Improvement In Overall Survival Rates Research Articles

Oncologic outcomes and trends in each colon cancer location and stages over the last two decades: insights from the SEER registry.

The main purpose of the study is to comprehensively evaluate population-level survival disparities stage-by-stage, according to specific anatomical colon segments, and based on prognosis as defined by lymph nodes among patients who have undergone curative resection for non-metastatic colon cancer. The study was conducted from the Surveillance Epidemiology and End Result (SEER) program from the USA. Patients who underwent surgery for colon adenocarcinoma between 2000 and 2019 were identified. Demographics and clinical and pathologic factors were compared amongst each other according to different colon segments, stages, and time periods. A total of 482,672 patients were identified and 195,105 of them met the inclusion criteria. Patients with proximal cancers were significantly older, more likely to be female, had a higher number of lymph nodes, and node positivity (p < 0.001). During the study period, an almost 10% improvement in overall survival rate was observed at 3 and 5years for each colon site and stage (p < 0.05). The study's findings revealed a notable improvement in overall and cancer-specific survival rates across all colon segments and stages in patients who underwent curative treatment for non-metastatic primary colon cancer from a nationwide database.

Neoadjuvant Chemotherapy With the Angiogenesis Inhibitor Bevacizumab for Locally Advanced Cervical Cancer.

We hypothesized that adding bevacizumab to platinum-based neoadjuvant chemotherapy - whose efficacy for patients with recurrent or metastatic cervical cancer has already been proven - could optimize the therapy regimen, leading to improved response rates and survival outcomes. Forty patients with histologically confirmed cervical cancer with FIGO stage IB3-IVA who received platinum-based neoadjuvant treatment between March 2008 and January 2019 in the Department of Obstetrics and Gynecology of University Hospital Cologne were analyzed. Twenty patients were treated with additional bevacizumab. The comparative cohort consisted of 18 patients treated with neoadjuvant chemotherapy alone. The response rates and clinical outcomes, including progression-free survival and overall survival, were evaluated. Neoadjuvant chemotherapy combined with bevacizumab significantly improved the response rate (p=0.046). The survival analysis showed that patients treated without bevacizumab had better progression-free survival up to FIGO stage IVA than patients treated with bevacizumab. However, overall survival was similar for both cohorts. For patients with advanced tumor stage, including FIGO IVB, progression-free survival and overall survival improved with the addition of bevacizumab. Pathological complete remission was a statistically significant prognostic factor for progression-free survival (p=0.039) but did not significantly affect overall survival (p=0.098). While bevacizumab did not demonstrate a significant improvement in overall survival rates, it was associated with a notable reduction in tumor size and showed a trend towards improved clinical response rates. These findings suggest that bevacizumab may have potential in optimizing the neoadjuvant treatment approach.

Incidence trends and factors affecting survival in mucinous adenocarcinoma of the lung: Insights from SEER data.

e20090 Background: Lung cancer is the second most common cancer in terms of incidence and the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of cases. Adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma are the main subtypes of NSCLC. Mucinous adenocarcinoma is the least common subtype of lung adenocarcinoma with poor prognosis. Our study aims to identify demographics, incidence trends, and factors impacting overall survival (OS) in mucinous adenocarcinoma of the lung. Methods: We conducted a retrospective cohort analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to investigate patients diagnosed with mucinous adenocarcinoma of the lung between the years 2000 and 2020. Demographics, treatment data were characterized using descriptive statistics. The Cox proportional regression analysis was used to identify the factors that impact the OS. Results: Between 2000-2020, a total of 7,953 patients were diagnosed with mucinous adenocarcinoma of the lung. The highest incidence of mucinous adenocarcinoma was in older adults, accounting for 67% of all cases. Females had a higher incidence rate at 53.6%. Caucasians comprised the majority of patients at 83.1%, followed by blacks at 8.8%. The majority of patients, 89.3% resided in urban areas, and 43.6% had annual incomes exceeding $75k. Most of the patients were married at 58.2%. The incidence trends revealed a significant increase from 2000 to 2020. The incidence rates were: 15.76% (2000 -2004), 16.37% (2005 -2009), 31.08% (2010 - 2014), and 36.79% (2015-2020). However, the survival rates improved over time (See table). Among the demographic factors: adults, females, Asian/ Natives/ &amp; other races combined, urban residence, higher annual income (&gt; $75k), and married status had better OS outcomes than their counterparts. Among disease stages, localized disease had the best, while regional disease had a better OS than distant disease. In terms of treatment, surgery was associated with better OS; interestingly, receipt of radiation or chemotherapy was not associated with better OS. The HRs of all these factors are shown in Table. Conclusions: Our study, the largest to date on mucinous adenocarcinoma of the lung, demonstrated a rising incidence yet with improved OS rates from 2000-2020. Our findings shed light on the demographics and other factors influencing OS in this rare subtype of NSCLC. [Table: see text]

