Receive Neoadjuvant Therapy Research Articles

Effectiveness of an Exercise and Educational-Based Prehabilitation Program in Patients with Breast Cancer Receiving Neoadjuvant Chemotherapy (PREOptimize) on Functional Outcomes: A Randomized Controlled Trial.

The study objective was to determine the effectiveness of a prehabilitation program to decrease postoperative musculoskeletal impairments in patients who have breast cancer and are receiving neoadjuvant therapy (NAT). Patients who had breast cancer and were receiving NAT before surgery were invited to participate in this randomized controlled trial. Patients randomized to the intervention group participated in a group-based prehabilitation program consisting of Nordic walking, resistance training, and therapeutic education from month 4 of NAT until before surgery. Patients in the control group received usual care (no prehabilitation). The main outcome was arm function measured with the short version of the Disabilities of the Arm, Shoulder and Hand questionnaire 1month after surgery. Other measures included pain, range of motion, functional capacity, cancer-related fatigue, handgrip strength, physical activity, and arm circumferences. A total of 64 patients were randomized during the study period, and 61 completed all assessments. A significant difference in the main outcome (short version of the Disabilities of the Arm, Shoulder and Hand questionnaire) was found before surgery as patients in the control group experienced worsening in arm function (mean difference = -9.84, 95% CI = -17.7 to -2). In addition, they also showed increased symptom frequency/severity according to the combined scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) (mean difference = +6.7 points, 95% CI = 13.4 to 0.1) compared to the intervention group. Prehabilitation also improved functional capacity (mean difference = 67.6m, 95% CI = 37.4 to 97.7) and physical activity levels and decreased cancer-related fatigue (mean difference = -1.3, 95% CI = -0.29 to -2.4) compared to the control group but had no effect on other secondary outcomes. After surgery, patients receiving prehabilitation also exhibited greater functional capacity at both 1 and 3months. No other difference was observed. A prehabilitation program was able to maintain arm function and increase functional capacity while decreasing fatigue in patients with breast cancer receiving NAT. Prehabilitation programs should be offered to patients with breast cancer to maintain functionality and enhance physical performance before surgery. An exercise program combined with therapeutic education in patients with breast cancer who receive neoadjuvant therapy before surgery can improve functional capacity and prevent declines of arm mobility and function.

National Landscape of Neoadjuvant Therapy in Potentially Resectable Colon Cancer

IntroductionSurgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. Methods169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. ResultsOf identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). ConclusionsIn a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.

Laparoscopic versus robotic pancreaticoduodenectomy: A NSQIP analysis comparing trends in patient selection and outcomes over 5-years

BackgroundComparison of laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy over time remains limited. This study aims to compare LPD and RPD and to describe the demographics and outcomes of patients undergoing MIS pancreaticoduodenectomy over 5-years. MethodsThe ACS-NSQIP (2016–2021) database was used to evaluate patients undergoing MIS pancreaticoduodenectomy comparing LPD versus RPD. Patient characteristics, and outcomes were compared and multivariable modelling evaluated factors associated with serious complications, and mortality. MIS approach, demographics, and outcomes were assessed yearly to evaluate trends over time. ResultsWe evaluated 1707 patients with 1148 (67.3 %) receiving RPD. Cohorts were similar with regards to demographic factors, however, patients undergoing RPD were less likely to be partially dependent (0.5 % vs. 1.6 %; p = 0.024), and more likely to receive neoadjuvant therapy (26.8 % vs. 21.7 %; p = 0.023).Bivariate analysis demonstrated similar operative duration (444.1 vs 429.9 min; p = 0.074), but shorter LOS (8.5 vs. 9.8 days; p < 0.001), and higher readmission rate (21.5 % vs. 15.6 %; p = 0.004) with RPD. Additionally, RPD required transfusion less often (10.5 % vs. 21.7 %; p < 0.001). Multivariable analysis demonstrated that LPD was not independently associated with serious complications (OR 1.27 p = 0.094) or mortality (OR 0.82, p = 0.611).Analysis of trends from 2016 to 2021 demonstrated similar patient selection and outcomes but a significant increase in MIS pancreaticoduodenectomy (281 to 428), primarily driven by an increase in RPD. ConclusionsComparing LPD and RPD there is no difference in serious complications or mortality. MIS pancreaticoduodenectomy has increased over the last 5 years but volumes remain small with similar demographics and outcomes over time.

