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Article ; Online: Cumulative burden of 144 conditions, critical care hospitalisation and premature mortality across 26 adult cancers.

Chang, Wai Hoong / Neal, Richard D / Forster, Martin D / Lai, Alvina G

2023 Volume 14, Issue 1, Page(s) 1484

Abstract: A comprehensive evaluation of the total burden of morbidity endured by cancer survivors remains unavailable. This study quantified the burden of 144 health conditions and critical care admissions across 26 adult cancers and treatment modalities in 243, ... ...

Abstract	A comprehensive evaluation of the total burden of morbidity endured by cancer survivors remains unavailable. This study quantified the burden of 144 health conditions and critical care admissions across 26 adult cancers and treatment modalities in 243,767 adults. By age 60, top conditions ranked by fold difference (cumulative burden in survivors divided by cumulative burden in controls) were haematology, immunology/infection and pulmonary conditions. Patients who had all three forms of treatment (chemotherapy, radiotherapy and surgery) experienced a high cumulative burden of late morbidities compared with patients who received radiotherapy alone. The top five cancers with the highest cumulative burden of critical care admissions by age 60 were bone (12.4 events per 100 individuals [CI: 11.6-13.1]), brain (9.0 [7.5-10.5]), spinal cord and nervous system (7.2 [6.7-7.8]), testis (6.7 [4.9-8.4]) and Hodgkin lymphoma (4.4 [3.6-5.1]). Conditions that were associated with high excess years-of-life-lost were haematological conditions (9.6 years), pulmonary conditions (8.6 years) and immunological conditions or infections (7.8 years). As the population of cancer survivors continues to grow, our results indicate that it is important to tackle long-term health consequences through enacting data-driven policies.
MeSH term(s)	Male ; Adult ; Humans ; Middle Aged ; Mortality, Premature ; Morbidity ; Hodgkin Disease ; Cancer Survivors ; Hospitalization ; Risk Factors
Language	English
Publishing date	2023-03-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-37231-3
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Article ; Online: Effect of statin treatment on the risk of cancer in patients with heart failure: A target trial emulation study.

Ju, Chengsheng / Lau, Wallis C Y / Chambers, Pinkie / Man, Kenneth K C / Forster, Martin D / Mackenzie, Isla S / Manisty, Charlotte / Wei, Li

Pharmacoepidemiology and drug safety

2024 Volume 33, Issue 3, Page(s) e5775

Abstract: Purpose: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin ... ...

Abstract	Purpose: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF. Methods: We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and >6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. Results: The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. >6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses. Conclusions: The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.
MeSH term(s)	Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Neoplasms/epidemiology ; Research Design ; Heart Failure/epidemiology ; Cognition
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors
Language	English
Publishing date	2024-03-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1099748-9
ISSN	1099-1557 ; 1053-8569
ISSN (online)	1099-1557
ISSN	1053-8569
DOI	10.1002/pds.5775
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Article ; Online: Evidence to guide the optimal timing for pre-chemotherapy blood tests for early breast, colorectal cancer and diffuse large B-cell lymphoma.

Chambers, Pinkie / Wei, Li / Forster, Martin D / Kipps, Emma / Wong, Ian C K / Jani, Yogini

Cancer medicine

2021 Volume 10, Issue 22, Page(s) 7996–8004

Abstract: Background: Re-designing services and processes to meet growing demands in chemotherapy services is necessary with increasing treatments. There is little evidence guiding the timing and thresholds to be attained of pre-chemotherapy blood assessments, ... ...

