Independent Factor For Disease-free Survival Research Articles

Abstract PO3-04-09: Prognoses of Patients with Hormone Receptor-Positive andHuman Epidermal Growth Factor Receptor 2-Negative BreastCancer Receiving Neoadjuvant Chemotherapy before Surgery:A Retrospective Analysis

Abstract Abstract: Purpose: To evaluate the clinical characteristics, pathological response, and prognostic significance of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). Methods: A survival analysis was performed to detect the factors related to recurrence and death in 3070 consecutive patients with HR+/HER2− BC who received NAC from 2011 to 2022. All patients received current “standard of care” following neoadjuvant therapy based on guidelines, including surgery and adjuvant endocrine therapy. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC 2+ and fluorescence in-situ hybridization-negative. Results: The complete pathological response (pCR) (ypT0/is ypN0) rate was 14.5%. The clinical tumor size (cT), ER scores, PR status, and Ki67 levels were related to pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 82.6% and 90.4%, respectively. PR, Ki67 levels, and postmastectomy radiotherapy were independent factors for DFS and OS, and the extranodal extension (ENE) correlated with DFS. However, pCR and HER2 status were related to OS. The pCR rate in PR negativity BC was significantly higher than that in PR positivity BC (21.1% vs. 12.2%, p = 0.000), but PR negativity BC had a poorer prognosis than PR positivity BC. HER2-low BC showed high ER scores (over 50%), PR positivity, large ypT, ENE, and lymphovascular invasion but a lower pCR rate than HER2-zero BC. Patients with HER2-low BC had shorter OS than those with HER2-zero BC (p = 0.037). However, there was no difference in DFS. Conclusions: Depending on PR status and HER2 status, patients with ER positivity and HER2 negativity exhibit different pathologic complete response rates to neoadjuvant chemotherapy and long-term outcomes, especially patients with PR negativity or HER2-low status. Keywords: breast cancer; neoadjuvant chemotherapy; survival; prognosis; PR; HER2-low Citation Format: Jin Zhang, Yan Liu, Shichao Zhang. Prognoses of Patients with Hormone Receptor-Positive andHuman Epidermal Growth Factor Receptor 2-Negative BreastCancer Receiving Neoadjuvant Chemotherapy before Surgery:A Retrospective Analysis [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 PO3-04-09.

A novel immune-nutritional score predicts response to neoadjuvant immunochemotherapy after minimally invasive esophagectomy for esophageal squamous cell carcinoma.

The role of neoadjuvant immunochemotherapy (NICT) has gradually attracted attention in recent years. To date, sensitive and reliable blood indicators to forecast the therapeutic response are still lacking. This study aimed to conduct a novel predictive score based on a variety of peripheral hematological immune-nutritional indicators to predict the therapeutic response in esophageal squamous cell carcinoma (ESCC) receiving NICT. There were 206 ESCC patients receiving NICT retrospectively recruited. With pathological complete response (pCR) as the dependent variable, independent risk variables of various peripheral blood immune-nutritional indexes were screened by logistic regression analyses to establish an integrative score. By logical regression analyses, lymphocyte to monocyte ratio (LMR) and body mass index (BMI) were independent risk factors among all immune-nutritional indices. Then, an integrative score named BMI-LMR score (BLS) was established. Compared with BMI or LMR, BLS was related to complications, especially for respiratory complication (P=0.012) and vocal cord paralysis (P=0.021). Among all patients, 61 patients (29.6%) achieved pCR after NICT. BLS was significantly related to pCR [odds ratio (OR)=0.269, P<0.001)]. Patients in high BLS cohort demonstrated higher 3-year overall survival (OS) (89.9% vs. 67.9%, P=0.001) and disease-free survival (DFS) (81.2% vs. 62.1%, P=0.001). BLS served as an independent factor of DFS [hazard ratio (HR) =2.044, P =0.020) and OS (HR =2.960, P =0.019). The BLS, based on immune-nutritional indicators of BMI and LMR, employed as a straightforward, accurate, and useful indicator of pCR and prognostic prediction in ESCC patients undergoing NICT.

Clinical efficacy and safety of adjuvant EGFR-TKIs for resected stage IB lung adenocarcinoma: A real-world study based on propensity score matching.

