Ivana Rizzuto - Academia.edu (original) (raw)
Papers by Ivana Rizzuto
Case Reports in Oncology, 2022
This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who prese... more This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.
Cochrane Database of Systematic Reviews, 2020
Early surgical treatment versus observational management for cervical intraepithelial neoplasia 2... more Early surgical treatment versus observational management for cervical intraepithelial neoplasia 2 (CIN2) (Protocol).
Cochrane Database of Systematic Reviews, 2021
Trusted evidence. Informed decisions. Better health.
The current study was carried out to evaluate the oncological outcomes in patients with borderlin... more The current study was carried out to evaluate the oncological outcomes in patients with borderline ovarian tumours (BOT) according to type of surgery (conservative surgery versus radical surgery), surgical approach, laterality of the tumour and histopathological parameters.
ePoster, 2019
Introduction/Background The current study was carried out to evaluate the oncological outcomes in... more Introduction/Background The current study was carried out to evaluate the oncological outcomes in patients with borderline ovarian tumours (BOT) according to type of surgery (conservative surgery versus radical surgery), stage at diagnosis and clinicopathological parameters. Methodology We enrolled patients with BOT of any FIGO stage, whom were surgically treated from 2005 to 2013 at the Gynecological Oncology Department of the Ipswich hospital, UK. The prognostic effects of stage, clinico-pathological features (micropapillary lesions, invasive implants and bilateral tumors) and surgical variables were evaluated using univariate/multivariate analysis. Results A total of 85 eligible patients were enrolled in the analysis. We had 42/85(49%) with serous, 35/85 (41%) with mucinous, 5/85(6%) with mixed mucinous-serous, 3/85 (4%) with endometroid histological subtypes. Among all the cohort of patients, 14/85 (16%) had recurrence within 5 years of follow-up. Multivariate analysis showed a significant association to relapse in the presence of micropapillary lesions and invasive implants at the histological report with RR 1.39 (95% CI 1.39–2.73) p -value < 0.001 and RR 4.44 (95% CI 2.26–8.69) p -value 0.002 respectively. FIGO stage RR 0.56 (95% CI 0.23–1.33) p -value 0.153, the presence of bilateral tumours RR 2.02 (95% CI 0.95–4.31) p -value 0.099 and conservative surgery RR 1.25 (95% CI 0.41–3.81) p -value 0.709 were not significantly associated to higher recurrence rate. Conclusion We confirm that BOT patients with micropapillary lesions and invasive implants have high risk of recurrence. These data can support clinicians in tailoring the best surgical strategy in young patients with BOT and in counseling patient about their prognosis after the diagnosis. Disclosure Nothing to disclose.
Gynecologic Oncology Reports, 2019
We evaluated the association between risk factors for endometrial cancer (EC) and sonographic end... more We evaluated the association between risk factors for endometrial cancer (EC) and sonographic endometrial thickness (ET) with FIGO stages at diagnosis. We also reported our experience in reliability of sonographic ET as screening tool for either histologic subtype I and II of EC. It was a case series study including 339 patients diagnosed with EC from 2010 to 2017 at the Ipswich Hospital, UK. Women with higher body mass index (BMI) presented at earlier stages when compared to women with lower BMIs (p-value = .046). By contrast, none of the variables: parity (p-value = .1630), use of HRT (p-value 0.7448), tamoxifen (p-value 0.0733) and diabetes (pvalue = .1665) were statistically associated to FIGO stages. The mean of ET measurement was not statistically significant associated (p-value 0.0625) to stages. There was no statistic difference on mean ET at diagnosis between histologic subtypes I or II (p-value 0.804). According to our experience, BMI is associated to FIGO stage and endometrial sampling (ES) should be included in the working diagnosis of EC to obtain an early diagnosis in women with high BMIs even in premenopausal. Ultrasonographic measurement of the endometrium is equally reliable at determining cancer, but not at differentiating histologic subtypes I and II uterine cancers. However, ET does not correlate to FIGO stages at diagnosis.
