Residual Nodal Disease Research Articles

Significance of Residual Nodal Disease in Clinically Node-Negative Breast Cancer After Neoadjuvant Chemotherapy.

Trials evaluating omission of axillary dissection (ALND) in patients with cN0 breast cancer with positive sentinel lymph nodes (SLNs) haveexcluded neoadjuvant chemotherapy (NACT). It remains unclear whether the data can be extrapolated to cN0 patients undergoing NACT. This study sought to identify factors associated with positive SLNs and additional disease on ALND in cT1-2N0 disease after NACT. The authors queried their database for cT1-2N0 patients treated with NACT followed by SLN biopsy from 1996 to 2022. Physical examination and ultrasound determined clinical nodal status. Multivariable logistic regression identified factors associated with positive SLNs and disease on ALND. Of 1930 patients, 234 (12.1%) had positive SLNs. Positive SLNs were predicted by hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) status (odds ratio [OR] 2.5; p < 0.0001), lobular histology (OR 1.8; p = 0.007), multifocality (OR 2; p = 0.001), grade 1 tumors (OR 2.5; p = 0.002), and cT2 category (OR 1.9; p = 0.004). Of the 234 patients with positive SLNs and known SLN metastasis size, 148 (63.2%) underwent ALND, and 39 (26.4%) had additional positive nodes. Increasing patient age predicted disease on ALND (OR 1.03; p = 0.02). No additional positive nodes on ALND were identified in patients with only isolated tumor cells compared with 12.3% who had micrometastases and 37.6% who had macrometastases (p = 0.01). During a 5-year median follow-up period of the SLN-positive patients, three (1.3%) experienced axillary recurrence and twoof the three underwent ALND at the initial surgerywith no additional positive nodes. In cT1-2N0 breast cancer, HR+/HER2- status, lobular histology, multifocality and cT2 category predicted positive SLNs after NACT. Older age predicted positive nodes on ALND. Patients with positive SLNs had low axillary recurrence rates. These findings support investigation into omission of ALND in cN0 breast cancer and a low volume of SLN disease after NACT.

Locally Advanced Childhood Nasopharyngeal Cancer: A Case Series

Nasopharyngeal carcinoma is a rare malignant tumor in childhood. To date, no consensus has been achieved concerning the recommendations for the management of childhood Nasopharyngeal carcinoma. Chemotherapy and radiotherapy are the main modalities in the management of nasopharyngeal carcinoma (NPC). Five cases (with an age range between 10 and 16 years), including one patient with stage III NPC and four patients with stage IV NPC, are reported in this study. All patients received four courses of induction chemotherapy followed by concurrent chemoradiation with cumulative irradiation, with a dose of 70 Gy in 33-37 fractions. Patients were treated with intensity modulated radiation therapy with simultaneous integrated boost technique using helical Tomotherapy. After two-year’s follow-up, four patients were achieved complete response, one patient showed residual disease in lymph nodes in the neck and bone metastases one year after the completion of treatment. Treatment side effects were well tolerated, there was no acute toxicity grade 3 or 4, and late toxicity consisted of chronic sinusitis, grade 1 xerostomia, and grade 1 skin fibrosis.

ASO Visual Abstract: Omission of Axillary Lymph Node Dissection in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy.

ASO Visual Abstract: Omission of Axillary Lymph Node Dissection in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy.

Differential prognostic value of residual nodal burden in breast cancer subtypes.

