Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial (2021)

Type of publication:
Journal article

Author(s):
Morgan, Robert D; McNeish, Iain A; Cook, Adrian D; James, Elizabeth C; Lord, Rosemary; Dark, Graham; Glasspool, Rosalind M; Krell, Jonathan; Parkinson, Christine; Poole, Christopher J; Hall, Marcia; Gallardo-Rincón, Dolores; Lockley, Michelle; Essapen, Sharadah; Summers, Jeff; Anand, Anjana; *Zachariah, Abel; Williams, Sarah; Jones, Rachel; Scatchard, Kate; Walther, Axel; Kim, Jae-Weon; Sundar, Sudha; Jayson, Gordon C; Ledermann, Jonathan A; Clamp, Andrew R

Citation:
The Lancet. Oncology; February 2021, 22(2). p. 277-288

Abstract:
BACKGROUNDPlatinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial.METHODSICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146.FINDINGSBetween June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29·5 months (IQR 15·6-54·3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14·4 months (95% CI 9·2-28·0; 297 events) for patients with a RECIST complete or partial response and 13·3 months (8·1-20·1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13·8 months (95% CI 8·8-23·4; 544 events) and 9·7 months (5·8-14·5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response.INTERPRETATIONThe RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient’s clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response.FUNDINGCancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

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A rare case of vulval myxoid chondrosarcoma (2015)

Type of publication:
Conference abstract

Author(s):
*Abdelsalam H., *Malcolm A.

Citation:
Journal of Pathology, September 2015, vol./is. 237/(S46)

Abstract:
Introduction: Primary Extraskeletal Myxoid Chondrosaroma (EMC) of the vulva is a rare mesenchymal neoplasm. The myxoid tumour differential diagnosis on a core biopsy can be quite challenging. To date, few cases have been reported in the literature. Case Report: A 42-year old woman noticed a swelling on the right side of the labia, thought to be a Bartholin’s cyst i n 2011. She was managed conservatively. She had drainage and marsupialization under general anaesthesia. This resulted in extreme bruising of the vulva. This was managed with antibiotics and non-steroidal anti-inflammatory medication, and it resolved after 3 weeks. Six months later, the patient presented again with a persistent vulval mass. A biopsy was obtained under general anaesthesia, and it showed a myxoid tumour with differential diagnosis of low grade chondroid tumour. An MRI was performed to assess the extent of the disease. The tumour was excised. At surgery, a 7 x 5 cm lobulated, extremely vascular vulval tumour was found. The tumour was inseparable from the inferior pubic ramus of the pelvic bone. A complete macroscopic resection was obtained. Histology confirmed low grade myxoid chondrosarcoma. Conculsion: Vulval lesions with unusual characteristics or insidious evolution in the labia majora or Bartholin’s glands area should be carefully and pr omptly investigated. Differential diagnosis of myxoid tumours in the vulva should include myxoid chondrosarcoma amongst other diagnoses.

High-grade vaginal intraepithelial neoplasia (VAIN2/3): comparison of clinical outcomes between treated and untreated patients in an observational cohort study (2015)

Type of publication:
Conference abstract

Author(s):
*Pandey B., *Papoutsis D., *Guttikonda S., *Ritchie J., *Reed N., *Panikkar J., *Blundell S.

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology, April 2015, vol./is. 122/(149)

