Loco-regional recurrence after surgical treatment of oral squamous cell carcinoma: Proposals for follow-up imaging based on literature, national guidelines and institutional experience.

The recurrence rate following the treatment of oral squamous cell carcinoma (OSCC) by primary surgery is about 10%-26%. The earliest possible diagnosis of residual tumour, recurrence of local tumour disease, and subsequent metastasis is essential for an improvement of the overall survival and of the survival period for affected patients. No international consensus exists for a post-therapeutic surveillance schedule for OSCCs. Based on a review of the literature, existing guidelines, and our institutional experience, we have established an algorithm for the follow-up of these patients regarding the timing and techniques of postoperative imaging. We recommend a follow-up interval of 6 weeks during the first half-year after discharge from hospital by single clinical and alternating clinical check-ups combined with computed tomography (CT) or magnetic resonance imaging (MRI), followed by an interval of 3 months in the second half-year, with clinical and radiological check-ups. In year 2, we recommend a follow-up interval of 3 months with single clinical and alternating clinical check-ups combined with CT or MRI. In year 3, we recommend screening every 6 months, both clinically and via imaging, because of the decreased risk of recurrence. From year 5 onwards, our recommendation is a clinical and imaging-based examination every 6-12 months, depending on patient risk factors and disease progression. Four standard imaging techniques, namely positron emission tomography (PET), CT, MRI, and ultrasound (US), are discussed concerning their range of application, sensitivity, and specificity. Furthermore, the technical aspects of our institutional protocols are described in detail. In highly frequented head and neck cancer centres, PET and US are of secondary importance, since CT and MRI are nowadays highly efficient tools in primary diagnostic and post-therapeutic surveillance.

Circulating tumor cells versus objective response assessment predicting survival in metastatic castration-resistant prostate cancer patients treated with docetaxel chemotherapy.

PURPOSE: Circulating tumor cell (CTC) counts might display a superior prognostic value for overall survival (OS) compared to objective response criteria (OR) in metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: CTCs were detected using the CellSearch™ System out of 122 samples during docetaxel chemotherapy (75 mg/m(2)) at baseline (q0) and after 1 (q1), 4 (q4) and 10 (q10) cycles, in mCRPC patients (n = 33). OR was evaluated by morphologic RECIST and clinical criteria after 4 (q4) and 10 (q10) cycles. RESULTS: For OS, analyses revealed a significant prognostic value for categorical (<5 vs. ≥5) CTC counts (q0, p = 0.005; q1, p = 0.001; q4, p < 0.001; q10, p = 0.002), RECIST (q4, p < 0.001; q10, p = 0.02) and clinical criteria (q4, p < 0.001; q10, p = 0.02). Concordance of CTC counts with OR revealed a sensitivity of 83.3-87.5 % and a specificity of 68.0-76.5 % with complementary discriminatory power for OS. Comparing CTC counts with concomitant OR at q4 in multivariate analyses, an independent prognostic value for OS was found for CTC counts (HR 3.3; p = 0.02) similar to clinical (HR 4.9; p = 0.02) and radiologic response (HR 3.4; p = 0.051). Comparing the predictive value for death, early post-treatment CTC counts at q1 demonstrated significant accuracy with an area under the curve of 79.5 % (p = 0.004) similar to CTC counts at q4 (76.7 %; p = 0.009). Radiologic and clinical response at q4 displayed accuracy similar to early CTC counts at q1 (72.2 %; p = 0.03 and 75.0 %; p = 0.02) despite low sensitivities. CONCLUSIONS: CTC counts appear to be an earlier and more sensitive predictor for survival and treatment response than current OR approaches and may provide complementary information toward individualized treatment strategies.

Impact of flexible body surface coil and patient table on PET quantification and image quality in integrated PET/MR.

