Long-term Disease-free Survival Research Articles

360. RECURRENCE PATTERNS AFTER PRIMARY SURGERY AND NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL ADENOCARCINOMA: ACROSS THE CROSS RECURRENCES

Abstract Background Our publication Across the CROSS in daily practice challenged the routine use of neoadjuvant chemoradiotherapy for locally advanced esophageal adenocarcinoma, showing a comparable 5-year overall and disease-free survival after primary surgery. This current study reevaluated overall and disease-free survival on long term and aimed to differentiate recurrence patterns and its final impact on overall survival. Methods This retrospective cohort study with propensity score-matched analysis included all surgically treated patients between 2000 and 2018 with locally advanced adenocarcinoma (cT1/2N+ or cT3/4N0/+). Exclusion criteria of the CROSS trial were applied. Patients were matched on age, Charlson comorbidity score, clinical tumor length, and lymph node status. The primary end point was time to recurrence. Results 149 propensity score-matched cases were defined in each group. There was still no significant difference after 10 years in median overall survival (33.6 vs 34.9 months, p=0.52) and median disease-free survival (14.1 vs 14.0 months, p=0.13) between both groups. Furthermore, nCRT resulted in a shorter time to overall recurrence (6.3 vs 11.5 months, p=0.004) and locoregional recurrence (6.3 vs 13.6 months, p=0.005). Additionally, overall survival after diagnosis of recurrence was also significantly shorter for nCRT patients than for primary surgery patients (6.9 vs 9.6 months, p=0.032). Conclusion Our propensity score-matched results indicate that primary surgery can offer a comparable long-term overall and disease-free survival as nCRT followed by surgery. Both overall and locoregional recurrences occur earlier in nCRT patients and overall survival after recurrence is significantly longer after primary surgery.

CD19 CAR T cells for B cell malignancies: a systematic review and meta-analysis focused on clinical impacts of CAR structural domains, manufacturing conditions, cellular product, doses, patient’s age, and tumor types

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient’s age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR’s hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies.

Nodal Response and Survival After Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer: 20-Year Experience from a Single Institution.

Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET. Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category. We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13). In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease.

AB001. Development of tumour-targeted therapy for the treatment of adult and paediatric high-grade gliomas.

Brain cancer patients, especially those suffering from high-grade gliomas (HGGs) face a bleak future with very dismal long-term disease-free survival outcomes due to the limited treatment options currently available. Therefore, there is an unmet need for new therapeutic intervention that extends patients' progress-free survival and improves their quality of life. A significant hurdle is the inability of current chemotherapy agents to cross the blood-brain barrier (BBB). BBB acts as a protective shield that filters the blood to ensure nothing harmful makes it to the brain. This protection is usually good, but it becomes a problem if you want to deliver therapeutic cancer drugs through it. This barrier blocks 98% of drugs from entering the brain. Even the ones that cross BBB are unevenly distributed in the normal brain and tumour tissue, resulting in mediocre treatment and severe side effects. We are developing drug delivery systems that can cross the BBB and facilitate the specific accumulation of drugs in the tumour tissue. This will significantly improve the efficacy of anticancer drugs in treating various brain cancers and reduce systemic toxicity. Our group has explored and developed BBB crossing and tumour targeting near infra-red dyes, which can be covalently attached to Food and Drug Administration (FDA)-approved chemotherapy agents (drug-dye conjugates), thereby delivering it to the tumour tissue. We synthesized such drug-dye conjugates to target various aberrant pathways in HGG and tested these conjugates against patient-derived HGG cell lines. One such conjugate was tested on a mouse model of glioblastoma, an aggressive form of HGG, and shown to cross the BBB and specifically accumulate in tumour tissue, bringing forth tumour burden reduction. The results obtained from this work serve as proof of principle that enables tumour-specific drug delivery to treat HGG. This work also paves the way for treating other brain cancers and central nervous system (CNS) disorders like Parkinson's and Alzheimer's disease, for which no adequate therapy exists.

