Prognostic value of initial [ 18 F]FDG PET/computed tomography volumetric and texture analysis-based parameters in patients with head and neck squamous cell carcinoma.

AIM OF WORK: To determine the predictive value of initial [ 18 F]FDG PET/computed tomography (CT) volumetric and radiomics-derived analyses in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Forty-six adult patients had pathologically proven HNSCC and underwent pretherapy [ 18 F]FDG PET/CT were enrolled. Semi-quantitative PET-derived volumetric [(maximum standardized uptake value (SUVmax) and mean SUV (SUVmean), total lesion glycolysis (TLG) and metabolic tumor volume (MTV)] and radiomics analyses using LIFEx 6.73.3 software were performed. RESULTS: In the current study group, the receiver operating characteristic curve marked a cutoff point of 21.105 for primary MTV with area under the curve (AUC) of 0.727, sensitivity of 62.5%, and specificity of 86.8% ( P value 0.041) to distinguish responders from non-responders, while no statistically significant primary SUVmean or max or primary TLG cut off points could be determined. It also marked the cutoff point for survival prediction of 10.845 for primary MTV with AUC 0.728, sensitivity of 80%, and specificity of 77.8% ( P value 0.026). A test of the synergistic performance of PET-derived volumetric and textural features significant parameters was conducted in an attempt to develop the most accurate and stable prediction model. Therefore, multivariate logistic regression analysis was performed to detect independent predictors of mortality. With a high specificity of 97.1% and an overall accuracy of 89.1%, the combination of primary tumor MTV and the textural feature gray-level co-occurrence matrix correlation provided the most accurate prediction of mortality ( P value < 0.001). CONCLUSION: Textural feature indices are a noninvasive method for capturing intra-tumoral heterogeneity. In our study, a PET-derived prediction model was successfully generated with high specificity and accuracy.

Predictive Value of FDG PET/CT Versus Bone Marrow Biopsy in Pediatric Lymphoma.

PURPOSE: The aim of this study was to explore the positive predictive value and negative predictive value of FDG PET/CT. The prognostic impact of tumor burden of bone marrow infiltrates was diagnosed by FDG PET/CT at initial presentation. METHODS: This retrospective study enrolled 140 pediatric patients with pathologically proven lymphoma (113 Hodgkin disease and 27 Non-Hodgkin lymphoma). All patients had pretherapy FDG PET/CT. Bone marrow biopsy (BMB), clinical, radiological, and follow-up data were also collected. The skeleton was divided into 8 segments, and a 5-point scoring system was used for assessment of BM infiltration burden. RESULTS: Among the 140 lymphoma patients, FDG PET/CT revealed positive BM involvement in 41 patients; 2 of them were false-positive with negative BMB and regional MRI results. Positive predictive value was 95.1% for PET/CT compared with 100% with BMB. All patients diagnosed with positive BMI by BMB were detected by FDG PET/CT. On the contrary, BMB missed 25 patients (17.9%) with statistically significant difference. Negative predictive value was 100% for PET/CT compared with 80.2% for BMB (P < 0.05). FDG PET/CT upstaged 17.9% of the enrolled patients. Bone marrow involvement based on the 5-point scoring system was assessed. No significant difference was demonstrated in therapy outcome between patient with focal BMI (score 2) and extensive BMI (score 5; P = 0.06). CONCLUSIONS: FDG PET/CT has optimum negative predictive value compared with BMB in detection of bone marrow infiltrations in pediatric lymphoma with upstaging cases missed with BMB. Prognostic impact of BMI based on the 5-point scoring system reveals that the main influence is presence or absence of BMI rather than its tumor burden.

Prognostic value of p27 in follicular thyroid carcinoma and its relation to radioactive iodine response: does it aid in the modification of risk stratification?

