Background: Although oncological palliative care is increasingly being offered by multidisciplinary teams, there is still a lack of data about some symptoms handled by these teams, such as dysphagia, in patients with advanced cancer outside swallow regions. This study aimed to estimate the occurrence of dysphagia in prognosis studies of adults with advanced cancer outside the head, neck, and upper gastrointestinal tract, and to determine if there is an association with mortality. Methods: A systematic review of studies that evaluated dysphagia and mortality was conducted (PROSPERO: CRD42021257172). Data sources: BVS, PubMed, CINAHL, Web of Science, and Scopus. Data between 2011 and 2023 were selected. Results: Among the 608 articles screened, only 14 were included, which covered different types of cancer, primarily Lung, and Genitourinary, Skin, Hematological, and Central Nervous System as well. Dysphagia demonstrated a variable frequency, and almost half of the studies found a percentage of dysphagia above 60%, appearing most as a symptom that affects health-related quality of life and prove to be a toxicity of treatment. The association between dysphagia and mortality was only evaluated in three articles that studied advanced lung cancer, in which, after controlling for covariates, swallowing disorders were associated with worse survival, with prevalences of dysphagia and hazard ratios of 78.5% (1.12 [1.04–1.20]), 4% (1.34 [1.28–1.35]), and 3% (1.40 [1.07–1.81]), respectively. Conclusions: The occurrence of dysphagia in advanced cancer outside the head, neck, and upper GI tract is common, and there seems to be an association with significantly decreased survival in patients with advanced lung cancer.
Keywords: Deglutition disorders; Neoplasms; Prognosis; Survival; Palliative care; Systematic review
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1186/s12904-023-01268-4.
Cancer is a leading cause of increased morbidity and mortality worldwide, accounting for nearly 10 million deaths in 2020, highlighting the need for studies on advanced cancer [[
Current evidence suggests that access to specialist palliative care consisting of a multidisciplinary team is required to facilitate the management of patients with multiple care needs [[
A multidisciplinary team can track the patient's worsening swallowing function and provide a stimulus to help the patient achieve better comfort, thus helping monitor this functional degradation [[
This study aimed to explore if dysphagia is a frequently reported symptom in the prognostic studies of adults with advanced cancer outside the head, neck and upper GI tract. It also explored the possibility of an association between survival and dysphagia of these population. For this study, a systematic review was performed and reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) [[
The following electronic databases were searched: LILACS, BBO, IBECS (BVS[
The eligibility criteria were confirmed through title, abstract, and full-text screenings. Observational and prognostic studies that analyzed dysphagia in patients with advanced cancer were included. Studies on adults with primary site cancer in the anatomic swallow regions were excluded. If a study did not specify the cancer diagnosis or mentioned a category of "other" (without a clear explanation of which types of cancer made up "other"), these studies were also excluded. The eligibility criteria are listed in Table 1.
Table 1 Eligibility criteria of the studies for the systematic review
Component criteria •Adults (⩾18 years old) •Diagnosed with dysphagia •Advanced cancer, with evidence of at least one of the following criteria: (1) Metastatic primary solid cancer (2) Locally advanced solid cancers (3) Advanced hematological neoplasms •Primary site cancer in head and neck or upper gastrointestinal tract •Observational studies: retrospective or prospective studies •Prognostic studies •Review articles, discussions, letters, editorials, comments, case reports, case series, case studies, cross-sectional studies, and qualitative studies Survival Prevalence of deglutition disorders English, Spanish, and Brazilian Portuguese Studies published from 2011 to 2023
The reference selection process was divided into four phases. In Phase 1, one reviewer (D.N.M.S.) excluded duplicates using the Rayyan QCRI platform [[
In Phase 3, the same reviewers (D.N.M.S. and V.L.P.G.) applied the eligibility criteria to the full text of the studies selected in Phase 2. During this phase of reading the entire article, if the reviewers found studies involving patients with primary site cancer in the head and neck or upper gastrointestinal tract, or those with brain metastases, or if they met any other item described in the exclusion criteria that had not been excluded in Phase 2 (due to the abstract not indicating it), they were excluded. When necessary, a third reviewer (A.A.L.F.) was consulted to reach a consensus in cases of disagreement between the first two reviewers.
