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20.pet scan in oncology

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20.pet scan in oncology

  1. 1. PET SCAN IN ONCOLOGY DR. ARNAB BOSE Dept. of Radiotherapy NRS Medical College, Kolkata 1
  2. 2.  Imaging often is the best means of noninvasively identifying and assessing tumors. With information gleaned from imaging studies, the prognosis can be established and treatment decisions made with greater certainty.  Broadly stated, cancer imaging can be performed using anatomic or functional imaging methods. 2
  3. 3.  The traditional imaging of the patient with cancer, and the most established methods, are based on anatomic imaging.  However, interest is increasing in more functional methods in cancer imaging.  Further, several anatomic imaging methods offer functional components that complement the anatomic method.  Hybrid images, derived from and displaying both functional and anatomic data, also are becoming more widely available, often coming from the same hybrid imaging machine. 3
  4. 4.  Anatomic imaging normally detects a phenotypic alteration that is sometimes, but not invariably, associated with cancer— a mass. However, with anatomic imaging, we often do not know whether masses are the result of malignant or benign etiologies, as in solitary pulmonary nodules or borderline-size lymph nodes.  Similarly, small cancers are undetectable with traditional anatomic methods, because they have not yet formed a mass. 4
  5. 5.  After surgery, it is even more difficult to assess for the presence of recurrent tumor with anatomic methods.  Post-treatment scans are complicated by the need for comparisons with normal anatomy to detect altered morphologic findings as a result of cancer.  Anatomic methods do not predict the response to treatment and do not quickly document tumors responding to therapy. 5
  6. 6.  Positron Emission Tomography ( P E T ), a functional imaging method, helps to address many of the limitations of anatomic imaging, and when combined with anatomic images in fusion images, is emerging as a particularly valuable tool, providing both anatomic precision and functional information in a single image set. 6
  7. 7.  PET provides information on the metabolic function of organs or tissues by detecting how cells process certain compounds such as glucose. Most cancer cells metabolize glucose at a much higher rate than normal tissues. By detecting increased radio-labelled glucose metabolism with a high degree of sensitivity, PET identifies cancerous cells, even at an early stage, when other imaging modalities may miss them. 7
  8. 8.  In a typical PET study, one administers a positron emitting radionuclide by intravenous injection. The radionuclide circulates through the bloodstream to reach a particular organ.  The positrons emitted by the radionuclide travels a distance of a few millimeters in tissue before it collides with a negatively charged electron. This collision annihilates the entire mass of the positron and electron, generating two photons with energy of 511 KeV each. 8
  9. 9.  These two photons travel at the speed of light in exactly opposite directions (i.e.180 degrees apart).  Coincident detection of these two photons by two oppositely positioned detectors in the PET scanner results in images with a much higher resolution compared with the conventional, single-photon nuclear medicine studies and produces the possibility of quantitative measurement of the tracer uptake in a volume of interest. 9
  10. 10. detector array  PET machines are composed of a ring of detectors within which the patient is gamma photon positioned . positron  The gamma photons emitted travel at the speed of light. Rather than radiotracer register the gamma photons as two separate events, the PET machine registers them as a paired event.  It does this through the establishment of time windows. If two gamma photons are detected within the same (small) time window, the camera records them as coming from the same annihilation event. As the gamma photons travel at 180 o to each other, the camera draws a line of flight between the two events and determines that the annihilation must have occurred along this line. 10
  11. 11.  The PET machine generates transverse images depicting the distribution of positron emitting radionuclides in the patient and uses annihilation coincidence detection to obtain projections of the activity distribution. The transverse images are obtained through the process of filtered back-projection.  Detectors used for coincidence detection in modern PET machines are scintillators made of bismuth germanate (BGO) or lutetium oxyorthosilicate doped with cerium (LSO:Ce) that transform the 0.511 MeV gamma ray energy into visible photons detected by photomultiplier tubes (PMTs). 11
  12. 12.  The radionuclides used in PET studies are produced by bombardment of an appropriate stable nuclide with protons from a cyclotron, thereby producing positron emitting radionuclides that are subsequently attached to clinically useful biological markers. 12