INTRODUCTION: Follicular thyroid carcinoma (FTC) is the second most common type of thyroid cancer. Genetic studies have demonstrated that the loss of expression and function of Cdk inhibitor p27 leads to the development of multiple-organ hyperplasia and malignancy, including thyroid carcinoma. AIM OF WORK: (1) To assess the prognostic value of the quantitative expression of p27 in correlation with clinicopathologic prognostic indicators in FTC. (2) To explore its predictive value in the assessment of response to radioactive I-131 therapy in metastatic FTC patients. MATERIALS AND METHODS: This retrospective study was conducted on 43 histopathologically confirmed FTC patients referred to the nuclear medicine department, National Cancer Institute, Cairo University between July 2001 and December 2010, for radioactive I-131 therapy. Clinicopathologic parameters, details of radioactive I-131 therapy and its outcome, and a serial follow-up serum thyroglobulin levels and I-131 whole body scan were obtained from their medical records. Quantitative expression of p27 using immunostaining was analyzed using paraffin blocks of thyroidectomy specimens in all patients. RESULTS: With respect to clinicopathologic characteristics, p27 expression was found to be significantly lower in patients with vascular invasion (P=0.024) and in patients with an advanced-stage disease (P=0.048). A significant difference was detected between the risk stratification and the quantitative expression of p27. A statistically significant difference was obtained with respect to immunohistochemical expression of p27 between the metastatic and nonmetastatic patients as well as age, growth characteristics, tumor size, vascular invasion, and extrathyroidal extension. Despite the observed trend in patients with a low p27 expression, to have a worse response to iodine therapy, and a poor overall survival, the point of statistical significance could not be reached. CONCLUSIONS: In this preliminary study, p27 quantitative expression appeared to provide a complementary valuable predictor with other prognostic variables for risk stratification in FTC patients. Response to I-131 therapy in FTC in relation to p27 expression should be thoroughly investigated including large-scale studies and more homogenous risk groups.

Oncoplastic volume replacement with latissimus dorsi myocutaneous flap in patients with large ptotic breasts. Is it feasible?

BACKGROUND: Oncoplastic breast conservative surgery has evolved as a safe alternative to the standard mastectomy in the treatment of early breast cancer. The procedure involves tumour resection with an adequate safety margin and either breast reshaping with volume displacement procedures (large or ptotic breasts) or volume replacement with latissimus dorsi myocutaneous flap (LDF) (small to medium sized non-ptotic breasts). A contra lateral mastopexy procedure is usually necessary with the volume displacement oncoplastic surgery, a procedure that is often rejected by a significant number of patients. This limits the choice of the reconstruction of breast defects in such patients to autologous tissues i.e. LDF. AIM: Aim is to evaluate the feasibility of volume replacement oncoplastic breast conservative surgery with latissimus dorsi myocutaneous flaps for patients with large ptotic breasts. This involves testing the oncologic safety in terms of adequate safety margin, the complications rate and the final cosmetic outcome. The loco regional recurrence rate will be recorded and compared with oncoplastic volume displacement for similar sized breast defects. PATIENTS AND METHODS: A group of 50 female patients with early breast cancers (T2) who presented to the department of surgery at the National Cancer Institute, Cairo, Egypt in the period between January 2004 and November 2009 were included in the study. Bilateral soft tissue mammography was carried out in all patient groups and was used to annually follow up the patients. All patients were detected with T2 N0 breast cancer by both clinical and radiological examinations. All patients underwent partial mastectomy and reconstruction with LDFs. RESULTS: The average age at presentation was 46.5±9years and the range was 26-65years. Most of the patients were subjected to partial mastectomy in 30 patients (60%), excision of a single quadrant from the four major quadrants was carried out in 15 patients (30%) where skin sparing wide local excision was carried out in only five patients (10%). The safety margin ranged from 1.1 to 3.2cm with an average of 1.8±0.5cm. There was no total flap loss in any patient where as we reported partial flap loss in two patients. Nipple and areola sloughing were reported in two patients, wound infection in five patients, haematoma in four patients, seroma in 16 patients, and donor site morbidity in six patients. The vast majority of patients were either satisfied (score >3 out of 5) (62%) or very satisfied (score 4 or more) (18%) with the results of reconstruction. CONCLUSION: The results of the current study showed the feasibility and the versatility of volume replacement oncoplastic surgery in patients with large ptotic breasts with myocutaneous flaps. The adequacy of safety margin and the acceptable complications rate as well as the comparable local recurrence rate to volume displacement oncoplastic surgery, make it a suitable alternative in a subset of patients who object an immediate contra lateral mastopexy procedure.

