分化型甲状腺癌的治疗及影响复发的因素分析

背景与目的:有关分化型甲状腺癌的治疗,目前仍存在不少争论,争论的焦点主要包括分化型甲状腺癌外科切除的合适范围、颈淋巴结清扫的适应证等。本文主要研究分化型甲状腺癌的外科治疗及影响其复发的因素。方法:回顾性分析1985年1月1日～1997年12月31日在中山大学肿瘤防治中心治疗的分化型甲状腺癌581例,研究分化型甲状腺癌的治疗方式和效果,分析影响其复发的因素。结果:在我院行首次手术治疗、以单侧腺叶加峡部切除术加或不加颈淋巴结清扫为主要治疗方式的377例分化型甲状腺癌中,28例复发,复发率为7.43%,对侧腺叶的复发率为0.80%。在外院行首次手术治疗、以局部肿物切除加或不加颈淋巴结切除为主要治疗方式的195例分化型甲状腺癌中,143例再行手术治疗,100例再次术后病理阳性,肿瘤残留率为69.93%,其中腺体阳性率为46.15%,颈淋巴结阳性率为48.95%,195例中有47例复发,复发率为24.10%。以局部肿物切除加或不加颈淋巴结切除为主要治疗方式的患者的复发率显著高于以单侧腺叶加峡部切除加或不加颈淋巴结清扫为主要治疗方式的患者(P<0.05)。结论:单侧腺叶加峡部切除术加或不加颈淋巴结清扫应作为原发灶局限于一侧腺叶的分化型甲状腺癌的首次手术治疗方式。首次手术方式影响分化型甲状腺癌的复发。     

Evaluation of the surgical completeness after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: To quantify the rate of patients without thyroid remnants, to identify predictive factors for the absence of residual thyroid tissue and to evaluate number, site, size and function of thyroid remnants after total thyroidectomy for differentiated thyroid carcinoma (DTC). METHODS: Thousand one hundred and seventy-eight patients who underwent total thyroidectomy for DTC were evaluated; 343 patients with lymph node or distant metastases and 115 patients with detectable thyroglobulin autoantibodies (TgAb) were excluded. (131)I ablative treatment (RAI) without preliminary diagnostic (131)I whole body scans (DxWBS), and 24-h (131)I quantitative neck uptake (RAIU test) and thyroglobulin (Tg) off L-T4 evaluation were performed in the remaining 720 pts. In 252 patients a 99mTc-pertechnetate pre-operative thyroid scan (99mTc-scan) was used for comparison with (131)I neck scans after RAI to evaluate site of thyroid remnants. Only patients with thyroid remnants were evaluated for successful ablation 6-10 months after RAI. RESULTS: Post-treatment whole body scan (TxWBS) demonstrated lack of thyroid remnants in 50/720 patients and the best predictive factors for the absence of residual thyroid tissue were RAIU <1% and undetectable Tg off L-T4. Thyroid remnants were present in 670/720 patients. In 252 patients with (99m)Tc-scan, 617 sites of functioning thyroid tissue were found: 381 within and 236 outside the thyroid bed. Complete successful ablation was achieved in 610/670 patients with thyroid remnants. CONCLUSIONS: This study confirms that most patients (93.1%) have thyroid remnant after total thyroidectomy for DTC. Most thyroid remnants were contralateral to tumour site and were even observed outside thyroid bed. However, a real total thyroidectomy, demonstrated by negative TxWBS, RAIU <1% and undetectable Tg off L-T4, was achieved in 6.9% of patients.     

