Search

Purpose: A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown. Patients and Methods: Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were retreated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were retreated with olaparib ± cediranib after RECIST CR/PR/stable disease to platinum and according to the platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib retreatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA), and BRCAm reversions were investigated in tumor and liquid biopsies. Results: Twenty-seven patients were treated (EP1 = 17, EP2 = 10), and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4 received olaparib retreatment for ≥6 months. Common grade ≥2 adverse events during olaparib retreatment were anemia, nausea, and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and retreatment differed (12.1 months vs. 4.4 months; P < 0.001). Functional HRD and SCNA did not predict PFS. A BRCA2 reversion mutation was detected in a post-olaparib liquid biopsy. Conclusions: A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious.

Background Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care have been introduced to maximise patient safety and protect staff. We aimed to identify factors influencing clinicians’ decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. Patients and Methods Electronic records of patients seen in a large UK tertiary cancer centre were reviewed. The frequency and type of changes to systemic anticancer therapy (SACT), as well as the factors predicting clinicians’ decision were assessed. Results A total of 418 patients; mean age 63±12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients [OR 1.028 (95% CI 1.010–1.047); p=0.002], and in patients who had already received higher number of cycles of SACT [OR 1.040 (95% CI 1.016–1.065); p=0.001]. A change in treatment was less likely further out of the first national lockdown [OR 0.837 (95% CI 0.758–0.925); p

BRCA2 reversion mutation detected in cell-free circulating DNA from patient 16.

Purpose:A single maintenance course of a PARP inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.Patients and Methods:Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were retreated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were retreated with olaparib ± cediranib after RECIST CR/PR/stable disease to platinum and according to the platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib retreatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA), and BRCAm reversions were investigated in tumor and liquid biopsies.Results:Twenty-seven patients were treated (EP1 = 17, EP2 = 10), and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4 received olaparib retreatment for ≥6 months. Common grade ≥2 adverse events during olaparib retreatment were anemia, nausea, and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and retreatment differed (12.1 months vs. 4.4 months; P < 0.001). Functional HRD and SCNA did not predict PFS. A BRCA2 reversion mutation was detected in a post-olaparib liquid biopsy.Conclusions:A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious.

Supplementary Methodology.

Liquid biopsy time points.

Supplementary Data from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

CCR Translation for the Article from Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging

Purpose: Little is known concerning the onset, duration, and magnitude of direct therapeutic effects of anti–vascular endothelial growth factor (VEGF) therapies. Such knowledge would help guide the rational development of targeted therapeutics from bench to bedside and optimize use of imaging technologies that quantify tumor function in early-phase clinical trials.Experimental Design: Preclinical studies were done using ex vivo microcomputed tomography and in vivo ultrasound imaging to characterize tumor vasculature in a human HM-7 colorectal xenograft model treated with the anti-VEGF antibody G6-31. Clinical evaluation was by quantitative magnetic resonance imaging in 10 patients with metastatic colorectal cancer treated with bevacizumab.Results: Microcomputed tomography experiments showed reduction in perfused vessels within 24 to 48 h of G6-31 drug administration (P ≤ 0.005). Ultrasound imaging confirmed reduced tumor blood volume within the same time frame (P = 0.048). Consistent with the preclinical results, reductions in enhancing fraction and fractional plasma volume were detected in patient colorectal cancer metastases within 48 h after a single dose of bevacizumab that persisted throughout one cycle of therapy. These effects were followed by resolution of edema (P = 0.0023) and tumor shrinkage in 9 of 26 tumors at day 12.Conclusion: These data suggest that VEGF-specific inhibition induces rapid structural and functional effects with downstream significant antitumor activity within one cycle of therapy. This finding has important implications for the design of early-phase clinical trials that incorporate physiologic imaging. The study shows how animal data help interpret clinical imaging data, an important step toward the validation of image biomarkers of tumor structure and function. (Clin Cancer Res 2009;15(21):6674–82)