Gynecologic Oncology Reports, 2019
We report the use of radical vaginal trachelectomy (RVT) with pelvic laparoscopic lymphadenectomy... more We report the use of radical vaginal trachelectomy (RVT) with pelvic laparoscopic lymphadenectomy (LPL) in patients with early stages cervical cancer (FIGO stage IA2-IB1). This is a case series prospectively collected over a 6-year period (2011-2017) at the Ipswich hospital, UK. Cases were compared to a group of women with a similar stage of cervical cancer, but treated with radical hysterectomy (RH) and pelvic lymphadenectomy (PL). A total of 19 patients (group 1) underwent RVT and LPL, and 51 (group 2) had RH and PL. We included: 5/19 (26%) stage IA2 and 14/19 (74%) stage IB1. Among those, we had: 12/19 (63%) cases of squamous cell carcinoma (SCC), 7/ 19(37%) of adenocarcinoma. Mean hospital stay was 2.7 days (range 2-4) in group 1 versus 4.8 days (range 3-8) group 2 (p-value = 0.173). The complication rate was not statistically different between the two groups 4/ 19(21%) and 7/51(14%) (p-value 0.169). The mean follow-up period was 47.3 months (range 7-78) in both groups. There were no cases of recurrence in group 1 and 2/51(4%) cases in group 2, but the difference was not significant (p-value = 0.497). In our experience RVT in well-selected patients is a safe treatment option with similar oncological outcomes when compared to patients undergoing more extensive surgery for the same early stage cervical cancer.
Journal of Clinical Oncology, 2015
Journal of Clinical Oncology, 2015
Journal of Clinical Oncology, 2014
ABSTRACT Background: Acelarin (NUC-1031) is a first-in-class nucleotide designed to overcome key ... more ABSTRACT Background: Acelarin (NUC-1031) is a first-in-class nucleotide designed to overcome key cancer cell resistance by having nucleoside transporter-independent cellular uptake, activity independent of deoxycytidine kinase and being resistant to cytidine deaminase inactivation. Methods: The ProGem1 study objectives were to establish the MTD, PK, safety profile and clinical activity of Acelarin in patients with advanced, rapidly progressing treatment-resistant or refractory solid tumours. Acelarin was administered by 10 minute IV injection on a weekly (D1, 8 and 15 of a Q28 schedule), or twice weekly schedule, for 6 cycles. Acelarin doses ranged from 375 to 1000 mg/m2. Compassionate use was allowed after 6 cycles for those benefiting from treatment. Results: To date, 29 patients (pts), with a mean age of 57 yrs (range 35-73 yrs), have been enrolled with: ovarian (5), breast (3), colorectal (3), mesothelioma (3), CUP (3), uterine (3), pancreatic (3), cholangiocarcinoma (2), lung (2), and other (2) primary disease. 26 pts had metastatic disease. Pts had received a mean of 2.6 prior lines of therapy (range 1-7). DLTs were: G3 raised AST in 1/6 at 725mg/m2; G4 thrombocytopenia in 1/6 at 750mg/m2; G4 injection site pain in 1 at 1000mg/m2; and G4 thrombocytopenia in 1/6 at 375mg/m2 twice weekly. The most common (>20%) adverse events (AEs) were grade 1-2, and reversible: thrombocytopenia (22%), fatigue (22%), and hypoalbuminaemia (21%). High intracellular levels of the active anti-cancer agent dFdCTP were rapidly achieved and maintained for 24 hours, confirming Acelarin’s ability to bypass the key resistance pathways. Responses evaluated by RECIST were: 5 PR (17%); 13 SD (45%); with an ITT Disease Control Rate (DCR) of 62%; and, an OTA DCR of 90% in patients refractory or resistant to standard chemotherapy. All 6 pts who received ≥2 cycles of Acelarin, and were refractory / relapsed on prior gemcitabine, achieved disease control. Disease control in all patients has been durable (range 3 to >12 months; mean 5.8 months). Conclusions: Acelarin is a well tolerated, first-in-class nucleotide that has achieved a high, durable Disease Control Rate (ITT 62%; OTA 90%) in a wide range of advanced refractory / resistant cancers. Clinical trial information: NCT01621854.