Residual cancer burden (RCB) index after neoadjuvant chemotherapy (NAC) is highly prognostic in patients with breast cancer (BC) but does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to precisely define the effect of RNB on survival by subtypes. Adult women with non-metastatic BC diagnosed from 2006 to 2021 in the National Cancer Database (NCDB) who received NAC followed by surgery within 8months were included. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival. 51,917 patients were included. After adjustment, ypN stage was the strongest predictor of mortality, with an odds ratio (OR) of 2.24 (95% CI 2.08-2.41) for ypN1 vs ypN0 and increased with increasing nodal burden-ypN2 vs ypN0 OR 5.03, 95% CI 4.60-5.51 and ypN3 vs ypN0 OR 8.85, 95% CI 7.88-9.93. Stratification of survival curves with higher RNB is most pronounced for triple-negative breast cancer (TNBC) with an absolute difference of 64% in 5-year overall survival between ypN0 and ypN3 patients, and lowest for the ER+/HER2- subtype with a 25% absolute difference in 5-year OS between ypN0 and ypN3 patients. On interaction analysis, ypN status was a stronger predictor of mortality for the TNBC subtype compared to other subtypes. RNB has a significantly different impact on survival by BC subtypes. Future study of optimal therapeutic strategies for patients with residual nodal disease after NAC should account for subtype-specific differences in prognosis.

Omission of Axillary Lymph Node Dissection in Patients with Residual Nodal Disease After Neoadjuvant Chemotherapy.

Axillary management after neoadjuvant chemotherapy (NAC) is evolving but axillary lymph node dissection (ALND) remains the standard of care for patients with residual nodal disease. The results of the Alliance A011202 trial evaluating the oncologic safety of ALND omission in this cohort are pending but we hypothesize that ALND omission is already increasing. The National Cancer Database was queried to identify patients diagnosed with cT1-3N1M0 breast cancer who underwent NAC and had residual nodal disease (ypN1mi-2) from 2012 to 2021. Temporal trends in omission of completion ALND were assessed annually. Multivariable logistic and Cox regression models were used to identify factors associated with ALND omission and overall survival (OS), respectively. A total of 6101 patients were included; the majority presented with cT2 disease (57%), with 69% HER2+, 23% triple-negative, and 8% hormone receptor-positive/HER2-. Overall, 34% underwent sentinel lymph node biopsy (SLNB) alone. Rates of ALND were the lowest in the last 4years of observation. After adjustment, treatment at community centers (vs. academic) and lower pathologic nodal burden were associated with omission of ALND. ALND omission was associated with a higher unadjusted OS (5-year OS: 86% SLNB alone vs. 84% ALND; log-rank p=0.03), however this association was not maintained after adjustment. Despite the impending release of the Alliance A011202 results, omission of ALND in patients with residual nodal disease after NAC is increasing. This practice appears more prominent in community centers and in patients with a lower burden of residual nodal disease. No association with OS was noted.

Differential Prognostic Value of Residual Nodal Burden in Breast Cancer Subtypes.

Residual cancer burden (RCB) index after neoadjuvant chemotherapy (NAC) is highly prognostic in patients with breast cancer (BC) but does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to precisely de ne the effect of RNB on survival by subtypes. Adult women with non-metastatic BC diagnosed from 2006-2021 in the National Cancer Database (NCDB) who received NAC followed by surgery within 8 months were included. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival. 51,917 patients were included. After adjustment, ypN stage was the strongest predictor of mortality, with an odds ratio (OR) of 2.24 (95% CI 2.08-2.41) for ypN1 vs ypN0 and increased with increasing nodal burden - ypN2 vs ypN0 OR 5.03, 95% CI 4.60-5.51 and ypN3 vs ypN0 OR 8.85, 95% CI 7.88-9.93. Stratification of survival curves with higher RNB is most pronounced for triple-negative breast cancer (TNBC) with an absolute difference of 64% in 5-year overall survival between ypN0 and ypN3 patients, and lowest for the ER+/HER2- subtype with a 25% absolute difference in 5-year OS between ypN0 and ypN3 patients. On interaction analysis, ypN status was a stronger predictor of mortality for the TNBC subtype compared to other subtypes. RNB has a significantly different impact on survival by BC subtypes. Future study of optimal therapeutic strategies for patients with residual nodal disease after NAC should account for subtype specific differences in prognosis.

Contemporary Axillary Surgical Management in Patients with Pathologically Node Positive Disease After Neoadjuvant Chemotherapy: A Survey of Members of the American Society of Breast Surgeons.

