Madeddu Clelia, Kotsonis Paraskevas, Lavra Fabrizio, Chiappe Giacomo, Melis Luca, Mura Ester, Scartozzi Mario, Macciò Antonio
Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Department of Gynecologic Oncology, Azienda Ospedaliera Brotzu, Cagliari, Italy.
Oncotarget. 2019 Mar 12;10(21):2012-2021. doi: 10.18632/oncotarget.26769.
The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy.
We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. The treatment choice was based on tumor PD-Ligand 1 assessment and NGS analysis for the identification of potential treatment targets. Outcomes included tumor objective response and patient-centered outcomes (pain, performance status and overall quality of life).
Laparoscopic surgery obtained an immediate symptom control and allowed the early start of medical treatment. One month after combined therapy start the patient achieved a significant improvement in performance status, pain, overall Quality of life and after 3 months she resumed working. After 3 and 6 months of treatment we observed an objective dimensional and metabolic response. Currently, after 24 months (and 48 cycles of nivolumab) the patient is continuing to benefit from treatment: she is in complete remission, with good performance status and she is working and leading a self-dependent life.
Our study strongly affirms the efficacy of an interdisciplinary approach including surgical and innovative medical strategies based on immunotherapy in patients with advanced chemo-resistant synchronous cervical and lung cancer. The present findings support the use of NGS to drive a targeted rational treatment especially in heavily pre-treated patients.
对患有多个同步肿瘤的患者进行治疗具有挑战性且复杂。使用下一代测序（NGS）可能有助于识别涉及两种肿瘤共同病因的基因中的种系突变，从而制定共同有效的治疗策略。
我们描述了一名年轻女性患者取得的意外积极结果。该患者患有复发性化疗耐药的IVB期宫颈癌和同步性IV期肺癌，接受了多学科治疗方法，包括姑息性手术，即腹腔镜全盆腔脏器切除术，随后采用抗程序性死亡（PD）-1抗体纳武单抗加小剂量节拍环磷酰胺的化疗免疫治疗方案。治疗选择基于肿瘤程序性死亡配体1（PD-L1）评估和NGS分析以确定潜在治疗靶点。结果包括肿瘤客观缓解以及以患者为中心的结果（疼痛、体能状态和总体生活质量）。
腹腔镜手术立即控制了症状，并使药物治疗得以尽早开始。联合治疗开始1个月后，患者的体能状态、疼痛和总体生活质量有了显著改善，3个月后她恢复了工作。治疗3个月和6个月后，我们观察到客观的尺寸和代谢缓解。目前，在24个月（以及48个周期的纳武单抗治疗）后，患者仍在持续从治疗中获益：她处于完全缓解状态，体能状态良好，正在工作并过着自立的生活。
我们的研究有力地证实了多学科治疗方法的有效性，该方法包括基于免疫疗法的手术和创新医疗策略，用于治疗晚期化疗耐药的同步性宫颈癌和肺癌患者。目前的研究结果支持使用NGS来推动有针对性的合理治疗，尤其是在经过大量前期治疗的患者中。
