Search

Background/aim: The potentially traumatic role of severe life-threatening medical conditions is still debated in psychiatry and not yet recognized, particularly among post-traumatic stress disorders. However, increasing evidence suggests the psychopathological impact of severe medical conditions related to their poor prognosis, high lethality, treatments heaviness and invasiveness. Ovarian cancer (OC) is one of the malignancies with the highest mortality and the aim of this study was to investigate post-traumatic stress and depressive symptoms in women 3 to 6 months after diagnosis., Patients and Methods: A sample of 83 women diagnosed with OC at different stages (from AI to IV) was recruited and assessed by means of the: Structural Clinical Interview for Mental Disorders according to DSM-5 (SCID-5), Trauma and Loss Spectrum Self-Report (TALS-SR), Impact Event Scale-Revised (IES-R), Hamilton Rating Scale for Depression (HAM-D), Mood Spectrum-Self Report (MOOD-SR), Work and Social Adjustment Scale (WSAS)., Results: Full data on the psychiatric assessments were available for 45 patients: 13 (28.9%) patients reported a diagnosis of PTSD. Patients with PTSD reported statistically significant higher depressive symptoms and more severe impact on work and social functioning compared to those without PTSD., Conclusion: Our results highlight the need to carefully assess the potentially traumatic burden of a diagnosis of OC and its association with depressive symptoms for their impact on patients' global functioning, in order to provide appropriate preventive and therapeutic interventions., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The expression of the cyclin-dependent kinase inhibitor p16 correlates with the presence of human papillomavirus. The purpose of this investigation was to assess the prognostic relevance of p16 expression in patients with vulvar squamous cell carcinoma (VSCC) treated with radical surgery followed by adjuvant (chemo) radiation in selected cases., Patients and Methods: Seventy-eight patients were analyzed retrospectively., Results: Positive p16 immunostaining was detected in 19 (24.4%) patients. Five-year disease-free survival (DFS) and 5-year overall survival (OS) were better in p16-positive compared to p16-negative patients (83.9% versus 37.3% p=0.002 and 91.7% versus 57.6%, p=0.003, respectively). p16 expression retained prognostic relevance at multivariate analysis for both DFS and OS., Conclusion: p16 expression was detected in 24.4% of patients with VSCC and was found to be an independent prognostic variable for both DFS and OS., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Endometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100'000 women, mainly affecting peri- or postmenopausal women. The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17)(q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors. Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy ± radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy ± radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation. LG-ESSs are indolent tumor with a 5-year overall survival (OS) of 80-100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with a median OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV. The aim of this review is to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background/aim: The aim of the study was to correlate the expression of mismatch repairs proteins (MMR), programmed-death-ligand1 (PDL-1), and estro-progestinic receptors (ER/PgR) in tissue samples from a series of cervical adenocarcinoma (ADC) patients with their clinicopathological features., Materials and Methods: Thirty-nine ADC specimens were retrospectively retrieved from the Division of Pathology of the University Hospital of Pisa from 2015 to 2021. Histological subtype, grade (G), Silva pattern, presence of lymph vascular space invasion (LVI), and perineural invasion (PNI) were annotated. On representative samples, immunostaining for ER/PgR, MLH1, PMS2, MSH2, MSH6, and PDL-1(sp142) was performed., Results: Thirty-five ADCs were HPV-associated usual type (24 invasive and 11 in situ), 2 were clear cell type, one was a minimal deviation adenocarcinoma (MDA), and one was an invasive stratified mucin-producing carcinoma (iSMC). ADC associated with LVI were mostly G2-3, whereas those associated also with PNI were G3 with Silva pattern C. No difference in the expression of ER/PgR was observed with a dichotomic age stratification (51 years) of patients. Only 6 ADCs were MMR-deficient, all of them were of the usual type (4 invasive and 2 in situ). The heterodimer MLH-1/PMS2 was the one most frequently altered (5/6), whereas only one case had MSH6 loss. None of ADCs express PDL-1, except iSMC which showed PDL-1 expression >1% in neoplastic cells., Conclusion: Both invasive and in situ usual type ADCs indicate MMR deficiency, highlighting how this could be an early event in tumorigenesis. None of the cases, except for iSMC, express PDL-1., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Screening for ovarian cancer in the