Pathological Negative Lymph Nodes Research Articles

Pattern of recurrence and overall survival in esophagogastric cancer after perioperative FLOT and Clinical Outcomes in MSI-H population: The PROSECCO Study.

e16068 Background: The FLOT4-AIO phase II/III trial established perioperative FLOT regimen as the new standard in Western countries for patients (pts) with locally advanced resectable gastric (GC) or gastroesophageal junction cancer (GEJC). Microsatellite instability (MSI-H) showed a favorable prognostic role and a concomitant negative predictive impact on the benefit of adjuvant and neoadjuvant 5-fluorouracil-based doublets, but its prognostic and predictive role in pts receiving perioperative FLOT treatment still remains unclear. Our study aims to explore the real-world efficacy of FLOT regimen and to describe histopathological features and clinical outcomes in the MSI-H subgroup population. Methods: This is a retrospective multi-center analysis including pts with GC and GEJC, treated with perioperative FLOT regimen in clinical practice and whose microsatellite status and survival data were available. The association of baseline characteristics, biomolecular and pathological features and overall survival (OS) were firstly assessed in univariate analyses by means of log-rank test, and significantly prognostic variables (p < .05) were included in a multivariable COX proportional hazard model. Results: A total of 250 pts (median age, 62, range 37-81, male 71.6%, ECOG PS 0, 82%) were treated at 11 Italian Oncology Units from January 2017 to June 2021. At a median follow-up time of 22.5 months (mos) (2.3 - 66.7 mos), 123/250 (49.2%) patients relapsed and 77/250 (30.8 %) died. In the global population the median disease-free survival (DFS) was 16,7 mos (95% CI 13,8–21,2) and the median OS 34,9 mos [95% confidence interval (CI) 28–NA]. MSI-H phenotype was found in 26 (10.4%) out of 250 analyzed tumors. Compared to MSS cases, MSI-H were more frequently identified in female (50% vs 25.9%, p = .001), elderly pts (age ≥ 70 years, 76.9% vs 9.4%, p = .003), Laurens’s intestinal type (54% vs 12%, p = .0076) and in pts with primary location tumor in antrum (38.5% vs 13.8%, p = .0004). No relevant differences have been noticed in R0 resections (88% and 96%, p = .06) and pathological complete responses (4.9 % and 3.8%, p = .718), however a statistically significant difference in the rate of pathological negative lymph-nodes between MSS and MSI-H cohort emerged (29.3% vs 65.4%, p = .0004). Compared to MSS tumor population, MSI-H subgroup has a tendency to better DFS (median not reached (NR) vs 15.7, p = .06), metastasis free survival (MFS, median NR vs 17.2 mos, p = .06) and OS (median 41 vs 34 mos, p = .07). Conclusions: These real-world data confirm the efficacy of FLOT perioperative regimen in pts with locally advanced GC/GEJC, maintained also in the MSI-H pts. Our study suggests a better outcome of MSI-H GC and GECJ pts treated with FLOT in comparison to MSS, due to increased rate of nodal status downstaging and despite a poor histological response in the resected tumor tissue of MSI-H pts.

Macrometastasis at selective lymph node biopsy: A practical going-for-the-one clinical scoring system to personalize decision making.

BACKGROUNDAxillary sentinel lymph node biopsy (SLNB) is standard treatment for patients with clinically and pathological negative lymph nodes. However, the role of completion axillary lymph node dissection (cALND) following positive sentinel lymph node biopsy (SLNB) is debated.AIMTo identify a subgroup of women with high axillary tumor burden undergoing SLNB in whom cALND can be safely omitted in order to reduce the risk of long-term complications and create a Preoperative Clinical Risk Index (PCRI) that helps us in our clinical practice to optimize the selection of these patients.METHODSPatients with positive SLNB who underwent a cALND were included in this study. Univariate and multivariate analysis of prognostic and predictive factors were used to create a PCRI for safely omitting cALND.RESULTSFrom May 2007 to April 2014, we performed 1140 SLN biopsies, of which 125 were positive for tumor and justified to practice a posterior cALND. Pathologic findings at SLNB were micrometastases (mic) in 29 cases (23.4%) and macrometastasis (MAC) in 95 cases (76.6%). On univariate analysis of the 95 patients with MAC, statistically significant factors included: age, grade, phenotype, histology, lymphovascular invasion, lymph-node tumor size, and number of positive SLN. On multivariate analysis, only lymph-node tumor size (≤ 20 mm) and number of positive SLN (> 1) retained significance. A numerical tool was created giving each of the parameters a value to predict preoperatively which patients would not benefit from cALND. Patients with a PCRI ≤ 15 has low probability (< 10%) of having additional lymph node involvement, a PRCI between 15-17.6 has a probability of 43%, and the probability increases to 69% in patients with a PCRI > 17.6.CONCLUSIONThe PCRI seems to be a useful tool to prospectively estimate the risk of nodal involvement after positive SLN and to identify those patients who could omit cALND. Further prospective studies are necessary to validate PCRI clinical generalization.

