ABSTRACT
OBJECTIVE: PARP (poly adenosine diphosphate [ADP]-ribose polymerase) inhibitors are approved as maintenance therapy in platinum sensitive ovarian cancer (OC), in first line and in the recurrent setting, regardless of BRCA mutational status. Real-world data after the introduction of these agents are needed to evaluate whether the benefit observed in phase III randomized clinical trials can be translated into clinical practice. The aim of our study was to provide real-life data on efficacy and safety of niraparib administered as maintenance in platinum sensitive relapsed OC patients (PSROC). METHODS: This retrospective/prospective observational study included relapsed OC patients that received niraparib as maintenance, at the time of platinum sensitive recurrence within the Italian expanded-access program. Clinical data at the time of diagnosis and at the time of recurrence were collected and analyzed. Median progression free survival (PFS) and overall survival (OS) were calculated as the time from start of niraparib treatment to subsequent radiologically confirmed relapse and death or last contact, respectively. RESULTS: Among 304 eligible patients, 260 (85%) had BRCA wild-type tumor and 36. (11.9%) were BRCA mutated. Median PFS was 9.1 months (95% CI: 6.9-11.2) and 10.3 months (95% CI: 7.0-13.5) in the BRCAwt and BRCAmut cohorts, respectively. Furthermore, median OS was 41.7 months (95% CI: 31.6-41.9) and 34.6 months (95% CI: N.E.) in the BRCAwt and BRCAmut cohorts, respectively. CONCLUSION: Data from this large real-life dataset suggested that maintenance with niraparib in the real-life setting of platinum sensitive OC recurrence is effective and well tolerated.
Subject(s)
Indazoles , Neoplasm Recurrence, Local , Ovarian Neoplasms , Piperidines , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Female , Piperidines/therapeutic use , Piperidines/administration & dosage , Piperidines/adverse effects , Indazoles/therapeutic use , Indazoles/administration & dosage , Indazoles/adverse effects , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Aged , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Neoplasm Recurrence, Local/drug therapy , Retrospective Studies , Adult , Prospective Studies , Aged, 80 and over , Maintenance Chemotherapy/methods , Progression-Free SurvivalABSTRACT
OBJECTIVE: To assess if the use of a V-Y reconstructive flap after excisional radical surgery positively influences the surgical outcomes in patients with vulvar cancer. METHODS: This was a multicenter, retrospective, controlled study. Surgical outcomes and complication rates of women with invasive vulvar cancer who underwent radical surgery and vulvar reconstruction and those who underwent radical surgery without the reconstruction step were compared. Only patients who underwent bilateral or unilateral V-Y advancement fascio-cutaneous flaps were included in the reconstruction group. Univariate and multivariate logistic regression models were used to analyze predicting variables for their association with complication rates. RESULTS: Overall, 361 patients were included: 190 (52%) underwent the reconstructive step after the excisional radical procedure and were compared with 171 (47.4%) who did not undergo the reconstructive step. At multivariate analysis, body mass index >30 kg/m2 (odds ratio (OR) 3.36, p=0.007) and diabetes (OR 2.62, p<0.022) were independently correlated with wound infection. Moreover, increasing age (OR 1.52, p=0.009), body mass index >30 kg/m2 (OR 3.21, p=0.002,) and International Federation of Gynecology and Obstetrics (FIGO) stages III-IV (OR 2.25, p=0.017) were independent predictors of wound dehiscence. A significant reduction in the incidence of postoperative wound complications among patients who underwent V-Y reconstructive flaps was demonstrated. This was correlated more significantly in women with lesions >4 cm. CONCLUSIONS: The adoption of V-Y flaps in vulvar surgery was correlated with reduced surgical related complications, particularly in vulnerable patients involving large surgical defects following excisional radical procedures.
Subject(s)
Plastic Surgery Procedures , Surgical Flaps , Vulvar Neoplasms , Humans , Female , Vulvar Neoplasms/surgery , Vulvar Neoplasms/pathology , Retrospective Studies , Middle Aged , Plastic Surgery Procedures/methods , Aged , Adult , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Aged, 80 and over , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathologyABSTRACT
BACKGROUND: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women's Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. OBJECTIVES: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. METHODS: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, PubMed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. OUTCOMES: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. CONCLUSION AND OUTLOOK: These formulations might provide effective options to best tailor therapies to each patient.
