Better Overall Survival In Patients Research Articles

Survival outcomes with curative intent hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric cancer with peritoneal metastasis.

e16070 Background: The prognosis of gastric cancer with peritoneal metastasis (GC-PM) remains dismal. Despite the many studies evaluating hyperthermic intraperitoneal chemotherapy and cytoreductive surgery (HIPEC-CRS) for GC-PM in various treatment settings, its curative role in combination with systemic chemotherapy remains unclear. Methods: To determine the survival benefit of CRS-HIPEC in patients with GC-PM, we conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines on primary studies from January 1, 2010 to December 31, 2023. Inclusion criteria were studies involving adults with GC and histologically proven PM who received curative intent gastrectomy, D2 lymphadenectomy, and systemic chemotherapy. Exclusion criteria were studies involving patients with GC without PM involvement and HIPEC utilized strictly for prophylactic purposes. The primary endpoint was overall survival (OS), with a focus on 1-year, 2-year, and 3-year survival outcomes. We performed a random effects meta-analysis of risk ratios using RevMan and assessed heterogeneity using I2. Results: Of 452 studies identified, we included 5 studies and a total of 524 patients with survival outcome of CRS-HIPEC and standard chemotherapy were compared. We observed significantly better OS for patients who received CRS+HIPEC compared to those who received systemic chemotherapy without CRS-HIPEC (odds ratio (OR) 0.50, 95% CI [0.39-0.65], I2= 3%, P < 0.00001). Further analysis demonstrated improved 1-year OS (OR 0.53, 95% CI [0.30-0.93], I2= 45%, p = 0.03), 2-year OS (OR 0.53, 95% CI [0.35-0.81], I2= 0%, p = 0.003), and 3-year OS (0.35, 95% CI [0.14-0.84], I2= 21%, p = 0.02). Low heterogeneity (3%) amongst all the groups suggests that variations within the subgroups did not impact the homogeneity of the dataset. Conclusions: Overall, use of CRS and HIPEC in addition to systemic chemotherapy resulted in statistically significant improvement in OS up to year 3 compared to standard palliative chemotherapy alone in patients with GC-PM. Further studies are warranted to evaluate HIPEC in the curative attempt setting, specifically in combination with emerging targeted therapies.

Clinical significance of the advanced lung cancer inflammation index in patients with limited-stage small cell lung cancer treated with chemoradiotherapy

The aim of the study was to investigate the prognostic significance of the advanced lung cancer inflammation index (ALI) in patients with limited-stage small-cell lung cancer (LS-SCLC) undergoing definite chemo-radiotherapy (CRT). We included 87 patients with LS-SCLC from South Korea, treated between 2005 and 2019 with definite CRT. ALI was calculated using body mass index, serum albumin, and neutrophil–lymphocyte ratio. We categorized 38 patients into the high ALI group (ALI ≥ 44.3) and 48 into the low ALI group (ALI < 44.3). Patients in the high ALI group exhibited longer overall survival (OS) than patients in the low ALI group. In multivariate analysis, prophylactic cranial irradiation (hazard ratio [HR] = 0.366, 95% confidence interval [CI] 0.20–0.66, P = 0.0008), and high ALI (HR = 0.475, 95% CI 0.27–0.84, P = 0.0103) were identified as independent prognostic factors for predicting better OS. Notably, a high ALI score was particularly indicative of longer survival in patients treated with the combination of etoposide and cisplatin. In conclusion, this study demonstrated that a high pretreatment ALI was significantly associated with better OS in patients with LS-SCLC undergoing definite CRT. This suggests that ALI could be a useful tool for predicting prognosis and guiding chemotherapy regimen selections in clinical practice for LS-SCLC.

The exploration of surgery and survival prediction in patients with peritoneal metastasis from gastric adenocarcinoma based on the SEER database.

