ypN0 Disease Research Articles

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Abstract PS01-01: Feasibility and oncological safety of targeted axillary dissection or sentinel lymph node biopsy in patients with clinically node-positive disease after neoadjuvant chemotherapy in the prospective MF-1803 NEOSENTITURK-study

Can Axillary Ultrasound Identify Node Positive Patients Who can Avoid an Axillary Dissection After Neoadjuvant Chemotherapy?

IntroductionAxillary lymph node dissection (ALND) is recommended for patients with invasive breast cancer with axillary metastasis treated with neoadjuvant chemotherapy (NAC) who do not have a nodal pathologic complete response (n-pCR). We hypothesized that patients with a single, ultrasound-suspicious, nonpalpable lymph node (LN) at diagnosis, who do not achieve an n-pCR, will have ypN1 disease on surgical pathology. MethodsThis retrospective study identified breast cancer patients in our institution from 2012 to 2020 with axillary metastasis treated with NAC who did not achieve an n-pCR and had an ALND. Patient's tumor characteristics, axillary ultrasound, and lymph node disease burden at the time of surgery were reviewed. ResultsFifty five patients met the criteria and 36% had one suspicious LN on ultrasound, 25% had 2, and 38% had >3. After chemotherapy, 64% had ypN1 disease, 29% had ypN2 disease, and 7% had ypN3 disease. Of the 20 patients with one abnormal LN on initial ultrasound, 17 (85%, 95% CI 61-96%) had ypN1 disease. Eleven patients with one abnormal LN on initial ultrasound also had no suspicious LNs on prechemotherapy physical exam; among these patients, 100% had ypN1 disease. ConclusionsFor breast cancer patients who do not achieve an n-pCR after NAC, pretreatment normal clinical axillary exam and prechemotherapy ultrasound showing only one abnormal LN is associated with ypN1 disease. It may be reasonable to consider omitting completion ALND in this subset of patients while awaiting the results of the Alliance A011202 trial.

Total Lymph Node Yield Is Associated with Prolonged Survival after Neoadjuvant Chemotherapy in ypN0 Gastric Cancer Patients

Introduction: Lymph node status after neoadjuvant chemotherapy (NAC) plays the main role in predicting the survival of gastric cancer (GC) patients who underwent curative gastrectomy after NAC. NAC can reduce the number of involved lymph nodes. However, it is unknown whether other variables are associated with the survival outcomes for ypN0 GC patients. It is unknown whether lymph node yield (LNY) has prognostic value in ypN0 GC patients treated with NAC plus surgery. Methods: In this retrospective study, we reviewed the data of patients treated with NAC plus gastrectomy and identified those with ypN0 disease. The LNY cut-off was calculated using the X-tile program to determine the greatest actuarial survival difference. Patients were categorized into the downstaged N0 (cN+/ypN0) and natural N0 (cN0/ypN0) groups based on nodal status. Multivariate analysis was used to identify the prognostic factors and the association between LNY and prognosis. Results: A total of 211 GC patients with ypN0 status were included. The optimal LNY cut-off was 23. Kaplan-Meier analysis revealed no significant difference in overall survival between the natural and downstaged N0 groups, while ypN0 GC patients with an LNY of ≥24 had significantly longer overall survival than those with an LNY of ≤23. Univariate analysis identified that LNY, cT stage, tumor location, ypT stage, perineural invasion, lymphovascular invasion, tumor size, Mandard tumor regression grade, and extent of gastrectomy were significantly associated with overall survival. Multivariate analysis confirmed that perineural invasion (hazard ratio, 4.246; p < 0.001), lymphovascular invasion (hazard ratio, 2.694; p = 0.048), and an LNY of ≥24 (hazard ratio, 0.394; p = 0.011) were independent prognostic factors. Conclusions: Patients with natural and downstaged ypN0 GC had similar overall survival after NAC. LNY was an independent prognostic factor in these patients, and an LNY of ≥24 predicted prolonged overall survival.

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer

IntroductionPatients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. Materials and methodsPatients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. ResultsBefore treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). ConclusionThese data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.

Are We Overestimating Rectal Cancer Nodal Involvement?

