Monique G.G. Hobbelink

Predictive value of tumor load in breast cancer sentinel lymph nodes for second echelon lymph node metastases

Background: The need for routine axillary lymph node dissection (ALND) in patients with invasive breast cancer and low-volume sentinel node (SN) involvement is questionable. Accurate prediction of second echelon lymph node involvement could identify those patients most likely to benefit from ALND. Methods: A consecutive series of 317 patients with invasive breast cancer and a tumor positive axillary SN followed by ALND was reviewed. Clinicopathologic features of the primary tumor and the SN were assessed as possible predictors of second echelon lymph node involvement. Results: Second echelon metastases were found in 116/317 cases (36.6%). Frequency of second echelon lymph node involvement in patients with isolated tumor cells (ITC, N = 23), micro- (N = 101) and macrometastases (N = 193) was 13%, 20% and 48%, respectively (p < 0.001). Based on the area % of SN occupied by tumor no subgroup of patients could be selected with less than 20% second echelon lymph node involvement. However, none of the patients with SN ITC or micrometastases and a primary tumor size ≤1 cm (N = 12, 3.8%) had second echelon lymph node involvement. Conclusions: Accurately measured SN tumor load predicts second echelon lymph node involvement. However, even in patients with ITC, the second echelon lymph nodes are involved in 13% justifying ALND.

Radio guided occult lesion localization (ROLL) for non-palpable invasive breast cancer.

Wire guided localization (WGL) for non‐palpable breast cancer is technically difficult and patient unfriendly. Radio guided occult lesion localization (ROLL) takes advantage of the possibility to detect the tumor through the nuclear tracer that is injected directly into the tumor for the sentinel node procedure.

Sentinel Lymph Node Mapping in Colon Cancer: Current Status

ABSTRACTBackgroundThe primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer.MethodsA systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated.ResultsThe literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye.ConclusionsSentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients.

The efficacy of 'Radio guided Occult Lesion Localization' (ROLL) versus 'Wire-guided Localization' (WGL) in breast conserving surgery for non-palpable breast cancer: A randomized clinical trial - ROLL study

BackgroundWith the increasing number of non palpable breast carcinomas, the need of a good and reliable localization method increases. Currently the wire guided localization (WGL) is the standard of care in most countries. Radio guided occult lesion localization (ROLL) is a new technique that may improve the oncological outcome, cost effectiveness, patient comfort and cosmetic outcome. However, the studies published hitherto are of poor quality providing less than convincing evidence to change the current standard of care.The aim of this study is to compare the ROLL technique with the standard of care (WGL) regarding the percentage of tumour free margins, cost effectiveness, patient comfort and cosmetic outcome.Methods/designThe ROLL trial is a multi center randomized clinical trial. Over a period of 2–3 years 316 patients will be randomized between the ROLL and the WGL technique. With this number, the expected 15% difference in tumour free margins can be detected with a power of 80%. Other endpoints include cosmetic outcome, cost effectiveness, patient (dis)comfort, degree of difficulty of the procedures and the success rate of the sentinel node procedure.The rationale, study design and planned analyses are described.Trial Registration(http://www.clinicaltrials.gov, study protocol number NCT00539474)

Prostate Perfusion In Patients With Locally Advanced Prostate Carcinoma Treated With Different Hyperthermia Techniques

PURPOSE We determined prostate perfusion in 18 patients with locally advanced prostate carcinoma treated with a combination of external beam irradiation and regional (10) or interstitial (8) hyperthermia. MATERIALS AND METHODS Perfusion values were calculated from temperature elevations due to constant applied power and from transient temperature measurements after a change in applied power. Students t test was used for comparing perfusion values with time and in the 2 groups. RESULTS At the start of regional hyperthermia treatment mean estimated perfusion plus or minus standard deviation was 10 +/- 8 ml./100 gm. per minute. At the end of treatment mean perfusion was increased to 14 +/- 2 ml./100 gm. per minute (p <0.01). Achieved thermal parameters were a mean temperature of at least 40.3C +/- 0.6C in 90% of the prostate, 40.9C +/- 0.6C in 50% and a mean maximum temperature of 41.6C +/- 0.6C. At the end of interstitial hyperthermia treatment estimated mean perfusion was 47 +/- 5 ml./100 gm. per minute, which was significantly different compared with the end of regional hyperthermia (p < 0(-7) ). Mean temperature was at least 39.4C +/- 0.9C in 90% of the prostate and 41.8C +/- 1.6C in 50%, while mean maximum temperature was 53.1C +/- 6.3C. Systemic temperature increased during regional hyperthermia up to 38.6C, whereas during interstitial hyperthermia body temperature was not elevated. CONCLUSIONS During interstitial hyperthermia perfusion values are higher than during regional hyperthermia. Hyperthermia causes increased prostate perfusion.