British Journal of Cancer, 2018
BACKGROUND: Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by ... more BACKGROUND: Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to enter the clinic and is designed to overcome these key resistance mechanisms. METHODS: Sixty-eight patients with advanced solid tumours who had relapsed after treatment with standard therapy were recruited to a dose escalation study to determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031. Pharmacokinetics and anti-tumour activity was also assessed. RESULTS: Sixty-eight patients received treatment, 50% of whom had prior exposure to gemcitabine. NUC-1031 was well tolerated with the most common Grade 3/4 adverse events of neutropaenia, lymphopaenia and fatigue occurring in 13 patients each (19%). In 49 response-evaluable patients, 5 (10%) achieved a partial response and 33 (67%) had stable disease, resulting in a 78% disease control rate. C max levels of the active intracellular metabolite, dFdCTP, were 217-times greater than those reported for equimolar doses of gemcitabine, with minimal toxic metabolite accumulation. The RP2D was determined as 825 mg/m 2 on days 1, 8 and 15 of a 28-day cycle. CONCLUSIONS: NUC-1031 was well tolerated and demonstrated clinically significant anti-tumour activity, even in patients with prior gemcitabine exposure and in cancers not traditionally perceived as gemcitabine-responsive.
Pharmacogenomics, 2017
Gemcitabine is an anticancer agent acting against several solid tumors. It requires nucleoside tr... more Gemcitabine is an anticancer agent acting against several solid tumors. It requires nucleoside transporters for cellular uptake and deoxycytidine kinase for activation into active gemcitabine-triphosphate, which is incorporated into the DNA and RNA. However, it can also be deaminated in the plasma. The intracellular level of gemcitabine-triphosphate is affected by scheduling or by combination with other chemotherapeutic regimens. Moreover, higher concentrations of gemcitabine-triphosphate may affect the toxicity, and possibly the clinical efficacy. As a consequence, different nucleoside analogs have been synthetized with the aim to increase the concentration of gemcitabine-triphosphate into cells. In this review, we summarize currently published evidence on pharmacological factors affecting the intracellular level of gemcitabine-triphosphate to guide future trials on the use of new nucleoside analogs.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 27, 2017
Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpr... more Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients we...
Journal of Gynecologic Surgery, 2014
Objective: The purpose of this study was to evaluate differences in outcomes on the basis of body... more Objective: The purpose of this study was to evaluate differences in outcomes on the basis of body mass index (BMI) in patients undergoing laparoscopic hysterectomy. Design: The study was a retrospective analysis. Methods: All cases of laparoscopic hysterectomy performed from May 2008 to May 2012 for benign, microinvasive cervical, early endometrial, and occult ovarian carcinoma were reviewed. There were 347 patients analyzed by BMI. As proposed by the World Health Organization classification system of obesity, patients were categorized by BMI. Ideal BMI was defined as being between 18.5 and 24.9 kg/m 2 , overweight was defined as having a BMI between 25 and 29.9 mg/m 2 , and obesity was defined as having a BMI ‡ 30 kg/m 2. Laparoscopic surgery was completed successfully in 338 patients, and 9 patients had their surgery converted to laparotomy for findings at the surgery, not for complications relating to the surgery, and, therefore, were excluded from the analysis. Results: Mean age was 51.1 years in the ideal group, 50.45 in the overweight group, and 55.49 in the obese group. The patients' ages ranged in all the samples between 31 and 94 years (p < 0.003). Mean operating time was 105.5 minutes, mean blood loss was 252 mL, and mean length of hospital stay was 2.4 days. There was not a significant difference among the three groups. Total major complication rate was 3.7% and early postoperative complication rate was 5. There was not a significant difference among the three groups. Urologic injury was present in 0.6% of all patients. Conclusions: Laparoscopic hysterectomy is feasible and safe, resulting in short hospital stay, minimal blood loss, and minimal operating time for patients in all BMI groups. The laparoscopic approach may extend the benefits of minimally invasive hysterectomy to the very obese, for whom abdominal surgery poses serious risk.
Gynecologic and Obstetric Investigation, 2015
Background/Aims: Operative laparoscopy (OL) is considered the gold standard surgical treatment of... more Background/Aims: Operative laparoscopy (OL) is considered the gold standard surgical treatment of ectopic pregnancy (EP). We questioned whether a training programme to foster OL treatment is able to ensure that all women needing surgical management are treated by OL irrespective of the site of EP, haemodynamic status and clinical complexity. Methods: A 13-year cohort study of 963 women who underwent surgical management was conducted. We instituted a ‘universal OL' programme in 2003 for the management of all the types of EP irrespective of the haemodynamic status. Results: There were 802 women in the prospective (2003-2013) and 161 in the retrospective arm (2000-2002). The rate of OL before 2003 was 34%. During the year of programme implementation, the OL rate rose from 89% in 2003 to 96% in 2004. It took 4 years to achieve a 100% OL rate in haemodynamically stable patients. In 2013, we were able to achieve OL treatment for all patients irrespective of haemodynamic status, the co...
