|
1
|
Restaino S, Pellecchia G, Arcieri M, Bogani G, Taliento C, Greco P, Driul L, Chiantera V, Ercoli A, Fanfani F, Fagotti A, Ciavattini A, Scambia G, Vizzielli G. Management for Cervical Cancer Patients: A Comparison of the Guidelines from the International Scientific Societies (ESGO-NCCN-ASCO-AIOM-FIGO-BGCS-SEOM-ESMO-JSGO). Cancers (Basel) 2024; 16:2541. [PMID: 39061181 PMCID: PMC11274772 DOI: 10.3390/cancers16142541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/11/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms.
Collapse
Affiliation(s)
- Stefano Restaino
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- PhD School in Biomedical Sciences, Gender Medicine, Child and Women Health, University of Sassari, 07100 Sassari, Italy
| | - Giulia Pellecchia
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Martina Arcieri
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
| | - Giorgio Bogani
- Gynaecological Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milano, Italy;
| | - Cristina Taliento
- Department of Medical Sciences, Obstetrics and Gynecology Unit, University of Ferrara, 44121 Ferrara, Italy; (C.T.); (P.G.)
- Department of Development and Regeneration, Woman and Child, KU Leuven, 3000 Leuven, Belgium
| | - Pantaleo Greco
- Department of Medical Sciences, Obstetrics and Gynecology Unit, University of Ferrara, 44121 Ferrara, Italy; (C.T.); (P.G.)
| | - Lorenza Driul
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | - Vito Chiantera
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90133 Palermo, Italy;
- Unit of Gynecologic Oncology, National Cancer Institute, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Alfredo Ercoli
- Department of Human Pathology in Adult and Childhood “G. Barresi”, University of Messina, 98122 Messina, Italy;
| | - Francesco Fanfani
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Anna Fagotti
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Andrea Ciavattini
- Woman’s Health Sciences Department, Gynecologic Section, Polytechnic University of Marche, 60121 Ancona, Italy;
| | - Giovanni Scambia
- Gynecologic Oncology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (F.F.); (A.F.); (G.S.)
| | - Giuseppe Vizzielli
- Clinic of Obstetrics and Gynecology, “Santa Maria della Misericordia” University Hospital, Azienda Sanitaria Universitaria Friuli Centrale, 33100 Udine, Italy; (S.R.); (G.P.); (L.D.); (G.V.)
- Department of Medicine, University of Udine, 33100 Udine, Italy
| | | |
Collapse
|
|
2
|
Wang Y, Qiu H, Lin R, Hong W, Lu J, Ling H, Sun X, Yang C. Advancements in the Understanding of Small-Cell Neuroendocrine Cervical Cancer: Where We Stand and What Lies Ahead. J Pers Med 2024; 14:462. [PMID: 38793044 PMCID: PMC11122604 DOI: 10.3390/jpm14050462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/04/2024] [Accepted: 04/26/2024] [Indexed: 05/26/2024] Open
Abstract
Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application.
Collapse
Affiliation(s)
- Yan Wang
- Life Sciences Institute, Zhejiang University, Hangzhou 310058, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou First People’s Hospital, Hangzhou 310006, China
- Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Hui Qiu
- Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Rongjie Lin
- Department of Radiotherapy, West China Xiamen Hospital of Sichuan University, Xiamen 361021, China
| | - Weiwei Hong
- Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
| | - Jiahao Lu
- Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Huan Ling
- Department of Ultrasound in Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Xiaoge Sun
- Department of Radiation Oncology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 750306, China
| | - Chunxu Yang
- Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| |
Collapse
|
|
3
|
Savelli Binsted A, Kassem Z, Le D, de Veciana M. Small Cell Cervical Carcinoma in Pregnancy: Therapeutic Options for an Aggressive Cancer Diagnosis. AJP Rep 2024; 14:e22-e25. [PMID: 38269128 PMCID: PMC10805566 DOI: 10.1055/s-0043-1777998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 10/22/2023] [Indexed: 01/26/2024] Open
Abstract
Neuroendocrine small cell cervical carcinoma is an aggressive cancer which accounts for approximately 1 to 3% of all cervical neoplasms. Therapy must be altered in pregnancy to optimize maternal-fetal outcomes. A 39-year-old woman presented for a routine prenatal visit and was noted to have a grossly abnormal cervix. Cervical biopsies confirmed small cell carcinoma. At 19 weeks' gestation, chemotherapy was initiated. The patient delivered at 34 weeks' gestation to initiate radiation therapy. Six months later, she was diagnosed with metastatic disease and died from cancer complications. In pregnancy, treatment modalities for small cell cervical carcinoma are based on the patient's gestational age at diagnosis. While aggressive early treatment is preferred, platinum-based chemotherapy can be initiated in the second trimester and radiation therapy delayed until delivery. Small cell cervical carcinoma complicating pregnancy requires aggressive treatment. Chemotherapy in the second trimester with planned delayed radiation therapy, may optimize fetal outcomes.
Collapse
Affiliation(s)
- Alyssa Savelli Binsted
- Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
| | - Zeinab Kassem
- Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
| | - David Le
- Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
| | - Margarita de Veciana
- Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, Virginia
| |
Collapse
|
|
4
|
Neuroendocrine Neoplasms of the Gynecologic Tract. Cancers (Basel) 2022; 14:cancers14071835. [PMID: 35406607 PMCID: PMC8998008 DOI: 10.3390/cancers14071835] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Revised: 04/01/2022] [Accepted: 04/01/2022] [Indexed: 01/11/2023] Open
Abstract
Simple Summary Neuroendocrine refers to the cells that synthesize and secrete messenger chemicals such as neuropeptides and amines. Neuroendocrine neoplasms (NENs) are aggressive tumors arising from neuroendocrine cells, with an annual incidence of 6.98/100,000 and a prevalence of 170,000 in the United States. Primary gynecologic NENs constitute ≤2% of female reproductive tumors. NENs of the gynecologic tract are associated with high recurrence rates and dismal prognosis, making their treatment challenging. This article focuses on the updated staging classifications, clinicopathological characteristics, imaging, and management of NENs of the gynecological tract. Abstract Gynecological tract neuroendocrine neoplasms (NEN) are rare, aggressive tumors from endocrine cells derived from the neuroectoderm, neural crest, and endoderm. The primary gynecologic NENs constitute 2% of gynecologic malignancies, and the cervix is the most common site of NEN in the gynecologic tract. The updated WHO classification of gynecologic NEN is based on the Ki-67 index, mitotic index, and tumor characteristics such as necrosis, and brings more uniformity in the terminology of NENs like other disease sites. Imaging plays a crucial role in the staging, triaging, restaging, and surveillance of NENs. The expression of the somatostatin receptors on the surface of neuroendocrine cells forms the basis of increasing evaluation with functional imaging modalities using traditional and new tracers, including 68Ga-DOTA-Somatostatin Analog-PET/CT. Management of NENs involves a multidisciplinary approach. New targeted therapies could improve the paradigm of care for these rare malignancies. This article focuses on the updated staging classifications, clinicopathological characteristics, imaging, and management of gynecologic NENs of the cervix, ovary, endometrium, vagina, and vulva, emphasizing the relatively common cervical neuroendocrine carcinomas among these entities.
