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Positron Emission Tomography In Oncology

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  • 1. POSITRON EMISSION TOMOGRAPHY IN ONCOLOGY F De Winter, C Van de Wiele, RA Dierckx Ghent University and University Hospital, Belgium
  • 2. POSITRON EMISSION TOMOGRAHY
    • PET technique : ‘a diagnostic method that creates high resolution, 3 dimensional tomographic images of the quantitative distribution of positron emitting radionuclides in the human body’
    • PET imaging : functional (<=> anatomical) indexes of blood flow, glucose metabolism, amino acid transport, protein metabolism, neuroreceptor status, oxygen consumption or even cell division…
    • Oncology : F-18 FDG, C-11 methionine, C-11 thymidine, C-11 tyrosine, etc….
  • 3. NUCLEAR MEDICINE : DIAGNOSIS
    • Conventional :
    • planar, wholebody,SPECT,..
    • single photon emitters :
    • Tc-99m, I-123
    • PET versus SPE(C)T
    • quantitation
    • sens & resolution +++
    • dual photon emitters :
    • C-11, N-13, O-15
        • F-18 FDG
  • 4. Radiopharmaceutical (eg FDG) electron 511 keV gamma ray 511 keV gamma ray positron positron + electron = 2 * 511 Kev (180°)
  • 5. BABY CYCLOTRON
  • 6. POSITRON EMISSION TOMOGRAHY SYSTEM
  • 7. 18 FLUORINE BONE PET
  • 8. 18 FLUORO DEOXYGLUCOSE (FDG)
  • 9. FDG UPTAKE MECHANISM
  • 10. NORMAL FDG PET SCAN
  • 11.  
  • 12. REIMBURSEMENT FOR FDG PET IN BELGIUM
    • Before July 1999 :
      • evaluation of myocardial viability before revascularisation
      • evaluation of suspected epileptogenic foci in refractory epilepsy
      • differentiation of tumour and radiation necrosis in brain tumours
    • After July 1999 :
      • new indications in oncology reimbursed
      • 13 PET centres allowed
  • 13. REIMBURSEMENT FOR FDG PET
    • A) SUSPICION OF LOCOREGIONAL RELAPSE = RESTAGING
    • 1) BRAIN TUMOUR
    • 2) BUCCAL OR PHARYNGEAL TUMOUR
    When other imaging modalities are not conclusive...
  • 14. REIMBURSEMENT FOR FDG PET
    • B ) SUSPICION OF RELAPSE = RESTAGING
    • a) LYMPHOMA
    • b) OVARIUM CARCINOMA
    • c) COLORECTAL TUMOUR
    When other imaging modalities are not conclusive...
  • 15. REIMBURSEMENT FOR FDG PET
    • C ) WHEN DECISION OF SURGERY MIGHT BE ALTERED IN THE WORKOUT = STAGING
    • a) LUNG TUMOUR
    • b) MALIGNANT MELANOMA
    • c) PANCREATIC TUMOUR
  • 16.  
  • 17. LOCOREGIONAL RESTAGING : BRAIN TUMOR RECURRENCE
    • PET :
      • FDG
      • Amino acid analogues
    • SPECT alternatives :
      • Thallium-201 :”potassium analogue”
      • Sesta MIBI : “mitochondrial activity”
      • Alfa methyltyrosine : aminoacid analogue
          • Low grade astrocytomas
  • 18.  
  • 19. LOCOREGIONAL RESTAGING : HEAD AND NECK CANCER
  • 20. POSSIBLE PET INDICATIONS FOR HEAD AND NECK CANCER
    • I STAGING OF THE NECK
    • II DIAGNOSIS OF RECURRENCE
    • III EVALUATION OF TREATMENT
    • IV EVALUATION OF CUP- SYNDROME
  • 21. HEAD AND NECK CANCER
    • 5% of all carcinomas world-wide (increasing)
      • vast majority squamous cell carcinoma
      • 40% early stage at diagnosis
      • problem of subclinical disease
    • LN involvement most important prognostic factor
      • N0: 5year survival > 50%
      • N+: 5year survival < 30%
    • Therapy
      • Early stages (40%): surgery or RT alone.
