muscle density not mass predicts for survival in newly diagnosed … · 2019-06-07 · background...
TRANSCRIPT
![Page 1: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/1.jpg)
Muscle Density not Mass predicts for Survival in Newly Diagnosed Epithelial Ovarian
Cancer
Dr Lucy Dumas
Clinical Research Fellow Gynaecology Unit
Royal Marsden NHS Foundation Trust
![Page 2: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/2.jpg)
Disclosure
I do not have any conflicts of interest to declare.
![Page 3: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/3.jpg)
Background 1.
• Around half of all new diagnoses of ovarian cancer are in women over the age of 651
• Outcomes are disproportionately poor with advancing age2,3
• Multifactorial; late presentation and more advanced stage at diagnosis, increased comorbidities, under-treatment, adverse tumour biology
• Need for better predictive and prognostic biomarkers1. NCIN. Trent Cancer Registry, the National Cancer Intelligence Network's lead registry in England for gynaecological cancers. Overview of Ovarian Cancer in
England: Incidence, Mortality and Survival. Available fromhttp://www.ncin.org.uk/publications/data_briefings/a_profile_of_ovarian_cancer_in_england2. Dumas L1, Ring A2, Butler J1, Kalsi T3, Harari D3, Banerjee S4. Improving outcomes for older women with gynaecological malignancies. Cancer Treat
Rev. 2016 Nov;50:99-1083. Dumas L, Bowen R, Thomas K, Gore M and Banerjee S. A Retrospective Review of Treatment Patterns, Toxicity Rates and Survival Outcomes in Women
over the age of 65 across two UK Cancer Centre. Poster 31 SIOG 2018
![Page 4: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/4.jpg)
Background 2.
• Sarcopenia (loss of muscle mass, quality and function) is increasingly prevalent in older adults1
• Association with frailty but relationship complex and remains unclear2,3
• Can be readily assessed on routine CT
• Loss of muscle mass has been shown to be associated with poorer survival outcomes4
1. Cruz-Jentoft, A.J., et al., Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing, 2010. 39(4): p. 412-23.
2. Williams, G.R., et al., Frailty and skeletal muscle in older adults with cancer. J Geriatr Oncol, 2018. 9(1): p. 68-73.3. Wilson, D., et al., Frailty and sarcopenia: The potential role of an aged immune system. Ageing Res Rev, 2017. 36: p. 1-10.4. Shachar, S.S., et al., Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review. Eur J Cancer, 2016. 57: p. 58-67
![Page 5: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/5.jpg)
Primary Objective
• To assess whether sarcopenia, in women over the age of 65 being considered for first line treatment of ovarian cancer, as defined by:
a) Skeletal muscle index (SMI) < 38.5 cm2/m2 and/or
b) Muscle density of 41HU or less
is associated with poorer progression-free and overall survival
![Page 6: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/6.jpg)
Retrospective case review (Local Institutional Approval): Royal Marsden NHS Foundation Trust
• August 2009-December 2015• Newly diagnosed epithelial ovarian cancer• 65 years or older at time of diagnosis• Baseline CT CAP available for review
n=208
Excluded (n=29)- No suitable CT baseline for analysis (non-contrast/muscle area not fully visualised at L3), - no height/weight data available
CT images assessed OsiriX software (two blinded assessors)
n=179
Demographic, treatment detail and outcome data collected
Baseline, mid-treatment and end of treatment CT CAP assessed
Methods
![Page 7: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/7.jpg)
Imaging analysis
• CT chest abdomen pelvis anonymised and saved to DICOM format for analysis on OsiriX software
• Skeletal muscle area (SMA cm2) at the level of L3
• Psoas, erector spinae, quadratus lumborum, transverse abdominus, external and internal obliques and rectus abdominus
• Height-standardised value of skeletal muscle index (SMI) derived (cm2/m2)
• Two assessors blinded to the clinical data evaluated SMA and subcutaneous adipose tissue area (SAT) using CT Hounsfield unit ranges of -29 to +150HU and -150 to +50HU respectively
• 10% of regions of interest (ROIs) generated verified by independent assessor
![Page 8: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/8.jpg)
Results
![Page 9: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/9.jpg)
Patient characteristics 1.• Mean age at diagnosis 73.4 (65-94)
