A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial (2024)

Type of publication:
Randomised controlled trial

Author(s):
Smith, Tim A D; West, Catharine M L; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J; Hussain, Syed A; *Denley, Helen; Hall, Emma; Porta, Nuria; Huddart, Robert A; James, Nick D; Choudhury, Ananya.

Citation:
EBioMedicine. 101:105032, 2024 Feb 21.

Abstract:
BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial.

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A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer (2024)

Type of publication:
Journal article

Author(s):
Holt, Simon; Verrill, Mark; *Pettit, Laura; Rigg, Anna; Hickish, Tamas; Archer, Caroline; Dent, Jo; Dillon, Marianne; Nathan, Mark; Barthelmes, Ludger; Rehman, Shazza; Sharaiha, Yousef; Innis, Paige; Sai-Giridhar, Priya; Khawaja, Saira.

Citation:
British Journal of Cancer. 2024 Feb 02.

Abstract:
BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score R assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of 787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.

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Pre-treatment plasma proteomics-based predictive biomarkers for immune related adverse events in non-small cell lung cancer (2023)

Type of publication:
Conference abstract

Author(s):
Naidoo J.; Reinmuth N.; Puzanov I.; Bar J.; Kamer I.; Koch I.; Moskovitz M.; Levy-Barda A.; Agbarya A.; Zer A.; Abu-Amna M.; Farrugia D.; Lotem M.; Price G.; Harkovsky T.; Hassani A.; Katzenelson R.; *Chatterjee A.; Yelin B.; Sela I.; Dicker A.; Elon Y.; Harel M.; Leibowitz R.

Citation:
Journal for ImmunoTherapy of Cancer. Conference: 38th Annual Meeting of the Society for Immunotherapy of Cancer's, SITC 2023. San Diego, CA United States. 11(Supplement 1) (pp A1356), 2023. Date of Publication: November 2023.

Abstract:
Background Immune-related adverse events (irAEs) resulting from immune checkpoint inhibitors (ICIs) can substantially affect patient quality of life and treatment trajectory. Currently, there are no reliable pre-treatment biomarkers for predicting the development of irAEs; hence, there is a clinical need for irAE predictive biomarkers. Methods Plasma samples were obtained at baseline from 426 non-small cell lung cancer (NSCLC) patients treated with ICIs as part of an ongoing multi-center clinical trial (NCT04056247; approved by local IRB committees from each site) with irAE-related information. Proteomic profiling of plasma samples was performed using the SomaScan assay (SomaLogic Inc.), enabling deep coverage of approximately 7000 proteins in each sample. A machine learning-based model was developed to predict significant irAEs arising up to 3 months from treatment initiation; significant irAEs were defined as irAEs with CTCAE grade >=3 or irAEs that induced treatment discontinuation. Using the model, we identified a set of plasma proteins, termed Toxicity Associated Proteins (TAPs), that serve as indicators of irAEs depending on their plasma level in the individual patient. Bioinformatic analysis was performed to decipher the biology underlying immunerelated toxicity implied by the TAPs. Results Overall, 60 patients experienced significant irAEs at early onset; 197 patients had low grade irAEs, irAEs at late onset or AEs that are not immune-related; and 169 patients did not display any adverse event. A computational model was generated to predict significant irAEs, showing a strong correlation between the predicted probability of significant irAEs and the observed rate of such events (R2= 0.92; pvalue <0.0001), implying good prediction capabilities. The prediction was based on a set of 449 TAPs. Interestingly, nearly half of these TAPs were previously identified as proteins associated with clinical benefit from ICI therapy, suggesting a close relationship between irAEs and clinical benefit, in accordance with previous reports. A detailed examination of the TAPs revealed some key findings. Patients who experienced irAEs had a larger number of TAPs related to neutrophils, inflammation, and cell death resistance, while the number of lymphocyte-related TAPs was low in these patients. Patients who did not experience irAEs displayed higher levels of extracellular matrix-related proteins. Conclusions We describe a novel computational model for predicting significant irAEs in patients with NSCLC based on proteomic profiling of pre-treatment plasma samples. The TAPs provide insights into the biological processes underlying irAEs. Early prediction of irAEs could enable personalized management plans and mitigation strategies to reduce the risk of irAEs in NSCLC.

Counselling and management of women with genetic predisposition to gynaecological cancers (2023)

Type of publication:
Journal article

Author(s):
*Malik, Naushabah; *Sahu, Banchhita

Citation:
European Journal of Obstetrics, Gynecology, & Reproductive Biology. 294:44-48, 2023 Nov 09.

