Tossicità Locale: mucosite e disfagia Anna Merlotti Radioterapia Busto Arsizio (VA) MUCOSITE •Frequenza •Patogenesi Patogenesi •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) MUCOSITE •Frequenza •Patogenesi Patogenesi •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) Ulcerative mucositis and associated sequelae in patients receiving radiotherapy for head and neck cancer. Da 34% a 43% con aggiunta cht Russo G et al. The Oncologist 2008;13:886-898 MUCOSITE •Frequenza •Patogenesi Patogenesi •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva PATHOBIOLOGY Historical belief of mucositis in cancer patients cytotoxic treatments kills rapidly dividing cells; cancerous and normal Current belief of mucositis in cancer patients series of simultaneous events beginning in the epithelium or submucosa and progressing to other tissue layers Working model of mucositis=5 phases I. Initiation II. Upregulation III. Signaling and Amplification IV. Ulceration V. Healing Sonis et al., 2004 Response of the oral mucosa ---Oral epithelium ---Basement membrane--- ----Lamina propia ------submucosa Sonis, S. (2004). Oral mucositis in cancer therapy. The Journal of Supportive Oncology, 3(3), 3-8. MUCOSITE •Frequenza •Patogenesi Patogenesi •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva Prevention and treatment of oral mucositis in patients with head and neck cancer treated with (chemo) radiation: report of an Italian survey. P. Bossi et al. July 2014, Volume 22, Issue 7, pp 1889-1896 Antimycotic prevention: preventive therapy with antibiotics or antimycotics is used by 47 % of the treating physicians; among these, antimycotic drugs are the most prescribed agents •60 % of the patients with CRT for HNC develop oropharyngeal candidosis •An Italian randomized trial showed a benefit with systemic fluconazole in comparison to placebo in preventing and delaying oropharyngeal candidosis •no difference in OM severity between the two group •concerns also regarding possible emergence of fluconazole-resistant fungal species type of scale used to assess OM Scala CTCAE 4.0 G0 WHO None RTOG No change over baseline G1 Asymptomatic or mild symptoms; intervention not indicated Oral soreness, erythema Injection/ may experience mild pain not requiring analgesic G2 Moderate pain; not interfering with oral intake; modified diet indicated Oral erythema, ulcers, solid diet tolerated Patchy mucositis which may produce an inflammatory serosanguinitis discharge/ may experience moderate pain requiring analgesia G3 Severe pain; interfering with oral intake Oral ulcers, liquid diet only Confluent fibrinous mucositis/ may include severe pain requiring narcotic G4 Life-threatening consequences; urgent intervention indicated Oral alimentation impossible Ulceration, hemorrhage or necrosis G5 Death MUCOSITE •Frequenza •Patogenesi Patogenesi •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva Systematic review of the literature Defining statement of consensus Consensus rounds : voting Threshold for Consensus > 75%, if not obtained come back to panel for modifications Statements to external reviewers, final voting round STATEMENTS No suggestions is possible about the superiority of one scale over another identification/correction of clinical and therapeutic variables increasing the propensity to develop more severe mucositis (e.g. poor oral hygiene, periodontal disease, low body mass index, weight loss before therapy, immunosuppression, radiotherapy total dose and weekly dose rate on oral and oropharyngeal mucosa, chemotherapy usage…) recommended to assess regularly oral mucositis at least once-a-week, with recommendation to the patient to communicate any further worsening of symptoms. no superiority of one mouthwash over saline or bicarbonate rinses is demonstrated Radiotherapy with the aim of maximal sparing of the mucosa outside any PTV. When intensity Modulated RT (IMRT) is used, the total dose to the mucosa outside any PTV should be planned to be limited to 30 Gy in 6-7 weeks. NOT RECOMMENDED (low evidence) Cryotherapy (vasocostriction could impact on treatment efficacy). Barrier agents such as sucralfate, GelClair® and Mucotrol® allopurinol gel application amifostine benzydamine mouthwashes (no direct comparison with bicarbonate) Chlorexidine mouthwash Glutamine NOT RECOMMENDED (low evidence) granulocyte macrophage colony-stimulating factor Topical misoprostol (and Prostaglandin E2) Antibiotic + antifungal pastilles The prophylactic treatment with systemic fluconazole (except immunodepressed pts) Steroids (both topical and systemic use) NSAIDS recombinant human KGF-1 (palifermin) in 2 randomized trials was shown to reduce the incidence of severe oral mucositis as assessed by physicians but the benefit was not paralleled by patient reported outcomes DISFAGIA Dolore malnutrizione Disgeusia Xerostomia Nausea sarcopenia/astenia Depressione anoressia DISFAGIA •Frequenza •Fisiopatologia Fisiopatologia •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva DISFAGIA •Frequenza •Fisiopatologia Fisiopatologia •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva Ulcerative mucositis and associated sequelae in patients receiving radiotherapy for head and neck cancer. PERDITA DI PESO SUPPORTO NUTRIZIONALE Russo G et al. The Oncologist 2008;13:886-898 DISFAGIA •Frequenza •Fisiopatologia Fisiopatologia •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva FASI DEGLUTIZIONE I fase (volontaria): orobuccale. Lingua, palato, ugola Masticazione Saliva (amilasi, lipasi) II fase (involontaria) faringea. Recettori nella parete faringea che stimolano il centro della deglutizione nel midollo allungato e ponte Chiusura ugola, elevazione laringe, chiusura glottide, abbassamento epiglottide, apertura sfintere esofageo superiore, chiusura dopo transito del bolo DISFAGIA •Frequenza •Fisiopatologia Fisiopatologia •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva Q8: Which are the main determinants that guide decision on gastrostomy placement before therapy (multiple choices allowed)? Hanno risposto: 108 Dose RT a muscoli costrittori a mucosa orofaringe Perdita di peso pre-trattamento Hanno saltato la domanda: 3 DISFAGIA •Frequenza •Fisiopatologia Fisiopatologia •Terapie di supporto cosa facciamo (survey) •Terapie di supporto cosa è meglio fare (Consensus) •Tossicità tardiva SINTOMI INALAZIONE/ASPIRAZIONE Simulation Computerized Tomography (S-CT) - based delineation of "Dysphagia Aspiration Related Structures” (DARS) and the collection of dosimetric parameters are suggested and encouraged, although not yet consolidated for routine use in clinical practice. A multimetric model (more than one parameter: e.g. Dmean, different DVHs) should be considered in order to evaluate DARS dose constraints PEG e SNG Prospective study of percutaneous endoscopic gastrostomy tubes versus nasogastric tubes for enteral feeding in patients with head and neck cancer undergoing (chemo)radiation J Corry et al. PEG patients had : significantly less weight loss at 6 weeks post-treatment high insertion site infection rate (41%) longer median duration of use (146 vs 57 days, p < .001) and more grade 3 dysphagia in disease-free survivors at 6 months (25% vs 8%, p = .07). Patient self-assessed general physical condition and overall quality of life scores were similar in both groups. Overall costs were significantly higher for PEG patients. solidi liquidi Grazie per l’attenzione
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