general population is a challenging issue. The aim of this review was to analyze both the studies based on serum CA125 assay and ultrasound (US) and the novel perspectives of clinical and biological research on this issue., Materials and Methods: The trials on the combination of serum CA125 and vaginal/pelvic US as well as the investigations on microRNA (miRNA)s, circulating tumor DNA and tumor protein 53 (TP53) variants in DNA purified from Pap smears have been critically analyzed., Results: Two large randomized trials failed to detect a reduction in ovarian cancer-related deaths in women who underwent serum CA125- and US-based screening compared to those who had no screening. The United Kingdom Collaborative Trial of Ovarian Cancer Screening reported a 39.2% higher incidence of stage I-II and 10.2% lower incidence of stage III-IV disease in women who underwent annual multimodal screening with serum CA125 and vaginal US compared to women who had no screening, but this stage shifting did not translate into a survival benefit. A longitudinal, multiple biomarker algorithm-based strategy might improve ovarian cancer detection compared with serial CA125 alone. The use of serum tumor-associated autoantibodies, circulating tumor DNA and microRNA is still investigational. The identification of TP53 clonal variants in DNA purified from Pap smears can detect early steps of serous ovarian carcinogenesis., Conclusion: The availability of sensitive next-generation sequencing-based approaches for TP53 assessment in PAP smears may allow the reliability of this genetic marker for early detection of ovarian cancer to be verified., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi., Patients and Methods: This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI)., Results: Of the 28 patients with PFI <6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI >12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI <6 months, 6-12 months, and >12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively., Conclusion: Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To assess the prognostic relevance of baseline and post-treatment skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) at the level of third lumbar vertebra in patients with ovarian cancer who underwent primary surgery and platinum-based chemotherapy., Patients and Methods: This retrospective investigation analyzed 134 patients who underwent staging computed tomography, surgery, chemotherapy and post-treatment computed tomography., Results: At univariate analysis, stage (p<0.0001), histotype (p=0.01), residual disease (p<0.0001) and treatment response (p<0.0001) correlated with progression-free survival (PFS), whereas age (p=0.004), stage (p=0.006), residual disease (p<0.0001) and treatment response (p<0.0001) were associated with overall survival (OS). Neither baseline nor post-treatment SMI and SMRA had prognostic relevance. At multivariate analysis, residual disease and treatment response correlated with PFS (p<0.0001 and p<0.0001) and OS (p=0.007 and p<0.0001), whilst age was an independent prognostic variable for OS (p=0.02)., Conclusion: Baseline and post-treatment SMI and SMRA did not correlate with patient outcome in this clinical setting., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Colon cancer (CC) and epithelial ovarian cancer (EOC) are common and severe neoplasms frequently sharing a massive inflammatory involvement of peritoneum. A detailed molecular characterization of such carcinomatosis has not been performed, so far., Methods: Omental adipocytes were isolated from thirty-three adult women who underwent primary surgery for CC or EOC. Expression of several pro-inflammatory genes was determined by real-time PCR and immunofluorescence. Data were related to the clinical phenotype of the patients., Results: CD68, FGFR1, and IL-6 were significantly more expressed in adipocytes from CC patients and VEGF in adipocytes from EOC. TNFα, TGFβ, or MCP-1, as well as the pro-inflammatory platform P2X7R-NLRP3, did not differ between the 2 cancers. White blood cell count, mirroring systemic inflammation, was related to adipocyte P2X7R (R = 0.508, p = 0.003), NLRP3 (R = 0.405; p = 0.02), and MCP-1 (R = 0.448; p = 0.009). P2X7R and NLRP3 were the only inflammatory factors significantly more expressed in patients carrying both omental and peritoneal carcinosis, who were also characterized by a higher leukocytosis. None of the tested inflammatory markers was associated with tumor grading for both neoplasms; however, the presence of metastases was associated with a higher adipocyte expression of FGFR1 and TGFβ., Conclusion: We show here that rarely measured molecules seem to specifically characterize omental carcinomatosis of CC or EOC, while more common inflammatory agents like TNFα, TGFβ, or MCP-1 do not; the P2X7R-NLRP3 complex marks omental and peritoneal carcinosis and is related to circulating white blood cells and MCP-1, involved in monocyte-macrophage tissue infiltration; increased TGFβ and FGFR1 characterize the tumoral dissemination., (© 2021 S. Karger AG, Basel.)

Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43-62%, a median progression-free survival (PFS) of 5.3-15 months and a median overall survival (OS) of 13.2-37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27-47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.

Background: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs., Methods: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure., Results: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients., Conclusions: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents.

Platinum/paclitaxel-based chemotherapy is able to obtain a clinical response in up to 80% of patients with advanced ovarian carcinoma, but most of them will subsequently develop recurrent disease. Several therapeutic approaches, including prolonged administration of the first-line regimen and the concomitant or sequential addition of a third cytotoxic agent to standard chemotherapy, failed to improve the clinical outcome of patients. In the last years, the implementation of the biological knowledge on ovarian carcinoma and the introduction of bevacizumab (BEV) and poly(ADP-ribose) polymerase inhibitors (PARPi) in first-line treatment have improved patient prognosis. In this review, we have analyzed the randomized clinical trials and real world observational studies on these issues, with the aim to suggest an algorithm for a rational use of BEV and PARPi in patients with newly diagnosed advanced ovarian carcinoma., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Clear cell carcinoma of the ovary is a rare and distinct histotype of epithelial ovarian carcinomas. Women diagnosed with clear cell carcinomas are usually younger and diagnosed at earlier stages than those with the most common high-grade serous histology. Endometriosis is considered a main risk factor for the development of clear cell carcinoma of the ovary, and it can be considered a precursor of of this tumor, as it is identified in more than 50% of patients with clear cell carcinoma. Different molecular pathways and alterations heve been identified in ovarian clear cell carcinoma, including the most common mutations of AT-rich interaction domain 1A [ARID1A] and phosphatidylinositol-4,5-bisphosphate 3-kinase [PIK3] catalytic subunit alpha [PIK3CA]. The prognosis of patients at early stage is favorable, while patients with advanced or recurrent disease experience a poor oncologic outcomes. Despite a lower rate of responses due to an intrinsic chemoresistance, the treatment strategy for advanced disease resembles the treatment of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and platinum-based chemotherapy. For this reason, the role of adjuvant chemotherapy in patients with stage I disease undergoing complete surgical staging is still under debate. Alternative treatments, including biological agents that target different pathways constitute the most promising treatment strategies, and well-designed, collaborative international trials should be designed in order to improve the oncologic outcomes and the quality of life of patients with this aggressive disease., (Copyright © 2021. Published by Elsevier Inc.)

Background: Perivascular epithelioid cell tumors (PEComa)s are mesenchymal neoplasms located at various anatomic sites, which usually express both melanocytic and myogenic markers., Case Report: A 60-year-old woman underwent laparotomy for a huge, heterogeneous, right ovarian mass. The histological examination of the surgical specimen revealed a neoplasm consisting of both cells with clear or eosinophilic cytoplasm and spindle cells in a myxoid stroma. Immunostaining was positive for human melanoma black-45, h-caldesmon, desmin, actin, and transcription factor 3. Cell atypias were moderate, mitoses were 4/10 high power fields (HPF) and margins were focally infiltrative. These findings pointed to a diagnosis of ovarian PEComa. Twenty-five months later, two subcutaneous lesions were surgically removed on the left trapezius muscle and the median subumbilical area, respectively. The former was a desmoid fibromatosis, whereas the latter was a recurrence of PEComa with greater nuclear pleomorphism and higher number of mitoses (26/50 HPF) compared to the primary tumor. The patient was free of disease 11 months later., Conclusion: A long-term follow-up of gynecological PEComas is strongly recommended., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer., Patients and Methods: This retrospective investigation analyzed 67 patients at first relapse., Results: At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival., Conclusion: Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