Finally, in Phase 4, the reviewers (D.N.M.S. and V.L.P.G.) checked the reference lists of the studies selected in Phase 3 and, once again, independently and blindly screened all titles and abstracts, as described in Phases 2 and 3. They excluded records and applied the eligibility criteria to the full text of the selected studies. Differences in decisions between the two reviewers were also resolved by the third reviewer (A.A.L.F.). A Cochrane review [[
Data were extracted from all included studies (by D.N.M.S.) using a spreadsheet. The following information was recorded for each study: author/year, place of study, study design, study population (cancer types, sample size, number of men and women, and measures of central tendency of age), healthcare setting, objectives, prevalence of dysphagia, diagnostic evaluation of dysphagia, outcomes, survival, types of survival analyses used, survival and dysphagia association, other prognostic factors, main results, and conclusions.
The articles included in this review comprised a heterogeneous range of methods that required multiple assessment tools. For quality assessment, all studies were evaluated by applying the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative [[
The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system [[
No studies were excluded based on the quality assessment.
A total of 608 records were identified using the search criteria. After removing duplicates, 485 articles were screened through their abstracts. Thirty-one articles were selected for full-text review, and after assessing their reference lists, 16 additional articles were included. Ultimately, 14 articles were chosen for final inclusion. Figure 1 provides a detailed depiction of this process, utilizing a flow diagram illustrating the literature search and selection criteria adapted from PRISMA.
Graph: Fig. 1PRISMA flow diagram
Six studies reported data from the last five years [[
Table 2 Summary of the included articles
Liu et al., 2023 [ Lung cancer (NSCLC and SCLC) 3634 (F = 1209, M = 2425); Mean age (SD): 60.2y (± 9.86) 3% Frequency during the hospital stay and 30 days after hospital admission (telephone follow-up): Patient-Generated Subjective Global Assessment* Median = Non-NIS group: 20.6 months, NIS group: 31.2 months, NIA days / 1.401 [1.07–1.81] Marmor et al., 2020 [ Lung cancer (NSCLC and SCLC) 201.674 (F = 95.144, M = 106.530) Age: < 80y: 82% of N total 8517 (4%) Retrospective data: ICD-9-CM (diagnostic codes for dysphagia) and CPT Median = with dysphagia: 8 months [95%CI 7–9] HR: 1.34 [95%CI 1.28–1.35] without dysphagia: 12 months [95%CI 11–13], NIA days / 1.34 [1.28–1.35] Abbas et al., 2019 [ Lung cancer (NSCLC) 63 (F = 22, M = 41) Median age (interquartile range) = 66.6y (57.2–72.1) 4 (7.1%) of 56 patients alive after 6 months Frequency not reported: CTCAE version 3.0* Median = 21 months Not Markos et al., 2019 [ Lung cancer (NSCLC) 42 (F = 7, M = 35) Mean age (range) = 68.4y (52–80) All patients Frequency not reported: cites the stages, but does not refer to which protocol Mean = 4 months Not Arscott et al., 2018 [ Melanoma Lung cancer (NSCLC) Kidney cancer Liver cancer Myeloma Sarcoma 30 (F = 9, M = 21) Median age at time of RT (range) = 61y (27–82) 9 (30%) Frequency not reported: CTCAE version 4.0* Median = 87 days Not Kim et al., 2018 [ Lung cancer (NSCLC and SCLC) 84 (F = 23, M = 61) Mean age (SD) = Stent group: 62.4y (± 11.5), Gastrostomy group: 58.5y (± 6.3) All patients Retrospective data: SEMS or PG placement HR: 0.682 Not Hatton et al., 2016 [ Lung cancer (NSCLC) 18 (F = 4, M = 14) Mean age (range) 70y (44–84) 16% Frequency not reported: CTCAE version 4.0* Rate: 2 years of survival = 49% Not Thier et al., 2016 [ Glioblastoma 57 (F = 18, M = 39) Mean age at death (SD) = 59y (± 11) 37 (65%) Daily: Signs, symptoms, and treatment strategies