Susanne Martina Eschmann

18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

PurposeThe aim of this study was to evaluate FDG-PET for assessment of therapy response and for prediction of patient outcome after neo-adjuvant radio-chemotherapy (NARCT) of advanced non-small cell lung cancer (NSCLC).MethodsSeventy patients with histologically proven stage III NSCLC underwent FDG-PET investigations before and after NARCT. Changes in FDG uptake and PET findings after completion of NARCT were compared with (1) the histology of tumour samples obtained at surgery or repeat mediastinoscopy, and (2) treatment results in terms of achieved operability and long-term survival.ResultsThe mean average FDG uptake of the primary tumours in the patient group decreased significantly during NARCT (p = 0.004). Sensitivity, specificity and overall accuracy of FDG-PET were 94.5%, 80% and 91%, respectively, for the detection of residual viable primary tumour, and 77%, 68% and 73%, respectively, for the presence of lymph node metastases. A negative PET scan or a reduction in the standardised uptake value (SUV) of more than 80% was the best predictive factor for a favourable outcome of further treatment. Progressive disease according to PET (new tumour manifestations or increasing SUV) was significantly correlated with an unfavourable outcome (p = 0.005). In this subgroup, survival of patients who underwent surgery was not significantly different from survival among those who did not undergo surgery, whereas for the whole patient group, complete tumour resection had a significant influence on outcome.ConclusionFDG-PET is suitable to assess response to NARCT in patients with stage III NSCLC accurately. It was highly predictive for treatment outcome and patient survival. PET may be helpful in improving restaging after NARCT by allowing reliable assessment of residual tumour viability.

Is standardised 18F-FDG uptake value an outcome predictor in patients with stage III non-small cell lung cancer?

PurposeRecent studies have demonstrated the relevance of 18F-FDG uptake as an independent prognostic factor for recurrence of operable non-small cell lung cancer (NSCLC). This corresponds with the experimental finding that FDG uptake correlates with the proliferative activity of tumour cells (Higashi et al., J Nucl Med 2000;41:85-92). On the basis of these observations, we studied the influence of FDG uptake on prognosis and occurrence of distant metastases in patients with advanced NSCLC.MethodsOne hundred and fifty-nine patients with NSCLC of UICC stage IIIA or IIIB were included in the study. In all patients, neoadjuvant treatment was planned to achieve operability. FDG PET was performed as an additional staging procedure prior to the initiation of therapy. Clinical outcome data in terms of overall survival, disease-free survival and incidence of distant metastases could be obtained for 137 patients and were correlated with the average standardised uptake value of the tumour (SUVavg). Furthermore, other factors influencing SUVavg and patient outcome (histological tumour type, grading, UICC stage, tumour size) were analysed.ResultsSUVavg was significantly influenced by tumour histology, UICC stage and tumour size. No significant difference could be shown for grading. In 38 out of the 159 patients (24%), FDG PET revealed previously unsuspected distant metastases. The incidence of distant metastases significantly correlated with SUVavg. Overall survival tended to decrease with increasing SUVavg; however, significance was only reached when a cut-off of 12.0 was applied (p=0.05).ConclusionFDG uptake is an independent prognostic factor in patients with UICC stage III NSCLC, although less distinctively so than has been reported for stage I/II tumours.

[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

PurposeThe observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT).Patients and MethodsIn 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was complemented with data from [68Ga]-DOTA-D Phe1-Tyr3-Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan®. Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package.ResultsThe integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible.ConclusionDOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.

Phase II Trial of a Trimodality Regimen for Stage III Non-Small-Cell Lung Cancer Using Chemotherapy As Induction Treatment With Concurrent Hyperfractionated Chemoradiation With Carboplatin and Paclitaxel Followed by Subsequent Resection: A Single-Center Study

PURPOSE We started a phase II trial of induction chemotherapy and concurrent hyperfractionated chemoradiotherapy followed by either surgery or boost chemoradiotherapy in patients with advanced, stage III disease. The purpose is to achieve better survival in the surgery group with minimum morbidity and mortality. PATIENTS AND METHODS Patients treated from 1998 to 2002 with neoadjuvant chemoradiotherapy and surgical resection for stage III NSCLC were analyzed. The treatment consisted of four cycles of induction chemotherapy with carboplatin/paclitaxel followed by chemoradiotherapy with a reduced dose of carboplatin/paclitaxel and accelerated hyperfractionated radiotherapy with 1.5 Gy twice daily up to 45 Gy. After restaging, operable patients underwent thoracotomy. Inoperable patients received chemoradiotherapy up to 63 Gy. Study end points included resectability, pathologic response, and survival. Results One hundred twenty patients were enrolled; 25% patients had stage IIIA, 73% had stage IIIB, and 2% stage IV. After treatment, 47.5% had downstaging, 29.2% had stable disease, and 23.3% had progressive disease. Thirty patients (25%) were not eligible for operation because of progressive disease, stable disease, and/or functional deterioration with one treatment-related death. The 30-day mortality was 5% in patients who underwent operation. The 5-year survival rate for 120 patients was 21.7%, and it was 43.1% in patients with complete resection. In postoperative patients with stage N0 disease, 5-year survival was 53.3%; if stage N2 or N3 disease was still present, 5-year survival was 33.3%. CONCLUSION Staging and treatment with chemoradiotherapy and complete resection performed in experienced centers achieve acceptable morbidity and mortality.

