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Nutritional status and symptom burden in advanced non-small cell lung cancer: results of the dietetic assessment and intervention in lung cancer (DAIL) trial
  1. Iain Phillips1,2,
  2. Lindsey Allan3,
  3. Adele Hug3,
  4. Naomi Westran3,
  5. Claudia Heinemann4,
  6. Madeleine Hewish5,
  7. Ajay Mehta5,
  8. Helen Saxby5 and
  9. Veni Ezhil5
  1. 1Edinburgh Cancer Centre, Western General Hospital, Edinburgh, UK
  2. 2College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland
  3. 3Department of Nutrition and Dietetics, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
  4. 4Department of Nutrition and Dietetics, Frimley Park Hospital NHS Foundation Trust, Frimley, UK
  5. 5St Lukes Cancer Centre, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK
  1. Correspondence to Dr Iain Phillips, Edinburgh Cancer Centre, Western General Hospital, Edinburgh EH4 2XU, UK; iain.phillips{at}nhslothian.scot.nhs.uk

Abstract

Introduction European Society for Clinical Nutrition and Metabolism guidelines recommend that patients with cancer should be screened for malnutrition at diagnosis. The dietetic assessment and intervention in lung cancer study investigated the nutritional status of patients with non-small cell lung cancer (NSCLC) and the need for dietetic intervention.

Methods In this observational cohort pilot study, patients with stage 3b and 4 NSCLC were assessed prior to starting first line systemic anticancer therapy (SACT) with a range of measurements and questionnaires. We report the outcomes related to the Patient Generated Subjective Global Assessment tool (PG-SGA),

Results 96 patients were consented between April 2017 and August 2019. The PG-SGA identified that 78% of patients required specialist nutritional advice; with 52% patients having a critical need for dietetic input and symptom management. Results were dominated by symptom scores. As a screening test, one or more symptoms or recent weight loss history had a sensitivity of 88% (95% CI 78.44% to 94.36%) and specificity of 95.24% (95% CI 76.18% to 99.88%) for need for dietetic intervention.

Conclusion A large proportion of patients with NSCLC have a high symptom burden and are at risk of malnutrition prior to starting SACT and would benefit from dietetic review. It is imperative that oncologists and healthcare professionals discuss weight loss history and symptoms with lung cancer patients to correct nutritional deficiencies and resolve symptoms prior to starting treatment.

  • lung
  • anorexia
  • cachexia
  • supportive care
  • quality of life

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Key messages

  • Based on the Patient Generated Subjective Global Assessment, the majority of patients with NSCLC due to start systemic anti-cancer treatment meet criteria to see a dietitian.

  • Patients due to start systemic anti-cancer treatment for NSCLC have a high symptom burden.

Introduction

Systemic anticancer treatment (SACT) for non-small cell lung cancer (NSCLC) is increasing in intensity and duration. Gold-standard treatment for incurable cancer can now include triplet or quadruplet therapy with a combination of immunotherapy, chemotherapy and antiangiogenic therapy.1 2 These treatments with ongoing maintenance regimens are leading to significantly better outcomes for some patients with advanced NSCLC.

Toxicity from treatment is likely to be too morbid for many patients, and may result in maximal treatment not being initiated or stopped early. In order to reduce this, there needs to be an increased focus on patient PS, one aspect of which is adequate nutritional status. Ross et al3 reported that 58% of patients with NSCLC reported weight loss at diagnosis and as a result were less likely to complete more than three cycles of chemotherapy. Weight loss in this group was independently associated with reduced response to treatment and shorter overall survival.

The prevalence of malnutrition and cancer cachexia has been well documented. It can vary according to diagnosis and stage of disease as well as the type of treatment offered. Stratton et al4 reported that 45%–60% of patients with lung cancer were affected while Li et al5 established that 40% of patients with advanced lung cancer were malnourished and another 40% were at risk of malnutrition. In recent years, identification of patients with malnutrition has been complicated by the rise in obesity rates. Those who are overweight or obese are often not considered to be at risk, and since nutritional screening is not routinely carried out in many UK cancer centres, significant weight loss may not be identified.

