DE LOS PROCESOS DESCONCENTRADOS Intendencia Regional de Quito

at Royal Surrey County

Aim: To identify whether weight loss at time of dietetic review was associated with poorer survival in patients with metastatic NSCLC? Standard practice at St Luke’s Cancer Centre is for health care professional-guided referrals to a Macmillan Oncology Dietitian, this can occur at any time during a patient’s cancer pathway, potentially before, during or after radical or palliative treatment.

Methods: As part of the dietetic service, a large database of weight change in patients reviewed by the dietetic team is collected prospectively. In collaboration with the dietitians, the oncology outcome database was interrogated, only patients with metastatic NSCLC were included, any patients with other types of cancer and those with early stage or locally advanced NSCLC were excluded. Percentage weight change was calculated. This data only included patients who had been assessed in person by a Macmillan Oncology Dietitian and so needed to be well enough to attend the hospital for that assessment. Patients were defined as (per the international definition) cachectic if they had lost more than 5% from their usual body weight in the last six months, as recorded on the database (Fearon et al., 2011). The NHS spine was used to identify those patients who had died. Overall survival for cachectic and non-cachectic patients was identified.

Results and Discussion: This cohort study showed that cachexia is a significant problem in advanced lung cancer and has an impact on overall survival. It is important to recognize that there maybe a selection bias as only patients seen by the dietetic service were included in this analysis. The vast majority of patients (76%) lost more than 5% of their usual total body weight at the time they were first seen by a Dietitian. Overall survival from time of dietitian review was significantly worse in patients with cachexia vs patients without cachexia (188 days vs 299 days, p=0.0078) (Hug, 2017). In a cohort whose median survival is 6-12 months, the

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difference of more than 3 months is significant, however, there may be other factors such as time to dietitan review, performance status, previous anti-cancer treatment and stage of disease. Figure 2 shows % weight change in this cohort, patient by patient, it shows that some patients lost very noteworthy amounts of weight. In this cohort, the median weight change was -9.4% (range 7.3% to -35.8%).

This study also showed that percentage loss of total body weight is more sensitive than BMI. In our study, we saw mean BMI decrease from 26.9kg/m2 _{to 23.2 kg/m}2 _{(BMI range at time of} review 13.3-62 kg/m2_{) which is still within the healthy range of 20.0kg/m}2 _{– 25.0kg/m}2_. Therefore using BMI to determine malnutrition and cachexia in lung cancer patients would not be a true reflection of this population. Other studies have shown that high BMI correlates with survival, but this means a patient would need to lose a large amount of weight to lower their BMI, data for the thesis supports the fact that change in BMI is relatively insensitive to weight loss (Bowden et al., 2017).

Patients

Figure 2: Graph showing a waterfall plot of % weight change by patient Patients to the left of the red line have lost more than 5% of usual body weight and were defined as cachectic. 76% of patients were cachectic in this cohort.

-40.00 -35.00 -30.00 -25.00 -20.00 -15.00 -10.00 -5.00 0.00 5.00 10.00 15.00 % w e ig h t lo ss 5%

Cachexia

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All patients were well enough to attend the cancer centre. 85% (264) of patients were receiving chemotherapy when referred to the dietitian. This data suggests that cachexia is a significant issue in patients receiving active palliative anti-cancer treatment.

Although Performance Status (PS) was not routinely recorded, the fact that patients were receiving chemotherapy with palliative intent suggests their PS was 2 or fitter when treatment was initiated.

This study shows that many patients with metastatic NSCLC lose a lot of weight and the majority are cachectic at the time they are reviewed by an oncology dietitian, it suggests how major weight loss in terms of refractory cachexia impacts on survival. This study was a very helpful starting point in identifying there was a need to further investigate weight loss in this population. The retrospective nature of this project illustrated its major limitation, which was that the time point of dietetic assessment was not consistent in the patient’s journey through diagnosis and treatment. The patients were reviewed when a health professional felt the patient needed to be seen by a dietitian. This lack of consistency would need to be remedied in future work. From this data, it was also not clear whether patients would have been cachectic at diagnosis, or whether this was a phenomenon that developed during treatment, or whether both scenarios could have occurred.

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Figure 3: Kaplan-Meier curve showing overall survival for patients with NSCLC classed as those with cachexia or without cachexia. Median survival for cachectic patients was 188 days and 299 days for non-cachectic patients. X= axis time in days.

This cohort data is limited by the fact that TNM staging and tissue type were not routinely recorded, and that usual body weight was self-reported by patients. It did not record the date of diagnosis and so there is likely to be variability in time between date of diagnosis and date of referral to the dietitian. This has the potential to introduce a source of lead time bias, if more weight is lost as more time passes since diagnosis, it could suggest an artificial relationship between weight loss and survival in advanced NSCLC. Although the time point may have been inconsistent, cachexia could have been under-estimated in this cohort as it did not include patients who had lost 2-5% of usual body weight and had co-existing sarcopenia or a BMI below 20. It may underestimate the rate of cachexia in this population, as sarcopenia is common in lung cancer (Stene et al., 2015).

In summary, it was felt that this work highlighted an important area of further investigation. Future work would assess patients at the same time point, the most consistent time point was felt to be diagnosis.

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7.4.2 Experiment 2: Is sarcopenia associated in a poorer outcome in NSCLC?

Aim: Sarcopenia is a loss of muscle mass and function, in combination with an overall decrease in function. There are multiple ways to assess sarcopenia, this can be radiological or functional in nature. Previous published data has shown that sarcopenia occurred in 14% of patients with stage 1 NSCLC (Tsukioka et al., 2017), when it was assessed by calculating the surface area of the psoas muscle (standardised for height), although in this study sarcopenia did not predict for post-operative complications, it did predict for grade 3 or greater toxicities in patient undergoing surgery for bowel cancer (Jones et al., 2015)

Methods: All patients from a lung MDT from July 2012-December 2013 with biopsy proven NSCLC were included. Patients were categorised by age and treatment, the overall data was presented separately (Ezhil, 2016). From this cohort all patients were included who met 2 criteria, firstly patients who had available imaging on the electronic PACS system, which included the transverse processes of the third lumbar vertebra and secondly a formally documented height measurement, available either from chemotherapy records or formal lung function testing.

Figure 4, example anterior-posterior and medial-lateral measurement of the left and right psoas muscle. The left psoas muscle is outlined in green and the right psoas muscle is outlined in magenta.