Positron emission tomography and sentinel lymph node dissection in breast cancer

Sentinel lymph node dissection (SLND) is emerging as the preferred method of axillary staging for breast cancer patients. To further the use of noninvasive techniques in breast cancer, positron emission tomography (PET) scans have been considered as an alternative axillary staging modality. In order to compare the 2 modalities, we studied 15 invasive breast cancer patients who had undergone a preoperative PET scan before sentinel lymphadenectomy. PET scans were compared to axillary pathology results, which were defined as the greatest diameter of nodal metastases. Primary tumor sizes ranged from 0.5 cm to 5.0 cm (median,1.5 cm) and all were ductal in origin except for 1 invasive lobular and 1 mucinous carcinoma. Ten women had completion axillary dissections. Sentinel lymph node dissection was successful in all patients with completion dissections and no false-negative results. Five patients had sentinel node metastases, but PET scans identified only 1 of these patients, resulting in 4 false-negative PET scans. Missed metastases ranged in size from a micrometastatic focus identified only by immunohistochemistry to a nodal tumor measuring 11 mm in diameter. In addition, 1 woman with a PET-positive axilla was tumor free by SLND and remains free of axillary recurrence 29 months postoperatively. Two women had mediastinal uptake by PET scanning and were found to be tumor free after computerized tomography. The results of this preliminary study suggest that PET scanning using current techniques can be used as an adjunct to SLND rather than as an alternative staging technique.     

Fluorodeoxyglucose-positron emission tomography and sentinel lymph node biopsy in staging primary cutaneous melanoma.

AIM: We report the value of sentinel lymph node (SLN) biopsy and fluorodeoxyglucose-positron emission tomography (FDG-PET) in relation to SLN biopsy in staging primary cutaneous melanoma. METHODS: Fifty-five patients with primary cutaneous melanoma >1.0 mm. Breslow thickness and no palpable regional lymph nodes underwent a FDG-PET scan before SLN biopsy. RESULTS: SLN's were retrieved in 53 patients. Melanoma metastases were found in the SLN of 13 patients. FDG-PET detected the lymph node metastases in two of the 13 patients with SLN metastases. In five patients FDG accumulation was recorded in a regional lymph node basin, while no tumour positive SLN was found. In eight patients FDG-PET showed increased activity at a site of possible distant metastasis. Metastatic disease was confirmed in one patient. No explanation for the positive FDG-PET result could be found in five cases. CONCLUSION: FDG-PET should not be considered in this group. SLN biopsy reveals regional metastases that are too small to be detected by FDG-PET. The prevalence of distant metastases is too small to justify routine use of FDG-PET.     

Positron emission tomography in cancer research and treatment

Positron emission tomography (PET), the imaging of pharmaceuticals labeled with positron-emitting radionuclides, is a rapidly growing modality for the diagnosis and management of cancer. PET yields high-quality images characterizing substrate metabolism, cellular proliferation, receptor density, and other parameters that can be used to identify cancer and evaluate its response to therapies. The technique mainly utilized in cancer management is FDG-PET, which exploits the abnormal glucose metabolism of cancer cells first characterized by Warburg. We discuss the principles of PET, the currently available instrumentation and radiopharmaceuticals, the efficacy of FDG-PET in the management of cancer, and the prospects for near-term advances in cancer using PET.     

The single-photon emission computed tomography/computed tomography: a new procedure to perform the sentinel node biopsy in patients with head and neck melanoma

The aim of this study was to define and validate a new technique to detect the sentinel node (SN) in patients treated for head and neck melanoma. In a small series of 23 head and neck melanoma patients, lymphatic mapping was followed by SN biopsy, using in 12 patients a new diagnostic imaging technique, single-photon emission computed tomography/computed tomography. The procedure is described and the major problems encountered are discussed. The preliminary data show that identification of SN using single-photon emission computed tomography/computed tomography never failed in 12 patients, and biopsies performed, compared with those in a standard group, took significantly less time (Mann-Whitney test P=0.006). In conclusion, the authors underline the possibility of a wide use for this technique.     

Sentinel node biopsy for oral and oropharyngeal squamous cell carcinoma in the previously treated neck

In patients with early stage oral or oropharyngeal squamous cell carcinoma (OSCC) sentinel node biopsy (SNB) is a reliable method to detect occult disease in the neck. However, patients with a history of surgery or radiotherapy in the neck may have aberrant lymphatic drainage caused by disruption of lymphatic channels. Therefore, treatment of the same levels at risk as in the primary setting may not be appropriate. The aim of our prospective observational study was to evaluate the clinical application of SNB in previously treated OSCC. Between 2003 and 2010 twenty-two patients were included. Lymph node mapping consisted of preoperative lymphoscintigraphy, SPECT/CT, intraoperative use of gamma-probe and patent blue. Endpoints were the sentinel node (SN) detection rate, unexpected lymphatic drainage patterns, negative predictive value and regional tumor control. 4/22 (18%) Patients were previously treated only on the contralateral site. The SN detection rate was 100% and unexpected drainage was found in 1/4 patients. The other 18 patients had ipsi- or bilateral previous neck treatment and a SN detection rate of 83%. The upstaging rate was 7% and 67% had unexpected lymphatic drainage patterns. The median follow-up was 22 months. Regional tumor control and negative predictive value were 100%. SNB in previously treated OSCC patients is feasible. SN detection is reliable and regional tumor control after staging by SNB is excellent. Moreover, SNB renders an assessment of the individual lymphatic drainage pattern, compensating for a potential variability after previous treatment of the neck.     

