Severe hyponatraemia in two patients with breast cancer caused by low-dose cyclophosphamide and precipitated by aprepitant (2022)

Type of publication:
Journal article

Author(s):
*Parikh S; *Pettit L; *AbdelGadir H

Citation:
BMJ Case Reports, 2022 Mar 22; Vol. 15

Abstract:
Two postmenopausal women with breast cancer developed acute confusion and seizures, less than 24 hours after the first cycle of neoadjuvant chemotherapy with fluorouracil, epirubicin and low-dose cyclophosphamide. They were found to have severe, life-threatening hyponatraemia with sodium levels of 113 and 115 mEq/L, respectively. Both women made a full recovery within 24 hours of admission with slow correction of sodium levels. Following investigational workup, the most likely diagnosis was cyclophosphamide-associated syndrome of inappropriate antidiuretic hormone secretion (SIADH). Aprepitant – a commonly used antiemetic and moderate cytochromeP450 3A4 inhibitor was identified as the precipitating factor. Aprepitant was discontinued and both women were successfully re-challenged with full dose cyclophosphamide in an outpatient setting with no subsequent adverse events. This is a typical case of a rare cause of a common medical problem. A systematic approach to diagnosis and treatment of hyponatraemia in an oncology patient requires awareness of toxicities of systemic anticancer agents.

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Observation versus screening spinal MRI and pre-emptive treatment for spinal cord compression in patients with castration resistant prostate cancer and spinal metastases in the UK (PROMPTS): an open-label, randomised, controlled, phase 3 trial (2022)

Type of publication:Randomised controlled trial

Author(s):Dearnaley, David; Hinder, Victoria; Hijab, Adham; Horan, Gail; *Srihari, Narayanan; Rich, Philip; Houston, J Graeme; Henry, Ann M; Gibbs, Stephanie; Venkitaraman, Ram; Cruickshank, Clare; Hassan, Shama; Miners, Alec; Mason, Malcolm; Pedley, Ian; Payne, Heather; Brock, Susannah; Wade, Robert; Robinson, Angus; Din, Omar; Lees, Kathryn; Graham, John; Worlding, Jane; Murray, Julia; Parker, Chris; Griffin, Clare; Sohaib, Aslam; Hall, Emma; PROMPTS investigators

Citation:The Lancet. Oncology; Mar 2022 [epub ahead of print]

Abstract:BACKGROUND Early diagnosis of malignant spinal cord compression (SCC) is crucial because pretreatment neurological status is the major determinant of outcome. In metastatic castration-resistant prostate cancer, SCC is a clinically significant cause of disease-related morbidity and mortality. We investigated whether screening for SCC with spinal MRI, and pre-emptive treatment if radiological SCC (rSCC) was detected, reduced the incidence of clinical SCC (cSCC) in asymptomatic patients with metastatic castration-resistant prostate cancer and spinal metastasis. METHODS We did a parallel-group, open-label, randomised, controlled, phase 3, superiority trial. Patients with metastatic castration-resistant prostate cancer were recruited from 45 National Health Service hospitals in the UK. Eligible patients were aged at least 18 years, with an Eastern Co-operative Oncology Group performance status of 0-2, asymptomatic spinal metastasis, no previous SCC, and no spinal MRI in the past 12 months. Participants were randomly assigned (1:1), using a minimisation algorithm with a random element (balancing factors were treatment centre, alkaline phosphatase [normal vs raised, with the upper limit of normal being defined at each participating laboratory], number of previous systemic treatments [first-line vs second-line or later], previous spinal treatment, and imaging of thorax and abdomen), to no MRI (control group) or screening spinal MRI (intervention group). Serious adverse events were monitored in the 24 h after screening MRI in the intervention group. Participants with screen-detected rSCC were offered pre-emptive treatment (radiotherapy or surgical decompression was recommended per treating physician's recommendation) and 6-monthly spinal MRI. All patients were followed up every 3 months, and then at month 30 and 36. The primary endpoint was time to and incidence of confirmed cSCC in the intention-to-treat population (defined as all patients randomly assigned), with the primary timepoint of interest being 1 year after randomisation. The study is registered with ISRCTN, ISRCTN74112318, and is now complete. FINDINGS Between Feb 26, 2013, and April 25, 2017, 420 patients were randomly assigned to the control (n=210) or screening MRI (n=210) groups. Median age was 74 years (IQR 68 to 79), 222 (53%) of 420 patients had normal alkaline phosphatase, and median prostate-specific antigen concentration was 48 ng/mL (IQR 17 to 162). Screening MRI detected rSCC in 61 (31%) of 200 patients with assessable scans in the intervention group. As of data cutoff (April 23, 2020), at a median follow-up of 22 months (IQR 13 to 31), time to cSCC was not significantly improved with screening (hazard ratio 0·64 [95% CI 0·37 to 1·11]; Gray's test p=0·12). 1-year cSCC rates were 6·7% (95% CI 3·8-10·6; 14 of 210 patients) for the control group and 4·3% (2·1-7·7; nine of 210 patients) for the intervention group (difference -2·4% [95% CI -4·2 to 0·1]). Median time to cSCC was not reached in either group. No serious adverse events were reported within 24 h of screening. INTERPRETATION Despite the substantial incidence of rSCC detected in the intervention group, the rate of cSCC in both groups was low at a median of 22 months of follow-up. Routine use of screening MRI and pre-emptive treatment to prevent cSCC is not warranted in patients with asymptomatic castration-resistant prostate cancer with spinal metastasis. FUNDING Cancer Research UK.

