Cystic form of cervical lymphadenopathy in adults. Guidelines of the French Society of Otorhinolaryngology (short version). Part 2-etiological diagnosis procedure: Clinical and imaging assessment.

INTRODUCTION: The authors present the guidelines of the French Society of Otorhinolaryngology (SFORL) for clinical and radiological assessment of cystic neck lymphadenopathy of unknown primary in adults. Most cases concern head and neck carcinoma metastasis, often in the oropharyngeal area, or less frequently differentiated thyroid carcinoma or non-keratinizing nasopharyngeal carcinoma. METHODS: A multidisciplinary task force was commissioned to carry out a review of the literature on the etiological work-up in cystic neck lymphadenopathy in adults: clinical examination, conventional imaging (ultrasound, CT, MRI) and metabolic imaging. Guidelines were drafted based on the articles retrieved, and graded A, B, C or expert opinion according to decreasing level of evidence. RESULTS: Oriented clinical examination, cervical and thyroid ultrasound scan and contrast-enhanced neck and chest CT scan are recommended in the assessment of cystic neck lymphadenopathy of unknown primary in adult patients. PET-CT is recommended prior to panendoscopy, to identify the primary tumor. CONCLUSION: Clinical and radiological assessment is fundamental for etiologic diagnosis of cystic neck lymphadenopathy in adult patients, and should be completed by cytological examination before in initiating treatment.

Multifocal recurrence on the transaxillary robotic thyroidectomy incision.

INTRODUCTION: Robotic thyroidectomy (RT) has been reported to achieve satisfactory results. However, its long-term oncological results have not been validated. The use of RT to treat thyroid cancer comprises specific risks that are not encountered with open thyroidectomy (OT). CASE SUMMARY: We report the case of a patient operated by two-stage RT for stage pT3a follicular carcinoma, followed by tumour seeding along the incision despite adjuvant Iodine-131 therapy and external beam radiotherapy. DISCUSSION: This case illustrates the limitations and insufficient perspective of RT for thyroid cancer, with the recent discovery of a risk of tumour seeding along the incision. Rigorous patient selection should help to avoid this risk of tumour seeding.

Cystic form of cervical lymphadenopathy. Guidelines of the French Society of Otorhinolaryngology - Head and Neck Surgery (SFORL). Part 1: Diagnostic procedures for lymphadenopathy in case of cervical mass with cystic aspect.

OBJECTIVES: The authors present the guidelines of the French Society of Otorhinolaryngology - Head and Neck Surgery Society on diagnostic procedures for lymphadenopathy in case of a cervical mass with cystic aspect. METHODS: A multidisciplinary work-group was entrusted with a review of the scientific literature on the topic. Guidelines were drawn up, then read over by an editorial group independent of the work-group, and the final version was drawn up. Guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: In adults presenting a cystic cervical mass, it is recommended to suspect cervical lymphadenopathy: in order of decreasing frequency, cystic metastasis of head and neck squamous cell carcinoma, of undifferentiated nasopharyngeal carcinoma, and of thyroid papillary carcinoma (Grade C). On discovery of a cystic cervical mass on ultrasound, architectural elements indicating a lymph node and a thyroid nodule with signs of malignancy should be screened for, especially if the mass is located in levels III, IV or VI (Grade A). Malignant lymphadenopathy should be suspected in case of cervical mass with cystic component on CT (Grade B), but benign or malignant status cannot be diagnosed only on radiological data (CT or MRI) (Grade A), and 18-FDG PET-CT should be performed, particularly in case of inconclusive ultrasound-guided fine needle aspiration biopsy (Grade C).

[Postoperative external beam radiotherapy for medullary thyroid carcinoma with high risk of locoregional relapse]. / Radiothérapie postopératoire des carcinomes médullaires de la thyroïde à haut risque de rechute locorégionale.

