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Stephen T Sonis - One of the best experts on this subject based on the ideXlab platform.
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Oral Mucositis due to high dose chemotherapy and or head and neck radiation therapy
Journal of The National Cancer Institute Monographs, 2019Co-Authors: Rajesh V Lalla, Stephen T Sonis, Michael T Brennan, Sharon M Gordon, David I Rosenthal, Dorothy M K KeefeAbstract:Oral Mucositis is a common side-effect associated with conventional cancer therapy and has also recently been reported in association with newly emerging cancer therapies. It is characterized as an inflammation of the Oral mucous membranes accompanied by many complex mucosal and submucosal changes. Ulcerative Oral Mucositis can cause significant Oral pain, impair nutritional intake, lead to local or systemic infection, and cause significant economic cost. In addition, it may necessitate interruptions in cancer therapy, thus adversely affecting patient prognosis. This review presents the current understanding of the pathogenesis of Mucositis and discusses evidence-based clinical management strategies for Oral Mucositis. In addition, key research questions for future investigation are identified, followed by a discussion of strategies to promote development and funding of the needed research.
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pharmacotherapy for the management of cancer regimen related Oral Mucositis
Expert Opinion on Pharmacotherapy, 2016Co-Authors: Alessandro Villa, Stephen T SonisAbstract:ABSTRACTIntroduction: Oral Mucositis is a frequent and devastating toxicity secondary to cancer treatment, which may affect 20–40% of patients receiving conventional chemotherapy and 60–85% of patients undergoing hematopoietic stem cell transplantation. The pathobiology of Mucositis includes a complex cascade of biologic events in which pro-inflammatory cytokines, ROS, second messengers, and the Oral microbiome contribute to tissue damage of the Oral mucosa. Management strategies to Oral Mucositis secondary to chemotherapy include preventative measures and therapeutic approaches.Area covered: A literature search of published animal and clinical studies was perform to review the epidemiology, pathophysiology and treatment options for cancer regimen-induced Mucositis. We also discuss new data coming from recent pertinent clinical trials.Expert opinion: Mucositis is one of the most common debilitating toxicities secondary to cancer treatment and can adversely affect patients’ quality of life. Epidemiological...
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serum amyloid p ameliorates radiation induced Oral Mucositis and fibrosis
Fibrogenesis & Tissue Repair, 2010Co-Authors: Lynne Murray, Michael Scott Kramer, David P Hesson, Brynmor A Watkins, E Fey, Rochelle L Argentieri, Furquan Shaheen, Darryl A Knight, Stephen T SonisAbstract:Purpose To evaluate the effect of the anti-fibrotic protein serum amyloid P (SAP) on radiation-induced Oral Mucositis (OM) and fibrosis in a hamster cheek-pouch model.
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role of the cyclooxygenase pathway in chemotherapy induced Oral Mucositis a pilot study
Supportive Care in Cancer, 2010Co-Authors: Rajesh V Lalla, Dorothy M K Keefe, Stephen T Sonis, Carol C Pilbeam, Stephen J Walsh, Douglas E PetersonAbstract:Oral Mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced Oral Mucositis. We collected blood, saliva, and Oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day −10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of Oral Mucositis was determined using the Oral Mucositis Index. Severity of pain due to Oral Mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Mean Mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in Mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in Mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced Mucositis.
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efficacy of palifermin keratinocyte growth factor 1 in the amelioration of Oral Mucositis
Core Evidence, 2009Co-Authors: Stephen T SonisAbstract:Purpose: Oral Mucositis is a significant toxicity of cytotoxic chemo- and radiation-therapy used to treat cancer. Palifermin is the first pharmaceutical/biological agent approved for the intervention of Oral Mucositis. The major objective of this review is to evaluate the evidence supporting the use of palifermin.
Douglas E Peterson - One of the best experts on this subject based on the ideXlab platform.
