Cokan A, Angeles MA, El Hajj H
… +29 more, Pervan M, Mateo-Kubach P, Viveros-Carreño D, Hablase R, Adán AC, Bilir E, Kahramanoglu I, Fumagalli D, Bizzarri N, Liehn L, Seminario N, Shushkevich A, David KL, Strojna A, Braun C, Kacperczyk-Bartnik J, Mahner S, Fotopoulou C, Heinzelmann-Schwarz V, Bosse T, Concin N, Ledermann J, Falconer H, Bhatt A, Abu-Rustum N, Eriksson AG, Fagotti A, Leary A, Ramirez PT
Int J Gynecol Cancer
· 2026 Apr · PMID 42184646
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Ferla S, Raimondo D, Virgilio A
… +2 more, Seracchioli R, Lemos N
Int J Gynecol Cancer
· 2026 May · PMID 42173755
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Deep infiltrating endometriosis and oncologic radical pelvic surgeries pose a significant risk of nerve damage. A thorough understanding of pelvic anatomy is essential for surgical precision and to avoid neurological com...Deep infiltrating endometriosis and oncologic radical pelvic surgeries pose a significant risk of nerve damage. A thorough understanding of pelvic anatomy is essential for surgical precision and to avoid neurological complications or dysfunctions. Laparoscopic cadaveric dissections, with their magnification and bloodless dissection advantages, provide a safe and effective training method for mastering pelvic neuroanatomy and refining surgical skills.
Flint ML, Shvygin A, Johannet P
… +7 more, Cohen S, Konner J, Tew WP, Grisham RN, Francis JH, Canestraro J, O'Cearbhaill RE
Int J Gynecol Cancer
· 2026 Apr · PMID 42172956
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OBJECTIVE: To characterize the incidence and clinical features of cataracts in patients with folate receptor α-positive recurrent high-grade serous ovarian cancer treated with mirvetuximab soravtansine-gynx, an antibody-...OBJECTIVE: To characterize the incidence and clinical features of cataracts in patients with folate receptor α-positive recurrent high-grade serous ovarian cancer treated with mirvetuximab soravtansine-gynx, an antibody-drug conjugate targeting folate receptor 1. METHODS: We conducted a single-center retrospective cohort study in patients treated with mirvetuximab soravtansine-gynx between February 2023 and January 2025. All patients underwent baseline and serial ophthalmologic assessments, and received prophylactic ophthalmic corticosteroids as required by mirvetuximab soravtansine-gynx US Prescribing Information. Cataracts were graded according to the Lens Opacities Classification System III. RESULTS: A total of 108 patients were identified. Median age at mirvetuximab soravtansine-gynx initiation was 65 years (range; 37-84). Of 108 patients, 73 (67.6%) had cataracts at baseline and/or during follow-up. Among 49 patients without baseline cataracts, new cataracts developed in 14 (28.6%). Among 40 patients (excluding an additional 18 with bilateral pseudophakia and 1 with bilateral aphakia) with baseline cataracts, 9 (22.5%) indicated cataract progression. Nuclear sclerosis was the predominate cataract sub-type (20/23). Patients with new/progressive cataracts received more mirvetuximab soravtansine-gynx cycles (median, 8 vs 5) than those who did not. Non-cataract ocular toxicity rates were similar across groups. CONCLUSIONS: Cataracts represent an under-recognized ocular adverse event associated with mirvetuximab soravtansine-gynx treatment. Although the etiology remains unclear, potentially related to mirvetuximab soravtansine-gynx exposure, ocular corticosteroids, or both, the frequency and tempo observed in this cohort underscore the need for close ophthalmologic monitoring. However, it is reassuring that cataracts can be treated with a minimally invasive procedure with generally excellent outcomes. Further research is warranted to elucidate underlying mechanisms and optimize supportive eye care strategies.