<h3>Purpose/Objective(s)</h3> Per current guidelines, rectal cancer is staged with pelvic MRI (or EUS if MRI contraindicated) to determine T- and N-stage. Those with ≥ clinical stage T3 (cT3) or N1 (cN1) are recommended to neoadjuvant treatment (NT). The specificity of MRI for N-staging of rectal cancer is ∼ 70% - this is lower than the specificity of MRI for T-staging. Thus, for those cancers for which NT is recommended based on N-staging, there is the potential that up to 30% of patients are over-staged. The current retrospective study aims to quantify the percentage of clinically lymph node positive (cN+) rectal cancers treated with NT that have pathologic complete nodal response (ypN0) with no treatment effect noted at surgical resection. <h3>Materials/Methods</h3> Cases of cN+ rectal cancer treated at our COC-Accredited INCP institutions between 2015 - 2020 were identified. Data were collected with regard to staging modality, clinical T- and N-stage, size of largest suspicious lymph node (LN) on MRI, NT-type (total neoadjuvant therapy (TNT) with capecitabine/RT (CRT), TNT with short course RT (SCRT), or neoadjuvant radiation or chemoradiation alone), ypN-stage, and treatment effect. We compared proportions of ypN0 cases by cT- and cN-stage, size of largest suspicious LN on MRI, and NT-type using multivariable logistic regression. <h3>Results</h3> A total of 64 cases of cN+ rectal cancer were identified. Fifty-three were staged by MRI, 2 by EUS, 2 by PET, and 7 by CT. Primary tumor staging was as follows: cTx = 2, cT1 = 1, cT2 = 10, cT3 = 36, cT4 = 15. Clinical N-stage was as follows: cN1 = 41, cN2 = 23. For 13 patients (20%), the recommendation for NT was based entirely on MRI N+ staging. Fifty-seven patients were treated with TNT: All with FOLFOX followed by 44 with CRT and 13 with SCRT. Seven patients were treated with neoadjuvant CRT or SCRT without neoadjuvant FOLFOX. Pathologic results showed residual ypN2 disease in 4 cases, ypN1 disease in 19 cases and ypN0 disease in 42 cases (65%) with treatment effect (n = 5) or possible treatment effect (n = 3) noted in 8 of those cases. ypN0 disease was seen in 57% (n = 4) receiving no TNT, 46% (n = 6) receiving TNT with SCRT, and 72% (n = 32) receiving TNT with CRT. Of the 13 patients with cTx-T2 tumors who received NT based on cN+ status, 10 (77%) had ypN0 disease and 1 had signs of treatment effect in a LN. On multivariable logistic regression, cN-stage (cN1 vs cN2) predicated for ypN+ disease with a hazard ratio of 5.15 for cN2 disease (<i>p</i> = 0.0076). cT-stage, size of largest suspicious LN on MRI and NT-type did not predict for yp nodal status. <h3>Conclusion</h3> In patients with cN+ rectal cancer (staged predominately by MRI), more than half of patients had no pathologic residual nodal disease and no treatment effect noted in the LN. While this finding is in line with the results of major randomized trials such as RAPIDO, it confirms a 65% rate of ypN0 disease following neoadjuvant treatment for cN+ rectal cancer in the setting of a 70% specificity of MRI for rectal cancer nodal staging. cN2 disease predicts for residual pathologic LN disease.

Validation of the Role of Postoperative Radiotherapy in Improving Disease-Free Survival of Patients with Stage III ypN2 Non-Small Cell Lung Cancer after Neoadjuvant Therapy Followed by Complete Resection – A Propensity-Score Matching Study