While cancer during pregnancy and its treatment has grown to be a popular topic in recent years, little is known on how to advise patients looking to conceive or conceiving after cancer treatment. The aim of this paper is to review the available literature on the impact of pregnancy on survivors of the most common childhood cancers, brain cancer, haematological malignancies, thyroid cancer, melanomas and sarcomas. Its main objective is to be a source of information for clinicians looking to counsel patients in these delicate moments exploiting all the available literature, albeit scarce. Given the available literature, we conclude that the presence of a multidisciplinary team is of great importance in supporting the patient and her loved ones when facing pregnancy with a previous cancer diagnosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background/aim: The aims of the study were: i) to assess the incidence of perineural invasion (PNI) in squamous cell carcinoma of the vulva and ii) to correlate PNI with common pathological prognostic variables and clinical outcome of patients., Patients and Methods: The hospital records of 64 patients with vulvar squamous cell carcinoma who underwent primary radical surgery were reviewed., Results: PNI was significantly related to stage (p=0.038), size (p=0.038), lymph-vascular space involvement (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion. Five-year disease-free survival was 30.0% in patients with PNI and 53.1% in those without PNI (p=0.018), and the corresponding 5-year overall survival was 50.0% and 77.1% (p=0.031), respectively., Conclusion: PNI was associated with common pathological prognostic variables and with a poorer clinical outcome in patients with vulvar squamous cell carcinoma., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC)., Patients and Methods: A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile., Results: A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed., Conclusion: Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Cervical cancer patients with distant or loco-regional recurrences not amenable by surgery or radiotherapy have limited treatment options, and their 5-year overall survival (OS) rates range from 5% to 16%. The purpose of this paper is to assess the results obtained with chemotherapy and biological agents in this clinical setting. Several phase II trials of different cisplatin (CDDP)-based doublets and a phase III randomized trial showing a trend in response rate, progression-free survival, and OS in favor of CDDP + paclitaxel (PTX) compared with other CDDP-based doublets have been reviewed. The factors predictive of response to chemotherapy as well as the benefits and risks of the addition of bevacizumab to CDDP + PTX have been analyzed. The FDA has recently approved pembrolizumab for patients with recurrent or metastatic cervical cancer in progression on or after chemotherapy whose tumors were PD-L1 positive. Interesting perspectives of clinical research are represented by the use of immune checkpoint inhibitors alone or in addition to chemotherapy, whereas PARP inhibitors and PI3K inhibitors are still at the basic research phase, but promising.

Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Low-grade serous ovarian carcinoma (LGSOC) is a distinct pathologic and clinical entity, characterized by less aggressive biological behavior, lower sensitivity to chemotherapy and longer survival compared with high-grade serous ovarian carcinoma. LGSOC often harbors activating mutations of genes involved in mitogen activated protein kinase (MAPK) pathway. Patients with disease confined to the gonad(s) should undergo bilateral salpingo-oophorectomy, total hysterectomy and comprehensive surgical staging, although fertility-sparing surgery can be considered in selected cases. Women with stage IA-IB disease should undergo observation alone after surgery, whereas observation, chemotherapy or endocrine therapy are all possible options for those with stage IC-IIA disease. Patients with advanced disease should undergo primary debulking surgery with the aim of removing all macroscopically detectable disease, whereas neoadjuvant chemotherapy followed by interval debuking surgery. After surgery, the patients can receive either carboplatin plus paclitaxel followed by endocrine therapy or endocrine therapy alone. Molecularly targeted agents, and especially MEK inhibitors and Cyclin-dependent kinase (CDK) inhibitors, are currently under evaluation. Additional research on the genomics of LGSOC and clinical trials on the combination of MEK inhibitors with hormonal agents, other molecularly targeted agents or metformin, are strongly warranted to improve the prognosis of patients with this malignancy.

