Objective To characterize cases of atypical placental site nodules (APSNs), including their clinical presentation, diagnosis, management, and outcomes at an urban academic institution. Methods Cases with a pathology diagnosis of APSN were reviewed from January 2019 to July 2024. Available slides were reviewed by pathologists and chart review was conducted for demographic and clinical information. Results Eleven cases of APSN were identified. Two cases were incidentally diagnosed after hysterectomy for other indications. Abnormal Papanicolaou testing (4/11, 36.4%) was the most common presenting symptom followed by menorrhagia (2/11, 18.2%). The median interval between antecedent pregnancy and diagnosis of APSN was 29.4 months (range: 2.7–288.0 months). All cases had increased trophoblastic cellularity (defined as >25% cellularity) and ≥ 5% Ki-67 proliferation index. Six cases had management and follow-up data available: 2 (25.0%) opted for hysterectomy and 4 (44.4%) chose conservative management. Additional pathology results included 1 APSN (16.7%), 1 placental site nodule (PSN) (16.7%), and 4 (66.7%) with no evidence of gestational trophoblastic disease. No case was associated with malignant gestational trophoblastic neoplasia (GTN) at time of diagnosis, final pathology, or subsequent follow-up when available. Discussion Most cases did not present with abnormal uterine bleeding or menorrhagia prior to diagnosis. Most were incidentally diagnosed following presentation for abnormal Papanicolaou testing. Due to the incidental nature of its diagnosis, APSN may be more prevalent than previously considered. We also observed no association of APSN with GTN. The clinical course of APSN may be overall more benign.
Objective: This study examines the association of socioeconomic status (SES) with delays in care and treatment timeline for endometrial cancer (EC) patients receiving primary surgery.Methods: This was a retrospective cohort study of patients who underwent surgical management of EC between 2018 and 2024. SES was determined by Area Deprivation Index (ADI) national percentile rank. Demographics, dates of symptom onset, provider visits, tissue diagnosis, and surgery were abstracted from the electronic medical record.Results: Of the 2191 patients who had surgical management for EC, we analyzed 185 (ADI1, most advantaged) and 257 (ADI4, least advantaged). Patients in ADI1 had a lower mean BMI (31.1 kg/m2 vs 35.6 kg/m2, p < 0.001). Although the majority of the cohort was White (91.0%), ADI4 included more Black patients (6.6% vs 1.1%, p = 0.003).Time from symptom onset to surgery was 30 days longer in ADI4 compared to ADI1 (126.0 days vs 96.0 days, p = 0.003). Specifically, time from symptom onset to first visit with a healthcare provider differed significantly between ADI1 and ADI4, with a median of 20.5 days versus 50.0 days (p < 0.001). There were no statistically significant differences in intervals between other care timepoints.Conclusions: The discrepancy in time to surgical management of EC was driven by delays in first provider visit, indicating that disparities are related to symptom recognition and access to initial evaluation rather than delays within specialty care. These findings can inform interventions for reducing socioeconomic and geographic disparities in endometrial cancer care.
Objectives: Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer characterized by slow disease progression and relative resistance to conventional chemotherapy. Disease recurrence is common, and guideline-directed treatment options may become exhausted, underscoring the need for novel therapeutic approaches. This case report describes the clinical course and treatment response of a patient with recurrent, KRAS G12C-mutated LGSOC after 5 lines of previous therapy who was treated with the KRAS G12C small-molecule inhibitor sotorasib.Methods: In this case study, a patient with recurrent Stage IC3 LGSOC, whose tumor tested positive for a KRAS G12C mutation, received sotorasib 960 mg as an off-label therapy after disease progression on available guideline-directed therapies.Results: Treatment with sotorasib resulted in an ongoing, partial response on CT scans at 2 and 7 months after therapy initiation. CA-125 normalized rapidly and remains within normal limits to date. The patient has experienced no adverse events and has been able to maintain adherence to therapy.Conclusions: This case study documents a clinically successful treatment using sotorasib in LGSOC. This represents a novel targeted therapy approach for patients with KRAS G12-mutated recurrent LGSOC, suggesting benefit in this population that has not been documented to date.
