Upfront Surgery In Patients Research Articles

Quantification of perineural invasion in pancreatic ductal adenocarcinoma: proposal of a severity score system.

Perineural invasion (PNI) is a common feature in pancreatic ductal adenocarcinoma (PDAC) and correlates with an aggressive tumor behavior already at early stages of disease. PNI is currently considered as a "present vs. absent" feature, and a severity score system has not yet been established. The aim of the present study was thus to develop and validate a score system for PNI and to correlate it with other prognostic features. In this monocentric retrospective study, 356 consecutive PDAC patients (61.8% upfront surgery patients, 38.2% received neoadjuvant therapy) were analyzed. PNI was scored as follows: 0: absent; 1: the presence of neoplasia along nerves < 3mm in caliber; and 2: neoplastic infiltration of nerve fibers ≥ 3mm and/or massive perineural infiltration and/or the presence of necrosis of the infiltrated nerve bundle. For every PNI grade, the correlation with other pathological features, disease-free survival (DFS), and disease-specific survival (DSS) were analyzed. Uni- and multivariate analysis for DFS and DSS were also performed. PNI was found in 72.5% of the patients. Relevant trends between PNI score and tumor differentiation grade, lymph node metastases, vascular invasion, and surgical margins status were found. The latter was the only parameter statistically correlated with the proposed score. The agreement between pathologists was substantial (Cohen's K 0.61). PNI severity score significantly correlated also with decreased DFS and DSS at univariate analysis (p < 0.001). At multivariate analysis, only the presence of lymph node metastases was an independent predictor of DFS (HR 2.235 p < 0.001). Lymph node metastases (HR 2.902, p < 0.001) and tumor differentiation grade (HR 1.677, p = 0.002) were independent predictors of DSS. Our newly developed PNI score correlates with other features of PDAC aggressiveness and proved to have a prognostic role though less robust than lymph nodes metastases and tumor differentiation grade. A prospective validation is needed.

Neoadjuvant chemotherapy versus upfront surgery as the initial treatment for patients with resectable, synchronous colorectal cancer liver metastases.

Although perioperative chemotherapy has been the standard treatment for colorectal cancer with resectable liver metastases (CRLM), studies that have compared neoadjuvant chemotherapy (NAC) and upfront surgery, especially in the setting of synchronous metastases are rare. We compared perioperative outcomes, overall survival (OS) and overall survival after recurrence (rOS) in a retrospective study of 281 total and 104 propensity score-matched (PSM) patients who underwent curative resection, with or without NAC, for synchronous CRLM, from 2006 to 2017. A Cox regression model was developed forOS. After PSM, 52 NAC and 52 upfront surgery patients with similar baseline characteristics were compared. Postoperative morbidity, mortality, and 5-year OS rate (NAC: 78.9%, surgery: 64.0%; p = 0.102) were similar between groups; however, the NAC group had better rOS (NAC: 67.3%, surgery: 31.5%; p = 0.049). Initial cancer stage (T4, N1-2), poorly differentiated histology, and >1 hepatic metastases were independent predictors of worse OS. Based on these factors, patients were divided into low-risk (≤1 risk factor, n = 115) and high-risk (≥2 risk factors, n = 166) groups. For high-risk patients, NAC yielded better OS than upfront surgery (NAC: 74.5%, surgery: 53.2%; p = 0.024). Although NAC and upfront surgery-treated patients had similar perioperative outcomes and OS, better postrecurrence survival was shown in patients with NAC. In addition, NAC may benefit patients with worse prognoses; therefore, physicians should consider patient disease risk before initiating treatment to identify patients who are most likely to benefit from chemotherapy.

