Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

Prognostic impact of dysphagia scores in patients with advanced resectable esophageal cancer who underwent radical esophagectomy after preoperative treatment.

BACKGROUND: Dysphagia caused by tumor strictures is a major symptom in patients with advanced esophageal cancer. However, the prognostic impact of dysphagia in resectable cases is insufficiently investigated. This study investigated the prognostic value of dysphagia scores in resectable advanced esophageal cancer who underwent radical esophagectomy after preoperative treatment. METHODS: This retrospective study enrolled 302 consecutive patients with advanced resectable esophageal cancer who received preoperative treatment. The preoperative dysphagia score was used to assess the relationship between tumor stricture and clinical outcomes. RESULTS: Almost half of the patients had dysphagia scores of 2-4 (n=152, 50.3%). A lower body mass index (BMI), circumferential tumors, and non-curative resection were significantly more as dysphagia scores worsened. Patients with dysphagia had significantly more advanced ypT stage and worse histopathological response than those without dysphagia. The 5-year disease-free survival rates for dysphagia scores 0-1, 2-3, and 4 were 52.9%, 35.3%, and 26.7% and for overall survival were 60.7%, 40.4%, and 26.7%, respectively. Multivariate analysis identified dysphagia score as an independent factor of overall survival, similar to surgical curability and ypN stage. The postoperative recurrence rate was significantly higher among patients with dysphagia scores of 2-3 (56%) and those of 4 (67%), compared to those with 0-1 (36%) (P<0.001 and 0.037, respectively). Furthermore, distant recurrence in dysphagia scores of 2-3 and 4 was higher than in 0-1 (26%, 46%, and 42%, respectively). CONCLUSION: Dysphagia score before initial treatment is associated with postoperative survival in patients with resectable advanced esophageal cancer.

The efficacy and safety of neoadjuvant immunochemotherapy in resectable stage I-III non-small cell lung cancer: a systematic review and network meta-analysis.

BACKGROUND: Neoadjuvant immunochemotherapy (NICT) is a new treatment method for resectable non-small-cell lung cancer (NSCLC). Network meta-analysis assessed efficacy, safety, and optimal treatment. METHODS: We searched for randomized controlled trials (RCTs) comparing NICT with neoadjuvant chemotherapy (NCT) in PubMed, Embase, Web of Science, Cochrane Library, and international conferences. Outcomes were surgical resection rate, pathological complete response(pCR),event-free survival (EFS), and Grade 3-5 treatment-related adverse events (TRAEs). RESULTS: RCTs of 3,387 patients, six treatment combinations, and two modalities were included. Meta-analysis showed that NICT yielded higher pCR and EFS rates than NCT. The toripalimab-chemotherapy combination had the highest surgical resection rate (OR = 1.68, 95% CI: 1.05-2.73), pCR (OR = 38.84, 95% CI: 11.05-268.19) and EFS (HR = 0.40, 95% CI: 0.28-0.58).This regimen worked well for patients with low programmed death-ligand 1 (PD-L1) expression or squamous cell pathology. For high PD-L1 expression and patients with NSCLC, neoadjuvant nivolumab with chemotherapy had the most efficacy. The incidence of treatment-related adverse events increased with longer treatment cycles, with perioperative nivolumab combined with chemotherapy showing the worst safety profile (RR = 1.32, 95% CI: 1.00-1.76), while neoadjuvant nivolumab combined with chemotherapy alone had the best safety profile (RR = 0.91, 95% CI: 0.68-1.21). Indirect comparison showed no survival benefit for neoadjuvant-adjuvant immunotherapy (HR = 0.93, 95% CI: 0.65-1.35). In the indirect comparison between the two immune checkpoint inhibitors(ICIs), although there was no significant difference in EFS (HR = 0.81, 95% CI: 0.61-1.08), PD-1 inhibitors may still be the most effective treatment option. CONCLUSIONS: NICT effectively and safely treats resectable NSCLC. The optimal treatment combination is typically toripalimab and chemotherapy. Treatment based on PD-L1 expression and pathological type is recommended.

Indications for Radiation in Pancreatic Adenocarcinoma: A Review.