Is There A Role of Post-Mastectomy Radiotherapy for T1-2 Breast Cancer Patients with Node-Positive Pathology who Develop Pathologic Negative Lymph Nodes after Neoadjuvant Chemotherapy and Mastectomy?

To assess the benefit of post-mastectomy radiotherapy (PMRT) in breast cancer (BC) patients with T1-2N1M0 who developed pathologic negative lymph nodes (pN0) after underwent neoadjuvant chemotherapy (NAC) and mastectomy. Patients with T1-2 tumors and positive lymph node(s) who became pN0 after NAC and mastectomy were screened from our prospectively maintained database. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoints included local recurrence-free survival (LRFS) and overall survival (OS). Propensity-score matching (PSM) was conducted for the comparison between PMRT and non-PMRT groups. Of the 142 eligible patients, 110 (77.5%) received PMRT and 32 (22.5%) did not. A median follow-up time was 72 months. Univariate analyses showed that 5-year RFS, LRFS, and OS rates were 88.7%, 94.5%, and 96.1% with PMRT and 72.4%, 90.1%, and 95.0% without PMRT, respectively, (P = 0.028; P = 0.151; P = 0.971). Multivariate analyses established PMRT as a significant prognostic factor for RFS rate (HR, 0.411; 95%CI, 0.175-0.968; P = 0.042). After a PSM analysis of 96 patients (64 in the PMRT group vs. 32 in the non-PMRT group), PMRT remained significant with improved RFS in univariate and multivariate analyses (with 5-year RFS rates of 90.1% vs. 72.7%, P = 0.016; HR, 0.321, 95%CI, 0.114-0.904, P = 0.031). In the subgroup of 48 (33.8%) patients with pathologic complete response (pCR) after NAC, PMRT did not affect RFS (HR, 0.226; 95%CI, 0.034-1.500; P = 0.123). PMRT may be beneficial for the pT1-2N1M0 patients with pN0 after NAC. Patients with pCR status might consider omitting the PMRT. Prospective studies are needed to further assess the effect of PMRT in this specific patient population.

LBA5 - The role of radiation therapy in clinically node-positive, pathological negative nodes after neoadjuvant chemotherapy in breast cancer patients: In sentinel node biopsy and trastuzumab era

BackgroundAlthough current guidelines recommend deciding on postmastectomy radiation therapy (PMRT) or regional nodal irradiation (RNI) after breast conserving surgery (BCS) depending on initial clinical stages before neoadjuvant chemotherapy (NAC), it is controversial whether adjuvant radiation therapy (RT) can be omitted for patients with excellent response. This retrospective study evaluates if PMRT or RNI after BCS significantly reduces locoregional recurrence rate in patients with clinically positive, pathologic negative lymph nodes (LNs) after NAC. MethodsFrom 1999 to 2016, 1831 women with breast cancer underwent NAC and surgery. Of them, 427 patients with clinically node-positive and pN0 disease were analyzed. ResultsMedian follow-up was 65.4 months. The 5-year locoregional relapse (LRRFS) and disease-free survival (DFS) rates were 96.9% and 88.3%, respectively. In patients with an initial nodal stage of cN2-3, RT significantly reduced LRR, with a hazard ratio (HR) of 0.132 (p = 0.009). However, RT was not shown to be effective in the cN1 group (HR = 0.893, p = 0.9). RT did not improve DFS, regardless of cN stage. PMRT/RNI was defined as the combined set of patients who received PMRT or received RT, including regional nodal irradiation (RNI) after BCS; the effects of PMRT/RNI were analyzed. PMRT/RNI significantly reduced LRR in the cN2-3 patient group (HR = 0.175, p = 0.03), but there was no significant effect for cN1 disease. Among 173 patients who underwent mastectomy, there were 108 and 65 patients, respectively, who received RT or no RT. Among all patients, PMRT had no effect on LRR (p = 0.7). However, among cN2-3 patients, PMRT significantly lowered LRR (HR = 0.10, p = 0.02), while there was no significant effect in cN1 patients. ConclusionsIn analysis of all patients and of mastectomy patients, RT consistently improved local control rate in the cN2 and higher patient group. Similar results were obtained in the combined analysis of PMRT and RNI after BCS. Therefore, in ypN0 patients graded cN2 or higher, RT including RNI is predicted to be absolutely necessary. No conclusion could be reached for cN1 disease. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

