Node-negative Disease Research Articles

Indocyanine Green Marking of Axillary Sentinel Lymph Nodes in Early Breast Cancer

AbstractAxillary sentinel lymph node excision (SLNE) in breast cancer patients with clinically node-negative disease may be carried out using different tracers. The standard tracer is technetium colloid (99mTc). Indocyanine green (ICG) can be used as an alternative. This study aimed to evaluate the clinical usefulness of this fluorescent dye in a standardized setting.A prospective, single-center cohort study carried out at the University Gynecological Hospital of Rostock from September 2023 to May 2024 carried out sentinel lymph node marking using only ICG in patients with breast malignancies. The ICG injection was administered immediately after the induction of anesthesia. Detection of the sentinel lymph node (SLN) was done using a laparoscopy system suitable for ICG. The aim was to determine the detection rate (DR) for SLNs marked exclusively using ICG and to record any complications. The costs of using ICG to mark SLNs were compared with those for 99mTc marking.During the study period, contraindications against marking with ICG were ascertained for five (3.8%) of 132 patients with planned SLNE. A total of 100 SLNEs were carried out after ICG marking in patients who met the inclusion criteria in the context of the study. A median of two SLNs were resected. The detection rate (DR) for SLNs was 98.0%. SLNs were identified in all obese patients. No serious systemic side effects occurred following ICG injection. Transient skin discoloration in the area around the injection site were observed in eight patients. The direct cost of ICG marking was 62.73 Euros, which was 170.36 Euros lower than the cost of 99mTc marking.The detection rate of axillary SLNs marked using ICG is high and the method is cost-effective, has few side effects and can also be used in obese patients. Contraindications against the administration of ICG are rare. Marking with ICG is a good alternative to the 99mTc method and offers advantages in terms of costs, logistics, no exposure to radiation, and patient comfort.

The prevalence of non-sentinel lymph node metastasis among breast cancer patients with sentinel lymph node involvement and its impact on clinical decision-making: a single-centred retrospective study.

Sentinel lymph node biopsy (SLNB) has become standard procedure for early breast cancer patients with clinically node negative disease. The patients with SLN metastasis normally underwent axillary lymph node dissection (ALND). However, the metastatic status of non-sentinel Lymph nodes (non-SLNs) varied significantly in different reports. Here, we evaluated the prevalence of non-SLNs metastasis among breast cancer patients with sentinel lymph node metastasis and its impact on clinical decision-making. We identified 892 female patients with operable cT1-3N0 invasive breast cancer who underwent ALND in our center due to SLN metastasis from 2017 to 2023, retrospectively. The prevalence of non-SLN metastasis among different clinicopathological traits and its correlation with the number of positive SLNs were analyzed. The optimal clinical decision-making was generalized. The median number of SLN+, SLN, non-SLN+ and non-SLN was 2, 4, 1 and 14 among the enrolled 892 female patients, respectively. 504 (56.50%) patients with SLN + had at least one metastatic lymph node in the harvested non-SLNs. Among the enrolled 892 female patients, 435 (48.77%) patients with 1 positive SLN, of which 180 (41.38%) had at least one additional metastatic non-SLNs. 242 (27.13%) patients with 2 positive SLNs, of which 146 (60.33%) had at least one metastatic non-SLNs. For the rest 215 (24.10%) patients with at least 3 metastatic SLNs, 178 (82.79%) had at least one metastatic non-SLNs. In the univariate analysis, the non-SLNs metastatic status was correlated with the number of SLNs+, tumor size, tumor grade, lymphovascular invasion (LVI) and molecular subtypes, but not histopathologic type. In the multivariate analysis, the risk of additional non-SLNs metastasis correlated with the number of SLNs+, SLNs, non-SLNs and LVI. Omiting ALND in patients with higher non-SLNs + rate outside the American College of Surgeons Oncology Group (ACSOG) Z0011 and the European Organization for Research and Treatment of Cancer (EORTC) 10,981-22023 AMAROS criteria should be considered with caution in clinical decision-making. To evaluate whether axillary radiotherapy and ALND provides equivalent regional control in breast cancer patients with obvious residual metastatic lymph nodes undesected in the axilla, a well-matched prospective randomized controlled trial is an urgent need.

Recent Noteworthy Studies in Thoracic Oncology.