• Mean BMI 25.7 (13-52), Mean BSA 1.69 (1.3-2.2)
• 35.8% SMI <38.5cm2/m2 , 78% mean muscle density <41HU
Association of increasing age and muscle density
Association of increasing age and muscle mass
-0.27 (p=0.012)0.05 (p=0.397)
![Page 10: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/10.jpg)
Patient characteristics 2. <HU41
n=140 (%)>HU41
n=39 (%)Total
n=179 (%)p-value
FIGO stage 3/4 84.3 74.4 82.1 0.152ECOG PS 2/3 32.8 15.4 29.0 0.034
High grade serous 72.9 79.5 74.3Endometrioid 4.3 5.1 4.5Clear Cell 2.9 0.0 2.2 0.258
Carcinosarcoma 6.4 7.7 6.7Low grade serous 4.3 0.0 3.4
Cardiovascular disease 35.7 17.9 31.8 p=0.035Hypertension 42.9 28.2 39.7 p=0.098Polypharmacy 42.9 30.8 51.4 p=0.163
Respiratory disease 11.4 7.7 10.6 p=0.503Diabetes 11.4 10.3 11.2 p=0.837Osteoarthritis 5.7 12.8 9.3 p=0.130
Patients with low muscle density were more likely to be performance status 2/3
![Page 11: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/11.jpg)
Treatment received
• 95.5% patients underwent chemotherapy • 49.4% Neoadjuvant• 39.3% Adjuvant • 13.0% Palliative
• 65% received platinum-doublet chemotherapy
• 73.4% patients underwent debulking surgery (primary or interval)• 71.9% of whom deemed optimally debulked
No statistically significance between treatment rates according to muscle density
![Page 12: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/12.jpg)
Progression-free survival by baseline muscle density
16.6 months (median)
HR 1.57 (p=0.039; 95%CI 1.024-2.306)
13.3 months (median)
![Page 13: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/13.jpg)
Overall survival by baseline muscle density
31.0 months (median)
56.6 months (median)
HR 1.98 (p=0.04; 95%CI 1.029-3.835)*
*Adjusted for Age, FIGO stage and Debulking status
![Page 14: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/14.jpg)
However…
•No significant relationship with SMI • (HR 0.86, p=0.465; 95%CI .0582-1.281)
![Page 15: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/15.jpg)
Chemotherapy tolerance<HU41 (n=131) >HU41 (n=39) Total (n=170) p value
n % n % n %
≥Grade 3 non-haematological toxicity 41 31.3 8 20.5 49 28.8 0.192
≥Grade 2 haematological toxicity 39 29.8 11 28.2 50 29.4 0.851
Completed 6 cycles 106 80.9 36 92.3 142 83.5 0.092
Early discontinuation of chemotherapy 25 19.1 3 7.7 28 16.5 0.092
Discontinued chemotherapy due to toxicity
16 12.2 0 0 16 9.4 0.001
Hospital admission during chemotherapy 46 35.1 9 23.7 55 32.5 0.185
Dose delay > 2 weeks 101 77.1 26 66.7 127 74.7 0.188
Trend towards increased rate of poorer chemotherapy tolerance in patients with low muscle density
![Page 16: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/16.jpg)
Risk of Grade ¾ non-haematological toxicities and early chemotherapy discontinuation with reducing muscle density
Univariate OR 0.96 (p=0.039; 95% CI 0.923-0.998) Univariate OR 1.04 (p=0.049; 95% CI 1.000-1.099 )
![Page 17: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/17.jpg)
Conclusions
• Reduced muscle density in a population of older women with newly diagnosed ovarian cancer is significantly associated with poorer overall survival• Loss of muscle density an earlier event than loss of muscle mass• More closely related to function/strength
• Reduced muscle density is associated with a trend towards poorer chemotherapy tolerance
• Absolute muscle mass (SMI) does not appear to be related with survival
![Page 18: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/18.jpg)
Limitations and further work
• Retrospective
• Heterogeneity of cohort
• No availability of frailty/geriatric assessment
Future work:• Prospective validation of these findings
• Prospective studies evaluating sarcopenia alongside GA as well as serum biomarkers of frailty/inflammation
• Incorporation of sarcopenia as a non-invasive biomarker into interventional clinical studies and….ultimately, routine clinical practice
![Page 19: Muscle Density not Mass predicts for Survival in Newly Diagnosed … · 2019-06-07 · Background 1. •Around half of all new diagnoses of ovarian cancer are in women over the age](https://reader033.vdocuments.us/reader033/viewer/2022041620/5e3e65c6551ab97249712b47/html5/thumbnails/19.jpg)
With thanks to…
Supervisory team and colleagues:
Professor Andrea RockallDr Susana Banerjee (Primary supervisor)
Dr Nina TunariuDr Elena Serena
Statistical support:
Mrs Karen ThomasMr Kyriakos Kouvelakis
And of course, our patients and their families