The Role of Postmastectomy Radiation Therapy in Clinical T1-3N1M0 Breast Cancer Patients With Pathological Negative Lymph Nodes After Neoadjuvant Chemotherapy and Mastectomy

The Role of Postmastectomy Radiation Therapy in Clinical T1-3N1M0 Breast Cancer Patients With Pathological Negative Lymph Nodes After Neoadjuvant Chemotherapy and Mastectomy

The role of postmastectomy radiotherapy in clinical T1-3N1M0 breast cancer patients with pathological negative lymph nodes after neoadjuvant chemotherapy and mastectomy

Objective: To analyze the outcomes of clinical T1-3N1M0 breast cancer patients with pathological negative axillary lymph nodes (ypN0) after neoadjuvant chemotherapy (NAC) and mastectomy, and investigate the role of postmastectomy radiotherapy (PMRT). Methods: A total of 185 patients with clinical T1-3N1M0 breast cancer treated between 1999 and 2013 were retrospectively reviewed. All patients were treated with NAC and mastectomy, and achieved ypN0. Of them, 89 patients received additional PMRT and 96 patients did not. 101 patients had clinical stage Ⅱ disease. 84 patients had clinical stage Ⅲ disease. The rates of locoregional recurrence (LRR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and differences were compared using the log-rank test. Univariate analysis was used to interpret the impact of clinical features and treatment on patients' outcome. Results: The 5-year rates of LRR, DM, DFS, and OS for all patients were 4.5%, 10.4%, 86.6%, and 97.1%, respectively. For patients with and without PMRT, the 5-year LRR rates were 1.1% and 7.5% (P=0.071), the 5-year DM rates were 5.1% and 15.0% (P=0.023), the 5-year DFS rates were 95.0% and 79.0% (P=0.008), and the 5-year OS rates were 100.0% and 94.5% (P=0.089) respectively. In univariate analysis, lymph-vascular space invasion (LVSI) was poor prognostic factor of LRR (P=0.001), < 40 years old and lack of PMRT was a poor prognostic factor for DM (P<0.05), lack of PMRT was a poor prognostic factor for DFS (P=0.008), primary lesion residual and mild-moderate pathological response to NAC were poor prognostic factors for OS (P<0.05). In the subgroup of Stage Ⅲ disease, for patients with and without PMRT, the 5-year LRR rates were 1.9% and 14.4% (P=0.041), the 5-year DFS rates were 91.9% and 67.4% (P=0.022), respectively. In the subgroup of Stage Ⅱ disease, for patients with and without PMRT, the 5-year DM rates were 0 and 11.5% (P=0.044), the 5-year DFS rates were 100.0% and 84.9% (P=0.023), respectively. Conclusions: The LRR rate of clinical T1-3N1M0 breast cancer patients who achieved ypN0 after NAC and mastectomy was low. PMRT decreased the DM rate and increased DFS rate in all patients, and significantly decreased the LRR rate in Stage Ⅲ disease. PMRT should be considered for patients with Stage Ⅲ disease, and further research is warranted to investigate the benefit of PMRT for Stage Ⅱ disease.