Subject(s)
Estrogen Replacement Therapy , Menopause , Female , Humans , Hormone Replacement Therapy , Drug Compounding , HormonesABSTRACT
OBJECTIVE: Endometrial carcinoma is the most common gynecological tumor in developed countries. Clinicopathological factors and molecular subtypes are used to stratify the risk of recurrence and to tailor adjuvant treatment. The present study aimed to assess the role of radiomics analysis in pre-operatively predicting molecular or clinicopathological prognostic factors in patients with endometrial carcinoma. METHODS: Literature was searched for publications reporting radiomics analysis in assessing diagnostic performance of MRI for different outcomes. Diagnostic accuracy performance of risk prediction models was pooled using the metandi command in Stata. RESULTS: A search of MEDLINE (PubMed) resulted in 153 relevant articles. Fifteen articles met the inclusion criteria, for a total of 3608 patients. MRI showed pooled sensitivity and specificity 0.785 and 0.814, respectively, in predicting high-grade endometrial carcinoma, deep myometrial invasion (pooled sensitivity and specificity 0.743 and 0.816, respectively), lymphovascular space invasion (pooled sensitivity and specificity 0.656 and 0.753, respectively), and nodal metastasis (pooled sensitivity and specificity 0.831 and 0.736, respectively). CONCLUSIONS: Pre-operative MRI-radiomics analyses in patients with endometrial carcinoma is a good predictor of tumor grading, deep myometrial invasion, lymphovascular space invasion, and nodal metastasis.
Subject(s)
Endometrial Neoplasms , Female , Humans , Lymphatic Metastasis , Endometrial Neoplasms/pathology , Magnetic Resonance Imaging/methods , Sensitivity and Specificity , Neoplasm Grading , Neoplasm InvasivenessABSTRACT
OBJECTIVE: Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS: This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS: Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION: Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.
Subject(s)
Endometrial Neoplasms , Neoplasm Staging , Endometrial Neoplasms/pathology , Female , Humans , Lymph Node Excision/methods , Lymph Nodes/pathology , Lymph Nodes/surgery , Retrospective Studies , Sentinel Lymph Node Biopsy/methodsABSTRACT
BACKGROUND: Cervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae. AIM: The purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy. METHODS: This is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period. OUTCOMES: Main outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function. RESULTS: Overall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P = .38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P = .016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P = .002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P = .03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P = .01) symptoms scales. CLINICAL IMPLICATIONS: The confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies. STRENGTHS AND LIMITATIONS: The study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design. CONCLUSION: LACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction. Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613-619.
Subject(s)
Quality of Life , Uterine Cervical Neoplasms , Case-Control Studies , Female , Humans , Hysterectomy , Neoadjuvant Therapy/adverse effects , Retrospective Studies , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/surgeryABSTRACT
OBJECTIVE: Comorbidity scores are increasingly used to reduce potential confounding in oncologic research. 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 are associated directly with 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.
Subject(s)
Endometrial Neoplasms , Proton Pump Inhibitors , Comorbidity , Endometrial Neoplasms/pathology , Female , Humans , Prognosis , Proportional Hazards Models , Retrospective StudiesABSTRACT
PURPOSE: We compared transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) for detecting myometrial infiltration, cervical involvement, and for measuring tumor volume in endometrial cancer patients. We also correlated tumor volume to worse histological prognostic factors. METHODS: We recruited women with a histological diagnosis of endometrial cancer between March 2019 and March 2021. Inclusion criteria were: age ≥ 18 years, written informed consent, biopsy-proven endometrial cancer, absence of previous neoadjuvant chemo- or radiotherapy treatment, patient suitable for primary surgery. Exclusion criteria were: advanced disease stage and other coexisting malignant tumors. TVUS and MRI were used, in the absence of any contraindication. We compared the preoperative imaging results with final histopathology. RESULTS: The accuracy of TVUS and MRI in evaluating myometrial infiltration, cervical invasion and tumor volume were comparable. A tumor volume ≥2 ml showed a positive correlation with worse histological prognostic factors, such as high tumor grade, diffuse lymphvascular space involvement (LVSI) and deep myometrial invasion (p < 0.05). CONCLUSION: TVUS should be used as first-line imaging modality, being more available, cost-effective, and more acceptable by patients. A careful local staging of endometrial cancer patients before surgery is fundamental in order to improve tailored treatment and minimize costs.