      • Late stages (60%) : surgery and (chemo)RT
  • 22. HEAD AND NECK CANCER : II LOCAL RECURRENCE
    • Incidence :
      • up to 50 % => initiation of salvage therapy
    • Diagnosis
        • clinical
            • delayed mucosal healing
            • persistent wound infection
        • CT, MRI
            • edema and / or fibrosis
            • haematoma
          • DD : post-therapeutic changes
        • FNA
            •  FN, morbidity
  • 23. HEAD AND NECK CANCER : LOCAL RECURRENCE
      • n sens spec
    • Lapela, 1995 15 PET 88 % 86 %
    • Anzai, 1995 12 PET 88 %/ 25% MRI-CT 100 %/ 75 %
    • Fishbein *, 1998 35 PET 100 % 64 %
    • Collins, 1998 37 PET 94 % 88 %
    • Farber, 1999 28 PET 86 % 93 %
    • Lapela, 2000 56 PET 84-95 % 84-93 %
    • * gold standard : > 6 M follow-up
  • 24. HEAD AND NECK CANCER CLINICAL STUDY
    • 44-year-old woman treated for carcinoma in the left retromolar trigonum; CT showed post-radiation necrosis;
    • routine PET suggestive for relapse: confirmed by surgery
  • 25. HEAD AND NECK CANCER CLINICAL STUDY
    • 57-year-old man with larynxca irradiated 18 months earlier;
    • Clinic and CT : left cervical, submental and submandibular nodes
    • PET : confirmation + supraclavicular and lung lesions.
    • RX thorax normal; lung metastases confirmed by CT
  • 26.  
  • 27. RESTAGING OF LYMPHOMA
    • High percentage of relapse
    • CT : 64% pts persistent abnormalities after completion of chemotherapy
    • Gallium-67 :
      • Sens for high grade of 85 %, for low grade of 60 %
      • Limitations = abdomen, resolution, scan after 24 hrs, dosimetry
    • In 9 studies using FDG PET in 192 pts sens of 80-100 % (Romer and Shwaiger, 1998)
      • PET and CT = in 89%
      • PET > CT in 10%
      • PET < CT in 1%
  • 28. RESTAGING OF LYMPHOMA
    • PET versus CT post Rx for detection of residual disease in 34 (17 NHL; 17 HD) patients undergoing RT and chemo (De Wit et al, Ann. Oncol 1997). Similar results Mikhaeel et al, Ann Oncol 2000, n 32
    • Caveats
    • diffusely increased uptake in bone marrow may be due to chemotherapy
    • in immunodepressed pts infections may mimic residual tumor
  • 29. LYMPHOMA
    • At present the data suggests FDG PET is superior to CT (and Ga-67) in:
      • detection of residual disease
      • detection of relapse
    • Data are forthcoming on the value of FDG PET relative to CT for
      • staging (Shah et al, Brit J Radiol 2000; n 29, 12 HD, 17 NHL : change in management in 34 %)
      • p redicting response and monitoring therapy
  • 30.  
  • 31. RESTAGING OF OVARIUM CARCINOMA
    • Limited (and less convincing) data in mixed populations
    • Romer et al, ROFO 1997; n 19 : sens of 83 %; spec of 54 %
    • Zimny et al; Nuklearmedizin 1997; n 26 : “PET is of limited value in the dd between ovarium ca and inflammatory processes”
    • Grab et al, Gynecol Oncol 2000; n 101 adnexal masses, 12 ovarian cancers : “negative MRI or PET results do not rule out early stage ovarian cancer”
    • Kubik-Huch et al, Eur Radiol 2000; n 19 : no significant difference between CT, MRI and PET for lesion characterization or detection of recurrent disease
  • 32.  