FLT3 and IDH1/2 Inhibitors for Acute Myeloid Leukemia: Focused Clinical Narrative Review of Forthcoming Drugs from an Indian Context

AbstractTherapeutic approaches for acute myeloid leukemia (AML) have witnessed minimal evolution in recent decades, primarily relying on advancements in supportive care and transplantation to drive improvements in overall survival rates. However, treatment with intensive chemotherapy may not be feasible for patients with advanced age or reduced fitness, and outcomes for patients with relapsed/refractory disease continue to be suboptimal. Several agents with a novel mechanism of action have been developed in the past decade and have shown efficacy in patients with both newly diagnosed and relapsed AML. Out of these, several FLT3 (FMS like tyrosine kinase 3) and IDH1/2 (isocitrate dehydrogenase 1/2) inhibitors have received regulatory approval in specific clinical settings and are available for clinical use. This is an actively expanding field with several ongoing clinical trials in advanced phases. We provide a focused narrative review of drugs from these two categories with available clinical data.

The Role of Adjuvant Therapy in Duodenal Adenocarcinoma and Intestinal Subtype Ampullary Carcinoma After Curative Resection.

To define the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC). DAC and iAC share a similar histologic differentiation but the benefit of adjuvant therapy remains unclear. Patients undergoing curative intent surgical resection for DAC and iAC between 2010 and 2021 at 5 high-volume centers were included. Patient baseline, perioperative, and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM). A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in patients with DAC was 101 months versus 155 months for patients with iAC ( P = 0.098). DAC had a higher rate of local (14.1% vs 1.2%, P < 0.001) and systemic recurrence (30.4% vs 3.5%, P < 0.001). Adjuvant therapy failed to improve OS in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors, had improved OS rates with adjuvant therapy (72 vs 44m, P = 0.044). Patients with iAC with N+ (190 vs 57m, P = 0.003), T3-T4 (177 vs 59m, P = 0.050), and perineural invasion (150 vs 59m, P = 0.019) had improved OS rates with adjuvant therapy. While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved OS in patients with DAC with perineural invasion and in patients with iAC with T3-T4 tumors, positive lymph nodes, and perineural invasion.

IMMUNE MICROENVIRONMENT AND PROGNOSIS OF TONGUE SQUAMOUS CELL CARCINOMAS

Objective To characterize immune cells in the tumor microenvironment of Tongue Squamous Cell Carcinoma (TSCC) and to evaluate its prognostic significance. Study Design forty-eight cases of TSCC were selected. Immunohistochemical reactions were carried out against CD3, CD4, CD8, CD20, CD68, CD1a, CD83, PD-1, and PD-L1; the analysis was performed to investigate the relation between the type of immune cells and clinical characteristics, such as tumor size, presence of local and distant metastasis, and overall survival. Results Analysis revealed that high expression CD3, CD8, CD20, and CD83 were statistically significant when associated with an improvement in overall survival rate. Conclusion Evidence to support the values higher of tumor-infiltrating lymphocytes (TILs) and mature dendritic cells (DC) are correlated with improvements in overall survival in TSCC patients, influenced by characteristics and behaviors of tumor and prognosis. To characterize immune cells in the tumor microenvironment of Tongue Squamous Cell Carcinoma (TSCC) and to evaluate its prognostic significance. forty-eight cases of TSCC were selected. Immunohistochemical reactions were carried out against CD3, CD4, CD8, CD20, CD68, CD1a, CD83, PD-1, and PD-L1; the analysis was performed to investigate the relation between the type of immune cells and clinical characteristics, such as tumor size, presence of local and distant metastasis, and overall survival. Analysis revealed that high expression CD3, CD8, CD20, and CD83 were statistically significant when associated with an improvement in overall survival rate. Evidence to support the values higher of tumor-infiltrating lymphocytes (TILs) and mature dendritic cells (DC) are correlated with improvements in overall survival in TSCC patients, influenced by characteristics and behaviors of tumor and prognosis.