As one of the most common diseases in terms of cancer-related mortality worldwide, gastric adenocarcinoma (GA) frequently develops peritoneal metastases (PMs) in advanced stages. Systemic therapy or optimal supportive care are recommended for advanced GA; however, patients frequently develop drug resistance. Surgical resection is not recommended for stage IV patients, and there have been some controversies regarding the role of it in GA patients with PMs. The aim of the study was to preliminarily evaluate the possible effect of surgical treatments on patients with only PMs from GA. Data were collected from the Surveillance, Epidemiology and End Results (SEER) database (year 2000-2022). A propensity score matching (PSM) was performed to reduce the influence of selection bias and confounding variables on comparisons. Then Cox proportional hazard regression, Kaplan-Meier analysis, and log-rank test were performed to assess the efficacy of surgical treatment in patients with PMs from GA. A total of 399 patients diagnosed with PMs from GA were enrolled for our analysis, of which, 180 (45.1%) patients did not receive surgery and 219 (54.9%) patients received surgery. Multivariate Cox regression analysis before PSM indicated higher rates of overall survival (OS) outcome for patients who had received surgery [hazard ratio (HR) =0.4342, 95% confidence interval (CI): 0.3283-0.5742, P<0.001]. After PSM, a total of 172 patients were enrolled, with 86 in each group. Multivariate Cox analysis showed that surgery was the independent factor reflecting patients' survival (HR =0.4382, 95% CI: 0.3037-0.6324, P<0.001). Subgroup survival analysis revealed that surgery may bring advantages to patients with grades I-IV, stages T1-T4, stage N0, and tumor size less than 71 mm (P<0.05). We also found that the OS of chemotherapy patients who had undergone surgery was better than that of chemotherapy patients who had not undergone surgery (P<0.01). Based on the SEER database, surgery has better OS for patients only with PMs from GA. Patients without lymph node metastasis and those who received chemotherapy before may benefit from surgery. These specific groups of patients may have surgery as an option to improve the prognosis.

Abstract 7650: An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC)

Abstract Introduction: Sarcopenia, progressive and generalized loss of skeletal muscle mass, is difficult and labor intensive to directly measure as it requires manual segmentations by radiologists from computed tomography (CT) scans. Sarcopenia has been shown to be a prognostic factor in some metastatic cancers. We evaluated the impact of sarcopenia derived via an automated segmentation algorithm on outcomes in the Phase 3 NSCLC clinical trial, CheckMate 227 (NCT02477826) Methods: The sarcopenia score assessment involves automated selection of the L3 vertebra level slice from abdominal or chest, abdomen, and pelvis (CAP) CT scans, followed by automated segmentation of the muscle area from that slice. Sarcopenia scores were derived from previously established definitions of sarcopenia, with values below 41 cm2/m2 for female patients (regardless of BMI) and below 43 cm2/m2 or 53 cm2/m2 for male (based on BMI &amp;lt; 25 kg/m2 or ≥ 25 kg/m2). Among the 967 patients with evaluable scans, sarcopenia at baseline was identified in 68.39% (n=329/481) patients receiving nivolumab (NIVO) with ipilimumab (IPI) and 70.2% (n=341/486) receiving chemotherapy (Chemo). Results: There was a trend of worse overall survival (OS) in patients with baseline sarcopenia across both treatment arms (minimum follow up 49.4 months). In patients with baseline sarcopenia vs ITT, median OS was 16.5 mo vs. 21.8 mo (p= 0.219) within the NIVO + IPI arm and 12.9 mo vs.15.0 mo (p= 0.273) within the Chemo arm respectively. Any increase in muscle mass from baseline to week 12 was associated with better OS for patients treated with NIVO+IPI (n=98) with sarcopenia at baseline compared to those without an increase in muscle mass (median OS 45.3 mo vs.19.5 mo, p= 0.012). This was not seen in those who received Chemo (n=87). Weight and muscle mass were moderately correlated at baseline (r=0.60). Conclusions: We found that in CheckMate 227, baseline sarcopenia is associated with numerically worse OS, regardless of treatment, leading to potential use as a negative prognostic biomarker. Patients with NSCLC receiving immunotherapy might benefit from changes in muscle mass being monitored during treatment. Validation of these findings in other studies and other tumor types is warranted. Citation Format: Wiem Safta, Rafael Santana-Davila, David Paulucci, William J. Geese, Diederik J. Grootendorst. An analysis of the prognostic role of sarcopenia derived with fully automated deep learning slice-based muscle estimation in patients with metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7650.