Impact of Thoracic Duct Resection on Long-Term Survival After Esophagectomy: Individual Patient Data Meta-analysis.

Radical esophagectomy, including thoracic duct resection (TDR), has been proposed to improve regional lymphadenectomy and possibly reduce the risk of locoregional recurrence. However, because of its impact on immunoregulation, some authors have expressed concerns about its possible detrimental effect on long-term survival. The purpose of this review was to assess the influence of TDR on long-term survival. PubMed, MEDLINE, Scopus, and Web of Science databases were searched through 15 March 2024. Overall survival (OS), cancer specific survival (CSS), and disease-free survival (DFS) were primary outcomes. Restricted mean survival time difference (RMSTD), risk ratio (RR), standardized mean difference (SMD), and 95% confidence intervals (CI) were used as pooled effect size measures. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology was employed to evaluate the certainty of evidence. The analysis included six studies with 5756 patients undergoing transthoracic esophagectomy. TDR was reported in 49.1%. Patients' ages ranged from 27 to 79 years and 86% were males. At 4-year follow-up, the multivariate meta-analysis showed similar results for the comparison noTDR versus TDR in term of OS [- 0.8 months, 95% confidence interval (CI) - 3.1, 1.3], CSS (0.1 months, 95% CI - 0.9, 1.2), and DFS (1.5 months, 95% CI - 2.6, 5.5). TDR was associated with a significantly higher number of harvested mediastinal lymph nodes (SMD 0.57, 95% CI 0.01-1.13) and higher risk of postoperative chylothorax (RR = 1.32; 95% CI 1.04-2.23). Anastomotic leak and pulmonary complications were comparable. TDR seems not to improve long-term OS, CSS, and DFS regardless of tumor stage. Routine TDR should not be routinely recommended during esophagectomy.

Sequencing of cellular therapy and bispecific antibodies for the management of diffuse large B-cell lymphoma.

Historically, management of relapsed or refractory (R/R) Diffuse large B-cell (DLBCL) following first-line chemoimmunotherapy has been second-line chemotherapy, followed by high-dose chemotherapy and consolidative autologous hematopoietic stem cell transplantation (auto-HSCT), resulting in durable remissions in approximately 40% of patients. In 2017, chimeric antigen receptor (CAR) T-cell therapy changed the landscape of treatment for patients with R/R DLBCL, with complete response rates ranging from 40-58% and long-term disease-free survival of >40% in the highest risk subgroups, including patients who relapsed after auto-HSCT. Since that time further studies have demonstrated improved overall response rates (ORRs) and survival outcomes in patients with primary refractory or early-relapse (relapse 50% of patients will relapse in the post-CAR T-cell setting. In the past two years, two CD20 x CD3 bispecific antibodies (BsAbs) were FDA approved for the treatment of R/R DLBCL after two or more lines of systemic therapy. These BsAbs have demonstrated ORRs exceeding 50% and durable remissions at > 2yrs of follow-up. Additionally, a notable treatment advantage of BsAbs is their ability to be administered in the community setting, making treatment more accessible for patients. The development and advancement of these novel therapies raise questions regarding the ongoing role of HSCT in the management of relapsed and refractory DLBCL and how to best sequence cellular and Bi-specific therapies to optimize patient outcomes.

Long-Term Analysis of NRG Oncology RTOG 0415: A Randomized Phase III Noninferiority Study Comparing Two Fractionation Schedules in Patients With Low-Risk Prostate Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).

Laparoscopic hepatectomy is a feasible and safe choice for primary hepatocellular carcinoma located at favorable location during the development period of a tertiary hospital: A case–control study

