Total Tumor Load Research Articles

Modelo predictivo de metástasis en ganglios axilares no centinela en cáncer de mama. Variables emergentes. Estudio MOTTO, parte I

IntroductionThe total tumour load (TTL) obtained from OSNA study in each of the sentinel lymph nodes has been identified as the most powerful predictor of axillary non-sentinel lymph node metastasis. In addition, the distinct molecular subtypes (MS) of breast cancer differ significantly not only in terms of incidence, prognosis and treatment but also in terms of the pattern of axillary metastatic involvement. We hypothesised that the prediction of metastatic disease in axillary lymphadenectomy could be enhanced by applying a predictive model based on the TTL and the intrinsic tumour subtype. ObjectiveTo evaluate the impact of the MS identified by immunohistochemistry on prediction of metastatic disease in axillary non-sentinel lymph nodes based on TTL. Material and methodsRetrospective, European multicenter study including 683 patients from 9 hospitals. ResultsUnivariate analysis identified 6 variables that were significantly correlated with axillary non-sentinel metastasis. Of these, the variables logarithmic value of the TTL, tumour diameter and MS diagnosed by immunohistochemistry were selected for multivariate analysis. The odds ratio estimated by the model were: logarithmic value of the TTL 1.527 (95% CI: 1.299-1.796), tumour diameter 1.503 (95% CI: 1.062-2.129) and MS 2.195 (95% CI: 1.246-3.867). ConclusionsThe strongest predictors of axillary involvement were MS, TTL and tumour diameter. These variables should be included in diagnostic algorithms as essential parameters for therapeutic decision-making on the axilla.

Observations on Solitary Versus Multiple Isolated Pancreatic Metastases of Renal Cell Carcinoma: Another Indication of a Seed and Soil Mechanism?

Isolated pancreas metastases are a rare type of metastasis of renal cell carcinoma, characterized by the presence of pancreatic metastases, while all other organs remain unaffected. In a previous study, we determined arguments from the literature which (a) indicate a systemic–haematogenic metastasis route (uniform distribution of the metastases across the pancreas and independence of the metastatic localization in the pancreas of the side of the renal carcinoma); and (b) postulate a high impact of a seed and soil mechanism (SSM) on isolated pancreatic metastasis of renal cell carcinoma (isPM) as an explanation for exclusive pancreatic metastases, despite a systemic haematogenous tumor cell embolization. The objective of the study presented was to search for further arguments in favor of an SSM with isPM. For that purpose, the factor’s histology, grading, and singular/multiple pancreas metastases were analyzed on the basis of 814 observations published up to 2018. While histology and grading allowed for no conclusions regarding the importance of an SSM, the comparison of singular/multiple pancreas metastases produced arguments in favor of an SSM: 1. The multiple pancreas metastases observed in 38.1% prove that multiple tumor cell embolisms occur with isPM, the exclusive “maturation” of which in the pancreas requires an SSM; 2. The survival rates (SVR), which are consistent with singular and multiple pancreas metastases (despite the higher total tumor load with the latter), prove that the metastasized tumor cells are not able to survive in all other organs because of an SSM, which results in identical SVR when the pancreatic foci are treated adequately.

Prognostic value of metabolic parameters on baseline 18F-FDG PET/CT in small cell lung cancer.

