Next generation sequencing driven successful combined treatment with laparoscopic surgery and immunotherapy for relapsed stage IVB cervical and synchronous stage IV lung cancer

Abstract

Background: 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.

Patients and methods: 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).

Results: 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.

Conclusion: 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.

Keywords: cervical cancer; immunotherapy; laparoscopic total pelvic exenteratio; next-generation sequencing; synchronous cancer.

Figure 1. Histological analysis of the lung and cervical cancer

(A) shows histology of non-small-cell-lung cancer adenocarcinoma. (B) shows histological findings of the squamous cervical cancer.

Figure 2. Positron emission tomography (PET) and computed tomography (CT) imaging

The imaging of the disease extent before laparoscopic total pelvic exenteratio (Panel A) show in particular in the upper scans a large area of intense hypercaptation of the metabolic tracer in the pelvis and in the lombo-aortic and common iliac lymph node (white arrows); in the lower scans multiple positive areas in the lung (apical segment of the right superior lobe, superior segment of the inferior lobe bilaterally, a medium postero-basal segment of the left inferior lobe (white arrows). (Panel B and C) shows the PET/CT and CT imaging before (panel B) and after (panel C) chemo-immunotherapy of the: 1-2) left lombo-aortic lymphnodes; 3) right lung nodules; 4-6) left lung nodules; 7) pelvic region.