Neutrophil/lymphocyte ratio (NLR) and albumin-globulin ratio (AGR): Correlations with outcomes in patients with stage I-III breast cancer.

e12548 Background: The ratios of blood-based inflammatory biomarkers, such as NLR and AGR, have been found to correlate with outcomes in various malignancies. Higher NLR values reflect a pro-inflammatory state and are generally associated with worse outcomes. Conversely, higher AGR values reflect a fitter nutritional status and/or less chronic inflammation, and may hence be associated with better outcomes. We aim to investigate the association between NLR and AGR with survival among stage I-III breast cancer patients treated curatively, and with pathological complete response (pCR) rates among patients who have undergone neoadjuvant chemotherapy (NACT). Methods: A retrospective study of stage I-III breast cancer patients treated in a healthcare cluster in Singapore from 2011-2017 was performed. Clinical data was extracted from a prospectively maintained registry alongside full blood count (FBC) and liver function test (LFT) results. FBC and LFT were performed either 1-month pre-chemotherapy or pre-operatively. pCR is defined as stage ypT0/isN0M0 among patients who have undergone NACT. Optimal cut-offs for the NLR and AGR values are determined by maximal Youden’s Index for pCR, DFS and OS. Multivariate logistic regression, with NLR, AGR, age, stage, grade, and subtype, was used, with survival data between groups compared using the Cox regression analysis and log-rank tests. Results: A total of 1,188 patients were included in our study, with 323 patients receiving NACT, and 865 patients undergoing upfront surgery. On multivariable analysis of patients treated with NACT, higher AGR was associated with higher pCR (cutoff &gt;1.3, HR 2.0, p=0.02) and better DFS (&gt;1.6, HR 0.4, p=0.02) while a higher NLR with worse DFS (&gt;4.1, HR 1.8, p=0.03). In upfront surgery patients, higher AGR was associated with better OS (cutoff &gt;1.2, HR 0.5, p=0.00) while a higher NLR predicted for worse OS (&gt;2.4, HR 1.6, p=0.02). Conclusions: Inflammatory markers may be useful in predicting response to NACT and prognosticating survival. Larger studies should be undertaken to explore their value in clinical decision making. [Table: see text]

Efficacy of Neoadjuvant Chemotherapy on Locally Advanced Gastric Adenocarcinoma in Terms of Downstaging and Resectability in a Tertiary Cancer Hospital

Background: Neoadjuvant chemotherapy (NACT) in carcinoma stomach was introduced in an effort to eliminate micro-metastasis and to improve resectablity before surgery which improves R0 resection rates. The aim of the current study was to evaluate the effect of neoadjuvant chemotherapy on downstaging and resectability rate in locally advanced gastric cancer. Material &amp; Methods: This was a single-center quasi-experimental study conducted in the Department of Surgical Oncology in collaboration with the Departments of Medical Oncology, Radiation oncology, and Pathology at the National Institute of Cancer Research and hospital, Dhaka, which is a tertiary care cancer hospital in Bangladesh, between January 2021 and June 2022.Patients with locally advanced adenocarcinoma stomach staged by contrast-enhanced computed tomography (CECT) were randomly included in this study by purposive sampling. Patients in Group I underwent upfront surgery Patients in Group II were started on neoadjuvant chemotherapy, either XELOX or FLOT regimen. Surgery was done following the response assessment CECT. We assessed R0 resection rate, age, sex, comorbidities, tumour size, TNM stage and complications were compared between the two groups. Response to NACT was assessed in Group II. Results: The mean age of patients in groups 1 &amp; 2 was 56 ± 11.06 and 55.70 ± 10.46 years of age respectively (p &gt; 0.05). Majority of the respondents (55/74) were male and 19 patients (26%) were female. Male to female ratio was (24/37 &amp;31/37) in group 1 and (31/37 &amp; 6/37) groups respectively (p &gt; 0.05). Out of 37 patients who received NACT, in 9 patients (24.32%) complete response was noted. Partial response was found in 20 cases (54.05%), p-value (&lt;.0001) while a stable disease was reported in three (8.1%) cases. 5 patients (13.51%) had progressive disease. In the upfront surgery group, R0 resection was feasible in 16 (43.2%) cases, and in the NACT plus surgery group, R0 resection was done in 29 (78.4%) cases. In group 1, R1 resection was done in considerable numbers (19/37) compared to group 2 (5/37), P=0.001. Three patients (8.1%) in group 2 and one (2.7) in group 1 had irresectable lesions. Conclusion: In this study it can be concluded that neoadjuvant chemotherapy could downstage tumour and increase tumor resectability rate in patients with locally-advanced gastric adenocarcinoma. However, further studies are necessary to confirm the effect of this modality on patients’ overall survival. We await survival analysis to further validate the role of NACT.

Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer: An analysis of SENTICOL I-II trials

IntroductionThe goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). Material and methodsSENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. ResultsA total of 104 patients were included: 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p = 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p = 0.04). ConclusionAlthough preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer.

Safety and feasibility of pancreas resection after a-smart in pancreatic cancer:Multicenter analysis

Background: Neoadjuvant chemotherapy coupled with radiotherapy (RT) may provide survival benefits when compared to upfront surgery in patients with borderline resectable pancreatic cancer. It is hypothesized that delivering precise, ablative doses of radiation allows for improved outcomes without increasing significant treatment-related toxicity. The purpose of the present study is to evaluate the safety and feasibility of surgical resection after neoadjuvant ablative stereotactic magnetic resonance-guided adaptive radiation therapy (A-SMART) in patients with pancreatic cancer.

Upfront surgery in patients with epithelial ovarian cancer and enlarged supradiaphragmatic lymph nodes associated with comparable to neoadjuvant chemotherapy

BackgroundThere is little data regarding the optimal approach to advanced epithelial ovarian cancer (EOC) with isolated extra-peritoneal disease in the cardiophrenic lymph nodes. This study assessed whether the prognosis and surgical outcomes are affected by the treatment approach among these patients.Material and methodsThis retrospective cohort study included patients with advanced EOC, who were treated 2012–2020. Computed tomography scans were reviewed for disease extent and the presence of enlarged supradiaphragmatic nodes (SDLN). Demographic, clinical and oncologic data were recorded. Characteristics and outcomes of patients with and without enlarged SDLN were evaluated, and outcomes of patients with enlarged SDLN who underwent upfront surgery and neoadjuvant chemotherapy were compared.ResultsAmong 71 women, 47 (66%) had enlarged supradiaphragmatic lymph nodes. Groups had similar baseline characteristics. Among 47 women who had enlarged SDLN. There was no significant difference in progression free survival among patients who had upfront cytoreduction compared to those who received neoadjuvant chemotherapy. Only one asymptomatic chest recurrence was observed.ConclusionPatients with enlarged SDLN have comparable outcomes with either upfront surgery or neoadjuvant chemotherapy. Moreover, the frequency of chest recurrences in patients presenting with enlarged SDLN is exceedingly low.

Five decades of progress in surgical oncology: Breast.

Surgery remains the single most effective treatment for breast cancer but coincident with a deeper understanding of tumor biology and advances in multidisciplinary care (encompassing breast imaging, systemic adjuvant therapy, radiotherapy, and genomics) continues to de-escalate, supported by strong level I data. We have moved from mastectomy to breast conservation, and from routine axillary dissection to sentinel lymph node biopsy to selective omission of axillary node staging altogether. We have further de-escalated through consensus over margin width in breast conservation, through improvements in neoadjuvant therapy, and by demonstrating no benefit for upfront surgery in patients with stage IV disease. For patients with ipsilateral breast tumor recurrence, reconservation surgery and reirradiation are promising. Cell cycle and immune checkpoint inhibitors, when added to conventional systemic therapy, have now moved beyond stage IV disease to phase III trials in the adjuvant and neoadjuvant settings, promising even further de-escalation of surgery. Finally, with genomic profiling we are moving away from the primacy of axillary node status for prognostication and into a new era allowing prediction of response to therapy.