Maximum standardized uptake value (SUV<inf>max</inf>) is the primary quantitave parameter given in 18F-FDG PET/CT reports. Calculations derived from three dimensional metabolic volumetric images have been proposed to be more successful than SUV<inf>max</inf> alone in prognostification with a lower interobserver variability in many cancers. We aimed to determine the prognostic value of metabolic parameters derived from 18F-FDG PET/CT studies in small cell lung cancer (SCLC) patient population with a long follow-up time. In this study, 38 consecutive SCLC patients (34M, 4F, age:65.76 ±8.18 years) who were referred to 18F-FDG PET/CT for staging between October 2006-January 2011 were included. SUV<inf>max</inf>, SUV<inf>mean</inf>, SUV<inf>peak</inf>, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated. Overall survival (OS) was calculated from the date of the initial PET/CT to death from any cause. Survival tables were obtained and Kaplan Meier curves were reconstructed. Mantel-Cox regression analysis was performed in order to investigate if any of these parameters have an effect on survival along with other clinical risk factors. Median SUV<inf>max</inf>, SUV<inf>mean</inf>, SUV<inf>peak</inf>, MTV, TLG and LDH values were calculated as 13.9 g/dL, 6.4 g/dL,10.69 g/dL, 147 cm3, 1898.52 and 375U/L respectively. Median follow-up was 761.23±873.21 days (25.37 months, range:110-3338 days). Since basal 18F-FDG PET/CT scans, all patients were lost in the follow-up except for two patients. MTV was a significant prognostic factor in SCLC patients. Estimated mean survival times were 261.0±45.6 (95% CI: 171.6-350.3) days in patients with MTV value above the calculated median 147, and 577.0±124.0 (95% CI: 333.7-820.2) days in patients with MTV<147. The difference was statistically significant with a P=0.037. Baseline whole body MTV reflecting total tumor load is a prognostic index in SCLC. SUV is insufficient to predict prognosis.

No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes.

564 Background: The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes a complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. Methods: Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2017 at our center. Results: A total of 321 patients underwent SNB assessed by OSNA with an average follow-up of 56 months. 320 were female and 1 male. Age range 27-89 years (mean 58.9). 85 % were ductal, 10 % lobular and 5 % other. 53.5% were luminal A, 28.66% luminal B, 7.78%, triple negative, 4.3%, Her2 positive and 4.3%. luminal B-Her2 positive.TTL was equal to 0 in 183 cases and greater than zero in 138 cases.71 cases showed a TTL higher than 15,000 copies. Only 21 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse and 8 metastatic disease. 12 have died, only two from metastatic breast cancer. Conclusions: Using Z0011 criteria, we have adequate clinical outcomes with a low rate of ALND; If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 3.3 (from 21 to 71); We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes; Work is in progress to increase our sample size.

P006. Does the Total Tumour Load (TTL) as detected by One Step Nucleic Acid Amplification (OSNA) predict Non Sentinel Node Positivity?

Introduction: It has been suggested that TTL can be used to predict non-sentinel node positivity in breast cancer by dividing patients into low (TTL<2.5x104) and high risk categories (TTL>2.5x104). This is of increasing relevance as there is a move to more conservative axillary treatment in the post ACOSOG Z0011 era. Our objective was to test this theory for validity.

P009. Does total tumour load in Sentinel lymph node biopsy assessed by OSNA predict further axillary node disease? Can it stratify which patients may benefit from axillary clearance?

P009. Does total tumour load in Sentinel lymph node biopsy assessed by OSNA predict further axillary node disease? Can it stratify which patients may benefit from axillary clearance?

