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1.
Expert Opin Pharmacother ; : 1-9, 2022 Aug 30.
Article in English | MEDLINE | ID: mdl-36002936

ABSTRACT

INTRODUCTION: Limited data on the role of pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer are available. AREAS COVERED: This article aims to provide an overview of the current treatment options for patients with vulvar cancer. PubMed (MEDLINE), Embase, CENTRAL, Scopus, and Web of Science databases, as well as ClinicalTrials.gov were searched to review the current evidence as well as future perspectives on the role of pharmacotherapy in patients with vulvar carcinoma. EXPERT OPINION: There has been no consensus on the pharmacotherapy for patients with locally advanced, recurrent, or metastatic vulvar cancer. Concurrent platinum-based chemoradiation is the most widely used treatment modality for primary treatment or for neoadjuvant settings. Chemotherapy in metastatic disease is considered a palliative treatment. Anti-EGFR tyrosine kinase inhibitors seem to show promising anti-tumor activity in patients harboring EGFR alteration. Similarly, growing evidence supports the adoption of immune checkpoint inhibitors in both neoadjuvant and metastatic settings. Molecular and genomic profiling is advocated to identify target mutations. The PI3K/AKT/mTOR and HER/ErbB pathways might represent two intriguing treatment options. Treatments directed against HPV are discussed as well. Further evidence is warranted to identify the best treatment modalities for patients with locally advanced, recurrent, and metastatic disease.

2.
J Gynecol Oncol ; 33(5): e69, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35882606

ABSTRACT

OBJECTIVE: To evaluate the efficacy and safety of systematic lymph node dissection (SyLND) at the time of interval debulking surgery (IDS) for advanced epithelial ovarian cancer (AEOC). METHODS: Systematic literature review of studies including AEOC patients undergoing SyLND versus selective lymph node dissection (SeLND) or no lymph node dissection (NoLND) after neoadjuvant chemotherapy (NACT). Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included severe postoperative complications, lymphocele, lymphedema, blood loss, blood transfusions, operative time, and hospital stay. RESULTS: Nine retrospective studies met the eligibility criteria, involving a total of 1,660 patients: 827 (49.8%) SyLND, 490 (29.5%) SeLND, and 343 (20.7%) NoLND. The pooled estimated hazard ratios (HR) for PFS and OS were, respectively, 0.88 (95% confidence interval [CI]=0.65-1.20; p=0.43) and 0.80 (95% CI=0.50-1.30; p=0.37). The pooled estimated odds ratios (ORs) for severe postoperative complications, lymphocele, lymphedema, and blood transfusions were, respectively, 1.83 (95% CI=1.19-2.82; p=0.006), 3.38 (95% CI=1.71-6.70; p<0.001), 7.23 (95% CI=3.40-15.36; p<0.0001), and 1.22 (95% CI=0.50-2.96; p=0.67). CONCLUSION: Despite the heterogeneity in the study designs, SyLND after NACT failed to demonstrate a significant improvement in PFS and OS and resulted in a higher risk of severe postoperative complications. TRIAL REGISTRATION: PROSPERO Identifier: CRD42022303577.


Subject(s)
Lymphedema , Lymphocele , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Female , Humans , Neoadjuvant Therapy , Postoperative Complications , Retrospective Studies
3.
Gynecol Obstet Invest ; 2022 Jul 06.
Article in English | MEDLINE | ID: mdl-35793638