Collapse
|
|
5
|
Yang XL, Guan WJ, Kou LN, Wang MM, Lai H, Wu DJ. A real-world, population-based study of the trends for incidence and prognosis in high-grade neuroendocrine tumor of cervix. Curr Probl Cancer 2021; 46:100800. [PMID: 34838343 DOI: 10.1016/j.currproblcancer.2021.100800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 09/21/2021] [Accepted: 10/15/2021] [Indexed: 11/16/2022]
Abstract
To explore the incidence and prognosis trends for high-grade cervical neuroendocrine tumor (HGCNET) and construct a nomogram to predict prognosis for HGCNET. Annual age-adjusted incidence of HGCNET from 1975 to 2015 was retrieved from the Surveillance, Epidemiology, and End Results program, the linear regression, poisson regression and annual percentage changes were used to assess the incidence trend. Also, trends for relative survival (RS) and overall survival (OS) in HGCNET patients from 1975 to 2015 were evaluated. From 1988 to 1975, 514 HGCNET patients were selected and divided into two cohorts with a ratio of 7:3. Nomogram to predict OS for these patients was constructed and validated. The incidence trend for HGCNET was unchanged in the past four decades (P = 0.734), but the proportion of HGCNET in diagnosed cervical cancer slightly increased from 0.9% in 1975 to 1.9% in 2015 (P < 0.001). The 5-year RS and OS for HGCNET in the study periods decreased steadily (RS: P = 0.009; OS: P = 0.008). Nomogram incorporating age, T stage, lymph-node positive, distant metastasis and surgery was constructed. The C-index of the nomogram was 0.716 (0.680-0.752), which was higher than the FIGO staging system. The incidence of HGCNET remained unchanged in the past four decades but the proportion of HGCNET has slightly increased. Besides, a steadily decreasing survival for HGCNET was observed in the study periods. A nomogram was constructed to better predict prognosis for HGCNET.
Collapse
Affiliation(s)
- Xi-Lin Yang
- Department of Radiation Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wen-Ju Guan
- Department of Oncology, Chengdu Second People's Hospital, Chengdu, China
| | - Ling-Na Kou
- Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Chengdu, China
| | - Ming-Ming Wang
- Department of Oncology, The first affiliated hospital of Chongqing Medical University, Chongqing, China
| | - Hua Lai
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| | - Da-Jun Wu
- Department of Radiation Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
| |
Collapse
|
|
6
|
Zhang DY, Huang GR, Ku JW, Zhao XK, Song X, Xu RH, Han WL, Zhou FY, Wang R, Wei MX, Wang LD. Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus. World J Clin Cases 2021; 9:9011-9022. [PMID: 34786384 PMCID: PMC8567530 DOI: 10.12998/wjcc.v9.i30.9011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 06/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients.
AIM To establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China.
METHODS The nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model.
RESULTS The C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging .
CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.
Collapse
Affiliation(s)
- Dong-Yun Zhang
- Department of Pathology, Nanyang Medical College, Nanyang 473061, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Gai-Rong Huang
- Department of Geriatrics, Henan People’s Hospital, Zhengzhou 450003, Henan Province, China
| | - Jian-Wei Ku
- Department of Endoscopy of The Third Affiliated Hospital, Nanyang Medical College, Nanyang 473061, Henan Province, China
| | - Xue-Ke Zhao
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Xin Song
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Rui-Hua Xu
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Wen-Li Han
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Fu-You Zhou
- Department of Thoracic Surgery, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
| | - Ran Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Meng-Xia Wei
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Li-Dong Wang
- State Key Laboratory of Esophageal Cancer Prevention and Treatment and Henan Key Laboratory for Esophageal Cancer Research of The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, Henan Province, China
| |
Collapse
|
|
7
|
Clinicopathological Analysis of Neuroendocrine Carcinoma of the Uterine Cervix: A Single-Institution Retrospective Review of 9 Cases. Int J Surg Oncol 2021; 2021:8290659. [PMID: 34567803 PMCID: PMC8463196 DOI: 10.1155/2021/8290659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 08/28/2021] [Indexed: 12/05/2022] Open
Abstract
Aim To evaluate the clinicopathological features affecting the recurrence and survival of 9 cases of neuroendocrine cancer of the cervix. Method We retrospectively analyzed 9 cervical neuroendocrine cancer cases identified among 453 cervical cancer patients between 2004 and 2021 at Akdeniz University Gynecological Oncology Outpatient Clinic. Kaplan–Meier survival analysis was used for progression-free survival (PFS) and overall survival (OS). Mathematical functions of mean, standard deviation, median, Min–Max values, and frequencies were used for descriptive statistics. The categorical data were expressed in numbers and percentages (%). Results Nine patients with neuroendocrine histological subtype were selected out of 453 patients diagnosed with cervical cancer (1.98%). The average overall survival time of the patients was 26 months. The 5-year survival rate was 53.3%, while the PFS was 62.5%. The most common subtype was small cell neuroendocrine cancer. Tumours were mostly locally advanced at the time of diagnosis. 3 patients' stage was 1b2, while 4 patients were 2b, 1 patient was 3c2r, and 1 patient was 4b. All tumours showed the immunohistochemical staining properties of neuroendocrine cancer. The main treatment modality applied to our patients was surgery + adjuvant CRT. The most used chemotherapeutic agents were cisplatin/carboplatin and etoposide. Recurrence was found in 3 cases, including 5 deaths. Conclusion Neuroendocrine tumour of the cervix is a rare subtype with a poor prognosis. Unfortunately, there is not yet a standard treatment protocol due to the limited number of comparative studies of surgery, chemotherapy, and radiotherapy based treatment schemes.