颈部超声、甲状腺球蛋白诊断复发分化型甲状腺癌

背景与目的：颈部超声与血清甲状腺球蛋白(thyroglobulin,Tg)是分化型甲状腺癌(differentiated thyroid carcinoma,DTC)术后随访的主要方法。刺激性Tg对分化型甲状腺癌的诊断价值已被充分证实,但抑制性Tg对DTC复发转移的诊断价值鲜有报道。该研究分析颈部超声及抑制性Tg对DTC复发转移的诊断价值。方法：回顾性分析2010年8月—2014年12月在北京协和医院行2次或以上手术,临床怀疑复发的DTC患者196例。选择其中入院前行甲状腺全切术后和(或)131I清甲治疗术后超声怀疑复发转移的患者共62例。分析转移性淋巴结超声特征以及抑制性Tg对DTC复发转移的诊断价值。结果：经病理证实,62例患者中59例为淋巴结转移,1例为局部复发,2例术后未发现明确复发转移。超声发现可疑淋巴结共121个,经病理证实转移性淋巴结92个,非转移性淋巴结25个,纤维组织3个,横纹肌组织1个。淋巴结内无回声、高回声及强回声对转移性淋巴结的阳性预测值均为100%,皮质内无回声及血流信号杂乱在转移性淋巴结和非转移淋巴结中差异有统计学意义。抑制性Tg阳性者(Tg≥0.2 ng/mL)49例,阴性者(Tg＜0.2 ng/mL)13例,抑制性Tg诊断颈部复发转移的准确率为82.3%,灵敏度为81.7%,特异度为100%。结论：皮质内无回声及血流信号杂乱是鉴别复发DTC颈部转移性淋巴结与非转移性淋巴结特异度较高的指标,抑制性Tg(Tg≥0.2 ng/mL)对DTC的复发转移有较高的诊断价值,颈部超声检查可发现血清Tg为阴性患者的复发转移病灶。     

Locally aggressive differentiated thyroid carcinoma

Local infiltration of adjacent anatomic structures and soft tissues of the neck from well-differentiated carcinoma of the thyroid gland is a relatively infrequent occurrence. We report our experience with 21 such cases seen in our department over the past 20 years. All patients were treated by total thyroidectomy and total or partial excision of the infiltrated adjacent structures. Papillary carcinoma was the most frequent type of primary tumor seen. Following the definitive surgery, all patients were scanned with radioactive iodine (131I). In case of isotope entrapment, a curative dose 131I was given. All patients in our series were required to receive thyroid hormone replacement. Four patients died as a result of their disease. Uncontrolled local disease and distant metastases were present at the time of death. Three patients died of unrelated causes. Two-thirds of the patients are still alive (from 1 to 19 years after the treatment).     

BRAF mutation-selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic-potentiated synergism with the mTOR inhibitor temsirolimus

We examined the therapeutic potential of a novel MEK inhibitor, RDEA119, and its synergism with the mTOR inhibitor, temsirolimus, in thyroid cancer cell lines. RDEA119 potently inhibited the proliferation of the 4 cell lines that harbored BRAF mutation but had no or modest effects on the other 4 cells that harbored wild-type BRAF (IC(50) of 0.034-0.217 μM vs. 1.413-34.120 μM). This inhibitory effect of RDEA119 in selected cell lines OCUT1 (BRAF V600E(+), PIK3CA H1047R(+)) and SW1376 (BRAF V600E(+)) was enhanced by combination with the mTOR inhibitor, temsirolimus. The PTEN-deficient cell FTC133 was highly sensitive to temsirolimus but insensitive to RDEA119, and simultaneous treatment with the latter enhanced the sensitivity of the cell to the former. The KAT18 (wild-type) cell was not sensitive to either drug alone but became sensitive to the combination of the 2 drugs. The drug synergy was confirmed by combination index and isobologram analyses. RDEA119 and temsirolimus also showed synergistic effects on autophagic death of OCUT1 and KAT18 cells selectively tested. Dramatic synergistic effects of the 2 drugs were also seen on the growth of FTC133 xenograft tumors in nude mice. Overall, the effects of the 2 drugs on cell proliferation or autophagic death, either alone or in combination, were more pronounced in cells that harbored genetic alterations in the MAP kinase and PI3K/Akt pathways. Thus, these results demonstrated the important therapeutic potential of the novel MEK inhibitor RDEA119 and its synergism with temsirolimus in thyroid cancer.     