Role of PET/CT in malignant pediatric lymphoma.

INTRODUCTION: Malignant pediatric lymphoma accounts for 10-15% of all pediatric cancers, (representing 2-3% of all malignancies), with a peak incidence between 5-9 years. Chemotherapy is usually the first and most common mode of treatment. The choice of treatment and prediction of prognosis depend on the histological type of tumor, initial staging, evaluating treatment response, and detection of early recurrence. Conventional imaging modalities have many limitations. PET/CT is more accurate, however so far the literature lacks the results of a large group of patients. AIM OF STUDY: To report the role of PET/CT in the above-mentioned objectives at the newly established Children's Cancer Hospital in Cairo, Egypt, which is one of the busiest dedicated pediatric oncology centers of such purposes in the world. All findings were proven by histopathology, clinically, and by clinical follow-up. PATIENT POPULATION: A total of 152 patients (35 girls and 117 boys) with histologically proven malignant lymphoma (117 HD, 35 NHL) were included in this study. They were divided into four groups. Group I: 41 patients for initial staging. Group II: 51 patients for evaluating early treatment response after two to three cycles of chemotherapy. Group III: 42 patients for evaluating treatment response 4-8 weeks after the end of their treatment. Group IV: 18 patients evaluated for long-term follow-up. Results of PET/CT were compared with the other conventional imaging modalities (CIM). RESULTS: The sensitivity, specificity, accuracy, and positive and negative predictive values of PET/CT and CIM were as follows: In Group I: PET/CT modified staging and treatment in 11 out of 41 cases (26.8%), upstaged 5(12.2%) patients and down-staged six (14.6%) patients. Group II: 100%, 97.7%, 98%, 85.7%, 100%, respectively, for PET/CT and 83%, 66.6%, 68.6%, 25%, 96.7% for CIM respectively Group III: At the end of chemotherapy 100%, 90.9%, 92.8%, 75%, 100%, respectively, for PET/CT and 55.5%, 57.5%, 57.1%, 26.3%, 82.6% for CIM, respectively. Group IV: For long-term follow-up, all the parameters scored 100% for PET/CT, 100%, 38.4%, 72.2%, 50%, 100% for CIM, respectively. CONCLUSION: PET/CT in pediatric lymphoma is more accurate than CIM. We recommend that it should be the first modality for all purposes in initial staging, evaluating treatment response and follow-up.

Role of 131-I MIBG Therapy in the Treatment of Advanced Neuroblastoma.

INTRODUCTION: Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most extracranial malignant solid tumor of childhood. Many therapeutic strategies has evolved over the last 20 years, based upon work by international cooperative groups and smaller cohort studies. Novel therapies to improve initial disease response and treatment of minimal residual disease are required to improve survival for these children with highrisk neuroblastoma. Radio-labeled MIBG therapy has been tried in the treatment of advanced stage 3&4 neuroblastoma in an attempt to improve patients' outcome. The use of radio-labeled MIBG to treat neuroblastoma has arisen from the high sensitivity and specificity of in-vivo MIBG imaging for detection of primary and metastatic tumors. AIM OF WORK: To determine the impact of MIBG therapy on neuroblastoma patients' outcome and its impact on their quality of life. PATIENTS AND METHODS: Thirty pediatric patients with stage 4 pathologically proven neuroblastoma are included in this study. Eighteen of the study patients (60%) were males and 12 (40%) were females. All the patients had partially responsive tumor to first-line therapy +/- surgey. 131-I MIBG doses ranged from 100 to 150mCi with number of courses ranged from 1-7 according to response and toxicity. RESULTS: Two patients achieved complete remission (CR) and were still disease-free after 64 &69 months. Nine patients showed partial remission (PR) to 131-I MIBG, all the nine patients were alive at 16-57 months (mean 30.6 months) among whom seven were alive with stable disease and two patients were alive with progressive disease (PD) at the end of study. Eighteen patients remained stable after 131-I MIBG therapy, among them six were alive with PD and four were alive with stable disease at the end of study, while the remaining eight patients died. The last patient developed PD and died within 15 months. The 5 years event free survival (EFS) was 48.2% and the overall survival (OS) was 69%. CONCLUSIONS: We concluded that 131-I MIBG therapy has favorable therapeutic effect for advanced neuroblastoma patients. Controlled clinical trials should be considered to evaluate the true potential of 131-I MIBG therapy. KEY WORDS: MIBG therapy - Advanced neuroblastoma.

