Adjuvant internal hepatic radiotherapy using colloidal 32P chromic phosphate in colorectal cancer

The purpose of the study is to investigate the value of adjuvant radiotherapy given in the form of colloidal chromic phosphate 32P suspension administered via portal vein, in preventing the growth of occult metastases in the liver. Twenty two patients (10 patients of treated group with 12 controls) were followed 12 months after operation. There was no significant change in the CBC and liver functions after administration of 32P labeled colloidal chromic phosphate. Although local recurrence rates were very similar in both groups of colorectal cancer (3/12 in the control group and 4/10 in the treated group), liver metastasis rates were quite different: 4/12 in the control group and none (0/10) in the treated group. In conclusion, 32P labeled colloidal chromic phosphate is expected to prevent liver metastases of completely resected colorectal cancer.     

Multidetector-row computed tomography angiography for planning intra-arterial chemotherapy pump placement in patients with colorectal metastases to the liver

PURPOSE: The purpose of this study was to evaluate the use of multidetector computed tomography (MDCT) in the preoperative arterial evaluation of patients scheduled to undergo intra-arterial chemotherapy pump placement. METHODS: Computed tomography scans of 30 patients with hepatic malignancies who were imaged with multiphase MDCT angiography for intra-arterial chemotherapy pump placement were retrospectively analyzed. Dual-phase helical CT was performed, and the arterial phase images were processed to depict the arterial anatomy and to identify pertinent anomalies. All findings were compared and correlated with surgical findings or catheter angiography if surgery was contraindicated. RESULTS: Arterial anomalies identified on CT angiography in 20 of 30 patients included a replaced right hepatic artery (RHA; n = 6) or left hepatic artery (LHA; n = 8), a replaced common hepatic artery (n = 1), an accessory RHA (n = 2) or LHA (n = 6), a replaced gastroduodenal artery (GDA; n = 2), an extrahepatic connection between the accessory RHA and the replaced RHA (n = 1), and a common origin composed of the GDA and RHA and LHA (n = 2). There were no additional arteries or anomalies identified by catheter angiography, when available, or during surgery. Only 1 variant, an accessory hepatic artery, was not located during surgery. In 2 patients, the surgical team decided that pump placement was not feasible because of overly complex anatomy as determined by CT angiography. Computed tomography angiography showed an overall sensitivity of 100% and specificity of 97%. CONCLUSIONS: Multidetector computed tomography angiography is accurate for the preoperative evaluation of normal and aberrant hepatic vasculature in patients under consideration for intra-arterial chemotherapy pump placement. Axial images alone permit recognition of vascular anomalies, including complex anatomy. Nevertheless, 3-dimensional rendering is useful to evaluate complex vascular anatomy and does not require catheter angiographic confirmation. In addition to aiding in selecting patients ideal for pump placement, MDCT permits noninvasive planning of their surgical approach.     

32P-磷酸铬间质给药在荷人胰腺癌裸鼠的体内生物学分布及形态学表现

目的 研究^32P-磷酸铬(^32P胶体)瘤体间质给药治疗BALB／c—nu／nu裸鼠荷人胰腺癌(Pc-3)移植瘤时在体内相应组织中的分布、药代动力学特点及全身毒性反应。方法 51只荷瘤裸鼠，经瘤体给予不同剂量^32P胶体或尾静脉给药，分批处死，动态观察^32P胶体在裸鼠体内放射性分布和组织器官形态学表现，观察体重变化和计数WBC和PLT，测量瘤体表面放射性计数率。结果 ^32P胶体瘤体间质注射后其放射性计数率明显高于其他器官组织，器官组织放射性计数率瘤体给药明显低于尾静脉给药。增体给药有效半减期为13d。形态学检查显示给药后大部分Pc-3细胞被破坏，并出现分化较好的瘤细胞；肝、脾、肺及淋巴结等重要器官组织的辐射损伤为可逆性．未见明显骨髓抑制现象。结论 ^32P胶体瘤体间质给药是治疗胰腺癌安全、简便、有效的核素介入疗法。     

EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds

Primary liver cancers (i.e. hepatocellular carcinoma or cholangiocarcinoma) are worldwide some of the most frequent cancers, with rapidly fatal liver failure in a large majority of patients. Curative therapy consists of surgery (i.e. resection or liver transplantation), but only 10-20% of patients are candidates for this. In other patients, a variety of palliative treatments can be given, such as chemoembolization, radiofrequency ablation or recently introduced tyrosine kinase inhibitors, e.g. sorafenib. Colorectal cancer is the second most lethal cancer in Europe and liver metastases are prevalent either at diagnosis or in follow-up. These patients are usually treated by a sequence of surgery, chemotherapy and antibody therapy [Okuda et al. (Cancer 56:918-928, 1985); Schafer and Sorrell (Lancet 353:1253-1257, 1999); Leong et al. (Arnold, London, 1999)]. Radioembolization is an innovative therapeutic approach defined as the injection of micron-sized embolic particles loaded with a radioisotope by use of percutaneous intra-arterial techniques. Advantages of the use of these intra-arterial radioactive compounds are the ability to deliver high doses of radiation to small target volumes, the relatively low toxicity profile, the possibility to treat the whole liver including microscopic disease and the feasibility of combination with other therapy modalities. Disadvantages are mainly due to radioprotection constraints mainly for (131)I-labelled agents, logistics and the possibility of inadvertent delivery or shunting [Novell et al. (Br J Surg 78:901-906, 1991)]. The Therapy, Oncology and Dosimetry Committees have worked together in order to revise the European Association of Nuclear Medicine (EANM) guidelines on the use of the radiopharmaceutical (131)I-Lipiodol (Lipiocis?, IBA, Brussels, Belgium) and include the newer medical devices with (90)Y-microspheres. (90)Y is either bound to resin (SIR-Spheres?, Sirtex Medical, Lane Cove, Australia) or embedded in a glass matrix (TheraSphere?, MDS Nordion, Kanata, ON, Canada). Since (90)Y-microspheres are not metabolized, they are not registered as unsealed sources. However, the microspheres are delivered in aqueous solution: radioactive contamination is a concern and microspheres should be handled, like other radiopharmaceuticals, as open sources. The purpose of this guideline is to assist the nuclear medicine physician in treating and managing patients undergoing such treatment.     

Radio-frequency ablation of colorectal liver metastases in 167 patients

The objective of this paper is to report our results from a prospective study of 167 patients with colorectal liver metastases treated with radio-frequency ablation (RFA). Three hundred fifty-four treatments were performed in 167 patients, 99 males, mean age 57 years (34–87). The mean number of metastases was 4.1 (1–27). The mean maximum diameter was 3.9 cm (1–12). Fifty-one (31%) had stable/treated extra-hepatic disease. Treatments were performed under general anaesthesia using US and CT guidance and single or cluster water-cooled electrodes (Valleylab, Boulder, CO). All patients had been rejected for or had refused surgical resection. Eighty percent received chemotherapy. Survival data were stratified by tumour burden at the time of first RFA. The mean number of RFA treatments was 2.1 (1–7). During a mean follow-up of 17 months (0–89), 72 developed new liver metastases and 71 developed progressive extra-hepatic disease. There were 14/354 (4%) major local complications and 22/354 (6%) minor local complications. For patients with 5 metastases, maximum diameter 5 cm and no extra-hepatic disease, the 5-year survival from the time of diagnosis was 30% and from the time of first thermal ablation was 26%. Given that the 5-year survival for operable patients is a median of 32%, our 5-year survival of 30% is promising.     

Does resection of small liver metastases from colorectal cancer improve survival of patients?