AIM: The surface coils of the Biograph mMR integrated PET/MR system were optimised for PET, but are otherwise unaccounted for. The patient table is still more massive than those of PET/CT devices. The goal was to assess those hardware effects on quantification, count statistics, image quality and scan time both with phantoms and in patients and to investigate their clinical relevance. PATIENTS, MATERIAL, METHODS: PET phantom data were acquired with and without the patient table. Image noise was expressed as relative standard deviation and compared to a state-of-the-art PET/CT scanner. Protocols of the phantom/patient study regarding the surface coils were similar. Thoraces/abdomens of 11 patients were scanned with and without a coil (1 BP, 4 min). Mean uptake and standard deviation in a cubical VOI were derived and expressed as SUV. RESULTS: The patient table reduced the number of true coincidences (trues) by 19% (PET/MR) and by 11% (PET/CT). The scan duration for the mMR had to be increased by approximately 30% to achieve a noise level comparable to that of the PET/CT. Decreased SUVs with coil observed in the phantom were confirmed by the patient study. By removing the coil, the mean liver SUV increased by (6 ± 2)%. With (+3 ± 14)%, the average change was similar in lesions, but exceeded 20% in almost one fifth of them. The number of trues grew by (6 ± 1)% for the patients and by 7% for the phantom. CONCLUSION: Due to the additional attenuation caused by MR hardware, PET scan durations would have to be increased compared to current PET/CTs to provide similar image noise levels. The effect of the coils is mostly in the order of statistical fluctuations. In tumour lesions, it is more pronounced and shows a larger variability. Therefore, coils should be included in the attenuation correction to ensure accurate quantification and thus comparability across PET/MR and PET/CT scanners and within patient populations.

[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]. / Ansprechen auf eine Docetaxeltherapie im LNCaP-Prostatakarzinom-Xenograft-Mausmodell. Untersuchung mit der [¹¹C]Cholin-Kleintier-PET/CT.

UNLABELLED: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT. ANIMALS, METHODS: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio). RESULTS: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group. CONCLUSION: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.

Choline PET and PET/CT in Primary Diagnosis and Staging of Prostate Cancer.

PET and PET/CT using [(11)C]- and [(18)F]-labelled choline derivates is increasingly being used for imaging of primary and recurrent prostate cancer. While PET and PET/CT with [(11)C]- and [(18)F]-labelled choline derivates in patients suffering from biochemical recurrence of prostate cancer has been examined in many studies that demonstrate an increasing importance, its role in the primary staging of prostate cancer is still a matter of debate.Morphological and functional imaging techniques such as CT, MRI and TRUS have demonstrated only limited accuracy for the diagnosis of primary prostate cancer. Molecular imaging with PET and PET/CT could potentially increase accuracy to localize primary prostate cancer. A considerable number of studies have examined the value of PET/CT with [(11)C]- and [(18)F]- labelled choline derivates for the diagnosis of primary prostate cancer with mixed results. Primary prostate cancer can only be detected with moderate sensitivity using [(11)C]- and [(18)F]choline PET and PET/CT. The detection rate depends on the tumour configuration. Detection is also limited by a considerable number of microcarcinomas that cannot be detected due to partial volume effects. Therefore small and in part rind-like tumours can often not be visualized. Furthermore, the differentiation between benign changes like prostatitis, high-grade intraepithelial neoplasia (HGPIN) or prostatic hyperplasia is not always possible. Therefore, at the present time, the routine use of PET/CT with [(11)C]- and [(18)F]-labelled choline derivates cannot be recommended as a first-line screening procedure for primary prostate cancer in men at risk. A potential application of choline PET and PET/CT may be to increase the detection rate of clinically suspected prostate cancer with multiple negative prostate biopsies, for example in preparation of a focused re-biopsy and may play a role in patient stratification with respect to primary surgery and radiation therapy in the future.

Imaging of hypoxia using PET and MRI.

