Positron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy

doi:10.1016/0360-3016(93)90259-X

International Journal of Radiation OncologyBiologyPhysics

Volume 27, Issue 2, 30 September 1993, Pages 455-464

https://doi.org/10.1016/0360-3016(93)90259-X Get rights and content

Abstract

$Purpose$ : Following radiation therapy, evaluation of viable tumor can often be difficult with anatomic imaging criteria (tumor size alone). In this study, the utility of biochemical imaging with the glucose analog 2-[F-181fluoro2-deoxy-D-glucose and positron emission tomography was investigated in patients treated with radiation therapy.

$Methods and Materials$ : Between 1990 and 1992, 19 patients were studied, including 15 patients with head and neck cancer, (4 oropharynx, 4 sinus, 3 larynx, 2 hypopharynx, 2 oral cavity [one patient], 1 nasopharynx~ and 4 patients with breast cancer. Post-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose studies were done in all patients, with 9 head and neck patients receiving pre-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose scans as well. Results were correlated with other imaging techniques and pathology.

$Results$ : Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose detected head and neck primary tumors and lymph node metastases in all nine pre-radiation scans, while magnetic resonance imaging failed to detect two primary tumors. Serial positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed a significant decrease in tumor activity after radiation therapy, compared to pre-radiation levels, (p < 0.05), except for two patients with increased uptake at the primary site. Biopsies of these two patients showed persistent/ recurrent disease after radiation therapy, which was not detected by magnetic resonance imaging. Six additional head and neck patients, with suspicious examination and inconclusive magnetic resonance imaging, were imaged with positron emission tomography after radiation therapy only. Five patients had increased positron emission tomography activity, with corresponding biopsies positive in four patients, and negative in one patient with clinically worsening symptoms. The remaining sixth patient had minimal and stable positron emission tomography uptake, and is improving clinically. Four patients had mammogram findings suspicious for recurrence after conservation treatment for breast cancer. Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed no focal activity in the breast in two patients, and increased activity in the area suspicious for recurrence in the other two patients. Biopsies correlated with positron emission tomography results.

$Conclusion$ : Changes and presence of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose activity correlated with pathologic findings in head and neck and breast cancer patients in this series. In patients with elevated or rising positron emission tomography activity after radiation therapy, persistent or recurrent disease was found in 89% of patients, ( $89$ ). Magnetic resonance imaging did not detect the head and neck recurrences, and mammography was suspicious in patients with both benign and malignant breast changes after radiation therapy. In addition, our data indicate that in head and neck patients with pre-radiation positron emission tomography scans, a significant decrease in activity should occur after radiaton therapy, if local control is to be expected.

References (40)

L.A. Forstrom
Positron emission tomography-The promise of metabolic imaging
W. Koh et al.
Imaging of hypoxia in human tumors with [F-18]fluoromisonidazole
Int. J. Radiat. Oncol. Biol. Phys.
(1992)
H.C. Padgett et al.
Computer-controlled radiochemical synthesis: A chemistry process control unit for the automated production of radiochemicals
Appl. Radiat. Isot.
(1989)
Y. Abe et al.
Assessment of radiotherapeutic effects on experimental tumors using 18F-2-fluoro-2-deoxy-D-glucose
Eur. J. Nucl. Med.
(1986)
S. Ali et al.
False-positive and falsenegative neck nodes
Head Neck Surg.
(1985)
J.W. Bailet et al.
Positron emission tomography: A new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy
Laryngoscope
(1992)
B.C. Chen et al.
Evaluation of primary head and neck tumor with PET-FDG (Abstr.)
Clin. Nucl. Med.
(1990)
M. Dahlbom et al.
Whole body positron emission tomography: Part I: Methods and performance characteristics
J. Nucl. Med.
(1992)
G. Di Chiro
Positron emission tomography using [18F]Fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool
Invest. Radiol.
(1986)
G. Di Chiro et al.
Cerebral Necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies
A.J.R.
(1988)

T.M. Guerrero et al.

Characterization of a whole body imaging technique for PET

IEEE Trans. Nucl. Sci.

