Significant Prognostic Factors Research Articles

Significance of absolute neutrophil count before allogeneic hematopoietic stem cell transplantation in adult patients with aplastic anemia.

The impact of absolute neutrophil count (ANC) before allogenic hematopoietic stem cell transplantation (HSCT) on the outcomes for patients with aplastic anemia (AA) remains unclear. We retrospectively evaluated the relationship between ANC before transplantation and patient outcomes, involving 883 adult Japanese patients with AA who underwent allogeneic HSCT as their first transplantation between 2008 and 2020. Patients were divided into three groups based on ANC: 0/µL (n = 116); 1-199 (n = 210); and ≥ 200 (n = 557). In the low ANC groups (ANC < 200), patient age was higher, previous anti-thymocyte globulin (ATG) treatments were infrequent, duration from diagnosis to transplantation was shorter, hematopoietic cell transplantation-comorbidity index (HCT-CI) was higher, ATG-based conditioning was used infrequently, and peripheral blood stem cell from related donor and cord blood were used frequently. In multivariate analysis, patient age, previous ATG treatment, HCT-CI, stem cell source, and ANC before transplantation were significantly associated with 5-year overall survival (OS) ("ANC ≥ 200": 80.3% vs. "ANC 1-199": 71.7% vs. "ANC 0": 64.4%). The cumulative incidence of bacterial infection, invasive fungal disease, and early death before engraftment were significantly higher in the low ANC groups. Among patients with ANC of zero before transplantation, younger patient age, shorter duration from diagnosis to transplantation, HCT-CI of 0, and bone marrow from related donor as stem cell source were significantly associated with better OS. Consequently, ANC before allogeneic HSCT was found to be a significant prognostic factor in adult patients with AA. Physicians should pay attention to ANC before transplantation.

Intratumoral metabolic heterogeneity by 18F-FDG PET/CT to predict prognosis for patients with thymic epithelial tumors.

The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001). HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline 18F-FDG PET/CT might be promising to identify patients with poor prognosis.

Does Condylar Morphology Affect Maxillary Repositioning in Bimaxillary Orthognathic Surgery?

This study aimed to measure the association between condylar morphology and a measure of the maxillary centroid following bimaxillary surgery using mandibular-dependent splints. The study included skeletal Class III and Class II malocclusion patients, excluding those with facial asymmetry. Based on computed tomography imaging patients were characterized into normal or abnormal temporomandibular joint (TMJ) groups. A computer-aided design/computer-aided manufacturing splints were fabricated to reposition the maxilla in Le Fort I osteotomy. The primary outcome measure was the absolute differences between the maxillary centroid's the planned and actual postoperative positions calculated by superimposing computed tomography scans. The secondary outcome was the measure of other variations in linear and angular maxilla discrepancies. The demographic covariates included the age and sex of the patients. The operative covariates consisted of the dentofacial deformity and the planned movement of the maxilla. Seventy patients with skeletal maxillofacial deformities were included for analysis: 44 patients in the normal and 26 in the abnormal TMJ group. The average maxillary misalignment was 1.04±0.48mm in the normal and 1.53±0.63mm in the abnormal TMJ group (P<0.001). A statistically significant relationship existed between the discrepancies of the maxillary centroid and dentofacial deformity (η=0.656, P<0.001). These findings suggest an increased propensity for maxillary malposition in skeletal Class II patients. Furthermore, condylar morphology is a significant prognostic factor influencing maxillary repositioning errors in bimaxillary surgery with mandibular-dependent splints.

Prognostic Factors and Impact of Therapeutic Intervention in Patients With Brain Metastases at the Initial Presentation.

Background Studies investigating the normative characteristics and prognosis of patients diagnosed with brain metastases (BMs) at the onset of cancer are scarce. Therefore, we analyzed real-world treatment options. Methodology This retrospective study enrolled 112 patients newly diagnosed with BM between May 2006 and October 2021. The variables examined included patients' age, sex, recurrence split analysis, Glasgow prognostic score (GPS), number of lesions, tumor size, peripheral brain tumor edema, targeted therapy, supportive care, chemotherapy, and date of onset. Prognostic factors were assessed using recursive partitioning analysis (RPA), graded prognostic assessment (GPA) scores, and GPS scoring, with magnetic resonance imaging (MRI) andcomputed tomography (CT) studies. Primary treatment comprised whole-brain radiotherapy (WBRT), with regular follow-up. Results Data from 112 survivors were analyzed, revealing a median overall survival time (MST) of 7.7 months, with some patients surviving beyond 24 months post-WBRT. Univariate analysis revealed associations between MST and RPA class, GPS, and treatment modalities (including targeted therapy and chemotherapy). RPA class 2, GPSof 0, and targeted therapy were identified as predictors of better prognosis in the multivariate analysis. In the subgroup not receiving chemotherapy, no significant difference in prognosis was seen between groups with or without WBRT. Conclusions Alongside RPA, scores indicating chronic inflammatory changes, including GPS, were confirmed as crucial prognostic factors. Moreover, treatment with molecularly targeted drugs correlated with favorable prognoses. The treatment-naïve group exhibited poorer prognoses, and WBRT was not deemed a significant prognostic factor in the chemotherapy group.