Abstract	Background: Re-designing services and processes to meet growing demands in chemotherapy services is necessary with increasing treatments. There is little evidence guiding the timing and thresholds to be attained of pre-chemotherapy blood assessments, namely neutrophils. Methods: A survey was developed and distributed to health professionals in the United Kingdom (UK) to examine current practice in timing and threshold values of neutrophils and platelets before treatment administration. This was followed by a retrospective cohort study, using data from electronic patient record systems; including patients initiating treatment between January 2013 and December 2018, to determine a safe timeframe for blood assessments; comparing neutrophil, platelet, creatinine and bilirubin levels at different time points. Results: The survey captured 25% of hospitals in the UK and variations were apparent in both the timing of assessments and thresholds needed, particularly for neutrophils. 616 (6.5%) of 4007 patients included had neutrophil levels measured twice within 7 days of treatment (with the first level taken beyond 3 days and the second test being within 3 days of treatment- the UK standard). Of the patients that attained an acceptable neutrophil level at their first test, five of the 616 (0.8%) became ineligible for administration from the test 2 level. 23% of patients improved their grade and became eligible for treatment. Little difference was observed for platelets. Conclusions: We have demonstrated that extending the timeframe for blood tests can be safe, however, this practice may cause unnecessary delays for patients if only an early test is relied on for eligibility.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms/diagnosis ; Colorectal Neoplasms/diagnosis ; Female ; Hematologic Tests/methods ; Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis ; Male ; Middle Aged ; Surveys and Questionnaires ; Young Adult
Language	English
Publishing date	2021-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.4316
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Article: Emerging resistance pathways in lung cancer: what has ROS-1 taught us?

Alrifai, Doraid / Forster, Martin D / Janes, Sam M

Translational lung cancer research

2018 Volume 7, Issue Suppl 1, Page(s) S9–S12

Language	English
Publishing date	2018-03-05
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr.2017.11.13
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Article: A Phase I Study of the Oral Dual-Acting Pan-PI3K/mTOR Inhibitor Bimiralisib in Patients with Advanced Solid Tumors.

Janku, Filip / Choong, Grace M / Opyrchal, Mateusz / Dowlati, Afshin / Hierro, Cinta / Rodon, Jordi / Wicki, Andreas / Forster, Martin D / Blagden, Sarah P / Yin, Jun / Reid, Joel M / Muller, Helene / Cmiljanovic, Natasa / Cmiljanovic, Vladimir / Adjei, Alex A

Cancers

2024 Volume 16, Issue 6

Abstract: Background: Bimiralisib is a pan-PI3K/mTOR inhibitor demonstrating antitumor efficacy in preclinical models. The objectives of this study were to identify a maximum tolerated dose (MTD), pharmacokinetics (PK), a dosing schedule, and adverse events (AEs) ...

Abstract	Background: Bimiralisib is a pan-PI3K/mTOR inhibitor demonstrating antitumor efficacy in preclinical models. The objectives of this study were to identify a maximum tolerated dose (MTD), pharmacokinetics (PK), a dosing schedule, and adverse events (AEs) in patients with advanced solid tumors. Patients and methods: Patients received oral bimiralisib to determine the MTD of one continuous (once daily) and two intermittent schedules (A: Days 1, 2 weekly; B: Days 1, 4 weekly) until progression or unacceptable AEs occurred. Results: The MTD for the continuous schedule was 80 mg, with grade three fatigue as the dose-limiting toxicity (DLT). No MTD was reached with intermittent schedules, with only one DLT in schedule B. PK analysis suggested that 140 mg (schedule A) was within the biologically active dose range and was selected for further exploration. The most frequent treatment-emergent AEs were hyperglycemia (76.2%) in the continuous schedule, and nausea (56-62.5%) in schedules A and B. The most frequent treatment-emergent > grade three AE for all schedules combined was hyperglycemia (28.6%, continuous schedule; 12.0%, schedule A; 12.5%, schedule B). There was one partial response in a head and neck squamous cancer patient with a NOTCH1 Conclusions: Bimiralisib demonstrated a manageable AE profile consistent with this compound class. Intermittent schedules had fewer > grade three AEs, while also maintaining favorable PK profiles. Intermittent schedule A is proposed for further development in biomarker-selected patient populations.
Language	English
Publishing date	2024-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16061137
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Article ; Online: Personalising monitoring for chemotherapy patients through predicting deterioration in renal and hepatic function.

