Multimodal treatment for resectable neuroendocrine carcinoma of the cervix

in Endocrine-Related Cancer
Authors:
Carmine Valenza Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy
Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy

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Francesca Spada Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Francesco Multinu Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Lavinia Benini Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Michele Borghesani Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Laura Algeri Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Manila Rubino Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Eleonora Pisa Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Lorenzo Gervaso Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Chiara Alessandra Cella Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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Silvestro Carinelli Division of Pathology and Laboratory Medicine, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Simone Bruni Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Gabriella Schivardi Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Giuseppe Curigliano Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy
Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy

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Vanna Zanagnolo Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Giovanni Aletti Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy
Division of Gynecologic Surgery, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy

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Nicoletta Colombo Division of Gynecologic Oncology, European Institute of Oncology, IRCCS, Via Ripamonti, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy

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Nicola Fazio Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti, Milan, Italy

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https://orcid.org/0000-0001-6869-0704

Correspondence should be addressed to G Aletti: giovanni.aletti@ieo.it

*(N Colombo and N Fazio contributed equally to this work)

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Non-metastatic neuroendocrine carcinoma of the cervix (NECC) is a rare and aggressive disease. Lacking prospective studies, the optimal multimodal treatment approach has not yet been clearly defined. This study aims to assess the clinical outcomes of patients with non-metastatic NECC treated with surgery and (neo)adjuvant chemotherapy, according to pathologic prognostic factors and multimodal treatments received. We retrospectively examined data from patients with non-metastatic NECC candidate to receive surgery and (neo)adjuvant chemotherapy and discussed at the European Institute of Oncology’s Multidisciplinary Neuroendocrine Tumor Board, between January 2003 and December 2021. Primary endpoints were event-free survival and overall survival. A total of 27 consecutive patients were evaluated, 15 with early stage NECC and 12 with a locally advanced NECC. Eight patients received neoadjuvant and 19 adjuvant platinum-based chemotherapy; 14 received adjuvant pelvic radiotherapy, half with external-beam radiation therapy alone, and half combined with brachytherapy. No patients progressed or relapsed during (neo)adjuvant chemotherapy. The median event-free survival was 21.1 months and the median overall survival was 33.0 months. Pathological FIGO stage ≥ IIB, adjuvant external-beam radiation therapy with or without brachytherapy emerged as significant and independent prognostic factors for event-free survival. Brachytherapy was also prognostic for overall survival. Non-metastatic NECC requires a multimodal approach, mainly weighted on the FIGO stage. The addition of brachytherapy should be considered, especially in patients with locally advanced disease. Because of the scarcity of robust clinical data, treatment strategy should be discussed in multidisciplinary board, taking into account patient.

 

