Worse Overall Survival Research Articles

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. Using the National Cancer Database (2010-2020), patients ≥ 70years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. Of the 17,609 patients included, 94% underwent upfront surgery (n=16,492) and the remaining underwent NAT (n=1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

Outcomes of Patients With Newly Diagnosed AML and Hyperleukocytosis.

AML presenting with hyperleukocytosis is associated with poor outcomes. We aim to understand the factors associated with early mortality and overall survival (OS) to help guide management and improve early mortality. We retrospectively reviewed data from 129 consecutive patients with newly diagnosed AML and a WBC count ≥100 × 109/L between January 2010 and April 2020. Logistic regression models estimated odds ratios for 4-week mortality. Cox proportional hazard models estimated hazard ratios for OS. The median age was 65 years (range, 23-86); the median WBC was 146 × 109/L (range, 100-687). Seventy-five (58%) patients had clinical leukostasis (CL). FLT3, NPM1, and RAS pathway mutations were detected in 63%, 45%, and 27% of patients, respectively. Cytoreduction consisted of hydroxyurea in 124 (96%) patients, cytarabine in 69 (54%), and leukapheresis in 31 (24%). The cumulative 4-week and 8-week mortality rates were 9% and 13%, respectively, all in patients age 65 years and older. By multivariate analysis, older age, CL, and thrombocytopenia <40 × 109/L were independently associated with a higher 4-week mortality rate. After a median follow-up of 49.4 months, the median OS was 14.3 months (95% CI, 7 to 21.6), with 4-year OS of 29%. Age 65 years and older, CL, tumor lysis syndrome, elevated LDH ≥2,000 U/L, elevated lactate ≥2.2 mmol/L, and poor-risk cytogenetics were independent factors associated with worse OS. Hyperleukocytosis is a life-threatening hematologic emergency. Early recognition and intervention including cytoreduction, blood product support, antibiotics, and renal replacement therapy may help mitigate the risk of morbidity and early mortality.

Incidence of metastatic tumors to ovary (Krukenberg) versus primary ovarian neoplasms associated with colorectal cancer surgery

BackgroundAn ovarian mass in the setting of colorectal cancer (CRC) can be concerning due to the uncertainty of it being metastatic disease or primary ovarian neoplasm, leading to different referral and treatment options. Our objective was to determine the incidence of ovarian metastasis compared to primary ovarian pathology in women diagnosed with CRC. MethodsWomen aged 18 years or older, diagnosed with CRC in 2014 were included. 806 records were screened for findings of an ovarian mass until 2023. Pathology was determined via resection, biopsy, or imaging with follow-up. ResultsForty women (5.0 %) had an ovarian mass; 11 at index surgery and 29 on follow-up. Median age at CRC diagnosis was 62.7 years. The incidence of Krukenberg tumour (KT) was 3.2 % accounting for 65 % of ovarian masses. Approximately 20 % presented with synchronous KTs (n = 5) and 53.8 % had synchronous peritoneal carcinomatosis (n = 14). On follow-up, KTs were found in 72.4 % of the patients (n = 21). The Overall Survival (OS) in the KT group was 7.8 % with median survival of 30.4 months. The median time to developing KTs was 20.8 months with 2-year disease-free survival of 19.2 %. Synchronous KT presentation was the only factor associated with worse OS on univariate and multivariate analysis (HR 7.23, 95 % CI 1.57–33.28, P < 0.05). ConclusionThe risk of developing KT in women with CRC is 3.2 %, of which most (72.4 %) present with metachronous disease within 2 years of CRC diagnosis. Initial evaluation by a gastrointestinal tumor group is warranted. SynopsisIn this multicenter study involving 806 women diagnosed with colorectal cancer, most ovarian masses that were detected during or following surgery are colorectal metastases and not primary ovarian pathology.

Sarcopenia and survival in colorectal cancer without distant metastasis: a systematic review and meta-analysis.

