Histological Lymph Node Involvement Research Articles

What can we learn from the 10 mm lymph node size cut-off on the CT in advanced ovarian cancer at the time of interval debulking surgery?

IntroductionThe benefit of a systematic lymphadenectomy is still debated in patients undergoing neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in ovarian cancer (OC). The objective of this study was to evaluate the predictive value of the pre-NACT and post-NACT CT in predicting definitive histological lymph node involvement. The prognostic value of a positive node on the CT was also assessed. Materiel and methodsA retrospective, unicentric cohort study was performed including all patients with ovarian cancer who underwent NACT and IDS with a lymphadenectomy between 2005 and 2018. CT were analyzed blinded to pathology, and nodes with small axis ≥ 10 mm on CT were considered positive. Sensitivity (Se), specificity (Sp), and negative (NPV) and positive predictive values (PPV) and their CI95% were calculated. The 2-year recurrence free survival (RFS) and 5-year overall survival (OS) was compared. Results158 patients were included, among which 92 (58%) had histologically positive lymph nodes. CT had a Se, Sp, NPV and PPV of 35%, 82%, 47% and 73% before NACT and 20%, 97%, 47% and 91% after NACT, respectively. Patients with nodes considered positive had a non-significant lower 2-year RFS and 5-year OS on the pre-NACT and post-NACT CT. Patients at ‘high risk’ (nodes stayed positive on the CT or became positive after NACT) also had a non-significant lower 2-year RFS and 5-year OS. ConclusionPresence of enlarged lymph nodes on CT is a weak indicator of lymph node involvement in patients with advanced ovarian cancer undergoing NACT. However, it could be used to assess prognosis.

Special Features of Metaplastic Breast Cancer in Tunisian Women

Introduction: Metaplastic breast carcinomas are a rare, heterogeneous group of breast malignancies characterized by an intrinsically aggressive histology and an unfavorable prognosis. Objective: To determine the clinical and pathological characteristics of metaplastic breast cancers in Tunisian patients, and evaluate their impact on its evolution. Methods: A retrospective study of 44 cases of metaplastic cancers archived during a 26-year period in the Cancer Registry of the Tunisian Center. Results: The frequency of metaplastic cancer was 0.97%. Mean age at diagnosis was 55.4 years (range 26 - 84). Average time to diagnosis was 5.5 months. Average clinical tumor size was 4.95 cm (range 1.5 - 15). Axillary ipsilateral adenopathy was present at diagnosis in 45.9%. The clinical stages IIB (31.8%) and IIA (22.7%) predominated. Squamous metaplasia was the most common (68%) followed by the heterologous mesenchymal subtype. Ganglionic invasion was histologically proven in 17 cases, of which 77% had only adenocarcinomatous contingents. Absence of hormone receptor expression and HER2 overexpression predominated. Primary surgery was carried out in 95% of cases. Average follow-up was 40 months (range 2 - 135). Average overall survival (OS) was 74 months, 63% at 5 years and 60% at 10 years. Average progression free survival (PFS) was 29 months (range 3 - 129), 38% at 5 years and 32% at 10 years. Factors significantly influencing OS and PFS were histological lymph node involvement (p = 0.001 and p = 0.002 respectively). Conclusion: Metaplastic breast cancer observed in Tunisian women constitutes a histological type with an unfavorable prognosis whose improvement requires a more adapted therapeutic strategy.