ABSTRACT Objectives: Laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC) has been well known for its advantages in the past 10 years, but little is known regarding its oncologic outcomes while the technique is being developed at an institution. This study aimed to evaluate the safety and effectiveness of LH for patients with primary HCC at favorable locations, focusing on postoperative short- and long-term outcomes during the development period. Materials and Methods We retrospectively reviewed patients diagnosed with primary HCC who underwent hepatectomy between January 2013 and December 2019 at Hualien Tzu Chi Hospital. Patients with HCC at favorable locations (anterolateral segments) were collected and divided into laparoscopic and open hepatectomy (OH) groups. The data for long-term outcomes, as the primary endpoint, and postoperative outcomes, as the secondary endpoint, were collected. Results: The review included 159 patients, among which 42 and 44 patients in favorable locations underwent open and laparoscopic hepatectomies, respectively. There were no significant differences in intraoperative blood loss, major complication rate, and 90-day mortality rate between the two groups. The laparoscopic group had a lower transfusion rate, shorter postoperative hospital stay, and lower 90-day readmission rate. There were no significant differences in 12-, 36-, and 60-month overall survival and disease-free survival. Conclusion: LH for favorably located HCC is the preferred surgical approach compared to OH due to the decreased transfusion rate, shorter postoperative hospital stay, and lower 90-day readmission rate. LH did not compromise the 90-day mortality rate with sustained long-term overall and disease-free survival. LH for favorably located HCC is a safe and effective surgical approach even during the development period.

Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiotherapy in patients with locally advanced rectal cancer: long-term results of the UNICANCER-PRODIGE 23 trial

The standard of care for the treatment of locally advanced rectal cancer (LARC) results in an excellent local disease control but the metastasis rates remain high. PRODIGE 23 demonstrated improved disease-free survival (DFS) and metastasis-free survival (MFS) with total neoadjuvant therapy versus standard of care in this population. Long-term analysis of overall survival (OS) is reported here. The study design, participants, and primary endpoint DFS have been reported for this multicenter, randomized, open-label, phase III trial investigating the neoadjuvant chemotherapy with mFOLFIRINOX (6 cycles) followed by chemoradiotherapy, surgery, and adjuvant chemotherapy (6 cycles), versus chemoradiotherapy, surgery, and adjuvant chemotherapy (12 cycles) in patients with locally advanced rectal adenocarcinoma under peritoneal reflection on magnetic resonance imaging, and staged cT3/T4. Key secondary endpoints included OS, MFS, and local and metastatic recurrence rate. With a median follow-up of 82.2 months, the 7-year DFS was 67.6% [95% confidence interval (CI) 60.7% to 73.9%] and 62.5% (95% CI 55.6% to 68.6%) [restricted mean survival time (RMST) difference 5.73 months, 95% CI 0.05-11.41 months, P= 0.048] in the neoadjuvant chemotherapy and the standard-of-care groups, respectively. The 7-year MFS was 79.2% (95% CI 73.0% to 84.4%) in the neoadjuvant chemotherapy group and 72.3% (95% CI 65.8% to 77.8%) in the standard-of-care group (RMST difference 6.1 months, 95% CI 0.93-11.37 months, P= 0.021). The 7-year OS was 81.9% (95% CI 75.8% to 86.6%) in the neoadjuvant chemotherapy group and 76.1% (95% CI 69.7% to 81.2%) in the standard-of-care group (RMST difference 4.37 months, 95% CI 0.35-8.38 months, P= 0.033). The safety profile remained unchanged since the previous analysis. Neoadjuvant chemotherapy with mFOLFIRINOX followed by chemoradiotherapy improved OS, confirmed long-term DFS and MFS benefits in LARC patients, and should be considered as one of the best options of care for these patients.

The effect of ileal resection length on postoperative complications and prognosis in right colon cancer