  13. 13.  The 18F radionuclide attached to the 2-fluoro-2-deoxy-D-glucose (FDG) molecule is the biological marker most commonly used in studies involving glucose metabolism in cancer diagnosis and treatment (2-[18F] fluoro-2-deoxy-d-glucose).  Tumor imaging with FDG is based on the principle of increased glucose metabolism of cancer cells. 13
  14. 14.  Like glucose, FDG is taken up by the cancer cells through facilitative glucose transporters (GLUTs).  Once in the cell, glucose or FDG is phosphorylated by hexokinase to glucose-6-phospate or FDG-6-phosphate, respectively.  Expression of GLUTs and hexokinase, as well as the affinity of hexokinase for phosphorylation of glucose or FDG, is generally higher in cancer cells than in normal cells. 14
  15. 15.  Glucose-6-phosphate travels farther down the glycolytic or oxidative pathways to be metabolized, in contrast to FDG-6- phosphate, which cannot be metabolized.  In normal cells,glucose-6-phosphate or FDG-6-phosphate can be dephosphorylated and exit the cells. In cancer cells, however, expression of glucose-6-phosphatase is usually significantly decreased, and glucose-6-phosphate or FDG-6- phosphate therefore can become only minimally dephosphorylated and remains in large part within the cell.  Because FDG-6-phosphate cannot be metabolized, it is trapped in the cancer cell as a polar metabolite, and it constitutes the basis for tumor visualization on PET. 15
  16. 16. NORMAL TUMOR Over expression of Glucose transporters Higher levels of Hexokinase Down-regulation of Glucose-6-phosphatase Anaerobic glycolysis, less ATP per glucose molecule, more glucose molecules needed for ATP production General increase in metabolism from high growth rates 16
  17. 17.  A potential range of clinical scenarios in oncology for which 18F-FDG-PET has shown to be worthwhile includes: i) The non-invasive characterization of the likelihood of malignancy of mass lesions, which are not readily amenable to biopsy, or for which biopsy attempts have already failed. ii) The detection of cancer in patients at significantly increased risk of malignancy on basis of elevated tumor markers, clinical symptoms or signs but in whom routine tests have failed to detect a cancer. 17
  18. 18. iii) Staging of high-risk malignancy amenable to potentially curative therapy for which disease extent is critical to treatment selection. iv) Planning of highly targeted therapy where delineation of disease is critical to efficient and safe treatment delivery and thereby, therapeutic success. v) Assessment of therapeutic response in diseases with a significant likelihood of treatment failure, and for which earlier demonstration of therapeutic failure may benefit the patient. vi) Surveillance of high-risk malignancies or evaluation at clinical relapse where salvage therapies exist and for which early intervention may be curative or prolong life. 18
  19. 19.  It is important to recognize that, being a tracer of glucose metabolism, 18F-FDG is not a ‘specific’ radiotracer for imaging malignant disease.  There are several benign conditions and many physiological processes that lead to increased uptake of this tracer.  These include, but are not limited to, normal wound healing, infection and inflammation, active muscle contraction during the uptake period, and activated brown fat. 19
  20. 20.  Normal organs, including the brain, liver, kidneys and bone marrow have relatively high 18F-FDG uptake, even under fasting conditions, and this provides background activity that may mask small lesions or malignancies with low glucose metabolism.  Such malignancies include some neuroendocrine tumors, mucinous tumors, differentiated teratomas, many prostate carcinomas, lobular breast cancer, some renal and hepatocellular carcinomas, and most bronchioloalveolar carcinomas.  The relatively poor 18F-FDG uptake of these tumors compromises the sensitivity of PET for the detection of tumor sites. 20
  21. 21.  The standardized uptake value (SUV) is a semi-quantitative measure of the tracer uptake in a region of interest that normalizes the lesion activity to the injected dose and body weight; SUV does not have a unit.  Despite initial enthusiasm, it is generally accepted that SUV should not be used to differentiate malignant from benign processes, and that the visual interpretation of PET studies by an experienced reader provides the highest accuracy. 21
  22. 22.  There are many factors influencing the calculation of SUV, such as the body weight and composition, the time between tracer injection and image acquisition, the spatial resolution of the PET scanner, and the image reconstruction algorithm.  Nonetheless, SUV may be useful as a measure to follow the metabolic activity of a tumor over time within the same patient and to compare different subjects within a research study under defined conditions. For example, the SUV of an individual tumor can be measured before and at different time points after therapy, and any change can be used as an index of therapeutic response. 22