Real-life long-term outcomes of upfront surgery in patients with resectable stage I-IIIA non-small cell lung cancer.

BackgroundTreatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I–IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010–2017.Patients and methodsData of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA).ResultsWith a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OS; but only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS.ConclusionsThe study showed favourable outcomes of resectable stage I–IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy.

A predictive model for recurrence after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by using preoperative clinical data and CT characteristics

BackgroundThe overall survival for patients with resectable PDAC following curative surgical resection hasn’t been improved significantly, as a considerable proportion of patients develop recurrence within a year. The purpose of this study was to develop and validate a predictive model to assess recurrence risk in patients with PDAC after upfront surgery by using preoperative clinical data and CT characteristics.MethodsThe predictive model was developed based on a retrospective set of 141 pancreatic cancer patients after surgery. A separate set of 77 patients was used to validate model. Between January 2017 and December 2019, all patients underwent multidetector pancreatic CT and upfront surgery. Univariable and multivariate Cox regression was used to determine the risk factors related to recurrence and then establish a nomogram to estimate the 1-year recurrence probability. The Harrell C-index was employed in evaluating the discrimination and calibration of the model.ResultsA total of 218 patients in this retrospective cohort. A recurrence model in nomogram form was developed with predictors including tumor size (hazard ratio [HR], 1.277; 95% CI 1.098, 1.495; P = 0.002), tumor density in the portal vein phase (HR, 0.598; 95% CI 0.424, 0.844; P = 0.003), peripancreatic infiltration (HR, 4.151; 95% CI 2.077, 8.298; P < 0.001), suspicious metastatic lymph node (HR, 2.561; 95% CI 1.653, 3.967; P < 0.001), Neutrophils/Lymphocytes ratio (HR, 1.111; 95% CI 1.016, 1.215; P = 0.020). The predictive nomogram had good discrimination capability with these predictors with an area under curve at 1 year of 0.84 (95%CI 0.77, 0.91) in the development set and 0.82 (95% CI 0.72, 0.92) and 0.84 (95% CI 0.74, 0.94) in the validation set for two radiologists reading respectively.ConclusionsThe model developed based on preoperative clinical data and CT characteristics of resectable pancreatic ductal adenocarcinoma patients, which can helpfully estimate the recurrence-free survival. It may be a useful tool for clinician to select optimal candidates for upfront surgery or neoadjuvant therapy.

β-catenin plus PROX1 immunostaining stratifies disease progression and patient survival in neoadjuvant-treated pancreatic cancer.

Wnt/β-catenin signaling is a highly conserved signaling pathway that regulates the transcription factor PROX1. The role of β-catenin and PROX1 in pancreatic cancer is ambiguous, as some studies have associated their expression with tumor regression and some with tumor progression. We have investigated their expression in surgically treated pancreatic cancer patients receiving neoadjuvant therapy (NAT), and patients treated upfront with surgery (US). We furthermore compared the expression of β-catenin and PROX1 between patients who had a good or poor response to NAT. We evaluated β-catenin and PROX1 expression through immunohistochemistry in 88 neoadjuvant and 144 upfront surgery patients by scoring the intensity of the immunopositivity as 0-3, corresponding to negative, weak, moderate, or strong. We developed a six-tier grading scheme for the neoadjuvant responses by analyzing the remaining tumor cells in surgical specimen histological sections. Strong β-catenin immunopositivity associated with improved survival in the patients with good NAT-response (≤10% residual tumor cells) (Hazard ratio [HR] 0.26 95%, confidence interval [CI] 0.07-0.88 p = 0.030). Additionally, the combined moderate β-catenin and PROX1 expression associated with improved survival (HR 0.20 95% CI 0.05-0-76 p = 0.018) among the good responders. Among the patients with a poor NAT-response (> 10% residual tumor cells), both strong β-catenin immunopositivity and strong combined β-catenin and PROX1 associated with shorter survival (HR 2.03 95% CI 1.16-3.55 p = 0.013, and HR 3.1 95% CI 1.08-8.94 p = 0.03, respectively). PROX1 alone was not associated with survival. Strong β-catenin immunopositivity and combined strong or moderate β-catenin and PROX1 immunopositivity associated with improved survival among the good NAT-responders and worse survival among the poor NAT-responders.