BackgroundThere is a lack of literature on the length of the terminal ileum to be resected in right hemicolectomy for colon cancer. Therefore, we aimed to determine the mean ileal loop length and the effect of this variation on postoperative complications and long-term oncological outcomes in patients who underwent right hemicolectomy.MethodsRight hemicolectomy surgeries performed for colon cancer in a tertiary care hospital between January 2011 and December 2018 were retrospectively analyzed from a prospective database. Two patient groups were established based on the mean length of the resected ileum above and below 7 cm. The two groups were compared for clinicopathological data, postoperative complications, mortality, long-term overall survival (OS) and disease-free survival (DFS). The factors contributing to OS and DFS were analyzed.ResultsThe study included 217 patients. Body mass index (BMI) values were significantly higher in the ileum resection length > 7 cm group (p = 0.009). Pathological N stage, tumor diameter, and number of metastatic lymph nodes were significantly higher in the ileum resection length > 7 cm group (p = 0.001, p = 0.001, and p = 0.026, respectively). There was no significant difference for postoperative complication and mortality rates between the two groups. The mean follow-up period was 61.2 months (2-120) in all patients. The total number of deaths was 29 (11.7%) while the 60-month OS was 83.5% and 50-month DFS was 81.8%. There was no significant difference between the groups in terms of OS and DFS rates (p > 0.05).ConclusionsExcessive resection of the distal ileum in right hemicolectomy does not provide any benefit in terms of prognosis and complications.The ileum resection length and values close to it in our study appear to be sufficient.

Comparative study of short-and long-term results in patients with perihilar cholangiocarcinoma undergoing surgical resection: does the extent and side of resection really affect outcome?

The surgical management of perihilar carcinoma (pCCA) is still subject of ongoing debate. To provide more clarity, this study was conducted to evaluate outcomes related to the side and extent of heatectomy in patients with pCAA. A total of 32 patients with curative resection for pCCA were identified from our prospective database. Short-and long-term clinical outcome data and histopathological results were compared between right-sided (R-H) and left-sided (L-H) hepatectomy. Nine patients (28.13%) underwent left-sided hepatectomy while a right-sided hepatectomy was accomplished in 23 patients (71.87%). In the R-H group hepatic conditioning of the future liver remnant (FLR) prior to extended resection was necessary in 13 cases (56.52%), and simultaneous pancreaticoduodenectomy was performed in 5 patients (21.74%). The arterial and portal venous reconstruction rates were 17.39% and 11.11% (P=1.00), and 60.87% and 33.33% (P=0.243) in the R-H and L-H groups, respectively. No statistically significant differences in short-term morbidity and mortality between both groups were observed. The rate of R0 resections was comparable (R-H: 78.26% versus L-H: 66.67%; P=0.654) resulting in similar long-term overall and disease-free survival rates after right-and left hepatectomy. In patients with pCCA, both right- and left-sided resections appear to be safe and feasible options with similar postoperative morbidity and oncologic outcomes. Consecutively, the ideal surgical approach should be patient-tailored based on anatomical considerations and the functional future liver capacity.

PRDM1 rs2185379, unlike BRCA1, is not a prognostic marker in patients with advanced ovarian cancer.

Ovarian cancer (OC) is mostly diagnosed in advanced stages with high incidence-to-mortality rate. Nevertheless, some patients achieve long-term disease-free survival. However, the prognostic markers have not been well established. The primary objective of this study was to analyse the association of the suggested prognostic marker rs2185379 in PRDM1 with long-term survival in a large independent cohort of advanced OC patients. We genotyped 545 well-characterized advanced OC patients. All patients were tested for OC predisposition. The effect of PRDM1 rs2185379 and other monitored clinicopathological and genetic variables on survival were analysed. The univariate analysis revealed no significant effect of PRDM1 rs2185379 on survival whereas significantly worse prognosis was observed in postmenopausal patients (HR = 2.49; 95%CI 1.90-3.26; p= 4.14 × 10 - 11) with mortality linearly increasing with age (HR = 1.05 per year; 95%CI 1.04-1.07; p= 2 × 10 - 6), in patients diagnosed with non-high-grade serous OC (HR = 0.44; 95%CI 0.32-0.60; p= 1.95 × 10 - 7) and in patients carrying a gBRCA1 pathogenic variant (HR = 0.65; 95%CI 0.48-0.87; p= 4.53 × 10 - 3). The multivariate analysis interrogating the effect of PRDM1 rs2185379 with other significant prognostic factors revealed marginal association of PRDM1 rs2185379 with worse survival in postmenopausal women (HR = 1.54; 95%CI 1.01-2.38; p= 0.046). Unlike age at diagnosis, OC histology or gBRCA1 status, rs2185379 in PRDM1 is unlikely a marker of long-term survival in patients with advance OC.