Pancreatic adenocarcinoma remains a deadly disease with 5 year overall survival of 10% among all stages. Standard of care for resectable disease remains surgical resection and adjuvant systemic therapy, but paradigms for borderline resectable and unresectable cases remain more nuanced. Radiation has been explored in the neoadjuvant, adjuvant, and definitive settings in a variety of randomized and non-randomized trials with mixed results. There is strong evidence to support the use of neoadjuvant radiation for borderline resectable pancreatic cancer. Utilization of radiation in the adjuvant setting remains unclear while the results of radiation therapy oncology group (RTOG) 0848 are pending.

Robotic-assisted Extended Thymectomy for Large Resectable Thymoma: 21 Years' Experience.

OBJECTIVE: This study aims to evaluate the perioperative and midterm oncological outcomes of robotic-assisted thoracic surgery (RATS) extended thymectomy for patients with large resectable thymomas compared to small thymomas. METHODS: This retrospective single-center study included 204 thymoma patients who underwent RATS extended thymectomy between January 2003 and February 2024. Patients were divided into two groups based on the thymoma size (5cm threshold). RESULTS: The study comprised 114 patients (55.9%) in the small thymoma (ST) group and 90 patients (44.1%) in the large thymoma (LT) group. No significant differences were found between the groups regarding gender, age, proportion of elderly patients, or pathologic high-risk classifications. Apart from a longer operative time (p=0.009) in the LT group, no differences were observed between the two groups regarding surgical parameters and postoperative outcomes. No deaths occurred within 30 days in either group. During a median follow-up of 61.0 months (95% CI: 48.96-73.04), four patients experienced recurrence (1.96%). No significant differences in the five-year overall survival (OS) rate (p=0.25) or recurrence-free survival (RFS) rate (p=0.43) were observed between groups. CONCLUSIONS: RATS extended thymectomy is technically feasible, safe, and effective for treating large resectable thymomas. Moreover, midterm outcomes for patients with completely resected large thymomas were comparable to those with small thymomas during a median follow-up period of up to five years.

Prognostic Impact of a Decrease in Serum Carbohydrate Antigen 19-9 Levels After Preoperative Therapy for 4 Months or More for Borderline Resectable Pancreatic Cancer Abutting Major Arteries.

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A).Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P-value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy.Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery.Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients.

Real-world retrospective study of anti-PD-1 antibody in combination with chemotherapy as a neoadjuvant treatment strategy for locally advanced resectable esophageal squamous cell carcinoma.

Background: Neoadjuvant therapy has become a mainstay of treatment for locally advanced resectable esophageal cancer. The objective of this research was to investigate the effectiveness and safety of neoadjuvant immunotherapy combined with chemotherapy in treating surgically removable esophageal squamous cell carcinoma (ESCC). Methods: From January 1, 2016 to April 1, 2023, we conducted a retrospective analysis of patients diagnosed with resectable esophageal cancer who underwent neoadjuvant immunotherapy combined with chemotherapy at The First Affiliated Hospital of Nanchang University. The primary endpoints of this study were pathologic complete response (pCR), major pathologic response (MPR) and disease-free survival (DFS). The secondary endpoints of this study were overall survival (OS), objective response rate (ORR) and safety. Results: A total of 122 patients with ESCC receiving neoadjuvant immune-chemotherapy (nICT) were included. Fifty-four patients achieved partial response (PR) and two patients achieved complete response (CR), with an ORR of 45.9%. Of the 106 patients who underwent surgery, a total of 28 patients achieved pCR (26.4%) and a total of 37 patients achieved MPR (34.9%). Grade 3 or higher adverse events occurred in 26 patients (21.3%). The most common postoperative complication was pneumonitis (25.5%). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy demonstrates satisfactory efficacy in the treatment of locally advanced ESCC, with manageable treatment-related adverse events and postoperative complications.

Advances in clinical trials on perioperative immune checkpoint inhibitors for resectable non-small cell lung cancer: A comprehensive review.