Randomized phase 2 study of nab-paclitaxel and gemcitabine with or without tocilizumab as first-line treatment in patients with advanced pancreatic cancer (PACTO).

4147 Background: Pancreatic cancer (PC) presents one of the most aggressive malignancies for which currently available treatments are modestly effective. We report the findings of a randomized phase 2 trial (NCT02767557) to test the efficacy of gemcitabine/nab-paclitaxel (gem/nab) with or without tocilizumab (toc), as first-line treatment in patients with locally advanced or metastatic PC. Methods: Prior to randomization, a safety cohort of 6 participants received gem 1000 mg/m2, nab 125 mg/m2 (days 1, 8, and 15 of each 28-day cycle) and toc 8 mg/kg (day 1 of each cycle). Participants were then randomized 1:1 to receive gem/nab or gem/nab/toc. Patients had modified Glasgow Prognostic Score of 1 or 2 and were stratified by performance status (PS) and stage. The primary endpoint was the overall survival (OS) rate at 6 months (OS6). Secondary end points included median progression-free survival (PFS), median OS, overall response rate (ORR), and safety. Results: A total of 147 patients were treated; 141 were randomized to receive gem/nab/toc (n = 70), or gem/nab (n = 71). As of January 9, 2023, the median follow-up was 8.1 months (IQR 4.2–13.9). OS6 was 68.6 % (95% CI, 56.3-78.1) in gem/nab/toc group and 62.0% (95% CI, 49.6-72.1) in gem/nab group (p = 0.41). No significant differences in the median OS or PFS were observed between the gem/nab/toc group and the gem/nab group (OS, 8.4 versus 8.0 months; HR, 0.75; 95% CI, 0.54-1.05; p = 0.10), and (PFS, 5.6 versus 5.5 months; HR, 0.85; 95% CI, 0.61-1.20; p = 0.36). The 12, 18 and 24-month OS rates were 37.1% (95% CI, 26.0%-48.3%), 27.1% (17.4%-37.8%), 10% (4.4%-18.3%) for gem/nab/toc and 28.2% (18.3%-38.9%), 7.0% (2.6%-14.5%), 2.8% (0.5%-8.8%) for gem/nab, respectively. The ORR was 37.1% (95% CI, 25.9%-49.5%) in gem/nab/toc group and 35.2% (24.2%-47.5%) in gem/nab group. The incidence of grade 3 or higher treatment related adverse events was 88.2% in gem/nab/toc and 63.4% in gem/nab group (p &lt; 0.001). Of those, neutropenia (55.3% versus 16.9%), and thrombocytopenia (40.8% versus 11.3%) were most common. Two and one treatment-related deaths, respectively, in gem/nab/toc and gem/nab group, occurred during the study. Conclusions: In patients with advanced PC, the addition of tocilizumab to gem/nab did not result in improved OS rate at 6 months. Although more patients were alive at 18 months in the gem/nab/toc, long-term survival rates exceeding 24 months were not different between groups. The biomarkers for selection of patients who might benefit from gem/nab combined with tocilizumab are to be identified. Clinical trial information: NCT02767557 .

Efficacy of post-first-line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta-analysis.

