Oncology

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

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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 (2024)

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Type of publication:
Journal article

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

Citation:
European Journal of Obstetrics, Gynecology, & Reproductive Biology. 294:44-48, 2024 Mar.

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.

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Biomarkers in Prostate Cancer: A Review (2024)

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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)

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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)

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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)

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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)

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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)

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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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