Adjuvant therapy for stage IB non-small cell lung cancer remains debatable. In this real-world study, we evaluate the efficacy and safety of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for resected stage IB lung adenocarcinoma. This real-world study recruited 249 patients diagnosed with stage IB disease after surgical resection between January 2013 and September 2021. Sixty-six (26.5%) patients received adjuvant targeted therapy (TKIs group), and 183 (73.5%) were enrolled in the clinical observation (CO) group. Propensity scores were matched to minimize the observed confounder effects between the two groups, and 59 patient pairs were matched. The primary endpoint was disease-free survival (DFS). In the TKI group, 38 (64.4%) patients chose to receive icotinib, 27.1% (16/59) received gefitinib, and 5 patients (8.5%) chose osimertinib. The median follow-up time was 30.8 months (range: 7-107 months). Two (3.4%) patients in the TKI group and 10 (16.9%) in the CO group experienced disease relapse. The 3-year DFS rates were 98.3% in the TKI group and 83.0% in the CO group (HR: 0.10; 95% CI: 0.01-0.78; p = 0.008). DFS differences were found in the entire cohort (p = 0.005) and the matched cohort (p = 0.024) between the two groups. Multivariate analysis showed that adjuvant EGFR-TKIs was an independent factor for DFS (HR: 0.211; 95% CI: 0.045-0.979; p = 0.047), along with poor cell differentiation (HR: 5.256; 95% CI: 1.648-16.769; p = 0.005), and spread through air spaces (HR: 5.612; 95% CI: 1.137-27.700; p = 0.034). None of the patients discontinued EGFR-TKIs owing to the low occurrence rate of treatment-related serious adverse events. Adjuvant EGFR-TKIs could significantly improve DFS among patients with stage IB lung adenocarcinoma compared with CO, with a safe and tolerable profile.

Clinicopathological and survival outcomes of 4L lymph node dissection in left lung adenocarcinoma and squamous cell carcinoma.

Whether 4L lymph node dissection (LND) should be performed remains unclear and controversial. Prior studies have found that station 4L metastasis was not rare and that 4L LND may provide survival benefits. The objective of this study was to analyze the clinicopathological and survival outcomes of 4L LND from the perspective of histology. This retrospective study included 74 patients with squamous cell carcinoma (SCC) and 84 patients diagnosed with lung adenocarcinoma (ADC) between January 2008 and October 2020. All patients underwent pulmonary resection with station 4L LND and were staged as T1-4N0-2M0. Clinicopathological features and survival outcomes were investigated based on histology. The study endpoints were disease-free survival (DFS) and overall survival (OS). The incidence rate of station 4L metastasis was 17.1% (27/158) in the entire cohort, with 8.1% in the SCC group, and 25.0% in the ADC group. No statistical differences in the 5-year DFS rates (67.1% vs. 61.7%, P=0.812) and 5-year OS rates (68.6% vs. 59.3%, P=0.100) were observed between the ADC group and the SCC group. Multivariate logistic analysis revealed that histology (SCC vs. ADC: OR, 0.185; 95% CI, 0.049-0.706; P=0.013) was independently associated with 4L metastasis. Multivariate survival analysis showed that the status of 4L metastasis was an independent factor for DFS (HR, 2.563; 95% CI, 1.282-5.123; P=0.008) but not for OS (HR, 1.597; 95% CI, 0.749-3.402; P=0.225). Station 4L metastasis is not rare in left lung cancer. Patients with ADC have a greater predilection for station 4L metastasis and may benefit more from performing 4L LND.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Prognoses of Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy before Surgery: A Retrospective Analysis

To evaluate the clinical characteristics, pathological response, and prognostic significance of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) after neoadjuvant chemotherapy (NAC). A survival analysis was performed to detect the factors related to recurrence and death in 3070 consecutive patients with HR+/HER2- BC who received NAC from 2011 to 2022. All patients received current "standard of care" following neoadjuvant therapy based on guidelines, including surgery and adjuvant endocrine therapy. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC 2+ and fluorescence in-situ hybridization-negative. The complete pathological response (pCR) (ypT0/is ypN0) rate was 14.5%. The clinical tumor size (cT), ER scores, PR status, and Ki67 levels were related to pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 82.6% and 90.4%, respectively. PR, Ki67 levels, and postmastectomy radiotherapy were independent factors for DFS and OS, and the extranodal extension (ENE) correlated with DFS. However, pCR and HER2 status were related to OS. The pCR rate in PR negativity BC was significantly higher than that in PR positivity BC (21.1% vs. 12.2%, p = 0.000), but PR negativity BC had a poorer prognosis than PR positivity BC. HER2-low BC showed high ER scores (over 50%), PR positivity, large ypT, ENE, and lymphovascular invasion but a lower pCR rate than HER2-zero BC. Patients with HER2-low BC had shorter OS than those with HER2-zero BC (p = 0.037). However, there was no difference in DFS. Depending on PR status and HER2 status, patients with ER positivity and HER2 negativity exhibit different pathologic complete response rates to neoadjuvant chemotherapy and long-term outcomes, especially patients with PR negativity or HER2-low status.

