Case report: Reproductive organ preservation and subsequent pregnancy for an infertility patient with lynch syndrome-associated synchronous endometrial cancer and colon cancer after treatment with a PD-1 checkpoint inhibitor

Currently, immune checkpoint inhibitors (ICIs) are the mainstay of treatment for Lynch syndrome patients. However, the tumor regression features in radiology and pathology are inconsistent for patients who are treated with ICIs, which sometimes confuses surgical decision-making. Here, we report a case in which a 36-year-old patient suffering from infertility was diagnosed with Lynch syndrome-associated synchronous endometrial cancer and colon cancer, and persistently enlarged left iliac paravascular lymph nodes were detected after receiving sintilimab treatment, a programmed cell death 1 (PD-1) receptor inhibitor. Fortunately, when she was about to undergo hysterectomy and bilateral salpingo-oophorectomy, intraoperative pathology examination did not reveal any cancer cells in these lymph nodes, and therefore, her reproductive organs were preserved. Later, the patient successfully conceived and gave birth to a healthy male neonate with no immune-related adverse events (irAEs) during an 11-month follow-up. This case indicates that surgeons should carefully inspect the imaging characteristics after immunotherapy and that organ preservation is possible even for patients who fail to achieve complete clinical regression, which is especially important for female patients of childbearing age.

[1]  T. Gambichler,et al.  Uncomplicated pregnancy and delivery under ongoing nivolumab therapy for metastatic melanoma. , 2022, Melanoma research.

[2]  G. Gullo,et al.  Biomolecular and Genetic Prognostic Factors That Can Facilitate Fertility-Sparing Treatment (FST) Decision Making in Early Stage Endometrial Cancer (ES-EC): A Systematic Review , 2022, International journal of molecular sciences.

[3]  J. Haanen,et al.  Immunotherapy for cancer treatment during pregnancy. , 2021, The Lancet. Oncology.

[4]  G. Scambia,et al.  Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification , 2021, International journal of molecular sciences.

[5]  A. S. Laganà,et al.  Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview , 2021, International journal of molecular sciences.

[6]  Yuki Yamamoto,et al.  Malignant melanoma treated with pembrolizumab during pregnancy: A case report and review of the literature , 2021, Molecular and clinical oncology.

[7]  F. Garcia-Bournissen,et al.  Pregnancy outcome after early exposure to nivolumab, a PD-1 checkpoint inhibitor for relapsed Hodgkin’s lymphoma , 2021, Clinical toxicology.

[8]  A. Andrikopoulou,et al.  Immune checkpoint inhibitor administration during pregnancy: a case series , 2021, ESMO open.

[9]  N. Raghuraman,et al.  Term Pregnancy After Complete Response of Placental Site Trophoblastic Tumor to Immunotherapy , 2021, Obstetrics and gynecology.

[10]  N. Johnson,et al.  Successful pregnancy and fetal outcome following previous treatment with pembrolizumab for relapsed Hodgkin's lymphoma , 2021, Cancer reports.

[11]  J. Haiduk,et al.  Pregnancy in a patient with metastatic uveal melanoma treated with nivolumab , 2021, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[12]  Qi Wang,et al.  Variations in incidence and mortality rates of endometrial cancer at the global, regional, and national levels, 1990-2019. , 2021, Gynecologic oncology.

[13]  O. Karaaslan,et al.  Novelties of ultrasound imaging for endometrial cancer preoperative workup. , 2020, Minerva medica.

[14]  G. Lippi,et al.  Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer , 2020, Pathology & Oncology Research.

[15]  G. Gullo,et al.  Closed vs. Open Oocyte Vitrification Methods Are Equally Effective for Blastocyst Embryo Transfers: Prospective Study from a Sibling Oocyte Donation Program , 2020, Gynecologic and Obstetric Investigation.

[16]  I. G. Glitza Oliva,et al.  Conception and viable twin pregnancy in a patient with metastatic melanoma while treated with CTLA-4 and PD-1 checkpoint inhibition. , 2020, Melanoma research.

[17]  P. Therasse Immune-Related Response Criteria , 2020, Definitions.

[18]  S. Garzon,et al.  Presence of Glandular Cells at the Preoperative Cervical Cytology and Local Recurrence in Endometrial Cancer , 2019, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[19]  V. Atkinson,et al.  Pregnancy with successful foetal and maternal outcome in a melanoma patient treated with nivolumab in the first trimester: case report and review of the literature. , 2019, Melanoma research.

[20]  A. Enk,et al.  Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy. , 2018, European journal of cancer.

[21]  M. Burotto,et al.  Viable Pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy. , 2018, Seminars in oncology.

[22]  C. Boland,et al.  Recent progress in Lynch syndrome and other familial colorectal cancer syndromes , 2018, CA: a cancer journal for clinicians.

[23]  David Moher,et al.  CARE guidelines for case reports: explanation and elaboration document. , 2017, Journal of clinical epidemiology.

[24]  G. Gullo,et al.  GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial , 2017, Journal of Assisted Reproduction and Genetics.

[25]  J. Degeorge,et al.  An Evaluation of the Impact of PD-1 Pathway Blockade on Reproductive Safety of Therapeutic PD-1 Inhibitors. , 2016, Birth defects research. Part B, Developmental and reproductive toxicology.

[26]  Bert Vogelstein,et al.  PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. , 2015, The New England journal of medicine.

[27]  A. Salama,et al.  Oncotargets and Therapy Dovepress Clinical Applications of Pd-1-based Therapy: a Focus on Pembrolizumab (mk-3475) in the Management of Melanoma and Other Tumor Types , 2022 .

[28]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[29]  B. Preston,et al.  Case Series , 2010, Toxicologic pathology.

[30]  Axel Hoos,et al.  Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response Criteria , 2009, Clinical Cancer Research.

[31]  Jan Willem van der Laan,et al.  An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. , 2009, Birth defects research. Part B, Developmental and reproductive toxicology.

[32]  H T Lynch,et al.  Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications , 2009, Clinical genetics.

[33]  R. Broaddus,et al.  Prospective determination of prevalence of lynch syndrome in young women with endometrial cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  K. Hongo,et al.  A case report and review of the literature , 2006, Journal of Neuro-Oncology.