(1990)

U. Haberkorn et al.

Glucose uptake, perfusion, and cell proliferation in head and neck tumors: Relation of positron emission tomography to flow cytometry

J. Nucl. Med.

(1991)

F.M. Hall

Letters to the editor: Breast microcalcifications after lumpectomy and radiation therapy

Radiology

(1989)

R.A. Hawkins et al.

Pet cancer evalutions with FDG

J. Nucl. Med.

(1991)

R.A. Hawkins et al.

PET in clinical oncology

Cancer Metast. Rev.

(1988)

R.A. Hawkins et al.

Effects of temporal sampling, glucose metabolic rates and disruptions of the blood brain barrier on the FDG model with and without a vascular component. Studies in human tumors with PET

J. Cereb. Bid. Flow Metab.

(1986)

P.J. Hillsamer et al.

Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic res onance imaging

Arch. Otolaryngol. Head Neck Surg.

(1990)

C. Hoh et al.

PET total body imaging of breast cancer with F-18 ion, and FDG (Abstr.)

J. Nucl. Med.

(1990)

C.K. Hoh et al.

PET imaging of primary extracranial head and neck tumors with FDG (Abstr.)

J. Nucl. Med.

(1991)

T. Ido et al.

Labelled 2-deoxy-D-glucose analogs: 18F-labeled 2-deoxy-2-fluoro-D-mannose, and 14C-2 deoxy-2-fluoro-D-glucose

J. Label. Compd. Radiopharm.

(1978)

Cited by (102)