儿童及青少年分化型甲状腺癌远处转移的临床病理学危险因素分析

背景与目的：近年来,儿童及青少年甲状腺癌发病率不断上升。探讨儿童及青少年分化型甲状腺癌（children and adolescents differentiated thyroid cancer, caDTC）远处转移的临床病理学危险因素。方法：回顾性分析2007年2月—2018年10月在北京协和医院核医学科就诊的年龄<21岁的69例DTC患者,合并远处转移的40例患者归入A组,无远处转移的29例患者归入B组,用t检验对比两组年龄,用χ²检验对比两组性别、甲状腺外侵犯、多灶及BRAF^V600E,用Mann-Whitney U检验对比两组肿瘤直径、T分期、N分期、术后¹³¹I治疗前刺激性甲状腺球蛋白（preablation-stimulated thyroglobulin,ps-Tg）及甲状腺球蛋白抗体（thyroglobulin antibody,TgAb）。通过受试者工作特征（receiver operating characteristic,ROC）曲线评估ps-Tg对远处转移的预测价值。应用多因素logistic回归分析确定远处转移的预测因子。结果：A组患者表现出更小的年龄、更易呈多灶性、更高的病理分期及更高的ps-Tg水平,而两组性别、甲状腺外侵犯、肿瘤直径及TgAb方面差异无统计学意义。ps-Tg与远处转移关系的ROC曲线的曲线下面积为0.900。ps-Tg最佳临界点为102.35 ng/mL,对应的灵敏度、特异度和阴性预测值分别为70.0%、100.0%和70.7%。进一步多因素logistic回归分析中,年龄和ps-Tg被证实是远处转移的预测因子。结论：低龄、高ps-Tg水平及多灶性等局部侵袭特征与caDTC的远处转移相关,以102.35 ng/mL作为ps-Tg的界值点对caDTC的远处转移具有预测价值。     

分化型甲状腺癌131I治疗前刺激性Tg与最佳治疗反应的关系

背景与目的：初始治疗（手术+¹³¹I+TSH抑制）后的疗效反应对动态评估患者的复发风险至关重要。本研究旨在探讨¹³¹I治疗前刺激性甲状腺球蛋白（preablative-stimulated thyroglobulin,ps-Tg）对最佳治疗反应的预测价值。方法：纳入中位随访74.5个月的分化型甲状腺癌（differentiated thyroid carcinoma,DTC）患者136例,根据治疗反应评估体系将其治疗效果分为4组：最佳治疗反应（excellent response,ER）（86例）、疗效不确切（indeterminate response,IDR）（18例）、血清学反应欠佳（biochemical incomplete response,BIR）（4例）和影像学反应欠佳（structural incomplete response,SIR）（28例）。采用χ²检验、Fisher精确检验和Kruskal-Wallis秩和检验比较4组患者的基本临床特征,建立ps-Tg及肿瘤大小与ER关系的受试者工作特征（receiver operating characteristic,ROC）曲线获得最佳界值点,对影响ER的因素进行多因素分析,进一步采用Kaplan-Meier曲线评估ps-Tg及肿瘤大小发生非ER的累积风险,使用log-rank法对差异进行统计学分析。结果：4组间ps-Tg水平、肿瘤大小、腺外侵犯、多灶性、淋巴结分期以及TNM分期差异有统计学意义（P＜0.05）,而性别和年龄差异无统计学意义（P＞0.05）。ps-Tg以及肿瘤大小与ER关系的ROC曲线下面积分别为0.865和0.666,当ps-Tg以9.05 ng/mL为界值预测ER时,灵敏度和特异度较高（分别为83.7%和80.0%）,肿瘤直径以1.05 cm为界值点时的灵敏度和特异度分别为53.5%和72.0%。多因素分析显示ps-Tg和肿瘤大小可以作为预测ER的独立因素（OR=20.571,P=0.015;OR=3.291,P=0.008）。随着肿瘤直径的增大,ps-Tg≥9.05组患者的非ER风险明显高于ps-Tg＜9.05组（P=0.000 3）。结论：ps-Tg（界值点为9.05 ng/mL）可用于预测本组患者最佳治疗反应,其与肿瘤大小结合可以更全面地预测初始治疗后的疗效。     