National guidelines recommend testing all cases of non-mucinous epithelial ovarian cancer (NMEOC) for germline (blood) and somatic (tumour) BRCA1/2 pathogenic variants (PVs). We performed paired germline and somatic BRCA1/2 testing in consecutive cases of NMEOC (n = 388) to validate guidelines. Thirty-four somatic BRCA1/2 (sBRCA) PVs (9.7%) were detected in 350 cases with germline BRCA1/2 (gBRCA) wild-type. All sBRCA PVs were detected in non-familial cases. By analysing our regional germline BRCA1/2 database there were 92/1114 (8.3%) gBRCA PVs detected in non-familial cases (only 3% ≥70 years old) and 245/641 (38.2%) in familial cases. Germline non-familial cases were dominated by BRCA2 in older women (8/271 ≥ 70 years old, all BRCA2). The ratio of sBRCA-to-gBRCA was ≤1.0 in women aged

The COVID-19 pandemic has resulted in unprecedented changes to the lives of patients with cancer. To evaluate the impact of the COVID-19 pandemic on the mental health and well-being of patients with colorectal cancer, we conducted a prospective longitudinal questionnaire study at a UK tertiary cancer centre. In total, 216 participants were included: mean age 65 years, 57% (n = 122) male, 92% (n = 198) of white ethnicity. Amongst participants who completed the screening psychometric questionnaire, 24% (n = 48/203) reported anxiety (GAD-7 ≥ 5), 15% (n = 31/204) depressive symptoms (PHQ-9 ≥ 10), 3% (n = 5/190) probable post-traumatic stress disorder (PC-PTSD-5 ≥ 4), and 31% (n = 66/213) poor well-being (WHO-5 < 50). In the subgroup (n = 95/216, 44%) who consented to and completed a follow-up survey 6 months later, there was a significant increase in the number of participants at risk of depression (4% vs. 13%, p = 0.021). Self-reported concern about the COVID-19 pandemic impacting one’s mental health is associated with increased likelihood of anxiety, depression, and poor well-being, in respective multivariate analyses. In conclusion, screening for the mental health impact of the COVID-19 pandemic is essential to ensure timely action from all key stakeholders and to avoid potentially longer-term detrimental consequences.

AimsClinical guidelines recommend testing both germline and tumour DNA for BRCA1/2 pathogenic variants (PVs) in non-mucinous high-grade epithelial ovarian cancer (NMEOC). In this study, we show that some tumour BRCA1/2 PVs are highly likely to be somatic based on certain clinical and variant characteristics, meaning it may not be necessary to test all NMEOC cases for germline BRCA1/2 PVs.MethodsAn observational study that included all tumour BRCA1/2 PVs detected in cases of NMEOC in the Northwest of England between July 2017 and February 2022. All tumour BRCA1/2 PVs were compared with PVs recorded in a prospectively gathered pan-cancer germline BRCA1/2 (gBRCA) testing database for the same geographical region (gBRCA1 PVs=910 and gBRCA2 PVs=922). Tumour BRCA1/2 PVs were categorised as common (≥1%), uncommon (ResultsOne hundred and thirteen tumour BRCA1/2 PVs were detected in 111 NMEOC cases. There were 69 germline and 44 somatic variants. The mean age at diagnosis for gBRCA and somatic BRCA1/2 (sBRCA) PVs was 56.9 and 68.5 years, respectively (Student's t-test pBRCA PVs were detected in non-familial cases. All tumour BRCA1/2 PVs with a variant allele frequency (VAF) BRCA1/2 PVs were present (common=31, uncommon=25) in the gBRCA testing database, while 89% of somatic-tumour BRCA1/2 PVs were absent (n=39).ConclusionsWe predict the likelihood of a tumour BRCA1/2 PV being somatic is 99.8% in non-familial cases of NMEOC diagnosed aged ≥75, where the VAF is ≤30% and there is no regional germline commonality.

