Diagnostic performance of imaging techniques for detecting of local recurrence after prostate brachytherapy.

PURPOSE: The purpose of this study was to evaluate MRI and fluorocholine PET/CT diagnostic performances for the detection of local recurrence following prostate brachytherapy for localised prostate cancer. MATERIAL AND METHODS: In this single-centre study, we retrospectively reviewed data from 21 patients treated by brachytherapy for localised prostate cancer and diagnosed with biochemical recurrence according to Phoenix Criteria, who underwent MRI and fluorocholine PET/CT. We included patients with local relapse suspicion according to imaging exams, with biopsy for the final assessment of local recurrence. Patient analysis data were supplemented by segment analysis using an 8-segment model. RESULTS: The fluorocholine PET/CT was positive for 81% and negative for 19% of patients. The sensitivity and specificity were 92% and 33% with diagnosis accuracy of 67%. The MRI was positive for 57% and negative for 43% of patients. The sensitivity and specificity were 67% and 56% with diagnosis accuracy of 62%. There was no statistically significant difference between fluorocholine PET/CT and MRI accuracy (P=0.63). On a segment-based analysis, the sensitivity and specificity were 44% and 82% for fluorocholine PET/CT with diagnosis accuracy of 78%. For MRI, specificity was 91% diagnosis accuracy was 82%. CONCLUSION: Both MRI and fluorocholine PET/CT permit to highlight local recurrence sites after prostate brachytherapy. Confirmation biopsies are, however, necessary since this accuracy is insufficient.

[Reprint of: New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Republication de : Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

[New guidelines for stage III melanoma (the French Cutaneous Oncology Group)]. / Actualisation des données concernant le mélanome stade III : nouvelles recommandations du groupe français de cancérologie cutanée.

Improved knowledge of sentinel node procedures coupled with the results of adjuvant clinical trials in stage III melanoma have prompted the French Cutaneous Oncology Group to propose new guidelines for the management of stage III melanoma. These guidelines comply with the principles of the evidence-based medicine.

French updated recommendations in Stage I to III melanoma treatment and management.

As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé in France. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2 cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in Stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of Stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3 years) is recommended for patients, but with greater emphasis on imaging.

[Update to the recommendations for management of melanoma stages I to III]. / Actualisation des recommandations de prise en charge du mélanome stades I à III.

As knowledge continues to develop, regular updates are necessary concerning recommendations for practice. The recommendations for the management of melanoma stages I to III were drawn up in 2005. At the request of the Société Française de Dermatologie, they have now been updated using the methodology for recommendations proposed by the Haute Autorité de Santé. In practice, the principal recommendations are as follows: for staging, it is recommended that the 7th edition of AJCC be used. The maximum excision margins have been reduced to 2cm. Regarding adjuvant therapy, the place of interferon has been reduced and no validated emerging medication has yet been identified. Radiotherapy may be considered for patients in stage III at high risk of relapse. The sentinel lymph node technique remains an option. Initial examination includes routine ultrasound as of stage II, with other examinations being optional in stages IIC and III. A shorter strict follow-up period (3years) is recommended for patients, but with greater emphasis on imaging.

Prognostic impact of 18F-FDG PET/CT staging and of pathological response to neoadjuvant chemotherapy in triple-negative breast cancer.