Despite prior attempts to evaluate the effects of sarcopenia on survival among patients with colorectal cancer (CRC), the results of these studies have not been consistent. The present study aimed to evaluate the association between sarcopenia and survival among patients having CRC without distant metastasis by aggregating multiple studies. We performed a literature search using computerized databases and identified additional studies from among the bibliographies of retrieved articles. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and meta-analyses were performed to evaluate overall survival (OS) and disease-free survival (DFS). Thirteen studies with up to 6600 participants were included in the meta-analyses, with a mean age of 63.6years (range: 18-93years). We found that preoperative sarcopenia was associated with worse OS (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.38-1.88) and worse DFS (HR: 1.57; 95% CI: 1.10-2.24). Compared with patients without sarcopenia after tumor resection, those with postoperative sarcopenia had worse OS (HR: 1.76; 95% CI: 1.47-2.10) and DFS (HR: 1.79; 95% CI: 1.46-2.20). These meta-analyses suggest that sarcopenia, no matter observed before or after tumor resection, is associated with worse OS and DFS in patients with CRC who have no distant metastasis.

Albumin-to-Globulin Ratio Combined with Neutrophil-to-Lymphocyte Ratio as a Prognostic Predictor in Multiple Myeloma with Renal Impairment.

The albumin-to-globulin ratio (AGR) and neutrophil-to-lymphocyte ratio (NLR) have been recently regarded as promising prognostic factors in various malignancies. The present study investigated the prognostic value of combining the AGR and NLR (ANS) for risk assessments in multiple myeloma (MM) with renal impairment (RI). From 2011 to 2018, 79 patients with MM and RI were enrolled in this study. Receiver operating curves (ROCs) were constructed to determine optimal AGR and NLR thresholds for predicting overall survival (OS) and progression-free survival (PFS) during follow up. The prognostic values of AGR, NLR, and ANS were evaluated with Cox regression and Kaplan-Meier methods. We also created a predictive nomogram for prognostic evaluations of OS and PFS, and the predictive accuracy was assessed with a concordance index (c-index). The ROC curves analyses showed that the optimal cut-off levels were 2.27 for NLR and 1.57 for AGR. A high NLR and a high ANS were significantly associated with worse OS and PFS. However, a high NLR combined with a low AGR was associated with worse OS. Multivariate analyses demonstrated that both the NLR and ANS were independent predictors for both OS and PFS and that a low AGR was an independent predictor of a reduced OS. The nomogram accurately predicted OS (c-index: 0.785) and PFS (c-index: 0.786) in patients with MM and RI. ANS may serve as a potential prognostic biomarker in patients with MM and RI. The proposed nomograms may facilitate prognostic predictions for patients with MM and RI.

Gleason Pattern 5 May Be a Prognostic Factor in Radium-223 Treatment.

Radium-223 treatment reduces the risk of death in patients with metastatic castration-resistant prostate cancer (CRPC). This study analyzed the prognostic factors in patients treated with radium-223 dichloride. Patients who received radium-223 dichloride were retrospectively analyzed. Prostate-specific antigen (PSA) response and alkaline phosphatase (ALP) decline rates were analyzed. Overall survival (OS) was evaluated using Kaplan-Meier curves, and prognostic factors for OS were assessed using Cox proportional hazards analysis. Fifty-six patients were included in the study. The five-year OS rate in patients after diagnosis of CRPC was 62.2% [95% confidence interval (CI)=27.55-112.45], while the five-year OS rate in patients at the initiation of radium-223 treatment was 21.3% (95%CI=17.20-36.79). Six patients (11.1%) had a >50% PSA decline rate, and 10 (17.9%) had a >50% ALP decline rate. Cox proportional hazards analysis showed that PSA levels at the initiation of radium-223 treatment [hazard ratio (HR)=1.00; 95%CI=1.00-1.00; p=0.0054] and Gleason Pattern (GP) 5 (HR=5.42; 95%CI=1.08-27.27; p=0.0400) were associated with OS. Patients with GP 5 had a significantly poorer prognosis compared with patients with a GP ≤4. Early administration of radium-223 as a first- or second-line treatment was not associated with OS compared with late administration of radium-223 as a third-line or later treatment. GP 5 and high PSA levels at radium-223 initiation were associated with worse OS. Radium-223 as first- or second-line treatment was not associated with OS. Therefore, a treatment strategy for CRPC based on GP 5 is needed.