International Journal of Gynecological Cancer, 2015
The aim of this study was to construct a prognostic index that predicts risk of relapse in women ... more The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods: A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results: Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (G0.33), intermediate (0.34Y0.67), and high (90.67) probability of relapse. Conclusions: The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support.
Protocols, 2010
... meta analysis. Obstetrics and Gynecology 2004;103:785–94. Mahdavi 2006 Mahdavi A, Pejovic T, ... more ... meta analysis. Obstetrics and Gynecology 2004;103:785–94. Mahdavi 2006 Mahdavi A, Pejovic T, Nezhat F. Induction of ovulation and ovarian cancer: a critical review of the literature. Fertility and Sterility 2006; 85(4):819–26. 6 ...
The Lancet Oncology, 2013
Background Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutat... more Background Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and altered end-organ hormone sensitivity might explain this organ-specifi c penetrance. We sought to identify diff erences in hormone regulation between carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations. Methods We assessed endometrial thickness for each menstrual cycle day (as an index of hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754 women known to be negative for the mutations. To quantify diff erences in endometrial thickness we focused on days 10-14 and days 21-26, and calculated the area under the curve. We then compared serum oestradiol and progesterone titres during these days of the menstrual cycle in the same groups. Follicular and luteal oestradiol and progesterone serum titres were grouped into quartiles and odds ratios were calculated with logistic regression. Findings Follicular phase endometrial thickness of carriers of the mutations adjusted for age and day of the menstrual cycle was higher (odds ratio [OR] 1•11, 95% CI 1•03-1•20; p=0•0063) and luteal phase endometrial thickness lower (0•90, 0•83-0•98; p=0•027) than for women negative for the mutations. Median luteal phase titres of progesterone were 121% higher (p=0•00037) in carriers than in women negative for the mutations, and for oestradiol were 33% higher (p=0•007)-ie, 59% of carriers had concentrations of serum progesterone that would have been in the top quartile of concentrations in the control group (OR 8•0, 95% CI 2•1-52•57; p=0•008). Interpretation Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesteroneknown risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women. Our fi ndings could not be explained by diff erential contraceptive pill use.
Journal of Minimally Invasive Gynecology, 2007
from 2003 to 2006. This difference was statistically significant (p less than 0.001). In 2006, 96... more from 2003 to 2006. This difference was statistically significant (p less than 0.001). In 2006, 96% of women requiring surgery were managed by laparoscopic surgery. Conclusion: The findings of this study indicate that it is possible to implement changes which increase and sustain a high rate of laparoscopic surgery for women with ectopic pregnancy requiring surgery in a district general hospital setting.
Case Reports in Oncology, 2022
This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who prese... more This report describes a highly unusual case of malignant peritoneal mesothelioma (MPM), who presented with abnormal menstrual bleeding due to diffuse infiltration of the uterus. MPM is a rare entity, which on initial clinical presentation can be indistinguishable from a primary gynecological malignancy such as ovarian cancer. As differential diagnosis is challenging among primary care physicians, gynecologists, gynecological oncologists, and pathologists, misdiagnosis and subsequent mismanagement are not uncommon. Immunohistochemical stains were required in our case to help to make the final diagnosis. We included multiple mesothelial markers such as calretinin, CK5/6, WT-1, and D240 in our analysis, in addition to epithelial markers such as Claudin-4, BerEP4, B72.3, and PAX-8, to exclude metastatic adenocarcinoma.
Cochrane Database of Systematic Reviews, 2020
Early surgical treatment versus observational management for cervical intraepithelial neoplasia 2... more Early surgical treatment versus observational management for cervical intraepithelial neoplasia 2 (CIN2) (Protocol).
Cochrane Database of Systematic Reviews, 2021
Trusted evidence. Informed decisions. Better health.