EO8 Initial experience with PSMA-radioguided surgery in prostate cancer patients

Introduction & Objectives: Staging of primary intermediate and high-risk prostate cancer patients before curative treatment usually comprises bone scintigraphy and CT orMRI of the abdomen. Recently, Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] as a novel 68Galliumlabelled ligand of the prostate-specific membrane antigen (68GaHBED-PSMA) has been developed. First reports state high sensitivity and specificity in the detection of prostate cancer lesions. Thus, the aim of this prospective analysis was to investigate 68Ga-HBED-PSMA PET/MR for staging in this patient cohort and correlate it with the results of postoperative histological findings. Material & Methods: This analysis included 53 patients prior to planned radical prostatectomy with intermediate or high-risk prostate cancer according to d’Amico classification. After injection of 100–150 MBq 68Ga-HBED-PSMA a fully-diagnostic PET/MR including multiparametric prostate MRI was performed and images were reviewed by one nuclear medicine physician and one radiologist in consensus. Visualization of local tumor, evidence of lymph node or distantmetastaseswas evaluated and compared to postoperative histological findings. Results: Despite unremarkable conventional imaging 68Ga-HBEDPSMA PET/MRI revealed metastasized disease in two patients who therefore did not undergo radical prostatectomy. Tumor involvement of the prostate could be visualized by 68Ga-HBED-PSMA PET in 88.3% of patients (45/51). In patients with PSMA-positive primary tumor 68Ga-HBED-PSMA PET detected 11 out of 13 patients with histological lymph node involvement (sensitivity: 84.6%) and correctly classified 31 out of 32 patients without histological evidence of lymph node metastases (specificity: 96.6%; accuracy 93.3%). Of note, the two patients with lymph node metastases that were missed by 68GaHBED-PSMA PET only showed micrometastasis in one lymph node. Conclusions: In this initial series, 68Ga-HBED-PSMA PET/MRI showed a high detection rate of the primary tumor within the prostate and proved to be of high sensitivity, specificity and accuracy regarding lymph node staging. Therefore, 68Ga-HBED-PSMA PET/MRI as single investigation might have the potential to stage intermediate and high-risk prostate cancer patients more accurately than standard imaging.

MP42-08 STAGING OF INTERMEDIATE AND HIGH-RISK PROSTATE CANCER USING WHOLE BODY 68GALLIUM-LABELLED LIGAND OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN PET/MRI

INTRODUCTION AND OBJECTIVES: Staging of primary intermediate and high-risk prostate cancer patients before curative treatment usually comprises bone scintigraphy and CT or MRI of the abdomen. Recently, Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] as a novel 68Gallium-labelled ligand of the prostate-specific membrane antigen (68Ga-HBED-PSMA) has been developed potentially detecting prostate cancer cells with high specificity. Thus, the aim of this prospective analysis was to investigate 68Ga-HBED-PSMA PET/MRI for staging in this patient cohort and correlate it with the results of postoperative histological findings. METHODS: This analysis included 38 patients (mean age 65.5, range 49-79 years) prior to planned radical prostatectomy with intermediate or high-risk prostate cancer according to d’Amico classification. After injection of 122 17 MBq 68Ga-HBED-PSMA a fully-diagnostic PET/MRI including multiparametric prostate MRI was performed and images were reviewed by one nuclear medicine physician and one radiologist in consensus. Visualization of local tumor, evidence of lymph node or distant metastases was evaluated and compared to postoperative histological findings. RESULTS: Despite unremarkable conventional imaging 68GaHBED-PSMA PET/MRI revealed metastasized disease in two patients who therefore did not undergo radical prostatectomy. Tumor involvement of the prostate could be visualized by 68Ga-HBED-PSMA PET in 95% of patients (36/38). 68Ga-HBED-PSMA PET/MRI detected 6 out of 11 patients with histological lymph node involvement (sensitivity: 55%) and correctly classified 24 out of 25 patients without histological evidence of lymph node metastases (specificity: 96%). Of note, three patients with lymph node metastases that were missed by 68Ga-HBED-PSMA PET/ MRI only showedmicrometastases and the other two patients also did not show a positive uptake of 68Ga-HBED-PSMA within the prostate. CONCLUSIONS: In this initial series, 68Ga-HBED-PSMA PET/ MRI showed a high detection rate of the primary tumor within the prostate and proved to be of high specificity regarding lymph node staging. Therefore, 68Ga-HBED-PSMA PET/MRI as single investigation might have the potential to stage intermediate and high-risk prostate cancer patients more accurately than standard imaging.