Combined radiation and chemotherapy versus monotherapy for anaplastic thyroid cancer: A SEER retrospective analysis

BackgroundThe effect of combined radiation and chemotherapy (combination therapy) versus monotherapy on anaplastic thyroid carcinoma (ATC) has not yet been clear. MethodsWe identified 516 ATC patients during 2010–2015 from the Surveillance, Epidemiology and End Results (SEER) database and evaluated their survival outcome using the Kaplan-Meier method, Cox regression analysis and propensity score matching (PSM) technique. ResultsThe median overall survival (OS) among the entire cohort was 3 months (95 % confidence interval [CI], 2.58–3.42 months), and the 6- and 12-month OS rates were 29 % (95 % CI, 25.01%–32.88 %) and 13 % (95 % CI, 10.60%–16.58 %), respectively. Multivariable analysis demonstrated that ATC patients not receiving radiotherapy or chemotherapy were unquestionably associated with worse OS (hazard ratio [HR] 3.000, 95 % CI, 2.390–3.764) and cancer-specific survival (CSS) (HR = 3.107, 95 % CI, 2.388–4.043), compared with those receiving combination therapy. However, combination therapy did not predict better prognosis compared with monotherapy (all P > 0.05). After PSM, the median OS and CSS were also not significantly improved in patients undergoing chemoradiotherapy versus chemotherapy alone (OS, P = 0.382; CSS, P = 0.420) or radiotherapy alone (OS, P = 0.065; CSS, P = 0.251). ConclusionCombination therapy, compared to monotherapy, does not have the expected improvement in survival beyond the benefits achievable with each single-modality treatment, necessitating further prospective research to tailor its treatment management.

Impact of pembrolizumab treatment duration on overall survival and prognostic factors in advanced non-small cell lung cancer: a nationwide retrospective cohort study

The efficacy of front-line pembrolizumab has been established in studies that limit treatment duration to 2 years, but decision to stop pembrolizumab after 2 years is often at physician's discretion. ATHENA is a retrospective cohort study using a comprehensive administrative database aimed firstly at exploring the optimal duration of pembrolizumab and secondly real-life prognosis factors in patients with advanced non-small cell lung cancer (NSCLC). Using the French National Health Insurance database (SNDS), we identified patients with incident lung cancer in France from 2015 to 2022. Treatments and patients' characteristics were extracted or inferred from hospital, outpatient care, pharmacy delivery reports. The duration's hazard ratio (HR) was estimated with Cox model weighted by inverse of propensity score to account for confounding. Prognostics factors in first line population were identified with Cox model selected by a LASSO procedure. 391,106 patients with lung cancer were identified, of whom 43,359 received up-front pembrolizumab for an advanced disease. There were 67% (29,040/43,359) of male and the median age at diagnosis was 65 years old. After a median follow-up time of 25.9 months (min-max, [0-97.6]), the median overall survival (OS) after pembrolizumab initiation in first line was 15.7 [CI 95, 15.3-16.0] months. In multivariable analysis, several covariables were independently associated with worse OS, including male sex with chemo-immunotherapy, age, hospital category, high deprivation index, inpatient hospitalization for first pembrolizumab, and history of diabetes, diuretic, beta blocker, painkiller prescription. At landmark time of 29 months after pembrolizumab initiation, continuation beyond 2 years was not associated with better OS than a fixed 2-year treatment, HR=0.97 [0.75-1.26] p=0.95. This study supports the notion that stopping pembrolizumab after 2 years could be safe for patients with advanced NSCLC. However, because observational studies are prone to confounding and selection bias, causality cannot be affirmed. This study did not receive any specific grant.

Outcomes of older adults with early-stage triple-negative breast cancer (TNBC) receiving chemotherapy: a single-institution experience.

Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database. Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate(MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints. Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293). Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

Association Between MRI-Based Radiomics Features and Regional Lymph Node Metastasis in Intrahepatic Cholangiocarcinoma and Its Clinical Outcome.