Imatinib is the standard first-line treatment for advanced gastrointestinal stromal tumors (GISTs); however, most patients eventually develop imatinib resistance, leading to considerable clinical challenges. Few direct comparisons have been made between different post-first-line therapies on clinical efficacy in advanced GIST following imatinib failure. Databases including PubMed, Embase, Scopus, Google Scholars, and Cochrane Library from inception to February 2023 were retrieved for randomized controlled trials evaluating the clinical efficacy of different post-first-line agents for advanced GIST following imatinib failure. Network and conventional meta-analysis were carried out using Stata/MP 16.0. Ripretinib showed significant improvement in progression-free survival (PFS) rates from the 2nd to the 12th month compared to placebo, while there was virtually no evidence that the rest active agents had a significant benefit at the 12th month. Masitinib, ripretinib, sunitinib, regorafenib, and pimitespib exhibited significantly longer median PFS than placebo, and pairwise comparisons indicated there were no significant differences among masitinib, ripretinib, and sunitinib. These post-first-line agents decreased the risk of disease progression or death by 65% (HR = 0.35, 95% CI: 0.26-0.47) compared to placebo. Ripretinib and sunitinib came into effect earlier and exhibited more consistent overall survival (OS) rate improvements than masitinib and pimitespib, while pairwise comparisons revealed no significant differences in these four active agents concerning the improvement in OS rate. These post-first-line agents decreased the risk of death by 39% (HR = 0.61, 95% CI: 0.44-0.83) over placebo for advanced GIST following imatinib failure. The active agents in our analysis as post-first-line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post-first-line treatment for advanced GIST following imatinib failure.

Lymph node yield as a measure of pancreatic cancer surgery quality

Evaluated lymph node (ELN) yield has been established as a promising measure of surgical quality. Research has suggested that an ELN of at least 15 in pancreatic cancer patients is associated with improved survival and staging metrics. The aim of this study was to determine what impact a high ELN yield of ≥15 has in a novel population. A retrospective cohort study was performed of patients with resectable, non-metastatic pancreatic adenocarcinoma who underwent neoadjuvant therapy followed by pancreatectomy using the National Cancer Database (NCDB 2004-2017). Patients who had <15 nodes examined and those who had ≥15 examined (high ELN) were compared. Univariate and multivariate analyses were performed to determine factors associated with ELN yield. A Cox proportional hazards model was used to identify factors associated with overall survival. A total of 5,930 patients were included; 58% of patients had ≥15 lymph nodes examined. High ELN was associated with significant improvement in overall survival rates (p<0.004) and perioperative outcomes including post-operative stay (p<0.0001), 30-day unplanned readmission (p<0.028), and 90-day mortality (p<0.001). Patients who were treated at facilities with a high procedure-specific surgery volume were more likely to receive high ELN surgeries than those treated at facilities with a low volume (HR = 2.86[95% CI = 2.36-3.47]). An ELN yield of ≥15 was a significant measure of surgical quality in this novel population as it was associated with improvements in survival and perioperative outcomes. However, considerable harvest disparities exist at the facility level.

Factors influencing outcomes in selective neck dissection in 661 patients with head and neck squamous cell carcinoma

BackgroundSelective neck dissection (SND) is the surgical treatment of choice in squamous cell carcinoma of the head and neck (HNSCC) with suspected or manifest metastases in the cervical lymph nodes. For SND to be successful, treated lymph node levels should be selected according to anatomic considerations and the extent of the disease. Aim of this study was to identify neck dissection levels that had an impact on individual prognosis.MethodsWe conducted a retrospective review of SND as part of primary treatment of HNSCC. Overall survival (OS) and regional control rates (RCR) were calculated for all patients treated at one academic tertiary referral center.Results661 patients with HNSCC were included, 644 underwent ipsilateral and 319 contralateral SND. Average follow-up was 78.9 ± 106.4 months. 67 (10.1%) patients eventually developed nodal recurrence. Tumor sites were oral cavity (135), oropharynx (179), hypopharynx (118) and larynx (229). Tumor categories pT1–pT4a, and all clinical and pathological nodal categories were included. Multivariate analysis indicated improved OS rates for patients undergoing SND in ipsilateral levels I and V as well as level III contralaterally. Analysis for tumor origin showed that SND in ipsilateral level I showed significantly improved OS in HNSCC of the oral cavity.ConclusionThe dissection of ipsilateral level I in oral cavity cancer was of particular relevance in our exploratory, retrospective analysis. To clarify the relevance for the determination of the extent of SND, this should be investigated prospectively in a more homogenous patient cohort.

Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable melanoma: Overall survival and response rates from RELATIVITY-047 (CA224-047)

360385 Background: RELATIVITY-047, a global, randomized, double-blind, phase II/III study, met its primary endpoint of progression-free survival (PFS). Relatlimab and nivolumab (RELA + NIVO) as a fixed-dose combination (FDC) demonstrated a significant PFS benefit (median PFS was 10.1 months [mo]; 95% CI, 6.4–15.7) with RELA + NIVO vs. 4.6 mo (95% CI, 3.4–5.6) with NIVO; hazard ratio (HR) 0.75 (95% CI, 0.6–0.9; p = .0055), with a manageable safety profile, compared to NIVO alone in patients with previously untreated metastatic or unresectable melanoma (Lipson EJ et al. J Clin Oncol 2021;39[15_suppl]:9503P). Here we report updated PFS and the first disclosure of secondary endpoints, overall survival (OS), and overall response rate (ORR). Methods: Patients were randomized 1:1 to receive RELA 160 mg + NIVO 480 mg FDC or NIVO 480 mg alone, given intravenously every 4 weeks, as previously described (Lipson EJ et al. J Clin Oncol 2021;39[15_suppl]:9503P). The primary endpoint of PFS per RECIST v1.1 was assessed by blinded independent central review (BICR). Secondary endpoints were OS and ORR by BICR, to be tested hierarchically. The OS boundary for statistical significance was p &lt; .04302 (2-sided) based on 69% power for a target HR of 0.75. Results: Patients (714 patients) were randomly selected to receive RELA + NIVO (355 patients) or NIVO (359 patients). Median follow-up was 19.3 mo. Updated median PFS was 10.2 mo (95% CI, 6.5–14.8) with RELA + NIVO vs. 4.6 mo (95% CI, 3.5–6.4) with NIVO (HR 0.78; 95% CI, 0.6–0.9). Median OS was not reached (NR; 95% CI, 34.2–NR) with RELA + NIVO vs. 34.1 mo (95% CI. 25.2–NR) with NIVO (HR 0.80; 95% CI, 0.6–1.0; p = .0593). OS rates at 12 mo were 77.0% (95% CI, 72.2–81.1) vs. 71.6% (95% CI, 66.6–76.0) and at 24 mo were 63.7% (95% CI, 58.1–68.7) vs. 58.3% (95% CI, 52.7–63.4) with RELA + NIVO vs. NIVO, respectively. Subsequent systemic therapy rates and types were generally similar between treatment groups. Confirmed ORR per BICR was 43.1% (95% CI, 37.9–48.4) with RELA + NIVO vs. 32.6% (95% CI, 27.8–37.7) with NIVO. Complete responses were observed in 16.3% of patients on RELA + NIVO vs. 14.2% on NIVO. Grade 3/4 treatment-related adverse events (TRAEs) were observed in 75 (21.1%) patients on RELA + NIVO and 40 (11.1%) on NIVO. There were four treatment-related deaths in the RELA + NIVO group and two in the NIVO group. TRAEs (any grade) leading to treatment discontinuation were observed in 54 (15.2%) patients on RELA + NIVO and 26 (7.2%) on NIVO. Conclusions: RELA + NIVO continued to demonstrate a PFS benefit vs. NIVO alone in patients with previously untreated metastatic or unresectable melanoma, consistent with the primary analysis. RELA + NIVO demonstrated a 20% reduction in risk of death and numerically improved OS rates vs. NIVO, although statistical significance was not reached for this secondary endpoint. ORR was higher with RELA + NIVO vs. NIVO. The safety profile of RELA + NIVO remained manageable with no new or unexpected safety signals. Clinical trial information: NCT03470922.