Clinical guidelines recommend testing both germline and tumour DNA forAn observational study that included all tumourOne hundred and thirteen tumourWe predict the likelihood of a tumour

Poly(ADP-ribose) polymerase (PARP) inhibitors improve survival in BRCA-mutant high-grade serous ovarian carcinoma. As a result, germline and somatic BRCA1/2 testing has become standard practice in women diagnosed with ovarian cancer. We outline changes in testing and detection rates of germline BRCA1/2 pathogenic variants (PVs) in cases of non-mucinous epithelial ovarian cancer diagnosed during three eras, spanning 12 years, within the North West of England, and compare the uptake of cascade testing in families identified by oncology-led mainstreaming versus regional genetics clinics. Eras included: Period 1 (20% risk threshold for testing): between January 2007 and May 2013; Period 2 (10% risk threshold for testing): between June 2013 and October 2017 and; Period 3 (mainstream testing): between November 2017 and November 2019. A total of 1081 women underwent germline BRCA1/2 testing between January 2007 and November 2019 and 222 (20.5%) were found to have a PV. The monthly testing rate increased by 3.3-fold and 2.5-fold between Periods 1–2 and Periods 2–3, respectively. A similar incidence of germline BRCA1/2 PVs were detected in Period 2 (17.2%) and Period 3 (18.5%). Uptake of cascade testing from first-degree relatives was significantly lower in those women undergoing mainstream testing compared with those tested in regional genetics clinics (31.6% versus 47.3%, P = 0.038). Mainstream testing allows timely detection of germline BRCA1/2 status to select patients for PARP inhibitors, but shortfalls in the uptake of cascade testing in first-degree relatives requires optimisation to broaden benefits within families.

Women diagnosed with non-mucinous high-grade epithelial ovarian cancer (EOC) in England are often reflex-tested for germline and tumour BRCA1/2 variants. The value of germline BRCA1/2 testing in women diagnosed aged ≥80 is questionable. We performed an observational study of all women diagnosed with non-mucinous high-grade EOC who underwent germline and tumour BRCA1/2 testing by the North West of England Genomic Laboratory Hub. A subgroup of women also underwent germline testing using a panel of homologous recombination repair (HRR) genes and/or tumour testing for homologous recombination deficiency (HRD) using Myriad’s myChoice® companion diagnostic. Seven-hundred-two patients successfully underwent both germline and tumour BRCA1/2 testing. Of these, 48 were diagnosed with non-mucinous high-grade EOC aged ≥80. In this age group, somatic BRCA1/2 pathogenic/likely pathogenic variants (PV/LPVs) were detected nine times more often than germline BRCA1/2 PV/LPVs. The only germline PV reported in a patient aged ≥80 was detected in germline and tumour DNA (BRCA2 c.4478_4481del). No patient aged ≥80 had a germline PV/LPVs in a non-BRCA1/2 HRR gene. Thirty-eight percent of patients aged ≥80 had a tumour positive for HRD. Our data suggest that tumour BRCA1/2 and HRD testing is adequate for patients diagnosed with non-mucinous high-grade EOC aged ≥80, with germline BRCA1/2 testing reserved for women with a tumour BRCA1/2 PV/LPVs.

Background The COVID-19 pandemic has imposed significant changes in cancer service delivery resulting in increased anxiety and distress in both patients and clinicians. We aimed to investigate how these changes have been perceived by patients diagnosed with colorectal cancer and identify determinants of increased anxiety. Patients and Methods An anonymised 32-item survey in a specialised lower gastrointestinal cancer outpatient clinics at a tertiary cancer centre in North West England between 18 May and 1 July 2020. Self-reported anxiety based on General Anxiety Disorder-7 (GAD-7) screening tool. Results Of 143 participants who completed the survey (response rate 67%), 115 (82%) were male and median age group was 61-70 years. 112 (78%) participants had telephone consultation (83% met needs), and 57 (40%) had radiological scan results discussed over the phone (96% met needs). In total, 23 (18%) participants were considered to have anxiety (GAD-7 score ≥ 5), with 7 (5.5%) scoring for moderate or severe anxiety. Those concerned about getting COVID-19 infection, and worried COVID-19 would have effect on their mental health, and affect their experience of cancer care, were most likely to have anxiety (p, We investigated colorectal patients’ perception of service changes imposed by COVID-19 and identified determinants of anxiety. A 32-item survey, including GAD-7 tool, was performed in a tertiary cancer centre. Of 143 participants, 23 (18%) have anxiety (GAD-7 ≥ 5); 7 (6%) moderate/severe anxiety. An easy and practical pre-screening assessment questionnaire can help identify those in more need of further support.