Cell cycle regulatory markers as potential prognostic biomarkers in uterine carcinosarcoma

The relevance of cell cycle regulatory markers with uterine carcinosarcoma was investigated. The immunohistochemical expression of p16, p53, and cyclin D1 were assessed using tissue microarray of 55 eligible patients. p16 and p53 showed a high rate of strong (+3) immune reaction in carcinomatous/sarcomatous components (61.8%/70.9% and 52.7%/56.4%, respectively). Cyclin D1 showed a 14.5%/7.3%of strong immune reaction in the carcinomatous/sarcomatous components. Strong expression of p16 was related to a higher rate of recurrence, lymph node metastasis, and bigger tumor size. Strong expression of cyclin D1 was related to the lower International Federation of Gynecology and Obstetrics (FIGO) stage and recurrence rate. In univariate regression analysis, FIGO stage, lymph node metastasis, p16, and cyclin D1 were prognostic factors for disease-free survival. FIGO stage, p16, p53, and cyclin D1 were prognostic factors for disease specific survival. In a multivariate regression analysis, FIGO stage and p16 in carcinomatous component were independent factors for disease-free survival (odds ratio (OR), 95% confidence interval (CI); 3.2 (1.1–9.6) and 3.5 (1.3–9.7); p = 0.035 and 0.017). p16 was a predictor of lymph node metastasis, tumor size, and prognostic outcome in uterine carcinosarcoma.

Prognostic factors for disease-free survival in postoperative patients with hepatocellular carcinoma and construction of a nomogram model.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high risk of invasion and metastasis along with a poor prognosis. To investigate the independent predictive markers for disease-free survival (DFS) in patients with HCC and establish a trustworthy nomogram. In this study, 445 patients who were hospitalized in The First Affiliated Hospital of Anhui Medical College between December 2009 and December 2014 were retrospectively examined. The survival curve was plotted using the Kaplan-Meier method and survival was determined using the log-rank test. To identify the prognostic variables, multivariate Cox regression analyses were carried out. To predict the DFS in patients with HCC, a nomogram was created. C-indices and receiver operator characteristic curves were used to evaluate the nomogram's performance. Decision curve analysis (DCA) was used to evaluate the clinical application value of the nomogram. Longer DFS was observed in patients with the following characteristics: elderly, I-II stage, and no history of hepatitis B. The calibration curve showed that this nomogram was reliable and had a higher area under the curve value than the tumor node metastasis (TNM) stage. Moreover, the DCA curve revealed that the nomogram had good clinical applicability in predicting 3- and 5-year DFS in HCC patients after surgery. Age, TNM stage, and history of hepatitis B infection were independent factors for DFS in HCC patients, and a novel nomogram for DFS of HCC patients was created and validated.

Preoperative computed tomography assessment of circumferential resection margin in retroperitonealized colon cancer predicts disease-free survival.

The aim of this retrospective study was to predict circumferential resection margin (CRM) involvement on preoperative CT, and prognostic impact of CRM assessment by CT (ctCRM) in patients with retroperitonealized colon cancer. This study included patients who underwent resection for ascending or descending colon cancer between July 2010 and February 2013. Positive ctCRM was defined as tumor distance to the retromesenteric plane of ≤ 1 mm. The origin of positive CRM was divided into primary tumor or other tumor components including lymph nodes, tumor deposits, or extramural venous invasions. Logistic regression analysis was performed to identify preoperative factors to predict pathologic CRM (pCRM). A Cox proportional hazards model was used in multivariable analysis to determine the preoperative factors affecting disease-free survival (DFS). A total of 274 patients (mean age, 64.0 years ± 11.0 [standard deviation]; 157 men) with retroperitonealized colon cancer were evaluated. Of 274 patients, 67 patients (24.5%) had positive CRM on surgical pathology. The accuracy of preoperative CT in predicting pCRM was 79.6% (218/274). Among preoperative factors, only CRM assessment on CT was independently associated with pCRM (p < 0.001). Positive ctCRM by primary tumor was an independent factor for DFS (HR, 3.362 [1.714-6.593]) and systemic recurrence (HR, 3.715 [1.787-7.724], but not for local recurrence on multivariable analyses. Preoperative CT can accurately predict pCRM, and positive ctCRM by primary tumor is an independent risk factor for DFS and systemic recurrence, but not for local recurrence in retroperitonealized colon cancer. • Preoperative CT can predict pathologic circumferential resection margin (CRM) with approximately 80% of accuracy in patients with retroperitonealized colon cancer. • Positive CRM by a primary tumor on preoperative CT is a poor prognostic factor for disease-free survival and systemic recurrence in patients with retroperitonealized colon cancer. • CRM involvement on CT was not associated with local recurrence in patients with retroperitonealized colon cancer.

