妊娠合并晚期结直肠癌肝转移病例分享

2018-10-11 周玮 肿瘤资讯

一般情况:女性患者,39岁,孕30W+。主诉:排便次数增多2月余。BMI:24.3 kg/m2,ADL:I级, ECOG评分:0分,BSA:1.65 m2。

病例介绍

一般情况:女性患者,39岁,孕30W+。主诉:排便次数增多2月余。BMI:24.3 kg/m2,ADL:I级, ECOG评分:0分,BSA:1.65 m2。

既往史及家族史:伯父直肠癌病史。

实验室检查: 肿瘤标记物:CEA 1142 ng/ml ,CA199 273 U/ml,余标志物正常。

肛门指检:距肛6 cm未及肿块,指套无染血。

肠镜检查:距肛7 cm可见一肿块,占据肠腔1/3 周,质脆,触之易出血。

病理活检:中分化腺癌。

TAUS:距肛7 cm肿块,T3N1。

影像学检查及评估:2017.2 胸部CT平扫:右上肺结节,建议随访。2017.2 腹部CT平扫:肝脏多发度密度灶,考虑转移。

图1 .2017.2胸腹部CT扫描显示右上肺结节及多发肝转移瘤模式图。

临床诊断及初始评估:根据影像学检查结果提示,患者诊断直肠癌合并同时性多发肝转移,且患者孕30W+。对于结直肠癌合并妊娠28-32周的患者,未发生严重并发症,不威胁孕妇生命安全,可在胎儿存活时,及时分娩或行剖宫术,之后再择期行结直肠癌根治术。鉴于上述原因,患者于2017.3.3终止妊娠,行剖宫产。2017.3.10 盆腔MRI增强:直肠中段癌,T3b,N2,CRM (+), EMVI (-)。2017.3.9 上腹部MR增强:肝脏多发占位,转移考虑。临床诊断:同时性直肠癌伴肝转移 (cT3bN2M1a IVA期)。

图2 .2017.3.10盆腔MRI增强提示直肠中段癌。

图3 .2017.3.9上腹部MRI增强提示多发肝转移。

病情评估及第一阶段治疗方案:患者诊断为直肠癌合并同时性多发肝转移,专家评估结果为原发病灶潜在可切除,但具有高度复发风险,而转移灶潜在可切除性尚不确定。患者目前的治疗目标为缩小肿瘤、缓解疾病和延长患者生存期。综合起来,给患者拟定的全程管理方案为先行术前新辅助治疗,待病灶控制稳定再择期进行直肠原发肿瘤和肝转移瘤切除。

第一阶段治疗疗效评价:患者目前RAS和BRAF基因检测结果尚不明确,综合考虑,2017.03.13给与患者FOLFIRI方案化疗一周期。后分子病理检测结果回报,提示:KRAS G12V 突变,NRAS、BRAF 野生型。2017.03.27-2017.05.08继续行FOLFIRI +贝伐珠单抗方案化疗四周期。化疗过程顺利,仅出现Ⅱ度骨髓抑制和轻度消化道反应。2017年5月疗效评估为PR。

图4 .化疗五周期后直肠中段原发灶变化情况。

图5.化疗五周期后肝转移瘤变化情况。

图6.化疗过程中肿瘤标记物呈持续降低态势。

第二阶段治疗方案及疗效评价:经过五周期化疗后,患者目前疗效评估为PR,直肠中段原发病灶和肝转移瘤转变为潜在可切除,拟继续给与患者原方案化疗和放疗治疗,待肿瘤进一步缩小后,择期行手术切除治疗。2017.05.08-2017.05.27期间,患者继续行FOLFIRI +贝伐珠单抗方案化疗两周期。2017.06.05-2017.06.09期间,行短程放疗 10MV-X SAD 100 DT 5000cGy 5F/5d。放疗结束后,于2017.06.20-2017.07.13期间,继续行FOLFIRI +贝伐珠单抗方案化疗两周期。CEA和CA199呈持续降低态势,疗效评估为PR。

