Terms Of Disease-free Survival Research Articles

Comparison between upfront surgery vs salvage surgery following definitive chemoradiation in the treatment of potentially curable locally advanced oral cavity cancer: a retrospective study

Background: We conducted a study to compare the outcomes of upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. This study aims to compare the short-term outcomes (postoperative morbidity, recurrence) & long-term outcomes (overall survival, disease-free survival) between upfront surgery and salvage surgery following definitive chemoradiation in locally advanced oral cavity squamous cell carcinoma. Methods: A total of sixty patients with locally advanced oral cavity squamous cell carcinoma (T4a, N1-N2b) were retrospectively analyzed between January 2021 and August 2023. Thirty patients underwent upfront surgery followed by adjuvant radiation (group 1) while another thirty patients underwent salvage surgery following definitive chemoradiation (group 2) (radiation dose- 66-70 Gy) Results: Morbidity was found to be significantly higher in the salvage surgery group (group 2) when compared to the upfront surgery group (group 1) with a p value of 0.003. There was no statistical significance between the two groups in terms of disease-free survival and overall survival. Conclusions: This retrospective study shows that there are no significant differences in overall survival and disease-free survival amongst patients of locally advanced oral cavity squamous cell carcinoma treated with upfront surgery and salvage surgery following definitive chemoradiation. Morbidity is significantly higher in the salvage surgery group.

Effect of adjuvant chemotherapy on the oncological outcome of rectal cancer patients with pathological complete response

BackgroundLocally advanced rectal cancer is typically treated using a combination of neoadjuvant chemoradiotherapy and total mesorectal resection. While achieving pathological complete response following neoadjuvant chemoradiotherapy has been recognized as a positive prognostic factor in oncology, the necessity of adjuvant chemotherapy for locally advanced rectal cancer patients with pathological complete response after surgery remains uncertain. The objective of this meta-analysis was to examine the impact of adjuvant chemotherapy on the oncological outcomes of rectal cancer patients who attain pathological complete response after neoadjuvant chemoradiotherapy.MethodsThis meta-analysis followed the guidelines outlined in the preferred reporting items for systematic review and meta-analysis (PRISMA). The Web of Science, PubMed, and Cochrane Library databases were systematically searched to identify relevant literature.ResultsA total of 34 retrospective studies, including 9 studies from the NCBD database, involving 31,558 patients with pathological complete response rectal cancer, were included in the meta-analysis. The included studies were published between 2008 and 2023. The pooled analysis demonstrated that adjuvant chemotherapy significantly improved overall survival (HR = 0.803, 95% CI 0.678–0.952, P = 0.011), and no heterogeneity was observed (I2 = 0%). Locally advanced rectal cancer patients with pathological complete response who underwent adjuvant chemotherapy exhibited a higher 5-year overall survival rate compared to those who did not receive adjuvant chemotherapy (OR = 1.605, 95% CI 1.183–2.177, P = 0.002). However, the analysis also revealed that postoperative ACT did not lead to improvements in disease-free survival and recurrence-free survival within the same patient population. Subgroup analysis indicated that pathological complete response patients with clinical stage T3/T4, lymph node positivity, and younger than 70 years of age may benefit from adjuvant chemotherapy in terms of overall survival.ConclusionsThe findings of this meta-analysis suggest that adjuvant chemotherapy has a beneficial effect on improving overall survival among rectal cancer patients with pathological complete response. However, no such association was observed in terms of disease-free survival and recurrence-free survival.

The Impact of Different Patterns of Residual Disease on Long-Term Oncological Outcomes in Breast Cancer Patients Treated with Neo-Adjuvant Chemotherapy.