ObjectiveTwo randomized phase III trials demonstrated the efficacy and safety of combining bevacizumab with front-line carboplatin/paclitaxel for advanced ovarian cancer. The OSCAR (NCT01863693) study assessed the impact of front-line bevacizumab-containing therapy on safety and oncologic outcomes in patients with advanced ovarian cancer in the UK.MethodsBetween May 2013 and April 2015, patients with high-risk stage IIIB–IV advanced ovarian cancer received bevacizumab (7.5 or 15 mg/kg every 3 weeks, typically for ≤12 months, per UK clinical practice) combined with front-line chemotherapy, with bevacizumab continued as maintenance therapy. Co-primary endpoints were progression-free survival and safety (NCI-CTCAE v4.0). Patients were evaluated per standard practice/physician’s discretion.ResultsA total of 299 patients received bevacizumab-containing therapy. The median age was 64 years (range 31–83); 80 patients (27%) were aged ≥70 years. Surgical interventions were primary debulking in 21%, interval debulking in 36%, and none in 43%. Most patients (93%) received bevacizumab 7.5 mg/kg with carboplatin/paclitaxel. Median duration of bevacizumab was 10.5 months(range ConclusionsMedian progression-free survival in this study was similar to that in the high-risk subgroup of the ICON7 phase III trial. Median progression-free survival was shortest in patients who did not undergo surgery.

IntroductionPoly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenic BRCA1/2 variant. Consequently, the demand for germline BRCA1/2 testing in ovarian cancer has increased substantially, leading to the screening of unselected populations of patients. We aimed to determine the prevalence of pathogenic germline BRCA1/2 variants in women diagnosed with epithelial ovarian cancer, categorised according to the established risk factors for hereditary breast and ovarian cancer syndrome and the Manchester BRCA Score, to inform risk stratification.MethodsA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germline BRCA1/2 testing by next-generation sequencing and multiplex ligation-dependent probe amplification.ResultsFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenic BRCA1/2 variant. The prevalence of pathogenic BRCA1/2 variants was >10% in women diagnosed with ovarian cancer earlier than 60 years of age (21%) and those diagnosed later than 60 years of age with a family history of breast and/or ovarian cancer (17%) or a medical history of breast cancer (34%). The prevalence of pathogenic BRCA1/2 variants was also >10% in women with a Manchester BRCA Score of ≥15 points (14%).DiscussionOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a >10% prevalence of germline pathogenic BRCA1/2 variants in epithelial ovarian cancer.

Pulmonary metastasectomy for sarcoma is surgery without proven benefit, and in the light of a randomized controlled trial examining pulmonary metastasectomy in colorectal cancer, it should be questioned.

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m(2), intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade >= 3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade >= 2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC.

