Naomi R Gonzales

Neuroendocrine neoplasms of the ovary: a review of 63 cases

To describe the clinicopathological characteristics and survival outcomes of ovarian neuroendocrine neoplasms from a curated registry. This is a retrospective cross-sectional study of patients in our registry with confirmed ovarian neuroendocrine neoplasms. We excluded patients with small cell carcinoma not otherwise specified, small cell hypercalcemic type, and those with neuroendocrine 'features' or 'differentiation.' Clinicopathological characteristics were described in two separate groups: patients with carcinoid tumors and patients with neuroendocrine carcinomas. Progression-free and overall survival were estimated with the Kaplan-Meier product-limit estimator in these two groups, and multivariable analysis was done to identify predictors of survival for neuroendocrine carcinomas only. A total of 63 patients met inclusion criteria, 13 (21%) with carcinoid tumors and 50 (79%) with neuroendocrine carcinomas. In the carcinoid tumor group, one patient (8%) was misdiagnosed. Two patients (15%) had a recurrence and the 5-year overall survival rate was 80% (95% CI 45% to 100%), with a lower bound of the median survival of 4.8 years (95% CI). In the neuroendocrine carcinoma group, 23 patients (46%) were misdiagnosed, 16 of whom (69%) received therapy with the presumption of a non-neuroendocrine carcinoma diagnosis. Thirty patients (60%) had a recurrence, and the 5-year overall survival rate was 24% (10%, 38%), with a median survival of 1.6 years (1.3, 3.3). Patients with carcinomas stage III or IV had an increased risk of progression/recurrence (HR=5.6; 95% CI 1.9 to 17.0) and death (HR=8.1; 95% CI 2.2 to 29.7) compared with those with stage I or II. Pure histology was associated with an increased risk of progression/recurrence (HR=2.3; 95% CI 1.0 to 5.2) compared with admixed histology. Most patients had neuroendocrine carcinomas, which were associated with a higher recurrence rate and worse survival than carcinoid tumors. A high proportion of patients in both groups were initially misdiagnosed, and a new association with endometrial hyperplasia was observed. Neuroendocrine admixed histology is associated with a higher risk of progression.

Survival outcomes in patients with recurrent mixed sex cord-stromal tumors of the ovary

Mixed sex cord-stromal tumors of the ovary contain combinations of granulosa cell tumor components-either adult or juvenile subtypes-and/or Sertoli-Leydig cell tumor elements. The objective of this study is to evaluate survival outcomes in recurrent mixed sex cord-stromal tumors. This is a retrospective cohort study of recurrent mixed ovarian sex cord-stromal tumors identified through the MD Anderson Rare Gynecologic Malignancy Registry between 2000 and 2025. Comparative cohorts with recurrent, histologically uniform adult granulosa cell tumors, juvenile granulosa cell tumors, and Sertoli-Leydig cell tumors were included. Demographic and clinical characteristics were compared using descriptive statistics. Progression-free survival after first recurrence and overall survival from first recurrence were assessed using Kaplan-Meier methods and compared using log-rank tests. Sixteen patients with recurrent mixed ovarian sex cord-stromal tumors were identified: 6 (37.5%) with adult granulosa cell plus Sertoli-Leydig cell tumors, 4 (25%) with juvenile granulosa cell plus Sertoli-Leydig cell tumors, and 6 (37.5%) with adult plus juvenile granulosa cell tumors. When comparing adult granulosa cell tumors to adult plus juvenile granulosa cell tumors, significant differences in median progression-free survival-2 (21.2 vs 8.7 months, p = .03) and overall survival (181.9 vs 83.8 months, p = .001) were observed. No significant differences in progression-free survival-2 (p = .7) or overall survival (p = .8) were noted between juvenile granulosa cell tumors and adult plus juvenile granulosa cell tumors. Among tumors with molecular testing results, 25% (1 of 4) of adult plus juvenile granulosa cell tumors, 25% (1 of 4) of adult granulosa cell plus Sertoli-Leydig cell tumors, and 33% (1 of 3) of juvenile granulosa cell plus Sertoli-Leydig cell tumors were positive for the c.C402G FOXL2 mutation. Recurrent adult plus juvenile granulosa cell tumors may exhibit more aggressive clinical behavior than uniform adult granulosa cell tumors, aligning more closely with juvenile granulosa cell tumors in recurrence outcomes.