Abstract:
Introduction We aimed to compare the clinical outcomes between treated and untreated patients with high-grade vaginal intraepithelial neoplasia (VAIN2/3) in our colposcopy unit. Methods The clinical records of all patients diagnosed with VAIN and vaginal cancer over the time period of 1981-2012 were retrieved and reviewed. The primary outcome was to identify the progression of treated versus untreated patients with VAIN2/3 to vaginal cancer and to compare persistent VAIN disease in both subgroups. The secondary outcome was to identify any associations between particular demographic features of treated/ untreated VAIN2/3 patients with their clinical outcome. Results During the time period of this observational cohort study 36 patients of which 11 patients with VAIN1, 19 with VAIN2/3 disease and 6 with vaginal cancer were identified. In those with VAIN2/3 (n = 19) the diagnosis was made in a younger age in the subgroup of treated patients (n = 8) versus the untreated patients (n = 11) (47 +/- 7.1 versus 54.3 +/- 11.5 years old). Nulliparity and smoking status were similar between the two cohorts. The median follow-up for the untreated women was 7 years (range 1-22 years). In the treated VAIN2/3 group, median time from diagnosis to treatment was 4 years (range 0.2-7 years), and median follow-up after treatment was 7 years (range 0.5-18 years). Treatment methods were ablation (n = 4), excision of lesion (n = 2) and vaginectomy (n = 2). There were no cases of treated VAIN2/3 patients (0%) that progressed to vaginal cancer, whereas n = 3 cases of untreated VAIN2/3 patients (21.4%) progressed to vaginal cancer. Following initial VAIN2/3 diagnosis, 8/11 cases of untreated VAIN2/3 (72.7%) had persistent disease as identified in follow-up cytology/colposcopy/vaginal biopsies. In the treated VAIN2/3 patients, 5/5 cases (100%) had persistent disease post-diagnosis but after treatment this decreased to 2/7 cases (28.5%). Conclusion Treated VAIN2/3 patients were of younger age but of similar smoking status and parity in comparison to untreated patients. Three cases of untreated VAIN2/3 progressed to vaginal cancer, whereas there were no such cases of patients receiving treatment for VAIN2/3. The VAIN2/3 patients who received treatment had a higher rate of persistent VAIN disease at followup post-diagnosis (100% versus 72.7%), but after treatment this rate fell down to 28.5%. Further studies are needed to conclude whether treatment of VAIN2/3 disease reduces the rate of VAIN disease persistence and affects the progression to vaginal cancer.

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Success rate of cold coagulation for the treatment of cervical intraepithelial neoplasia: a retrospective analysis of a series of cases (2015)

Type of publication:
Journal article

Author(s):
*Parry-Smith W, *Underwood M , De Bellis-Ayres S, *Bangs L, Redman CW, *Panikkar J.

Citation:
Journal of Lower Genital Tract Disease, January 2015, vol./is. 19/1(17-21), 1089-2591;1526-0976 (13 Jan 2015)

Abstract:
OBJECTIVE: To establish the cure rate at 1 year of patients who have undergone cold coagulation for the treatment of cervical intraepithelial neoplasia (CIN).DESIGN: Retrospective review of data for all patients at Shrewsbury and Telford NHS Trust who had undergone cold coagulation as part of their treatment for CIN between 2001 and 2011. Follow-up data up to December 2012 were analyzed. SETTING: Colposcopy Department, Shrewsbury and Telford NHS Trust, United Kingdom.POPULATION: Women undergoing cold coagulation for the treatment of CIN between 2001 and 2011, with cytologic follow-up until December 2012. METHODS: Patients were identified using a local colposcopy database. Data were obtained via the local histopathology reporting systems. Statistical analyses were performed using Stata/IC 10.1 software. MAIN OUTCOME MEASURES: Posttreatment cytology and whether subsequent treatment was required, with histology results. RESULTS: Data on 557 patients were collected and analyzed. Pre-cold coagulation treatment histologic findings were CIN 1 in 156 patients (28.01%), CIN 2 in 260 patients (46.68%), and CIN 3 in 141 patients (25.31%). The median length of time between cold coagulation treatment and first follow-up smear, used to calculate cure rates at around 1 year, was 406 days (interquartile range 123 days, range 169-3,116 days). The cure rate after cold coagulation was 95.7% at around 1 year. CONCLUSIONS: Cold coagulation has a cure rate comparable to that of excisional treatments such as large loop excision of the transformation zone and should be considered more widely in patients undergoing primary treatment for CIN, where there is no suspicion of invasive disease on history, examination and cytologic results.