Abstract P3-03-17: No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes

Abstract BACKGROUND The study of sentinel lymph nodes (SLN) assessed by One Step Nucleic Acid Amplification (OSNA, Sysmex, Kobe, Japan) creates a new variable, Total Tumor Load (TTL). This variable is defined as the total number of CK19 mRNA copies in all positive SLN (copies/microL). The latest edition of the Spanish Oncological Gynecology Society (SEGO) Guideline (2017) proposes complete axillary lymph node dissection (ALND) when TTL is 15,000 copies or more in early breast cancer. In our center we are using OSNA to ascertain if there is axillary node involvement but the decision to proceed to ALND is based on Z0011 criteria. We want to determine if there is a correlation between clinical outcomes and TTL values, between TTL and pathological variables and if TTL is a useful tool to decide when to complete an ALND. METHODS Clinicopathological and follow up data were obtained from all patients with invasive breast cancer and SLN assessed by OSNA between 2011 and end of 2016 at our center. RESULTS A total of 277 patients underwent SNB assessed by OSNA with an average follow-up of 56.4 months. 276 were female and 1 male. Age range 27-88 years (mean 58,7). 86,2 % were ductal, 10,8 % lobular and 2,8 % other. 51.9% were luminal A, 51.98% luminal B, 28.51%, triple negative, 5% Her2 positive and 5% luminal B-Her2 positive. TTL was equal to 0 in 155 cases and greater than zero in 122 cases.68 cases showed a TTL higher than 15,000 copies. Only 19 cases met Z0011 criteria and had ALND. As of now, 3 patients have had locoregional relapse (TTL = 0 in 2 cases and 18,000 copies in one) and 5 metastatic disease (none with simultaneous locoregional recurrence). 7 patients have died (one from metastatic breast cancer, 1 febrile neutropenia, 2 septic shock unrelated to chemotherapy, 2 from other tumors, 1 encephalopathy). BASELINE DATA N=277VARIABLE N%AGE,MEDIAN RANGE 58,7 (27-88) TUMOR TYPEDuctal23986,2 Lobular3010,8 Others82,8IMMUNOPHENOTYPELuminal A14451,98 Luminal B7928,51 Luminal B-HER2145 HER2 positive14 Triple Negative269,3TOTALL TUMORAL LOAD (TTL)=015556 &amp;gt;012244AXILLARY LYMPH NODE DISECTIONS 196,8TTL&amp;gt;15000 6824,5LOCOREGIONAL RELAPSES 31 CONCLUSIONS 1. Using Z0011 criteria, we have adequate clinical outcomes with a very low rate of ALND and locoregional recurrences. 2. If we had based the axillary management on TTL values we would have multiplied the number of ALND by a factor of 2,7 (from 18 to 50). 3. We have observed a tendency to higher TTL in luminal phenotypes and to lower TTL in HER2 positive and triple negative subtypes. 4. Work is in progress to increase our sample size. Citation Format: Tur R, Parra J, Martin R, Alés-Martinez JE. No relationship of axillary total tumor load (TTL) by PCR (OSNA) in early breast cancer and local and distant clinical outcomes [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-17.

Abstract P3-03-14: Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC)

