Predictive model for risk of severe gastrointestinal toxicity following chemotherapy using patient immune genetics and type of cancer: a pilot study

Coller, Janet K.; White, Imogen A.; Logan, Richard M.; Tuke, Jonathan; Richards, Alison; Mead, K.; Karapetis, Christos Stelios; Bowen, Joanne M.

doi:10.1007/s00520-014-2481-z

Cited by 19 publications

(20 citation statements)

References 8 publications

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“…Clinical practice guidelines on these topics would greatly facilitate the provision of evidence‐based care. Future trials evaluating pharmacological and nonpharmacological interventions aimed at reducing these symptoms should use validated patient self‐report tools to evaluate outcomes in real time, evaluate the contribution of parental anxiety to the child's perception of symptom severity, and explore the utility of biomarkers for identifying patients at risk of a higher symptom burden …”

Section: Discussionmentioning

confidence: 99%

Anxiety, pain, and nausea during the treatment of standard‐risk childhood acute lymphoblastic leukemia: A prospective, longitudinal study from the Children's Oncology Group

Dupuis

Mitchell

et al. 2016

Cancer

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BACKGROUND This prospective study describes the procedure-related anxiety, treatment-related anxiety, pain, and nausea experienced by children with standard-risk acute lymphoblastic leukemia (ALL) during the first year of treatment. METHODS This study was undertaken at 31 Children’s Oncology Group (COG) sites. Eligible children who were 2 to 9.99 years old were enrolled in a COG trial for patients with newly diagnosed standard-risk ALL from 2005 to 2009. Parents completed a demographic survey at the baseline and the Pediatric Quality of Life Inventory 3.0 Cancer Module (proxy version) and the General Functioning Scale of the Family Assessment Device 1, 6, and 12 months after the diagnosis. The association between patient-related (age, sex, ethnicity, and treatment), parent-related (marital status and education), and family-related factors (functioning, income, and size) and symptom scores was evaluated. RESULTS The mean scores for procedure-related anxiety, treatment-related anxiety, and pain improved during the first year of treatment (P < .0389). The mean nausea score was poorer 6 months after the diagnosis in comparison with the other assessments (P = .0085). A younger age at diagnosis was associated with significantly worse procedure-related anxiety (P = .004). An older age (P = .0002) and assignment to the intensified consolidation study arm (P = .02) were associated with significantly worse nausea. CONCLUSIONS Children with ALL experienced decreasing treatment-related anxiety, procedure-related anxiety, and pain during the first year of treatment. In comparison with scores at 1 and 12 months, nausea was worse 6 months after the diagnosis. Minimization of procedure-related anxiety in younger children and improved nausea control in older children and those receiving more intensified treatment should be prioritized.

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Section: Discussionmentioning

confidence: 99%

Anxiety, pain, and nausea during the treatment of standard‐risk childhood acute lymphoblastic leukemia: A prospective, longitudinal study from the Children's Oncology Group

Dupuis

Mitchell

et al. 2016

Cancer

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“…Firstly, we should have a basic understanding of the mechanisms behind the chemotherapy-induced intestinal mucositis. The ruling points of view on chemotherapy-induced IM might include the dysbiosis of the intestinal microbiota or the activation of intestinal mucosal immune system [18-20]. The intestinal tumor was one of the reasons which cause the derangement in the intestinal mucosa barrier function, therefore, chemotherapy treatment also aggravated the dysfunction of intestinal barrier that present as the infiltration of inflammation cells, damage of intestinal mucous, and then appearing diarrhea and body weight loss [15].…”

Section: Discussionmentioning

confidence: 99%

Bifidobacterium Infantis Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Regulating T Cell Immunity in Colorectal Cancer Rats