The consequences of cancer-related malnutrition have been shown in studies to result in impaired response to chemotherapy, reduced quality of life, increased chemotherapy-induced toxicity, chemotherapy dose reductions, stopping or delaying treatment, shorter overall survival and higher mortality rates.6–11

European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend that all patients with cancer should be screened for malnutrition as soon after diagnosis as possible.12 Nutritional screening is used to identify those at risk of malnutrition and those who need dietetic intervention. There are a number of nutritional screening tools validated and routinely used internationally including: the Malnutrition Universal Screening Tool, Mini-Nutritional Assessment, Subjective Global Assessment (SGA) and the Patient SGA (PG-SGA).13–15

The PG-SGA (short and full forms) was adapted from the SGA tool and is the only tool validated for use with oncology outpatients.16 17The short form gives an abbreviated PG-SGA score and is completed by patients. It includes self-reported weight and weight change, changes in food intake, nutrition impact symptoms that may affect food intake (table 1) and limitations of physical function. The second half of the PG-SGA requires a formal dietitian or clinician assessment and provides information on the presence of metabolic stress and a subjective physical examination. The full PG-SGA score generated from the whole tools gives an assessment category (A, B or C) and nutrition triage recommendation.14

Table 1

List of nutrition impact symptoms listed in box 3 of the PG-SGA questionnaire

Given the fact that lung cancer often presents late, that some patients are not fit for treatment at diagnosis and that cancer-related malnutrition is prevalent in this cohort, nutritional screening as soon after a cancer diagnosis as possible is vital. Identifying problems early will help to ensure that patients are able tolerate SACT more successfully. To date, most studies looking at the nutritional status of cancer patients have been heterogeneous and included only small numbers of patients.18 Nutritional status is not always assessed at diagnosis and before starting treatment and so it is impossible to extrapolate whether malnutrition is as a result of the disease, or the effects of SACT.

The dietetic assessment and intervention in lung c ancer (DAIL) study is the first step in understanding the complex issues around weight loss, nutrition, quality of life and outcomes in advanced NSCLC at diagnosis, prior to starting SACT.

The trial involved completion of a range of questionnaires and assessments by patients with NSCLC at diagnosis and prior to starting palliative SACT with the intention of determining the proportion of patients who were nutritionally compromised at diagnosis, and therefore, met the established criteria for dietetic referral.

Methods

The trial was carried out at two sites in Surrey, St Luke’s Cancer Centre (SLCC) at the Royal Surrey County Hospital (RSCH), Guildford, and Frimley Park Hospital (FPH). Additionally, patients from four peripheral sites were invited to come to SLCC for a one-off appointment to participate in the trial. Patients were approached about the trial either when attending their new-patient appointment with their oncologist or when attending the prechemotherapy nurse-led clinic.

The trial was included on the National Institute for Health Research clinical trials portfolio for lung cancer.

Patients were eligible if they were due to receive first line SACT for biopsy-proven NSCLC. Patients could consent to the study if they had previously had palliative radiotherapy and if their PS was sufficient for SACT to be part of their treatment plan. Any patients having second or subsequent line treatment or those who had already started treatment were not eligible. Participation in the study was required prior to their first cycle of treatment. It was felt that approximately 100 patients would be sufficient to give an indication of dietetic need in this patient group.

The trial consisted of a one-off appointment with an oncology dietitian when informed consent was obtained. Participants completed a number of questionnaires and underwent a series of assessments including: height, weight, body mass index (BMI), PG-SGA, EORTC quality of life survey for cancer (C30) and lung cancer (LC13), spirometry, handgrip strength, radiological measurement of sarcopenia, G8 frailty score and a Charlson Comorbidity Index.19–21 In this paper, we present the results of the PG-SGA.