were registered using the standardized protocol + additional information from the patients' charts* Mean = 48 weeks Not Bradley et al., 2015 [ Lung cancer (NSCLC) 465 (F = 188, M = 277) Median (range) = 60 Gy group: 64y (38–83), 74 Gy group: 64y (41–83), Cetuximab group: 64y (38–83), No-cetuximab group: 64y (37–82) 139 (31%) Frequency not reported: CTCAE version 3.0* Median (months) 60 Gy group: 28.7 = 1.38 [1·09–1·76], 74 Gy group: 20.3, p = 0.004 | Cetuximab group: 25 = 1.07 [0.84–1.35], No-cetuximab group: 24.0, Not Koekkoek et al., 2014 [ Highgrade Glioma 178 (F = 53, M = 125); Mean age at diagnosis, years (SD)—59.7 (12.5) Dysphagia prevalence at 3 months before death = 7.5%, Dysphagia prevalence at 1 week before death = 24.5% Physicians who had been involved in EOL care for these patients were invited to complete questionnaires on the EOL phase Median = Group with grade IV—10.6 months [9.2–12.1], Group with grade III = 12.4 months [10.6–14.1], p ≥.05 Not Ansari et al., 2014 [ Thymoma 45 (F = 18, M = 27) Mean age (range) = 43y (45.4 ± 17.7) 3 (7%) Every 3 months for the first 2 years Every 4 months during the third year Every 6 months in the fourth and fifth years and annually thereafter: history and physical examination* Rate (5 years of survival = 70.8%, 10 years of survival = 62.9%) Not Ediebah et al., 2014 [ Lung cancer (NSCLC) 391 (F = 136, M = 255) Median age (range) = Group A: 57y (27–75), Group B: 57y (28–75), Group C: 56y (31–75) 307 (78.5%) Every 6 weeks: global health status/QOL scale* Median = (F = 9.6 months, M = 7.2 months) NIA days / 1.12 [1.04–1.20] Oberije et al., 2014 [ Lung cancer (NSCLC and SCLC) 155 (F = 69, M = 86) Mean age (SD) = NSCLC group: 64.7y (± 10.5), SCLC group: 65.5y (± 8.8) Grade ≥ 3 dysphagia = NSCLC group: 14 (11.6%), SCLC group: 3 (12.0%) Any timepoint during or after the end of RT, with a maximum of 4 weeks: CTCAE version 3.0* NIA Not Schuette et al., 2012 [ Lung cancer (NSCLC) 95 (F = 29, M = 66) Mean age (SD) = Placebo group: 64.2y (± 7.7), Treatment group: 61.6y (± 9.8) Grade ≥ 2 dysphagia = Palifermin group: 30 subjects (61%), Placebo group: 32 subjects (70%) Grade ≥ 3 dysphagia = Palifermin group: 11 subjects (22%), Placebo group: 13 subjects (28%) Grade 4 dysphagia = reported for one subject in the palifermin group Twice weekly: CTCAE version 3.0* Median = Placebo: 319 days, Palifermin: 513 days Not
N total sample, HR hazard ratio, CI confidence interval, F female, M male, SD standard deviation, y years old, RT radiotherapy, NSCLC non-small cell lung cancer, SCLC small cell lung cancer, *not exclusively to evaluate dysphagia, NIS nutrition impact symptoms, EOL end-of-life, CTCAE NCI common terminology criteria for adverse events, SEMS self-expandable metallic stent, PG percutaneous gastrostomy, NIA no information available, ICD-9-CM International Classification of Diseases, Ninth Revision, Clinical Modification, CPT Current Procedural Terminology
Seven articles did not report the settings of the studies [[
Seven articles reported deterioration in functional status of the patients; two found good performance status in the upper 40% of the overall sample using the World Health Organization performance status (WHO-PS) [[
Ten studies were conducted on a population with advanced lung cancer [[
A prevalence of dysphagia above 60% has been reported in five the studies considered in this review [[
Graph: Fig. 2Prevalence of dysphagia at subgroup lung cancer
Only one multicenter randomized trial [[
Three studies had a low risk of bias associated with Level A of methodological assessment. Most studies presented high and moderate risks of bias, often due to the observed effect of the prognostic factors on the outcome, which was very likely to be distorted by confounders and because the selected statistical model produced spurious or biased results.