Accuracy of parathyroid imaging: a comparison of planar scintigraphy, SPECT, SPECT-CT, and C-11 methionine PET for the detection of parathyroid adenomas and glandular hyperplasia.

PURPOSE To compare the accuracy of planar scintigraphy, single photon emission computed tomography (SPECT), SPECT-CT, and positron emission tomography (PET) with C-11 methionine for the pre-operative detection of parathyroid adenomas. MATERIALS AND METHODS We retrospectively evaluated the pre-operative studies of 60 patients with primary (n=56) and secondary (n=4) hyperparathyroidism. In 25/60 patients (Group 1), only planar scans were obtained, and additional SPECT and SPECT-CT were carried out in 35/60 patients (Group 2). PET or PET-CT with C-11 methionine was conducted in 8/60 patients (Group 3). RESULTS The results of the planar scans (Group 1) were true positive in 19/25 patients and false negative in 6/25 patients (sensitivity per patient, 76%). Histopathology confirmed 27 adenomas and two hyperplasia. Planar imaging identified 20/29 of these pathologies, whereas 9/29 were missed (sensitivity per adenoma, 69%). SPECT (Group 2) results were true positive in 34/35 patients and false negative in only one case (sensitivity per patient, 97%). On a lesion-based analysis, 38 adenomas were identified, and two were missed (sensitivity per adenoma, 95%). The sensitivities of SPECT and SPECT-CT were equal; however, SPECT-CT provided superior topographic information. C-11 methionine PET (Group 3) results were true positive in all eight patients. In one case, surgery confirmed two ipsilateral adenomas, only one of which was identified by PET (sensitivity per patient, 100%; per adenoma, 88.9%). CONCLUSION SPECT is superior to planar imaging. SPECT-CT has identical sensitivity compared to SPECT alone, but it provides additional topographic information. The sensitivity of PET appears to be even higher compared to SPECT. In the case of negative scintigraphic findings and proven hyperparathyroidism, additional C-11 methionine PET or PET-CT is recommended.

