Quantitative and clinical implications of the EARL2 versus EARL1 [18F]FDG PET-CT performance standards in head and neck squamous cell carcinoma.

BACKGROUND: The EANM Research Ltd. (EARL) guidelines give recommendations for harmonization of [18F]FDG PET-CT image acquisition and reconstruction, aiming to ensure reproducibility of quantitative data between PET scanners. Recent technological advancements in PET-CT imaging resulted in an updated version of the EARL guidelines (EARL2). The aim of this study is to compare quantitative [18F]FDG uptake metrics of the primary tumor and lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC) on EARL2 versus EARL1 reconstructed images and to describe clinical implications for nodal staging and treatment. METHODS: Forty-nine consecutive patients with HNSCC were included. For all, both EARL1 and EARL2 images were reconstructed from a singular [18F]FDG PET-CT scan. Primary tumors and non-necrotic lymph nodes ≥ 5 mm were delineated on CT-scan. In the quantitative analysis, maximum standardized uptake values (SUVmax) and standardized uptake ratios (SURmax, i.e., SUVmax normalized to cervical spinal cord uptake) were calculated for all lesions on EARL1 and EARL2 reconstructions. Metabolic tumor volume (MTV) and total lesion glycolysis were compared between EARL1 and EARL2 using different segmentation methods (adaptive threshold; SUV2.5/3.5/4.5; SUR2.5/3.5/4.5; MAX40%/50%). In the qualitative analysis, each lymph node was scored independently by two nuclear medicine physicians on both EARL1 and EARL2 images on different occasions using a 4-point scale. RESULTS: There was a significant increase in SUVmax (16.5%) and SURmax (9.6%) of primary tumor and lymph nodes on EARL2 versus EARL1 imaging (p < 0.001). The proportional difference of both SUVmax and SURmax between EARL2 and EARL1 decreased with increasing tumor volume (p < 0.001). Absolute differences in MTVs between both reconstructions were small (< 1.0 cm3), independent of the segmentation method. MTVs decreased on EARL2 using relative threshold methods (adaptive threshold; MAX40%/50%) and increased using static SUV or SUR thresholds. With visual scoring of lymph nodes 38% (11/29) of nodes with score 2 on EARL1 were upstaged to score 3 on EARL2, which resulted in an alteration of nodal stage in 18% (6/33) of the patients. CONCLUSIONS: Using the EARL2 method for PET image reconstruction resulted in higher SUVmax and SURmax compared to EARL1, with nodal upstaging in a significant number of patients.

68Ga-PSMA Uptake in Angiolipoma.

Ga-PSMA PET/CT is an imaging technique used in staging and detection of prostate cancer. However, enhanced uptake on Ga-PSMA PET/CT scan has also been ascribed to other malignant and benign lesions. We report on a case of a 56-year-old man with treated prostate carcinoma who had a Ga-PSMA PET/CT scan for restaging. Ga-PSMA uptakes in the prostatic bed and in multiple subcutaneous lesions were seen. Histopathology of a subcutaneous lesion revealed angiolipoma. It is important to be aware of the existence of the growing amount of reports on enhanced Ga-PSMA uptake unrelated to prostate cancer.

Sentinel node biopsy and concomitant probe-guided tumor excision of nonpalpable breast cancer.

BACKGROUND: Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a large group of patients. METHODS: Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of (99m)Tc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was used to guide the excision. RESULTS: At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%). Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination. Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary recurrence were observed. CONCLUSIONS: Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single dose of (99m)Tc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique.

Ultrasonography and fine-needle aspiration cytology in the preoperative evaluation of melanoma patients eligible for sentinel node biopsy.

BACKGROUND: Ultrasonography with fine-needle aspiration cytology (FNAC) has proven to be a valuable diagnostic tool in the preoperative workup of patients with breast cancer or penile cancer eligible for sentinel lymph node biopsy. The aim of this study was to evaluate the use of this technique in the initial assessment of patients with primary cutaneous melanoma. METHODS: A total of 107 patients with cutaneous melanoma eligible for sentinel node biopsy with clinically negative nodes were studied prospectively. Patients underwent ultrasonography of potentially involved basins and FNAC in case of a suspicious lymph node. The sentinel node procedure was omitted in patients with tumour-positive lymph nodes in lieu of lymph node dissection. RESULTS: Ultrasonography with FNAC correctly identified disease preoperatively in two of the 107 patients (2%). Thirteen of the 22 patients (59%) with a suspicious node on ultrasonographic imaging but a tumour-negative fine-needle aspirate were shown to have involved nodes. Of the 85 patients with ultrasonographically normal nodes, 25 (29%) were shown to have metastases. Of the total of 43 involved basins, 16 contained metastases > 2 mm and 25 < or = 2 mm. CONCLUSIONS: In our hands, the sensitivity and specificity of preoperative ultrasonography to detect lymph node involvement in patients with melanoma are 34% and 87%, respectively. In combination with FNAC, this is 4.7% and 100%, respectively. This yield is insufficient for this technique to be used as a routine diagnostic tool in the selection of patients eligible for sentinel node biopsy.