Chambers, Pinkie / Watson, Matthew / Bridgewater, John / Forster, Martin D / Roylance, Rebecca / Burgoyne, Rebecca / Masento, Sebastian / Steventon, Luke / Harmsworth King, James / Duncan, Nick / Al Moubayed, Noura

Cancer medicine

2023 Volume 12, Issue 17, Page(s) 17856–17865

Abstract: Background: In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to identify those patients that need closer monitoring, enabling ...

Abstract	Background: In those receiving chemotherapy, renal and hepatic dysfunction can increase the risk of toxicity and should therefore be monitored. We aimed to develop a machine learning model to identify those patients that need closer monitoring, enabling a safer and more efficient service. Methods: We used retrospective data from a large academic hospital, for patients treated with chemotherapy for breast cancer, colorectal cancer and diffuse-large B-cell lymphoma, to train and validate a Multi-Layer Perceptrons (MLP) model to predict the outcomes of unacceptable rises in bilirubin or creatinine. To assess the performance of the model, validation was performed using patient data from a separate, independent hospital using the same variables. Using this dataset, we evaluated the sensitivity and specificity of the model. Results: 1214 patients in total were identified. The training set had almost perfect sensitivity and specificity of >0.95; the area under the curve (AUC) was 0.99 (95% CI 0.98-1.00) for creatinine and 0.97 (95% CI: 0.95-0.99) for bilirubin. The validation set had good sensitivity (creatinine: 0.60, 95% CI: 0.55-0.64, bilirubin: 0.54, 95% CI: 0.52-0.56), and specificity (creatinine 0.98, 95% CI: 0.96-0.99, bilirubin 0.90, 95% CI: 0.87-0.94) and area under the curve (creatinine: 0.76, 95% CI: 0.70, 0.82, bilirubin 0.72, 95% CI: 0.68-0.76). Conclusions: We have demonstrated that a MLP model can be used to reduce the number of blood tests required for some patients at low risk of organ dysfunction, whilst improving safety for others at high risk.
MeSH term(s)	Humans ; Retrospective Studies ; Creatinine ; Machine Learning ; Sensitivity and Specificity ; Bilirubin
Chemical Substances	Creatinine (AYI8EX34EU) ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6418
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Article ; Online: A Phase I Trial of the Dual MET Kinase/OCT-2 Inhibitor OMO-1 in Metastatic Solid Malignancies Including MET Exon 14 Mutated Lung Cancer.

Pruis, Melinda A / Krebs, Matthew G / Plummer, Ruth / De Vos, Filip / Angevin, Eric / Prenen, Hans / Forster, Martin D / Clack, Glen / Van der Aa, Annegret / Tjwa, Marc / Jansen, Ellen / Perera, Timothy / Lolkema, Martijn P

The oncologist

2023 Volume 28, Issue 12, Page(s) e1248–e1258

Abstract: Introduction: Targeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients' outcomes. The development of more potent MET ... ...

Abstract	Introduction: Targeted therapy in non-small cell lung cancer (NSCLC) patients with mesenchymal epithelial transition (MET) exon 14 skipping mutations (METex14) and MET amplifications has improved patients' outcomes. The development of more potent MET kinase inhibitors could further benefit these patients. The aim of this trial is to determine the safety and recommended phase 2 dose (RP2D) of OMO-1 (an oral dual MET kinase/OCT-2 inhibitor) and to assess preliminary clinical efficacy in METex14-positive NSCLC and other MET-positive solid tumors. Materials and methods: This was a first-in-patient, open-label, multicenter study of OMO-1 in patients with locally advanced or metastatic solid malignancies. A standard 3 + 3 dose escalation design was utilized starting at a dose level of 100 mg BID continuously. Preliminary efficacy was investigated in patients with METex14-positive NSCLC, and MET amplified NSCLC and other solid tumors (MET basket). Results: In the dose-escalation part, 24 patients were included in 5 dose levels ranging from 100 mg twice daily (BID) to 400 mg BID. Most common adverse events (≥ 20%) were nausea, fatigue, vomiting, increased blood creatinine, and headache. The RP2D was determined at 250 mg BID. In the expansion cohorts, 15 patients were included (10 in METex14-positive NSCLC cohort and 5 in MET basket cohort) and received either 200 or 250 mg BID. Eight out of the 10 patients with METex14 positive NSCLC had stable disease as the best response. Conclusion: OMO-1 was tolerated at the dose of 250 mg BID and shows initial signs of MET inhibition and anti-tumor activity in METex14 mutated NSCLC patients.
MeSH term(s)	Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Proto-Oncogene Proteins c-met/genetics ; Protein Kinase Inhibitors/adverse effects ; Neoplasms, Second Primary/genetics ; Exons ; Mutation
Chemical Substances	Proto-Oncogene Proteins c-met (EC 2.7.10.1) ; Protein Kinase Inhibitors
Language	English
Publishing date	2023-05-31
Publishing country	England
Document type	Clinical Trial, Phase I ; Multicenter Study ; Journal Article
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyad146
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Patient factors and their impact on neutropenic events: a systematic review and meta-analysis.