A Correlation Evaluation Between the Peripheral Blood Index and the Prognosis of Advanced Esophageal Squamous Cell Carcinoma Patients Treated with Camrelizumab.

This study aimed to investigate the relationship between peripheral blood indices and the efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) patients treated with camrelizumab. We retrospectively analyzed 64 patients who received camrelizumab for advanced ESCC at the Second People's Hospital of Lianyungang City between July 2020 and June 2022. The study included examination of the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic inflammation index (SII), the lymph-to-monocytes ratio (LMR), the absolute lymphocyte count (ALC), and lactate dehydrogenase (LDH). We used multivariate logistic regression analysis to explore the link existing between peripheral blood and the efficacy of treatment. Determination of potential prognostic factors for Progression-free survival (PFS) and Overall survival (OS) using Cox regression analysis. The nomogram model was developed based on the results of the Cox multivariate analysis. Patients were divided into three groups according to the reduction in LDH and LDL levels before treatment, and the Kaplan-Meier survival curves for the three groups were compared and ROC curves for LDH combined with PLR were plotted. Lower LDH (OR=6.237, 95% CI: 1.625-23.944) were independently associated with disease control rates(DCR). LDH was independently correlated with PFS (HR: 0.227 95% CI: 0.099-0.517). LDH and PLR were independently linked to OS. The C index of the nomogram model is 0.819, indicating good predictive performance. Kaplan-Meier Survival Curve suggested better OS in patients with reduced pretreatment LDH and PLR. The area under the ROC curve showed that the LDH index combined with the PLR index predicts patient survival better than the index alone. LDH combined with PLR predicted prognosis in patients with ESCC treated with camrelizumab.

Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

Comparative efficacy of combined CTLA-4 and PD-1 blockade vs. PD-1 monotherapy in metastatic melanoma: a real-world study

BackgroundIn light of the substantial toxicity associated with combined CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), we assessed its efficacy and safety against anti-PD-1 monotherapy (nivolumab or pembrolizumab) in patients with metastatic melanoma under real-world conditions.MethodsWe conducted a retrospective observational study involving 962 patients with stage IV metastatic melanoma who initiated adjuvant treatment between January 2017 and December 2021 across outpatient clinics in the United States. We adjusted for variables such as age, sex, ECOG performance status, comorbidity index, social deprivation index, metastatic sites, BRAF mutation status, and year of treatment. Outcomes included overall survival (OS) and post-treatment hospitalizations, analyzed using propensity score adjustment and inverse probability of treatment weighted Kaplan–Meier estimators.ResultsAfter adjusting for all variables, no significant difference in OS was observed between treatment protocols in the overall cohort (P = 0.417). In patients with multi-organ metastasis (involvement of more than two organ systems), combined CTLA-4 and PD-1 blockade was associated with improved OS (P = 0.033). Conversely, monotherapy yielded significantly better OS in patients with oligo-organ metastasis (involvement of two or fewer organ systems; P = 0.008). Patients with oligo-organ metastasis also experienced higher hospitalization rates due to immune-related adverse events when treated with combination therapy (31.2% vs. 8.5%, P < 0.001).ConclusionsOur real-world data indicate that combined CTLA-4 and PD-1 blockade is most beneficial for patients with multi-organ metastasis, while those with oligo-organ metastasis fare better with PD-1 monotherapy. The underlying reasons for these observations—whether they are due to differences in the characteristics of multi- and oligo-metastatic melanomas or the risk-benefit profile of the therapies—remain to be elucidated. These findings underscore the need for a nuanced approach to treatment regimens for stage IV melanoma patients.

