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Clinical approach to the patient

Università degli Studi di Palermo Facoltà di Medicina e Chirurgia Dipartimento di Oncologia Cattedra di Oncologia Medica Uos Terapie Oncologiche Innovative Prof. S. Palmeri. Clinical approach to the patient. Mediterranean School of Oncology Rome , March 6, 2010. What is my tumor origin ?.

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Clinical approach to the patient

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  1. Università degli Studi di PalermoFacoltà di Medicina e Chirurgia Dipartimento di Oncologia Cattedra di Oncologia Medica Uos Terapie Oncologiche Innovative Prof. S. Palmeri Clinicalapproachto the patient MediterraneanSchoolofOncology Rome, March 6, 2010

  2. Whatismytumororigin?

  3. Unknown primary tumor “Despite the increasing array of sophisticated diagnostic tools, oncologists have struggled to understand a subset of pts with metastatic cancer in whom detailed investigations fail to identify a primary anatomic site (3-5%)”

  4. Unknown primary tumor:definition • Histologically confirmed metastatic cancer • Failing to identify the primary site after: • Detailed medical history • Complete physical examination (including breast and pelvic in women,testicular and prostate in men) • Full blood count and biochemistry, urinalysis and stool occult blood testing • Chest rx • Abdomen and pelvis CT • Mammography • Other (sign or symptom-guided!!)….but: • Not yet standardized (different diagnostic work up)!

  5. N=302 pz UnknownprimarytumorA clinicalstudyof 302 consecutive autopsiedpatients(Le Chevalier 1988)

  6. Unknown primary tumor: clinical and biological features • The most frequent primary tumors in CUP pts don’t include some of the most common neoplasms in the general pop, as breast and prostate • Early dissemination • Clinical absence of the primary tumor at diagnosis • Unpredictable metastatic pattern • Wide spectrum of signs and symptoms (> 50% of pts present with multiple sites of disease) • Aggressive behaviour • Life expectancy:6-9 mo

  7. Unknown primary tumor: main sites of disease Le Chevalier Kirsten Abbruzzese (n=302) (n=286) (n=657) Nodes 37% 14% 37% Lung 19% 16% 28% Bone 13% 16% 28% Liver 5% 19% 31% Pleura 2% 12% 12% Peritoneum 1% 6% 6% Brain 10% 8% 8% Skin 9% 1% 2% Adrenal gl 0 0 2%

  8. Unknown primary tumor: comparison of metastatic involvement of common sites with known primary carcinomas vs CUP Metastaticorgan site involvement (%)* *Ptspresentingwith CUP in whom the primary site wassubsequentlydiscovered Knownprimaries:2287, CUP in whomprimary site discovered:413

  9. Unknown primary tumor: the dilemma for the oncologist

  10. Unknown primary tumor: the dilemma for the oncologist Search? Rapidlytreat?

  11. Unknown primary tumor • More tailored therapy • Better knowledge about prognosis and natural history • The physician may believe to fail serving the patient adequately • The patient is reassured • The family is reassured Whysearch?

  12. Unknown primary tumor • Poorprognosis • Extensivediagnostic work-up maybeexpensive and not conclusive • < 20% of CUP ptshave a primary site oftheircanceridentifiedantemortem and in 15-30% ofcases the originremainocculteven at autopsy • Avoid long waitings • Risksfrom invasive diagnosticmodalities • The patientisreassured • The family isreassured Whyrapidlytreat?

  13. Unknownprimarytumor: clinicalapproachto the patient

  14. Unknown primary tumor The natural history is diverse and dependent on multiple variables: • Age • N. of metastatic sites • Dominant area of disease • Histology

  15. Unknown primary tumor evaluation of the patient

  16. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  17. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  18. Unknown primary tumor: evaluation of the patient History: • Critical !! • It can define areas of concerns (e.g. respiratory system in a smoker with a supraclavicular node,cough and hemoptysis) • History of previous biopsies or removed lesions or past spontaneously regressing lesions • Family history can be helpful (specific ethnic group, hereditary syndromes)

  19. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  20. Unknown primary tumor: evaluation of the patient Physical Examination: Should be rigorous Include careful palpation of the thyroid, breasts, nodes, liver, prostate DRE Genital examination  Aspects often overlooked in CUP patients  Can provide the probable diagnosis  Formulate a directed laboratory and radiographic evaluation

  21. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  22. Unknown primary tumor: evaluation of the patient Clinicalmanifestations: • Extremelyvaried • Symptoms and signssimilartothoseofptswithadvancedmalignanciesofknownorigin • The most common symptoms/signs at presentation: • generaldeterioration : 73% • digestive symptoms: 58% • liverenlargement: 58% • abdominalpain: 56% • respiratorysymptoms: 45% • ascites: 26% • nodeenlargement: 16%

  23. Unknown primary tumor

  24. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  25. Unknown primary tumor: evaluation of the patient Laboratorystudies: Complete bloodcellcount (anemia) Ironmetabolism (irondeficiencypossiblechronic GI blood loss) Urinalysis (microscopichematuria or proteinuria) Liverfunctionstudiesincluding HBV,HCV markers Tumormarkers (b-HCG, AFP, PSA, CEA, CA 125) ?

