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Brachytherapy

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

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Brachytherapy

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  1. 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

  2. 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

  3. 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

  4. Implant radioactive seeds into tumors Emit continueous low energy γ rays Interact with biomacromolecule Cell death and mutation leading to cancer Injury of tissues and cells

  5. Animal experiment Clinical research

  6. Experimental design • Human pancreatic cancer Sw1990 cell • BABL/c was inoculated into the dorsal side ofright lower extremity inguinal region of nudemice • Passaged for 3 tims subcutaneously, initiate the experiments after tumor formation was stablized

  7. Experimental method Subcutaneous pancreatic cancer xenograft in nude mice Seed implantation group Control group

  8. Change of xenograft volume in nude mice

  9. Comparison of tumor inhibition rate

  10. HEstaining Obvious liquefaction necrosis can be seen in the centeral area of Experimental group tumor, there are sparse cells aroud the necrosis area (×100) There is no or little necrosis area in center of control group tumor, there are multiple tumor cells (×100)

  11. HEstaining Experimental group positive TK1 staining cells are exiguous（×200） Control group positive TK1 staining cells are abundent （×200）

  12. CT引导下放射性粒子植入实体肿瘤的基础与临床研究CT引导下放射性粒子植入实体肿瘤的基础与临床研究

  13. Preliminary result • 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

  14. Introduction Pancreatic cancer is a devastating disease and the prognosis remains poor Few patients are eligible for curative surgical resection Alternative therapeutic options are in demand ZM. Wang MD, Shanghai Ruijin Hospital

  15. Traditional therapy vs. External irradiation therapyvs. percutaneous seed implantation ZM. Wang MD, Shanghai Ruijin Hospital

  16. 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-125 125I placement was routinely used at our institution for recurrent tumors at various sites The aim of this study was to test its feasibility for pancreatic lesions Current Controversies

  17. Methods and materials Patient population December 2004 to August 2007, 31 consecutive patients were included in this prospective, nonrandomized study  Patients were diagnosed by CT or MRI with histological confirmation of the diagnosis by FNA All patients enrolled displayed contraindications to surgery or had rejected surgical treatment due to personal reasons 11th IO 2010, May23

  18. Methods and materials The total volume of each tumor was calculated with the treatment planning system (TPS) before implantation The expected number of implanted seed was calculated according to the modified level formula Patients were kept in our radiooncology/interventional ward with an usual stay of 4 full days ZM. Wang MD, Shanghai Ruijin Hospital

  19. Methods and materials Clinical benefit response was derived from measurement of pain, functional impairment and weight loss Patients were examined by CT after the operation Response rate was defined as the sum of CR and PR Local tumor control was defined as the absence of tumor progression (SD+PR+CR)

  20. 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 Hospital

  21. 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

  22. 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

  23. Results Change of Karnofsky physical score % (cases) Iodine-125 Therapy in Advanced Pancreatic Cancer

  24. Results Change of pain score % (cases) Iodine-125 Therapy in Advanced Pancreatic Cancer

  25. 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 months Median survival time for pure seeds implantation (21 cases) was 7 months median survival time for drug-seeds combined was 11 month

  26. Pre-implant CT scan (Case one) ZM. Wang MD, Shanghai Ruijin Hospital

  27. Post-implant CT scan ZM. Wang MD, Shanghai Ruijin Hospital

  28. Pre-implant CT scan (Case Two)

  29. Post-implant CT scan 术后CT扫描 术中穿刺碘粒子植入

  30. Post-implant CT scan

  31. Pre-implant CT scan (Case Three) 病例2 男性 76岁 胰腺癌（胰体尾部）

  32. Post-implant CT scan 术后CT扫描

  33. Pre-implant CT scan (Case Four)

  34. Post-implant CT scan 术后CT二维重建

  35. Post-implant CT scan

  36. 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

  37. Discussion Percutaneous image-guided seed implantation has attracted increasing attention Extensive experiences with this technique had been collected targeting liver and lung malignancies The 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

  38. Technical points during the procedure Patients fasted for 24 hours Ensure steady breath movement during the procedure Pancreatic secretion was inhibited Transgress stomach is safer than intestine, avoiding colon especially when using large-bore needles For patients with jaundice, do PTCD first Immediate CT scan post implantation was done to verify the distribution of the seeds ZM. Wang MD, Shanghai Ruijin Hospital

  39. Drug-seeds combined therapy There is data suggests that local control rates can be enhanced by the addition of chemotherapy In our study the median survival time between the two groups reached statastically significant and encouraged further evaluation ZM. Wang MD, Shanghai Ruijin Hospital

  40. 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

  41. 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

  42. 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

  43. Thanks for your attention

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