131I难治性分化型甲状腺癌分子靶向治疗进展

放射性碘难治性分化型甲状腺癌患者因病灶摄碘功能不佳而无法从131I等传统治疗方法中获益。近年来,甲状腺癌分子病理学研究新成果为甲状腺癌的分子诊断和靶向治疗提供了新的契机,相关分子靶向治疗的临床试验和荟萃分析均取得了可喜的结果。本文从临床角度对放射性碘难治性分化型甲状腺癌分子靶向治疗的最新进展进行综述。     

超声对低分化和未分化甲状腺癌的诊断价值

目的 探讨超声对低分化甲状腺癌(PDTC)和未分化(间变性)甲状腺癌(UTC)的诊断价值.方法 应用彩色多普勒超声对22例PDTC和UTC的甲状腺形态、大小、回声、边界、内部砂粒、血流分布等声像图表现及其内部血流状况进行观察,并与手术、活组织病理检查病理结果对照;扫查颈部及气管食管沟区淋巴结.根据甲状腺双叶或单叶弥漫性病变及局部淋巴结的超声表现,结合临床表现,判断甲状腺病变的性质.结果 术前或活组织病理检查前超声检出甲状腺单叶肿物16例,左甲9例,右甲7例.双叶肿物6例.超声提示UTC 2例,甲状旁腺癌1例,慢性淋巴细胞性甲状腺炎1例,其余提示甲状腺恶性肿瘤.结论 超声检查可提高PDTC和UTC的检出率和诊断率.     

首次131I治疗前刺激性甲状腺球蛋白在预测颈部及远处转移性分化型甲状腺癌的意义

背景与目的：由于受到残余甲状腺等多种因素的影响,刺激性甲状腺球蛋白(stimulated thyroglobulin,sTg)在首次¹³¹I治疗前对分化型甲状腺癌(differentiated thyroid carcinoma,DTC)复发转移的诊断价值尚有争议。该研究旨在探讨sTg在首次¹³¹I治疗前预测DTC患者颈部及远处转移的意义。方法：106例行甲状腺全切术及颈淋巴结清扫术的DTC患者,首次¹³¹I治疗前1天测sTg水平,¹³¹I治疗后5~7 d行¹³¹I全身显像和SPECT/CT断层融合显像。根据是否存在转移,将所有患者分为无转移组(M0)和颈部淋巴结转移组(M1)和远处转移组(M2),比较组间sTg值差异有无统计学意义,并通过ROC曲线及最佳诊断界值点(diagnostic critical point,DCP)评估sTg值预测转移的价值。结果：M0组、M1组和M2组的sTg值的四分位数间距分别为0.47~9.57、12.34~50.86和69.47~462.00 ng/mL。M1组、M2组与M0组的sTg相比差异均有统计学意义(P<0.01和P<0.01)。sTg值的ROC曲线下面积分别为0.872、0.964,DCP分别为23.95和20.93 ng/mL,灵敏度、特异度、准确度分别为68.42%、100%、92.31%和85.71%、100%、95.40%。结论：首次¹³¹I治疗前检测sTg值对DTC转移有重要的预测价值,对远处转移的预测价值更大。     

分化型甲状腺癌二次手术安全性探讨

目的：探讨分化型甲状腺癌二次手术的安全性。方法：回顾分析2003年7月-2010年2月63例分化型甲状腺癌二次手术相关资料,对二次手术的并发症进行分析。结果：二次手术并发症发生率17.46%（11/63）,暂时性甲状旁腺损伤发生率为7.94%（5/63）,暂时喉返神经损伤发生率为4.76%（3/63）,2周后声音嘶哑逐步恢复,1例发生永久性喉返神经损伤,先行呼吸机正压给氧待患者呼吸困难好转再行声带成形手术后患者呼吸困难消失,气管损伤发生率为3.17%（2/63）。结论：分化型甲状腺癌二次手术因解剖组织结构改变,二次手术并发症发生率较高,进行二次手术应熟悉解剖、掌握术中操作技巧及谨慎操作。     