  26. Unknown primary tumor: tumor markers Young pts with mediastinal or retroperitoneal mass Extragonadal germ cell tumor αFP, βHCG ♀,adenoca,axillary nodes Breast CA 15-3,CEA ♀, ascitis ± pelvic mass Ovarian CA 125 ♂, multiple bone or lung mts Prostate PSA,PAP Pts with disseminated adenopaties Lymphomas β2microglobulin

  27. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  28. Unknown primary tumor:definition • Notstandardized (extentofevaluation) • Histologicallyconfirmedmetastaticcancer • Failingtoidentify the primary site after: • Detailedmedicalhistory • Complete physicalexamination (includingbreast and pelvic in women,testicular and prostate in men) • Full bloodcount and biochemistry, urinalysis and stooloccultbloodtesting • Chestrx • Abdomen and pelvis CT • Mammography • Other (sign or symptom-guided)

  29. Unknown primary tumor: evaluation of the patient Obiettivi: Pathologicevaluation: • Accurate pathologicassessmentisessential • The lesionis neoplastic and primary/metastatic • Light microscopy • Immunohistochemistry • Electron microscopy • Biological studies

  30. Unknown primary tumor: histology • Well-moderatelydifferentiatedadenoca 50% • Undifferentiated or poorlydifferentiatedca 30% • Squamouscellca 15% • Undifferentiatedneoplasms 5% (including neuroendocrine tumors, lymphomas, germcelltumors, melanomas, sarcomas and embryonalmalignancies)

  31. Unknown primary tumor: evaluation of the patient Pathologicevaluation: • Light microscopy (classify the tumorintobroadgroupssuchas carcinoma, sarcoma or lymphoma; nothelpful in 35% ofcases) • Immunohistochemistry (peroxidase-labeledAbagainst AFP,b-HCG, PSA, CK7, CK 20, TTF-1) • Electron microscopy (adenoca: microvilli and mucin,neuroendocrine tumors: secretorygranules, melanoma: premelanosomes) • Biologicalstudies(abnormalitiesofchrom 12 in germcelltumors, gene profiling, overexpressionof p53, bcl-2, Her-2/neu)

  32. Unknown primary tumor Close communication clinician  pathologist

  33. Unknown primary tumor: evaluation of the patient Obiettivi: • History • PhysicalExamination • Clinicalmanifestations • Laboratorystudies • Pathologicevaluation • Imaging

  34. Unknown primary tumor: evaluation of the patient Imaging: Initialradiographicstudies: chestx-ray and abdomen CT Abdomen CT :detection of the primary site in 30-35% Imaging or endoscopyof the upper and lower GI tractindicatedifabdominalcomplaints, ascites, livermetastases Mammography and MRI (in the settingofisolatedaxillaryadenopathy MRI very sensitive in detectingoccultprimary >75%) PET (occultprimaryH&Ncancers)

  35. History A 52-year-old patient with history of metastatic squamous cell cancer of left posterior cervical lymph node from unknown primary. PET Findings PET/CT localized the primary in the region of the left tonsil.

  36. Unknown primary tumor Integrationofvariousdiagnosticmodalities in CUP management Varadhachary, SeminOncol 2009

  37. Unknown primary tumor Recommended general approach  directed evaluation based upon clinical presentation and pathologic findings

  38. Unknownprimarytumor: main aims in the evaluation of the patient

  39. Unknown primary tumor: main aims in the evaluation of the patient Obiettivi: • Researchof the primarytumor • Evaluationof the extentofdisease • Rapididentificationofcurablepatientsubsets

  40. Unknown primary tumor:prognosis • Histology: -squamocellularca OS=6 mo - adenoca OS =8 mo - undifferentiated or poordifferentiatedca OS=19 mo - neuroendocrine ca betterprognosis OS=23 mo • T • N°ofinvolvedsites ( OS 1 site= 10 mo, 2 = 8 mo, 3 = 6 mo) • PS • N vs liver

  41. MD Anderson approachto the patientwithnewlydiagnosed carcinoma ofunknownprimary site Important treatable subsets and their management • Women with isolated axillaryadenopathy  Same as for stage II breast cancer • Present recommended management: axillary dissection, axillary RT, systemic CT, breast RT if MRI positive or suspicious • 10 y DFS=65% • Prognosis not as favorable in men with axillaryadenopathy only

  42. MD Anderson approachto the patientwithnewlydiagnosed carcinoma ofunknownprimary site Important treatable subsets and their management • Women with peritoneal carcinomatosis (papillary adenocarcinoma) • Same as for stage III ovarian cancer • Median survival=16 -24 mo

  43. MD Anderson approachto the patientwithnewlydiagnosed carcinoma ofunknownprimary site Important treatable subsets and their management • Extragonadal germ cell syndrome  Same as for nonseminomatous germ cell tumor

  44. MD Anderson approachto the patientwithnewlydiagnosed carcinoma ofunknownprimary site Important treatable subsets and their management • Neuroendocrine carcinoma • Same as for carcinoid/pancreatic islet cell carcinoma; • cisplatin-based CT for poorly differentiated neuroendocrine tumors

  45. MD Anderson approachto the patientwithnewlydiagnosed carcinoma ofunknownprimary site Important treatable subsets and their management • High- and mid-cervical adenopathy (squamous cell carcinoma) • Surgical resection of palpable disease + curative RT to the neck • 30-50% 5-y survival rates

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