Application of 21-gene recurrence risk score in patients with breast cancer

Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

Prognostic value of circulating tumor DNA testing in surgically resected pancreatic cancer.

4134 Background: The majority of patients with pancreatic cancer who undergo curative intent resection have recurrence, but optimal surveillance is unknown. Circulating tumor DNA (ctDNA) tests, custom-designed multiplex-PCR tumor assays unique to each patient’s tumor, may assist in monitoring for recurrence. Methods: We performed a single center retrospective review of patients with surgically resected pancreatic cancer who had at least 1 ctDNA test performed post-operatively between 8/1/21 and 11/13/23 with Natera Inc.’s Signatera assay. Primary outcomes were documented radiographic progression and death. Results: 74 patients were identified, of whom 36 were positive for ctDNA at any point during the study (median follow up from surgery 19.1 months) while 38 remained negative for ctDNA (15.3 months). There was no difference in age (≥ or &lt; 70), sex, or race. Positive ctDNA at any time point was associated with advanced stage disease (p=0.013), positive resection margins (p=0.008), and having received neoadjuvant therapy (p=0.005). Those with any positive ctDNA were more likely to have radiographic progression (p&lt;0.0001) or death (p=0.0005) by the end of the study. These differences remained when the population was examined in subgroups of first post-operative ctDNA positive, first ctDNA negative but at least one subsequent ctDNA positive, and all ctDNA negative. In Cox proportional hazard models, both any positive ctDNA test and positive first ctDNA test (first ctDNA limited to ≤120 days post-op) were associated with higher risk of radiographic progression and/or death compared to never testing positive for ctDNA and negative first ctDNA test, respectively (HR 12.6 (3.0-51.9), p=0.0005; HR 5.6 (1.4-22.8), p=0.02). Conclusions: Positive ctDNA tests, both in the immediate post-operative and subsequent settings, are associated with higher risk of radiographic progression or death in patients with resected pancreatic cancer. These data suggest that ctDNA testing provides independent, meaningful prognostic information superior to traditional pathologic risk factors and CA19-9 testing alone. These findings have implications for future clinical study design and decisions about surveillance and treatment. [Table: see text]

Choice of adjuvant therapy for HER2-positive breast cancer in real clinical practice: analysis of physician preferences in the Russian Federation

Adjuvant therapy with trastuzumab made a significant contribution to improving disease-free and overall survival rates in patients with HER2-positive breast cancer. However, in a number of clinical situations the risk of disease recurrence remains increased. Carrying out neoadjuvant treatment followed by post-neoadjuvant therapy, depending on the degree of pathomorphological response, is the modern standard, allowing to cure a significantly larger number of patients. This became possible thanks to the expansion of the arsenal of terget anti-Her drugs and the introduction into real clinical practice of double anti-HER2 blockade (trastuzumab + pertuzumab) and an antibody conjugate with a cytostatic drug – trastuzumab emtansine. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of HER2-positive breast cancer” was conducted. The survey involved 50 specialists from different regions of the country who are directly involved in developing a treatment plan for patients, which allows them to reflect the preferences of leading chemotherapists regarding tactics for HER2-positive breast cancer. This publication reflects the results of part of the survey, devoted to the choice of adjuvant and post-neoadjuvant therapy for HER2-positive breast cancer. Identified a clear positive trend in favor of neoadjuvant treatment followed by post-neoadjuvant therapy using modern targeted drugs such as pertuzumab and trastuzumab emtansine. The survey results show that 68% of patients with RCB-II–III residual tumor receive post-neoadjuvant trastuzumab emtanzine, in 2021 this figure was only 24%. The absolute majority of patients who have not received neoadjuvant therapy, but have N2–3 stage, receive double anti-HER2 therapy with trastuzumab + pertuzumab in the adjuvant setting. High adherence to the therapy was noted, as 97% of patients complete the planned course of T-DM1, and 91.2% of patients complete a year of adjuvant anti-HER2 therapy. These figures are noticeably higher than the indicators of registration studies. Issues of effectiveness come to the fore in choosing therapy. Issues of drug availability remain relevant, but are not decisive. The survey also revealed factors that were not obvious at first glance and influenced treatment results.