DNMT1-mediated epigenetic suppression of FBXO32 expression promoting cyclin dependent kinase 9 (CDK9) survival and esophageal cancer cell growth

ABSTRACT Esophageal cancer (EC) is a common and serious form of cancer, and while DNA methyltransferase-1 (DNMT1) promotes DNA methylation and carcinogenesis, the role of F-box protein 32 (FBXO32) in EC and its regulation by DNMT1-mediated methylation is still unclear. FBXO32 expression was examined in EC cells with high DNMT1 expression using GSE163735 dataset. RT-qPCR assessed FBXO32 expression in normal and EC cells, and impact of higher FBXO32 expression on cell proliferation, migration, and invasion was evaluated, along with EMT-related proteins. The xenograft model established by injecting EC cells transfected with FBXO32 was used to evaluate tumor growth, apoptosis, and tumor cells proliferation and metastasis. Chromatin immunoprecipitation (ChIP) assay was employed to study the interaction between DNMT1 and FBXO32. HitPredict, co-immunoprecipitation (Co-IP), and Glutathione-S-transferase (GST) pulldown assay analyzed the interaction between FBXO32 and cyclin dependent kinase 9 (CDK9). Finally, the ubiquitination assay identified CDK9 ubiquitination, and its half-life was measured using cycloheximide and confirmed through western blotting. DNMT1 negatively correlated with FBXO32 expression in esophageal cells. High FBXO32 expression was associated with better overall survival in patients. Knockdown of DNMT1 in EC cells increased FBXO32 expression and suppressed malignant phenotypes. FBXO32 repressed EC tumor growth and metastasis in mice. Enrichment of DNMT1 in FBXO32 promoter region led to increased DNA methylation and reduced transcription. Mechanistically, FBXO32 degraded CDK9 through promoting its ubiquitination.

Prognostic Value of CXCR6 and the Correlation with Immune Infiltration in the Microenvironment of Skin Cutaneous Melanoma.

Increasing evidence has demonstrated that CXCRs are associated with the tumor infiltration of immune cells and regulate the tumor immune response. However, the prognostic value of CXCRs expression in patients with skin cutaneous melanoma (SKCM) remains unclear. In this study, we aimed to investigate the expression characteristics of CXCRs in SKCM tissues, analyze their prognostic value and the correlation with immune cell infiltration. Multiple public databases were used for exploration, including GEPIA2, GSCA, ULCAN, Metascape, STRING, TIMER2.0, HPA, and Cistrome DB database. And a confirmation experiment was conducted on melanoma mice with flow cytometry. Compared with normal tissues, lower expression of CXCR2/7/8 and higher expression of CXCR3/4 were found in SKCM tissues. CXCR3/4/6 were abnormally expressed in each pathological stage. Moreover, CXCRs were closely related to immune-related biological functions, and mainly interacted with CXCLs. The high expression of CXCR3/5/6 indicated better overall survival of patients. Among them, CXCR6 had the most significant prognostic value, and was most related to tumor infiltration of CD8+T cells, which was verified in melanoma mice. Finally, ETS1 and STAT5B were predicted as the transcription factor of CXCR6. Our findings play an important role in the study of prognostic markers in patients with SKCM.

Clinical Significance and Expression Pattern of RIP5 and VGLL4 in Clear Cell Renal Cell Carcinoma Patients Treated with Sunitinib.

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5-RIP5 and Vestigial Like Family Member 4-VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.