  • 33. COLORECTAL CARCINOMA : RESTAGING
    • 15 % of malignant tumors
        • 70 % operable  1/3 recurrence
    • CT/MRI : DD posttherapeutic changes
        • edema
        • fibrosis (scar)
    • For PET reimbursement no CEA criteria
  • 34. COLORECTAL CARCINOMA : RESTAGING
    • Patient based 18-FDG PET results
    • Authors n(pts) n(sites) Sens Spec
    • Schiepers, 1995 76 94 % 98 %
    • Pounds, 1995 33 47 96 % 87 %
    • Daenen, 1996 19 29 95 % 67 %
    • Ogunbiyi, 1997 58 96 % 86 %
    • Delbeke, 1998 52 166 92 % 92 %
    • TOTAL 238 94 % 87 %
  • 35. COLORECTAL CARCINOMA : RESTAGING
    • 18-FDG PET results, local pelvic recurrence
    • Authors n sens spec accur
    • Schiepers, 1995
            • 76, PET 93 % 97 % 95 %
            • CT 60 % 72 % 65 %
    • Hustinx, 1998
            • 27 PET 90 % 71 % 85 %
            • CT 85 % 60 % 80 %
    • Ogunbiyi, 1997
            • 47 PET 91 % 100 % 95 %
            • CT 52 % 80 % 70 %
            • MRI 64 % 75 % 65 %
    • Ito,, 1996
            • 37 PET 100 % 100 % 100 %
    • Keogan, 1997 ,
            • 18 PET 92 % 80 % 89 %
  • 36.  
  • 37.  
  • 38. STAGING OF LUNG CARCINOMA
    • I SOLITARY PULMONARY NODULE
    • II MEDIASTINAL STAGING IN NSCLC
    • III DISTANT METASTASIS
  • 39. LUNG CARCINOMA : I SOLITARY PULMONARY NODULE DIFFERENTIAL DIAGNOSIS
    • malignant tumours : lung, lymphoma, metastasis…
    • benign tumours : hamartoma, lipoma
    • infectious : abscess, tuberculoma…
    • vasculitis : RA, sarcoidosis…
    • congenital : bronchogenic cyst
    • various : hematoma, infarct…
  • 40. SOLITARY PULMONARY NODULE
    • Belgium: ± 5000 new cases/yr
      • 50-60% of SPN are benign (Khouri et al, 1987)
      • 20-40% of resected nodules are benign (Midthun et al, 1992)
    • Few CT criteria for diagnosis (Quint et al, 1995)
      • Detection of benign pattern of calcification
      • Stability of the nodule over the last 2 years
      • Size < 20 mm 80% benign; > 40 mm always malignant (Vaylet, 1999)
  • 41. SOLITARY PULMONARY NODULE gold standard histology
    • Authors n sensitivity specificity
    • Patz, 1993 51 89 % 100 %
    • Dewan, 1993 30 95 % 80 %
    • Wahl, 1994 23 100 % 100 %
    • Lowe, 1994 88 97 % 88 %
    • Dewan, 1995 35 100 % 78 %
    • Duhaylonso,1996 87 97 % 82 %
    • Gupta, 1996 61 93 % 88 %
    • Bury, 1996 103 98 % 95 %
    • Lowe, 1998 89 92 % 90 %
  • 42. SOLITARY PULMONARY NODULE
    • FDG PET:
      • high sensitivity of ± 96% and specificity of ± 90% for malignancy ;
      • depending on local prevalence of known causes of FP (aspergillosis, tuberculosis…)
    • PET versus CT + TTNA
      • PPV of 94 % for PET versus 86 % for CT + TTNA (Dewan et al, Chest 1995 on 35 pts)
      • TTNA: high complication rate (pneumothorax, hemoptoe)
    • FDG PET gives additional information on N and M stage (> 50% M+ at diagnosis)
  • 43. DIFFERENTIAL DIAGNOSIS OF SOLITARY PULMONARY NODULES
  • 44. SOLITARY PULMONARY NODULES: CONCLUSIONS (Rigo et al)
    • FDG PET for 15 mm < SPN < 40 mm
    • negative => wait and see
      • clinical-radiological follow-up >1 yr
      • no histologic confirmation necessary
