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Clinical utility of FDG–PET for radiation oncology—predict early regrowth of malignant tumor after irradiation
International Congress Series 1264 (2004) 84 – 87
www.ics-elsevier.com
Clinical utility of FDG–PET for radiation oncology—predict early regrowth of malignant tumor after irradiation Tomio Inoue, Izumi Koike * Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
Abstract. Aim: We evaluate a presence of residual tumor in the radiation field just after completion of therapy by using the FDG – PET scan. Methods and materials: A total of 20 patients (13 men and 7 women; age range, 30 – 88 years) with malignant tumors were included in this study. All patients received radiation. FDG – PET studies were performed twice in all 20 patients. The first PET study was performed prior to the initiation of therapy, and the second was performed within 10 days after completion of radiation therapy. Results: Retention index [RI: (SUVmax on delayed image SUVmax on early image)/SUVmax on early image] showed a significant difference between patients with relapse and no relapse. Conclusions: Dual time point FDG – PET imaging just after irradiation can predict early regrowth of malignant tumors at 3 months postradiation therapy. D 2004 Published by Elsevier B.V. Keywords: FDG – PET; Radiotherapy; Malignant tumor
1. Introduction An early and accurate evaluation of the effect of radiation therapy on malignant lesions may help guide appropriate patient management after irradiation. Although conventional noninvasive imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), may provide excellent morphological information for the detection of primary or metastatic lesions, these modalities often cannot differentiate between recurrent or residual tumor and posttreatment changes. Furthermore, conventional imaging modalities may be an inaccurate early assessment tool because morphological changes may not appear immediately after completion of radiation therapy. FDG –PET has been proven to be clinically useful for initial diagnosis, staging, and restaging of various malignant tumors. Because FDG accumulates not only in residual malignant tumor cells but also in reactive inflammatory cells after irradiation, the clinical utility of FDG – PET for assessing residual tumor cells immediately following the completion of radiation
* Corresponding author. Tel.: +81-45-787-2696; fax: +81-45-786-0369. E-mail address: [email protected] (I. Koike). 0531-5131/ D 2004 Published by Elsevier B.V. doi:10.1016/j.ics.2004.01.004
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85
therapy is still controversial because subacute inflammatory reaction by radiation effect may cause an intense FDG uptake in the irradiation field. Can we evaluate the presence of residual tumor in the radiation field just after the completion of therapy by using the FDG –PET scan? 2. Aim The purpose of this study is to clarify whether dual time point FDG – PET can predict early regrowth of malignant tumors at 3 months postradiation therapy. 3. Methods and materials 3.1. Patients A total of 20 patients (13 men and 7 women; age range, 30– 88 years) treated by irradiation were included in this study. Four had hypopharyngeal cancer, three had esophageal cancer, three had tongue cancer, three had malignant lymphoma, two had paranasal cancer, one had oropharyngeal cancer, one had lung cancer, one had retroperitoneal sarcoma, one had pelvic cancer, and one had uterine cervical cancer. Twenty-six lesions were evaluated in this study. The therapeutic regimens were as follows: nine patients had chemoradiation therapy, eight had external radiation therapy alone, two had interstitial brachytherapy, and one had a combined therapy of external radiation and interstitial brachytherapy. 3.2. Protocol Prior to and just after completion of radiotherapy, we measured tumor volume using CT or ultrasonic tomography (US). We evaluated early tumor response just after radiotherapy completion and classified it into three grades: no change (NC), partial response (PR), and complete remission (CR). We evaluated outcome at 3 months postradiation therapy. Residual/recurrent tumors were confirmed in six patients by CT/US image interpretation that showed increased tumor volume (n = 4) or histopathological testing revealing squamous cell carcinoma (n = 2). FDG –PET studies were performed twice in all 20 patients. The first PET study was performed prior to initiation of therapy, and the second was performed within 5 days after completion of radiation therapy. We draw a circular region of interest of approximately 35– 55 pixels (5.6 – 8.8 cm2) on the SUV image over the area that included the site of maximum FDG accumulation in the lesion. Maximum SUV in the ROI was defined as tumor SUV. Using data derived from early and delayed images in the second study just after the completion of radiation therapy, we calculated the retention index (RI), namely, (SUVmax on delayed image SUVmax on early image)/SUVmax on early image. The significance of the difference in SUVmax, RI, and percent reduction of tumor volume between the patients with and without residual/recurrent tumors at 3 months postirradiation were statically analyzed by means of the nonparametric Mann – Whitney U test.
