Presentazione sul tema: "LE OPZIONI TERAPEUTICHE NEL TUMORE DEL POLMONE"— Transcript della presentazione:
1 LE OPZIONI TERAPEUTICHE NEL TUMORE DEL POLMONE CORSO INTERATTIVO SULLEMALATTIE RESPIRATORIE FUMO CORRELATEModena 12 Dicembre 2003LE OPZIONI TERAPEUTICHENEL TUMORE DEL POLMONEFausto BarbieriDipartimento Oncologia ed EmatologiaPoliclinico di ModenaUniversita’ di Modena e Reggio Emilia
3 Metastasi extratoraciche Linfonodi controlaterali NSCLC: stadiazioneLinfonodiInvasioneParete toracicaMetastasi extratoracicheBronco principaleStadio 0Schematic diagram showing examples of some tumor stages.Stage 0 (carcinoma in situ) - tumor is confined to the airway lining.Stage IA (T1 N0 M0) - tumor has spread to nearby lung tissue but has not reached the main bronchus.Stage IIB (T2 N1 M0) - tumor has reached main bronchus and local lymph nodes.Stage IIIB (T4 N3 M0) - tumor has invaded chest wall, trachea and the contralateral lymph nodes.Stage IV (T1 N0 M1) - distant metastasis present in the brain.Stadio IAStadio IIBStadio IIIBLinfonodi controlateraliStadio IV
4 NSCLC: stadio alla diagnosi 50251510Stadio IV stadio IIIB stadio IIIA stadio I-II
5 NSCLC: sopravvivenza per stadio IAIBIIAIIBIIIAIIIBIV
6 NSCLC: opzioni terapeutiche Stadio localizzato (I-IIIA N1)chirurgia (radioterapia se non candidato a CH)Malattia locoregionale (IIIA-IIIB selezionati)chemioterapia + radioterapia + chirurgiaMalattia avanzata (IIIB-IV)chemioterapia + terapia supportoFor localized tumors (stage 0, I, II), surgery is usually the treatment of choice. Radiotherapy may be used in patients who are medically unsuitable for surgery. The role of induction chemotherapy in these early stages is still under investigation.Locally or regionally advanced tumors (stage III) are usually too extensive curative surgery, but are still confined to the chest. The standard treatment is chemotherapy plus radiotherapy. Downstaging the tumor with chemotherapy (with or without radiotherapy) may allow surgery in certain cases.Advanced tumors (stage IV) are treated with chemotherapy. Palliative radiotherapy may be used to relieve symptoms.1. PDQ Treatment Guidelines.
7 NSCLC stadio 0-IIIA N1 Intervento chirurgico (lobectomia, ecc) resezioni non anatomiche solo in casi particolariRT curativa se CH controindicatadosaggio > 60 GyChemioterapia adiuvante ?Radioterapia adiuvante?Chemioterapia neoadiuvante?Stadio 0: Terapia fotodinamica (in paz. selezionati)Surgery is the treatment of choice, lobectomy, pneumonectomy (removal of entire lung), segmentectomy or wedge resection depending on the patient.1Curative radiotherapy may be used in patients with contra-indications to surgery.130-50% of patients resected for stage I/II NSCLC may later develop regional or distant metastases. Adjuvant chemotherapy or radiotherapy following surgery, and neoadjuvant chemotherapy, are currently under investigation.11. PDQ Treatment Guidelines.