Background: In the UK, trametinib (T) is recommended for the treatment of recurrent or progressive low grade serous ovarian cancer (LGSOC) following endocrine therapy (ET) and at least one platinum (Plat) based chemotherapy (ChT) regimen, as an alternative to cytotoxic ChT under interim COVID-19 arrangements. Methods: We conducted a multicentre retrospective study of patients (pts) treated with T in the UK. Eligible pts were adults with recurrent LGSOC who commenced T prior to November 2020. Results: Twenty-eight pts were included (median age 53.5, 19-75). 93% had stage 3-4 disease at presentation. Prior to commencing T, pts received a median of 1.5 lines of ChT (range 0-8) and 1 line (0-3) of ET. Four pts had received ≥3 lines of ChT. Thirty-six per cent had platinum resistant disease (relapse

Objective Vascular co-option is a resistance mechanism to anti-angiogenic agents, but combinations of anti-vascular agents may overcome this resistance. We report a phase 1b and randomised phase 2 trial to determine the safety and efficacy of pazopanib with fosbretabulin. Methods Eligible patients had recurrent, epithelial ovarian cancer with a platinum-free interval (PFI) of 3 to 12 months. Patients were stratified according to PFI (>6 versus ≤6 months) and prior bevacizumab use. Results Twelve patients were treated in the phase 1b. Commonest grade ≥ 2 adverse events (AEs) were hypertension (100%), neutropenia (50%), fatigue (50%), vomiting (50%). There was one DLT (grade 3 fatigue). The recommended phase 2 dose level was fosbretabulin 54 mg/m2 on days 1, 8 and 15 and pazopanib 600 mg once daily (od), every 28 days, which was then compared to pazopanib 800 mg od in a randomised phase 2 trial. Twenty-one patients were randomised (1:1) in the phase 2 trial. In phase 1b and phase 2, four patients treated with pazopanib and fosbretabulin developed reversible, treatment-related cardiac AEs, leading to premature discontinuation of the study. In the phase 2 trial, the median PFS was 7.6 months (95% CI 4.1-not estimated) versus 3.7 months (95% CI 1.0–8.1) in favour of the experimental arm (HR 0.30, 95% CI 0.09–1.03, P = .06). Conclusions It remains unclear whether pazopanib with with fosbretabulin is an efficacious regimen to treat epithelial ovarian cancer. Effective cardiac risk mitigation is needed to increase the tolerability and maximize patient safety in future trials.

Background The use of home parenteral nutrition (HPN) for palliative indications is increasing internationally and is the leading indication in some countries. Discharge on HPN can be complex in metabolically unstable patients and requires intestinal failure expertise. Methods Between 2012 and 2018, we performed a retrospective analysis aiming to assess the impact of a novel remote discharge pathway for palliative HPN patients. This was evaluated using a quality improvement approach. Results One hundred and twenty-five patients with active malignancy [mean (range) age 58 (25-80) years] were referred to the intestinal failure unit (IFU) for remote discharge. Of 82 patients were discharged from the oncology Centre on HPN using the pathway. The remaining 43 patients either declined HPN or the Oncology team felt that the patient became too unwell for HPN or died prior to discharge. There was an increase in patients referred for remote discharge from 13 in 2012 to 43 in 2017. The mean number of days between receipt of referral by the IFU to discharge on HPN from the oncology centre reduced from 29.4 days to 10.1 days. Following remote discharge, the mean number of days on HPN was 215.9 days. Catheter-related blood stream infection rates in this cohort were very low at 0.169 per 1000 catheter days. Conclusions This is the first study to demonstrate the remote safe, effective and rapid discharge of patients requiring palliative HPN between two hospital sites. This allows patients with a short prognosis more time in their desired location.

Background Malignant bowel obstruction (MBO) is a common cause of morbidity and mortality in women diagnosed with ovarian cancer. Earlier detection of MBO may improve patient outcomes. There are currently no screening tools to assist detection.Aim We report a screening questionnaire that can be used to detect MBO, and how the severity score for key clinical symptoms correlate with radiological evidence of MBO from ovarian cancer.Design A case–control study in which patients with relapsed, metastatic ovarian cancer were asked to answer 10 questions related to key clinical symptoms associated with intestinal obstruction. The study group included women with CT-confirmed MBO, whereas the control group had no evidence of MBO. Patients scored each question according to severity from 1 (least severe) to 5 (most severe).Setting/participants Between 1 June and 31 December 2016, 37 women completed the screening questionnaire.Results Patients in the study group (n=17) reported significantly higher (ie, more severe) scores for abdominal pain, nausea, vomiting and constipation. In contrast, differences in severity scores between groups did not differ significantly in response to questions regarding abdominal swelling, borborygmi, diarrhoea or loss of appetite. All patients in the study group more frequently stated that their symptoms had deteriorated within the 2 months prior to completing the questionnaire.Conclusion Here we report the key clinical symptoms associated with radiologically-confirmed MBO in relapsed, metastatic ovarian cancer. We recommend healthcare practitioners focus on these specific symptoms during patient consultations in order to improve risk stratification of MBO.