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chemotherapy or radiation induced Oral Mucositis
Dental Clinics of North America, 2014Co-Authors: Rajesh V Lalla, Deborah P Saunders, Douglas E PetersonAbstract:SUMMARY Oral Mucositis is a significant toxicity of systemic chemotherapy and of RT to theHN14(6):50515.3. Vera-Llonch M, Oster G, Ford CM, et al. Oral Mucositis and outcomes of alloge-neic hematopoietic stem-cell transplantation in patients with hematologic malig-nancies. Support Care Cancer 2007;15(5):4916.4. Vera-Llonch M, Oster G, Hagiwara M, et al. Oral Mucositis in patients undergoingradiation treatment for head and neck carcinoma. Cancer 2006;106(2):32936.5. Managing Oral Mucositis in patients with hematologic malignancies. J SupportOncol 2006;4(2):79.6. Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiologyof Mucositis. Support Care Cancer 2013;21(7):207583.7. Sonis ST. The pathobiology of Mucositis. Nat Rev Cancer 2004;4(4):27784.8. SonisST, OsterG,FuchsH, etal.OralMucositisandtheclinicalandeconomicout-comesofhematopoieticstem-celltransplantation.JClinOncol2001;19(8):22015.9. Elting LS, Cooksley CD, Chambers MS, et al. Risk, outcomes, and costs ofradiation-induced Oral Mucositis among patients with head-and-neck malig-nancies. Int J Radiat Oncol Biol Phys 2007;68(4):111020.10. Duncan GG, Epstein JB, Tu D, et al. Quality of life, Mucositis, and xerostomia fromradiotherapy for head and neck cancers: a report from the NCIC CTG HN2 ran-domized trial of an antimicrobial lozenge to prevent Mucositis. Head Neck 2005;27(5):4218.11. Bellm LA, Epstein JB, Rose-Ped A, et al. Patient reports of complications of bonemarrow transplantation. Support Care Cancer 2000;8(1):339.12. Elting LS, Cooksley C, Chambers M, et al. The burdens of cancer therapy. Clinicaland economic outcomes of chemotherapy-induced Mucositis. Cancer 2003;98(7):15319.13. Trotti A, Bellm LA, Epstein JB, et al. Mucositis incidence, severity and associatedoutcomes in patients with head and neck cancer receiving radiotherapy with orwithout chemotherapy: a systematic literature review. Radiother Oncol 2003;66(3):25362.
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chemotherapy or radiation induced Oral Mucositis
Dental Clinics of North America, 2014Co-Authors: Rajesh V Lalla, Deborah P Saunders, Douglas E PetersonAbstract:Oral Mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of Oral Mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of Oral Mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies.
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systematic review of Oral cryotherapy for management of Oral Mucositis caused by cancer therapy
Supportive Care in Cancer, 2013Co-Authors: Douglas E Peterson, Joanne M Bowen, Kerstin Ohrn, Monica Fliedner, Judith Lees, Charles Lawrence Loprinzi, Takehiko Mori, Anthony Osaguona, D S Weikel, Sharon EladAbstract:Purpose This systematic review analyzed the strength of the literature and defined clinical practice guidelines for the use of Oral cryotherapy for the prevention and/or treatment of Oral Mucositis caused by cancer therapy.
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role of the cyclooxygenase pathway in chemotherapy induced Oral Mucositis a pilot study
Supportive Care in Cancer, 2010Co-Authors: Rajesh V Lalla, Dorothy M K Keefe, Stephen T Sonis, Carol C Pilbeam, Stephen J Walsh, Douglas E PetersonAbstract:Oral Mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced Oral Mucositis. We collected blood, saliva, and Oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day −10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of Oral Mucositis was determined using the Oral Mucositis Index. Severity of pain due to Oral Mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Mean Mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in Mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in Mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced Mucositis.
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management of Oral Mucositis in patients who have cancer
Dental Clinics of North America, 2008Co-Authors: Rajesh V Lalla, Stephen T Sonis, Douglas E PetersonAbstract:Oral Mucositis is a clinically important and sometimes dose-limiting complication of cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of life, and have a significant economic impact. The pathogenesis of Oral Mucositis is multifactorial and complex. This review discusses the morbidity, economic impact, pathogenesis and clinical course of Mucositis. Current clinical management of Oral Mucositis is largely focused on palliative measures such as pain management, nutritional support and maintenance of good Oral hygiene. However, several promising therapeutic agents are in various stages of clinical development for the management of Oral Mucositis. These agents are discussed in the context of recently updated evidence-based clinical management guidelines.