Outcome of Transarterial Radioembolization in the Treatment of Hepatocellular Carcinoma: Glass Versus Resin Microsphere.

To compare the treatment outcomes of glass and resin microspheres for the treatment of hepatocellular carcinoma (HCC) and evaluate the prognostic factors that influence the outcomes. We retrospectively reviewed 251 consecutive patients who underwent radioembolization for the treatment of HCC at a single tertiary center. Imaging responses after radioembolization were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) 1.1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to identify the prognostic factors. A total of 195 patients were included in this study (glass microsphere, n = 75; resin microsphere, n = 120). The complete and objective response rates were 16.0% and 50.7% in the glass microsphere group and 17.5% and 58.3% in the resin microsphere group, respectively. Median PFS was 241days in the glass microsphere group and 268days in the resin microsphere group (p = 0.871). Median OS was 29months in the glass microsphere group and 40months in the resin microsphere group (p = 0.669). The only significant prognostic factor was bilobar tumor distribution, which favored resin microspheres (p = 0.023). Procedure-related adverse events occurred more frequently in the resin microsphere group (glass, 2.7% vs. resin, 5.0%; p < 0.001). Glass and resin microspheres for the treatment of HCC did not show a significant difference in survival, though major adverse events occurred more frequently with the use of resin microspheres.

Outcomes in Nonmetastatic Hormone Receptor-Positive HER2-Negative Pure Mucinous Breast Cancer: A Multicenter Cohort Study.

Although considered a favorable subtype, pure mucinous breast cancer (PMBC) can recur, and evidence for adjuvant therapy is limited. We aimed to compare outcomes of nonmetastatic PMBC with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) to address these uncertainties. Individual patient-level data from 6 centers on stage I-III hormone receptor-positive and HER2-negative PMBC, IDC, and ILC were used to analyze recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), and to identify prognostic factors for PMBC. Data from 20,684 IDC cases, 1,475 ILC cases, and 943 PMBC cases were used. Median follow-up was 6.6 years. Five-year RFI, RFS, and OS for PMBC were 96.1%, 94.9%, and 98.1%, respectively. On multivariable Cox regression, PMBC demonstrated superior RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) compared with IDC. ILC showed comparable outcomes to IDC. Fewer than half (48.7%) of recurrences in PMBC were distant, which was a lower rate than for IDC (67.3%) and ILC (80.6%). In contrast to RFI, RFS events were driven more by non-breast cancer deaths in older patients. Significant prognostic factors for RFI among PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70). No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age. A separate SEER database analysis also did not find any association of improved survival with adjuvant chemotherapy in these subgroups. Compared with IDC, PMBC demonstrated superior RFI, RFS, and OS. Lymph node negativity, adjuvant radiotherapy, and endocrine therapy were associated with superior RFI. Adjuvant chemotherapy was not associated with better outcomes.

Olaparib maintenance therapy for platinum-sensitive relapsed ovarian cancer at a single institution: A retrospective study.