Resection Margin Status and Long-Term Outcomes after Pancreaticoduodenectomy for Ductal Adenocarcinoma: A Tertiary Referral Center Analysis.

The influencing role of resection margin (R) status on long-term outcomes, namely overall (OS) and disease-free survival (DFS), after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) is not still clear. The aim of this study is to evaluate the prognostic impact of R status after PD and to define tumor characteristics associated with a positive resection margin (R1). All PDs for PDAC performed between 2012 and 2023 were retrospectively enrolled. The effect of R status, patient clinico-demographic features, and tumor features on OS and DFS were assessed. One-hundred and sixty-seven patients who underwent PD for PDAC were included in the study. R0 was achieved in 105 cases (62.8%), while R1 was evidenced in 62 patients (37.1%). R1 was associated with a decreased OS (23 (13-38) months) as compared to R0 (36 (21-53) months) (p = 0.003). Similarly, DFS was shorter in R1 patients (10 (6-25) months) as compared to the R0 cohort (18 (9-70) months) (p = 0.004), with a consequent higher recurrence rate in cases of R1 (74.2% vs. 64.8% in the R0 group; p = 0.04). In the multivariate analysis, R1 and positive lymph nodes (N+) were the only independent influencing factors for OS (OR: 1.6; 95% CI: 1-2.5; p = 0.03 and OR: 1.7; 95% CI: 1-2.8; p = 0.04) and DFS (OR: 1.5; 95% CI: 1-2.1; p = 0.04 and OR: 1.8; 95% CI: 1.1-2.7; p = 0.009). Among 111 patients with N+ disease, R1 was associated with a significantly decreased DFS (10 (8-11) months) as compared to R0N+ patients (16 (11-21) months) (p = 0.05). In conclusion, the achievement of a negative resection margin is associated with survival benefits, particularly in cases of N1 disease. In addition, R0 was recognized as an independent prognostic feature for both OS and DFS. This further outlines the relevant role of radical surgery on long-term outcomes.

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study)

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

Intentional Dural Resection during en bloc Spinal Resection Could Provide a Secure Surgical Margin for Patients with Recurrent Spinal Tumors.

It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. All six patients were followed up for 24 to 46 months (mean follow-up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection-related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long-term disease-free survival with acceptable complications and satisfying neurological function.

Comparison of laparoscopic and open surgery for colorectal malignancy in obese patients: a propensity score-weighted cohort study.

Insufficient evidence exists to ascertain the long-term prognosis in patients with obesity undergoing laparoscopic surgery versus open surgery for colorectal cancer. Employing an institutional database from 2009 to 2019, we assessed individuals with a BMI of greater than or equal to 30kg/m 2 who underwent surgery for primary stage I-III colorectal adenocarcinoma. The authors used propensity score-weighted analysis to compare short-term and oncologic outcomes between laparoscopic and open surgical approaches. This study enrolled 473 patients (open vs. laparoscopic surgery: 220 vs. 253; median follow-up period, 60months). The laparoscopy group showed a significantly longer operative time (252 vs. 212 min), a higher anastomotic-leakage rate (5.14% vs. 0.91%), and a greater proportion of Clavien-Dindo class greater than III complications (5.93% vs. 1.82%). The open group showed a higher wound infection rate (7.27% vs. 3.16%) and a higher readmission rate (6.36% vs. 2.37%). After propensity score weighting, laparoscopy was inferior to open surgery in terms of long-term overall survival (hazard ratio: 1.43), disease-free survival (1.39), and recurrence rate (21.1% vs. 14.5%). In the subgroup analysis, female patients, older individuals, stage III patients, patients with rectal cancer, and those who underwent surgery after 2014 showed inferior long-term outcomes after laparoscopy. Laparoscopic colorectal cancer surgery for patients with obesity requires significant caution. Despite good short-term outcomes, this procedure is associated with hidden risks and poor long-term prognoses. In female patients, older individuals, stage III patients, patients with rectal cancer, and those treated in the late surgery era subgroups, caution is advised when performing laparoscopic surgery.

