Oncology

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial (2023)

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Type of publication:
Journal article

Author(s):
Joharatnam-Hogan N.; Hatem D.; Cafferty F.H.; Petrucci G.; Cameron D.A.; Ring A.; Kynaston H.G.; Gilbert D.C.; Wilson R.H.; Hubner R.A.; Swinson D.E.B.; Cleary S.; Robbins A.; MacKenzie M.; Scott-Brown M.W.G.; Sothi S.; Dawson L.K.; Capaldi L.M.; Churn M.; Cunningham D.; Khoo V.; Armstrong A.C.; Ainsworth N.L.; Horan G.; Wheatley D.A.; Mullen R.; Lofts F.J.; Walther A.; Herbertson R.A.; Eaton J.D.; O'Callaghan A.; Eichholz A.; Kagzi M.M.; Patterson D.M.; Narahari K.; Bradbury J.; Stokes Z.; Rizvi A.J.; Walker G.A.; Kunene V.L.; *Srihari N.; Gentry-Maharaj A.; Meade A.; Patrono C.; Rocca B.; Langley R.E.

Citation:
British Journal of Cancer. 129(4):706-720, 2023 Sep.

Abstract:
Background: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. Method(s): Urinary 11-dehydro-thromboxane B2(U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. Result(s): In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. Conclusion(s): Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

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Dysphagia-optimised intensity-modulated radiotherapy versus standard intensity-modulated radiotherapy in patients with head and neck cancer (DARS): a phase 3, multicentre, randomised, controlled trial (2023)

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Type of publication:
Journal article

Author(s):
Nutting C.; Finneran L.; Roe J.; Sydenham M.A.; Beasley M.; Bhide S.; Boon C.; Cook A.; De Winton E.; Emson M.; Foran B.; Frogley R.; Petkar I.; *Pettit L.; Rooney K.; Roques T.; Srinivasan D.; Tyler J.; Hall E.

Citation:
Lancet Oncology. 24(8):868-880, August 2023

Abstract:
BACKGROUND: Most newly diagnosed oropharyngeal and hypopharyngeal cancers are treated with chemoradiotherapy with curative intent but at the consequence of adverse effects on quality of life. We aimed to investigate if dysphagia-optimised intensity-modulated radiotherapy (DO-IMRT) reduced radiation dose to the dysphagia and aspiration related structures and improved swallowing function compared with standard IMRT. METHOD(S): DARS was a parallel-group, phase 3, multicentre, randomised, controlled trial done in 22 radiotherapy centres in Ireland and the UK. Participants were aged 18 years and older, had T1-4, N0-3, M0 oropharyngeal or hypopharyngeal cancer, a WHO performance status of 0 or 1, and no pre-existing swallowing dysfunction. Participants were centrally randomly assigned (1:1) using a minimisation algorithm (balancing factors: centre, chemotherapy use, tumour type, American Joint Committee on Cancer tumour stage) to receive DO-IMRT or standard IMRT. Participants and speech language therapists were masked to treatment allocation. Radiotherapy was given in 30 fractions over 6 weeks. Dose was 65 Gy to primary and nodal tumour and 54 Gy to remaining pharyngeal subsite and nodal areas at risk of microscopic disease. For DO-IMRT, the volume of the superior and middle pharyngeal constrictor muscle or inferior pharyngeal constrictor muscle lying outside the high-dose target volume had a mandatory 50 Gy mean dose constraint. The primary endpoint was MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after radiotherapy, analysed in the modified intention-to-treat population that included only patients who completed a 12-month assessment; safety was assessed in all randomly assigned patients who received at least one fraction of radiotherapy. The study is registered with the ISRCTN registry, ISRCTN25458988, and is complete. FINDINGS: From June 24, 2016, to April 27, 2018, 118 patients were registered, 112 of whom were randomly assigned (56 to each treatment group). 22 (20%) participants were female and 90 (80%) were male; median age was 57 years (IQR 52-62). Median follow-up was 39.5 months (IQR 37.8-50.0). Patients in the DO-IMRT group had significantly higher MDADI composite scores at 12 months than patients in the standard IMRT group (mean score 77.7 [SD 16.1] vs 70.6 [17.3]; mean difference 7.2 [95% CI 0.4-13.9]; p=0.037). 25 serious adverse events (16 serious adverse events assessed as unrelated to study treatment [nine in the DO-IMRT group and seven in the standard IMRT group] and nine serious adverse reactions [two vs seven]) were reported in 23 patients. The most common grade 3-4 late adverse events were hearing impairment (nine [16%] of 55 in the DO-IMRT group vs seven [13%] of 55 in the standard IMRT group), dry mouth (three [5%] vs eight [15%]), and dysphagia (three [5%] vs eight [15%]). There were no treatment-related deaths. INTERPRETATION: Our findings suggest that DO-IMRT improves patient-reported swallowing function compared with standard IMRT. DO-IMRT should be considered a new standard of care for patients receiving radiotherapy for pharyngeal cancers. FUNDING: Cancer Research UK.