PURPOSE: To assess the outcome of locally advanced medullary thyroid carcinoma treated with surgery and adjuvant external beam radiotherapy. PATIENTS AND METHODS: Twenty-nine consecutive patients with non-metastatic medullary thyroid carcinoma treated in our institution between January 1995 and December 2012 were retrospectively evaluated. All underwent curative-intended optimal surgery, followed by external beam radiotherapy because of high risk of locoregional relapse. Twelve patients were stage III, 16 IVa and 1 IVb. Positive surgical margins were present in 11 cases (10 R1 and 1 R2). Median and average preradiotherapy serum calcitonin were 141pg/mL and 699pg/mL, respectively. Fourteen patients received 3D-conformal radiotherapy and 15 received intensity-modulated radiotherapy. Median prescribed dose was 63Gy to the high-risk volumes and 54Gy to the low-risk volumes. Treatment was delivered in 30 fractions. The median gap between surgery and radiotherapy was 1.9months. Median follow-up was 76.4months. RESULTS: Kaplan-Meier estimates of 5-year locoregional relapse-free survival and overall survival were 79 and 96 %, respectively. Among the five locoregional relapses, two were related to a macroscopic metastatic cervical lymph node that was unfortunately not removed during the lymphadenectomy. Eight of ten patients with microscopic positive margins (R1) were controlled regarding the thyroidectomy bed. Eight patients had normal serum calcitonin after external beam radiotherapy, of whom only one developed a locoregional relapse during follow-up. Regarding the 21 patients with persistent positive serum calcitonin after treatment, only ten developed a macroscopic locoregional or distant relapse. One grade III and no grade IV acute morbidity were reported. Fifteen patients reported grade II chronic morbidity and no grade III/IV. CONCLUSION: Maximal surgery followed by adjuvant external beam radiotherapy as a treatment for locally advanced medullary thyroid carcinoma provides a high rate of long-term locoregional control and overall survival with limited toxicity. Postoperative external beam radiotherapy should be considered when patients present features indicating a high risk of locoregional relapse.

The retrospective binning method improves the consistency of phase binning in respiratory-gated PET/CT.

This study assesses the accuracy of prospective phase-gated PET/CT data binning and presents a retrospective data binning method that improves image quality and consistency. Respiratory signals from 17 patients who underwent 4D PET/CT were analysed to evaluate the reproducibility of temporal triggers used for the standard phase-based gating method. Breathing signals were reprocessed to implement retrospective PET data binning. The mean and standard deviation of time lags between automatic triggers provided by the Real-time Position Management (RPM, Varian) gating device and inhalation peaks derived from respiratory curves were computed for each patient. The total number of respiratory cycles available for 4D PET/CT according to the binning mode (prospective versus retrospective) was compared. The maximum standardized uptake value (SUV(max)), biological tumour volume (BTV) and tumour trajectory measures were determined from the PET/CT images of five patients. Compared to retrospective binning (RB), prospective gating approach led to (i) a significant loss in breathing cycles (15%) and (ii) the inconsistency of data binning due to temporal dispersion of triggers (average 396 ms). Consequently, tumour characterization could be impacted. In retrospective mode, SUV(max) was up to 27% higher, where no significant difference appeared in BTV. In addition, prospective mode gave an inconsistent spatial location of the tumour throughout the bins. Improved consistency with breathing patterns and greater motion amplitude of the tumour centroid were observed with retrospective mode. The detection of the tumour motion and trajectory was improved also for small temporal dispersion of triggers. This study shows that the binning mode could have a significant impact on 4D PET images. The consistency of triggers with breathing signals should be checked before clinical use of gated PET/CT images, and our RB method improves 4D PET/CT image quantification.

Routine FDG PET-CT in patients with a high-risk localized melanoma has a high predictive positive value for nodal disease and high negative predictive value for the presence of distant metastases.

BACKGROUND: FDG PET-CT is the superior imaging modality for the detection of visceral metastases (M+) in patients with melanoma. Conflicting evidence exists regarding its role for the initial staging of patients with high risk localized melanoma (large Breslow Thickness (BT) and/or ulceration). OBJECTIVE: To assess the role of routine staging with FDG PET-CT in melanoma patients with localized high risk melanoma. METHODS: Forty-eight consecutive patients with 1 < BT < 4 mm with ulceration and with BT ≥ 4 mm were staged with PET-CT. PET-CT procedures were performed on a GE Discovery ST® scanner. PET-CT findings for regional nodal status and presence of distant metastatic disease were collected. The gold standard for nodal assessment was pathological examination. The gold standard for M+ was conventional imaging and clinical follow-up, confirmed by biopsy whenever feasible. RESULTS: No patient had a positive PET-CT for M+. Six patients (13%) had a non-conclusive PET-CT; none of them presented with M+ within 6 months. Forty-three patients (90%) had a negative PET-CT, amongst them only one patient (2.5%) presented with M+ within a year. Six patients had FDG-avid lymph nodes in the drainage territory of the primary melanoma, either SLNB or lymph node dissection confirmed metastatic nodal involvement. The predictive positive value of PET for regional node involvement was 100%. COMMENTS: FDG PET-CT does not seem to be effective at detecting M+ at baseline staging in patients with high risk localized melanoma. However, it has a high negative predictive value for the presence of M+ at 6 months and a high positive predictive value for nodal involvement.