ABSTRACT

OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic researches. This is of paramount importance in endometrial cancer (EC) since it is characterized by quite indolent behavior. Here, we aim to evaluate the impact of various comorbidities and concurrent medications used on survival outcomes, adopting the age-adjusted Charlson comorbidity index (A-CCI). DESIGN: This is an observational study. Charts of 257 EC patients were retrieved. METHODS: We retrospectively evaluated data of patients who underwent surgical treatment for EC. A-CCI was calculated by summing the weighted comorbidities and age of each patient. A binomial value was assigned to different comorbidities and different drugs. Oncologic outcomes were evaluated using Cox proportional hazard models adjusted for age. RESULTS: A-CCI ≥ 3 correlated with more aggressive tumor features (47.6% vs 26.8%, p= 0.001), higher risk of recurrence (29.7% vs 11.6%, p= 0.001), death (20.7% vs 7.1%, p=0.002) and death due to disease (16.6% vs 6.3%, p=0.012). Considering comorbidities and drugs at parsimonious multivariable analysis model: cardiac disease, liver disease, and proton pump inhibitors (PPIs) use were independent predictors of disease-free survival. Cardiac disease, autoimmune disease, and PPIs use were independent predictors of overall survival. Diabetes was the only independent predictor for cause-specific survival. LIMITATIONS: The major limitation of the present study is its retrospective nature and the relatively small sample size that limit the possibility to have firm conclusions. CONCLUSION: Patients with EC are characterized by a high burden of comorbidities. Comorbidities impact directly survival outcomes. Further attention is needed to improve the active management of comorbidities soon after EC treatments. Interventional studies are needed to improve patients' outcomes.

4.
Cancers (Basel) ; 14(11)2022 May 31.
Article in English | MEDLINE | ID: mdl-35681720

ABSTRACT

PURPOSE: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions. METHODS: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables. RESULTS: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74). CONCLUSIONS: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.

5.
Vaccines (Basel) ; 10(1)2021 Dec 23.
Article in English | MEDLINE | ID: mdl-35062673

ABSTRACT

OBJECTIVE: To evaluate the safety and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine in gynecologic oncology patients under chemotherapy. METHODS: A prospective cohort study including gynecologic oncology women who were under chemotherapy or had completed it within 6 months at the time of the study. All patients received a two-dose schedule of the Pfizer-BioNTech COVID-19 vaccine. Results were compared with a control group of healthy women vaccinated in the same period. RESULTS: Overall, 44 oncologic patients with a mean age of 61.3 ± 10.7 years were enrolled: 28 (63.6%) had ovarian cancer, 9 (20.4%) endometrial, and 7 (16%) cervical. The IgG antibody titer after 1 month from vaccination was low in 9 (20.5%) patients, moderate in 21 (47.7%), and high in 14 (31.8%). The 3-month titer was null in 2 (4.5%) patients, low in 26 (59.1%), moderate in 13 (29.5%), and high in 3 (6.8%). Patients ≥ 50 years reported lower 1-month (p = 0.018) and 3-month (p = 0.004) titers compared with <50 years. Patients with BMI < 30 kg/m2 had a higher 1-month titer compared with BMI ≥ 30 kg/m2 (p = 0.016). Compared with healthy women (n = 44), oncologic patients showed a lower 3-month titer (p < 0.001). None of the patients experienced serious adverse effects. CONCLUSIONS: The COVID-19 vaccine was safe and immunogenic in gynecologic oncology patients under chemotherapy. Serological monitoring and further vaccine shots should be considered to boost protection.

6.
Gynecol Oncol ; 164(3): 505-513, 2022 03.
Article in English | MEDLINE | ID: mdl-35063281

ABSTRACT

BACKGROUND: Previous findings showed that cediranib-olaparib increased PFS in women with recurrent platinum-sensitive ovarian cancer compared to olaparib alone. METHODS: BAROCCO trial randomized 123 patients: 80mg/m2 paclitaxel weekly up to 24 weeks (control), olaparib 300mg tablets twice daily together with 20mg cediranib daily (continuous schedule) or with 20mg cediranib 5 days/week (intermittent schedule) until progression. The primary objective was the PFS comparison between each experimental arm and the control (alpha one-sided 5%; power 80%; HR 0.5). RESULTS: The median platinum-free interval was 1.9 months, 60% of patients had been pretreated with 3 or more chemotherapy lines. Median PFS for paclitaxel, the continuous, and the intermittent schedules were 3.1, 5.6, and 3.8 months. The HR for PFS in the continuous arm vs control was 0.76 (90% CI: 0.50-1.14, p = 0.265). The HR for PFS in the intermittent arm vs control was 1.03 (90% CI: 0.68-1.55, p = 0.904). Treatment was discontinued due to adverse events in 15%, 20%, and 5% of patients in the control, continuous and intermittent arms. Grade ≥ 3 anemia and diarrhea and hypertension of any grade occurred only in the experimental arms, and peripheral neuropathies and alopecia only in the control arm. Five serious adverse drug reactions occurred and two were fatal: one in the control and one in the continuous arm. CONCLUSIONS: The combination of cediranib-olaparib was not superior to chemotherapy in terms of PFS in heavily pretreated platinum-resistant ovarian cancer patients. However, this oral doublet, is active and may offer a non-chemotherapy option in this difficult to treat population. CLINICAL TRIAL IDENTIFICATION: IRFMN-OVA-7289, EudraCT: 2016-003964-38, NCT03314740.