Axillary lymph node dissection (ALND) is increasingly omitted for breast cancer patients with pathologic nodal disease after neoadjuvant chemotherapy (NAC). This study aimed to understand when and why surgeons consider omitting ALND after NAC. The American Society of Breast Surgeons membership was surveyed, and responses were tabulated. To identify patterns, multiple correspondence analyses followed by cluster analysis on coordinates provided by the former were performed. Chi-squared analyses determined whether cluster characteristics were significantly (P < 0.05) associated with omission of ALND. Of members, 328/2172 (15.1%) completed the survey. Most (60.7%) always offer sentinel lymph node surgery to cN1 patients who respond to NAC, and many (43.9%) sometimes omit ALND in the setting of residual nodal disease. Respondents less often consider omitting ALND with increasing volume of pathologic nodal disease after NAC and are less likely to omit ALND among patients with cN1 disease at presentation than cN0 (P < 0.05 across all volumes). Respondents cited radiation administration (74.1%) and belief that ALND would not improve locoregional (48.2%), distant recurrence or survival (47.6%) outcomes when axillary radiation is administered as reasons to omit ALND. The respondent group comprising male private practice surgeons, practicing ≥ 21 years, consider omitting ALND significantly more frequently. Surgeons sometimes consider ALND omission for patients with pathologic nodal disease after NAC but are more likely to do so in cN0 patients and patients with smaller volumes of nodal disease. These decisions are largely based on perceived lack of oncologic benefit despite absence of prospective data supporting this deescalation.

Targeted axillary dissection reduces residual nodal disease in clinically node- positive breast cancer after neoadjuvant chemotherapy

BackgroundAny advantage of performing targeted axillary dissection (TAD) compared to sentinel lymph node (SLN) biopsy (SLNB) is under debate in clinically node-positive (cN+) patients diagnosed with breast cancer. Our objective was to assess the feasibility of the removal of the clipped node (RCN) with TAD or without imaging-guided localisation by SLNB to reduce the residual axillary disease in completion axillary lymph node dissection (cALND) in cN+ breast cancer.MethodsA combined analysis of two prospective cohorts, including 253 patients who underwent SLNB with/without TAD and with/without ALND following NAC, was performed. Finally, 222 patients (cT1-3N1/ycN0M0) with a clipped lymph node that was radiologically visible were analyzed.ResultsOverall, the clipped node was successfully identified in 246 patients (97.2%) by imaging. Of 222 patients, the clipped lymph nodes were non-SLNs in 44 patients (19.8%). Of patients in cohort B (n=129) with TAD, the clipped node was successfully removed by preoperative image-guided localisation, or the clipped lymph node was removed as the SLN as detected on preoperative SPECT-CT. Among patients with ypSLN(+) (n=109), no significant difference was found in non-SLN positivity at cALND between patients with TAD and RCN (41.7% vs. 46.9%, p=0.581). In the subgroup with TAD with axillary lymph node dissection (ALND; n=60), however, patients with a lymph node (LN) ratio (LNR) less than 50% and one metastatic LN in the TAD specimen were found to have significantly decreased non-SLN positivity compared to others (27.6% vs. 54.8%, p=0.032, and 22.2% vs. 50%, p=0.046).ConclusionsTAD by imaging-guided localisation is feasible with excellent identification rates of the clipped node. This approach has also been found to reduce the additional non-SLN positivity rate to encourage omitting ALND in patients with a low metastatic burden undergoing TAD.

Neoadjuvant chemotherapy with bevacizumab for locally advanced vulvar cancer

ObjectivesExternal beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects....