The majority of breast cancer (BC) patients treated with neo-adjuvant chemotherapy (NAC) achieves a pathologic partial response with different patterns of residual disease. No clear correlation between these patterns and oncological results was described. Our aims were to define the predictive factors for different patterns of residual disease and compare the outcomes between the scattered versus the circumscribed pattern. We reviewed 219 postoperative surgical specimens. Patients were divided into two groups: scattered versus circumscribed. Disease-free survival (DFS), distant DFS (DDFS), and overall survival (OS) were analyzed. The scattered and circumscribed patterns were assessed in 111 (50.7%) and 108 (49.3%) patients. Two independent predictive factors for the circumscribed pattern were identified: discontinuation of NAC cycles (p = 0.011), and tumor size post-NAC >18 mm (p = 0.022). No difference was observed in terms of DFS and DDFS. Patients with the scattered pattern exhibited a statistically significant better OS. Discontinuation of NAC cycles, tumor size >18 mm, triple-negative BC, and ypN+ were associated with increased recurrence and poorer survival. Discontinuation of NAC cycles and tumor size are independent factors associated with patterns of residual disease. The scattered pattern presents better survival. Understanding the relationship between NAC, the residual pattern, and differences in survival outcomes offers the potential to optimize the therapeutic approaches.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer: A meta-analysis.

The effectiveness of neoadjuvant therapy in esophageal cancer (EC) treatment is still a subject of debate. To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemotherapy (nCT) for locally advanced EC (LAEC). A comprehensive search was conducted using multiple databases, including PubMed, EMBASE, MEDLINE, Science Direct, The Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biomedical Literature Database Article. Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected. The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival. The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate (OSR) [odds ratio (OR) = 0.95], complete response rate (OR = 3.15), and R0 clearance rate (CR) (OR = 2.25). However, nCT demonstrated a better 5-year OSR (OR = 1.02) than nCRT. Moreover, when compared to nCRT, nCT showed reduced risks of cardiac complications (OR = 1.15) and pulmonary complications (OR = 1.30). Overall, both nCRT and nCT were effective in terms of survival outcomes for LAEC. However, nCT exhibited better performance in terms of postoperative complications.

The Clinical and Pathological Characteristics That Differentiate Cases With "Low Estrogen Receptor Expression" From Triple-Negative Breast Cancer.

Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Effect of histological breast cancer subtypes invasive lobular versus non-special type on survival in early intermediate-to-high-risk breast carcinoma: results from the SUCCESS trials

BackgroundInvasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival.MethodsFrom 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan–Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models.ResultsIn the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77–1.21, p = 0.743) for DFS, 1.13 (95% CI 0.85–1.50, p = 0.414) for OS, 1.21 (95% CI 0.89–1.66, p = 0.229) for BCSS, and 0.95 (95% CI 0.73–1.24, p = 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients.ConclusionsOur results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.

Prognostic value of the ratio of pretreatment carcinoembryonic antigen to tumor volume in rectal cancer.

As a commonly used biomarker in rectal cancer (RC), the prognostic value of carcinoembryonic antigen (CEA) remains underexplored. This study aims to evaluate the prognostic value of pretreatment CEA/tumor volume in RC. This retrospective study included patients who underwent pretreatment magnetic resonance imaging (MRI) with histologically confirmed primary rectal adenocarcinoma from November 2012 to April 2018. Patients were divided into high-risk and low-risk groups according to the median values of CEA/Diapath (CEA to pathological diameter), CEA/DiaMRI (CEA to MRI tumor diameter), and CEA/VolMRI (CEA to MRI tumor volume). Cox regression analysis was utilized to determine the prognostic value of CEA, CEA/Diapath, CEA/DiaMRI, and CEA/VolMRI. Stepwise regression was used to establish nomograms for predicting disease-free survival (DFS) and overall survival (OS). Predictive performance was estimated by using the concordance index (C-index) and area under curve receiver operating characteristic (AUC). A total of 343 patients [median age 58.99 years, 206 (60.06%) males] were included. After adjusting for patient-related and tumor-related factors, CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in distinguishing high-risk from low-risk patients in terms of DFS [hazard ratio (HR) =1.83; P=0.010] and OS (HR =1.67; P=0.048). Subanalysis revealed that CEA/VolMRI stratified high death risk in CEA-negative individuals (HR =2.50; P=0.038), and also stratified low recurrence risk in CEA-positive individuals (HR =2.06; P=0.024). In the subanalysis of stage II or III cases, the highest HRs and the smallest P values were observed in distinguishing high-risk from low-risk patients according to CEA/VolMRI in terms of DFS (HR =2.44; P=0.046 or HR =2.41; P=0.001) and OS (HR =1.96; P=0.130 or HR =2.22; P=0.008). The nomograms incorporating CEA/VolMRI showed good performance, with a C-index of 0.72 [95% confidence interval (CI): 0.68-0.79] for DFS and 0.73 (95% CI: 0.68-0.80) for OS. Higher CEA/VolMRI was associated with worse DFS and OS. CEA/VolMRI was superior to CEA, CEA/Diapath, and CEA/DiaMRI in predicting DFS and OS. Pretreatment CEA/VolMRI may facilitate risk stratification and treatment decision-making.

