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Background: Hemoglobin (Hb), white blood cell (WBC), and polymorphonuclear neutrophil (PMN) blood counts may be correlated with outcomes in patients with locally advanced cervical cancer. Methods: Hb, WBC, and PMN counts were measured at diagnosis and during concomitant cisplatin‐based chemoradiotherapy (CCRT) in a retrospective sample of 103 patients between 2010 and 2017. Red blood cell (RBC) transfusions were also recorded. The associations between hematological variables and patient overall survival (OS) and recurrence‐free survival (RFS) were assessed by Cox regression models. Results: The 3‐year OS and RFS rates were 81.4% and 76.8%, respectively. In addition to tumor size and smoking, OS and RFS were found to be significantly associated with changes in WBC and PMN counts from the first to the last cisplatin cycle. Hb count throughout the treatment and RBC transfusions were not predictive of outcome. Conclusions: This study found no association between Hb count or RBC transfusions and outcome. The daily practice of maintaining the Hb count above 12 g/dL during CCRT should be weighed against the potential risks of transfusions. Drops in WBC and PMN counts during treatment positively impacted OS and RFS and could, therefore, serve as biomarkers during CCRT to adapt the follow‐up and consider the need for adjuvant systemic treatments. [ABSTRACT FROM AUTHOR]

Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 being investigated in several solid tumor types. We report final results from patients with recurrent microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) endometrial cancer treated with retifanlimab in a POD1UM-101 expansion cohort. Eligible patients (≥18 years; histologically proven/unresectable/recurrent, MSI-H/dMMR endometrial cancer; checkpoint inhibitor naive) received retifanlimab 500 mg intravenously every 4 weeks for ≤2 years. Primary endpoint was safety/tolerability. At data cutoff (May 17, 2023), 76 patients had received at least one retifanlimab dose. Median (range) age was 67 (49–88) years; 88.2% of patients had recurrent metastatic disease and 80.3% had visceral metastases. Seventy-five patients (98.7%) had received at least one prior systemic therapy. Median retifanlimab exposure was 10.0 (0.03–25.9) months; 23 patients completed treatment. 38 patients (50.0%) had grade ≥3 treatment-emergent adverse events (TEAEs), most commonly anemia (n = 10 [13.2%]). 63 patients (82.9%) had treatment-related AEs (TRAEs; grade ≥3, n = 14 [18.4%]); most common was fatigue (n = 14 [18.4%]). Two patients had TEAEs that led to death; no TRAEs were fatal. 39 patients had objective responses (51.3%; 95% CI, 39.6−63.0%); 19 patients (25.0%) had complete response and 20 (26.3%) had partial response. Median progression-free survival was 12.2 months; 30 patients (76.9%) had duration of response (DOR) ≥12 months. Median DOR was not reached after median follow-up time of 26.0 months. Retifanlimab was generally well tolerated and demonstrated encouraging anti-tumor activity in patients with pre-treated recurrent MSI-H/dMMR endometrial cancer. • We evaluated safety and anti-tumor activity of retifanlimab in patients with recurrent MSI-H/dMMR endometrial cancer. • Retifanlimab was generally well tolerated and demonstrated a safety profile typical of the PD-(L)1 inhibitor class. • Objective response rate of 51% (95% CI, 39.6–63.0%) was observed with retifanlimab; median DOR was not reached. • Retifanlimab represents a potential new treatment option for patients with recurrent MSI-H/dMMR endometrial cancer. [ABSTRACT FROM AUTHOR]

Background: Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody-drug conjugate, in this patient population.Methods: This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396.Findings: 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1-13·0). The confirmed objective response rate was 24% (95% CI 16-33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes.Interpretation: Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.Funding: Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups. [ABSTRACT FROM AUTHOR]

Purpose: To develop machine learning models to predict para-aortic lymph node (PALN) involvement in patients with locally advanced cervical cancer (LACC) before chemoradiotherapy (CRT) using 18F-FDG PET/CT and MRI radiomics combined with clinical parameters. Methods: We retrospectively collected 178 patients (60% for training and 40% for testing) in 2 centers and 61 patients corresponding to 2 further external testing cohorts with LACC between 2010 to 2022 and who had undergone pretreatment analog or digital 18F-FDG PET/CT, pelvic MRI and surgical PALN staging. Only primary tumor volumes were delineated. Radiomics features were extracted using the Radiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Different prediction models were trained using a neural network approach with either clinical, radiomics or combined models. They were then evaluated on the testing and external validation sets and compared. Results: In the training set (n = 102), the clinical model achieved a good prediction of the risk of PALN involvement with a C-statistic of 0.80 (95% CI 0.71, 0.87). However, it performed in the testing (n = 76) and external testing sets (n = 30 and n = 31) with C-statistics of only 0.57 to 0.67 (95% CI 0.36, 0.83). The ComBat-radiomic (GLDZM_HISDE_PET_FBN64 and Shape_maxDiameter2D3_PET_FBW0.25) and ComBat-combined (FIGO 2018 and same radiomics features) models achieved very high predictive ability in the training set and both models kept the same performance in the testing sets, with C-statistics from 0.88 to 0.96 (95% CI 0.76, 1.00) and 0.85 to 0.92 (95% CI 0.75, 0.99), respectively. Conclusions: Radiomic features extracted from pre-CRT analog and digital 18F-FDG PET/CT outperform clinical parameters in the decision to perform a para-aortic node staging or an extended field irradiation to PALN. Prospective validation of our models should now be carried out. [ABSTRACT FROM AUTHOR]

