Abstract Objective To investigate the impact of morcellation on survival outcomes of patients affected by undiagnosed uterine sarcoma. Methods This is a retrospective study performed in 8 referral ...centers of MITO group. Data of women undergoing morcellation for apparent benign uterine myomas who were ultimately diagnosed with stage I uterine sarcoma on final pathology were compared with data of women who did not undergo morcellation. Uterine sarcoma included: leiomyosarcomas (LMS), smooth muscle tumors of uncertain malignant potential (STUMP), low-grade endometrial stromal sarcomas (LG-ESS) and undifferentiated uterine sarcomas (UUS). Two-year survival outcomes were evaluated using Kaplan-Meir and Cox models. Results Overall 125 patients were identified: 31(24.8%), 21(16.8%) and 73(58.4%) patients had power morcellation during laparoscopy, non power morcellation during open surgery and non morcellation during open procedures, respectively. Considering patients affected by LMS, morcellation did not correlated with disease-free survival. However, patients undergoing either morcellation or power morcellation experienced a 3-fold increase risk of death in comparison to patients who had not morcellation (p = 0.02). A trend towards an increase of recurrence was observed for patients undergoing morcellation for STUMP (HR 7.7, p = 0.09); while no differences in survival outcomes were observed for patients with LG-ESS and UUS. Conclusions Our data suggest that morcellation increase the risk of death in patients affected by undiagnosed LMS. Further prospective studies are warranted in order to assess the risk to benefit ratio of power morcellator utilization in patients with apparent benign uterine myomas.
Vulvar dermatofibrosarcoma protuberans is an extremely rare disease. Its rarity can hamper the quality of treatment; deeper knowledge is necessary to plan appropriate management. The purpose of this ...review is to analyse the data reported in the literature to obtain evidence regarding appropriate disease management.
We made a systematic search of the literature, including the terms "dermatofibrosarcoma protuberans", "vulva", and "vulvar", alone or in combination. We selected articles published in English from two electronic databases, PubMed and MEDLINE, and we analysed their reference lists to include other potentially relevant studies.
We selected 39 articles, with a total of 68 cases reported; they were retrospective case reports and case series. Dermatofibrosarcoma protuberans of the vulva tends towards local recurrence; an early and timely pathological diagnosis, together with an appropriate surgical approach, are of utmost importance to ensure free margins and maximise the curative potential.
Even if this is an indolent disease and it generally shows a good prognosis, appropriate management may help in reducing the rate of local recurrences that may hamper patients' quality of life. Management by a multidisciplinary team is highly recommended.
To date, T cells redirected with CD19-specific chimeric antigen receptors (CAR) have gained impressive success in B-cell malignancies. However, treatment failures are common and the occurrence of ...severe toxicities, such as cytokine release syndrome (CRS), still limits the full exploitation of this approach. Therefore, the development of cell products with improved therapeutic indexes is highly demanded.
In this project, we investigated how CD4 and CD8 populations cooperate during CD19 CAR-T cell responses and what is their specific role in CRS development. To this aim, we took advantage of immunodeficient mice reconstituted with a human immune system (HuSGM3) and engrafted with the B-cell acute lymphoblastic leukemia cell line NALM-6, a model that allows to thoroughly study efficacy and toxicity profiles of CD19 CAR-T cell products.
CD4 CAR-T cells showed superior proliferation and activation potential, which translated into stronger stimulation of myeloid cells, the main triggers of adverse events. Accordingly, toxicity assessment in HuSGM3 mice identified CD4 CAR-T cells as key contributors to CRS development, revealing a safer profile when they harbor CARs embedded with 4-1BB, rather than CD28. By comparing differentially co-stimulated CD4:CD8 1:1 CAR-T cell formulations, we observed that CD4 cells shape the overall expansion kinetics of the infused product and are crucial for maintaining long-term responses. Interestingly, the combination of CD4.BBz with CD8.28z CAR-T cells resulted in the lowest toxicity, without impacting antitumor efficacy.
Taken together, these data point out that the rational design of improved adoptive T-cell therapies should consider the biological features of CD4 CAR-T cells, which emerged as crucial for maintaining long-term responses but also endowed by a higher toxic potential.
Assessment of HRD status is now essential for ovarian cancer patient management. A relevant percentage of high-grade serous carcinoma (HGSC) is characterized by HRD, which is caused by genetic ...alterations in the homologous recombination repair (HRR) pathway. Recent trials have shown that not only patients with pathogenic/likely pathogenic
variants, but also
/HRD patients, are sensitive to PARPis and platinum therapy. The most common HRD test is Myriad MyChoice CDx, but there is a pressing need to offer an alternative to outsourcing analysis, which typically requires high costs and lengthy turnaround times. In order to set up a complete in-house workflow for HRD testing, we analyzed a small cohort of HGSC patients using the CE-IVD AmoyDx HRD Focus Panel and compared our results with Myriad's. In addition, to further deepen the mechanisms behind HRD, we analyzed the study cohort by using both a custom NGS panel that analyzed 21 HRR-related genes and FISH analysis to determine the copy numbers of
and
. We found complete concordance in HRD status detected by the Amoy and the Myriad assays, supporting the feasibility of internal HRD testing.
