Using ultrasound and palpation for predicting axillary lymph node status following neoadjuvant chemotherapy - Results from the multi-center SENTINA trial.

BACKGROUND: With the growing importance of neoadjuvant systemic therapy (NST) the assessment of post neoadjuvant axillary status is of increasing importance especially in patients who presented initially with suspicious nodes (cN1). This study aims to investigate the predictive value of palpation and axillary ultrasound of formerly cN1 patients following NST. PATIENTS AND METHODS: The SENTINA trial (SENTinel NeoAdjuvant) is a 4-arm prospective multicenter study designed to evaluate the role of sentinel node biopsy (SLNB) in the context of neoadjuvant systemic treatment (NST) of breast cancer patients. RESULTS: 1240 patients from 103 institutions entered the trial. 715 (arm C n = 592; arm D n = 123) patients, who presented initially cN1 underwent clinical evaluation of lymph node status following NST. Palpation alone demonstrated a sensitivity of 8.3%, specifity of 94.8% and a negative predictive value (NPV) of 46.6%. Ultrasound alone revealed a sensitivity of 23.9%, specificity 91.7%, and a NPV of 50.3%.The investigators combined classification (palpation and ultrasound) resulted in a sensitivity of 24.4%, specificity 91.4%, and a NPV of 50.3%. Investigators classified the axilla nodes as being unsuspicious (cN0) following NST in 592/715 patients; of them 298 (50.3%) were pN0, 151 (25.5%) had 1-2 histologically involved nodes and 143 (24.2%) had >2 histologically involved nodes. CONCLUSION: The diagnostic accuracy of ultrasound and palpation following NST is unacceptably low and additional tools for evaluation of the axillary lymph node status following NST are urgently needed.

Prevalence and distribution pattern of nodal metastases in advanced ovarian cancer.

The objective of this study was to examine the relevance of pelvic and para-aortic lymph node involvement and the tumour characteristics affecting nodal metastases and survival in primary advanced ovarian cancer. A total of 130 consecutive patients were retrospectively investigated. All the patients received stage-related surgery with pelvic and para-aortic lymphadenectomy. The median follow-up was 53.5 months. The clinicopathological parameters and distribution pattern of nodal metastases were evaluated. Lymph node metastases were detectable in 74.62% of the cases. Overall, both pelvic and para-aortic nodes were affected in 35.9% of the patients, whereas 13.3% had metastases only in the pelvic and 13.3% only in the para-aortic lymph nodes. Histological grade 1/2 and 3, serous and endometrioid histology were independent predictors of nodal metastasis. Serous and endometrioid cancers have shown a predilection for metastasis to the pelvic lymph nodes alone, both to the pelvic and the para-aortic nodes, or the para-aortic nodes alone. Overall survival was significantly positively affected by serous histology with positive nodes (P=0.043). It is crucial to investigate the risk factors and metastatic patterns of such patients in a multicenter analysis to evaluate individual subgroups. Prospective studies are required to investigate the prognostic effect of lymphadenectomy in advanced ovarian cancer and its association with histology and distribution pattern of nodal metastasis.

Role of Pelvic and Para-aortic Lymph Node Metastases in Optimally Cytoreduced Advanced Ovarian Cancer.

AIM: To delineate the role of pelvic and para-aortic node involvement in patients with optimally cytoreduced (R≤1 cm; R=residual tumor) stage IIIC ovarian cancer. PATIENTS AND METHODS: Ninety-five consecutive optimally cytoreduced patients with primary stage IIIc ovarian cancer underwent stage-related surgery and adjuvant platinum-based chemotherapy, with a median follow-up of 53.5 months. All patients underwent systematic lymphadenectomy. On average, 24.7 pelvic and para-aortic lymph nodes were removed per patient (range=1-60 nodes); Patients were stratified into three groups to evaluate nodal involvement (ratio of affected to resected nodes): 0: no lymph node metastases; >0-0.5: >0 and fewer than 50% of involved nodes; >0.5-1: more than 50% of nodes involved. Clinical parameters were retrospectively evaluated. RESULTS: Most often, serous histology, histological grade 3 and a node ratio >0-≤0.5 (61.1%) were detected. Complete cytoreduction (R=0 mm) had significant best prognostic impact compared to R>0 mm-1 cm (overall survival: p=0.047, progression-free survival: p<0.001). Nodal involvement was associated with serous histology and grade 3 tumor. Best overall survival was associated with a node ratio >0-≤0.5 (p=0.011). A solitary affection of the pelvic or rather para-aortic nodes was detected in 22.1% vs. 16.%, respectively; a combined affection of pelvic and paraaortic nodes were detected in 34.8%. CONCLUSION: The goal is optimal cytoreduction in advanced ovarian cancer. More extensive pelvic and para-aortic lymphadenectomy seems to play an important role in providing accurate staging in optimally-cytoreduced advanced ovarian cancer and the node ratio might give prognostic information. Current prospective studies should investigate if these data have therapeutic implications and may be considered in future staging.