Sia TY, Zhou Q, Devlin S
… +14 more, Iasonos A, Hatoum S, Haney K, Kraiem S, Dagher C, Alwaqfi R, Doria ER, Weigelt B, Ellenson LH, Aghajanian C, Liu YL, Leitao MM, Abu-Rustum NR, Mueller JJ
Int J Gynecol Cancer
· 2026 Apr · PMID 42172955
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OBJECTIVE: The International Federation of Gynecology and Obstetrics 2023 endometrial cancer staging system includes 21 sub-stages and proposes a shift from pure anatomical staging to an approach incorporating histology,...OBJECTIVE: The International Federation of Gynecology and Obstetrics 2023 endometrial cancer staging system includes 21 sub-stages and proposes a shift from pure anatomical staging to an approach incorporating histology, grade, lymphovascular invasion, and molecular classification. We sought to evaluate the overall survival prognostic ability of the International Federation of Gynecology and Obstetrics 2023 endometrial cancer staging system compared with the International Federation of Gynecology and Obstetrics 2009 system. METHODS: We collected clinicopathologic characteristics, molecular profiling results, and survival outcomes for all patients with a new diagnosis of endometrial cancer treated at our institution between 2016 and 2020. All cases underwent pathology review by a gynecologic pathologist at our institution. An International Federation of Gynecology and Obstetrics 2009 and 2023 stage was assigned. We applied Rϵ statistics based on an isotonic proportional hazards model to compare prognostic ability between the 2 staging systems. RESULTS: Of 2067 patients with endometrial cancer, 952 (46%) underwent tumor molecular profiling. When comparing International Federation of Gynecology and Obstetrics 2009 and 2023 staging, 538 (26.0%) patients were upstaged and 100 (4.8%) were downstaged in the 2023 system. Five-year overall survival estimates were similar across most stages between the 2 staging systems, with some exceptions: the International Federation of Gynecology and Obstetrics 2023 IA3 sub-stage demonstrated improved outcomes (100% vs 70.3% for International Federation of Gynecology and Obstetrics 2009 IIIA) and the IICm group had poorer prognosis (73% vs 86.8% for International Federation of Gynecology and Obstetrics 2009 II). Using isotonic proportional hazards regression models, the 2023 model slightly numerically outperformed the 2009 model for overall survival (Rϵ 0.546 vs 0.415); however, adjusted 95% confidence intervals were under-developed. CONCLUSIONS: Using a real-world, large, well-annotated cohort of patients with endometrial cancer with expert pathology review, we were able to calculate 5-year progression-free and overall survival rates for each sub-stage. The International Federation of Gynecology and Obstetrics 2023 model demonstrated slightly improved prognostic discrimination compared with the International Federation of Gynecology and Obstetrics 2009 model; however, small patient numbers in each sub-stage and concerns regarding over-fitting limit this analysis.
Moro F, Barreca A, Ciancia M
… +9 more, Chiappa V, Carazita V, Pedrini V, Giannarelli D, Mascilini F, Zannoni GF, Fanfani F, Fagotti A, Testa AC
Int J Gynecol Cancer
· 2026 Apr · PMID 42172954
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OBJECTIVE: To assess the diagnostic performance of ultrasound-guided biopsy, in addition to feasibility and major complication rates, in discriminating between leiomyomas and sarcomas in patients with suspicious myometri...OBJECTIVE: To assess the diagnostic performance of ultrasound-guided biopsy, in addition to feasibility and major complication rates, in discriminating between leiomyomas and sarcomas in patients with suspicious myometrial lesions. METHODS: PubMed, Scopus, and Web of Science were searched from inception to January 28, 2026. Retrieved studies were imported into Rayyan software for screening. The study protocol was registered in the International Prospective Register of Systematic Reviews database (registration number CRD420261295521). We included studies enrolling patients with myometrial lesions suspected of malignancy who underwent ultrasound-guided biopsy and reported diagnostic accuracy, feasibility, and/or major complications. Prospective and retrospective cohort studies, cross-sectional studies, randomized controlled trials, and case series were eligible. Reviews without original data, conference abstracts, and studies with very small sample sizes were excluded. Study selection and data extraction were performed independently by 2 reviewers, with discrepancies resolved by a senior reviewer. Methodologic quality of studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. Summary sensitivity and specificity were calculated and reported with 95% confidence intervals. RESULTS: A total of 1607 articles were screened, and 5 studies were included in the analysis. The included studies (2002-2026) involved 8 to 453 participants. The most used approach was trans-cervical biopsy guided by trans-abdominal or trans-rectal ultrasound followed by trans-vaginal approach. Feasibility was high (95.9% adequate samples), and major complications were rare (0.2%). Pooled sensitivity and specificity were calculated from 3 studies and were both 1.00 with 95% confidence interval 0.86 to 1.00 and 0.98 to 1.00, respectively. Risk of bias was primarily related to flow and timing whereas the index test showed low risk. CONCLUSION: Ultrasound-guided biopsy appears to be an accurate and safe method for diagnosing suspicious myometrial lesions. These conclusions are based on a limited number of studies with small cohorts. Larger prospective investigations are needed to confirm these findings and to determine whether small histologic samples adequately reflect heterogeneity of myometrial tumors.