In this paper, we review recent prospective surgical studies on resectable esophageal and lung cancer. A narrative literature review was performed using the terms 'resectable esophageal cancer' and 'multimodal therapy' and 'resectable non-small cell lung cancer'. Prospective surgical trials performed from 2010 to 2023 were identified and analyzed. gov was queried for ongoing studies. The studies on esophageal cancer demonstrate the benefits of neoadjuvant chemoradiation, compared with surgery alone, and the emerging role of immunotherapy as part of induction and adjuvant treatment protocols. The selected studies on lung cancer demonstrate the evolving role of sublobar resection for patients with peripheral node-negative clinical stage IA1 disease and the developing role of neoadjuvant and adjuvant immunotherapy for patients with stage II-IIIA disease. The methods of treating patients with resectable esophageal or lung cancer are changing. Efforts to limit patient morbidity and optimize tumor treatment before surgery are increasingly being pursued and these approaches will likely continue to evolve as tumor biology and long-term pharmacologic mechanisms of action become clearer. Personalized medicine strategies that are based on tumor characteristics and the host genetic profile remain on the horizon, not yet ready for adoption in routine clinical practice.

Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium.

The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.

Reductions in recurrence in women with early breast cancer entering clinical trials between 1990 and 2009: a pooled analysis of 155 746 women in 151 trials

Distant recurrence in women with oestrogen receptor-positive early breast cancer persists at a constant rate for more than 20 years after diagnosis, with little equivalent data for oestrogen receptor-negative breast cancer. Using the database of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) we investigated rates of distant breast-cancer recurrence in oestrogen receptor-positive and oestrogen receptor-negative tumours and trends in outcomes over time. In this pooled analysis of randomised controlled trial data, patients in the EBCTCG database of more than 650 000 women in trials of treatment for early-stage breast cancer were screened for eligibility. Women were eligible if they were enrolled between 1990 and 2009 and newly diagnosed with oestrogen receptor-positive breast cancer and scheduled for at least 5 years of endocrine therapy, or oestrogen receptor-negative disease, and if they were younger than 75 years at diagnosis, had a tumour diameter of 50 mm or less, and fewer than ten positive axillary lymph nodes, and no evidence of distant metastases at entry. Trial of neoadjuvant therapy, or those in which adjuvant therapy was unclear, and women with oestrogen receptor-negative, progesterone receptor-positive disease, or those for whom outcome or baseline data were missing were excluded. The primary outcome was time to first distant recurrence as defined by each trial, ignoring any locoregional recurrence or contralateral breast cancer. 10-year risks of distant recurrence by period of diagnosis were compared using Cox regression adjusted for patient and tumour characteristics, trial, and assigned treatment. Of the 652 258 women with early breast cancer in the EBCTCG database on Jan 17, 2023, patient-level data were available from 151 randomised trials that included 155 746 women. Rates of distant tumour recurrence improved similarly in women with oestrogen receptor-positive and oestrogen receptor-negative tumours. 80·5% of the improvement for oestrogen receptor-positive disease and 89·8% of the improvement for eostrogen receptor-negative disease was explained by changes in patient and tumour characteristics and improved treatments, but remained significant (p<0·0001). More recently diagnosed patients were more likely to have node-negative disease. 10-year distant recurrence risks during 1990-99 versus 2000-09 were as follows: for node-negative disease, 10·1% versus 7·3% for oestrogen receptor-positive disease and 18·3% versus 11·9% for oestrogen receptor-negative disease; for disease with one to three positive nodes, 19·9% versus 14·7% for oestrogen receptor-positive disease and 31·9% versus 22·1% for oestrogen receptor-negative disease; and for disease with four to nine positive nodes, 39·6% versus 28·5% for oestrogen receptor-positive disease and 47·8% versus 36·5% for oestrogen receptor-negative disease. After adjustment for therapy, rates were reduced by 25% (oestrogen receptor-positive disease) and 19% (oestrogen receptor-negative disease) after 2000 versus the 1990s, with similar improvements observed in oestrogen receptor-positive disease beyond 5 years. Most of the improvement in trial outcomes is explained by a greater proportion of women with lower-risk disease entering trials and improved adjuvant treatment. After adjustment, women diagnosed since 2000 have about a fifth lower rate of distant recurrence than the 1990s. Long-term risks of distant recurrence for oestrogen receptor-positive disease remain, but are about a tenth lower now than in our previous report. Cancer Research UK, UK Medical Research Council.

Impact of Adjuvant Chemotherapy on Resected Intraductal Papillary Mucinous Neoplasm-Derived Pancreatic Cancer: Results From an International Multicenter Study.