Fluorodeoxyglucose positron emission tomography fails to detect distant metastases at initial staging of melanoma patients with metastatic involvement of sentinel lymph node.

BACKGROUND: Positron emission tomography (PET) using fluorodeoxyglucose (FDG) has proven to be more sensitive and accurate than other imaging modalities for the detection of distant metastases in patients with melanoma. Sentinel lymph node (SLN) status is the most important prognostic factor in melanoma patients with no evidence of distant metastasis. OBJECTIVES: To assess the rate of distant metastases in patients with a positive SLN biopsy (SLNB). METHODS: Forty-six consecutive patients with a positive SLNB underwent PET or PET-computed tomography within 6 weeks of the SLNB procedure. The patients did not present any clinical sign of nodal involvement or of distant metastasis. PET findings were classified as positive, negative or nonconclusive. RESULTS: No patient had a positive PET scan for distant metastasis. Six patients (13%) had a nonconclusive PET scan; none of them presented distant metastasis within 12 months. Forty patients (87%) had a negative PET scan; among them five (12%) presented with distant metastasis within 12 months. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography failed to detect distant metastases at initial staging in patients with a positive SLNB, even in patients who presented with distant metastases within 12 months after the FDG PET scan. These results could be explained by the low prevalence of macroscopic metastatic disease at this stage and by the important delay between the onset of the spread of microscopic metastatic disease and the identification by PET scan of macroscopic metastatic disease.

Accuracy of 18-fluoro-2-deoxy-D-glucose positron emission tomography in the pretherapeutic detection of occult para-aortic node involvement in patients with a locally advanced cervical carcinoma.

PURPOSE: Patients with locally advanced cervical cancer (LACC) are usually treated with concurrent chemoradiotherapy. Extended-field chemoradiotherapy is indicated in case of para-aortic node involvement at initial assessment. 18-Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18-FDG PET/CT) is currently considered to be the most accurate method of detection of node or distant metastases. The goal of this study was to evaluate the accuracy of PET at detecting para-aortic lymph node metastases in LACC patients with a negative morphological imaging. METHODS: Patients from five French institutions with LACC and both negative morphologic (magnetic resonance imaging, CT scan) and functional (PET or PET/CT) findings at the para-aortic level and distantly were submitted to a systematic infrarenal para-aortic node dissection either by laparoscopy or laparotomy. On the basis of pathological results, sensitivity, specificity, and positive and negative predictive values of PET/CT were assessed for para-aortic lymph node involvement. RESULTS: A total of 125 LACC patients (stage IB2-IVA disease with two local recurrences) fulfilled the inclusion criteria. All had an ilio-infrarenal para-aortic lymphadenectomy, either by laparoscopy (n = 117) or laparotomy (n = 8). Twenty-one patients (16.8%) had pathologically proven para-aortic metastases. Among them, 14 (66.7%) had negative PET/CT. Overall morbidity of surgery was 7.2%. All but one of the complications were mild and did not delay chemoradiotherapy. Sensitivity, specificity, and positive and negative predictive value of the PET/CT were 33.3, 94.2, 53.8, and 87.5%, respectively, for the detection of microscopic lymph node metastases. CONCLUSIONS: Laparoscopic staging surgery seems warranted in LACC patients with negative PET scan who are candidates for definitive concurrent chemoradiotherapy or exenteration.

Hybrid imaging by SPECT/CT for sentinel lymph node detection in patients with cancer of the uterine cervix.