Int J Gynecol Cancer
· 2026 May · PMID 42172953
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OBJECTIVE: Impact factor bias, in which positive results are preferentially published in higher-impact journals, may influence evidence visibility and interpretation. Whether such an impact factor bias exists in gynecolo...OBJECTIVE: Impact factor bias, in which positive results are preferentially published in higher-impact journals, may influence evidence visibility and interpretation. Whether such an impact factor bias exists in gynecologic oncology trials remains unclear. We evaluated the association between study outcome and journal impact factor in phase III gynecologic oncology randomized controlled trials. METHODS: A meta-epidemiologic analysis was conducted of phase III gynecologic oncology randomized controlled trials identified through ClinicalTrials.gov up to May 2024. Only completed, two-arm, superiority-design trials (as this allows for a clear and unambiguous interpretation of trial results) with published primary endpoint data were included. Data extracted for each publication included impact factor at the year of publication, number of enrolled patients, duration of follow-up, disease site, number of authors, country of first and senior author based on primary institutional affiliation, and primary outcome (classified as positive if the intervention arm demonstrated statistically significant superiority over the control arm). The primary outcome was the journal impact factor stratified by study results. Univariate and exploratory multivariable analyses were performed to identify factors associated with higher journal impact factors. RESULTS: A total of 36 eligible trials were identified, published between 2009 and 2024; 47.2% reported positive primary outcomes. The median journal impact factor across all studies was 35.1 (interquartile range; 18.3-51.6) (range; 3.7-158.5). Trials with positive outcomes were published in journals with significantly higher impact factors than those with negative outcomes (44.5 [interquartile range; 18.7-71.5] vs 24.0 [interquartile range; 5.3-44.5], p =.034). The number of authors was also greater in positive studies (median 21 vs 16, p =.032). In multivariable linear regression, a positive primary outcome was the only independently associated factor with a higher journal impact factor. Positive outcomes were published in journals with, on average, 32.6 (95% confidence interval 6.4-58.8) point higher impact factors, respectively. Follow-up duration and sample size were not significant predictors. CONCLUSIONS: Positive phase III gynecologic oncology trials were published in higher-impact journals, with outcome positivity independently associated with impact factor. This pattern may affect evidence visibility and highlights the need to support dissemination of high-quality negative studies.