Abstract:
OBJECTIVE: To review the literature with reference to counselling and management of women with genetic predisposition to gynaecological cancers. METHODS: Histochemical analysis, ultrasound, blood investigations, genetic testing, screening and risk-reducing surgery (RRS) are important tools for the management of gynaecological cancers and mortality reduction. Counselling can assist in timely management of gynaecological cancers. Systematic reviews, review articles, observational studies and clinical trials on PubMed, published in the English language, were included in this review. RESULTS: The management of women with genetic predisposition to gynaecological cancers through screening tests and RRS has led to a significant decrease in the risk of malignancy through RRS in cases with BRCA1 and BRCA2 gene mutations. RRS and screening have also been found to reduce the mortality rate and increase the survival rate in women with BRCA1 and BRCA2 gene mutations. The efficacy of endometrial cancer surveillance in women with Lynch syndrome is still unproven. RRS has not been reported to be effective in women with Cowden syndrome. The risk of ovarian malignancies in individuals with germline mutations remains minimal in the general population in comparison with genetic mutations. CONCLUSION: Genetic testing and RRS should be implemented in addition to genetic counselling for proper management and mortality reduction of women predisposed to gynaecological cancers.

Biomarkers in Prostate Cancer: A Review (2024)

Type of publication:
Journal article

Author(s):
Ahmadieh, Nizar; Zeidan, Toufic; Chaaya, Celine; *Cain, David; Aoude, Marc; Abouchahla, Anita; Kourie, Hampig Raphael; Nemer, Elie.

Citation:
The Gulf Journal of Oncology. 1(44):81-93, 2024 Jan.

Abstract:
BACKGROUND: Prostate cancer (PC) is the second most common cancer in men worldwide. It's the second leading cause cancer men in death. Prognostic tests based on molecular and biomarker analysis of tumor tissue may improve risk stratification of prostate cancer 2. MATERIALS AND METHODS: After a search on Pubmed for PC biomarkers, 72 papers responded to the objectives and will be included in the review. RESULTS: A plethora of biomarkers are predictive for the prognosis of PC and its response to certain therapies, while others, once thought to be indicative of prognosis in PC, were not. CONCLUSIONS: This study can help in the development of diagnostic and prognostic tests of PC and contribute to the ongoing research into already existing tests.

A Literature Review of Perioperative Outcomes of Robotic Radical Nephrectomy (RRN) Versus Laparoscopic Radical Nephrectomy (LRN) for Renal Cell Carcinoma (RCC) (2023)

Type of publication:Journal article

Author(s):Alzamzami, Muhannad; Geirbely, Alsamoal; *Ahmed, Mohamed B; Osman, Rabab; Gandhi, Rahi; Mohammed, Mahmoud; Elhadi, Mohammed; Kodera, Ahmed

Citation:Cureus. 15(11):e49077, 2023 Nov.

Abstract:Renal cell carcinoma (RCC) is an adenocarcinoma of the renal cortex. Radical nephrectomy remains the standard of care for managing massive renal tumours. Robotic-assisted radical nephrectomy is an increasing alternative technique to laparoscopic radical nephrectomy (LRN). The da Vinci Surgical System allows for improved dexterity, increased visualisation, tremor filtration and an ergonomic setting to enhance surgeon comfort. The aim was to compare the perioperative outcomes pertaining to operative time, intraoperative complications, blood loss and length of hospital stay between the robotic and LRN for RCC. Studies that compared the perioperative findings between robotic radical nephrectomy (RNN) and LRN for RCC were included. The literature review was carried out according to the Cochrane collaboration standards where applicable. Highly sensitive search strategies like MeSH terms and controlled vocabularies were used to identify relevant studies that compare the RNN outcomes to the LRN. Following the literature search, a total of 73 articles were collected, 60 articles were excluded at the stage of reviewing the titles, eight articles were excluded after reading the abstracts, and five articles were included in this paper. Five studies were included in this analysis, with a total sample size of 1770 patients, 735 were in the robotic arm, and 1035 were in the laparoscopic arm. Generally, there were no differences between both arms in terms of demographic data and age of patients. Closer analysis of the perioperative outcomes did not reveal significant differences between the two groups related to the estimated blood loss, length of hospital stay or post-operative complications. The laparoscopic techniques have less operative time than the robotic ones. RRN is an expanding approach for patients with RCC with some potential technical benefits over laparoscopic ones. RRN is similar to LRN in the perioperative outcomes, with few potential drawbacks of RRN, including higher costs. However, a prospective comparison of RRN with LRN in many cases at multiple centres with long-term oncological results best illustrates the status of RRN versus LRN.

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P2.23-07 Crucial, Complex, Caring: A Professional Development Framework for Lung Cancer Nurse Specialists (2023)

Type of publication:Conference abstract

Author(s):Clayton K.J.; Fenemore J.; Barton P.; Roberts J.; Ivey S.; *McAdam J.; Shepherd P.; Magee L.