8 NCSLC: tipi di intervento chirurgico PneumonectomiaLobectomiaSegmentectomiaWedge-resection
9 NSCLC stadio I: chirurgia TIPO DI INTERVENTO CHIRURGICO recidiva per tipo di intervento0.10500.09Tassorecidivalocoreg.(per persona/anno)0.0840p=0.008p<0.050.070.0630locoregionale% recidiva0.050.04200.030.02100.01The recurrence rate after surgery appears to be higher for limited surgery than for lobectomy.The left-hand graph shows the locoregional recurrence rate (per patient per year) in 247 patients with stage IA (T1 N0) NSCLC, who were randomized to either lobectomy or limited (segment or wedge) resection. The recurrence rate was three times higher in the patients undergoing limited resection, and the death rate was increased by 30%.1Similarly, a retrospective non-randomized study in 173 patients with stage I NSCLC found that the percentage of patients experiencing a local or regional recurrence within 5 years was higher in patients undergoing anatomic segmentectomy than lobectomy.21. Ginsberg RJ, Rubinstein LV. Ann Thorac Surg 1995; 60:2. Warren WH, Faber LP. J Thorac Cardiovasc Surg 1994; 107:00.0Resezionelimitata(n=122)Lobectomia(n=125)Segmen-tectomia(n=68)Lobectomia(n=105)TIPO DI INTERVENTO CHIRURGICOWarren & Faber 1994Ginsberg & Rubinstein1995
10 NSCLC stadio I-II: RT Sopravvivenza in base al dosaggio 807060Disease-free survival (%)50403020A retrospective review investigated survival in 152 patients with stage I and II NSCLC, who were unable to undergo surgery for medical reasons and received radiotherapy instead.1The graph shows 2-year disease-free survival by tumor stage (T1, T2 or T3) and radiation dose.1T1 tumors treated with radiation doses of 65 Gray or more had the best disease-free survival rate, 73% at 2 years.1 This is comparable to the overall 2-year survival rates of approximately 75% (segmentectomy) and approximately 90% (lobectomy) reported separately for resected patients with stage I (T1 or T2, N0) NSCLC.21. Dosoretz DE, et al. Int J Radiation Oncology Biol Phys 1992; 24: 3-9.2. Warren WH, Faber LP. J Thorac Cardiovasc Surg 1994; 107:10Globale>65 Gy<60 GyDOSAGGIO RTDosoretz et al 1992
12 NSCLC: Chemioterapia adiuvante Studi randomizzati N. PazStadioSchemaS 5a (CH/CH+CT)SGACLC309I – III AP/DOX/UFT58 / 62WADA323P/VDS/U VS U49 / 61 / 64METANALISI1394P-based48 / 53KELLER488II – III AP/VP1639 (rt) / 38ALPI1209MVP +/- RT37 / 40TADA267I – IIIAUFT58 / 74 (8a)TSUBOI979I85 / 89IALT1867P/VP16-VNR40 / 45
13 NSCLC stadio III: opzioni terapeutiche Chirurgia (in paz. selezionati in stadio IIIA)Chemioterapia CHRT postoperatoria (pN2)RT o Chemioradioterapia?Chemioterapia (stadio IIIB con versamento pleurico)Stage IIIA:1surgery alone in highly selected caseschemotherapy combined with radiotherapy, chemotherapy plus radiotherapy followed by surgery, or chemotherapy after surgery (encouraging results for patients with good performance status)surgery and postoperative radiation therapy (can improve local control, but there is controversy over whether it improves survival)radiation therapy (long-term survival benefit in 5-10% of patients; patients with high performance status are most likely to benefit).Stage IIIB:1radiation therapy alone (patients with advanced disease and high performance status are most likely to benefit)chemotherapy combined with radiation therapy (modest survival benefits compared with radiation therapy alone)chemotherapy and/or radiation therapy followed by surgerychemotherapy alone (for patients with malignant pleural effusion).1. PDQ Treatment Guidelines.
14 NSCLC: Chemioterapia neoadiuvante Studi randomizzati N.PazStadioTerapiaRO% Resez.SMPASS1413IIIA N2CHPE+CH-4386851629ROSELL30MIC+CH60901020ROTH3228CEP+CH3566611164DEPIERRE119109IB-IIIAN1MIP+CH782637* Sopr. a 3 anni
