Neuroendocrine Cervical Cancer Research Articles

Neuroendocrine cervical cancer: Have we made any steps forward in its management?

IntroductionNeuroendocrine tumors (NEC) were first described by Albores-Saavedra in 1972 and these tumors account for only 0.9% to 1.5% of all invasive cervical cancers.1,2 The most common type is small cell neuroendocrine carcinoma (SCNEC) of the cervix, which accounts for 80% of cases.2 The poor prognosis despite advances in treatment remains still a huge problem, so the aim of our review is to cover all current therapeutic options. MethodWe searched for all available interventional studies, reviews, case reports and meta-analyses published from 1995 to 2023. ResultsIn 2017 Castle et al.9 published a systematic review and meta-analysis and concluded that SCNC and large cell neuroendocrine carcinoma (LCNC) are, in most cases, caused by HPV, primarily HPV18 and HPV16. Comparative genomics data suggest that cervical NEC may be genetically more similar to common cervical cancer subtypes than to extra-cervical SCNEC of the lung and bladder.13 Surgery is recommended as the primary treatment in early stages of disease, with radical hysterectomy and nodal assessment followed by adjuvant pelvic radiotherapy and/or chemotherapy. However, simple hysterectomy may be adequate when followed by adjuvant radiotherapy with concurrent cisplatin and etoposide as additional chemotherapy.15 Considering that pathologic and clinical behavior is similar to small cell lung cancer, patients usually receive platinum and etoposide as part of their primary therapy.16 The recurrent disease remains a major clinical problem, because there is no standard treatment modality for these patients, and individualized therapy is recommeded. ConclusionCurrent therapeutic modalities are mainly based on experience in the treatment of SCNEC of the lung. Certainly, a multidisciplinary approach is very important inorder to design a personalized management plan.

Total hysterectomy versus radical hysterectomy in neuroendocrine cervical cancer: a SEER-database analysis

PurposeWe conducted this study to evaluate the efficacy of total hysterectomy versus radical hysterectomy in the treatment of neuroendocrine cervical cancer (NECC).MethodsEligible NECC patients were identified from the Surveillance, Epidemiology and End Results (SEER) database. Demographic characteristics, clinical treatment and survival of the patients were collected. The overall survival (OS) and cancer-specific survival (CSS) were estimated by Kaplan–Meier analysis with log-rank test.ResultsA total of 286 patients were included, with 104 patients undergoing total hysterectomy and 182 patients undergoing radical hysterectomy. The 5-year OS were 50.8% in the total hysterectomy group and 47.5% in the radical hysterectomy group (p = 0.450); and the corresponding 5-year CSS were 51.6% and 49.1% (p = 0.494), respectively. Along with surgery, radiotherapy was given to 49.0% of patients in the total hysterectomy group and 50.5% in the radical hysterectomy group; and chemotherapy was administered to 77.9% of patients in the total hysterectomy group and 85.7% in the radical hysterectomy group. Unexpectedly, in patients who received adjuvant radiotherapy with or without chemotherapy, the OS was superior in the total hysterectomy group compared with the radical hysterectomy group (p = 0.034). While in patients who received chemotherapy alone and those who received neither radiotherapy nor chemotherapy, the OS still remained comparable between the total hysterectomy and radical hysterectomy group.ConclusionCompared with radical hysterectomy, total hysterectomy was not associated with compromised survival prognosis in patients with NECC. Total hysterectomy has the potential to be a surgical alternative in the multimodal management of NECC.

Advancements in the Understanding of Small-Cell Neuroendocrine Cervical Cancer: Where We Stand and What Lies Ahead.

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.

Abstract 1389 PET/CT scan improves detection of metastatic disease compared with CT scan alone in women with high-grade neuroendocrine cervical cancer: a NeCTuR study

Abstract 1389 PET/CT scan improves detection of metastatic disease compared with CT scan alone in women with high-grade neuroendocrine cervical cancer: a NeCTuR study

PET/CT scan improves detection of metastatic disease compared with CT scan alone in women with high-grade neuroendocrine cervical cancer: a NeCTuR study

ObjectiveTo determine the optimal imaging modality for women with high-grade neuroendocrine carcinoma of the cervix.MethodsWomen with high-grade neuroendocrine carcinoma of the cervix who had undergone a computed tomography (CT) scan...