Following participation in the trial and completion of the assessments, patients were provided with appropriate dietary advice depending on their nutritional status, and were reviewed subsequently during SACT for as long as dietetic input was required as per standard of care at SLCC.

This was a pilot study and the initial statistical analysis was expressed as proportions. Any other results are hypothesis generating. With these results we aim to help develop a randomised trial of dietetic intervention, we wanted to use this study to clarify the proportion of patients that need to see a dietitian, particularly to answer whether we should include all patients or just those with dietetic need.

Results

Study population

A total of 96 patients with stage 3B and 4 NSCLC were consented to the study from RSCH (n=76) and FPH (n=20) between April 2017 and August 2019. A total of 188 patients were screened. Median age was 68 years (ranging from 42 to 83 years). Fifty-eight per cent were men and 42% were women. The majority of participants (71%) were diagnosed with adenocarcinoma of the lung, 24% with squamous cell carcinoma and 5% with an unspecified NSCLC. Treatment modalities included palliative chemotherapy (55%), immunotherapy (28%), a combination of chemotherapy and immunotherapy (5%) and 12% were due to start a Tyrosine Kinase inhibitor. Seventy-five per cent of participants had a performance status (PS) of 0–1, 21% had a PS of 2 and the remaining four patients had a PS of 3–4.

Nutritional status and PG-SGA scores

Mean BMI of the whole cohort was 25.7 kg/m2 (15.0–45.3 kg/m2). Mean self-reported weight loss in the past month was 4.1% (range 0%–23.3%) and was assessed during completion of the PG-SGA (short form) screening tool. Forty-four patients (46%) self-reported weight loss in the 1 month prior to entering the trial. Thirty-five per cent (n=33) of the total cohort had lost more than 5% of their total body weight and were classed as having cancer cachexia.22

Mean PG-SGA short form score was 10 (ranging from 1 to 24). A total of 78% (n=75) of all participants scored over 4, indicating that the majority required intervention by a dietitian, and 52% of the whole cohort scored over 9 showing a critical need for improved symptom management and/or nutrition support from a dietitian. Critical need to see a dietitian was common in patients with all sub types of NSCLC: squamous, adenocarcinoma and NSCLC non-specific type (61%, 47% and 80%, respectively). It was also common in those receiving chemotherapy alone and immunotherapy alone. During the study period, those with PD-L1 >50% (programmed death kigand 1, tumour biomarker for immunotherapy) would have been eligible to receive single agent immunotherapy, suggesting that need for a dietitian is common in PD-L1 positive (74% of patients on immunotherapy) and PD-L1 negative tumours (85% of patients on chemotherapy). Weight loss and symptom burden was more frequent in those scoring more highly on the PG-SGA. Percentage weight loss, along with rising PG-SGA scores and need to see a dietitian was common in all histological sub types and across all treatment modalities.

Patients with a higher PG-SGA overall score lost a greater percentage of body weight over the previous 1 month with an average of 6.7%. The PG-SGA Global Rating scores demonstrated that 30% of participants were well nourished (A), 51% were mild to moderately malnourished (B) and 19% were severely malnourished (C).

There was a statistically significant difference (χ2 test, p=0.00001) between the weight loss of over 5% total body weight experienced by those who were shown to have a critical need to see a dietitian (PG-SGA score ≥9) compared with the rest of the cohort in the trial. Table 2 shows the characteristics of patients as per PG-SGA scores.

Table 2

Breakdown of PG-SGA scores according to patient characteristics (including weight loss), tumour and treatment characteristics

Symptoms and PG-SGA scores

Nutritional intake was not affected by symptoms in 39 patients (40.6%) (table 3). The remaining 57 patients (59.4%) reported a total of 202 symptoms between them. A total of 154 out of the 202 symptoms were directly nutrition or gastrointestinal tract related. Thirty-four out of the 57 patients (59.6%) experienced more than three symptoms.