Routine positron emission tomography and positron emission tomography/computed tomography in melanoma staging with positive sentinel node biopsy is of limited benefit

Positron emission tomography (PET) is increasingly used for the staging and management of melanoma. The aim of this study was to evaluate the role of PET or PET/ computed tomography (CT) as a routine procedure in patients with positive sentinel node biopsy (SNB). Thirty patients with melanoma of Breslow thickness greater than 1 mm who had PET or PET/CT scans performed within 100 days after a positive SNB were reviewed retrospectively. Two patients (6%) had a positive PET scan, none of which were melanoma related. The first patient had a synchronous neuroendocrine thyroid tumour and the second patient had increased uptake in the chest wall, which proved to be old trauma. Lymph node dissection was positive in five cases (16%). With a median follow-up of 24 months, 21 patients remained disease free. In none of the 30 cases did the early PET scan after a positive SNB alter subsequent melanoma management. The role of PET scanning soon after a positive sentinel node biopsy seems to be of limited benefit. It is questionable whether any imaging is beneficial at this stage. The results of this review suggest that PET scanning might not be indicated for this group of patients.     

A new approach to pre-treatment assessment of the N0 neck in oral squamous cell carcinoma: the role of sentinel node biopsy and positron emission tomography

OBJECTIVES: Pre-operative staging of the clinically N(0) neck in patients with oral squamous cell carcinoma is hindered by the relatively high false negative/positive rates of conventional imaging techniques. The aim of this study is to evaluate the utility of (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) and sentinel lymph node (SLN) imaging and biopsy to determine the true disease status of the loco-regional lymphatics. METHODS: Nineteen patients with biopsy proven disease without palpable or radiological evidence of neck metastases underwent pre-operative (18)F-FDG PET and SLN imaging. All patients underwent whole-body FDG PET and a single view of the head and neck. SLN technique was performed using four peri-tumoural injections of (99m)Tc labeled albumin colloid each of 10 MBq. Dynamic and static imaging followed in the antero-posterior and lateral projections. At operation 1 ml of 2.5% Patent Blue Dye and a hand held gamma probe (Neoprobe 1500) were used in combination to identify and remove the SLN. Surgery then continued along conventional lines including a neck dissection. Histology of the resultant specimen was correlated with that of the SLN and pre-operative imaging. RESULTS: In all patients SLN harvesting was feasible. In 15/19 patients the SLN(s) and the residual neck dissection were -ve for tumour. In 3/19 patients the SLN(s) were +ve for tumour as were other neck nodes. In 1/19 patients the SLN was -ve but another single tumour +ve node was identified in the neck. This patient occurred early in our series with a SLN close to the primary tumour. (18)F-FDG PET failed to identify nodal disease in all four patients with histologically proven lymph node metastases. The size of these nodes ranged from 12 mm x 10 mm x 3 mm to 25 mm x 15 mm x 10 mm. CONCLUSION: SLN imaging and biopsy with probe and Patent Blue Dye guided harvest is feasible in patients with oral squamous cell carcinoma and can predict cervical nodal status. (18)F-FDG PET may be less useful.     

Prospective study of fluorodeoxyglucose-positron emission tomography imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy.

PURPOSE: To prospectively compare positron emission tomography (PET) imaging of regional lymph node basins to sentinel node biopsy (SNB) in patients with American Joint Committee on Cancer (AJCC) stage I, II, and III melanoma localized to the skin. METHODS: Patients with cutaneous melanoma with Breslow's depth greater than 1 mm (AJCC T2-4N0M0) or localized regional cutaneous recurrence (TxN2bM0) underwent whole-body imaging of glucose metabolism with fluorodeoxyglucose (FDG) PET followed by SNB. PET scans were interpreted in a blinded fashion and compared with histologic analyses of SNB specimens and clinical follow-up examination. Nodal tumor volumes were estimated. RESULTS: Eighty-nine lymph node basins were evaluated by FDG-PET and SNB in 70 assessable patients. Eighteen patients (25.7%) had lymph node metastases at the time of FDG-PET imaging: 17 proved by SNB (24.3%) and one by follow-up examination (1.4%). Median tumor volume in positive sentinel node basins was 4.3 mm3 (range, 0.07 to 523 mm3). Sensitivity of SNB for detection of occult regional lymph node metastases was 94.4%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 98.6%. Sensitivity of FDG-PET was 16.7%, specificity was 95.8%, PPV was 50%, and NPV was 81.9%. At a median follow-up duration of 16.6 months, seven patients (10%) developed recurrent disease. PET predicted one recurrence (14.3%) in a node basin missed by SNB. CONCLUSION: FDG-PET is an insensitive indicator of occult regional lymph node metastases in patients with melanoma because of the minute tumor volumes in this population. FDG-PET does not have a primary role for staging regional nodes in patients with clinically localized melanoma.     