Personalized prognostic prediction tool for high-grade neuroendocrine cervical cancer: a SEER database analysis and single-center validation

PurposeCervical high-grade neuroendocrine carcinoma (CHGNEC) is a rare but highly aggressive cancer. The purpose of this study is to develop a prognostic nomogram that can accurately predict the outcomes for CHGNEC patients.MethodsWe analyzed clinical data from the Surveillance, Epidemiology, and End Results (SEER) database of CHGNEC patients, including small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC). We investigated patient characteristics and prognosis, and developed a prognostic nomogram model for cancer-specific survival in CHGNEC patients. External validation was conducted using real clinical cases from our hospital.ResultsOur study included 306 patients from SEER database, with a mean age of 49.9 ± 15.5 years. Most of the patients had SCNEC (86.9%). Among them, 170 died from the disease, while 136 either survived or died from other causes. Our final predictive model identified age at diagnosis, stage 1 status, stage 4 status, T1, N0, and surgery of the primary site as independent prognostic factors for CHGNEC. We validated our model using a group of 16 CHGNEC patients who underwent surgery at our center. The external validation showed that the prognostic nomogram had excellent discriminative ability, with an area under the receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.49–1.00) for the prediction of 3-year cancer-specific survival (CSS) and an AUC of 0.85 (95% CI 0.62–1.00) for the prediction of 5-years CSS. The random survival forest model achieved an AUC of 0.80 (95% CI 0.56–1.00) for 3-years CSS and 0.91 (95% CI 0.72–1.00) for 5-years CSS, indicating its adequacy in predicting outcomes for CHGNEC patients.ConclusionOur study provides an excellent nomogram for predicting the prognosis of CHGNEC patients. The prognostic nomogram can be a useful tool for clinicians in identifying high-risk patients and making personalized treatment decisions.

Application of preoperative FDG-PET/CT parameters for predicting prognosis of high-grade neuroendocrine cervical cancer: A single-center, retrospective (1312)

Application of preoperative FDG-PET/CT parameters for predicting prognosis of high-grade neuroendocrine cervical cancer: A single-center, retrospective (1312)

Application of preoperative fluorodeoxyglucose-PET/CT parameters for predicting prognosis of high-grade neuroendocrine cervical cancer.

High-grade neuroendocrine cervical cancer (HGNECC) is a rare and aggressive cervical cancer subtype. In this study, we aimed to evaluate the prognostic value of fluorodeoxyglucose-PET/computed tomography (CT) parameters for HGNECC. This single-center retrospective study included 29 patients with HGNECC who underwent fluorodeoxyglucose-PET/CT scan followed by surgery between 2006 and 2016. The median follow-up period was 40 (range, 4-184) months. After surgery, the resection margins were tumor-negative in 28 patients (96.6%), 8 (27.6%) patients had parametrial tumor invasion, and 7 patients (24.1%) tested positive for lymph node metastasis. The tumor recurred in 20 patients (69%) and 18 patients (62.1%) died during the observation period. In the univariate analyses, age and total lesion glycolysis (TLG) were associated with worse disease-free survival (DFS) (age, hazard ratio 1.056, 95% CI 1.014-1.100, P = 0.009; TLG2.5, hazard ratio 1.003, 95% CI 1-1.006, P = 0.033; and TLG3.0, hazard ratio 1.003, 95% CI 1-1.006, P = 0.034). In the multivariate analyses, older age and higher TLG3.0 were identified as independent poor prognostic factors for DFS (age, hazard ratio 1.058, 95% CI 1.014-1.104, P = 0.009; TLG3.0, hazard ratio 1.004, 95% CI 1-1.007, P = 0.033), while resection margin involvement was identified as an independent factor to predict poor overall survival (hazard ratio 20.717, 95% CI 1.289-332.964, P = 0.032). Among the preoperative fluorodeoxyglucose-PET/CT parameters, TLG3.0 may be useful for predicting DFS in patients with HGNECC.

Opportunities Missed: Cervix Cancer Screening Failures in Women Aged 65 and Older.