Subject(s)
Endometrial Neoplasms , Humans , Female , Adolescent , Prospective Studies , Prognosis , Neoplasm Invasiveness/pathology , Endometrial Neoplasms/diagnostic imaging , Endometrial Neoplasms/pathology , Myometrium/diagnostic imaging , Myometrium/pathology , Magnetic Resonance Imaging , Biomarkers , Neoplasm Staging , Sensitivity and SpecificityABSTRACT
OBJECTIVE: The purpose of this study was to evaluate the feasibility and safety in terms of prognostic significance and perioperative morbidity and mortality of cytoreduction in patients affected by advance ovarian cancer and hepato-biliary metastasis. METHODS: Patients with a least one hepatobiliary metastasis who have undergone surgical treatment with curative intent of were considered for the study. Perioperative complications were evaluated and graded with Accordion severity Classification. Five-year PFS and OS were estimated using the Kaplan-Meier curve. RESULTS: Sixty-seven (20.9%) patients had at least one metastasis to the liver, biliary tract, or porta hepatis. Forty-four (65.7%) and 23 (34.3%) patients underwent respectively high and intermediate complexity surgery according. Complete cytoreduction was achieved in 48 (71.6%) patients with hepato-biliary disease. In two patients (2.9%) severe complications related to hepatobiliary surgery were reported. The median PFS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) was 19 months [95% confidence interval (CI) 16.2-21.8] and 8 months (95% CI 6.1-9.9). The median OS for the patients with hepato-biliary involvement (RT = 0 vs. RT > 0) 45 months (95% CI 21.2-68.8 months) and 23 months (95% CI 13.9-32.03). CONCLUSIONS: Hepatobiliary involvement is often associated with high tumor load and could require high complex multivisceral surgery. In selected patients complete cytoreduction could offer survival benefits. Morbidity related to hepatobiliary procedures is acceptable. Careful evaluation of patients and multidisciplinary approach in referral centers is mandatory.
Subject(s)
Digestive System Diseases , Ovarian Neoplasms , Carcinoma, Ovarian Epithelial , Cytoreduction Surgical Procedures , Female , Humans , Ovarian Neoplasms/surgery , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of the present article was to discuss currently available evidence on the impact of frailty assessment on adverse postoperative outcomes and survival in patients undergoing surgery for gynecological cancer. METHODS: Systematic search of Medline (PubMed) and Embase databases until September 30, 2020. Key inclusion criteria were: (1) randomized or observational studies; (2) patients undergoing non-emergent surgery for gynecological malignancies; (3) preoperative frailty assessment. RESULTS: Through the process of evidence acquisition, twelve studies including 85,672 patients were selected and six tools were evaluable: 30-item frailty index, 40-item frailty index, modified frailty index (mFI), John Hopkins Adjusted Clinical Groups index, Fried frailty criteria, Driver's tool. The prevalence of frailty varied roughly from 6.1% to 60% across different series included. The mFI was the most adopted and predictive instrument. Pooled results underlined that frail patients were more likely to develop 30-day postoperative complications (OR:4.16; 95%CI 1.49-11.65; p:0.007), non-home discharge (OR:4.41; 95%CI: 4.09-4.76; p < 0.001), ICU admission (OR:3.99;3.76-4.24; p < 0.001) than the non-frail counterpart. Additionally, frail patients experienced worse oncologic outcomes (disease-free and overall survivals) than non-frail patients. CONCLUSION: The present systematic review demonstrated that preoperative frailty assessment among gynecologic oncology patients is essential to predict adverse outcomes and tailor a personalized treatment. The mFI appeared as the most used and feasible tool in daily practice, suggesting that tailored therapeutic strategies should be considered for patients with 3 or more frailty-defining items.
Subject(s)
Frailty/diagnosis , Genital Neoplasms, Female/surgery , Cytoreduction Surgical Procedures/methods , Female , Frailty/epidemiology , Gynecologic Surgical Procedures/methods , Humans , Observational Studies as Topic , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Preoperative Care/methods , Prognosis , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
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 AssessmentABSTRACT
INTRODUCTION: The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer. METHODS: This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. RESULTS: Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. CONCLUSION: Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.
Subject(s)
BRCA1 Protein/drug effects , BRCA2 Protein/drug effects , Carcinoma, Ovarian Epithelial/drug therapy , Cytoreduction Surgical Procedures/methods , Neoplasm Recurrence, Local/drug therapy , Phthalazines/therapeutic use , Piperazines/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Carcinoma, Ovarian Epithelial/mortality , Female , Humans , Middle Aged , Mutation , Phthalazines/pharmacology , Piperazines/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Progression-Free Survival , Retrospective StudiesABSTRACT
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 , PrognosisABSTRACT
Patients with metastatic and recurrent cervical cancer (CC) have a poor prognosis with limited palliative treatment options. Increasing understanding of the cellular aberrations inherent to cancer cells has allowed the development of therapies to target biological pathways, an important step toward the individualization of cancer therapy. The poly (ADP-ribose) polymerase (PARP) family of enzymes is important in several DNA repair pathways. Drugs that inhibit these PARP enzymes have been investigated in many types of cancer and their application in the treatment of gynecologic malignancies has rapidly evolved. Although the majority of data for PARPi in gynecologic malignancies has been specifically regarding ovarian cancer, their role in the treatment of uterine and CC is currently being investigated. This review will examine PARP inhibitors in CC, summarizes the critical clinical trials of PARP inhibitors that have been completed, provides an overview of the on-going trials, presents the confirmed conclusions and notes the issues that need to be addressed in future studies.