Chambers, Pinkie / Jani, Yogini / Wei, Li / Kipps, Emma / Forster, Martin D / Wong, Ian C K

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

2019 Volume 27, Issue 7, Page(s) 2413–2424

Abstract: Background: Neutropenia is associated with an increased risk of mortality and hospitalisation. Strategies, including the prescribing of colony-stimulating growth factors (CSFs), are adopted when a high risk (> 20%) of neutropenic complications are seen ... ...

Abstract	Background: Neutropenia is associated with an increased risk of mortality and hospitalisation. Strategies, including the prescribing of colony-stimulating growth factors (CSFs), are adopted when a high risk (> 20%) of neutropenic complications are seen in the clinical trial setting. With a diverse treatment population that may differ from the patient groups recruited to studies, appropriate prescribing decisions by clinicians are essential. At present, results are conflicting from studies evaluating the risks of certain patient attributes on neutropenic events; we aimed to aggregate these associations to guide future management. Design: A systematic review with a meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Studies were identified through a literature search using MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to December 1, 2017. Studies were included into a meta-analysis if they adjusted for confounders; analyses were conducted in STATA v 15.1 SE. Results: A total of 4415 articles were retrieved by the search with 37 meeting the inclusion criteria and 12 eligible for meta-analysis. Meta-analysis was conducted for increasing age and yielded a pooled odds ratio of 1.39 (1.11, 1.76, I Conclusions: Results can enhance current guidance in prescribing primary prophylaxis for treatments that either fall marginally under the internationally recognised 20% neutropenia risk.
MeSH term(s)	Humans ; Neoplasms/blood ; Neoplasms/drug therapy ; Neutropenia/chemically induced ; Neutropenia/therapy
Language	English
Publishing date	2019-04-16
Publishing country	Germany
Document type	Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	1134446-5
ISSN	1433-7339 ; 0941-4355
ISSN (online)	1433-7339
ISSN	0941-4355
DOI	10.1007/s00520-019-04773-6
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Zs.A 3697: Show issues

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Article ; Online: Biphenotypic sinonasal sarcoma: European multicentre case-series and systematic literature review.

Turri-Zanoni, Mario / Dalfino, Gianluca / Lechner, Matt / Dallan, Iacopo / Battaglia, Paolo / Facco, Carla / Franzi, Francesca / Gravante, Giacomo / Ferrari, Marco / Terzakis, Dimitrios / Jay, Amrita / Forster, Martin D / Ambrosoli, Andrea Luigi / Bignami, Maurizio / Georgalas, Christos / Herman, Philippe / Nicolai, Piero / Lund, Valerie J / Castelnuovo, Paolo

Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale

2023 Volume 42, Issue 6, Page(s) 545–553

Abstract: Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and ... ...