Valeur pronostique des sous-types moléculaires et du Ki67 pour les cancers du sein indemnes d’envahissement ganglionnaire après mastectomie : expérience de l’institut Curie–hôpital René-Huguenin et revue de la littérature

PurposeTo evaluate the prognostic value of Ki67 expression, breast cancer molecular subtypes and the impact of postmastectomy radiotherapy in breast cancer patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy. Patients and methodsSix hundred and ninety-nine breast cancer patients with pN0 status after modified radical mastectomy, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumours were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of locoregional recurrence associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. ResultsAt a median follow-up of 56months, 17 patients developed locoregional recurrence. Five-year locoregional recurrence-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the postmastectomy radiotherapy (n=191) and no-postmastectomy radiotherapy (n=508) subgroups. No constructed subtype was associated with an increased risk of locoregional recurrence. A Ki67 above 20% was the only independent prognostic factor associated with increased locoregional recurrence (hazard ratio, 4.18; 95% CI, 1.11 to 15.77; P<0.0215). However, postmastectomy radiotherapy was not associated with better locoregional control in patients with proliferative tumours. ConclusionKi67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after modified radical mastectomy. The benefit of adjuvant radiotherapy in patients with proliferative tumours should be further investigated in prospective studies.

Detection of micrometastases and its clinical significance in sentinel and non-sentinel lymph nodes from early cervical carcinoma

To investigate the clinical significance of micrometastasis detection in sentinel lymph nodes (SLN) from patients with early cervical carcinoma. Thirty patients with early cervical carcinoma were studied to identify SLN intraoperatively using methylene blue. One lymph node was removed randomly from palpable SLN and other pelvic lymph nodes (nSLN) in each patient, so 268 lymph nodes were collected and cut into two halves, one half of the lymph node was used to analyze the expression of cytokeratin 19 (CK19) mRNA by real-time fluorescence quantitative polymerase chain reaction to determine the presence of micrometastasis, the other half was examined by routine histology with HE staining. 67 SLNs were detected in 28 cases (93.3%). Pelvic lymph nodes of 6 cases were confirmed pathological metastasis. The sensitivity of SLN detection was 66.7%, the accuracy rate was 96.4%, and the false negative rate was 16.7%. Among 268 lymph nodes (including 9 lymph nodes with pathological metastasis) detected by real-time fluorescence quantitative polymerase chain reaction, 68 lymph nodes were pathological negative but had micrometastasis, accounting for 26.3% (68/259) in pathologically negative lymph nodes. Among 24 patients with pathological negative lymph nodes, 16 cases had micrometastasis, accounting for 66.7% in those patients. Among 16 patients with micrometastasis, SLN of 3 cases were negative, but nSLN were micrometastasis, so the SLN false-negative rate rose to 18.2%. There were no significant relationships between pelvic lymph nodes micrometastasis and perivascular space involvement, deep stromal invasion and tumor grade (all P > 0.05). The micrometastasis rate of nSLN in patients with SLN micrometastasis was 100%, significantly higher than that in the patients with SLN non-micrometastasis (27.3%, P < 0.01). Real-time fluorescence quantitative polymerase chain reaction is a sensitive method to detect SLN micrometastasis. SLN micrometastasis may be an effective complement to SLN pathology to predict nSLN metastasis. Pelvic lymph nodes micrometastases have no significant relationship with pathological risk factors in cervical cancer and prognosis of patients.

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

A Phase II Study of Concurrent Docetaxel, Epirubicin and Cyclophosphamide as a Neoadjuvant Chemotherapy Regimen in Patients with Locally Advanced Breast Cancer

Background: Neoadjuvant chemotherapy with concurrent docetaxel, doxorubicin and cyclophosphamide is commonly used for patients with locally advanced breast cancer. Epirubicin is another anthracycline used in breast cancer but the concurrent use of epirubicin and taxane is not well-established. We conducted a single institution, phase II study to assess the efficacy and safety of concurrent docetaxel, epirubicin and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen in breast cancer. Methods: Patients with newly diagnosed locally advanced breast cancer defined as T2 >3 cm, T3, T4 with any N, or any T with N1-3 were eligible. A chemotherapy regimen of docetaxel 75mg/m2, epirubicin 75mg/m2 and cyclophosphamide 600mg/m2 was given with filgrastim support every 3 weeks for 6 cycles. The primary end-point was pathologic complete response rate. Results: Twenty patients were enrolled from 2003 to 2006. The median age was 51 (29-70) year-old. Eight patients were premenopausal. Ten patients had positive hormone receptors. Four patients had HER2 positive receptor. Nineteen patients completed six cycles of TEC chemotherapy. The pathologic complete response rate was 25%. Eight of sixteen patients with N1-3 disease had pathological negative lymph nodes. With a median follow up of 57.5 (16-71) months, four patients relapsed including one death from recurrence. The estimated 5 year relapse-free survival was 79.3% and the 5-year overall survival was 94.7%. No patient had cardiac failure or death during treatment. The most common grade 3-4 toxicity was neutropenia (35%). Conclusion: TEC regimen is a well- tolerated and effective neoadjuvant chemotherapy regimen for locally advanced breast cancer that results in a pathologic complete response rate of 25%.