28 Background: Increased levels of anxiety and distress in both patients and physicians have been reported in response to the significant impact COVID-19 has on cancer service delivery globally. We aimed to investigate how these changes have been perceived by patients diagnosed with colorectal cancer and identify determinants of increased anxiety. Methods: Survey (32-item) of consecutive patients diagnosed with colorectal cancer attending a large tertiary comprehensive cancer centre in the United Kingdom (18 May to 1 July 2020). Self-reported GAD-7 (both paper/electronic forms) was used as a screening tool for anxiety. Statistical analyses of associations:Chi-square, Fisher’s exact, and uni- and multi-variable analyses were performed using SPSS v19 and R. Results: A total of 143 patients (response rate 67%), 82% male, and median age of 61-70 years were included. Majority of patients had telephone consultation (78%), including 40% who had scan results discussed over the phone; with favourable feedback received with both respectively. Twenty-three patients (18%) were considered to have anxiety, with 7 (6%) scoring for moderate or severe anxiety. Three items asked patients if they had concerns about getting COVID-19, were worried that COVID-19 would have effect on mental health, and affect their experience of cancer care. Patients answering positively to any of these items were most likely to have anxiety; multivariate analysis – OR 2.361 (95% CI 1.187-4.694, p=0.014), 3.219 (95% CI 1.401-7.395, p=0.006) and 3.206 (95% CI 1.036-9.920, p=0.043), respectively. Majority of the patients did not feel that they needed support during the pandemic period and hence the available well-being services were not used. Patients felt that friends and family had been very supportive but less so the primary care services (p

Poly(ADP-ribose) polymerase inhibitors significantly improve progression-free survival in platinum-sensitive high-grade serous and endometrioid ovarian carcinoma, with greatest benefits observed in women with a pathogenicA cohort of sequential epithelial ovarian cancer cases recruited between June 2013 and September 2018 underwent germlineFive hundred and fifty-seven patients were screened. Of these, 18% had inherited a pathogenicOur study suggests that age at diagnosis, family history of breast and/or ovarian cancer, medical history of breast cancer or a Manchester BRCA Score of ≥15 points are associated with a10% prevalence of germline pathogenic

IntroductionStandard of care treatment for women who develop relapsed ovarian cancer includes sequential platinum- and/or paclitaxel-based chemotherapy, with reducing disease-free intervals. Once platinum resistance develops, treatment options become limited and dose-dense regimens may be offered. We report the efficacy and safety of dose-dense cisplatin with gemcitabine chemotherapy for relapsed platinum-resistant ovarian cancer.MethodsA retrospective analysis of all patients with relapsed, platinum-resistant ovarian, primary peritoneal or fallopian tube cancer treated with cisplatin 35 mg/m2 of body surface area by intravenous infusion with gemcitabine 1000 mg/m2 of body surface area by intravenous infusion on days 1 and 8 of every 21-day treatment cycle between 1 January 2009 and 1 June 2017.ResultsNinety-four eligible patients had received a median of three (range one–eight) prior lines of cytotoxic therapy for relapsed ovarian cancer. Sixty patients (64%) had received ≥ 1 prior dose-dense chemotherapy regimen. Dose-dense cisplatin with gemcitabine was associated with a median progression-free survival (PFS) of 4.4 months (95% CI 3.6 to 5.3) and overall survival of 7.6 months (95% CI 5.6 to 9.6). The median PFS for dose-dense cisplatin with gemcitabine as first- (n = 34), second- (n = 42), and third-line or later (n = 18) dose-dense therapy was 4.2 (95% CI 3.2 to 5.2), 5.0 (95% CI 3.5 to 6.5), and 4.2 (95% CI 3.3 to 5.1) months respectively. The RECIST objective response rate for first-, second-, and third-line dose-dense cisplatin with gemcitabine was 23%, 14 %, and 7 % respectively. The most common grade 3 – 4 adverse events were thrombocytopenia (20%), anemia (18%), and neutropenia (14%).DiscussionDose-dense cisplatin with gemcitabine provides modest efficacy whether it is used as a first- or subsequent line of dose-dense chemotherapy to treat relapsed platinum-resistant ovarian cancer and the toxicity is manageable with supportive measures.