EGFR-TKI as neoadjuvant treatment in patients with NSCLC with EGFR sensitive mutation: A retrospective real-world analysis.

8081 Background: This study aimed to evaluate the efficacy and outcome of Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) as preoperative neoadjuvant treatment in patients with NSCLC and EGFR sensitive mutation. Methods: A retrospective analysis was conducted. Patients with resectable stage I-III NSCLCs and received neoadjuvant treatment with any generation of EGFR-TKI before surgical resection were enrolled. The primary endpoint were major pathological response (MPR) and objective response rate (ORR), the second endpoints included diseases down staging, surgical outcomes, disease-free survival (DFS) and overall survival (OS). Results: A total of 58 patients were enrolled. Female accounted for 62.1% and most of them (77.6%) were never-smoker. Forty-five (77.6%) patients received the first generation of EGFR-TKI and 11 received the third. The median duration of EGFR-TKI before surgery was 3.6 months (0.7-19.5m). Nine (15.5%) patients achieved MPR and one patient (1.71%) achieved pathological complete response (pCR). The ORR was 60.3% (35/58) according to RECIST v1.1. Eighteen patients achieved TNM downstaging with T downstaging occurred in 44.8% of patients and N downstaging was about 32.8%. Majority of patients (96.6%) underwent thoracoscopic surgery and the rate of R0 resection was 82.8% (48/58). The DFS and OS of the whole cohort was 25.7months and not reached respectively. Patients with MPR had statistically improved outcomes than those without. What noticeable was that patients with tumor regression grade 3 (13/58) (residual viable tumor cells counts for 10% to 50%) also demonstrated a significant benefit from EGFR-TKI preoperative treatment than those with TRG4 or 5 (residual viable tumor cells&gt;50%) (p = 0.01). We define patients with TRG1 to TRG3 as deep pathological regression (DPR) and the rest as non-DPR, and the DPR cohort showed significantly prolonged DFS than those with non-DPR (median DFS, 60.9 vs 16.7 months; HR, 0.29 (95%CI: 0.11-0.74), p = 0.006), the data of OS was not mature. Subgroup analysis validated DPR was an independent predictive factor for DFS. Conclusions: EGFR-TKI as neoadjuvant therapy had good effect on tumor pathological regression and disease downstaging, DPR patients were more likely to achieve long-term disease-free survival. Patients with NDPR should be closely followed up and appropriate adjuvant therapy was necessary after surgery due to the high risk of reccurence.

Abstract PO5-17-01: Pre-treatment tumor infiltrating lymphocytes are associated with higher likelihood of pathologic complete response among black women with TNBC receiving neoadjuvant chemoimmunotherapy