New insights into HER2-low breast cancer brain metastasis: A retrospective analysis

BackgroundA considerable number of patients with breast cancer will suffer from brain metastasis in the advanced setting. The HER2 status serves as a significant prognostic factor and the reference of applying treatment for patients with breast cancer brain metastasis (BCBM). MethodsBetween January 2010 and July 2021, patients with BCBM who had available HER2 status were identified. The patients with HER2 1+ in immunohistochemistry (IHC) or IHC 2+ and fluorescence in situ hybridization (FISH) negative were categorized as HER2-low. Comparisons were conducted between the HER2-low and HER2-zero population. The primary endpoint was overall survival (OS) after the diagnosis of BCBM. Survival outcomes were assessed using Kaplan-Meier curves with log-rank test and Cox proportional hazards model. ResultsIn this study, we analyzed 71 patients with the HER2-low breast cancer subtype and 64 patients with the HER2-zero subtype. Despite the limited sample size, our findings revealed a significantly better OS for patients with HER2-low cancer compared to their HER2-zero counterparts (26 m vs 20 m, p = 0.0017). This trend was particularly notable in the HR-negative group (26 m vs 13 m, p = 0.0078), whereas no significant difference was observed among the HR-positive patients. Furthermore, Cox regression analysis revealed that the HER2-low status was an independent prognostic factor for better survival in the HR-negative patients (p = 0.046 in multivariate analysis). ConclusionsPatients diagnosed with HER2-low BCBM exhibited a more favorable prognosis than those with HER2-zero BCBM, particularly within the HR-negative subgroup. The low expression of HER2 is supposed to be linked to the prolonged survival of BCBM patients.

Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma

BackgroundMajor histocompatibility complex (MHC) class I chain-related protein (MIC) is a stress-induced ligand released from multiple myeloma (MM) cells during progression, and soluble MIC impairs natural killer group 2D (NKG2D)...

Efficacy of lenvatinib versus sorafenib in the primary treatment of advanced hepatocellular carcinoma: A meta-analysis.

Molecular-targeted agents such as lenvatinib and sorafenib have been approved to treat hepatocellular carcinoma (HCC). However, the choice between these two agents in the primary treatment for advanced HCC is still under debate with conflicting results. We sought to evaluate the efficacy of lenvatinib and sorafenib in patients with HCC. We performed a systematic literature search using PubMed, Embase, and Scopus for relevant articles from inception until February 10, 2023. The primary outcome of this meta-analysis was overall survival (OS). The secondary outcomes were progression-free survival (PFS), time to progression, objective response rate (ORR), and disease control rate (DCR). A total of 13 studies with 3705 patients (1635 on lenvatinib and 2070 on sorafenib) were included in our analysis. The mean age of the patients in both groups was comparable (66.81 vs 65.9 years). Pooled analysis of primary outcomes showed that, compared with sorafenib, lenvatinib was associated with significantly better OS in patients treated with these drugs (HR 0.82, 95% CI: 0.69-0.97, P = 0.02). Pooled analysis also showed that PFS (HR 0.67, 95% CI: 0.57-0.78, P < 0.00001) and time to progression (HR 0.49, 95% CI: 0.31-0.79; P = 0.004) were significantly better in the lenvatinib group compared to the sorafenib group. It also showed that the lenvatinib group had significantly better ORR (odds ratio [OR] 5.43, 95% CI: 3.71-7.97; P < 0.00001) and DCR (OR 2.35, 95% CI: 1.75-3.16; P < 00001) than the sorafenib group. Our study shows that lenvatinib is superior to sorafenib regarding OS and PFS in patients with advanced HCC.

Abstract LB_A10: Efficacy of ATR inhibitor berzosertib plus topotecan or topotecan alone in patients with relapsed small cell lung cancer: A randomized clinical trial