Clinical significance of metabolic superscan in patients with hyperthyroidism.

BACKGROUND: Hyperthyroid patients commonly complain of generalized bony aches, which are frequently overlooked due to the more prominent symptoms of cardiovascular and nervous disturbances. Hyperthyroid patients are expected to have abnormal bone metabolism as part of the generalized hypermetabolic status. The aim of this study is to verify the presence of metabolic bone superscan in association with the hypermetabolic stats in various groups of hyperthyroidism. Secondly, to correlate these superscan features with the various laboratory results in hyperthyroid patients. MATERIAL AND METHODS: Forty-five hyperthyroid patients confirmed by clinical and laboratory results were enrolled in this work. In all patients, a (99m)Tc-pertechnetate thyroid uptake scan was acquired. On a different day, total body bone scan was acquired three hours post IV injection of 555-925 MBq of (99m)Tc-MDP. Serum FT3, FT4, TSH, Ca++, alkaline phosphatase (AP) and parathyroid hormone (PTH) were monitored in all patients as markers of thyroid and bone metabolism. Ten cases with no thyroid diseases were included as a control group. Patients with thyroiditis or long history of antithyroid drugs for more than one year were excluded from the study. RESULTS: The patients were subdivided into three groups: Graves disease (GD) (n = 30), toxic nodular goiter (TNG) (n = 10) and autonomous toxic adenoma (AT) (n = 5). The TSH for the whole group was significantly suppressed compared to the control group with higher suppression in the Graves disease group than in the TNG or AT groups. (99m)Tc-pertechnetate uptake values in the Graves disease group were significantly higher than the TNG and AT groups (p < 0.05). Metabolic superscan (MSS) was noted in 90% of the Graves cases, 20% in TNG and in none of the AT group. There were no significant differences regarding Ca+, AP and PTH between the Graves and non-Graves groups (p > 0.05). CONCLUSIONS: Disturbances in bone metabolism are more prevalent in Graves disease than in other types of hyperthyroidism. The addition of the bone scan to the diagnostic work up of patients with Graves disease is a sensitive indicator for metabolic bone changes and could help in the future management and follow up for this group of patients.

The value of simultaneous co-registration of 99mTc- MDP and 131Iodine in metastatic differentiated thyroid carcinoma.