Abstract Introduction NAC has been used for downsizing of the tumour in breast and axilla to allow more conservative surgery. In the NAC setting, intraoperative assessment of sentinel lymph node(s) (SLN) is still considered necessary1. Current awareness of the prognostic value for axillary nodal down-staging has renewed interest in analysis of SLN post-NAC. In this study we want to examine the clinical utility of OSNA (based on CK19 mRNA detection) as a method of intra-operative analysis of SLN to assist real-time decision-making for axillary surgery post-NAC in early breast cancer (EBC). Methods Retrospective analysis of prospective data on 399 consecutive patients with EBC who received NAC followed by breast surgery with SLN biopsy (408 axillae) and assessment by OSNA, from September 2011 to January 2018 at the Royal Marsden Hospital (UK). OSNA readouts from the Sysmex RD-100i were collected separate to and blinded from clinico-pathological data. A negative or benign pre-treatment axillary ultrasound scan or indeterminate ultrasound with negative or benign axillary cytology/histology prior to NAC was considered cN0. Univariate analysis (significance at p&amp;lt;0.05) was used to identify risk of recurrence. Patients had a median (mean) follow up of 32.5 (36) months. Results The median age at diagnosis was 49 years, median BMI 26, 41 EBC (10%) were screen-detected, 292 (72%) were grade 3 and the most frequent phenotype was receptor triple negative (n=132, 32%). Of 408 axillae, 248 (60%) were initially cN0, of which 113 (46%) had a pathological complete response (pCR) in the breast. SLN in 54 (22%) cN0 patients were positive on OSNA, of which only 6 (9%) had further involved axillary nodes all 6 of which were ER+ Her2-. The remaining 160 (40%) axillae were cN1 of which 87 (54%) had conversion to ypN0 including 55 (34%) with both ypT0ypN0. Axillary lymphadenectomy (AL) was performed in 79 (19%) patients overall, of which n=22 (28%) were cN0 and 57 (72%) were cN1. Of these, 30 (53%) of the cN1 and 6 of 22 (45%) of cN0 had at least 1 additional positive AL node. Overall 59 (14.4%) patients relapsed. A significantly worse rate of relapse was observed in cN1 compared to cN0 patients (37/159 (23.3%) versus 22/244 (9%), p&amp;lt;0.001). Combined pCR of both breast and axilla (in cN1, n=54) was associated with a significantly reduced risk of relapse and death (p&amp;lt;0.001) compared to those without pCR of either breast or axilla (n=62). Of the latter 18 (29%) relapsed (including 10 deaths). The mean of both the single highest node tumour load (and total nodal tumour load), as measured by CK19mRNA copies/ul on OSNA, were significantly higher at 90,000 (98,300) for those who relapsed versus 23,100 (25,100) for those without relapse (p=0.027). Conclusions The OSNA assay is an accurate tool for axillary SLN analysis in patients after NAC and was helpful in intra-operative axillary management. OSNA reduces the need for a second surgery for AL in 20% of breast cancer patients with a positive-SLN after NAC and might offer additional prognostic value. Reference 1. NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Breast Cancer.2016.Version 2.2016. Citation Format: Muscara F, Christaki G, Richardson C, O'Connell R, Padmanabhan P, Warwick J, Lee Y, Smith I, Nerurkar A, Osin P, Krupa K, Rusby J, Roche N, Gui G, MacNeil F, Barry P. Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-14.

The prognostic value of volumetric reduction of the target lesions after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma

We explored whether the volumetric reduction ratio of target lesion after induction chemotherapy (IC) had any prognostic value in nasopharyngeal carcinoma (NPC). From 2013 to 2016, 72 NPC patients treated with PCF (paclitaxel, cisplatin, 5-fluorouracil) IC followed by cisplatin-based concurrent chemoradiotherapy were analyzed. The volumes of target lesions before and after IC and survival conditions were assessed. For all cases, volumetric reduction ratios of the total tumor load ≥ optimal cutoff values were significantly associated with increased 2-year progression-free survival, locoregional failure-free survival, and distant metastasis-free survival (DMFS) rates, and for cervical lymph nodes, the volumetric reduction ratio ≥ optimal cutoff value was significant for DMFS (all P < .05). Accordingly, the optimal cutoff values were 24.56% (AUC = 60.5%), 23.91% (AUC = 57.7%), 29.77% (AUC = 75.8%), and 34.17% (AUC = 62.5%), respectively. Volumetric reductions of target lesions after IC are independent survival predictors for NPC, especially for those with N2/N3 disease.

Nomogram to predict non-sentinel lymph node status using total tumor load determined by one-step nucleic acid amplification: first report from Thailand.

Axillary staging is a significant prognostic factor often used to determine the treatment course for breast cancer. One-step nucleic acid amplification (OSNA) is now the most accepted method for intra-operative assessment of sentinel lymph nodes (SLN) as it can semi-quantitatively determine the tumor burden in these SLN. Axillary lymph node dissection (ALND) may be omitted in patients with limited disease in the axilla. The objective was to create nomogram for prediction of non-sentinel lymph node (NSLN) status using OSNA to avoid unnecessary ALND. Patients with invasive breast cancer T1-T3 and clinically negative axillary lymph nodes underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent ALND. Correlations between total tumor load (TTL), clinicopathological parameters, and NSLN status were analyzed by Chi square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis. The total number of patients who underwent SLN biopsies was 278. There were 89 patients with positive SLN. NSLNs were positive in 40 patients. Larger tumor size, presence of lymphovascular invasion (LVI) and higher log TTL were independent factors that predicted positive NSLN. TTL can discriminate NSLN status with area under the ROC curve of 0.789 (95% CI 0.686-0.892). Two nomograms using different parameters obtained pre- and post-operatively can predict NSLN involvement with better area under the ROC curve (0.801, 95% CI 0.702-0.900 and 0.849, 95% CI 0.766-0.932, respectively). Nomograms using results obtained via OSNA can predict NSLN status, as well as aid in deciding to omit the use of ALND.