Real world outcomes of 2,339 patients with early-stage triple-negative breast cancer (TNBC) treated in British Columbia.

e23274 Background: TNBC represents 15-20% of all breast cancers, and tends to exhibit more aggressive features, more frequent distant metastasis and overall worse prognosis than other breast cancer subtypes. The treatment landscape for early-stage TNBC has changed considerably in the last decade, with new additions to neoadjuvant therapy (NAT) aimed at improving pathologic responses and outcomes. In this study, we assess real world data regarding treatment and outcomes in those with early-stage TNBC. Methods: The BC Cancer Breast Cancer Outcomes Unit database contains prospectively collected data on patients residing in British Columbia and diagnosed with breast cancer since 1989. This retrospective study evaluated patients diagnosed with stage I-III TNBC from 2010 to 2019. During this era, regimens containing anthracyclines and taxanes were routinely used. TNBC was defined as per ASCO-CAP guidelines as ER≤1%, PR≤1% and negative HER 2 (0, 1+ by immunohistochemistry, or 2+ ISH negative). Outcomes of interest included event free survival (EFS), overall survival (OS), and pathologic complete response (pCR). Results: 2,339 patients withstage I-III TNBC were identified with a mean follow up of 6.5 years. OS was 87% (95% CI 85-88%) at 3-years and 79% (95% CI 77-80%) at 5-years. The presenting stage was a significant prognostic factor, with 5-year EFS of 89%, 81% and 51%- and 5-year OS of 90%, 80%, and 53% for stages I, II, and III, respectively. There was an increase in NAT use in 2019 (n = 82/230,35.7%) when compared to 2010 (n = 20/227, 8.8%). The most common neoadjuvant regimens used included anthracycline and taxane chemotherapies (n = 343,81.4%), with only a small number receiving neoadjuvant platinum chemotherapy (n = 52, 12.4%). Pathological complete response (pCR) was achieved in 24.5% (103/421) of patients who received NAT. Patients with pCR had improved 5- year EFS (91% vs. 57%, HR 0.26 [95% CI 0.15-0.45]) and 5-year OS (90% vs. 59%, HR 0.26 [95% CI 0.15-0.45]) compared to those with residual disease. The subgroup that received salvage capecitabine had a poor 3-year EFS at 22% but was enriched for patients with residual nodal disease after NAT (n = 77/130, 59.2%). Conclusions: This real-world study of TNBC in the era prior to routine immunotherapy (IO), highlights the poor prognosis of TNBC, particularly patients with locally advanced disease and those who did not achieve pCR, despite adjuvant capecitabine. This stresses the need for advances in NAT and salvage therapies for TNBC with residual disease at high risk of recurrence. [Table: see text]

Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (OPBC-03/SAKK 23/16/IBCSG 57-18/ABCSG-53/GBG-101-TAXIS).

TPS611 Background: Axillary lymph node dissection (ALND) is standard of care for most patients with clinically node-positive breast cancer (cN+BC), either in the adjuvant setting or in case of residual nodal disease after neoadjuvant chemotherapy (NACT). At least one quarter of patients with breast cancer experience long term morbidity after ALND. The TAXIS trial was designed to investigate if axillary radiotherapy (ART) can replace ALND in patients with cN+ BC who underwent tailored axillary surgery (TAS), which is recognized as one of the most important uncertainties and controversies in axillary management of patients with breast cancer. Methods: To test the remaining indications for ALND in clinical practice, we designed the international, multicenter, phase-III, non-inferiority, randomized controlled TAXIS trial to be pragmatic (average PRECIS-2 score of 4.44). Accordingly, most study domains follow usual care conditions, including eligibility (following routine indications for ALND in clinical practice), surgical skills and techniques, and follow up. The radiation oncology protocol included detailed recommendations and an extensive quality assurance program, which was developed to address the limitations of prior landmark trials and increase acceptability among recruiters. The main objective of the trial is to demonstrate that treatment with TAS and ART is non-inferior to TAS and ALND in terms of disease-free survival (DFS) of patients with cN+ BC detected by imaging or palpation in the upfront surgery setting or in case of residual disease after NACT. Randomization at a 1:1 ratio is mainly performed intraoperatively to either use TAS followed by ALND and regional nodal irradiation excluding the dissected axilla as a target volume (arm A) or to use TAS followed by regional nodal irradiation including the full axilla (arm B). The sample size is based on the primary endpoint DFS. With a type I error of 5% and a power of 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm). The sample size was calculated to be 1500 patients (750 per arm). Enrolment started in July 2018 and will stop after reaching 1500 patients, which is expected to be completed by Q4/2025. With currently 51 active sites from Europe, Canada and Korea within the network of the Oncoplastic Breast Consortium (OPBC), &gt;950 patients were randomized by January 2024. Another 14 sites in Europe, USA, and South America will join the trial in 2024. The interim analysis (after 20% of the required events) is expected for Q4/2024 and will be reviewed by the IDMC. The primary endpoint analysis is planned in Q4/2030. Clinical trial information: NCT03513614 .