<h3>Purpose/Objective(s)</h3> Although the Lung ART study, a phase III trial, showed that postoperative radiotherapy (PORT) could not significantly improve the disease-free survival (DFS) of patients with pN2 non-small cell lung cancer (NSCLC) after complete resection. However, its subgroup analysis showed that PORT did significantly improve the DFS of those with ypN2 NSCLC after neoadjuvant therapy and surgery. Our study aimed to validate the effect of PORT on the survival of patients with ypN2 NSCLC. <h3>Materials/Methods</h3> Patients was filtrated from our center from 2004 to 2021. The inclusion criteria of patients were as follows: 1) diagnosed with NSCLC; 2) accepted neoadjuvant systematic treatments including chemotherapy, tyrosine kinase inhibitors (EGFR, ALK), or immune checkpoint inhibitors; 3) received complete resection (R0 resection); 4) with stage III ypN2 disease (AJCC 8^th). We excluded patients with multiple primary malignant tumors and those who died within four months after surgery. The primary endpoint was DFS. The second endpoints were overall survival (OS) and locoregional recurrence-free survival (LRFS). Propensity-score matching (PSM) was used to match the baseline characteristics between the PORT group and the non-PORT group. Kaplan-Meier method was used to estimate the endpoints. All data were analyzed using R 4.1.2. <h3>Results</h3> Totally 185 patients were included in the final analysis. There were 49 patients (26.5%) with PORT. After 1:1 PSM between the PORT group and the non-PORT group, 82 patients remained with 41 in each group. The baseline characteristics of majority in the matched cohort were as follows: male (75.6%), smoking history (79.3%), performances scores 0-1 (100%), adenocarcinoma (47.6%), grade 3-4 (58.5%), receiving neoadjuvant chemotherapy (91.5%), lobectomy (82.9%), ypT1-2 (78.9%), and ypN2b (51.2%). The median age of patients was 58. The median numbers of examined and positive lymph nodes were 20.5 and 6. The median follow-up time was 49.5 months. The median DFS of the PORT group and the non-PORT group were 25.5 months vs. 18.6 months, with the 5-year DFS rates of 43.4% vs. 24.8%, respectively (P=0.044). The median LRFS of the two groups were not reached vs. 56.8 months, with the 5-year LRFS rates of 89.1% vs. 39.8% (P<0.001). The median OS of the two groups were not reached vs. 67.7 months, with the 5-year OS rates of 76.7% vs. 34.8% (P=0.092). <h3>Conclusion</h3> For patients with stage III ypN2 NSCLC after neoadjuvant systematic therapy followed by complete resection, PORT can significantly improve the DFS and LRFS, but failed to improve OS. However, the results need to be clarified by prospective randomized clinical trials.

Clinical Understaging, Treatment Response, and Survival Among Esophageal Adenocarcinoma Patients

IntroductionSelecting appropriate management for patients with esophageal adenocarcinoma (EA) is predicated on accurate clinical staging information. Inaccurate information could lead to inappropriate treatment and suboptimal survival. We investigated the relationship between staging accuracy, treatment, and survival. MethodsThis was a national cohort study of EA patients in the National Cancer Data Base (2006-2015) treated with upfront resection or neoadjuvant therapy (NAT). Clinical and pathological staging information was used to ascertain staging concordance for each patient. For NAT patients, Bayesian analysis was used to account for potential downstaging. We evaluated the association between staging concordance, receipt of NAT, and survival through hierarchical logistic regression and multivariable Cox regression. ResultsAmong 7635 EA patients treated at 877 hospitals, 3038 had upfront resection and 4597 NAT followed by surgery. Relative to accurately staged patients, understaging was associated with a lower likelihood (odds ratio [OR] 0.04 95% confidence interval [CI] 0.02-0.05) while overstaging was associated with a greater likelihood of receiving NAT (OR 1.98 [1.53-2.56]). Relative to upfront surgery, treatment of cT1N0 patients with NAT was associated with a higher risk of death (HR 3.08 [2.36-4.02]). For accurately or overstaged cT3-T4 patients, NAT was associated with a lower risk of death whether downstaging occurred (ypN0 disease—HR 0.67 [0.49-0.92]; N+ disease—HR 0.55 [0.45-0.66]) or not (ypN + disease—HR 0.78 [95% CI 0.65-0.93]). ConclusionsClinical understaging is associated with receipt of NAT which in turn may have a stage-specific impact on patients’ survival regardless of treatment response. Guidelines should account for the possibility of inaccurate clinical staging.

Durvalumab (D) and PET-directed chemoradiation (CRT) after induction FOLFOX for esophageal adenocarcinoma: Final results.