The prognostic relevance of node metastases in optimally cytoreduced advanced ovarian cancer.

PURPOSE: To delineate the relevance of pelvic and para-aortic node involvement in optimally cytoreduced (residual tumour <1 cm) stage IIIC ovarian cancer patients. METHODS: Ninety-five consecutive optimally cytoreduced (R ≤ 1 cm) patients with primary stage IIIc ovarian cancer underwent stage-related surgery and got adjuvant platinum-based chemotherapy. Median follow-up: 53.5 months. All patients got systematic lymphadenectomy. On average, 24.7 pelvic and para-aortic lymph nodes were removed per patient (range 1-60 nodes). Patients were stratified into three groups to evaluate node involvement (ratio: affected to resected nodes): (1) (=0); (2) (>0-≤ 0.5) >0 and ≤ 50 % of affected nodes; (3) (>0.5-≤ 1) >50 % of affected nodes. Clinical parameters were retrospectively evaluated. Kaplan-Meier survival curve was used to evaluate the prognostic value. RESULTS: Most often serous histology, histologic grade 3 and a node ratio >0-≤ 0.5 (61.1 %) were detected. Complete cytoreduction (R = 0 mm) has significant best prognostic impact compared to R > 0 mm-1 cm (OS: p = 0.047, PFS: p = 0.00). Node involvement was associated with serous histology and grade 3. Increasing node ratio leads to significant decreased OS (p = 0.019) and significant best OS was associated with node ratio >0-≤0.5. CONCLUSIONS: The goal is optimal cytoreduction in advanced ovarian cancer. More extensive lymphadenectomy seems to play an important role in providing an accurate staging, and the node ratio might give prognostic information. Current prospective studies like the LION study (AGO-Ovar) had to investigate if these data have therapeutic implications and may be considered in future staging.

The Prognostic Role of Optimal Cytoreduction in Advanced, Bowel Infiltrating Ovarian Cancer.

AIM: In locally advanced ovarian cancer with bowel involvement appropriate surgical treatment is still controversial. Objective was to delineate factors to select those most likely to benefit from radical surgery in patients with locally advanced ovarian cancer. METHODS: Therefore, we retrospectively evaluated 207 consecutive patients with primary stage IIB-IV ovarian cancer who underwent primary surgery between 2000 and 2007. Every patient received stage-related surgery and adjuvant platinum-based chemotherapy. Median follow-up was 53.5 months. Data collected included stage, histology, extent of cytoreduction and type of bowel resection. Univariate survival analyses were performed to investigate variables associated with outcome. RESULTS: Optimal cytoreduction (OCR) (R ≤ 1 cm) was achieved in 76.8%. Most patients presented histologic grade 2/3 (96.6%), serous ovarian cancers (84.1%) and lymph node involvement (52.2%). Complete cytoreduction (R = 0 mm) has significant best prognostic impact in FIGO IIB-IV (p = .026). Regarding bowel involvement, bowel resection was performed in 82 patients (39.6%). In this subgroup of patients complete cytoreduction led to significant better overall survival than R > 0 mm-1 cm, even in FIGO IIIC-IV patients (p = .027); this fact is independent of bowel resection. Noticeably, for survival bowel resection achieving residual tumor mass below 1 cm was also one main prognostic factor and even recurrence rate was associated with residual tumor mass. CONCLUSION: Our findings suggest that the major prognostic factor in patients with advanced ovarian cancer needing colorectal resection is completeness of cytoreduction. Therefore, in advanced ovarian cancer patients, multivisceral surgery is indicated to achieve OCR (R ≤ 1 cm) with or without bowel resection with best prognostic impact.

Detection of nonpigmented endometriotic lesions with 5-aminolevulinic acid-induced fluorescence.

STUDY OBJECTIVE: To evaluate the feasibility of fluorescence diagnosis of nonpigmented (red and white) endometriotic lesions with 20 mg/kg of 5-aminolevulinc acid (5-ALA) 5-7 and 10-14 hours before surgery. DESIGN: Prospective analysis (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Twenty-four consecutive patients with suspected endometriosis undergoing laparoscopy. INTERVENTION: Laparoscopic surgery under white light illumination and fluorescence diagnosis. MEASUREMENTS AND MAIN RESULTS: The total number of endometriotic lesions detected under white light illumination was compared with the number of lesions detected with fluorescence diagnosis. Fluorescence diagnosis yielded an overall improvement of 35% in the detection of nonpigmented endometriotic lesions compared with white light illumination. Sensitivity (91%) and specificity (79%) were similar 5-7 and 10-14 hours before surgery. CONCLUSION: The dosage of 20 mg/kg body weight of 5-ALA is feasible for fluorescence diagnosis of nonpigmented endometriosis. Sensitivity of fluorescence diagnosis with 20 mg/kg is similar to that achieved with a 30-mg/kg dose. Sensitivity does not change within the application period 5-7 and 10-14 hours before surgery.