Abstract Background: Patients with relapsed small cell lung cancer (SCLC) have a poor prognosis and few therapeutic options, especially after standard treatment of platinum doublet chemotherapy +/- immunotherapy. SCLC is characterized with high replication stress. A previous single-arm phase 2 study showed anti-tumor activity with the addition of ataxia-telangiectasia–mutated and rad3-related (ATR) kinase inhibitor berzosertib to topotecan. This study aimed to investigate whether the addition of berzosertib to topotecan improves clinical outcomes in patients with relapsed SCLC. Patients and methods: The randomized, open-labeled phase 2 study recruited patients with SCLC and relapse after one or more prior therapies from 16 US cancer centers as members of the National Cancer Institute Cancer Therapy Evaluation Program. Patients previously treated with topotecan were not eligible. Eligible patients were randomly assigned to receive topotecan (arm 1: 1.25 mg/m2 intravenously on days 1 through 5) alone or with berzosertib (arm 2: 210 mg/m2 intravenously on days 2 and 5), in 21-day cycles. Randomization was stratified by sensitivity to first-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Secondary endpoints included overall survival (OS), objective response rate (ORR), and duration of response (DOR) in the overall population and in platinum-sensitive or -resistant patients. Results: Between December 2019 and December 2022, sixty patients were randomly assigned to receive topotecan alone (n=20) or in combination of with berzosertib (n=40). After a median potential follow-up of 21.3 months, there was no difference in PFS between the two arms [median: 3.0 months in arm 1 versus 3.9 months in arm 2, hazard ratio (HR) (95% CI): 0.80 (0.46 to 1.41), P = 0.44]. OS was significantly longer with the combination [5.4 months in arm 1 versus 8.9 months in arm 2, HR (95% CI): 0.53 (0.29 to 0.96), P = 0.033]. Of 57 evaluable patients, a numerically higher ORR was observed in patients receiving the combination: 5.6% (1/18, 95% CI: 0.1% to 27.3%) in arm 1 versus 25.6% (10/39, 13.0% to 42.1%) in arm 2. In an unplanned post hoc analysis, the depth of target lesion responses was significantly associated with better OS in patients on the combination arm (adjusted P = 0.022 by landmark analysis), suggesting that the deeper tumor regressions by the combination of berzosertib and topotecan may have eventually contributed to OS improvement. Adverse event profiles were similar between the two arms. Conclusions: In this randomized clinical trial, berzosertib plus topotecan did not improve PFS compared with topotecan alone in patients with relapsed SCLC. However, the combination significantly improved OS, suggesting potential efficacy of replication-stress targeted therapies in SCLC. Citation Format: Nobuyuki Takahashi, Zhonglin Hao, Liza C Villaruz, Jun Zhang, Jimmy Ruiz, W. Jeffrey Petty, Hirva Mamdani, Jonathan W Riess, Jorge Nieva, Jose M Pachecho, Alexander D Fuld, Elaine Shum, Aman Chauhan, Samantha Nichols, Hirity Shimellis, Jessie McGlone, Linda Sciuto, Danielle Pinkiert, Chante Graham, Meenakshi Shelat, Robbie Kattappuram, Melissa Abel, Brett Schroeder, Deep Upadhyay, Manan Krishnamurthy, Ajit Kumar Sharma, Rajesh Kumar, Justin Malin, Christopher W Schultz, Shubhank Goyal, Christophe E Redon, Yves Pommier, Mirit I Aladjem, Steven D Gore, Seth M Steinberg, Rasa Vilimas, Parth Desai, Anish Thomas. Efficacy of ATR inhibitor berzosertib plus topotecan or topotecan alone in patients with relapsed small cell lung cancer: A randomized clinical trial [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A10.

Vitamin C and D supplementation in acute myeloid leukemia

AbstractRecent studies have highlighted the role of vitamin C and D in acute myeloid leukemia (AML). In 2018, we changed our practices to add both vitamins to the supportive care for all consecutive patients with AML undergoing intensive chemotherapy. In this study, we compared the outcomes of patients treated before and after this change in practice. From 2015 to 2020, 431 patients were included, 262 of whom received no supplementation and 169 of whom received vitamin supplementation. Vitamin C and vitamin D was administered from day 10 of chemotherapy until hematologic recovery from induction and consolidation. Most patients presented at diagnosis with low levels of vitamin C and D. Upon recovery from induction, vitamin D levels among the vitamin C/D group significantly increased compared with those at diagnosis, and pretransplant levels were significantly higher in the vitamin C/D group compared with the control group (median of 33 vs 19 ng/mL; P < .0001). During induction, the rates of bacterial or fungal infection, hemorrhage, or macrophage activation syndrome were lower in the vitamin C/D group, whereas there was no difference in response rate, relapse incidence, and overall survival (OS). However, the multivariate analysis for OS showed a significant interaction between vitamin C/D and NPM1 mutation, meaning that vitamin C/D supplementation was significantly and independently associated with better OS in patients with NPM1 mutations (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.30-0.90; P = .019) compared with patients with wild-type NPM1 (HR, 1.01; 95% CI, 0.68-1.51; P = .95). In conclusion, vitamin C/D supplementation is safe and could influence the outcomes of patients with AML undergoing intensive chemotherapy.