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Management And Assessment Of Indeterminate (U3) Thyroid Nodules: A 5-Year Multisite Retrospective Study (2023)

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Type of publication:
Journal article

Author(s):
*Patel R.; *Conybeare A.; *Panesar H.; *Badrol S.; *Sood S.

Citation:
Journal of Ayub Medical College, Abbottabad : JAMC. 35(2) (pp 216-219), April 2023.

Abstract:
BACKGROUND: The U grading of Ultrasound scan (USS) is used to assess the likelihood of malignancy in a thyroid nodule and help determine those that warrant an FNAC confirmation. All those of a U3-5 warrant an FNAC for confirmation and typing. This study aims to review the follow-up practice and the likelihood of picking up a malignancy on subsequent USS and FNAC, for those determined as an indeterminate U3 nodule. METHOD(S): We retrospective reviewed the trust database (Portal) for patients who had a U3 nodule reported on USS identified, and clinical, operative and outcomes data were analysed. RESULT(S): 258 scans were identified over a 5-year period. The average age was 59 (range 15- 95) years old at first USS with a female to the male sex ratio of 4:1. The average number of USS that each patient prior to final diagnosis had averaged at 2.8 (range 1-12). Of those with an initial Thy status, 64 (33%) were benign (Thy2) and a further 49 (25%) were non diagnostics (Thy1). Over time, only 7 nodules were upgraded to a potential malignancy. Of those who underwent surgery, a final histological diagnosis was obtained in 41 cases. Only Thy1, 2 and 3f produced benign final histology results. CONCLUSION(S): For those indeterminate (U3) nodules of Th1-3f, electing for a watch and wait management strategy is reasonable for up to 2.5 years and 4 follow-up scans at an interval of 6-12 months should be implemented. A Thy2 result on a U3 nodule should not be taken as completely reassuring, a high index of suspicion of malignancy must be maintained.

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Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol (2023)

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Type of publication:
Journal article

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Sachdeva, Ashwin; Jones, Craig; Hoyle, Alex; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Gilson, Clare; Rush, Hannah; Abdel-Aty, Hoda; Amos, Claire L; Murphy, Claire; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Parkar, Nazia; Pugh, Cheryl; Diaz-Montana, Carlos; Pezaro, Carmel; Grant, Warren; Saxby, Helen; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzouebi, Mymoona; Parikh, Omi; Robinson, Angus; Montazeri, Amir H; Wylie, James; Zarkar, Anjali; Cathomas, Richard; Brown, Michael D; Jain, Yatin; 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.

Citation:
Lancet Oncology. 24(5):443-456, 2023 May.

Abstract:
BACKGROUND: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. METHODS: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0-2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). FINDINGS: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86-107) in the abiraterone trial and 72 months (61-74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76.6 months (95% CI 67.8-86.9) in the abiraterone group versus 45.7 months (41.6-52.0) in the standard of care group (hazard ratio [HR] 0.62 [95% CI 0.53-0.73]; p<0.0001). In the abiraterone and enzalutamide trial, median overall survival was 73.1 months (61.9-81.3) in the abiraterone and enzalutamide group versus 51.8 months (45.3-59.0) in the standard of care group (HR 0.65 [0.55-0.77]; p<0.0001). We found no difference in the treatment effect between these two trials (interaction HR 1.05 [0.83-1.32]; pinteraction=0.71) or between-trial heterogeneity (I2 p=0.70). In the first 5 years of treatment, grade 3-5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (<1%) with standard of care in the abiraterone trial). INTERPRETATION: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years.

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MYC/BCL6 Double Hit Lymphoma Negative For (3;8) BCL6:MYC Fusion is Associated With Inferior Survival, in Contrast with T(3;8) Positive Pseudo-Double Hit Lymphoma (2023)

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Type of publication:
Conference abstract

Author(s):
Maybury, B. D.; James, L.; Chadderton, N.; Dowds, J.; Venkatadasari, I.; Riley, J.; Qureshi, I.; Talbot, G.; Giles, H. V.; Phillips, N. J.; Gonzalez, M. Vega; Rakesh, P.; Haslam, A.; Davies, D.; Moosai, S.; Lane, S. A.; *Shenouda, A.; Cherian, G. V.; Kaudlay, P. K.;Starczynski, J.; et al

Citation:
Hematological Oncology, June 2023 Supplement 1; 41: 205-207.