Dorothy M K Keefe - One of the best experts on this subject based on the ideXlab platform.
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Oral Mucositis due to high dose chemotherapy and or head and neck radiation therapy
Journal of The National Cancer Institute Monographs, 2019Co-Authors: Rajesh V Lalla, Stephen T Sonis, Michael T Brennan, Sharon M Gordon, David I Rosenthal, Dorothy M K KeefeAbstract:Oral Mucositis is a common side-effect associated with conventional cancer therapy and has also recently been reported in association with newly emerging cancer therapies. It is characterized as an inflammation of the Oral mucous membranes accompanied by many complex mucosal and submucosal changes. Ulcerative Oral Mucositis can cause significant Oral pain, impair nutritional intake, lead to local or systemic infection, and cause significant economic cost. In addition, it may necessitate interruptions in cancer therapy, thus adversely affecting patient prognosis. This review presents the current understanding of the pathogenesis of Mucositis and discusses evidence-based clinical management strategies for Oral Mucositis. In addition, key research questions for future investigation are identified, followed by a discussion of strategies to promote development and funding of the needed research.
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Microbiota and their role in the pathogenesis of Oral Mucositis
Oral Diseases, 2014Co-Authors: Barbara Vanhoecke, Tine De Ryck, Andrea M Stringer, Ton Van Der Wiele, Dorothy M K KeefeAbstract:Oral Mucositis in patients undergoing cancer therapy is a significant problem. Its prevalence ranges between 20 and 100%, depending on treatment type and protocols and patient-based variables. Mucositis is self-limiting when uncomplicated by infection. Unfortunately, the incidence of developing a local or systemic infection during the course of the treatment is very high. At this stage, it is unclear which role Oral microbiota play in the onset, duration, and severity of Oral Mucositis. Nevertheless, there is growing interest in this underexplored topic, and new studies are being undertaken to unravel their impact on the pathogenesis of Mucositis.
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prevention of Oral Mucositis in children receiving cancer therapy a systematic review and evidence based analysis
Oral Oncology, 2013Co-Authors: Akram F Qutob, Sumant Gue, Tamas Revesz, Richard M Logan, Dorothy M K KeefeAbstract:This systematic review investigated, critically appraised, and rated the evidence on agents used to prevent Oral Mucositis in children. A comprehensive search of the relevant literature was performed up to December 2011. Articles were included according to the inclusion/exclusion criteria and were critically appraised for validation and quality assessment using a checklist consisting of 18 categories. Each article was then rated for its strength of evidence. 16,471 articles were retrieved from 19 different databases and then reduced to 27 articles that fit the inclusion criteria. Five articles on Oral care protocols supported their use to prevent Oral Mucositis in children. Seven articles on chlorhexidine mouthwash and three on laser therapy had conflicting evidence of its use. The preventative agents that were supported by one or two articles included: benzydamine mouthwash, iseganan mouthwash, granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash, Oral/enteral glutamine, Oral propantheline and cryotherapy, Oral cryotherapy, Oral sucralfate suspension, prostaglandin E2 tablets, and chewing gum. The reduction in the rates of occurrence of Oral Mucositis when using agents of fair (B) to good (A) evidence ranged from 22% to 52%. In conclusion, this review suggests the use of Oral care protocols to prevent Oral Mucositis in children because of their strength of evidence (fair to good). The authors suggest avoiding agents with fair to good evidence against their use (Oral sucralfate suspension, prostaglandin E2 tablets, and GM-CSF mouthwash). Agents with conflicting evidence (chlorhexidine mouthwash (used solely), laser therapy, and glutamine) should also be avoided until further research confirms their efficacy.