265P - Nomogram to predict non-sentinel lymph node status of breast cancer using total tumor load determined by one-step nucleic acid amplification (OSNA)

265P - Nomogram to predict non-sentinel lymph node status of breast cancer using total tumor load determined by one-step nucleic acid amplification (OSNA)

Intraoperative Nomograms, Based on One-Step Nucleic Acid Amplification, for Prediction of Non-sentinel Node Metastasis and Four or More Axillary Node Metastases in Breast Cancer Patients with Sentinel Node Metastasis

BackgroundOne-step nucleic acid amplification (OSNA) for cytokeratin 19 messenger RNA is an intraoperative diagnostic procedure for the detection of lymph node metastasis.ObjectiveThis study aimed to construct intraoperative nomograms using OSNA for the prediction of non-sentinel lymph node (NSLN) metastasis and four or more axillary lymph node (ALN) metastases.MethodsOf the 4736 breast cancer patients (T1-3, N0) who underwent sentinel lymph node (SLN) biopsy and had SLNs examined intraoperatively with OSNA, 623 with SLN metastasis treated with completion ALN dissection (cALND) were retrospectively analyzed, and were randomly divided into training (n = 312) and validation (n = 311) sets.ResultsOf the clinicopathological parameters available preoperatively and intraoperatively, the multivariate analysis of the training set revealed that clinical tumor size and total tumor load (TTL) determined by OSNA were significantly associated with NSLN metastasis, and that clinical tumor size, number of macrometastatic SLNs, and TTL were significantly associated with four or more ALN metastases. Nomograms for NSLN metastasis and four or more ALN metastases were constructed using these parameters, and their area under the receiver operating characteristic curve (AUC) of the validation set were both 0.70, with a diagnostic accuracy similar to that of previously reported postoperative nomograms.ConclusionsWe constructed intraoperative nomograms using OSNA for the prediction of NSLN metastasis and four or more ALN metastases. These nomograms are as accurate as the conventional postoperative nomograms and might be helpful for decision making regarding the indication for cALND or the choice of adjuvant chemotherapeutic regimens and radiation field.

Utility of One-Step Nucleic Acid (OSNA) cytokeratin-19 amplification assay total tumour load (TTL) in survival prediction, in primary operable invasive breast carcinoma

Introduction: One-Step Nucleic acid Amplification (OSNA) can be used to quantitatively stage axillary node involvement in patients with breast carcinoma. Recently, OSNA total CK19mRNA copy number (total tumour load, TTL) has been shown to correlate with disease-free, local recurrence-free and overall-survival. We assessed the utility of OSNA TTL as a substitute for histological axillary node staging in determining prognosis within two prediction models.

One step nucleic acid amplification cytokeratin 19 mRNA copy numbers as a predictor of axillary status in breast cancer: An assessment of average copy number and total tumour load

One step nucleic acid amplification cytokeratin 19 mRNA copy numbers as a predictor of axillary status in breast cancer: An assessment of average copy number and total tumour load

SPECT/CT With the PSMA Ligand 99mTc-MIP-1404 for Whole-Body Primary Staging of Patients With Prostate Cancer.