Positron Emission Tomography and head and neck cancers: Recurrence and post-treatment surveillance
2008, Medecine Nucleaire
Les récidives des cancers des voies aérodigestives supérieures (VADS) sont fréquentes, précoces et de mauvais pronostic. La surveillance post-thérapeutique a pour but de détecter une récidive le plus précocement possible pour pouvoir réaliser un traitement de rattrapage à visée curative. Les patients les plus à risque sont les cancers localement avancés. L’imagerie morphologique – scanner et imagerie par résonance magnétique (IRM) – peut parfois être limitée par les remaniements liés à la chirurgie et à la radiothérapie et ne permet pas toujours un diagnostic précoce. L’histologie pose le problème de sa morbidité en tissu irradié et du biais d’échantillonnage. La tomographie d’émission de positons (TEP) au 18F-fluoro-déoxy-glucose (FDG) a des performances supérieures aux techniques conventionnelles pour la recherche et la stadification d’une récidive, d’autant plus qu’elle est réalisée à trois mois de la fin des traitements. Sa sensibilité et sa valeur prédictive négative sont excellentes et permettent d’éviter des explorations multiples et invasives en cas de TEP-FDG négative. Au contraire, sa spécificité et sa valeur prédictive positive relativement limitées nécessitent de poursuivre les investigations en cas d’examen positif, pour éliminer les faux positifs. Dans le diagnostic de récidive, la TEP-FDG a un maximum d’impact sur la prise en charge et constitue un « standard ». En revanche, la réalisation d’une TEP-FDG systématique de surveillance n’est pas encore validée. Elle est recommandée dans les cas difficiles et dans le cadre de protocoles d’évaluation.
Recurrence of head and neck squamous cell carcinomas occurs early and currently, with poor prognosis. Post-therapeutic surveillance aims to diagnose a recurrence as early as possible in order to perform curative salvage therapy. The risk of recurrence is highest in locally advanced cancers. Morphological imaging, including Computed Tomography (CT Scan) and magnetic resonance imaging, can be limited by the anatomic changes following surgery and radiotherapy, and sometimes cannot provide early diagnosis of recurrence. Histology presents some risk of morbidity, especially in irradiated tissues, and sampling error. Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose (FDG) is superior to conventional imaging for the diagnosis and staging of recurrence, especially when it is performed three months after the end of treatments. FDG-PET has high sensitivity and negative predictive value for recurrence, so that further morphological and invasive investigations should not be performed in case of negative examination. On the other hand, because of its limited specificity and positive predictive value, any positive PET finding should be documented, in order to avoid false positives findings. The diagnosis of recurrence is the field of application in which FDP-PET has the greatest impact on head and neck cancer management: it is considered as a standard. However, the interest of FDG-PET during systematic follow-up has not yet been confirmed. PET should only be performed in difficult cases and within evaluation protocols.
Positron emission tomography in head and neck squamous cell carcinomas
2006, Annales d'Oto-Laryngologie et de Chirurgie Cervico-Faciale
La tomographie pas émission de positons (TEP) au ¹⁸F-Fluorodeoxyglucose est un examen qui s’impose de plus en plus en oncologie et semble devenir indispensable dans la prise en charge des carcinomes épidermoïdes de la tête et du cou.
Dans ce dossier thématique sont exposées les indications les plus courantes de la TEP : bilan initial, adénopathies cervicales métastatiques sans site primitif décelable et enfin le suivi post-thérapeutique.
Les avantages et limites de cet examen sont exposés, à partir de notre expérience et des données de la littérature. Des schémas décisionnels sont proposés pour chaque indication afin d’optimiser l’utilisation de cet examen dans la prise en charge de ces carcinomes épidermoïdes.
Les autres champs d’application de la TEP sont évoqués comme l’évaluation de la réponse au traitement en cours de chimiothérapie, l’intérêt de cet examen en radiothérapie ainsi que les développements biochimiques en cours portant sur les nouveaux traceurs.
¹⁸F-Fluorodeoxyglucose positron emission tomography (PET) is an imaging modality which is becoming increasingly esential in oncology, especially in the management of head and neck squamous cell carcinomas (SCC).
The most common uses of the PET are listed in this thematic study: initial staging, cervical lymph node metastases from an unknown primary tumor and post-therapeutic follow-up. The advantages and drawbacks of this imaging tool are wheighed here according to both our experience and data from the literature. Decision schemes are suggested for each use so as to optimize the use of this imaging modality in the management of these SCC.
Other fields of application for the PET are mentioned, such as the in-progress evaluation of response to chemotherapy, the interest of this imaging tool in radiotherapy as well as current biochemical developments concerning new tracers.
PET in head and neck cancers
2006, Presse Medicale
La TEP au FDG est utile lorsqu’on a diagnostiqué un cancer des voies aérodigestives supérieures (VADS) ou qu’on le soupçonne sans que l’histologie de la tumeur n’en ait apporté la preuve (sauf dans les tumeurs des glandes salivaires où cet examen n’est pas contributif) : elle permet par exemple de mettre en évidence des adénopathies suspectes dans des cas cliniquement N0, de déceler des sites suspects de métastases à distance ou de second cancer, et de préciser le pronostic. Du fait de la finesse des structures anatomiques en cause, la TEP bénéficie grandement, dans les cancers des VADS, de la fusion avec la TDM.
Dans l’évaluation précoce de l’efficacité de la chimiothérapie, l’absence d’une diminution significative de la fixation du FDG au bout d’un ou 2 cycles en prédit l’inefficacité : on pourra modifier le schéma thérapeutique. En revanche, si la disparition de la fixation du FDG est un élément de bon pronostic en ORL, elle ne peut affirmer l’absence de tout tissu cancéreux viable à l’issue de la chimiothérapie, néoadjuvante en particulier. La TEP au FDG trouve aussi une indication en fin de traitement pour évaluer la réponse et caractériser d’éventuelles masses résiduelles.
La recherche de récidive et la restadification d’une récidive connue est probablement l’indication où l’impact est le plus grand ; il faut savoir réaliser la TEP au FDG suffisamment tôt, et peut-être de façon systématique, pour que la récidive ait une chance d’être curable, mais suffisamment à distance des gestes thérapeutiques, pour éviter les résultats faux positifs liés à l’inflammation pour une bonne part. La stratégie reste à préciser ainsi que la place éventuelle de la TEP à la fluoroéthyltyrosine (FET) dans la recherche d’une récidive de ces carcinomes épidermoïdes.
