Positron Emission Tomography And Assessment Of Cancer Therapy

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Positron Emission Tomography And Assessment Of Cancer Therapy

  1. 1. Positron-Emission Tomography and Assessment of Cancer Therapy Malik E. Juweid, M.D., and Bruce D. Cheson, M.D. N Engl J Med 2006; 354:496-507, Feb 2, 2006. Review Articles
  2. 2. Concepts of PET 1. a noninvasive imaging technique 2. positron-emitting isotopes (11C, 13N, 15O, 18F) 3. provide a functional or metabolic assessment of normal tissues or disease conditions 4. Clinical applications in oncology : diagnosis, staging, restaging, monitoring response
  3. 3. Oncologic PET Tracers- 18F-FDG most commonly used in oncologic PET  the only oncologic PET tracer approved  by the Food and Drug Administration (FDA) for routine clinical use
  4. 4. Oncologic PET Tracers- 18F-FDG Increased uptake of 18F-FDG  -> reflects elevated glucose consumption -> evidenced by (1) the overexpression of glucose transporter proteins at the tumor cells‘ surface (2) increased levels of active hexokinase demonstrated in many tumors
  5. 5. Oncologic PET Tracers- 18F-FDG hexokinase www.petscanonline.com/ faq/faq_fr.asp www.petscanonline.com/
  6. 6. Oncologic PET Tracers- 18F-FDG Increased uptake of 18F-FDG  1. moderate-to-high uptake -> most lung, colorectal, esophageal, stomach, head and neck, cervical, ovarian, and breast cancers and in melanoma and most types of lymphoma ->infectious and inflammatory processes, inflammatory changes after surgery or irradiation, and thymic or bone marrow hyperplasia after treatment 2. variable and unpredictable -> prostate cancer
  7. 7. PET vs Conventional Radiologic Imaging conventional radiologic imaging techniques,  such as CT and MRI -> tumor's anatomical or morphologic features, for example — density, size, and shape  PET -> assesses functional or metabolic characteristics of the tumor -> detects clinically relevant changes even when no changes or minimal ones are detected by morphologic imaging (early detection) -> differentiation between malignant and benign processes
  8. 8. Applications in Assessment of Cancer after Therapy widespread use in oncology recently due to  1. Second-generation PET scanners : a larger field of view, improved resolution and sensitivity 2. PET–CT 3. Centers for Medicare and Medicaid Services (CMS)
  9. 9. Applications in Assessment of Cancer after Therapy CMS to approve reimbursement for  1. the staging and restaging of non–small-cell lung, esophageal, colorectal, breast, and head and neck cancers, as well as lymphoma and melanoma 2. the monitoring of the response to treatment of breast cancer 3. the staging of cervical cancer (recently)
  10. 10. PET 健保給付適應症 ( 台灣 ) 1. 乳癌分期及治療後評估 2. 大腸癌、直腸癌、食道癌、頭頸部癌 ( 不包含腦瘤及甲狀 腺癌 ) 、肺癌 ( 非小細胞性 ) 、淋巴癌及黑色素癌之診斷 ,分期及復發後之再分期 3. 存活心肌偵測  4. 癲癇病灶術前評估 5. 肺癌 (SPN) 6. 甲狀腺癌復發後之再分期 7. 以電腦斷層或磁振造影無法分期或診斷者 8. 配合腫瘤治療計畫及療效評估者。 http://www3.vghtc.gov.tw/nm/PET/PAGE5.HTM
  11. 11. Applications in Assessment of Cancer after Therapy 一 . Monitoring Response to Treatment 二 . Restaging 三 . Requirement for Pretreatment PET before Restaging PET 四 . Appropriate Time Point for Restaging with PET 五 . Viable Tumor vs. Necrosis or Fibrosis in Residual Masses 六 . Detection of Recurrence in Asymptomatic Patients 七 . False Positive Findings on Restaging with PET 八 . Effect of Restaging with PET on Quality of Life in Cancer 九 . Cost-Effectiveness of Restaging with PET
  12. 12. Applications in Assessment of Cancer after Therapy 一 . Monitoring Response to Treatment 1. breast cancer : the only currently approved clinical indication 2. lymphomas and esophageal, stomach, colorectal, head and neck, and non– small-cell lung cancers : no published reports have clearly demonstrated that PET results were used to alter treatment
  13. 13. Applications in Assessment of Cancer after Therapy 二 . Restaging 1. Clinical approved : (1) breast, colorectal, esophageal, head and neck, and non–small-cell lung cancers, as well as melanoma and lymphoma (2) suspected recurrent thyroid cancer of follicular-cell origin after thyroidectomy and radioiodine ablation in patients with a negative 131I whole-body scan and an elevated level of serum thyroglobulin