图7 .第二阶段治疗后直肠中段原发灶变化情况。

图8 .第二阶段后肝转移瘤变化情况。

第三阶段治疗方案及疗效评估:经过短程放疗和四周期FOLFIRI +贝伐珠单抗化疗后,患者原发病灶和肝转移病灶均转化为可切除病灶,拟择期给与患者手术切除治疗。2017.7.28行FOLFIRI方案围手术期化疗一周期,2017.8.29 腹腔镜辅助直肠癌根治术+术中超声定位+肝转移瘤切除。术后病理:(直肠) 溃疡型中分化腺癌,浸润累犯至浆膜下,上下切缘阴性,淋巴结见癌转移 (3+/12); 左肝外叶、左肝内叶、右肝前叶、右肝后叶见多灶腺癌,考虑转移性。术后诊断:直肠癌 肝多发转移 (ypT3N1bM1a IVA期)。

第四阶段治疗方案及疗效评估:既往研究显示,经动脉的化疗栓塞(TACE) 对于结直肠癌肝转移具有较好的临床疗效和安全性。因此,2017.9.29患者接受TACE治疗。2017.10.5患者行术后单药贝伐单抗治疗一周期,2017.10.23-2017.11.8继续行FOLFIRI +贝伐珠单抗方案化疗四周期,期间患者病情稳定。2017.12月至此,行卡培他滨+贝伐珠单抗维持治疗八周期,肿瘤标记物CEA、CA199一直处于正常值范围,病灶一直处于稳定状态。





图9 .术后化疗及维持治疗后肝转移瘤变化情况。

病例难点与亮点:

1. 妊娠期结直肠癌的症状经常会被妊娠期间出现的不适反应所掩盖,导致患者就诊不及时而延误病情,患者预后通常较差。妊娠期间,很多常规检查的开展同样会受到限制。结肠镜检查和病理活检作为结直肠癌诊断的“金标准”,通常不推荐用于妊娠女性。主要原因是,上述检查可能会引起严重的妊娠并发症,甚至可能会导致流产。若结直肠癌合并妊娠28-32周,且未发生严重并发症,不威胁孕妇生命安全,可在胎儿存活时,及时分娩或行剖宫术,之后再择期行结直肠癌根治术。本例患者为一孕30w+患者,原发病灶潜在可切除,肝多发转移,综合考虑后,给与患者终止妊娠,并行剖宫产。之后给与患者化疗和放疗治疗,使得潜在可切除病灶转变为可切除病灶,最终行腹腔镜辅助直肠癌根治术+肝转移瘤切除治疗。

2. 联合化疗应当作为能耐受化疗的转移性结直肠癌患者的一、二线治疗。推荐以下化疗方案:FOLFOX/FOLFIRI±西妥昔单抗 (推荐用于KRAS、NRAS、BRAF基因野生型患者),CapeOx/FOLFOX/FOLFIRI/±贝伐珠单抗。本例患者治疗前KRAS和BRAF基因状态尚未明确,因此选择FOLFIRI方案化疗一周期。后患者分子病理检测结果示:KRAS: G12V 突变;NRAS、BRAF 野生型。在后续化疗治疗中,选择FOLFIRI+贝伐单抗治疗。

3. 该患者直肠中段癌合并同时性多发肝转移,原发灶初始状态潜在可切除,而肝转移病灶复发风险高,且转移数目众多、转移灶直径较大。因此考虑先行术前新辅助治疗,待病灶控制稳定再择期进行直肠原发肿瘤和肝转移瘤切除。术前联合应用FOLFIRI+贝伐单抗方案全身化疗和局部放疗治疗,可以最大限度缩小肿瘤,降低复发,更多保留正常肝实质,为后续肝转移瘤手术治疗创造了有利条件。目前患者肝脏手术后至2018年4月随访仍处于NED状态,PFS达到8个月。该病例凸显了对于妊娠合并结直肠癌肝转移患者的全程管理理念,FOLFIRI联合贝伐单抗、放疗对于结直肠癌肝转移患者具有较强的缩瘤作用,同时合理安排治疗策略可以获得较好的肿瘤病理缓解和手术安全性。

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    2018-10-11 天地飞扬

    了解一下,谢谢分享!

    0

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    2018-10-11 医者仁心5538

    学习了

    0

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