Vivian Bongers

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study

BACKGROUND The prognostic meaning and thus indication for adjuvant therapy of lymphogenic micrometastases in breast cancer patients is still under debate. PATIENTS AND METHODS From 1999 to 2007, 703 patients with (c)T(1-2)N(0) breast cancer underwent surgery including sentinel lymph node biopsy. Examination of sentinel lymph nodes consisted of hematoxylin and eosin and immunohistochemistry staining following serial sectioning of the sentinel node. Patients were divided into four groups: (p)N(0) (n=423), (p)N(1micro) (n=81), (p)N(1a) (n=130) and (p)N(>or=1b) (n=69). Median follow-up was 40 months. RESULTS At the end of follow-up, 53 patients had died and 64 had recurrent disease. Compared with (p)N(0) and following adjustment for possible confounders, including adjuvant systemic treatment, overall survival was not significantly different for (p)N(1micro) while significantly worse for (p)N(1a) and (p)N(>or=1b) {hazard ratio (HR) [95% confidence interval (CI)]: 0.59 [0.14-2.58], 4.31 [1.85-10.01], 10.66 [4.04-28.14], respectively}. Likewise, disease-free survival was not significantly different for (p)N(1micro) and worse for (p)N(1a) and (p)N(>or=1b) (HR [95% CI]: 1.43 [0.67-3.02], 2.79 [1.37-5.66], 7.13 [3.27-15.54], respectively). Distant metastases were more commonly observed in the (p)N(1micro) than in the (p)N(0) group, but still not as common as in the (p)N(1a) or (p)N(>or=1b) group (HR [95% CI]: 4.85 [1.79-13.18], 10.34 [3.82-28.00], 23.25 [7.88-68.56], respectively). CONCLUSION Although the risk of distant metastases was higher in patients in the (p)N(1micro) than in the (p)N(0) group, no statistically significant differences were observed in overall or disease-free survival between (p)N(0) and (p)N(1micro). Micrometastatic lymph node involvement in itself should not be an indication for adjuvant chemotherapy in breast cancer patients.

Cost-Effectiveness of Dual-Head 18F-Fluorodeoxyglucose PET for the Detection of Recurrent Laryngeal Cancer

The study is based upon 80 patients, suspected of having recurrent laryngeal cancer, who underwent an 18F-FDG PET study on a coincidence camera and a laryngoscopic biopsy under general anaesthesia. The potential value of 18F-FDG PET in the detection of local relapses of laryngeal cancer after radiotherapy by use of a coincidence camera was prospectively assessed, and a cost-effectiveness analysis was performed retrospectively. The effectiveness of 18F-FDG PET is reflected in sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) using comparison with the biopsy results as a gold standard. In case of a negative biopsy result, follow-up was continued for a minimum of one year. The results showed a sensitivity of 100%, a specificity of 85%, a PPV of 87%, and a NPV of 100%. Costs per patient of a 18F-FDG PET scan were 682 euro, whereas the saved costs by reducing CT-scans and panendoscopies were 618 euro. In this scenario implementation of 18F-FDG PET scintigraphy in the detection of recurrent laryngeal cancer has additional costs of 64 euro per patient. However, panendoscopy related complications, and potential improvement in quality of life due to early detection of recurrent disease were not taken into account in this study. In conclusion, the technical efficacy of 18F-FDG PET in the detection of recurrent laryngeal cancer is high. 18F-FDG PET is more accurate than CT, and in addition the cost-effectiveness ratio of 18F-FDG PET lies within an acceptable range and has further improvement potential when a quality of life factor is included in a prospective cost-effectiveness analysis.

123i-mibg heart-to-mediastinum ratio is influenced by high-energy photon penetration of collimator septa from liver and lung activity