Background Mirvetuximab Soravtansine (MIRV) is an antibody–drug conjugate targeting folate receptor alpha (FRα), expressed in most ovarian cancers. Pivotal trials reported favorable outcomes but used stringent eligibility criteria, and real-world effectiveness and toxicity remain incompletely characterized. We evaluated overall survival (OS), progression-free survival (PFS), and toxicity among a general gynecologic oncology population treated with MIRV for recurrent ovarian cancer. Methods This retrospective study analyzed data from patients with recurrent ovarian cancer who received MIRV at a tertiary NCI-designated cancer center and an affiliated private hospital between November 2022 and April 2025. Demographics, disease and treatment characteristics, and toxicities were abstracted from the electronic medical record. OS and PFS were estimated using the Kaplan–Meier method. Multivariable Cox proportional hazards models assessed associations between clinical factors and survival. Results Sixty-six patients received MIRV. Most had stage IIIC-IVB disease (89%), 86% had a PS of 0 or 1, and 77% had received ≥3 prior therapeutic regimens. Most (52%) had platinum-resistant disease, and FRα expression was positive in 77% of cases. Median OS was 16.4 months (95% CI 12.4 to NE) and PFS was 5.3 months (95% CI 4.1–7.1). OS and PFS did not differ by platinum status. ECOG PS >1 was associated with worse OS (median 6.0 vs 20.3 months for PS 0–1; P = 0.0006). Toxicity was common (91%). Conclusion MIRV demonstrates clinically meaningful survival, but outcomes are strongly influenced by performance status. Patients with ECOG PS >1 should be counseled about substantially shorter survival, and clinicians should anticipate and manage MIRV toxicities.
Objective:Real-time kinetics of circulating tumor DNA (ctDNA) during active concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) remain poorly characterized. We evaluated peri-treatment ctDNA dynamics in a real-world safety-net cohort using a commercially available tumor-informed assay. Methods:We retrospectively reviewed serial ctDNA measurements (Signatera) in 17 LACC patients who underwent definitive CCRT, with or without induction chemotherapy and immune checkpoint inhibitor therapy. Patients were classified by longitudinal ctDNA kinetics as Sustained clearance, Persistent/Re-positive, or Negative. Results:Baseline ctDNA was detectable in 15 of 17 patients (88%); patients were classified as Sustained clearance (n = 8), Persistent/Re-positive (n = 7), or Negative (n = 2). With mean follow-up of 273 ± 148 days, all 5 clinical recurrences occurred in the Persistent/Re-positive group (5/7 vs 0/8; Fisher's exact P = 0.007), representing a strong but preliminary association. Among 8 non-induction-treated patients with detectable baseline ctDNA and ≥ 2 assessments spanning baseline and intra-CCRT, molecular clearance during active CCRT occurred in 5 (62.5%), first observed between days 27 and 43; none developed recurrence. Trajectories were frequently non-monotonic, with isolated negative results within otherwise-positive courses. ctDNA preceded imaging-based recurrence in three of five recurrent patients by a median of 124 days (range 70-240). Three recurrent patients were considered candidates for total pelvic exenteration. Conclusions:Detectable ctDNA declined rapidly during CCRT but frequently followed a non-monotonic trajectory. Serial rather than isolated measurements appear necessary to interpret molecular response during active treatment. Prospective studies are warranted to determine whether trajectory-based ctDNA monitoring can improve risk stratification and recurrence detection.
Objectives To evaluate the guideline concordance, accuracy, and completeness of unprompted ChatGPT-4 and Gemini responses to gynecologic oncology case vignettes benchmarked against NCCN guidelines across five clinical domains for patient education and medical training. Methods Ten clinical vignettes encompassing five topics were proposed to reflect common yet complex decision-making scenarios in gynecologic oncology. Each vignette was posed without prompting in publicly-available versions of ChatGPT-4 and Gemini in 2025. Responses were independently scored by five board-certified gynecologic oncologists using a 0–2 scale. Scores were based on concordance with 2025 NCCN Guidelines. Descriptive statistics summarized performance patterns, and inter-rater reliability was measured using Gwet's AC1. Results Across all domains, Gemini achieved a slightly higher overall concordance with NCCN guidelines than ChatGPT (mean score 1.82 vs. 1.62), with 82% and 64% of responses, respectively, rated as accurate and complete. There was one isolated instance of inaccurate (score of 0) output graded. Domain-specific analysis revealed that ChatGPT demonstrated a nonsignificant inferior average concordance compared to Gemini in all clinical categories. Both models showed lower completeness in survivorship and adjuvant treatment topics. Qualitative reviewer feedback highlighted clinically relevant omissions and interpretive nuances. Conclusions Although neither ChatGPT nor Gemini consistently outperformed the other in specific clinical domains, Gemini's slightly higher average overall concordance with NCCN guidelines underscores its potential advantages over ChatGPT. AI may provide largely accurate, guideline concordant clinical reasoning across diverse gynecologic oncology scenarios. Variability and occasional inaccuracies underscore the need for clinical oversight before integration into care pathways or patient guidance.