ObjectivesAdvanced-stage, platinum-resistant, ovarian cancer can be treated with dose-intense chemotherapy; one such regimen includes intravenous cisplatin and oral etoposide. To minimize the toxicity associated with weekly cisplatin, pretreatment and posttreatment hydration is required, often necessitating inpatient, overnight admission. We report a shorter, within-day regimen for delivering weekly cisplatin.MethodsThis was a retrospective study to assess the use of standard (inpatient; treatment time of 12 hours) versus modified (outpatient; treatment time of 4 hours) regimens. The primary outcome included all-grade and grade 3/4 adverse events. Secondary outcomes included clinical benefit response and, median progression-free survival and overall survival.ResultsBetween January 2012 and December 2014, 66 women with metastatic ovarian cancer received dose-intense weekly cisplatin and oral etoposide (n = 45 standard, n = 21 modified). The commonest all-grade adverse events were anemia (96% vs 90%, standard and modified, respectively), fatigue (73% vs 67%), neutropenia (71% vs 76%), hypocalcemia (51% vs 43%), and thrombocytopenia (49% vs 57%). There were no statistically significant differences in the incidence or grades of adverse events. The clinical benefit response was 53% in the standard group and 62% in the modified group (P = 0.9). The median progression-free survival was 4.2 and 6.5 months (incidence rate ratio, 1.22; 95% confidence interval, 0.71–2.15; P = 0.29), and median overall survival was 6.6 and 8.4 months (incidence rate ratio, 1.83; 95% confidence interval, 1.04–3.35; P = 0.03), in favor of the modified regimen.ConclusionsOur shorter, within-day regimen for delivering dose-intense weekly cisplatin and oral etoposide to treat platinum-resistant metastatic ovarian cancer is safe and efficacious.

AIM:To characterise venous thromboembolism (VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring.METHODS:We performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal (GO) cancer and 1299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index. Patients were classified as low risk (0 points), intermediate risk (1 to 2 points) or high risk (3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE.RESULTS:The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli (PE) were more common in advanced than in localised CRC (50% vs 21% of events respectively) and lower limb deep vein thrombosis (DVT) were more common in localised than in advanced CRC (62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score (94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be factored into clinical risk assessment scores.CONCLUSION:The Khorana score has low sensitivity for thrombotic events in CRC and cannot discriminate low risk patients in high risk cancer sites such as GO cancer.

Aim: Malignant bowel obstruction (MBO) in ovarian cancer is poorly understood. Methods: This retrospective cohort study analyzed 129 patients with ovarian cancer and MBO. Results: At presentation, 69 (53%) had platinum-resistant, 37 (29%) platinum-sensitive and 23 (18%) chemotherapy-naive disease. In patients receiving chemotherapy following the MBO episode, median overall survival (OS) was 107 days for chemotherapy-naive patients compared with 83 and 86 for platinum-sensitive or platinum-resistant patients (p = 0.98). OS was inferior for best supportive care (45 days) compared with chemotherapy (152 days) or surgery (124 days; p < 0.001). The Manchester Bowel Obstruction Score using Eastern Cooperative Oncology Group and obstruction level discriminated patients by median OS of 181 days (neither) versus 98 days (one) versus 42 days (both; p < 0.01). Conclusion: The Manchester Bowel Obstruction Score may aide treatment stratification.