FDG PET is useful when cancer in the head or neck (except for tumors of the salivary glands, which cannot be characterized accurately) is diagnosed or suspected but not confirmed by biopsy. It can, for example, find evidence of suspicious lymph nodes in clinically N0 necks, detect foci suggestive of distant metastases or second cancers, and provide useful prognostic information. Because it can be very difficult to identify anatomical structures and landmarks on PET images in the head and neck region, PET/CT fusion is very helpful in this area.
In early assessment of chemotherapy, the absence of a significant reduction in FDG uptake after one or two cycles predicts lack of efficacy and thus indicates the need to modify the regimen. Conversely, the disappearance of FDG foci indicates effective treatment and good prognosis but cannot rule out the persistence of any malignant tissue at the end of treatment, especially neoadjuvant.
Diagnostic impact is probably greatest in monitoring for recurrence and restaging known recurrence: FDG PET should be performed - perhaps routinely - early enough that curative options are still open, but long enough after the end of treatment to avoid false positive results from inflammation. The strategy and timing of FDG PET during follow-up should be determined in more detail in the future, as should the role (if any) of fluorotyrosine (FET) PET in squamous cell carcinoma.
<sup>18</sup>F-FDG-PET for evaluation of the response to concurrent chemoradiation therapy with intensity-modulated radiation technique for Stage T4 nasopharyngeal carcinoma
2006, International Journal of Radiation Oncology Biology Physics
Purpose: This article evaluates [¹⁸F] fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) findings as a predictor for local responders (R) vs. nonresponders (NR) in nasopharyngeal carcinoma (NPC) patients with Stage T4 lesions, before and at 3 months after completion of concurrent chemotherapy and radiation therapy (CCRT).
Methods and Materials: From January 2002 to November 2003, 39 T4 NPC patients were enrolled. All had magnetic resonance imaging and ¹⁸F-FDG-PET, both before and 3 months after CCRT. Any residual/recurrent lesions were confirmed histopathologically.
Results: Of the 39 eligible patients, after a follow-up of 24.2 ± 9.5 months, 35 became disease-free and 4 had residual or recurrent disease. Marginal differences in standard uptake values (SUV) were observed (10.9 ± 5.3 vs. 15.6 ± 3.4, p = 0.058) between R and NR before treatment, and value changes of SUV before and after CCRT were not significantly different. However, highly significantly lower values of SUV were noted for R than for NR 3 months after completion of CCRT (2.1 ± 0.8 vs. 5.5 ± 3.2, p = 0.001). One hundred percent positive and negative predictive values were observed for SUV values of 4.0, set 3 months after completion of CCRT.
Conclusions: Neither the pretreatment SUV nor the changes of SUV between pretreatment and posttreatment were significant predictors for local response. SUV at 3 months after completion of CCRT was a significant determinator for local response. The cutoff of 4.0 for SUV at 3 months after completion of CCRT was useful to be offered as a diagnostic reference for recurrent or residual tumor for NPC treatment.
Evaluation of efficacy and clinical impact of positron emission tomography with 18f fluoro-deoxyglucose (FDG) in patients with suspicion of recurrent laryngeal carcinoma
2006, Acta Otorrinolaringologica Espanola
Evaluar la eficacia y el impacto clínico de la PET-FDG en la detección de recurrencias en pacientes tratados de carcinoma epidermoide de laringe
Se estudiaron de forma retrospectiva 15 pacientes, con sospecha de recurrencia, y pruebas morfológicas convencionales equívocas. A todos se les realizó una PET-FDG (ECAT HR+) tras la inyección de 370-444 MBq de 18-FDG. Los resultados de la PET fueron evaluados por tres médicos nucleares, y se confirmaron por histología o por seguimiento clínico superior a 12 meses
La prevalencia de la recurrencia en nuestra serie fue del 86,6%, obteniéndose 13 verdaderos positivos y 2 verdaderos negativos. La PET modificó la actitud terapéutica en 10 pacientes, obteniendose un impacto clínico del 63,3%. La exactitud diagnóstica, sensibilidad y especificidad fue del 100%
La PET-FDG es la técnica de elección para evaluar los pacientes con sospecha de recurrencia de carcinoma de laringe, que presentan pruebas morfológicas convencionales equívocas
To evaluate the efficacy and clinical impact of FDG-PET in patients with suspected recurrent laryngeal carcinoma
15 patients, with suspicion of recurrent laryngeal carcinoma and ambiguous conventional imaging modalities. In all patients a whole body scan was performed with FDG-PET in fasting patients following i.v. administration of 370-444 MBq FDG. The results were confirmed by histology and clinical evolution (follow-up period >12 months)
Prevalence of recurrence was 86.6%. FDG-PET was positive in 13 patients, with confirmation in all cases, and 2 were true negative (TN). Overall sensitivity, specificity, PPV, NPV and accuracy were 100%. FDG-PET changed the modality of treatment in 10 patients (clinical impact 63.3%)
FDG-PET has high clinical impact in patients with a suspicion of recurrent laryngeal carcinoma, and should be incorporated to the diagnostic protocols before making a therapy decision
Early evaluation of the response to radiotherapy of patients with squamous cell carcinoma of the head and neck using <sup>18</sup>FDG-PET
2005, Oral Oncology
The aim was to evaluate the efficacy of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-d-glucose (FDG) in early discrimination of response to definitive radiotherapy (RT) in patients with squamous cell carcinoma of the head and neck (SCCHN). Twenty-four patients who underwent FDG-PET scans before and after radiotherapy for nondisseminated SCCHN at the Asan Medical Center between August 2001 and September 2002 were prospectively evaluated. Initial FDG-PET scans were performed within 1 month before RT, and follow-up FDG-PET scans were performed 1 month after completion of RT. FDG-PET images were analyzed by standard uptake value (SUV). All patients were followed for more than 6 months. Pretreatment SUV ranged from 3.4 to 14.0 (median, 6.0), while posttreatment SUV ranged from ground level to 7.7 (median, 2.0). In evaluating residual tumors in these SCCHN patients, the overall sensitivity of FDG-PET was 100%, while its overall specificity was 87%. FDG-PET is effective in evaluating the response to radiation in patients with SCCHN. Timing the follow-up FDG-PET scan 1 month after completion of RT was not too rapid for evaluating the response to radiation.