Abstract	Objective: Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade cancer that was included from the 4th edition of WHO classification of head and neck tumours. The purpose of this study is to analyse clinical behaviour, pattern of recurrences and survival outcomes of this neoplasm. Methods: Retrospective review of patients affected by BSNS who were treated via an endoscopic-assisted approach in 6 European tertiary-care referral hospitals. Cases of BSNS described in literature since 2012 to date were fully reviewed, according to PRISMA guidelines. Results: A total of 15 patients were included. Seven patients were treated via an endoscopic endonasal approach, 4 with endoscopic transnasal craniectomy, and 4 via a cranio-endoscopic approach. Adjuvant treatment was delivered in 2 cases. After a mean follow-up of 27.3 months, systemic metastasis was observed in 1 case; the 5-year overall survival and disease-free survival rates were 100% and 80 ± 17.9%, respectively. Conclusions: BSNS is a locally aggressive tumour with a low recurrence rate and encouraging survival outcomes if properly treated with surgical resection and free margins followed by adjuvant radiotherapy for selected cases. Endoscopic-assisted surgery is safe and effective as an upfront treatment within a multidisciplinary care protocol.
MeSH term(s)	Humans ; Paranasal Sinus Neoplasms/surgery ; Disease-Free Survival ; Retrospective Studies ; Sarcoma/pathology ; Multicenter Studies as Topic
Language	English
Publishing date	2023-01-18
Publishing country	Italy
Document type	Systematic Review ; Journal Article
ZDB-ID	604898-5
ISSN	1827-675X ; 0392-100X
ISSN (online)	1827-675X
ISSN	0392-100X
DOI	10.14639/0392-100X-N2087
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Article ; Online: Understanding Molecular Testing Uptake Across Tumor Types in Eight Countries: Results From a Multinational Cross-Sectional Survey.

Chambers, Pinkie / Man, Kenneth K C / Lui, Vivian W Y / Mpima, Sheila / Nasuti, Paola / Forster, Martin D / Wong, Ian C K

JCO oncology practice

2020 Volume 16, Issue 8, Page(s) e770–e778

Abstract: Purpose: The growth in understanding of molecular biology and genomics has augmented the development of targeted cancer treatments; however, challenges exist in access to molecular testing, an essential precursor to treatment decision-making. We used ... ...

Abstract	Purpose: The growth in understanding of molecular biology and genomics has augmented the development of targeted cancer treatments; however, challenges exist in access to molecular testing, an essential precursor to treatment decision-making. We used data from a cross-sectional survey to evaluate the differences in uptake of molecular testing. Methods: Using the aggregated results of a questionnaire developed and distributed to clinicians by IQVIA, including treatment details and investigations undertaken for patients, we compared proportions of patients receiving molecular testing and targeted treatment by cancer type for the United Kingdom, France, Italy, Germany, Spain, South Korea, Japan, and China. We used multivariable logistic regression methods to understand the effect of country on the odds of receiving a molecular test. Results: There was a total of 61,491 cases. Across countries and cancer types, uptake rates for molecular testing ranged between 2% and 98%, with the greatest differences seen in gastric cancers (range, 23% to 70%), and significant variations were observed for both European and Asian countries. China consistently demonstrated a significantly reduced uptake for all molecular tests assessed; however; uptake of drug treatment in gastric cancers after testing positive for the human epidermal growth factor receptor 2 gene was higher than in some European countries (China, 85%; European range, 8% to 66%). The uptake of epidermal growth factor receptor gene testing was greater in some Asian countries relative to the United Kingdom, where incidence of lung cancer is higher (Japan: odds ratio, 3.1 [95% CI, 2.6 to 3.8]; South Korea: odds ratio, 2.7 [95% CI, 2 to 3.4]). Conclusion: We have highlighted inequity in access to molecular testing and subsequent treatments across countries, which warrants improvements.
MeSH term(s)	Asia ; China ; Cross-Sectional Studies ; Europe ; France ; Germany ; Humans ; Italy ; Japan ; Molecular Diagnostic Techniques ; Republic of Korea ; Spain ; United Kingdom
Language	English
Publishing date	2020-03-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/JOP.19.00507
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