Because the size of metastases greatly affects their detection, we retrospectively investigated the influence of the size of liver metastases on survival after hepatic surgery. The subject group study consisted of 77 patients who underwent liver surgery for metastases from colorectal cancer. The survival rate after hepatic surgery was analysed using multivariate Cox's proportional hazards model with the following variables: (1) size of dominant metastases (Small: < 3 cm; Medium: > or = 3 cm and < 6 cm; Large: > or = 6 cm); (2) synchronous versus metachronous resection; (3) solitary versus multiple metastases. The size of dominant metastases (p = 0.035) and synchronous versus metachronous resection (p = 0.0009) were independently associated with survival after liver resection. No association was found, however, for solitary versus multiple metastases. The survival of the Large group was much poorer than that of the Small group (p = 0.0168) and that of the Medium group (p = 0.0205), with statistically significant differences. No statistically significant difference was seen between the Small and the Medium groups (p = 0.7963). This study showed that long-term survival following resection of metastases was much poorer when metastases were 6 cm or greater in diameter. With regard to metastases less than 6 cm in diameter, resection of the smallest of these (less than 3 cm) did not appear to improve survival.     

Peritoneoscintigraphy in detection of improper placement of peritoneal catheter into bowel lumen prior to chromic phosphate P-32 therapy. A case report

Radionuclide peritoneoscintigraphy has been used prior to chromic phosphate P-32 (P-32CP) intraperitoneal therapy to assure proper placement of the catheter in the peritoneal cavity, to exclude loculation, and to predict inadequate distribution of P-32CP. This is a case report of the detection of a peritoneal catheter improperly placed into the bowel lumen by pretherapy radionuclide peritoneoscintigraphy, and this case demonstrates the distinguishing characteristics of the radiocolloid distribution secondary to an intraluminal injection relative to an intraperitoneal injection.     

Portal scanning for liver metastases in colorectal carcinoma

In a prospective study over 2 years, 14 patients suffering from colorectal cancer had radionuclide liver scans performed via the portal route. Technetium-99m-labelled macro-aggregates of human serum albumen were injected via the cannulated umbilical vein, distributed through the portal system of the liver and their presence recorded by a gamma camera. Of 11 patients with clinically normal livers and no metastases found at laparotomy, five had abnormal portal scans, two of these dying from multiple liver metastases during follow-up. None of the patients with normal portal scans died with liver metastases within the 2-year study period.     

Diffusion-weighted MR imaging in liver metastases of colorectal cancer: reproducibility and biological validation

Objectives

Before diffusion-weighted imaging (DWI) can be implemented in standard clinical practice for response monitoring, data on reproducibility are needed to assess which differences outside the range of normal variation can be detected in an individual patient. In this study we assessed the reproducibility of the apparent diffusion coefficient (ADC) values in colorectal liver metastases. To provide a biological basis for these values, their relation with histopathology was assessed.

Methods

DWI was performed twice in 1 week in patients scheduled for metastasectomy of colorectal liver metastases. Correlation between ADC values and apoptosis marker p53, anti-apoptotic protein BCL-2, proliferation marker Ki67 and serum vascular endothelial growth factor (VEGF) concentration were assessed.

Results

A good reproducibility coefficient of the mean ADC (coefficient of reproducibility 0.20 × 10^?3?mm²/s) was observed in colorectal liver metastases (n?=?21). The ADC value was related to the proliferation index and BCL-2 expression of the metastases. Furthermore, in metastases recently treated with systemic therapy, the ADC was significantly higher (1.27 × 10^?3?mm²/s vs 1.05 × 10^?3?mm²/s, P?=?0.02).

Conclusions

The good reproducibility, correlation with histopathology and implied sensitivity for systemic treatment-induced anti-tumour effects suggest that DWI might be an excellent tool to monitor response in metastatic colorectal cancer.

