Sergi Vidal-Sicart

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma

BACKGROUND Sentinel‐lymph‐node biopsy is associated with increased melanoma‐specific survival (i.e., survival until death from melanoma) among patients with node‐positive intermediate‐thickness melanomas (1.2 to 3.5 mm). The value of completion lymph‐node dissection for patients with sentinel‐node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel‐node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph‐node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma‐specific survival. Secondary end points included disease‐free survival and the cumulative rate of nonsentinel‐node metastasis. RESULTS Immediate completion lymph‐node dissection was not associated with increased melanoma‐specific survival among 1934 patients with data that could be evaluated in an intention‐to‐treat analysis or among 1755 patients in the per‐protocol analysis. In the per‐protocol analysis, the mean (±SE) 3‐year rate of melanoma‐specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log‐rank test) at a median follow‐up of 43 months. The rate of disease‐free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log‐rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log‐rank test); these results must be interpreted with caution. Nonsentinel‐node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph‐node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma‐specific survival among patients with melanoma and sentinel‐node metastases. (Funded by the National Cancer Institute and others; MSLT‐II ClinicalTrials.gov number, NCT00297895.)

Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case–control study

Background: Cutaneous melanoma spreads preferentially through the lymphatic route and sentinel lymph node (SLN) status is regarded as the most important predictor of survival. Aims: To evaluate whether tumour lymphangiogenesis and the expression of vascular endothelial growth factor C (VEGF-C) is related to the risk of SLN metastasis and to clinical outcome in a case–control series of patients with melanoma. Methods: Forty five invasive melanoma specimens (15 cases and 30 matched controls) were investigated by immunostaining for the lymphatic endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using computer assisted morphometric analysis. Results: Peritumorous lymphatic vessels were more numerous, had larger average size, and greater relative area than intratumorous lymphatics. The number and area of peritumorous and intratumorous lymphatics was significantly higher in melanomas associated with SLN metastasis than in non-metastatic melanomas. No significant difference in VEGF-C expression by neoplastic cells was shown between metastatic and non-metastatic melanomas. Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was the most significant predictor of SLN metastasis (p = 0.04). Using multivariate analysis, peritumorous LV density was an independent variable affecting overall survival, whereas the intratumorous LV area approached significance (p = 0.07). Conclusions: This study provides evidence that the presence of high peritumorous and intratumorous lymphatic microvessel density is associated with SLN metastasis and shorter survival. The intratumorous lymphatic vessel area is the most significant factor predicting SLN metastasis. The tumour associated lymphatic network constitutes a potential criterion in the selection of high risk patients for complementary treatment and a new target for antimelanoma therapeutic strategies.

EANM-EORTC general recommendations for sentinel node diagnostics in melanoma

The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to “general consensus” and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer

Abstract.We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treament. Three levels of response were considered: good – when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial – when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response – if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.

Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients

PurposeDespite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions.MethodsThe study involved 383 consecutive women diagnosed with early breast cancer with T1 or T2 tumours. Eight patients had a bilateral tumour, which brought the total to 391 lesions. Lymphoscintigraphy was performed on the day before surgery by injection of 99mTc-labelled nanocolloid. The injection site was subdermal (68 patients), peritumoural (107 patients) or intratumoural (216 patients). During surgery a gamma probe was used to guide the surgeon and the SLNs were removed. SLNs were analysed by a conventional pathological study and processed for H&E examination and immunohistochemistry.ResultsLymphoscintigraphy detected at least one SLN in 369 out of the 391 procedures (94.4%). SLNs were found in the axillary chain in 367 cases and in the internal mammary chain in 55. In two of these 55 cases (3.6%), the SLN was the only one detected. There was no drainage to the internal mammary chain in any case of subdermal injection but such drainage was found in 15.9% of cases with peritumoural injection and 17.6% of those with intratumoural injection. Compared with tumours located in the outer quadrants, a higher percentage of tumours located in the inner quadrants showed drainage to the internal mammary chain (p<0.001). A total of 42 SLNs in the internal mammary chain could be removed in 32 patients without appreciable morbidity. In 20 cases both axillary and internal mammary SLNs were negative, in four both were positive, and in five axillary SLNs were positive and internal mammary SLNs were negative. More interestingly, in the remaining patient with both axillary and internal mammary SLNs, the axillary SLN was negative while malignant cells were found in the internal mammary region. In the evaluation of the clinical impact of internal mammary SLN biopsy, we found that staging was modified from pN1a to pN1c in four patients and, more importantly, from pN0 to pN0(i+) in one patient. The change in stage led to a modification of the postoperative treatment plan with respect to radiotherapy and systemic therapy.ConclusionEvaluation of the SLNs in the internal mammary chain provides more accurate staging of breast cancer patients. If internal mammary sampling is not performed, patients can be understaged. This technique can offer a better indication of those patients who will benefit from selective treatment options like radiotherapy to this region or systemic therapy.