Subject(s)
Neoplasm Recurrence, Local/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerases/genetics , Uterine Cervical Neoplasms/drug therapy , Adenosine Diphosphate/genetics , Antineoplastic Agents/therapeutic use , Female , Humans , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: Endometrial cancer currently represents the most frequent gynecologic malignancy in Western countries, and the seventh most common cancer in women. For advanced-stage disease, the recurrence risk is high, and the site of the relapse is heterogeneous with localized or spread peritoneal disease. There are few therapeutic strategies, and the quality of life is poor. CASES PRESENTATION: We present 3 cases of peritoneal-spread recurrences of endometrial cancer in patients with advanced stage at diagnosis. The patients had been subjected to multiple lines of chemotherapy including re-challenging with platinum regimens, pegylated liposomal doxorubicin, and taxane, with progression of disease. These patients came to us with abdominal distension, dyspnea, elevated CA 125, and presence of ascites. After paracentesis with a single administration of intraperitoneal chemotherapy based on carboplatin, all 3 patients showed improvement in their quality of life and breathing as well as reduction of fatigue and anorexia. No complications occurred. CONCLUSION: Although only 3 cases are reported, the exceptional results and the absence of side effects observed strongly warrant future trials to investigate the role intraperitoneal chemotherapy can have both as palliative treatment of refractory ascites and as salvage therapy in advanced endometrial cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ascites/pathology , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Drug Resistance, Neoplasm , Female , Humans , Infusions, Parenteral , Middle Aged , Neoplasm Staging , Recurrence , Retreatment , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
OBJECTIVES: To analyze the diagnostic accuracy of two-dimensional (2D) and three-dimensional transvaginal ultrasound (3D TV-US) for evaluation of parametrial status in locally advanced cervical cancer patients after neoadjuvant chemotherapy (NACT), using histology as the gold standard. METHODS: Consecutive patients with histologically confirmed cervical cancer were staged according to FIGO (International Federation of Gynaecology and Obstetrics) criteria. All IB2-IIIB FIGO stage patients were examined by 2D and 3D TV-US and magnetic resonance imaging (MRI) at the diagnosis time (T0) and after NACT. At T0, the US evaluation of parametrial involvement was compared to MRI before treatment. The results of US and MRI examinations of parametrial status after NACT were compared with the histological specimen. RESULTS: We enroled 51 consecutive patients in the study. Before chemotherapy, clinical examination under anaesthesia identified parametrial involvement in 48 patients, ultrasonography in 46 patients, and MRI in 49 patients. The agreement between US and MRI was 94%. The sensitivity of US for parametrial status was 93.8%, with a positive predictive value of 97.8%, using MRI as the standard. The correlation between US and MRI was statistically significant (p = 0). After chemotherapy, histological examination of surgical specimens identified parametrial involvement in 3 patients. Ultrasonography correctly identified those cases with parametrial infiltration, recording a sensitivity of 100%, specificity of 90.9%, positive predictive value of 50%, and negative predictive value of 100%. The MRI had a sensitivity of 100%, specificity of 45.5%, positive predictive value of 14.3%, and negative predictive value of 100%, respectively. The concordance in the identification of the presence/absence of infiltration between US and MRI with histology was 90% (p = 0.001) and 61%, respectively, after chemotherapy treatment. Particularly, in defining the degree of infiltration, the agreement between US and MRI with histology was 90 and 58%, respectively. CONCLUSION: In locally advanced cervical cancer patients, 2D/3D TV-US can be considered accurate in the evaluation of parametrial infiltration to assess the response to NACT. It could be included as a diagnostic method in the preoperative work-up of cervical cancer.
