Journal of Cancer Research and Therapeutics Medknow Publications on behalf of the Association of Radiation Oncologists of India (AROI) ISSN: 0973-1482 EISSN: 1998-4138 Vol. 6, Num. 3, 2010, pp. 290-295

Journal of Cancer Research and Therapeutics, Vol. 6, No. 3, July-September, 2010, pp. 290-295

Original Article

Usefulness of whole body FDG18 PET-CT imaging in comprehensive oncologic management - initial experience

Ashish S Kumar¹, Manas T Mayank², Mayur V Kandedia³, Yogesh M Mistry⁴

¹ Department of Radiation Oncology, Kailash Cancer Hospital & Research Institute, Vadodara, Gujarat, India
² Department of Nuclear Medicine, Kailash Cancer Hospital & Research Institute, Vadodara, Gujarat, India
³ Department of Radiodiagnosis, Kailash Cancer Hospital & Research Institute, Vadodara, Gujarat, India
⁴ Department of Oncopathology, Kailash Cancer Hospital & Research Institute, Vadodara, Gujarat, India

Correspondence Address:Ashish S Kumar, Quarter no 7, Muniseva Ashram post- Goraj, TA- Waghodia, Vadodara, Gujarat 391760, India, xray.beam@yahoo.in

Code Number: cr10065

PMID: 21119255

DOI: 10.4103/0973-1482.73362

Abstract

Keywords: Fluorine-18-flurodeoxyglucose, positron emission tomography, computed tomography

Introduction

Standard radiologic imaging modalities are based on morphologic diagnostic criteria such as contrast enhancement and nodal size that do not always reflect true staging. After treatment, these anatomical imaging are widely used to evaluate response and early diagnosis of recurrence. However, because of anatomical distortion by surgery or radiotherapy, the distinction between post- treatment changes and recurrence or residual disease is difficult to make with imaging modalities that rely on morphologic criteria. ^[1] Fluorine-18-flurodeoxyglucose (FDG) positron emission tomography (PET) plays an increasing role in primary staging, ^[2] pre therapy and post therapy management of cancer. ^[3],[4] PET, a functional imaging modality, assesses the metabolic status of treatment and has been proved to be superior to CT and MRI in differentiating recurrence from post radiotherapy and surgery changes in treated patients as well as diagnosis of distant metastasis. ^[5] PET imaging is limited by lack of anatomic boundaries and the exact location of suspicious findings is therefore difficult. Variable physiological and inflammatory uptake of FDG mainly after treatment can also confuse understanding of suspicious foci. The combined imaging modality PET-CT allows sequential acquisition in a single session that provides information about anatomical changes along with metabolic changes associated through disease process with precise localization. Various literatures suggest the role of hybrid PET-CT imaging in the modern comprehensive oncologic management. ^[6]

Materials and Methods

Whole body FDG18 PET-CT scan was requested for various clinical reasons i.e. treatment response evaluation, staging and radiotherapy planning.

Scanning procedure :Scanner: BGO plus, full ring PET-CT (GE discovery STE), Radio-isotope: 18F-FDG-370 MBq and 45 min uptake period. Study mode: PET-3D mode and CT-120KvAutomA. Extent of study: Vertex to lower end of thigh. Contrast: Diluted oral contrast/I.V. non-ionic contrast.

A total of 29 initial different patients were evaluated by nuclear medicine physician, radiologist and treating physicians together since we have started PET-CT imaging facility in our hospital. None of these 29 patients had PET-CT imaging before, but all had routine CT imaging (2 to7 days before PET-CT) for routine staging, radiotherapy planning and response evaluation. These all PET-CT scans were evaluated in three different groups with different purposes namely treatment response evaluation, staging and radiotherapy planning, respectively. These scans were then compared with routine CT imaging performed earlier at various places including our hospital (range two to seven days).

First group: (n=12) FDG18 PET-CT scan was used for diagnosis of suspected recurrence or residual disease following curative radio-chemotherapy. Evaluation was done after achievement of more than three months (range of >3 to 7 months) of radio-chemotherapy to avoid false positive results. ^[14] Patient profile is described in [Table - 1].