The reduction in lung cancer mortality rates over the past decade can be partially ascribed to advancements in immunotherapy. Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for advanced non-small cell lung cancer (NSCLC) and have recently been evaluated in multiple clinical trials to confirm their safety and efficacy in the neoadjuvant, adjuvant and perioperative settings for patients with resectable NSCLC. The Food and Drug Administration (FDA) has granted approval for adjuvant atezolizumab following platinum-doublet chemotherapy, neoadjuvant nivolumab and platinum-doublet chemotherapy, adjuvant pembrolizumab after platinum-doublet chemotherapy, and neoadjuvant/adjuvant pembrolizumab for resectable NSCLC, with potential forthcoming approvals for additional agents or indications. Novel data, approvals, and emerging research findings are dramatically shifting the accepted standards of care over just a few years. Despite these advances, the optimal application of these treatments is not entirely straightforward. This article summarizes the biological rationale for immunotherapy and the important clinical trials regarding perioperative ICIs. We also further outline the controversies and future directions to better guide the individualized treatment of NSCLC patients.

Proposal of "borderline resectable" colorectal liver metastases based on analysis of risk factors for early surgical failure.

PURPOSE: We aimed to define borderline resectable colorectal liver metastases (CRLM) based on the analysis of risk factors for early surgical failure and investigate the efficacy of neoadjuvant chemotherapy in these patients. METHODS: This was a retrospective analysis of a multi-institutional cohort of patients diagnosed with technically resectable CRLM. Early surgical failure within 6 months of liver surgery was defined as ESF6. We classified CRLM into three grades (A, B, and C) according to the definition of the Japanese Society for Cancer of the Colon and Rectum. RESULTS: Among the 249 patients with technically resectable CRLM, 46 (18.5%) developed ESF6. The survival rate of these patients was significantly lower than that of the patients without ESF6. In the multivariate analysis of synchronous CRLM patients, no neoadjuvant chemotherapy, Grade B/C, and Charlson comorbidity index ≥ 3 were independent predictors of ESF6. Among patients with synchronous and Grade B/C CRLM, ESF6 rates, surgical failure-free survival, and overall survival in the neoadjuvant chemotherapy group were significantly better relative to the upfront surgery group. CONCLUSIONS: Patients with synchronous and Grade B/C CRLM are at a high risk of early surgical failure, have a poor long-term prognosis, and can be defined as borderline resectable and good candidates for neoadjuvant chemotherapy.

Preoperative camrelizumab combined with chemotherapy for borderline resectable ESCC: A single-arm, prospective, phase 2 study.

BACKGROUND: We investigated the safety and efficacy of preoperative camrelizumab combined with chemotherapy for treating thoracic borderline resectable esophageal squamous cell carcinoma (Br-ESCC) (ChiCTR2200056728). METHODS: Patients with thoracic Br-ESCC received intravenous camrelizumab plus chemotherapy and underwent esophagectomy. The primary endpoint was the pathologic complete response (pCR) rate. We introduced computed tomography and endoscopic examination into the diagnostic criteria to increase its reproducibility. Additionally, we defined a new resection status, Rbr+/-, for Br-ESCC. FINDINGS: Thirty-one patients with Br-ESCC were ultimately enrolled in this study. Overall, 71.0% (22/31) of the patients underwent esophagectomy. R0 resection was achieved in 81.8% of patients (18/22). pCR and major pathological response were observed in 40.9% (9/22) and 63.6% (14/22) of the resected patients, respectively. Eighteen R0 resection patients were redefined according to our Rbr definition; 61.1% (11/18) were classified as Rbr+ resection, and 38.9% (7/18) were classified as Rbr- resection. With a median postoperative follow-up of 17.9 months, 4 patients out of 11 who underwent Rbr+ resection experienced local recurrence (2 of whom achieved pCR). However, no patients (0/7) who underwent Rbr- resection experienced local recurrence. CONCLUSIONS: Esophagectomy after neoadjuvant immunochemotherapy is a promising radical treatment for Br-ESCC. R0 resection was achieved in 81.8% of patients, and a pCR was observed in 40.9% of resected patients. Even after complete excision, Rbr+ resection leads to a higher rate of local recurrence in patients with Br-ESCC. FUNDING: This study was supported by the Key Scientific Research Projects of the Institutions of Higher Learning in Henan Province (no. 21A320032).

Outcomes of Resectable Gallbladder Cancer: A Retrospective Analysis From a Tertiary Care Centre in India.