Abstract:

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Detailed Sub-study Analysis of the SECRAB Trial: Quality of Life, Cosmesis and Chemotherapy Dose Intensity (2023)

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Type of publication:
Journal article

Author(s):
Fernando IN; Lax S; Bowden SJ; Ahmed I; Steven JH; Churn M; Brunt AM; *Agrawal RK; Canney P; Stevens A; Rea DW Authors Full Name Fernando, I N; Lax, S; Bowden, S J; Ahmed, I; Steven, J H; Churn, M; Brunt, A M; Agrawal, R K; Canney, P; Stevens, A; Rea, D W.

Citation:
Clinical Oncology (Royal College of Radiologists). Volume 35, pages 397-407, 2023 Mar 20.

Abstract:
AIMS: SECRAB was a prospective, open-label, multicentre, randomised phase III trial comparing synchronous to sequential chemoradiotherapy (CRT). Conducted in 48 UK centres, it recruited 2297 patients (1150 synchronous and 1146 sequential) between 2 July 1998 and 25 March 2004. SECRAB reported a positive therapeutic benefit of using adjuvant synchronous CRT in the management of breast cancer; 10-year local recurrence rates reduced from 7.1% to 4.6% (P = 0.012). The greatest benefit was seen in patients treated with anthracycline-cyclophosphamide, methotrexate, 5-fluorouracil (CMF) rather than CMF. The aim of its sub-studies reported here was to assess whether quality of life (QoL), cosmesis or chemotherapy dose intensity differed between the two CRT regimens. MATERIALS AND METHODS: The QoL sub-study used EORTC QLQ-C30, EORTC QLQ-BR23 and the Women's Health Questionnaire. Cosmesis was assessed: (i) by the treating clinician, (ii) by a validated independent consensus scoring method and (iii) from the patients' perspective by analysing four cosmesis-related QoL questions within the QLQ-BR23. Chemotherapy doses were captured from pharmacy records. The sub-studies were not formally powered; rather, the aim was that at least 300 patients (150 in each arm) were recruited and differences in QoL, cosmesis and dose intensity of chemotherapy assessed. The analysis, therefore, is exploratory in nature. RESULTS: No differences were observed in the change from baseline in QoL between the two arms assessed up to 2 years post-surgery (Global Health Status: -0.05; 95% confidence interval -2.16, 2.06; P = 0.963). No differences in cosmesis were observed (via independent and patient assessment) up to 5 years post-surgery. The percentage of patients receiving the optimal course-delivered dose intensity (>=85%) was not significantly different between the arms (synchronous 88% versus sequential 90%; P = 0.503). CONCLUSIONS: Synchronous CRT is tolerable, deliverable and significantly more effective than sequential, with no serious disadvantages identified when assessing 2-year QoL or 5-year cosmetic differences.

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Global impact of COVID-19 pandemic on gastric cancer patients (2023)

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Type of publication:
Journal article

Author(s):
Herrera-Kok J.H.; Parmar C.; Bangash A.H.; Samadov E.; Demirli Atici S.; Cheruvu C.V.; Abouelazayem M.; Yang W.; Galanis M.; Di Maggio F.; Isik A.; *Bandopyadaya S.; Viswanath Y.K.

Citation:
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. (no pagination), 2023. Date of Publication: 02 Mar 2023.[epub ahead of print]

Abstract:

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High BMI at breast cancer diagnosis associated with significantly more metastatic disease, and increased likelihood of death from breast cancer recurrence (2023)

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Type of publication:
Conference abstract

Author(s):
*Lake, Blossom; Damery, Sarah; *Wilson, Mandy; *Appleton, Donna; Jolly, Kate

Citation:
European Journal of Surgical Oncology, February 2023, Volume 49(2), pages E87-E88

Abstract:
Background: 50% of patients with breast cancer are overweight or obese, with the West Midlands having second highest rate of obesity in the UK. Elevated BMI has been associated with breast cancer recurrence. This study looked at recurrence in Shropshire breast cancer survivors.

Treatment and outcomes of patients with gastrointestinal toxicity following immunotherapy: A large multi-center retrospective study in the United Kingdom by the National Oncology Trainees Collaborative for Healthcare Research (NOTCH) (2022)

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Type of publication:
Conference abstract

Author(s):
Swaminathan M.; Angelakas A.; Baxter M.; Cotton J.; Dobeson C.B.; Feeney L.; Gault A.C.; Hughes D.J.; Jones C.; Lee R.; Mughal S.A.; *Parikh S.P.; Pritchard M.; Rodgers L.J.; Rowe M.P.; Salawu A.T.; Shotton R.; Tinsley N.; Tivey A.; Olsson-Brown A.C.;

Citation:
Immuno-Oncology and Technology. Conference: ESMO Immuno-Oncology Congress 2022. Geneva Switzerland. 16(Supplement 1) (no pagination), 2022. Article Number: 100230. Date of Publication: December 2022.