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Rare histological subtypes of breast cancer: A study of 10 years' experience at (SATH) UK District General Hospital (2022)

Type of publication:Conference abstract

Author(s):*Mansour A.; *Pettit L.

Citation:European Journal of Surgical Oncology; Feb 2022; vol. 48 (no. 2)

Abstract:Background: Breast cancer is a heterogeneous disease with different histologic subtypes, molecular characteristics, oestrogen receptors (ER) and HER2 status. Common subtype include lobular and ductal cancers. The rare subtypes are a heterogeneous group with differing behaviour specific for each subtype. This study aims to determine the clinicopathological features, management pathway and survival outcome of rare subtypes of invasive breast cancer (IBC) at a single U.K. hospital.Material(s) and Method(s): Data was obtained from the department of Cellular Pathology at The Shrewsbury and Telford Hospital (SATH) NHS Trust. All patients diagnosed with a rare subtype of breast cancer from January 2005 to December 2014 were identified. The histology diagnosis of a rare subtype of breast cancer was reviewed. Biological behaviour, management, follow up and prognosis were obtained from surgical and oncology clinic letters. Also, survival data and cause of death when applicable is reviewed from Clinical Portal (our hospital digital documentation system). Patients with imaging, after the introduction of the digital format to the system in 2012, were also reviewed.
Result(s): Total number of patients diagnosed with IBC was 3049. 201 patients (6.59%) were identified to have a rare subtype of IBC. Patients were divided into subgroups according to their specific rare subtype and included mucinous, tubular, medullary, metaplastic, papillary, neuroendocrine, cribriform, apocrine, malignant phyllodes, angiosarcoma, lymphoma and metastatic from non-breast primary. Some cancers had good prognosis with 100% 5 years overall survival like tubular carcinoma and some have poor prognosis like metaplastic and angiosarcoma.Conclusion(s): Our experience with these heterogeneous groups of rare subtypes of breast cancer identified the clinical behaviour and prognosis of each type. This could be the basis to improve the management of these subtypes and for further studies to improve the outcome for patients with identified breast cancer known to have poorer prognosis.

Her-2 expression pattern evaluation in breast invasive lobular carcinoma and its association to the clinicopathomorphological characteristics and female sex hormones expression in 71 cases (2022)

Type of publication:Conference abstract

Author(s):Barron M.; Asaad A.; Ali S.; Chicken W.; Elamass M.; Alkistawi F.; Abdalla Al-Zawi A.S.; *Khan K.A.; Idaewor P.; Osayi K.

Citation:European Journal of Surgical Oncology; Feb 2022; vol. 48 (no. 2)