Subject(s)
Ovarian Neoplasms , Peripheral Nervous System Diseases , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/etiology , Female , Humans , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/etiology , Paclitaxel , Phthalazines , Piperazines , Quinazolines
7.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34948446

ABSTRACT

Ovarian cancer (OC) is the second most common cause of death in women with gynecological cancer. Considering the poor prognosis, particularly in the case of platinum-resistant (PtR) disease, a huge effort was made to define new biomarkers able to help physicians in approaching and treating these challenging patients. Currently, most data can be obtained from tumor biopsy samples, but this is not always available and implies a surgical procedure. On the other hand, circulating biomarkers are detected with non-invasive methods, although this might require expensive techniques. Given the fervent hope in their value, here we focused on the most studied circulating biomarkers that could play a role in PtR OC.


Subject(s)
Biomarkers, Tumor/blood , Drug Resistance, Neoplasm , Ovarian Neoplasms/metabolism , Female , Humans , Ovarian Neoplasms/blood , Platinum/therapeutic use , Prognosis
8.
Gynecol Oncol Rep ; 38: 100880, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34926761

ABSTRACT

•Ovarian cancer is the most lethal among gynecological cancers.•Carboplatin-based chemotherapy identifies as the main systemic treatment for ovarian cancer patients.•Almost one every three patients treated with carboplatin experiences hypersensitivity reactions.•Patients may experience breakthrough reactions during drug desensitization.•Omalizumab represents a promising new treatment to overcome carboplatin hypersensitivity.

9.
Front Oncol ; 11: 769280, 2021.
Article in English | MEDLINE | ID: mdl-34900718

ABSTRACT

Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metastatic breast cancer-olaparib and talazoparib-based on two phase III trials, which showed a progression-free survival benefit when compared to chemotherapy. Safety profile was manageable with supportive therapies and dose reductions/interruptions. In addition, other PARP inhibitors are currently under investigation, such as talazoparib, rucaparib, and veliparib. Subsequently, we will discuss the potential role of PARP inhibitors in the future. Clinical research areas are investigating PARP inhibitors in combination with other agents and are including patients without germline BRCA mutations: ongoing phase II/III studies are combining PARP inhibitors with immunotherapy, while phases I and II trials are combining PARP inhibitors with other targeted agents such as ATM and PIK3CA inhibitors. Moreover, several clinical trials are enrolling patients with somatic BRCA mutation or patients carrying mutations in genes, other than BRCA1/2, involved in the homologous recombination repair pathway (e.g., CHECK2, PALB2, RAD51, etc.).

10.
Cancers (Basel) ; 13(16)2021 Aug 12.
Article in English | MEDLINE | ID: mdl-34439215

ABSTRACT

The actual role of chemotherapy in vulvar cancer is undeniably a niche topic. The low incidence of the disease limits the feasibility of randomized trials. Decision making is thus oriented by clinical and pathological features, whose relevance is generally weighted against evidence from observational studies and clinical practice. The therapeutic management of vulvar cancer is increasingly codified and refined at an individual patient level. It is of note that the attitude towards evidence sharing and discussion within a multidisciplinary frame is progressively consolidating. Viable options included in the therapeutic armamentarium available for vulvar cancer patients are frequently an adaption from standards used for cervical or anal carcinoma. Chemotherapy is more frequently combined with radiotherapy as neo-/adjuvant or definitive treatment. Drugs commonly used are platinum derivative, 5-fluorouracil and mitomicin C, mostly in combination with radiotherapy for radiosensitization. Exclusive chemotherapy in the neo-/adjuvant setting comprises platinum-derivative, combined with bleomicin and methotrexate, 5-fluorouracil, ifosfamide or taxanes. In advanced disease, current regimens include cisplatin-based chemoradiation, with or without 5-fluorouracil, or doublets with platinum in combination with a taxane. Our work is also enriched by a concise excursus on the biologic pathways underlying vulvar cancer. Introductory hints are also provided on targeted agents, a rapidly evolving research field.