Survival rates and safety associated with chemoradiotherapy followed by surgery and chemoradiotherapy alone for patients with T4 esophageal cancer: a systematic review and meta-analysis

Background The optimal treatment approach for T4 esophageal cancer is not well established. We aimed to perform a systematic review and meta-analysis to determine the survival rates and safety of chemoradiotherapy followed by surgery (CRT-S) and chemoradiotherapy alone (CRT) in patients with T4 Nany M0 esophageal cancer. Materials and Methods We searched databases for eligible prospective or retrospective studies. The outcomes of interest were overall survival (OS) at 1, 3 and 5 years, treatment-related fistula formation and mortality rates. Meta-analyses were performed using the random effects models separately for studies evaluating CRT-S and CRT. Subgroup analyses were performed based on histology, radiation dose, chemotherapy regimen and duration of the interval between CRT and surgery. Results We identified 23 studies including 1,119 patients with predominantly squamous cell carcinoma (93%) and adenocarcinoma (3%) histology. The OS rates of patients receiving CRT-S were 65%, 36% and 20% at 1, 3 and 5 years, respectively. The OS rates of patients receiving CRT were 30%, 11% and 10% at 1, 3 and 5 years, respectively. Treatment-related fistula formation rates were 4% for CRT-S and 9% for CRT. Treatment-related mortality rates were 3% for both groups. Subgroup analyses showed that the interval of >2 months between CRT and surgery was associated with significantly improved OS rates at 1, 3 and 5 years. Conclusion Chemoradiotherapy is an efficacious treatment approach for T4 esophageal cancer, with clinically acceptable rates of treatment-related fistula formation and mortality. Tri-modality approach with surgery can be considered in carefully selected patients. Our study findings should be interpreted with caution due to the lack of high-quality evidence. Randomized controlled trials are warranted to confirm these findings.

Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives.

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blocking of inhibitory receptors and have shown promising results in preclinical models and studies on the adult population. However, paediatric malignancies present unique features, and so far, experience with these agents is limited. In the current review, we present an overview of efficacy and safety data from case reports, case series, and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents, and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

Mutation of MUC16 Is Associated With Tumor Mutational Burden and Lymph Node Metastasis in Patients With Gastric Cancer.

BackgroundLymph node metastasis (LNM) is a critical factor in determining the prognosis of gastric cancer (GC), but its underlying mechanism remains unclear. The tumor mutational burden (TMB) has recently been recognized as a biomarker for predicting prognosis and response to immune checkpoint inhibitors, while mucin 16, cell surface associated (MUC16) is frequently mutated in GC. This study explored whether MUC16 mutation status is associated with TMB, LNM, and prognosis in patients with GC.MethodsSomatic mutation data were downloaded from three GC cohorts. TMB values were calculated and associations between the TMB and clinical characteristics were analyzed. The mutational landscapes of these three GC cohorts were individually explored and visualized using waterfall diagrams. Univariate logistic regression and Kaplan-Meier survival analysis were performed to screen for mutated genes associated with LNM and overall survival (OS). Associations between MUC16 mutations and TMB, microsatellite instability (MSI), LNM, and tumor microenvironment signatures were explored.ResultsTMB was associated with LNM and OS in patients with GC. Analyzing the three GC cohorts (The Cancer Genome Atlas-Stomach Adenocarcinoma, International Cancer Genome Consortium [ICGC]-China, and ICGC-Japan) revealed that MUC16 was one of the most frequently mutated genes in patients with GC. MUC16 mutations were associated with better prognosis, including lower LNM rates and improved OS rates. In addition, MUC16 mutation status was associated with TMB and MSI statuses. Fifteen upregulated and 222 downregulated genes were identified in patients with MUC16 mutations, compared to in those in patients with wild-type MUC16. An altered tumor microenvironment signature was also identified in GC samples with MUC16 mutations; it was characterized by significantly decreased infiltration regarding stromal cells, CD4+ T cells, and macrophages.ConclusionMUC16 mutation status was associated with TMB, microsatellite status, LNM, and survival in patients with GC. These findings may provide new insights into the mechanism of LNM and could act as a signpost for prognostic predictions and immunotherapy guidance for patients with GC.

MiR-1246 Promotes Laryngeal Squamous Cell Carcinoma Progression by Interacting with THBS1.