4029 Background: Induction FOLFOX followed by PET-directed CRT prior to surgery demonstrated positive results in the CALGB 80803 study. We investigated the safety and efficacy of adding D, an anti-PD-L1 antibody, to PET-directed CRT. Methods: Patients (pts) with locally advanced esophageal/GEJ adenocarcinoma were enrolled. Pts received 2 cycles of mFOLFOX6 prior to repeat PET/CT. PET responders (≥35% reduction in SUV (PETr)) received 5-FU/capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 weeks prior to CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts with R0 resections received adjuvant D 1,500mg q4W ×6. The primary endpoint was the pathologic complete response (pCR) rate. Results: 36 pts were enrolled. Clinical ≥T3 disease was seen in 32 pts (88.9%, cT4 = 3) and ≥N1 in 23 (63.9%) pts. PD-L1 CPS was ≥1 in 25 (71.4%) of 35 tested with 14 (40%) ≥5. Microsatellite instability (MSI) was identified in 3 (8.3%) pts. 25 (70%) pts were PETr. Preop treatment was well tolerated with no new safety signals. Three pts had disease progression prior to surgery. pCR was identified in 8 (22.2%) pts and 22 (64.7%) had major pathologic response (MPR; ypTanyN0 + ≥90% response). Those with MSI tumors had ≥90% treatment response (1 pCR, 1: ypT1aN0 99% response, 1: ypT2N0, 90% response). 17 (73.9%) of 23 cN+ pts had ypN0 disease. MPR was associated with PD-L1 ≥1 (p = 0.03) and with a higher tumor mutational burden (TMB; p = 0.016) on MSK-IMPACT testing. Adjuvant D was commenced in 27 pts, with a median number of 6 cycles. Early discontinuation was due to risks of visits due to COVID19 (4, 15%), progressive disease (3, 11%), late surgical complications (2, 7%) and immune toxicity (1, 4%). With a median follow-up of 30 months, OS rates were 92% [95%CI: 83%-100%] and 85 % [95%CI: 74%-98%] at 12 and 24 months post induction. 12 and 24-month PFS rates were 81% [95%CI: 69%-95%] and 71% [95%CI: 58%-88%] respectively. In the 33 operated pts, 12 and 24-month disease free survival was 82% [95%CI: 70%-96%] and 78% [95%CI: 65%-94%], respectively. In addition to SUV on PET, total lesion glycolysis (TLG) was correlated with pathologic response. In cases with borderline change in SUV, TLG could predict response to treatment. One PETnr with 30.8% reduction in SUV had 88.1% reduction in TLG and pCR. Conversely, a PETr (-36.3%) who had an increase in TLG (39.3%) had only 40% treatment response on pathology. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT prior to surgery is safe and appears effective with a high rate of pathologic response, as well as encouraging survival data. PD-L1 CPS≥1 and higher TMB may be associated with MPR. TLG is a novel PET variable that should be studied prospectively. Additional correlatives and comparison to a cohort treated with standard PET-directed CRT will be presented. Clinical trial information: NCT02962063.

The Impact of Regional Nodal Irradiation on the Outcomes After Neoadjuvant Chemotherapy in Node Positive Breast Cancer Patients With ypN0: Interim Analysis of a Prospective Randomized Trial

To evaluate the impact of regional nodal irradiation (RNI) on the loco-regional recurrence free survival (LRFS), distant metastases free survival (DMFS) and overall survival (OS) in breast cancer patients with node positive disease who received neoadjuvant chemotherapy (NAC) and became ypN0.From January 1st 2016 till December 31st 2019, 231 patients with node positive breast cancer who received NAC and became ypN0 were randomized to receive whole breast irradiation/post mastectomy irradiation with or without RNI. One hundred and twelve patients were included in the regional nodal irradiation arm (RNI+) and 119 patients were included in the no regional nodal irradiation arm (RNI-).Median follow up was 24 months (range, 1-55 months). No regional nodal failures were recorded in both groups. The actuarial LRFS was 98.2% in the RNI+ arm and 100% in the RNI- arm (P 0.28). The actuarial DMFS was 93.6% in the RNI+ arm and 97.4% in the RNI- arm (P 0.93). The actuarial OS was 96.3% in the RNI+ arm and 99.1% in the RNI- arm (P 0.75). Cox univariate regression analysis revealed initial tumor size > 5 cm (HR 1.276, CI 1.054-1.543, P 0.012) was the only factor associated with increased incidence of distant metastases. Age younger than 35 years was associated with worsened survival (HR 0.866, CI 0.760-0.986, P 0.03).In the current interim analysis, omission of regional nodal irradiation did not compromise the outcomes in clinically node positive patients who received NAC and had ypN0 disease.

