Using PET in Malignant Melanoma Place your logo here

Oncology Imaging Computed Tomography (CT) Photon attenuation Anatomy Magnetic Resonance (MR) Spin flip time Anatomy (blood flow) Ultrasound (US) Sound attenuation Anatomy Conventional Nuclear Radioactive tracer Function Medicine (NM) uptake Positron Emission Radioactive tracer Function Tomography (PET) uptake Function

18F-FDG Pharmacokinetics Plasma Cell Glucose FDG Glucose-6-P FDG-6-P FDG participates in the first step of glucose metabolism, but cannot be further metabolized and is trapped inside the cell where it is retained in proportion to the rate of glycolosis.

Normal distribution pattern of 18F-FDG After IV injection, FDG is distributed to all organs of the body in proportion to cellular glucose metabolism. Normal biodistribution will demonstrate uptake in the brain, evidence of excretion via the urinary and GI systems, faint hepatic uptake, some bone & soft tissue uptake, and variable cardiac uptake Cancer cells are highly metabolic and utilize glucose at 3-5x the rate of normal cells.

Oncology Imaging Clinical Applications of PET Characterization of radiographic abnormalities Detection of radiographically occult lesions Staging – initial evaluation of the extent of disease Restaging - evaluation of the extent of recurrent disease (resectability) Evaluation of response to therapy 3

Characterization of Radiographic Abnormalities 66 yr old w/ ovarian cancer & brain mets treated w/stereotactic radiosurgery & chemotherapy; developed right hemiplegia 2 wks prior to PET. Treated w/steroids, symptoms resolved. A new mass or nodule is identified by conventional imaging (x-ray, CT, MRI, US) and the physician needs to determine what it is.

Characterization of Radiographic Abnormalities 61 year old woman with ovarian cancer and brain metastases treated with whole brain and stereotactic radiation

Characterization of Radiographic Abnormalities 66 year old man with pancoast tumor of the right lung – new adrenal mass. CT shows enlargement of the right adrenal gland, adenoma vs metastasis.

Accuracy of PET in characterizing adrenal masses Differentiation of Benign from Malignant Adrenal Masses Sensitivity Specificity Yun 2001 100% (18/18) 94% (30/32) J Nucl Med 2001;42:1795 Erasmus 1997 100% (23/23) 80% (8/10) Am J Roentgenol 1997;168:1361 Maurea 1996 100% (7/7) 100% (6/6) Radiol Med 1996;92:782 Boland 1995 100% (14/14) 100% (10/10) Radiology 1995;194:131 3

Detection of a radiographically occult lesion 61 yr old man s/p partial colectomy for sigmoid cancer, rising CEA level to 44.8. Negative CT, CEA scan, bone scan, colonoscopy. PET demonstrates FDG uptake; biopsy = adenocarcinoma. Abnormal lab values or physical symptoms indicate possible cancer or cancer spread, but conventional imaging is normal

Staging after initial diagnosis of cancer To determine extent of disease and select the most appropriate treatment course Surgery Induction chemo and/or radiation therapy prior to surgery Systemic therapy Palliative therapy Images courtesy of Macapinlac, UT MD Anderson Cancer Center

Restaging a known or suspected recurrence 76 yr old with locally recurrent cervical cancer, CT shows pelvic adenopathy, scheduled for pelvic exenteration. PET positive for disease beyond pelvis. To determine extent of disease, particularly if planned treatment is local/regional surgery or radiation therapy to confirm suspicion of recurrence

Restaging a known recurrence Repeat positive right breast excisional biopsy. Conventional imaging negative and pt scheduled for right mastectomy PET results: Widespread liver metastases 7 cm abdominal mass (!) Unsuspected left breast tumor Bone metastases, left acetabulum Impact: Mastectomy cancelled and chemotherapy initiated Restaging a Known Recurrence In this case, a patient with a history of Rt. Breast cancer, post wedge resection, chemo and radiation therapy, presented with elevated tumor markers and a new right breast mass. The excisional breast biopsy was positive for metastatic breast cancer. Restaging by conventional imaging was negative and she was scheduled for a mastectomy. Tumor markers remained elevated after the excisional biopsy (should have returned to zero if that were the sole metastatic lesion). PET was performed to confirm extent of disease prior to surgery. PET demonstrated widespread liver metastases, a 7 cm abdominal mass, unsuspected Lt breast tumor, and a bone lesion on the left acetabulum. Her mastectomy was cancelled and she received high dose chemotherapy. Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

Restaging a known recurrence Restaging at completion of therapy The post treatment scan demonstrated complete resolution of her metastatic disease and confirmed the effectiveness of the chemotherapy. Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

Evaluating response to therapy To determine effectiveness of treatment and whether additional treatment is necessary Testicular cancer patient with apparent complete response to chemotherapy Images: Northern California PET Imaging Center

Melanoma Problem: Continuous rising global incidence over recent years due to changing exposure of the population to UV light Increased awareness, improvements in skin screening & early detection have resulted in decreased mortality despite the annual increased incidence Characterized by aggressive metastatic spread through the lymph system, in an unpredictable pattern, at a very early point in the disease

Melanoma Problem: Only curative treatment – early detection & surgical removal of the primary tumor and any isolated metastases, followed by chemotherapy Prognosis is highly correlated with depth of invasion in the skin, the thickness of the melanoma at resection, and the presence of lymph node or distant metastases No curative approach exists for disseminated metastatic spread - experimental trials with various immunotherapy drugs