The benefit of adjuvant therapy for intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) remains unclear because of severely limited evidence. Although biologically distinct entities, adjuvant therapy practices for IPMN-derived PDAC are largely founded on pancreatic intraepithelial neoplasia-derived PDAC. We aimed to evaluate the role of adjuvant chemotherapy in IPMN-derived PDAC. This international multicenter retrospective cohort study (2005-2018) was conceived at the Verona Evidence-Based Medicine meeting. Cox regressions were performed to identify risk-adjusted hazard ratios (HR) associated with overall survival (OS). Kaplan-Meier curves and log-rank tests were employed for survival analysis. Logistic regression was performed to identify factors motivating adjuvant chemotherapy administration. A decision tree was proposed and categorized patients into overtreated, undertreated, and optimally treated cohorts. In 1,031 patients from 16 centers, nodal disease (HR, 2.88, P < .001) and elevated (≥37 to <200 µ/mL, HR, 1.44, P = .006) or markedly elevated (≥200 µ/mL, HR, 2.53, P < .001) carbohydrate antigen 19-9 (CA19-9) were associated with worse OS. Node-positive patients with elevated CA19-9 had an associated 34.4-month improvement in median OS (P = .047) after adjuvant chemotherapy while those with positive nodes and markedly elevated CA19-9 had an associated 12.6-month survival benefit (P < .001). Node-negative patients, regardless of CA19-9, did not have an associated benefit from adjuvant chemotherapy (all P > .05). Based on this model, we observed undertreatment in 18.1% and overtreatment in 61.2% of patients. Factors associated with chemotherapy administration included younger age, R1-margin, poorer differentiation, and nodal disease. Almost half of patients with resected IPMN-derived PDAC may be overtreated or undertreated. In patients with node-negative disease or normal CA19-9, adjuvant chemotherapy is not associated with a survival benefit, whereas those with node-positive disease and elevated CA19-9 have an associated benefit from adjuvant chemotherapy. A decision tree was proposed. Randomized controlled trials are needed for validation.

Prognosis of isolated tumor cells and use of molecular classification in early stage endometrioid endometrial cancer

ObjectiveWe assessed the prognosis and molecular subtypes of early stage endometrioid endometrial cancer with isolated tumor cells within sentinel lymph nodes (SLNs) compared with node negative disease.MethodsPatients diagnosed with stage...

382. NUMBER OF LYMPH NODES RESECTED IS ASSOCIATED WITH OVERALL SURVIVAL IN PATHOLOGICALLY NODE-NEGATIVE ESOPHAGEAL CANCER

Abstract Background Lymphadenectomy is a key part of curative resection of esophageal cancer, with multiple quality assurance systems suggesting a minimum of 15 lymph nodes should be resected and subjected to pathological examination. Nevertheless, whether the absolute number of nodes resected is a surrogate marker for quality in surgery and staging, or has therapeutic benefit is debated. The aim of this study was to determine the impact of lymphadenectomy on survival in patients with resected pathologically node-negative disease (both treated and untreated with neoadjuvant therapy). Methods A review of our institutional prospectively maintained database was conducted from 2010-2020 inclusive. Inclusion criteria were patients undergoing esophagectomy for esophageal cancer aged 18+ who consented to data inclusion. Exclusion criteria were patients undergoing resection for benign disease, patients with Siewert III tumours undergoing gastrectomy or extended total gastrectomy, patients undergoing re-operative surgery, or patients where final pathology was not available. Univariable and multivariable analyses were performed as appropriate. Results 195 patients (49%) had pathologically node negative disease, with median lymph node count of 25. 47% of patients were clinically node positive, but pathologically node negative following neoadjuvant therapy. On univariable survival analysis, number of nodes resected was a significant predictor of overall survival (HR 0.96, 0.93-0.98, p=0.001). On multivariable analysis, R status (HR 4.9, 1.2-21.1, p=0.03), number of nodes resected (HR 0.97, 0.94-0.99, p=0.02) and prior cN+ status (HR 2.28, 1.16-4.49, p=0.02) were predictors of overall survival. Patients with cN0, (y)pN0 disease had improved overall survival compared with cN+, (y)pN0 (median not reached vs 43.4 months, p=0.04). Conclusion Lymphadenectomy is a key part of resection of esophageal cancer. In pathologically node negative patients, the extent of lymphadenectomy remains a key predictor of overall survival. Conversion from clinically node positive to pathologically node negative disease is associated with worse outcomes compared to clinically and pathologically node negative disease. Even in early stage cancer, a thorough, multi-field lymphadenectomy should be encouraged.

Conservative Management of Vulvar Cancer-Where Should We Draw the Line?

Vulvar cancer is a rare disease, and cure rates were low until the mid-20th century. The introduction of an en bloc radical vulvectomy and bilateral groin and pelvic lymph node dissection saw them rise from 15-20% to 60-70%. However, this very radical surgery was associated with high physical and psychological morbidity. Wounds were usually left open to granulate, and the average post-operative hospital stay was about 90 days. Many attempts have been made to decrease morbidity without compromising survival. Modifications that have proven to be successful are as follows: (i) the elimination of routine pelvic node dissection, (ii) the use of separate incisions for groin dissection, (iii) the use of unilateral groin dissection for lateral, unifocal lesions, (iv) and radical local excision with 1 cm surgical margins for unifocal lesions. Sentinel node biopsy with ultrasonic groin surveillance for patients with node-negative disease has been the most recent modification and is advocated for patients whose primary cancer is <4 cm in diameter. Controversy currently exists around the need for 1 cm surgical margins around all primary lesions and on the appropriate ultrasonic surveillance for patients with negative sentinel nodes.