15 NSCLC stadio III: CT/RT vs RT 0.00.51.01.52.0RT + CT miglioreRT (controllo)miglioreBuenos AiresBrusselsFLCSG 2EssenSLCSGCEBI 138WSLCRG/FIPerugiaCALGB 8433EORTC 08842SWOG 8300aSWOG 8300bSubtotalep=0.005A meta-analysis used data from 11 randomized clinical trials which compared radiotherapy with radiotherapy plus cisplatin-based chemotherapy in patients with locally advanced NSCLC.1The graph shows the hazard ratio (relative risk of death) and confidence intervals for each of the 11 trials. The square represents the mean hazard ratio for each trial, and the outer and inner bars show the 95% and 99% confidence intervals. The size of the square represents the size of the trial.The center of the diamond represents the overall hazard ratio from all the trials combined, and its ends represent the 95% confidence interval.The majority of the trials reported a hazard ratio of <1 (to the left of the solid vertical line), indicating superior survival in the groups treated with radiotherapy plus chemotherapy.The overall hazard ratio was 0.87, indicating a 13% lower risk of death for the patients receiving combination treatment (p=0.005).Combined chemotherapy and radiotherapy is an appropriate treatment for patients with good performance status and weight loss of <5%. However, radiotherapy alone may be more appropriate for patients with stage III NSCLC with poor performance status or weight loss of 5% or more during the preceding 3-6 months.21. Non-small Cell Lung Cancer Collaborative Group. Br Med J 1995; 311:2. Juretic A, et al. Ann Oncology 1999; 10 (suppl. 6): S93-S98.NSCLC Collaborative Group 1995
16 NSCLC stadio IIIB-IV: vecchi vs nuovi regimi BSCregimi con CDDP anni 80Regimi con CDDP anni 90% risposteobiettive3040Sopravv.Mediana (m)67 - 89 - 10Sopravv1 anno (%)1020
17 NSCLC stadio IIIB-IV: schemi di chemioterapia studi randomizzatiRO (%)263814232721.321.017.315.3SM(mesi)220.127.116.11.07.87.4CRINO’ 1998BELANI 1998KELLY 1999SCHILLER 2000SchemaMitomicina/ifosfamide/cisplatinoGemcitabina/cisplatinoEtoposide/cisplatino Paclitaxel/cisplatinoVinorelbina/cisplatinoPaclitaxel/carboplatinoPaclitaxel/cisplatinoDocetaxel/cisplatinoRecent randomized trials have clearly demonstrated the benefit of combining cisplatin with new active agents in NSCLC, resulting in increased tumor response and prolonged median survival compared with treatment with cisplatin alone.However, at present, none of the new agent - platinum combinations has been shown to be clearly superior. Results of two large phase III trials reported at ASCO1,2 show a broad range of response rates (15-27%) with these new combinations, but this does not translate into a significant impact on median survival (range months).1. Kelly K, et al. Proc ASCO 1999;18:(abs 1777)1. Schiller JH, et al. Proc ASCO 2000;19:(abs 2)
18 NSCLC: BSC vs Chemioterapia Metanalisi N. StudiRisultatiConclusioniSOUQUET7↓ Mortalità a3 e 6 m.CT raccomandataGRILLI6Sopravvivenza(6 sett.)CT in paz. selezionatiMARINO8SM 3.9 vs 6.7 m.NSCLC COLL.GROUP11SM 6 vs 8 m.;16 vs 26% a 1 a.CT migliorasopravvivenza
19 NSCLC: Chemioterapia di II linea Studi randomizzati N PazRO %SM m.S 1-a.pSHEPERDBSCTXT10075100103-64.6719290.047FOSSELLATXT 100TXT 75VNR/IFX12312711912815.632100.012HANNAPMTX 500285286Nrnr7.98.330N.S.