In this study, we aimed to investigate patient characteristics, efficacy, prognostic factors, and safety of olaparib maintenance therapy for platinum-sensitive recurrent ovarian cancer at our institution. Patients responding to platinum-based therapy and starting olaparib maintenance therapy for recurrent epithelial ovarian, fallopian tube, or peritoneal cancer at Kurume University Hospital between January 2018 and November 2021 were enrolled in the study. Their data were extracted retrospectively from medical records. In all, 50 patients were included. The median (range) age of the patients, follow-up time, and duration of olaparib maintenance therapy were 62 (39-87) years, 21.6 (2.2-45.9) months, and 7.2 (2-45.9) months, respectively. Among the 29 patients tested for homologous recombination (HR) status, 22 (75.9%) were positive for HR deficiency (HRD), 12 (54.5%) of whom had BRCA-positive tumors. The median progression-free survival was 8.9 months (95% confidence interval: 6.2-12.6), and the median overall survival was 27.1 months (95% confidence interval: 22.5-40.3). Multivariate analysis of prognostic factors revealed that HRD was an independent prognostic factor for both progression-free survival and overall survival. The most common adverse event was nausea (any grade, n = 30, 60%), resulting in drug interruption (n = 23, 46%), dose reduction (n = 17, 34%), and discontinuation of treatment (n = 1, 2%). Olaparib maintenance therapy for recurrent platinum-sensitive ovarian cancer at our institution was effective, with acceptable adverse events. HRD was the most significant prognostic factor for patients with recurrent platinum-sensitive ovarian cancer.

Prognostic significance of HER2 loss after HER2-targeted neoadjuvant treatment in patients with HER2-positive locally advanced breast cancer

Loss of human epidermal growth factor receptor 2 (HER2) expression can be seen in almost 25–30 % patients after HER2 receptor directed neoadjuvant treatment. These patients have unclear clinical outcomes in previous studies. We aimed to investigate the importance of HER2 loss, additionally with predictive factors for the loss of HER2. This was a retrospective and multicenter study that included 272 HER2-positive BC patients with no pathological complete response who received neoadjuvant chemotherapy plus HER2-targeted treatments. The factors that may affect the loss of HER2 detected by immunohistochemistry(IHC) and the association with survival were analyzed.The rate of HER2 loss after neoadjuvant treatments(NAT) was 27.9 % (n = 76). Disease recurrence was observed in 18(23.7 %) patients with HER2 loss, while it was detected in 62 (31.7 %) patients without HER2 loss(p = 0.23). Pre and post-NAT ER status, and post-NAT ki-67 status had a significant impact on disease-free survival(DFS) (p = 0.0012, p = 0.004, and p = 0.04, respectively).There were no significant association between DFS and loss of HER2 (p = 0.64) and dual anti-HER2 blockade (p = 0.21). Pre-NAT clinical stage (HR:1.65 p = 0.013), post-NAT LN status (HR:3.18, p = 0.02) and pre-NAT ER status (HR:0.24, p = 0.041) were significant independent prognostic factors for DFS while post-NAT residual disease in axillar tissue was an independent prognostic factor for OS (HR:1.54 p = 0.019). Moreover, age (<40 years vs ≥40 years) (p = 0.031) and tumor grade (p = 0.004) were predictive factors for HER2 loss. Our results showed that HER2 loss did not affect survivals. However, young age and being high grade tumor may predict HER2 loss.

Association between intraoperative findings and postoperative knee range motion after cruciate-retaining total knee arthroplasty.

Total knee arthroplasty (TKA) alleviates pain and improves daily living activities in individuals with end-stage osteoarthritis of the knee. However, up to 20% of patients have sub-optimal outcomes after TKA. No studies have clarified the intraoperative factors that affect postoperative range of motion (ROM) after cruciate-retaining (CR) TKA. Thus, this study aims to clarify these factors. Patients with knee osteoarthritis with varus knee deformity who underwent CR-TKA between May 2019 and December 2020 were included in this study. One year after surgery, patients were stratified into two groups based on knee flexion: Group F (over 120∘) and Group NF (below 120∘). Patient backgrounds including age, body mass index, hip knee angle, preoperative range of motion for both extension and flexion, intraoperative center joint-gap measurements of 0∘, 30∘, 45∘, 60∘, 90∘, and 120∘ of knee flexion using a tensor, intraoperative anterior-posterior (AP) laxity measurements of 30∘ and 90∘ of knee flexion using an instrumental laximeter were compared between the groups. Univariate analyses between the groups were used to construct the initial model. The receiver operating characteristic curve was also analyzed. The predictive variables included in the final model were selected by stepwise backward elimination. Intraoperative AP laxity with 30∘ of knee flexion smaller than 10.8 mm was a significant positive prognostic factor (OR: 1.39, 95% CI: 1.08-1.79, P= 0.011) of postoperative ROM over 120∘ of knee flexion one year after surgery. The sensitivity, specificity, PPV, and NPV were 70.9%, 82.4%, 92.9%, and 46.7%, respectively. Intraoperative AP laxity smaller than 10.8 mm was a significant positive predictive factor for obtaining knee flexion greater than 120∘ one year after surgery when using CR-TKA and its PPV was high up to 92.9%.