Abstract B051: GSTT2 modulates the bladder tumor environment and response to BCG Immunotherapy

Abstract The purpose of this study was to elucidate the impact of Glutathione -S-transferase Theta 2 (GSTT2) loss on the response of bladder tumors to Mycobacterium Bovis, Bacillus Calmette Guerin (BCG) immunotherapy. GSTT2 gene expression is controlled by a promoter deletion that occurs frequently in 25-29% of Asians and 41% of Caucasians. The GSTT2 promoter deletion correlated with better response to BCG therapy in a retrospective analysis of patients who received less BCG therapy. To understand this response, we generated GSTT2 knockout mice to elucidate the role of GSTT2 in BCG immunotherapy. Female C57BL/6J mice from GSTT2 wildtype (WT) and KO backgrounds were orthotopically implanted with MB49-PSA cells (murine MB49 cells secreting human PSA). To view the impact of GSTT2 loss on BCG immunotherapy, mice were treated with only 4 instillations of BCG Tokyo. This therapeutic schedule would not result in a high cure rate and but was chosen as we expected it to provide insights into the anti-tumor response. Mice were treated weekly with intravesical BCG Tokyo instillations and tumor growth was monitored by urinary PSA secretion. Final tumor presence was confirmed by real-time PCR analysis of PSA gene expression. One day after the last instillation the bladders (n=7) were harvested for single cell RNA sequencing (Parse Biosciences). Cell clusters were identified by their gene expression profiles. The response to BCG in terms of the cure rate was similar in KO and WT mice (cure rate of 18-20%) but several genes were differentially expressed. Genes with a Log2FC value of +1.5 in KO mice (Peak1, Rpph1, Gphn and Gm19551) and -1.5 in KO (Rora, Tshz2, Sh3gl2, Ankfn1, Rbms3, Naaladl2, Prkn, Mecom, Fmo5, Saa3, Tmprss2, C3, Gm10800 and Gm10801) relative to WT mice were examined. Based on the literature, these genes either block tumor progression (Rora, Tshz2, Sh3gl2 and Gphn); promote tumor progression (Ankfn1, Rbms3, Naaladl2, Prkn, Mecom, Fmo5, Tmprss2, Saa3, C3, Peak1, Rpph1) or modulate immune cells (C3, Saa3 and Rpph1). The majority of these genes were not previously associated with bladder cancer. Interrogation of the TCGA database showed that high expression of Gphn, Peak1 and GSTT2 correlated with poorer outcomes in bladder cancer patients in terms of disease-free survival (HR=1.9 log rank p=0.00038). While expression of the genes downregulated in KO mice and GSTT2 resulted in better outcomes with lower expression of all the genes (HR=1.4, log rank p=0.042). This data indicates that the loss of GSTT2 expression impacts the response of tumors to BCG immunotherapy, primarily by modulating the expression of genes associated with cancer progression and the expression of genes in multiple cell types. Given the common loss of GSTT2 expression in man this gene may be a parameter that should be evaluated in further detail in patients receiving BCG immunotherapy. Citation Format: Ratha Mahendran, Mugdha Vijay Patwardhan, Qin Kane Toh, Edmund Chiong. GSTT2 modulates the bladder tumor environment and response to BCG Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B051.

Impact of Adjuvant Radiotherapy in Squamous Cell Carcinoma of the Oral Cavity with Perineural Invasion.