AimThe 123I-metaiodobenzylguanidine (123I-MIBG) late heart-to-mediastinum ratio (H/M) is a well-established prognostic parameter in patients with chronic heart failure (CHF). However, 123I presents imaging problems owing to high-energy photon emission leading to penetration of collimator septa and subsequent reduction in image quality. Most likely this affects the H/M ratio and may subsequently lead to incorrect patient risk classification. In this prospective study we assessed the intrapatient variation in late H/M ratio between low-energy high-resolution (LEHR) and medium-energy (ME) collimators in patients with CHF. Materials and methodsFifty-three patients with CHF (87% male, age 63±8.3 years, left ventricular ejection fraction 29±7.8) referred for 123I-MIBG scintigraphy were enrolled in the study. In each patient, after the administration of 185 MBq 123I-MIBG, early (15 min after injection) and late (4 h after injection) planar anterior thoracic images were acquired with both LEHR and ME collimators. Early and late H/M ratios were calculated on the basis of the mean count densities from the manually drawn regions of interest (ROIs) over the left ventricle and a predefined fixed ROI placed in the upper mediastinum. Additional ROIs were drawn over the liver and lungs. Liver/lung to myocardium and liver/lung to mediastinal ratios were calculated to estimate the effect of collimator septa penetration from liver and lung activity on the myocardial and mediastinal ROIs. ResultsThe mean LEHR collimator-derived parameters were lower compared with those from the ME collimator (late H/M 1.41±0.18 vs. 1.80±0.41, P<0.001). Moreover, Bland–Altman analysis showed that with increasing late H/M ratios the difference between the ratios from the two collimator types increased (R2=0.73, P=0.001). Multivariate regression analysis showed that almost 90% of the variation in the difference between ME and LEHR late H/M ratios could be explained by scatter from the liver in both the mediastinal and myocardial ROIs (R2=0.90, P=0.001). Independent predictors for the difference in the late H/M between ME and LEHR were the liver-to-heart ratio and the liver-to-mediastinum ratio assessed by ME (standardized coefficient of −1.69 and 1.16, respectively) and LEHR (standardized coefficient of 1.24 and −0.90, respectively) (P<0.001 for all). ConclusionIntrapatient comparison in H/M between the ME and LEHR collimators in patients with CHF showed that with increasing H/M the difference between the ratios increased in favour of the ME collimator. These differences could be explained by septal penetration of high-energy photons from both the liver and the lung in the mediastinum and myocardium, being lowest when using the ME collimator. These results strengthen the importance of the recommendation to use ME collimators in semiquantitative 123I-MIBG studies.

The use of scintimammography for detecting the recurrence of loco-regional breast cancer: histopathologically proven results.

Background99mTc tetrofosmin scintimammography has been shown to be an accurate diagnostic test in patients with a symptomatic breast lesion and for whom a non-diagnostic mammogram has been obtained. Since a physical examination and conventional imaging modalities have their limitations in the detection of recurrent breast cancer, and survival is related to the extent of recurrent disease, complementary imaging modalities are warranted. AimTo evaluate the role of 99mTc tetrofosmin scintimammography in detecting the recurrence of loco-regional breast cancer. Patients and methodsFifty-four patients underwent 55 scintimammography studies because either there were clinical indications of breast metastases, or there was a recurrence of metastases in the chest wall, and/or an evaluation of axillary, parasternal, supraclavicular and/or infraclavicular lymph node metastases was required. Planar breast imaging was performed 10 min after intravenous injection of 700 MBq 99mTc tetrofosmin. Results99mTc tetrofosmin scintimammography was diagnostic in 50 of the 55 studies. An unknown lung metastasis was detected in one patient, and an unknown bone metastasis of the sternum was detected in another. Tumour involvement remained undetected in one neck node metastasis. Three patients had false positive scintimammography results, with 99mTc tetrofosmin uptake in an axillary, infraclavicular and parasternal lymph node, respectively. A fourth patient showed 99mTc tetrofosmin uptake in the scar, which appeared to be an inflammatory lesion, proven by a histopathological biopsy and 1 year clinical follow-up. Conclusion99mTc tetrofosmin scintimammography accurately detected 100% of the local recurrences independently of the extent of the preceding surgical intervention. The sensitivity and specificity of the technique for the detection of regional recurrent disease were 93% and 90%, respectively. These results are substantially higher than those of other imaging modalities.

Interferon-alpha induced changes in CEA expression in patients with CEA-producing tumours

Abstract.Enhancement of antigen expression could result in improved tumour targeting using antibodies directed to the antigen. In this study we performed radioimmunoscintigraphy using 99mTc-CEA-Scan to analyse the effect of interferon-alpha (IFN-α) in enhancing the expression of carcinoembryonic antigen (CEA) in ten patients with CEA-producing tumours. Furthermore, we investigated the feasibility of a future therapeutic study with this antibody fragment labelled with rhenium-186. Although IFN-α gave rise to a significant increase in antibody uptake by the tumour, the absolute antibody uptake in the tumour appeared to be poor, with a mean of 0.475% of injected dose (ID) in the tumour before IFN-α, rising to 0.562% ID in the tumour after IFN-α. Pharmacokinetic analysis demonstrated no significant alterations after IFN-α. In conclusion, the administration of IFN-α is an attractive way to achieve enhanced tumour targeting, although the increase was of little clinical significance in this patient population and using this antibody fragment.

The value of renal scintigraphy in the conservative management of a patient with tuberous sclerosis.

The diagnostic dilemma to differentiate angiomyolipomas from renal cell carcinoma has been resolved by computerized tomography and sonography. However, these imaging modalities are incapable of estimating the functional contribution of individual kidneys. Renal scintigraphy can be used for a quantitative impression of renal function and is, therefore, of additional value in monitoring conservatively treated tuberous sclerosis patients as shown by the case report.