Background:Mucinous endometrial carcinoma of gastric type (MCG) is a rare and aggressive malignancy with no established standard of care. Biomarkers of homologous recombination deficiency (HRD), including BRCA1/2 alterations and genomic signatures, are increasingly used to predict sensitivity to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), but their utility in rare gynecologic cancers remains unclear. Case presentation:We report a 52-year-old female with metastatic TP53-abnormal endometrial MCG. Whole-genome and transcriptome analysis identified a pathogenic germline BRCA1 mutation with somatic loss of heterozygosity (LOH), resulting in biallelic BRCA1 loss. A high HRDetect score (0.96) further supported an HRD phenotype. The patient achieved an initial partial response to frontline platinum-based chemotherapy. However, despite genomic evidence predicting PARPi sensitivity, she experienced rapid disease progression within three months of completion of platinum and starting maintenance niraparib. Retrospective copy-number signature analysis classified the tumor as a non-HRD signature characterized by high ploidy rather than classic BRCA-associated genomic scarring. To further investigate treatment response, a patient-derived xenograft (PDX) model was established. The model faithfully recapitulated the clinical phenotype, showing response to cisplatin but intrinsic resistance to the PARP inhibition. Conclusion:This case demonstrates a discordance between genomic HRD biomarkers and therapeutic response. Despite germline BRCA1 mutation, somatic LOH, and a high HRDetect score, platinum response was not durable and PARPi sensitivity was not observed. These findings highlight the limitations of current HRD biomarkers in rare gynecologic cancers and support integrating functional and genomic approaches to guide precision oncology.
ObjectiveTrastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate, received FDA approval on April 5, 2024 for HER2-expressing solid tumors based on the phase II DESTINY-PanTumor02 trial (n = 40 per tumor type). Despite rapid clinical adoption, real-world evidence in gynecologic cancers remains limited. This study aims to address this gap.MethodsThis single-center retrospective cohort study included patients with ovarian cancer (OC) or endometrial cancer (EC) who received T-DXd between September 2022 and January 2026. Primary outcomes were real-world progression free survival (rwPFS) and real-world response rate (rwRR). Secondary outcomes included real-world disease control rate (rwDCR), safety, and time on treatment (TOT). Exploratory analysis aimed to evaluate predictors of progression or death on T-DXd using multivariate cox regression.ResultsAs of February 2026, 40 patients (20 OC, 20 EC) received T-DXd, with a median follow-up of 23 months. All 40 were analyzed for PFS; 37 were response evaluable. HER2 IHC expression was 12.5% 1+, 62.5% 2+, and 20% 3+. Median rwPFS was 6.2 months (95% CI, 3.3-8.6), with a rwRR of 45.9% and rwDCR of 67.6%. rwRR increased significantly with HER2 expression (1+ 16.7%, 2+ 39.1%, 3+ 86%, p = 0.03). In multivariate analysis, PARP inhibitor exposure was associated with significantly shorter PFS (HR 4.36, p = 0.04). Four patients (10%) developed pneumonitis: three (7.5%) grade 1/2, and one (2.5%) grade 3. Conclusions:T-DXd demonstrated promising real-world clinical outcomes in OC and EC that mirror DESTINY-PanTumor02. Responses were observed across HER2 IHC expression levels (1+ to 3+), with highest rwRR among HER2 3+. Prior PARP inhibitor exposure was associated with significantly shorter PFS, warranting further exploration.