Second group: (n=10) FDG18: PET-CT scan was used as an additional diagnostic tool where CT scan with intravenous contrast, alone was unconvincing. These patients were initially considered for curative radiotherapy (radical/adjuvant) +/- chemotherapy but had suspicious distant metastatic lesions and less apparent loco-regional tumor extent in radiotherapy planning CT scan. Patient profile is described in [Table - 2].

Third group - (n=7): This group included all head and neck cancer patients. FDG18 PET-CT scan was used like conventional CT scan for delineating gross target volume (GTV) during simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) where hypermetabolic volume or biologic target volume delineated on PET image (GTV-PET) was compared with gross target volume delineated on CT image (GTV-CT). Patient profile is described in [Table - 3].

Before target delineation, all patients were simulated in treatment position with thermoplastic mask as immobilization device. Both CT and PET scans were acquired sequentially while patient remained positioned in the thermoplastic mask. Subsequently, target delineation was completed on registered images of PET (GTV-PET) and CT (GTV-CT) with the help of advantage-simMD workstation (GE) separately. In first and second group, FDG uptake was recorded corresponding to primary, regional and distant site of involvement by the disease process. In third group, the change in target volume obtained from PET images with respect to CT images was recorded in excel sheets. We also analyzed cost-benefit concern with FDG18 PET-CT imaging as compared to conventional CT imaging in terms of overall expenditure to the population during cancer management for second group of patients.

Results

In first group (n=12), 6/12 (50 %) patients had distant systemic disease, 4/12 (33%) had residual regional disease and 7/12 (58%) had residual/recurrent local disease [Table - 4]. This residual/recurrent and distant involvement by the disease in the form of hypermetabolic FDG uptake was subsequently correlated with microscopic pathological examination. 1 (8%) patient had suspicious local active disease (borderline metabolic uptake of SUV 2.4) and 1 (8%) patient had solitary lung metastasis on PET-CT that turned out to be negative for recurrent/metastatic disease after histopathological examination. In second group (n=10), 3/10 (30%) patients had distant systemic disease where CT imaging was not showing involvement [Table - 5]. 1/10 (10%) patient had generalized disease spread where PET-CT imaging picked the primary site. 4/10 (25%) patients had variable extent of disease involvement in PET-CT as compared to CT imaging that changed the technique of radiotherapy treatment. In 2/10 (20%) patients, PET-CT facilitated to change the line of management. In third group (n=7) that specifically addressed the radiotherapy planning process of head and neck cancers, PET delineated volume (GTV-PET) was significantly higher (10-50%) than CT delineated volume (GTV-CT) for local site [Table - 6]. For regional involvement, PET delineated volume correlated well with CT delineated volume with the difference of <10%. When we analyzed the cost-benefit issue for second group of patients, we found 3/10 patients, who were initially taken for curative treatment that usually cost Rs 60 thousand per patient, and were now shifted to palliative treatment that usually cost Rs 10 thousand per patient at our hospital. After considering overall cost to this population group including cost for PET-CT imaging and average treatment cost, we found PET-CT imaging does not add burden, but in actual fact it guided clinicians to accept right treatment approach.

Discussion

After definitive radio-chemotherapy, the accuracy of combined PET-CT imaging to detect residual/recurrent local disease was higher than that of contrast-enhanced CT imaging (7/12 vs 4/12) in first group of patients. In our study, the overall specificity of CT imaging in detecting residual or recurrent disease was 71.4% and specificity of 80% as compared with 100% and 100 %, respectively for PET-CT imaging. One patient who had suspicious borderline FDG uptake was not considered as true positive case for PET-CT imaging. Similarly, overall sensitivity for CT imaging for detecting residual regional disease was 100% and specificity of 50% as compared with 100% and 100 %, respectively, for PET-CT imaging. Sensitivity and specificity of PET-CT imaging for detecting distant metastatic disease was 100% and 83.3%, respectively. Definitive radiation therapy with chemotherapy is increasingly used in patients to preserve organ function. Accurate assessment of treatment response has become crucial in these patients because salvage therapies such as surgery, additional chemotherapy or radiation therapy can be initiated in a timely manner in those in whom treatment fails. ^[7] Current anatomic imaging methods based on recognition of abnormal masses are inadequate in assessing whether or not viable tumor is present. ^[8] The metabolic information from FDG18 PET has been reported to be very useful in the assessment [Figure - 1],[Figure - 2],[Figure - 3] of treatment response. ^[9]