The evaluation of the quality of evidence by GRADE was applied to the 14 articles, graded as follows: four were Level A [[
The details of the quality assessments (methodology and evidence) are provided in Table 3.
Table 3 Quality assessment
References and year of publication STROBE QUIPS GRADE 20 A Level HIGH 1-M; 2-L; 3-H; 4-H; 5-H; 6-M A 20 A Level MODERATE 1-L; 2-M; 3-M; 4-L; 5-L; 6-L B 20 A Level HIGH 1-M; 2-L; 3-L; 4-L; 5-H; 6-M C 11 B Level HIGH 1-H; 2-H; 3-M; 4-H; 5-H; 6-H C 19 A Level HIGH 1-L; 2-L; 3-L; 4-M; 5-H; 6-H B 19 A Level LOW 1-M; 2-L; 3-L; 4-L; 5-L; 6-L A 14 B Level HIGH 1-H; 2-M; 3-M; 4-M; 5-H; 6-H B 18 A Level HIGH 1-L; 2-M; 3-L; 4-L; 5-H; 6-H C 15 B Level HIGH 1-H; 2-H; 3-M; 4-M; 5-H; 6-H B 17 A Level LOW 1-M; 2-L; 3-L; 4-L; 5-H; 6-L C 17 A Level LOW 1-L; 2-L; 3-L; 4-L; 5-L; 6-L A 20 A Level LOW 1-L; 2-L; 3-L; 4-M; 5-L; 6-L A 17 A Level HIGH 1-L; 2-M; 3-L; 4-L; 5-H; 6-M C 20 A Level MODERATE 1-L; 2-L; 3-M; 4-M; 5-M; 6-L B
STROBE Studies were scored by quality using Strengthening the Reporting of Observational Studies in Epidemiology initiative: A Level = more than 80% (≥ 17), B Level = 50 to 80% (10 until 16) QUIPS Quality In Prognosis Studies tool: 1 – Study participation, 2—Study attrition, 3—Prognostic factor measurement, 4—Outcome measurement, 5—Study confounding, 6—Statistical analysis and reporting, L Low risk of bias, M Moderate risk of bias, H High risk of bias, QUIPS LOW 6 low´s or 5 low's + 1 moderate, QUIPS MODERATE 6 moderate's or 2 moderate´s + 4 low's, QUIPS HIGH 6 high's or ≥ 1high´s or ≥ 3 moderate's GRADE Grading of Recommendations Assessment, Development and Evaluation system: A = High evidence, B = Moderate evidence, C = Low evidence
This systematic review of prognosis studies involving patients with advanced cancer outside the head, neck, and upper GI tract revealed that the occurrence rate of dysphagia ranged from 4 to 78%, with an association with survival represented by hazard ratios ranging between 1.12 and 1.40. These high levels of variability likely stem from differences in demographics, sample sizes, cancer types, oncological treatments, types of dysphagia, measurement tools for assessing swallowing disorders, clinical assessment frequency, and healthcare settings. This combination may limit our ability to firmly establish the true prevalence of dysphagia and its association with survival in this specific population. Nevertheless, when examined in detail, the articles addressed at least one of the two research questions, prompting us to document the issues preventing the answering of all research questions and the possibility of conducting a meta-analysis. Furthermore, it is necessary to discuss swallowing disorders in these types of tumors outside of anatomical swallowing regions precisely because the decision-making process regarding nutrition and hydration in the care of this population remains unclear. Therefore, these issues need to be explored and carefully analyzed.