Melanoma Staging Thin lesions = Breslow thickness of < 0.75mm Very low incidence of nodal or distant metastases Intermediate thickness melanomas = 0.76–4.0 mm 25-57% incidence of lymph node metastases 8-15% incidence of distant metastases Thicker melanomas > 4mm 62% likelihood of nodal metastases 72% likelihood of distant metastases The prognosis for patients with malignant melanoma is highly correlated with the depth of invasion in the skin, the thickness of the melanoma tumor at the time of resection, and the presence of lymph node or distant metastases. Melanomas with a Breslow thickness of less than 0.75 mm have a very low incidence of nodal and distant metastases and thus PET is not used for staging of these patients. Intermediate-thickness melanomas (0.76-4.0 mm) have a 25-57% incidence of lymph node metastases and an 8% to 15% incidence of distant metastases. Melanomas thicker than 4 mm have a 62% likelihood of nodal metastases and a 72% likelihood of distant metastases. Source: Ann Surg 1981; 193:436-440

Melanoma Staging Early stage, thin melanomas: Surgical resection and pathologic examination of the sentinel lymph node (first node of the lymphatic bed draining a malignant tumor) If sentinel node is free of tumor, the remainder of the nodes in that basin are likely to be disease free Sentinel node biopsy is highly sensitive Surveillance for recurrence

Melanoma Staging Intermediate – thick melanomas: PET – most effective staging tool for assessing nodal spread & distant metastases Assess entire skin surface & all organ systems for tumor invasion MRI brain In multiple studies of over 200 patients: PET sensitivity & specificity between 83% and 91% Conventional imaging: sensitivity of 88%, specificity of 75% PET routinely detected numerous, new, unsuspected metastatic lesions – better assessment of tumor burden Case management change in 26% of patients Source: Gambhir et all. JNM 2001; 42:1S-93S

Melanoma Staging Study of 100 high risk patients (lesions > 1.5mm) compared the accuracy of PET to conventional imaging: PET = 92% Conventional imaging = 77% CT was better for small lung lesions (87% vs 69%) PET was better in the abdomen (100% vs 27%) PET was better for cervical node metastases (100 % versus 66%) Source: Cancer 82:9, pp 1664-1671. 1998

Melanoma Staging 53 y/o female with a history of right calf melanoma, local excision and skin graft placement. Positive sentinel lymph node biopsy. Evaluated for extent of metastatic disease. CT: no evidence of abnormal mediastinal or hilar lymph nodes PET: multiple lesions in the mediastinum suspicious for metastatic disease. Trapezius muscle uptake, bilaterally - artifact Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

Melanoma Restaging & Response to Therapy PET: Evaluate palpable lymph nodes discovered on physical exam Clarify questionable lymph node findings identified by CT or ultrasound Evaluate other abnormal findings on conventional imaging studies Determine full extent of disease when surgery is considered for an apparent isolated metastasis Monitor response to new immunotherapy & biochemical treatments (interleukin-2, GCSF, tomoxifen)

Melanoma Evaluate Extent of Recurrence 39 year old man with history of melanoma, chest xray showed a possible left lung nodule

Melanoma Restaging 52 y/o female with history of Rt inguinal melanoma. S/P resection of lesions with chemotherapy. Patient presents with recurrence in the Rt groin. CT: post surgical changes in anterior-medial aspect of Rt thigh. No adenopathy or soft tissue mass identified. Findings could be related to radiation changes PET: intense FDG uptake in Rt inguinal region, diffuse liver metastases, single splenic mets, probably Rt sternal or parasternal mets. Surgery cancelled, high dose chemo Images courtesy of Landis Griffeth, MD, PhD, North Texas Clinical PET Institute

Melanoma Summary PET: Determine the stage of thick melanoma lesions at presentation Assess nodal spread from lesions of intermediate thickness Confirm recurrence of disease Monitor response to treatment Restage for extent of disease before surgical removal of any isolated metastases Surveillance for high risk patients

Problems and Pitfalls False negative: Size less than 10 mm Diabetes fasting blood glucose level >150 mg/dl Histology low grade glioma low grade lymphoma bronchoalveolar carcinoma mucinous adenocarcinoma thyroid, liver, kidney, prostate CA

Problems and Pitfalls Non-Malignant (false) positives: Infection granuloma, abscess, pneumonia Inflammation pneumonitis, wounds, arthritis, reactive nodes Uncertain sarcoid Benign tumors thyroid, parathyroid, carcinoid, colon Autoimmune rheumatoid nodules, thyroiditis Miscellaneous fractures, Paget’s disease

PET in Oncology Summary Clinical Applications of PET Characterization of radiographic abnormalities Detection of radiographically occult lesions Staging – initial evaluation of the extent of disease Restaging - evaluation of the extent of recurrent disease (resectability) Evaluation of response to therapy Benefits of PET Imaging Impact on patient mgmt (identifies most appropriate course of treatment for a specific patient) Avoid unnecessary biopsies or surgeries Reduce patient risk, improves patient outcome Determine patient response to therapy

PET in Oncology Conclusions Every patient does not need PET, but many will benefit from the addition of PET into their staging/restaging work up The information provided by PET and CT is complementary PET is not perfect - there are false negative and false positive results PET often changes the treatment plan, usually by avoiding futile surgery

PET in Oncology Conclusions A negative PET scan usually eliminates the need for biopsy or surgery – avoid complications associated with unnecessary invasive procedures A negative PET scan rules out cancer with a high degree of confidence A positive PET scan usually indicates malignancy, but should be confirmed with biopsy PET should be used to determine the extent of malignancy any time surgery or local radiation therapy is considered as the definitive treatment The predictive or prognositic power of PET following therapy is greater than CT

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