分化型甲状腺癌二次手术安全性探讨

目的:探讨分化型甲状腺癌二次手术的安全性。方法:回顾分析2003年7月-2010年2月63例分化型甲状腺癌二次手术相关资料,对二次手术的并发症进行分析。结果:二次手术并发症发生率17.46%(11/63),暂时性甲状旁腺损伤发生率为7.94%(5/63),暂时喉返神经损伤发生率为4.76%(3/63),2周后声音嘶哑逐步恢复,1例发生永久性喉返神经损伤,先行呼吸机正压给氧待患者呼吸困难好转再行声带成形手术后患者呼吸困难消失,气管损伤发生率为3.17%(2/63)。结论:分化型甲状腺癌二次手术因解剖组织结构改变,二次手术并发症发生率较高,进行二次手术应熟悉解剖、掌握术中操作技巧及谨慎操作。     

Metabolic changes enhance the cardiovascular risk with differentiated thyroid carcinoma--a case control study from Manipal Teaching Hospital of Nepal

Objective: To evaluate several metabolic changes in patients with differentiated thyroid carcinoma (DTC )which enhance cardiovascular risk in the western region of Nepal. Materials and Methods: This hospital basedcase control study was carried out using data retrieved from the register maintained in the Department ofBiochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between 1st January, 2009 and 31st December,2011. The variables collected were age, gender, BMI, glucose, insulin, HbA1C, CRP, fibrinogen, total cholesterol,triglycerides, HDL, LDL, VLDL, f-T3, f-T4, TSH. One way ANOVA was used to examine statistical significanceof differences between groups, along with the Post Hoc test LSD for comparison of means. Results: fT3 valueswere markedly raised in DTC cases (5.7±SD1.4) when compared to controls (2.2±SD0.9). Similarly, fT4 valueswere also moderately raised in cases of DTC (4.9±SD1.3 and 1.7 ±SD0.9). In contrast, TSH values were loweredin DTC cases (0.39±SD0.4) when compared to controls (4.2 ±SD 1.4). Mean blood glucose levels were decreasedwhile insulin was increased and HDL reduced (39.5±SD4.7 as compared to the control 43.1±SD2.2). Conclusion:Cardiovascular risk may be aggravated by insulin resistance, a hypercoagulable state, and an atherogenic lipidprofile in patients with differentiated thyroid cancer.     

甲状腺球蛋白和抗甲状腺球蛋白抗体在分化型甲状腺癌疗效评价中的价值

目的探讨甲状腺球蛋白(TG)、抗甲状腺球蛋白抗体(A-TG)在分化型甲状腺癌(DTC)患者131I治疗后疗效评价中的应用价值。方法选取2008年1月至2013年2月间收治的106例DTC患者,按照TG水平将106例DTC患者分为TG阳性组(20例,TG≥30ng/ml)和TG阴性组(86例,TG<30ng/ml),另选35例健康人作为对照组,治疗前、治疗后2个月及6个月时测定血清TG和A-TG水平。结果 TG阴性组患者在治疗后2个月时TG水平为(13.51±3.81)ng/ml,显著低于治疗前(P<0.05)。TG阳性组患者治疗后2个月时TG水平为(70.17±5.71)ng/ml,显著低于治疗前(P<0.05),TG阴性组差异有统计学意义(P<0.05)。TG阴性组患者治疗2个月后A-TG升高者占19.8%,6个月后升高者占17.9%;TG阳性组患者治疗2个月后A-TG升高者占40.0%,6个月后升高者占30.0%,两组间差异均有统计学意义(P<0.05)。远处转移者患者TG水平升高者占58.3%,显著高于颈部转移者(34.6%),差异有统计学意义(P<0.05)。结论 TG有助于对手术切除甲状腺后行131I清甲治疗或转移灶治疗后患者病情的判断,但是无法避免A-TG对TG的干扰,因此临床需要同时检测患者血清A-TG水平,以便更加准确地判断患者疗效及预后。     

Optimization of the risk-benefit ratio of differentiated thyroid cancer treatment

The vast majority of differentiated thyroid cancers (DTC) are characterized by an innocuous nature, excellent patient survival, and limited treatment requirement. However, a significant proportion of affected patients is prone to receiving overtreatment, due to undertreatment concerns associated with the difficulty to differentiate them from a small minority affected by aggressive DTC. Identification of prognostic factors and development of staging systems has helped to reduce the proportion of overtreatment in DTC. However, the absolute number of overtreated patients continues to increase, as a result of an on-going incidence surge in early DTC associated with the increased application and sensitivity of modern diagnostic tools. In the present paper, we describe how DTC treatment can be optimized by thoughtful evidence-based balancing of oncologic safety against treatment associated morbidity.     