The current study was carried out to evaluate the oncological outcomes in patients with borderlin... more The current study was carried out to evaluate the oncological outcomes in patients with borderline ovarian tumours (BOT) according to type of surgery (conservative surgery versus radical surgery), surgical approach, laterality of the tumour and histopathological parameters.
ePoster, 2019
Introduction/Background The current study was carried out to evaluate the oncological outcomes in... more Introduction/Background The current study was carried out to evaluate the oncological outcomes in patients with borderline ovarian tumours (BOT) according to type of surgery (conservative surgery versus radical surgery), stage at diagnosis and clinicopathological parameters. Methodology We enrolled patients with BOT of any FIGO stage, whom were surgically treated from 2005 to 2013 at the Gynecological Oncology Department of the Ipswich hospital, UK. The prognostic effects of stage, clinico-pathological features (micropapillary lesions, invasive implants and bilateral tumors) and surgical variables were evaluated using univariate/multivariate analysis. Results A total of 85 eligible patients were enrolled in the analysis. We had 42/85(49%) with serous, 35/85 (41%) with mucinous, 5/85(6%) with mixed mucinous-serous, 3/85 (4%) with endometroid histological subtypes. Among all the cohort of patients, 14/85 (16%) had recurrence within 5 years of follow-up. Multivariate analysis showed a significant association to relapse in the presence of micropapillary lesions and invasive implants at the histological report with RR 1.39 (95% CI 1.39–2.73) p -value < 0.001 and RR 4.44 (95% CI 2.26–8.69) p -value 0.002 respectively. FIGO stage RR 0.56 (95% CI 0.23–1.33) p -value 0.153, the presence of bilateral tumours RR 2.02 (95% CI 0.95–4.31) p -value 0.099 and conservative surgery RR 1.25 (95% CI 0.41–3.81) p -value 0.709 were not significantly associated to higher recurrence rate. Conclusion We confirm that BOT patients with micropapillary lesions and invasive implants have high risk of recurrence. These data can support clinicians in tailoring the best surgical strategy in young patients with BOT and in counseling patient about their prognosis after the diagnosis. Disclosure Nothing to disclose.
Gynecologic Oncology Reports, 2019
We evaluated the association between risk factors for endometrial cancer (EC) and sonographic end... more We evaluated the association between risk factors for endometrial cancer (EC) and sonographic endometrial thickness (ET) with FIGO stages at diagnosis. We also reported our experience in reliability of sonographic ET as screening tool for either histologic subtype I and II of EC. It was a case series study including 339 patients diagnosed with EC from 2010 to 2017 at the Ipswich Hospital, UK. Women with higher body mass index (BMI) presented at earlier stages when compared to women with lower BMIs (p-value = .046). By contrast, none of the variables: parity (p-value = .1630), use of HRT (p-value 0.7448), tamoxifen (p-value 0.0733) and diabetes (pvalue = .1665) were statistically associated to FIGO stages. The mean of ET measurement was not statistically significant associated (p-value 0.0625) to stages. There was no statistic difference on mean ET at diagnosis between histologic subtypes I or II (p-value 0.804). According to our experience, BMI is associated to FIGO stage and endometrial sampling (ES) should be included in the working diagnosis of EC to obtain an early diagnosis in women with high BMIs even in premenopausal. Ultrasonographic measurement of the endometrium is equally reliable at determining cancer, but not at differentiating histologic subtypes I and II uterine cancers. However, ET does not correlate to FIGO stages at diagnosis.
Gynecologic Oncology Reports, 2019
We report the use of radical vaginal trachelectomy (RVT) with pelvic laparoscopic lymphadenectomy... more We report the use of radical vaginal trachelectomy (RVT) with pelvic laparoscopic lymphadenectomy (LPL) in patients with early stages cervical cancer (FIGO stage IA2-IB1). This is a case series prospectively collected over a 6-year period (2011-2017) at the Ipswich hospital, UK. Cases were compared to a group of women with a similar stage of cervical cancer, but treated with radical hysterectomy (RH) and pelvic lymphadenectomy (PL). A total of 19 patients (group 1) underwent RVT and LPL, and 51 (group 2) had RH and PL. We included: 5/19 (26%) stage IA2 and 14/19 (74%) stage IB1. Among those, we had: 12/19 (63%) cases of squamous cell carcinoma (SCC), 7/ 19(37%) of adenocarcinoma. Mean hospital stay was 2.7 days (range 2-4) in group 1 versus 4.8 days (range 3-8) group 2 (p-value = 0.173). The complication rate was not statistically different between the two groups 4/ 19(21%) and 7/51(14%) (p-value 0.169). The mean follow-up period was 47.3 months (range 7-78) in both groups. There were no cases of recurrence in group 1 and 2/51(4%) cases in group 2, but the difference was not significant (p-value = 0.497). In our experience RVT in well-selected patients is a safe treatment option with similar oncological outcomes when compared to patients undergoing more extensive surgery for the same early stage cervical cancer.