Positron emission tomography imaging of colorectal cancer.

Continued improvements in the diagnosis and treatment of colorectal cancer are based on a clearer understanding of the pathophysiological processes underlying the disease and how it affects the patient. The addition of information derived from fluorine-18-labeled deoxyglucose (FDG) positron emission tomography (PET) scans to the cross-sectional imaging data enables a clearer understanding of the pathophysiology of the disease process. In particular, FDG PET scans are capable of demonstrating disease that mimics normal structures on conventional imaging, as well as finding disease in otherwise normal-sized lymph nodes. Abnormal areas of FDG uptake in the setting of known colorectal cancer are almost always due to recurrent disease. In addition, FDG PET offers great promise in the evaluation of treatment response, particularly as more targeted therapies become available. This report covers the basic principles underlying PET imaging, including the biochemistry of FDG and methods of PET analysis. We then, review the clinical indications for FDG PET scanning in colorectal cancer.     

Safety of sentinel node biopsy in pregnant patients with breast cancer.

BACKGROUND: Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) have typically been contraindicated for pregnant patients diagnosed with breast cancer because they are considered unsafe. PATIENTS AND METHODS: Twenty-six premenopausal non-pregnant patients who were candidates for LS underwent peritumoral injection of approximately 12 MBq of 99mTc-HSA nanocolloids. Static [15 min and 16 h post-injection (p.i.)] and whole-body (16 h p.i.) scintigraphic images were acquired. Activity concentration in the urine (0-2, 2-4, 4-8, 8-16 h p.i.) was evaluated by a gamma-counter. Activity in the bloodstream was measured at 4 and 16 h p.i. Thermoluminescent dosimeters (TLD) were placed, before tracer injection, on the injection site, between injection site and epigastrium (two points), and on the epigastrium, umbilicus and hypogastrium, and were removed before surgery. RESULTS: Scintigraphic images showed no radiotracer concentration except in the injection site and in the sentinel node. In all patients, the total activity excreted within the first 16 h was <2% of the injected activity. Activity in the blood pool was, at each time point, <1% of the injected activity. In 23 of 26 patients, all absorbed dose measurements were lower than the sensitivity of the TLD (<10 microGy); in the remaining three patients, the absorbed doses at the level of epigastrium, umbilicus and hypogastrium were in the following ranges: 40-320, 120-250 and 30-140 microGy, respectively. CONCLUSIONS: According to our standard technique (12 MBq of 99mTc-HAS), LS and SLNB can be performed safely during pregnancy, since the very low prenatal doses from this diagnostic procedure, when properly performed, do not significantly increase the risk of prenatal death, malformation or mental impairment.     

Positron emission tomography in gastric and esophageal cancer

PURPOSE OF REVIEW: Positron emission tomography using the positron emitting glucose analogue 18F-fluorodeoxyglucose has recently emerged as a promising metabolism-based whole-body imaging tool for cancer diagnosis and follow-up. Several reports have recently appeared indicating the potential and limitations of this technique. The review limits its scope to the recent advances of 18F-fluorodeoxyglucose positron emission tomography in the clinical management of gastric and esophageal cancer. RECENT FINDINGS: New studies have been reported on the use of 18F-fluorodeoxyglucose positron emission tomography to assess the early and late metabolic response of a gastroesophageal tumor to chemo(radiation) therapy. The metabolic response as measured by serial 18F-fluorodeoxyglucose positron emission tomography, performed before and during treatment or some weeks thereafter, can be used to predict the clinical and histopathologic response. Moreover, the metabolic positron emission tomography response seems to be related to overall and disease-free survival. SUMMARY: Gastroesophageal 18F-fluorodeoxyglucose positron emission tomography could add significant diagnostic information to the different phases of patient management. At initial diagnosis of esophageal cancer, positron emission tomography detects more distant lymph node and organ metastases compared with conventional diagnostics, allowing a more accurate selection of the most appropriate treatment. Serial 18F-fluorodeoxyglucose positron emission tomography performed before and during chemotherapy allows early identification of nonresponding tumors. 18F-fluorodeoxyglucose positron emission tomography performed after a treatment allows accurate assessment of the residual tumor load. 18F-fluorodeoxyglucose positron emission tomography allows accurate detection and restaging of recurrent disease.