Comparison of treatment strategies based on clinical and pathological nodal status in resectable gastric adenocarcinoma.

To determine the optimal multimodal treatment strategy between perioperative chemotherapy (PEC), postoperative chemoradiation therapy (POCR), and postoperative chemotherapy (POC) in resected gastric cancer (GC) patients based on nodal status. In this retrospective analysis, the National Cancer Database was used to identify resected non-metastatic GC (2006-2016). Patients were stratified by clinical nodal status-negative (cLN-) and positive (cLN+). In patients with cLN- disease who underwent upfront resection and were upstaged to pathological LN+, overall survival (OS) was compared between POC and POCR. In patients with cLN- and cLN+ disease, OS was compared between PEC, POCR, and POC. Kaplan-Meier survival estimate, log-rank test, and multivariable Cox proportional hazards analysis were performed. We identified 7827 patients (cLN- 4828; cLN+ 2999). On multivariable analysis in patients with cLN- disease who underwent upfront resection (n = 4314) and were upstaged to pLN+ disease (70%), POCR (n = 2300, aHR 0.78, 95% CI 0.70-0.87, p < 0.001) was associated with improved OS compared to POC (n = 907). No significant difference was noted between POCR (n = 766, aHR 1.11, 95% CI 0.88-1.40, p = 0.39) and POC (n = 341) in patients with pLN- disease. On multivariable analysis in all patients with cLN- disease, POCR (n = 3066) was significantly associated with improved OS (aHR 0.84, 95% CI 0.75-0.92, p < 0.01) compared to POC (n = 1248). No significant difference was noted between POCR (aHR 1.0, 95% CI 0.70-1.01, p = 0.958) and PEC (n = 514). These results remained consistent in patients with cLN+ disease (POCR = 1602, POC = 720, PEC = 677). Postoperative chemoradiation is associated with improved survival in GC patients upstaged from clinically node-negative disease to pathologically node-positive disease. Negative clinical nodal disease status is not a reliable indicator of pathological nodal disease.

Volumetric Modulated Arc Therapy for High-Risk and Very High-Risk Locoregional Prostate Cancer in the Modern Era: Real-World Experience from an Asian Cohort.

This study retrospectively evaluates the clinical outcomes of definitive volumetric modulated arc therapy (VMAT) for high-risk or very high-risk locoregional prostate cancer patients from an Asian institution. Consecutive patients who received VMAT (76 Gy in 38 fractions) between January 2017 and June 2022 were included. Whole pelvic radiotherapy (WPRT) (46 Gy in 23 fractions) was employed for clinically node-negative disease (cN0) and a Roach estimated risk of ≥15%, as well as simultaneous integrated boost (SIB) of 55-57.5 Gy to node-positive (cN1) disease. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints included radiographic relapse-free survival (RRFS), metastasis-free survival (MFS) and prostate cancer-specific survival (PCSS). A total of 209 patients were identified. After a median follow-up of 47.5 months, the 4-year actuarial BRFS, RRFS, MFS and PCSS were 85.2%, 96.8%, 96.8% and 100%, respectively. The incidence of late grade ≥ 2 genitourinary (GU) and gastrointestinal (GI) toxicity were 15.8% and 11.0%, respectively. No significant difference in cancer outcomes or toxicity was observed between WPRT and prostate-only radiotherapy for cN0 patients. SIB to the involved nodes did not result in increased toxicity. International Society of Urological Pathology (ISUP) group 5 and cN1 stage were associated with worse RRFS (p < 0.05). PSMA PET-CT compared to conventional imaging staging was associated with better BRFS in patients with ISUP grade group 5 (p = 0.039). Five-year local experience demonstrates excellent clinical outcomes. PSMA PET-CT staging for high-grade disease and tailored pelvic irradiation based on nodal risk should be considered to maximize clinical benefit.