Dong

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Intestinal mucositis (IM) is a commonly encountered side effect in cancer patients receiving chemotherapy. This study aimed to investigate the effect of Bifidobacterium infantis (B. infantis) in attenuating the severity of chemotherapy-induced intestinal mucositis by regulating the T cell subsets in rats with colorectal cancer (CRC). Methods: Thirty male Sprague-Dawley (SD) rats were injected dimethyl hydrazine (DMH) subcutaneously for 10 weeks, and then injected SW480 cells in rectal mucosa to create a CRC model, and the rats were randomly divided into three groups: Control group (saline + saline), Chemotherapy group (saline + 5-FU+Oxaliplatin), B. infantis group (B. infantis + 5-FU+Oxaliplatin). IM was evaluated based on diarrhea severity, intestinal villus height, crypt depth, pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), T cell subsets (CD4⁺ IL17A⁺ cells and CD4⁺ CD25⁺ Foxp3⁺ Tregs) and related cytokine profiles. Results: The results showed that the B. infantis group demonstrated a higher body weight (BW) and intestinal villus height and a deeper crypt depth compared to the Chemotherapy group. The level of IL-6, IL-1β and TNF-α which increased by chemotherapy, was lowered by B. infantis administration. Real time reverse transcription- polymerase chain reaction (RT-PCR) showed B. infantis reduced relative expression of Th17 and Th1 cells related cytokines, and increased relative expression of CD4⁺ CD25⁺ Foxp3⁺ Tregs related cytokines. Furthermore, Flow cytometry analysis showed B. infantis reduced CD4⁺ IL17A⁺ cells and increased CD4⁺ CD25⁺ Foxp3⁺ Tregs in mesenteric lymph nodes (MLNs) compared to the Chemotherapy group. Conclusion: B. infantis effectively attenuates chemotherapy-induced intestinal mucositis by decreasing Th1 and Th17 response and increasing CD4⁺ CD25⁺ Foxp3⁺ Tregs response.

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“…This approach is supported by observations relating genetic testing on DNA extracted from saliva to severe CIGT, in which key immunogenetic factors relating to the TNF-a and TLR2 have been correlated with more severe toxicity. 79 Whether the patient's gut microbiome profile pre-cancer treatment could also predict toxicity severity is largely unknown, particularly in the setting of chemotherapy-induced damage. However, this idea was first postulated by Touchefeu et al, 50 and more recently by Wardill and Tissing.…”

Section: Future Opportunities For Risk Prediction and Modificationmentioning

confidence: 99%

The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

Secombe

Coller

Gibson

et al. 2018

Intl Journal of Cancer

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Chemotherapy-induced gastrointestinal toxicity (CIGT) occurs in up to 80% of all patients undergoing cancer treatment, and leads to symptoms such as diarrhoea, abdominal bleeding and pain. There is currently limited understanding of how to predict an individual patient's risk of CIGT. It is believed the gut microbiome and its interactions with the host's innate immune system plays a key role in the development of this toxicity and potentially other toxicities, however comprehensive bioinformatics modelling has not been rigorously performed. The innate immune system is strongly influenced by the microbial environment and vice-versa. Ways this may occur include the immune system controlling composition and compartmentalisation of the microbiome, the microbiome affecting development of antigen-presenting cells, and finally, the NLRP6 inflammasome orchestrating the colonic host-microbiome interface. This evidence calls into question the role of pre-treatment risk factors in the development of gastrointestinal toxicity after chemotherapy. This review aims to examine evidence of a bidirectional interaction between the gut microbiome and innate immunity, and how these interactions occur in CIGT. In the future, knowledge of these interactions may lead to improved personalised cancer medicine, predictive risk stratification methods and the development of targeted interventions to reduce, or even prevent, CIGT severity.

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Predictive model for risk of severe gastrointestinal toxicity following chemotherapy using patient immune genetics and type of cancer: a pilot study

Abstract: This is the first report of immune genetic variability, together with cancer type, being predictive of severe CIGT risk. These outcomes are being validated in a larger patient population.

Cited by 19 publications

References 8 publications

Anxiety, pain, and nausea during the treatment of standard‐risk childhood acute lymphoblastic leukemia: A prospective, longitudinal study from the Children's Oncology Group

Anxiety, pain, and nausea during the treatment of standard‐risk childhood acute lymphoblastic leukemia: A prospective, longitudinal study from the Children's Oncology Group

Bifidobacterium Infantis Ameliorates Chemotherapy-Induced Intestinal Mucositis Via Regulating T Cell Immunity in Colorectal Cancer Rats

The bidirectional interaction of the gut microbiome and the innate immune system: Implications for chemotherapy‐induced gastrointestinal toxicity

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