Simple conization and lymphadenectomy for the conservative treatment of stage IB1 cervical cancer. An Italian experience

Objectives Simple conization represents a plausible treatment scheme for managing stage IA1-2 tumors conservatively. However its curative potential has not been widely exploited as regards stage IB1 lesions. Recent studies suggest that, in selected circumstances, patients with stage IB1 disease undergoing radical hysterectomy could have been safely cured by simple hysterectomy and even by cervical conization. Methods Patients with stage IB1 cervical cancer desiring conservative management underwent simple conization and pelvic lymphadenectomy in three Italian institutes. Results Thirty-six women received the conservative treatment since 1995 to 2010. Median age was 31 (range 24–40) years and median tumor size was 11.7 mm (range 8–25 mm). Adenocarcinoma was present in 12 cases (33%) and grade 3 neoplasia in 5 (14%). Lymph-vascular space involvement was detected in five patients (14%). Eleven had already a child while two had experienced an early abortion and a fetal loss at second trimester. After a median follow-up of 66 months (range 6–168) only one pelvic lymphnodal relapse was observed. Twenty-one pregnancies occurred in 17 patients and 14 live babies have been born (two preterm at 27 and 32 weeks) while one is ongoing. Three first-trimester miscarriages, one second-trimester fetal loss, an ectopic pregnancy and a termination of pregnancy have been recorded. Five patients decided to undergo hysterectomy after 3–12 years after conservative therapy: in one residual microinvasive adenocarcinoma was found. Conclusions Cervical conization represents a feasible conservative management of stage IB1 cervical cancer and shows a low risk of relapse, provided that patients are selected carefully. Conization would be suitable to treat stage IB lesions smaller than 15–20 mm. with pathologic negative lymphnodes.

Phase II study of combined docetaxel, epirubicin, and cyclophosphamide as a neoadjuvant chemotherapy regimen in patients with locally advanced breast cancer in a single institution.

e11040 Background: Neoadjuvant chemotherapy with anthracycline and taxane combinations is a standard approach for locally advanced breast cancer. One commonly used regimen is docetaxel, doxorubicin and cyclophosphamide. Epirubicin is another anthracycline used in breast cancer but the combined use of epirubicin and taxane is not well established. We conducted a single institution, phase II study to assess the efficacy of combined docetaxel, epirubicin and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen. Methods: Eligible patients were female with newly diagnosed locally advanced breast cancer defined as T2 > 3 cm, T3-4, any N, or any T, N1-3, M0. A chemotherapy regimen of docetaxel 75 mg/m2, epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2 was given with growth factor support every 3 weeks for 6 cycles. All patients had surgery within 3-6 weeks after completion of chemotherapy. Primary end-point was pathologic complete response (pCR). Results: Twenty-one patients were registered from December 2003 to December 2006. One patient was excluded because of history of thyroid cancer. Median age was 51 (29-70). Eight patients (40%) were premenopausal. Ten patients (50%) had negative tumor hormone receptors. Four patients (20%) who had HER2/neu overexpression received adjuvant trastuzumab. All but one patient completed 6 cycles of TEC chemotherapy. One patient refused to receive the last cycle of chemotherapy. Fourteen patients (70%) had lumpectomy and 6 patients (30%) underwent mastectomy. The pCR rate was 25%. Eight of 16 patients with N1-3 disease (50%) had pathological negative lymph nodes. With a median follow up of 57.5 (16-71) months, 4 patients (20%) relapsed with 1 died from recurrence. The estimated 5-year relapse free survival is 79%. No patient had cardiac failure or death during treatment. The most common grade 3-4 toxicity was neutropenia (35%). Conclusions: Combined TEC regimen is a feasible, well-tolerated and effective neoadjuvant chemotherapy regimen for locally advanced breast cancer that results in a pCR rate of 25%. No significant financial relationships to disclose.