Abstract:Background: HER2 status is considered as an important prognostic and predictive factor in breast cancer treatment The cellular E-cadherin protein (encoded by the CDH1 gene) is expressed in the breast epithelial cells. Its function is functions is epithelial-to epithelial cell adhesion and epithelial-to-mesenchymal transition. Invasive lobular carcinoma (ILC) is characterised by the absence of E-cadherin expression, usually its oestrogen /progesterone positive however lack Her-2 amplification. Approximately, about 20% of breast cancers are Her2 +ve. The evidence revealed that, HER2 amplification or overexpression is encountered predominantly in invasive ductal carcinomas (NST) of high nuclear grade and infrequently in pleomorphic lobular carcinomas. The aim is to analyse the Her-2 expression pattern in breast invasive lobular carcinoma.Material(s) and Method(s): The clinical records of 71 patients diagnosed in the period between 2014 -2019,with ILC has been analysed. The lobular phenotype was confirmed by the absence of E-cadherin expression. We have evaluated the following criteria: clinico-pathologic variables, female sex hormone receptor status as well as Her-2 expression status.Result(s): ILC cases has been identified in 71 cases, the age ranges between 39-85 yrs, with mean of 68.In 22.% of cases, the phenotype was mixed ILC& invasive ductal carcinoma. Her-2 overexpression detected in 13% cases, 89% of Her2+ve group are above 65 years of age. Her2 overexpression was more associated with ER+ve group (13%), where 60% were ER+ve,PR+ve and Her2-ve, also 23% noticed to have PR-ve status. Triple negative status was seen only in two cases(2.8%), one of them was pleomorphic lobular carcinoma, both cases age was > 80 yrs.Ki-67 was tested in 58 patients, it was low or moderate in 66%, 7% was Her2 +ve with high Ki-67.Her2+ve status was associated with tumour grade 2 in 7% of cases, grade 3(1.4%) and grade 1 (4%).Conclusion(s): ER expression is noticed to in HER2+ classical ILCs, in spite of the fact that the level of expression is significantly low, compared with the Her2ve- disease.

Pancreatic enzyme replacement therapy in patients with pancreatic cancer: A national prospective study (2021)