Tc-MIP-1404 (Progenics Pharmaceuticals, Inc, New York, NY) is a novel ligand binding to prostate-specific membrane antigen suitable for SPECT. There are, as yet, no data concerning its use in whole-body primary staging and its interobserver variability in patients with prostate cancer (PC) prior to therapy. A search of our clinical database from April 2013 to May 2017 yielded 93 patients with histologically confirmed cancer in whom Tc-MIP-1404 SPECT/CT had been performed for primary whole-body staging before therapy. Whole-body planar and SPECT/CT images of the lower abdomen and thorax had been obtained 3 to 4 hours postinjection of 706 ± 72 MBq Tc-MIP-1404. Images were visually analyzed for extent and location of abnormal uptake by 2 experienced nuclear physicians. Interobserver agreement for detection of primary tumor and metastatic lesions was assessed. In addition, SUVs of prostate-specific membrane antigen-positive regions of the prostate were determined in all patients, and from these, a variable reflecting total tumor load in the prostate gland was calculated (TUprostate). Follow-up reports of subsequent therapeutic interventions were available in 52 (56%) of all patients with a median follow-up of 18 months. In 90 (97%) of 93 patients, prostate uptake above background was detected as correlate of the histologically diagnosed PC. Forty-eight lymph node and 29 bone metastases were detected in 16 and 9 patients, respectively. In addition, 3 patients had disseminated bone metastases. No distant organ metastases were found. Interobserver agreement was high for the overall scan result (97%), as well as for the detection of the primary tumor (97%), of lymph node metastases (97%), and of bone metastases (99%). Recurrence of PC occurred in 5 patients in whom follow-up was available (10%). TUprostate was significantly higher in patients with Gleason scores of 8 or greater compared with patients with Gleason scores of 7 or less and at prostate-specific antigen (PSA) serum levels of 10 ng/mL or greater compared with PSA serum levels of 10 ng/mL or less. TUprostate of greater than 26 in the primary tumor predicted the occurrence of lymph node or bone metastases with a sensitivity of 82% and specificity of 76%. MIP-1404 SPECT/CT has a high accuracy and low interobserver variability in the diagnosis of PC and allows detection of lymph node and bone metastases in a significant proportion of as yet untreated PC patients. TUprostate is correlated with Gleason score and PSA serum concentration and allows prediction of the occurrence of lymph node and bone metastases with moderate accuracy at primary staging.

Abstract P3-01-19: Relationship of axillary total tumor load (TTL) by OSNA (one step nucleic acid amplification) in early breast cancer and clinical outcomes using strict Z0011 study criteria for axilla management

Abstract Background: The study of sentinel lymph node (SNL) assessed by OSNA provides a new variable, Total Tumoral Load (TTL).This variable is defined as the amount of CK19 mRNA copies number in all positives SLN. TTL has been showed to predict the axillary node status and has been analysed to determine its usefulness in the axillary surgical management. Based on TTL values different cut-off points have been proposed (last 25.000 copies) to establish a new tool to practice axillary lymph node dissection (ALND). We present the follow-up data of at least 5 years of breast cancer patients who underwent ALND according, strictly, to Z0011 trial criteria. We hypothesized that there will be no correlation between TTL and locoregional relapse if Z0011 are followed. Methods: Clinicopathological and follow up data were obtained from patients with invasive breast cancer and SLN assessed by OSNA between 2011 and 2012 at Complejo Asistencial de Ávila, Spain. ALND was decided based on Z0011 study criteria independently of TTL. All patients have been followed for a minimun of 5 years. Results: A total of 106 patients underwent SN assessed by OSNA, age range 27-85 years (mean 58,96). Of them 90% were ductal, 7,5% lobular and 2% others. By inmunophenotype: Luminal A 55%, Luminal B 28%, Triple Negative 9,4%, Her2 positive 3,7% and Luminal B-Her2 positive 2,8%. TTL was equal to zero in 58 cases and greater than zero in 48 cases with a range of 280-2.700.000 copies. Only 5 cases met ALND criteria (average TTL 68.164). Average TTL in cases without ALND was 111.000. For the time being, none of them has had locoregional relapse (median follow up 65 months). 3 patients have died one metastatic desease (Negative SN), one uterine cervix cancer and one neutropenic fever. Baseline and outcomes dataVARIABLE N%Age, years (median, range) 59 (27-85) Tumour TypeDuctal9690,5 Lobular87,5 Others21,8InmunophenotypeLuminal A5955,6 Luminal B3028,3 Luminal B-Her232,8 Her243,7 Triple Negative109,4Total Tumoral Load (TTL)=05854,7 &amp;gt;04845,2Axillary Lymph Node Dissection (ALND) 254,7TTL &amp;gt;25.000 2321,7Locoregional relapse 00Overall Survival 95,2 Conclusions: -Using Z0011 criteria and OSNA no locoregional recurrence has been observed so far. -TTL did not predict risk of recurrence -If we had based axillary management only on TTL values (i.e higher than 25.000 copies) we would have unnecessarily increased the number of lymphadenectomies in a 22%. This is an ongoing study that designed to increased the sample size and obtain longer follow-up data. Citation Format: Tur R, De Grado C, Martin MR, De Castro J, Filipovich E, Segovia B, Ceballos J, Parra J, Revestido R, Alés-Martínez JE. Relationship of axillary total tumor load (TTL) by OSNA (one step nucleic acid amplification) in early breast cancer and clinical outcomes using strict Z0011 study criteria for axilla management [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-19.