Abstract PO4-25-08: Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population

Abstract Secretory breast carcinoma (SBC) is a rare and distinct disease, comprising approximately 0.01% of all breast carcinomas. This is a case of an 8-year-old boy who presented with a 1.5-year history of a non-tender, slowly enlarging left subareolar mass, not associated with nipple discharge. Serologic workup revealed minimally elevated prolactin with normal-range FSH, LH, estradiol and testosterone, as well as normal-range beta-hCG, LDH and AFP. Ultrasound showed a circumscribed solid hypoechoic lesion with internal arterial vascularity, favoured to represent a sebaceous cyst. Excisional biopsy was performed, and histologic examination revealed the classic intra- and extracellular secretory material typically seen in SBC. Immunohistochemical (IHC) stains for mammaglobin, S-100 and high molecular weight keratin (CK5) were positive. ER was positive, though not strong staining, and PR and HER2 were negative. A screen for NTRK fusions with pan-TRK IHC was positive. No skin, perineural or lymphovascular invasion was identified. RNA-based NGS demonstrated ETV6-NTRK3 fusion and confirmed the diagnosis of SBC. The patient underwent mastectomy and SLNB, which showed no residual tumor and no positive lymph nodes. A full metastatic work-up was not performed and the patient did not receive neoadjuvant therapy. First described as “juvenile breast carcinoma,” SBC has since been recognized to occur across a wide age range, with most cases occurring in adults. SBC in male pediatric patients is exceptionally rare, with fewer than 20 cases reported in the literature. In this demographic, SBC is usually detected clinically as a subareolar mass not associated with nipple discharge, and appears as a well-circumscribed mass on imaging, mimicking benign entities. SBC is usually detected at a low stage, treated surgically, and follows a clinically indolent course with excellent outcomes. Positive axillary nodes have been identified in a few male children, who subsequently underwent chemo- and/or radiotherapy, with no recorded recurrences in these cases. Distant metastases are an extremely uncommon feature of SBC and have not been reported in the pediatric male population; however, due to the rarity of this diagnosis, particularly in this demographic, robust long-term follow-up data are still lacking. The name “secretory” derives from the histologic appearance of the dense eosinophilic secretory material seen in tumor lumina and bubbly material in the cytoplasm of tumor cells. Similar to the cytologic characteristics of other translocation-driven neoplasms, SBC shows minimal pleomorphism. Mitoses are absent or rare. IHC stains are typically positive for S-100 and high molecular weight keratins and negative for ER, PR, and HER2. Despite the immunophenotypic similarities to triple negative/basal-like carcinomas (TNBC/BLC) the molecular relationship between SBC and TNBC/BLC is unclear. Though initially defined by its distinctive secretions on histology, SBC is now chiefly characterized by a balanced translocation, t(12;15)(p13;q25), resulting in oncogenic ETV6-NTRK3 fusion. Recent cases have demonstrated this using a variety of molecular techniques, including FISH, RT-PCR, and in our case, RNA-based NGS. This translocation also characterizes non-breast secretory carcinomas and has been identified in several other neoplasms, including pediatric mesenchymal tumours and adult acute myeloid leukemia. The rarity of SBC, particularly in the male pediatric population, underlines the necessity of this case report. Additionally, this case highlights the importance of considering SBC as a potential diagnosis in male children presenting with a breast mass, even in the presence of benign imaging characteristics. Table 1: Clinicoradiologic and pathomolecular characteristics of SBC in pediatric males AND, axillary node dissection; CT, chemotherapy; ER, estrogen receptor; FISH, fluorescence in situ hybridization; LE, local excision; MRM, modified radical mastectomy; nd, no data; NED, no evidence of disease; NGS, next-generation sequencing; NS, nodal sampling; PA, periareolar; PR, progesterone receptor; RA, retroareolar; RM, radical mastectomy; PCR, polymerase chain reaction; RT, radiotherapy; SA, subareolar; SLNB, sentinel lymph node biopsy; SM, simple mastectomy; WLE, wide local excision *Not reported as strong staining Table 2: Immunohistochemical phenotype of secretory breast carcinoma EMA, epithelial membrane antigen; ER, estrogen receptor; PR, progesterone receptor *Not reported as strong staining Table 3: Laboratory investigations AFP, alpha fetoprotein; FSH, follicle stimulating hormone; hCG, human chorionic gonadotropin; LDH, lactate dehydrogenase; LH, luteinizing hormone Citation Format: Rebecca Brassington, Svetlana Silverman, Ioana Bratu. Secretory breast carcinoma (SBC) in an 8-year-old male: Report of an exceptionally rare case with review of clinicoradiologic and pathomolecular findings of SBC in the male pediatric population [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 PO4-25-08.

