析应用体部大分割放疗技术治疗肝转移癌的疗效及安全性。方法 回顾性分析2007-2016年间本院收治的行体部大分割放疗的45例肝转移癌患者的病历资料。其中男20例,女25例,中位年龄58岁(25~83岁),中位KPS=80。原发肿瘤部位以结直肠癌(14例)、乳腺癌(9例)和肺癌(6例)为主。观察并分析体部大分割放疗后的效果和不良反应。结果 中位随访时间为23.5个月,中位生存期26.0个月(95%CI为21.4~30.6)。45例患者中21例发生肝外转移,共治疗52个肝转移病灶,行1个病灶放疗者34例。剂量分割为45 Gy分3次、60 Gy分10~15次。中位GTV和PTV分别为 10.1 cm³(0.3~175.2 cm³)和29.8 cm³(5.0~209.6 cm³)。17例患者的肝脏CT图像与MRI图像融合,43例患者采用IMRT技术。中位PTV剂量为60 Gy (40~60 Gy),BED为90 Gy (60~132 Gy)。放疗后1年肿瘤局部控制率、无瘤生存率和总生存率分别为94%、27%和91%。末次随访时,6例患者病死于肝转移和肝功能异常。结论 体部大分割放疗对肝转移癌是安全有效的。     

Radiation sterilisation of cultured human brain tumour cells for clinical immune tumour therapy

The aim is to investigate the radiosensitivity of noninfected cultured human glioma cells to ascertain that intracutaneously administered cells are viable enough to produce interferon-gamma but not able to proliferate. Cell cultures were established from five patients undergoing brain tumour surgery. By karyotyping, we found four malignant (three glioblastoma multiforme (GBM), one giant cell glioma) and one normal. The cells were irradiated with (137)Cs-gamma rays at absorbed dose levels of 0, 20, 40, 60, 80, 100 and 120 Gy. The fraction of viable cells was examined by MTT incorporation assay. The average of the data obtained from three GBM cell cultures was fitted to an exponential model. The parameters were: extrapolation number n=0.85+/-0.10, mean lethal dose D(0)=12.4+/-3.2 Gy and an additional uncertainty parameter deltaS=0.14+/-0.03. By setting deltaS=0, the corresponding values of the parameters were n=0.86+/-0.16 and D(0)=30.0+/-8.1 Gy. The rate of proliferation was examined by (3)H-thymidine incorporation. The average of the proliferation data obtained from three GBM cell cultures was fitted to an exponential model yielding n=0.943+/-0.005 and D(0)=5.8+/-0.5 Gy for deltaS=0.057+/-0.005, and by setting deltaS=0, n=1.00+/-0.02 and D(0)=8.4+/-1.6 Gy. No outgrowth of plated cells was observed after 4 weeks at an absorbed dose of 100 Gy. This absorbed dose is recommended for irradiation of 2 x 10(6) glioma cells used for clinical immunisation.     

Present and future of home anti-cancer chemotherapy for unresectable recurrence of colorectal cancer

Continuous hepatic arterial infusion chemotherapy (HAI) was performed for 100 colorectal cancer patients with unresectable liver metastases in our outpatient clinic. The administration schedule was 5-FU 250 mg/day for 7 days every other week. In this study, 93 cases were evaluable. The average dose of 5-FU was 24 g (3.0-66.5 g). The response rate was 59.1% (CR: 4 cases, PR: 51 cases, NC: 12 cases and PD: 26 cases). The prognostic outcome was significantly prolonged in the effective cases (50% survival duration was as follows: CR: 764 days, PR: 620 days, NC: 255 days and PD: 152 days). The complication rate with HAI was 15.1%, but nobody died from these complications. Hepatectomy after HAI was performed in 19 cases (20.4%) because of the effect of HAI. The three-year survival rate was 35.3% for HAI with hepatectomy and 3.8% for only HAI. There was statistically significant difference (p < 0.0001) between these two groups. Hepatectomy after HAI is a new strategy for unresectable liver metastasis of colorectal cancer. Recently, we performed home systemic chemotherapy using 5-FU for 3 recurrent patients of colorectal cancer and were able to continue this therapy safely for more than 2 months.     

