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头颈部肿瘤的 放疗与营养

头颈部肿瘤的 放疗与营养. 复旦大学附属肿瘤医院放疗科 胡超苏. 头颈部肿瘤原发疾病部位. 口腔 咽. 喉. 鼻腔. 副鼻窦. 头颈部肿瘤概况. 发生率占所有新发肿瘤的 3-6% 饮酒、吸烟是共同病因 > 90% 为头颈部鳞癌 (SCCHN) HPV 感染 可能为预后 因素 早期患者 (I, II) 治愈率较高 (> 80%) 局部晚期及转移者预后较差 5 年生存率 < 40%. 头颈部鳞癌的预后. I 期、 II 期 占所有患者约 1/3 60%-80% 可根治性切除 / 放疗 常伴第二原发癌，几率甚至高于局部复发 III 期、 IV 期

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头颈部肿瘤的 放疗与营养

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  1. 头颈部肿瘤的放疗与营养 复旦大学附属肿瘤医院放疗科 胡超苏

  2. 头颈部肿瘤原发疾病部位 口腔 咽 喉 鼻腔 副鼻窦

  3. 头颈部肿瘤概况 • 发生率占所有新发肿瘤的3-6% • 饮酒、吸烟是共同病因 • > 90%为头颈部鳞癌(SCCHN) • HPV感染可能为预后因素 • 早期患者(I, II)治愈率较高(> 80%) • 局部晚期及转移者预后较差 • 5年生存率< 40%

  4. 头颈部鳞癌的预后 • I期、II期 • 占所有患者约1/3 • 60%-80%可根治性切除/放疗 • 常伴第二原发癌，几率甚至高于局部复发 • III期、IV期 • 占所有患者约2/3 • 常需多学科综合治疗 • 40%-80%会出现局部复发 • 10%-30%出现远处转移

  5. Most patientshaveregionaldiseaseat diagnosis Prognosisbystage 1.SEER Cancer Statistics Review, 1975–2010, National Cancer Institute. Bethesda, MD 2.Ko C, Citrin D. Oral Dis 2009;15:121–132 3.Argiris A, et al. Cancer 2004;101:2222–2229

  6. 治疗方法

  7. Treatment and Treatment-Related Side Effects • Treatment: • Surgery • Radiotherapy (RT) • Combination of RT and chemotherapy • Result: • Poor food intake

  8. 病人因素 • 老年 • 治疗前体重下降或者吞咽困难 • 一般状况差 • 烟酒嗜好 • 气管切开等

  9. 肿瘤因素 原发肿瘤巨大 喉或下咽肿瘤

  10. 手术 副作用 术后并发症 感染 • 口咽功能差 咽瘘 伤口裂开 • 吞咽困难

  11. 放化疗 (CRT) • 副作用 • 咀嚼 / 吞咽困难 • 恶心 • 味觉改变 • 口干 • 唾液改变 • 口炎 • 黏膜炎 • 厌食

  12. 绝大多数放疗患者有不同程度体重丢失 前瞻性队列研究 533例头颈部癌根治性放疗 WEIGHT LOSS IMPACTS QOL IN HEAD AND NECK CANCER 1. A negative change in score on the subscales global QOL, physical, role, emotional, cognitive, and social functioning indicates a deterioration in global QOL/functioning 2. A negative change in score on the subscales fatigue, social eating and social contact indicates a decrease in symptoms, a positive score is an increase in symptoms. ∗Significantly different (P < 0.05) compared to patients without weight loss, obtained by univariate linear regression analyses More Than 10% Weight Loss in Head and Neck Cancer Patients During Radiotherapy Is Independently Associated with Deterioration in Quality of Life. Nutr Cancer. 2013;65(1):76-83

  13. 随着放疗的进行患者的营养状况不断恶化 SGA：主观全面评价法 头颈部肿瘤患者放疗期间营养状态及营养干预效果的研究. 中国协和医科大学.2008:35-36