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role of the cyclooxygenase pathway in chemotherapy induced Oral Mucositis a pilot study
Supportive Care in Cancer, 2010Co-Authors: Rajesh V Lalla, Dorothy M K Keefe, Stephen T Sonis, Carol C Pilbeam, Stephen J Walsh, Douglas E PetersonAbstract:Oral Mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced Oral Mucositis. We collected blood, saliva, and Oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day −10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of Oral Mucositis was determined using the Oral Mucositis Index. Severity of pain due to Oral Mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Mean Mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in Mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in Mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced Mucositis.
Rajesh V Lalla - One of the best experts on this subject based on the ideXlab platform.
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Oral Mucositis due to high dose chemotherapy and or head and neck radiation therapy
Journal of The National Cancer Institute Monographs, 2019Co-Authors: Rajesh V Lalla, Stephen T Sonis, Michael T Brennan, Sharon M Gordon, David I Rosenthal, Dorothy M K KeefeAbstract:Oral Mucositis is a common side-effect associated with conventional cancer therapy and has also recently been reported in association with newly emerging cancer therapies. It is characterized as an inflammation of the Oral mucous membranes accompanied by many complex mucosal and submucosal changes. Ulcerative Oral Mucositis can cause significant Oral pain, impair nutritional intake, lead to local or systemic infection, and cause significant economic cost. In addition, it may necessitate interruptions in cancer therapy, thus adversely affecting patient prognosis. This review presents the current understanding of the pathogenesis of Mucositis and discusses evidence-based clinical management strategies for Oral Mucositis. In addition, key research questions for future investigation are identified, followed by a discussion of strategies to promote development and funding of the needed research.
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chemotherapy or radiation induced Oral Mucositis
Dental Clinics of North America, 2014Co-Authors: Rajesh V Lalla, Deborah P Saunders, Douglas E PetersonAbstract:Oral Mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of Oral Mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of Oral Mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies.
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chemotherapy or radiation induced Oral Mucositis
Dental Clinics of North America, 2014Co-Authors: Rajesh V Lalla, Deborah P Saunders, Douglas E PetersonAbstract:SUMMARY Oral Mucositis is a significant toxicity of systemic chemotherapy and of RT to theHN14(6):50515.3. Vera-Llonch M, Oster G, Ford CM, et al. Oral Mucositis and outcomes of alloge-neic hematopoietic stem-cell transplantation in patients with hematologic malig-nancies. Support Care Cancer 2007;15(5):4916.4. Vera-Llonch M, Oster G, Hagiwara M, et al. Oral Mucositis in patients undergoingradiation treatment for head and neck carcinoma. Cancer 2006;106(2):32936.5. Managing Oral Mucositis in patients with hematologic malignancies. J SupportOncol 2006;4(2):79.6. Al-Dasooqi N, Sonis ST, Bowen JM, et al. Emerging evidence on the pathobiologyof Mucositis. Support Care Cancer 2013;21(7):207583.7. Sonis ST. The pathobiology of Mucositis. Nat Rev Cancer 2004;4(4):27784.8. SonisST, OsterG,FuchsH, etal.OralMucositisandtheclinicalandeconomicout-comesofhematopoieticstem-celltransplantation.JClinOncol2001;19(8):22015.9. Elting LS, Cooksley CD, Chambers MS, et al. Risk, outcomes, and costs ofradiation-induced Oral Mucositis among patients with head-and-neck malig-nancies. Int J Radiat Oncol Biol Phys 2007;68(4):111020.10. Duncan GG, Epstein JB, Tu D, et al. Quality of life, Mucositis, and xerostomia fromradiotherapy for head and neck cancers: a report from the NCIC CTG HN2 ran-domized trial of an antimicrobial lozenge to prevent Mucositis. Head Neck 2005;27(5):4218.11. Bellm LA, Epstein JB, Rose-Ped A, et al. Patient reports of complications of bonemarrow transplantation. Support Care Cancer 2000;8(1):339.12. Elting LS, Cooksley C, Chambers M, et al. The burdens of cancer therapy. Clinicaland economic outcomes of chemotherapy-induced Mucositis. Cancer 2003;98(7):15319.13. Trotti A, Bellm LA, Epstein JB, et al. Mucositis incidence, severity and associatedoutcomes in patients with head and neck cancer receiving radiotherapy with orwithout chemotherapy: a systematic literature review. Radiother Oncol 2003;66(3):25362.