Abstract:
Background: Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of many cancers, but their use has been associated with the development of gastrointestinal (GI) toxicities such as colitis and hepatitis. Method(s): A multi-center retrospective study across 12 National Health Service centers across the United Kingdom (UK) was conducted by the UK National Oncology Trainees Collaborative for Healthcare Research (NOTCH) over a 2-year period. The study included patients receiving ICIs for malignant melanoma, non-small lung cancer and renal cell cancer as standard of care. Occurrence of clinically significant (>=grade 2) GI toxicity was assessed and correlated with subsequent treatment and outcomes. Multiple logistic regression was used to assess correlation. For overall survival (OS), Kaplan-Meier and log-rank tests were utilised. Result(s): The cohort included 2049 patients. 1230 (60%) were male with a median age of 66. Colitis occurred in 182 (8.9%) patients and hepatitis in 129 (6.3%). Of the patients where treatment was recorded, 129 (70.9%) received treatment with systemic steroids alone and 37 (20.3%) required second-line immunosuppressants (IS) in the colitis group. In the hepatitis group, 101 (78.3%) had steroids alone with 19 (14.7%) having IS. Improved OS was found in patients who experienced colitis (HR 2.59 95%CI: 2.15 to 3.11, p<0.0001) and hepatitis (HR 2.26, 95%CI: 1.84 to 2.79, p=<0.0001) compared to those with no adverse events. Pre-existing autoimmune disease (p=0.02) and combination ICIs (p=0.006) were predictors of colitis that required IS whilst grade 2 and 3 hepatitis (p<0.001) were predictors of hepatitis needing IS. The use of IS did not affect OS significantly in the colitis group (p=0.372) but did correlate with survival in the hepatitis group (p=0.037). Patients that were able to continue treatment with ICIs after toxicity had an increased OS in both groups (p<0.001). Conclusion(s): Patients with GI toxicity following treatment with ICIs have improved OS. The use of IS did not significantly affect OS which suggests they should continue to be utilised in the treatment of GI toxicity. Legal entity responsible for the study: United Kingdom National Oncology Trainees Collaborative for Healthcare Research (NOTCH).

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Effectiveness of weight loss interventions in breast cancer survivors: a systematic review of reviews (2022)

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Type of publication:Systematic Review

Author(s):*Lake B; Damery S; Jolly K

Citation:BMJ Open, 2022 Oct 07; Vol. 12 (10), pp. e062288

Abstract:Background: Elevated body mass index (BMI) in breast cancer survivors (BCS) is associated with cancer recurrence and poorer treatment response. Guidelines recommend 5%-10% weight loss for overweight or obese BCS.Objectives: To assess effectiveness of lifestyle interventions for female BCS on weight loss, BMI, body composition, health-related quality of life (HRQoL), physical functioning, psychosocial measures, biomarkers.Design: Systematic review of reviews and meta-analyses.Setting: All clinical settings.Participants: Adult female BCS (active treatment or post-treatment).Methods: Medline, Embase, CINAHL, PsycINFO, Cochrane Library (including Database of Abstracts of Reviews of Effects) were searched for systematic reviews published in English between 1990 and 2022, with weight, BMI or body fat as primary outcome. Narrative reviews, editorials, letters, conference abstracts were excluded. Review quality was assessed using the Joanna Briggs Institute quality assessment tool.Results: 17 reviews were included. Twelve reported significant reductions in one or more anthropometric outcomes: weight -1.36 kg (95% CI:-2.51 to -0.21) to -3.8 kg (95% CI: -5.6 to -1.9); BMI -0.89 kg/m 2 (95% CI: -0.15 to -0.28) to -3.59 kg/m 2 (95% CI: -6.29 to 0.89) or body fat -1.6% (95% CI: -2.31 to -0.88) to -2.6% (95% CI not reported). Significant reductions in two or more anthropometric outcomes were reported in 7/12 reviews, with effective interventions comprising aerobic exercise/aerobic exercise plus resistance training (n=5), or diet and exercise with or without counselling (n=2). Significant improvements were also reported for HRQoL (8/11 reviews), mental health (4/7) and physical functioning (2/3). Group interventions comprising aerobic exercise or aerobic exercise plus resistance training were most likely to improve outcomes.Conclusions: Lifestyle interventions can significantly improve outcomes for BCS. Multimodal interventions are likely to have the greatest impact in reducing weight, BMI and body fat. Further research must define the optimal combination, intensity and duration of effective interventions.

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