Abstract 3218: Radiomic biomarkers to optimize treatment decision and predict patient outcomes in serous ovarian carcinoma

Abstract Background: There are two first-line treatment recommendations for advanced ovarian cancer: i) upfront cytoreductive debulking followed by chemotherapy and ii) neoadjuvant chemotherapy prior to surgical debulking. The choice between these two treatment strategies is controversial as there are no standardized guidelines for clinical decision support. As such, there remains a critical unmet need to identity biomarkers to personalize the most effective treatment strategies. The primary objective of this study is to identify and validate radiomic biomarkers that predict treatment response among patients with high-grade serous ovarian cancer treated with upfront surgical debulking. Methods: Intratumoral radiomic features (n=308) were extracted from pre-treatment contrast-enhanced CT images; analyses were conducted to remove correlated, non-stable, and non-reproducible features. Patients treated with upfront surgery (N=182) were split into training (N=91) and test (N=91) cohorts and a cohort of patients treated with upfront neoadjuvant (N=116) was used to determine if the radiomic features were prognostic or predictive. Overall (OS) and progression-free survival (PFS) were the main endpoints. Classification and Regression Tree analysis was used to identity the most informative radiomic features in the training cohort, which were then analyzed in the test cohort and the upfront neoadjuvant cohort. Results: Decision tree analysis identified a volumetric feature, ROI volume center of mass (CoM) in X direction, as the most informative radiomic feature which stratified upfront surgery patients into high- and low-risk. In the training cohort, high-risk patients were associated with significantly worse OS versus low-risk patients (HR=2.01; 95% CI 1.07-3.77 vs. 1.00 and 5-year OS=39.9% vs. 56.1%, respectively; log-rank p-value=0.03). In the test cohort, the high- vs. low-risk patients were also associated with poor OS (HR=2.23; 95% CI 1.19-4.17 vs. 1.00 and 5-year OS=23.3% vs. 51.3%, respectively; log-rank p-value=0.01). This radiomic feature was not associated with OS among patients with upfront neoadjuvant (HR=1.23; 95% CI 0.73-2.07 vs. 1.00 and 5-year OS=23.9% vs. 36.6%, respectively; log-rank p-value=0.44). Similar findings were observed for PFS. Conclusion: Utilizing standard-of-care imaging, we identified and validated a predictive radiomic feature associated with outcomes among patients with high-grade serous ovarian cancer treated with upfront surgical debulking but not among patients treated with neoadjuvant chemotherapy. This radiomic biomarker, which describes the location of center of mass inside the tumor in pixels in the x-direction, could be potentially utilized as clinical decision support to guide first-line treatment options. This study was generously funded by a Miles for Moffitt pilot grant. Citation Format: Jaileene Perez-Morales, Christelle M. Colin Leitzinger, Sweta K. Sinha, Melissa J. McGettigan, Daniel K. Jeong, Olya Stringfield, Mahmoud Abdala, Natarajan Raghunand, Robert J. Gillies, Jing-Yi Chern, Lauren C. Peres, Matthew B. Schabath. Radiomic biomarkers to optimize treatment decision and predict patient outcomes in serous ovarian carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3218.

Treatment Strategy for Esophageal Squamous Cell Carcinoma With Endoscopic Intramural Metastasis.