Abstract ED05-01: Demystifying the Axilla: Challenging scenarios in the upfront surgery setting and after NAC

Abstract Management of the axilla has evolved significantly over time, with a trend toward less extensive axillary surgery. While historically, all patients underwent axillary lymph node dissection (ALND) due to the Halstedian belief that ALND was essential for the cure of breast cancer, advances in systemic therapy, radiotherapy, and understanding of tumor biology have resulted in the abandonment of ALND for a large proportion of patients having upfront surgery with limited nodal disease, and in those with no residual nodal disease after neoadjuvant systemic therapy. Over time, axillary management has become increasingly complicated, with significant variability in real-world management for different clinical scenarios. In this talk, we will address challenging scenarios in axillary management, both in the upfront surgery setting and after neoadjuvant chemotherapy (NAC). In the upfront surgery setting, we will address management of a positive sentinel node in patients treated with mastectomy, management of ≥ 3 positive sentinel nodes after lumpectomy or mastectomy, and the use of sentinel lymph node biopsy for patients with clinically node-positive hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer. In the setting of patients receiving NAC, we will discuss the optimal approach to the axilla in patients with residual disease after NAC, and in those with locally advanced breast cancer. As we move away from ALND in low-risk scenarios where data from randomized and prospective trials have demonstrated oncologic safety, we await results from ongoing clinical trials to provide us with high-level evidence regarding the safety of omission of ALND in high-risk patients with more extensive nodal disease. Citation Format: A. Barrio. Demystifying the Axilla: Challenging scenarios in the upfront surgery setting and after NAC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr ED05-01.

Abstract PO4-02-10: Predictive Factors of Nodal Upstaging at Time of Surgery in Clinically Node Negative Patients Undergoing Neoadjuvant Chemotherapy