11.
Crit Rev Oncol Hematol ; 162: 103344, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33933568

ABSTRACT

Primary gynecologic neuroendocrine carcinomas (gNECs) are a heterogeneous spectrum of rare and highly aggressive neoplasms, accounting for about 2% of all gynecologic malignancies, which mostly resemble the small cell lung carcinoma (SCLC). Due to the lack of standardized treatment guidelines, their management poses a noteworthy clinical challenge. Currently, cumulative data retrieved from the management of SCLC and from retrospective studies supports a multimodality strategy, based on surgery, chemotherapy, and radiotherapy. Nevertheless, the prognosis remains poor and recurrences are extremely frequent. Hence, there is an urgent need for novel treatment options and promising molecular targets. Recently, there has been an increasing interest on the potential role of immune checkpoint inhibitors, especially in the recurrent setting. However, only scant evidence exists and there is still a long road ahead. A solid collaboration between gynecologists and oncologists worldwide is required to improve the treatment of these puzzling tumors.


Subject(s)
Carcinoma, Neuroendocrine , Genital Neoplasms, Female , Lung Neoplasms , Neuroendocrine Tumors , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/epidemiology , Carcinoma, Neuroendocrine/therapy , Female , Humans , Neoplasm Recurrence, Local , Retrospective Studies
12.
J Clin Med ; 10(7)2021 Apr 06.
Article in English | MEDLINE | ID: mdl-33917435

ABSTRACT

Human papillomaviruses (HPVs) are associated with invasive malignancies, including almost 100% of cervical cancers (CECs), and 35-70% of oropharyngeal cancers (OPCs). HPV infection leads to clinical implications in related tumors by determining better prognosis and predicting treatment response, especially in OPC. Currently, specific and minimally invasive tests allow for detecting HPV-related cancer at an early phase, informing more appropriately therapeutical decisions, and allowing for timely disease monitoring. A blood-based biomarker detectable in liquid biopsy represents an ideal candidate, and the use of circulating HPV DNA (ct-DNA) itself could offer the highest specificity for such a scope. Circulating HPV DNA is detectable in the greatest part of patients affected by HPV-related cancers, and studies have demonstrated its potential usefulness for CEC and OPC clinical management. Unfortunately, when using conventional polymerase chain reaction (PCR), the detection rate of serum HPV DNA is low. Innovative techniques such as droplet-based digital PCR and next generation sequencing are becoming increasingly available for the purpose of boosting HPV ct-DNA detection rate. We herein review and critically discuss the most recent and representative literature, concerning the role of HPV ctDNA in OPC and CEC in the light of new technologies that could improve the potential of this biomarker in fulfilling many of the unmet needs in the clinical management of OPC and CEC patients.

13.
Int J Med Sci ; 18(10): 2245-2250, 2021.
Article in English | MEDLINE | ID: mdl-33859534

ABSTRACT

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment. Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres. Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients. Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Furans/therapeutic use , Ketones/therapeutic use , Neoadjuvant Therapy/methods , Triple Negative Breast Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant/methods , Female , Humans , Middle Aged , Neoplasm Staging , Progression-Free Survival , Retrospective Studies , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/mortality , Triple Negative Breast Neoplasms/pathology
14.
In Vivo ; 35(2): 1277-1283, 2021.
Article in English | MEDLINE | ID: mdl-33622931