Lipid Metabolism Pathway Genes and Lung Cancer: ACADSB rs12220683G>C Is Associated with Better Survival Outcome in Patients with Non-Small Cell Lung Cancer

Introduction: Altered lipid metabolism has been reported to be associated with prognosis in multiple cancers. This study aimed to investigate the association of polymorphisms in lipid metabolism pathway genes with survival outcomes in patients with surgically resected non-small cell lung cancer (NSCLC). Methods: In total, 744 patients with surgically resected NSCLC (380 in the discovery cohort and 364 in the validation cohort) were included in this study. The association between 176 polymorphisms of lipid metabolism pathway genes and the clinical outcomes of NSCLC patients was analyzed. Results: Among the polymorphisms investigated, ACADSB rs10902859G>A was associated with significantly better overall survival (OS) in the discovery, validation, and combined cohorts. ACADSB rs10902859G>A was located in the repressed region and had strong linkage disequilibrium (D′ = 1.00 and r2 = 0.94), with rs12220683G>C located in the H3K4me3 peak region, which indicates the presence of active promoters. ACADSB rs12220683G>C was also associated with better OS in the discovery, validation, and combined cohorts (in a dominant model; adjusted hazard ratio [aHR] = 0.53, 95% confidence interval [CI] = 0.30–0.94, p = 0.03; aHR = 0.37, 95% CI = 0.15–0.89, p = 0.03; and aHR = 0.47, 95% CI = 0.29–0.75, p = 0.002, respectively). In vitro luciferase assay demonstrated that the promoter activity of ACADSB was significantly increased in the rs12220683 variant C allele compared with that in the wild G allele (p = 3 × 10−5). Conclusion: These results suggest that ACADSB rs12220683G>C increases promoter activity and that increased ACADSB expression may result in better OS in patients with surgically resected NSCLC.

C reactive protein/Albumin ratio as predictor of prognosis in castration resistant metastatic prostate cancer.

To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

Results of the compassionate program of inotuzumab ozogamicin for adult patients with relapsed or refractory acute lymphoblastic leukemia in Spain.

The prognosis of relapsed B cell precursor acute lymphoblastic leukemia (B-ALL) is poor and few patients can be successfully rescued with conventional therapies. Inotuzumab ozogamicin (IO), an antibody against the CD22 antigen linked to calicheamicin, has been approved as a rescue treatment in relapsed/refractory (R/R) B-ALL. This was an observational, retrospective, multicenter study of adult patients included in the Spanish program of compassionate use of IO in centers from the PETHEMA group (Programa Español de Tratamientos en Hematología). Thirty-four patients with a median age of 43 years (range, 19-73) were included. Twenty patients (59%) were refractory to the last treatment, IO treatment was given as ≥3rd salvage treatment in 25 patients (73%) and 20 patients (59%) received allogeneic hematopoietic stem cell transplantation before IO treatment. After a median of 2 cycles of IO, 64% of patients achieved complete response (CR)/complete response with incomplete recovery. The median response duration, progression-free survival and overall survival (OS) were 4.7 (95%CI, 2.4-7.0 months), 3.5 (95%CI, 1.0-5.0 months) and 4 months (95%CI, 1.9-6.1 months) respectively, with better OS for patients with relapsed B-ALL versus refractory disease (10.4 vs. 2.5 months, respectively) (p = .01). There was a trend for better OS for patients with first CR duration >12 months (7.2 months [95%CI, 3.2-11.2] vs. 3 months [95% CI, 1.8-4.2] respectively) (p = .054). There was no sinusoidal obstruction syndrome (SOS) event during IO treatment, but three patients (9%) developed grade 3-4 SOS during alloHSCT after IO treatment. Our study showed slightly inferior outcomes of the pivotal trial probably due to poorer risk factors and late onset of IO therapy of recruited patients. Our results support early use of IO in relapsed/refractory ALL patients.