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role of the cyclooxygenase pathway in chemotherapy induced Oral Mucositis a pilot study
Supportive Care in Cancer, 2010Co-Authors: Rajesh V Lalla, Dorothy M K Keefe, Stephen T Sonis, Carol C Pilbeam, Stephen J Walsh, Douglas E PetersonAbstract:Oral Mucositis can be a significant and dose-limiting complication of high-dose cancer therapy. Mucositis is a particularly severe problem in patients receiving myeloablative chemotherapy prior to bone marrow or hematopoetic stem cell transplant (HSCT). The cyclooxygenase (COX) pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins, including prostaglandin E2 (PGE2) and prostacyclin (PGI2). The objective of this small (n = 3) pilot study was to examine the role of the COX pathway in causing mucosal injury and pain in chemotherapy-induced Oral Mucositis. We collected blood, saliva, and Oral mucosal biopsy specimens from three autologous HSCT patients at the following time-points before and after administration of conditioning chemotherapy: Day −10, +10, +28, and +100, where day 0 is day of transplant. RNA extracted from full-thickness tissue samples was measured by RT-PCR for the following: COX-1, COX-2, microsomal prostaglandin E synthase (mPGES), IL-1β, and TNF-α. Blood and saliva samples were measured by ELISA for PGE2 and PGI2, which are markers of COX activity. Severity of Oral Mucositis was determined using the Oral Mucositis Index. Severity of pain due to Oral Mucositis was measured using a Visual Analog Scale. Relationships between the different variables were examined using Spearman rank correlation coefficients. Mean Mucositis and pain scores increased significantly after administration of chemotherapy and then gradually declined. The correlation between changes in Mucositis and pain scores was strong and statistically significant. The following additional correlations were statistically significant: between tissue COX-1 and pain; between tissue mPGES and pain; between salivary PGE1 and pain; between salivary PGI2 and pain. Other relationships were not statistically significant. Our finding of significant associations of pain scores with tissue COX-1 and mPGES, as well as salivary prostaglandins, is suggestive of a role for the cyclooxygenase pathway in Mucositis, possibly via upregulation of pro-inflammatory prostaglandins. However, our small sample size may have contributed to the lack of significant associations between COX-2 and other inflammatory mediators with mucosal injury and pain. Thus, additional studies with larger numbers of subjects are warranted to confirm the involvement of the cyclooxygenase pathway in chemotherapy-induced Mucositis.
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management of Oral Mucositis in patients who have cancer
Dental Clinics of North America, 2008Co-Authors: Rajesh V Lalla, Stephen T Sonis, Douglas E PetersonAbstract:Oral Mucositis is a clinically important and sometimes dose-limiting complication of cancer therapy. Mucositis lesions can be painful, affect nutrition and quality of life, and have a significant economic impact. The pathogenesis of Oral Mucositis is multifactorial and complex. This review discusses the morbidity, economic impact, pathogenesis and clinical course of Mucositis. Current clinical management of Oral Mucositis is largely focused on palliative measures such as pain management, nutritional support and maintenance of good Oral hygiene. However, several promising therapeutic agents are in various stages of clinical development for the management of Oral Mucositis. These agents are discussed in the context of recently updated evidence-based clinical management guidelines.
Martin G Mccabe - One of the best experts on this subject based on the ideXlab platform.