Journal of Clinical Oncology, 2015
Journal of Clinical Oncology, 2015
Journal of Clinical Oncology, 2014
ABSTRACT Background: Acelarin (NUC-1031) is a first-in-class nucleotide designed to overcome key ... more ABSTRACT Background: Acelarin (NUC-1031) is a first-in-class nucleotide designed to overcome key cancer cell resistance by having nucleoside transporter-independent cellular uptake, activity independent of deoxycytidine kinase and being resistant to cytidine deaminase inactivation. Methods: The ProGem1 study objectives were to establish the MTD, PK, safety profile and clinical activity of Acelarin in patients with advanced, rapidly progressing treatment-resistant or refractory solid tumours. Acelarin was administered by 10 minute IV injection on a weekly (D1, 8 and 15 of a Q28 schedule), or twice weekly schedule, for 6 cycles. Acelarin doses ranged from 375 to 1000 mg/m2. Compassionate use was allowed after 6 cycles for those benefiting from treatment. Results: To date, 29 patients (pts), with a mean age of 57 yrs (range 35-73 yrs), have been enrolled with: ovarian (5), breast (3), colorectal (3), mesothelioma (3), CUP (3), uterine (3), pancreatic (3), cholangiocarcinoma (2), lung (2), and other (2) primary disease. 26 pts had metastatic disease. Pts had received a mean of 2.6 prior lines of therapy (range 1-7). DLTs were: G3 raised AST in 1/6 at 725mg/m2; G4 thrombocytopenia in 1/6 at 750mg/m2; G4 injection site pain in 1 at 1000mg/m2; and G4 thrombocytopenia in 1/6 at 375mg/m2 twice weekly. The most common (>20%) adverse events (AEs) were grade 1-2, and reversible: thrombocytopenia (22%), fatigue (22%), and hypoalbuminaemia (21%). High intracellular levels of the active anti-cancer agent dFdCTP were rapidly achieved and maintained for 24 hours, confirming Acelarin’s ability to bypass the key resistance pathways. Responses evaluated by RECIST were: 5 PR (17%); 13 SD (45%); with an ITT Disease Control Rate (DCR) of 62%; and, an OTA DCR of 90% in patients refractory or resistant to standard chemotherapy. All 6 pts who received ≥2 cycles of Acelarin, and were refractory / relapsed on prior gemcitabine, achieved disease control. Disease control in all patients has been durable (range 3 to >12 months; mean 5.8 months). Conclusions: Acelarin is a well tolerated, first-in-class nucleotide that has achieved a high, durable Disease Control Rate (ITT 62%; OTA 90%) in a wide range of advanced refractory / resistant cancers. Clinical trial information: NCT01621854.
British Journal of Cancer, 2018
BACKGROUND: Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by ... more BACKGROUND: Gemcitabine is used to treat a wide range of tumours, but its efficacy is limited by cancer cell resistance mechanisms. NUC-1031, a phosphoramidate modification of gemcitabine, is the first anti-cancer ProTide to enter the clinic and is designed to overcome these key resistance mechanisms. METHODS: Sixty-eight patients with advanced solid tumours who had relapsed after treatment with standard therapy were recruited to a dose escalation study to determine the recommended Phase II dose (RP2D) and assess the safety of NUC-1031. Pharmacokinetics and anti-tumour activity was also assessed. RESULTS: Sixty-eight patients received treatment, 50% of whom had prior exposure to gemcitabine. NUC-1031 was well tolerated with the most common Grade 3/4 adverse events of neutropaenia, lymphopaenia and fatigue occurring in 13 patients each (19%). In 49 response-evaluable patients, 5 (10%) achieved a partial response and 33 (67%) had stable disease, resulting in a 78% disease control rate. C max levels of the active intracellular metabolite, dFdCTP, were 217-times greater than those reported for equimolar doses of gemcitabine, with minimal toxic metabolite accumulation. The RP2D was determined as 825 mg/m 2 on days 1, 8 and 15 of a 28-day cycle. CONCLUSIONS: NUC-1031 was well tolerated and demonstrated clinically significant anti-tumour activity, even in patients with prior gemcitabine exposure and in cancers not traditionally perceived as gemcitabine-responsive.
