Mesotelioma Maligno INTERVENTIONAL DIAGNOSTICS · Mesotelioma Pleurico Maligno INTERVENTIONAL DIAGNOSTICS FRANCESCO FACCIOLO Department of Surgical Oncology Division of Thoracic Surgery

NEOPLASIE TORACICHEPOST‐IASLC: UPDATES DA SIDNEY

Lucca, 27‐28 Novembre 2013

Mesotelioma Pleurico Maligno

INTERVENTIONAL DIAGNOSTICSINTERVENTIONAL DIAGNOSTICS

FRANCESCO FACCIOLODepartment of Surgical Oncology

Division of Thoracic SurgeryNational Cancer Institute “Regina Elena”, Rome

MPM/ INTERVENTIONAL DIAGNOSTICS

WHAT IS THE GOAL?WHAT IS THE GOAL?

MPM/INTERVENTIONAL DIAGNOSTICS

• TO ADDRESS THE APPROPRIATE TREATMENT• TO ADDRESS THE APPROPRIATE TREATMENT

– SECURE / ACCURATE ANATOMOPATHOLOGICAL DIAGNOSIS

– STAGING / ASSESSMENT OF SURGICAL INDICATIONSS G G / SS SS O SU G C C O S

– COLLECTION OF ADEQUATE BIOLOGICAL TISSUE


WHAT ARE THE INSTRUMENTS?WHAT ARE THE INSTRUMENTS?

MPM/INTERVENTIONAL DIAGNOSTICS

• STAGING / COLLECTION OF BIOLOGICAL TISSUE

– MEDIASTINAL NODES/ EBUS; EUS; CERVICAL MEDIASTINOSCOPY; EXTENDED MEDIASTINOSCOPY; ANTERIOR MEDIASTINOTOMY

– PLEURAE/ VATS; EXTRAPLEURAL MINITHORACOTOMY U / S; U O CO O(BIOPSIES)

PERITONEAL CAVITY/ LAPAROSCOPY; PERITONEAL– PERITONEAL CAVITY/ LAPAROSCOPY; PERITONEAL LAVAGE AND CYTOLOGY


WHAT ARE THE RULES?WHAT ARE THE RULES?


UPDATED GUIDELINES FOR PATHOLOGICAL DIAGNOSIS OF MPM FROM IMIG (EXCERPT)DIAGNOSIS OF MPM FROM IMIG (EXCERPT):

•ADEQUATE BIOPSIES/ LESS COMMONLY: CYTOLOGY, EXFOLIATIVE AND FNA

•CYTOLOGY/ ADEQUATE FLUID AMOUNT FOR CELL-BLOCKS OR SMEARS

•MORPHOLOGIC FEATURES AND NUCLEAR GRADE TO PREDICT SURVIVAL/ CYTOLOGIC DIAGNOSIS OF “MPM EPITHELIOID TYPE”SURVIVAL/ CYTOLOGIC DIAGNOSIS OF “MPM EPITHELIOID TYPE” MIGHT BE NOT SUFFICIENT IN THE FUTURE

APART FROM DIAGNOSTIC DIFFICULTIES/ THE FREQUENT•APART FROM DIAGNOSTIC DIFFICULTIES/ THE FREQUENT PRACTICE OF LITIGATION IN CASES OF MM MAKES PATHOLOGISTS RELUCTANT TO DIAGNOSE MESOTHELIOMA WITHOUT HISTOLOGIC CONFIRMATORY EVIDENCEWITHOUT HISTOLOGIC CONFIRMATORY EVIDENCE

HUSAIN AN ET AL. - ARCH PATHOL LAB MED 2012


VATS – MINITHORACOTOMY/ INDICATIONS

•VATS/ PROCEDURE OF CHOICE WHEN POSSIBLE; DIRECT INSPECTION; MULTIPLE BIOPSIES MULTIPLE SITES; PALLIATIONINSPECTION; MULTIPLE BIOPSIES, MULTIPLE SITES; PALLIATION

•EXTRAPLEURAL MINITHORACOTOMY/ OBLITERATION OF THE PLEURAL SPACE; CONTRAINDICATION TO GENERAL ANESTHESIA;PLEURAL SPACE; CONTRAINDICATION TO GENERAL ANESTHESIA; PREDETERMINED INOPERABILITY


IS THERE ANYTHING MORE TO SAY?