Early invasive cervical cancer: MRI and CT predictors of lymphatic metastases in the ACRIN 6651/GOG 183 intergroup study

Purpose To compare MRI, CT, clinical exam and histopathological analysis for predicting lymph node involvement in women with cervical carcinoma, verified by lymphadenectomy. Methods A 25-center ACRIN/GOG study enrolled 208 patients with biopsy-proven invasive cervical cancer for MRI and CT prior to attempted curative radical hysterectomy. Each imaging study was interpreted prospectively by one onsite radiologist, and retrospectively by 4 independent offsite radiologists, all blinded to surgical, histopathological and other imaging findings. Likelihood of parametrial and uterine body involvement was rated on a 5-point scale. Tumor size measurements were attempted in 3 axes. Association with histologic lymph node involvement, scored as absent, pelvic only and common iliac or paraaortic, was evaluated using Cochran–Mantel Haenszel statistics, univariate and multivariate logistic regression, generalized estimating equations, accuracy statistics and ROC analysis. Results Lymphatic metastases were found in 34% of women; 13% had common iliac nodal metastases, and 9% had paraortic nodal metastases. Based on the retrospective multi-observer re-reads, the average AUC for predicting histologic lymph node involvement based on tumor size was higher for MRI versus CT, although formal statistic comparisons could not be conducted. Multivariate analysis showed improved model fit incorporating predictors from MRI, but not from CT, over and above the initial clinical and biopsy predictors, although the increase in discriminatory ability was not statistically significant. Conclusion MRI findings may help predict the presence of histologic lymph node involvement in women with early invasive cervical carcinoma, thus providing important prognostic information.

Molecular staging of lymph nodes from 60 patients with mycosis fungoides and Sézary syndrome: correlation with histopathology and outcome suggests prognostic relevance in mycosis fungoides

Histological evidence of lymph node involvement is associated with a poor prognosis in patients with cutaneous T-cell lymphoma (CTCL). To determine whether T-cell receptor (TCR) gene analysis is of prognostic relevance in CTCL. TCR gene analysis was performed on lymph node specimens from 60 patients with mycosis fungoides (MF) and Sézary syndrome (SS) using a highly sensitive polymerase chain reaction (PCR)/single-strand conformational polymorphism analysis and results were correlated with skin, overall clinical and histological lymph node stages. The frequency with which a T-cell clone was detected in lymph node samples from patients with MF increased with skin stage, overall clinical stage and with the degree of histological involvement: six of 19 patients with uninvolved lymph nodes or limited histological involvement (LN0-2) and 13 of 14 patients with advanced histological involvement (LN3-4) had a detectable T-cell clone. In SS, 22 of 27 patients had a detectable lymph node T-cell clone. The clonal patients had a poorer prognosis than nonclonal patients (median survival from biopsy of > 72 months vs. 16 months for MF and 41.5 vs. 16.5 months for SS). Regression analysis confirmed that TCR gene analysis identifies a group of MF patients with a worse prognosis (P = 0.013). However, the molecular lymph node stage did not provide independent prognostic information in this cohort of patients in multivariate analysis. Molecular staging in MF and SS using a PCR-based method for TCR gene analysis provides additional information to histological examination. Specifically, this study identified a group of MF patients with early lymph node involvement with a poorer prognosis. However, a larger prospective study of patients with MF and early histological lymph node involvement is required to confirm whether molecular staging of lymph nodes provides independent prognostic information in a multivariate model.

What is the yield of regional lymph node dissection following sentinel lymph node involvement in patients with breast cancer?

10782 Background: Sentinel lymph node is a minimally invasive and accurate staging procedure for patients with invasive breast cancer. Histological SLN involvement with cancer cells requires regional lymph node dissection. Aim: To verify if subgroups of patients with sentinel lymph node involvement in which the risk of histological involvement of additional regional lymph nodes is minimal can be identified. Methods: Ninety six consecutive patients with invasive breast cancer and tumour size less than two centimeters by mammography, had lymphoscintigraphy with colloidal 99Tc and radioisotope-guided sentinel lymph node biopsy in the University Hospital of Zaragoza from 1999 to 2005.Pathological assessment included serial sections of the sentinel lymph node with inmunohistochemistry for cytokeratins in selected cases.39 patients had histological involvement and are presented in this analysis. Results: All 39 patients were females. Median tumour size was 20 mm (range 5–52) Median number of resected sentinel lymph node was 2 (range 1–5) Median number of involved sentinel lymph node was 1 (range 1–4) Regional lymph node dissection was performed in all patients (Axillary dissection in 31; internal mammary dissection in 1, both in 7). Median number of nodes was 13 (range 2–34) At least 1 additional involved lymph node was found in 19 patients (48%) We have correlated patient age, menopausal status, pathological tumour size, histological grade, estrogen receptors, progesterone receptors and Her2 with the risk of histological lymph node involvement in regional lymph node dissection. Conclusions: Tumour size was significantly associated to such risk: No significant financial relationships to disclose.