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  • Bajaj A, Frumovitz M, Martin B, Jhingran A, Albuquerque KV, Yen A, Jones EL, Gaffney DKK, Christensen MC, Ayala-Peacock DN, et al.2018 Small cell carcinoma of the cervix: definitive chemoradiation for locally advanced disease. International Journal of Radiation Oncology Biology Physics 102 S85S86. (https://doi.org/10.1016/j.ijrobp.2018.06.226)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bermúdez A, Vighi S, Garcı´a A & & Sardi J 2001 Neuroendocrine cervical carcinoma: a diagnostic and therapeutic challenge. Gynecologic Oncology 82 3239. (https://doi.org/10.1006/gyno.2001.6201)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Caruso G, Palaia I, di Donato V, Pernazza A, Gallo R, Perniola G, Leopizzi M, della Rocca C, Muzii L & & Panici PB 2021 Radical surgery after neoadjuvant chemotherapy for locally advanced neuroendocrine cancer of the cervix. Anticancer Research 41 44314438. (https://doi.org/10.21873/anticanres.15250)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cohen JG, Kapp DS, Shin JY, Urban R, Sherman AE, Chen LM, Osann K & & Chan JK 2010 Small cell carcinoma of the cervix: treatment and survival outcomes of 188 patients. American Journal of Obstetrics and Gynecology 203 347.e1347.e6. (https://doi.org/10.1016/j.ajog.2010.04.019)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dongol S, Tai Y, Shao Y, Jiang J & & Kong B 2014 A retrospective clinicopathological analysis of small-cell carcinoma of the uterine cervix. Molecular and Clinical Oncology 2 7175. (https://doi.org/10.3892/mco.2013.193)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gadducci A, Carinelli S & & Aletti G 2017 Neuroendrocrine tumors of the uterine cervix: a therapeutic challenge for gynecologic oncologists. Gynecologic Oncology 144 637646. (https://doi.org/10.1016/j.ygyno.2016.12.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gardner GJ, Reidy-Lagunes D & & Gehrig PA 2011 Neuroendocrine tumors of the gynecologic tract: a Society of Gynecologic Oncology (SGO) clinical document. Gynecologic Oncology 122 190198. (https://doi.org/10.1016/j.ygyno.2011.04.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hoskins PJ, Swenerton KD, Pike JA, Lim P, Aquino-Parsons C, Wong F & & Lee N 2003 Small-cell carcinoma of the cervix: fourteen years of experience at a single institution using a combined-modality regimen of involved-field irradiation and platinum-based combination chemotherapy. Journal of Clinical Oncology 21 34953501. (https://doi.org/10.1200/JCO.2003.01.501)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Janopaul-Naylor JR, Shen Y, Qian DC & & Buchwald ZS 2021 The abscopal effect: a review of pre-clinical and clinical advances. International Journal of Molecular Sciences 22 11061. (https://doi.org/10.3390/ijms222011061)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kim C, Salvo G, Ishikawa M, Chen TC, Jhingran A, Bhosale P, Ramalingam P & & Frumovitz M 2023 The role of postoperative radiation after radical hysterectomy for women with early-stage neuroendocrine carcinoma of the cervix: a meta-analysis. Gynecologic Oncology 170 328332. (https://doi.org/10.1016/j.ygyno.2023.01.036)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lee JM, Lee KB, Nam JH, Ryu SY, Bae DS, Park JT, Kim SC, Cha SD, Kim KR, Song SY, et al.2008 Prognostic factors in FIGO stage IB–IIA small cell neuroendocrine carcinoma of the uterine cervix treated surgically: results of a multi-center retrospective Korean study. Annals of Oncology 19 321326. (https://doi.org/10.1093/annonc/mdm465)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lin AJ, Hassanzadeh C, Markovina S, Schwarz J & & Grigsby P 2019 Brachytherapy and survival in small cell cancer of the cervix and uterus. Brachytherapy 18 163170. (https://doi.org/10.1016/j.brachy.2018.11.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nasu K, Hirakawa T, Okamoto M, Nishida M, Kiyoshima C, Matsumoto H, Takai N & & Narahara H 2011 Advanced small cell carcinoma of the uterine cervix treated by neoadjuvant chemotherapy with irinotecan and cisplatin followed by radical surgery. Rare Tumors 3 e6. (https://doi.org/10.4081/rt.2011.e6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • NCCN. NCCN Clinical Practice Guidelines in Oncology. Cervical Cancer (Version 1.2023). Plymouth Meeting, PA, USA: National Comprehensive Cancer Network, 2023. (available at: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Salvo G, Gonzalez Martin A, Gonzales NR & & Frumovitz M 2019 Updates and management algorithm for neuroendocrine tumors of the uterine cervix. International Journal of Gynecological Cancer 29 986995. (https://doi.org/10.1136/ijgc-2019-000504)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Salvo G, Ramalingam P, Flores Legarreta A, Jhingran A, Gonzales NR, Chisholm GB & & Frumovitz M 2021 Role of radical hysterectomy in patients with early-stage high-grade neuroendocrine cervical carcinoma: a NeCTuR study. International Journal of Gynecological Cancer 31 495501. (https://doi.org/10.1136/ijgc-2020-002213)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Satoh T, Takei Y, Treilleux I, Devouassoux-Shisheboran M, Ledermann J, Viswanathan AN, Mahner S, Provencher DM, Mileshkin L, Åvall-Lundqvist E, et al.2014 Gynecologic cancer InterGroup (GCIG) consensus review for small cell carcinoma of the cervix. International Journal of Gynecological Cancer 24(Supplement 3) S102S108. (https://doi.org/10.1097/IGC.0000000000000262)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI & & Zaino RJ 1999 A Randomized Trial of Pelvic radiation therapy versus No Further Therapy in Selected Patients with Stage IB Carcinoma of the cervix after radical hysterectomy and Pelvic Lymphadenectomy: a gynecologic oncology group study. Gynecologic Oncology 73 177183. (https://doi.org/10.1006/gyno.1999.5387)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stecklein SR, Jhingran A, Burzawa J, Ramalingam P, Klopp AH, Eifel PJ & & Frumovitz M 2016 Patterns of recurrence and survival in neuroendocrine cervical cancer. Gynecologic Oncology 143 552557. (https://doi.org/10.1016/j.ygyno.2016.09.011)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tempfer CB, Tischoff I, Dogan A, Hilal Z, Schultheis B, Kern P & & Rezniczek GA 2018 Neuroendocrine carcinoma of the cervix: a systematic review of the literature. BMC Cancer 18 530. (https://doi.org/10.1186/s12885-018-4447-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wharton D, Kim E, Pagan J, Small W, Jaboin J & & Ayala-Peacock D 2020 Patterns of care and outcomes for small cell carcinoma of the cervix: a national retrospective analysis of 542 cases. Advances in Radiation Oncology 5 412418. (https://doi.org/10.1016/j.adro.2019.08.008)

    • PubMed
    • Search Google Scholar
    • Export Citation