Clinical implications of sentinel nodes outside the axilla and internal mammary chain in patients with breast cancer.

PURPOSE: The aim of this study was to determine the incidence, location, surgical identification rate, tumor status, and clinical implications of sentinel nodes outside the axilla and internal mammary chain. PATIENTS AND METHODS: In 785 breast cancer patients, pre-operative lymphoscintigraphy was performed after intratumoral injection of 116 MBq 99mTc-labeled nanocolloid (0.2 ml; 3.1 mCi). Sentinel nodes were pursued using a gamma-ray detection probe and vital blue dye. RESULTS: Lymphoscintigraphy visualized sentinel nodes outside the axilla and internal mammary chain in 91 of the 785 patients (12%). Sentinel nodes (106) were identified in 80 patients. These nodes were found in the following locations: 50 in the breast, 31 in the infraclavicular fossa, 19 between the pectoral muscles, and 6 within the supraclavicular bed. Eighteen nodes contained a metastasis (17%) and were removed from 16 patients. The treatment strategy was adjusted in 12 of them with the addition of adjuvant local or systemic therapy. Two additional patients with an unusually situated tumor-negative sentinel node were spared an axillary node dissection that would otherwise have been performed. CONCLUSION: Unusually situated sentinel nodes were visualized in 12% of the patients. The treatment was adjusted in 18% of patients in whom these nodes were identified.

Additional axillary metastases and stage migration in breast cancer patients with micrometastases or submicrometastases in sentinel lymph nodes.

BACKGROUND: In patients with breast cancer, micrometastases and submicrometastases are increasingly found in sentinel nodes when step sectioning and/or immunohistochemical staining are applied. The aims of the current study were to investigate the incidence of micro- and submicrometastases in the sentinel node, to estimate the risk of additional metastases in the remaining axillary lymph nodes, and to consider implications for staging and treatment. METHODS: A total of 2150 breast cancer patients who had undergone axillary sentinel node biopsy between 1999 and 2004 were retrospectively evaluated. RESULTS: In all, 649 patients (30%) had a tumor-positive axillary sentinel node. Of these 649 patients, 148 had (23%) micrometastases and 105 (16%) submicrometastases. Of the 148 patients with micrometastases, 106 underwent axillary lymph node dissection (ALND) and additional metastases were found in 20 patients (19%). Sixteen (15%) had macrometastases and were upstaged. The other 4 patients had additional micrometastases. Seven of the 106 patients (7%) received additional systemic treatment based on the findings in the axillary lymph nodes. Fifty-four of the 105 patients with submicrometastases underwent ALND. Two (4%) of them had additional macrometastases and were upstaged and 2 had additional micrometastases. None received additional treatment based on the ALND findings. CONCLUSIONS: Of the involved sentinel nodes, 23% contained micrometastases and 16% submicrometastases. Additional macrometastases were found in 15% and 4%, respectively, and treatment was altered in 7%. Based on these findings, offering additional treatment of the axilla is suggested in patients with micrometastases, but refraining from ALND in patients with submicrometastases in their sentinel node.

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

BACKGROUND: Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. METHODS: Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. RESULTS: Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. CONCLUSIONS: Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Ultrasonography and fine-needle aspiration cytology can spare breast cancer patients unnecessary sentinel lymph node biopsy.

BACKGROUND: Some 30% to 40% of the breast cancer patients scheduled for sentinel node biopsy have axillary metastasis. Pilot studies suggest that ultrasonography is useful in the preoperative detection of such nodes. The aims of this study were to evaluate the sensitivity of preoperative ultrasonography and fine-needle aspiration cytology for detecting axillary metastases and to assess how often sentinel node biopsy could be avoided. METHODS: Between October 1999 and December 2003, 726 patients with clinically negative lymph nodes were eligible for sentinel node biopsy. A total of 732 axillae were examined. Preoperative ultrasonography with subsequent fine-needle aspiration cytology in case of suspicious lymph nodes was performed in all patients. The sentinel node procedure was omitted in patients with tumor-positive axillary lymph nodes in lieu of axillary lymph node dissection. RESULTS: Ultrasound and fine-needle aspiration cytology established axillary metastases in 58 (8%) of the 726 patients. These 58 were 21% of the total of 271 patients who were proven to have axillary metastasis in the end. Of the patients with ultrasonographically suspicious lymph nodes and negative cytology, 31% had tumor-positive sentinel nodes. Patients with preoperatively established metastases by ultrasonography and fine-needle aspiration cytology had more tumor-positive lymph nodes (P < .001) than patients with metastases established later on. CONCLUSIONS: The sensitivity of ultrasonography and fine-needle aspiration cytology is 21%, and unnecessary sentinel node biopsy is avoided in 8% of the patients. This approach improves the selection of patients eligible for sentinel node biopsy.