PURPOSE: Mortality is high in patients with locally advanced triple-negative breast cancer (TNBC), especially in those with residual tumour after neoadjuvant chemotherapy (NAC). The aim of this study was to determine if pretreatment (18)F-FDG PET/CT staging and pathological findings after NAC could together allow stratification of patients into prognostic groups. METHODS: Initial staging with (18)F-FDG PET/CT was performed prospectively in 85 consecutive patients with stage II/III TNBC. Correlations between PET findings and disease-specific survival (DSS) were examined. In patients without distant metastases on PET staging, the impact of pathological response to NAC on DSS was examined. Patterns of recurrence were also analysed. RESULTS: (18)F-DG PET/CT revealed distant metastases in 11 of 85 patients (12.9 %). Among 74 M0 patients, 23 (31.1 %) showed a pathological complete response (pCR) at surgery, while 51 had residual invasive disease (no pCR). DSS differed considerably among the three groups of patients (log-rank P < .001): among patients with occult metastases on baseline PET/CT, 2-year DSS was 18.2 %, and among patients without initial metastases on PET/CT, 5-year DSS was 61.3 % in patients without pCR after NAC and 95.2 % in those with pCR. Of the 51 patients who did not achieve pCR, 21 relapsed (17 developed distant metastases). The sites of distant recurrence were: lung/pleura (nine patients), brain (eight patients), liver (six patients), distant lymph nodes (six patients) and bone (five patients). CONCLUSION: In patients with clinical stage II/III TNBC, (18)F-FDG PET/CT findings at initial staging and pathological response at the end of NAC allow three groups of patients with quite different prognoses to be defined. Extraskeletal recurrences predominated. Specific follow-up strategies in patients with TNBC who do not achieve pCR deserve investigation.

HER2-overexpressing breast cancer: FDG uptake after two cycles of chemotherapy predicts the outcome of neoadjuvant treatment.

BACKGROUND: Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes. METHODS: During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. ¹8F-fluorodeoxyglucose (¹8F-FDG)-PET/computed tomography (CT) was performed at baseline (PET1) and after two cycles of chemotherapy (PET2). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUVmax at PET1, PET2 and ΔSUVmax) was examined with the t-test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis. RESULTS: Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them ¹8F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUVmax value at PET2 (AUC=0.91) vs 0.67 for SUVmax at PET1 and 0.86 for ΔSUVmax. The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET2, no matter whether in breast or axilla, vs 11.8% in patients with uptake ≤3 (P=0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%. CONCLUSION: The level of residual ¹8F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.

Modern PET imaging for paragangliomas: relation to genetic mutations.

AIM AND METHODS: Paragangliomas (PGL) are neural crest-derived tumours that are found along the autonomic neural network throughout the body and can be multiple and/or metastatic. Nuclear medicine imaging in combination with conventional imaging is required to fully delineate the extent of the disease. The performance of molecular imaging modalities is widely dependent on tumour biology. RESULTS: In the present paper we discuss the recent publications focused on the role of positron emission tomography (PET) imaging and the relationship between tracer uptake patterns and genetic mutations associated with the disease. CONCLUSION: Recent advances in genetic and molecular pathogenesis of PGL have allowed for the identification of new molecular diagnostic and therapeutic radiopharmaceuticals tailored to genetic abnormalities. However, the optimal diagnostic imaging algorithm remains to be determined.

[PET-CT for evaluation of the solitary pulmonary nodule: an update]. / TEP-TDM pour l'exploration du nodule pulmonaire solitaire: acquis et perspectives.

INTRODUCTION: Positron emission tomography (PET) with 18F-FDG has become an important tool for the characterization of solitary pulmonary nodules (SPN). BACKGROUND: The results of the main meta-analyses show that the sensitivity and specificity of 18F-FDG PET for determining malignancy of SPN are close to 95% and 80% respectively. The limits of the technology are now well known. False negative results are mainly due to certain histological types with low metabolic activity (such as bronchiolo-alveolar carcinoma and typical carcinoid), or small size (nodules less than 8 mm). False positives are mainly represented by granulomatous and infectious processes. VIEWPOINTS: A gain in accuracy occurred with the advent of hybrid PET/CT machines that combine the functional data from 18FDG-PET and the morphological data of computed tomography. Improved imaging protocols (eg. injection of iodinated contrast media) could further enhance the performance of PET-CT. Further improvements will rely on respiratory synchronization protocols and on the advent of new PET tracers. CONCLUSION: 18F-FDG PET-CT should be performed for any nodule over 8 mm in size when the pre-test probability of malignancy is not deemed negligible.

[PET/CT in breast cancer: an update]. / Différents rôles de la TEP-TDM en sénologie : mise au point.