Tumor hypoxia is the result of an inadequate supply of oxygen to tumor cells which can be caused by multiple factors. It is associated with aggressive local tumor growth and invasion, increased risk of metastasis, higher resistance to radiotherapy (RT) and chemotherapy, overall resulting in a poor clinical prognosis. Many locally advanced solid tumors may exhibit hypoxic and/or anoxic tissue areas that are heterogeneously distributed within the tumor mass. As hypoxia is a negative prognostic factor concerning response to radiotherapy and chemotherapy, in vivo measurement of tumor hypoxia could be helpful to identify patients with worse prognosis or patients that could benefit from appropriate treatments such as intensity modulated radiotherapy (IMRT) that may accurately conform the dose distribution to small intratumoral regions showing differences in the oxygen level. A manifold of different methods to assess the oxygen tension (pO2) in tissues have been developed, each of them offering advantages as well as drawbacks. They range from invasive direct measurement techniques of the pO2 in tissue by using a polarographic electrode, to non-invasive imaging techniques such as positron emission tomography (PET) or magnetic resonance imaging (MRI). This article provides an overview over the various methods, with a particular emphasis on PET and MRI for imaging of hypoxia, and reviews their performance in preclinical and clinical studies.

The detection rate of [11C]choline-PET/CT depends on the serum PSA-value in patients with biochemical recurrence of prostate cancer.

PURPOSE: An increase of the serum PSA-level is a sensitive in vitro marker for recurrent prostate cancer. However, it remains difficult to differentiate between local, regional or distant recurrent disease. The aim of this study was to assess the relationship between the detection rate of [(11)C]Choline-PET/CT and the serum PSA-level in patients with a biochemical recurrence of prostate cancer with the view towards localisation of recurrent disease. METHODS: Sixty-three patients (mean age, 68.8 +/- 6.9; range, 45-83 years) with biochemical recurrence after primary therapy for prostate cancer were included in the analysis. Mean PSA-levels were 5.9 +/- 9.7 ng/ml (range, 0.2-39 ng/ml; median, 2.15). Of the 63 patients, 17 were under anti-androgen therapy at the time of [(11)C]Choline PET/CT. Patients underwent a [(11)C]Choline-PET/CT study after injection of 656 +/- 119 MBq [(11)C]Choline on a Sensation 16 Biograph PET/CT scanner. RESULTS: Of the 63 patients, 35 (56%) showed a pathological [(11)C]Choline uptake. The detection rate of [(11)C]Choline-PET/CT showed a relationship with the serum PSA-level: The detection rate was 36% for a PSA-value <1 ng/ml, 43% for a PSA-value 1-<2 ng/ml, 62% for a PSA-value 2-<3 ng/ml and 73% for a PSA-value >or=3 ng/ml. Anti-androgen therapy did not show a significant effect on the detection rate of [(11)C]Choline-PET/CT (p = 0.374). CONCLUSION: As an important result our study shows that even for PSA-values <1.0 ng/ml the detection efficiency of [(11)C]Choline-PET/CT is 36%. Furthermore, the detection rate of [(11)C]Choline-PET/CT shows a positive relationship with serum PSA-levels in patients with biochemical recurrence of prostate cancer after primary therapy. Therefore, in these patients, [(11)C]Choline PET/CT allows not only to diagnose but also to localise recurrent disease with implications on disease management (localised vs systemic therapy).

Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a pilot study.

PURPOSE: Hypoxia is an important negative prognostic factor for radiation treatment of head and neck cancer. This study was performed to evaluate the feasibility of use of (18)F-labelled fluoroazomycin arabinoside ([(18)F]FAZA) for clinical PET imaging of tumour hypoxia. METHODS: Eleven patients (age 59.6 +/- 9 years) with untreated advanced head and neck cancer were included. After injection of approximately 300 MBq of [(18)F]FAZA, a dynamic sequence up to 60 min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h p.i., static whole-body PET (n = 5) or PET/CT (n = 6) imaging was performed. PET data were reconstructed iteratively (OSEM) and fused with CT images (either an external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs) and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues. Also, the tumour volume displaying a T/M ratio >1.5 was determined. RESULTS: Within the first 60 min of the dynamic sequence, the T/M ratio generally decreased, while generally increasing at later time points. At 2 h p.i., the tumour SUV(max) and SUV(mean) were found to be 2.3 +/- 0.5 (range 1.5-3.4) and 1.4 +/- 0.3 (range 1.0-2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0 +/- 0.3 (range 1.6-2.4). The tumour volume displaying a T/M ratio above 1.5 was highly variable. At 2 h p.i., [(18)F]FAZA organ distribution was determined as follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung. CONCLUSION: [(18)F]FAZA PET imaging appears feasible in head and neck cancer patients, and the achieved image quality is adequate for clinical purposes. Based on our initial results, [(18)F]FAZA warrants further evaluation as a hypoxia PET tracer for imaging of cancer.