Favorable outcome with sentinel lymph node biopsy alone after neoadjuvant chemotherapy in clinically node positive breast cancer at diagnosis: Turkish Multicentric NEOSENTI-TURK MF-18-02-study

PurposeFactors affecting local outcome were evaluated in patients with clinically node-positive (cN+) breast cancer at diagnosis, who underwent sentinel lymph node biopsy (SLNB) alone after neoadjuvant chemotherapy (NAC). MethodsBetween 2004 and 2018, 303 cytopathology-proven cN (+) patients in a multicentric registry, who received NAC and underwent SLNB alone were analysed. All patients had regional nodal irradiation. ResultsMedian age was 46 (23–70). Of those, 211 patients had ypN0 disease (69.6%), whereas 92 patients had ypN (+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastases (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 36 months (24–172), one patient (0.3%) with macrometastatic SLN was found to have locoregional recurrence as chest wall and supraclavicular LN metastases at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were 87% and 95%, respectively. Patients with cT3/4 (HR = 2.41, 95% CI; 1.14–5.07), non-luminal molecular pathology (HR = 2.60, 95% CI, 1.16–5.82), and non-pCR in the breast (HR = 2.11, 95% CI, 0.89–5.01) were found to have an increased HR compared to others in 5-year DFS. However, no difference could be found between ypN0 and ypN ITC and micrometastasis (HR = 1.23, 95% CI, 0.44–3.47), whereas there was a slight increase in HR of patients with ypN macrometastasis versus ypN0 (HR = 1.91, 95% CI, 0.63–5.79). ConclusionALND could be avoided in meticulously selected cN (+) patients who underwent SLNB after NAC having breast and/or nodal pCR, cT1-2, or low volume residual nodal disease with luminal pathology, as long as axillary radiotherapy is provided.

Impact of Persistent N2 Disease and Lymph Node Ratio on Oncological Outcomes after Multimodal Treatment in Pre-Operative Histologically Proven N2 Disease Non-Small-Cell Lung Cancer

Objective: The objectives of our retrospective analysis were to estimate the oncological long-term results of patients with ypN2 and to evaluate the impact of lymph node ratio (LNR) on overall (OS) and disease-free survival (DFS). Methods: We analysed all consecutive patients (n=85) undergoing neoadjuvant chemotherapy (NAC) and surgery for pre-operative pathologically proven stage IIIA-B (N2) NSCLC from 2014 to 2020. Median LNR (0.29 or 29%) was selected as threshold for grouping. Survival was estimated using the Kaplan-Meier method. Cox regression was used to test the association between OS, DFS and covariates. Results: Post-operative mortality was 3.5%. The median follow-up was 21 months (range 6-69 months). The 5-year OS and DFS of the cohort were 41% and 20%. Patients with LNR&gt;0.29 (n=13; 15.3%) showed a trend toward worse survival than patients with LNR0 (n=44; 51.8%) with a 5-year OS of 56% VS 14% (p=0.077), confirmed as a trend at the multivariable analysis (HR 2.28; p=0.066). At the univariate analysis a worse DFS was observed for ypN2 patients (n=58; 68.2%) compared with nodal downstaging (46% vs 25% 3-year DFS, p=0.039). DFS was different according to LNR: 3-year DFS was 14% in patients with LNR&gt;0.29 while it reached 44% in patients with LNR 0 (p=0.043) and 62% in LNR&lt;0.29 (p=0.03). LNR&gt;0.29 was the only significant predictor (HR 2.89; p=0.047) of reduced DFS at the multivariable analysis. Conclusion: patients with ypN2 disease after NAC showed acceptable oncological outcomes and this finding is true for patients with low burden of nodal disease assessed by LNR.

Factors Associated with Nodal Pathologic Complete Response Among Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: Results of CALGB 40601 (HER2+) and 40603 (Triple-Negative) (Alliance).

