Zeynep Burak

EANM-EORTC general recommendations for sentinel node diagnostics in melanoma

The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to “general consensus” and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

Sentinel node in breast cancer procedural guidelines.

ContentProcedure guidelines for scintigraphic detection of sentinel node in breast cancer are presented.AuthorsThe paper was written by several experts in this field on behalf of the European Association of Nuclear Medicine Oncology and Dosimetry committees and approved by the Executive Committee.

Joint Practice Guidelines for Radionuclide Lymphoscintigraphy for Sentinel Node Localization in Oral/Oropharyngeal Squamous Cell Carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision of whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method for determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histologic nodal staging and avoids overtreating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This document is designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. Preparation of this guideline was carried out by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial (SENT) Committee.

Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee.

To use MIBI or not to use MIBI? That is the question when assessing tumour cells

Abstract99mTc-sestamibi (MIBI) is a well-known tumour imaging agent. Its retention within tumour cell mitochondria is related to perfusion and to the magnitude of the electrical gradient, reflecting cell viability. Several internal cell factors modulate this uptake; for example, multidrug resistance membrane proteins (Pgp and MRP1) and anti-apoptotic BCl-2 protein of the outer mitochondrial membrane can limit retention of MIBI. At the early stage of cell apoptosis, the electrical driving forces of MIBI uptake are impaired, and influx and accumulation are reduced. It seems clear that MIBI can be used before treatment to detect drug resistance, assess anti-apoptotic status and predict treatment efficacy. Although it has been suggested that MIBI might be used to monitor tumour response to treatment, MIBI is unable to differentiate tumours with ongoing apoptosis from those developing drug resistance.

Tc-99m MIBI SPECT in prediction of prognosis in patients with small cell lung cancer

PurposeThe purpose of this study was to evaluate whether the degree of technetium-99m methoxyisobutylisonitrile (MIBI) uptake and its retention in delayed imaging in small cell lung cancer (SCLC) was correlated with the response to multiagent chemotherapy and to investigate if there was a relationship between the survival time of patients with SCLC and Tc-99m MIBI SPECT tumor uptake parameters at the time of diagnosis.MethodsBetween 1998 and by December 2004, 40 patients with SCLC were studied with Tc-99m MIBI SPECT at the time of diagnosis. The patients were classified by a follow-up CT as good responders (complete or partial remission) and poor responders (stable disease or progressive disease). Following i.v. administration of 740 MBq Tc-99m MIBI, SPECT imaging at 30 minutes (early) and 2 hours (delayed) was performed. Regions of interests were placed over the tumors and contralateral normal lung tissue on one transverse section. The uptake ratio of the lesion to that in the contralateral normal lung was obtained from early images (early ratio; ER) as well as delayed images (delayed ratio; DR). The retention index (RI%) was measured as: RI% = [(DR - ER)/ER] x 100. Tc-99m MIBI tumor uptake parameters were compared with chemotherapeutic response and survival time.ResultsOf 40 patients, 29 patients were good responders (72.5%) and 11 patients were poor responders (27.5%). RI% of Tc-99m MIBI SPECT in the group of good response was significantly higher than in that with poor response (p < 0.05). On the other hand, there was no significant difference between the two groups with respect to ER or DR values. Four of 40 patients were still alive with disease (10%). The patient survival time varied from 1 to 70 months (mean survival time = 12.9 ± 13.4 months). There was no significant difference between the survival time of patients with respect to ER or DR of Tc-99m MIBI SPECT imaging. When median RI% was accepted as a cut-off value (-3.85%), patients with higher RI% values had a longer survival time (12 months) when compared with those with low RI% (8 months), p < 0.05.ConclusionOur results suggest that Tc-99m MIBI SPECT could accurately predict the chemotherapy response in patients with SCLC. RI% of Tc-99m MIBI SPECT is recommended to differentiate patients with a poor response to chemotherapy and good responders, and RI% of Tc-99m MIBI SPECT appears as the only parameter that may be useful in predicting the survival of patients with SCLC.

The role of Tc-99m sestamibi imaging in predicting clinical response to chemotherapy in lung cancer

Multidrug resistance (MDR) is a major problem in lung cancer. Tc-99m methoxyisobutyl isonitrile (MIBI) has been demonstrated to be a non-invasive marker to diagnose MDR1 related P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) expression in various solid tumors. The aim of this study was to evaluate the relationship between the degree of Tc-99m MIBI uptake and its retention on delayed images and the response to chemotherapy in lung cancer. Twenty-three patients (1 woman and 22 men, age range 40–67 years) with lung cancer (9 small cell and 14 non-small cell) were examined with Tc-99m MIBI imaging before chemotherapy. After i.v. administration of 740 MBq Tc-99m MIBI, planar and SPECT imaging at 30 minutes and 2 hours was performed. Tumor to normal lung uptake ratio (T/N) and percent retention were measured. Response to chemotherapy was evaluated according to follow-up CT and grouped as complete responders (CR), partial responders (PR) and non-responders (NR). Clinical follow-up and CT evaluation revealed that 12 patients had partial remission, 4 patients had complete remission and 7 patients had no-remission after chemotherapy. Statistically, there was no significant correlation between early (30 min), delayed (2 hr) T/N ratios and percent retention of Tc-99m MIBI with chemotherapeutic response of the lung cancer among the three groups (p>0.05). Results of the current study imply that Tc-99m MIBI uptake and the retention index may not correlate with chemotherapy response in lung cancer, so that the accuracy of this method needs to be verified in a larger series with additional investigation at the molecular level.