Weekly Paclitaxel Improves Pathologic Complete Remission in Operable Breast Cancer When Compared With Paclitaxel Once Every 3 Weeks

To determine the impact a change in schedule of paclitaxel administration from once every 3 weeks to frequent administration would have on the pathologic complete response (pCR) rate in the breast and lymph nodes for patients with invasive breast cancer treated with primary systemic chemotherapy (PST). Patients with clinical stage I-IIIA breast cancer were randomly assigned to receive PST of paclitaxel doses administered either weekly (for a total of 12 doses of paclitaxel) or once every 3 weeks (four cycles), followed by four cycles of fluorouracil/doxorubicin/cyclophosphamide (FAC) in standard doses every 3 weeks. Two different doses of paclitaxel were used based on lymph node status defined by ultrasound and fine needle aspiration. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after completion of all chemotherapy. A total of 258 patients were randomly assigned to receive doses of paclitaxel administered either weekly or once every 3 weeks, followed by FAC. Of these 258 patients, 110 patients had histologic lymph node involvement and 148 patients had clinical N0 disease. Weekly paclitaxel followed by FAC was administered to 127 patients and once-every-3-weeks paclitaxel followed by FAC was administered to 131 patients. Clinical response to treatment was similar between groups (P = .25). Patients receiving weekly paclitaxel had a higher pCR rate (28.2%) than patients treated with once-every-3-weeks paclitaxel (15.7%; P = .02), with improved breast conservation rates (P = .05). The change in schedule of paclitaxel from once every 3 weeks to a more frequent administration significantly improved the ability to eradicate invasive cancer in the breast and lymph nodes.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma

To evaluate the therapeutic results obtained with (192)Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. (192)Ir brachytherapy was performed according to the "Paris system" with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meier method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.

The prognoses of tumours detected in the UK breast screening programme (NHS BSP) analysed by the Nottingham Prognostic Index (NPI)

The Nottingham Prognostic Index (NPI) is an integrated prognostic index used to predict patient survival for women with invasive breast cancer. The index is based on invasive tumour size, histological lymph node stage and tumour grade. The value of such an index has been questioned in small invasive breast cancers and it has been suggested that size is the only necessary prognostic determinant. The aims of this study were to determine the extent of regional lymph node involvement and survival in women with small invasive breast cancers and to assess the value of the NPI. Between 1976 and 1994, 2684 women aged ≤70 years were treated for primary operable invasive breast cancers of ≤5 cm in maximum diameter, of which 318 measured ≤1 cm. Follow-up data were evaluated to determine histological factors important in predicting survival outcomes in women with cancers ≤1 cm in diameter and comparing their survival according to the NPI with all women treated for primary operable breast cancers ≤5 cm in maximum diameter. Histological lymph node involvement was demonstrated in 56/318 (18%) of cancers of ≤1 cm in diameter. Significant survival differences were demonstrated for small breast cancers according to lymph node stage, vascular invasion and histological tumour grade. Only lymph node stage and histological tumour grade were independent prognostic indicators using a multivariate Cox model. The survival curves for small tumours stratified by the NPI were similar to those of cancers up to 5 cm in diameter. The results indicate that lymph node staging and histological grading are still important prognostic determinants for breast cancers ≤1 cm in diameter. An axillary node staging procedure should be performed for all invasive breast cancers ≤1 cm in diameter. The NPI remains relevant for small breast cancers.