Pharmacogenomics, 2017
Gemcitabine is an anticancer agent acting against several solid tumors. It requires nucleoside tr... more Gemcitabine is an anticancer agent acting against several solid tumors. It requires nucleoside transporters for cellular uptake and deoxycytidine kinase for activation into active gemcitabine-triphosphate, which is incorporated into the DNA and RNA. However, it can also be deaminated in the plasma. The intracellular level of gemcitabine-triphosphate is affected by scheduling or by combination with other chemotherapeutic regimens. Moreover, higher concentrations of gemcitabine-triphosphate may affect the toxicity, and possibly the clinical efficacy. As a consequence, different nucleoside analogs have been synthetized with the aim to increase the concentration of gemcitabine-triphosphate into cells. In this review, we summarize currently published evidence on pharmacological factors affecting the intracellular level of gemcitabine-triphosphate to guide future trials on the use of new nucleoside analogs.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 27, 2017
Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpr... more Purpose To establish the performance of screening with serum cancer antigen 125 (CA-125), interpreted using the risk of ovarian cancer algorithm (ROCA), and transvaginal sonography (TVS) for women at high risk of ovarian cancer (OC) or fallopian tube cancer (FTC). Patients and Methods Women whose estimated lifetime risk of OC/FTC was ≥ 10% were recruited at 42 centers in the United Kingdom and underwent ROCA screening every 4 months. TVS occurred annually if ROCA results were normal or within 2 months of an abnormal ROCA result. Risk-reducing salpingo-oophorectomy (RRSO) was encouraged throughout the study. Participants were observed via cancer registries, questionnaires, and notification by centers. Performance was calculated after censoring 365 days after prior screen, with modeling of occult cancers detected at RRSO. Results Between June 14, 2007, and May 15, 2012, 4,348 women underwent 13,728 women-years of screening. The median follow-up time was 4.8 years. Nineteen patients we...
Journal of Gynecologic Surgery, 2014
Objective: The purpose of this study was to evaluate differences in outcomes on the basis of body... more Objective: The purpose of this study was to evaluate differences in outcomes on the basis of body mass index (BMI) in patients undergoing laparoscopic hysterectomy. Design: The study was a retrospective analysis. Methods: All cases of laparoscopic hysterectomy performed from May 2008 to May 2012 for benign, microinvasive cervical, early endometrial, and occult ovarian carcinoma were reviewed. There were 347 patients analyzed by BMI. As proposed by the World Health Organization classification system of obesity, patients were categorized by BMI. Ideal BMI was defined as being between 18.5 and 24.9 kg/m 2 , overweight was defined as having a BMI between 25 and 29.9 mg/m 2 , and obesity was defined as having a BMI ‡ 30 kg/m 2. Laparoscopic surgery was completed successfully in 338 patients, and 9 patients had their surgery converted to laparotomy for findings at the surgery, not for complications relating to the surgery, and, therefore, were excluded from the analysis. Results: Mean age was 51.1 years in the ideal group, 50.45 in the overweight group, and 55.49 in the obese group. The patients' ages ranged in all the samples between 31 and 94 years (p < 0.003). Mean operating time was 105.5 minutes, mean blood loss was 252 mL, and mean length of hospital stay was 2.4 days. There was not a significant difference among the three groups. Total major complication rate was 3.7% and early postoperative complication rate was 5. There was not a significant difference among the three groups. Urologic injury was present in 0.6% of all patients. Conclusions: Laparoscopic hysterectomy is feasible and safe, resulting in short hospital stay, minimal blood loss, and minimal operating time for patients in all BMI groups. The laparoscopic approach may extend the benefits of minimally invasive hysterectomy to the very obese, for whom abdominal surgery poses serious risk.