THOROUGH INVASIVE ASSESSMENT – 1/ EVIDENCE FOR

•NODAL STATUS – 1/ BETTER PROGNOSIS FOR N0 COMPARED TO N+ EXCLUSION OF N3 DISEASETO N+; EXCLUSION OF N3 DISEASE

•NODAL STATUS – 2/ EBUS AND EUS MAY YIELD UP TO 36%NODAL STATUS 2/ EBUS AND EUS MAY YIELD UP TO 36% MORE POSITIVE NODES IN CLINICAL N0 DISEASE

•PERITONEAL DISEASE/ UP TO 44% OF POSITIVE PERITONEAL LAVAGE REPORTED IN EXTENDED PREOPERATIVE ASSESSMENT PROTOCOLS


THOROUGH INVASIVE ASSESSMENT – 2/ CONCERNS

•NODAL STATUS – 1/ N+ BEHAVIOUR IN MPM DIFFERS FROM NSCLC:HOW TO INTERPRET POSITIVE RESULTS FROM MEDIASTINAL ASSESSMENT?

•NODAL STATUS – 2/ EBUS AND EUS RESULTS RELY ON NEEDLE ASPIRATION CYTOLOGY: NOT TO BE USED TO ACHIEVE AN INITIAL DIAGNOSIS OF MPM SHOULD BE PRECEDED BYINITIAL DIAGNOSIS OF MPM – SHOULD BE PRECEDED BY PLEURAL BIOPSIES

•NODAL STATUS – 3/ NEGATIVE EBUS AND EUS SHOULD BE FOLLOWED BY INVASIVE MEDIASTINAL ASSESSMENT

•PERITONEAL ASSESSMENT/ PATIENT’S COMPLIANCE??


SURGICAL CONSIDERATIONS – VATS/ 1

•ASSESSMENT OF OPERABILITY/ CARDIOPHRENIC ANGLE; PERICARDIAL INVOLVEMENT; MEDIASTINAL INFILTRATIONPERICARDIAL INVOLVEMENT; MEDIASTINAL INFILTRATION

•PLEURAL TALCAGE/ PRELIMINARY TO MAJOR SURGERY; RESOLUTION OF SYMPTOMSRESOLUTION OF SYMPTOMS

•PLEURAL BIOPSIES/ RESPECT ENDOTHORACIC FASCIA; MULTIPLE SITES ADEQUATE HISTOLOGIC SPECIMENSMULTIPLE SITES; ADEQUATE HISTOLOGIC SPECIMENS


SURGICAL CONSIDERATIONS – VATS/ 2

•VATS/ SHOULD BE PREFERABLY PERFORMED BY THE SAME SURGEON UNDERTAKING MAJOR SURGERY (WHEN NOTSURGEON UNDERTAKING MAJOR SURGERY (WHEN NOT EXCLUDED)

VATS/ THORACOPORTS ACCESSES SHOULD LIE ON THE LINE OF•VATS/ THORACOPORTS ACCESSES SHOULD LIE ON THE LINE OF FUTURE THORACOTOMY


FUTURE DIRECTIONS?


NEW PERSPECTIVES

•SURGERY IS NO MORE JUST A MATTER OF SURGERY – 1/INTERVENTIONAL DIAGNOSIS NEEDED TO OBTAIN ADEQUATE TISSUE FOR MOLECULAR ANALYSESTISSUE FOR MOLECULAR ANALYSES

•SURGERY IS NO MORE JUST A MATTER OF SURGERY – 2/ IN VITRO COLTURES OF NEOPLASTIC CELLS USEFUL TO PREDICTVITRO COLTURES OF NEOPLASTIC CELLS USEFUL TO PREDICT CHEMOSENSITIVITY*

SURGERY IS NO MORE JUST A MATTER OF SURGERY 3/ IN•SURGERY IS NO MORE JUST A MATTER OF SURGERY – 3/ IN VITRO COLTURES OF NEOPLASTIC STEM CELLS

•SURGERY IS NO MORE JUST A MATTER OF SURGERY – 4/ NEW TRENDS IN TRANSLATIONAL RESEARCH: IDENTIFICATION OF NEW GENOMIC MARKERS ISOLATED FROM THE PRIMARY TUMOR THAT CAN BE FOUND IN PERIPHERAL BLOOD

* our experience reported in Canino C, et al. Oncogene 2011


HARD TIMES?


