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. 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. 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. 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. Oncologic PET Tracers- 18F-FDG
hexokinase
www.petscanonline.com/ faq/faq_fr.asp
www.petscanonline.com/

7. 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

8. 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

9. 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)

10. 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)

11. 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

12. 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

13. 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

14. 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

15. 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)

17. 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

18. 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.)

19. 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

20. 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 )

21. 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)

22. 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.)

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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.

30. 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

31. 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

32. 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