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.     

Radiosurgery for brain metastasis: impact of CTV on local control.

PURPOSE: The purpose of the present analysis was to assess whether adding a 1 mm margin to the gross tumour volume (GTV) improves the control rate of brain metastasis treated with radiosurgery (RS). PATIENTS AND METHODS: All the patients had one or two brain metastases, 30 mm or less in diameter, and only one isocentre was used for RS. There were 23 females and 38 males. The median age was 54 years (34-76). The median Karnofsky performance status was 80 (60-100). At the time of RS, 23 patients had no evidence of extracranial disease and 38 had a progressive systemic disease. Thirty-eight patients were treated up-front with only RS. Twenty-three patients were treated for relapse or progression more than 2 months after whole brain radiotherapy. From January 1994 to July 1995, clinical target volume (CTV) was equal to GTV without any margin (33 metastases). From August 1995 to August 2000, CTV was defined as GTV plus a 1 mm margin (45 metastases). A dose of 20Gy was prescribed to the isocentre and 14Gy at the margin of CTV. RESULTS: The median follow-up was 10.5 months (1-45). The mean minimum dose delivered to GTV was 14.6Gy in the group without a margin and 16.8Gy in the group with a 1 mm margin (P<0.0001). The response of 11 metastases was never assessed because patients died before the first follow-up. Ten metastases recurred, eight in the group treated without a margin and two in the group treated with a 1 mm margin (P=0.01). Two-year local control rates were 50.7+/-12.7% and 89.7+/-7.4% (P=0.008), respectively. Univariate analysis showed that the treatment group (P=0.008) and the tumour volume (P=0.009) were prognostic factors for local control. In multivariate analysis, only the treatment group with a 1 mm margin was an independent prognostic factor for local control (P=0.04, RR: 5.8, 95% CI [1.08-31.13]). There were no significant differences, either in overall survival rate or in early and late side effects, between the two groups. CONCLUSION: Adding a 1 mm margin to the GTV in patients treated with RS significantly improves the probability of metastasis control without increasing the side effects.     

NRG Oncology/RTOG 0438: A Phase 1 Trial of Highly Conformal Radiation Therapy for Liver Metastases

PurposeThis study aimed to determine the feasibility and maximally tolerated dose of hypofractionated, conformal radiation therapy (RT) in patients with liver metastases.Methods and materialsNonsurgical patients with ≤5 liver metastases (sum of maximal diameter of all lesions ≤8 cm) were included in the study. There were 4 dose levels: 35 Gy, 40 Gy (starting level), 45 Gy, and 50 Gy, in 10 fractions. The clinical target volume included metastases identified on contrast computed tomography or magnetic resonance imaging with a 5-mm margin within the liver. The planning target volume margin ranged from 4 to 30 mm, depending on breathing motion. Dose-limiting toxicities were defined as RT-related grade ≥4 hepatic or gastrointestinal toxicities or thrombocytopenia occurring within 90 days of the start of RT.ResultsA total of 26 patients with metastases from colorectal (8 patients), breast (7 patients) and other malignancies (11 patients) were enrolled between November 2005 and December 2010. Twenty-three patients were evaluable (8, 7, and 8 on the 40, 45, and 50 Gy dose levels, respectively). Two patients assigned to 50 Gy received 35 Gy owing to normal tissue limits, so 2 additional patients were treated to 50 Gy. There were no dose-limiting toxicities on any of the dose levels. On the 45 Gy dose level, 1 patient developed reversible grade 3 enteritis (37 days from RT start) and diarrhea (22 days); another patient developed grade 3 lymphopenia (23 days). At the 50 Gy dose level, 1 patient had grade 3 hyperglycemia (74 days), and another patient developed grade 3 lymphopenia (13 days), colonic hemorrhage (325 days), and colonic gastrointestinal obstruction (325 days). With a potential median follow-up of 66.1 months (range, 34.6-89.0 months), no other late toxicities were observed.ConclusionsTreatment of liver metastases with 50 Gy in 10 fractions was feasible and safe in a multi-institutional setting.