Number Of Tumor-positive Nodes Research Articles

Sentinel lymph node melanoma metastases: Assessment of tumor burden for clinical prediction of outcome in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)

PurposeAs clinical management decisions in patients with Stage III melanoma have become more complex, precise pathologic characterization of sentinel lymph node (SLN) metastases has become critical to guide management. The extent of SLN involvement correlates with risk of adverse outcomes, but reported methods of disease quantification vary. We examined SLN metastases from patients participating in an international clinical trial and compared several methods of tumor burden quantification. MethodsSLNs from 146 node-positive patients in the first Multicenter Selective Lymphadenectomy Trial (MSLT-I) were centrally-reviewed and characterized by number of tumor-positive nodes, percent nodal area tumor replacement, maximum dimension of largest metastasis, tumor penetrative depth, number of tumor foci, metastasis microanatomic location, and extracapsular extension. These data were analyzed for correlation with non-SLN metastasis and melanoma-specific survival (MSS). ResultsThe median number of tumor-involved SLNs was 1. The median maximum metastasis dimension was 1.11 mm. Median SLN area involvement was 1.5%. Tumor burden measures were highly correlated with each other. Factors associated with non-SLN metastasis by univariable analysis were primary tumor ulceration and extent of metastases. Tumor thickness, ulceration, non-SLN metastasis and multiple measures of SLN tumor burden were significantly related to MSS on univariable analysis. After multivariable adjustment, number of involved SLNs (p = 0.05) and percent nodal area tumor replacement (p = 0.02) were independent predictors of MSS. ConclusionCentral review of MSLT-I pathology indicates that primary tumor and SLN tumor characteristics predict non-SLN metastasis and MSS. Percent nodal involvement was more powerfully prognostic than the more commonly used maximum dimension of largest metastasis.

A critical evaluation of lymph node ratio in head and neck cancer.

In head and neck squamous cell carcinoma (HNSCC), the search for better prognostic factors beyond TNM-stage is ongoing. Lymph node ratio (LNR) (positive lymph nodes/total lymph nodes) is gaining interest in view of its potential prognostic significance. All HNSCC patients at the Netherlands Cancer Institute undergoing neck dissection for lymph node metastases in the neck region between 2002 and 2012 (n=176) were included. Based on a protocol change in specimen processing, the cohort was subdivided in two distinct consecutive periods (pre and post 2007). The prognostic value of LNR, N-stage, and number of positive lymph nodes for overall survival was assessed. The mean number of examined lymph nodes after 2007 was significantly higher (42.3) than before (35.8) (p=0.024). The higher number concerned mostly lymph nodes in level V. The mean number of positive lymph nodes before 2007 was 3.3 vs. 3.6 after 2007 (p=0.745). By multivariate analysis of both pre- and post-2007 cohort data, two factors remained associated with an increased hazard of dying: N2 [HR 2.1 (1.1-4.1) and 2.4 (1.0-5.8)] and >3 positive lymph nodes [HR 2.0 (1.1-3.5) and 3.1 (1.4-6.9)]. Hazard ratio for LNR >7% was not significantly different: pre 2007 at 2.2 (1.3-3.8) and post 2007 at 2.1 (1.0-4.8, p=0.053). In this study, changes in specimen processing influenced LNR values, but not the total number of tumor positive nodes found. Therefore, in HNSCC, the number of positive nodes seems a more reliable parameter than LNR, provided a minimum number of lymph nodes are examined.

Pre-chemotherapy 18F-FDG PET/CT upstages nodal stage in stage II–III breast cancer patients treated with neoadjuvant chemotherapy

In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2-3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2-3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.

Contemporary Management of Regional Nodes in Penile Cancer—Improvement of Survival?

The management of regional nodes of penile squamous cell carcinoma has changed with time due to improved knowledge about diagnosis and treatment. To determine whether changes in the treatment of regional nodes have improved survival, we compared contemporary 5-year cancer specific survival of patients with squamous cell carcinoma of the penis with that of patients in previous cohorts. In an observational cohort study of 1,000 patients treated during 56 years 944 were eligible for analysis. Tumors were staged according to the 2009 TNM classification, and patients were divided into 4 cohorts of 1956 to 1987, 1988 to 1993, 1994 to 2000 and 2001 to 2012, reflecting changes in clinical practice regarding regional nodes. Kaplan-Meier survival curves with the log rank test and Cox proportional hazards modeling were used to examine trends in 5-year cancer specific survival. The 5-year cancer specific survival of patients with cN0 disease treated between 2001 and 2012 was 92% compared to 89% (1994 to 2000), 78% (1988 to 1993) and 85% (1956 to 1987). The 5-year cancer specific survival improved significantly since 1994, the year dynamic sentinel node biopsy was introduced, at 91% (1994 to 2012) vs 82% (1956 to 1993) (p = 0.021). This conclusion still holds after adjustment for pathological T stage and grade of differentiation (HR 2.46, p = 0.01). Extranodal extension, number of tumor positive nodes and pelvic involvement in node positive (pN+) cases were associated with worse 5-year cancer specific survival. Despite less surgery being performed on regional nodes, 5-year cancer specific survival has improved in patients with cN0 disease. The number of tumor positive nodes, extranodal extension and pelvic involvement were highly associated with worse cancer specific survival in patients with pN+ disease. In this group other treatment strategies are needed as no improvement was observed.