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4. Results and discussion We investigated the relationship between patients’ outcome and SUV-related indices of FDG –PET. The retention index showed a significant difference between patients with relapse and no relapse. Three other indices derived from FDG –PET, pre-SUV, early SUV, and delayed SUV, after irradiation, indicated no significant differences between patients with residual tumors and those without residual tumors at 3 months. Percent reduction in tumor volume just after irradiation also showed a significant difference (Table 1). All lesions with residual tumor revealed less than 80% tumor volume reduction just after the completion of radiation therapy. However, among 17 lesions without residual tumor, five lesions in five patients showed less than 80% tumor volume reduction just after completion of radiation therapy All nine lesions, in six patients with residual tumor, showing more than 0.1 on the retention index revealed residual tumors 3 months later (negative predictive value, 100%). Nine out of 13 lesions with more than 0.1 on the retention index showed detectable residual tumors 3 months later (positive predictive value, 69.2%). However, the other four lesions with more than 0.1 on the retention index had no detectable residual tumors, were locally advanced, and were demonstrated histopathologically to be squamous cell carcinomas (three tumors) or a desmoplastic small round cell tumor (one tumor). Tumor sites were esophagus (n = 2), frontal sinus (n = 1), and sacrum (n = 1). The analysis of SUV in either conventional FDG –PET (at 1 h postinjection) or delayed FDG –PET (at 3 h postinjection) could not evaluate therapeutic effect on tumor cells just after the completion of irradiation. FDG uptake in reactive inflammatory cells induced by irradiation may increase SUV in the lesion within the radiation field. SUVs at single time points may not be reliable to characterize residual tumors. In our study, only the retention index of FDG could be useful for predicting residual tumor (Table 1). In addition, no lesions with less than 0.1 RI revealed residual tumors. Consequently, we attempted to apply this phenomenon to the evaluation of therapeutic effect on tumor cells just after completion of fractionated irradiation.
Table 1 Results of semiquantitative indices and percent reduction in tumor volume Index
Residue + (n = 9)
Pre-SUVa Early SUVb Delayed SUVc RId Reduction (%)
9.200 F 4.071 3.224 F 1.925 4.225 F 2.896 0.320 F 0.265 41.4 F 26.7
Values are mean F standard deviation. a Maximum SUV at early scan before treatment. b Maximum SUV at early scan after treatment. c Maximum SUV at delayed scan after treatment. d Retention index on posttreatment image.
Residue
(n = 17)
8.686 F 5.468 2.694 F 2.207 2.729 F 2.557 0.008 F 0.214 81.4 F 21.2
P value NS NS NS < 0.0025 < 0.0005
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Tumor size measurement by CT has long been the standard method of assessing therapeutic effect on malignant tumors. On the other hand, tumor metabolism assessed by FDG –PET may change earlier than the volume reduction measured by CT and MRI. In our study, even if masses remained just after radiation, those with less than 0.1 RI showed no recurrent disease at 3 months postradiation therapy. 5. Conclusions Dual time FDG –PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors. This imaging technique might prove to be an important tool for evaluating the need for additional treatment.
www.ics-elsevier.com
Clinical utility of FDG–PET for radiation oncology—predict early regrowth of malignant tumor after irradiation Tomio Inoue, Izumi Koike * Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan
Abstract. Aim: We evaluate a presence of residual tumor in the radiation field just after completion of therapy by using the FDG – PET scan. Methods and materials: A total of 20 patients (13 men and 7 women; age range, 30 – 88 years) with malignant tumors were included in this study. All patients received radiation. FDG – PET studies were performed twice in all 20 patients. The first PET study was performed prior to the initiation of therapy, and the second was performed within 10 days after completion of radiation therapy. Results: Retention index [RI: (SUVmax on delayed image SUVmax on early image)/SUVmax on early image] showed a significant difference between patients with relapse and no relapse. Conclusions: Dual time point FDG – PET imaging just after irradiation can predict early regrowth of malignant tumors at 3 months postradiation therapy. D 2004 Published by Elsevier B.V. Keywords: FDG – PET; Radiotherapy; Malignant tumor
1. Introduction An early and accurate evaluation of the effect of radiation therapy on malignant lesions may help guide appropriate patient management after irradiation. Although conventional noninvasive imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI), may provide excellent morphological information for the detection of primary or metastatic lesions, these modalities often cannot differentiate between recurrent or residual tumor and posttreatment changes. Furthermore, conventional imaging modalities may be an inaccurate early assessment tool because morphological changes may not appear immediately after completion of radiation therapy. FDG –PET has been proven to be clinically useful for initial diagnosis, staging, and restaging of various malignant tumors. Because FDG accumulates not only in residual malignant tumor cells but also in reactive inflammatory cells after irradiation, the clinical utility of FDG – PET for assessing residual tumor cells immediately following the completion of radiation
* Corresponding author. Tel.: +81-45-787-2696; fax: +81-45-786-0369. E-mail address: [email protected] (I. Koike). 0531-5131/ D 2004 Published by Elsevier B.V. doi:10.1016/j.ics.2004.01.004
T. Inoue, I. Koike / International Congress Series 1264 (2004) 84–87
85