Standardised uptake values from PET/CT images: comparison with conventional attenuation-corrected PET.

PURPOSE: In PET/CT, CT-derived attenuation factors may influence standardised uptake values (SUVs) in tumour lesions and organs when compared with stand-alone PET. Therefore, we compared PET/CT-derived SUVs intra-individually in various organs and tumour lesions with stand-alone PET-derived SUVs. METHODS: Thirty-five patients with known or suspected cancer were prospectively included. Sixteen patients underwent FDG PET using an ECAT HR+scanner, and subsequently a second scan using a Biograph Sensation 16PET/CT scanner. Nineteen patients were scanned in the reverse order. All images were reconstructed with an iterative algorithm (OSEM). Suspected lesions were grouped as paradiaphragmatic versus distant from the diaphragm. Mean and maximum SUVs were also calculated for brain, lung, liver, spleen and vertebral bone. The attenuation coefficients (mu values) used for correction of emission data (bone, soft tissue, lung) in the two data sets were determined. A body phantom containing six hot spheres and one cold cylinder was measured using the same protocol as in patients. RESULTS: Forty-six lesions were identified. There was a significant correlation of maximum and mean SUVs derived from PET and PET/CT for 14 paradiaphragmatic lesions (r=0.97 respectively; p<0.001 respectively) and for 32 lesions located distant from the diaphragm (r=0.87 and r=0.89 respectively; p<0.001 respectively). No significant differences were observed in the SUVs calculated with PET and PET/CT in the lesions or in the organs. In the phantom, radioactivity concentration in spheres calculated from PET and from PET/CT correlated significantly (r=0.99; p<0.001). CONCLUSION: SUVs of cancer lesions and normal organs were comparable between PET and PET/CT, supporting the usefulness of PET/CT-derived SUVs for quantification of tumour metabolism.

PET and PET/CT studies of tumor tissue oxygenation.

Hypoxia has been identified as a major adverse prognostic factor for tumor progression and for resistance to anticancer treatment. Various approaches have been evaluated to assess tumor hypoxia in vivo. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumor oxygenation, thus offering the potential to optimize and individualize a therapy for patients suffering from cancer. The current PET tracers and animal models for the study of tissue hypoxia including aspects of small animal PET imaging are reviewed in this paper. Special emphasis is placed on human PET studies assessing tumor hypoxia in patients with different tumor entities, various anticancer therapies (chemotherapy, radiation therapy, hypoxia targeting chemotherapy) as well as studies deriving prognostic factors and outcome data. Methodological advantages underpinning PET/CT in the imaging of hypoxia are discussed. The great promise of PET/CT is its potential as a single imaging modality for whole body staging providing both anatomical and biological information on the tumor as a whole. It allows a more precise estimation of the hypoxic tumor volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). Finally, PET and PET/CT are discussed in the framework of individualized therapies with its special significance for intensity modulated radiation therapy and selective dose escalation in hypoxic tumor regions as well as more systemic approaches such as hypoxia-directed cytotoxins.

[Scintigraphic procedures in internal medicine--indications, limits, possibilities]. / Szintigraphische Verfahren in der Inneren Medizin -- Indikationen, Grenzen, Möglichkeiten.

Scintigraphy continues to play an important diagnostic role in internal medicine. Many diagnostic questions can only be answered with scintigraphic methods. The application of specific radiopharmaceutical tracers offers the unique possibility to visualize ongoing functional changes, associated with diseases concerning internal medicine. The diagnostic potential of modern scintigraphic procedures such as PET for internal medicine is not yet sufficiently used and will continue to grow with hybrid systems, such as PET-CT and SPECT-CT.