INTRODUCTION: Conventional lymphoscintigraphy provides planar images with little spatial information on location of pelvic sentinel lymph nodes (SLN). SPECT has better spatial resolution and, in combination with anatomic accuracy provided by CT improves SLN preoperative localization. The aim of the study was to report on the results of hybrid imaging of SLN in early cervical cancer patients treated at Claudius Regaud Cancer Center. METHODS: Stages IA-IB1 cervical cancer patients undergoing preoperative SPECT/CT for SLN detection were analysed. RESULTS: Forty-one patients were included. A 100% SLN detection rate was achieved when a combined technique (radiotracer and blue dye) was used. At least one SLN was clearly visualized by SPECT/CT in 39 of 41 patients (95%) and full anatomic concordance with intraoperative anatomical location of SLN was found in 37 of the 39 patients with at least one SLN identified by SPECT/CT (95%). Location of removed SLN included the external and internal iliac area in 88% patients, the common iliac area in 10.5%, and the inframesenteric para-aortic area in 1.5%. No SLN was found in the infrarenal para-aortic region. Lymph node involvement was identified in 5 patients (12.1%). SLN correctly predicted lymph node involvement in all node-positive patients. However, SPECT/CT failed to identify 1 of the 5 metastatic SLN. DISCUSSION: SPECT/CT accurately detected preoperative SLN topography and enhanced diagnostic sensitivity of SLN imaging, improving surgical approach to patients with cervical cancer staging. Diagnostic quality of anatomic landmarks of CT images of SPECT/CT could be further improved by the use of contrast injected CT.

[An individualized prognosis for truncal melanoma? A series of 77 cases]. / Les mélanomes du tronc ont-ils un pronostic individualisable ? A propos d'une série de 77 cas.

AIMS: Truncal melanoma is characterized by lymphatic drainage to single or multiple basins, affecting different anatomic regions. Since the introduction of sentinel lymph node biopsy (SLN) several questions have aroused in regard to this particular drainage. However, published data available on SLN anatomic distribution and on the prognostic value of multiple-nodal drainage is controversial. The aim of the present study was to provide further evidence based on our own experience. METHODS: From January 2003 through December 2006, a total of 77 melanoma of the trunk were diagnosed and treated at our institution. Systematic lymphoscintigraphy was obtained for all patients, followed by removal of SLN and in-transit lesions. When SLN metastasis was detected a complete lymphadenectomy was performed and adjuvant immunotherapy with interferon was administered. Statistical analysis was performed using Chi2 and Fisher's exact tests for categoric variables and Kaplan-Meier curves for survival. RESULTS: Lymphoscintigraphy visualized 70.1% of single and 28.6% of multiple-nodal drainage (uninterpretable data). The rate of SLN macrometastasis ranged from 7.8 to 14.3%. Micrometastasis were found in 6.5% of patients. Positive SLN were discovered in 12.9% (17/54) of single-nodal and 18.6% (2/22) of multiple-nodal drainage. Melanoma's topography significantly influenced lymphatic drainage distribution, with 28.6% of single-nodal and 71.4% of multiple-nodal drainage for central tumors, and with 79.4% of single-nodal and 19.1% of multiple-nodal drainage for lateral tumors. The group with multiple-nodal drainage was associated non-significantly with primary tumor ulceration, 39 vs 24%. The Breslow thickness did not associate to multiple-nodal drainage. There were no differences in the rate of lymph node metastasis between both groups, 18 vs 12.9%. After a median follow-up of 47 months, prognosis was similar regardless of SLN status, with 80.3% overall survival for negative SLN and 81.3% for positive SLN. Single or multiple drainage did not affect survival rates significantly, with 84% survival for single-nodal drainage and 95% for multiple-nodal drainage. CONCLUSIONS: Primary tumor location (medial location) was the principal risk factor for multi-nodal drainage: lymphoscintigraphy was the best technique for lymphatic drainage assessment. Primary tumor location with single or multi-nodal drainage did not influence the rate of positive SLN and had similar disease-free and overall survival. For us, truncal melanoma has not a different prognosis than melanoma of extremities.

[Systematic neck dissection in squamous cell carcinoma of the oral cavity]. / Evidement cervical systématique dans les cancers épidermoïdes de la cavité orale.

OBJECTIVES: To evaluate the neck control after prior surgical management of patients with squamous cell carcinoma of the oral cavity and to quantify the ratio of patients among whom neck dissection did not have a real therapeutic value. To discuss the usefulness of the sentinel node biopsy in this group of patients. METHOD: Retrospective analysis of patients with epidermoid carcinoma of the oral cavity who had systematically a neck dissection. RESULTS: Thirty-nine files of patients have been processed. We found 45% patients classified pN0 (among whom about one half where classified pT4). With a mean follow-up of 19 months, we did not find any cervical lymph node relapse. Five patients died (13.5%) without any cervical disease. CONCLUSION: The systematic cervical lymph node dissection remains the most effective means to obtain the neck control of squamous cell cancers of the oral cavity. It however was applied without therapeutic value for 45% of the patients of this series. The validation of the sentinel node concept as a method of cervical staging should make it possible to avoid this surgical procedure in more than one third of the cases.