Abstract PO1-03-11: Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled Study

Abstract Background: Triple-negative breast cancer (TNBC) is recognized for its aggressive nature and unfavorable prognosis. Immune checkpoint inhibitors have demonstrated promising antitumor activity in both neoadjuvant and metastatic settings. This study aimed to assess the efficacy and safety of camrelizumab, an anti-PD-1 antibody, in conjunction with chemotherapy as a neoadjuvant treatment for early-stage TNBC. Methods: This two-phase prospective, multicenter, randomized controlled study was initiated with the enrollment of previously untreated stage II-III TNBC patients in the first phase. They received neoadjuvant therapy comprising six 3-week cycles of camrelizumab (200 mg, q3w), along with nab-paclitaxel (220 mg/m2, q3w) and carboplatin (AUC 5, q3w). In the second phase, patients were enrolled and randomized 1:1 to either the camrelizumab plus nab-paclitaxel and carboplatin group or the nab-paclitaxel plus carboplatin group. The present report covers the data from the first phase of the study. The primary endpoint was the total pathological complete response (tpCR, ypT0/is ypN0) rate. Secondary endpoints included breast pathological complete response (bpCR, ypT0/is) rate, objective response rate (ORR), event-free survival (EFS), residual cancer burden (RCB), and safety. This study is registered with ClinicalTrials.gov, under the identifier NCT04907344. Results: Between September 2021 and March 2023, 39 patients were enrolled in the first phase. A total of 35 (89.7%) were node-positive. Among the 32 patients with evaluable efficacy, the tpCR rate was 59.4% (19/32), and the bpCR rate was 68.8% (22/32). The ORR at the end of neoadjuvant treatment stood at 87.2% (34/39). Among the 39 patients, 11 (28.2%) experienced grade 3 or higher treatment-related adverse events, the most common of which were thrombocytopenia (6 [15.4%]), leucopenia (5 [12.8%]), neutropenia (5 [12.8%]), alanine aminotransferase increased (2 [5.1%]), aspartate aminotransferase increased (1 [2.6%]), and hypothyroidism (1 [2.6%]). Adverse events leading to discontinuation of any agent occurred in 5 (12.8%) patients, while adverse events leading to delay in treatment occurred in 7 (17.9%) patients. Serious treatment-related adverse events were reported by 4 (10.4%) patients. Conclusions: In patients with early TNBC, the neoadjuvant treatment of camrelizumab in combination with nab-paclitaxel and carboplatin demonstrated a high pCR rate with an acceptable safety profile. The second phase of the study is currently in progress to validate these findings. Citation Format: Weipeng Zhao, Xin Wang, Bin Zhang, Yehui Shi, Chen Wang, Xu Wang, Shufen Li, Chunfang Hao, Ning Lu, Yongsheng Jia, Li Zhang, Lan Zhang, Weixin Sun, Xuchen Cao, Zhongsheng Tong. Camrelizumab in Combination with Nab-Paclitaxel and Carboplatin versus Nab-Paclitaxel and Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer: A Multicenter, Open-Label, Randomized Controlled Study [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 PO1-03-11.

Abstract PO4-02-01: Characterization of immune and malignant cell evolution upon treatment pressure with aromatase inhibitors in locally advanced estrogen positive breast cancer

