Evaluation of PET/CTRole in Diagnosis and Management of Pediatric Malignancy

Abaza A 1 .and ElShanshoury G 2 . 1. Assistant Prof. of Safety and Prevention of Oncologyin Radiation Protection Department, Nuclear and Radiological Regulatory Authority, Cairo, Egypt. PhD, M.D in Childhood Studies & Pediatric Oncology, AinShams University, Cairo, Egypt. 2. Assistant Prof.of Applied Statisticin Radiation Safety Department,Nuclear and Radiological Regulatory Authority, Cairo, Egypt.PhD inApplied Statistic,Ain-Shams University, Cairo, Egypt. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


ISSN: 2320-5407
Int. J. Adv. Res. 5(1), 408-419 409 local recurrence at the end of treatment; and 96.20%, 98.30%, 92.60%, and 99.10% after 1y of treatment. The sensitivities and specificities of 18F-FDG PET/CT for initial staging of malignant lymphomas are83.3%-100% and 93.75%-100% respectively. It ranged 66.70%-100% and 91.30%-100% respectively in sarcoma and 86.70%-100% and 95.80%-100% respectively in Neuroblastoma. Conclusion: The study concluded that the 18F-FDG PET/CT is the gold standard for noninvasive functional imaging in oncology. Technical developments in PET scanning in cancer management may increase the precision of radiotherapy planning and thus improve tumor control and reduce treatment-related morbidity. Recommendation regarding the use of PET/CT in the management of pediatric malignancy to facilitates the sparing of normal structures and the escalation of dose.

Introduction:-
The presence of distant metastases is one of the most important prognostic factors in most cancer patients. Most tumors are classified according to the TNM staging system, and treatment is modified when distant metastases are present. Disease localized to primary sites and to regional lymph nodes is generally treated with curative strategies, including surgery, chemotherapy, and radiotherapy. In contrast, palliative treatment of patients with metastatic disease consists of less aggressive strategies. Moreover, distant metastases usually occur late during the course of cancer, whereas second primary cancers may be found even in early-stage patients. Early detection of distant metastases and second primary cancers is a fundamental precondition for guiding precise staging and optimal management (Xu et  The study aimed to retrospectively reviewed our initial clinical experience with FDG PET/CT in pediatric malignancies to evaluate the efficacy of this new imaging system and to determine if PET/CT provided additional 410 diagnostic information on disease status; the study also, evaluate the efficacy of this imaging technique in the management of some pediatric malignancies.

Materials and methods:-
One hundred and eighty pediatric patients (118(65.6%)male and 62(34.4%) female) with suspected or known malignancy, evaluated by 18 F-FDG imaging using a combined PET/CT system, between January 2011 and January 2015, included in the study. The male to female ratio was 2.27:1.The patient' stage was from 6 month to 19 years (y) old with a median age of 12 y at their first PET/CT examination. 141 (78.3%) of the patients were below 10 years old.One hundred patients had lymphoma (82 Hodgkin and 18 Non-Hodgkin), 26 had sarcoma, and 54 had neuroblastoma. The indication, purpose, and findings of each PET/CT examination were reviewed, in addition to other imaging findings as well as clinical information including follow-up results for >1 y from their last PET/CT examination.PET/CT examination was performed for whole body in all patients (720 scan) for initial diagnosis &staging and for restaging of recurrent malignancy. It is also, performed to assess cancer response to therapy and after therapy as a routine follow-up procedure or for further evaluation of suspected recurrence or for secondary malignancy.
One thousandand eighty suspicious sites were evaluated in the 180 included patients. Patients were selected according to their reports which indicate areas of increased FDG uptake. PET findings were considered positive when uptake occurred at sites of previous disease, in asymmetrical lymph nodes or in nodes unlikely to be affected by inflammation (mediastinal, except for hilar, and abdominal). PET findings were adjudged negative for neoplastic localizations in the following instances: physiological uptake (urinary, muscular, thymic or gastrointestinal), symmetrical nodal uptake, very low uptake and non-focal uptake. PET findings were compared with the results of other diagnostic procedures (including CT and ultrasound), biopsy findings and follow-up data.
After at least 4 h of fasting, a total body PET scan was done one hour after IV injection of 300 MBq of 18 F-FDG. 64 MSCT scan was performed using GE Discovery VCT simultaneously and used for attenuation correction, anatomical localization and diagnosis. Max. Variant of SUV; a semi-quantitative analysis would be done for selected ROI.s and the normal threshold is <2.5.