21 NSCLC: nuovi farmaci Inibitori Topoisomerasi (CPT11,ecc) Nuovi antifolati (MTA)Nuovi Taxani (BAY )Inibitori EGFR (MoAb o TKI)Antiangiogenetici (antiVEGF,ecc)Inibitori MMP (Marimastat,ecc)Oligonucleotidi antisenso (ISIS 3521,ecc)Vaccini antitumorali (IGN 101,ecc)Anti COX2 (Celecoxib,ecc)Terapia genicaIn order to replicate DNA, the two strands must be separated, which causes strain in adjacent areas of the helix. The strain is relieved by DNA topoisomerases, which make a transient break in the DNA backbone to permit unwinding. Topoisomerase inhibitors increase the frequency of these breaks, which eventually triggers programmed cell death.1DNA synthesis requires a constant supply of nucleotides. The supply of the thymidylate nucleotide can be blocked by inhibition of thymidylate synthase. This enzyme is the target of antifolate drugs such as ZD9331,2 multitargeted antifolate (MTA, LY231514),3 and the benzoquinolone 1843U89.41. Fortune JM, et al. Biochemistry 1999; 38:2. Plummer R, et al. Eur J Cancer 1999; 35: S4, 285.3. Rusthoven JJ, et al. J Clin Oncol 1999; 17:4. Hanlon MH, Ferone R. Cancer Res 1996; 56:
22 NSCLC: Studi clinici con inibitori dell’EGFR DisegnoSM (m.)GATZEMEIERGC vs GC+Herceptin7.2 / 6.3 (TTP)IDEAL 1IDEAL 2INTACT 1INTACT 2Iressa 250 vs 500 mgCT vs CT + Iressa 250/5008.2 / 8.08.1 / 8.011.1 / 9.9 / 9.99.9 / 9.8 / 8.7BONOMITRIBUTETALENTTarceva 150 mgCT vs CT + Tarceva 1509.0ND
24 SCLC: stadiazione Malattia estesa: Tumore non confinato all’emitorace di origine ometastasi a distanzaMalattia limitata:Tumore confinato all’ emitorace di origine e/o al mediastino e/o ai linfonodi sovraclaveariMetastatic disease is present at diagnosis in most patients with SCLC. Thus, survival is usually not affected by small changes in the amount of locoregional tumor involvement, as it is for NSCLC. Thus, the detailed TNM staging previously described, although relevant is not commonly employed for staging SCLC.Instead, a simple 2-stage system, limited or extensive stage SCLC, is used.In limited-stage disease the tumor is confined to the hemithorax of origin, the mediastinum and the supraclavicular nodes, which can be encompassed within a ‘tolerable radiation’ therapy port.1The extensive-stage of SCLC encompasses any tumor too widespread to be included within the definition of limited-stage and any patients with distant metastasis.11. Zelen M. Cancer Chemother Rep 1973; 4:PDQ Guidelines 2000
25 SCLC: sopravvivenza % Pazienti Mal. limitata Mal. Estesa Based on US figures from , 5-year survival in patients with SCLC is 6.2%.1Disease stage is one of the most important prognostic factors in SCLC. In a randomised study, in which two combination chemotherapy regimens were compared, prognostic factors were analysed in 286 patients. Disease stage was the primary pretreatment predictor of 3-year survival; 19.2% of patients with limited-stage disease survived for 3 years, compared with 3.5% with extensive-stage disease.2 The median survival duration for patients treated with combination chemotherapy is 10 to 14 months for patients with limited-stage and 7 to 11 months for those with extensive-stage, the most commonly diagnosed SCLC.3References1. Ries LAG, et al (eds). SEER Cancer Statistics Review, , National Cancer Institute, Bethesda, MD, 2001.2. Kawahara M, et al. Jpn J Clin Oncol 1997; 27:3. Zöchbauer-Müller S, et al. Ann Oncol 1999; 10 (Suppl 6): S83-S91.Mal. limitataMal. EstesaRies et al 2001
26 SCLC: opzioni terapeutiche Malattia limitatachirurgia solo per noduli perifericichemio-radioterapiaMalattia estesachemioterapia + radioterapia in casi selezionatiPCI in caso di risposta completaFor localized tumors (stage 0, I, II), surgery is usually the treatment of choice. Radiotherapy may be used in patients who are medically unsuitable for surgery. The role of induction chemotherapy in these early stages is still under investigation.Locally or regionally advanced tumors (stage III) are usually too extensive curative surgery, but are still confined to the chest. The standard treatment is chemotherapy plus radiotherapy. Downstaging the tumor with chemotherapy (with or without radiotherapy) may allow surgery in certain cases.Advanced tumors (stage IV) are treated with chemotherapy. Palliative radiotherapy may be used to relieve symptoms.1. PDQ Treatment Guidelines.