ABSTRACT

BACKGROUND/AIM: Treatment of locally advanced cervical cancer (LACC) consists of concomitant chemoradiation or neoadjuvant chemotherapy (NACT) plus radical surgery (RS). This study analyzed the prognostic role of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), tumor infiltrating lymphocytes (TILs), and PD-L1 expression in LACC patients, treated with NACT+RS. PATIENTS AND METHODS: We prospectively analyzed 37 LACC patients treated from December 2016 to September 2019. Patients were submitted to pelvic examination, biopsy and imaging. RESULTS: In 65% of cases, a nodal involvement was present at pre-treatment MRI. All cancers showed the presence of stromal TILs and PD-L1 staining of inflammatory cells. No significant correlations were found between clinicopathological parameters and the number of TILs and PDL-1 at baseline. After NACT, 29 patients (78%) were submitted to RS; 28% of patients showed pathological complete response, 62% partial response and 10% stable disease. Seven (24%) patients reported a positive node. Patients with high levels of stromal TILs and low NLR and PLR showed a significantly better response to NACT. No significant correlation was observed between PD-L1 expression and response to NACT. CONCLUSION: The number of TILs, the expression of PDL1, and NLR and PLR ratios correlate significantly with the response of LACC patients to NACT.


Subject(s)
Neoadjuvant Therapy , Uterine Cervical Neoplasms , Female , Humans , Lymphocytes , Lymphocytes, Tumor-Infiltrating , Prognosis , Uterine Cervical Neoplasms/drug therapy
15.
Expert Opin Drug Saf ; 20(6): 641-650, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33555963

ABSTRACT

Introduction: Advanced, persistent or recurrent cervical cancer in patients not amenable to curative surgery or radiotherapy predicts a dismal prognosis. Systemic chemotherapy based on paclitaxel/cisplatin ± bevacizumab is the current standard of care. However, once progression occurs, the possibility of alternative treatment options is very limited.Areas covered: The usefulness of capecitabine has been well-established against several cancer types, including head and neck, breast, and colorectal cancer. This review covers current literature evidence on the clinical efficacy and safety of capecitabine in cervical cancer treatment, either as monotherapy or combined with other agents or chemo-radiotherapy.Expert opinion: Recent clinical data, albeit scant, suggested a promising role for capecitabine both as monotherapy in patients with platinum-resistant cervical cancer and in combination with cisplatin in chemotherapy-naïve patients with metastatic or recurrent cervical cancer. In our opinion, capecitabine, especially in combination regimens, could represent a valid treatment option and further research is warranted to better understand its effectiveness in these challenging patients.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Capecitabine/administration & dosage , Uterine Cervical Neoplasms/drug therapy , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/adverse effects , Combined Modality Therapy , Female , Humans , Neoplasm Recurrence, Local , Uterine Cervical Neoplasms/pathology
16.
Case Rep Oncol ; 13(3): 1317-1324, 2020.
Article in English | MEDLINE | ID: mdl-33250748

ABSTRACT

Although ovarian cancer often presents as a widespread disease, metastases to the breast and/or axillary lymph nodes are a very rare event, accounting for only 0.03-0.6% of all breast cancers. Its early recognition and accurate distinction from primary breast cancer are of crucial importance to choose an adequate systemic therapy over unnecessary surgeries. We presented the case of a 53-year-old woman who was diagnosed with breast metastases 2 years after the diagnosis of advanced primary serous ovarian cancer. The patient underwent primary cytoreductive surgery and platinum-based chemotherapy in combination with bevacizumab, followed by bevacizumab maintenance for 18 months. After 2 years of negative follow-ups, the disease unexpectedly spread to the left breast and axillary lymph nodes. No axillary lymph node dissection or breast surgery was performed. The patient received axillary radiotherapy and multiple chemotherapy lines: gemcitabine/cisplatin, liposomal doxorubicin, topotecan, olaparib/cediranib, paclitaxel, and cisplatin. Unfortunately, none of these treatments improved her prognosis and she died 3 years after the disease recurrence. Ovarian cancer metastasis to the breast reveals a disseminated disease with a poor prognosis. Currently, no valid treatment options are available as the disease shows multidrug chemoresistance. In the era of precision medicine, the characterization of genetic and molecular markers may play a role in offering new promising targeted therapies.

