Research Papers:

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

Clelia Madeddu, Paraskevas Kotsonis, Fabrizio Lavra, Giacomo Chiappe, Luca Melis, Ester Mura, Mario Scartozzi and Antonio Macciò _

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Oncotarget. 2019; 10:2012-2021. https://doi.org/10.18632/oncotarget.26769

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Clelia Madeddu1, Paraskevas Kotsonis2, Fabrizio Lavra2, Giacomo Chiappe2, Luca Melis3, Ester Mura4, Mario Scartozzi1 and Antonio Macciò2

1 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

2 Department of Gynecologic Oncology, Azienda Ospedaliera Brotzu, Cagliari, Italy

3 Department of Nuclear Medicine, Azienda Ospedaliera Brotzu, Cagliari, Italy

4 Department of Pathology, Azienda Ospedaliera Brotzu, Cagliari, Italy

Correspondence to:

Antonio Macciò,email: [email protected]

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

Received: January 21, 2019     Accepted: February 22, 2019     Published: March 12, 2019


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.

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