Regional lymph node metastasis (LNM) assessment is crucial for predicting intrahepatic cholangiocarcinoma (iCCA) prognosis. However, imaging assessment has limitations for identifying LNM. To investigate the association between MRI radiomics features, regional LNM status, and prognosis in iCCA. Retrospective. Two hundred ninety-six patients (male = 197) with surgically confirmed iCCA. 1.5 T and 3.0 T. DWI, T2WI, and contrast-enhanced T1WI. Clinical information, radiologic, and MRI-based radiomics features associated with LNM status were collected to establish models. Performance of MRI, PET/CT, and the combined LNM models were compared in training (N = 207) and test (N = 89) datasets. Overall survival (OS) was compared based on LNM status. The independent features were selected by 5-fold cross-validation. The performance of MRI, PET/CT, and the models was evaluated using the area under receiver operating characteristic curve (AUC). Univariable and multivariable Cox regression were used to identify independent variables for OS. Kaplan-Meier curves were compared with the log-rank test between LNM positive and negative groups. P < 0.05 was considered statistically significant. Intrahepatic duct dilatation, enhancement pattern, and CA19-9 were independent clinicoradiologic features. The radiomics model was constructed by the independent radiomics features extracted from T2WI and delay phase T1WI. The combined LNM model showed AUC of 0.888, 0.884, and 0.811 in training, validation, and test cohorts with a positive net benefit. PET/CT exhibited similar sensitivity to the combined LNM model (0.750 vs. 0.733, P > 0.999) while the combined LNM model showed higher specificity (0.703 vs. 0.630, P = 0.039) in the test cohort. High risk of regional LNM was significantly associated with worse OS (median: 24 months) than low risk (median: 30 months, P < 0.0001). The combined LNM model has the strongest correlation with LNM status for mass-forming iCCA patients. 3 TECHNICAL EFFICACY: Stage 2.

Prognostic impact of myosteatosis in patients with colorectal cancer undergoing curative surgery: an updated systematic review and meta-analysis.

Colorectal cancer (CRC) is a global health concern, and identifying prognostic factors can improve outcomes. Myosteatosis is fat infiltration into muscles and is a potential predictor of the survival of patients with CRC. This systematic review and meta-analysis aimed to assess the prognostic role of myosteatosis in CRC. PubMed, Embase, and Cochrane CENTRAL were searched up to 1 August 2023, for relevant studies, using combinations of the keywords CRC, myosteatosis, skeletal muscle fat infiltration, and low skeletal muscle radiodensity. Case-control, prospective, and retrospective cohort studies examining the association between myosteatosis and CRC outcomes after curative intent surgery were eligible for inclusion. Primary outcomes were overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). A total of 10 studies with a total of 9,203 patients were included. The pooled hazard ratio (HR) for OS (myosteatosis vs. no myosteatosis) was 1.52 [95% confidence interval (CI), 1.38-1.67); for CSS, 1.67 (95% CI, 1.40-1.99); and for DFS, 1.89 (95% CI, 1.35-2.65). In patients with CRC undergoing curative intent surgery, myosteatosis is associated with worse OS, CSS, and DFS. These findings underscore the importance of evaluating myosteatosis in patients with CRC to improve outcomes.

Tumor-intrinsic and Cancer-associated Fibroblast Subtypes Independently Predict Outcomes in Pancreatic Cancer.