Collapse
|
|
8
|
Chen J, Sun Y, Chen L, Zang L, Lin C, Lu Y, Lin L, Lin A, Dan H, Chen Y, He H. Prognostic factors and treatment of neuroendocrine tumors of the uterine cervix based on the FIGO 2018 staging system: a single-institution study of 172 patients. PeerJ 2021; 9:e11563. [PMID: 34268005 PMCID: PMC8269661 DOI: 10.7717/peerj.11563] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 05/14/2021] [Indexed: 11/25/2022] Open
Abstract
Objective This study aimed to explore the prognostic factors and outcomes of patients with neuroendocrine tumors (NETs) of the cervix and to determine appropriate treatment. Methods A single-institution retrospective analysis of 172 patients with NETs was performed based on the new International Federation of Gynecology and Obstetrics (FIGO 2018) staging system. Results Among the 172 eligible patients, 161 were diagnosed with small cell neuroendocrine carcinoma (SCNEC), six with large cell neuroendocrine carcinoma, four with typical carcinoid tumors and one with SCNEC combined with an atypical carcinoid tumor. According to the FIGO 2018 staging guidelines, 31 were stage I, 66 were stage II, 57 were stage III, and 18 were stage IV. The 5-year survival rates of patients with stage I–IV disease were 74.8%, 56.2%, 41.4% and 0%, respectively. The 5-year progression-free survival rates of patients with stage I–IV disease were 63.8%, 54.5%, 30.8% and 0%, respectively. In the multivariate analysis, advanced FIGO stage, large tumor and older age were identified as independent variables for 5-year survival in patients with stage I–IV disease. FIGO stage, tumor size and para-aortic lymph node metastasis were independent prognostic factors for 5-year progression-free survival in patients with stage I–IV disease. For the patients receiving surgery (n = 108), tumor size and pelvic lymph node metastasis were independent prognostic factors for 5-year survival, and pelvic lymph node metastasis for 5-year progression-free survival. In stage IVB, at least six cycles of chemotherapy (n = 7) was associated with significantly better 2-year OS (83.3% vs. 9.1%, p < 0.001) and 2-year PFS (57.1% vs. 0%, p = 0.01) than fewer than six cycles of chemotherapy(n = 11). Conclusion Advanced FIGO stage, large tumor, older age and lymph node metastasis are independent prognostic factors for NETs of the cervix. The TP/TC and EP regimens were the most commonly used regimens, with similar efficacies and toxicities. Standardized and complete multimodality treatment may improve the survival of patients with NETs.
Collapse
Affiliation(s)
- Jian Chen
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Yang Sun
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Li Chen
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Lele Zang
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Cuibo Lin
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Yongwei Lu
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Liang Lin
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - An Lin
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Hu Dan
- Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Yiyu Chen
- Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Haixin He
- Department of Gynecological-Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China
| |
Collapse
|
|
9
|
Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study. ACTA ACUST UNITED AC 2021; 57:medicina57060548. [PMID: 34072478 PMCID: PMC8227555 DOI: 10.3390/medicina57060548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/24/2021] [Accepted: 05/27/2021] [Indexed: 12/05/2022]
Abstract
Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.
Collapse
|
|
10
|
Chromogranin A Expression in Rectal Neuroendocrine Tumors Is Associated With More Aggressive Clinical Behavior and a Poorer Prognosis. Am J Surg Pathol 2020; 44:1496-1505. [PMID: 32735108 DOI: 10.1097/pas.0000000000001526] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Although rectal neuroendocrine tumors (NETs) with an L-cell phenotype and small size are generally less clinically serious, the new 2019 World Health Organization (WHO) classification system has categorized all of these lesions as malignant. Identifying biomarkers of rectal NETs is thus important for stratifying their clinical behavior. Chromogranin A protein expression was assessed in 538 endoscopically or surgically resected rectal NETs and compared with clinicopathologic factors to identify its clinical and prognostic significance. All of the rectal NETs analyzed (100%) were synaptophysin positive, but chromogranin A labeling was only detected in 111 cases (20.6%). Chromogranin A expression in the rectal NETs was more commonly associated with older age (50 y and older; P=0.013), male sex (P=0.002), radical resection (P=0.003), large tumor size (≥1 cm; P=0.038), muscularis propria invasion (P=0.002), lymphovascular (P=0.014) and perineural (P<0.001) invasion, an involved resection margin (P=0.028), and lymph node metastasis (P=0.003). Patients with chromogranin A expression had higher plasma chromogranin A levels (P=0.023) than those without chromogranin A expression during follow-up. The 10-year disease-free survival rate in rectal NET patients with chromogranin A expression (91.5%) was significantly shorter than the negative cases (99.7%) by both univariate (hazard ratio=14.438; 95% confidence interval: 2.911-71.598; P<0.001) and multivariate (hazard ratio=12.099; 95% confidence interval, 2.044-71.608; P=0.006) analyses. In summary, rectal NETs that are positive for chromogranin A are less common than those with synaptophysin expression and show more aggressive clinical behavior. Chromogranin A is therefore a prognostic indicator of higher recurrence risk in patients with endoscopically or surgically resected rectal NETs.
