Application of distance matrices to define associations between acute toxicities in colorectal cancer patients receiving chemotherapy

Aprile, Giuseppe; Ramoni, Marco; Keefe, Dorothy; Sonis, Stephen T.

doi:10.1002/cncr.23182

Cited by 69 publications

(56 citation statements)

References 25 publications

(19 reference statements)

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“…We found fatigue, nausea, intestinal disorders and hand-foot syndrome to be the most common symptoms reported by next of kin. This is confirmed by other studies investigating patients (Aprile et al, 2008;Berger et al, 2010;Goldberg et al, 2007;Griffin-Sobel, 2006;Hallquist Viale and Sommers, 2007;Henry et al, 2008;Kearney et al, 2008). However, the next of kin reported that nausea worsened with every treatment, whereas other studies on patients, in contradiction, have found that nausea decreases after every treatment (Henry et al, 2008;Kearney et al, 2008).…”

Section: Discussionsupporting

confidence: 68%

The next of kin experiences of symptoms and distress among patients with colorectal cancer: Diagnosis and treatment affecting the life situation

Ekholm

Grönberg

Börjeson

et al. 2013

European Journal of Oncology Nursing

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Section: Discussionsupporting

confidence: 68%

The next of kin experiences of symptoms and distress among patients with colorectal cancer: Diagnosis and treatment affecting the life situation

Ekholm

Grönberg

Börjeson

et al. 2013

European Journal of Oncology Nursing

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“…In a cohort of colorectal cancer patients, findings indicated the occurrence of localised (ulceration, abdominal pain, diarrhoea and malabsorption) as well as systemic (fatigue, nausea, infection and depression) toxicities in clusters. The recognition of concurrent occurrence of tissue-based and systemic toxicities has caused a shift in the potential applications of toxicity models to investigate regimen-related toxicity rather than tissuespecific toxicity [5]. Understanding toxicity clusters in response to different chemotherapy and/or radiotherapy regimens in different cancer types will aid in advancing mechanistic research and perhaps will also push forward the development of a systemic biomarker of toxicity.…”

Section: Links To Other Toxicitiesmentioning

confidence: 99%

“…Symptoms include pain, ulceration, nausea and vomiting, diarrhoea and rectal bleeding [3,4] and depend on the area affected. Systemic effects of oral and GI mucositis include fatigue, malnutrition, sepsis and occasionally death [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Emerging evidence on the pathobiology of mucositis

Al‐Dasooqi

Sonis

Bowen

et al. 2013

Support Care Cancer

168

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Background Considerable progress has been made in our understanding of the biological basis for cancer therapyinduced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. Methods Panel members reviewed the biomedical literature on mucositis pathobiology published between January 2005 and December 2011.Results Recent research has provided data on the contribution of tissue structure changes, inflammation and microbiome changes to the development of mucositis. Additional research has focused on targeted therapyinduced toxicity, toxicity clustering and the investigation of genetic polymorphisms in toxicity prediction. This review paper summarizes the recent evidence on these aspects of mucositis pathobiology. Conclusion The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity.

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“…TLR4 has also been hypothesised to mediate chemotherapy-induced pain through central glial activation (9), with strong clinical evidence showing chemotherapy-induced gut toxicity is often paralleled by the symptom of pain (16,17). This is suggestive of common underlying mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Irinotecan-Induced Gastrointestinal Dysfunction and Pain Are Mediated by Common TLR4-Dependent Mechanisms

Wardill

Gibson

Sebille

et al. 2016

Molecular Cancer Therapeutics

121

124

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Strong epidemiological data indicate that chemotherapy-induced gut toxicity and pain occur in parallel, indicating common underlying mechanisms. We have recently outlined evidence suggesting that TLR4 signaling may contribute to both side effects. We therefore aimed to determine if genetic deletion of TLR4 improves chemotherapy-induced gut toxicity and pain. Forty-two female wild-type (WT) and 42 Tlr4 null (−/−) BALB/c mice weighing between 18 and 25 g (10–13 weeks) received a single 270 mg/kg (i.p.) dose of irinotecan hydrochloride or vehicle control and were killed at 6, 24, 48, 72, and 96 hours. Bacterial sequencing was conducted on cecal samples of control animals to determine the gut microbiome profile. Gut toxicity was assessed using validated clinical and histopathologic markers, permeability assays, and inflammatory markers. Chemotherapy-induced pain was assessed using the validated rodent facial grimace criteria, as well as immunologic markers of glial activation in the lumbar spinal cord. TLR4 deletion attenuated irinotecan-induced gut toxicity, with improvements in weight loss (P = 0.0003) and diarrhea (P < 0.0001). Crypt apoptosis was significantly decreased in BALB/c-Tlr4−/−billy mice (P < 0.0001), correlating with lower mucosal injury scores (P < 0.005). Intestinal permeability to FITC-dextran (4 kDa) and LPS translocation was greater in WT mice than in BALB/c-Tlr4−/−billy (P = 0.01 and P < 0.0001, respectively). GFAP staining in the lumbar spinal cord, indicative of astrocytic activation, was increased at 6 and 72 hours in WT mice compared with BALB/c-Tlr4−/−billy mice (P = 0.008, P = 0.01). These data indicate that TLR4 is uniquely positioned to mediate irinotecan-induced gut toxicity and pain, highlighting the possibility of a targetable gut/CNS axis for improved toxicity outcomes. Mol Cancer Ther; 15(6); 1376–86. ©2016 AACR.

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Application of distance matrices to define associations between acute toxicities in colorectal cancer patients receiving chemotherapy

Cited by 69 publications

References 25 publications

The next of kin experiences of symptoms and distress among patients with colorectal cancer: Diagnosis and treatment affecting the life situation

The next of kin experiences of symptoms and distress among patients with colorectal cancer: Diagnosis and treatment affecting the life situation

Emerging evidence on the pathobiology of mucositis

Irinotecan-Induced Gastrointestinal Dysfunction and Pain Are Mediated by Common TLR4-Dependent Mechanisms

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