Intraoperative prediction of the two axillary lymph node macrometastases threshold in patients with breast cancer using a one-step nucleic acid cytokeratin-19 amplification assay.

The aim of the present study was to assess the sensitivity, specificity and practicality of using a one-step nucleic acid amplification (OSNA) assay during breast cancer staging surgery to predict and discriminate between at least 2 involved nodes and more than 2 involved nodes and facilitate the decision to provide axillary conservation in the presence of a low total axillary node tumour burden. A total of 700 consecutive patients, not treated with neo-adjuvant chemotherapy, received intraoperative sentinel lymph node (SLN) analysis using OSNA for cT1-T3 cN0 invasive breast cancer. Patients with at least one macrometastasis on whole-node SLN analysis underwent axillary lymph node dissection (ALND). The total tumour load (TTL) of the macrometastatic SLN sample was compared with the non-sentinel lymph node (NSLN) status of the ALND specimen using routine histological assessment. In total, 122/683 patients (17.9%) were found to have an OSNA TTL indicative of macrometastasis. In addition, 45/122 (37%) patients had NSLN metastases on ALND with a total positive lymph node burden exceeding the American College of Surgeons Oncology Group Z0011 trial threshold of two macrometastatic nodes. The TTL negative predictive value was 0.975 [95% confidence interval (CI), 0.962–0.988]. The area under the curve for the receiver operating characteristic curve was 0.86 (95% CI, 0.81–0.91), indicating that SLN TTL was associated with the prediction (and partitioning) of total axillary disease burden. OSNA identifies a TTL threshold value where, in the presence of involved SLNs, ALND may be avoided. This technique offers objective confidence in adopting conservative management of the axilla in patients with SLN macrometastases.

Prediction of Non-Sentinel Lymph Node Metastasis by Molecular Assay in Whole Sentinel Lymph Node Analysis in Breast Cancer Patients

Objective: To determine whether the total tumor load (TTL) as indicated through the one-step nucleic acid amplification(OSNA) assay can be a predictive factor of non-sentinel lymph node (SLN) metastasis in early breast cancer patients.Material and Method: The records of 102 patients with cT1-3N0 breast cancer who had an intraoperative SLN evaluationperformed through an OSNA assay at Songklanagarind Hospital between 1 January 2015 and 30 May 2016 were examined.Results: Univariate analysis found TTL, tumor size, presence of lymphovascular invasion, and macrometastasis weresignificant predictive factors of non-SLN metastasis. In the multivariate analysis, TTL was the only predictive factor withstatistical significance (OR 1.1, 95% CI=1.0, 1.2). The area under the receiver operating characteristics (ROC) curve ofTTL was 0.9 (95% CI=0.8, 0.9).Conclusion: TTL is a significant predictive factor of non-SLN metastasis in early breast cancer patients.