Ribero L, Fumagalli D, De Vitis LA
… +7 more, Caruso G, Schivardi G, Aletti G, Colombo N, Kumar A, Ramirez PT, Multinu F
Int J Gynecol Cancer
· 2026 Apr · PMID 42167107
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In advanced ovarian cancer, complete cytoreductive surgery is a cornerstone of treatment, yet defining which patients are "fit for surgery" remains challenging. Although guidelines emphasize comprehensive pre-operative e...In advanced ovarian cancer, complete cytoreductive surgery is a cornerstone of treatment, yet defining which patients are "fit for surgery" remains challenging. Although guidelines emphasize comprehensive pre-operative evaluation, standardized assessment tools are lacking, and clinical practices vary widely across institutions. This narrative review synthesizes current evidence on individual patient-related factors that influence surgical fitness, reviews risk-assessment algorithms designed to guide patient selection, and examines the emerging role of pre-habilitation in optimizing perioperative outcomes. A structured literature search of MEDLINE, Embase, and Cochrane databases (January 2004-September 2024), supplemented by targeted PubMed searches (January 2005-April 2025), identified studies evaluating aging, comorbidity, frailty, nutrition, sarcopenia, and pre-habilitation in relation to surgical outcomes. Eligible studies included systematic reviews, randomized controlled trials, and prospective or retrospective cohorts of patients undergoing primary or interval cytoreduction. After application of the inclusion criteria, 33 studies encompassing 41,580 patients were included. The evidence consistently demonstrates that older age (particularly ≥80 years), frailty, comorbidity burden, and malnutrition are associated with increased post-operative complications and mortality following cytoreductive surgery. Several predictive models and nomograms integrating these factors have been developed to estimate perioperative risk, though most lack multi-center external validation. Implementation of an evidence-based triage algorithm that incorporates key patient characteristics and anticipated surgical complexity has been associated with meaningful reductions in post-operative mortality in institutional practice. Emerging data on multi-modal pre-habilitation suggest feasibility and potential benefits, including lower complication rates, shorter hospital stays, and earlier initiation of chemotherapy, though evidence remains preliminary. Current evidence on surgical fitness in ovarian cancer is limited by heterogeneous definitions, retrospective study designs, lack of prospective validation, and inconsistent reliance on clinical judgment alone. Standardized, externally validated tools, consensus-based thresholds for surgical candidacy, and results from ongoing randomized pre-habilitation trials are needed to guide clinical decision-making and improve patient outcomes.
Korgaonkar S, Prabhu VS, Parikh RC
… +5 more, Paranjpe R, Davis KL, Kruger S, Green AK, Makker V
Int J Gynecol Cancer
· 2026 Apr · PMID 42167106
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OBJECTIVE: The Study-309/KEYNOTE-775 trial demonstrated significantly improved outcomes with lenvatinib plus pembrolizumab (lenvatinib+pembrolizumab) versus chemotherapy. Lenvatinib+pembrolizumab is recommended in the Un...OBJECTIVE: The Study-309/KEYNOTE-775 trial demonstrated significantly improved outcomes with lenvatinib plus pembrolizumab (lenvatinib+pembrolizumab) versus chemotherapy. Lenvatinib+pembrolizumab is recommended in the United States for patients with non-microsatellite instability-high/mismatch repair proficient advanced or recurrent endometrial cancer who have progressed following prior systemic therapy. We evaluated the comparative effectiveness and clinical outcomes of lenvatinib+pembrolizumab versus single-agent chemotherapy as second-line or later treatment in this population. METHODS: This physician-led retrospective medical record review involved data extraction from records of eligible adult women in the United States with non-microsatellite instability-high/mismatch repair proficient advanced endometrial cancer who had progressed following previous systemic therapy and received lenvatinib+pembrolizumab or single-agent chemotherapy. Stabilized inverse probability of treatment-weighted analyses were used to compare real-world objective response rate, real-world progression-free survival, and overall survival. RESULTS: Data were extracted for 97 patients treated with lenvatinib+pembrolizumab and 107 treated with single-agent chemotherapy (median age: 57.7 and 57.1 years at treatment initiation, respectively). Most patients were White (61.9%; 60.7%), diagnosed at stage IV (56.7%; 58.0%), and had endometrioid histology (83.5%; 67.3%). Favorable stabilized inverse probability of treatment-weighted response profiles were observed for lenvatinib+pembrolizumab versus chemotherapy, including objective response rate (41.6% vs 28.2%), and median times (95% confidence interval) for progression-free survival (13.1 [9.0 to 15.4] vs 8.4 [5.8 to 11.1] months) and overall survival (19.6 [16.9 to 26.3] vs 13.5 [11.9 to 17.6] months). Odds ratios/hazard ratios (95% confidence interval) for objective response rate (odds ratio 2.4 [1.3 to 4.4], p =.005) and progression-free survival (hazard ratio 0.6 [0.4 to 0.9], p <.001) were statistically significant, but not for overall survival (hazard ratio 0.7 [0.4 to 1.0], p =.083). Multi-variable Cox regression findings were consistent with the stabilized inverse probability of treatment weighting analysis. CONCLUSIONS: Significant clinical benefit of lenvatinib+pembrolizumab in the second-line or later vs single-agent chemotherapy was observed, confirming the Study-309/KEYNOTE-775 findings for use as later-line standard of care in patients with non-microsatellite instability-high/mismatch repair proficient advanced endometrial cancer.