Relatively few Chinese patients access tertiary cancer services in North West England. We investigated the reasons behind this using a culturally sensitive questionnaire. The questionnaire, completed by 214 Chinese people in English, Cantonese or Mandarin, evaluated the Chinese population's access and satisfaction with primary care, understanding of cancer and awareness of local cancer services. Ninety-five per cent of respondents were registered with a general practitioner (GP) and 75% had accessed primary care in the last year. Satisfaction with GP consultations was high but a third of respondents reported a lack of confidence in local National Health Service (NHS) services. Only 57% of eligible women had attended cervical screening programmes. The overall understanding of the causes and treatment of cancer and cancer services in the North West was poor. Despite registration with primary healthcare, the Chinese population under-utilise cancer prevention programmes and tertiary cancer services because of a lack of awareness and understanding of cancer services in the North West. A significant proportion of the population is dissatisfied with the perceived slow service and lack confidence in services, with 41% considering using healthcare abroad. These data highlight the critical need to engage with, educate and support the Chinese population if they are to access NHS cancer services.

Background: 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis. Methods: Patients with advanced solid tumours received GSAO in a dose-escalation trial according to a standard '3 + 3' design that was guided by toxicity and, for the final dose escalation, by arsenic PK data. Results: A total of 34 patients were treated with GSAO across 9 dose levels (1.3-44.0 mg/m2). Treatment was well tolerated with few adverse events. An additional three patients were enrolled at the 12.4 mg/m 2 dose level following a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m2 dose level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal atrial fibrillation). Conclusions: The MTD of GSAO was 22.0 mg/m2/day. There was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of an anti-vascular effect of GSAO. © 2013 Springer-Verlag Berlin Heidelberg.

We audited the accuracy of the Systemic Anti-Cancer Therapy dataset as a resource for rapid analysis of outcomes for patients, in this example, receiving Cancer Drug Fund funded monoclonal antibodies to treat metastatic colorectal cancer. We concluded that the Systemic Anti-Cancer Therapy dataset is a potentially valuable resource for rapidly determining survival outcome for patients treated with chemotherapy.

Introduction: Treatment on a clinical trial isconsidered to be beneficial to oncology patients.However, supportive evidence for this is scarce. Trialeffect describes the phenomenon of improved healthoutcomes in patients treated with standard of care(SOC) on trial compared to those receiving SOCoutside of a clinical trial. We evaluated trial effect inpatients with ovarian cancer treated at our tertiarycancer centre.Methods: We performed a retrospective cohort studyof patients with ovarian cancer treated at The ChristieNational Health Service Foundation Trust. Patientstreated on one of three first-line clinical trials:(SCOTROC-4, ICON-5, ICON-7) were matched (for age,International Federation of Gynaecology and Obstetricsstage, surgical status and performance status) withindividuals receiving the same SOC off trial. Survivalwas calculated using Kaplan-Meier methodology.Results: 60 patients were evaluated; 30 on trial and30 on SOC off trial. The median progression-freesurvival (PFS) was 21.8 months (control group) and25.9 months (trial group), median overall survival (OS)was 64.3 months (control group) and 68.9 months(trial group). There was no difference in PFS (log-ranktest: HR 0.87 (95% CI 0.48 to 1.54), p=0.6) or OS(log-rank test: HR 0.87 (95% CI 0.46 to 1.64), p=0.7)between groups.Conclusions: Patient survival was similar regardless iftreated on trial or as SOC. Our findings do not supporttrial effect, at least in a tertiary cancer centre. Clinicaltrial participation in specialised cancer centrespromotes best practice to the benefit of all patients.These findings may impact discussions round consentof patients to trials and organisation of oncologyservices.