Tumor grade and progesterone receptor status in predicting benefit of chemotherapy in high genomic risk breast cancer

ABSTRACT Background Not all eligible breast cancer (BC) patients could afford the expensive test of 21-gene recurrence score (RS) assay. This study aimed to identify clinicopathological factors associated with high-risk RS and examine whether these factors correlate with the benefit of chemotherapy. Research design and methods Patients diagnosed with early-stage BC, node-negative, and estrogen receptor-positive disease were identified from the Surveillance, Epidemiology, and End Results Oncotype DX database. Result We included 74,605 patients. Those with higher grade (p < 0.001) and progesterone receptor-negative (PR Neg) (p < 0.001) had the highest odds of a high-risk RS. Among them, 3.2%, 10.1%, 39.1%, 18.6%, 41.6%, and 80.1% had high-risk RS tumors in PR-positive (PR Pos)/well-differentiated (G1), PR Pos/moderately differentiated (G2), PR Pos/poorly and/or undifferentiated (G3), PR Neg/G1, PR Neg/G2, and PR Neg/G3 groups, respectively. Receipt of chemotherapy was associated with improved breast cancer-specific survival (p = 0.010) and overall survival (p < 0.001) in high-risk RS cohort. However, there were no survival benefits from chemotherapy in patients with PR Neg/G3 disease and other groups after stratification by grade and PR status (all p ≥ 0.05). Conclusion Our study aids in refining patient selection for the RS testing, which is crucial given its economic implications. However, 21-gene RS remains pivotal for treatment decision-making.

Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA

BackgroundTriple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC).MethodsPatients with TNBC were enrolled between 2017–2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher’s exact tests were used for comparisons between groups and Kaplan–Meier analysis used for survival outcomes.ResultsIn total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively).ConclusionsEarly clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

Detrimental Impact of Chemotherapy Dose Reduction or Discontinuation in Early Stage Triple-Negative Breast Cancer Treated With Pembrolizumab and Neoadjuvant Chemotherapy: A Multicenter Experience

BackgroundPembrolizumab combined with neoadjuvant chemotherapy (NAC) is the current standard of care in early stage triple-negative breast cancer (TNBC) based on higher event-free survival and pathological complete response (pCR) in Keynote-522 (KN-522) clinical trial. However, this aggressive five-drug regimen is associated with increased risks for immune-related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen as well as factors predictive of pCR and irAEs. MethodsWe identified and abstracted data from 153 early-stage TNBC patients treated with the KN-522 regimen between July 1, 2021, and December 31, 2023, at 4 academic institutions in the U.S. Descriptive analysis was conducted, univariate and multivariate analyses were performed to identify factors associated with pCR and irAEs. ResultsThe median age was 52 years (interquartile range, 42-60years), with 66% White and 24% Black patients with stage I/II (67%), node-negative disease (58%), grade 3 (86%) tumors, and ≥1 comorbidities (68%). Approximately 21% discontinued pembrolizumab, because of toxicity; ∼50% received a lower relative dose intensity (RDI) of chemotherapy (dose reduction or discontinuation). Of the 153 patients, 99 (64.7%) achieved pCR and 83 (54%) experienced an irAE, with 18 (12%) having ≥ grade 3 irAE. The majority (90%) of the irAEs were observed during neoadjuvant phase. Stage I/II versus stage III disease (OR 1.55, CI 1.04-2.33, P = .03), age (OR 0.96, CI 0.93-0.99, P = .01) and full versus reduced RDI of NAC (OR 1.53, CI 1.04-2.26, P = .03) were associated with higher pCR rates on multivariate analyses. Fewer cycles of pembrolizumab were associated with a higher likelihood of irAEs (OR 1.52, CI 1.07-2.16, P = .02), likely explained by the early discontinuation and receipt of less than 8 cycles of pembrolizumab in patients who experienced irAEs. ConclusionsOur study validates the clinical efficacy of KN-522 regimen; however, we observed a higher incidence of irAEs (54%) in this real-world population. Lower stage and younger age were associated with higher likelihood of achieving pCR. Toxicity-related chemotherapy dose reduction or discontinuation was observed to adversely impact the likelihood of achieving pCR.

Outcomes of Resectable Gallbladder Cancer: A Retrospective Analysis From a Tertiary Care Centre in India.