Collapse
|
|
11
|
Gill CM, Orfanelli T, Yoxtheimer L, Roy-McMahon C, Suhner J, Tomita S, Kalir T, Liu Y, Houldsworth J, Kolev V. Histology-specific FGFR2 alterations and FGFR2-TACC2 fusion in mixed adenoid cystic and neuroendocrine small cell carcinoma of the uterine cervix. Gynecol Oncol Rep 2020; 34:100668. [PMID: 33241100 PMCID: PMC7672274 DOI: 10.1016/j.gore.2020.100668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 10/25/2020] [Accepted: 10/26/2020] [Indexed: 01/28/2023] Open
Abstract
Neuroendocrine small cell carcinoma of the uterine cervix portends a dismal prognosis with limited treatment options. Rarely, tumors of mixed-lineage appear in gynecologic malignancies. Here, we report a 77-year-old woman who presented with complete uterine prolapse and 4-month history of vaginal bleeding. Histopathologic evaluation revealed a mixed adenoid cystic carcinoma and neuroendocrine small cell carcinoma of the uterine cervix. The tumor was PD-L1 and HPV 35 positive. The patient was treated with up-front surgery and adjuvant radiation. Independent, histology-specific alterations in FGFR2 and a FGFR2-TACC2 fusion were identified. Progression of disease occurred within 6 months for which she received chemotherapy and immunotherapy. However, the patient expired within a year. We comprehensively review how screening for and targeting of FGFR alterations in recurrent and metastatic cervical cancer might serve as a touchstone for future treatment regimens.
Collapse
Affiliation(s)
- Corey M Gill
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Theofano Orfanelli
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Lorene Yoxtheimer
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Christine Roy-McMahon
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jessa Suhner
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Shannon Tomita
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Tamara Kalir
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Yuxin Liu
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Jane Houldsworth
- Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Valentin Kolev
- Department of Obstetrics and Gynecology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| |
Collapse
|
|
12
|
Lin LM, Lin Q, Liu J, Chu KX, Huang YX, Zhang ZK, Li T, Dai YQ, Li JL. Prognostic factors and treatment comparison in small cell neuroendocrine carcinoma of the uterine cervix based on population analyses. Cancer Med 2020; 9:6524-6532. [PMID: 32705800 PMCID: PMC7520332 DOI: 10.1002/cam4.3326] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 06/14/2020] [Accepted: 06/30/2020] [Indexed: 01/07/2023] Open
Abstract
Objective We aimed to assess the impact of the treatment modality on the outcome of small cell neuroendocrine cervical carcinoma (SCNEC) using the Surveillance Epidemiology and End Results (SEER) database. Methods Patients from the SEER program between 1981 and 2014 were identified. Significant factors for cancer‐specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan‐Meier survival and Cox regression methods. Results A total of 503 SCNEC patients were identified. The 5‐year CSS and OS were 36.6% and 30.6%, respectively. The International Federation of Gynecology and Obstetrics (FIGO) stage I to IV distributions was 189 (37.6%), 108 (21.5%), 95 (18.9%), and 111 patients (22.0%), respectively. Within the patients with known treatment strategies, 177 (45.9%) were treated with radical surgery and 209 (54.1%) underwent primary radiotherapy. Local treatment strategies were independent prognostic factor for CSS and OS. The 5‐year CSS for radical surgery and primary radiotherapy was 50.0% and 27.9%, respectively (P < .001). The 5‐year OS for those who received radical surgery and primary radiotherapy was 57.8%, and 29.6%, respectively (P < .001). In FIGO stage I SCNEC, patients treated with radical surgery had superior CSS (P = .001) and OS (P = .003) than those with primary radiotherapy. However, in FIGO stage II and III SCNEC, there were no differences in CSS and OS with respect to different local treatment strategies. Our results also found that the addition of brachytherapy impacted OS in the FIGO stage III SENCE (P = .002). The 5‐year CSS and OS of patients with FIGO IV were only 11.7% and 7.1%, respectively. Conclusions SCNEC is a rare disease with aggressive clinical behavior. The findings indicate that radical surgery should be suggested for early‐stage SCNEC and combining radiation therapy with brachytherapy should be suitable for patients with advanced stage.
Collapse
Affiliation(s)
- Li-Mei Lin
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Qin Lin
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Jun Liu
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Ke-Xin Chu
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Yun-Xia Huang
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Zong-Kai Zhang
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Tao Li
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Ya-Qing Dai
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| | - Jin-Luan Li
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital, School of Medicine, Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, China
| |
Collapse
|
|
13
|
Liu H, Zhang Y, Chang J, Liu Z, Tang N. Differential expression of neuroendocrine markers, TTF-1, p53, and Ki-67 in cervical and pulmonary small cell carcinoma. Medicine (Baltimore) 2018; 97:e11604. [PMID: 30045295 PMCID: PMC6078665 DOI: 10.1097/md.0000000000011604] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Small cell carcinoma (SCC) is a highly malignant neuroendocrine tumor that may occur in many anatomic sites of the body.In this study, we compared the different expression of neuroendocrine markers, thyroid transcription factor 1 (TTF-1), p53, and Ki-67 in 23 cases of cervical SCC and 56 cases of pulmonary SCC using immunohistochemistry.Our study showed that cervical SCC had a younger onset age than pulmonary counterpart. Although both had the similar morphological features, different immunohistochemical expression panel was observed in this study. As neuroendocrine tumors, SCC of cervix and lung had similar immunoreactive staining for CD56 and chromogranin A, but the expression of the synaptophysin in cervical SCC was significantly higher than that in pulmonary SCC (P = .007). The TTF-1 expression of pulmonary SCC illustrating diffuse and strong positivity in tumor cell nuclei was significantly higher than that of the cervical SCC (P = .003). There was only 1 case showing p53 protein over-expression in the 23 cases of cervical SCC, and p53 over-expression was observed in 42.9% of pulmonary SCC (P = .001). Only 9 cases of cervical SCC showed ≥80% of the Ki-67 proliferation index, while it was found in 94.6% of pulmonary SCC (P < .001).The different immunohistochemical expressions of these 2 kinds of SCCs may be related with their pathogenetic mechanism, and these differences may be helpful in the identification of the origins of the metastatic SCC with unknown primary site.