Abstract Background Aromatase inhibitors (AIs) are commonly used in the management of estrogen receptor-positive (ER+) breast cancer, as they effectively reduce estrogen levels which inhibits tumor growth and recurrence. In postmenopausal women with ER+ breast cancer, aromatase inhibitors are increasingly used in selected patients as neoadjuvant therapy to reduce the tumor burden before surgery and to improve overall treatment outcomes. Clinical trial The NEOLETEXE trial aimed to treat postmenopausal patients with locally advanced breast cancer. It was a neoadjuvant, randomized, open-label, intra-patient, cross-over, single-center phase II clinical trial. Most patients presented large T3/T4 tumors and/or N2/N3 involvement. Patients were randomly assigned to receive neoadjuvant therapy with either letrozole (2.5 mg daily) or exemestane (25 mg daily) for 3 months followed by a cross-over to the alternative AI for another 3 months followed by surgery. A total of 102 patients were enrolled in the NEOLETEXE trial. Aim of the study We aim at using single-cell analyses at different time points of treatment, to characterize evolutionary trajectories of cancer and immune cells in 23 patients from the NEOLETEXE trial. Methods Tumor biopsies taken before treatment (baseline) at crossover (after 3 months) and end of neoadjuvant therapy (after 6 months), were analyzed by single-cell RNA (scRNA), T cell receptor (TCR), and B cell receptor (BCR) sequencing. The data were first processed using cellRanger and the Seurat package. Results The main cell types found in tumors were identified through clustering of the scRNA data. We then focused on the epithelial cells to first distinguish between the normal and malignant epithelial cells using the InferCNV algorithm. For each patient, the analysis of inferred copy number events allowed to elucidate the genetic background of clones resistant or sensitive to aromatase inhibitors. This analysis unveiled the evolutionary dynamics of tumor heterogeneity during treatment. We next examined CD4, CD8, NK cells, and macrophages, using RNA velocity and diffusion pseudotime using CellRank and scVelo to delineate the differentiation trajectories of immune cell types. Conclusions We created a detailed map that provides a high-resolution view of the diverse cell types present in tumor biopsies from the NEOLETEXE trial. We characterize the impact of therapies on the evolutionary dynamics of both cancer and immune cells. Our analyzes sought insights into the underlying factors that contribute to the sensitivity and resistance to aromatase inhibitors. Citation Format: Leonard Schmiester, Salim Ghannoum, Marie Fongård, Marius Bjørnstad, Knut Selsås, Stephanie Geisler, Manouchehr Seyedzadeh, Unn-Cathrin Buvarp, Torben Lüders, Diether Lambrechts, Marianne Lyngra, Arnoldo Frigessi, Vessela Kristensen, Jürgen Geisler, Xavier Tekpli. Characterization of immune and malignant cell evolution upon treatment pressure with aromatase inhibitors in locally advanced estrogen positive 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 PO4-02-01.

Neoadjuvant Chemotherapy and Radiation Improves Recurrence-free and Overall Survival in Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.

The objective of this study is to analyze the outcomes of patients with resectable/borderline resectable PDAC who receive total neoadjuvant therapy vs upfront surgery. Patients who were treated at a single institution from 2006 to 2021 were included. The primary outcome was overall survival (OS). Secondary outcomes included disease free survival (DFS), rates of lymph node positivity, and R0 resection. All survival analyses were performed with intention-to-treat. 26 patients received neoadjuvant chemotherapy and radiation (TNT), 28 received neoadjuvant chemotherapy only (NAC), and 168 received upfront surgery. Demographics were comparable across all three groups. Patients who received TNT or NAC had longer OS and DFS compared to the surgery first patients (P < .01). Patients who received TNT had a lymph node positivity rate of 0% at time of surgery compared to 5.3% and 13.3% in the NAC and surgery-first groups, respectively (P < .01). The rate of R0 resection did not differ between groups (P = .17). Patients with resectable/borderline resectable PDAC who receive neoadjuvant therapy have longer OS and RFS relative to those who receive upfront surgery.

Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer: A Retrospective Multicenter Cohort Study.

According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group], (2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group]. Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38.9%) than patients with HER2 (2+)/ISH+ (18.1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months (P = .556). The addition of trastuzumab or trastuzumab plus pertuzumab to neoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52.17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype (P < .001). HER2E showed increased PCR rates compared to non-HER2E (P = .004). Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential.

Retrospective analysis of preoperative application of triple-modal pre-rehabilitation on postoperative recovery of colorectal cancer patients.

To retrospectively analyze the difference between triple-modal pre-rehabilitation and common treatment in patients with colorectal cancer (CRC). A total of 145 patients with CRC diagnosed by pathology and admitted to our hospital for surgery between June 2020 and June 2022 were included in the study. All patients were divided into two groups: the triple-modal pre-rehabilitation group (pre-rehabilitation group) and the common treatment group. The triple-modal pre-rehabilitation strategy included exercise (3-5 times per week, with each session lasting more than 50min), nutritional support, and psychological support. The study was designed to assess the potential of the pre-rehabilitation intervention to accelerate postoperative recovery by assessing the 6-min walk test, nutritional indicators, and HADS score before and after surgery. The pre-rehabilitation intervention did not reduce the duration of initial postoperative recovery or the incidence of postoperative complications, but it did increase the patients' exercise capacity (as determined by the 6-min walk test), with the pre-rehabilitation group performing significantly better than the common group (433.0 (105.0) vs. 389.0 (103.5), P < 0.001). The study also found that triple-modal pre-rehabilitation was beneficial for the early recovery of nutritional status in surgical patients and improved anxiety and depression in patients after surgery, especially in those who had not received neoadjuvant therapy. The triple-modal pre-rehabilitation strategy is of significant importance for reducing stress and improving the functional reserve of patients with colorectal cancer (CRC) during the perioperative period. The results of our study provide further support for the integration of the triple-modal pre-rehabilitation strategy into the treatment and care of CRC patients.