Key Points

? ADC values are becoming important oncological biomarkers ? DWI provides reproducibile ADC values in colorectal liver metastases ? The coefficient of reproducibility of the mean ADC is 0.20 × 10 ^?3 ? mm ² /s ? ADC values correlate with proliferation index and are related to BCL-2 expression     

不可手术结直肠癌肝转移瘤二程放疗疗效和安全性分析

目的 分析不可手术结直肠癌肝转移瘤接受二程放疗的疗效和安全性。方法 回顾性收集2017—2023年于北京大学肿瘤医院接受二程放疗的28例不可手术结直肠癌肝转移患者的资料,分析二程放疗的可行性。结果 28例患者二程放疗后中位随访时间为20.2个月。二程放疗距首程放疗的中位时间为11.1个月。首程放疗和二程放疗的中位生物有效剂量(BED)分别为100和96 Gy,分别有25例(89.3%)和24例(85.7%)患者接受了体部立体定向放射治疗。首程放疗和二程放疗的正常肝脏平均受量的2 Gy分次的等效剂量(EQD2)分别为10.1和 7.9 Gy。二程放疗后的完全缓解率和部分缓解率分别为54.5%和18.2%,客观反应率为72.7%。二程放疗后基于患者的2年的累积局部失败率为17.0%,基于病灶的2年的累积局部失败率为15.1%,1年无进展生存(PFS)为27.4%,3年总生存(OS)为46.7%。二程放疗后患者的耐受性良好,大部分患者(75.0%)出现1~2级急性不良反应,只有1例(3.6%)患者出现3级急性不良反应。结论 对于不可手术结直肠癌肝转移患者,二程放疗安全有效。     

立体定向放射治疗在结直肠癌肝转移中的临床应用

目的 评价立体定向放射治疗（SBRT）在结直肠癌肝转移（CLM）中的治疗效果,为合理选择治疗手段提供依据。方法 解放军306医院收治的28例患者,包括男17例,女11例,中位年龄63.8岁（31~86岁）,共计54个病灶,行立体定向放射治疗。平静呼吸状态下的CT增强扫描影像分别进行大体肿瘤体积（GTV）、临床靶区体积（CTV）和计划靶区体积（PTV）的勾画,CTV为GTV外放5 mm,GTV为CTV外放5~10 mm。以50%~60%等剂量曲线作为处方剂量曲线,单次3~6 Gy,总剂量39~45 Gy,等效生物剂量50.7~65.3 Gy。治疗后3个月开始复查,以增强CT或MR显示的病灶体积的变化做为评价疗效的依据。根据RTOG毒性诊断标准对不良反应进行诊断和分级,比较局控率和生存率。结果 所有患者均顺利完成治疗,中位随访时间为15.1个月（3~30个月）,随访终点有7例患者存活。局控率为79.2%,1年和2年的总生存率分别为82.7%和48.6%。病灶体积与局控率关系密切,当体积小于14 cm³时,肿瘤局控率明显高于病灶体积大于65 cm³时（χ² = 4.17,P<0.05）。病灶体积大于180 cm³时,肿瘤局控率为零。不良反应包括治疗后乏力（60.7%）,1、2级消化道反应（28.6%）,一过性1、2级骨髓抑制（46.4%）,一过性转氨酶增高（17.8%）。全组未发生3级以上及晚期不良反应。结论 立体定向放射治疗可做为选择性病例尤其是不能手术的结直肠癌肝转移患者的首选局部治疗手段。     

结直肠癌肝转移综合介入治疗的临床应用

目的:探讨介入治疗结直肠癌肝转移(colorectal liver metastases,CLM)的临床疗效。方法:将77例无法手术切除或切除不完全的CLM分为2组,治疗组39例先行TACE,1周后在CT引导下行瘤体内注射无水乙醇,然后注入超液化碘油与丝裂霉素+阿霉素混合乳剂适量。对照组38例仅行TACE。结果:治疗组CR 4例(10.2%),PR 34例(87.2%),有效率(CR+PR)97.4%,中位生存期为42个月,1年、3年、5年生存率分别为91.7%、45.8%、31.3%。对照组CR 1例(2.6%),PR28例(73.7%),有效率(CR+PR)76.3%,中位生存期为23个月,1年、3年、5年生存率分别为71.0%、22.6%、9.6%。治疗组明显高于对照组,差异有统计学意义(P<0.05)。无严重并发症发生。结论:介入治疗是不能根治性切除的肝转移瘤患者的有效治疗方法,综合性介入治疗的有效率和生存率明显优于单纯肝动脉化疗栓塞。     