Palliative treatment of painful disseminated bone metastases with 186Rhenium-HEDP in patients with lung cancer.

AIM: The aim of this study was to determine if patients with lung cancer and metastatic bone pain due to disseminated secondary bone disease, can benefit from the treatment with (186)Re-HEDP and to discuss the criteria useful for selecting those patients. METHODS: Twenty-four patients were included in this study and they received 1295 MBq (186)Re-HEDP. All patients underwent (99m)Tc-MDP bone scan before treatment from which the bone scan index (BSI) was determined (mean=18.7+/-17.1%). Most patients underwent CT scan of the painful areas from which the osteolytic element of their bone lesions as well as possible infiltration of the soft tissues was determined. Patients with predominantly osteolytic metastases at the sites considered to be the origin of pain in the CT scan, were excluded. All patients were under analgesic therapy, 22/24 were taking opiates. Pain was estimated by the visual analogue scale (VAS) before the application of (186)Re-HEDP and over the following 8 weeks. The possible myelotoxicity of (186)Re was assessed. RESULTS: The mean VAS score was 6.9+/-2.5 before the application and 3.2+/-2.6 after therapy. Pain relief was obtained in 23/24 patients. Sixty-two percent of the patients exhibited clinically significant pain relief of at least 3 VAS score. The dosage of opiates was decreased in 77% of the patients and could be discontinued in 4 of them. Myelotoxicity was observed in 1 patient. Ninety-one percent of our patients showed improvement in the parameters that assess the quality of life. CONCLUSION: The application of a standard dose of (186)Re-HEDP in patients with lung cancer and painful disseminated bone metastases has a satisfactory pain alleviating effect. The easy application and very low myelotoxicity are important factors in this group of patients. A better analgesic effect of the (186)Re-HEDP application can be expected if combined estimation of the (99m)Tc-MDP bone scan and the CT scan is used.

Uptake and washout of 99mTcV-dimercaptosuccinic acid and 99mTc-sestamibi in the assessment of histological type and grade in breast cancer.

This study was performed to investigate the relationship between histological type and grade, with the uptake and washout of 99mTc-hexakis-2-methoxyisobutylisonitrile (99mTc-sestamibi, 99mTc-MIBI) and 99mTcV-dimercaptosuccinic acid (99mTcV-DMSA) in breast cancer. Forty-five patients with histologically proven breast cancer had previously been referred for 99mTcV-DMSA and/or 99mTc-MIBI scintimammography. Twenty-five of them underwent both 99mTcV-DMSA and 99mTc-MIBI scintigraphy in a double phase study. Lateral prone and anterior supine images were acquired at 15 and 60 min after administration of 740-925 MBq of each radiotracer. Uptake ratios and retention index were calculated and correlated with histology and grade of malignancy. Histology showed eight different histotypes: 77.7% were infiltrating ductal or lobular carcinomas. Mammography was definitely positive in 32/45, indeterminate in 10 and negative in three cases (sensitivity 71%). 99mTcV-DMSA was true positive in 37/40 (sensitivity 92.5%) and 99mTc-MIBI in 28/30 (sensitivity 93.3%) breast cancers. Uptake ratios were significantly higher in ductal than in lobular carcinomas on 99mTcV-DMSA and 99mTc-MIBI scintigrams at early and delayed phases. Grade II carcinomas had significantly lower values of retention index (rapid washout) than grade III carcinomas. This finding was statistically significant only on 99mTc-MIBI scans and was observed in ductal and lobular carcinomas. The retention index did not show any significant difference between ductal and lobular carcinomas. Uptake ratios were also not statistically different between grade II and III cancers. It is concluded that 99mTc-MIBI and 99mTcV-DMSA uptake in breast cancer is probably related to histological type and may distinguish ductal from lobular carcinomas. To a certain degree, the washout rate may reflect the histological grade, but since grade is not the only factor influencing this phenomenon it should be explored further in conjunction with other parameters by multivariate analysis in order to clarify eventual indirect correlations.