    • positive => invasive exploration
  • 45. LUNG CANCER
        • small cell lung cancer (oat cell): 20%
        • non small cell lung cancer: 80%
          • epidermoid carcinoma: 50%
          • adenocarcinoma / bronchioloalveolair ca: 10% / 3%
          • large cell carcinoma: 18%
    Therapy/prognosis depends on TNM stage
  • 46. LUNG CANCER : II&III STAGING OF NSCLC
        • RX thorax, CT-thorax
        • fiber-bronchoscopy and biopsy
          • 90% + if central ca
          • 25-35% failure if small and peripheral ca
        • TTNA and mediastinoscopy
        • blood sample:
          • liver tests, CEA, NSE, cortisol, AP, calcium,…
        • CT-brain
        • ultrasound or CT abdomen: liver? adrenals?
        • bone scan
  • 47. STAGING OF NSCLC : N STAGING
  • 48. STAGING OF NSCLC
    • Mediastinoscopy invasive and expensive with sensitivity of (only) 87% ...
    • Majority of pts with intended curative resection ultimately die of metastatic disease (usually within 2 yrs): understaging…
    • Are non invasive techniques capable of screening equally well or better for N2N3 disease?
    • Or can they identify patients with M+ better?
  • 49. NSCLC MEDIASTINAL STAGING
    • Authors n sens spec
    • Wahl, 1994
            • 12 PET 82 % 81 %
            • CT 64 % 44 %
    • Scott, 1994
            • 25 PET 66 % 86 %
    • Bury, 1995
            • 20 PET 90 % 80 %
            • CT 63 % 66 %
    • Chin, 1995
            • 30 PET 78 % 81 %
            • CT 56 % 87 %
    • Sasaki, 1996
            • 29 PET 76 % 98 %
            • CT 65 % 87 %
    • Bury, 1997
            • 109 PET 100% 94 %
    • Erasmus, 1997
            • 27 PET 100% 80 %
    • Vansteenkiste, 1997
            • 50 PET (-CT) 67 % 97 %
            • PET (+ CT)93 % 97 %
            • CT 67 % 59 %
  • 50. STAGING OF NSCLC : N STAGING Van Steenkiste et al, Chest, 1997
  • 51. STAGING OF NSCLC : N STAGING
    • 68 yr old man with hemoptoe
    • CT : left upper lobe nodule and enlarged LN in the homo- and heterolateral mediastinum (N3)
    FDG-PET : high uptake in primary tumour but no focal abnormality in the mediastinum
  • 52. STAGING OF NSCLC : M STAGING
        • Bone: whole body FDG-PET vs bone scan (EJNM 1998)
          • equal sensitivity of 90%
          • specificity of 98% versus 61%
        • Liver: FDG-PET vs CT :
          • sensitivity of 97% vs 93% and
          • specificity of 88% vs 75% (Ann Oncol 1998)
        • Adrenals: ( Am J Roentg, 1997)
          • up to 60% of detected masses are nonmalignant
          • biopsy is often required after CT or MRI
          • PET sensitivity of 100 % and specificity of 80%
  • 53. STAGING OF NSCLC : CONCLUSIONS
        • PET negative (very high NPV) => thoracotomy
          • mediastinoscopy could be omitted in up to 74% of patients eligible for surgery
        • PET N + => confirmation mediastinoscopy
          • no potentially curable patients are withdrawn from surgery
          • PET only incidentally false negative in minimal N2 disease (stage IIIA)
        • Whole body PET for detection of distant metastasis : very high NPV
  • 54.  