  14. Enteral feeding tubes in patients undergoing definitive Enteral feeding tubes in patients undergoing definitive  chemoradiation therapy for head-and-neck cancer: a critical review ShlomoA;Int J RadiatOncolBiol Phys. 2012 Nov 1;84(3):581-9

  15. Rates of feeding tube use in randomized chemoradiation therapy trials ShlomoA;Int J RadiatOncolBiol Phys. 2012 Nov 1;84(3):581-9

  16. Potential relative advantages of prophylactic vs reactive enteral feeding tube use ShlomoA;Int J RadiatOncolBiol Phys. 2012 Nov 1;84(3):581-9

  17. Correlation between dose-volume parameters of organs at risk and swallowing outcomes in patients treated with chemo-IMRT ShlomoA;Int J RadiatOncolBiol Phys. 2012 Nov 1;84(3):581-9

  18. Proposed algorithm for nutritional support during chemoradiotherapy ShlomoA;Int J RadiatOncolBiol Phys. 2012 Nov 1;84(3):581-9

  19. High Weight Loss during Radiation Treatment Changes the Prognosis in Under-/Normal Weight Nasopharyngeal Carcinoma Patients for the Worse: A Retrospective Analysis of 2433 Cases 中山大学肿瘤防治中心 夏云飞教授 PLOS ONE Volume 8 e68660，2013

  20. 病人情况及分组 • BMI groups:<18.5 kg/m2, underweight, UW; 18.5–,23.0 kg/m2, normal • weight, NW; >23.0 kg/m2, overweight/obese, OW PLOS ONE Volume 8 e68660，2013

  21. 高体重丢失 (HWL; >5%) • 低体重丢失 (LWL;<5%) PLOS ONE Volume 8 e68660，2013

  22. Baseline characteristics by weight loss status in patients with nasopharyngeal carcinoma (n = 2433). PLOS ONE Volume 8 e68660，2013

  23. PLOS ONE Volume 8 e68660，2013

  24. Unadjusted analysis for 5-year OS, DSS, LRFS, and DMFS rates PLOS ONE Volume 8 e68660，2013

  25. OS for NPC patients after radical radiotherapy in 2×3 grouping by BMI levels and weight loss status PLOS ONE Volume 8 e68660，2013

  26. Multiple-adjusted analysis for OS and DSS among the whole population (n = 2433). PLOS ONE Volume 8 e68660，2013

  27. 放疗延迟及中断的病人预后不良（头颈癌） Int J RadiatOncolBiol Phys. 2010;78(3):675-681

  28. 放疗延迟及中断的病人预后不良（头颈癌） • Int J RadiatOncolBiol Phys. 2010;78(3):675-681

  29. 放疗延迟及中断的病人预后不良（头颈癌） • Int J RadiatOncolBiol Phys. 2010;78(3):675-681

  30. 总疗程时间对鼻咽癌疗效的影响 • Luo：中断>20天与<20天，5年局控率分别为15.5%和27.4% • Lee: T1无明显影响，但总剂量有影响。 • Kwong：延长1周，5年局控率62%→44%（p=0.006），5年无瘤生存率47%→31%(p=0.001) • 加速分割可提高局控

  31. 营养不良是放疗的不良预后因素 Laryngoscope. 2008;118(7):1180-1185

  32. 营养不良是放疗的不良预后因素 Laryngoscope. 2008;118(7):1180-1185

  33. 营养不良是放疗的不良预后因素 Disease-free survival (mo) in the body mass index (BMI) >25 group (dotted line) compared with BMI <25(solid line) Laryngoscope. 2008;118(7):1180-1185

  34. 营养不良是放疗的不良预后因素 Overall survival (mo) in the body mass index (BMI) >25 group (dotted line) compared with BMI <25 (solid line). Laryngoscope. 2008;118(7):1180-1185

  35. 癌症患者的营养干预治疗性调整 • 拓宽治疗指数 • 提高治疗疗效 • 减少毒性副作用 • 早期及良好设计的营养疗法+特定营养素，如 • ω-3 脂肪酸 • 谷氨酰胺 癌症的营养干预具有额外效应和特定作用- 提升对肿瘤治疗的耐受性和反应