Purpose: Intramural metastasis (IM) in esophageal squamous cell carcinoma (ESCC) is sometimes found, and the prognosis of ESCC patients with pathologically diagnosed IM is known to be dismal. However, there are few reports on ESCC patients with clinically diagnosed IM.Methods: This study assessed 2,772 ESCC patients who underwent endoscopy for initial evaluation. Among them, 85 patients (3.1%) were diagnosed with endoscopic IM. In this study, we investigated these patients’ characteristics, survival among the groups stratified by the treatment modalities, and survival predictors.Results: Of 85 patients, 76 (89.4%) had T3 or T4 tumors, 73 (85.9%) had nodal metastases, and 36 (42.4%) had M1 diseases. Curative-intent treatment could be given to 63 patients (74.1%) with a median survival time (MST) of 15.6 months (95% CI: 10.7-20.4). As initial treatment, upfront surgery (US), neoadjuvant chemotherapy (NAC) using cisplatin and 5-fluorouracil (CF), neoadjuvant chemoradiotherapy, and definitive chemoradiotherapy (dCRT) were given to 17 (27.0%), 27 (42.9%), 2 (3.2%), and 17 patients (27.0%), respectively. dCRT was preferred for T4 tumors compared with US or NAC (P = 0.02). The MST of US and NAC patients was 19.3 (95% CI: 12.9-25.6) and 23.4 months (95% CI: 9.4-37.4), respectively. No significant difference was noted between US and NAC patients (P= 0.89).Conclusion: The prognosis of ESCC patients with endoscopic IM is poor even if curative-intent treatment is done. Moreover, no significant survival benefit of NAC with CF for these patients was observed when compared with US.

Abstract P2-13-02: Pathologic nodal staging and systemic therapy among patients with cT1-2N0 HER2+ breast cancer: A prospective single institution cohort analysis

Abstract Background: The optimal systemic therapy strategy, neoadjuvant vs adjuvant therapy, for patients with small clinically node negative HER2+ breast cancers is uncertain. The goal of this study was to evaluate the incidence of pathologic nodal disease in cT1-2 N0 HER2+ patients, treated with upfront surgery or neoadjuvant chemotherapy (NAC), to better define selection criteria for initial treatment approach. Methods: Our prospectively maintained database was queried for cT1-2 N0 HER2+ breast cancer patients diagnosed 2/12/2015 - 10/13/2020 (after publication of the Adjuvant Paclitaxel and Trastuzumab trial). Patients without axillary surgery were excluded (n =23). HER2 positivity was defined per ASCO/CAP guidelines. Pre-NAC and/or pre-operative axillary ultrasound was not routinely performed. Patient characteristics and rates of pN+ disease were compared by treatment strategy using Chi square and Wilcoxon rank-sum tests. Nodes with isolated tumor cells were considered negative (pN0) in the upfront surgery setting but positive (pN+) after NAC. Logistic regression determined factors associated with pN+ disease. Results: A total of 579 eligible patients were identified; 368 (63.6%) were treated with upfront surgery and 211 (36.4%) with NAC. Upfront surgery patients were older (median 55 years [range 23-88] vs 49 [24-79], p&amp;lt;0.001); less frequently had grade 3 disease (58.4% vs 67.3%, p=0.008); less frequently had T2 tumors (14.4% vs 82.5%, p&amp;lt;0.001); and less frequently underwent axillary ultrasound (21.2% vs 62.6%, p&amp;lt;0.001). NAC included multi-chemotherapy regimens in 46 (21.8%) and more than one HER2-targeted regimens in 165 (78.2%). The incidence of pN+ disease was 73/368 (19.8%) among upfront surgery patients and 26/211 (12.3%) among NAC patients (p=0.021). Among upfront surgery patients, there was a significant difference in the distribution of pN+ across T categories (p&amp;lt;0.001) with an increased rate in patients with cT1c and cT2 tumors (Table 1). There was no difference in use of ALND between upfront surgery (22/368 [6.0%]) and NAC patients (18/211 [8.5%], p=0.173). Hormone-receptor status did not impact rate of pN+ disease (OR 1.024, 95% CI: 0.601-1.747, p=0.929). Among upfront surgery patients, adjuvant systemic therapy (excluding endocrine therapy) was given in 269 (73.1%) including paclitaxel/trastuzumab in 158 (42.9%) and other regimens to include multi-chemotherapy regimens in 111 (30.2%). Conclusions: In this large cohort of cT1-2 N0 HER2+ breast cancer patients, treatment with NAC was associated with lower rates of pN+ compared to those undergoing upfront surgery. Despite these differences, ALND rates were similar. In upfront surgery patients, the higher rate of pN+ disease in patients with cT1c-T2 tumors suggests an opportunity for more comprehensive radiographic examination of the axilla in this subgroup. Further investigation could also focus on tailoring NAC regimens for HER2+ cN0 patients who are presently undergoing upfront surgery. Table 1.Pathologic nodal stage among upfront surgery and NAC patientsUpfront Surgery (N=368)pN+pN0P valuecT category&amp;lt; 0.001T1mi (N=48)6 (10.4%)42 (89.6%)T1a (N=26)3 (11.5%)23 (88.5%)T1b (N=87)7 (8.0%)80 (92.0%)T1c (N=154)38 (24.7%)116 (75.3%)T2 (N=53)19 (35.8%)34 (64.2%)NAC (N=211)ypN+ypN0P valuecT category0.719T1b (N=7)1 (14.3%)6 (85.7%)T1c (N=30)5 (16.7%)25 (83.3%)T2 (N=174)20 (11.5%)154 (88.5%) Citation Format: Anna Weiss, Adrienne G. Waks, Alison Laws, Sara M. Tolaney, Eric P. Winer, Elizabeth A. Mittendorf, Ann H. Partridge, Tari A. King. Pathologic nodal staging and systemic therapy among patients with cT1-2N0 HER2+ breast cancer: A prospective single institution cohort analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-02.