The Effect of chemo- and radiotherapy on tumor necrosis in soft tissue sarcoma– does it influence prognosis?

BackgroundSoft tissue sarcomas (STSs) are a heterogeneous group of tumors. Wide surgical resection is standard, often combined with neoadjuvant chemotherapy, radiotherapy, or both. Studies have shown the predictive value of tumor necrosis in bone sarcoma (BS); however, the role of necrosis in STS after neoadjuvant therapies is still unclear. This study aimed to investigate the role of chemo- and radiotherapy in the formation of tumor necrosis and to evaluate the influence of tumor necrosis on overall survival and local recurrence-free survival. Data from BS patients and patients who did not receive neoadjuvant therapy were compared.MethodsA total of 779 patients with STS or BS were treated surgically. In all patients, tumor-specific factors such as type, size, or grading and the type of adjuvant therapy were documented. Local recurrence (LR), the diagnosis of metastatic disease, and survival during follow-up were evaluated.ResultsA total of 565 patients with STS and 214 with BS were investigated. In STS, 24.1% G1 lesions, 34.1% G2 lesions, and 41.8% G3 lesions were observed. Two hundred twenty-four of the patients with STS and neoadjuvant therapy had either radiotherapy (RTx) (n = 80), chemotherapy (CTx) (n = 93), or both (n = 51). Three hundred forty-one had no neoadjuvant therapy at all. In STS, tumor necrosis after neoadjuvant treatment was significantly higher (53.5%) than in patients without neoadjuvant therapy (15.7%) (p < 0.001). Patients with combined neoadjuvant chemo-/radiotherapy had substantially higher tumor necrosis than those with radiotherapy alone (p = 0.032). There was no difference in tumor necrosis in patients with combined chemo-/radiotherapy and chemotherapy alone (p = 0.4). The mean overall survival for patients with STS was 34.7 months. Tumor necrosis did not influence survival in a subgroup of G2/3 patients. In STS with no neoadjuvant therapy and grading of G2/3, the correlation between necrosis and overall survival was significant (p = 0.0248). There was no significant correlation between local recurrence (LR) and necrosis.ConclusionSTS shows a broad spectrum of necrosis even without neoadjuvant chemo- or radiotherapy. After CTx or/and RTx necrosis is enhanced and is significantly pronounced with a combination of both. There is a trend toward higher necrosis with CTx than with RTx. Grading substantially influences the necrosis rate, but necrosis in soft-tissue sarcoma following neoadjuvant therapy does not correlate with better survival or a lower local recurrence rate, as in bone sarcomas.

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

Neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer (NORPACT-1): a multicentre, randomised, phase 2 trial

The value of the improved percutaneous and intravenous contrast-enhanced ultrasound diagnostic classification in sentinel lymph nodes of breast cancer.

Metastatic burden of sentinel lymph node (SLN) in breast cancer patient is the basis for the decision to choose SLN biopsy or axillary lymph node dissection (ALND). However, the diagnostic performance of the previous percutaneous contrast-enhanced ultrasound (P-CEUS) and intravenous contrast-enhanced ultrasound (IV-CEUS) pattern were not satisfied. This study aimed to establish new classification based on structural characteristics for P-CEUS and IV-CEUS of SLN in breast cancer and evaluate the diagnostic efficacy. This retrospective study included consecutive breast cancer patients who had not received neoadjuvant therapy in the First Affiliated Hospital of Sun Yat-sen University between June 2019 and December 2021. Conventional ultrasound, P-CEUS and IV-CEUS were performed. The new classification methods for P-CEUS and IV-CEUS of SLN were established based on structural characteristics of SLN. Pathology was considered as the gold standard, the diagnostic efficacy of P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound in SLNs was analyzed. The detection rate of SLN by P-CEUS in 368 patients was 95.42%. The P-CEUS pattern of SLNs was divided into six types. The IV-CEUS sequence was divided into three types. The IV-CEUS mode was divided into four types. Among the 438 SLNs detected by P-CEUS, 105 (23.97%) were malignant and 333 (76.03%) were benign. Among the previously classified P-CEUS, P-CEUS, IV-CEUS and combined contrast-enhanced ultrasound, the latter had the highest diagnostic efficacy (P<0.05), with sensitivity, specificity, positive predictive value, negative predictive value, accuracy and area under curve (AUC) of 81.90% (86/105), 97.30% (324/333), 90.53% (86/95), 94.46% (324/343), 93.61% (410/438) and 0.896 (0.864-0.923), respectively. The new classification of the P-CEUS and IV-CEUS features of SLNs was performed based on structural characteristics of lymph nodes. Compared with the previously classified P-CEUS, the new classification method has higher diagnostic performance. The combination of new classified P-CEUS and IV-CEUS is helpful to further improve the diagnostic performance of SLNs.