MicroRNAs (miRNAs) have been confirmed to be related to the occurrence and progress of multiple cancers, including laryngeal squamous cell carcinoma (LSCC). The present work focused on exploring the role of miR-1246 in LSCC and investigating the possible mechanisms. miR-1246 expression levels within clinical LSCC tissues and cell lines (TU212 and AMC-HN-8) were detected through quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Then the overall survival (OS) rates of LSCC patients with different miR-1246 expressions were assessed by the Kaplan-Meier method. In addition, the roles of miR-1246 in the proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells were measured by colony formation, flow cytometry, wound-healing, and Western blot (WB) assays, respectively. Moreover, TargetScan was carried out to predict the miR-1246 targets (thrombospondin-1, THBS1), further confirmed by a dual-luciferase reporter assay. Afterward, the negative relationship between miR-1246 and THBS1 was assessed by qRT-PCR and WB. Furthermore, the restoring effects of THBS1 on TU212 and AMC-HN-8 functional roles transfected with miR-1246 inhibitor were further investigated. miR-1246 expression levels were increased in clinical LSCC tissues and cell lines. Patients with low miR-1246 expression exhibited improved OS rates. In addition, miR-1246 down-regulation notably suppressed cell proliferation and migration and induced cell apoptosis of TU212 and AMC-HN-8 cells. Moreover, THBS1 was predicted and confirmed as a direct target of miR-1246 and negatively related to miR-1246 expression. Mechanically, THBS1 inhibition partially rescued the effects of the miR-1246 inhibitor on proliferation, apoptosis and migration of TU212 and AMC-HN-8 cells. This study provides an experimental basis suggesting the potential of miR-1246/THBS1 as the novel markers for LSCC.

Is There a Role for Perioperative Radiotherapy in Surgically Resected Stage IV Rectal Cancer? A Propensity Score Matched Analysis

This study aimed to determine whether perioperative radiotherapy (RT) improves outcomes in stage IV rectal cancer patients treated with primary surgical resection and systemic chemotherapy and to identify predictive factors for selection of patients for these approaches.We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 2010 and 2015 with stage IV rectal cancer, but without brain or bone metastases. After applying the exclusion criteria, a total of 26,132 patients were included in the analysis; propensity score matching was used to balance their individual characteristics.Overall, 3283 (12.6%) patients received perioperative RT; the 3-year overall survival (OS) rates were 43.6% in the surgery group and 50.5% in the surgery with RT group (P < 0.001). The survival benefit of RT was maintained after propensity score matching and multivariate adjustment (HR 0.70, 95% CI, 0.66-0.81, P < 0.001). Interaction testing of the prognostic variables revealed a significant interaction between RT and the presence of lung metastasis (P < 0.001): the benefit of RT was observed only in patients without lung metastases (3-year OS 52.1% vs. 44.1%, P < 0.001), but it was observed regardless of liver metastases. Additionally, we developed a web-based calculator (http://bit.do/mRC_surv) to provide individualized estimates of OS benefit based on the receipt of perioperative RT.Perioperative RT significantly improved OS rates, especially in patients without lung metastases. We successfully developed a nomogram and web-based calculator that could predict survival benefit with the addition of RT for these patients.

Upfront Surgery vs. Primary Chemoradiation in an Unselected, Bicentric Patient Cohort with Oropharyngeal Squamous Cell Carcinoma-A Matched-Pair Analysis.

Simple SummaryOropharyngeal squamous cell carcinoma (OPSCC) is a common malignancy of the upper aerodigestive tract with rising incidence. While surgical and non-surgical approaches are applied in curative treatment, none of these has proven superior to date. In this study, we investigated overall survival in an unselected, bicentric cohort of patients with OPSCC and compared upfront surgery vs. primary chemoradiation treatments. A matched-pair analysis was performed to exclude confounding factors and reduce bias. Our results suggest that regardless of the treatment modality chosen, overall survival rates are comparable in both cohorts. As a consequence, future studies on functional outcome of patients with OPSCC are mandatory to identify the treatment modality most likely resulting in improved quality of life in patients with OPSCC.The two pillars of therapy for oropharyngeal squamous cell carcinoma (OPSCC) are upfront surgery and primary chemoradiotherapy. Substantial regional preferences exist with regard to the selection of treatment. Despite new therapeutic approaches, patient survival remains poor, with an approximate overall survival (OS) rate of 50% at five years. This study was conducted to investigate a potential survival benefit depending on the treatment modality in OPSCC patients. We retrospectively collected data of 853 patients with histologically confirmed OPSCC from the Giessen and Maastricht cancer databases. To identify risk factors affecting survival, a Cox-proportional hazard model was applied to 442 patients with complete data sets. Based on this cohort a matched-pair analysis with 158 patients was performed to compare OS rates of patients treated either with upfront surgery or primary chemoradiation. For the collective cohort, patients treated with upfront surgery had significantly improved OS rates compared to patients treated with primary chemoradiation. In the matched-pair analysis adjusted for patients’ T-, N- and HPV-status as well as risk profile, we observed that both treatment approaches offered equivalent OS rates. Our study emphasizes that treatment recommendations should be made whenever possible on the basis of side-effect profiles caused by the therapeutic approach used. To draw further conclusions, results of the ongoing “best of” (NCT2984410) study are eagerly awaited, investigating the functional outcome after treatment of OPSCC patients.