ASO Visual Abstract: Neoadjuvant Therapy Versus Upfront Surgery for Patients with Clinical Stage II and III Esophageal Squamous Cell Carcinoma—A Cost-Effectiveness Analysis

ASO Visual Abstract: Neoadjuvant Therapy Versus Upfront Surgery for Patients with Clinical Stage II and III Esophageal Squamous Cell Carcinoma—A Cost-Effectiveness Analysis

Preoperative oncologic therapy and the prolonged risk of venous thromboembolism in resectable pancreatic cancer.

BackgroundPancreatic cancer is one of the most prothrombotic cancers. Among patients receiving preoperative chemotherapy followed by surgery, chemotherapy and surgery represent a compound risk for venous thromboembolism (VTE), rendering the postoperative time a period of interest. We aimed to analyze whether preoperative oncologic therapy increases the risk for VTE after surgery and identify which characteristics associate with VTE.MethodsWe first identified patients surgically treated for pancreatic cancer at Helsinki University Hospital between 2000 and 2017, collecting the following data: gender, age at surgery, preoperative medication, body mass index (BMI), preoperative chemo(radio)therapy, tumor size, positive node ratio, perineural and perivascular invasion, tumor grade, surgical technique, postoperative anticoagulation, adjuvant therapy, time of VTE, time of local disease recurrence, time of distant metastasis, and time of death. With a follow‐up period of at least 2 years or until death, we compared a total of 93 preoperative oncologic therapy and 291 upfront surgery patients (n = 384, median age 66.5 years).ResultsPreoperative oncologic therapy increased the risk for thrombosis after surgery (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.03–2.53). The VTE incidence rate remained high for up to 2 years after surgery. BMI ≥30 kg/m2, prior anticoagulation, and disease recurrence (p < 0.05, respectively) associated with VTE. VTE is also associated with shorter overall survival (HR 3.25; 95% CI 2.36–4.44). In 71.6% (95% CI 60.5–81.1) of patients, VTE was diagnosed after disease recurrence.ConclusionsPreoperative oncologic therapy represents an independent risk factor for VTE, not only during the immediate postoperative period but up to 2 years after surgery. VTE is associated with obesity, prior anticoagulation, and disease recurrence and diminishes overall survival.

Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials

IntroductionNeoadjuvant therapy may improve survival compared with upfront surgery in patients with resectable and borderline resectable pancreatic cancer, but high-quality evidence is lacking. MethodsWe systematically searched for randomised trials comparing neoadjuvant therapy with upfront surgery for resectable and borderline resectable pancreatic cancer published since database inception until December 2020. The primary outcome was overall survival (OS) by intention-to-treat with subgroup analyses for resectability status. Meta-analyses using a random-effects model were performed. Certainty of evidence was assessed using the GRADE approach. ResultsSeven trials with 938 patients were included. All trials included a neoadjuvant gemcitabine-based chemo(radio)therapy arm. None of the studies used adjuvant FOLFIRINOX. Neoadjuvant therapy improved OS (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52–0.85; P = 0.001; I2 = 46%) compared with upfront surgery. This represents an increase in median OS from 19 to 29 months. In the subgroup of resectable pancreatic cancer (i.e., venous contact ≤180°, no arterial contact), no statistically significant difference in OS was observed (HR 0.77, 95% CI 0.53–1.12; P = 0.18; I2 = 20%). In the subgroup of borderline resectable pancreatic cancer (i.e. venous contact >180°, any arterial contact), neoadjuvant therapy improved OS (HR 0.61, 95% CI 0.44–0.85; P = 0.004; I2 = 59%). The GRADE certainty of evidence was high for the outcome of OS. ConclusionsNeoadjuvant therapy improves OS compared with upfront surgery in patients with borderline resectable pancreatic cancer. More evidence is required on whether neoadjuvant therapy improves survival for patients with resectable pancreatic cancer.

Neoadjuvant chemotherapy for colorectal liver metastases: A contemporary review of the literature.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide, and up to 50% of patients with CRC develop colorectal liver metastases (CRLM). For these patients, surgical resection remains the only opportunity for cure and long-term survival. Over the past few decades, outcomes of patients with metastatic CRC have improved significantly due to advances in systemic therapy, as well as improvements in operative technique and perioperative care. Chemotherapy in the modern era of oxaliplatin- and irinotecan-containing regimens has been augmented by the introduction of targeted biologics and immunotherapeutic agents. The increasing efficacy of contemporary systemic therapies has led to an expansion in the proportion of patients eligible for curative-intent surgery. Consequently, the use of neoadjuvant strategies is becoming progressively more established. For patients with CRLM, the primary advantage of neoadjuvant chemotherapy (NCT) is the potential to down-stage metastatic disease in order to facilitate hepatic resection. On the other hand, the routine use of NCT for patients with resectable metastases remains controversial, especially given the potential risk of inducing chemotherapy-associated liver injury prior to hepatectomy. Current guidelines recommend upfront surgery in patients with initially resectable disease and low operative risk, reserving NCT for patients with borderline resectable or unresectable disease and high operative risk. Patients undergoing NCT require close monitoring for tumor response and conversion of CRLM to resectability. In light of the growing number of treatment options available to patients with metastatic CRC, it is generally agreed that these patients are best served at tertiary centers with an expert multidisciplinary team.

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer.

IntroductionAlthough surgical resection is necessary, it is not sufficient for long‐term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up‐front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19‐9; and (C) receipt of adjuvant chemotherapy.MethodsThe National Cancer Data Base (2010–2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre‐operative CA19‐9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention‐to‐treat (ITT) basis.ResultsTwelve thousand and eighty‐nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT‐neoadjuvant cohort (27.9 vs. 22 months) to UFS.ConclusionDespite the perceived benefit of UFS, only 1‐in‐5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT‐neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of ‘optimal’ survival benefit with UFS in anatomically resectable PDAC.

Neoadjuvant Chemoradiation Impacts the Prognostic Effect of Surgical Margin Status in Pancreatic Adenocarcinoma.

Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p=0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p<0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p<0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p=0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p=0.70). Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.