Aim: To assess the correlation between contrast-enhanced computed tomography (CE-CT) and positron-emission tomography (PET)/CT results and surgical and pathological findings in patients with recurrent platinum-sensitive ovarian cancer who underwent secondary cytoreduction., Patients and Methods: 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT with/without CE-CT were performed before 56 cytoreductive surgeries in 49 patients with suspicious recurrent ovarian cancer., Results: 18 F-FDG PET/CT showed higher sensitivity and diagnostic accuracy compared with CE-CT for both the whole series (100% versus 90.6%, respectively, and 97.8% versus 85.3%), and the 24 cases in which both examinations were performed (100% versus 87.0% and, respectively, 95.8% versus 83.3%). The addition of CE-CT to 18 F-FDG PET/CT did not improve its diagnostic reliability., Conclusion: 18 F-FDG PET/CT appears to be the more reliable imaging technique for the evaluation of patients with suspicious recurrent ovarian cancer, and for the selection of those more suitable for secondary cytoreductive surgery., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred., Patients and Methods: The hospital records of 138 complete responders after chemotherapy with (n=58) or without (n=80) bevacizumab were reviewed., Results: Both survival after recurrence and overall survival were related to age (≤61 vs. >61 years, p=0.002 and p=0.0001), performance status (0 vs. ≥1, p=0.002 and p=0.001), histotype (serous vs. non serous, p=0.005 and p=0.01), time to recurrence (≥12 vs. <12 months, p<0.0001 and p<0.0001) and treatment at recurrence (surgery plus chemotherapy vs. chemotherapy, p=0.01 and p=0.004), but not to first-line treatment., Conclusion: This investigation failed to detect a more aggressive behavior of recurrent ovarian cancer after bevacizumab-containing primary treatment., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The aim of the study was to assess the clinical outcome of patients with malignant transformation of an ovarian mature teratoma., Patients and Methods: This study was conducted on 23 patients who underwent primary surgery at three Italian Gynecological Centers. Histologically, nine (39.1%) patients had squamous cell carcinoma, five (21.7%) had a thyroid carcinoma, six (26.1%) had a carcinoid, one (4.3%) patient had papillary renal carcinoma, one (4.3%) had medulloblastoma and one (4.3%) had intestinal-type mucinous adenocarcinoma., Results: All six patients with stage I squamous cell carcinoma had no evidence of disease (NED) after a median time of 141 months. Of the three patients with stage IIb-IIIc squamous cell carcinoma, two had NED after 119 and 154 months, and one died of the disease 9 months after diagnosis. All five women with stage I thyroid carcinoma had NED after a median of 60 months. Of the six patients with stage I carcinoid, five had NED after a median of 168 months, whereas one died due to carcinoid heart disease. The three patients with stage I renal carcinoma, medulloblastoma and mucinous adenocarcinoma had NED after 24, 141 and 149 months, respectively., Conclusion: The clinical outcome of early-stage malignancies associated with mature ovarian teratomas is excellent following treatment., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Adenocarcinoma accounts for 10-25% of all cervical cancers, and its relative and absolute rate has raised over the past decades. Most, but not all the authors, reported that adenocarcinoma has a greater propensity to lymph node, ovarian and distant metastases and a worse prognosis compared with squamous cell carcinoma. However, whether histologic type is an independent prognostic factor is still a debated issue. Moreover, adenocarcinoma is a very heterogenous disease, including different histological subtypes. Whereas radical hysterectomy and definitive radiotherapy achieve the same clinical outcome in early stage squamous cell carcinoma, surgery seems to obtain better survival compared with definitive radiotherapy in early stage adenocarcinoma. Chemoradiation is the standard treatment for locally advanced cervical cancer regardless of histologic type, although several retrospective studies showed that patients with adenocarcinoma were more likely to die than those with squamous cell carcinoma both before and after concurrent chemoradiation era. The prognostic relevance of biological variables, such as cyclin-dependent kinase inhibitors, p53, cyclooxygenase-2 [COX-2], cell surface tyrosine-kinases and programmed death-ligand [PD-L1], is still under investigation. Palliative chemotherapy is the only treatment option for persistent or recurrent cervical adenocarcinoma not amenable with surgery and radiotherapy. The use of immune checkpoint inhibitors as well as a therapeutic strategy targeting cell surface tyrosine kinases should be adequately explored in this clinical setting., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Mature cystic teratomas of the ovary have an incidence of 1.2-14.2 cases per 100.000 people per year. Malignant transformation occurs in approximately 2% of the cases, and usually consists of squamous cell carcinoma. The preoperative detection is difficult and the diagnostic accuracy of ultrasound, magnetic resonance imaging, and computed tomography is debated. The diagnosis is frequently made in the operating room or on final histological examination. Standard treatment consists of bilateral salpingo-oophorectomy, total hysterectomy and comprehensive surgical staging in early disease and optimal cytoreductive surgery in advanced disease. Paclitaxel/carboplatin- based chemotherapy is the most used adjuvant treatment, whereas more aggressive regimens can be adopted in patients with high tumor burden or recurrent disease. The efficacy of radiotherapy is still unproven. The prognosis is poor when the tumor has spread beyond the ovary. There are few information to provide commonly accepted guidelines for this malignancy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To assess the clinical outcome of patients with high-risk early-stage endometrial cancer and negative pelvic nodes who received adjuvant platinum-based chemotherapy plus vaginal brachytherapy (VBT)., Methods: This investigation assessed 80 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for stage Ib-II, grade 2-3 endometrioid (n = 43) or stage Ia-II nonendometrioid (n = 37) endometrial cancer., Results: Five-year local control rate, 5-year disease-free survival, and 5-year overall survival were 97, 87, and 97%, respectively, for endometrioid carcinoma, and 66, 50, and 72%, respectively, for nonendometrioid carcinoma., Conclusions: This retrospective study appears to show that adjuvant platinum-based chemotherapy plus VBT achieve very good results in endometrioid carcinoma. This combined treatment seems to be less effective in nonendometrioid carcinoma., (© 2019 S. Karger AG, Basel.)