17.
Gynecol Oncol ; 161(1): 4-10, 2021 04.
Article in English | MEDLINE | ID: mdl-33223220

ABSTRACT

OBJECTIVE: The aim of this study was to assess the impact of surgical complexity on postoperative complications and mortality, according to patient's frailty (mFI) following surgery for ovarian cancer. METHODS: Patients undergoing cytoreductive surgery for ovarian cancer from 2008 to 2018 were identified from our database. A surgical complexity score from 1 to 3 was used to assess the extent of surgery (simple to complex, respectively). mFI with 11 variables, based on mapping the Canadian Study of Health and Aging Frailty Index to the NSQIP comorbidities was evaluated. Data were analyzed using Fisher exact test, independent sample t-test, and logistic regression. RESULTS: Of 263 patients identified, 33% reported at least one postoperative complication and 6% had severe complications. BMI ≥ 30 (p = 0.04) increased mFI (p = 0.04) and high-complexity surgery (p < 0.001) were independent predictors of severe complications (G3-G5). Patients with high frailty index score (mFI ≥ 3) who underwent intermediate or high-complexity surgery were at higher risk of severe complications ranging from 29.4% to 50. CONCLUSIONS: The combined evaluation of mFI and surgical complexity expected may identify patients at higher risk for severe morbidity allowing to stratify patients who are less likely to tolerate a surgical extensive treatment.


Subject(s)
Carcinoma, Ovarian Epithelial/surgery , Frailty/diagnosis , Ovarian Neoplasms/surgery , Aged , Canada/epidemiology , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/pathology , Cytoreduction Surgical Procedures/adverse effects , Cytoreduction Surgical Procedures/methods , Cytoreduction Surgical Procedures/statistics & numerical data , Female , Frailty/epidemiology , Frailty/mortality , Humans , Logistic Models , Middle Aged , Models, Statistical , Morbidity , Multivariate Analysis , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Predictive Value of Tests , Risk Assessment
18.
Cancers (Basel) ; 12(10)2020 Oct 01.
Article in English | MEDLINE | ID: mdl-33019700

ABSTRACT

Glycosylation, the posttranslational linking of sugar molecules to proteins, is notoriously altered during tumor transformation. More specifically in carcinomas, GalNAc-type O-glycosylation, is characterized by biosynthetically immature truncated glycans present on the cancer cell surface, which profoundly impact anti-tumor immune recognition. The tumor-associated glycan pattern may thus be regarded as a biomarker of immune modulation. In epithelial ovarian cancer (EOC) there is a particular lack of specific biomarkers and molecular targets to aid early diagnosis and develop novel therapeutic interventions. The aim of this study was to investigate the ovarian cancer O-glycoproteome and identify tumor-associated glycoproteins relevant in tumor-dendritic cell (DC) interactions, mediated by macrophage galactose-like C type lectin (MGL), which recognizes the tumor-associated Tn O-glycan. Lectin weak affinity chromatography (LWAC) was employed to probe the O-glycopeptidome by MGL and Vicia villosa agglutinin (VVA) lectin using glycoengineered ovarian cancer cell lines and ovarian cancer tissues as input material. Biochemical and bioinformatics analysis gave information on the glycan arrangement recognized by MGL in tumor cells. The potential MGL binders identified were located, as expected, at the cell membrane, but also within the intracellular compartment and the matrisome, suggesting that MGL in vivo may play a complex role in sensing microenvironmental cues. The tumor glycoproteins binders for MGL may become relevant to characterize the interaction between the immune system and tumor progression and contribute to the design of glycan targeting-based strategies for EOC immunotherapeutic interventions.