Survivin, β-catenin, and ki-67 immunohistochemical expression in canine perivascular wall tumors: Preliminary assessment of prognostic significance.

High survivin expression has been correlated with poor outcomes in several canine tumors but not in soft tissue tumors (STTs). Survivin is a target gene of the Wnt/β-catenin pathway, which is involved in human STT oncogenesis. Immunohistochemistry for survivin, β-catenin, and Ki-67 was performed on 41 canine perivascular wall tumors (cPWTs), and statistical associations of protein expression and histopathologic and clinical variables with clinical outcomes were investigated. Immunohistochemically, there was nuclear positivity (0.9%-12.2% of tumor cells) for survivin in 41/41 (100%), cytoplasmic positivity (0 to > 75% of tumor cells) for survivin in 31/41 (76%), nuclear positivity (2.9%-67.2% of tumor cells) for β-catenin in 24/41 (59%), and cytoplasmic positivity (0% to > 75% of tumor cells) for β-catenin in 23/41 (56%) of cPWTs. All tumors expressed nuclear Ki-67 (2.2%-23.5%). In univariate analysis and multivariate analysis (UA and MA, respectively), every 1% increase of nuclear survivin was associated with an increase of the instantaneous death risk by a factor of 1.15 [hazard ratio (HR) = 1.15; P = .007]. Higher nuclear survivin was associated with grade II/III neoplasms (P = .043). Expression of cytoplasmic survivin, nuclear and cytoplasmic β-catenin, and nuclear Ki-67 were not significantly associated with prognosis in UA nor MA. Tumor size was a significant prognostic factor for local recurrence in UA [subdistribution HR (SDHR) = 1.19; P = .02] and for reduced overall survival time in MA. According to UA and MA, a unitary increase of mitotic count was associated with an increase of the instantaneous death risk by a factor of 1.05 (HR = 1.05; P = .014). Nuclear survivin, mitotic count, and tumor size seem to be potential prognostic factors for cPWTs. In addition, survivin and β-catenin may represent promising therapeutic targets for cPWTs.

Surgical outcome and risk scoring to predict survival after hepatic resection for hepatocellular carcinoma with portal vein tumor thrombosis.

The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA-II, neutrophil-to-lymphocyte ratio, and albumin-bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors-tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

Pathological T3 Non-Small Cell Lung Cancer with satellite nodules: Number or size, what does matter?

BackgroundNon-small Cell Lung Cancer (NSCLC) with intralobar satellite nodule are defined as T3 (T3SN). We investigated the main features of these tumors and analyzed their impact on Overall Survival (OS). MethodsThis was a retrospective multicentric study including all pT3SN NSCLC operated on between 2005 and 2020, excluding patients with multifocal ground-glass opacities; who received induction therapies; N3 or stage IV. The diameter of largest (LgN) and smallest nodule (SmN), the total diameter (sum of diameter of all nodules, TS), and the number of SN were measured. ResultsAmong 102 patients, 64.7 % were male. 84.3 % of patients had one SN (84.3 %), 9.8 % two SN while 5.9 % more than 2 SN. 63 patients were pN0. LgN (p = 0.001), SN (p = 0.005) and TS (p = 0.014) were significantly related to lymph-node metastasis; the LgN and TS were related to visceral pleural invasion (p < 0.001).Five-year OS was 65.1 %; at univariable analysis more than 2 satellite nodules, LgN and TS were significantly related to worse OS; at multivariable analysis, TS (Hazard Ratio [HR] 1.116 95 % Confidence Interval [CI] 1.008–1.235, p = 0.034) was an independent prognostic factors for OS. No significant prognostic factors were found for DFS at multivariable analysis.In pN0 patients, LgN (HR 1.051, 95 % CI 1.066–1.099, p = 0.027) and non-adenocarcinoma (HR 5.315 CI 95 % 1.494–18.910, p = 0.010) influenced OS. ConclusionsTumor size is related to tumor's local invasiveness. TS is an independent prognostic factor for OS. Patients with more than 2 SN seem to be at higher risk for death and recurrence.

Development and Validation of a Prognostic Nomogram for Breast Cancer Patients With Multi-Organ Metastases: An Analysis of the Surveillance, Epidemiology, and End Results Program Database.