Effect of primary polychemotherapy after sentinel lymph node biopsy on the necessity for lymphadenectomy in stage II breast cancer patients

e11589 Background: Sentinel lymph node (SLN) biopsy is the standard procedure for assessing axillary status in stage I-II breast cancer patients. Realizing this procedure before the administration of primary polichemotherapy would reduce the number of unnecesary lymphadenectomy in patients with negative sentinel lymph node. Methods: From January 2006 to May 2008, twenty-one patients with breast cancer on stage II-IIIA were included in the study. The median age was of 49 years (range 22–74y). The median palpable tumour size was of 3.5cm (range 1.8–6.0) and by ultrasonography 2.0cm (range 1.8–5.0cm.). Stage II:19 and Stage III:2 (cT:6.0cm.). Breast biopsy was performed in all cases with: IDC:20. G1:9 (42,8%), G:2:11(52%) and G3:1(4,76%). ER+:18 (85,7%), PR+:13 (61,9%), HER2 (+):6 (28,5) and triple negative:3 (14,2%).The scheme of treatment was: 4Epi: 90mg/M2 and Cyclophosphamide 600mg/M2 day 1/3w/4cycles, followed by paclitaxel (P) 100mg/M2 day 1/wekly/8. Trastuzumab was given during one year 4/2mg/Kg and started with (P). Tumorectomy and limphadenectomy was planned, followed by radiotherapy ± Hormonotherapy ± trastuzumab. Results: The 21 patients were evaluable for the analysis. The median sentinel lymph nodes resected was of 2 (range 2–6). The SLN biopsy was positive in 12 (57,1%) cases and negative in 9 (42,8%). Followed the primary chemotherapy, tumorectomy and axillary lymphadenectomy (AL) were performed in all 21 cases. The 12 positive SLN showed in the AL 9/12 (75%) pN0 and the 9 negative SLN showed in the AL 0/9 (0%) pN1. There were 4/20 (20%) completely pathological tumour response and 4/20 (20%) cases with only isolated malignant cells. The treatment was well tolerated with not a case of grade 3–4 toxicity. Conclusions: The primary chemotherapy given after the biopsy of sentinel lymph node was very effective showing in the lymphadenectomy a high percentage of pathologic negative lymph nodes (9/12) and an overall tumour response of 40% (8/20) with 4/20 (20%) completely pathological response and 4/20 (20%) cases with only isolated malignant cells. No significant financial relationships to disclose.

Molecular markers expression in mediastinal nodes from resected stage I non-small cell lung cancer (NSCLC): Prognostic impact and potential role as markers of occult micrometastasis

21016 Background: 5-y surv in surgically resected St I NSCLC is 60–70% whereas in cases with affected lymph nodes (LN) it is &lt; 50%. The main risk factor for recurrence is nodal disease. Current histopathologic analysis can miss occult micrometastases in nodal tissues at initial diagnosis. Detection of micromets with a more sensitive technique would be useful to define a high-risk population selecting patients (p) for postop treatment. We assessed the role of several genes mRNA expression in pathological negative LN from resected St I NSCLC p as markers of occult micromets and correlated the results with relapse, and survival. Methods: Paired tumor and histological negative LN (n=344) obtained by systematic mediastinal lymphadenectomy from 38 surgically resected St I NSCLC p were analyzed for the presence of 12 genes mRNA expression using RT-Q-PCR in an ABIPRISM 7500. RNA was extracted using ABIPRISM 6100. Specifically designed primers and probes were purchased from Applied Biosystems as Assay-on-demand; GADPH was used as an endogenous control. Samples were also analyzed by ICH for LN staging. Results: 38 NSCLC p; 12 adenoca, 16 squamous cell, 10 undifferentiated . From the 12 tested genes CEA and PLUNC were found with high expression in lung tissue and low or null expression in normal LN. We consider molecular + LN those in which expression of CEA or PLUNC was detected. In the 344 pathological negative LN, 13% (44/344) were positive for CEA, 16% (54/344) for PLUNC. The expression patterns were similar for both markers. At a median follow-up of 24 mo (9–46) 11 p had died from NSCLC and 1 had died without recurrence. None of the living p had tumor recurrence. For the prognostic assessment, molecular + LN were classified as N1 and N2. Median DFS was 15 ± 11.74 mo in p with N2 molecular + nodes was and has not yet reached in cases of molecular (-) LN (p=0.028). Median survival of p with N2 molecular positive nodes was 17.3 ± 5.7 mo and has not yet reached (p= 0.0083) for molecular (-) LN. Conclusions: CEA and PLUNC mRNA expression could be used as molecular markers of occult micrometastases in mediastinal LN showing a prognostic effect . CEA and PLUNC expression provides a tool for selecting high-risk p considered for adjuvant therapies No significant financial relationships to disclose.