Type of publication:Journal article

Author(s):Harvey P.R.; McKay S.C.; Wilkin R.J.W.; Layton G.R.; Powell-Brett S.; Okoth K.; Trudgill N.; Roberts K.J.; Baker G.; Brom M.K.; Brown Z.; Farrugia A.; Haldar D.; Kalisvaart M.; Marley A.; Pande R.; Patel R.; Stephenson B.T.F.; Baillie C.; Croitoru C.; Eddowes P.J.; Elshaer M.; Farhan-Alanie M.M.; Laing R.; Mann K.; Materacki L.; Nandi S.; Pericleous S.; Prasad P.; Rinkoff S.; Selvaraj E.; Shah J.; Sheel A.R.G.; Szatmary P.; Williams P.; Milburn J.; Bekheit M.; Ghazanfar M.; Curry H.; Persson P.; Rollo A.; Thomson R.; Harper S.; Varghese S.; Collins J.; Stupalkowska W.; Afzal Z.; Badran A.; Barker J.; Hakeem A.; Kader R.; Saji S.; Sheikh S.; Smith A.C.D.; Stasinos K.; Steinitz H.; Malik H.; Burston C.; Carrion-Alvarez L.; Shiwani M.; Ahmad G.; Allen T.; Darley E.; Patil S.; Brooks C.; Cresswell B.; Welsh F.; Cook C.; Smyth R.; Booth R.; West M.; King A.; Tucker O.; Phelan L.; Burahee A.; Devogel C.; Javed A.; Kay R.; Khan S.; Leet F.; Troth T.; Ward A.; Young J.; Murray E.; Gray T.; Johnson R.; Lockwood S.; Young R.; Zhou G.; Portal J.; Rees J.; Arnold B.; Scroggie D.; Abeysekera K.W.M.; Asif A.; Hay F.; Maccabe T.; Pathak S.; Robertson H.; Sandberg C.; Woodland H.; Charalabopoulos A.; Kordzadeh A.; Anderson J.; Napier D.; Hodges P.; Jones G.; Sheiybani G.; Archer T.; Khan A.; Kirk S.; Walker N.; Hassam U.; Wong I.; Silva M.; Jones K.; Allen J.; Abbas S.H.; Harborne M.; Majid Z.; Eardley N.; Reilly I.; Wadsworth P.; Bell C.; Holloway K.; Stockton W.; Thomas R.; Williams K.J.; Canelo R.; Tay Y.; Adnan M.; Aroori S.; Rajaretnam N.; Rekhraj S.; Wilkins A.; Nelapatia R.; Verebcean M.; Braithwaite S.; Apollos J.; Robertson N.; Belgaumkar A.; Brant A.; Shahdoost A.; French J.J.; Sen G.; Thakkar R.; Kanwar A.; Klaptocz J.; Rodham P.; O'Riordan B.; Maharaj G.; Davies M.; Higgs S.; Cutting J.; Joseph M.; Backhouse L.; Butler J.; Cooper J.; O'nions T.; Shaukat S.; Kumar A.; George V.; Ingmire J.; Saha A.; Coe P.; Noor R.; Lykoudis P.; Elshaer A.; Andreou A.; Clarke T.; Davies O.; Rimmer P.; Kanakala V.; Mitra V.; Akol G.; Burgess M.; Elzubier M.; Jones R.; Majumdar D.; Wescott H.; Bailey A.; Gomez M.; Herman O.; Deguara J.; Whitehead-Clarke T.; Gorard L.; Law R.; Leung L.Y.; Whitelaw D.; Adil M.; Krivan S.; Waters J.; Fernandes R.; Mealey L.; Merh R.; Okaro A.; Shepherd J.; O'Reilly D.; Pilkington J.; Hussain Z.; Ingram S.; Stott M.C.; Abbott S.; Bhamra N.; Hirri F.; Lee K.; Murrell J.; Resool S.; Taylor M.; King M.; Madhotra R.; Ayubi H.; Ali J.; Chander N.; Mckune G.; Wothers T.; Shingler G.; Mortimer M.; Dykes K.; Edwards H.; Menon S.; Gautham A.; Ali I.; Anjum R.; Brookes M.; Wilkinson B.; Tait I.; Noaman I.; Wilson M.; Mogan S.; Rushbrook S.; Hyde S.; Baker S.; Hall P.; Lucas H.; Pease J.; Millar A.; Tariq Z.; Blad W.; Cunningham M.; Hall M.; Luthra P.; Seymour K.; Aawsaj Y.; Jones M.; Elliott D.; Finch J.G.; Rajjoub Y.; Gupta A.; Molloy P.; Mykoniatis I.; Atallah E.; Albraba E.; Asimba V.; Baxter A.; Chin A.; Vojtekova K.; Ong L.; Modi H.N.; Muscara F.; Perry M.; Katz C.; Shaban N.; Dichmont L.; Dissanayake T.; Mostafa W.; Ghosh D.; Hwang S.; Bajomo O.; Lloyd T.; Wye J.; Holt A.; Pathanki A.; Townsend S.; Babar N.; Giovinazzo F.; Kennedy L.; Kandathil M.; King D.; Pillai M.; Glen P.; Holroyd D.; Drozdzik S.; Kourounis G.; Thompson J.; McNally S.; Thomas I.; Reddy Y.; Subar D.; Heywood N.; Khoo E.; Austin A.; Awan A.; Tan H.; Kasi M.; Prasad S.; Baqai M.; Abd Alkoddus M.; Al-Allaf O.; Mitchell K.; Mole S.; Yoong A.; Fusai G.; Brown S.; Bulathsinhala S.; Gilliland J.; Boyce T.; Al-Ardah M.; Matthews E.; Wakefield C.; Hou D.; Thomasset S.; Guest R.; Falconer S.; Hughes M.; Johnston C.; Kung J.W.C.; Lee E.; McNally E.; Sherif A.E.; Stutchfield B.; Baron R.D.; Dunne D.F.J.; Dickerson L.D.; Exarchou K.E.; Knight E.; Whelan P.; Hutchins R.; Wilson P.; Phillpotts S.; Badrulhisham F.; Dawes A.; Derwa Y.; Rajagopal S.; Ramoutar S.; Vaik T.; Bhogal R.H.; McLaren N.; Policastro T.; *Butterworth J.; *Riera M.; *Ismail A.; *Ahmed A.; *Alame R.; *Alford K.; *Banerjee S.; *Bull C.; *Kirby G.; Athwal T.; Hebbar S.; Ishtiaq J.; Kamran U.; Abbasi A.; Kamarul-bahrin M.; Banks A.; Khalil A.; Karanjia N.; Trivedi D.; Chakravaratty S.; Frampton A.; Gabriella J.; Pinn G.; Colleypriest B.; Betteridge F.; Murugiah D.; Rossiter A.; Yong K.; Sellahewa C.; Chui K.; Ehsan A.; Fisher N.; Iyer S.; McMurtry H.; Garbutt G.; Mahgoub S.; Alleyne L.; Harvey J.; Johnson K.; Richards E.; Palaniyappan N.; Bowler C.; Inumerable R.; Abu M.; Suhool A.; Talbot T.; Westwood J.; Zumbo G.; Osborne A.; Botes A.; Dyer S.; Thomas-Jones I.; Merker L.; Przemioslo R.; Roderick M.; Valverde J.; Zerafa A.; Barker S.; Wan A.; Lalani R.; Barrett C.; Kapirial N.; McCarthney K.; Ramamoorthy R.; Yalchin M.; Huggett M.; Macutkiewicz C.; Smith A.; Buchanan A.; Burke J.; Goodchild G.; Keane M.G.; Potts J.; Disney B.; McFarlane M.; Baker E.; Bullock S.; Coleman S.; Mcardle C.; Morgan J.; Mozdiak E.; Obisesan A.; O'Flynn L.; Mowbray N.; de Berker H.T.; Driscoll P.; Alberts J.C.; Sadien I.D.; Webb K.; Khalil H.; Parmar C.; Sadigh D.; Seyed-Safi P.; Shala L.; Somasundaram M.; Bryce G.; McCormack K.; Jamieson W.; Mitchell L.; Cheung D.; Hicken B.; Abbas N.; Kurian A.; Tahir I.; Spearman J.; Johnston T.; Jones C.