Oncological Safety of Skipping Axillary Lymph Node Dissection in Patients with Clinical N0, Sentinel Node-Positive Breast Cancer Undergoing Total Mastectomy

ObjectiveThis study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive.MethodsThis study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group.ResultsMean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70–2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69–5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02).ConclusionCollectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.

A randomized controlled trial of CAPEOX vs observation in patients with early-stage colorectal cancer with positive MRD after curative surgery (CAREME).

TPS225 Background: Most patients (pts) with early-stage colorectal cancer (CRC) have a good prognosis, but some still relapse shortly after surgery. Effective methods to assess the risk of recurrence in these pts and guide adjuvant chemotherapy (ACT) decision-making are lacking. Increasing studies have shown that circulating tumor DNA (ctDNA) can detect minimal residual disease (MRD) and identify pts with a high risk of recurrence. ACT could improve survival of MRD-positive pts with stage Ⅱ CRC suggested by recent studies, whether it is appropriate for those with stage Ⅰ or clinically low-risk stage Ⅱ CRC remains unknown. Methods: CAREME is a multicenter randomized controlled clinical trial aimed at investigating the benefit of chemotherapy for MRD-positive pts with early-stage CRC. Pts with resected stage Ⅰ or Ⅱ CRC will be evaluated by oncologists. Those who did not receive neoadjuvant therapy and are deemed suitable for active surveillance (i.e., ACT is not needed) will undergo a postoperative ctDNA test using MinerVa MRD assay (a tumor-informed assay covering 769 cancer-related genes). Pts with mismatch repair-deficient tumors will be excluded and stage Ⅱ pts should have no traditional high-risk features according to clinical practice guidelines. Pts with positive ctDNA (N = 38) will be equally randomized into two groups: treatment group (Arm A) or surveillance group (Arm B). Arm A will receive 8 cycles of CAPEOX therapy while pts in Arm B will not receive any ACT; both groups will undergo ctDNA tests at 6 months after randomization and be followed up every 3 months. The primary endpoint is 18-month recurrence-free survival, and a key secondary endpoint is ctDNA clearance at 6 months after randomization. Tumor samples from the pts will be collected for MRD assay and exploratory research. Accrual started in February 2023. Support: Genecast Biotechnology Company. Clinical trial information: NCT05699746 .

Development and Validation of a Prognostic Model for Postoperative Anastomotic Recurrence in Siewert II or III Adenocarcinomas Without Neoadjuvant Therapy in an East Asian Population.

Anastomotic recurrence leads to poor prognosis in patients with Siewert II or III adenocarcinoma who undergo radical gastrectomy and do not receive neoadjuvant therapy. We aimed to establish a prognostic model to evaluate the risk of postoperative anastomotic recurrence in patients with Siewert II or III adenocarcinoma who did not receive neoadjuvant therapy. We included 366 patients with Siewert II or III adenocarcinoma who were treated with radical gastrectomy without neoadjuvant therapy at Fujian Provincial Hospital (FPH) between 2012 and 2018 as the development cohort. Cox regression was used to verify prognostic factors for anastomotic recurrence, and a nomogram was established. The nomogram was externally validated using a combined cohort of two external centers. Patients were classified into high- or low-risk groups according to the diagnostic threshold and nomogram scores, and recurrence-related survival analysis was analyzed. The average age was 64.6 years, and 285 patients were male. All surgeries were successfully performed (185 open vs 181 laparoscopic). The 3-year anastomotic recurrence rate was significantly lower in the low-risk group (3.5% vs 18.8%, P < 0.001). The predictive performance was verified in the external validation cohort. This model better stratified patient survival than the American Joint Committee on Cancer (AJCC) TNM staging system. This novel nomogram with surgical margin, postoperative tumor node metastasis (pTNM) stage, and neural invasion as prognostic factors has a significant predictive performance for the risk of anastomotic recurrence after radical gastrectomy in patients with Siewert II or III adenocarcinoma.