儿童及青少年分化型甲状腺癌核医学诊治中国专家共识（2022年版）

儿童及青少年分化型甲状腺癌（differentiated thyroid carcinoma in children and adolescents,caDTC）与成人存在较大差异,用于指导成人甲状腺癌的指南及治疗策略不完全适用于儿童及青少年。因此,来自核医学科、甲状腺外科、内分泌科、超声科、病理科及分子生物等甲状腺领域的专家组成编委会共同参与针对儿童及青少年人群的分化型甲状腺癌诊治共识的编撰。本共识的制定基于实用性、本土性及治疗手段可及性的原则,内容包括caDTC的流行病学、检查手段、治疗策略（手术、放射性碘、靶向及内分泌治疗）及随访等,基本涵盖caDTC的常见临床管理。     

不同年龄儿童及青少年分化型甲状腺癌患者的临床病理学特征与131I治疗分析

背景与目的： 既往研究已发现18岁以下的儿童及青少年分化型甲状腺癌（differentiated thyroid carcinoma,DTC）与成人DTC在临床病理学特征、远期预后等方面存在差异,但对其内部不同年龄段之间,特别是青春期前、围青春期和青春期之间的特征研究较少,因此本研究旨在探讨不同年龄组儿童及青少年DTC的临床病理学特征及首次¹³¹I治疗效果的差异。方法： 回顾性分析四川大学华西医院2006年7月—2022年1月收治的156例儿童及青少年DTC患者。根据年龄分为青春期前（0岁<年龄≤10岁）、围青春期（10岁<年龄≤14岁）及青春期（14岁<年龄≤18岁）3组,比较3组的临床病理学特征、初始复发危险度分层、首次¹³¹I治疗后动态风险评估及刺激性甲状腺球蛋白（stimulated thyroglobulin,sTg）水平在首次¹³¹I治疗后的变化。结果： 3组患者的性别、原发肿瘤最大直径、包膜侵犯、T分期、N分期及切除淋巴结阳性转移比例差异无统计学意义（P>0.05）。3组患者的远处转移率分别为63.2%、42.1%和20.2%（χ²=16.839,P=0.000）,高危患者分别占88.9%、60.5%和46.4%（χ²=12.447,P=0.009）。3组患者首次¹³¹I治疗后动态风险评估的差异有统计学意义（χ²=21.744,P=0.001）,其中3组患者的疗效满意（excellent response,ER）比例分别为10.5%、25.0%和38.1%;结构性疗效不佳（structural incomplete response,SIR）比例分别为68.4%、52.8%和25.8%;生化疗效不佳（biochemical incomplete response,BIR）比例分别为21.1%、13.9%和14.4%。63例患者接受了第2次¹³¹I治疗且TgAb低于40 U/mL,首次¹³¹I治疗后3组的中位sTg降幅分别为41.31%、38.02%和60.38%（H=4.642,P=0.098）。结论： 儿童及青少年DTC中0~10岁组患者的远处转移率和高危复发风险最高,首次¹³¹I治疗后ER的结局最少,青春期前儿童DTC的发生、发展机制和治疗值得进一步研究。     

Preclinical evaluation of PI3K inhibitor BYL719 as a single agent and its synergism in combination with cisplatin or MEK inhibitor in nasopharyngeal carcinoma (NPC)