Non-axillary breast cancer recurrences after sentinel node biopsy.

BACKGROUND AND OBJECTIVES: The primary lymphatic pathway of patients with breast cancer is toward the axilla, but lymph drainage is also possible towards the internal mammary chain and the supraclavicular fossa. In the current article, the development of breast cancer recurrences at these two sites after sentinel lymph node biopsy is reviewed. METHODS: Since 1997, 803 patients underwent sentinel lymph node biopsy with intratumoral injection of 99mTc-nanocolloid and patent blue dye in The Netherlands Cancer Institute. All sentinel nodes as visualized on the lymphoscintigraphy images were pursued. The patients were followed prospectively for a median period of 34 months. Patients with a lymph node recurrence outside the axilla were identified and their lymphatic mapping procedures were reviewed. RESULTS: Four of the 803 patients (0.5%) developed regional lymph node recurrences outside the axilla. One recurrence was located in the internal mammary chain, the other three in the supraclavicular bed. One or two of these patients also had an axillary recurrence. The sentinel node procedure had failed in two of the four patients. CONCLUSION: The incidence of nodal recurrences outside the axilla is low. Although all extra-axillary sentinel nodes were pursued, some of these recurrences concern missed sentinel nodes that harbor metastasis. Identification of all sentinel nodes and subsequent treatment of the involved basins may reduce the risk of breast cancer recurrences in these unusual locations.

The posterior lymphatic network of the breast rediscovered.

Although the posterior lymphatic network of the breast has been described at the end of the 18th century, this anatomical entity had been almost forgotten. The observation of an increased visualization of extra-axillary sentinel nodes after image guided intralesional radiocolloid injection in non-palpable breast tumors has focused our attention again on the lymphatics on the posterior surface of the breast.

Rationale for superficial injection techniques in lymphatic mapping in breast cancer patients.

One of the most avidly debated issues in lymphatic mapping is where the tracers are best deposited in patients with breast cancer. The four superficial approaches are easy to perform and have several other distinct advantages. They are based on the hypothesis that the entire breast parenchyma and the overlying skin drain to a common node in the axilla because of their common embryological origin. Evidence is presented that casts doubt upon the correctness of this assumption. Tracer administration close to the tumor site appears to be the safest approach for the time being. Excellent results can be obtained with this latter approach, despite the fact that it is technically more demanding.

Dexrazoxane pre-treatment protects skinned rat cardiac trabeculae against delayed doxorubicin-induced impairment of crossbridge kinetics.

1. Dexrazoxane (DXR, ICRF-187) has been shown both in animal studies and clinical trials to provide a substantial cardioprotection when co-administered with anthracycline drugs like Doxorubicin (DOX). In a previous study, we showed that chronic DOX treatment in rats is associated with a clear impairment of the crossbridge kinetics and shift in myosin iso-enzymes. 2. The present study was adopted to investigate whether the cardioprotective action of DXR involves preservation of the normal actin-myosin interaction. Rats were treated for 4 weeks with either DOX at a weekly dose of 2 mg kg(-1) (i.v.), or were pre-injected with DXR (40 mg kg(-1), i.v.) at a 20 : 1 dose ratio 30 min prior to the DOX infusion. Rats receiving saline or DXR alone were included in the experiments. Cardiac trabeculae were isolated 4 weeks after the last infusion and were skinned with detergent. 3. Crossbridge turnover kinetics were studied after application of rapid length perturbations of varying amplitudes in Ca(2+)-activated preparations. DXR treatment offered a significant protection against the DOX-induced impairment of the crossbridge kinetics in isolated cardiac trabeculae. Time constants describing transitions between different crossbridge states were restored to normal in both the quick release protocol and the slack-test. DXR prevented the shift from the 'high ATPase' alpha-myosin heavy chain (MHC) isoform towards the 'low-ATPase' beta-MHC isoform in the ventricles. 4. We conclude that pre-administration of DXR in rats greatly reduces the deleterious effects of chronic DOX treatment on the trabecular actin - myosin crossbridge cycle. Preventing direct deleterious effects on the actin - myosin crossbridge system may provide a new target for preventing or reducing DOX-related cardiotoxicity and may enable patients to continue the treatment beyond currently imposed limits.