De-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) requires careful patient selection. We seek to determine predictors of nodal pathologic complete response (ypN0) among patients treated on CALGB 40601 or 40603, which tested NAC regimens in HER2+ and triple-negative breast cancer (TNBC), respectively. A total of 760 patients with stage II-III HER2+ or TNBC were analyzed. Those who had axillary surgery before NAC (N = 122), or who had missing pretreatment clinical nodal status (cN) (N = 58) or ypN status (N = 41) were excluded. The proportion of patients with ypN0 disease was estimated for those with and without breast pathologic complete response (pCR) according to pretreatment nodal status. In 539 patients, the overall ypN0 rate was 76.3% (411/539) to 93.2% (245/263) in patients with breast pCR and 60.1% (166/276) with residual breast disease (RD) (P < 0.0001). For patients who were cN0 pretreatment, the ypN0 rate was 88.8% (214/241), 96.3% (104/108) with breast pCR, and 82.7% (110/133) with RD. For patients who were cN1, 66.2% (157/237) converted to ypN0, 91.7% (111/121) with breast pCR and 39.7% (46/116) with RD. For patients who were cN2/3, 65.6% (40/61) converted to ypN0, 88.2% (30/34) with breast pCR and 37.0% (10/27) with RD. On multivariable analysis, only pretreatment clinical nodal status and breast pCR/RD were associated with ypN0 status (both P < 0.0001). Breast pCR and pretreatment nodal status are predictive of ypN0 axillary nodal involvement, with < 5% residual nodal disease among cN0 patients who experience breast pCR. These findings support the incorporation of axillary surgery de-escalation strategies into NAC trials.

Abstract PS4-32: Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer

Abstract Background: Expression of immune checkpoint receptors (ICR) on tumor infiltrating lymphocytes (TILSs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Expressions of ICRs were examined immunohistochemically by staining surgical specimen (n=61) using specific monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4. Positivity was defined staining &amp;gt;1% on TILs. Results: Median age was 49 (24-76) years. The majority patients were clinically T3-4 (n=31, 50.8%), and clinically N1-3 (n=58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas TILs associated positivites for PD1, PDL-1, LAG3 and TIM-3 were 62.3%, 50.9%, 26.2%, 68.9%. High expression of CTLA-4 was found to be associated with a better chemotherapy response (OR=7.94, 95%CI: 0.9-70.12, p=0.06), whereas TIM-3 positivity was contrarly associated with a worse chemotherapy response (OR=0.253, 95%CI: 0.066-0.974, p=0.047) as measured by MDACC Residual Cancer Burden Index. At a 47-month follow-up, patients with ypN0 disease (DFS; HR=0.31, 95% CI: 0.12-0.83, p=0.02 and DSS; HR=0.21, 95% CI:0.07-0.62, p=0.005) and CTLA-4 high expression on TILs (DFS; HR=0.38, 95% CI=0.17-0.85, p=0.019 and DSS; HR=0.34, 95% CI:0.15-0.78, p=0.01) were found to have improved survival. Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1 and TIM-3 were highly expressed in TNBC after NAC. Our results more favor an immuncheckpoint inhibitor therapy via CTLA-4 alone or in combination with other immune check point inhibitors against PDL-1 and/or TIM-3 in addition to NAC in advanced TNBC. Citation Format: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen. Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-32.

Abstract PS1-26: Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study

Abstract BACKGROUND: Omitting axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) in patients with locally advanced breast cancer (LABC) after neoadjuvant chemotherapy (NAC) is still controversial. In this study, we evaluated factors affecting local recurrence and outcome in patients with LABC, who underwent SLNB alone after NAC. METHODS: Between 2004 to 2018, 320 patients with clinically node-positive LABC who received NAC and underwent SLNB alone after negative axillary staging were analyzed. All patients had breast and/or regional nodal irradiation. RESULTS: Median age was 46 (23-70). Of those, 228 patients had ypN0 disease (71.25%), whereas 92 patients had ypN(+) disease including 19 (20.6%) isolated tumor cells (ITC), 33 micrometastasis (35.9%) and 40 macrometastases (43.5%). At a median follow-up of 37 months (24-172), one patient (0.3%) with macrometastatic SLN having extracapsular extension was found to have locoregional recurrence at the 60th month. Five-year disease-free survival (DFS) and disease specific survival (DSS) rates were found as 87% and 95%, respectively. Patients with cT3&amp;4 (HR=2.22, 95% CI; 1.07-4.62), non-luminal molecular pathology (HR=2.71, 95% CI, 1.23-5.97), and non-pCR in the breast (HR=2.21, 95% CI, 0.94-5.17) were found to have an increased HR compared to others in 5-year DFS. However, no significant differences could be found between patients ypN0, ypN-ITC&amp;micrometastasis and ypN-macrometastasis regarding 5-year DFS and DSS rates. CONCLUSIONS: ALND could be safely avoided in selected patients with LABC who underwent SLNB after NAC having cT1-2, luminal pathology, breast and/or nodal pCR or low volume nodal disease, as long as axillary radiotherapy is provided. Citation Format: Neslihan Cabioglu, Hasan Karanlık, Mahmut Muslumanoglu, Guldeniz Karadeniz Çakmak, Didem Can Trablus, Mustafa Tukenmez, Yeliz E. Ersoy, Cihan Uras, Baha Zengel, Selman Emiroğlu, Ayfer Kamalı Polat, Levent Yeniay, Enver Ozkurt, Halil Kara, Kamuran Ibis, Adnan Aydiner, Vahit Ozmen, Abdullah Igci. Sentinel lymph node biopsy alone in locally advanced breast cancer after neoadjuvant chemotherapy: Turkish multicentric neosenti-turk MF-18-02-study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-26.