The prognosis of small primary breast cancers

The Nottingham Prognostic Index (NPI) is an integrated prognostic index used to predict patient survival for women with invasive breast cancer. The index is based on invasive tumour size, histological lymph node stage and tumour grade. The value of such an index has been questioned in small invasive breast cancers and it has been suggested that size is the only necessary prognostic determinant. The aims of this study were to determine the extent of regional lymph node involvement and survival in women with small invasive breast cancers and to assess the value of the NPI. Between 1976 and 1994, 2684 women aged ≤70 years were treated for primary operable invasive breast cancers of ≤5 cm in maximum diameter, of which 318 measured ≤1 cm. Follow-up data were evaluated to determine histological factors important in predicting survival outcomes in women with cancers ≤1 cm in diameter and comparing their survival according to the NPI with all women treated for primary operable breast cancers ≤5 cm in maximum diameter. Histological lymph node involvement was demonstrated in 56/318 (18%) of cancers of ≤1 cm in diameter. Significant survival differences were demonstrated for small breast cancers according to lymph node stage, vascular invasion and histological tumour grade. Only lymph node stage and histological tumour grade were independent prognostic indicators using a multivariate Cox model. The survival curves for small tumours stratified by the NPI were similar to those of cancers up to 5 cm in diameter. The results indicate that lymph node staging and histological grading are still important prognostic determinants for breast cancers ≤1 cm in diameter. An axillary node staging procedure should be performed for all invasive breast cancers ≤1 cm in diameter. The NPI remains relevant for small breast cancers.

658 Prognostic factors in breast cancer less than 3 cm without histologic lymph node involvement

Axillary lymph node involvement is thè most important prognostic indicator for breast cancer. Nevertheless, nearly 25% of patients with histologic negative lymph node will develop distant metastasis. Between 1974 and 1985, 201 patients with breast cancer, less than 3 cm, without axillary lymph node involvement were followed in thè “Centre René Gauducheau”. Thè aim of our study was to analyse on this population which clinical and histological parameters were correlated with local recurrence or distant metastasis. We realise a multivariate analysis using thè Cox model. We showed that hormonal status, age and multifocality were significantly and independently correlated with locai recurrences, and that pathologic grading (SBR), tumor localization in thè breast were prognostic factors of distant metastasis. Finally we found that thè nuclear grading (MSBR) 4 or 5 permit to determine in thè population SBR II, a sub-group of women associated with a high risk of metastatic evolution, in which it will be probably necessary to discuss systemic adjuvant therapy to prevent distant metastasis. Axillary lymph node involvement is thè most important prognostic indicator for breast cancer. Nevertheless, nearly 25% of patients with histologic negative lymph node will develop distant metastasis. Between 1974 and 1985, 201 patients with breast cancer, less than 3 cm, without axillary lymph node involvement were followed in thè “Centre René Gauducheau”. Thè aim of our study was to analyse on this population which clinical and histological parameters were correlated with local recurrence or distant metastasis. We realise a multivariate analysis using thè Cox model. We showed that hormonal status, age and multifocality were significantly and independently correlated with locai recurrences, and that pathologic grading (SBR), tumor localization in thè breast were prognostic factors of distant metastasis. Finally we found that thè nuclear grading (MSBR) 4 or 5 permit to determine in thè population SBR II, a sub-group of women associated with a high risk of metastatic evolution, in which it will be probably necessary to discuss systemic adjuvant therapy to prevent distant metastasis.

Induction of the metastatic phenotype in rat mammary benign tumour cells by the gene for p9Ka a novel calcium-binding protein

Induction of the metastatic phenotype in rat mammary benign tumour cells by the gene for p9Ka a novel calcium-binding protein

Differentiated thyroid carcinoma in childhood: long term follow-up of 72 patients.

Seventy-two children with differentiated thyroid cancer who were 16 years old or younger at the time of initial treatment were followed for a median time of 13 yr. Initially, 18% had lung metastases, and 74% had palpable lymph nodes. Capsular invasion was found in 67%, and histological lymph node involvement in 90%. The recurrent laryngeal nerve chain and the jugulo-carotid chain were involved with the same frequency (greater than 80%). The anterior superior mediastinum was involved only in patients with involvement of the recurrent laryngeal nerve chain. Forty-three patients had a complete remission after initial treatment. In patients without distant metastases for whom surgery was macroscopically incomplete, relapses occurred 5 times more frequently than in patients whose surgery was complete. Six patients died from thyroid carcinoma at ages ranging from 19-44 yr, 12-33 yr after initial treatment, and 1 died from intercurrent disease. Despite favorable long term survival (90.3% at 20 yr), the standardized mortality ratio was equal to 8.1. This study underlines the need for complete surgical treatment and compulsive follow-up, which should be continued throughout the patient's life, in order to detect and effectively treat relapses of thyroid cancer.