Radiomics signature for predicting postoperative disease-free survival of patients with gastric cancer: development and validation of a predictive nomogram.

PURPOSE Radiomics can be used to determine the prognosis of gastric cancer (GC). The objective of this study was to predict the disease-free survival (DFS) after GC surgery based on computed tomography-enhanced images combined with clinical features. METHODS Clinical, imaging, and pathological data of patients who underwent gastric adenocarcinoma resection from June 2015 to May 2019 were retrospectively analyzed. The primary outcome was DFS. Radiomics features were selected using Least Absolute Shrinkage and Selection Operator algorithm and converted into the Rad-score. A nomogram was constructed based on the Radscore and other clinical factors. The Rad-score and nomogram were validated in the training and validation groups. RESULTS Totally, 179 patients were randomly divided into the training (n=124) and validation (n=55) groups. In the training group, validation group, and overall population, the Rad-score could be divided into categories indicating low, moderate, and high risk of recurrence, metastasis, or death; all risk categories showed a significant difference between the training, validation, and overall population groups (all P < .001). Positive lymph nodes (hazard ratio (HR)=3.07, 95% CI: 1.52-6.23, P=.002), cancer antigen-125 (HR=3.24, 95% CI: 1.54-6.80, P=.002), and the Radscore (HR=0.73, 95% CI: 0.61-0.87, P < .001) were independently associated with DFS. These 3 variables were used to construct a nomogram. In the training group, the areas under the curve at 3 years were 0.758 and 0.776 for the Rad-score and the nomogram, respectively, while they were both 1.000 in the validation group. The net benefit rate was analyzed using a decision curve in the training and validation groups, and the nomogram was superior to the single Rad-score. CONCLUSION Rad-score is an independent factor for DFS after gastrectomy for GC. The nomogram established in this study could be an effective tool for the clinical prediction of DFS after gastrectomy.

MRI outcome evaluation in patients with IB2 and IIA2 squamous cervical cancer stages: preliminary results

ObjectivesTo evaluate the therapeutic effect of neoadjuvant therapy (NAT) followed by radical hysterectomy and concurrent chemoradiotherapy (CCRT) in stage IB2 and IIA2 squamous cervical cancer (SCC) and investigate the value of apparent diffusion coefficient (ADC) in outcome evaluation of different treatment strategies in the patients.MethodsA total of 149 patients with IB2 and IIA2 SCC who underwent pretreatment MRI and DWI scan were included. Patients were treated with NAT + RH or CCRT. Clinical indices and pathological factors were recorded. The imaging indices were measured including tumor size and tumor ADC values. Intraclass correlation coefficient was employed to evaluate the consistency of the indices measured by two observers. ROC curves were used to evaluate the cutoff values of clinical and imaging indices. Kaplan–Meier and Cox proportional hazard model were used to analyze the independent factors of disease-free survival (DFS).ResultsThe median follow-up period was 42.3 months. SCC-Ag, ADCmax and ADCmin were independent factors for DFS in the entire cohort. SCC-Ag, ADCmin and vascular invasion were independent factors for DFS in NAT + RH group. ADCmax and ADCmin were independent factors for DFS in CCRT group. ADCmin was the strongest independent factor for DFS in NAT + RH group, while ADCmax was that in CCRT group.ConclusionThe NAT + RH patients had similar DFS to that of CCRT in IB2 and IIA2 SCC, which could be a potential feasible alternative treatment. ADCmin and ADCmax were more valuable in evaluating the outcome of patients who underwent NAT + RH or CCRT, respectively.

Down-regulated expression of miR-99a is associated with lymph node metastasis and predicts poor outcome in stage IB cervical squamous cell carcinoma: a case-control study.