It is important to emphasize that the decision-making process regarding nutrition and hydration in the care of a patient with advanced head and neck cancer is generally complex [[
Our review highlights the disparity in dysphagia occurrence in patients with advanced cancer outside the head, neck, and upper GI tract. There is little evidence that people have dysphagia, even though they are already known to suffer from distressing GI symptoms. This may, in part, be related to the absence of studies designed exclusively to evaluate dysphagia in cancer outside the head, neck, and upper GI tract. Moreover, no information was available about the use of tools designed exclusively for dysphagia screening and evaluation in either of the methodological designs of articles selected at out review, except for the study on pre-existing dysphagia [[
Only one study showed an association between dysphagia and functional impairment, with dysphagia being one of the main symptoms observed during the last 10 days before death [[
The setting in which the study is conducted is one example that contributes to describing the functional status of the population. In outpatient settings, patients are accessed much earlier in the disease continuum and typically exhibit a better functional status. Conversely, in inpatient care, patients tend to be more unstable and are more likely to experience disruptions in various bodily functions, such as swallowing. However, in our review, most of the articles did not report the settings of the studies. Furthermore, knowing the patient's functional impairment helps the multidisciplinary team to assess prognosis and the assessment of symptoms associated with this deterioration in functional status, such as dysphagia. Nevertheless, we did not find any associations in our review. This lack of data impacts prognostication and consequentially could make it more difficult for clinical decisions [[
The potential causes of dysphagia in advanced malignant neoplasms outside the head, neck, and upper GI tract remain unclear in the existing literature. In our review, we identified possible associations that may broadly contribute to swallowing difficulties. It was observed that lung cancer, often associated with the toxicity of treatment, was the most common cause of swallowing problems [[
However, despite the consideration of these listed potential causes, our review did not identify any studies that comprehensively explain the pathophysiology of deglutition disorders in individuals with advanced malignant tumors outside the head, neck, and upper GI tract, which concursed with the findings by Kenny et al. [[
Ediebah et al. [[
We chose to research only studies that evaluated survival and prognosis because these types of studies mostly have the general objective of helping to make decisions about healthcare based on reliable prognostic information [[
The risk of death associated with dysphagia in our review was comparable to that reported by Kenny et al. [[
This review has several limitations. First, this systematic review found that most observational studies did not control for all potential confounders, and not all included studies had comparison groups, as reflected by the heterogeneity of the findings, as evidenced by the different types of cancer sites, cancer treatments, dysphagia types, and other differences. However, we conducted an extensive quality assessment to allow readers to draw their own conclusions. Second, the heterogeneity among all quantitative and statistical analyses of survival might have introduced some bias in the interpretation of the analyses. Third, owing to the limited number of articles addressing symptom prevalence and the heterogeneity of the populations, meta-analysis could not be performed. This is further evidenced by the lack of data on dysphagia parameters according to cancer site and/or treatment type. Finally, it is possible that some studies were not identified due to the choice of search terms and the selection of databases. The broad term "swallow" was deliberately avoided in the search strategy. It was deemed unlikely that any studies of advanced cancer outside the head, neck, and GI tract would contain this term in their title or abstract. Nevertheless, it is possible that some dysphagia screening tools were missed because of the exclusion of these broad search terms. Together, these factors could limit the quality of the evidence collected and analyzed in this review. An alternative methodology such as a scoping review may be useful in the future to describe the dysphagia prevalence in this heterogeneous group.
Despite these limitations, one crucial strength is that this review provides the first systematic description of dysphagia in patients with cancer outside the head, neck, and GI tract in prognostic studies. These findings reinforce the importance of evaluating, monitoring, and treating dysphagia in cancer patients to help them achieve a better quality of life.