Table 3

Number of symptoms reported by patients (total cohort 96 patients)

Symptom burden recorded in box 3 of the PGSGA made up a large proportion of the total score; 25% or more of the total PG-SGA score in 53% of the cohort (n=51). In 16 patients, the symptom burden was 50% or more of the total score, symptom score did appear to heavily influence need to see a dietitian. Table 4 shows that the most common symptom reported by 41 patients (42.6%) was lack of appetite. Twenty-nine patients reported fatigue (30.2%), 25 patients reported early satiety (26.0%) and 23 patients reported constipation (24.0%).

Table 4

Number of patients experiencing each nutrition impact symptom

Table 2 shows the results for using either self-reported weight loss in the last 2 weeks (as per box 1 of the PG-SGA), as well as a reported symptom (as per box 3 of the PG-SGA, table 1). When both questions are combined as a single screening test, they give a sensitivity of 88% and a specificity of 95%. Answering yes to either question has a high sensitivity and specificity to requiring dietetic intervention (table 5).

Table 5

The potential screening ability of asking patients if they have lost weight in the last 2 weeks or whether they have a symptom from box 3 of the PG-SGA

DISCUSSION

This study showed that the majority of patients (78%) with advanced NSCLC required intervention by either a dietitian or other trained healthcare professional to provide dietary advice and to help with the management of symptoms in order to prevent further decline in PS. Fifty patients (52%) scored 9 or more, indicating that more than half of patients in this population needed urgent dietetic intervention and symptom management prior to treatment starting. This highlights an unmet need in patients with advanced lung cancer. Patients are not routinely screened for malnutrition and the authors are aware there is a nationwide lack of specialist dietetic services available to patients with lung cancer.

The DAIL trial results mirror previous data that suggests that malnutrition is common in lung cancer patients, although previous studies have a wide range of values, between 35% and 65%.3 23 24 These results suggest that nutritional and symptom screening is essential in this population. Over half of the cohort (52%) had lost weight and were heading into SACT with an established calorie deficit, which was likely to be exacerbated during treatment.

ESPEN guidelines recommend that all patients with cancer should have nutritional screening, but acknowledges the lack of evidence behind this.12 Recent Macmillan Prehabilitation guidelines recommend early nutrition screening, assessment and intervention at any stage of the cancer pathway, including palliative treatment.25

One of the strengths of this study is the homogeneous nature of the patient population. The cohort were all diagnosed with either stage 3B or stage 4 NSCLC and deemed to be fit to be consented for SACT by their oncologist. Previous lung cancer studies have been heterogeneous, for example, including both radical and palliative radiotherapy patients.23

Patients eligible to consent to this study were all deemed well enough for SACT and yet still had a significant symptom burden. This study suggests that symptoms are more common in those with greater weight loss and therefore are more in need of dietetic input. Early screening using a standardised tool has identified an unmet need in patients with advanced lung cancer. Treating these symptoms early, and providing appropriate dietetic support, could enhance quality of life, but it is not clear whether clinical outcomes can be improved.

The PG-SGA is a validated tool to assess nutritional status and provides a useful interventional triage system, but the full PG-SGA requires time for the patient to complete and training for a health professional to interpret. The implementation of widespread nutritional screening is challenging in a resource-limited healthcare setting, particularly with a lack of readily available specialist oncology dietitians. Adequate nutritional screening, if acted on, could potentially improve quality of life, reduce symptom burden and identify a high-risk cohort who need further intervention to reduce the incidence of malnutrition and improve treatment tolerance and outcomes.

Dietetic randomised intervention has only been tested in lung cancer in one small trial by Leedo et al.26 Forty patients were randomised to either existing diet or energy-rich and protein-rich main meals and snacks, delivered three times per week. The intervention group improved standard Chair Stand Test after 6 and 12 weeks (p<0.01) compared with the control group. This strategy had potential benefits on multiple measures of QoL (although did not reach statistical significance) including: improved QoL, functional score, handgrip strength, symptom and performance scores.