Background Lymph node metastasis (LNM) accounts for the most important route of metastasis for cervical cancer. Yet, the status of LNM is different in patients with similar clinico-pathological variables. It has been revealed that microRNAs are widely involved in the occurrence and development of various malignancies, and the tumor-suppressive or promoting effects of microRNA-99 (miR-99) family have been previously reported. This study sought to investigate the predictive value of miR-99a for lymphogenous spread and its effect on the survival of patients with early-stage cervical squamous cell cancer (CSCC).MethodsPatients with stage IB squamous cervical cancer who were treated surgically between October 2015 and November 2018 were enrolled. A total of 21 formalin-fixed paraffin-embedded tissues of pathologically confirmed positive lymph nodes were retrieved, and an additional 21 tissues of negative lymph nodes from patients well-matched on baseline characteristics were collected as the control group. TaqMan real-time quantitative polymerase chain reaction was used to examine the expression levels of miR-99a in the samples. Differential expression levels of miR-99a were compared between the 2 groups using independent sample t-test. Furthermore, the associations between miR-99a expression level and clinico-pathological parameters of these 42 patients was evaluated by Chi-square test or Fisher’s exact-probability method, and their effects on survival were assessed using Kaplan-Meier product-limit method.ResultsThere were no significant differences in baseline clinico-pathological parameters between the 2 groups (P>0.05). The expression levels of miR-99a in the node-positive group and control group were 1.61±3.09 and 16.77±30.40, respectively (P=0.029). Downregulated expression of miR-99a was closely related to depth of invasion (DOI) and lymph-vascular space invasion (P<0.05). Univariate analysis revealed that downregulated miR-99a and deeper DOI were associated with worse 5-year disease-free survival, while multivariate analysis showed that only the expression level of miR-99a was an independent factor for disease-free survival (HR =0.120; 95% CI: 0.015–0.979; P=0.048). Patients with downregulated miR-99a tended to have more unfavorable overall survival, but the difference did not reach statistical significance.Conclusions MiR-99a plays an inhibitory role in the pathogenesis of lymph node metastasis and may serve as a novel prognostic biomarker for patients with CSCC.

Different Characteristics and Survival between Surgically Resected Pure and Combined Pulmonary Large Cell Neuroendocrine Carcinoma.

Large cell neuroendocrine carcinoma (LCNEC) is a rare high-grade neuroendocrine carcinoma of the lung. Little is known about the differences between the pure and combined LCNEC subtypes, and thus we conducted this study to provide more comprehensive insight into LCNEC. We reviewed 221 patients with pure LCNEC (P-LCNEC) and 120 patients with combined LCNEC (C-LCNEC) who underwent pulmonary surgery in our hospital to compare their clinical features, driven genes' status (EGFR/ALK/ROS1/KRAS/BRAF), and adjuvant chemotherapy regimens. Propensity score matching (PSM) was applied to reduce selection bias. The P-LCNEC group included a higher proportion of males and smokers than the C-LCNEC group. Furthermore, the C-LCNEC group had higher incidences of visceral pleural invasion (VPI), EGFR mutation and ALK rearrangement compared with the P-LCNEC group. Expression of neuroendocrine markers (CD56, CGA, and SYN) and recurrence patterns were not significantly different between the two groups. The P-LCNEC group had better disease-free survival (DFS) and overall survival (OS) compared with the C-LCNEC group (median DFS: 67.0 vs. 28.1 months, p=0.021; median OS: 72.0 vs. 45.0 months, p=0.001), which was further confirmed by the PSM method (p=0.004 and p<0.001, respectively). Adjuvant chemotherapy was also an independent factor for DFS and OS. Subgroup analysis found that regardless of whether it was for the entire LCNEC group or the P- and C-LCNEC subtypes, the small cell lung cancer (SCLC) regimens presented with superior survival compared with the non-small cell lung cancer (NSCLC) regimens. P-LCNEC was associated with more favorable prognosis compared with C-LCNEC. SCLC-based adjuvant chemotherapy was more appropriate for LCNEC patients than NSCLC-based regimens, regardless of whether they were the pure or combined LCNEC subtypes. C-LCNEC patients may be the potential beneficiary of targeted therapy.

Neoadjuvant chemoradiotherapy is superior to chemotherapy alone in surgically treated stage III/N2 non-small-cell lung cancer: a retrospective single-center cohort study