Current guidelines indicate postoperative radiotherapy (PORT) in oral squamous cell carcinoma (OSCC) with perineural invasion (PNI), however, its real benefit has never been proven. The aim of our study is to investigate the benefit of PORT in OSCC patients with PNI in terms of survival and disease control. The Pubmed/MEDLINE, Cochrane Library, and Scopus databases. Patients with PNI + OSCC treated with primary surgery were extracted from the included studies. The pooled logHR was calculated by comparing patients who underwent PORT to those who underwent only observation for overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and locoregional control (LRC). About 690 patients with primary OSCC and PNI were included from nine studies. 374 (54.2%) patients underwent PORT, while 316 (45.8%) underwent observation. Analyses showed non-significant difference between the two groups for OS (HR: 1.01; 95% CI: 0.38-2.69), DSS (HR: 2.03; 95% CI: 0.54-7.56), and LRC (HR: 0.89; 95% CI: 0.53-1.50). They showed a significant difference in terms of DFS (HR: 0.86; 95% CI: 0.77-0.97). The real benefit of PORT in OSCC patients with PNI is still unclear, although it may have a positive impact on DFS. Clinicians should consider individual patient's characteristics, tumor factors, and treatment goals when deciding whether to recommend PORT. Further studies are needed to clarify which entity of PNI really benefits from PORT. NA Laryngoscope, 134:2019-2027, 2024.

Effectiveness comparison of third-generation EGFR-TKI as initial and sequential therapy in adjuvant treatment for EGFR mutation-sensitive stage IIIA non-small cell lung cancer after surgery

IntroductionAlthough third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) Osimertinib has been approved as adjuvant therapy for resected stage IIIA non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, the optimal treatment sequencing of EGFR-TKIs, particularly whether Osimertinib should be the initial or sequential therapy following the first-generation EGFR-TKIs remains uncertain. MethodsA retrospective analysis was conducted on a cohort of patients with EGFR-mutated stage IIIA NSCLC who received treatment with either first-generation EGFR-TKIs or Osimertinib (third-generation) alone, or in sequential combination, at a single institution. The data analysis involved using the Kaplan-Meier method, log-rank test, and Cox regression. ResultsOut of the total 148 patients with stage IIIA NSCLC included in the study, 76 individuals underwent treatment with either first-generation EGFR-TKIs (referred to as subgroup “1″) or exclusively Osimertinib (subgroup “0 + 3″), or a sequential combination of the two (subgroup “1 + 3″) following surgery. Both univariate and multivariate analyses demonstrated that there were no discernible disparities in terms of disease-free survival and overall survival between subgroup " 1″ and " 1 + 3,” nor between subgroup " 0 + 3″ and “1 + 3". ConclusionThe findings from this study indicate that the introduction of third-generation EGFR-TKI Osimertinib did not yield enhanced survival benefits when compared to the first-generation drug in patients with stage IIIA completely resected NSCLC who were administered EGFR-TKIs as part of their postoperative adjuvant treatment. Additionally, within the observed sample size of this cohort, the sequential use of Osimertinib alongside first-generation EGFR-TKI did not demonstrate superiority over using either the first-generation EGFR-TKI or Osimertinib alone in terms of postoperative survival.

Depth of Invasion: Influence of the Latest TNM Classification on the Prognosis of Clinical Early Stages of Oral Tongue Squamous Cell Carcinoma and Its Association with Other Histological Risk Factors.

The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors. A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05. Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival (p = 0.043), but not with respect to overall survival (p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes (p = 0.012), perineural invasion (p = 0.004) and tumour differentiation grade (p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion. Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

Prise en charge des stades précoces : place des thérapies ciblées en périopératoire: Management of early stages: the role of peri-operative targeted therapies

Targeted therapies are the cornerstone of the treatment of NSCLC with oncogenic addiction. Their evaluation in early stages NSCLC is more recent and involves a different methodological approach. At present, the results relate exclusively to NSCLC with EGFR mutation. While previous studies failed to validate the efficacy of adjuvant EGFR inhibitors, the ADAURA study recently demonstrated a benefit in terms of disease-free survival and overall survival. These results modify the therapeutic algorithm for these patients, although the methodological limitations leave many questions unanswered.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study

