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Chemotherapy dose-capping due to obesity and its impact on survival


Project Description

Obesity is associated with risk for several cancer types, including colorectal and breast cancers (1). Obesity also predicts for a poor outcome after cancer treatment. This might partly be explained by the clinical practice of ’dose-capping’ - in other words, patients might be sub-optimally treated because they are obese.
We already have a clinical PhD student (Corinna Slawinski) looking at this in colorectal cancer, and you will work with her to explore other cancer types as well - mainly through systematic review processes.
Primary outcome measure: first-dose chemotherapy capping
Secondary outcome measures: subsequent-dose chemotherapy capping, adherence
Questions:
1. Is the clinical practice of dose-capping attributed to obesity prevalent across several cancer types (for example, colorectal, breast, ovarian cancers)
2. What is the impact of dose-capping on survival endpoints in different cancer types? The survival endpoints will include overall survival, cancer-specific survival and either disease-free or progression-free survival.
Research plan:
1. This literature review will build upon previous reviews from the Renehan team (2, 3)
2. Based on the literature review, the research team will re-group and determine whether a formal meta-analysis of these data is feasible and appropriate
3. Individual-level data will be sought through Project Data Sphere (https://www.projectdatasphere.org/projectdatasphere/html/home), a free-available repository of > 150 trials in oncology. This database is free to academics and has been used the Renehan team before. With these data, the student will target a selection of cancer types (colorectal, breast, ovarian) and their trials to (i) address Q1 above; and (ii) undertake time-to-event analyses to evaluate the effect of dose-capping on survival endpoints.
4. For a student that makes rapid progress, there will be opportunities to use mediation (statistical) analyses to effect understand the impact of dose-capping on survival.

Training/techniques to be provided:
Lead supervisor meetings are weekly in the first 6 months; fortnightly thereafter.
There are monthly lab meetings and monthly virtual journal clubs. Students will present their work and bring new ideas to lab meetings.
All PhD studentships include multi-disciplinary inputs with quarterly face-to-face supervisor meetings.
As the student matures, they are encouraged to develop autonomy and independence.
Lab culture
The ‘lab’ culture is one of integration, continuity, synergism, cross-covering, and collaboration.
Examples:
(i) Integration: sharing of ICD codes for obesity-related cancers;
(ii) Continuity: a year 3 student directing a year 1 student to optimal resources;
(iii) Synergism: running models of similar hypothesis testing for different cancer types;
(iv) Cross-covering: named individuals deputising to recruit patients into studies measuring liver fat using advanced MR imaging;
(v) Collaboration: includes several collaborations within the Manchester NIHR Biomedical Research Centre Cancer Prevention and Early Detection (PED) theme (lead: Renehan) https://www.manchesterbrc.nihr.ac.uk/our-research/cancer-ped/obesity-related-cancers-opportunity-prevention-early-detection/

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 1 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Carroll J, Protani M, Walpole E, Martin JH. Effect of obesity on toxicity in women treated with adjuvant chemotherapy for early-stage breast cancer: a systematic review. Breast Cancer Res Treat 2012; 136(2): 323-30.
2. Au-Yeung G, Webb PM, DeFazio A, Fereday S, Bressel M, Mileshkin L. Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). Gynecol Oncol 2014; 133(1): 16-22.
3. Ligibel JA, Alfano CM, Courneya KS, et al. American Society of Clinical Oncology position statement on obesity and cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014; 32(31): 3568-74.
4. Renehan AG, Harvie M, Cutress RI, et al. How to Manage the Obese Patient With Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016; 34(35): 4284-94.
5. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer 2015; 15(8): 484-98.

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