This study aimed to determine the screening history and associated outcomes of women diagnosed with cervical cancer after age 65. All patients from 2012 to 2021 diagnosed with squamous, adenocarcinoma, neuroendocrine, or adenosquamous cervical cancer after age 65 in a single managed care organization (MCO) were included in this retrospective cohort study. Demographic, medical, screening, pathologic, follow-up, and treatment data were extracted. Statistical analysis was done using chi-square test and logistic regression. Cancer-specific survival was estimated using the Kaplan-Meier method. Of 2,175 patients screened, 209 met inclusion criteria. Only 26.3% of patients had appropriate cervical cancer screening and 41% of patients died of their disease. Managed care organization membership duration of more than 5 years positively correlated with proper cervical cancer screening ( p < .001); however, 64% of the long-term members still did not meet criteria to end screening at age 65, with 42.6% of these patients having more than 25 physician visit opportunities to address screening. Increased physician visits correlated with earlier stage at diagnosis of cervical cancer ( p = .012). Median cancer-specific survival was significantly better in properly screened patients at 68 vs 30 months, respectively ( p = .03). Most patients diagnosed with cervical cancer after age 65 did not have adequate previous screening, including those who were MCO members for more than 5 years. There were many missed opportunities for screening, despite multiple provider touchpoints. The authors' data suggest that adequate screening confers a survival benefit secondary to earlier stage at diagnosis. Further study in this age group is needed to redefine the criteria to end cervix cancer screening.

Impact of adjuvant chemotherapy on the overall survival of patients with resectable bulky small cell neuroendocrine cervical cancer: a JSGO-JSOG joint study.

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment. The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition). There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p<0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p<0.01). SNCEC tumors >4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in patients with recurrent high-grade neuroendocrine cervical cancer: a Neuroendocrine Cervical Tumor Registry (NeCTuR) study

Recurrent high-grade neuroendocrine cervical cancer has a very poor prognosis and limited active treatment options. This study aimed to evaluate the efficacy of the 3-drug regimen of topotecan, paclitaxel, and bevacizumab in women with recurrent high-grade neuroendocrine cervical cancer. This retrospective cohort study used data from the Neuroendocrine Cervical Tumor Registry (NeCTuR), which include data abstracted directly from medical records of women diagnosed with high-grade neuroendocrine carcinoma of the cervix from English- and Spanish-speaking countries. The study compared women with recurrent high-grade neuroendocrine cervical cancer who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy forrecurrence and women with recurrent high-grade neuroendocrine cervical cancer who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen. Patients continued chemotherapy until disease progression or the development of unacceptable toxic effects. Progression-free survival from the start of therapy for recurrence to the next recurrence or death, overall survival from the first recurrence, and response rates were evaluated. The study included 62 patients who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and 56 patients who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen for recurrence. The median progression-free survival rates were 8.7 months in the topotecan, paclitaxel, and bevacizumab regimen group and 3.7 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for disease progression of 0.27 (95% confidence interval, 0.17-0.48; P<.0001). In the topotecan, paclitaxel, and bevacizumab regimen group, 15% of patients had stable disease, 39% of patients had a partial response, and 18% of patients had a complete response. Compared with patients in the non-topotecan, paclitaxel, and bevacizumab regimen group, significantly more patients in the topotecan, paclitaxel, and bevacizumab regimen group remained on treatment at 6 months (31% vs 67%, respectively; P=.0004) and 1 year (9% vs 24%, respectively; P=.02). The median overall survival rates were 16.8 months in the topotecan, paclitaxel, and bevacizumab regimen group and 14.0 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for death of 0.87 (95% confidence interval, 0.55-1.37). Combination therapy with topotecan, paclitaxel, and bevacizumab was an active regimen in women with recurrent high-grade neuroendocrine cervical cancer and improved progression-free survival while decreasing the hazard ratio for disease progression.

Detection of HPV RNA in Extracellular Vesicles from Neuroendocrine Cervical Cancer Cells.

Background: Neuroendocrine carcinoma of the cervix (NECC) is an aggressive and rare type of cervical cancer. The five-year overall survival is low at 30% and there is no standardized therapy based on controlled trials for this type of tumour. Most are locally advanced or metastasized at the time of the diagnosis. Extracellular vesicles (EVs) could be a carrier of viral DNA/RNA, given their vital role in cellular communication. The content of EV derived from NECC cells has not been investigated due to the lack of cell line, and it is not known whether they contain human papillomaviruses (HPV) DNA/RNA or not. Methods: The presence of viral E7 DNA/RNA in EVs purified from a culture of a recently established NECC cell line, GUMC-395, was evaluated by using droplet digital polymerase chain reaction (ddPCR). These EVs were characterized using nanoparticle tracking analysis (NTA) for size distribution, transmission electron microscopy (TEM) for morphology, Western blot for CD63, and bioanalyser for RNA quantity and quality. Results: HPV16 viral-RNA, but not DNA, was detected in EVs from GUMC-395 using ddPCR. NTA identified EVs with a mean diameter of 105.0 nm, TEM confirmed normal morphological shape and size, and Western blot analysis confirmed the presence of EV-associated proteins CD63. The EVs were found to be enriched with small RNAs using a bioanalyser. Conclusions: HPV16 RNA is found in EVs from a neuroendocrine cervical cancer and could be involved in the pathogenesis of the disease and used as a diagnostic biomarker.