First Experiences of Radiation Treatment Planning with PET/CT

Background:Positron emission tomography/computed tomography (PET/CT) is composed of modern CT and PET technology in one machine enabling examinations of patients in one session in the same position. Its value for modern radiation treatment planning is under investigation.Methods:In 53 patients with head-and-neck (n = 11), non-small cell lung (n = 16), prostate (n = 14) and other cancers (n = 12), a PET/CT investigation was performed. During the diagnostic examination process an integrated scan under radiation treatment-planning conditions was included. Interpretation and delineation of macroscopic tumor were done in an interdisciplinary approach. Treatment changes occurred after critical interpretation of the PET/CT findings by the responsible radiotherapist. Analysis is descriptive with regard to changes in treatment intention, mode, radiation volumes and doses.Results:Examinations were well tolerated. CT datasets in treatment position could be used for planning. Delineation of macroscopic tumor led to changes of the planning target volume after PET/CT 15 times, total dose was modified twelve times. PET/CT examinations led to changes of the general treatment mode in 19 cases. Using the separate CT and PET datasets, fusion in the planning software was easily performed in all patients due to the use of the same positioning and immobilization devices in PET/CT.Conclusion:Despite the low number of patients and an expectable bias of selection, the first results are encouraging to perform more extended and detailed trials of this technology in radiotherapy planning. Whether PET/CT is superior to PET alone is part of ongoing investigations.Hintergrund:Die Positronenemissionstomographie/Computertomographie (PET/CT) ist eine Weiterentwicklung der Einzelkomponenten moderner CT- und PET-Technologie in einer kombinierten Hybridmaschine, die eine Untersuchung in einer Sitzung in derselben Position ermöglicht. Die Bedeutung für die moderne Strahlentherapie wird intensiv erforscht.Methodik:Bei 53 Patienten mit fortgeschrittenen Kopf-Hals- (n = 11), nichtkleinzelligen Bronchial- (n = 16) und Prostatakarzinomen (n = 14) sowie anderen Tumoren (n = 12) wurde eine PET/CT durchgeführt. Während der diagnostischen Untersuchung wurden die Patienten in Bestrahlungsposition gelagert und ein Scan zur Bestrahlungsplanung integriert. Die Interpretation und Einzeichnung makroskopischen Tumors wurden in einem interdisziplinären Ansatz aus erfahrenem Strahlentherapeut, Nuklearmediziner und radiologischem Diagnostiker vollzogen. Änderungen der Behandlung wurden eingeleitet, wenn sich nach kritischer klinischer Abschätzung der PET/CT-Ergebnisse relevante neue Befunde ergaben. Die Analyse ist deskriptiv in Bezug auf Änderungen von Behandlungsmodalität, -intention, Bestrahlungsvolumen und -dosis.Ergebnisse:Die Untersuchungen mit der PET/CT wurden von den Patienten gut toleriert. Die CT-Datensätze in Behandlungsposition konnten für die Planung verwendet werden. Die Einzeichnung des makroskopischen Tumors führte nach 15 Untersuchungen (26%) zu Änderungen des Planungszielvolumens. Die Gesamtdosis wurde nach zwölf PET/CT-Untersuchungen (21%) modifiziert. PET/CT führte 19-mal (33%) zu Änderungen des generellen Behandlungsmodus. Die separaten CT- und PET-Datensätze der Patienten in derselben Position mit denselben Immobilisierungshilfen konnten zur Fusion in der Planungssoftware einfach genutzt werden.Schlussfolgerung:Trotz der relativ niedrigen Patientenzahl und eines möglichen Selektionsfehlers sind die ersten Ergebnisse erfolgversprechend, um weitere, ausgedehntere Untersuchungen mit großen Patientenzahlen durchzuführen. Inwieweit die kombinierte PET/CT den Einzelkomponenten mit späterer Fusion überlegen ist, sollte in diesem Zusammenhang evaluiert werden.

Kostenüberlegungen zur ganzkörper-MRT und PET-CT im rahmen des onkologischen stagings

PURPOSE The aim of this study was to evaluate and discuss economic aspects of whole-body MRI and PET/CT in oncologic staging. Considerations from the perspective of the health care system, the radiologist, and the patients are presented. MATERIALS AND METHODS Costs of both whole-body techniques are compared with the conventional radiologic diagnostic recommendations of the AWFM (Arbeitsgemeinschaft Wissenschaftlich Medizinischer Fachgesellschaften) in oncologic staging of the five most frequent tumor entities. Temporal and monetary aspects are calculated. Invasive, endoscopic, and endosonographic techniques are regarded as essential and cannot be replaced by other techniques. Thus only the minimal potential for cost reduction is quantified. RESULTS In the German system there is no cipher to correctly balance whole-body MRI and PET/CT. Using the frequently applied ciphers 5700-5730 and 5378, 5489 (factor 1.0) total costs were 440.45 euros, and adding the cipher for additional series 545.37 euros (60 min examination time) for whole-body MRI and 774.74 euros (879.66 euros) (60/90 min examination time) for whole-body PET/CT. Using the common factor 1.8 costs were 981.66 and 1583.38 euros. On the basis of a simple full cost analysis total costs of whole-body PET/CT were higher than of whole-body MRI by a factor of about 2.0 (about 1123 vs 575 euros). There were substantial monetary and temporal differences between tumor entities. In extended bronchial carcinoma 375.32 euros and 55 min can be saved using whole-body MRI in comparison to conventional recommended techniques and using whole-body PET/CT 88.14 euros and 45 min. In tumor entities of lower stages with thus less essential radiologic diagnostics the potential for cost reduction is substantially lower. CONCLUSION Whole-body imaging techniques make it possible to reduce the number of necessary separate radiologic examinations and thus time in oncologic staging. A substantial reduction of health care costs seems to be possible in many tumor entities but differences between different tumor entities are decisive.

[Cost considerations for whole-body MRI and PET/CT as part of oncologic staging].