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interventions for preventing Oral Mucositis in patients with cancer receiving treatment Oral cryotherapy
Cochrane Database of Systematic Reviews, 2015Co-Authors: Philip Riley, Annemarie Glenny, H V Worthington, Anne Littlewood, Jan E Clarkson, Martin G MccabeAbstract:Background Oral Mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high risk patients. Ulceration can lead to severe pain and difficulty eating and drinking, which may necessitate opioid analgesics, hospitalisation and nasogastric or intravenous nutrition. These complications may lead to interruptions or alterations to cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative Oral Mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Oral cryotherapy is a low-cost, simple intervention which is unlikely to cause side-effects. It has shown promise in clinical trials and warrants an up-to-date Cochrane review to assess and summarise the international evidence. Objectives To assess the effects of Oral cryotherapy for preventing Oral Mucositis in patients with cancer who are receiving treatment. Search methods We searched the following databases: the Cochrane Oral Health Group Trials Register (to 17 June 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 5), MEDLINE via Ovid (1946 to 17 June 2015), EMBASE via Ovid (1980 to 17 June 2015), CANCERLIT via PubMed (1950 to 17 June 2015) and CINAHL via EBSCO (1937 to 17 June 2015). We searched the US National Institutes of Health Trials Registry, and the WHO Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching databases. Selection criteria We included parallel-design randomised controlled trials (RCTs) assessing the effects of Oral cryotherapy in patients with cancer receiving treatment. We used outcomes from a published core outcome set registered on the COMET website. Data collection and analysis Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. We contacted study authors for information where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. Main results We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced Oral Mucositis. All studies were at high risk of bias. The following results are for the main comparison: Oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancers Oral cryotherapy probably reduces Oral Mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop Oral Mucositis, Oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing Oral Mucositis, is 4 people (95% CI 3 to 5). The results were similar for moderate to severe Oral Mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6). Severe Oral Mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe Oral Mucositis, Oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT) Oral cryotherapy may reduce Oral Mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop Oral Mucositis, Oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3, although the uncertainty surrounding the effect estimate means that the 95% CI ranges from 2 NNTB, to 111 NNTH (number needed to treat in order to harm one additional person, i.e. for one additional person to develop Oral Mucositis). The results were similar for moderate to severe Oral Mucositis (RR 0.43, 95% CI 0.17 to 1.09, 5 studies, 270 analysed, low quality evidence). NNTB 3 (95% CI 2 NNTB to 17 NNTH). Severe Oral Mucositis is probably reduced (RR 0.38, 95% CI 0.20 to 0.72, 5 studies, 270 analysed, moderate quality evidence). Where 427 per 1000 would develop severe Oral Mucositis, Oral cryotherapy would reduce this to 162 (95% CI 85 to 308), NNTB 4 (95% CI 3 to 9). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance, and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies. There was limited or no evidence on the secondary outcomes of this review, or on patients undergoing other chemotherapies, radiotherapy, targeted therapy, or on comparisons of Oral cryotherapy with other interventions or different Oral cryotherapy regimens. Therefore no further robust conclusions can be made. There was also no evidence on the effects of Oral cryotherapy in children undergoing cancer treatment. Authors' conclusions We are confident that Oral cryotherapy leads to large reductions in Oral Mucositis of all severities in adults receiving 5FU for solid cancers. We are less confident in the ability of Oral cryotherapy to reduce Oral Mucositis in adults receiving high-dose melphalan before HSCT. Evidence suggests that it does reduce Oral Mucositis in these adults, but we are less certain about the size of the reduction, which could be large or small. However, we are confident that there is an appreciable reduction in severe Oral Mucositis in these adults. This Cochrane review includes some very recent and currently unpublished data, and strengthens international guideline statements for adults receiving the above cancer treatments.