Subject(s)
Imaging, Three-Dimensional/methods , Ultrasonography, Doppler/methods , Uterine Cervical Neoplasms/diagnostic imaging , Uterine Cervical Neoplasms/drug therapy , Chemotherapy, Adjuvant , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Positron Emission Tomography Computed Tomography/methods , Prospective Studies , Uterine Cervical Neoplasms/pathologyABSTRACT
PURPOSE: The objective of this study was to evaluate the impact of hormone replacement therapy (HRT) on the prognosis in endometrial cancer (EC) survivors. METHODS: The research was conducted using the following electronic databases: MEDLINE (PubMed), Web of Science, ClinicalTrial.gov, and Cochrane Library. We performed a review of studies published from January 1986 to January 2019. We selected studies that included EC patients submitted to surgery with curative intent and postoperative use of HRT. RESULT: Seven of 1,332 abstracts considered were eligible: 4 retrospective series, 1 prospective study, 1 randomized controlled trial, and 1 population study. Globally in the observed studies there was not a significant increase in the recurrence rate, measured by the relative risk, in the EC survivors using HRT compared with the controls in tumour stages I and II. The bias was that HRT was prescribed only to low-risk patients, who were young and had a low stage of disease. CONCLUSION: This systematic review shows that HRT use had no negative effect on prognosis in EC survivors in tumour stages I and II.
Subject(s)
Cancer Survivors , Endometrial Neoplasms/mortality , Hormone Replacement Therapy , Endometrial Neoplasms/drug therapy , Female , Humans , Neoplasm Recurrence, Local/epidemiology , PrognosisABSTRACT
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/surgeryABSTRACT
The aim of the present study was to evaluate the effect of medical treatment of ovarian endometriomas on cyst diameter, associated pain, and ovarian reserve as measured with antral follicle count (AFC) and anti-Mullerian hormone (AMH). In this prospective study, 32 patients with unilateral endometrioma associated with pelvic pain, underwent 6-month medical treatment with dienogest. Before treatment, and at the end of 6 months of treatment, patients underwent evaluation of endometrioma diameter and AFC at transvaginal ultrasonography, measurement of AMH, and evaluation of associated pain. Mean cyst diameter was 4.0 ± 1.3 cm at baseline, and 2.4 ± 1.2 cm after 6 months of treatment (p < .0001), for a reduction in diameter of 40% and a reduction in volume of 79%. Mean visual analog scale score at enrollment was 6.3 ± 2.0, with a significant improvement at 6 months (0.9 ± 1.0, p < .0001). AFC for the affected ovary improved from 4.2 ± 2.8 at baseline, to 8.6 ± 4.2 cm after 6 months (+105%; p < .0001). AMH did not change significantly from baseline (3.40 ± 2.32 ng/mL) to end of treatment (2.80 ± 1.90 ng/mL, -18%, p = .27). Medical treatment with dienogest significantly reduces endometrioma diameter and associated pain, whereas the ovarian reserve appears to be preserved, with a significant improvement of AFC and no significant change in AMH.
Subject(s)
Endometriosis/drug therapy , Hormone Antagonists/therapeutic use , Nandrolone/analogs & derivatives , Ovarian Diseases/drug therapy , Ovarian Follicle/diagnostic imaging , Ovarian Reserve , Pelvic Pain/physiopathology , Adult , Anti-Mullerian Hormone/metabolism , Endometriosis/complications , Endometriosis/diagnostic imaging , Endometriosis/physiopathology , Female , Humans , Nandrolone/therapeutic use , Ovarian Diseases/complications , Ovarian Diseases/diagnostic imaging , Ovarian Diseases/physiopathology , Pain Measurement , Pelvic Pain/etiology , Treatment Outcome , UltrasonographyABSTRACT
BACKGROUND: Chemotherapy at the end of life is a complex and challenging problem in medical oncology. Patients affected by ovarian cancer (OC) often experience a chronicization and slow progression of their disease, and chemotherapy is proposed until the end of life. METHODS: We retrospectively analyzed data from patients affected by OC treated at our department and having died in the period between 2007 and 2017 and evaluated the frequency of antineoplastic treatments until the end of life, the chemotherapy-related toxicity, mortality, and the most frequent palliative care measure adopted. RESULTS: A total of 110 OC deaths, after a median overall patient survival of 52.8 months (range 4-232), were analyzed. 77.3% of the patients presented with FIGO stage IIIC OC at diagnosis and 12.7% with FIGO stage IV OC. 89% of the histological types were serous papillary. The median age was 55 years (range 31-82) at diagnosis and 60 years (range 33-84) at death. Of the 110 patients analyzed, 85 (77%) had undergone chemotherapy over the last 3 months of life and 38% had chemotherapy even during the last month of life. The overwhelming majority of patients (81%) needed supportive therapies. Despite the treatments received, the majority of the patients died at home, 19% died in hospital, and only 4.5% died in hospice. The quality of life of these patients decreased dramatically in the last 30 days, but best supportive care improved the symptoms. CONCLUSIONS: End-of-life chemotherapy for OC patients is a thorny problem. More studies and a multidisciplinary approach are needed to better treat these patients.