Abstract Background: High risk, early-stage triple negative breast cancer (TNBC) is a heterogenous disease that is associated with early recurrence and high mortality, particularly among black women as compared to their white counterparts. Pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) is a strong-predictor of long-term disease-free survival in TNBC, and the KEYNOTE-522 trial demonstrated that the addition of immunotherapy (pembrolizumab) to NACT resulted in a higher likelihood of pathologic complete response (pCR) in high-risk early-stage TNBC. Following these findings, the standard of care has been to administer the K522 regimen (K522R) in the neoadjuvant setting for patients with high risk early-stage TNBC. However, our understanding of the clinical and tumor characteristics to prognosticate response to K522 are lacking, and additional real-world data is needed to better understand if these variables differ among race. Methods: We evaluated 76 patients who were treated with the K522R at our institution. There were slides available from 29 patients’ pre-treatment biopsies for pathology review. In the available slides, tumor infiltrating lymphocytes (TIL) were evaluated as the percentage of lymphocytes in the stroma within the tumor area. For the remaining cases that did not have available slides, these variables were retrieved from pathology reports and patients’ charts. Patient characteristics including age, race and body mass index (BMI) were acquired via retrospective chart review. These clinicopathologic variables were correlated with pCR, which was defined by the absence of invasive carcinoma in the breast and axillary lymph nodes at the time of surgery. Binary logistic regression analysis was performed to correlate the above variables with pCR versus residual disease (RD). Results: Seventy-six pre-treatment biopsy specimens treated with the K522R were evaluated. The patient population spanned a broad spectrum of age, body habitus, and race, with mean age 55, mean BMI 28.3, and predominantly black (over 60 percent) population. At the time of analysis, 64 of the 76 patients had completed the K522R and subsequently undergone surgery at our institution. Of the 64 patients who had undergone definitive surgery, 31 (48.4%) achieved pCR. In univariate analysis, pre-treatment TIL was significantly associated with attainment of pCR, with TIL of 28.5% (± 19.1) in patients who achieved pCR versus 9.73% (± 9.40) in those who had RD (95% CI 1.03-1.21, p=0.014*). When TIL was further stratified by race, mean percentage of TIL was significantly higher among black women who achieved pCR (27.5% ± 4.7) compared to black women with RD (12.2% ± 3.05) (95% CI 0.021 – 0.197, p=0.016*). Additionally, mean percentage of TIL was higher overall among black women when compared to the white patients in our cohort, though this finding was not statistically significant (p=0.252). Conclusion: Our real-world data demonstrates high levels of pre-treatment TIL are significantly associated with achievement of pCR in patients with TNBC treated with the K522 regimen. When TIL was further stratified by race, black patients were found to have higher TIL than white patients. Within the black population, a statistically significant difference in TIL percentage was found in those achieving pCR compared to those with RD. It is well understood that black women often have poorer breast cancer outcomes than white women, and our finding of higher TIL percentage among this population, along with the significant association between TIL and attainment of pCR with chemoimmunotherapy, could have important implications for optimization of therapy. Further exploration of this phenomenon in larger, diverse breast cancer populations is warranted. Citation Format: Sarah Wood, Ji-Hoon Lee, Yuan Gao, Xiaoxian Li, Jane Meisel. Pre-treatment tumor infiltrating lymphocytes are associated with higher likelihood of pathologic complete response among black women with TNBC receiving neoadjuvant chemoimmunotherapy [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 PO5-17-01.

Abstract 5254: The “off-the-shelf ”CD19-CAR-Vδ1T cells demonstrated an enhanced therapeutic effect on B-cell malignancy models

Abstract Background: The commercialization of autologous chimeric antigen receptor T cell (CAR-T) is hindered by the expensive and time-consuming manufacturing process, presenting major challenges. The development of allogeneic products is proposed as an alternative strategy to overcome these obstacles. Vδ1T cells, possessing active homing capability, are known to infiltrate tumor tissues and have been linked with favorable patient prognosis due to their direct killing effect via innate immunity and their sensitive T cell receptors that can broadly recognize tumor antigens. Unlike conventional αβ T cells, Vδ1 TCRs are not restricted by major histocompatibility complexes (MHCs), thus preventing the development of graft-versus-host disease (GVHD). Therefore, Vδ1T cells were hypothesized to be a superior candidate for universal CAR-T cells. Nevertheless, the small portion of Vδ1T cells (less than 1%) in peripheral blood posts a significant challenge for CMC and production. Here we present the successful development of CD19-CAR-Vδ1T cells, which demonstrate enhanced therapeutic efficacy on B-cell malignancy models. Methods: High-purity CD19-CAR-Vδ1T cells were prepared using PersonGen's proprietary platform technology. Multiple CAR structures were tested for cytotoxicity, and the fourth-generation CAR-transduced Vδ1 cells designated as UTAA09 exhibited sustained killing of CD19+ target cells. UTAA09 underwent in-depth research regarding its anti-tumor efficacy and safety. Results: The Vδ1T cell purity exceeded 95%, while the residual TCRαβ count remained under 1%. The CAR transduction efficiency remained stable across batches, with medium CAR+~30%, and up to 2×1011 UTAA09 cells were harvested in compliance with GMP standards. The presence of secreted IL-2 significantly increased the persistence of UTAA09 in vitro, and UTAA09 showed comparable anti-tumor activity and expansion rates to CD19-CAR-αβT cells. Notably, no exhaustion phenotype was detected for UTAA09 after multiple antigen stimulation processes. Moreover, UTAA09 lacked detectable IL-17A, indicating a non-promoting characteristic in tumor growth. In the xenograft model, significant inhibition of tumor growth was observed in all mice, of which 40% achieved long-term disease-free survival (p&amp;lt;0.01) . On days 5, 12, and 19 after the administration of UTAA09, Vδ1T cells underwent significant expansion in all 5 mice tested. Subsequent analysis confirmed that the majority of these expanded Vδ1T cells were CAR+ cells, indicating the specific and long-lasting expansion of CD19-CAR+ Vδ1T cells in vivo. Importantly, none of the mice experienced significant weight loss, demonstrating the safety and outstanding in vivo effectiveness of UTAA09. Conclusion: UTAA09 shows potential as an off-the-shelf allogeneic cellular therapy for the treatment of B-cell malignancies and autoimmune diseases derived from B cells. Citation Format: Dan Chen, Fengtao You, Cheng Chen, Shufen Xiang, Ping Zhang, Hai Wu, Zhong Zheng, Min Wang, Xingbing Wang, Huimin Meng, Nan Yang, Bozhen Zhang, Lin Yang. The “off-the-shelf ”CD19-CAR-Vδ1T cells demonstrated an enhanced therapeutic effect on B-cell malignancy models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5254.