To assess the utility of tumor-intrinsic and cancer-associated fibroblast (CAF) subtypes of pancreatic ductal adenocarcinoma (PDAC) in predicting response to neoadjuvant therapy (NAT) and overall survival (OS). PDAC remains a deadly disease with limited treatment options, and both the tumor as well as the microenvironment play an important role in pathogenesis. Gene expression-based tumor-intrinsic subtypes (classical and basal-like) have been shown to predict outcomes, but tumor microenvironment subtypes are still evolving. RNA-sequencing was performed on 114 deidentified resected PDAC tumors. Clinical data were collected by retrospective chart review. Single sample classifiers were used to determine classical and basal-like subtypes as well as tumor-permissive permCAF and tumor-restraining restCAF subtypes. Survival was analyzed using the log-rank test. Patients who received NAT had an increase in OS, with a median survival of 27.9 months compared with 20.1 months for those who did not receive NAT, but the difference did not reach statistical significance (hazard ratio: 0.64, P =0.076). Either tumor-intrinsic or CAF subtypes alone were associated with OS regardless of NAT or no NAT, and patients with classical or restCAF subtypes had the best outcomes. When evaluated together, patients with the classical-restCAF subtype had the best OS and basal-permCAF the worst OS ( P <0.0001). Patients undergoing NAT with the classical-restCAF subtype demonstrated the longest OS compared with the other groups ( P =0.00041). CAF subtypes have an additive effect over tumor-intrinsic subtypes in predicting survival with or without neoadjuvant FOLFIRINOX in PDAC. Molecular subtyping of both tumor and CAF compartments of PDAC may be important steps in selecting first-line systemic therapy.

Kidney-Sparing Surgery Has Equivalent Oncological Outcomes to Radical Nephroureterectomy for Ureteral Urothelial Carcinoma.

Introduction and Objective: Kidney-sparing surgery (KSS) for upper tract urothelial cancer (UTUC) has gained increasing interest recently. However, there is limited contemporary data regarding the role of KSS in ureteral urothelial carcinoma. Therefore, we investigated the survival outcomes of ureteral urothelial carcinoma after KSS from a large, prospective international UTUC registry. Methods: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included patients with UTUC who received KSS or radical nephroureterectomy (RNU) between 2014 and 2019. In this study, we included patients with ureteral UTUC only. Study outcomes included overall survival (OS), cancer-specific survival (CSS), upper tract recurrence-free survival (RFS), intravesical RFS, progression-free survival (PFS), and metastasis-free survival (MFS). Propensity score matching (PSM) was performed to balance the tumor features' differences between groups. Results: Of the 391 patients with ureteral UTUC, 309 (79.0%) received RNU and 82 (21.0%) received KSS by ureteroscopy with laser ablation (n = 28) or segmental resection (n = 54). After PSM, there were no differences in OS (p = 0.525), CSS (p = 0.487), upper tract RFS (p = 0.147), intravesical RFS (p = 0.989), PFS (p = 0.617), and MFS (p = 0.336) between KSS and RNU. There were no significant differences between ureteroscopic ablation and segmental resection in OS, CSS, intravesical RFS, PFS, and MFS with RNU. Proximal ureteral UTUC had worse OS and CSS outcomes than other tumor locations following segmental resection. Conclusions: In patients with ureteral UTUC, no significant differences in long-term survival outcomes were observed between KSS and RNU. Proximal ureteral UTUC had worse survival outcomes over other tumor locations following segmental resection.