Predictive factors of isolated tumor cells and micrometastases in axillary lymph nodes in breast cancer

INTRODUCTION Since the introduction of the sentinel lymph node biopsy (SLNB) in patients with breast cancer, micrometastases and isolated tumor cells are detected frequently in the SLN. As such, they offer an opportunity to study the development of regional metastases in breast cancer. PATIENTS AND METHODS Between June 1999 and November 2010 1418 patients with cT1-2N0 breast cancer underwent SLNB. Primary tumor characteristics and information regarding regional lymph node involvement were collected prospectively. Patients were categorized into four levels of lymph node involvement: pN0, pN0(i+), pN1mi and pN ≥ 1a. An univariate analysis and a binary logistic regression analysis were performed to assess the relation between patient- and tumor characteristics and lymph node involvement. RESULTS Increasing tumor size and younger age were associated with a higher risk of pN1mi and pN ≥ 1a and a lower chance of pN0 and pN0(i+). Triple negative molecular subtype was associated with a decreased risk of pN1mi and pN ≥ 1a. Tumor size was positively related to overall occurrence of regional lymph node metastases in a linear manner. CONCLUSION Patients with larger tumors, no triple negative disease, and younger age showed a decreased chance of both pN0 and pN0(i+) and an increased risk of both pN1mi and pN ≥ 1a. There seems to be a gradual shift in risk pattern from pN0 to pN0(i+) to pN1mi and to pN ≥ 1a-disease. The presence of the smallest metastases remained fairly constant over time when compared to macrometastases. This constant presence suggests that the risk of seeding and outgrowth of metastases remains constant over time.

Ultrasound-guided sentinel node procedure for nonpalpable breast carcinoma.

PurposePeritumoral and periareolar tracer injection techniques lead to different lymphatic drainage in sentinel lymph node biopsy procedures. In a prospective study, the visualization and identification rates of the ultrasound (US)-guided tracer injection technique for palpable and nonpalpable breast tumors were evaluated. MethodsIn 1262 consecutive patients with cT1-2N0 breast cancer, sentinel lymph node biopsy was performed following peritumoral tracer injection. In the case of nonpalpable breast lesions, Tc-99m nanocolloid injections were given using a 7.5 MHz US probe. In the case of ultrasonographically nonvisible microcalcifications, the US-guided injection technique was wire guided. ResultsIn 331 patients with nonpalpable breast lesions (26.2%), the lymphoscintigraphic visualization and surgical retrieval rates of axillary sentinel lymph nodes (SLNs) were 98.5 and 99.4%, respectively. For internal mammary (IM) SLNs, these rates were 21.1 and 17.8%, respectively. These rates were similar in patients with palpable and nonpalpable tumors. Axillary metastases were detected in 38.7% of the patients with palpable tumors versus 16.5% of those with nonpalpable tumors (P<0.001), whereas IM metastases were found in 4.8 and 3.0% of patients, respectively (P=0.165). ConclusionIn nonpalpable breast lesions, the US-guided injection technique is an accurate technique for SLN identification and retrieval. The substantial rates of IM metastases in both palpable and nonpalpable lesions favor a peritumoral tracer injection technique.

Abstract P4-14-08: Intraoperative ultrasound guidance for excision of non-palpable breast cancer

Background: The effectiveness of intraoperative ultrasound (IOUS) for preoperative localization of non-palpable breast cancers within the operation theatre has not been studied extensively. In this prospective cohort study, we compared margin status, re-excision rate and excised volume of IOUS to guidewire localization (GWL). Methods: A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999–2010. GWL was performed in 138 (54%) and IOUS in 120 (46%) patients. Tumour dimensions, resection volume, margin status and re-excision rates were compared by means of multivariate regression analysis. Calculated resection ratios, i.e. indicating the amount of excess tissue resection, were calculated by dividing the total resection volume by the optimal resection volume (the tumor diameter plus a 1.0 cm margin) and compared between the groups. Results: The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm), while lesions in the GWL group consisted more often of microcalcifications only (19% vs. 3%). Tumour free resection margins were obtained in more than 93% of patients (93.5% with GWL vs. 93.3% with IOUS, P = .958) and re-excision was performed in 11.0% of patients undergoing GWL and 12.5% of patients undergoing IOUS ( P = .684). In both groups, resection volumes were similar, but IOUS led to more optimal tissue resection (calculated resection ratio 4.33 vs 3.30, P = .018). After adjustment for tumor diameter, radiological findings and presence of DCIS, the difference in calculated resection volumes was no longer significant. Conclusion: For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumour removal, re-excision rate and excised volume. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-08.

Malignant Melanoma: European Practice

For many years, the subject of elective lymph node dissection has been one of the most important controversies in the management of patients with malignant melanoma. The status of the regional lymph nodes is a critical component in staging patients with newly diagnosed melanoma, since lymph node involvement in these patients is known to be an unfavourable prognostic factor [1].