Malignant transformation occurs in 1.5-2% of mature cystic teratomas (MCT)s of the ovary and usually consists of squamous cell carcinoma, whereas other malignancies are less common. Diagnosis and treatment represent a challenge for gynecologic oncologists. The preoperative detection is very difficult and the diagnostic accuracy of imaging examinations is uncertain. The tumor is usually detected post-operatively based on histopathologic findings. This paper reviewed 206 consecutive patients who underwent surgery for a histologically-proven MCT of the ovary between 2010 and 2017. Malignant transformation occurred in 3 (1.5%) of them, and consisted of squamous cell carcinoma in one, type 2 papillary renal carcinoma in one, and papillary thyroid carcinoma in another one. The paper reported the clinical, radiological and histological features of these cases and reviewed the literature data on the treatment options., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy., Patients and Methods: Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months)., Results: Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease., Conclusion: NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To assess the patterns of recurrence of node-positive endometrial cancer patients., Patients and Methods: This investigation assessed 82 patients who received different postoperative treatments., Results: Recurrence developed in 36 patients after a median time of 13.5 months, and involved the vagina, pelvic nodes, para-aortic nodes and distant sites in 5, 8, 16 and 17 patients, respectively. Five-year progression-free survival (PFS) and 5-year overall survival (OS) were 51.1% and 59.8%. PFS and OS were significantly better for endometrioid than for non-endometrioid tumors. There was a trend towards a better outcome for patients who underwent chemotherapy±radiotherapy compared to those who received radiotherapy alone. Among the former, there was a better 5-year PFS (65.8% versus 33.7%, p=0.038) in patients who received platinum/paclitaxel-based regimens compared to those who received platinum-based chemotherapy., Conclusion: Disease recurred in 43.9% of patients, and platinum/paclitaxel-based chemotherapy plus radiotherapy appeared to be the best adjuvant treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To assess preliminary results with dose-dense neoadjuvant chemotherapy (NACT) prior to surgery or concurrent chemo-radiotherapy (CCRT) in cervical cancer., Patients and Methods: Thirty patients received weekly paclitaxel (80 mg/m 2 ) plus carboplatin (AUC2) for 6 cycles followed by radical hysterectomy in 16 (stage Ib 2 -IIb), conisation in one (stage Ib1), and CCRT in 13 (stage Ib 2 -IIb). Median follow-up of survivors was 12 months (range=3-22)., Results: Among the surgically treated patients, clinical overall response rate (RR) was 82.3%, optimal pathological RR was 17.6%, and suboptimal pathological RR with intra-cervical residual disease was 41.2%. Only one patient relapsed. Among the CCRT treated patients, partial RR after NACT was 76.9% and complete RR after CCRT was 58.3%. However, 42.8% of complete responders recurred. Toxicity was acceptable., Conclusion: Dose-dense NACT seems to achieve promising RRs with manageable toxicity in cervical cancer. Investigation on larger series with longer follow-up is warranted., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)