Experience of the Izmir Pediatric Oncology Group on Neuroblastoma: IPOG-NBL-92 Protocol

This multicentric study aimed to bring neuroblastoma patients together under IPOG-NBL-92 protocol and evaluate the results within the period between 1992 and 2001 in Izmir. Sixty-seven neuroblastoma patients from 4 pediatric oncology centers in Izmir were included in the study. IPOG-NBL-92 protocol modified from German Pediatric Oncology (GPO)-NB-90 protocol was applied: Patients in stage 1 received only surgery, while surgery plus 4 chemotherapy courses (cisplatin, vincristine, ifosfamide) were given in stage 2 and surgery plus 6 chemotherapy courses (cisplatin, vincristine, ifosfamide, epirubicin, cyclophosphamide) were given in stages 3 and 4 patients. In patients who were kept in complete remission (CR), a maintenance therapy of one year was applied. Radiotherapy was given to the primary site following induction chemotherapy plus surgery in stages 3 and 4 patients with partial remission (PR). The stages of the patients were as follows: 5% in stage 1, 39% in stage 3, 49% in stage 4, and 7% in stage 4S. Primary tumor site was abdomen in 88% of cases. CR rates were as 100% in stage 1, 76% in stage 3, 35% in stage 4, and 75% in stage 4S. Relapse was observed in 32% of patients in a median of 19 months. The median follow-up time for survivors was 33 (17-102) months. Five-year OS rate was 31% and the EFS rate was 30% in all patients. Five-year overall and event-free survival rates were 63 and 30% in stage 3, but 6 and 5%, respectively, in stage 4 patients. Univariate analysis established that the age, stage, primary tumor site, and high LDH and NSE levels conferred a significant difference. The IPOG-NBL-92 protocol has proved to be satisfactory with tolerable toxicity and reasonable CR and survival rates. However, more effective treatments suitable to Turkeys social and economic conditions are urgently needed for children over 1 year of age with advanced neuroblastoma.

Technetium-99m-DTPA aerosol scintigraphy in amiodarone induced pulmonary toxicity in comparison with Ga-67 scintigraphy

Amiodarone hydrochloride, which is used in life-threatening cardiac tachyarrhythmia, has been known to cause amiodarone induced pulmonary toxicity (AIPT) as a complication. In this study we aimed to investigate the clinical value of technetium-99m diethylene triamine penta-acetic acid (DTPA) aerosol lung scintigraphy in patients with AIPT in comparison with gallium-67 (Ga-67) scan. The study group included 26 cases, 7 patients with diagnosis of AIPT (Group A), 8 patients receiving amiodarone therapy but without AIPT (Group B) and 11 healthy subjects as a control group (Group C). All patients underwent Ga-67 and Tc-99m-DTPA aerosol scintigraphy in addition to various laboratory tests, Ga-67 scintigraphy was positive in 4 of 7 AIPT patients but quite normal in Group B. A positive correlation was found (r=0.52, p<0.05) between kep values determined by Tc-99m-DTPA aerosol scintigraphy and the cumulative dose of amiodarone. The mean kep values were 2.04%±0.85% min, 1.30%±0.42% min and 0.86%±0.19% min for groups A, B and C, respectively. The mean clearance rate of group A was significantly faster than that of normals (p<0.0005) and group B (p=0.028). In addition, there was a significant difference between groups B and C (p=0.015).In conclusion, Ga-67 lung scintigraphy is a useful method for the detection of AIPT but Tc-99m-DTPA aerosol scintigraphy offers better results than Ga-67 scintigraphy. Early changes in Tc-99m-DTPA clearance may be observed in patients receiving amiodarone. The kep value in patients with AIPT is noticeably increased with respect to the control group. With its favorable physical properties, low cost, lower radiation burden and its ability to be used as an objective measure for the pulmonary clearance rate, Tc-99m-DTPA aerosol scintigraphy appears to be promising in patients receiving amiodarone therapy.

Treatment results of osteosarcoma of the extremity in children and adolescents at Ege University Hospital.

Twenty-five patients were treated for osteosarcoma of the extremity at Ege University Hospital. Eight of them were metastatic. All patients received cisplatin, doxorubicin, ifosfamide, and methotrexate preoperatively. Twenty-three patients underwent surgery at around week 15 (11-18 weeks). All but one underwent limb-sparing surgery. While good responders continued to receive the same drugs, poor responders were given the same regimen before 1996, but high-dose ifosfamide alone after 1996. For all patients the projected event-free survival (EFS) rates were 63.5% at 2 years and 53% at 5 years. The projected overall survival (OS) rates were 72% at 2 years and 62% at 5 years. For nonmetastatic patients, 5-year EFS and OS rates were 67% as compared with metastatic patients (25 and 50%)( p = .01 for EFS; p > .05 for OS). The results show that nonmetastatic patients with osteosarcoma of the extremity have favorable prognosis on this therapy regimen, allowing a high rate of limb-sparing surgery.