The authors discuss the various roles of 18F-FDG PET/CT in the management of breast cancer. Roles of new tracers such as F-18 fluoro-L-thymidine (a marker of cell proliferation), 18-fluoro-17-B-estradiol (marker of estrogen receptor) and sodium fluoride (marker of bone matrix) are also mentioned. There is little justification for the use of FDG-PET/CT in patient with clinically T1 (< or = 2 cm) N0 tumours. Notably, it cannot be used as a substitute to SLNB "sentinel lymph node biopsy" for axillary staging due to limited sensitivity for the detection of small metastases. The case is different in higher risk patients, and especially so in patients with locally advanced disease. FDG-PET/CT in these patients might depict lymph node involvement in the level III of Berg or in supraclavicular or internal mammary basins. It might also uncover occult distant metastases, notably, early osteomedullary infiltration. Thus, for these tumors, initial PET/CT can enable better intramodality treatment planning or a change in treatment. PET/CT as a whole-body examination is also very efficient in case of suspicion of recurrence. On the other hand, many studies show that this functional imaging could be used to assess early response to neoadjuvant chemotherapy or to chemotherapy of metastatic disease. 18FDG-PET/CT could thus become an unavoidable modality to answer various clinical situations.

Thyrotropin variations may explain some positive radioiodine therapy scans in patients with negative diagnostic scans.

UNLABELLED: Thyroglobulin (Tg) is a specific marker of residual thyroid cancer or tumor recurrence. In patients with elevated Tg levels and negative diagnostic radioiodine (131I) whole-body scans (dWBS), administration of a therapy dose may reveal foci that were not initially apparent. The aim of this study was to identify factors, other than 131I activity, which might explain why a post-therapy 131I whole-body scan is sometimes positive despite a negative dWBS. PATIENTS AND METHODS: We reviewed data on all patients with elevated Tg levels and negative dWBS with 185 MBq 131I off-T4 at followup, who subsequently received an empiric therapy dose of 3700 MBq of 131I. During a 5-yr period, 22 patients met these criteria. 131I therapy could be given immediately after negative dWBS in 9 patients, with an average of 8 extra days of hypothyroidism. In the other 13 patients, therapy was given an average of 8 months later. RESULTS: The therapy scan was negative in 16 patients, while it showed uptake in the thyroid bed in 5 patients and distant metastases in two. In the latter two patients, the TSH level was suboptimal at the time of dWBS (9 and 25 microIU/ml), and had risen to 34 and 70 microIU/ml respectively at the time of therapy. Overall, a positive scan following therapy occurred in 7 patients (6/9 patients treated immediately and 1/13 patients treated in a separate setting; p<0.01). In patients with positive therapy scans, the mean TSH level was 73 microIU/ml at the time of dWBS and 103.5 microIU/ml at the time of therapy (41% increase; p<0.05). In patients with negative therapy scans the mean TSH level was 84 microIU/ml at dWBS and 86 microIU/ml at the time of the therapy scan (2% increase). CONCLUSIONS: Our study suggests that interval increase in TSH level with a longer period of stimulation may have contributed to making the whole-body scan positive at the time of therapy. Nowadays, patients with elevated Tg are directly given a therapy dose of 131I. Special care should be taken when preparing patients who have been on suppressive levothyroxine therapy for a long time, in order to avoid misclassifying the tumor as non-functioning.

[Sentinel node biopsy in breast cancer]. / La technique du ganglion sentinelle dans le cancer du sein: quelques considérations récentes.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

[Advantages of PET-CT in the work-up of cervical cancer]. / Intérêts de la TEP-TDM pour le cancer du col de l'utérus.

The present paper addresses the advantages and limits of PET-CT in the work-up of cervical cancer. PET-CT is not to be overlooked in initial staging. It is useful to assess involvement of pelvic and lumbar lymph nodes. It can improve staging accuracy and help guide initial treatment such as optimisation of radiation therapy fields. Given its limited spatial resolution however, PET does not seem so adequate to document tumours less than 5 mm in diameter. It is not warranted for staging carcinoma in situ (FIGO stage 0) or preclinical carcinoma (FIGO stage 1A1 and 1A2). Furthermore MRI performances are best as far as local extension and tumour volume measurement are concerned. PET brings prognostic information. High initial uptake in tumour tissue or persistent increased uptake at completion of treatment indicates rather poor prognosis. PET is useful to evaluate therapy, but its exact role in this issue remains to be further refined. Finally, PET-CT can document early recurrence of disease.