The majority of patients with advanced ovarian germ cell cancer are treated by cisplatin-based chemotherapy. Despite adequate first-line treatment, nearly one third of patients relapse and almost ...half develop cisplatin-resistant disease, which is often fatal. The treatment of cisplatin-resistant disease is challenging and prognosis remains poor. There are limited data on the efficacy of specific chemotherapeutic regimens, high-dose chemotherapy with autologous progenitor cell support and targeted therapies. The inclusion of patients in clinical trials is strongly recommended, especially in clinical trials on the most frequent male germ cell tumors, to offer wider therapeutic opportunities. Here, we provide an overview of current and potential new treatment options including combination chemotherapy, high-dose chemotherapy and molecular targeted therapies, for patients with cisplatin-resistant ovarian germ cell tumors.
Fertility loss due to cancer treatment can be a devastating experience for women and the couple. Undergoing fertility preservation can be a complex decision from both a medical and emotional point of ...view. The aim of the present study was to evaluate which socio-demographic and psychological factors predict a high motivation to undergo fertility preservation.
Fifty-eight female cancer patients who accessed an Oncofertility Unit completed: a questionnaire to collect socio-demographic characteristics and the level of motivation, the Beck-Depression Inventory-II, the State-Trait Anxiety Inventory-Y, and the Fertility Problem Inventory.
Almost half of the sample (44.8%) declared a high motivation. At multiple logistic regression analysis only the "Need for parenthood" subscale of the FPI predicted a high motivation. We alternatively evaluated as possible predictor the construct "Representations about the importance of parenthood" (i.e., the sum of the "Need for Parenthood" and "Rejection of childfree lifestyle" subscales) in place of the two separate subscales. At multiple logistic regression analysis, only this variable predicted a high motivation to undergo fertility preservation.
The most important predictor of a high motivation to undergo fertility preservation is the individual desire for parenthood. This implies that, regardless of socio-demographic characteristics, any woman of childbearing age should receive an appropriate counseling about fertility preservation.
Abstract Background Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a ...clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery. Methods 400 chemonaïve epithelial ovarian cancer patients, age ≥ 18, ECOG PS 0–2 were eligible to receive C (AUC 5 d1, q21) plus P (175 mg/m2 d1, q21) and B (15 mg/kg d1 q21) for 6 cycles followed by B maintenance until cycle 22nd. Results 79 patients (20%) underwent IDS. Overall, 74 patients received at least one administration of B before IDS. Median age was 61.2, 70% of the patients had FIGO IIIC disease. The median number of cycles before IDS was 3 both for chemotherapy and bevacizumab respectively. A residual disease ≤ 1 cm was achieved in 64 patients (86.5%). Four percent of the patients experienced fever and 4% required blood transfusion after surgery. Surgical wound infection and/or dehiscence, pelvic abscess, intestinal sub-occlusion and fistula were experienced by one patient each. Conclusions In the MITO16A-MaNGO OV2A phase 4 trial, combined chemotherapy and bevacizumab did not hamper IDS and the rate of perioperative complications was similar to what expected without bevacizumab. These data support the hypothesis that adding bevacizumab to first line chemotherapy for ovarian cancer might not be denied to patients for whom IDS is planned.
Abstract Objective Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological ...signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database. Methods Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson's and Scott's criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan–Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival. The degree of concordance was evaluated by Cohen's Kappa measures. Results Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (62% vs 23%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002) and a higher prevalence of squamous and mucinous metaplasia. The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) ( p = 0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis. Conclusions The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a 40 molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancers.
Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid ...trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.
Gestational trophoblastic disease includes a rare group of benign and malignant tumors derived from abnormal trophoblastic proliferation. Malignant forms are called gestational trophoblastic ...neoplasia (GTN) and include invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor. Standard treatment of GTN is chemotherapy. The regimen of choice mainly depends on the FIGO prognostic score. Low-risk and high-risk GTN is treated with single-agent or multiagent chemotherapy, respectively. In the case of chemoresistance, immunotherapy may represent a new therapeutic strategy.
Literature obtained from searches on PubMed concerning GTN and immunotherapy was reviewed.
Programmed cell death 1 (PD-1) and its ligands (PD-L1/2) are expressed in GTN. Published data on PD-1/PD-L1 inhibitors alone in GTN were available for 51 patients. Pembrolizumab is an anti-PD-1 inhibitor used in chemoresistant forms of GTN. In the TROPHIMMUN trial, Avelumab, a monoclonal antibody inhibiting PD-L1, showed promising results only in patients with GTN resistant to monochemotherapy. Conversely, in patients with resistance to multiagent chemotherapy, treatment with Avelumab was discontinued due to severe toxicity and disease progression. The association of Camrelizumab and Apatinib could represent a different treatment for forms of GTN refractory to polychemotherapy or for relapses.
Anti-PD-1 or anti-PD-L1 might represent an important new treatment strategy for the management of chemoresistant/refractory GTN.
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