27 SCLC: chemioterapia di combinazione Cisplatino/Etoposide (PE)Ciclofosfamide/Adriamicina/vincristina (CAV)Ifosfamide/Carboplatino/Etoposide (ICE)Ciclofosfamide/Adriamicina/Etoposide (CAE)Cisplatino/CPT11Cisplatino/TopotecanCisplatino/Gemcitabina/EtoposideCarboplatino/PaclitaxelMultiple chemotherapeutic agents possess single-agent activity against SCLC. A number of combination chemotherapy protocols have demonstrated activity in patients with limited-stage SCLC, with overall response rates of 80-95%.These include cisplatin/etoposide (PE), cisplatin/etoposide/vincristine (PEV), cyclophosphamide/doxorubicin/vincristine (CAV), cyclophosphamide/ doxorubicin/etoposide (CAE) and cyclophosphamide/doxorubicin/ vincristine/etoposide (CAVE).In patients with limited stage disease median survivals of 12.4 and 15.1 months have been reported following treatment with CAV and CAVE, respectively. 1,2 In addition, the complete response rate was 16% and 48%, with CAV and CAVE, respectively.1,2There is some evidence that alternating chemotherapy regimens (PE/CAV) in patients with limited disease may be beneficial.1,3There is no compelling evidence that maintenance chemotherapy prolongs survival for patients with SCLC. In fact it may produce more toxicity and thus negatively impact on the quality of life.41. Fukuoda M, et al. J Natl Cancer Inst 1991; 83:2. Goodman GE, et al. J Clin Oncol 1990; 8:3. Johnston BE, et al. J Clin Oncol 1996; 14:4. Giaccone G, et al. J Clin Oncol 1993; 11:Zöchbauer-Müller and Huber 1999
28 SCLC-ML: chemio-radioterapia Metanalisi su 13 studi 100Chemioterapia + RT (n=1111)80Chemioterapia (n=992)Sopravv.%p=0.001604020A meta-analysis of the 13 largest trials showed that combined chemotherapy and chest RT was more effective than chemotherapy alone. In this study, administration of thoracic RT led to a 14% reduction in mortality rate (p=0.001), which corresponded to a 5% increase in the 3-year survival rate.1A similar result was also demonstrated in another meta-analysis of 11 randomized trials.2 Most of the benefit occurred in patients <55 years.Thus, in limited stage SCLC, combination chemotherapy plus chest RT is considered a standard treatment for patients with limited-disease SCLC.31. Pignon JP, et al. N Engl J Med 1992; 327:2. Warde P, Payne D. J Clin Oncol 1992; 10:3. PDQ Guidelines, 2000.12345AnniPignon et al 1992
29 SCLC: Trattamento della malattia limitata CH poliCT/RT combinate1/3esternoNodulosolitarioT2poliCT + RTconcomitante2/3interniSCLC-MLpoliCT + RTconcomitanteBuon PSEven for a small solitary nodule that has been completely resected subsequent chemotherapy is indicated.1The majority of patients diagnosed with positive mediastinal nodes undergo combination chemotherapy with concurrent chest radiotherapy (RT).1,2Patients presenting with superior vena cava syndrome or patients with poor performance status and extensive cormordid disease can be treated with combination chemotherapy without RT.1Prophylactic cranial irradiation (PCI) can be considered in patients who are in complete remission following treatment with chemotherapy with or without chest irradiation.1,21. NCCN Guidelines, 2000.2. PDQ Guidelines, 2000.Tutte le restantipresentazioniCattivo PSpoliCT RTNCCN guidelines 2000
30 LD-SCLC: RT profilattica cerebrale No PCI (n=149)PCI (n=145)p<10-138060% Recidivecerebrali4020Despite the high response rates to chemotherapy, after 2 years the risk of brain metastasis is 50-80%, resulting in extremely low survival rates. This study showed that patients who are in complete remission have a 60% risk of developing CNS metastases within 2 to 3 years of treatment, and administration of PCI reduces the risk by more than 50%.1Several randomized studies have failed to demonstrate a benefit for PCI in improving overall survival, and side effects, such as neuropsychiatric abnormalities have been a concern.However, neurological abnormalities have been shown to exist in 30-40% of SCLC patients prior to PCI and a recent meta-analysis demonstrated an absolute 5.4% increase in 3-year survival rate in favor of PCI.2It is now generally accepted that PCI should be administered to patients with limited-stage disease in complete remission after induction chemotherapy.21. Arriagada R, et al. J Natl Cancer Inst 1995; 87:2. Zöchbauer-Müller S, et al. Ann Oncol 1999; 10 Suppl 6:1224364860MesiArriagada et al 1995