Nasopharyngeal carcinoma (NPC) is endemic to Southeast Asia and over 40% of NPC tissues harbor PIK3CA amplifications. This study aims to study the preclinical activity of a novel PI3K inhibitor, BYL719, in 6 NPC cell lines: C666-1, CNE-2, HK1, HK1-EBV, HONE-1 and HONE-1-LMP1. Over 70% of growth inhibition was attained when NPC cell lines were exposed to increasing concentrations of BYL719, with IC₅₀ values at the low micro-molar range. Two BYL719-sensitive cell lines that harbor PIK3CA mutations, CNE-2 and HONE-1, were selected for further analysis on the effect of BYL719 on cell cycle progression, apoptosis and PI3K signaling. BYL719 significantly reduced the phosphorylation of Akt, and the Akt-mTOR axis downstream effector S6 in these 2 cell lines, but a feedback activation of MAPK was observed at 72 hours post-treatment. BYL719 induced G₀/G₁ cell cycle arrest and apoptosis in both cell lines. In 3D cell culture models, the growth of NPC spheroids was significantly inhibited in a dose-depending manner. When BYL719 was combined with a MEK inhibitor (AZD6244) in a 3D cell culture system, strong synergism on NPC cell growth was observed with attenuation of MAPK activation. A synergistic inhibitory effect on growth was observed when BYL719 was combined with higher dose levels of cisplatin. These data suggest that BYL719 has preclinical activity in NPC cell lines especially in those which harbor PIK3CA mutation. Combination with a MEK inhibitor maybe a useful strategy that warrants further investigation.     

Family history of cancer and risk of sporadic differentiated thyroid carcinoma

BACKGROUND:

Thyroid cancer incidence in the United States, particularly in women, has increased dramatically since the 1980s. Although the causes of thyroid cancer in most patients remain largely unknown, evidence suggests the existence of an inherited predisposition to development of differentiated thyroid carcinoma (DTC). Therefore, the authors explored the association between sporadic DTC and family history of cancer.

METHODS:

In a retrospective hospital‐based case‐control study of prospectively recruited subjects who completed the study questionnaire upon enrollment, unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the DTC risk associated with first‐degree family history of cancer.

RESULTS:

The study included 288 patients with sporadic DTC and 591 cancer‐free controls. Family history of thyroid cancer in first‐degree relatives was associated with increased DTC risk (adjusted OR, 4.1; 95% CI, 1.7‐9.9). All DTC cases in patients with a first‐degree family history of thyroid cancer were cases of papillary thyroid carcinoma (PTC) (adjusted OR, 4.6; 95% CI, 1.9‐11.1). Notably, the risk of PTC was highest in subjects with a family history of thyroid cancer in siblings (OR, 7.4; 95% CI, 1.8‐30.4). In addition, multifocal primary tumor was more common among PTC patients with first‐degree family history of thyroid cancer than among PTC patients with no first‐degree family history of thyroid cancer (68.8% vs 35.5%, P = .01).

CONCLUSIONS:

The study suggests that family history of thyroid cancer in first‐degree relatives, particularly in siblings, is associated with an increased risk of sporadic PTC. Cancer 2012;. © 2011 American Cancer Society.     

Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer

Lenvatinib is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptors 1–3, fibroblast growth factor receptors 1–4, RET, KIT, and platelet-derived growth factor receptor-α. Lenvatinib is approved as a monotherapy for the treatment of radioiodine-refractory differentiated thyroid cancer and in combination with everolimus for the second-line treatment of advanced renal cell carcinoma. Lenvatinib is also under investigation for the treatment of several malignancies including unresectable hepatocellular carcinoma. Although lenvatinib is associated with favorable efficacy, it is associated with adverse events (AEs) that the clinician will have to closely monitor for and proactively manage. Most of these AEs are known class effects of VEGF-targeted therapies, including hypertension, diarrhea, fatigue or asthenia, decreased appetite, and weight loss. This review summarizes the safety profile of lenvatinib and offers guidance for the management of both frequent and rare AEs. We discuss the potential mechanisms underlying these AEs and present practical recommendations for managing toxicities. The development of treatment plans that include prophylactic and therapeutic strategies for the management of lenvatinib-associated AEs has the potential to improve patient quality of life, optimize adherence, minimize the need for dose reductions, treatment interruptions, or discontinuations, and maximize patient outcomes.