Update on the diagnosis and therapy of distant metastases of differentiated thyroid carcinoma.

Differentiated thyroid cancer, when adequately treated, has an overall good prognosis. However, 10-15% of patients develop distant metastases. The presence of metastases is an important prognostic factor that negatively affects survival. For (131)I-avid distant metastases, (131)I therapy is a very effective treatment modality that induces complete remission in about a third of patients. These figures may be even higher in case of early diagnosis, when tumor burden is still limited. Additional measures may include surgery and/or external beam radiation therapy. Cytotoxic chemotherapy is largely ineffective in patients with progressive, poorly differentiated cancer. These patients should be candidates for trials with new molecularly targeted therapeutic agents. In this paper, a review of diagnostic modalities, prognostic factors and therapeutic options for patients with distant metastases is proposed. In particular, the prognostic value of the early discovery of metastatic disease will be underlined.

Overview on the use of recombinant human thyrotropin in thyroid cancer of follicular cell origin.

Stimulation by recombinant human thyroid-stimulating hormone (rhTSH) has gained wide acceptance as an alternative to thyroid hormone withdrawal in the management of patients with differentiated thyroid cancer. RhTSH has the advantage to avoid both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the risk of cancer growth due to the long-lasting endogenous thyrotropin stimulation. RhTSH is a heterodimeric glycoprotein produced by recombinant DNA technology that has the ability to stimulate thyroglobulin production and radioiodine uptake by thyroid cells. RhTSH is now widely used in the follow-up of thyroid cancer patients in order to improve sensitivity of thyroglobulin (Tg) measurement as well as in preparation of (131)I diagnostic whole-body scan. Although initially approved only for diagnostic purposes, rhTSH has been now approved both in Europe and in the United States for remnant ablation in low-risk patients. As far as residual or metastatic cancer treatment, rhTSH has been initially used on a compassionate need basis for elderly and frailer patients and for patients in whom the withdrawal of thyroid hormone was medically contraindicated. Nowadays, there is a trend for widening the use of rhTSH in therapy, in order to avoid hypothyroidism and the concern about the effect of prolonged endogenous thyroid-stimulating hormone stimulation on cancerous cells. Unfortunately, the studies which address the efficacy of rhTSH in cancer treatment are still scarce and the opportunity of its clinical application remains controversial. In addition, rhTSH has been shown to improve the accuracy of [(18)F]-2-fluoro-deoxy-D-glucose positron emission tomography to detect non-functioning thyroid cancer. Although all studies agree on that rhTSH is much better tolerated from the clinical point of view than thyroid hormone withdrawal, there is some controversy about its comparative ability to raise Tg levels and concentrate radioiodine in cancerous thyroid cells. The aim of this paper is to review the performances of rhTSH as compared to hypothyroidism, considering Tg stimulation and diagnostic whole-body scan sensitivity during follow-up, and its effectiveness for normal remnant ablation and for therapy of metastatic disease.

Kinetics of intracolloidal iodine in thyroid of iodine-deficient or equilibrated newborn rats. Direct imaging using secondary ion mass spectrometry.

The most significant impact of the Chernobyl accident is the increased incidence of thyroid cancers among children. In order to accurately estimate the radiation dose provided by radioiodines, it is important to examine how the distribution of newly incorporated iodine varies with time and if this distribution varies according to the iodine status. The kinetic distribution of intra colloidal newly organified iodine in the rat immature thyroid was recorded and analysed using the ionic nanoprobe NanoSims50. Our observations imply that in case of radioiodine contamination, the energy deposits vary (i) with time, (ii) from one follicle to another, and (iii) from one cell to another inside the same follicle regardless the iodine status. The kinetic heterogeneity of iodine distribution must be take in account in thyroid dose evaluation.