Survival outcomes of stage I small cell lung cancer (SCLC) treated with stereotactic body radiation therapy (SBRT) versus external beam radiation therapy (EBRT): An NCDB analysis.

e20638 Background: Patients with stage I (T1/T2a, N0) SCLC have a 5-year survival of 48% after surgical resection. Unfortunately, 70% of limited stage patients are inoperable and thus reliant on definitive radiation. The use of SBRT has increased 16-fold from 2004-2013 with continued widespread acceptance due to its safety and projected efficacy; however, there is no category one evidence to support this practice. Currently NCCN guidelines cite experience of SBRT in 117 patients from two studies. The impact of SBRT versus EBRT with or without chemotherapy is not yet well defined and requires more evidence to influence treatment decisions. Methods: We used National Cancer Database (NCDB) to identify 4,012 patients with clinical stage I SCLC treated with surgery, or EBRT with chemotherapy, or SBRT with or without chemotherapy from 2011 to 2020. The primary outcome analyzed was overall survival (OS). Secondary analyses evaluated differences amongst age, gender, race, institution, and Charlson Comorbidity Index (CCI). Kaplan-Meier (KM) plots were used to examine survival outcomes and descriptive analysis was performed to examine the characteristics of clinical variables by the different treatment modalities. Cox regression analysis was used to identify factors associated with OS. Results: The utilization of surgery and SBRT in stage I SCLC has increased over the last fifteen years. As of 2020, SBRT volume has increased 657-fold and is combined with chemotherapy in more than 50% of cases. From 2010-2019, those who were treated with surgery-based therapy had a survival advantage (HR 0.64 95%CI 0.58-0.71, p &lt; 0.01) compared to multimodality radiotherapy techniques. For those treated with definitive radiation, there was no significant difference between EBRT with chemotherapy and SBRT with or without chemotherapy (HR 1.11 95%CI 0.97-1.28, p = 0.135). Patients treated with SBRT alone experienced a significantly shorter median OS of 20.4 months compared to those who received SBRT with chemotherapy (median OS 34.3 months, HR 1.74 95%CI 1.38-2.20, p &lt; 0.01). Multivariate analysis revealed better OS for patients under the age of 64 (HR 0.51 95%CI 0.44-0.58, p &lt;0.01) and those with lower CCI (CCI 0, HR 0.82 95%CI 0.70-0.90, p&lt; 0.01); worse OS for males (HR 1.26 95%CI 1.16-1.37, p &lt; 0.01); and no difference between academic or non-academic institutions (HR 0.92 95%CI 0.84-1.01, p= 0.094), white versus black (HR 0.84 95%CI 0.71-1.00, p = 0.054) or non-white patients (HR 1.06 95%CI 0.75-1.50, p = 0.736). Conclusions: Our preliminary results suggest surgery-based multimodality therapy is associated with a higher survival for medically operable patients. There was no survival advantage of EBRT with chemotherapy compared to SBRT especially when chemotherapy is given. Further statistical analysis is underway to confirm these trends and survival differences.

Interim 3‐Dimensional volumetric response (3DVR) is associated with better overall survival of patients (pts) with primary central nervous system lymphoma (PCNSL)

Interim 3‐Dimensional volumetric response (3DVR) is associated with better overall survival of patients (pts) with primary central nervous system lymphoma (PCNSL)