BackgroundThere is lack of consensus whether neoadjuvant chemoradiotherapy (CHT/RT) is superior to neoadjuvant chemotherapy (CHT) alone in patients with potentially resectable stage III/N2 non-small-cell lung cancer (NSCLC).Patients and methodsWe retrospectively evaluated clinical parameters and outcomes in patients with clinical stage III/N2 NSCLC treated with neoadjuvant CHT/RT versus CHT followed by surgery. Nearest-neighbor propensity score (PS) matching was used to correct for pretreatment differences.ResultsA total of 84 patients were enrolled. Thirty-four (40%) and 50 (60%) patients received CHT/RT or CHT followed by curative-intent surgery, respectively. Overall 90-day mortality and morbidity were 0% versus 0.04% and 21% versus 18%, respectively, with no significant difference between the CHT/RT and the CHT-alone cohorts (P = 0.51 and P = 0.70). In the PS-matched cohort, complete pathological response was recorded in 25% after CHT/RT versus 0% after CHT at the time of surgery. Patients receiving neoadjuvant CHT/RT exhibited significantly better 5-year disease-free survival (DFS) [45% versus 16% CHT group; hazard ratio (HR) 0.43, P = 0.04]; 5-year overall survival (OS) was 75% after CHT/RT and 21% after CHT (HR 0.37, P = 0.001). CHT/RT more often induced pathological mediastinal downstaging (P = 0.007), but CHT/RT remained the only independent factor for DFS and OS and did not depend on mediastinal downstaging.ConclusionsIn this retrospective PS-matched long-term analysis, neoadjuvant CHT/RT conferred improved DFS and OS compared with CHT alone in stage III/N2 NSCLC. These highly challenging results require confirmation in well-designed randomized controlled trials conducted at highly specialized thoracic oncology centers.

Establishment and Validation of Prognostic Nomograms Based on Serum Copper Level for Patients With Early-Stage Triple-Negative Breast Cancer.

Background: Altered copper levels have been observed in several cancers, but studies on the relationship between serum copper and early-stage triple-negative breast cancer (TNBC) remain scare. We sought to establish a predictive model incorporating serum copper levels for individualized survival predictions. Methods: We retrospectively analyzed clinicopathological information and baseline peripheric blood samples of patients diagnosed with early-stage TNBC between September 2005 and October 2016 at Sun Yat-sen University Cancer Center. The optimal cut-off point of serum copper level was determined using maximally selected log-rank statistics. Kaplan-Meier curves were used to estimate survival probabilities. Independent prognostic indicators associated with survival were identified using multivariate Cox regression analysis, and subsequently, prognostic nomograms were established to predict individualized disease-free survival (DFS) and overall survival (OS). The nomograms were validated in a separate cohort of 86 patients from the original randomized clinical trial SYSUCC-001 (SYSUCC-001 cohort). Results: 350 patients were eligible in this study, including 264 in the training cohort and 86 in the SYSUCC-001 cohort. An optimal cut-off value of 21.3 μmol/L of serum copper was determined to maximally divide patients into low- and high-copper groups. After a median follow-up of 87.1 months, patients with high copper levels had significantly worse DFS (p = 0.002) and OS (p < 0.001) than those with low copper levels in the training cohort. Multivariate Cox regression analysis revealed that serum copper level was an independent factor for DFS and OS. Further, prognostic models based on serum copper were established for individualized predictions. These models showed excellent discrimination [C-index for DFS: 0.689, 95% confidence interval (CI): 0.621–0.757; C-index for OS: 0.728, 95% CI: 0.654–0.802] and predictive calibration, and were validated in the SYSUCC-001 cohort. Conclusion: Serum copper level is a potential predictive biomarker for patients with early-stage TNBC. Predictive nomograms based on serum copper might be served as a practical tool for individualized prognostication.

The Safety and Feasibility of Laparoscopic Surgery for Very Low Rectal Cancer: A Retrospective Analysis Based on a Single Center’s Experience

In this work we intend to validate the long-term oncologic outcomes for very low rectal cancer over the past 20 years and to determine whether laparoscopic procedures are useful options for very low rectal cancer. A total of 327 patients, who electively underwent laparoscopic rectal cancer surgery for a lesion within 5 cm from the anal verge, were enrolled in this study and their long-term outcomes were reviewed retrospectively. Of 327 patients, 70 patients underwent laparoscopic low anterior resection (LAR), 164 underwent laparoscopic abdominal transanal proctosigmoidocolectomy with coloanal anastomosis (LATA), and 93 underwent laparoscopic abdominoperineal resection (APR). The conversion rate was 1.22% (4/327). The overall postoperative morbidity rate was 26.30% (86/327). The 5-year disease free survival (DFS), 5-year overall survival (OS), and 3-year local recurrence (LR) were 64.3%, 79.7%, and 9.2%, respectively. The CRM involvement was a significant independent factor for DFS (p = 0.018) and OS (p = 0.042) in multivariate analysis. Laparoscopic APR showed poorer 5-year DFS (47.8%), 5-year OS (64.0%), and 3-year LR (17.6%) than laparoscopic LAR (74.1%, 86.4%, 1.9%) and laparoscopic LATA (69.2%, 83.6%, 9.2%). Laparoscopic procedures for very low rectal cancer including LAR, LATA, and APR could be good surgical options in selective patients with very low rectal cancer.