Objective:To evaluate the prevalence and prognostic relevance of pretreatment computed tomography-defined sarcopenia in women with cervical cancer treated with definitive radiotherapy with or without concurrent chemotherapy. Methods:This retrospective cohort study included women aged 18 years or older with FIGO 2018 stage IB2 to IVA cervical cancer who initiated definitive radiotherapy, with or without radiosensitizing chemotherapy, between January 2016 and December 2018 at CAISM/UNICAMP, Campinas, Brazil. Follow-up continued through 2022 to ensure a minimum follow-up period to evaluate 5-year survival outcomes. Women with prior malignancy treated with chemotherapy or radiotherapy, unavailable or non-measurable pretreatment computed tomography, pregnancy, or death before treatment initiation were excluded. Pretreatment sarcopenia was defined as skeletal muscle index <38.9 cm2/m2 using bilateral psoas and paraspinal linear measurements at L3 on planning computed tomography. Treatment response followed World Health Organization response definitions. Progression-free survival and overall survival were estimated using Kaplan-Meier methods and compared with log-rank tests. Cox proportional hazards models and multivariable logistic regression were performed to estimate hazard ratios (HR), odds ratios (OR), and 95% confidence intervals. Results:Among 210 included women, 79 (37.6%) had pretreatment sarcopenia. Most patients had squamous histology (176/210, 83.8%), advanced FIGO stage III/IV disease (120/210, 57.1%), and received chemotherapy (177/210, 84.3%). Sarcopenia was more frequent among women aged <50 years, premenopausal women, women with body mass index <25 kg/m2, and women with anemia. Complete or stable response occurred in 100 patients, whereas progression or recurrence occurred in 110; sarcopenia was more common among patients with progression or recurrence. In univariable analysis, pretreatment sarcopenia was associated with worse progression-free survival (HR 1.70, 95% CI 1.15 to 2.51) and overall survival (HR 1.75, 95% CI 1.11 to 2.75). In multivariable Cox regression, complete response to treatment was the only factor independently associated with overall survival (HR 0.07, 95% CI 0.02 to 0.18, p < 0.0001). Multivariable logistic regression showed a trend for higher sarcopenia prevalence in women aged <50 years (OR 1.73, 95% CI 0.98 to 3.05, p = 0.057). Conclusion:Pretreatment CT-defined sarcopenia was common and associated with poorer survival outcomes in univariable analysis, although treatment response remained the strongest independent prognostic factor in women with cervical cancer treated with definitive chemoradiotherapy.
OBJECTIVE:To evaluate the real-world efficacy and safety of cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer (R/M CC), including patients from subgroups underrepresented in clinical trials. METHODS:We conducted a single-center, retrospective cohort study of 25 consecutive patients with R/M CC treated with cemiplimab between April 2023 and April 2025. Outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Responses were assessed by RECIST version 1.1, and treatment-emergent adverse events (TEAEs) were graded according to CTCAE version 5.0. RESULTS:The median follow-up was 12.6 months. The ORR was 16.0% (95% CI, 4.5-36.1%) and the DCR was 64.0% (95% CI, 42.5-82.0%). The median PFS was 2.8 months (95% CI, 2.1-3.5), and the median OS was 12.6 months (95% CI, 5.1-20.1). All patients with recurrence confined to a previously irradiated field achieved disease control. No treatment-related deaths occurred. CONCLUSIONS:Cemiplimab demonstrated manageable toxicity and clinically meaningful disease control in routine practice, including patients with biologically aggressive tumors or recurrences in previously irradiated fields.
Aim Sentinel lymph node (SLN) mapping has become the standard approach for lymph node (LN) assessment in patients with low-risk endometrial cancer (EC). However, until its coverage by the Japanese national health insurance system in 2025, pelvic lymphadenectomy (PLA) had been routinely performed for nodal assessment in Japan. The resection of circumflex iliac nodes distal to the external iliac nodes (CINDEIN) in PLA is associated with an increased risk of lymphedema. CINDEIN preservation in EC patients reduces the risk of lymphedema; however, the impact of CINDEIN preservation on recurrence patterns and prognosis is unclear. Therefore, we herein examined the effects of CINDEIN preservation on recurrence patterns, survival outcomes, and lymphedema in patients with low-risk EC. Methods We retrospectively analyzed 65 patients with preoperatively diagnosed low-risk EC who underwent PLA as their initial treatment between January 2016 and December 2024. Patients were divided into two groups according to whether CINDEIN was resected or preserved, and treatment effects and prognosis were evaluated.Results: Lymphedema was noted in 1 case in the CINDEIN-preserved group (2.7%) and in 7 in the CINDEIN-resected group (25%), demonstrating a significant difference (P = 0.017). Recurrence was noted in 4 cases in the CINDEIN-preserved group and in 2 in the CINDEIN-resected group (P > 0.05). There were no significant differences in PFS or OS between the two groups. Conclusions CINDEIN preservation may be performed on patients with low-risk EC without worsening their prognosis and correlated with a reduced risk of lymphedema.