BackgroundWe aimed to analyze the benefit of adjuvant chemotherapy in high-risk stage II colon cancer patients and the impact of high-risk factors on the prognostic effect of adjuvant chemotherapy.MethodsThis study is a multi-center, retrospective study, A total of 931 patients with stage II colon cancer who underwent curative surgery in 8 tertiary hospitals in China between 2016 and 2017 were enrolled in the study. Cox proportional hazard model was used to assess the risk factors of disease-free survival (DFS) and overall survival (OS) and to test the multiplicative interaction of pathological factors and adjuvant chemotherapy (ACT). The additive interaction was presented using the relative excess risk due to interaction (RERI). The Subpopulation Treatment Effect Pattern Plot (STEPP) was utilized to assess the interaction of continuous variables on the ACT effect.ResultsA total of 931 stage II colon cancer patients were enrolled in this study, the median age was 63 years old (interquartile range: 54–72 years) and 565 (60.7%) patients were male. Younger patients (median age, 58 years vs 65 years; P < 0.001) and patients with the following high-risk features, such as T4 tumors (30.8% vs 7.8%; P < 0.001), grade 3 lesions (36.0% vs 22.7%; P < 0.001), lymphovascular invasion (22.1% vs 6.8%; P < 0.001) and perineural invasion (19.4% vs 13.6%; P = 0.031) were more likely to receive ACT. Patients with perineural invasion showed a worse OS and marginally worse DFS (hazardous ratio [HR] 2.166, 95% confidence interval [CI] 1.282–3.660, P = 0.004; HR 1.583, 95% CI 0.985–2.545, P = 0.058, respectively). Computing the interaction on a multiplicative and additive scale revealed that there was a significant interaction between PNI and ACT in terms of DFS (HR for multiplicative interaction 0.196, p = 0.038; RERI, -1.996; 95%CI, -3.600 to -0.392) and OS (HR for multiplicative interaction 0.112, p = 0.042; RERI, -2.842; 95%CI, -4.959 to -0.725).ConclusionsPerineural invasion had prognostic value, and it could also influence the effect of ACT after curative surgery. However, other high-risk features showed no implication of efficacy for ACT in our study.Trial registrationThis study is registered on ClinicalTrials.gov, NCT03794193 (04/01/2019).

Mismatch Repair Deficiency in Biliary Tract Cancer: Prognostic Implications and Correlation with Histology

Introduction: Mismatch repair (MMR) deficiency represents a biomarker and therapeutic target in various neoplasms, but its role in biliary tract cancers (BTCs) remains misunderstood. Methods: MMR status was retrospectively assessed using immunohistochemistry in 163-BTCs patients. We identified MMR proficiency (pMMR)/deficiency (dMMR) according to the loss of MMR proteins (MLH1, PMS2, MSH2, MSH6). The primary objective of the study was to assess the incidence of dMMR in BTCs; the secondary purpose was to explore its association with prognosis and clinical features. Results: dMMR was recorded in 9 patients, and it was strongly associated with mucinous histology (p < 0.01). Regarding the prognostic effect, in 122-radically resected patients, disease-free survival (DFS) resulted significantly shorter in dMMR patients compared to pMMR patients (10.7 vs. 31.3 months, p = 0.025) and so did nodal status (48.2 vs. 15.3 months in N0 vs. N+) (p < 0.01). Moreover, dMMR confirmed its prognostic role in terms of DFS at multivariate analysis (p = 0.03), together with nodal status (p = 0.01), and resection margin (p = 0.03). In 103 M+ patients (encompassing 41 metastatic de novo and 62 recurred after surgery patients) there were not differences between dMMR and pMMR regarding survival analyses. Conclusions: dMMR status is strongly correlated with mucinous histology and represents an independent prognostic factor in terms of disease relapse in patients with resected BTC. Implications for Practice: MMR may play an independent role in promoting an aggressive behaviour in patients with radically resected BTC. These results could be useful in improving the selection of patients after resection and, above all, should justify the evaluation of MMR status as a therapeutic target in BTC, especially in patients with atypical histology.

Anatomic versus non-anatomic resection for early-stage intrahepatic cholangiocarcinoma: a propensity score matching and stabilized inverse probability of treatment weighting analysis