Added Value of Intraoperative Real-Time Imaging in Searches for Difficult-to-Locate Sentinel Nodes

Localization of sentinel lymph nodes can be challenging if they are in difficult anatomic locations or near high radiotracer activity. The purpose of this study was to assess the value of intraoperative real-time imaging using a portable γ-camera in conjunction with a conventional γ-counting probe when it is difficult to localize the sentinel node. Methods: After 99mTc-nanocolloid injection, patients with various malignancies underwent presurgical lymphoscintigraphy followed by surgery (usually the next day). We evaluated 20 patients who required sentinel lymph node biopsy and in whom the location or other characteristics of the sentinel node would make intraoperative retrieval difficult. During surgery, the sentinel node was localized using a portable γ-camera together with a hand-held γ-probe. A 153Gd pointer or 125I seed was used to better depict the sentinel node location in real time. Results: Using only a conventional hand-held γ-probe, surgeons were able to definitively localize the sentinel node in 15 of 20 patients. Intraoperatively, the portable γ-camera showed uptake by the definite sentinel node in 19 of 20 patients and helped to precisely localize the node with the hand-held γ-probe in 4 patients. In 1 of these patients, the sentinel node was metastatic. Conclusion: The combination of a standard hand-held γ-probe and real-time imaging provided by a portable γ-camera offers a high intraoperative detection rate in patients with difficult sentinel node localization as assessed by presurgical lymphoscintigraphy.

Sentinel lymph node biopsy in breast cancer patients: subdermal versus peritumoural radiocolloid injection.

Background and aims Sentinel lymph node (SLN) biopsy has been widely used in the management of melanoma and breast cancer. The aims of this study were (1) to compare the results obtained with the two main injection techniques, the peritumoural and subdermal; and (2) to determine the reliability of SLN to predict the regional lymph node status. Method We prospectively studied 80 women (mean age 56 years) with breast cancer. Thirty-four of them were T1 and the remaining 46 were T2. Patients were divided into two groups. Group A, 36 patients were injected subdermally, surrounding the tumour site. Group B, 44 patients were injected peritumourally guided by ultrasound if non-palpable. Planar images were performed 15 min after the injection and continued until SLN identification. Before surgery, blue dye injection was administered similarly to the radiocolloid. After incision, a hand-held gamma probe was used to reach the SLN. All nodes harvested were analysed by classic pathology techniques. Results Overall, lymphoscintigraphy allowed the detection of SLN in 75/80 patients (94%). All subdermal lymphoscintigraphies were positive (36/36) compared with 89% of peritumoural (39/44). Blue dye detected SLN in 23/31 patients (74%) after subdermal injection and in 24/34 patients (71%) after peritumoural injection. The sensitivity to localize the SLN with lymphoscintigraphy+blue dye+gamma probe was 92% (33/36) within the subdermal group and 91% (40/44) within the peritumoural group. Overall, five false negative SLN were found. All of these corresponded to T2 tumours with a size greater than 2.5 cm. The negative predictive value and the accuracy were 93% and 94%, respectively, for the subdermal group and 90% and 93% for the peritumoural group. Conclusions (1) Our results indicate that both techniques have similar results. However, we suggest that T2 tumours with a size greater than 2.5 cm should be excluded from the SLN technique, in order to improve the accuracy and negative predictive value. (2) Lymphoscintigraphy is essential for visualizing the SLN, and blue dye can be helpful when the gamma probe does not localize the SLN.