Multi-organ metastases represent a substantial life-threatening risk for breast cancer (BC) patients. Nonetheless, the current dearth of assessment tools for patients with multi-organ metastatic BC adversely impacts their evaluation. We conducted a retrospective analysis of BC patients with multi-organ metastases using data from the SEER database from 2010 to 2019. The patients were randomly allocated into a training cohort and a validation cohort in a 7:3 ratio. Univariate COX regression analysis, the LASSO, and multivariate Cox regression analyses were performed to identify independent prognostic factors in the training set. Based on these factors, a nomogram was constructed to estimate overall survival (OS) probability for BC patients with multi-organ metastases. The performance of the nomogram was evaluated using C-indexes, ROC curves, calibration curves, decision curve analysis (DCA) curves, and the risk classification system for validation. A total of 3626 BC patients with multi-organ metastases were included in the study, with 2538 patients in the training cohort and 1088 patients in the validation cohort. Age, grade, metastasis location, surgery, chemotherapy, and subtype were identified as significant independent prognostic factors for OS in BC patients with multi-organ metastases. A nomogram for predicting 1-year, 3-year, and 5-year OS was constructed. The evaluation metrics, including C-indexes, ROC curves, calibration curves, and DCA curves, demonstrated the excellent predictive performance of the nomogram. Additionally, the risk grouping system effectively stratified BC patients with multi-organ metastases into distinct prognostic categories. The developed nomogram showed high accuracy in predicting the survival probability of BC patients with multi-organ metastases, providing valuable information for patient counseling and treatment decision making.

Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. The median OS was 16.7months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Liver Resection in Synchronous Bilobar versus Unilobar Colorectal Liver Metastases: A Retrospective Analysis of Oncological Outcomes and Patient Survival

Introduction: Resection of colorectal liver metastasis has emerged as the standard treatment. Our study compares oncological outcomes of patients with resected synchronous bilobar versus unilobar colorectal liver metastasis. Methods: This retrospective study presents long-term follow-up data of 105 consecutive patients with primary colorectal cancer and synchronous liver metastasis. All patients underwent primary tumor and metastasis resections between 2007 and 2019. Results: Fifty-five patients with bilobar and 50 patients with unilobar colorectal liver metastases were included. No significant difference in overall, tumor-specific, or recurrence-free survival was observed between patients with bilobar and unilobar metastases. After case-control matching, the results were confirmed in patients with similar tumor burdens. In the multivariate analysis, chemotherapy following liver metastasis resection was a significant prognostic factor associated with improved overall survival (hazard ratio 0.518, 95% confidence interval: 0.302–0.888, p = 0.017). Conclusion: Overall survival, as well as tumor-specific and recurrence-free survival, did not differ between patients with unilobar and bilobar liver metastasis. These findings contribute to the understanding that primary tumor and metastasis resection in eligible patients improve long-term outcomes.

Prognostic value of perioperative changes in the prognostic nutritional index in patients with surgically resected non-small cell lung cancer.

This single-institution retrospective cohort study was conducted to assess the prognostic significance of perioperative changes in the prognostic nutritional index (PNI) in patients who underwent surgery for non-small cell lung cancer (NSCLC). Clinicopathological data were collected from 441 patients who underwent lobectomy for NSCLC between 2010 and 2016.The PNI ratio (postoperative PNI/preoperative PNI) was used as an indicator of perioperative PNI changes. Prognostic differences were investigated based on PNI ratios. The optimal cut-off value of the PNI ratio for overall survival (OS) was set at 0.88 using a receiver operating characteristic curve. The PNI ratio was inversely related to a high smoking index, interstitial lung disease, and postoperative pulmonary complications. The 5-year OS rates for the high vs. low PNI ratio groups were 88.2% vs. 68.5%, respectively (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.90-4.86). Multivariable analysis revealed that a low PNI ratio was significantly associated with poor prognosis (HR: 2.94, 95% CI: 1.77-4.87). The PNI ratio was a more sensitive indicator than postoperative PNI status alone for identifying patients at high risk of mortality, particularly those with non-lung cancer causes. The perioperative PNI change is a significant prognostic factor for patients with NSCLC.

