primary clinical study of ct- guided iodine-125 seed implantation therapy in patients with advanced...
TRANSCRIPT
Primary Clinical Study of CT-guided Iodine-125 Seed Implantation Therapy in Patients with Advanced
Pancreatic Cancer
上海交通大学医学院附属瑞金医院卢湾分院 王忠敏
Brachytherapy
1898 年居里夫人发现镭
1905 年即进行了第 1 例镭针插管治疗
1930 年 Paterson 及 Parker 建立了曼切斯特（ Manchester ）系统
1935 年小居里夫妇发现了人工放射性同位素
80 年代中期，现代近距离治疗迅速发展
生物学优势（外放疗相比）
• 肿瘤局部治疗的持续时间长• 放射治疗的剂量较低• 对周围正常组织的损伤小• 对肿瘤细胞的杀伤力强
Implant radioactive seeds into tumors
Emit continueous low energy γ rays
Injury of tissues and cellsCell death and mutation
leading to cancer
Interact with biomacromolecule
Animal experiment
Clinical research
Human pancreatic cancer Sw1990 cell
BABL/c was inoculated into the dorsal side of right lower extremity inguinal region of nude mice
Passaged for 3 tims subcutaneously, initiate the experiments after tumor formation was stablized
Experimental designExperimental design
Subcutaneous pancreatic cancer xenograft in nude mice
Seed implantation group
Control group
Experimental methodExperimental method
Change of xenograft volume in nude mice
Comparison of tumor inhibition rate
Obvious liquefaction necrosis can be seen in the centeral area of Experimental group tumor, there are sparse cells aroud the necrosis area (×100)
HE staining
There is no or little necrosis area in center of control group tumor, there are multiple tumor cells (×100)
Experimental group positive TK1 staining cells are exiguous （ ×200 ）
Control group positive TK1 staining cells are abundent （ ×200 ）
HE staining
碘 -125 放射粒子组织间植入治疗属放射治疗， 对周围正常器官组织无明显放射损伤
裸鼠移植瘤组织植入碘 -125 粒子后，实验组心、 肺、肝、肾、脾脏外观大致正常，病理检查未 见明显放射性炎症表现
Preliminary resultPreliminary result
ZM. Wang MD, Shanghai Ruijin Hospital
Introduction
Pancreatic cancer is a devastating disease
and the prognosis remains poorFew patients are eligible for curative surgical
resectionAlternative therapeutic options are in demand
Traditional therapy vs. External irradiation therapy vs. percutaneous
seed implantation
ZM. Wang MD, Shanghai Ruijin Hospital
External irradiation therapy was regarded as insensitive to pancreatic cancer and associated with more systemic side effects
Radioactive iodine-125 seed implantation has minimal surgical trauma and few complications
The most commonly used isotope is iodine-125125I placement was routinely used at our institution for
recurrent tumors at various sitesThe aim of this study was to test its feasibility for
pancreatic lesions
Current Controversies
11th IO 2010, May 23
Methods and materials
Patient populationo December 2004 to August 2007, 31 consecutive patients
were included in this prospective, nonrandomized study o Patients were diagnosed by CT or MRI with histological
confirmation of the diagnosis by FNAo All patients enrolled displayed contraindications to
surgery or had rejected surgical treatment due to personal reasons
ZM. Wang MD, Shanghai Ruijin Hospital
Methods and materials
The total volume of each tumor was calculated with the treatment planning system (TPS) before implantationThe expected number of implanted seed was calculated according to the modified level formulaPatients were kept in our radiooncology/interventional ward with an usual stay of 4 full days
Methods and materials
Clinical benefit response was derived from measurement of pain, functional impairment and weight loss
Patients were examined by CT after the operationResponse rate was defined as the sum of CR and
PR Local tumor control was defined as the absence of
tumor progression (SD+PR+CR)
Methods and materials
10 patients received concurrent chemotherapy with arterial infusion of gemcitabin and 5-fluorouracil (5-Fu)