Defective efficacy of retinoic acid treatment in patients with metastatic thyroid carcinoma.

Radioiodine (I-131) therapy is of proven efficacy for differentiated thyroid carcinoma. However, its efficacy relies on specific uptake mechanisms, which may be lost during the evolution of the disease. Attempts to increase the iodine uptake of such tumors have been made using retinoic acid because it exerts redifferentiating effects on thyrocytes. This study aims to assess the capability of the retinoic acid (RA) treatment to reinforce iodine 131-irradiation efficacy for metastatic and progressive multi-irradiated thyroid cancer. In this clinical prospective study, 11 patients (mean age +/- 1 SD = 61 +/- 12 years, sex ratio M/F = 5/6) with a progressive disease despite iterative surgery and iodine irradiations were treated with 13-cis-retinoic acid (1.5 mg/kg day) over 8 weeks prior to I-131 irradiation. The redifferentiating effect of RA was evaluated by serum thyroglobulin (Tg) monitoring during RA treatment and qualitative analysis of iodine uptake on the post-therapeutic whole body scan. The clinical usefulness of RA treatment was assessed by clinical follow-up, Tg monitoring, and tumor size. No serious event that could possibly be related to the treatment was reported. The mean follow up time was 24.2 +/- 12 months (range 3-46 months). Iodine uptake was only slightly improved in two patients. Nevertheless, the clinical benefits of RA seem to be very poor. Five patients died of a metastatic disease. Five others presented new clinical evidences of a progressive disease. In conclusion, this prospective study demonstrates the absence of efficacy of I-131 irradiation combined with RA for the treatment of patients with aggressive, rapidly growing metastatic thyroid cancer. Thus, patients with highly aggressive disease, rapidly growing in a short period from 2 to 6 months, should not be considered for RA therapy.

Iodine-131 pharmacokinetics in patients on hemodialysis for end stage renal disease: clinical implications.

AIM: Curative treatment of thyroid cancer is a major issue for patients with end stage renal disease (ESRD) undergoing dialysis because they might not be included in a renal transplant protocol once they have overcome this disease. Since 131I is mostly eliminated by the kidneys, there is concern regarding the toxicity, efficacy and feasibility of 131I-therapy of anuric dialyzed patients. METHODS: This paper reports on 131I uptake and elimination from remnant thyroid tissue (T), salivary glands (SG), stomach (S) and blood, after administration of 3.7 GBq of 131I for 2 patients on twice weekly dialysis for ESRD. RESULTS: Compared to normal renal function patients, radio-iodine recirculation is observed, and SG and blood irradiation is about 6 times higher, but the dose delivered to the thyroid is not significantly enhanced. Dialysis removes more 131I from SG, S and blood than from T. Anticipated dialysis will reduce irradiation by 38% for the blood, 45% for SG and 34% for T. CONCLUSIONS: Therefore, a higher 131I amount could then be used, providing that accurate personalized dosimetry is previously performed using 131I pharmacokinetic models. Concerning radiation protection issues, no significant dialysis equipment contamination is noted, and nurses and medical staff exposure remains below 0.2 mSv.

[The impact of 18F-fluorodeoxyglucose positron emission tomography on the 3D conformal radiotherapy planning in patients with non-small cell lung cancer]. / Intérêt de la tomographie par émission de positons au [18F]-fluoro-2-désoxyglucose dans la détermination des volumes cibles de radiothérapie. Application à l'irradiation conformationnelle des cancers bronchiques non à petites cellules.

Traditional radiation treatment planning relies on density imaging such as Computed Tomography for anatomic information of various structures of interest including target and normal tissues. However, the difficulties to distinguish malignant from normal tissue on CT slides often leads to inaccurate outlining of the GTV and/or to geographic misses. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) has shown an increase in both sensitivity and specificity over CT in locoregional staging of patients with non-small cell lung cancer (NSCLC). The co registration of FDG-PET images to the data of the CT planning offers the radiation oncologist the possibility to include functional information into the target outlining. For the treatment of patients with NSCLC, it has been shown that the use of FDG-PET images: 1) modified the shape and volume of radiation fields in 22-62% of cases, mainly due to a better nodal staging and distinction of atelectasis from tumor and; 2) significatively reduced the interobserver and intraobserver variability. This paper reviews the results reported in the literature. Challenges and proposed solutions are discussed.