Collapse
|
|
14
|
Yin L, Li J, Wei Y, Ma D, Sun Y, Sun Y. Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient receiving tamoxifen: A case report and literature review. Medicine (Baltimore) 2018; 97:e10900. [PMID: 29879027 PMCID: PMC5999514 DOI: 10.1097/md.0000000000010900] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
RATIONALE Small cell carcinoma of the ovary (SCCO) is a rare and aggressive extra-pulmonary variant of small cell tumors of uncertain histogenesis. The pathogenesis and optimal treatment of SCCO is unclear. We present a very rare case of a synchronous primary ovarian small cell carcinoma and endometrioid adenocarcinoma of the uterus in a patient after 2 years of tamoxifen treatment for breast cancer. This is the first such report in the English literature. PATIENT CONCERNS A 46-year-old woman had a history of left breast cancer that was treated with a simple mastectomy and sentinel lymph node biopsy in 2013. The post-operative pathology was invasive ductal carcinoma of the left breast. she had been taking tamoxifen for 2 years. The patient underwent an exploratory laparotomy to reduce the tumor burden, improve bowel compression symptoms, and promote defecation in 2015. The post-operative pathology revealed a rare, simultaneous occurrence of two tumors (endometrial adenocarcinoma and SCCO [pulmonary type]). DIAGNOSES Primary ovarian small cell carcinoma of pulmonary type with coexisting endometrial carcinoma in a breast cancer patient. INTERVENTIONS The patient received 3 courses of chemotherapy after operation. The effect was not apparent and the general health status was poor. OUTCOMES The patient died of progressive disease 7 months post-operatively. LESSONS The present case suggests that tamoxifen use might be among many etiologic factors in SCCO development. Despite its rarity, SCCO requires a high degree of attention in clinical work because it is an aggressive tumor that has a poor prognosis.
Collapse
Affiliation(s)
- Lei Yin
- Department of General Surgery, Huzhou Central Hospital, Huzhou
| | - Jianning Li
- The Central Sterile Supply Department, Affiliated Hospital of Shandong Academy of Medical Sciences
| | - Yunhai Wei
- Department of General Surgery, Huzhou Central Hospital, Huzhou
| | - Dejian Ma
- School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences
- The Fourth Surgical Department, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan
| | - Yamei Sun
- Department of Clinical Laboratory, Zhucheng People's Hospital of Shandong Province, Zhucheng, China
| | - Yanlai Sun
- The Fourth Surgical Department, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan
| |
Collapse
|
|
15
|
Influence of clinicopathological characteristics and comprehensive treatment models on the prognosis of small cell carcinoma of the cervix: A systematic review and meta-analysis. PLoS One 2018; 13:e0192784. [PMID: 29641578 PMCID: PMC5894955 DOI: 10.1371/journal.pone.0192784] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 03/21/2018] [Indexed: 01/11/2023] Open
Abstract
Small cell carcinoma of the cervix (SCCC) is a rare primary neuroendocrine cervical carcinoma with a high degree of invasiveness. SCCC is prone to early-stage lymph node and distant metastases and characterized by a poor prognosis. Currently, there is no standard treatment. This study aimed to evaluate the clinicopathological factors and treatment models that influence SCCC prognosis through a systematic review and meta-analysis, to improve the diagnosis and treatment of SCCC. A comprehensive search was performed in multiple medical literature databases to retrieve studies on the clinical prognosis of SCCC published in China and abroad as of March 1, 2017. Twenty cohort studies with 1904 patients were analyzed. Meta-analysis showed statistical significance for the following factors: FIGO staging (hazard ratio [HR] = 2.63, 95% confidence interval [CI]: 2.13–3.24; odds ratio [OR] = 3.72, 95% CI: 2.46–5.62), tumor size (HR = 1.64, 95% CI: 1.25–2.15), parametrial involvement (HR = 2.40, 95% CI: 1.43–4.05), resection margin (HR = 4.09, 95% CI: 2.27–7.39), lymph node metastasis (OR = 2.09, 95% CI: 1.18–3.71), depth of stromal invasion (HR = 1.99, 95% CI: 1.33–2.97), neoadjuvant chemotherapy (HR = 2.06, 95% CI: 1.14–3.73), and adjuvant chemotherapy (HR = 1.63, 95% CI: 1.26–2.12; OR = 1.48, 95% CI: 1.02–2.16). FIGO staging, tumor size, parametrial involvement, resection margin, depth of stromal invasion, and lymph node metastasis can be used as clinicopathological characteristics for the prediction of SCCC prognosis. Neoadjuvant chemotherapy tended to improve prognosis. Our findings suggest that neoadjuvant chemotherapy plus adjuvant chemotherapy may be the preferred strategy. However, adjuvant radiotherapy appeared to cause no significant improvement in prognosis. Therefore, the clinical application of radiotherapy and the relationship between radiotherapy and clinicopathological factors need to be re-examined. The results of this study should be validated and developed in formal, well-designed multicenter clinical trials.
Collapse
|
|
16
|
Zhou J, Wu SG, Sun JY, Tang LY, Lin HX, Li FY, Chen QH, Jin X, He ZY. Clinicopathological features of small cell carcinoma of the uterine cervix in the surveillance, epidemiology, and end results database. Oncotarget 2018; 8:40425-40433. [PMID: 28415576 PMCID: PMC5522189 DOI: 10.18632/oncotarget.16390] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 03/03/2017] [Indexed: 12/18/2022] Open
Abstract
To investigate the clinicopathological characteristics and survival of small cell carcinoma of the cervix using Surveillance, Epidemiology, and End Results database. Patients with a diagnosis of small cell carcinoma of the cervix were included between 1988 and 2012. Kaplan-Meier method and Cox regression models were used. A total of 487 patients were included. Of the patients with known International Federation of Gynecology and Obstetrics stage and tumor grade, the stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly or undifferentiated histology. The 5-year cause specific survival and overall survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing age, advanced stage, and treatment by primary radiotherapy were associated with worse survival outcomes. Small cell carcinoma of the cervix is a rare disease with aggressive characteristics and prone to metastasize and is dismal in prognosis. Reduced survival was associated with increasing age, advanced stage, and treatment by primary radiotherapy.