Role of total tumour load of sentinel lymph node on survival in early breast cancer patients

BackgroundAxillary staging (pN) is considered one of the most important prognostic factors in breast cancer patients. However, the Z0011 study data drastically reduced the number of surgical axillary dissections in a selected group of patients, limiting the prognostic information relating to axillary involvement to the sentinel lymph node (SLN). It is known that there is a relationship between SLN total tumour load (TTL) and axillary involvement. The objective of this study is to analyse the relationship between the TTL and outcomes in patients with early stage breast cancer. Patients and methodsclinicopathological and follow-up data were collected from 950 patients with breast cancer between 2009 and 2010 on whom SLN analysis was conducted by molecular methods (One Step Nucleic Acid Amplification, Sysmex, Kobe, Japan). ResultsTTL (defined as the total number of CK19 mRNA copies in all positive SLN) correlates with disease free survival (HR, 1.08; p = 0.000004), with local recurrence disease free survival (HR = 1.07; p = 0.0014) and overall survival (HR: 1.08, p = 0.0032), clearly defining a low-risk group (TTL <2.5 × 104 CK19 mRNA copies/μL) versus a high-risk group (>2.5 × 104 CK 19 mRNA copies/μL). ConclusionsSLN TTL permits the differentiation between two patient groups in terms of DFS and OS, independently of axillary staging (pN), age and tumour characteristics (size, grade, lymphovascular invasion). This new data confirms the clinical value of low axillary involvement and could partially replace the information that staging of the entire axilla provides in patients on whom no axillary lymph node dissection is performed.

Lymph node pooling: a feasible and efficient method of lymph node molecular staging in colorectal carcinoma

Background Pathologic lymph node staging is becoming a deficient method in the demanding molecular era. Nevertheless, the use of more sensitive molecular analysis for nodal staging is hampered by its high costs and extensive time requirements. Our aim is to take a step forward in colon cancer (CC) lymph node (LN) pathology diagnosis by proposing a feasible and efficient molecular method in routine practice using reverse transcription loop-mediated isothermal amplification (RT-LAMP).ResultsMolecular detection of tumor cytokeratin 19 (CK19) mRNA with RT-LAMP was performed in 3206 LNs from 188 CC patients using two methods: individual analysis of 1449 LNs from 102 patients (individual cohort), and pooled LN analysis of 1757 LNs from 86 patients (pooling cohort). A median of 13 LNs (IQR 10–18) per patient were harvested in the individual cohort, and 18 LNs (IQR 13–25) per patient in the pooling cohort (p ≤ 0.001). The median of molecular assays performed in the pooling cohort was 2 per patient (IQR 1–3), saving a median of 16 assays/patient. The number of molecular assays performed in the individual cohort was 13 (IQR 10–18), corresponding to the number of LNs to be analyzed. The sensitivity and specificity of the pooling method for LN involvement (assessed by hematoxylin and eosin) were 88.9% (95% CI 56.5–98.0) and 79.2% (95% CI 68.9–86.8), respectively; concordance, 80.2%; PPV, 33.3%; NPV, 98.4%. The individual method had 100% sensitivity (95% CI 72.2–100), 44.6% specificity (95% CI 34.8–54.7), 50% concordance, 16.4% PPV, and 100% NPV. The amount of tumor burden detected in all LNs of a case, or total tumor load (TTL) was similar in both cohorts (p = 0.228).ConclusionsLN pooling makes it possible to analyze a high number of LNs from surgical colectomies with few molecular tests per patient. This approach enables a feasible means to integrate LN molecular analysis from CC specimens into pathology diagnosis and provides a more accurate LN pathological staging with potential prognostic implications.