Role of CEA, PLUNC and CK19 mRNA expression in lymph nodes from resected stage I non-small cell lung cancer (NSCLC) patients (p) as markers of occult micrometastasis. A pilot study

9654 Background: 5-year survival for p with surgically resected stage IA-IB (NSCLC) is 70 and 38%. Recurrence of the disease is probably due to undetected systemic occult micrometastases (OM) at the time of initial diagnosis in the histopathologic analysis.The detection of OM would require a more sensitive and specific technique and would be of the greatest interest to define a high risk population and select p for postoperative adjuvant treatments. Objective: to assess the role of CEA, PLUNK and CK19 mRNA expression in pathological negative lymph nodes (LN) from resected stage I NSCLC p as markers of OM and correlate the results with relapse. Methods: paired tumour and histological negative LN (n=84) from 10 p were analyzed for the presence of CEA, CK19 and PLUNC mRNA expression using quantitative real-time PCR Q-PCR. RNA was extracted; GADPH was used as an endogenous control.Samples were also analyzed by immunohistochemistry for LN staging. Results: 10 NSCLC p;7 males;age range:47–77;5 adenoca, 3 squamous cell ca and 2 undiff tumours. CK19 and PLUNC were found to be expressed in tumour tissue of all p.CEA did not express in one of the squamous cell ca. tissues. In the 84 pathological negative LN, 23, 8% (20/84) were positive for CEA, 20%(17/84) for PLUNC,100%(84/84) for CK19 mRNA expression. Most LN positive for CEA were positive for PLUNC as well. The expression pattern were very similar for both markers in all 10 p analyzed.6/10 p showed positive lymph nodes and 4/10 were negatives.1/10 p relapsed after 11 mo of surgery and died after 18 mo. P had detectable levels of CEA and PLUNC mRNA in LN assessed by Q-PCR. The 9 p that did not relapse, 4 had no detectable LN expression levels of these markers and 5 had detectable LN expression levels (median follow-up of 12,5 mo; range 4–18 mo). Conclusions: CK19 has shown to be non specific tumoral marker since it were found to be expressed in all LN tested. But CEA and PLUNC have shown to be specific markers of OM.This fact could be of prognostic relevance and maybe a tool for select high-risk patients considered for adjuvant therapies.50 p are being assessed to corroborate this finding. Final data will be presented. No significant financial relationships to disclose.

Prognostic significance of lymph node reactivity in the control of pathologic negative node squamous cell carcinomas of the oral cavity

Identification of high-risk patients and defining prognostic factors may be useful in the treatment of head and neck cancer. The role of the lymph node reactivity is still obscure. The value of the node reactivity pattern as a predictor of tumor control in oral cavity cancer was analyzed. Retrospective analysis of patients with oral cavity squamous cell carcinoma (OCSCC), submitted to tumor resection and neck dissection, with pathologic negative lymph nodes (pN0). Dominant node reactivity pattern was defined as lymphocytic predominance (LP), germinal centers (GC), normal (NL), sinus hystiocytosis (SH), and lymphocytic depletion (LD). Clinical and pathological characteristics of patients free of disease (DF) were compared with those of patients with control failure (CF), which included local, regional, and distant recurrences. Of the 26 patients with pN0 OCSCC, prevalence of SH was found in 10 cases, GC in 13, and LD, NL and PL in 1 case each. Comparing CF and DF groups, there was no significant statistical difference regarding: age, gender, performance status index, weight loss, smoking and drinking habits, complementary treatment, average follow-up, tumor grade or thickness, margins, or tumor inflammatory and desmoplastic reaction. Although there was a higher proportion of perineural invasion and larger tumors in the CF group, the difference was not statistically significant either. Germinal centers or LP were noted in only 27% of the CF group and in 73% of the DF group. Collectively, NL, SH, or LD patterns were observed in 73% of CF. This incidence was statistically different from 27% of the DF group (P <0.05). Lymph node reactivity pattern seems to be a prognostic index in pN0 OCSCC patients. Prospective analysis is advised to confirm these results. Prophylactic neck dissection as a staging procedure could select high-risk patients even when no metastasis is found.