Abstract PO3-17-02: Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years

Abstract Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years Ahrong Ham1, Sewon Lee1, Jungmin Jo1, Soo Ji Hong2, Ji Eun Lee2, Haena Lee2, Sungchan Gwark2, Jeongshin An2, Hyun Goo Kim2, Jun Woo Lee2, Joohyun Woo2, Woosung Lim2, Byung-In Moon2, Sei Hyun Ahn2, Hye Ah Lee3, Kyoung Eun Lee1 1 Division of Hematology and Oncology, Department of Internal Medicine, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 2 Department of Surgery, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea 3 Clinical Trial Center, Ewha Womans University Mokdong hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea Purpose: Over the last two decades, treatment landscapes for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) have shown remarkable growth with the development of drugs targeting HER2. The standard of care for HER2+ MBC has continued to change with the ongoing development of new anti-HER2 therapies. We aimed to provide a comprehensive analysis of HER2-targeted therapies, clinical characteristics, and treatment outcomes in real-world practice of HER2+ MBC patients over the past 20 years. Methods: Patients who received palliative chemotherapy with HER2+ MBC between 2000 and 2022 were analyzed. We derived cohorts of two groups with or without anti-HER2 containing therapies. Patients receiving multiple anti-HER2 therapies throughout the entire period of treatment were further analyzed according to treatment regimen. The progression-free survival for palliative first-line (PFS1), and overall survival (OS) were compared between groups. A multivariate Cox regression model was used to investigate predictors of survival outcome in HER2+ MBC. Results: A total of 185 patients were analyzed. Median age was 49 years (IQR, 42-56 years). 47 patients (25.4%) were initially diagnosed with de novo stage IV disease. Visceral metastases were found in 95 patients (51.4%). The median PFS1 was 3.9 months (without anti-HER2 therapy) versus 15.6 months (with anti-HER2 therapy) between two groups (P&amp;lt; 0.001). Likewise, the median OS was significantly improved in anti-HER2 therapy group (34.0 months vs. 70.5 months, P=0.010). As a result of confirming the difference in OS according to the type of anti-HER2 therapies during the entire period of treatment by correspondence analysis, significant improvement was found when two or three types of anti-HER2 were used (without anti-HER2 vs. 2 types of anti-HER2, P=0.009; without anti-HER2 vs. 3 types of anti-HER2, P=0.010). Interestingly, when analyzed by treatment regimen, trastuzumab (H) + pertuzumab (P), HP + TDM-1, and H + TDM-1 significantly improved OS over regimens without anti-HER2 (without anti-HER2 vs. HP, P=0.009; without anti-HER2 vs. HP + TDM-1, P=0.013; without anti-HER2 vs. H + TDM-1, P=0.028, respectively). HP + TDM-1 therapies significantly improved survival rate compared to H single containing regimen (P=0.029). Based on our multiple Cox regression model, visceral metastasis was a significant poor OS prognostic factor and two and three types of anti-HER2 therapies were associated better OS prognosis (visceral metastasis: HR=2.40, P=0.003; 2 types of ant-HER2: HR=0.29, P=0.001; 3 types of anti-HER2: HR=0.22, P=0.018, respectively). Conclusions: Anti-HER2 therapies significantly improved PFS1 and OS. Continuing treatment by changing anti-HER2 therapies may act as a better prognostic factor. Further prospective studies are required. Citation Format: Ahrong Ham, Sewon Lee, Jungmin Jo, Soo Ji Hong, Ji Eun Lee, Haena Lee, Sungchan Gwark, Jeongshin An, Hyun-Goo Kim, Jun Woo Lee, Joohyun Woo, Woosung Lim, Byung-In Moon, Sei Hyun Ahn, Hye Ah Lee, Kyoung Eun Lee. Analysis of clinical benefit in the real world of HER2-positive metastatic breast cancer following the development of anti-HER2 therapeutics over the past 20 years [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 PO3-17-02.