经肝动脉灌注32P-玻璃微球联合化疗栓塞治疗肝癌的临床研究

目的探讨经肝动脉超选择性灌注32P-玻璃微球联合化疗栓塞治疗肝癌的方法、疗效、影响因素和吸收剂量估算方法.方法采用经肝动脉超选择性段性挤压式栓塞及半肝栓塞的方法灌注32P-玻璃微球、超液化碘油和吡柔比星(THP)混悬液治疗30例肝癌患者,术后行β轫致辐射显像,结合分区模型,估算肿瘤、非瘤肝组织和肺组织的吸收剂量.采用不含32P-玻璃微球的混悬液化疗栓塞治疗26例肝癌患者作为对照组.结果实验组反应率(70.0%)明显高于对照组(42.3%)(χ2＝4.362,P<0.05);实验组6、12、18个月生存率分别为100.00%、76.67%、43.33%,对照组为92.31%、61.54%、19.23%.估算肿瘤组织的平均吸收剂量(130.34±54.53)Gy,非瘤肝组织为(34.73±13.41)Gy,肺组织2.1～16.3 Gy.肿瘤吸收剂量≥120 Gy的反应率(100%)高于剂量＜120 Gy的反应率(47.1%)(χ2= 9.832,P＜0.01).结论经肝动脉采用超选择性段性挤压式栓塞及半肝栓塞的方法灌注32P-玻璃微球联合化疗栓塞治疗肝癌是1种安全有效的方法.术后β轫致辐射显像结合分区模型估算肿瘤组织和非瘤肝组织的吸收剂量,为剂量学研究提供了1个可行的方法.     

胃、结（直）肠癌肝转移的介入治疗（附55例报告）

目的 评价胃、结(直)肠癌肝转移瘤介入治疗效果及影响因素。方法采用Seldinger法经股动脉插管,治疗胃癌、结(直)肠癌肝转移21例、34例。化疗药物选择5一Fu、PDD、ADM或ADM与碘化油乳剂作栓塞治疗。结果(1)胃、结(直)肠癌肝转移瘤总有效率(CR PR)为64％;(2)34例转移瘤碘化油沉积CT分为四型：均匀型占20％,非均匀型占39％,环型占9％,无碘油沉积型占32％;(3)转移瘤疗效最好为单发、多血供病灶及均匀碘化油蓄积;(4)64％病例治疗后出现肝外转移。结论介入化疗栓塞治疗为胃、结(直)肠癌肝转移有效的姑息治疗手段。     

Prognostic value of ADC measurements in predicting overall survival in patients undergoing 90Y radioembolization for colorectal cancer liver metastases

AimTo assess the ability of diffusion-weighted imaging (DWI) in predicting the overall survival in patients who underwent Yttrium 90 radioembolization (⁹⁰Y-RE) for colorectal liver metastases (CLM) with other well-established clinical and imaging parameters by comparing the pre- and post-treatment apparent diffusion coefficient (ADC) values of the lesions.MethodsA total of 81 metastatic lesions of 27 consecutive patients who underwent DWI before and after the ⁹⁰Y-RE session were enrolled in the study. ADC values were calculated from the entire (ADC_e) and peripheral (ADC_p) tumor on pre- and post-treatment DWI, and any relative increase in ADC >0% accepted as a functional imaging response. The impact of functional imaging response in addition to other well-known parameters including Response Evaluation Criteria in Solid Tumors (RECIST), hepatic tumor burden, Eastern Cooperative Oncology Group performance status (ECOG–PS) and the presence of extrahepatic metastases in predicting overall survival (OS) was assessed using Kaplan-Meier curves and Cox-regression analyses.ResultsThe median OS of the patients was 10 months (range, 6–20 months) while the median OS of the responders being significantly longer than the non-responders for ADC_e and ADC_p (median 11 vs 7 months, P = 0.003; median 12 vs. 7 months, P < 0.0001, respectively). The RECIST score was also significantly affected the OS (progressive or stable disease median 8 months vs. partial response 15 indent months, P = 0.019). The other parameters including hepatic tumor burden, gender, ECOG score, the involvement of the liver lobes, and the presence of extrahepatic metastases were not associated with the OS. In multivariate analysis, only ADC_p remained as an independent predictor of OS (P = 0.003, HR = 19.878).ConclusionAny increase in relative ADC_p or ADC_e values after Y90-RE treatment was associated with longer OS in CLM patients, and DWI seems to be valuable imaging biomarker in predicting OS in CLM patients during the early post-interventional period after ⁹⁰Y-RE.     