Abstract A022: Synthetic lethality of ERBB2 and CCND1 in breast cancer at scale

Abstract Introduction: Synthetically lethal mutations offer unique molecular targets for oncologic therapy. At scale, synthetic lethality (SL) is observed when alterations to one gene alone do not correspond with worse overall survival (OS), but simultaneous expression with another gene does correspond with worse OS. Mutually exclusive gene expression is not a requirement for SL. Existing breast cancer (BC) literature suggests synthetic lethality between CKS1B and PLK1, as well as BRCA1/BRCA2 and PARP1. Unaltered RB1 and altered CCND1 are also known to exhibit SL in the HER2-deficient environment of triple-negative BC. CCND1 and ERBB2 are typically amplified in invasive ductal carcinoma, with ERBB2 amplifications correlating to larger tumor size. This relationship is not observed in invasive lobular carcinoma, although expression of E2F1, a downstream transcription factor of CCND1, is inversely correlated with tumor grade. Methods: Our in silico approach investigated SL between ERBB2 and CCND1 in breast invasive carcinoma without distinction to lobular or ductal origin (TCGA, PanCancer Atlas 2018). We identified 17 genes of interest based on molecular alterations present in &amp;gt;10% of the sample (n=1084) and common mentions in BC literature. SL was determined if alterations to one gene alone did not significantly worsen OS, while alterations to two genes corresponded with worse OS. Results: Twenty-three SL interactions were observed. CCND1 and ERBB2 were selected because neither gene significantly worsened OS alone (p=0.915 &amp; p=0.0951 respectively). However, patients with alterations to both genes had significantly worse OS compared to those with alterations to one gene alone. CCND1 and ERBB2 alterations were present in 14.9% and 13.7% of the sample, respectively. HR=2.568 (p=0.0138) for SL patients compared to those with CCND1 alterations alone; HR=2.244 (p=0.0497) for SL patients compared to those with ERBB2 alterations alone. Mutual exclusivity was not significantly observed (p=0.084). Multivariate analysis was performed using Cox regression models; neither age (older or younger than 55 years) nor race (White, Black, Asian) confounded our results due to p&amp;gt;0.05. Conclusion: Our findings support potential therapeutic use of CCND1 targets in HER2+ BC, specifically for patients with SL between CCND1 and ERBB2. These include PLK1 inhibitors, commonly used in estrogen receptor-positive patients with CDK4/6 inhibitor resistance, along with HER2 inhibitors. A combination of MAP2K and PIK3CA inhibitors should also be investigated in HER2+ BC patients with CCND1 amplification, since HER2+ colorectal cancer patients have been demonstrated to fare better with this treatment. Citation Format: Rishi Nair, Evan P. White, Roy Khalife, Anthony M. Magliocco. Synthetic lethality of ERBB2 and CCND1 in breast cancer at scale [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A022.

Epidemiology, prognostic factors, and treatment of head and neck mucoepidermoid carcinoma: Analysis of the surveillance, epidemiology, and end results database

ObjectivesTo investigate prognostic factors in patients with head and neck Mucoepidermoid Carcinoma (MEC), especially the impact of treatment modalities on survival. MethodsPatients with primary head and neck MEC between 2000 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic factors related to Overall Survival (OS) and Cancer-Specific Survival (CSS), as well as the impact of treatments, were evaluated by multivariable Cox regression analysis. ResultsWe identified 2692 patients diagnosed with head and neck MEC, of whom 1397 (51.89%) had a parotid gland primary, 569 (22.14%) died, and 341 (12.67%) died of MEC. Older age (≥53 years), males, unmarried, lower income, tumor site in other head and neck areas, higher tumor grade, larger tumor size, and higher stage were related to poorer OS and CSS. Patients who did not undergo surgery (HR=3.20, 95% CI 2.45‒4.18) had worse OS, while no significant difference was detected between partial and total organ excision on patients’ OS (p=0.729). For combination therapy, patients who received radiotherapy only (HR=3.21, 95% CI 2.27–4.53) or no surgery and no radiotherapy (HR=2.59, 95% CI 1.83–3.67) were correlated with worse OS (vs. surgery only), but no significant difference was detected between surgery only and surgery combined with radiotherapy on patients’ OS (p=0.218). For CSS, the corresponding results were consistent with OS. ConclusionSurgical resection only may be a better survival option for head and neck MEC.

A novel liver-function-indicators-based prognosis signature for patients with hepatocellular carcinoma treated with anti-programmed cell death-1 therapy