Diagnostic Accuracy of Axillary Ultrasound for Prediction of Axillary Pathologic Response after Neoadjuvant Treatment in Breast Cancer.

Background: In the era of NAT, to accurately predict pathologic response is a great challenge, which might influence surgical approach for breast and axilla. Axillary staging via imaging methods as an adjunct have long been used with various reported accuracy rates. However, the role of preoperative axillary ultrasonography (AUS) in clinical N0 patients after NAT is still controversial. The primary goal of the present study was to evaluate the precision of preoperative AUS for identifying pathologic complete response (ypCR = ypT0, ypN0) after NAT. Methods: A single-institution, retrospective review of a prospectively maintained database was analyzed to identify breast cancer patients treated with NAT. Only those patients who underwent AUS and 18F-FDG-PET/CT before and after NAT with documentation of clinical and radiological response were incorporated for outcome analysis. Results: In 253 consecutive invasive breast cancer patients axillary ypN0 disease was achieved in 67.19%. In 11.23% ynon-pCR patients AUS failed to detect residual disease presence 80% of which were ITCs and micrometastases. Macrometastasis was present in 21.73% (55/253) of the cases 98.18% (54/55) of which was determined by AUS. Overall accuracy for axillary pCR was found to be 89.32% for AUS and 76.28 % for 18-FDG-PET/CT. The false negative rate (FNR) of AUS and 18-FDG-PET/CT was 12.04% and 15.59%, respectively. The PPV of AUS was higher in Luminal-like tumors (%87.69), whereas HER-2 positive (%100) and triple-negative (93.47%) subtypes had higher NPV. Conclusions: AUS is a beneficial tool with the potential of accurate prediction of pCR in more than 80% of patients following NAT. Nevertheless, in cases of residual ITCs and micrometastasis the accuracy of US should be interrogated cautiously.

Trastuzumab + FOLFOX6/FLOT as perioperative therapy for HER2-positive resectable gastric cancer and cardioesophageal transition: RussTrastPraсtik study (interim analysis)

Objective. The aim of this study was to evaluate the efficacy and safety of trastuzumab in combination with the FLOT/FOLFOX regimen in the perioperative treatment of resectable HER2-positive locally advanced gastric cancer. Methods. 15 patients were included in two groups; 4 patients were treated with trastuzumab (Herticad®, BIOCAD) + FLOT and 11 patients were treated with trastuzumab (Herticad®, BIOCAD) in combination with FOLFOX. The primary endpoint was incidence of disease stage reduction, tumor regression rate (TRG), change in HER2 tumor status, disease-free and overall survival. Results. Тrastuzumab in combination with FLOT/FOLFOX has a good therapeutic effect and a safety profile in the perioperative treatment of patients with resectable HER2-positive advanced gastric cancer (complete tumor regression [TRG1] was morphologically confirmed in 20% of patients, no pathomorphosis or minimal manifestations [TRG3/TRG4] in 40% of patients, in 40% of patients it was possible to achieve significant pathomorphological tumor regression [TRG2]). In addition, trastuzumab + FLOT gives better results in terms of tumor regression rate than FOLFOX + trastuzumab (cN+/ypN0 disease stage reduction in the T + FLOT group was 100%, whereas in the T + FOLFOX group it was only 30.0%). The HER2 status of the tumor changes against the background of preoperative PCT with the inclusion of trastuzumab (a loss of HER2/ neu protein overexpression was detected in 60% of patients).