Background Gallbladder carcinoma (GBC) has deleterious outcomes, but due to its reduced incidence in Western countries, there is a paucity of data on this disease. Here we report the outcomes of a retrospective analysis of resectable gallbladder cancer from a tertiary cancer centre in eastern India. The primary objective of this study is to evaluate the overall survival (OS) and relapse-free survival (RFS) rates among patients with resectable GBC. Methods A retrospective analysis was carried out on patients who underwent radical surgery between 2007 and 2022 and received various neoadjuvant and adjuvant chemotherapy methods. Patients who had adjuvant chemoradiotherapy concurrently or who did not receive adjuvant therapy were excluded. All the baseline clinicopathological characteristics were retrieved from electronic medical records. The survival data were collected from records of follow-up visits as well as telephonic calls to the patients who were lost to follow-up. Simple proportions were used for baseline characteristics, and the Kaplan-Meier method was used for survival analysis. Results A total of 161 patients were identified, and data were captured from electronic medical records. The included patients' ages ranged between 26 and 80 years, with a median age of 56 years. Among the participants, 103 were female (64%) and 58 (36%) were male. Among the 161 patients, the median number of lymph nodes harvested was nine (ranging from one to 43), and only three patients were margin-positive. The tumour, nodes, and metastasis (TNM) distributions were as follows: pT2 in 111 patients (70.25%), pT3 in 44 patients (27.85%), and pT4 in three patients (1.90%). The nodal statuses were pN0 in 91 patients (61.9%), pN1 in 51 patients (34.69%), and pN2 in five patients (3.4%). The majority (64%) received single-agent capecitabine, 27% received gemcitabine-based platinum doublet therapy, and 4.3% received neoadjuvant therapy. Of the full sample, 2.4% received concurrent adjuvant chemo plus radiation therapy, and three patients did not receive any adjuvant therapy. Additionally, among the 161 patients, 34.16% had a relapse, with 47% being local and 52% being distant relapses. The median follow-up was 49 months (interquartile range (IQR) 23-71 months). The 24-month RFS rate was 67.1% (SD+/- 4.3%), and the 24-month OS rate was 78.1% (SD+/- 4.1%). Conclusion Our data, which is from one of the largest samples from India, show that resectable gallbladder cancer has very good outcomes after radical surgery and adjuvant chemotherapy. There was a higher proportion of T2 and node-negative disease, which could have led to better survival compared to published literature.

Guideline-Concordant Surgical Care for Lobular Versus Ductal Inflammatory Breast Cancer

IntroductionQuality of surgical care is understudied for lobular inflammatory breast cancer (IBC), which is less common, more chemotherapy-resistant, and more mammographically occult than ductal IBC. We compared guideline-concordant surgery (modified radical mastectomy [MRM] without immediate reconstruction following chemotherapy) for lobular versus ductal IBC.Methods Female individuals with cT4dM0 lobular and ductal IBC were identified in the National Cancer Database (NCDB) from 2010–2019. Modified radical mastectomy receipt was identified via codes for “modified radical mastectomy” or “mastectomy” and “≥10 lymph nodes removed” (proxy for axillary lymph node dissection). Descriptive statistics, chi-square tests, and t-tests were used.ResultsA total of 1456 lobular and 10,445 ductal IBC patients were identified; 599 (41.1%) with lobular and 4859 (46.5%) with ductal IBC underwent MRMs (p = 0.001). Patients with lobular IBC included a higher proportion of individuals with cN0 disease (20.5% lobular vs. 13.7% ductal) and no lymph nodes examined at surgery (31.2% vs. 24.5%) but were less likely to be node-negative at surgery (12.7% vs. 17.1%, all p < 0.001). Among those who had lymph nodes removed at surgery, patients with lobular IBC also had fewer lymph nodes excised versus patients with ductal IBC (median [interquartile range], 7 (0–15) vs. 9 (0–17), p = 0.001).ConclusionsLobular IBC patients were more likely to present with node-negative disease and less likely to be node-negative at surgery, despite having fewer, and more frequently no, lymph nodes examined versus ductal IBC patients. Future studies should investigate whether these treatment disparities are because of surgical approach, pathologic assessment, and/or data quality as captured in the NCDB.

Role of serum α-Klotho level in patients with breast carcinoma.

e15031 Background: The Klotho gene regulates multiple intracellular signalling pathways involving FGF-23, Insulin, IGF1, TGF-β1, Wnt/β-catenin and mammalian targets of rapamycin. The Klotho gene is downregulated in cancer and has a tumour suppressor role. Only a few studies have been done assessing its role in various cancers. None has looked into its association with all the clinicopathological characteristics of Carcinoma breast along with Pathological complete response (PCR). In August 2022, an oral senolytic form of Klotho was identified making it a possible and targetable protein. Methods: This was a Prospective cross-sectional study. Patients with biopsy-proven carcinoma breast who were previously untreated and had no significant past history were included. 84 patients were studied. Serum αKlotho level was estimated before initiating any treatment and its association with clinicopathological characteristics and with PCR was analysed. Results: A total of 84 patients were studied. The mean age was 50.76 years. Amongst our patients 65% were Estrogen Receptor (ER)+, 41.6% HER2+ and 11.9% were TNBC. 11.9% were of T1 stage, 29.8% T2, 19% T3, and 39.3% were T4. 16.7% had N0, 48.8% N1, 14.3% N2 and 20.2% had N3 stage. 20.2% were metastatic (MBC) and 79.8% were non-metastatic. 33.3% had grade 3 tumours, 56% grade 2 and 10.7% had grade 1. 61.9% were treated with NACT. The mean serum αKlotho level was 1.81ng/ml ranging from 0-5.15ng/ml. The αKlotho level was 2.04ng/ml in ER+ and 1.37ng/ml in ER-negative (p 0.011). As the Nottingham grade of the tumour increased from 1 to 3, αKlotho level decreased, with a mean value of 3.54ng/ml in grade 1, 1.71ng/ml in grade 2, and 1.42ng/ml in grade 3 (p 0.001). As the T stage increased from 1 to 4, αKlotho level decreased from 2.6ng/ml to 1.61ng/ml. Patients with N0 had a higher αKlotho of 2.92ng/ml, N1 had 1.64ng/ml, N2 1.79ng/ml, and N3 had 1.31ng/ml (p 0.001). MBC had a lower level of 1.47ng/ml than non-metastatic(1.9ng/ml). αKlotho level negatively correlated with ki67 with a correlation coefficient of -0.2. Among the patients who received NACT, we analysed 36 patients for the correlation with PCR. αKlotho level in patients who attained PCR was 1.58ng/ml and in those who did not attain PCR was 1.64ng/ml which was not significant. Conclusions: Klotho gene is identified to have a tumour suppressor role and its product αKlotho seems to have a protective role in Carcinoma breast. We found that patients with a higher serum αKlotho level had a lower histological grade(p 0.001) and a Node-negative (p 0.001) disease. Non-metastatic patients and patients with lower Ki 67 had high αKlotho levels. However, we could not find any significant association between αKlotho level and PCR. This is the first study with a large sample size done to look at the association of serum αKlotho with clinicopathological characteristics of carcinoma breast and that has found a significant association of αKlotho levels with higher grade and Node-negative disease.