Clinical characteristics and prognostic factors of 70 patients with Sézary syndrome: a single-institutional experience at Moffitt cancer center

Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2–4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 patients diagnosed with SS treated at a high-volume tertiary cancer center between 2000 and 2018. Overall survival at 1 and 5 years was 84.1% and 50.7%, respectively. Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors. Five patients presented with circulating large granular lymphocytic proliferation and had a favorable prognosis. Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response. Therapeutic advancements and the comprehensive treatments used in a multidisciplinary clinic improved OS rates.

Is There a Role for Perioperative Pelvic Radiotherapy in Surgically Resected Stage IV Rectal Cancer?: A Propensity Score-matched Analysis.

This study aimed to determine whether perioperative pelvic radiotherapy (RT) improves outcomes in stage IV rectal cancer patients treated with primary surgical resection and systemic chemotherapy and to identify predictive factors for selection of patients for these approaches. We searched the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed between 2010 and 2015 with stage IV rectal cancer, but without brain or bone metastases. After applying the exclusion criteria, a total of 26,132 patients were included in the analysis; propensity score matching was used to balance their individual characteristics. Overall, 3283 (12.6%) patients received perioperative RT; the 3-year overall survival (OS) rates were 43.6% in the surgery group and 50.5% in the surgery with RT group (P<0.001). The survival benefit of RT was maintained after propensity score matching and multivariate adjustment (hazard ratio: 0.70; 95% confidence interval: 0.66-0.81; P<0.001). Interaction testing of the prognostic variables showed a significant interaction between RT and the presence of lung metastasis (P<0.001): the benefit of RT was observed only in patients without lung metastases (3 y OS 52.1% vs. 44.1%, P<0.001), but it was observed regardless of liver metastases. In addition, we developed a web-based calculator (http://bit.do/mRC_surv) to provide individualized estimates of OS benefit based on the receipt of perioperative pelvic RT. Perioperative pelvic RT significantly improved OS rates, especially in patients without lung metastases. We successfully developed a nomogram and web-based calculator that could predict survival benefit with the addition of RT for these patients.

Racial and Ethnic Disparities in Laryngeal Cancer Care.

There is a long history of racial and ethnic disparities in healthcare and they continue to persist in contemporary society. These disparities have the potential to negatively affect morbidity and mortality in racial and ethnic minorities diagnosed with laryngeal cancer. Diagnosis, medical treatment, and rehabilitation for laryngeal cancer have improved considerably, leading to improvements in overall survival rates and physical, social, and psychological functioning. Yet members of minority and underrepresented groups are at an increased risk for experiencing reduced access to quality care and delays between diagnosis and treatment, and as a result have lower survival rates. Increasing health providers' awareness of racial and ethnic disparities in laryngeal cancer is necessary to facilitate changes in patient and provider education, clinical practice, and health policies. The purpose of this review is to summarize current literature on disparities in laryngeal cancer diagnosis, treatment, and rehabilitation among Black and Hispanic patients. We present recent data from the Surveillance, Epidemiology, and End Results database to examine trends in laryngeal cancer and patient, provider, and health systems factors that may perpetuate these disparities. In addition, we offer interventions to address racism and other racial and ethnic biases in laryngeal cancer care and describe research and legislative actions that are needed to reduce disparities in this area.