  • 55. STAGING MALIGNANT MELANOMA
    • High sensitivity for superficial LN and visceral lesions
      • Ideal for follow-up of pts with high risk of recurrence or metastasis, in combination with CT for brain and lungs
    • Lower sensitivity for
      • Pulmonary lesions
      • Small skin lesions
      • Miliary involvement of larger organs
      • Brain metastasis (contrast)
      • Tumor sites with important necrosis
  • 56.  
  • 57. STAGING PANCREAS TUMOR
    • Differential diagnosis between malignancy and chronic pancreatitis : increases diagnostic accuracy as compared to CT and ERCP
      • Sens of 88 % and spec of 88 % (Keogan et al, Am J Roentgenol 1998 : n 37)
      • Problem acute pancreatitis (Shreve, EJNM 1998)
    • Detection of metastasis :
      • for hepatic metastasis sens of 70 % and spec of 95 %
      • for LN staging sens of 49 % and spec of 63 %
      • missing metastasis < 1 cm or poorly localized peritoneal metastatic spread
      • ( Diederichs et al, Pancreas 2000 : n 159 pts : 89 malignant, 70 benign)
  • 58.  
  • 59. FDG PET: PRACTICALITIES
    • Low glycemia
      • Sober > 4 hours , no caloric drinks or glucose infusion
    • - overnight fasting for morning scan
    • - light breakfast if afternoon scanning
      • No glucose containing drinks
      • In diabetics : optimal metabolic control : insulin?
    • Good hydration :
      • 0.5 l H2O extra + 20 mg furosemide iv
      • background activity + radiation
    • Muscle relaxation :
      • 5-10 mg diazepam po
  • 60. FDG PET: PRACTICALITIES
    • Complementary anatomical information (CT, MRI) for exact localization of hot spots (N2?N3?; rib vs pleura?)
    • Information about
      • recent/concurrent surgery (min 3 months),
      • chemotherapy (before third cycle)
      • radiotherapy (3-4 months)
      • medication that stimulates bone marrow (growth factors)
    • Bladder catheterisation may be warranted for evaluation of pelvic tumours close to the bladder
    • Total time: 2 hours
  • 61.  
  • 62. TOWARDS …
    • N ew indications for the same tumors
      • diagnosis, (re)staging of NSLC, colorectal, lymphoma, malignant melanoma
      • therapy monitoring early after start chemotherapy
    • => early switch to second line therapy
    • 2) New tumours
      • uterusca, germ cell tumours, osteosarcoma,
      • cfr USA : oesophagusca, breastca…
    • 3) New technology : new detectors, coregistration, etc
    • 4) New tracers : fluorine chemistry, …
  • 63. IMAGE FUSION : PET + CT
  • 64. IMAGE FUSION
  • 65.  