Chemotherapy was initiated one week after and repeated up to four cycles
Follow-up visits at 1 month, 3 month, and every 3 months for clinical examination, blood sampling, and CT examination
ZM. Wang MD, Shanghai Ruijin HospitalZM. Wang MD, Shanghai Ruijin Hospital
适应症
• 实体瘤（如前列腺癌）的根治性治疗• 实体瘤术后残余组织的预防性治疗• 转移性肿瘤病灶或术后孤立性肿瘤转移灶而失去
手术价值者• 无法手术的原发肿瘤的姑息性治疗
禁忌证
• 放射性治疗不宜 ( 如血液病等 ) 及有麻醉禁忌等• 病灶范围广泛• 恶液质、全身衰竭• 肿瘤部位有活动性出血、坏死或溃疡• 严重糖尿病
Iodine-125 Therapy in Advanced Pancreatic Cancer
Results
Change of Karnofsky physical score % (cases)
Karnofsky score
100 90 80 70 60 50
Pre-op 0 （ 0/31 ） 3.2 （ 1/31 ）
9.7(3/31) 41.9(13/31) 35.5(11/31) 9.7 （ 3/31 ）
Post-op 0 （ 0/31 ） 48.4(15/31) 16.1(5/31) 9.7(3/31) 19.4(6/31) 6.4(2/31)
Results
Change of pain score % (cases)
Iodine-125 Therapy in Advanced Pancreatic CancerIodine-125 Therapy in Advanced Pancreatic Cancer
No Pain (%) Mild Pain (%) Moderate Pain (%)
Severe Pain (%)
Pre-op 6.5 （ 2/31 ） 22.5(7/31) 32.3(10/31) 38.7(12/31)
Post-op 38.7(12/31) 32.3(10/31) 16.1(5/31) 12.9(4/31)
Results
Overall responding rate (CR+PR) =61.3% Local tumor control rate was 90.3%Median survival time for the whole group was 10.31 monthsMedian survival time for pure seeds implantation (21 cases) was 7 monthsmedian survival time for drug-seeds combined was 11 month
Pre-implant CT scan (Case one)
ZM. Wang MD, Shanghai Ruijin Hospital
Post-implant CT scan
ZM. Wang MD, Shanghai Ruijin Hospital
Pre-implant CT scan (Case Two)
术后 CT 扫描术中穿刺碘粒子植入
Post-implant CT scan
Post-implant CT scan
病例 2 男性 76 岁 胰腺癌（胰体尾部）
Pre-implant CT scan (Case Three)
术后 CT 扫描
Post-implant CT scan
Pre-implant CT scan (Case Four)
Post-implant CT scan
术后 CT 二维重建
Post-implant CT scan
Complications
No serious complications encountered 2 seeds of radioactive 125I found to migrate
to liver in 2 patients Leukopenia and renal function impairment
were found in 4 patients of drug-seeds
combination group
Iodine-125 Therapy in advanced Pancreatic Cancer
DiscussionPercutaneous image-guided seed implantation
has attracted increasing attentionExtensive experiences with this technique had
been collected targeting liver and lung
malignanciesThe most commonly used isotope is 125I , and 125I placement has become a routine treatment
for recurrent tumors at various sites in our
institution ZM. Wang MD, Shanghai Ruijin Hospital
Technical points during the procedure
Patients fasted for 24 hoursEnsure steady breath movement during the procedurePancreatic secretion was inhibitedTransgress stomach is safer than intestine, avoiding colon especially when using large-bore needlesFor patients with jaundice, do PTCD firstImmediate CT scan post implantation was done to verify the distribution of the seeds
ZM. Wang MD, Shanghai Ruijin Hospital
Drug-seeds combined therapy
There is data suggests that local control rates
can be enhanced by the addition of
chemotherapyIn our study the median survival time between
the two groups reached statastically
significant and encouraged further evaluation
ZM. Wang MD, Shanghai Ruijin Hospital
Conclusions
This study suggested that CT-guided brachytherapy using 125I seeds implantation appeared to be safe, effective, less complicated and could produce adequate pain relief for treating unresectable pancreatic cancer
Iodine-125 Therapy in Advanced Pancreatic Cancer
国内临床尚有许多问题需要解决 • 临床应用适应症选择标准不一，造成不同医院应用放射
性粒子植入治疗技术后疗效评价缺乏标准，尤其在放射性粒子治疗肿瘤的过程中，现在面临的缺乏行业管理标准和操作技术规范
• 如不同增殖速率的肿瘤如何选择不同放射性核素 , 以获得最大的杀伤效应
• 粒子种植治疗仍是局部治疗手段，是外科和外放疗的补充和延伸，单纯放射性粒子植入治疗并不能解决所有肿瘤治疗问题，如何合理、科学地与外科、外放疗和化疗结合，最大限度发挥粒子植入治疗的优势
展 望
• 由于放射性粒子植入治疗恶性肿瘤创伤小，靶区剂量分布较均匀和对周围正常组织损伤较小等特点，在临床应用展现了广阔的前景
• 同样放射性粒子植入技术治疗肿瘤需要多学科联合，特别需要准确的治疗计划、娴熟的治疗技术和严谨的术后质量评估
Thanks for your attentionThanks for your attention