BackgroundThe liver function reserve has a significant impact on the therapeutic effects of anti-programmed cell death-1 (PD-1) for hepatocellular carcinoma (HCC). This study aimed to comprehensively evaluate the ability of liver-function-based indicators to predict prognosis and construct a novel prognostic score for HCC patients with anti-PD-1 immunotherapy.MethodsBetween July 2018 and January 2020, patients diagnosed with HCC who received anti-PD-1 treatment were screened for inclusion in the study. The valuable prognostic liver-function-based indicators were selected using Cox proportional hazards regression analysis to build a novel liver-function-indicators-based signature (LFIS). Concordance index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), and Kaplan–Meier survival curves were utilized to access the predictive performance of LFIS.ResultsA total of 434 HCC patients who received anti-PD-1 treatment were included in the study. The LFIS, based on alkaline phosphatase-to-albumin ratio index, Child–Pugh score, platelet-albumin score, aspartate aminotransferase-to-lymphocyte ratio index, and gamma-glutamyl transpeptidase-to-lymphocyte ratio index, was constructed and identified as an independent risk factor for patient survival. The C-index of LFIS for overall survival (OS) was 0.692, which was higher than the other single liver-function-based indicator. The AUC of LFIS at 6-, 12-, 18-, and 24-month were 0.74, 0.714, 0.747, and 0.865 for OS, respectively. Patients in the higher-risk LFIS group were associated with both worse OS and PFS. An online and easy-to-use calculator was further constructed for better application of the LFIS signature.ConclusionThe LFIS score had an excellent prognosis prediction ability superior to every single liver-function-based indicator for anti-PD-1 treatment in HCC patients. It is a reliable, easy-to-use tool to stratify risk for OS and PFS in HCC patients who received anti-PD-1 treatment.

Immune-related adverse events and their effects on survival outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

The use of immune checkpoint inhibitors (ICIs) has become the standard of care for non-small cell lung cancer. The purpose of this study was to systematically review the literature to determine whether the occurrence of immune-related adverse events (irAEs) following the use of ICIs predicts different clinical outcomes in non-small cell lung cancer (NSCLC). Relevant studies from the time of database creation to July 20, 2023, were systematically searched to explore the differences in clinical outcomes in patients with advanced NSCLC with or without irAEs. The outcome indicators included the occurrence of irAEs, progression-free survival (PFS), and overall survival (OS). 25 studies met the inclusion criteria. Of these studies, 22 reported the effect on OS, and 19 reported the effect on PFS. The results showed that for patients with NSCLC, the occurrence of irAEs after receiving immunotherapy showed a statistically significant benefit over the absence of irAEs for OS (HR=0.55,95% CI=0.46-0.65) and PFS (HR=0.55 95% CI=0.48-0.64), but severe irAEs (grades 3-5) were associated with worse OS (HR=1.05, 95% CI=0.87-1.27). Compared with gastrointestinal, lung, and hepatitis, irAEs of the skin and endocrine system tend to predict better OS and PFS. The occurrence of irAEs, especially mild and early irAEs, indicates better OS and PFS in patients with NSCLC treated with ICIs, irrespective of patient characteristics, type of ICIs, and irAEs. However, Grade 3 or higher toxicities resulted in worse OS. https://www.crd.york.ac.uk/prospero/, identifier CRD42023409444.

Association between class III obesity and overall survival in previously untreated younger patients with acute myeloid leukemia enrolled on SWOG S1203.

There has been ongoing debate on the association between obesity and outcomes in acute myeloid leukemia (AML). Currently few studies have stratified outcomes by class I obesity, class II obesity, and class III obesity, and a more nuanced understanding is becoming increasingly important with the rising prevalence of obesity. We examined the association between body mass index (BMI) and outcomes in previously untreated AML in younger patients (age ≤60) enrolled in SWOG S1203 (n = 729). Class III obesity was associated with an increased rate of early death (p = 0.004) and worse overall survival (OS) in multivariate analysis (hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.62-3.80 versus normal weight). Class III obesity was also associated with worse OS after allogeneic hematopoietic cell transplant (HR 2.37, 95% CI 1.24-4.54 versus normal weight). These findings highlight the unique risk of class III obesity in AML, and the importance of further investigation to better characterize this patient population.

Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.