This review demonstrates a lack of data about the periods of occurrence involving a swallowing disorder and the dysphagia pathophysiology of patients with advanced cancer outside the head, neck, and upper GI tract; however, it was illustrated that swallowing disorders are a common symptom burden, which seems to be associated with survival in such patients. Therefore, it is expected that these populations may take advantage of speech therapists' palliative approach. More studies investigating survival and dysphagia association should be encouraged so that the decision-making for nutrition and hydration can be based on evidence.
Furthermore, these patients still have an unmet need for palliative care, especially to control symptoms such as dysphagia. Patients' care, especially through a multidisciplinary approach, can provide effective and timely interventions. This may improve patients' HRQoL and well-being.
The occurrence of dysphagia in advanced cancers outside the head, neck, and upper GI tract is reported to be common, and there seems to be an association with significantly decreased survival in patients with advanced lung cancer. The prevalence of swallowing problems and their association with survival is still not well understood due to a lack of research using specific tools to swallowing evaluation.
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.
We thank National Council for Scientific and Technological Development (CNPq) for the AALF Research Productivity Grant (315094/2020-6).
SILVA DNM: Engaged in the conception and design, analysis, and interpretation of data, drafted the article, reviewed the final version of the article, and approved its publication. VICENTE LCC: Engaged in conception and design, critical revision of the article, analysis and interpretation of the data, technical and material support, review of the final version of the article, and approval of its publication.GLORIA VLP: Engaged in the analysis and interpretation of data, critical revision of the manuscript, technical support, reviewed the final version of the article, and approved its publication.FRICHE AAL: Engaged in the conception and design, critical revision of the manuscript, analysis and interpretation of data, statistical analysis, technical and material support, reviewed the final version of the article, and approved its publication.
This research received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.
All data generated or analysed during this study are included in this published article [and its supplementary information files].
Not applicable.
Not applicable.
The authors declare no competing interests.
Graph: Additional file 1.
• BBO
- Base de dados Bibliografia Brasileira de Odontologia
• BVS
- Biblioteca Virtual em Saúde
• CI
- Confidence interval
• CINAHL
- Cumulative Index to Nursing and Allied Health Literature
• CTCAE
- Common Terminology Criteria for Adverse Events
• DMP
- Decision-Making Process
• EBP
- Evidence-Based Practice
• ECOG-PS
- Eastern Cooperative Oncology Group Performance Status
• EIU
- Economist Intelligence Unit
• EOL
- End-of-life
• F
• Female
• GI
- Gastrointestinal
• GRADE
- Grading of Recommendations Assessment, Development and Evaluation
• HR
- Hazard ratio
• HRQoL
- Health-Related Quality of Life
• IBECS
- Índice Bibliográfico Español en Ciencias de la Salud
• ID
- Identity Document
• KPS
- Karnofsky Performance Status Scale
• LILACS
- Índice da Literatura Científica e Técnica da América Latina e Caribe
• M
• Male
• MEDLINE
- Medical Literature Analysis and Retrieval System Online
• N
- Total sample
• NIA
- No information available
• NIH
- National Institutes of Health
• NIS
- Nutritional Impact Symptoms
• NSCLC
- Non-Small Cell Lung Cancer
• PCC
- Person-Centered Care
• PG
- Percutaneous Gastrostomy
• PRISMA
- Preferred Reporting Items for Systematic reviews and Meta-analyses
- PROSPERO
- Prospective Register of Systematic Reviews
• QUIPS
- Quality In Prognosis Studies tool
• RT
- Radiotherapy
• SCLC
- Small Cell Lung Cancer
• SD
- Standard Deviation
• SEMS
- Self-Expandable Metallic Stent
• STROBE
- Strengthening the Reporting of Observational Studies in Epidemiology
• WHO-PS
- World Health Organization performance status
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