Behandelingsgerelateerde urgenties in de oncologie Peeters M, Rolfo Ch, Specenier P
Definitie van oncologische urgenties
Spoedeisende Oncologie = acuut medisch handelen bij een patiënt bij wie een kwaadaardige tumor, de complicaties van een oncologische behandeling en/of symptomen
van
metastasering
invasieve/non-invasie-interventie mortaliteit of ernstige morbiditeit
Hoekstra HJ et al. Oncologie, 8e herziene druk, 2011
directe vereisen
diagnostiek ter
en
een
voorkoming
van
Graad v. Toxiciteit
Urgentie ‘potentiëel’
Von Hoff D et al. N Engl J Med 2013;369:1691-703
Ziekte
Radiotherapie
Therapie
Chirurgie
Urgenties
Chemotherapie Systemische Therapie Doelgerichte Therapie
Radiotherapie-gerelateerde urgenties
- Acute effecten: huid, beenmerg en gastrointestinaal dagen/weken na start therapie zelflimiterend en reversibel
- Laattijdige effecten: nier, long en hart maanden/jaren na therapie fibrotische reactie
Radiotherapie-gerelateerde urgenties
Bestralingsenteritis
Acuut Chronisch
- diarree, nausea, krampen, (perforatie) - obstructie,…
Chirurgie-gerelateerde urgenties
Hals/Mediastinale Fistel
Stenose van Anastomose
‘Multidisciplinaire’ urgenties
ChemoR/ 5-FU/Cispl.
ChemoR/ 5-FU/Cispl.
Rest
Radiation, 20 x 1.8 Gy
Week 1
Week 2
Week 3
Week 4
Surgery
Week 5-8 Week 9
Balans tussen Inflammatie & Fibrose
Chirurgie-gerelateerde urgenties
De voornaamste doodsoorzaak na een pancreasoperatie is het ontstaan van een pancreasfistel of -lekkage ter hoogte van de pancreasreconstructie.
Systemische therapie gerelateerde urgenties Diarree
Nausea, Braken
Alopecia Boeken over Biotechnologie
Hematologisch
Systemische therapie gerelateerde urgenties Diarree
- 76-jarige patiënt, goede performantie, alleenwonend - stabiele angor, randnormale nierfunctie - Diagnose: levergemetastaseerd coloncarcinoom
ziekte
= geen nood voor intensieve combinatie
patiënt = ‘pillekes’ is gemakkelijk familie = bezig, wonen ver
Diarree
- Therapie: capecitabine 2 x 1250 mg/m²/14 d dag 9
: waterige diarree, mucositis
dag 12 : deshydratatie, angor – opname via spoed
1. Informeren 2. Adviseren 3. Contacteren
PREVENTIE
Systemische therapie gerelateerde urgenties Diarree
Nausea, Braken
Alopecia Boeken over Biotechnologie
Hematologisch
Systemische therapie gerelateerde urgenties Hematologisch - 33-jarige patiënt, hoesten en 38.8 °C één week na chemo
geen koorts op spoed, geen bijzonderheden bij klinisch onderzoek amoxicillin en ontslag - na 24 uur: algemene achteruitgang en herhospitalisatie met septische shock (neutrofielen: 0.02 x 109/l)
Febrile neutropenia – definitions
• NCCN: 1 x fever > 38.3 orally or > 38 for 1 hour and ANC < 500/µl or < 1000/µl and predicted decline to <
500/µl over next 48 hours • (ESMO: axillary temperature >38.5 C lasting >1 h in the context of an ANC <500/µl)
• Rectal temperature measurements discouraged
Febrile neutropenia – history • Comorbidity • Time since last chemotherapy • Type of last chemotherapy • Recent use of antibiotics • Prior documented infections
• HIV • Use of medications (cave corticosteroids !) • Others at home with similar symptoms • Recent administration blood products
Febrile neutropenia – physical examination • Complete physical exam; vital parameters • Intravenous access device • Skin • Lungs and sinus • Alimentary tract: mouth, pharynx, esophagus, bowel, rectum • Perirectal, perivaginal, perineal region • Genitourinary discharges
• Central nervous system Cave: signs and symptoms of inflammation frequently attenuated
Febrile neutropenia – work up
• Complete blood cell (CBC) count with differential leukocyte count and platelet count • serum levels of creatinin and blood urea nitrogen • C reactive protein • Serum electrolytes • Hepatic transaminase enzymes, and total bilirubin • Coagulation screen • Urinalysis
Febrile neutropenia – work up • At least 2 sets of blood cultures (10 ml into aerobic + 10 ml into anaerobic bottle)
o a set collected simultaneously from each lumen of an existing CVC, if present, and from a peripheral vein site; o 2 blood culture sets from separate venipunctures should be sent if no CVC present (2 sets: 80-90 % detection rate; > 3 sets: 96 % detection rate)
• Culture specimens from all other sites of suspected infection o o o o o
Urine: symptoms, catheter , abnormal urinalysis Sputum Skin lesions (venous access site) Stool if diarrhea (Clostridium difficile toxin assay) CSF if meningitis suspected
Febrile neutropenia – work up
• Chest radiograph (if respiratory symptoms present or outpatient therapy considered) • Consider pulse oxymetry • Viral cultures mucosa
vesicular/ulcerated
lesions
skin
or
• CT head, sinuses, abdomen, pelvis as clinically indicated
LAAG RISICO
Febriele Neutropenie HOOG RISICO
Febrile neutropenia – Low Risk
• Expected neutropenia < 7 days and no active medical co-morbidity • and stable and adequate
– hepatic function – and renal function • Outpatient at diagnosis
• Good performance status (0 or 1)
• Factors predicting readmission on outpatient treatment:
o age >70 years o grade of mucositis >2
o poor performance status o ANC < 100/µl
Freifeld AG et al. Clin Infect Dis. 2011; 52(4):427-31
Febrile neutropenia: low risk: outpatient treatment ?
