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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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