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interventions for preventing Oral Mucositis in patients with cancer receiving treatment cytokines and growth factors
Cochrane Database of Systematic Reviews, 2015Co-Authors: Philip Riley, Annemarie Glenny, H V Worthington, Anne Littlewood, Jan E Clarkson, Luisa Fernandez M Mauleffinch, Martin G MccabeAbstract:Background Oral Mucositis is a side effect of chemotherapy, head and neck radiotherapy, and targeted therapy, affecting over 75% of high-risk patients. Ulceration can lead to severe pain and difficulty with eating and drinking, which may necessitate opioid analgesics, hospitalisation and supplemental nutrition. These complications may disrupt cancer therapy, which may reduce survival. There is also a risk of death from sepsis if pathogens enter the ulcers of immunocompromised patients. Ulcerative Oral Mucositis can be costly to healthcare systems, yet there are few preventive interventions proven to be beneficial. Cytokines and growth factors may help the regeneration of cells lining of the mouth, thus preventing or reducing Oral Mucositis and its negative effects. Objectives To assess the effects of cytokines and growth factors for preventing Oral Mucositis in patients with cancer who are receiving treatment. Search methods Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (searched 10 May 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 4) in the Cochrane Library (searched 10 May 2017); MEDLINE Ovid (1946 to 10 May 2017); Embase Ovid (7 December 2015 to 10 May 2017); CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature; 1937 to 10 May 2017); and CANCERLIT PubMed (1950 to 10 May 2017). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. Selection criteria We included parallel-design randomised controlled trials (RCTs) assessing the effects of cytokines and growth factors in patients with cancer receiving treatment. Data collection and analysis Two review authors independently screened the results of electronic searches, extracted data and assessed risk of bias. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. Main results We included 35 RCTs analysing 3102 participants. Thirteen studies were at low risk of bias, 12 studies were at unclear risk of bias, and 10 studies were at high risk of bias. Our main findings were regarding keratinocyte growth factor (KGF) and are summarised as follows. There might be a reduction in the risk of moderate to severe Oral Mucositis in adults receiving bone marrow/stem cell transplantation after conditioning therapy for haematological cancers (RR 0.89, 95% CI 0.80 to 0.99; 6 studies; 852 participants; low-quality evidence). We would need to treat 11 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 6 to 112). There might be a reduction in the risk of severe Oral Mucositis in this population, but there is also some possibility of an increase in risk (RR 0.85, 95% CI 0.65 to 1.11; 6 studies; 852 participants; low-quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to prevent the outcome to 14 to cause the outcome). There is probably a reduction in the risk of moderate to severe Oral Mucositis in adults receiving radiotherapy to the head and neck with cisplatin or fluorouracil (RR 0.91, 95% CI 0.83 to 1.00; 3 studies; 471 participants; moderate-quality evidence). We would need to treat 12 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 7 to infinity). It is very likely that there is a reduction in the risk of severe Oral Mucositis in this population (RR 0.79, 95% CI 0.69 to 0.90; 3 studies; 471 participants; high-quality evidence). We would need to treat 7 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 5 to 15). It is likely that there is a reduction in the risk of moderate to severe Oral Mucositis in adults receiving chemotherapy alone for mixed solid and haematological cancers (RR 0.56, 95% CI 0.45 to 0.70; 4 studies; 344 participants; moderate-quality evidence). We would need to treat 4 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 3 to 6). There might be a reduction in the risk of severe Oral Mucositis in this population (RR 0.30, 95% CI 0.14 to 0.65; 3 studies; 263 participants; low -quality evidence). We would need to treat 10 adults with KGF in order to prevent one additional adult from developing this outcome (95% CI 8 to 19). Due to the low volume of evidence, single-study comparisons and insufficient sample sizes, we found no compelling evidence of a benefit for any other cytokines or growth factors and there was no evidence on children. There did not appear to be any serious adverse effects of any of the interventions assessed in this review. Authors' conclusions We are confident that KGF is beneficial in the prevention of Oral Mucositis in adults who are receiving: a) radiotherapy to the head and neck with cisplatin or fluorouracil; or b) chemotherapy alone for mixed solid and haematological cancers. We are less confident about a benefit for KGF in adults receiving bone marrow/stem cell transplant after conditioning therapy for haematological cancers because of multiple factors involved in that population, such as whether or not they received total body irradiation (TBI) and whether the transplant was autologous (the patients' own cells) or allogeneic (cells from a donor). KGF appears to be a relatively safe intervention. Due to limited research, we are not confident that there are any beneficial effects of other cytokines and growth factors. There is currently insufficient evidence to draw any conclusions about the use of cytokines and growth factors in children.