Laparoscopic liver resection is superior to radiofrequency ablation for small hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched studies.

The approach in small hepatocellular carcinoma (HCC) is controversial, no prospective randomized trials to compare ablative or surgical approaches. We compared the surgical and oncological outcomes after laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in small HCC patients based on matched cohort studies that performed propensity score matching (PSM). We systemically searched the PubMed, Cochrane Library, Embase, Web of Science, and the Chinese BioMedical Literature (CBM) databases. All published propensity score-matched studies that compared LH and RFA for small HCC were included in this study. Eight studies with a total of 1273 small HCC cases were included. The results of the meta-analysis revealed that there was no significant difference in the 1- year overall survival (OS) rate between the two groups, whereas the LH group had significantly higher 3- year overall survival rate (RR = 1.14, 95% CI 1.08-1.20, p < 0.00001) as well as 1- and 3-year disease-free survival (DFS) rates (RR = 1.31, 95% CI 1.22-1.42, p < 0.00001; RR = 1.66, 95% CI 1.46-1.90, p < 0.00001) than the RFA group. Meanwhile, the local recurrence rate and intrahepatic distant recurrence rate were significantly lower in the LH group than in the RFA group (RR = 0.29, 95% CI 0.20-0.42, p < 0.00001; RR = 0.67, 95% CI 0.49-0.92, p = 0.01). In comparison with the LH group, the RFA group had a lower incidence of overall and major postoperative complications (RR = 1.81, 95% CI 1.47-2.24, p < 0.00001; RR = 2.76, 95% CI 1.48-5.12, p = 0.001), but there was no significant difference in postoperative mortality between the two groups. In addition, further comparison of single postoperative complications showed that the incidence of ascites was lower in the RFA group than in the LH group (RR = 3.62, 95% CI 1.64-7.96, p = 0.001), whereas there was no significant difference in the incidence of postoperative bleeding, abdominal infection and bile leakage between the two groups (RR = 3.50, 95% CI 0.74-16.61, p = 0.11; RR = 5.00, 95% CI 0.59-42.23, p = 0.14; RR = 4.00, 95% CI 0.45-35.23, p = 0.21). Besides, the hospital stay was shorter in the RFA group than in the LH group (MD = 4.29, 95% CI 2.06-6.53, p = 0.0002). Our meta-analysis demonstrated that in comparison with RFA in the treatment of small HCC, LH provided superior long-term OS and DFS together with lower rates of local and intrahepatic distant recurrence after surgery. However, RFA was associated with better short-term outcomes.