Background:Folate receptor alpha (FRα) is frequently expressed in ovarian high-grade serous carcinomas and is a clinically actionable biomarker targeted by FDA-approved mirvetuximab soravtansine (MIRV) for platinum-resistant disease with high expression (≥75% of tumor cells with ≥2+ staining). However, longitudinal variability in FRα expression remains poorly understood. We evaluated temporal FRα expression changes in paired ovarian cancer specimens. Methods:We performed a retrospective study of epithelial ovarian malignancies at Mayo Clinic Florida (2013-2025) in patients with ≥2 tumor specimens available. Tumors were classified as FRα-positive when ≥75% of viable tumor cells showed moderate-to-strong (2+ and/or 3+) staining and categorized as concordant or discordant based on changes in FRα status. Associations between clinicopathologic variables and FRα variability were evaluated using Fisher exact and Kruskal-Wallis tests. Results:Sixty-six patients (median age 66 years), most with advanced-stage high-grade serous carcinoma (65/66), had paired tumor specimens. FRα expression was concordant in 77.3% of cases and discordant in 22.7%. Negative-to-positive conversion occurred more frequently than positive-to-negative conversion (16.7% vs 6.1%). No significant associations were identified between FRα variability and clinicopathologic factors, including age, grade, stage, treatment setting, prior chemotherapy exposure, MIRV use, specimen type, sampling site, baseline FRα expression, or timing intervals. In patients treated with neoadjuvant chemotherapy, negative-to-positive conversion was numerically more frequent, although not statistically significant (25% vs 9%; p = 0.479). Conclusions:FRα expression in ovarian carcinomas is generally stable over time, with concordance observed in most paired specimens. However, discordance in approximately one-quarter of cases suggests spatial and/or temporal tumor heterogeneity.
Objectives:To evaluate temporal trends in estrogen replacement therapy (ERT) utilization among younger gynecologic cancer survivors. Methods:We conducted a cross-sectional study using the Merative MarketScan Research Database from January 1, 2013, through December 31, 2021. We included female patients aged 18-51 years with a diagnosis or history of gynecologic cancer. Annual prevalence of ERT use was calculated, and trends over time were assessed using annual percent change (APC) and 95% confidence intervals (CIs). Results were assessed across cancer types and age groups. Results:ERT utilization increased from 10.9% in 2013 to 14.1% in 2021 among all gynecologic cancer survivors (APC 3.41%, 95% CI 2.13-4.71%). Increasing ERT use was observed across all gynecologic cancer subgroups and age categories during the study period. Ovarian cancer survivors consistently had the greatest prevalence of ERT use, whereas uterine cancer survivors had the lowest prevalence across the study period. Among the age sub-groups, the 18-34 years old age group had the largest increase in ERT utilization, from 6.8% to 10.5% (APC 5.68%, 95% CI 3.1-8.33) over the study period. Conclusions:ERT utilization among younger gynecologic cancer survivors increased between 2013 and 2021. As ERT use continues to rise in this population, further research is needed to identify patient-, provider-, and system-level factors associated with prescribing and uptake and to evaluate gaps in menopausal survivorship care.
Background:Adult cervical embryonal rhabdomyosarcoma (ERMS) is an exceptionally rare malignant mesenchymal tumor, and evidence regarding its clinicopathologic characteristics, optimal management, and prognostic factors remains limited. We report an aggressive case of adult cervical ERMS and provide a contemporary review of the literature. Case presentation:A 50-year-old woman presented with abnormal vaginal bleeding and was diagnosed with cervical ERMS following histopathologic and immunohistochemical evaluation. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by adjuvant vincristine, actinomycin D, and cyclophosphamide (VAC) chemotherapy. Despite multimodal treatment, she developed rapid pelvic recurrence, progressive disease, and recurrent vaginal bleeding requiring palliative radiotherapy and died 13 months after diagnosis. To better characterize adult cervical ERMS, we reviewed English-language reports published between 2015 and 2026. Forty-one previously reported adult cases with sufficient clinical information were identified. The median age at diagnosis was 38 years, and the median tumor size was 5 cm. Most patients presented with stage I disease and were treated with surgery combined with chemotherapy, most commonly VAC-based regimens. Overall outcomes were generally favorable. Uncommon clinical presentations and associated conditions included uterine inversion, pregnancy-associated disease, cerebral venous sinus thrombosis, melanoma, and DICER1-associated alterations. Conclusion:Adult cervical ERMS demonstrates substantial clinical heterogeneity. Although most reported patients achieve favorable outcomes with multimodal treatment, a subset may experience aggressive disease characterized by rapid recurrence and poor prognosis. Greater molecular characterization, particularly regarding DICER1-associated alterations, may improve risk stratification and support more individualized treatment strategies.