Intratumoral lymphatic vascular density is an independent factor for disease-free and overall survival in advanced stage oral squamous cell carcinoma

The presence of lymphatic and blood vessels in oral squamous cell carcinoma (OSCC) should play a key role in progression and dissemination. This study aimed to evaluate the correlation between the lymphatic and blood vessel densities with prognostic outcomes in advanced stage OSCC. Immunohistochemical reactions for D-240, CD34, and CD105 were performed in 88 advanced stage OSCC cases located at the oral tongue and the floor of the mouth. The lymphatic vascular density (LVD), blood vascular density (BVD), and neoformed vascular density (NVD) were assessed by counting positive reactions in 4 hotspot areas, both intratumoral (IT) and peritumoral (PT), at high magnification (× 40). High IT LVD was associated with extracapsular spread of lymph node metastasis (P=.03). Recurrence rates were correlated with IT LVD (P < .0001), IT BVD (P=.036), and IT NVD (P=.047), and overall survival was associated with high IT LVD (P=.0016) and IT NVD (P=.009). Yet, IT LVD was an independent factor for disease-free survival and for overall survival based on the Cox proportional hazards model. Our results suggest that high IT LVD has a strong impact on survival outcomes in advanced stage OSCC.

Mutant p53 and Twist1 Co-Expression Predicts Poor Prognosis and Is an Independent Prognostic Factor in Breast Cancer.

PurposeThe basic helix-loop-helix transcription factor (bHLH) transcription factor Twist1 plays a key role in embryonic development and tumorigenesis. p53 is a frequently mutated tumor suppressor in cancer. Both proteins play a key and significant role in breast cancer tumorigenesis. However, the regulatory mechanism and clinical significance of their co-expression in this disease remain unclear. The purpose of this study was to analyze the expression patterns of p53 and Twist1 and determine their association with patient prognosis in breast cancer. We also investigated whether their co-expression could be a potential marker for predicting patient prognosis in this disease.MethodsTwist1 and mutant p53 expression in 408 breast cancer patient samples were evaluated by immunohistochemistry. Kaplan-Meier Plotter was used to analyze the correlation between co-expression of Twist1 and wild-type or mutant p53 and prognosis for recurrence-free survival (RFS) and overall survival (OS). Univariate analysis, multivariate analysis, and nomograms were used to explore the independent prognostic factors in disease-free survival (DFS) and OS in this cohort.ResultsOf the 408 patients enrolled, 237 (58%) had high mutant p53 expression. Two-hundred twenty patients (53.9%) stained positive for Twist1, and 188 cases were Twist1-negative. Furthermore, patients that co-expressed Twist1 and mutant p53 (T+P+) had significantly advanced-stage breast cancer [stage III, 61/89 T+P+ (68.5%) vs. 28/89 T-P- (31.5%); stage II, 63/104 T+P+ (60.6%)vs. 41/104 T-P- (39.4%)]. Co-expression was negatively related to early clinical stage (i.e., stages 0 and I; P = 0.039). T+P+ breast cancer patients also had worse DFS (95% CI = 1.217–7.499, P = 0.017) and OS (95% CI = 1.009–9.272, P = 0.048). Elevated Twist1 and mutant p53 expression predicted shorter RFS in basal-like patients. Univariate and multivariate analysis identified three variables (i.e., lymph node involvement, larger tumor, and T+P+) as independent prognostic factors for DFS. Lymph node involvement and T+P+ were also independent factors for OS in this cohort. The total risk scores and nomograms were reliable for predicting DFS and OS in breast cancer patients.ConclusionsOur results revealed that co-expression of mutant p53 and Twist1 was associated with advanced clinical stage, triple negative breast cancer (TNBC) subtype, distant metastasis, and shorter DFS and OS in breast cancer patients. Furthermore, lymph nodes status and co-expression of Twist1 and mutant p53 were classified as independent factors for DFS and OS in this cohort. Co-evaluation of mutant p53 and Twist1 might be an appropriate tool for predicting breast cancer patient outcome.