Abstract Introduction: Neoadjuvant chemotherapy (NAC) can be given with the intent of downstaging breast cancer or to provide prognostic information prior to any surgical intervention in both node negative (N0) and node positive patients (pts). Residual nodal disease following neoadjuvant chemotherapy generally indicates poorer overall prognosis relative to those who are node negative. Several risk factors have been postulated to predict the presence of occult lymph node metastasis: age at diagnosis, tumor size, status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor (HER-2), and BMI. NAC has been shown to eradicate axillary lymph node metastasis in up to 40% of pts. This study aims to evaluate characteristics of clinically N0 pts who underwent NAC and were upstaged to node positive status at the time of surgery. We hope to identify patient related factors that may help predict the presence of occult nodal disease as well compare pathological complete response rate (PCR) in the breast between N0 and patients who were upstaged. Methods: Data was collected through retrospective chart review of the Stroger Cook County electronic medical records system (CERNER). Pts treated at John H. Stroger Hospital from 2017-2021 with a new diagnosis of cT2-T3 invasive breast cancer who were clinically and radiologically node negative and received NAC were included. We compared demographic data, staging information, cancer characteristics and pathologic complete response rates (PCR) in the breast between those who remained node negative and those who had positive sentinel lymph nodes at the time of surgery. Pts with prior breast cancer diagnosis and those who underwent treatments at an outside institution were excluded. Statistical analysis included 2-tailed t-test and 2-tailed fisher’s (p&amp;lt; 0.05). Results: A total of 98 pts were identified, 62 with complete data for analysis,11 were upstaged at the time of surgery. When comparing pts who had nodal upstaging to those that remained node negative at time of surgery there was no significant difference between average BMI (28.5), age of diagnosis (58 years). Most pts (73%) were T2 at presentation, of those with nodal upstaging at time of surgery, 20% were T3 or higher, while only 5% of those who were not upstaged at surgery were greater than T3 (NS). Upstaged pts had an average tumor size of 4.16 cm while non-upstaged on average were 2.85 cm (P&amp;lt; 0.01). ER positive pts (ER+) and PR positive (PR+) were more likely to have nodal upstaging post op (P&amp;lt; 0.0012, P&amp;lt; 0.0013) when compared to ER negative (ER-) and PR negative (PR-) respectively. The distribution of receptor status was significantly different between groups, the most common receptor status in upstaged patients was triple positive (63%) while triple negative was most common in non-upstaged (41%). Triple positive pts were more likely to be upstaged than those with other receptor statuses (64% vs 40%, p 0.0004). There was a 100% PCR rate in the breast among non-upstaged pts compared to 10% of upstaged patients (P&amp;lt; 0.0001). Among all triple negative pts, 42% had PCR, of ER-/PR-/HER2+, 60% had a PCR, ER+/HER 2 negative had a 40% PCR. Conclusion: Pts with larger presenting tumor size who are node negative at presentation and have undergone chemotherapy are more likely to have occult positive nodes at the time of surgery. ER positive pts and triple positive pts are also more likely to have occult positive nodes at time of surgery. While our sample is small, our breast PCR rate is consistent with other published literature. Further investigation confirming this with larger samples and multi-institutional investigation may help to establish these relationships and elucidate a predictive model. The optimal management of these patients is worthy of further study. Citation Format: Rangel Melissa, Julia Alexieva, Alison Coogan, Elizabeth Marcus, Julie Wecsler. Predictive Factors of Nodal Upstaging at Time of Surgery in Clinically Node Negative Patients Undergoing Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-10.

Abstract PO3-18-11: A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

Abstract Background: Patients with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than patients who have a pathologic complete response (pCR). Escalation of therapy in patients with RD using post-neoadjuvant T-DM1 has become the new standard of care, leading to improved invasive disease-free survival (iDFS), but patients with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes, and central nervous system recurrences are a challenge. More effective treatment strategies are urgently needed. Alliance A011801 (CompassHER2 RD) is an escalation trial for patients with high-risk HER2+ RD after neoadjuvant systemic therapy, evaluating the addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to post-neoadjuvant T-DM1. Methods: Eligibility and Intervention: Patients with high-risk HER2+ RD (i.e., ER-, node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 + placebo, vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of paclitaxel and trastuzumab +/- pertuzumab. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (~15-30% will be participants in the CompassHER2 pCR de-escalation companion trial [NCT04266249]; these patients must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801). Patients who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is improved with addition of tucatinib to T-DM1 in patients with HER2+ EBC with RD after neoadjuvant systemic therapy; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in patients with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints are also being evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-), and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% &amp; 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 patients; activation and estimated completion dates are 01/6/21 and ~ 01/2028. Accrual as of 7/10/2023: 438 patients. Support: U10CA180821, U10CA180882; Seagen Inc; https://acknowledgments.alliancefound.org. ClinicalTrials.gov Identifier: NCT04457596 Citation Format: Ciara O'Sullivan, Karla Ballman, Linda McCall, Tyler Zemla, Anna Weiss, Melissa Mitchell, Victoria Blinder, Nadine Tung, William Irvin, Myounghee Lee, Sailaja Kamaraju, Matthew Goetz, W. Fraser Symmans, Virginia Borges, Ian Krop, Ann Partridge, Lisa Carey. A011801 (CompassHER2 RD): Postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-18-11.