therapy is still controversial because subacute inflammatory reaction by radiation effect may cause an intense FDG uptake in the irradiation field. Can we evaluate the presence of residual tumor in the radiation field just after the completion of therapy by using the FDG –PET scan? 2. Aim The purpose of this study is to clarify whether dual time point FDG – PET can predict early regrowth of malignant tumors at 3 months postradiation therapy. 3. Methods and materials 3.1. Patients A total of 20 patients (13 men and 7 women; age range, 30– 88 years) treated by irradiation were included in this study. Four had hypopharyngeal cancer, three had esophageal cancer, three had tongue cancer, three had malignant lymphoma, two had paranasal cancer, one had oropharyngeal cancer, one had lung cancer, one had retroperitoneal sarcoma, one had pelvic cancer, and one had uterine cervical cancer. Twenty-six lesions were evaluated in this study. The therapeutic regimens were as follows: nine patients had chemoradiation therapy, eight had external radiation therapy alone, two had interstitial brachytherapy, and one had a combined therapy of external radiation and interstitial brachytherapy. 3.2. Protocol Prior to and just after completion of radiotherapy, we measured tumor volume using CT or ultrasonic tomography (US). We evaluated early tumor response just after radiotherapy completion and classified it into three grades: no change (NC), partial response (PR), and complete remission (CR). We evaluated outcome at 3 months postradiation therapy. Residual/recurrent tumors were confirmed in six patients by CT/US image interpretation that showed increased tumor volume (n = 4) or histopathological testing revealing squamous cell carcinoma (n = 2). FDG –PET studies were performed twice in all 20 patients. The first PET study was performed prior to initiation of therapy, and the second was performed within 5 days after completion of radiation therapy. We draw a circular region of interest of approximately 35– 55 pixels (5.6 – 8.8 cm2) on the SUV image over the area that included the site of maximum FDG accumulation in the lesion. Maximum SUV in the ROI was defined as tumor SUV. Using data derived from early and delayed images in the second study just after the completion of radiation therapy, we calculated the retention index (RI), namely, (SUVmax on delayed image SUVmax on early image)/SUVmax on early image. The significance of the difference in SUVmax, RI, and percent reduction of tumor volume between the patients with and without residual/recurrent tumors at 3 months postirradiation were statically analyzed by means of the nonparametric Mann – Whitney U test.
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T. Inoue, I. Koike / International Congress Series 1264 (2004) 84–87
4. Results and discussion We investigated the relationship between patients’ outcome and SUV-related indices of FDG –PET. The retention index showed a significant difference between patients with relapse and no relapse. Three other indices derived from FDG –PET, pre-SUV, early SUV, and delayed SUV, after irradiation, indicated no significant differences between patients with residual tumors and those without residual tumors at 3 months. Percent reduction in tumor volume just after irradiation also showed a significant difference (Table 1). All lesions with residual tumor revealed less than 80% tumor volume reduction just after the completion of radiation therapy. However, among 17 lesions without residual tumor, five lesions in five patients showed less than 80% tumor volume reduction just after completion of radiation therapy All nine lesions, in six patients with residual tumor, showing more than 0.1 on the retention index revealed residual tumors 3 months later (negative predictive value, 100%). Nine out of 13 lesions with more than 0.1 on the retention index showed detectable residual tumors 3 months later (positive predictive value, 69.2%). However, the other four lesions with more than 0.1 on the retention index had no detectable residual tumors, were locally advanced, and were demonstrated histopathologically to be squamous cell carcinomas (three tumors) or a desmoplastic small round cell tumor (one tumor). Tumor sites were esophagus (n = 2), frontal sinus (n = 1), and sacrum (n = 1). The analysis of SUV in either conventional FDG –PET (at 1 h postinjection) or delayed FDG –PET (at 3 h postinjection) could not evaluate therapeutic effect on tumor cells just after the completion of irradiation. FDG uptake in reactive inflammatory cells induced by irradiation may increase SUV in the lesion within the radiation field. SUVs at single time points may not be reliable to characterize residual tumors. In our study, only the retention index of FDG could be useful for predicting residual tumor (Table 1). In addition, no lesions with less than 0.1 RI revealed residual tumors. Consequently, we attempted to apply this phenomenon to the evaluation of therapeutic effect on tumor cells just after completion of fractionated irradiation.
Table 1 Results of semiquantitative indices and percent reduction in tumor volume Index
Residue + (n = 9)
Pre-SUVa Early SUVb Delayed SUVc RId Reduction (%)
9.200 F 4.071 3.224 F 1.925 4.225 F 2.896 0.320 F 0.265 41.4 F 26.7
Values are mean F standard deviation. a Maximum SUV at early scan before treatment. b Maximum SUV at early scan after treatment. c Maximum SUV at delayed scan after treatment. d Retention index on posttreatment image.
Residue
(n = 17)
8.686 F 5.468 2.694 F 2.207 2.729 F 2.557 0.008 F 0.214 81.4 F 21.2
P value NS NS NS < 0.0025 < 0.0005
T. Inoue, I. Koike / International Congress Series 1264 (2004) 84–87
87
Tumor size measurement by CT has long been the standard method of assessing therapeutic effect on malignant tumors. On the other hand, tumor metabolism assessed by FDG –PET may change earlier than the volume reduction measured by CT and MRI. In our study, even if masses remained just after radiation, those with less than 0.1 RI showed no recurrent disease at 3 months postradiation therapy. 5. Conclusions Dual time FDG –PET imaging just after irradiation is potentially useful for predicting early regrowth of malignant tumors. This imaging technique might prove to be an important tool for evaluating the need for additional treatment.