  23. 23.  Research in PET radiochemistry has provided access to many alternative tracers for oncology at the present time.  Many of these tracers have been evaluated in both pre clinical and clinical studies.  Some have the ability to uniquely characterize specific aspects of tumour biology and, as a result, to offer several diagnostic advantages in comparison with 18F-FDG in particular types of tumours. 23
  24. 24. 24
  25. 25.  Sensitivity describes how often the imaging test would give a “positive result” in a patient with cancer (i.e., true- positive [TP] finding). A test with high sensitivity has a low number of false-negative results.  Specificity is the frequency with which a test result is negative if no disease is present, or the true-negative (TN) ratio. A highly specific test has a low frequency of false- positive results  Accuracy is 100 * (TP + TN)/(TP + FP + TN + FN). A highly accurate test is one with a low prevalence of false-positive and false-negative results. 25
  26. 26. PET Scan in Lung Cancer  PET has an overall sensitivity of more than 90% and a specificity of about 85% for diagnosing malignancy in primary and metastatic lung lesions; the sensitivity of PET for bronchoalveolar lung cancer and carcinoid of the lung is about 60%, and the specificity of PET for lung cancer is lower in areas with a high prevalence of granulomatous lung disease.  It is expected that the use of PET for diagnosing malignancy in indeterminate lung nodules will continue to grow as more patients are diagnosed with nodules on CT performed for other indications or as a screening test. 26
  27. 27.  FDG-PET is useful in staging of lung cancer by detecting mediastinal nodal involvement PET has greater sensitivity and specificity than CT, but it is still imperfect. Nodes that appear involved by PET or CT should be sampled for confirmation of their status when such information will lead to alterations in clinical management, particularly when deciding whether to consider resection.  FDG-PET has also been studied for evaluating the response to pre-operative chemotherapy or chemo-radiation and for distinguishing between viable tumor and fibrosis in patients who have received RT or chemotherapy, or both, in assessing local disease control in patients treated non-operatively. 27
  28. 28.  PET is justified instead of a battery of other tests (e.g., bone scan, CT, MRI) to assess for distant metastases.  PET is more sensitive (90% vs. 80%) and more specific (90% vs. 70%) than bone scan in detecting bone metastases from NSCLC; PET has a sensitivity and specificity of greater than 90% in detecting adrenal metastases from NSCLC. Brain CT or MRI is still needed because PET cannot reliably detect brain metastases because of physiologically intense brain uptake of FDG.  For patients with stage IV tumors, PET may be able to indicate the most accessible site for biopsy. 28
  29. 29.  PET is also useful in restaging NSCLC. In particular, PET appears to be more sensitive than CT in differentiating post-irradiation change from local recurrence, although differentiating these two entities remains a challenge. The post-irradiation change in the chest can remain intense on PET for up to several years. In differentiating local recurrence from post-irradiation change, the intensity of uptake and its shape should be taken into account 29
  30. 30. PET Scan in Lymphoma  Positron emission tomography (especially fused PET/CT) is superior to conventional CT in staging of Hodgkin’s disease and non-Hodgkin’s lymphoma; however, there is no definite evidence that PET changes the initial management of lymphoma patients. Nonetheless, because most recurrences occur at the sites of the primary disease, pre-treatment PET appears helpful in identifying recurrence. 30
  31. 31.  Hodgkin’s disease and high-grade NHL are mostly markedly avid for FDG and almost always visible on PET, whereas low- grade NHL can be only mildly intense and, in rare cases, completely invisible on PET.  Intense spleen uptake (i.e., more intense than the liver) before chemotherapy is a reliable indicator of its involvement, but spleen involvement by lymphoma cannot be excluded with normal uptake.  PET cannot be used to reliably evaluate bone marrow involvement. 31
  32. 32.  The most promising role of PET in lymphoma management appears to be in therapy monitoring: early prediction of response to chemotherapy (i.e., interim or midway PET) and evaluation of a residual mass for active lymphoma at the completion of chemotherapy (i.e., end-of-treatment PET).  The decrease of uptake associated with effective chemotherapy seen on interim PET precedes the anatomic changes seen on CT by weeks to months. Overall, metabolic changes on interim PET after one or a few cycles of chemotherapy are reliable predictors of response, progression- free survival rates, and overall survival rates. 32
  33. 33.  End-of-treatment PET has proven impact in patient care. At the completion of chemotherapy, CT demonstrates a residual mass at the initial site of disease in as many as 50% of patients. On the end-of-treatment PET, these patients demonstrate increased FDG uptake in the area of residual lymphoma in contrast to those without active lymphoma. The positive predictive value of residual uptake at the completion of chemotherapy is more than 90%.  In follow-up of patients in remission, PET is more sensitive than CT in detecting recurrent disease. 33