31 Terapia del SCLC-ME ES-SCLC M.estesa Sintomatico/grave Osso poliCT (+ ev. PCI)M.estesaRTSintomatico/graveES-SCLCOssoAsintomaticopoliCTSintomaticoRT+ poliCTM. Estesa +ProblemispecificiSNCSince disseminated disease is present in patients with extensive-stage SCLC, combination chemotherapy is the most important treatment modality.1,2Combination chemotherapy plus chest RT does not improve survival in patients with extensive disease, compared with chemotherapy alone.1However, radiation therapy plays an important role in palliation of symptoms of the primary tumor and of metastatic disease, particularly in the brain, spinal cord and bone.1,2For severely debilitated patients with extensive disease, a low intensity chemotherapy regimen may provide palliation with low associated toxicity.1. PDQ guidelines, 2000.2. NCCN guidelines, 2000.AsintomaticoPoliCT (± RT)MidollospinaleRT + steroidi poi poliCTNCCN guidelines 2000
32 SCLC: risposta alla terapia MALATTIA LIMITATARisposte obiettive: 85% (~30% complete)Sopravvivenza mediananon trattati: 3 mesitrattati: 18 mesiSopravvivenza a 5 anni 10-20%MALATTIA ESTESARisposte obiettive: 70% (~15% complete)non trattati: 6 settimanetrattati: 9 mesiSopravvivenza a 5 anni < 5%The combination chemotherapy regimens commonly used in extensive-stage SCLC appear to have similar relative effectiveness; with overall response rates of 70-85%, complete response rates of 10-40% and median survivals of 7-11 months.1 Long-term survivors are rare.1. PDQ Guidelines, 2000.PDQ guidelines 2000
33 SCLC recidivo: opzioni terapeutiche TerapiasintomaticaChemioterapia diII linea o inserimentoIn studio clinicoRefrattario(durante CT)SCLCrecidivatoRecidiva precoce(entro 3 mesi)Palliative therapy is very important in patients with recurrent SCLC. Palliation of symptoms with short-term local control and external-beam radiation therapy can be carried out.1 In addition, in patients with intrinsic endobronchial obstructing lesions or extrinsic compression, endobronchial laser therapy and/or brachytherapy may be beneficial.1 Endobronchial stents can be inserted in patients with malignant airway obstruction.1Late relapsing patients with a long-treatment-free interval frequently respond to combination chemotherapy, which may be identical to their first-line treatment (response rates of up to 50-60%).1Both refractory and early relapsing patients with a short treatment-free interval, only have a small chance of responding to any drug.1,2 These patients are candidates for Phase II studies with new agents.1,21. PDQ Guidelines, 2000.2. Huisman C, et al. Cancer Treatment Rev 1999; 25:Ripresa terapia diI lineaTardivaNB. 95% recidivanoSopravv. Media dalla recidiva 4-6 mesiNCCN Guidelines 2000
34 SCLC: nuovi farmaci Classe Farmaco Taxani docetaxel; paclitaxel Inibitori topoisomerasiAnaloghi del platinoRetinoidiAgenti alchiilantiAntimetabolitiInibitori MMPVaccini antitumoraliOligonucleotidi antisensoInibitori c-kitFarmacodocetaxel; paclitaxelirinotecan; topotecanZD0473tretinoinanitrullinaGemcitabinaMarimastat,PrinomastatAnti BEC-2ISIS 5132STI 571There is clearly a need for new drug regimens to improve survival in patients with SCLC and there are several new drugs showing encouraging results in clinical trials for SCLC. As single agents in extensive- stage SCLC patients, the taxoid, docetaxel gives comparable survival outcomes to that of standard single agent treatment.1,2 Docetaxel is currently in Phase II combination trials. The response rates of paclitaxel and irinotecan as single agents in Phase II trials were also similar to those of established drugs, and they are also currently being examined in combination chemotherapy trials.3,4ZD0473 is a platinum drug designed with the capacity to overcome acquired or de novo resistance, particularly to overcome thiol-mediated resistance. Phase II trials of this drug are ongoing in a number of tumour types including SCLC and NSCLC5The 9-cis retinoid, tretinoin has demonstrated cytotoxicity against SCLC cells in vitro.6 It is currently in Phase II trials in the USA. Nitrullyn, an alkylating agent is currently in Phase II trials in patients with SCLC in Russia.1. Hesketh PJ, et al. Cancer J Sci Am 1999; 5:2. Postmus PE, et al. Sem Oncol 1998; 25:3. Ettinger DS. Sem Rad Oncol 1999; 9:4. Zöchbauer-Müller S, et al. Ann Oncol 1999; 19: S83-S91.5. Trigo JM, et al. Proc Am Soc Clin Oncol 1999; 18: 169.6. Rosati R, et al. Anticancer Res 1998; 18:
35 Altri provvedimenti terapeutici Metastasi isolata a SNC o surreneintervento chirurgico (+ RT se SNC)Sindrome VCSposizionamento stent cavalesteroidi, RT e/o CT, eccOstruzione bronchialelaserterapia disostruttivaposizionamento di stent bronchialeLocalizzazione rachideaDecompressione chirurgica entro 48 oreRT, steroidi, eccVersamento pleurico neoplasticoposizionamento di drenaggio toracicochemioterapia intracavitaria e/o talcaggio pleuraTerapie di supporto