  36. Prophylactic Percutaneous Endoscopic Gastrostomy Tube Placement inTreatment of Head and Neck Cancer: A Comprehensive Review and Call for Evidence-Based Medicine • Julie L. Locher • 739文献 • 比较用与不用的情况 • 优势与缺点 • 并发症情况 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 3, May 2011

  37. 应用情况 • 两个临床研究患者均预防应用NGB或者PEG。 • Raykher报道所有患者应用 (n = 163)，在置管时， 66% 无吞咽困难或吞咽痛 • 感染率 7.4%,管移位率13%,对 PEG依赖的平均时间为 251 天。 • Lawson 对102 例患者预防应用 • 感染率8.8%,管移位率11.8%对 PEG依赖的平均时间为 4.4月。 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 3, May 2011

  38. 预防性置管的优点 • 体重下降减少 • 治疗中断减少 • 由于营养不良的住院减少 • QOL 在 6 月时高于对照组 • 局部控制率，死亡率，BMI无明显变化 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 3, May 2011

  39. 预防性置管的不足 • 漏 • 感染 • 移位 • 便秘，腹泻 • 低血糖，高血糖 • 对PEG的依赖 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 3, May 2011

  40. A Disease-Specific Enteral Nutrition Formula ImprovesNutritional Status and Functional Performance in PatientsWith Head and Neck and Esophageal Cancer UndergoingChemoradiotherapy: Results of a Randomized, Controlled,Multicenter Trial • Rainer Fietkau Cancer September 15, 2013

  41. 入组标准 • 2006-2009 • 年龄18 以上 • 病理证实 • 同期放化疗 • body mass index16-30/m2 • Kondrup-评分 3 或者subjective global assessment • (SGA) B or C • 预计生存>6 月 • 放化疗开始即行 PEG Cancer September 15, 2013

  42. 排除标准 • 转移性肿瘤，有第二肿瘤, • 妊娠、哺乳 • 严重心脏病 • 严重腹泻，胰岛素依赖型糖尿病I 及 II型, • 对研究药物过敏 Cancer September 15, 2013

  43. 营养药物 • 研究组给予 500 mL特定设计肠内营养品, 包含脂肪 (40% of energy [EN%]), 蛋白质 (27 EN%), 及 n-3 脂肪酸 (2.0 g EPA and 0.85 g DHA);碳水化合物 (33 EN%). • 对照组给予500 mL肠内标准营养品（Fresubin energy fibre (蛋白质, 15EN%; 碳水化合物, 50 EN%). • 连续应用最多14周 • 两组均给予标准营养品以保持30-33 kcal/kg • 同期化疗为DDP或者Carboplatin Cancer September 15, 2013

  44. 评价指标 • Body cell mass体细胞质量 • Fat-free mass, lipid mass, total body water, extracellular water, intracellular water • body weight, body mass index, skin fold thickness, and mid-arm circumference • Kondrup score 和 the subjective global assessment (SGA) • QLQ-C30 Cancer September 15, 2013

  45. 研究设计 Cancer September 15, 2013

  46. 结果 Cancer September 15, 2013

  47. Cancer September 15, 2013

  48. 体质细胞指数 Changes of body cell mass from baseline adjusted for center (mean 6 standard error) after chemoradiotherapy and during the follow-up period Cancer September 15, 2013

  49. 副反应 • 与营养有关的副反应（AEs ）研究组 (6/55 [10.9%])低于对照组 (14/56 [25.0%]), (P=0.0535, chi-square test). • 与肿瘤治疗 (CRT)相关的副作用在研究组为 (51/55)，对照组为(46/56)，无显著性差异 (P=0.093) Cancer September 15, 2013

  50. 结论 • 研究提示该营养品改善患者放化疗期间的营养和功能状态 • 可能与营养品中加入EPA和DHA有关 • 两种营养品均安全，耐受性好 Cancer September 15, 2013

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