Abstract PO2-23-05: Practice patterns and outcomes in the ongoing neoadjuvant ATNEC trial: node marking, response to NACT and breast conservation rates

Abstract Background In ATNEC trial, cT1-3N1M0 patients receive NACT followed by SNB/TAD. If the sentinel nodes(SNs) have converted to benign(ypN0), patients are randomly assigned to Axillary Treatment vs no Axillary Treatment. The study promotes standardized node marking procedures and includes a radiotherapy quality assurance program. Objectives – This study prospectively evaluates practice patterns, NACT response, adoption of node marking, rates of marked node identification, and breast conservation rates in the ongoing ATNEC trial across 70 centers in the UK. The trial aims to recruit 1900 patients. Materials and Methods Data from 196 randomized patients (median age: 54 [range: 28-79] years; median BMI: 26.5 [range: 17.6-51.1]) from December 2021 to June 28, 2023, across 70 UK centers were analyzed. These patients presented with cT1-3N1M0 breast cancer, received NACT, and exhibited no residual nodal disease (ypN0) on SNB/TAD. Results Among the randomised patients 54%(106) were post-menopausal, 71%(140) underwent breast conserving surgery(BCS) and 29%(56) mastectomy. At presentation, 12% (23) had T3, 63% (124) had T2, and 23% (46) had T1 tumors. Grade 3 tumors accounted for 70% (138) of cases. Among the patients, 60% (117) were HER2 positive, 31% (61) were triple negative, and 9% (18) were HER2 negative (ER or PgR positive). Anthracycline and taxane-based NACT were administered to 57% (106), while 38% (71) received a platinum-containing regimen. During SNB/TAD, a median of 4 nodes (interquartile range, 3-5) were removed. Among 184 patients with node marking data, 74% (136) had the involved node marked. The marked node was successfully removed in 94% (128) of these patients. Clip/coil only, Magseed and black dye were the commonest techniques used for node marking. The marked node was the sentinel node in 83% (106) of cases. Among 185 randomized patients with post-NACT response data, 68% (125) achieved a complete pathological response (pCR) in the breast, while 8% (15) had DCIS only and 22% (41) had invasive cancer. Among 105 patients with complete breast tumor response on imaging, 15% (16) had residual DCIS or invasive cancer. In the subset of patients with partial response or stable breast tumors on imaging (69 patients), 46% (32) had no residual tumor on histology (ypT0). Furthermore, 14% (26) exhibited partial or stable disease in the axilla on imaging but achieved complete pathological response on histology. Conclusions HER2-positive and triple-negative breast cancer cases predominate among patients undergoing NACT in the UK. Although 68% achieved a complete pCR (ypT0) in the breast, rates of BCS remain low. Notably, around 75% of randomized patients underwent node marking, with an intra-operative identification rate of 94%, demonstrating the successful implementation of node marking in the UK through the ATNEC trial. Citation Format: Amit Goyal, Andrea Marshall, Sophie Nicholls, Natalie Hammonds, Beatrix Elsberger, Duncan Wheatley, Janice Rose, Helen-Teresa Edwards, Abeer Shaaban, Roeum Butt, Gareth Jackson, Tara Homer, Luke Vale, Samreen Ahmed, Shama Puri, Sophie Gasson, Julie Bruce, Helen Higgins, Janet Dunn. Practice patterns and outcomes in the ongoing neoadjuvant ATNEC trial: node marking, response to NACT and breast conservation rates [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-05.

Neoadjuvant chemotherapy for breast cancer: Pathologic response rates but not tumor size, has an independent prognostic impact on survival.

