PURPOSE Despite aggressive therapy, a third of patients with HNSCC will relapse within 2 years. A... more PURPOSE Despite aggressive therapy, a third of patients with HNSCC will relapse within 2 years. Accurate and timely detection of recurrence is critical for attempting surgical salvage and may offer a survival benefit. There is no standard approach for integrating diagnostic imaging into surveillance. While several preliminary studies have suggested that PET/CT yielded higher sensitivity than high resolution CT (HRCT), the performance of repeat PET/CT in early detection of relapse has not been well investigated. Our objective was to retrospectively examine the efficacy of PET/CT vs HRCT in a surveillance setting in indentification of recurrence. METHOD AND MATERIALS A total of 462 PET/CT examinations in 99 HNSCC patients obtained between June 2005-Jan 2010 were reviewed following definitive therapy. All patients were followed with clinical examination, endoscopy, PET/CT, and HRCT with a median of 4 follow-up scans (range= 3-9). The HRCTs were reviewed without and then with the corres...
This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal... more This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal muscles secondary to activation of the patient's vocal folds and related laryngeal muscles during speech. Twenty-four patients undergoing routine PET scans were randomized into two groups to ascertain the relationship between FDG uptake in the laryngeal region and speech. One group was assigned to talk and the other group remained silent during the injection and uptake period of FDG. FDG uptake in the laryngeal muscles in the scans was correlated with speech. Patients who spoke continually during the uptake period had high-grade FDG uptake, those who spoke intermittently had low-grade uptake and those who remained silent had no detectable increase in FDG uptake in the region of the larynx. The relationship between the degree of laryngeal muscle uptake and speech provides useful information to allow differentiation of physiological from pathological uptake in the neck.
In radioimmunotherapy, myelotoxicity due to bone marrow radiation- absorbed dose is the predomina... more In radioimmunotherapy, myelotoxicity due to bone marrow radiation- absorbed dose is the predominant factor and frequently is the dose-limiting factor that determines the maximum tolerated dose (MTD). With 90Y- and 131I-labeled monoclonal antibodies, it has been reported that myelotoxicity cannot be predicted on the basis of the amount of radioactive dose administered or the bone marrow radiation-absorbed dose (BMrad), estimated using blood radioactivity concentration. As part of a phase I dose-escalation study in patients with prostate cancer with 90Y-DOTA-J591 (DOTA � 1,4,7,10-tetraazacyclododecane- N,N�,N�,N�-tetraacetic acid) (90Y-J591) and 177Lu- DOTA-J591 (177Lu-J591), we evaluated the potential value of several factors in predicting myelotoxicity. Methods: Seven groups of patients (n � 28) received 370–2,775 MBq/m2 (10–75 mCi/m2) of 177Lu-J591 and 5 groups of patients (n � 27) received 185–740 MBq (5–20 mCi/m2) of 90Y-J591. Pharmacokinetics and imaging studies were performed f...
PURPOSE With the recent advent of integrated PET-CT systems as well as using a better reading sca... more PURPOSE With the recent advent of integrated PET-CT systems as well as using a better reading scale, diagnostic accuracy, particularly, the specificity of FDG-PET imaging may be improved. Our aim was to evaluate the diagnostic accuracy of FDG-PET using an integrated PET-CT system using different internal references in the differentiation of benign from malignant SPN. METHOD AND MATERIALS A total 75 pts with a SPN (1-3 cm, median: 1.5 cm) underwent PET/CT imaging. SUVmax calculated for all nodules. The accuracy of PET/CT was compared using biopsy (64 pts) and/or clinical follow-up including repeat PET/CT studies (median 7 months) as gold-standard. Visual interpretation with a 5-point ordinal scale was performed using both the mediastinal blood pool (MBP) and liver as internal references. Lesion-to-reference organ ratios were obtained using contralateral background, mediastinal blood pool (MBP) and the liver. ROC curves were generated for ratios to differentiate between benign and mal...
ABSTRACT We evaluated the predictive value of I-PET after one course of chemoimmunotherapy in pat... more ABSTRACT We evaluated the predictive value of I-PET after one course of chemoimmunotherapy in patients with newly diagnosed DLBCL. 112 DLBCL patients were enrolled. All patients had PET/CT scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International harmonization project criteria (IHP) and to Deauville 5 point scale (D 5PS) with scores 1-3 considered negative (D 5PS>3) and D 5PS with scores 1-4 considered negative (D5PS=5). Ratios of tumorSUVmax to liverSUVmax were also analyzed. We found no difference in progression-free survivals (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS>3. The 2-year PFS using D 5PS=5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p=0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish a D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET positive and PE...
Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have th... more Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response-adapted treatment guided by early interim positron emission tomography (PET) -computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely.
Early prediction of response to therapy may offer the potential to identify patients who will ben... more Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and...
PET is a unique form of diagnostic imaging that observes in vivo biologic changes using radiophar... more PET is a unique form of diagnostic imaging that observes in vivo biologic changes using radiopharmaceuticals that closely mimic endogenous molecules. 18F-FDG, which allows the evaluation of glucose metabolism, is the most commonly used tracer in on- cology because of the practical half-life of 18F (110 min), com- pared with other short-lived positron emitters. 18F-FDG uptake in tumors is proportional
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005
111In-Labeled antibodies and peptides have been routinely used as chemical and biologic surrogate... more 111In-Labeled antibodies and peptides have been routinely used as chemical and biologic surrogates for 90Y-labeled therapeutic agents. However, recent studies have shown that there are significant differences in biodistribution between 111In- and 90Y-labeled agents. Yttrium and lutetium metals favor the +3 oxidation state, similar to indium, but there are minor differences in the solution and coordination chemistries among these metals. These 3 metals, however, form strong complexes with the macrocyclic chelator, 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). We, therefore, compared the pharmacokinetics and biodistribution of 111In- and 177Lu-labeled J591 antibody. The radiation dosimetry of 90Y-J591 was estimated based on both 111In and 177Lu data to validate the usage of 111In as a chemical and biologic surrogate for 90Y. J591 is a deimmunized monoclonal antibody with specificity for the extracellular domain of prostate-specific membr...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2004
In patients with carcinoma of the head and neck and of the esophagus, metabolic and functional im... more In patients with carcinoma of the head and neck and of the esophagus, metabolic and functional imaging by PET with (18)F-FDG has a pivotal role in the evaluation of tumor response to therapy, specifically, in the prediction of progression-free survival and overall survival. Metabolic imaging allows the detection of biochemical changes within tumor cells as opposed to identifiable morphologic changes. Anatomic imaging modalities do not reliably differentiate between responders and nonresponders early during the course of follow-up. The correlation between histopathologic tumor response after preoperative therapy and clinical prognosis is well established for many cancers. Squamous carcinoma of the head and neck and esophageal carcinoma demonstrate avid (18)F-FDG uptake. For these cancers, (18)F-FDG PET parallels histopathologic findings in its ability to detect residual viable tumor; therefore, it is a valuable tool for the noninvasive assessment of histopathologic tumor response in ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
Our aim was to ascertain the relationship between the degree of 99mTc-MIBI uptake and the level o... more Our aim was to ascertain the relationship between the degree of 99mTc-MIBI uptake and the level of p-glycoprotein (Pgp) expression determined by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) techniques in patients with hematologic malignancy. A total of 21 samples (19 patients) were evaluated. Two patients had repeat studies after therapy. Thirteen samples were studied at the time of initial diagnosis and 8 during relapse after therapy. After MIBI imaging, either bone marrow aspiration or peripheral blood was obtained for flow cytometric and RT-PCR analyses. Flow cytometry was performed using two different antibodies. After the injection of 555 MBq MIBI, whole-body and pelvic spot images were acquired using a dual-head gamma camera. The uptake in the bone marrow was evaluated against the background (adjacent soft tissue) by both qualitative (scoring system) and quantitative (tm/bkg ratios) analyses. For flow cytometry, the limit for Pgp overexpression w...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree ... more In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree of MIBI accumulation with the expression of P-glycoprotein (Pgp) in tumor tissues in a total of 46 patients with lung cancer. All patients underwent early (30 min) and delayed (3 hr) MIBI imaging and bronchoscopic biopsy before initiation of chemo- or radiotherapy. The interval between biopsy and imaging varied between 2 and 10 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of Pgp. Normal tissue and tumor washout rates and tumor-to-background ratios were correlated with the level of Pgp expression. There was an inverse correlation between tumor-to-background ratios and the density of Pgp (p = 0.001), whereas there was no appreciable correlation between tumor washout rates of MIBI and the level of Pgp expression (p = 0.414). The current data ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography ... more Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients wa...