11016 Background: A011502 is a phase 3 randomized double-blind clinical trial that enrolled high-risk nonmetastatic breast cancer (BC) patients (pts) and randomized pts to aspirin 300 mg daily vs. placebo. There was no significant difference in invasive disease-free survival (iDFS) between the two arms. A secondary objective was to determine the association of inflammation-affiliated factors (stress, depression, poor sleep quality and pain) with iDFS and overall survival (OS). We hypothesized that these baseline factors are associated with worse clinical outcomes. Methods: At baseline, 2735, 2720, 2422 and 2610 pts completed Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale Revised (CESD-R) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high stress (27-40). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( &gt; 5).Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Associations between the measures of interest and outcomes were performed with multivariable Cox models controlling for age, body mass index, time since diagnosis, race, ethnicity, hormone receptor status and treatment arm. Results: Median follow up was 35 months. The associations from multivariable Cox model are shown in Table 1. Pts who reported high PSS had significantly worse iDFS and (non-significant) worse OS. Moderate/severe average (avg) pain was significantly associated with worse iDFS and OS. Poor sleep quality and depression were associated with worse iDFS and OS but not statistically significant. Conclusions: Pts reporting higher stress and pain at baseline had worse outcomes. We acknowledge that both pain and stress may be related to other non-cancer issues (chronic comorbidities). Our study highlights the need for clinical trials to consider including questionnaires to assess pt-reported outcomes. Future studies are warranted to determine if measures to decrease pain and stress would improve BC outcomes. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . NCT02927249: Clinical trial information: NCT02927249 . [Table: see text]

Cancer associated macrophages in blood correlates with poor outcomes in patients with clinically resectable disease in gastrointestinal cancers.

e15052 Background: Gastrointestinal (GI) cancers, i.e., pancreatic (PC), colorectal (CC), and esophageal (EC), are known to be both highly aggressive and clinically underdiagnosed, resulting in high rates of relapse after standard neoadjuvant therapy with curative intent resection. While cancer biomarkers (i.e. CEA, CA19-9) can aid in identifying early relapse post-resection, they lack accuracy and do not aid in identifying underdiagnosed patients. Recently, a circulating phagocytic macrophage engorged to ≥50 µm, i.e. cancer-associated macrophage-like cells (CAMLs), were identified in GI cancers and associated with highly aggressive cancer subtypes. However, monitoring CAMLs pre- and post-surgery and their clinical value in minimal residual disease remains unexplored. In this pilot study, we prospectively evaluated the blood of n = 133 patients with GI cancer pre- and post-surgery to assess CAMLs in resectable disease, and their association with progression free survival (PFS), relapse free survival (RFS), and overall survival (OS). Methods: In a single-blind multi-institutional prospective pilot study, we recruited n = 133 GI patients with newly diagnosed clinically resectable disease (n = 118), or with metastatic disease scheduled for curative resection post systemic therapy (n = 15). Whole peripheral blood (7.5mL) was drawn prior to neoadjuvant chemotherapy and/or radiation therapy at T1, and a post-surgery sample (T2) was obtained. CAMLs were filtered, stained with cytokeratin &amp; CD45, and enumerated for CAML engorgement of ≥50 µm, as previously described. Cox proportional regression hazard ratios for PFS, RFS &amp; OS using univariate and multivariate analyses were run over 96 months. Results: Of the patients with clinically resectable EC (n = 36/133), PC (n = 75/133) or CC (n = 22/133), 32% of patients (n = 43/133) did not undergo curative resection. T1 samples drawn pre-surgery were available from n = 105 patients and T2 samples drawn post-surgery were available from = 52 patients. Engorged ≥50 µm CAMLs were found in 51% (n = 53/105) of T1 patients and were significantly associated with worse PFS (HR = 3.4 CI95% 2.0-5.8, p &lt; 0.001) and worse OS (HR = 63.5 CI95% 2.0-6.1, p &lt; 0.001), compared to patients with &lt; 50 µm CAMLs. Additionally, engorged ≥50 µm CAMLs were found in 60% (n = 31/52) of T2 patient samples and were associated with significantly worse RFS (HR = 5.7, CI95% 2.4-13.2, p &lt; 0.001) and OS (HR = 5.3, CI95% 2.2-13.3, p &lt; 0.001) compared to patients with &lt; 50 µm CAMLs. Conclusions: These data suggest that GI cancer patients with CAMLs ≥50µm prior to curative intent resection have high rates of progression, and their presence post surgery may identify patients with residual disease that are likely to relapse. Given these results, more refined studies should evaluate CAMLs ability to identify such at risk patients who may benefit from alternative therapeutic approaches.