Abstract PO4-05-13: Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis

Abstract Introduction: Deleted in Liver Cancer 1 Protein, DLC1, also known as StAR Related Lipid Transfer Domain Containing 12 (StarD12), is a known negative regulator of the Rho GTPases and at the cellular level regulates cell migration. DLC1 gene transcription produces multiple isoforms of the DLC1 protein. The present study examined the clinical and prognostic implications of DLC1 isoforms, DLC1/V1/V2/V3, in relationship with Rho GTPases in human breast cancer. Methods: Expression of three DLC1 isoforms was evaluated in a cohort of breast cancer tissues and against the clinical, pathological and clinical outcome of patients. DLC1 expression was also assessed and compared against Rho GTPases, including Rho and Rho GTP Dissociation Inhibitor (Rho GDI), in the same cohort. Results: DLC1/V3 had a significant impact on the overall survival of patients and high levels were linked to shorter survival (Hazard Ratio=3.551 (95%CI 1.332-9.471, p=0.011), a prediction that was independent of other factors in multivariate analysis. RUC analysis demonstrated a significant predictive value for bone metastasis with DLC1/V3 (RUC=0.714, p=0.020), showing a Hazard ratio of 9.0 (1.8-44.5, p=0.007). Similarly, high DLC1/V2 expression was also linked to a shorter overall survival (p=0.035). DLC1/V2 did not show a significant correlation with bone metastasis. In contrast to V3 and V2 variants, DLC1 had a marginal overall survival benefit for the patients, in that patients with high DLC1 had a longer survival (p=0.056). DLC1/V3 had a contrasting correlation with Rho-A (r=-0.203, p=0.015) and Rho-GDI-G (r=0.194, p=0.019) and the combined expression of DLC1/V3 and RhoA/Rho-GDI-G further identified patients with poorer clinical outcome. Conclusions: DLC1 and its variants have differing impacts on breast cancer; whereas DLC1 appears to be a tumour suppressive molecule, its variant isoform-3 was more oncogenic and a significant negative prognostic factor, together with its regulators Rho and Rho GDI. Citation Format: Binbin Cong, Jane Lane, Xiaoshan Cao, Tracey Martin, Robert E Mansel, Eleri Davies, Wen Jiang. Expression of DLC1/STARD12 and variants in clinical breast cancer and implication in skeletal metastasis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-13.

Abstract PO1-27-07: Is HER2-low a biologically distinct breast cancer (BC) subtype? Prognosis and pathological complete response rate after neoadjuvant treatment (NAT) in early breast cancer (BC) HER2 negative

Abstract Background: Overexpression of HER2 is a significant prognostic and predictive factor in early breast cancer. HER2 positive tumors are those scored by immunohistochemistry (IHC) 3+ or 2+ with amplification by in situ hybridization (ISH). These tumors may benefit from HER2-targeted treatment and additionally, in early HER2-positive BC, achieving a complete pathological response after neoadjuvant treatment improves patient survival. In recent years, new anti-HER2 antibody-drug conjugates have proven effective for HER2 low BC (defined as IHC score 1+ or 2+ not amplified) in the metastatic disease setting; however, in HER2-low early BC, studies testing novel anti-HER2 antibody-drug conjugates as neoadjuvant therapy (NAT) are ongoing. Currently, we don´t know exactly whether HER2 expression can influence the pathological response rate after NAT or disease-free survival (DFS) in these patients compared to HER2-zero (IHC 0). The aim of our study is to determine the impact on response rate to NAT and survival outcomes in early HER2-negative BC. Methods: We conducted a retrospective study in two hospitals in Andalucia, Spain. Patients with early HER2 negative BC treated with NAT from January 2015 to June 2022 were included. Patients were divided into HER2 low patients (IHC 1+ or 2+ not amplified) and HER2 0 (IHC 0). We collected clinical and pathological characteristics, pathological response rate using the Residual Cancer Burden (RCB) system where a complete pathological response (pCR) was defined as ypT0/ypTis and ypN0, and survival outcomes. The primary objective of the study was to analyze the pCR rate after NAT according to HER2 score, and secondary objectives were to assess disease-free survival and overall survival (DFS and OS rates). Results: 574 patients were included (100% women). 397 patients had hormone receptors (luminal BC) on these tumors, and 177 did not have them, i.e., triple-negative BC (TNBC). 225 patients were HER2-zero, and 312 patients were HER2-low (253/312 patients had luminal BC and 59/312 patients were TNBC). The pCR in HER2-low patients was 17.3% and 23.1% in HER2-zero patients (p=0.047). For luminal BC patients, the pCR was 16.7% in HER2-low tumors and 13.7% in HER2-zero tumors (p=0.29). Similarly, there was no difference in pCR rates in TNBC patients (45.8% in HER2-low and 53.8% in HER2-zero tumors, respectively, (p=0.958). The overall survival (OS) at 96 months was 88.7% (95% CI 85.6%-92%). Regarding survival outcomes, neither HER2 expression level was associated with higher 8-year DFS: 81.1% in HER2-low patients (95% CI 75.7%-86.8%) and 74.9% in HER2-zero patients (95% CI 62.3%-90.1%) p=0.64. There was no difference between histological subtypes at 8-years regarding DFS rate: 80.5% (95% CI 74.3%-87.2%) in luminal HER2-low patients and 76.3% (95% CI 60.8%-95.7%) in luminal HER2-zero patients, p=0.22; 83.8% in TNBC HER2-low (95% CI 74.5%-94.2%) and 77.5% in TNBC HER2-zero patients (95% CI 69.4%-86.6%) p=0.26. We also didn´t find significant differences in terms of OS. For HER2-low patients, the 8-year OS was 90.9% (95% CI 87%-94.9%) and for HER2-zero patients, it was 86.4% (95% CI 80.8%- 92.5%) p=0.46. There were also no differences in OS for different histological subgroups with an 8-year OS in luminal HER2-low breast cancer patients of 92.5% (95% CI 88%-96.7%) and 87% in HER2-zero (95% CI 78.9%-96.1%) p=0.91. In patients with triple-negative breast cancer phenotype, the OS was 84.2% for HER2-low (95% CI 74.5%-95.2%) and 85.3% for HER2-zero (95% CI 77.9%-93.4%) p=1. Conclusions: We found no difference in survival outcomes and response rate to conventional NAT between HER2-low and HER2-zero expression levels. Therefore, our data do not support the hypothesis of HER2-low as a biologically specific breast cancer subtype. Further research on this approach with HER2 antibody-drug conjugate schemes as an alternative to traditional NAT schemes is warranted. Citation Format: Ana Gil-Torralvo, Yeray Rodriguez, Alejandro Falcon, David Morales, Mónica Cejuela, Isabel Miras, Marta Amérigo, Manuel Ruíz - Borrego, Juan Bayo, Francisco Javier Salvador Bofill. Is HER2-low a biologically distinct breast cancer (BC) subtype? Prognosis and pathological complete response rate after neoadjuvant treatment (NAT) in early breast cancer (BC) HER2 negative [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-07.