  14. 14. Applications in Assessment of Cancer after Therapy 二 . Restaging 2. review of studies reported from 1993 to 2000 (1) sensitivity : 80 to 95 percent (2) specificity : 75 to 90 percent (3) accuracy : 80 to 90 percent PS. More recent studies : more accurate (owing to use of higher-resolution PET scanners and PET–CT systems)
  15. 15. Detection of Recurrent Breast Carcinoma on PET-CT with 18 F-FDG The 74-year-old woman in  this image had stage IV inflammatory breast cancer and had completed six cycles of doxorubicin and cyclophosphamide in October 2004. PET–CT and contrast-enhanced CT scans obtained at that time were negative. The patient was then given trastuzumab and was doing well clinically. PET–CT was performed for restaging in August 2005. Coronal, sagittal, and axial views on PET (Panel A) and on integrated PET–CT (Panel B) show disease recurrence with widespread bony metastases
  16. 16. Detection of Recurrent Cervical Carcinoma on PET-CT with 18 F-FDG The 36-year-old woman in this image  underwent concurrent radiation therapy and chemotherapy for stage IIB squamous-cell cervical carcinoma in November 2003. A para-aortic nodal recurrence was found and treated with additional radiation therapy and chemotherapy in July 2004, and a cervical recurrence was found and treated with additional chemotherapy in November 2004. PET–CT was performed for restaging in January 2005. A sagittal view (Panel A) and coronal view (Panel B) on PET–CT, as well as axial CT (Panel C) and PET (Panel D) images, show increased uptake of 18F-FDG in a nonpalpable, left supraclavicular lymph node of under 1 cm (arrows). Metastasis was confirmed by biopsy. (Images are courtesy of Mallinckrodt Institute of Radiology, St. Louis.)
  17. 17. Applications in Assessment of Cancer after Therapy 三 . Requirement for Pretreatment PET before Restaging PET  The majority of patients undergoing restaging with PET did not undergo PET before treatment, because : (1) cost (2) not thought to contribute to the initial diagnosis or staging (3) a very high percentage of the tumor types that are approved by the CMS for restaging with PET are consistently 18F-FDG–avid PS. baseline PET might be considered only for tumor types with less predictable avidity, such as marginal-zone lymphoma
  18. 18. Applications in Assessment of Cancer after Therapy 四 . Appropriate Time Point for Restaging with PET  detection of residual or recurrent tumors varies with the type of therapy 1. completion of chemotherapy, chemoimmunotherapy, or chemohormonal therapy : after four weeks 2. radiation or chemoradiation : after two to three months 3. surgery : after one to two months (at the site of the recent surgery )
  19. 19. Applications in Assessment of Cancer after Therapy 五 . Viable Tumor vs. Necrosis or Fibrosis in Residual Masses after treatment 1. most relevant in lymphoma or testicular cancer 2. avoid unnecessary toxic therapy to a nonviable mass 3. allows the early administration of salvage therapy persistent tumors (after been confirmed by biopsy)
  20. 20. CT before and after Therapy and PET after Therapy in a Patient with Diffuse Large-Cell Lymphoma CT performed before the start of therapy  shows a tumor mass in the splenic hilum (Panel A, arrow). The patient also had enlarged celiac nodes (not shown). After six cycles of therapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, CT showed a 5.1-by-6.6 cm residual mass in the splenic hilum (Panel B, arrow). PET that was performed after the termination of therapy shows no evidence of increased uptake in the residual mass (Panel C, arrow), indicating that the mass shown on CT is fibrosis and not residual lymphoma. The patient had no evidence of disease at 29.5 months of follow-up. (Images are reprinted from Juweid et al with the permission of the publisher.)