Neoadjuvant pertuzumab, docetaxel, carboplatin, and trastuzumab (PTCH) regimen in patients with HER2 positive early, locally advanced, and oligometastatic breast cancer: Real-world Indian experience.

e12556 Background: Pertuzumab/docetaxel/carboplatin/trastuzumab (PTCH) regimen constitutes one of the standard neoadjuvant treatments in human epidermal growth factor receptor-2 (HER2) positive breast cancer. The real-world outcomes of its use from the Indian sub-continent are lacking. Methods: We retrospectively reviewed the medical records of 114 HER2-positive BC patients presenting with nonmetastatic or oligometastatic disease and treated with a uniform PTCH regimen in a neoadjuvant setting at the All India Institute of Medical Sciences, New Delhi, India, between Jan 2015 to May 2023. Total six cycles of PTCH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), carboplatin (AUC 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were administered with primary GCSF prophylaxis. The primary outcome was invasive disease-free survival (iDFS). The secondary outcomes included pathological complete response (pCR) rates, overall survival (OS), and toxicity. Adjuvant trastuzumab is used for patients achieving pCR, while for patients not achieving pCR option of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab was decided based on patient affordability. Results: One hundred and fourteen (114) patients were included with a median age of 47 years (range, 23-70). Overall, 52 (45.6%) patients had hormone-positive disease and 73 (64.01%) were premenopausal. Forty patients (35.08%) had stage II, 62 (54.38%) had stage III, and 12(10.5%) had oligometastatic disease. Sixty-one (53.5%) patients underwent breast conservation surgery and pCR was observed in 62 (54.38%) cases. With a median follow-up of 31 months, the 3-year iDFS was 81.5% and overall OS was not reached. Median iDFS was 33 months in patients with node-positive disease and was not reached in patients with node-negative disease. Three-year iDFS was 68.1% in patients who achieved pCR and 49.8% in those who did not achieve pCR (p=0.001). Grade 3/4 toxicity was seen in 26.7% of patients which caused dose modification and interruption in 13.9% of patients. The most common grade 3/4 toxicity was diarrhea in16 (14.03%) cases and thrombocytopenia in 11 (9.6)% cases . Febrile neutropenia was seen in 4 (3.5%) patients. Four patients (3.5%) had a reversible decrease in cardiac left ventricular ejection fraction. Conclusions: In a real-world context, PTCH is an effective and safe anthracycline-free regimen for use in curative (adjuvant and neoadjuvant) setting for HER2 positive breast cancer in Indian women Using neoadjuvant PTCH may improve pCR and obviate the need for adjuvant T-DM1 after surgery making it a cost-effective strategy in limited recourse setting. The survival outcomes were significantly better among those with node-negative disease and among those who achieved a pCR.