Background:Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery has demonstrated survival benefits in advanced ovarian cancer. However, the safety of HIPEC administration in patients with indwelling ventriculoperitoneal (VP) shunts remains unknown, as no prior cases have been reported. Theoretical risks include shunt infection, chemical ventriculitis, and potential central nervous system (CNS) metastasis via retrograde flow through the shunt catheter. The absence of established management guidelines poses a significant challenge for clinicians treating ovarian cancer patients with concurrent VP shunts. Case Presentation:A 60-year-old G1P1 with a 6-year history of a programmable VP shunt for hydrocephalus secondary to cerebellar hemangioblastoma presented with high-grade serous ovarian carcinoma, FIGO stage IIIA2. Following neoadjuvant chemotherapy, she underwent interval debulking surgery with cisplatin-based HIPEC. A multidisciplinary approach was employed: neurosurgery externalized the VP shunt catheter from the peritoneal cavity and wrapped it in metronidazole-soaked gauze during HIPEC administration and the shunt was replaced at case completion. Postoperative vancomycin, cefepime, and metronidazole were provided for five days for meningitis prophylaxis. The patient experienced no shunt-related complications and was discharged on postoperative day 4. At 10-month follow-up, she demonstrated excellent oncologic response with CA-125 normalization and no evidence of shunt malfunction or CNS involvement. Conclusion:This case demonstrates that HIPEC can be safely performed in patients with indwelling VP shunts when a multidisciplinary strategy incorporating intraoperative shunt externalization and antimicrobial prophylaxis is utilized. This approach expands treatment options for ovarian cancer patients with VP shunts who may otherwise be excluded from potentially beneficial HIPEC therapy.
Objectives Brain metastases (BM) from gynecologic malignancies are rare and associated with poor prognosis. Antibody–drug conjugates (ADCs) have demonstrated systemic benefit, however their intracranial activity and toxicity remain poorly characterized because most clinical trials exclude central nervous system (CNS) disease. We describe a case series of patients with gynecologic cancers and BM treated with ADCs. Methods Patients with gynecologic malignancies received ≥1 ADC cycle after a diagnosis of BM between January 2022 and December 2025 were identified through the electronic medical record. Clinical characteristics, ADC type and timing relative to BM diagnosis, CNS-directed therapy, intracranial response, radiation necrosis (RN), and patient-level outcomes were summarized. CNS-progression-free survival, extracranial- progression-free survival, and overall survival were described. Results Eight patients received ADC therapy after BM diagnosis: 6 ovarian/fallopian tube cancers, 1 endometrial and 1 cervical cancer. At BM presentation, all underwent local intervention; 7 patients received radiotherapy and 2 underwent craniotomy. At subsequent CNS progression, 2 patients received ADC therapy with deferred radiation. Across 12 ADC regimens, best intracranial response was partial response in 3 (25.0%), stable disease in 7 (58.3%), progressive disease in 1 (8.3%), and not evaluable in 1 (8.3%). RN occurred in 2 of 7 irradiated patients. Conclusions This case series highlights the feasibility and activity of ADC therapy in patients with gynecologic cancers and BM, while underscoring important toxicity considerations. The observed intracranial responses and cases of RN support prospective, multi-institutional evaluation of ADC activity and ADC–radiotherapy sequencing in future clinical trials.