Statistical Analysis:-
An important goal in diagnostic medicine research is to estimate and compare the accuracies of diagnostic tests which provide reliable information about a patient's condition and influence patient care. The purpose of a diagnostic test is to classify or predict the presence or absence of a condition or a disease. The clinical performance of a diagnostic test is based on its ability to correctly classify subjects into relevant subgroups ( Sensitivity and specificity are characteristics of the test but they do not help a clinician to interpret the results of an individual test (Peacock and Peacock, 2011). Therefore it is important to know how good the test is at predicting the true positives, i.e., the probability that the test will give the correct diagnosis. This is captured by the following predictive values -Prevalence (prior probability) is defined as the prior probability of the disease before the test is carried out (Peacock and Peacock, 2011). It is a measure of disease that allows us to determine a person's likelihood of having a disease. Therefore, a prevalence rate is the total number of cases of a disease existing in a population divided by the total population .  The true positive andnegative sites of the 1080 regions analyzed, was 562and 493respectively.The overall sensitivities, specificities & positive and negative predictive values of the imaging system for all the suspicious sites were 98.1%, 97.2%, 97.6% and 97.8% respectively (Tables 2-4).   The sensitivities and specificities of 18F-FDG PET/CT for initial staging of malignant lymphomas were ranged 83.3%-100% and 93.75%-100% respectively. They ranged 66.70%-100% and 91.30%-100% respectively in STS and 86.70%-100% and 95.80%-100% respectively in Neuroblastoma.The negative and positive predictive valuesin evaluating the stage of lymphoma were 93.30%-100% and 40.00%-100% respectively. They ranged from 83.30%-100% and 33.30%-100% in STS and 95.10%-100% and 0.00%-100% in neuroblastoma respectively (Table 5).