  34. 34. PET Scan in Head & Neck Cancers  In initial staging of head and neck tumors, PET has a sensitivity and specificity of about 90% for nodal staging, and PET therefore is more sensitive and specific than CT or MRI. A weakness of PET is its low sensitivity (30%) for nodal disease in patients with disease in the neck at clinical stage N0.  In addition to local staging, PET can detect synchronous cancers and distant metastases. In initial staging of head and neck cancers, a PET scan is overall most helpful in patients with locally advanced disease because these patients have a risk of 10% or greater for distant disease. 34
  35. 35.  For restaging of head and neck tumors after radiation therapy, PET is highly sensitive; however, the optimal time to perform PET is a matter of debate. There is a higher likelihood of false-positive findings when PET is performed earlier than 3 months after irradiation.  For patients presenting with metastatic neck nodes with unknown primary PET is useful in the search for the original lesion. 35
  36. 36. PET Scan in Colorectal Cancers  PET is highly sensitive in detecting distant hepatic and extra-hepatic metastases.  Considering the higher sensitivity of PET in detecting distant metastases and the introduction of intravenous contrast media to the CT portion of fused PET/CT, it is conceivable that PET/CT will be increasingly employed in pre-operative staging of colorectal cancer; the contrast- enhanced CT portion of PET/CT can be used instead of conventional CT or MRI for evaluation of anatomic resectability of liver metastases. 36
  37. 37.  PET plays an important role in restaging of colorectal cancer and is even more important now that it is known that treatment of limited metastatic disease can be curative.  PET can visualize the site of the local and distant disease when recurrence is suspected based on the clinical findings, findings on other imaging modalities, or an increasing CEA level with sensitivity and specificity higher than 90% 37
  38. 38. PET Scan in Breast Cancer  PET can increase the detectability of small primary breast cancers and may be especially useful in evaluating patients with dense breast tissue. Its role in routine patient care is under investigation.  In evaluating the axillary lymph nodes, PET does not play any role because of its low sensitivity (60%) despite relatively high specificity (80%). In contrast, PET is relatively sensitive (85%) and specific (90%), and it is superior to CT (sensitivity of 54%, specificity of 85%) in evaluation of the internal mammary chain lymph node for metastases. 38
  39. 39.  The main role of PET in breast cancer lies in the investigation of distant metastases and response monitoring.  Compared with CT, PET has a higher sensitivity (90% vs. 40%) but lower specificity (80% vs. 95%) in detecting metastatic disease.  Overall, PET has the same sensitivity as bone scan in detecting bone metastases (both about 90%), but PET appears to be somewhat more sensitive than bone scan for osteolytic lesions and somewhat less sensitive than bone scan for osteoblastic lesions. PET has a higher specificity than bone scan in detecting bone metastases (95% vs. 80%). 39
  40. 40.  In patients with advanced breast cancer undergoing neo-adjuvant chemotherapy, PET may differentiate responders from non-responders as soon as the first cycle of therapy has been completed. This may help improve patient management by avoiding ineffective chemotherapy and supporting the decision to continue dose-intensive pre-operative chemotherapy in responding patients. 40
  41. 41. In esophageal and gastric cancers, PET is useful to assess for distant disease. PET is routinely used in the staging of esophageal cancer, and it has the potential to be used for monitoring the effect of neo-adjuvant therapy. In ovarian, uterine, and cervical cancers, PET is used to assess for recurrent disease. In cervical cancer, PET plays an important role in nodal staging and can have a role in radiotherapy planning. In malignant melanoma, PET is used to evaluate the presence of distant metastases. In sarcoma, the most intense areas on PET have usually the highest grade and should be considered in planning the biopsy. 41
  42. 42. This is a very interesting case of a 67 year old gentleman with three pulmonary nodules on CT scan. He was referred for PET/CT, which showed only one of the three nodules was FDG avid. A subsequent biopsy of the FDG avid nodule showed adenocarcinoma. The surgeon and the patient decided to resect all three nodules. The pathology of the three nodules showed adenocarcinoma, a more peripheral area of infarct from tumor embolus and in the other lung a benign hamartoma. In this particular case, PET/CT accurately identified the malignant nodule from the other two benign nodules. 42
  43. 43. thank you 43

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