Neuroendocrine cervical carcinomas: genomic insights, controversies in treatment strategies, and future directions: a NeCTuR study

Neuroendocrine cervical carcinomas are rare, aggressive tumors with a high risk of early metastasis and poor survival outcomes. Despite existing therapies, over half of patients experience recurrence or progression after primary treatment, and survival after recurrence remains limited. Survival rates have not significantly improved over the past several decades, underscoring an urgent need for better therapeutic options. The rarity of neuroendocrine cervical carcinoma has precluded randomized trials, leaving treatment strategies to be guided by small retrospective studies or adapted from protocols for small cell lung cancer. However, as we gain a deeper understanding of its unique origin, genomic landscape, and biological characteristics, it has become clear that neuroendocrine cervical carcinoma requires distinct management strategies. Key questions in managing neuroendocrine cervical carcinoma remain unanswered: does adjuvant radiation therapy improve outcomes for early-stage disease? Should neoadjuvant chemotherapy be considered for patients with bulky, localized tumors? Can immunotherapy improve outcomes when added to chemoradiation in locally advanced cases? Should immunotherapy be a standard option for recurrent disease? Addressing these questions requires a thorough understanding of the unique molecular and biological characteristics of neuroendocrine cervical carcinoma and its clinical behavior. This review aims to provide an updated summary of the molecular landscape of neuroendocrine cervical carcinoma, highlighting features that distinguish it from small cell lung cancer and align with other types of cervical cancer. We discuss current treatment approaches, identify gaps in knowledge, and examine paradigm-shifting clinical trials that have significantly impacted survival outcomes in cervical cancer and small cell lung cancer, translating these insights into potential strategies for neuroendocrine cervical carcinoma. By focusing on the unique aspects of neuroendocrine cervical carcinoma, this review emphasizes the need for specialized treatment strategies for this challenging disease.

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

To determine the optimal imaging modality for women with high-grade neuroendocrine carcinoma of the cervix. Women with high-grade neuroendocrine carcinoma of the cervix who had undergone a computed tomography (CT) scan and combined positron emission tomography with computed tomography (PET/CT) scan within 4 weeks of each other were identified from the NeCTuR Cervical Tumor Registry. One radiologist reviewed all CT scans, and another radiologist reviewed all PET/CT scans. The radiologists denoted the presence or absence of disease at multiple sites. Each radiologist was blinded to prior reports, patient outcomes, and the readings of the other radiologist. With findings on PET/CT used as the gold standard, sensitivity, specificity, and accuracy were calculated for CT scans. Fifty matched CT and PET/CT scans were performed in 41 patients. For detecting primary disease in the cervix, CT scan had a sensitivity of 85%, a specificity of 46%, and an accuracy of 74%. For detecting disease spread to the liver, CT scan had a sensitivity of 80%, a specificity of 89%, and an accuracy of 86%. For detecting disease spread to the lung, CT had a sensitivity of 89%, a specificity of 68%, and an accuracy of 77%. Of the 14 patients who had scans for primary disease work-up, 4 (29%) had a change in their treatment plan due to the PET/CT scan. Had treatment been prescribed on the basis of the CT scan alone, 2 patients would have been undertreated, and 2 would have been overtreated. A CT scan is inferior to a PET/CT scan in assessment of metastatic disease in women with high-grade neuroendocrine carcinoma of the cervix. Almost one-third of patients with newly diagnosed high-grade neuroendocrine cervical cancer would have received incorrect therapy had treatment planning been based solely on a CT scan. We recommend a PET/CT scan for both initial work-up and surveillance in women with high-grade neuroendocrine carcinoma of the cervix.

Impact of pelvic radiation therapy in patients with early neuroendocrine cervical carcinoma and no residual disease in the radical hysterectomy specimen: a NeCTuR study

The impact of adjuvant pelvic radiation therapy on the rate and location of recurrences was evaluated in patients with early-stage (IA1-IB2) neuroendocrine cervical carcinoma who underwent prior conization or polypectomy with no residual disease and negative nodes in the subsequent upfront radical hysterectomy specimen. As a secondary objective, disease-free and overall survival were analyzed. We searched the Neuroendocrine Cervical Tumor Registry (NeCTuR) to identify patients with clinical early-stage neuroendocrine cervical carcinoma with no residual disease in the specimen from upfront radical surgery and negative nodes. Patients who received pelvic radiation therapy were compared with those who did not, regardless of whether they received adjuvant chemotherapy. Twenty-seven patients met the inclusion criteria, representing 17% of all patients with clinical early-stage disease who underwent upfront radical hysterectomy included in the NeCTuR registry. The median age was 36.0 years (range 26.0-51.0). Six (22%) patients had stage IA, 20 (74%) had stage IB1, and one (4%) had stage IB2 disease. Seven (26%) patients received adjuvant radiation therapy and 20 (74%) did not. All seven patients in the radiation group and 14 (70%) in the no-radiation group received adjuvant chemotherapy (p=0.16). Fifteen percent (4/27) of patients had a recurrence, 14% (1/7) in the radiation group and 15% (3/20) in the no-radiation group (p=0.99). In the radiation group the recurrence was outside the pelvis, and in the no-radiation group, 67% (2/3) recurred outside the pelvis and 33% (1/3) recurred both inside and outside the pelvis (p=0.99). In the radiation group the 5-year disease-free and overall survival rates were 100% while, in the no-radiation group, the 5-year disease-free and overall survival rates were 81% (95% CI 61% to 100%) (p=0.99) and 80% (95% CI 58% to 100%) (p=0.95), respectively. For patients with no residual disease and negative nodes in the upfront radical hysterectomy specimen, our study did not find that pelvic radiation therapy improves survival.