Abstract PO3-05-02: Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort

Abstract Background: In patients (pts) with early breast cancer (BC), the level of expression of estrogen receptor (ER) evaluated by immunohistochemistry is prognostic and predictive while progesterone receptor (PR) expression has an additional prognostic value. Allred scoring combines the percentage of positive cells and the intensity of staining. It is widely used for treatment choice for early BC. In metastatic setting, its role is less defined. Methods: The ESME database is a French National cohort of all consecutive pts who initiated a first-line treatment for metastatic BC (MBC) between January 2008 and December 2020 in one of the 18 French Comprehensive Cancer Centers (NCT03275311). For this study, we selected pts with HER2- MBC, known ER expression and intensity percentages, known PR status and who received endocrine-based therapy as first-line metastatic treatment. Primary objective was to evaluate the overall survival (OS) and first line progression-free survival (PFS1) under endocrine therapy according to ER and PR expression level. ER expression was defined using Allred score on the last available tumor sample. PR status was defined using a positive (≥10%)vs negative ( &amp;lt; 10%) threshold. Secondary objective was to evaluate clinical PFS1 whether de novo or recurrent MBC and according to type of first line therapy (mono- vs combined endocrine therapy). Results: In the ER+ ± PR+/HER2- population, 8269 pts had information on ER percentage and staining intensity. Median follow-up was 53.4 months (95%CI [51.9; 54.7]). Allred score distribution, OS and PFS1 are described in table 1. Median OS was 43.1 months [41.1; 45.0] for the PR- group compared with 52.3 months [50.5; 54.4] for the PR+ group. After adjustments, patients with a PR- tumour had still a worse prognosis (HR=1.20, 95%CI [1.12-1.28], p&amp;lt;0.001). Median PFS1 was 10.2 months[9.6; 10.8]and 14.8 months[14.2; 15.4] for pts with PR- vs PR+ tumour (HR=1.36 (1.29-1.43), p&amp;lt;0.001) and PR status remained significant prognostic factor independently of de novo or recurrent status and association or not with a targeted therapy. Conclusion: ER expression evaluated using the Allred scoring, as well as PR positivity, retain prognostic value in first-line MBC patients. Table 1 : OS and PFS according to Allred status, de novo status and type of endocrine therapy. * Selected variables on multivariate model include PR status, age, SBR grade, histological subtype, number of metastatic site, type of metastasis (non visceral, visceral, brain visceral), HER 2 (0 vs 1-2), metastatic-free interval, mono- vs combined endocrine therapy. Citation Format: Marie Alexandre, Florence Castan, Thibault De La Motte Rouge, Audrey Mailliez, Etienne Brain, Thomas Bachelot, Monica Arnedos, Florence Dalenc, Jean-Marc Ferrero, Vincent Massard, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Anthony Gonçalves, Anca Berghian, Aude-marie Savoye, Jean-Sébastien frenel, Lise Bosquet, Suzette Delaloge, William Jacot. Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort [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 PO3-05-02.