Discussion:-
Successful management of solid tumors in children requires imaging tests for accurate disease detection, characterization, and treatment monitoring. Technologic developments aim toward the creation of integrated imaging approaches that provide a comprehensive diagnosis with a single visit. These integrated diagnostic tests are not only convenient for young patients but also save direct and indirect health-care costs by streamlining procedures, minimizing hospitalizations, and minimizing school or work time lost for children and their parents (Uslu et al.,  2015). Pediatric malignancies are regarded as distinct from adult malignancies in view of their low frequency, treatment strategy, and expected prognosis. Special attention should be required in interpreting images of pediatric patients, taking these conditions into consideration (Tatsumi et al., 2007). However, modern radiotherapy techniques heavily rely on high-quality medical imaging. PET provides biologic information about the tumor, complementary to anatomic imaging. Integrated PET/CT has found its way into the practice of radiation oncology, and 18 F-FDG PET is being introduced for radiotherapy planning. The functional information possibly augments accurate delineation and treatment of the tumor and its extensions while reducing the dose to surrounding healthy tissues. In addition to 18 F-FDG, other PET tracers are available for imaging specific biologic tumor characteristics determining radiation resistance (Troost et al., 2015).
PET is used for many cancers for diagnosis, initial staging, assessment of treatment response (Meta et al., 2001) guidelines (Special Report, Podoloff et al., 2007). He evaluates patients with lymphoma, colorectal cancer, and head and neck cancer. Current National Comprehensive Cancer Network guidelines also, do not recommend surveillance. Nevertheless, PET/CT is commonly used for surveillance (Wagner-Johnston et al., 2011). Possible risks of using PET/CT for surveillance include overtreatment based on false-positives and unnecessary radiation exposure (Huang et al., 2009; Patel et al.,2013/2015). Therefore, a negative follow-up 18F-FDG PET scan is a strong indicator of absence of disease relapse, whereas a positive scan should be validated with other imaging modalities or biopsy (Rhodes et al., 2006). Several recent studies have demonstrated that routine follow-up by 18F-FDG PET/CT and other imaging techniques may be 415 overused for routine surveillance of patients with HL, contributing to increased cost and radiation exposure without a clear survival benefit (Nievelsteinet al., 2012; Levineet al., 2006;Rathore et al., 2012). More data are needed to determine which patient group will benefit from which surveillance test for how long and at which frequency (Uslu et al., 2015).
Early detection of distant malignancies in cancer patients is crucial for guiding subsequent staging procedures and treatment (Xu et al.,2012/2015).Accordingly to the results of the study of Tatsumi  . As absence of FDG uptake on the residual soft tissue is known to be a strong indicator for better prognosis in adults, accurate interpretation with confidence is valuable in managing patients in a post-treatment status. PET/CT has an advantage over CI or PET alone in this regard as well (Tatsumi et al., 2007).Furthermore, Choi et al., 2014, in a study of 30 neuroblastoma patients, found that 18F-FDG PET is more sensitive than CT in the evaluation of distant lymph node involvement and can help in detecting recurrent lymph node metastases. Therefore, 18F-FDG PET/CT might be particularly helpful in older patients who present with small, resectable primary tumors and chronic lymph node metastases (Uslu et al., 2015). However false-positives were noted because of thymic rebound, inflamed lymph nodes, physiologic cardiac uptake (Depas et al., 2005), infections or inflammation (Rhodeset al., 2006), and reconverted marrow. This is a typical false-positive paradox, that is, false-positive results are more probable than true-positive when the overall population has a low incidence of a condition (Uslu et al.,  2015).
The ideal timing for a PET/CT after CRT has yet to be established, although, most commonly, within the literature, scans 3 months post CRT are used with the hope of minimizing post-treatment inflammation, maximizing potential tumor cell kill after CRT and without delaying the scan for too long to allow progression of residual disease (Sherriff et al., 2015).On the other hand,post-CRT PET/CT does aid subsequent management decisions. Patients with a negative PET/CT scan after radical CRT have a 91.8% chance of remaining free of local recurrence 19 months post treatment. A higher SUV max on the post-CRT PET/CT may predict local recurrence and warrants further investigation (Sherriff et al., 2015).A substantial fraction (≤65%) of patients with positive PET results will still be cured, and patients with negative or positive results seem to do well if their PETresults are negative at the completion of chemotherapy (typically 6 cycles) (Sher et al., 2009) , 2006). In the current study, the overall sensitivities and specificities of the imaging system for detecting the local recurrence were 94.60% and 97.50% respectively at the end of treatment and were 96.20% and 98.30% after 1y of treatment. More evidence is needed on diagnostic algorithms for the detection of tumor recurrence (Uslu et al., 2015).

Conclusion:-
PET with the glucose analog, 18 F-FDG PET, is increasingly recognized as a powerful tool in evaluating patients with various malignant tumors (Rohren et al 2004). Recently, combined PET and CT systems (PET/CT) have emerged as promising imaging modalities and are being more routinely used in clinical situations(von Schulthess et al 2006). Despite growing numbers of reports on imaging adult malignancies with PET/CT, little data have been reported so far about the clinical relevance of this modality in pediatric patients. This study aimed to retrospectively evaluate the efficacy of FDG PET/CT imaging system in the management of some pediatric malignancy and to determine if it provided additional diagnostic information on disease status; during the last 4 years (y). The study concluded that the 18 F-FDG PET/CT is the gold standard for noninvasive functional imaging in oncology. It is a useful technique for the staging and follow-up of pediatric malignancy. Technical developments in PET scanning in cancer management may increase the precision of radiotherapy planning and thus improve tumor control and reduce treatment-related morbidity. It has a very high but not absolute specificity for pediatric malignancy. Thus, combined PET/CT imaging had an impact on patient management affecting both the diagnostic and therapeutic approach. Recommendation regarding the use of PET/CT in the management of pediatric malignancy to facilitates the sparing of normal structures and the escalation of dose.