19.
Virchows Arch ; 478(3): 517-525, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32915266

ABSTRACT

Cancer immunotherapy has significantly improved the management of many malignancies in recent years. Although cervical cancer is the second most common women's cancer in the world, there are still few information about the role of checkpoint inhibitors in this neoplasm, especially in the neoadjuvant setting. In the present study, we retrieved 38 consecutive patients with squamous cell cervical cancer who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical surgery. Pre-therapy biopsies were evaluated for the presence of tumor-infiltrating lymphocytes (TILs), including T (both cytotoxic CD8+ and helper CD4+) and B lymphocytes, macrophages, natural-killer cells, and eosinophils. Immunohistochemistry was performed to characterize the inflammatory cells and to evaluate programmed death-ligand 1 (PD-L1) expression on both neoplastic and inflammatory cells. We divided our study population in three groups using three cut-offs (< 10%, 10-40%, >40%), for both TILs and PD-L1 evaluation. Pathological response to NACT was obtained from the histological reports of the post-therapy surgical specimens. We observed that all cases showed stromal TILs, with a predominance of CD3+/CD4+ T helper cells, thus supporting the strong immunogenic potential of cervical cancer. The vast majority of neoplasms expressed PD-L1: 100% on immune cells and 92% on tumor cells. Firstly, we noticed that the percentage of neoplastic cells PD-L1+ was positively associated with high TIL percentage (p = 0.0073) and with increased PD-L1 expression on inflammatory cells (p = 0.0297). Secondly, we observed a significant correlation between both the percentage (p = 0.0105) of TILs and the expression of PD-L1 (p = 0.01045) on inflammatory cells and pathological response to NACT. These results suggest that cervical cancer could be a good target for immunotherapy, also in the neoadjuvant setting. Furthermore, PD-L1 expression was significantly associated with stromal TILs that interestingly may predict pathological response to NACT.


Subject(s)
B7-H1 Antigen/analysis , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Uterine Cervical Neoplasms/immunology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Chemotherapy, Adjuvant , Cisplatin/therapeutic use , Clinical Decision-Making , Databases, Factual , Female , Humans , Hysterectomy , Immunohistochemistry , Immunophenotyping , Lymphocytes, Tumor-Infiltrating/pathology , Middle Aged , Neoadjuvant Therapy , Paclitaxel/therapeutic use , Predictive Value of Tests , Retrospective Studies , Treatment Outcome , Tumor Microenvironment , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/therapy
20.
Oncology ; 98(11): 807-813, 2020.
Article in English | MEDLINE | ID: mdl-32892198

ABSTRACT

INTRODUCTION: Different imaging techniques were introduced to improve preoperative clinical staging of locally advanced cervical cancer (LACC) with transvaginal ultrasound (TV-US) or transrectal ultrasound (TR-US) representing a promising staging technique in the evaluation of the local extension of the disease for invasive tumors. The aim of this study was to evaluate the response to neoadjuvant chemotherapy (NACT) in LACC by 2D/3D ultrasound examination. MATERIALS AND METHODS: We prospectively enrolled patients affected by histologically and clinically confirmed LACC. All patients were scheduled for 3 cycles of platinum-based NACT followed by radical surgery. The ultrasound examination was performed at every cycle and within 10 days before surgery. The parameters evaluated were: the volume (automatically computed by the VOCAL software) and the mass vascularization. RESULTS: From March 2010 to March 2019, 157 women were recruited. Among these patients, 12 of them were excluded: 6 for the presence of distant metastases, 4 for rare histology, and 2 for severe comorbidities not allowing the protocol treatment. Seventeen patients after NACT were excluded because they were not amenable to radical surgery. Thus, 128 were considered for the final analysis of whom 106 (83%) were considered responders to NACT by histology. The sensibility and specificity of ultrasound with regard to the response to chemotherapy compared to histological specimen were 94 and 82%, respectively, with an accuracy of 92%. The positive predictive value and negative predictive value were 96 and 75%, respectively. Finally, we found that nonetheless there was a trend towards a continuous response to chemotherapy among patients who were considered responders to NACT at pathological examination; the major volume and vascularization index (VI) reduction were observed during the first 2 cycles (74, 71% and 47, 63%, respectively). On the contrary, non-responders showed an initial reduction of the VI (4.86 consisting of 33%, 95% CI 0.79-8.92, p = 0.013), but no significant modification in tumour volume along NACT. CONCLUSION: 2D/3D ultrasound is useful in assessing early response to NACT in patients with LACC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/drug therapy , Adult , Aged , Chemotherapy, Adjuvant , Female , Humans , Imaging, Three-Dimensional/methods , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prospective Studies , Ultrasonography/methods , Uterine Cervical Neoplasms/surgery
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