Survival risk prediction model for patients with pT1\u20133 N0M0 esophageal squamous cell carcinoma after R0 esophagectomy with two-field lymphadenectomy for therapeutic purposes

BackgroundThe overall survival (OS) remains unsatisfactory in patients with esophageal squamous cell carcinoma (ESCC) after extended esophagectomy with two-field lymphadenectomy. Therefore, this retrospective study aimed to identify the risk factors that contribute to the low survival of patients with pT1–3N0M0 ESCC.MethodsPatients with pT1–3N0M0 ESCC who only underwent R0 esophagectomy with two-field lymphadenectomy in our department from January 2008 to December 2012 were retrospectively enrolled in this study and medical records were reviewed. Postoperative OS, disease-free survival (DFS), recurrence-free survival (RFS), and locoregional recurrence-free survival (LRFS) were analyzed sequentially.ResultsThis study recruited a total of 488 patients, whose follow-up visits were completed at the end of December 2019. The five-year OS, DFS, RFS and LRFS rates were 62.1, 53.1, 58.3 and 65.6%, respectively. Multivariate Cox analysis identified patient age, site of the lesion, small mediastinal lymph nodes in CT imaging (SLNs in CT), dissected lymph nodes (LNs), and stage of esophageal malignancy as independent risk factors for OS of the patients. Of these factors, the site of the lesion, SLNs in CT and stage of the cancer were determined to be independent factors for DFS, RFS and LRFS. Based on all five factors, the recursive partitioning analysis (RPA) score system was developed to stratify the patients into low-, medium- and high-risk groups, which were found to possess significantly different rates of OS, DFS, RFS and LRFS (p < 0.001).ConclusionsSeveral factors were associated with the survival of patients with pT1–3 N0M0 ESCC who underwent extended esophagectomy with two-field lymphadenectomy. These factors contributed to the RPA scoring system, which could stratify the risk of postoperative survival and may expedite the initiation of postoperative adjuvant therapy.

Abstract PS2-30: The expression of PD-L1 (Ventana SP142) in HER2-positive breast cancer and its relationship with clinicopathological characteristics

Abstract Objective: This article aims to investigate the correlation between the expression of PD-L1 and tumor-infiltrating lymphocytes, clinicopathological features and prognosis in HER2-positive breast cancer.Methods: This study included 156 cases of HER2-positive breast cancer. Three 2mm tumor cores were selected for each case, and the expression of PD-L1 on ICs was detected by Immunohistochemistry. Statistical software SPSS 24.00 was used for analysis, χ2 test and Fisher exact test were used for correlation and consistency analysis; Logistic regression analysis was used for multivariate analysis; Kaplan-Meier analysis was used for univariate survival; Cox regression analysis was used for multivariate survival; TILs and PD-L1 correlation was analyzed by Spearman rank; P&amp;lt;0.05 was considered statistically significant.Results: In HER2-positive breast cancer the expression rate of PD-L1 on ICs was 31.4%. In HER2-positive breast cancer the expression of PD-L1 on ICs was significantly correlated with the tumor size, the presence or absence of lymphovascular invasion, the expression of TILs, CD4 and CD8 (P&amp;lt;0.05); obtained using Logistic multivariate regression analysis The tumor size, the presence or absence of vascular tumor plugs, the expression of TILs and CD8 were independent factors affecting PD-L1 expression (P &amp;lt;0.05). Spearman rank correlation analysis showed that TILs infiltration level was positively correlated with interstitial immune cell PD-L1 expression in HER2-positive breast cancer patients (r = 0.486,P &amp;lt;0.05). Univariate survival analysis of disease-free survival (DFS) for HER2-positive breast cancer the patient's tumor size, lymphovascular invasion, lymph node metastasis, TILs, tumor immune microenvironment classification-CD4 (TIME-CD4) and tumor immune microenvironment classification-CD8 (TIME-CD8) has a significant effect on patients' DFS (P&amp;lt;0.05); multivariate survival analysis revealed that patients had lymphovascular invasion, TILs, TIME-CD4 and TIME-CD8 as HER2-positive breast cancer independent factors of DFS (P&amp;lt;0.05).Conclusions: The expression of PD-L1 on ICs in HER2-positive breast cancer is related to tumor size, presence or absence of lymphovascular invasion, TILs,CD4 expression and CD8 expression.The independent influencing factors of disease-free survival in patients with HER2-positive breast cancer are the presence or absence of lymphovascular invasion, TILs, TIME-CD4 and TIME-CD8. Among them, patients with no lymphovascular invasion and higher levels of tumor infiltrating lymphocytes had better prognosis; CD4-/PD-L1- group had better prognosis in the TIME-CD4 and CD8+/PD-L1- group had better prognosis in the TIME-CD8. There is a positive correlation between TILs infiltration level and PD-L1 expression, suggesting that HER2-positive breast cancer patients can be accurately treated according to different TILs infiltration levels and PD-L1 expression.Key words: breast cancer; HER2-positive;PD-L1;TILs Citation Format: Ningning Zhang, Yueping Liu. The expression of PD-L1 (Ventana SP142) in HER2-positive breast cancer and its relationship with clinicopathological characteristics [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-30.