Preoperative sentinel node mapping with 99mTc-nanocolloid SPECT–CT significantly reduces the intraoperative sentinel node retrieval time in robot assisted laparoscopic cervical cancer surgery

OBJECTIVE To compare preoperative sentinel node (SN) mapping with planar lymphoscintigraphy (LSG) to single photon emission computed tomography with computed tomography (SPECT-CT) for differences in intraoperative SN retrieval time in surgically treated cervical cancer patients. METHODS In cervical cancer patients planned for radical surgery, one day preoperatively, 220-290 MBq technetium-99m-nanocolloid was injected intracervically in four quadrants. Subsequent SN mapping was performed by either LSG (09.2009-03.2011) or SPECT-CT (03.2011-10.2012). The SN resection, by four armed robot assisted laparoscopy, was based on blue dye and technetium-99m and followed by pelvic lymph node dissection. Timing of perioperative care, including SN procedure times, was prospectively registered. RESULTS Out of the 62 subjects included, 33 (53.2%) underwent LSG and 29 (46.8%) SPECT-CT. No significant differences in baseline characteristics were observed. Bi- and unilateral SN visualization rates were 75.8% and 15.2% for LSG versus 86.2% and 6.9% for SPECT-CT (p=0.299 and p=0.305, respectively). Intraoperative bi/unilateral SN detection occurred in 84.8% and 9.1% of LSG subjects versus 89.7% and 3.4% for SPECT-CT (p=0.573 and p=0.616). Correlation in SN location between mapping and surgery was low for LSG (Spearman ρ=0.098; p=0.449) but high for SPECT-CT (ρ=0.798; p<0.001). Bilateral intraoperative SN retrieval times for LSG and SPECT-CT were 75.4±33.5 and 50.1±15.6 min, resulting in an average difference of 25.4 min (p=0.003). CONCLUSION SPECT-CT significantly reduces intraoperative SN retrieval with a clinically relevant time compared to LSG. The trend towards better bilateral visualization rates and significantly higher anatomical concordance may partly explain the observed difference in SN retrieval time.

Implementation of sentinel node biopsy in breast cancer patients in the Netherlands

BACKGROUND This population-based study describes the implementation of the sentinel node biopsy (SNB) in breast cancer patients in the Netherlands. We examined the extent of use over time of SNB in women who were considered eligible for SNB on the basis of their clinical status. METHODS The study included a total of 35,465 breast cancer patients who were diagnosed with T1-2 tumours (5.0 cm), negative axillary lymph node status and no distant metastases upon clinical examination between 1st January 1998 and 31st December 2003 in six Comprehensive Cancer Centre regions in the Netherlands. Information on axillary surgery was classified as SNB alone, SNB+axillary lymph node dissection (ALND), ALND alone or none. Patterns of use of axillary surgery were summarised as the proportion of patients receiving each surgery type. RESULTS Overall, 25.7% of patients underwent SNB alone, 19.1% underwent SNB+ALND, 50.0% had ALND alone and 5.2% did not have axillary surgery. SNB was more common in women who had breast-conserving surgery: 50.5% of patients who received breast-conserving surgery underwent SNB compared to 40.7% of patients who had mastectomy (p<0.0001). Amongst patients receiving breast-conserving treatment, 31.7% had SNB as final axillary surgery, whilst 20.5% of patients who had mastectomy had SNB alone (p<0.0001). The proportion of women who underwent a SNB alone or in combination with ALND increased over the period 1998-2003, from 2.1% to 45.8% and from 6.7% to 24.8%, respectively. There were marked differences in the patterns of dissemination of the use of SNB between regions: by 2003, the difference between the regions with the highest and lowest proportion of use was 25%. CONCLUSIONS SNB has become the standard-of-care for the treatment of breast cancer patients clinically diagnosed with T1-2 tumours, clinically negative lymph nodes and without distant metastases. In 2003, 70.6% of patients with early breast cancer in the Netherlands received SNB, and within this group, 64.9% of patients had SNB as the final axillary treatment. Implementation of SNB may depend on factors associated with regional organisation of care.