PURPOSE Despite aggressive therapy, a third of patients with HNSCC will relapse within 2 years. A... more PURPOSE Despite aggressive therapy, a third of patients with HNSCC will relapse within 2 years. Accurate and timely detection of recurrence is critical for attempting surgical salvage and may offer a survival benefit. There is no standard approach for integrating diagnostic imaging into surveillance. While several preliminary studies have suggested that PET/CT yielded higher sensitivity than high resolution CT (HRCT), the performance of repeat PET/CT in early detection of relapse has not been well investigated. Our objective was to retrospectively examine the efficacy of PET/CT vs HRCT in a surveillance setting in indentification of recurrence. METHOD AND MATERIALS A total of 462 PET/CT examinations in 99 HNSCC patients obtained between June 2005-Jan 2010 were reviewed following definitive therapy. All patients were followed with clinical examination, endoscopy, PET/CT, and HRCT with a median of 4 follow-up scans (range= 3-9). The HRCTs were reviewed without and then with the corres...
This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal... more This study describes the physiological uptake of 18F-fluoro-2-deoxyglucose (FDG) by the laryngeal muscles secondary to activation of the patient's vocal folds and related laryngeal muscles during speech. Twenty-four patients undergoing routine PET scans were randomized into two groups to ascertain the relationship between FDG uptake in the laryngeal region and speech. One group was assigned to talk and the other group remained silent during the injection and uptake period of FDG. FDG uptake in the laryngeal muscles in the scans was correlated with speech. Patients who spoke continually during the uptake period had high-grade FDG uptake, those who spoke intermittently had low-grade uptake and those who remained silent had no detectable increase in FDG uptake in the region of the larynx. The relationship between the degree of laryngeal muscle uptake and speech provides useful information to allow differentiation of physiological from pathological uptake in the neck.
In radioimmunotherapy, myelotoxicity due to bone marrow radiation- absorbed dose is the predomina... more In radioimmunotherapy, myelotoxicity due to bone marrow radiation- absorbed dose is the predominant factor and frequently is the dose-limiting factor that determines the maximum tolerated dose (MTD). With 90Y- and 131I-labeled monoclonal antibodies, it has been reported that myelotoxicity cannot be predicted on the basis of the amount of radioactive dose administered or the bone marrow radiation-absorbed dose (BMrad), estimated using blood radioactivity concentration. As part of a phase I dose-escalation study in patients with prostate cancer with 90Y-DOTA-J591 (DOTA � 1,4,7,10-tetraazacyclododecane- N,N�,N�,N�-tetraacetic acid) (90Y-J591) and 177Lu- DOTA-J591 (177Lu-J591), we evaluated the potential value of several factors in predicting myelotoxicity. Methods: Seven groups of patients (n � 28) received 370–2,775 MBq/m2 (10–75 mCi/m2) of 177Lu-J591 and 5 groups of patients (n � 27) received 185–740 MBq (5–20 mCi/m2) of 90Y-J591. Pharmacokinetics and imaging studies were performed f...
PURPOSE With the recent advent of integrated PET-CT systems as well as using a better reading sca... more PURPOSE With the recent advent of integrated PET-CT systems as well as using a better reading scale, diagnostic accuracy, particularly, the specificity of FDG-PET imaging may be improved. Our aim was to evaluate the diagnostic accuracy of FDG-PET using an integrated PET-CT system using different internal references in the differentiation of benign from malignant SPN. METHOD AND MATERIALS A total 75 pts with a SPN (1-3 cm, median: 1.5 cm) underwent PET/CT imaging. SUVmax calculated for all nodules. The accuracy of PET/CT was compared using biopsy (64 pts) and/or clinical follow-up including repeat PET/CT studies (median 7 months) as gold-standard. Visual interpretation with a 5-point ordinal scale was performed using both the mediastinal blood pool (MBP) and liver as internal references. Lesion-to-reference organ ratios were obtained using contralateral background, mediastinal blood pool (MBP) and the liver. ROC curves were generated for ratios to differentiate between benign and mal...
ABSTRACT We evaluated the predictive value of I-PET after one course of chemoimmunotherapy in pat... more ABSTRACT We evaluated the predictive value of I-PET after one course of chemoimmunotherapy in patients with newly diagnosed DLBCL. 112 DLBCL patients were enrolled. All patients had PET/CT scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International harmonization project criteria (IHP) and to Deauville 5 point scale (D 5PS) with scores 1-3 considered negative (D 5PS>3) and D 5PS with scores 1-4 considered negative (D5PS=5). Ratios of tumorSUVmax to liverSUVmax were also analyzed. We found no difference in progression-free survivals (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS>3. The 2-year PFS using D 5PS=5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p=0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish a D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET positive and PE...
Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have th... more Recent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response-adapted treatment guided by early interim positron emission tomography (PET) -computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely.
Early prediction of response to therapy may offer the potential to identify patients who will ben... more Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and...
PET is a unique form of diagnostic imaging that observes in vivo biologic changes using radiophar... more PET is a unique form of diagnostic imaging that observes in vivo biologic changes using radiopharmaceuticals that closely mimic endogenous molecules. 18F-FDG, which allows the evaluation of glucose metabolism, is the most commonly used tracer in on- cology because of the practical half-life of 18F (110 min), com- pared with other short-lived positron emitters. 18F-FDG uptake in tumors is proportional
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2005
111In-Labeled antibodies and peptides have been routinely used as chemical and biologic surrogate... more 111In-Labeled antibodies and peptides have been routinely used as chemical and biologic surrogates for 90Y-labeled therapeutic agents. However, recent studies have shown that there are significant differences in biodistribution between 111In- and 90Y-labeled agents. Yttrium and lutetium metals favor the +3 oxidation state, similar to indium, but there are minor differences in the solution and coordination chemistries among these metals. These 3 metals, however, form strong complexes with the macrocyclic chelator, 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). We, therefore, compared the pharmacokinetics and biodistribution of 111In- and 177Lu-labeled J591 antibody. The radiation dosimetry of 90Y-J591 was estimated based on both 111In and 177Lu data to validate the usage of 111In as a chemical and biologic surrogate for 90Y. J591 is a deimmunized monoclonal antibody with specificity for the extracellular domain of prostate-specific membr...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2004
In patients with carcinoma of the head and neck and of the esophagus, metabolic and functional im... more In patients with carcinoma of the head and neck and of the esophagus, metabolic and functional imaging by PET with (18)F-FDG has a pivotal role in the evaluation of tumor response to therapy, specifically, in the prediction of progression-free survival and overall survival. Metabolic imaging allows the detection of biochemical changes within tumor cells as opposed to identifiable morphologic changes. Anatomic imaging modalities do not reliably differentiate between responders and nonresponders early during the course of follow-up. The correlation between histopathologic tumor response after preoperative therapy and clinical prognosis is well established for many cancers. Squamous carcinoma of the head and neck and esophageal carcinoma demonstrate avid (18)F-FDG uptake. For these cancers, (18)F-FDG PET parallels histopathologic findings in its ability to detect residual viable tumor; therefore, it is a valuable tool for the noninvasive assessment of histopathologic tumor response in ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
Our aim was to ascertain the relationship between the degree of 99mTc-MIBI uptake and the level o... more Our aim was to ascertain the relationship between the degree of 99mTc-MIBI uptake and the level of p-glycoprotein (Pgp) expression determined by flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) techniques in patients with hematologic malignancy. A total of 21 samples (19 patients) were evaluated. Two patients had repeat studies after therapy. Thirteen samples were studied at the time of initial diagnosis and 8 during relapse after therapy. After MIBI imaging, either bone marrow aspiration or peripheral blood was obtained for flow cytometric and RT-PCR analyses. Flow cytometry was performed using two different antibodies. After the injection of 555 MBq MIBI, whole-body and pelvic spot images were acquired using a dual-head gamma camera. The uptake in the bone marrow was evaluated against the background (adjacent soft tissue) by both qualitative (scoring system) and quantitative (tm/bkg ratios) analyses. For flow cytometry, the limit for Pgp overexpression w...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1998
In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree ... more In a prospective study, we correlated the washout rates of 99mTc-sestamibi (MIBI) and the degree of MIBI accumulation with the expression of P-glycoprotein (Pgp) in tumor tissues in a total of 46 patients with lung cancer. All patients underwent early (30 min) and delayed (3 hr) MIBI imaging and bronchoscopic biopsy before initiation of chemo- or radiotherapy. The interval between biopsy and imaging varied between 2 and 10 days. All patients had radiologically detectable tumors. Immunohistochemical studies were performed on paraffin sections using a monoclonal antibody, JSB-1, developed against the internal epitope of Pgp. Normal tissue and tumor washout rates and tumor-to-background ratios were correlated with the level of Pgp expression. There was an inverse correlation between tumor-to-background ratios and the density of Pgp (p = 0.001), whereas there was no appreciable correlation between tumor washout rates of MIBI and the level of Pgp expression (p = 0.414). The current data ...
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2014
Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography ... more Negative [(18)F]fluorodeoxyglucose (FDG) -positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients wa...
Uploads
Papers by Lale Kostakoglu