Added value of FDG-PET imaging in the diagnostic workup for yttrium-90 radioembolisation in patients with colorectal cancer liver metastases

Objective

Yttrium-90 radioembolisation (Y90-RE) is recommended for unresectable, chemorefractory liver-dominant disease; however, the incidence of extrahepatic disease (EHD) is high. FDG-PET may have additional value to CT in demonstrating EHD. Our aim was to evaluate the added diagnostic value of FDG-PET to abdominal CT and study the influence of FDG-PET findings on treatment decisions.

Methods

All consecutive patients with colorectal cancer liver metastases (CRCLM) referred for Y90-RE were included. Patients who underwent both CT and FDG-PET in the diagnostic workup were selected. Imaging reports were scrutinised for documented sites of EHD, and changes of management due to FDG-PET findings were determined.

Results

A total of 42 patients were included. Findings on CT and FDG-PET matched in 20 patients (no EHD, n?=?15; identical EHD, n?=?5). In 4 patients, lesions detected on CT were not FDG-avid, and in 18 patients, FDG-PET showed more lesions than CT (P?<?0.05). In 7/42 patients (17 %) a change of management was made based on the additional FDG-PET findings, i.e. exclusion from Y90-RE treatment (n?=?6) and change in treatment plan (whole liver rather than segmental treatment, n?=?1).

Conclusions

In patients with CRCLM referred for Y90-RE, FDG-PET showed significantly more EHD and led to a considerable change of management.

Key Points

? Yttrium-90 radioembolisation is a locoregional treatment for liver tumours ? Detection of extrahepatic lesions, for which CT is widely used, is crucial ? FDG-PET shows significantly more extrahepatic lesions compared to CT ? FDG-PET findings led to a considerable change in treatment decisions     

Percutaneous radiofrequency ablation for pulmonary metastases from colorectal cancer: midterm results in 27 patients

PURPOSE: To retrospectively evaluate the midterm outcomes (eg, safety, local efficacy, and survival) after radiofrequency (RF) ablation for pulmonary metastases from colorectal cancer. MATERIALS AND METHODS: Twenty-seven patients (19 men and eight women; mean age, 61.6 years) with 49 pulmonary metastases (mean long axis diameter, 1.5 cm) from colorectal cancer underwent 41 percutaneous computed tomography (CT)-guided RF ablation sessions. Follow-up examinations were performed with CT by using contrast medium administration in all patients; positron emission tomography was performed in five patients. The safety of the procedure, local tumor control, and patient survival were evaluated. Multiple variables were analyzed to determine prognostic factors. RESULTS: Pneumothorax occurred after 20 of the 41 sessions (49%), three of which necessitated chest tube placement. A small pleural effusion was found after six of the 41 sessions (15%). No major hemorrhagic event was observed. None of the patients died due to the procedure. The median follow-up period was 20.1 months (range, 11.2-47.7 months). The primary and secondary technique effectiveness rates were 72% and 85%, respectively, at 1 year, 56% and 62% at 2 years, and 56% and 62% at 3 years. The overall survival rates after RF ablation were 96% at 1 year, 54% at 2 years, and 48% at 3 years. The presence of extrapulmonary metastasis was determined to be a prognostic factor (P = .001). CONCLUSIONS: The midterm outcomes of percutaneous RF ablation for colorectal pulmonary metastases appear promising. The presence of extrapulmonary metastasis had an adverse effect on survival after RF ablation.