Collapse
Affiliation(s)
- Juan Zhou
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - San-Gang Wu
- Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Jia-Yuan Sun
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Li-Ying Tang
- Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College of Xiamen University, Xiamen, People's Republic of China
| | - Huan-Xin Lin
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Feng-Yan Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Qiong-Hua Chen
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Xin Jin
- Faculty of Basic Medicine, Medical College, Xiamen University, Xiamen, People's Republic of China
| | - Zhen-Yu He
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| |
Collapse
|
|
17
|
Ku JW, Zhang DY, Song X, Li XM, Zhao XK, Lv S, Hu SJ, Cheng R, Zhou FY, Wu HF, Wang LD. Characterization of tissue chromogranin A (CgA) immunostaining and clinicohistopathological changes for the 125 Chinese patients with primary small cell carcinoma of the esophagus. Dis Esophagus 2017; 30:1-7. [PMID: 28575250 DOI: 10.1093/dote/dox041] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Indexed: 12/11/2022]
Abstract
The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological staging system and to clarify the mechanisms of CgA protein in PSCE progression and prognosis.
Collapse
Affiliation(s)
- J W Ku
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - D Y Zhang
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University.,Department of Pathology of Nanyang Medical College, Nanyang
| | - X Song
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - X M Li
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University.,Department of Pathology, Women and Infants Hospital of Zhengzhou, Zhengzhou
| | - X K Zhao
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - S Lv
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - S J Hu
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - R Cheng
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| | - F Y Zhou
- Department of Surgery, Anyang Tumor Hospital, Anyang, Henan, China
| | - H F Wu
- Department of Pathology of Nanyang Medical College, Nanyang
| | - L D Wang
- Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University
| |
Collapse
|
|
18
|
Xie S, Song L, Yang F, Tang C, Yang S, He J, Pan X. Enhanced efficacy of adjuvant chemotherapy and radiotherapy in selected cases of surgically resected neuroendocrine carcinoma of the uterine cervix: A retrospective cohort study. Medicine (Baltimore) 2017; 96:e6361. [PMID: 28296773 PMCID: PMC5369928 DOI: 10.1097/md.0000000000006361] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The aim of the present study is to identify the prognostic factors of overall survival and examine the effects of adjuvant chemotherapy and radiotherapy on the overall survival in neuroendocrine carcinoma of the uterine cervix (NECUC) patients.Forty-eight surgically treated patients were retrospectively recruited and clinicopathologic characteristics and treatments were reviewed. Kaplan-Meier product-limit method and Cox proportional-hazards regression were utilized for univariate and multivariate analyses.The median follow-up time was 20.6 months and the median overall survival was 30.7 months. The estimated 2-year and 5-year overall survival rates were 57.5% and 31.3%, respectively. Forty patients had ≤ stage IIA disease and 8 had >IIA disease. Univariate analysis identified the clinical stage ≤ IIA (P = 0.042), tumor size ≤ 4 cm (P = 0.005), negative lymph nodes metastasis (P < 0.001), depth of stromal invasion ≤ 1/2 (P = 0.001), negative parametrial involvement (P = 0.004), and weak staining of synaptophysin (P = 0.037), and chromogranin (P = 0.011) as the prognostic factors for an improved overall survival, while chemotherapy and radiotherapy were not prognostic factors in the whole cohort. However, surgery combined with chemotherapy and radiotherapy produced a survival advantage over surgery alone in patients with large tumors (P = 0.006). The combination of surgery and chemotherapy (with or without radiotherapy) did not show any significant difference in overall survival for small tumors (P = 0.816), compared with no chemotherapy (with or without radiotherapy). In addition, radiotherapy for tumors with squamous cell carcinoma or adenocarcinoma components achieved a better survival (P = 0.01), and there was a tendency of an unfavorable survival for radiotherapy in homogeneous carcinoma (P = 0.099). Tumor size was an independent prognostic factor in the multivariate analysis (HR: 12.724, 95% CI: 1.697-95.423, P = 0.013).In conclusion, clinicopathologic features significantly influence a NECUC patient's outcome. Tumor size and tumor histology can influence the effect of adjuvant chemotherapy and radiotherapy on overall survival. We recommend that platinum-based adjuvant chemotherapy should be used in all cases, while radiotherapy should be reserved for the selected NECUC patients whose tumors have mixed histology.
Collapse
Affiliation(s)
- Sixia Xie
- Department of Obstetrics and Gynecology
| | | | - Fan Yang
- Department of Pathology, West China Second University Hospital, Sichuan University
| | | | | | - Ji He
- Department of Obstetrics and Gynecology
| | - Xiaoling Pan
- Department of Obstetrics and Gynecology
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, P. R. China
| |
Collapse
|
|
19
|
Zhou J, Yang HY, Wu SG, He ZY, Lin HX, Sun JY, Li Q, Guo ZW. The local treatment modalities in FIGO stage I-II small-cell carcinoma of the cervix are determined by disease stage and lymph node status. Cancer Med 2016; 5:1108-15. [PMID: 26990881 PMCID: PMC4924369 DOI: 10.1002/cam4.687] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2015] [Revised: 02/04/2016] [Accepted: 02/05/2016] [Indexed: 12/27/2022] Open
Abstract
The purpose of this study was to identify the optimal local treatment modalities for International Federation of Gynecology and Obstetrics (FIGO) stage I-II small-cell carcinoma of the cervix (SCCC), including cancer-directed surgery (CDS) and/or radiotherapy (RT). The Surveillance Epidemiology and End Results (SEER) database was used to identify SCCC patients from 1988 to 2012, and analyzed using Kaplan-Meier survival and Cox regression proportional hazard methods to determine factors significant for cause-specific survival (CSS) and overall (OS). A total of 208 patients of SCCC were enrolled. The median follow-up time was 31 months. Fifty-eight (27.9%) patients were treated with primary CDS, 88 (42.3%) patients underwent CDS combined with RT, and 62 (29.8%) patients were treated with primary RT. Univariate and multivariate analyses showed that local treatment modalities were independent prognostic factors for CSS and OS. Patients who had undergone CDS had better CSS and OS, compared with patients who had been treated with combined CDS and RT or RT alone. The 5-year CSS and OS of entire group was 49.8% and 46.4%, respectively. The 5-year CSS in the groups of patients receiving CDS, CDS combined with RT, and RT alone were 67.9%, 49.7%, and 32.6%, respectively (P < 0.001). The 5-year OS in patients treated with CDS, CDS combined with RT, and RT alone were 64.9%, 46.2%, and 28.8% (P < 0.001). Primary surgery was associated with improved CSS and OS for FIGO stage I and lymph node negative disease. Primary surgery is the most effective local treatment for FIGO stage I-II SCCC, as adjuvant RT or radical RT does not improve survival compared to radical surgery, especially in patients with FIGO stage I and lymph node negative disease.