PURPOSE The aim of this study was to evaluate and discuss economic aspects of whole-body MRI and PET/CT in oncologic staging. Considerations from the perspective of the health care system, the radiologist, and the patients are presented. MATERIALS AND METHODS Costs of both whole-body techniques are compared with the conventional radiologic diagnostic recommendations of the AWFM (Arbeitsgemeinschaft Wissenschaftlich Medizinischer Fachgesellschaften) in oncologic staging of the five most frequent tumor entities. Temporal and monetary aspects are calculated. Invasive, endoscopic, and endosonographic techniques are regarded as essential and cannot be replaced by other techniques. Thus only the minimal potential for cost reduction is quantified. RESULTS In the German system there is no cipher to correctly balance whole-body MRI and PET/CT. Using the frequently applied ciphers 5700-5730 and 5378, 5489 (factor 1.0) total costs were 440.45 euros, and adding the cipher for additional series 545.37 euros (60 min examination time) for whole-body MRI and 774.74 euros (879.66 euros) (60/90 min examination time) for whole-body PET/CT. Using the common factor 1.8 costs were 981.66 and 1583.38 euros. On the basis of a simple full cost analysis total costs of whole-body PET/CT were higher than of whole-body MRI by a factor of about 2.0 (about 1123 vs 575 euros). There were substantial monetary and temporal differences between tumor entities. In extended bronchial carcinoma 375.32 euros and 55 min can be saved using whole-body MRI in comparison to conventional recommended techniques and using whole-body PET/CT 88.14 euros and 45 min. In tumor entities of lower stages with thus less essential radiologic diagnostics the potential for cost reduction is substantially lower. CONCLUSION Whole-body imaging techniques make it possible to reduce the number of necessary separate radiologic examinations and thus time in oncologic staging. A substantial reduction of health care costs seems to be possible in many tumor entities but differences between different tumor entities are decisive.

Improved detection of splenosis in patients with haematological disorders: the role of combined transmission-emission tomography

Abstract. The purpose of this study was to evaluate the use of combined transmission and emission tomography (TET) for correct localisation of heterotopic splenic tissue and differentiation of splenosis from other masses. The TET technique comprises the fusion of SPET and CT data obtained using the same imaging device to allow perfect overlap of anatomical and functional images. TET was performed in seven patients who either had haematological disorders and relapsing anaemia or thrombocytopenia after splenectomy or were under immunosuppression for different reasons. These patients presented 20 equivocal lesions on CT or MRI. Presence of splenic tissue was investigated using technetium-99m labelled colloids or heat-damaged red blood cells. Findings of spleen scintigraphy, TET and CT or MRI were compared with respect to localisation of splenosis and correct classification of lesions by CT or MRI. Histological validation was achieved by surgery or biopsy in all cases. All 20 lesions demonstrated by CT or MRI were correctly classified by TET as splenosis. Three additional lesions initially overlooked by CT or MRI could be detected. Diagnostic relevance was highest for intrahepatic, intrapulmonary or pleural splenic implants. It is concluded that TET allows exact localisation of heterotopic splenic tissue in patients with suspected splenosis.

Neoadjuvant Chemoradiation With Paclitaxel/Carboplatin for Selected Stage III Non–Small-Cell Lung Cancer: Long-Term Results of a Trimodality Phase II Protocol

PURPOSE To evaluate, in a Phase II trial conducted August 1998 through January 2001, the efficacy of neoadjuvant chemotherapy followed by chemoradiotherapy and definitive surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), Stages IIIA bulky and selected Stage IIIB. PATIENTS AND METHODS Staging of LA-NSCLC included computed tomography of cranium, thorax, and abdomen, whole-body positron emission tomography, and video mediastinoscopy. Induction chemotherapy with weekly paclitaxel and carboplatin was followed by hyperfractionated accelerated thoracic radiotherapy (45 Gy) with simultaneous weekly paclitaxel and carboplatin. Four to six weeks after completion of induction therapy, restaging and resection of primary tumor and lymph nodes was intended. RESULTS A total of 59 consecutive patients were enrolled, 25% with Stage IIIA bulky disease, 65% with Stage IIIB, and 10% with Stage IV (excluded from further analysis). Forty-one patients completed induction therapy; in 52.4% a functional (positron emission tomography) downstaging was proven. Thirty-two patients (59.3%) underwent complete tumor resection, and 5 patients had an exploratory thoracotomy only. Histopathologic downstaging was proven in 59.4% and complete response in 21.9%. Hospital mortality was 5.4%. Median duration of follow-up for living patients was 62.1 months. Overall median survival was 22.6 months, 58.2 months for completely resected patients. During induction chemotherapy, Grade 3/4 granulocytopenia occurred in 8% of patients; the most common Grade 3/4 toxicity of chemoradiation was esophagitis, in 26.4% of patients. CONCLUSIONS Induction paclitaxel/carboplatin with hyperfractionated accelerated chemoradiotherapy followed by complete tumor resection demonstrates high efficacy in LA-NSCLC and offers a promising chance of long-term survival.