Using PET in Lymphoma 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

Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL) Problem: 74,340 new U.S. cases in 2008 (HD = 8,220; NHL = 66,120) 20,510 cancer deaths in 2008 (HD = 1,350; NHL = 19,160) HD 85% 5 yr survival rate: NHL 63% 5 yr survival rate Most patients with newly diagnosed Hodgkin’s are curable w/ stage adjusted radiation therapy and/or combination chemotherapy regimens Prognosis is dependent on histology, stage of disease at presentation and treatment response Source: American Cancer Society. Cancer Facts and Figures 2008. Atlanta

Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL) Differences between HD & NHL factor into diagnosis and treatment: Hodgkin’s begins as a unifocal disease located in a single group of malignant lymph nodes and spreads via adjacent lymph node groups Limited disease (stage I or II) is treated with radiation therapy & is curative for a high percentage of patients Patients with advanced disease have poorer prognosis – treated with chemotherapy

Lymphoma Non-Hodgkin’s (NHL) NHL is multifocal disseminated disease and is classified as low, intermediate or high grade based on histocytology More likely to develop non-nodal metastases Require a combination of chemo & radiation therapy Often resistant or relapse and require high dose chemotherapy & bone marrow transplantation Low grade NHL has a better prognosis if left untreated, does not respond well to chemo High grade NHL is rapidly fatal if untreated – long remissions & cures can be induced with therapy

Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL) Staging – physical examination CT of the neck, chest, abdomen & pelvis Limitations – lymph node evaluation by size, difficulty in evaluating spleen, liver or bone marrow Gallium67 imaging Limitations – noisy images, variable uptake by tumors, limited detection of abdominal disease, multi-day exam Bone marrow biopsy Limitations – invasive aspiration & biopsy w/ sensitivity limited by sampling error (disease may be present in the marrow, but not in the area sampled)

Lymphoma Hodgkin’s (HD) & non-Hodgkin’s (NHL) Staging – Role for PET Avid uptake by virtually all lymphomas (uptake does correlate with grade of tumor & degree of proliferation) Higher sensitivity & specificity for detection of nodal & extranodal disease than anatomic imaging Higher image quality allows improved detection of CNS, abdominal and pelvic lesions over Ga67 Detection of focal bone marrow disease Evaluation of CNS lymphomas – differentiate inflammatory lesions & tumor extension (HIV + patients) Degree of uptake is predictive of patient outcome

Lymphoma Staging Pre Post PET provides information which can aid the physician in more accurately staging Lymphoma. Conventional staging modalities are useful, but have their limitations. Diagnostic criteria cannot be based on size alone. Small malignant nodules may be missed by conventional imaging, and enlarged lymph nodes may be benign. Conventional imaging may not detect involvement of the spleen, liver or bone marrow. In this case, a 28 year old female was diagnosed with Hodgkin’s disease through a left cervical lymph node biopsy. A PET•CT scan was recommended for initial staging, which revealed extensive lymphadenopathy with markedly increased FDG uptake consistent with the patient’s known history of Hodgkin’s disease. Chemotherapy was implemented and the follow-up PET scan after completion of therapy showed that the treatment had been effective. 28 year old female with newly diagnosed Hodgkin’s disease through left cervical lymph node biopsy. PET•CT for initial staging. Extensive lymphadenopathy with markedly increased FDG uptake consistent with the patient’s known history of Hodgkin’s disease. Images courtesy of Barry Siegel MD, Barnes Jewish Hospital, St. Louis, MO

PET in Lymphoma PET imaging for initial staging of lymphoma: Can alleviate numerous other tests that have lower accuracies like illiac bone marrow biopsies for lymphoma patients Takes care of debate over residual lymph nodes PET imaging for restaging of lymphoma: Baseline and Post-Tx PET improves direct assessment of residual masses Improves assessment of response to therapy (at end vs. interim) Improves prognostic assessment (at end vs. interim)

Lymphoma Staging Delbeke et al, used PET in initial staging 45 patients: PET alone: staging accuracy = 91% Combined conventional staging modalities accuracy = 84% PET correctly changed the stage of 16% of patients, but under staged 7% (absent or low tumor uptake) Major advantage was assessment of bone marrow involvement Recommend PET in conjunction with conventional staging methods Source: Delbeke, MIB 2002. Vol 4:1, 105-114

Lymphoma Restaging & Response to Therapy Restaging & Response to therapy: Role for PET Identification of recurrence Identification of residual lymphoma after treatment Differentiate viable tissue from fibrosis Proven prognostic value – residual FDG uptake s/p treatment is a strong predictor or relapse or progression of disease as well as a predictor of survival FDG PET CT # of PTS Sens Spec Sens Spec 711 92 93 92 10 Source: Gambhir, JNM Vol 42:5, pp 16S-20S. 2001

Lymphoma Restaging 53 y/o female, history of HD, s/p stem cell transplant CT: adenopathy in the celiac and porta hepatis abdominal lymph nodes. ? active HD PET: markedly abnormal, FDG uptake throughout the body consistent with active Hodgkin's disease PET confirmed active disease, high dose chemotherapy treatment implemented. Images courtesy of Landis K. Griffeth, MD, PhD, North Texas Clinical PET Institute

Lymphoma Summary Summary: Role for PET Staging the disease before treatment Monitoring response to therapy Detecting recurrence Correlation of uptake with prognosis

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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