Collapse
Affiliation(s)
- Juan Zhou
- Xiamen Cancer Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Hong-Yi Yang
- Xiamen Cancer Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - San-Gang Wu
- Xiamen Cancer Center, Department of Radiation Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China
| | - Zhen-Yu He
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, China
| | - Huan-Xin Lin
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, China
| | - Jia-Yuan Sun
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, China
| | - Qun Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, 510060, China
| | - Zhan-Wen Guo
- Department of Radiation Oncology, The General Hospital of Shenyang Military Area Command, Shenyang, 110840, China
| |
Collapse
|
|
20
|
Zhou J, Sun JY, Chen SY, Li FY, Lin HX, Wu SG, He ZY. Prognostic value of lymph node ratio in patients with small-cell carcinoma of the cervix based on data from a large national registry. Onco Targets Ther 2015; 9:67-73. [PMID: 26730205 PMCID: PMC4694687 DOI: 10.2147/ott.s96206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Objective To investigate the prognostic value of the lymph node ratio (LNR) in patients with small-cell carcinoma of the cervix (SCCC) after cancer-directed surgery using a population-based national registry (Surveillance Epidemiology and End Results [SEER]). Methods We retrospectively reviewed the data of SCCC patients in the SEER database from 1980 to 2012. The prognostic impact of LNR with respect to cause-specific survival (CSS) and overall survival (OS) was analyzed. Results A total of 118 patients with SCCC were identified. The median follow-up was 30.5 months. All these patients were treated with cancer-directed surgery and lymphadenectomy. Sixty (50.8%) patients had nodal metastases. The median LNR was 0.16 in patients with positive lymph nodes. Univariate analysis showed that prognostic factors such as International Federation of Gynecology and Obstetrics (FIGO) stage, nodal status, LNR, and local treatment modalities affected CSS and OS (P<0.05). Multivariate analysis showed that LNR was an independent prognostic factor for CSS and OS. Patients with a higher LNR had worse CSS (hazard ratio [HR]: 8.832; 95% confidence interval [CI]: 3.762–20.738; P<0.001) and OS (HR: 8.462; 95% CI: 3.613–19.821; P<0.001). LNR was associated with CSS and OS by stage, especially in FIGO stage I–II patients. Conclusion LNR is an independent prognostic factor in SCCC patients and it may help to individualize adjuvant therapy.
Collapse
Affiliation(s)
- Juan Zhou
- Department of Obstetrics and Gynecology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Jia-Yuan Sun
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Shan-Yu Chen
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Feng-Yan Li
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - Huan-Xin Lin
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| | - San-Gang Wu
- Department of Radiation Oncology, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, People's Republic of China
| | - Zhen-Yu He
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China
| |
Collapse
|
|
21
|
Gynecologic Cancer InterGroup (GCIG) consensus review for small cell carcinoma of the cervix. Int J Gynecol Cancer 2015; 24:S102-8. [PMID: 25341572 DOI: 10.1097/igc.0000000000000262] [Citation(s) in RCA: 72] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Small cell carcinoma of the cervix (SCCC) is a rare histological entity of uterine cervical cancer. Compared with other common histological types, squamous cell carcinoma or adenocarcinoma, the outcome of SCCC is poor because of the high incidence of nodal or distant metastasis even with early stage. In this review, current consensus of epidemiology, pathology, and initial treatment for SCCC will be discussed.
Collapse
|
|
22
|
Chen TC, Huang HJ, Wang TY, Yang LY, Chen CH, Cheng YM, Liou WH, Hsu ST, Wen KC, Ou YC, Hung YC, Lai HC, Ho CM, Chang TC. Primary surgery versus primary radiation therapy for FIGO stages I-II small cell carcinoma of the uterine cervix: A retrospective Taiwanese Gynecologic Oncology Group study. Gynecol Oncol 2015; 137:468-73. [PMID: 25797082 DOI: 10.1016/j.ygyno.2015.03.015] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2014] [Accepted: 03/12/2015] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. METHODS We reviewed the medical records and histological files of 144 patients with FIGO stages IA-IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. RESULTS There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P=0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy (n=14, including 12 stages IB2-IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery (n=97, including 40 stages IB2-IIB) (P=0.046). CONCLUSIONS None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I-II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.
Collapse
Affiliation(s)
- Tze-Chien Chen
- Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Graduate Institute of Medical Sciences, Taipei Medical University, Taiwan; General Education Center, Tatung University, Taipei, Taiwan
| | - Huei-Jean Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan; Chang Gung University Medical College, Taoyuan, Taiwan
| | - Tao-Yeuan Wang
- Department of Pathology, Mackay Medical College and Mackay Memorial Hospital, New Taipei City, Taiwan; Mackay Medicine, Nursing and Management College, New Taipei City, Taiwan
| | - Lan-Yan Yang
- Gynecologic Cancer Research Center, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan
| | - Chi-Hau Chen
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Min Cheng
- Department of Obstetrics Gynecology, National Cheng Kung University, Tainan, Taiwan
| | - Wen-Hsiung Liou
- Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Shih-Tien Hsu
- Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kuo-Chang Wen
- Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Che Ou
- Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Kaohsiung, Taiwan
| | - Yao-Ching Hung
- Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Cheng Lai
- Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; Department of Obstetrics and Gynecology, School of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Chih-Ming Ho
- Gynecologic Cancer Center, Cathay General Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan; School of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ting-Chang Chang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan, Taiwan; Chang Gung University Medical College, Taoyuan, Taiwan.
| |
Collapse
|
|
23
|
WANG QING, LIU YIHONG, XIE LI, HU WENJING, LIU BAORUI. Small cell carcinoma of the uterine cervix in pregnancy: A case report and review of the literature. Oncol Lett 2015; 9:91-95. [PMID: 25435939 PMCID: PMC4246688 DOI: 10.3892/ol.2014.2668] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2014] [Accepted: 09/26/2014] [Indexed: 11/06/2022] Open
Abstract
The occurrence of cervical cancer during pregnancy is extremely rare, particularly small cell carcinoma. Small cell cervical carcinoma (SCCC) is a neuroendocrine tumor with a poor prognosis. This study presents the case of an 18-year-old female with stage IB2 SCCC complicated by pregnancy, who was treated with chemotherapy and radiotherapy. The patient was diagnosed shortly after giving birth, and is the youngest female case to be reported in the world. The patient was treated with cisplatin and etoposide chemotherapy and radiotherapy. Complete remission was achieved following neoadjuvant chemotherapy and radiotherapy, and the patient remains in clinical remission eight months following treatment. Cytological screening, colposcopy and if necessary, biopsy, and selective conization at 14-20 weeks should be considered in the patient evaluation.