Marth C, Lorusso D, Bidziński M
… +27 more, Scollo P, Vardar MA, Oaknin A, Kaen DL, Nogueira-Rodrigues A, Miller DS, Hasegawa K, MacKay H, Moore RG, Santin AD, Yunokawa M, Romero I, Pignata S, Baron-Hay S, Kim YM, Amit A, Ghamande S, Danska-Bidzinska A, Tarnawski R, Wang PH, Yu Z, Slomovitz BM, Okpara CE, McKenzie J, Meng R, Orlowski R, Makker V
Int J Gynecol Cancer
· 2026 Apr · PMID 42167105
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OBJECTIVE: We report outcomes for the sub-group of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment in the phase 3 Study 309/KEYNOTE-775 (NCT0351...OBJECTIVE: We report outcomes for the sub-group of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment in the phase 3 Study 309/KEYNOTE-775 (NCT03517449) and ENGOT-en9/LEAP-001 (NCT03884101). METHODS: Study 309/KEYNOTE-775 enrolled participants with advanced/recurrent/metastatic endometrial cancer with disease progression after 1 previous line of platinum-based chemotherapy (2 allowed if initially given as [neo]adjuvant therapy). ENGOT-en9/LEAP-001 enrolled participants with stage III-IV or recurrent, radiographically apparent endometrial cancer and no previous chemotherapy or disease progression ≥6 months after (neo)adjuvant platinum-based chemotherapy. In both trials, participants were randomized 1:1 to lenvatinib 20 mg once daily+pembrolizumab 200 mg every 3 weeks or chemotherapy (doxorubicin or paclitaxel in Study 309/KEYNOTE-775, carboplatin+paclitaxel in ENGOT-en9/LEAP-001). Overall survival and progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review) were primary endpoints. RESULTS: In Study 309/KEYNOTE-775 (n = 300), median (95% confidence interval) overall survival was 17.4 (14.0 to 22.8) months with lenvatinib+pembrolizumab and 13.3 (10.9 to 15.5) months with chemotherapy (hazard ratio [95% confidence interval], 0.67 [0.52 to 0.87]). Median (95% confidence interval) progression-free survival was 7.2 (5.6 to 8.0) and 3.9 (3.6 to 5.4) months (hazard ratio [95% confidence interval], 0.52 [0.40 to 0.68]). Objective response rates were 34.3% versus 16.6%. In ENGOT-en9/LEAP-001 (n = 121), median (95% confidence interval) overall survival was 35.4 (26.6 to not reached) months with lenvatinib+pembrolizumab and 22.1 (16.4 to 34.8) months with chemotherapy (hazard ratio [95% confidence interval], 0.66 [0.42 to 1.03]). Median (95% confidence interval) progression-free survival was 15.0 (8.3 to 21.0) and 8.3 (6.2 to 10.2) months (hazard ratio [95% confidence interval], 0.52 [0.33 to 0.81]). Objective response rates were 63.5% versus 43.1%. In both trials, the most common treatment-related adverse events with lenvatinib+pembrolizumab were hypertension (62.4%/60.3%) and hypothyroidism (58.2%/60.3%). CONCLUSIONS: In this sub-group analysis of participants who only received neoadjuvant, adjuvant, or neoadjuvant+adjuvant platinum-based chemotherapy before enrollment, lenvatinib+pembrolizumab demonstrated better anti-tumor activity and favorable outcomes versus chemotherapy with manageable safety. Lenvatinib+pembrolizumab is approved for patients with advanced endometrial cancer and could be considered an effective treatment option in this sub-group.