155. Locoregional lymph node involvement on 18F-FDG PET/CT and estimation of risk for locoregional recurrence in stage II–III breast cancer patients

Background: Risk for locoregional recurrence (LRR) in breast cancer depends on tumor size and the number and location of tumor-positive locoregional nodes. Postoperative irradiation of chest wall and/or locoregional nodes is advised in patients at high risk for LRR, but remains controversial in patients at intermediate risk. Treatment with neoadjuvant chemotherapy (NAC) hinders risk estimation and radiotherapy planning even further, since conventional locoregional staging techniques are inaccurate and/or do not provide information on number of tumor-positive nodes.

Patterns of regional node irradiation therapy following breast-conserving surgery: Report from the National Cancer Data Base 2003-2007.

1101 Background: A recent randomized trial (MA.20) showed that regional nodal irradiation (RNI) in addition to breast irradiation in high risk node negative and 1-3 node positive patients undergoing breast-conserving therapy (BCT) reduced the risk of recurrence and improved disease-free survival. We investigated the trends of RNI use in the United States and related factors for the use of RNI using the National Cancer Data Base. Methods: This study includes 292,598 stage I-III breast cancer patients without neoadjuvant therapy who underwent BCT from 2003-2007. We investigated pathological, patient, and facility factors related to RNI use, by multivariable logistic regression, with odds ratio (OR) estimations. Results: The proportion of radiotherapy use after BCT slightly declined from 78.6% in 2003 to 75.6% in 2007. The use of breast irradiation plus RNI decreased from 10.8% in 2003 to 8.3% in 2007 (p<0.0001). The number of tumor positive lymph nodes strongly determined the use of additional RNI: 4.4% patients with negative nodes, 22.8% patients with 1-3 nodes, and 39.7% patients with 4 or more nodes received breast irradiation plus RNI after undergoing BCT (p<0.0001). The proportion of patients undergoing RNI significantly decreased over the study period from 43.3% to 37.2% in the 4+ node positive group, and from 23.6% to 22.0% in the 1-3 node positive group. At comprehensive community cancer centers, 25.5% patients with 1-3 positive nodes were treated with breast irradiation plus RNI (vs. 23.2% in community cancer centers and 21.1% in academic/research cancer centers). Among node negative patients, 11.5% of those with tumor size greater than 5 cm received additional RNI, compared to 4.3% in patients with tumors less than 5cm (p<0.0001). Other significant factors related to RNI use included higher tumor grade, younger age, facility location, and facility volume. Conclusions: The use of RNI varies by number of tumor positive nodes and facility factors. Only 22.8% of patients with 1-3 positive nodes underwent RNI. Future studies are needed to determine if the use of RNI will increase after publication of the MA.20 trial especially for the 1-3 node positive group.

Can Surgical Therapy Alone Achieve Long-Term Cure of Melanoma Metastatic to Regional Nodes?

Anecdotal reports of melanoma recurrence 15 years after complete lymphadenectomy have led to claims that the onset of nodal metastasis invariably signals systemic metastases and a terminal diagnosis. Few series in the literature are able to refute this assertion. We therefore examined rates of long-term (> 15-25 years) survival for patients with regional (nodal) melanoma. We performed an analysis of patients with American Joint Committee on Cancer stage III melanoma entered into a prospective database for the last 30 years. All patients were seen at the treating institution within 4 months of their diagnosis and monitored thereafter. All patients underwent complete lymphadenectomy. Patients receiving melanoma vaccines were excluded. Statistical comparisons used Chi-square analysis and the log-rank test. At a maximum follow up of 386 months (32 years) for the population of 1422 patients, rates of 15-, 20-, and 25-year melanoma-specific survival were 36% +/- 1%, 35% +/- 1%, and 35% +/- 1%, respectively. When patients were stratified by clinical status of regional lymph nodes, survival rates were significantly lower (P = 0.001) if nodes were palpable. The number of tumor-positive nodes (P < 0.0001), the pathological primary tumor stage (P = 0.005), age (P = 0.0001), and gender (P = 0.002) also were significantly related to long-term survival. Long-term survivors of melanoma metastatic to regional lymph nodes are not uncommon, and the extremely low rate of recurrence beyond 15 years suggests that this disease-free interval is usually synonymous with cure. Although some risk factors decrease the likelihood of long-term survival, the high overall rates of extended survival in all risk groups clearly support surgical management as the primary treatment for regional metastatic melanoma.