  21. 21. Applications in Assessment of Cancer after Therapy 六 . Detection of Recurrence in Asymptomatic Patients  Several studies : among patients who 1. have no symptoms or only mild ones 2. but who have an elevated tumor marker level -> tumor restaging with PET can detect and localize disease recurrence -> whether the detected disease is resectable
  22. 22. Detection of Occult Recurrent Colon Cancer by PET-CT with 18 F-FDG The 82-year-old man in this image presented with a slightly elevated level of carcinoembryonic antigen (3.4 ng per milliliter) one year after the completion of adjuvant chemotherapy for right-sided colon cancer. Coronal, sagittal, and axial views on PET, which was performed one month later with the use of a PET–CT scanner, show a focal area of increased uptake just below the inferior portion of the right lobe of the liver (Panel A, arrows). This mass corresponds to a new 1.2-cm soft-tissue density on CT (Panel B, arrows), as is clearly shown on the fused PET–CT images (Panel C, arrows). Three months later, the patient underwent laparotomy, which confirmed that this omental mass was recurrent colon adenocarcinoma. The tumor was successfully resected without complications
  23. 23. Applications in Assessment of Cancer after Therapy 七 . False Positive Findings on Restaging with PET 1. physiologic processes : brown fat and cyclic gynecologic activity 2. infectious and inflammatory processes : such as pneumonia, histoplasmosis, and sarcoidosis -> Careful history taking ! 3. rebound thymic hyperplasia in children and young adults
  24. 24. Applications in Assessment of Cancer after Therapy 八 . Effect of Restaging with PET on Quality of Life in Cancer ->unaware ->Recent literature Porceddu SV, Jarmolowski E, Hicks RJ, et al. Utility of positron  emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck 2005;27:175-181. Yao M, Graham MM, Smith RB, et al. Value of FDG PET in  assessment of treatment response and surveillance in head-and- neck cancer patients after intensity modulated radiation treatment: a preliminary report. Int J Radiat Oncol Biol Phys 2004;60:1410-1418
  25. 25. Applications in Assessment of Cancer after Therapy 八 . Effect of Restaging with PET on Quality of Life in Cancer Porceddu SV, Jarmolowski E, Hicks RJ, et al. Utility of positron emission tomography  for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck 2005;27:175-181. -> Patients who (1) achieving a complete response at the primary site (2) having a residual abnormality in the neck (3)being PET negative -> approximately 12 weeks after treatment do not require neck dissection and can be safely observed
  26. 26. PET and Contrast-Enhanced CT before and after Therapy in a Patient with Base-of-Tongue Cancer (Stage I with Nodal Involvement [T1N3]) Both PET and CT scans  performed before the start of therapy show bilateral cervical lymphadenopathy (Panel A, arrows). CT performed eight weeks after chemoradiation shows a residual soft-tissue mass in the right neck (Panel B, arrow). The post-therapy PET performed at that time was negative. The patient did not undergo neck dissection and had no evidence of disease at follow-up 30 months after therapy Porceddu SV, Jarmolowski E, Hicks RJ, et al. Utility of positron emission tomography for the detection of disease in residual neck nodes after (chemo)radiotherapy in head and neck cancer. Head Neck 2005;27:175-181
  27. 27. Applications in Assessment of Cancer after Therapy 八 . Effect of Restaging with PET on Quality of Life in Cancer Yao M, Graham MM, Smith RB, et al. Value of FDG PET in assessment of treatment response and  surveillance in head-and-neck cancer patients after intensity modulated radiation treatment: a preliminary report. Int J Radiat Oncol Biol Phys 2004;60:1410-1418 -> FDG PET is useful in the posttreatment management of head-and-neck cancer patients treated with IMRT -> highly accurate in the detection of persistent and recurrent disease after treatment and allows salvage treatment to be initiated in a timely manner -> provides prognostic information concerning the risk of recurrence after curative therapy.
  28. 28. Applications in Assessment of Cancer after Therapy 九 . Cost-Effectiveness of Restaging with PET 1. per scan in the United States : $1,800 to $1,900 2. Studies : restaging of colorectal cancer as well as head and neck cancers -> cost savings because of changes in management -> avoidance of inappropriate, costly treatments (unresectable) 3. periodic PET scanning in patients with no clinical or biochemical evidence of disease -> should be avoided
  29. 29. Applications in Assessment of Cancer after Therapy 十 . Radiation Dose from PET Scans 1. a single PET scan : 10 mSv PS. a chest CT : 8 mSv 2. a single PET–CT : 20 mSv PS. The potential benefit from restaging with PET usually far exceeds any potential risk
  30. 30. Conclusions powerful imaging tools in clinical oncology for  (1) the accurate restaging of established disease (2) the detection of occult tumors (3) the reliable prediction of the nature of residual masses that are difficult to evaluate with conventional imaging after therapy (4) evaluating for response or lack of response at a very early stage in the course of treatment -> shorten the time required to evaluate the efficacy of drugs or to determine the optimal therapeutic intervention

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