P-208 Is there a role for adjuvant chemotherapy in ypN0 disease rectal cancer patients?

Several studies attempted to identify prognostic factors to predict long-term outcomes and support adjuvant chemotherapy (ACh) after neoadjuvant chemoradiation (NACRT) in rectal cancer. Currently, there is no definitive evidence that ACh is able to improve disease-free survival (DFS). We aimed to evaluate the impact of ACh in DFS in pathological node-negative (ypN0) rectal cancer patients.

Does Post Mastectomy Radiotherapy Reduce Loco-Regional Recurrence Rates in all Clinical Stages of Breast Cancer Following a Complete Pathological Response to Neoadjuvant Chemotherapy? A Systematic Review and Meta-Analysis of the Literature

The role of post-mastectomy radiotherapy (PMRT) has not been qualified in contemporary cohorts that have achieved complete pathological response (pCR) following neoadjuvant chemotherapy (NAC). This systematic review evaluated loco-regional recurrence (LRR) rates following PMRT for patients with pCR or pathologically lymph node negative disease (ypN0) after NAC. We identified seven papers that described LRR in 415 patients with pCR following NAC. Pooled analysis demonstrated clear benefit of PMRT on LRR (OR: 0.2 [95% CI: 0.06–0.58; p = 0.003]) and this was most pronounced in stage III/IV disease (OR: 0.12 [95% CI: 0.04–0.44; p = 0.0012]), as well as of benefit in ypN0 disease. PMRT appears to be effective in reducing LRR following pCR or ypN0 in advanced breast cancer but requires further investigation.

Predictive factors for omitting lymphadenectomy in patients with node-positive breast cancer treated with neo-adjuvant systemic therapy.

A pathologic complete response (pCR) in the axilla occurs in 30%-40% of patients with initially node-positive breast cancer after neo-adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node-positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy-proven node-positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki-67>30 (OR 1.98; 95% CI, 1.146-3.381), HER2 positivity (OR 2.6; 95% CI, 1.354-5.108), nonluminal molecular-like subtype (OR 4.15; 95% CI, 2.068-5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110-7.081). After a mean follow-up of 61months, distant disease-free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03-8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular-like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.

Safety and Efficacy of Neoadjuvant DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] Chemotherapy Regimen in Patients with Locally Advanced Gastric and Gastro-Esophageal Junction Cancers: A Single Center Experience from India

Background: The role of chemotherapy in Gastric Cancer is constantly evolving with various neoadjuvant and adjuvant strategies. Several chemotherapeutic agents are used in the treatment of locally advanced gastric cancer (LAGC) namely Platinum based compounds (Cisplatin, Oxaliplatin), Fluoropyrimidines like 5-Flurouracil [(5-FU), Capecitabine)], Taxanes (Docetaxel) and Anthracyclines (Epirubicin). Various doublet and triplet combination chemotherapy regimens have been used for neo-adjuvant chemotherapy (NACT) in LAGCs. In this study we evaluated the safety and efficacy of docetaxel based triplet regimen DOF [Docetaxel, Oxaliplatin, 5-Fluorouracil] in LAGC. Material and methods: 50 Newly diagnosed patients of Locally Advanced Gastric Cancer (stage II or III) deemed fit to receive chemotherapy were included in our study. After 3 cycles of neoadjuvant chemotherapy, patients were assessed based on radiological and pathological response. Results: 50 Patients were included in our study of which majority were male (32), median age at presentation was 55 years and 24 patients presented with a history of gastrointestinal reflux disease (GERD). The most common hematological toxicities observed in our study were anemia (61.2%), neutropenia (42.6%, febrile neutropenia constituted 6%) and thrombocytopenia (13.2%). The most common gastro-intestinal [GI] toxicities observed in our study included nausea (69.2%), vomiting (31.2%), diarrhea (34%), oral mucositis (14%) and constipation (6.6%). We found that safety profile of DOF regimen was favorable with majority of patients tolerating the regimen well. The Overall Response Rate (68%), Disease Control Rate (96%) and Resectability Rate (80%) were higher compared to western studies. Pathological CR (17.5%), ypN0 disease status (42.5%) and nodal down staging (52%), all showed positive correlations with survival outcomes. Conclusion: DOF regimen is an effective and feasible option for neoadjuvant treatment of LAGC in an Indian population.