Impact of the initial site of metastases on post-recurrence survival for neuroendocrine cervical cancer

ObjectiveTo summarize the risk factors and emphasize the prognostic importance of the site of recurrent neuroendocrine cervical cancer (NECC).MethodsWe enrolled 88 patients who developed recurrence after radical surgery for pathological stage I–IVa primary NECC between January 2003 and 30 December 2020 and classified these cases into 7 groups based on the initial recurrence. The risk factors for post-recurrence survival (PRS) were analyzed by Kaplan–Meier and Cox regression methods.ResultsAmong 88 NECC patients, nearly all patients (95.50%) experienced progression within 3 years. The time to progression was significantly longer in patients with lung recurrence than in patients without lung recurrence (p = 0.008). After the first recurrence, the median follow-up was 11.1 months (range 2.37–65.50 months), and the 5-year PRS was only 20.6%. The depth of invasion in the primary surgery, number of recurrent sites, abdominal organ recurrence were correlated with PRS by univariate analysis. Multivariate analyses revealed that the number of recurrent sites (p = 0.025) and abdominal organ recurrence (p = 0.031) were independent prognostic factors. Notably, the combination of immune checkpoint inhibitors and chemotherapy, with or without surgery, showed a 43.8% objective response rate in recurrent NECC.ConclusionPatients with abdominal organ recurrence need more sophisticated therapy. The combination of immune therapy and chemotherapy might be an opportunity for recurrent NECC.

Therapeutic strategy analysis of patients with advanced stage high-grade neuroendocrine cervical cancer: A real-world multicenter study.

To explore the management of high-grade neuroendocrine cervical cancer (HGNECC) since there has been no standard treatment for it. Data on the management of HGNECC were retrospectively analyzed. Patients with FIGO stage IIB to IVB HGNECC from six hospitals were enrolled. The Kaplan-Meier method was used for survival analysis. Prognostic factors were determined using a Cox proportional-hazards regression model. A total of 43 patients were included in the study. The multivariate analysis showed that chemotherapy was the preferred treatment as it improved progression-free survival (PFS; P=0.008) and overall survival (OS; P=0.005). Distance metastasis was a significant negative prognostic factor for OS (P=0.002), while radical surgery was a significant positive prognostic factor for PFS (P=0.05). Compared with those who had received cisplatin and etoposide (≥5 cycles), patients who had received paclitaxel plus platinum-based chemotherapy showed better PFS and OS. Five patients (two at stage IIB and three at stage IV) showed relatively long-term survival. Of these patients, four had undergone radical surgery including tumor-debulking, while three also received adjuvant chemotherapy. Paclitaxel plus cisplatin or paclitaxel plus carboplatin may be more effective than etoposide plus cisplatin. Radical surgery followed by chemotherapy may be a favorable alternative intervention for selected patients with advanced stage cancer.

PD-L1, PARP1, and MMRs as potential therapeutic biomarkers for neuroendocrine cervical cancer.