Citation:Journal of Thoracic Oncology. Conference: 2023 World Conference on Lung Cancer. Singapore Singapore. 18(11 Supplement) (pp S397), 2023. Date of Publication: November 2023.

Abstract:Introduction: Lung cancer specialist nursing is a varied, valuable and rewarding career, and the need for lung cancer nurse specialists (LCNS) is increasing. Lung Cancer Nursing UK (LCNUK) wants to encourage nurses to aspire to becoming an LCNS, and to support those already working in lung cancer teams to flourish professionally. We want employers to recognise LCNS' capabilities and to recruit and reward them accordingly. LCNUK therefore set out to draft the first professional development framework for LCNS. The Framework is intended to guide nurses, line managers and employers on the core skills, knowledge and expertise that LCNS will gain and demonstrate as they progress in role. Method(s): LCNUK convened a working group which reviewed exemplars and supporting literature., aligned with the four pillars of advanced practice. Feedback on the draft was sought from expert stakeholders and was approved by the LCNUK Steering Committee. The Framework was developed in a collaboration between LCNUK and MSD, who funded a policy consultancy to provide support. LCNUK retained editorial independence. Result(s): The Framework sets out the qualifications, clinical skills, knowledge, leadership and management and research capabilities that LCNUK expects aspiring and existing LCNS to demonstrate or be working towards. It includes case studies of nurses' career journeys and an example of a successful case for job matching and re-banding. The Framework is available on the LCNUK website at. Conclusion(s): The Framework asserts the crucial role of LCNS in managing safety-critical and complex patient care and in leading service delivery and improvement. We hope it will prove a valuable tool to nurses, employers and policymakers in understanding the complexity and importance of this essential role. Following collaboration with European lung cancer nursing colleagues, via ELCC 2022, while not implemented the value and importance of the framework has been acknowledged by Croatian colleagues.The framework has also been welcomed and acknowledged by the devolved nations of the United Kingdom, Wales, Scotland and Northern Ireland.

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Pleural-based giant solitary fibrous tumour with associated hypoglycaemia: unusual presentation with pulmonary hypertension in a patient with Doege-Potter syndrome (2023)

Type of publication:
Journal article

Author(s):
*Gohir, Qasim; Ghosh, Shilajit; *Bosher, Olivia; Crawford, Emma; *Srinivasan, Koottalai; *Moudgil, Harmesh

Citation:
Clinical Medicine, Sep2023; 23(5): 518-520.

Abstract:
Refractory hypoglycaemia in a patient with a solitary fibrous tumour (SFT) is very rare and was first reported in 1930 independently by Doege and Potter, leading to it being named 'Doege–Potter syndrome'. Here, we report the unusual case of a 77-year-old woman with a giant solitary fibrous pleural tumour who presented with complicating pulmonary hypertension and associated heart failure with hypoglycaemia, and subsequently underwent curative resection of the pleural mass with clinical improvement.

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Psychological distress in lung cancer: patient selfassessment versus lung cancer nurse specialist (LCNS) judgement (2023)

Type of publication:
Conference abstract

Author(s):
Walker S.; Lamonby V.; Orwin R.; *McAdam J.; Bate G.; Vick J.; Elrick N.; Shepherd P.; Flint A.; Dalrymple P.

Citation:
Lung Cancer. Conference: 21st Annual British Thoracic Oncology Group Conference 2023. Belfast United Kingdom. 178(Supplement 1) (pp S76), 2023. Date of Publication: April 2023.

Abstract:
Aims: Distress Thermometer (DT) tool compares LCNS' clinical judgment of patients' psychological distress to patients' self-reported assessment. Method(s): Few studies examine nurses' abilities assessing distress in patients, only one focusing lung cancer. They suggest Nurse Specialists within cancer settings struggle identifying distress using clinical judgement. The Distress Thermometer, a self-reported validated tool, can be used to screen for distress in cancer patients, but cannot replace comprehensive assessment. LCNUK members were surveyed May 2022. 44% used validated assessment tools and 75% confirmed these influenced management. LCNS each assessed 12 patients using The Distress Thermometer, face to face or telephone, occurring following first patient contact. The LCNS used DT tool assessing their perception of patient's distress level. Patients were asked to assess themselves using the same tool. Result(s): 45% assessments scored were identical 36.7% LCNS scored higher than patient 18.3% LCNS scored lower than patient 68.3% LCNS assessments within one DT point of patient Average difference of score between patient and LCNS was 0.4. 93.8% telephone assessments within 1 DT point 54.5% F2F assessments within 1 DT point Conclusion(s): LCNS's have excellent clinical judgement assessing patient distress, comparable to patient's self-assessment in most cases.

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

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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