We investigated the pathologic complete response rates (pCR) and survival outcomes of early breast cancer patients who underwent neoadjuvant chemotherapy (NAC) over 14 years at a French comprehensive cancer center and reported pCR and survival outcomes by tumor subtypes and size. From January 2005 to December 2018, 1150 patients receiving NAC were identified. Correlations between cT stage, breast tumor response, axillary lymph node response, pCR, surgery, and outcomes were assessed. pCR was defined as (ypT0/ypTis) and (ypN0/pN0sn). A pCR was reached in 31.7% (365/1150) of patients and was strongly associated with tumor subtypes, but not with tumor size (pretreatment cT category). Luminal-B Her2-negative and triple-negative (TN) subtypes, cN1 status, older age, and no-pCR had an independent negative prognostic value. Overall survival (OS), relapse-free survival (RFS), and metastasis-free survival (MFS) were not significantly different for cT0-1 compared to cT2 stages. In Cox-model adjusted on in-breast pCR and pN status, ypN1 had a strong negative impact (OS, RFS, and MFS: HR = 3.153, 4.677, and 6.133, respectively), higher than no in-breast pCR (HR = 2.369, 2.252, and 2.323). A negative impact of no pCR on OS was observed for cN0 patients and TN tumors (HR = 4.972) or HER2-positive tumors (HR = 11.706), as well as in Luminal-B Her2-negative tumors on MFS (HR = 2.223) and for Luminal-A on RFS (HR = 4.465) and MFS (HR = 4.185). Achievement of pCR, but not tumor size (pretreatment cT category), has an independent prognostic impact on survival. These results suggest potential NAC benefits in patients with small tumors (<2 cm), even in absence of clinically suspicious lymph nodes. Residual lymph node disease after NAC is the most powerful adverse prognostic factor.

Oncologic Outcome of Patients With Pathologic T0 Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

To investigate the oncologic outcomes of patients with esophageal squamous cell carcinoma (ESCC) who have achieved a pathologic complete response (pCR) of the primary tumor (ypT0) after neoadjuvant chemoradiotherapy (NCRT). Patients with thoracic ESCC who underwent scheduled NCRT followed by surgery at our hospital between January 2010 and December 2022 were retrospectively analyzed. Only patients with ypT0 disease were enrolled in this study. A total of 118 patients were ultimately enrolled in this study. Ninety-two patients achieved pCR in the primary tumor and lymph nodes (ypT0N0), while 26 patients had residual metastatic disease in 52 lymph nodes (ypT0N+). Forty-five of the 52 lymph nodes with residual tumors were abdominal lymph nodes. Positive lymph nodes were more often observed in patients with tumors located in the lower third of the esophagus. The 1-, 3-, and 5-year overall survival (OS) rates for the entire study group were 96.5%, 79.5%, and 77.1%, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 90.5%, 76.8%, and 69.0%, respectively. According to multivariate analyses, pN classification was an independent predictor of both OS and DFS (P < 0.05), while sex and cT classification were also found to be independent prognostic factors for DFS (P < 0.05). Residual nodal metastatic disease in patients with ypT0 ESCC after NCRT was more often found in the abdominal lymph nodes. pN classification was an independent predictor of both OS and DFS for ypT0 ESCC patients after NCRT.

Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

Assessment of the impact of residual tumors at different sites post-neoadjuvant chemotherapy on prognosis in breast cancer patients and development of a disease-free survival prediction model.

Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer patients predicts worse outcomes than pathological complete response. Differing prognostic impacts based on the anatomical site of residual tumors are not well studied. The study aims to assess disease-free survival (DFS) in breast cancer patients with different residual tumor sites following NAC and to develop a nomogram for predicting 1- to 3-year DFS in these patients. A retrospective cohort study. Retrospective analysis of 953 lymph node-positive breast cancer patients with residual disease post-NAC. Patients were categorized into three groups: residual disease in breast (RDB), residual disease in lymph nodes (RDN), and residual disease in both (RDBN). DFS compared among groups. Patients were divided into a training set and a validation set in a 7:3 ratio. Prognostic factors for DFS were analyzed to develop a nomogram prediction model. RDB patients had superior 3-year DFS of 94.6% versus 85.2% for RDN and 81.8% for RDBN (p < 0.0001). Clinical T stage, N stage, molecular subtype, and postoperative pN stage were independently associated with DFS on both univariate and multivariate analyses. Nomogram integrating clinical tumor-node-metastasis (TNM) stage, molecular subtype, pathological response demonstrated good discrimination (C-index 0.748 training, 0.796 validation cohort), and calibration. The location of residual disease has prognostic implications, with nodal residuals predicting poorer DFS. The validated nomogram enables personalized DFS prediction to guide treatment decisions.