Gynecologic and Obstetric Investigation, 2015
Background/Aims: Operative laparoscopy (OL) is considered the gold standard surgical treatment of... more Background/Aims: Operative laparoscopy (OL) is considered the gold standard surgical treatment of ectopic pregnancy (EP). We questioned whether a training programme to foster OL treatment is able to ensure that all women needing surgical management are treated by OL irrespective of the site of EP, haemodynamic status and clinical complexity. Methods: A 13-year cohort study of 963 women who underwent surgical management was conducted. We instituted a ‘universal OL' programme in 2003 for the management of all the types of EP irrespective of the haemodynamic status. Results: There were 802 women in the prospective (2003-2013) and 161 in the retrospective arm (2000-2002). The rate of OL before 2003 was 34%. During the year of programme implementation, the OL rate rose from 89% in 2003 to 96% in 2004. It took 4 years to achieve a 100% OL rate in haemodynamically stable patients. In 2013, we were able to achieve OL treatment for all patients irrespective of haemodynamic status, the co...
International Journal of Gynecological Cancer, 2015
The aim of this study was to construct a prognostic index that predicts risk of relapse in women ... more The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods: A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results: Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (G0.33), intermediate (0.34Y0.67), and high (90.67) probability of relapse. Conclusions: The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support.
Protocols, 2010
... meta analysis. Obstetrics and Gynecology 2004;103:785–94. Mahdavi 2006 Mahdavi A, Pejovic T, ... more ... meta analysis. Obstetrics and Gynecology 2004;103:785–94. Mahdavi 2006 Mahdavi A, Pejovic T, Nezhat F. Induction of ovulation and ovarian cancer: a critical review of the literature. Fertility and Sterility 2006; 85(4):819–26. 6 ...
The Lancet Oncology, 2013
Background Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutat... more Background Penetrance for breast cancer, ovarian cancer, or both in carriers of BRCA1/BRCA2 mutations is disproportionately high. Sex hormone dysregulation and altered end-organ hormone sensitivity might explain this organ-specifi c penetrance. We sought to identify diff erences in hormone regulation between carriers of BRCA1/2 and women who are negative for BRCA1/2 mutations. Methods We assessed endometrial thickness for each menstrual cycle day (as an index of hormone regulation) in 393 scans from 228 women in the UK Familial Ovarian Cancer Screening Study (UK FOCSS) known to carry either mutation and 1573 scans from 754 women known to be negative for the mutations. To quantify diff erences in endometrial thickness we focused on days 10-14 and days 21-26, and calculated the area under the curve. We then compared serum oestradiol and progesterone titres during these days of the menstrual cycle in the same groups. Follicular and luteal oestradiol and progesterone serum titres were grouped into quartiles and odds ratios were calculated with logistic regression. Findings Follicular phase endometrial thickness of carriers of the mutations adjusted for age and day of the menstrual cycle was higher (odds ratio [OR] 1•11, 95% CI 1•03-1•20; p=0•0063) and luteal phase endometrial thickness lower (0•90, 0•83-0•98; p=0•027) than for women negative for the mutations. Median luteal phase titres of progesterone were 121% higher (p=0•00037) in carriers than in women negative for the mutations, and for oestradiol were 33% higher (p=0•007)-ie, 59% of carriers had concentrations of serum progesterone that would have been in the top quartile of concentrations in the control group (OR 8•0, 95% CI 2•1-52•57; p=0•008). Interpretation Carriers of BRCA1/BRCA2 mutations are exposed to higher titres of oestradiol and progesteroneknown risk-factors for breast cancer. Higher titres of oestradiol in carriers are compatible with this hormone having a role in ovarian carcinogenesis in such women. Our fi ndings could not be explained by diff erential contraceptive pill use.
Journal of Minimally Invasive Gynecology, 2007
from 2003 to 2006. This difference was statistically significant (p less than 0.001). In 2006, 96... more from 2003 to 2006. This difference was statistically significant (p less than 0.001). In 2006, 96% of women requiring surgery were managed by laparoscopic surgery. Conclusion: The findings of this study indicate that it is possible to implement changes which increase and sustain a high rate of laparoscopic surgery for women with ectopic pregnancy requiring surgery in a district general hospital setting.