  • 66. BREAST CARCINOMA
    • PET potential
      • T DD benign vs. malignant
      • N axillary lymph node evaluation
      • M distant metastases evaluation
      • Therapy monitoring
    • T : DD benign vs. malignant
      • radiodense breasts
      • young, hormone replacement, augmentation
      • occult primary lesion (N+)
      • multicentric and multifocal disease
  • 67. BREAST CARCINOMA, T
    • Authors (n pts / benign/malignant) sens% spec%
    • Tse, 1992 14 (4/10) 80% 100 %
    • Adler, 1993 35 (8/27) 96 % 100 %
    • Hoh, 1993 20 (3/17) 88 % 33 %
    • Dehdrasti, 1995 22 (8/24) 88 % 100 %
    • Avril, 1996 72 (31/41) 92 % 97 %
    • Scheidhauer, 1996 30 (7/23) 91 % 86 %
  • 68. BREAST CARCINOMA
    • N STAGING
      • for therapeutic implication & prognostic value
    • Presently axillary dissection
      • high cost & moderate morbidity
    • => an imaging test that could accurately determine the extent of disease at initial presentation would be of great value
  • 69. BREAST CARCINOMA, N axillary
    • Authors n sens % spec %
    • Wahl, 1991 7 100 % N/A
    • Tse, 1992 10 57 % 100 %
    • Adler, 1993 20 90 % 100 %
    • Hoh, 1993 14 67 % 100 %
    • Nieweg, 1993 5 100 % N/A
    • Multi-center, 1993 49 96 % 96 %
    • Avril, 1996 51 79 % 96 %
    • Scheidhauer, 1996 18 100 % 89 %
    • Utech, 1996 124 100 % 75 %
  • 70. BREAST CARCINOMA
    • M+
      • overall sensitivity > 85 %
      • positive predictive value 94 %
    • Therapy response
      • 18 FDG decrease following therapy antedates a decrement in tumor size by 1.5-2 months
            • Wahl et al., 1993 , J Clin Oncol, n = 11
            • Minn et al., 1989 , Eur J Nucl Med, n = 10
  • 71. BREAST CARCINOMA : DIAGNOSIS
  • 72. BREAST CARCINOMA : NODAL STAGING
  • 73. BREAST CARCINOMA : METASTASIS ? Bone scan suspicious; MRI doubtful; PET neg (TN)
  • 74. HEAD AND NECK CANCER : I STAGING
    • Accurate diagnosis of the nodal status of the neck is extremely important for treatment planning and prognosis
      • N-stage dependent on localisation & extent of primary tumour
      • Clinical staging 15-50% FN as compared to CT/MRI (Curtin et al, Radiology 1998)
    • CT NPV 84%, PPV 50%; MRI NPV 79%, PPV 52%
      • CT/MRI criteria based on LN volume and inhomogeneity problematic : reactive enlargement vs tumour-infiltrated LN
      • quid N0 studies ?
    • PET high sens & spec for detecting malignant tissue (primary tumour, LN, second tumour, metastasis)
      • FP : inflammation
      • FN : micrometastases, resolution
  • 75. N STAGING: COMPARISON OF FDG PET WITH CONVENTIONAL STAGING
    • Sens. Spec .
    • Braams, 1995, n = 60
            • PET 91 % 88 %
            • NMR 36 % 94 %
    • Lauderbacher , 1995, n = 22
            • PET 90 % 96 %
            • NMR 78 % 71 %
    • Myers , 1998, n = 14
            • PET 78 % 100 %
            • CT 57 % 90 %
    • Adams , 1998, n = 60
            • PET 90 % 94 %
            • CT 82 % 85 %
            • NMR 80 % 85 %
            • US 72 % 79 %
    • Myers , 1998, n = 12
            • PET 100 % 100 %
            • CT 40 % 88 %
  • 76. HEAD AND NECK CANCER
    • III EVALUATION OF TREATMENT
      • PET becomes negative when tumour response is achieved <=> anatomical imaging (necrosis, fibrosis)
      • Early postradiation PET can be FN: waiting for 3-4 months is advised (Rege et al., 1993)
      • No such delay period is warranted after chemotherapy => early adaptation of therapy possible (Haberkorn et al, 1993)
    • IV EVALUATION OF CUP SYNDROME
      • PET useful in detecting occult primary tumours in 30-50 % when anatomic imaging methods are negative ( Kole et al., Cancer 1998; Aasar et al., Radiology 1999; Lassen et al, Eur J Cancer 1999; Safa et al, Cancer J Sci Am 1999)
      • Comparative studies needed
  • 77.  
  • 78. HEAD AND NECK CANCER CLINICAL STUDY
    • 50 year old woman with left palpable neck mass
    • Palpable mass of the tongue found (+ on MRI and PET)
    • 2 LN both positive on MRI and PET
  • 79. IMPORTANCE OF METABOLIC PREPARATION