BackgroundRadical resection is still the most cost-effectiveness curative strategy for intrahepatic cholangiocarcinoma (ICC), but it remains controversial on the survival benefit of anatomic resection (AR). In this study, we sought to compare the oncologic outcomes between AR versus non-AR (NAR) as the primary treatment for early-stage ICC patients.MethodsData of ICC patients who underwent hepatectomy and staged at AJCC I were retrospectively collected from 12 hepatobiliary centers in China between Dec 2012 and Dec 2015. Propensity score matching (PSM) and stabilized inverse probability of treatment weighting (IPTW) analysis were performed to minimize the effect of potential confounders, and the perioperative and long-term outcomes between AR and NAR groups were compared.ResultsTwo hundred seventy-eight ICC patients staged at AJCC I were eligible for this study, including 126 patients receiving AR and 152 patients receiving NAR. Compared to the NAR group, the AR group experienced more intraoperative blood loss before and after PSM or stabilized IPTW (all P > 0.05); AR group also experienced more intraoperative transfusion after stabilized IPTW (P > 0.05). In terms of disease-free survival (DFS) and overall survival (OS), no significant differences were observed between the two groups before and after PSM or stabilized IPTW (all P > 0.05). Multivariable Cox regression analyses found that AR was not an independent prognostic factor for either DFS or OS (all P > 0.05). Further analysis also showed that the survival benefit of AR was not found in any subgroup stratified by Child–Pugh grade (A or B), cirrhosis (presence or absence), tumor diameter (≤ 5 cm or > 5 cm) and pathological type (mass-forming or non-mass-forming) with all P > 0.05.ConclusionSurgical approach does not influence the prognosis of patients with stage I primary ICC, and NAR might be acceptable and oncological safety.

Efficacy of hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery for advanced or recurrent ovarian cancer: a systematic evaluation and meta-analysis.

This meta-analysis was performed to investigate the safety and efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with cytoreductive surgery (CRS) in the treatment of advanced or recurrent ovarian cancer. An electronic search of databases, including PubMed, Embase, Cochrane, Medline, and Web of Science, was performed to collect controlled studies on HIPEC combined with CRS administered for advanced ovarian cancer. Meta-analysis was conducted based on the outcome indicators extracted from the included studies, including disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Twelve pieces of literature were included, involving 1,622 participants, with 694 participants in the control group and 928 in the study group. In terms of DFS, the pooled hazard ratio (HR) was 0.70 (95% CI: 0.58, 0.84), with an HR of 0.77 (95% CI: 0.64, 0.93) in the treatment-naïve subgroup and an HR of 0.54 (95% CI: 0.40, 0.74) in the secondary cytoreduction subgroup. In terms of OS, the pooled HR was 0.63 (95% CI: 0.52, 0.77), with an HR of 0.67 (95% CI: 0.54, 0.83) in the treatment-naïve subgroup and an HR of 0.47 (95% CI: 0.29, 0.77) in the secondary cytoreduction subgroup. With regard to AEs, the pooled odds ratio (OR) was 0.79 (95% CI: 0.68, 0.92). The benefits of CRS plus HIPEC for the management of advanced ovarian cancer are significant but also associated with an increased risk of adverse events. Thus, clinical use of this co-administration requires caution.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Immunonutrition supplementation for resectable gastric cancer during standard perioperative chemotherapy (CT) FLOT: A pivotal study, I–SUPPLY.

57 Background: Gastric carcinomas (GC) can be divided into immunogenic and immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs) such as Natural Killer (NK), activated CD8+, CD3+ and CD4+ memory T cells. High ImmunoScore (IS) (positive cells/mm2 for each marker (CD8+, CD3+, Foxp3+) in the Core Tumour and Invasive Margins) is strongly related to better prognosis of GC patients in terms of Disease-Free Survival and Overall Survival. ICs activation and consequent immunogenic TME requires high nutrient absorption and synthesis accumulation of protein, lipid and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing the available micronutrients to ICs therefore leading to an immunosuppressive TME phenotype. Methods: This is a translational, prospective, non-randomized study. Primary endpoint is to assess if enteral immune nutrition (EIN) supplementation during the acme of the activity of cytotoxic of perioperative FLOT (docetaxel, oxaliplatin and 5-fluorouracil) in stage II-III GC can revert the TME in favour of ICs over TCs, witnessed by an increase of IS in surgical specimen over biopsy controls. A steady amount of EIN with Arginine, Omega-3-fatty acids, Glutamine and ribonucleic acid, will be added to patient’s diet from day 3 to 8 of each FLOT cycle, twice a day. We plan to use Image analysis software for automatic tumor detection and quantification of CD3+ and CD8+ stained cells whose densities will be converted into IS with pre-defined cutoffs. IS utilizes standardized percentile values (0 to 100%). We identify IS as Low, Intermediate (Int) and High with a mean percentile of 0-25%, &gt;25-70%, &gt;70-100% respectively. Two-group classifications are planned, corresponding to IS Low and Int-High. To better define the kind of tumor infiltrating cells (TILs) and assess the amount of immune suppressive cells, more IHC scoring will be evaluated: helper T-cells CD4+, CD8 T memory (CD 103+), T regulatory (both CD4+ and Foxp3+/CD105+), Macrophages M1 (CD 68+) and M2 (CD 163+). Results: Based on historical controls the rate of Int-High IS (&gt;25-70%, &gt;70% respectively) is about 64%, we expect to find a 20% increase of Int-High IS GC over biopsy control (internal validation cohort). To detect an increase in the percentage of high IS among patients treated with EIN (estimated around 85%) compared to biopsy controls (estimated around 64%) assuming a probability α and β of 0.2, the required sample size will be of 21 patients with resectable GC receiving EIN supplementation plus standard CT. To define the sample size a single proportion test was used. Conclusions: Our hypothesis is that EIN given during perioperative CT might prevent the establishment of an unfavourable TME for ICs in both auxotrophic and non-auxotrophic malignancies, thus leading to an increase of GC immunogenic pattern.