WALLS SHRINKING?

•RECENT TRENDS IN LITERATURE/ WILLING TO REDUCE THE FIELD OF INDICATIONS FOR RADICAL SURGERY IN MPM (ESPECIALLY FOROF INDICATIONS FOR RADICAL SURGERY IN MPM (ESPECIALLY FOR EPP) – M.A.R.S., M.A.R.S. 2 AND OTHER RECENTS SERIES (E.G.: LANDZUDSKY’S)

•CHAIN EFFECT/ THESE WORKS ARE DESTINED TO AFFECT THE INDICATIONS TO INTERVENTIONAL DIAGNOSTICS AS WELL

•WHAT SHOULD BE THE SURGEON’S ATTITUDE TOWARDS PATIENTS WITH MPM?/ PROPOSING A HEAVY BURDEN OF INVASIVE DIAGNOSTICS BUT EXCLUDING MAJOR SURGERY?


DIAGNOSTIC PATH

resulting therapeutic options


MORE SURGERY! LESS SURGERY!MORE SURGERY!

•HISTOLOGIC DIAGNOSISMORE TISSUE!

LESS SURGERY!

•EPPPOSSIBLY HARMFUL!MORE TISSUE!

•DETERMINATION OF SUBTYPESMORE TISSUE!

POSSIBLY HARMFUL!

•EXTENDED P/DMAYBE NOT RADICAL!MORE TISSUE!

•MOLECULAR ANALYSESMORE TISSUE!

MAYBE NOT RADICAL!

•MAJORITY OF SUBTYPESMAYBE NOT AFFECTED BYMORE TISSUE!

•STAGINGMULTIPLE BIOPSIES,

MAYBE NOT AFFECTED BY SURGERY!

•LEGAL LITIGATIONS!,DIRECT EXPLORATION,

MEDIASTINAL ASSESSMENT!


WHAT TO DO?


CONCLUSIONS/ 1

•INVASIVE DIAGNOSTICS/ ARE MANDATORY IN A DISEASE AS COMPLEX AS MALIGNANT PLEURAL MESOTHELIOMACOMPLEX AS MALIGNANT PLEURAL MESOTHELIOMA

•COST-BENEFIT EVALUATION/ MUST BE MADE BETWEEN DIAGNOSTIC AGGRESSIVENESS AND INTENSITY OF FOLLOWINGDIAGNOSTIC AGGRESSIVENESS AND INTENSITY OF FOLLOWING TREATMENT

NEW PERSPECTIVES/ RELY ON WIDE AVALAIBILITY OF•NEW PERSPECTIVES/ RELY ON WIDE AVALAIBILITY OF BIOLOGICAL SAMPLES, THUS INVOLVING SURGEONS, RATHER THAN SUPERSEDING THEM


CONCLUSIONS/ 2

•SURGERY FOR MPM/DEFINITIVE POSITIONS ON MAJOR SURGERY (EPP) SHOULD BE TAKEN CAUTIOUSLY: MORE ACCURATE (= INVASIVE?) DIAGNOSTICS SHOULD LEAD TO MORE ACCURATE PATIENTS’ SELECTION, RATHER THAN TO EXCLUSION OF SURGERY.

•KEYWORDS TO MAJOR SURGERY FOR MPM/•KEYWORDS TO MAJOR SURGERY FOR MPM/• SELECTION• SELECTION• SELECTION

AND…• SELECTION


THANK YOUTHANK YOU

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Mesotelioma Maligno INTERVENTIONAL DIAGNOSTICS · Mesotelioma Pleurico Maligno INTERVENTIONAL DIAGNOSTICS FRANCESCO FACCIOLO Department of Surgical Oncology Division of Thoracic Surgery