• The anti-pseudomonal activity of levofloxacin 500 mg daily is probably inadequate, but it may be sufficient at 750 mg daily • Oral treatment if applicable: amoxy/clav + cipro
• Moxifloxacin 400 mg/day
Worth LJ et al. Intern Med J 2011; 41(1b):121-9
Febrile neutropenia: high risk Hospitalization for IV empirical antibiotic therapy In general: Monotherapy with an anti-pseudomonal β-lactam cefepime piperacillin-tazobactam ceftazedime a carbapenem (meropenem or imipenem-cilastatin)
Vancomycin is not recommended as a standard part of the initial antibiotic regimen History of serious hypersensitivity: clindamycin + ciprofloxacin or aztreonam + vancomycin
Mechanisms of Thrombocytopenia
• ChemoRx • Radiation Rx • Bone marrow tumor infiltration • Hypersplenism • DIC • Infection - induced • ITP
Spontaneous bleeds can occur if platelets < 10 K
All hemorrhagic manifestations
Gross hematuria, melena, and hematemesis
Slichter SJ. Transfusion Medicine Reviews 2004;18:153-167
Slichter SJ. Transfusion Medicine Reviews 2004;18:153-167
Profylactische transfusie van bloedplaatjes: drempelwaarde
• Geen risicofactoren: 10.000/µl • Risicofactoren (koorts, hyperleucocytose,
Stollingsproblemen, snelle daling): 20.000/µl • Heelkunde: 50.000/µl • CVC: 30.000/µl
Hoge Gezondheidsraad Goede transfusiepraktijken in ziekenhuizen januari 2010; HGR nr. 8381
EXTRAVASATIE
Lewis MA et al. CA Cancer J Clin. 2011;61:287–314
Lewis MA et al. CA Cancer J Clin. 2011;61:287–314
DMSO indicates dimethyl sulfoxide
Lewis MA et al. CA Cancer J Clin. 2011;61:287–314
Lewis MA et al. CA Cancer J Clin. 2011;61:287–314
Systemische therapie gerelateerde urgenties
Anti-EGFR
Anti-VEGF
Anti-VEGF
Hurwitz H et al. N Engl J Med 2004;350:2335-42
Khorana AA. Am J Hematol 2012;87:S82–S87
Relative risk Chemotherapy No Metastases Metastases Radiotherapy No Metastases Metastases Surgery No Metastases Metastases Hormone therapy Prostate cancer No Metastases Metastases Breast cancer No Metastases No Metastases
Blom JW et al. J Thromb Haemost 2006;4:529–35
2 2.3 0.8 0.7 1.1 0.9
1.8 1.3 1.2 1.2
Battinelli EM et al. Hematol Oncol Clin N Am 2012;26:345–367
Khorana AA. Am J Hematol 2012;87:S82–S87
Telangiectasia
Hyperpigmentation
Hair changes
Anti-EGFR – pulmonaire toxiciteit
Panitumumab (n = 496)
Cetuximab (n = 503)
29 (5.8) 20 (4.0) 9 (1.8)
50 (9.9) 34 (6.8) 16 (3.2)
0 (0)
1 (0.2)
Skin and subcutaneous tissue AEs Any grade Grade 3 Grade 4 Serious
430 (86.7) 60 (12.1) 2 (0.4) 1 (0.2)
440 (87.5) 48 (9.5) 0 (0) 0 (0)
Hypomagnesaemia Any grade Grade 3 Grade 4
143 (28.8) 27 (5.4) 9 (1.8)
95 (18.9) 10 (2.0) 3 (0.6)
Infusion reactions Any grade Grade 3 Grade 4
14 (2.8) 1 (0.2) 0 (0)
63 (12.5) 5 (1.0) 4 (0.8)
Diarrhoea Any grade Grade 3 Grade 4
91 (18.3) 7 (1.4) 3 (0.6)
89 (17.7) 9 (1.8) 0 (0.0)
Adverse events, n (%)
Fatal AEs Colon cancer Others Treatment-related fatal AEs
Price T et al. Lancet Oncol 2014;15:569-79
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