Molecular algorithms may estimate the risk of recurrence and death for patients with endometrial cancer (EC) and may impact treatment decisions. To detect microsatellite instabilities (MSI) and p53 mutations, immunohistochemistry (IHC) and molecular techniques are used. To select the most appropriate method, and to have an accurate interpretation of their results, knowledge of the performance characteristics of these respective methods is essential. The objective of this study was to assess the diagnostic performance of IHC versus molecular techniques (gold standard). One hundred and thirty-two unselected EC patients were enrolled in this study. Agreement between the two diagnostic methods was assessed using Cohen's kappa coefficient. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of the IHC were calculated. For MSI status, the sensitivity, specificity, PPV and NPV were 89.3%, 87.3%, 78.1% and 94.1%, respectively. Cohen's kappa coefficient was 0.74. For p53 status, the sensitivity, specificity, PPV, and NPV were 92.3%, 77.1%, 60.0% and 96.4%, respectively. Cohen's kappa coefficient was 0.59. For MSI status, IHC presented a substantial agreement with the polymerase chain reaction (PCR) approach. For the p53 status, the moderate agreement observed between IHC and next generation sequencing (NGS) methods implies that they cannot be used interchangeably. [ABSTRACT FROM AUTHOR]

Key Clinical Message We report a rare case of primary osteosarcoma of the breast in a patient who presented a calcified fibroadenoma one year before the appearance of the malignant lesion. We describe the follow-up of the patient and the discovery of a similar osteosarcoma in the other breast one year later. [ABSTRACT FROM AUTHOR]

Cardiac intimal sarcoma is extremely rare and aggressive primary malignant cardiac tumors. Here, we reported the case of a young man initially operated for a tumor of the left atrium, causing a dynamic obstruction of the mitral valve and (mis‐)diagnosed as a myxoma at the histopathological analysis. Patient presented a local recurrence at 3 months and was reoperated. Pathology revealed this time the presence of an intimal sarcoma. Patient received adjuvant chemotherapy. Despite a good local control, the 1‐year follow‐up positron emission tomography scan revealed the presence of a metastasis in the left adrenal gland that was surgically resected. This article aims to highlight the risk of misdiagnosis in case of cardiac tumors, the hypothetical concept of malignant transformation of a cardiac myxoma, the aggressive course of the extremely rare cardiac intimal sarcoma, and the therapeutic modalities available to treat this pathology. [ABSTRACT FROM AUTHOR]

Background.To evaluate efficacy and toxicity of radio-chemotherapy (RCT) and MR-guided pulsed-dose-rate (PDR) adaptive brachytherapy (IGABT) for locally advanced cervical cancer (LACC). Material and methods.Between 2007 and 2014 85 patients with FIGO stage 1B1 N+ or ≥ 1B2 cervical cancer were treated with RCT+ IGABT. The treatment consisted of a pelvic± paraaortic external beam radiotherapy (EBRT) (45–50.4 Gy ± 10 Gy boost to primary tumor and/or to pathologic lymph nodes) with concurrent cisplatin followed by 25–35 Gy of PDR IGABT in 30–50 pulses. The ratio of 3D-CFRT/IMRT was 61/24 patients. Dose-volume parameters of high-risk clinical target volume (HR-CTV), intermediate-risk clinical target volume (IR-CTV) and D2cm3organs at risk (OARs) were reported. Local control (LC), cancer-specific survival (CCS) and overall survival (OS) were analyzed actuarially and morbidity crude rates were scored using CTCAEv4.0. Results.Mean follow-up was 36 months (range 6–94). The mean D90 and D98 for HR-CTV was 84.4 ± 9 Gy and 77 ± 8.1 Gy, while for IR-CTV was 69.1 ± 4.3 Gy and 64.8 ± 4.3 Gy, respectively. The mean D2cm3for OARs was the following: bladder: 77.3 ± 10.5 Gy, rectum: 65 ± 6.8 Gy, sigmoid: 63 ± 7.9 Gy and intestine: 64.0 ± 9.1 Gy. Three year LC, CSS and OS were: 94%, 85% and 81%. The three-year regional- and distant control rates were 95% and 74%. Node negative patients had significantly higher three-year CSS (100 vs. 72%, p = 0.016) and OS (92 vs. 72%, p = 0.001) compared to node positive ones. Three-year actuarial late Grade ≥ 3 morbidity was the following: GI: 8%, GU: 5%, Vaginal: 8%. The frequency of Grade ≥ 3 hematological toxicities including anemia/leukopenia/neutropenia/thrombocytopenia were 8.6%/34.7%/24.3%/24.3%, respectively. Conclusion.This large mono-institutional experience builds up further evidences that IGABT in conjunction with RCT should be the standard of care for patients suffering LACC. [ABSTRACT FROM PUBLISHER]