Survival Outcomes and Patterns of Care for Stage II or III Resected Gastric Cancer by Race and Ethnicity

Many multimodality treatment regimens exist for gastric adenocarcinoma, including neoadjuvant vs adjuvant chemotherapy, radiation, or both. Neoadjuvant therapy is recommended in the United States for patients with locally advanced gastric cancer; however, it is unknown whether the outcomes of neoadjuvant therapy are associated with race and ethnicity. To evaluate the differences in outcomes by race and ethnicity of patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy. This retrospective cohort study examined the National Cancer Database from the American College of Surgeons for patients with clinical stage II or III gastric adenocarcinoma, excluding gastric cardia tumors, undergoing surgical resection procedures from January 2006 to December 2019. Statistical analysis was performed from December 2021 to May 2023. Patients were stratified by race and ethnicity, and their outcomes were analyzed for those who received and did not receive neoadjuvant therapy. The Cox proportional hazard model was used to compare overall survival (OS) between racial and ethnic groups (Asian, Black, Hispanic, and White) overall and according to receipt of neoadjuvant therapy. Among those who received neoadjuvant therapy, proportional differences in pathological responses were calculated in each group. Among a total of 6938 patients in the cohort, 4266 (61.4%) were male; mean (SD) age was 65.9 (12.8) years; 1046 (15.8%) were Asian, 1606 (24.3%) were Black, 1175 (17.8%) were Hispanic, and 3540 (53.6%) were White. Compared with other races and ethnicities, the group of White patients had significantly more who were 65 years or older with more comorbidities. White patients underwent surgical resection procedures alone without neoadjuvant or adjuvant therapy more frequently than other races and ethnicities. Asian and Black patients had the highest proportion of being downstaged or achieving pathological complete response after neoadjuvant therapy. In multivariate models, perioperative chemotherapy was associated with improved OS (HR, 0.79 [95% CI, 0.69-0.90]), whereas number of positive lymph nodes and surgical margins were associated with the largest decreases in OS. Asian and Hispanic race and ethnicity were associated with significantly improved OS compared with Black and White races (eg, Asian patients: HR, 0.64 [95% CI, 0.58-0.72]; and Hispanic patients: HR, 0.77 [95% CI, 0.69-0.85]). Black race was associated with improved OS compared with White race when receiving neoadjuvant therapy (HR, 0.78 [95% CI, 0.67-0.90]). In this large nationwide cohort study of survival outcomes among patients with resected clinical stage II or III gastric cancer, there were significant differences in response to treatment and OS between different racial and ethnic groups.

Prognostic significance of tumor budding in patients with pancreatic invasive ductal carcinoma who received neoadjuvant therapy

Neoadjuvant therapy is commonly used for invasive pancreatic ductal carcinoma (PDAC). Tumor budding and high podoplanin expression in cancer-associated fibroblasts (CAFs) are prognostic factors in patients with various carcinomas including PDAC who have not received neoadjuvant therapy. In this study, we investigated whether tumor budding and podoplanin-positive CAFs are associated with outcomes in Japanese PDAC patients with neoadjuvant therapy. Histopathological findings of surgically resected PDACs with neoadjuvant therapy from 2005 to 2018 were reviewed (n = 97). With reference to International Tumor Budding Consensus Conference recommendations, tumors were evaluated for budding at 20 × magnification (/0.785 mm2) and at 40 × magnification (/0.237 mm2; mean number of fields: 3) for podoplanin expression in CAFs (%). Overall survival, disease-free survival, and disease-specific survival (DSS) were analyzed using the log-rank test and Cox proportional hazards model. After adjusting for T category, N category, resection margin, and adjuvant therapy, multivariate analyses demonstrated that tumor budding at 40 × magnification was an independent prognostic factor for worse DSS (hazard ratio: 2.41, p = 0.022). Tumor budding at 20 × magnification and podoplanin-positive CAFs tended to be associated with worse DSS; however, these findings were not statistically significant. Our findings indicate that tumor budding is an independent prognostic factor in PDAC patients with neoadjuvant therapy.