ObjectiveNeuroendocrine cervical cancer (NECC) is a rare cervical cancer with high aggressivity that causes poor prognosis even in the early stage. Given other neuroendocrine carcinomas and other types of cervical cancer have been proved to have expression of programmed cell death protein 1 ligand 1(PD‐L1) and poly ADP‐ribose polymerase‐1(PARP1), we would measure and analyze these proteins in this invasive cancer. The purpose of this study is to investigate the application value of PD‐1/PD‐L1 and PARP1 inhibitors in NECC.MethodsThe NECC cases in our center with formalin‐fixed paraffin‐embedded tissue blocks were collected, and immunohistochemical (IHC) staining of PD‐L1, PARP1, Mismatch repair proteins (MMRs), and P53 was performed. Chi‐square test was used to analyze associations between various protein expressions. We analyzed the efficacy of immunotherapy in a recent patient with secondary recurrence after two courses of chemotherapy.ResultsAfter rigorous screening, 20 cases were finally included. Three cases did not undergo surgical treatment because of their advanced stage. Twelve (60%) developed distant metastases or relapsed within five years, and most of them within two years. The positive rate of PD‐L1 and PARP1 were 70% and 75% respectively. Among all the cases, microsatellite instability (MSI) was seen in six cases (30%) and abnormal p53 expression was in 15 patients (75%). PD‐L1 was associated with PARP1 expression in the MSI subgroup. The patient treated with chemotherapy + VEGF inhibitor (VEGFi) + programmed cell death protein 1(PD‐1) inhibitor had an excellent improvement in clinical symptoms, tumor markers, and mass size.ConclusionThe IHC results of PD‐L1, PARP1, and MMRs suggested that NECC was the target of immunotargeted therapy. Our case confirmed that immune checkpoint therapy was effective in patients with PD‐L1 positive and MMRs loss. Considering the clinical practicability, more cases should be collected, and effective biomarkers still need to be further searched.

The role of radiotherapy in neuroendocrine cervical cancer: SEER-based study.

There are few randomised prospective data or guidelines for the treatment of neuroendocrine cervical cancer (NECC). In addition, the role of radiotherapy (RT) in NECC remains controversial. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of RT for the treatment of NECC. Particular attention was paid to the different role of RT in patients with or without a metastasis (M1 or M0). The SEER database was queried for studies on NECC. We limited the year of diagnosis to the years 2000 to 2015. A Pearson's two-sided Chi-squared test, the Kaplan-Meier method and Cox regression analysis models were used for statistical analyses. The overall survival (OS) was studied for the overall group and between-subgroup groups. NECC was an aggressive disease with a mean OS of only 46.3 months (range of 0-196 months, median of 23 months). No significant differences were shown between the surgery (S) and S + RT groups (p = 0.146) in the M0 (without metastasis) arm. However, there was a statistically significant difference in OS between the S and S + RT groups in the M1 (with metastasis) arm (median of 44.6 months for the S group and 80.9 months for the S + RT group), p = 0.004. The mean survival was significantly longer for M0 patients than for M1 patients when treated with S only (S arm), that is, 82.1 months versus 44.6 months, respectively (log-rank p = 0.000). We also noted that when patients received adjuvant RT (S + RT arm), there were no significant differences between the M0 and M1 groups (median of 90.6 and 81.0 months, p = 0.704, respectively). Age at diagnosis, chemotherapy, T stage and N stage were significant factors for OS in the M0 arm. Interestingly, radiotherapy was the only significant factor for OS with a multivariate HR for death of 0.502 (95% CI 0.206-0.750, p = 0.006) in the M1 arm. RT may be carefully used in patients who are negative for metastases. Using SEER data, we identified a significant survival advantage with the combination of radiotherapy and surgery in NECC with metastases. This suggests that active local treatment should be conducted and has a significant impact on OS, even if a distant metastasis has occurred.

Патоморфологическая оценка клинического случая нейроэндокринной опухоли шейки матки

The article describes our own observation of neuroendocrine cervical cancer, which is one of the rare variants of tumors of this localization. With the help of histological and immunohistochemical studies, a small-cell variant of neuroendocrine carcinoma of the vaginal portion of the cervix uteri with invasion into the wall of the cervical canal and into the thickness of the myometrium of the uterine body was verified, with metastases in the fallopian tubes, in the ovaries, in the pelvic lymph nodes and in the greater omentum.

Microscopic parametrial compromise in surgically treated high-grade neuroendocrine cervical carcinoma

Objective: Most patients with early-stage high-grade neuroendocrine cervical cancer (HGNECC) undergo radical hysterectomy and pelvic lymphadenectomy; however, most will receive postoperative radiation and chemotherapy. Our aim was to determine the incidence of parametrial involvement (PI) in patients with clinical early-stage HGNECC and to evaluate factors associated with parametrial compromise.

Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms.

PURPOSEHigh-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape.PATIENTS AND METHODSNinety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs.RESULTSThe median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors (P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found.CONCLUSIONThis large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

Evaluation of PARP and PDL-1 as potential therapeutic targets for women with high-grade neuroendocrine carcinomas of the cervix

ObjectivesWomen with recurrent high-grade neuroendocrine cervical cancer have few effective treatment options. The aim of this study was to identify potential therapeutic targets for women with this disease.MethodsSpecimens from patients...