BACKGROUND: The lack of anatomical details in standard (131)Iodine whole body scanning ((131)I WBS) interferes with the proper localization of metastatic differentiated thyroid carcinoma (DTC) lesions. In addition, nearby or overlapping variable physiological distribution of (131)I may affect the specificity of (131)I uptake, giving indeterminate results. The aim of this study was to demonstrate the clinical usefulness of simultaneous co-registration of (99m)Tc MDP bone scanning as an anatomical landmark with (131)I scanning in the evaluation of metastatic DTC. MATERIAL AND METHODS: Twenty-five patients (16 females and 9 males, mean age +/- SD = 52 +/- 13 years) with metastatic DTC (17 papillary, 8 follicular), were included. Whole body scanning using a 256 x 1024 matrix and an 8 cm/min scan rate were obtained 48 hours after oral administration of 185-370 MBq 131I and 2 hours after IV administration of 185-370 MBq (99m)Tc MDP using a dual head gamma camera equipped with high energy parallel hole collimators. Occasionally, additional simultaneous co-registration of localised detailed images was also performed using a 256 x 256 matrix size. The two planar images were fused with optional fusion of SPECT images. The data from standard (131)I scanning and fused (131)I/ (99m)Tc-MDP scanning were separately assessed by two nuclear medicine physicians. Fusion images were considered to improve image interpretation in comparison with standard (131)I scanning when they provided better localization of lesions. RESULTS: All lesions in the present study were validated by radiological images and clinical follow up for at least 12 months. Forty-eight metastatic lesions were confirmed as follows: 2 in the skull, 10 in the neck, 20 in the thorax, 12 in the pelvic-abdominal region and 4 in the extremities. Standard (131)I WBS showed 54 extra-thyroidal foci with 8 false positive lesions of which 2 were located in the scalp and 6 in the pelvic-abdominal region extra-skeleton (i.e. sensitivity 100%, specificity 86%). Out of the 48 validated lesions, 16 were indeterminately localized: 10 in the thorax (3 mediastinal nodal lesions, 5 vertebral lesions and 2 ribs) and 6 in the pelvic-abdominal region (2 upper sacral, 2 sacroiliac region and 2 ischial bone). Fusion images confirmed the precise localization of the pathological uptake in the validated 48 lesions (sensitivity 100%, specificity 100%). There were 2 (4%) indeterminate lesions in fused planar imaging that were clearly localized via fused SPECT images. CONCLUSIONS: Fusion images using simultaneous co-registration of (131)I and (99m)Tc MDP scanning is a simple and feasible technique that improves the anatomically limited interpretation of scintigraphy using (131)I alone in patients with metastatic differentiated thyroid carcinoma. The diagnostic advantage of this technique seems to be more apparent in the thoracic and pelvic- abdominal regions in contrast to the neck and extremities.

Bone metastases in muscle-invasive bladder cancer.

PURPOSE: To address the necessity of incorporating isotopic bone scan in the routine staging work-up of muscle invasive bladder cancer patients, we analyzed the data in our files to determine the incidence of bone metastasis in such patients. The rate of subsequent development of bone metastasis along the natural history of the disease was also investigated. PATIENTS AND METHODS: A total of 179 files of consecutive bladder cancer patients who presented to the National Cancer Institute, Cairo University, between January 2000 and December 2001 were reviewed to check the percentage of positive bone scans on presentation and to check the subsequent development of distant metastases and bone metastasis in these patients' records. RESULTS: Amongst the 179 patients, 26 (14.5%) had bone metastasis on presentation, a finding that showed a statistically significant correlation with the increasing depth of muscle invasion; 61.5% of the metastatic cases had deep muscle invasion,19.2% had superficial muscle invasion and there was no muscle invasion in 7.7% (p=0.000). Transitional cell carcinoma was the pathology in 92.3% of those patients, while only 7.7% had squamous cell carcinoma (p=0.036). The cumulative 3-year incidence of bone-metastasis in the non metastatic patients after treatment mounted to 19.4 +/- 4.4%. The cumulative 3-year bone metastasis incidence in the 153 patients was higher with increasing clinical stage; 8.4 +/- 8% for c-stage 2 and 49.1 +/- 18.5% for c-stage 4 (p=0.046). As for the p-category of the tumor in the 130 patients who underwent operation, the incidence increased with higher p-stages (p=0.006). Though pelvic nodal involvement was not associated with statistically significant increase in the incidence of bone metastases, yet when incorporated as one of the 3 risk factors (grade>3, p (3) 4a and LN positive at surgery) according to which patients were grouped, there was a statistically significant difference in the incidence between patients with no risk factors, only 1 and 2 or more factors (p=0.021). CONCLUSION: Meticulous search for bone metastasis alone or as a component of distant failure in the newly diagnosed bladder cancer patients is crucial to offer them the proper management and avoid undue radical surgical procedures. Thus bone scan is suggested to be performed routinely in patients with evidence of muscle invasion.