Baxter E, Robledo KP, Janda M
… +1 more, Obermair A
Int J Gynecol Cancer
· 2026 Apr · PMID 42167104
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OBJECTIVE: The feMMe phase 2 randomized trial demonstrated that approximately 60% of participants with endometrial hyperplasia with atypia or clinical stage 1, International Federation of Gynecology and Obstetrics grade...OBJECTIVE: The feMMe phase 2 randomized trial demonstrated that approximately 60% of participants with endometrial hyperplasia with atypia or clinical stage 1, International Federation of Gynecology and Obstetrics grade 1 endometrioid adenocarcinoma had a pathological complete response after 6 months of treatment with the levonorgestrel intra-uterine device (NCT01686126). The objective of this study was to determine the long-term oncological and reproductive outcomes of a sub-group of feMMe trial participants in Queensland. METHODS: A total of 96 feMMe trial participants from 6 sites in Queensland were contacted to participate in this study, and 52 (54%) consented. Medical records were retrieved for 51 participants, and 44 participants completed questionnaires. RESULTS: Median follow-up time after trial completion was 18.9 months (range; 0.2-45.1). Of the 33 participants who had a pathological complete response at trial completion, 21 of 33 (64%) had a sustained complete response throughout follow-up (range; 6.7-43.5). Recurrence developed in 8 of 33 participants (24%). The probability of recurrence-free survival was 93% (95% confidence interval 84% to 100%) at 12 months and 74% (95% confidence interval 59% to 93%) at 24 months. Four of 33 participants (12%) did not have endometrial sampling beyond trial completion. Of the 19 participants who did not have a pathological complete response at trial completion, 4 of 19 (21%) went on to achieve a complete response. Persistent disease occurred in 5 of 19 participants (26%), and 10 of 19 participants (53%) did not have endometrial sampling beyond trial completion. Overall, 21 of 52 participants (40%) had a hysterectomy. Diagnostic concordance between the latest biopsy and the hysterectomy specimen was 62% (13 of 21; κ = 0.44). Four participants attempted to conceive, and the live birth rate was 50%. CONCLUSIONS: Long-term follow-up of feMMe trial participants demonstrated that most participants who developed a pathological complete response at trial completion were likely to sustain this response, while those who did not respond at trial completion were likely to require a hysterectomy for disease control.
Watson GA, Murtas F, Chawla T
… +9 more, Zhang L, Rouzbahman M, Pulenzas N, Toor H, Donnelly C, Han K, Croke J, Mackay H, Kim SR
Int J Gynecol Cancer
· 2026 Apr · PMID 42143439
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Uterine sarcomas are rare heterogeneous neoplasms, comprising only a small percentage of uterine malignancies. There is a diverse array of uterine sarcoma sub-types, each with distinct molecular, clinical, and behavioral...Uterine sarcomas are rare heterogeneous neoplasms, comprising only a small percentage of uterine malignancies. There is a diverse array of uterine sarcoma sub-types, each with distinct molecular, clinical, and behavioral features. In recent years, there has been significant advancement in all facets of the multi-disciplinary management of uterine sarcomas. Despite this, several challenges regarding optimization of treatment remain. While early-stage uterine sarcomas are potentially curable with surgery, there remains a high risk of recurrence, with the lungs and liver being common sites for distant spread. In the case of oligometastatic disease, local treatment may be offered in select patients and may improve survival. In the metastatic setting, advances in our histopathologic understanding of these rare cancers have allowed for the development and utilization of more targeted treatments; however, it is evident that there is a need for more efficacious and clinically meaningful therapeutic options. These patients often experience significant morbidity as a consequence of their disease and/or treatment, and palliative care support early in the disease course may improve quality of life and goal-concordant care. Additional large-scale, international multi-center collaboration is needed to further optimize multi-disciplinary management for these patients. In this review, we provide a comprehensive update on the management of advanced uterine sarcomas, and discuss novel therapeutic and supportive strategies in the multi-disciplinary management of these rare malignancies.