View all citing articles on Scopus

^☆: Presented as the recipient of the Resident Essay Award at ASTRO on November 10, 1992, San Diego, CA.

^∗: Department of Radiation Oncology, Jonsson Comprehensive Cancer Clinic, UCLA School of Medicine.

^†: Division of Nuclear Medicine and Biophysics, Department of Radiological Sciences, UCLA School of Medicine.

View full text

Radiation oncologic imagingPositron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy☆

Abstract

Int. J. Radiat. Oncol. Biol. Phys.

Appl. Radiat. Isot.

Assessment of radiotherapeutic effects on experimental tumors using 18F-2-fluoro-2-deoxy-D-glucose

Eur. J. Nucl. Med.

False-positive and falsenegative neck nodes

Head Neck Surg.

Positron emission tomography: A new, precise imaging modality for detection of primary head and neck tumors and assessment of cervical adenopathy

Laryngoscope

Evaluation of primary head and neck tumor with PET-FDG (Abstr.)

Clin. Nucl. Med.

Whole body positron emission tomography: Part I: Methods and performance characteristics

J. Nucl. Med.

Positron emission tomography using [18F]Fluorodeoxyglucose in brain tumors. A powerful diagnostic and prognostic tool

Invest. Radiol.

Cerebral Necrosis after radiotherapy and/or intraarterial chemotherapy for brain tumors: PET and neuropathologic studies

A.J.R.

Characterization of a whole body imaging technique for PET

IEEE Trans. Nucl. Sci.

Glucose uptake, perfusion, and cell proliferation in head and neck tumors: Relation of positron emission tomography to flow cytometry

J. Nucl. Med.

Letters to the editor: Breast microcalcifications after lumpectomy and radiation therapy

Radiology

Pet cancer evalutions with FDG

J. Nucl. Med.

PET in clinical oncology

Cancer Metast. Rev.

Effects of temporal sampling, glucose metabolic rates and disruptions of the blood brain barrier on the FDG model with and without a vascular component. Studies in human tumors with PET

J. Cereb. Bid. Flow Metab.

Improving diagnostic accuracy of cervical metastases with computed tomography and magnetic res onance imaging

Arch. Otolaryngol. Head Neck Surg.

PET total body imaging of breast cancer with F-18 ion, and FDG (Abstr.)

J. Nucl. Med.

PET imaging of primary extracranial head and neck tumors with FDG (Abstr.)

J. Nucl. Med.

Labelled 2-deoxy-D-glucose analogs: 18F-labeled 2-deoxy-2-fluoro-D-mannose, and 14C-2 deoxy-2-fluoro-D-glucose

J. Label. Compd. Radiopharm.

Radiation oncologic imaging
Positron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy☆