Several studies in lymphoma and esophageal cancer have shown that PET-CT imaging has a higher accuracy compared with CT imaging for the assessment of residual disease and is also predictive of patient outcome. ^{[10],[11],[12]} In our study, PET-CT produced one false-positive result in a patient with increased FDG uptake in the lung. It is usually accepted that radiation therapy may result in substantial inflammatory changes that can result in increased FDG uptake corresponding to metabolic activity of the affected tissue. ^[13] We found the FDG uptake in the radiation field to be generally diffuse and of low or moderate intensity; though false-positive PET-CT imaging findings caused by the increased metabolic activity of inflammatory and reparative changes may not be entirely avoidable. A significant advantage of PET-CT imaging is the ability to precisely localize areas of abnormal metabolic activity and guide subsequent biopsies. ^[14] In second group, four patients′ PET-CT imaging showed different extent of disease involvement at primary site and it guided radiation oncologist to select the technique of radiation that has optimal therapeutic ratio (3DCRT vs IMRT). Three patients who had distant metastasis were shifted to palliative therapy but solitary liver metastasis was detected in one patient, only on PET image underwent metastectomy followed by adjuvant therapy [Figure - 4],[Figure - 5],[Figure - 6]. In our study, patient presented with unknown primary had primary disease in kidney. ^[15] In IMRT, precise definition of the GTV was crucial to achieve a good outcome. Underestimation of the tumor volume implies local failure and overestimation consequences in more radiation- induced toxicities. In cases with unclear tumor boundaries on CT and MRI, PET-CT imaging could be helpful in the delineation of tumor predominantly in evaluating borderline disease such as swollen tissue adjacent to tumor. ^[16],[17] In our series, PET-CT delineated volume was significantly higher (10-50%) than CT delineated volume intended for (difference range 5.3 cc to 38 cc) local site. For regional involvement, PET delineated volume correlated well with CT delineated volume with the difference of <10% (difference range 4cc to 11.3 cc). Although the quality of the information obtained from biologic imaging is unquestionable in most cases, the quantitative interpretation of PET signals is less obvious. Stringent region growing algorithms of PET signals might not respect the individual situation at its best. Standardized computed tools are at risk for biased interpretation. In fact, a fixed threshold to define the edge of a target will result in underestimation of the target volume, which may explain the observations that PET-defined target radiotherapy may reduce portal beams frequently. ^[18] We accepted visual methods rather than quantitative methods for target delineation to avoid biased interpretation. ^[19] The most accurate method of margin definition for the target lesions is yet to be defined. Another concern encountered in our series is the mismatch between PET and CT data when patient remained positioned in thermoplastic mask for approximately 45 min. Coregistration error should always be considered and corrected for radiotherapy treatment planning. Scanning time can be reduced (15-20 min) by scanning only the head and neck region on CT as well as PET, and because this requires fewer amounts of FDG and smaller CT field, it will reduce the total radiation exposure for the patient. PET-CT has limited use in the setting of response-adapted radiotherapy because of difficulty in differentiation in the mucositis and target volume on the FDG-PET-CT.

Conclusions

Though our study includes less number of patients with the initial use of FDG18 PET-CT imaging, we realized that rate of distant metastasis is much higher which frequently get unobserved because of conventional approach of investigation specially in developing countries where resources and awareness is not homogenously distributed. Even in institutes where PET-CT facility is not there, concern should be given for much generous CT imaging. FDG18 PET-CT imaging has potential to change the way of conventional IMRT planning especially in head and neck cancer patients. Though investment cost for an institute is higher, it does not add burden to the patient group.

References

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