The Microanatomic Location of Metastatic Breast Cancer in Sentinel Lymph Nodes Predicts Nonsentinel Lymph Node Involvement

BackgroundThe majority of sentinel node (SN) positive breast cancer patients do not have additional non-SN involvement and may not benefit from axillary lymph node dissection (ALND). Previous studies in melanoma have suggested that microanatomic localization of SN metastases may predict non-SN involvement. The present study was designed to assess whether these criteria might also be used to be more restrictive in selecting breast cancer patients who would benefit from an ALND.MethodsA consecutive series of 357 patients with invasive breast cancer and a tumor-positive axillary SN, followed by an ALND, was reviewed. Microanatomic SN tumor features (subcapsular, combined subcapsular and parenchymal, parenchymal, extensive localization, multifocality, and the penetrative depth from the SN capsule) were evaluated for their predictive value for non-SN involvement.ResultsNon-SN metastases were found in 136/357 cases (38%). Microanatomic location and penetrative depth of SN metastases were significant predictors for non-SN involvement (<0.001); limited penetrative depth was associated with a low frequency of non-SN involvement with a minimal of 10%.ConclusionsMicroanatomic location and penetrative depth of breast cancer SN metastases predict non-SN involvement. However, based on these features no subgroup of patients could be selected with less than 10% non-SN involvement.

99mTc SPECT/CT Versus Planar Lymphoscintigraphy for Preoperative Sentinel Lymph Node Detection in Cervical Cancer: A Systematic Review and Metaanalysis

We aimed to compare SPECT/CT and lymphoscintigraphy on overall and bilateral sentinel lymph node (SLN) detection in cervical cancer patients. Methods: A systematic search was performed on August 1, 2014, in PubMed, Embase, Scopus, and the Cochrane library. The syntax was based on synonyms of the terms cervical cancer, SPECT/CT, and lymphoscintigraphy. Retrieved articles were screened on their title/abstract and considered eligible when an SLN procedure was performed using both imaging modalities and if detection results were reported. Two independent reviewers assessed all included studies on methodologic quality using QUADAS-2. Studies were pooled on their odds ratios (ORs) with a random-effects model. Results: The search yielded 962 unique articles, of which 8 were ultimately included. The studies were recent retrospective or prospective cohort studies of limited size (n = 7–51) but sufficient methodologic quality. The median overall detection (≥1 SLN in a patient) was 98.6% for SPECT/CT (range, 92.2%–100.0%) and 85.3% for lymphoscintigraphy (range, 70.0%–100.0%). This corresponded to a pooled overall SLN detection OR of 2.5 (95% CI, 1.2–5.3) in favor of SPECT/CT. The reported median bilateral detection (≥1 SLN in each hemipelvis) was 69.0% for SPECT/CT (range, 62.7%–79.3%) and 66.7% for lymphoscintigraphy (range, 56.9%–75.8%), yielding a pooled OR of 1.2 (95% CI, 0.7–2.1). No significant difference in the number of visualized SLNs was observed at a pooled ratio of 1.2 (95% CI, 0.9–1.6). Conclusion: In cervical cancer patients, preoperative SLN imaging with SPECT/CT results in superior overall SLN detection in comparison with planar lymphoscintigraphy.

Morphometry of isolated tumor cells in breast cancer sentinel lymph nodes: metastases or displacement?

Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.