Citation:Pancreatology; Sep 2021; vol. 21 (no. 6); p. 1127-1134

Abstract:Objective: UK national guidelines recommend pancreatic enzyme replacement therapy (PERT) in pancreatic cancer. Over 80% of pancreatic cancers are unresectable and managed in non-surgical units. The aim was to assess variation in PERT prescribing, determine factors associated with its use and identify potential actions to improve prescription rates. Design(s): RICOCHET was a national prospective audit of malignant pancreatic, peri-ampullary lesions or malignant biliary obstruction between April and August 2018. This analysis focuses on pancreatic cancer patients and is reported to STROBE guidelines. Multivariable regression analysis was undertaken to assess factors associated with PERT prescribing. Result(s): Rates of PERT prescribing varied among the 1350 patients included. 74.4% of patients with potentially resectable disease were prescribed PERT compared to 45.3% with unresectable disease. PERT prescription varied across surgical hospitals but high prescribing rates did not disseminate out to the respective referring network. PERT prescription appeared to be related to the treatment aim for the patient and the amount of clinician contact a patient has. PERT prescription in potentially resectable patients was positively associated with dietitian referral (p = 0.001) and management at hepaticopancreaticobiliary (p = 0.049) or pancreatic unit (p = 0.009). Prescription in unresectable patients also had a negative association with Charlson comorbidity score 5-7 (p = 0.045) or >7 (p = 0.010) and a positive association with clinical nurse specialist review (p = 0.028). Conclusion(s): Despite national guidance, wide variation and under-treatment with PERT exists. Given that most patients with pancreatic cancer have unresectable disease and are treated in non-surgical hospitals, where prescribing is lowest, strategies to disseminate best practice and overcome barriers to prescribing are urgently required.

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Healing pattern of the cervical stroma following cold coagulation treatment for cervical intraepithelial neoplasia: A case report (2022)

Type of publication:
Journal article

Author(s):
*Papoutsis D; *Williams J; *Underwood M; *Parry-Smith W

Citation:
Oncology letters; 2022 Mar; Vol. 23 (3), pp. 81

Abstract:
Cold coagulation of the cervix for cervical intraepithelial neoplasia (CIN), when compared with cervical excision, has previously demonstrated comparable cure rates and a reduction in the rate of spontaneous preterm birth. In the present report the healing pattern in the cervices of two women after cold coagulation is described. Both women underwent cold coagulation due to CIN3, which was found on pre-treatment cervical punch biopsies. They were followed up after cold coagulation and at 7 and 18 months, respectively, they underwent cervical excision. The histopathological slides from the excised specimen were reviewed, which represents the healed cervix after cold coagulation. A clear boundary of collagenisation was noted in the superficial stroma, which appeared to stop at the junction with the healthy muscular stroma. The collagenised superficial stroma depth, which represents the area that was thermally ablated and has now healed, measured 1.6 and 1.5 mm for the two women, respectively, which is less compared with that typically removed by cervical excision. Observations from these two cases indicate that cold coagulation does not appear to disrupt the deep tissue architecture of the cervix and could therefore explain the reduced levels of adverse obstetric morbidity in patients who underwent cold coagulation ablative treatment of the cervix, which has been previously reported.