Valoración del ganglio centinela combinando SPECT/TAC con la imagen planar y su importancia para el acto quirúrgico

The sentinel node biopsy procedure is based on the hypothesis of the existence of an orderly and predictable pattern of lymphatic drainage to a regional lymph node basin. This results in the consideration of all lymph nodes with direct drainage from the primary tumor as sentinel nodes. The sentinel node is not necessarily the hottest or the most nearby node, although this is often the case. Lymphoscintigraphy has been an essential component for preoperative sentinel node identification. With the new generation of multimodality gamma cameras, SPECT/CT has been incorporated into the sentinel node procedure. The resulting SPECT/CT fused images depict sentinel nodes in an anatomical landscape providing a helpful roadmap for surgeons. Therefore, it is necessary to define the role of SPECT/CT in relation to the classical planar lymphoscintigraphy for the identification of sentinel nodes. To understand the combined use of lymphoscintigraphy and SPECT/CT, the criteria for sentinel node identification on preoperative images must be specified. The authors, based on their experience in this field, present tentative criteria to identify lymph nodes as sentinel nodes both in planar and SPECT/CT images and classify them into different categories. The use of these scintigraphic categories to characterize radioactive lymph nodes is also helpful for surgical decision making.

Colaboración especialValoración del ganglio centinela combinando SPECT/TAC con la imagen planar y su importancia para el acto quirúrgicoEvaluation of the sentinel lymph node combining SPECT/CT with the planar image and its importance for the surgical act

The sentinel node biopsy procedure is based on the hypothesis of the existence of an orderly and predictable pattern of lymphatic drainage to a regional lymph node basin. This results in the consideration of all lymph nodes with direct drainage from the primary tumor as sentinel nodes. The sentinel node is not necessarily the hottest or the most nearby node, although this is often the case. Lymphoscintigraphy has been an essential component for preoperative sentinel node identification. With the new generation of multimodality gamma cameras, SPECT/CT has been incorporated into the sentinel node procedure. The resulting SPECT/CT fused images depict sentinel nodes in an anatomical landscape providing a helpful roadmap for surgeons. Therefore, it is necessary to define the role of SPECT/CT in relation to the classical planar lymphoscintigraphy for the identification of sentinel nodes. To understand the combined use of lymphoscintigraphy and SPECT/CT, the criteria for sentinel node identification on preoperative images must be specified. The authors, based on their experience in this field, present tentative criteria to identify lymph nodes as sentinel nodes both in planar and SPECT/CT images and classify them into different categories. The use of these scintigraphic categories to characterize radioactive lymph nodes is also helpful for surgical decision making.

Usefulness of strontium-89 for bone pain palliation in metastatic breast cancer patients.

Most studies of prostate cancer have shown that strontium-89 chloride (89Sr) is effective in the palliation of metastatic bone pain, refractory to conventional analgesia. The aim of this study was to evaluate the usefulness of 89Sr for bone pain palliation in breast cancer patients. Forty women were treated with 148 MBq of 89Sr. Six patients were retreated, receiving two or more doses. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. The response was good in 60% of the patients and partial in 32%; there was no response in the remaining 8% (pre-treatment Karnofsky ⩽60). The duration of the response was 120±143 days. In the patients retreated, the response was good in 83% and partial in 17%, without significant differences compared with the first dose, but the pre-treatment Karnofsky and the duration of the efficacy were lower (P<0.05). A transient and slight decrease of leukocyte and platelet counts after the first month of treatment with 89Sr was observed. In conclusion, breast cancer patients with metastatic bone pain can benefit from therapy with 89Sr. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose. A low functional performance status could be a cause of the lower effectiveness of 89Sr.