Collapse
Affiliation(s)
- QING WANG
- The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - YI-HONG LIU
- The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China
| | - LI XIE
- Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - WEN-JING HU
- Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| | - BAO-RUI LIU
- Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu 210008, P.R. China
| |
Collapse
|
|
24
|
Atienza-Amores M, Guerini-Rocco E, Soslow RA, Park KJ, Weigelt B. Small cell carcinoma of the gynecologic tract: a multifaceted spectrum of lesions. Gynecol Oncol 2014; 134:410-8. [PMID: 24875120 DOI: 10.1016/j.ygyno.2014.05.017] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Revised: 05/15/2014] [Accepted: 05/20/2014] [Indexed: 01/23/2023]
Abstract
OBJECTIVE Small cell carcinoma (SmCC) of the female genital tract constitutes a diagnostic and clinical challenge given its rarity and the lack of standardized therapeutic approaches. Here we review the morphological, clinical and molecular features of gynecologic SmCCs and discuss potential areas for future research. METHODS Data for this review article were identified by searches of PubMed, EMBASE and the Internet using the search terms "small cell carcinoma" or "neuroendocrine carcinoma" and "gynecologic", "uterine cervix", "cervix", "uterus", "endometrium", "ovary", "vagina", "fallopian tube" or "vulva", and research articles published in English between 1972 and February 2014 were included. RESULTS SmCCs arising from different organs within the gynecologic tract share the same histopathologic characteristics, which closely resemble those of small cell lung carcinoma. The expression of at least one immunohistochemical neuroendocrine marker is a common finding. The uterine cervix is the most frequent site of SmCC in the female genital tract. HPV infection seems to play a role in the development of cervical SmCC but not in cancers of other gynecologic sites. FIGO stage is an established prognostic factor, in particular in SCCs of the cervix. Irrespective of the site, SmCCs of the gynecologic tract display an aggressive clinical behavior with few reported long-term survivors. The therapeutic management includes surgery, radiotherapy and chemotherapy. CONCLUSIONS Despite the potential differences in etiology and risk factors, SmCCs from different sites of the gynecologic tract have similar morphologic appearances and clinical behavior. Recent genomic analyses of small cell carcinoma of the lung have revealed potential driver genomic alterations. We posit that the comprehensive genomic characterization of gynecologic SmCCs may lead to the identification of markers that result in an improvement of diagnostic reproducibility of SmCCs of the gynecologic tract, and of molecular aberrations that may be exploited therapeutically in subgroups of the disease.
Collapse
Affiliation(s)
- Maria Atienza-Amores
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Institute of Biomedicine of Seville/HUVR/CSIC/University of Seville, Seville, Spain
| | - Elena Guerini-Rocco
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; School of Pathology, University of Milan, Italy
| | - Robert A Soslow
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kay J Park
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Britta Weigelt
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
| |
Collapse
|
|
25
|
Huang L, Liao LM, Liu AW, Wu JB, Cheng XL, Lin JX, Zheng M. Analysis of the impact of platinum-based combination chemotherapy in small cell cervical carcinoma: a multicenter retrospective study in Chinese patients. BMC Cancer 2014; 14:140. [PMID: 24575810 PMCID: PMC3939817 DOI: 10.1186/1471-2407-14-140] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Accepted: 02/21/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Small cell cervical carcinoma (SCCC) is a rare, aggressive tumor with a poor prognosis. However, information in relation to its treatment is scarce due to the limited numbers of patients. The aim of this study was to establish whether platinum-based combination chemotherapy may by beneficial in this patient population. METHODS We carried out a multicenter, retrospective study comprising of 72 Chinese patients with SCCC. The patients were treated between 1995 and 2010 at Sun Yat-sen Memorial Hospital or the Cancer Center of Sun Yat-Sen University, and at the First Affiliated Hospital of Shantou University Medical College, China. RESULTS Of the 72 patients, 46/72 (63.9%) had Federation of Gynecology and Obstetrics (FIGO) stage Ia-Ib2 and 26/72 (36.1%) had stage IIa-IV disease. Surgery was performed in 63/72 (87.5%) patients, 61/72 (84.7%) patients received chemoradiotherapy and 35/72 (48.6%) received radiotherapy. The 3-year overall survival (OS) and disease-free survival (DFS) rates were as follows: Ia (100%, 100%); Ib1 (62%, 57%); Ib2 (53%, 48%); IIa (36%, 23%); IIb (29%, 21%); IIIb (50%, 50%); and IV (0%, 0%), respectively. The estimated 3-year OS and DFS rates in patients who received platinum-based combination chemotherapy (etoposide + cisplatin [EP], or paclitaxel + cisplatin [TP]) as part of their adjuvant treatment were 64.8% and 63.0%, respectively, compared to 25.2% and 22.0% in those who did not (P = 0.0003; P = 0.0003). Univariate analysis showed that platinum-based combination chemotherapy was associated with improved survival compared to other chemotherapy techniques or no chemotherapy (OS: HR = 0.227; 95% CI, 0.099-0.524; P = 0.001; DFS: HR = 0.210; 95% CI, 0.087-0.506; P = 0.001). Multivariate analysis identified FIGO stage, lymphatic metastasis and platinum-based combination chemotherapy as independent prognostic factors for improved survival in patients with SCCC. CONCLUSIONS Platinum-based combination chemotherapy (with EP or TP) can improve the 3-year survival outcomes in patients with SCCC. Therefore, it should be considered an important component in a future standardized treatment strategy for SCCC.
Collapse
Affiliation(s)
- Long Huang
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi, China.
| | | | | | | | | | | | | |
Collapse
|