Research trials have been done in other cancer types including a study in older patients receiving chemotherapy for lymphoma or carcinoma, which showed that dietetic intervention improved the ability of patients to meet a target energy and protein intake. This did not affect overall survival or chemotherapy related outcomes. Less than one in five patients in the study had lung cancer.27 Dietetic counselling has been shown to improve patient quality of life, energy and protein intake and weight gain, in other types of cancer.28–30

A small Japanese case–control study has shown that the combination of dietetic counselling and nutritional supplements increased) the chance of gaining weight, when compared with controls (OR 8.4, 95% CI 1.6 to 42; p=0.01).31

The DAIL trial highlights the significant nutritional needs of patients with advanced lung cancer and demonstrates the potentially beneficial role that dietitians could have in their care. Our results show that weight loss is common at diagnosis, which may lead to further deterioration in nutritional status during treatment. It is unclear whether earlier dietetic intervention, that is, at presentation to respiratory clinics, could reduce weight loss and improve nutritional status. This study shows the unintended benefit of screening for symptoms in this population. Treating these is likely to improve QoL. If the need for dietitians in the core lung MDT could be proven and formally recognised by clinical guidelines, for example, National Institute for Health and Care Excellence (NICE), European Society for Medical Oncology (ESMO), funding for staffing may be easier to obtain.

Further research is required to ascertain the impact of dietetic counselling in this patient group. It is important to investigate whether it could benefit patients by reducing delays to treatment, alleviating nutrition impact symptoms and ultimately improving treatment outcomes.

Weight loss in lung cancer is likely to have a range of aetiologies. Dietetic counselling and intervention can be an inexpensive service that meets a range of needs in cancer patients, which include, assessing dietary intake, social issues affecting food intake (eg, such as difficulties in shopping and cooking) and concerns and anxieties around food.

When a patient sees their oncologist for the first time the discussion is usually centred around treatment options, which have become more complex over recent years, thereby limiting time to address other factors. Weight loss and nutrition impact symptoms are often not explored due to resource limitations and for fear of overburdening patients with excessive information.

The cause of weight loss in the DAIL patient group is likely to be multi-factorial. In order to effectively reverse cancer-related weight loss a multimodality approach is required. This is likely to include effective management of the cancer with SACT, appropriate treatment of symptoms, pharmacological treatment of cachexia and the pro inflammatory milieu and adequate nutritional/dietetic intervention. The next step is to understand the potential benefits on quality of life and patient outcomes with an intervention study comparing dietetic assessment and dietetic counselling versus standard of care.

Conclusion

The DAIL trial shows that a high proportion of patients with NSCLC have a high symptom burden and meet the criteria to be referred to a dietitian prior to starting SACT. It suggests that identifying patients at risk of malnutrition does not require the whole PG-SGA. Screening could involve asking the patient if they have lost any weight in the last 2 weeks and if they have any symptoms as detailed in the PG-SGA.

It is imperative that oncologists and healthcare professionals discuss recent history of weight loss and symptom burden with all patients with lung cancer to correct deficiencies and resolve symptoms prior to starting treatment. This could enable early identification of patients at risk of malnutrition who would benefit from dietetic input. It is, therefore, reasonable to suggest that dietitians be considered core members within the lung cancer pathway. As a result, significantly more dietetic resources are likely to be required in the future.

References

Footnotes

  • Twitter @LindseyAllan6

  • Contributors All authors contributed to trial design and patient recruitment. The manuscript was prepared by IP, LA, AH and NW. It was reviewed by the other authors.

  • Funding This work was partially supported by an Educational grant from Chugai Pharma UK, which funded extra time spent carrying out and writing up the DAIL study.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Ethical approval was obtained from the Camberwell St Giles Research Ethics Committee, London (reference 16/LO/2143).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. Deidentified data are currently held by Royal Surrey County Hospital Research department.