O-277 Safety of pregnancy after early breast cancer in young women with hormone receptor-positive disease: a systematic review and meta-analysis

Abstract Study question Is it safe to have a pregnancy in women with prior history of hormone receptor-positive early breast cancer? Summary answer Pregnancy following breast cancer treatments in young women with history of hormone receptor-positive disease is safe with no detrimental effect on patients’ prognosis. What is known already Breast cancer is the most common malignancy diagnosed in women of reproductive age. Both physicians and patients continue to have concerns about a potential detrimental effect of pregnancy after breast cancer, particularly in the setting of hormone receptor-positive disease. In recent years, several studies have demonstrated the safety of pregnancy after anticancer treatments in breast cancer survivors. Study design, size, duration A systematic literature search of Medline, Embase and Cochrane library with no language or date restriction up to January 1st, 2023, was performed following the PRISMA guidelines. We included retrospective or prospective case-control and cohort studies as well as prospective clinical trials comparing survival outcomes of premenopausal female patients with reported pregnancy or not after diagnosis and treatment for hormone receptor-positive breast cancer. Participants/materials, setting, methods Included patients were childbearing potential age women with a prior history of hormone receptor-positive early breast cancer. Outcomes of interest were disease-free survival and overall survival. Hazard ratios (HR) with 95% confidence intervals (CI) were extracted. Higgins I2 index was used to evaluate the degree of inconsistency in the results of the included studies. Pooled HRs were considered statistically significant with a P value of &amp;lt; 0.05 (two-sided). Main results and the role of chance Eight studies were eligible to be included in the final analysis. A total of 3,805 patients with hormone receptor-positive breast cancer were included in these studies, of whom 1,285 had a pregnancy after treatments. Median follow-up of the included studies ranged from 3.81 years to 15.8 years. In three studies (n = 987 patients) reporting on disease-free survival outcomes, no difference was observed between patients with or without a subsequent pregnancy (HR 0.96, 95% CI 0.75 – 1.24, p = 0.781). Six studies (n = 3,504 patients) reported outcomes in terms of overall survival: patients with a pregnancy after breast cancer had better overall survival compared with those without a pregnancy (HR 0.46, 95% CI 0.27 – 0.77, p &amp;lt; 0.05). At the subgroup analysis on timing of pregnancy, no detrimental effect of pregnancy after breast cancer in terms of disease-free survival was observed for patients achieving a late pregnancy (defined as 2 or 5 years after diagnosis) as compared to patients without a subsequent pregnancy (HR 1.08, 95% CI 0.80 – 1.46, p = 0.611). Increased disease-free survival was observed in patients with an early pregnancy (HR 0.63, 95% CI 0.47 – 0.85, p &amp;lt; 0.05). Limitations, reasons for caution This meta-analysis is based on abstracted data and most of the studies are retrospective cohort studies. Median follow-up in a large proportion of the studies was shorter than 10 years. Adjuvant hormone therapy before and after pregnancy was not available in many studies included. Wider implications of the findings Our results strengthen the evidence that having a pregnancy in women with prior history of hormone receptor-positive breast cancer is safe. Trial registration number not applicable