Real-world (RW) risk of recurrence among patients (pts) diagnosed with stage II-III HR+/HER2− early breast cancer (EBC) treated with endocrine therapy (ET) in the US.

e12533 Background: Despite improved management of HR+/HER2− EBC, pts experience recurrences while on or up to decades after ending standard-of-care (SOC) ET. Addition of adjuvant (adj) cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), ribociclib and abemaciclib, to SOC ET resulted in significant improvement of outcomes in pts with HR+/HER2− EBC at risk of recurrence. In NATALEE, ribociclib showed invasive disease-free survival (iDFS) benefit in a broader population, including select node-negative (N0) disease. This RW study describes short-term recurrence in pts with HR+/HER2− stage II-III EBC treated with SOC adj ET ± chemotherapy (CT) in the last decade in the US, prior to use of adj CDK4/6is. Methods: A medical record review from large academic (Memorial Sloan Kettering Cancer Center) and community (Tennessee Oncology) oncology practices was conducted. Adult women with stage II-III HR+/HER2− BC (AJCC 8) who underwent surgical resection and initiated adj ET between Jan 2012 and Dec 2018 were included. Pts were randomly selected for equal distribution by year of adj ET initiation. Study measures were summarized descriptively. Kaplan-Meier method was used to estimate 3-, 5-, and 7-y iDFS and distant disease–free survival (DDFS). Results: Medical charts of 992 pts were analyzed (median follow-up from initiation of adj ET, 6.3 y). Median age was 58 y. Most pts (76.7%) had stage II disease at diagnosis, 64.0% received CT, and 34.2% were premenopausal. In total, 35.8% of pts were N0. Among all N0 pts, ≈41.4% had high-risk tumor features, as defined by NATALEE: &gt;5 cm, 9.3%; 2-5 cm with G3, 25.9%; 2-5 cm with G2 + high genomic risk, estimated at 6.2%. N1(1-3) and N2/N3 (≥4) involvement was seen in 46.8% and 17.4% of pts, respectively. Analyses of iDFS/DDFS showed cumulative risk of invasive disease recurrence, predominantly distant disease, over 7 y in 21.4% across all stage II/III pts and 25.7% among the N0 pts meeting NATALEE criteria. Conclusions: This RW analysis from 2 major academic and community centers in the US confirms pts with stage II-III HR+/HER2− EBC, including select pts with N0 disease, experience considerable risk of recurrence, as early as during the adj treatment period cumulating over time. These findings warrant the consideration for tolerable treatment escalation for pts with stage II-III HR+/HER2− EBC.

A phase 1/2 study of vusolimogene oderparepvec (RP1) in primary melanoma (mel) to reduce the risk of sentinel lymph node (SLN) metastasis.

TPS9614 Background: The majority of the 80,000 newly diagnosed mel patients in the US have localized early-stage disease and undergo wide local excision (WLE) with or without SLN biopsy. The SLN is a critical prognostic marker and pivotal to immune response initiation, and fosters tumor-mediated immune suppression and pre-metastatic niches. Thus, SLN is a key target for local immune intervention. Vusolimogene oderparepvec (RP1), a locally administered oncolytic immunotherapy, provides a unique opportunity for intervention following mel diagnosis, prior to definitive surgical management. Derived from the HSV1 strain RH018A, RP1 exhibits superior killing on human tumor cell lines, designed with deletions in neurovirulence factors (ICP34.5 and ICP47) and immune-stimulating elements (increased US11 expression, GM-CSF and GALV-GP R-) to maximize oncolytic potency and induce cell death. Preclinical and clinical data demonstrate RP1's robust antitumor efficacy in advanced mel. This trial addresses a crucial gap in understanding RP1's impact on SLN dynamics, holding promise for preventing disease recurrence in this high-risk population. We hypothesize that in mel patients with high risk, clinically node negative disease (pT3b-T4b), administration of RP1 will reduce rates of SLN positivity compared to a historic control by favorably reshaping the immune landscape of the primary tumor, SLN and peripheral blood. Methods: This investigator-initiated, single site, open label, non-randomized phase 1/2 pilot study (NCT06216938) will enroll 25 patients with high-risk, clinically node-negative mel (pT3b-T4b). Major eligibility criteria include diagnosis of pT3b, T4a, or T4b non-uveal mel with visible residual tumor or positive initial biopsy margins, ECOG 0 or 1 and adequate organ function on screening labs. Patients will receive 3 doses (1ml/dose) of RP1, locally injected at the primary tumor site before standard WLE and SLN biopsy (SLNB). The first dose on day 1 will be 10e6 pfu/ml, followed by 10e7 pfu/ml for the next two doses on days 15 and 21, administered over 4-5 weeks before WLE and SLNB. Surgery occurs within 35 days of the 1st RP1 injection to avoid delays in definitive treatment. Biopsies and blood samples are obtained pre- and post-treatment. Patients will be followed for up to 3 years. Safety assessments include physical exams, labs, and adverse events (AE) monitoring. The primary endpoint is the rate of SLN positivity in the overall cohort, calculated by comparing the observed rates to the expected number of positive SLNs for that cohort using the Melanoma Institute of Australia's Prediction Tool. Secondary endpoints include safety and tolerability of RP1, RFS and OS. Exploratory correlative assays will compare the immunophenotype in primary tumor and the SLN (IHC) and in peripheral blood (flow cytometry) between baseline and on treatment. Clinical trial information: NCT06216938 .