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Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol (2022)

Type of publication:
Systematic Review

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Amos, Claire L; Atako, Nafisah; Pugh, Cheryl; Buckner, Michelle; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Gilson, Clare; Rush, Hannah; Bowen, Jo; Lydon, Anna; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzoueb, Mymoona; Parikh, Omi; Robinson, Angus; Syndikus, Isabel; Wylie, James; Zarkar, Anjali; Thalmann, George; de Bono, Johann S; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet; Dec 2021 [epub ahead of print]

Abstract:
BACKGROUND Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

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Direct to surgery treatment of suspected lung cancer – results from a UK lung cancer multidisciplinary team (MDT) (2021)

Type of publication:
Conference abstract

Author(s):
*Manoj Marathe, *Tinaye Mandishona, *Harmesh Moudgil, *Nawaid Ahmad, *Emma Crawford, *Annabel Makan, *Koottalai Srinivasan

Citation:
European Respiratory Journal 2021 58 Suppl 65, OA2640

Abstract:
Introduction: The selective resection of suspicious nodules and masses without pre-operative tissue diagnosis is an established treatment that can shorten time to curative lung cancer treatment. We evaluated the outcomes of this practice in our local MDT.
Methods: We performed a retrospective review of 84 patients with curatively resectable single lung lesions who underwent surgical resection from January 2017 to December 2018 without histological diagnosis.
Results: Malignancy was confirmed in 68/84 (81%) patients. 57/68 patients were diagnosed with a primary lung malignancy and 11/68 with metastatic disease. Figures 1 and 2 show significant and non significant differentiators determined by the chi squared test.
Conclusion: These results support the use of spiculated and / or irregular lesion appearance along with SUV uptake >=2.5 as significant pre-histology differentiators of malignant and benign lesions. Neither past history of cancer nor size of lesion in isolation were predictive of malignancy. Our study gives further evidence that a direct-to-surgery approach is a suitable treatment option for appropriate suspicious nodules.

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The largest transcriptomic resource for radiotherapy-treated high-risk prostate cancer: paving the way for companion diagnostic biomarkers (2021)

Type of publication:Conference abstract

Author(s):Thiruthaneeswaran N.; Bibby B.; Pereira R.; More E.; Hoskin P.; Bristow R.; Choudhury A.; West C.; Wylie J.; *Denley H.; Henry A.

Citation:Journal of Medical Imaging and Radiation Oncology; Sep 2021; vol. 65 ; p. 252

Abstract:Purpose: The Cancer Genome Atlas (TCGA) is a valuable resource for developing and validating gene signatures for personalising treatments. TCGA samples came from patients who received heterogeneous treatments-dominated by surgery. Improving the biological precision of radiotherapy is hampered by the lack of well annotated cohorts that reflect patient populations relevant for radiation oncologists. We aimed to generate transcriptomic data from needle core biopsies for a large multicentre cohort of high-risk prostate cancer patients and use the data to validate published gene signatures. Methods and materials: A total of 478 NCCN classified high-risk patients treated from 2008-2016 were identified: 244 patients received intensity modulated radiotherapy (IMRT) to the prostate only (BEDalpha/beta 1.5-3Gy of 120-180 Gy) and 234 patients received IMRT to the prostate and a high dose rate (HDR) brachytherapy boost (BEDalpha/beta 1.5-3Gy 159-265 Gy). Androgen deprivation was given to all patients for 3-36 months. Biochemical failure was defined as prostate-specific antigen (PSA) rise of >=2 ng/ml above nadir post-radiotherapy. The primary clinical end-point was 7-year biochemical relapse-free survival (bRFS). Gene expression data were generated from diagnostic needle core biopsies using Affymetrix Clariom S arrays. Two (28-gene and 32 gene) published hypoxia gene signatures and a tumour radiosensitivity index (RSI) were tested for prognostic significance [1-3]. Result(s): The median follow-up for the entire cohort was 6.3 years. Both the 28 gene (p = 0.021) and 32-gene (p = 0.033) hypoxia signatures were prognostic for 7-year bRFS. Non-prostate hypoxia signatures were not prognostic. The bRFS for radioresistant (RSI-R) vs radiosensitive (RSI-S) was prognostic in the IMRT EBRT only cohort (p = 0.01) and not in the HDR boost cohort (p = 0.8). Conclusion(s): We generated the largest high-risk prostate radiotherapy cohort with full gene expression data and showed its value in validating published gene signatures. The RSI signature should be explored further to select patients with high-risk prostate cancer who should benefit from dose escalation with a HDR brachytherapy boost. This resource will be a valuable asset for future research generating and validating signatures for personalising radiotherapy in men with prostate cancer.

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Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study (2021)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative (includes *Blair J, *Lakhiani A, *Parry-Smith W, *Sahu B of Shrewsbury and Telford Hospital NHS Trust)

Citation:
The Lancet Oncology;  November 2021, Volume 22, Issue 22, Pages 1507-1517

Abstract:
Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.
Methods; This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.
Findings; Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.
Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.

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