Background:Uterine leiomyosarcoma (uLMS) is an aggressive malignancy with limited advanced-stage treatments. Actionable molecular alterations like ALK fusions are extremely rare but present critical opportunities for targeted therapy. Case Presentation:A 59-year-old woman with stage IV uLMS, initially misdiagnosed as uterine fibroids, underwent a hysterectomy in 2008. Recurrence was confirmed in 2011. Over the following decade, she developed progressive pelvic disease requiring multiple debulking surgeries, arterial embolizations, and pembrolizumab, which was stopped due to progression and adrenal insufficiency. Her course was complicated by obstructive uropathy and bowel perforation. Next-generation sequencing identified an ALK-DCTN1 fusion. She was commenced on the ALK inhibitor ceritinib at 450 mg daily, later reduced to 300 mg due to transaminitis. Treatment yielded significant tumour regression and durable partial remission. A May 2025 PET-CT showed no FDG-avid disease and no evidence of new local recurrence or distant metastasis, consistent with a metabolic complete response, although stable residual pelvic lesions persisted. Conclusion:This case underscores the importance of comprehensive molecular profiling in advanced uLMS. It demonstrates that targeting rare ALK rearrangements with ceritinib can achieve sustained disease control after conventional therapies have failed or were poorly tolerated.
Background:Malignant transformation of ovarian mature cystic teratomas (MCTs) occurs in 0.17-2% of cases, with squamous cell carcinoma comprising over 80%. Transformation to goblet cell adenocarcinoma is exceedingly rare, and optimal management remains undefined. Case:A 39-year-old woman with a history of prior ovarian cystectomy for MCT presented with severe abdominal pain and bilateral adnexal masses. Tumor markers were elevated (CA-125 76 U/mL, CEA 175 ng/mL, CA 19-9139 U/mL). She underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and surgical staging. Intraoperative findings included a 21 cm right and 15 cm left ovarian mass with hemoperitoneum. Final pathology demonstrated goblet cell adenocarcinoma arising from MCT with contralateral ovarian involvement. No tumor was identified in the appendix. Immunohistochemistry was positive for SATB2, CK20, and CDX2, and negative for CK7 and PAX8, consistent with intestinal-type differentiation, with focal synaptophysin positivity indicating neuroendocrine features. Postoperative imaging revealed suspicious retroperitoneal lymphadenopathy. Given that standard germ cell regimens target totipotent biology and platinum-taxane regimens address Mullerian-derived epithelial ovarian carcinoma - neither of which reflects the histology seen - a histology-directed approach favoring GI-based chemotherapy was adopted, treating by cell type rather than site of origin. She is currently on third line treatment given disease progression. Conclusion:Goblet cell adenocarcinoma arising in ovarian MCT is a rare entity without standardized treatment guidelines. The intestinal-type immunophenotype supports extrapolation from appendiceal goblet cell adenocarcinoma treatment paradigms, favoring gastrointestinal over traditional gynecologic chemotherapy regimens. Further collaborative reporting is needed to define optimal management for this rare tumor.
Objectives:Timely recognition of pre-diagnosis symptoms plays a key role in early diagnosis of endometrial cancer (EC). Symptom profiles may vary by conditions such as fibroids or obesity which are differentially distributed by race. We describe pre-diagnosis symptom reporting among EC survivors by race, fibroids history, and body mass index (BMI). Methods:We calculated prevalence ratios (PR) and 95% confidence intervals (CI) for 6 menstrual and 7 non-menstrual self-reported, pre-diagnosis symptoms using Poisson regression. We assessed participants' pre-diagnosis knowledge about postmenopausal bleeding and reporting of symptoms to healthcare providers. Results:Among 638 Carolina Endometrial Cancer Study participants, 36% self-identified as Black or African American and 64% as White. Women with fibroids (versus without) were more likely to report heavy periods (PR = 1.23, 95% CI 1.09-1.40), periods of >7 days (PR = 1.37, 95% CI 1.09-1.71), and non-menstrual symptoms (PR = 1.15, 95% CI 1.05-1.25). Women with a BMI >30 kg/m2 (versus ≤30) were more likely to report both menstrual (PR = 1.07, 95% CI 1.01-1.14) and non-menstrual (PR = 1.12, 95% CI 1.01-1.24) symptoms, particularly fatigue (PR = 1.40, 95% CI 1.12-1.74). After adjustment for age, fibroids history, and BMI, reported symptom experience profiles did not vary by race. Most (90%) women who reported postmenopausal bleeding discussed their symptoms with a provider; relatively few (23%) were aware of bleeding as a potential symptom of endometrial cancer. Conclusions:Pre-diagnosis symptom profiles varied by fibroids and obesity among endometrial cancer survivors. Low knowledge pertaining to postmenopausal bleeding as a potential symptom for endometrial cancer suggests opportunity for improved patient education.