Background Gallbladder carcinoma (GBC) has deleterious outcomes, but due to its reduced incidence in Western countries, there is a paucity of data on this disease. Here we report the outcomes of a retrospective analysis of resectable gallbladder cancer from a tertiary cancer centre in eastern India. The primary objective of this study is to evaluate the overall survival (OS) and relapse-free survival (RFS) rates among patients with resectable GBC. Methods A retrospective analysis was carried out on patients who underwent radical surgery between 2007 and 2022 and received various neoadjuvant and adjuvant chemotherapy methods. Patients who had adjuvant chemoradiotherapy concurrently or who did not receive adjuvant therapy were excluded. All the baseline clinicopathological characteristics were retrieved from electronic medical records. The survival data were collected from records of follow-up visits as well as telephonic calls to the patients who were lost to follow-up. Simple proportions were used for baseline characteristics, and the Kaplan-Meier method was used for survival analysis. Results A total of 161 patients were identified, and data were captured from electronic medical records. The included patients' ages ranged between 26 and 80 years, with a median age of 56 years. Among the participants, 103 were female (64%) and 58 (36%) were male. Among the 161 patients, the median number of lymph nodes harvested was nine (ranging from one to 43), and only three patients were margin-positive. The tumour, nodes, and metastasis (TNM) distributions were as follows: pT2 in 111 patients (70.25%), pT3 in 44 patients (27.85%), and pT4 in three patients (1.90%). The nodal statuses were pN0 in 91 patients (61.9%), pN1 in 51 patients (34.69%), and pN2 in five patients (3.4%). The majority (64%) received single-agent capecitabine, 27% received gemcitabine-based platinum doublet therapy, and 4.3% received neoadjuvant therapy. Of the full sample, 2.4% received concurrent adjuvant chemo plus radiation therapy, and three patients did not receive any adjuvant therapy. Additionally, among the 161 patients, 34.16% had a relapse, with 47% being local and 52% being distant relapses. The median follow-up was 49 months (interquartile range (IQR) 23-71 months). The 24-month RFS rate was 67.1% (SD+/- 4.3%), and the 24-month OS rate was 78.1% (SD+/- 4.1%). Conclusion Our data, which is from one of the largest samples from India, show that resectable gallbladder cancer has very good outcomes after radical surgery and adjuvant chemotherapy. There was a higher proportion of T2 and node-negative disease, which could have led to better survival compared to published literature.

Advancing Pancreatic Cancer Surgical Treatments and Proposal of New Approaches.

Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems-the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition-assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center's neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy's Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes.

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Safety and Feasibility of Neoadjuvant-Modified FOLFIRINOX in Elderly Patients with Pancreatic Cancer.

The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase (p = 0.0173) and alanine aminotransferase (p = 0.0378) and nausea (p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate (p = 0.3381), postoperative severe complication rates (p = 0.2450), and postoperative hospital stay (p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC.

Enhancing Neoadjuvant Virotherapy's Effectiveness by Targeting Stroma to Improve Resectability in Pancreatic Cancer.

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering the infiltration of oncolytic viruses and various therapeutic drugs-such as antibodies, adoptive cell therapy agents, and chemotherapeutic agents-in reaching the tumor site. Recently, a growing emphasis has been placed on targeting major acellular components of tumor stroma, such as hyaluronic acid and collagen, to enhance drug penetration. Oncolytic viruses can be engineered to express proteolytic enzymes that cleave hyaluronic acid and collagen into smaller polypeptides, thereby softening the desmoplastic stroma, ultimately leading to increased viral distribution along with increased oncolysis and subsequent tumor size regression. This approach may offer new possibilities to improve the resectability of patients diagnosed with BR and LA PDAC.

Trends and Disparities in Robotic Surgery Utilization for Non-Small Cell Lung Cancer.

INTRODUCTION: Robotic surgery has become an increasingly utilized approach for resectable lung cancer. However, availability may be limited for certain patient populations, underscoring inequity in access to innovative surgical techniques. We hypothesize that there is an association between social determinants of health and robotic surgery utilization for resectable non-small cell lung cancer (NSCLC). METHODS: We queried the National Cancer Database (2010-2019) for patients with clinical stage I-III NSCLC who underwent resection, stratifying the cohort based on surgical technique. Multivariable logistic regression analysis was performed to identify associations between sociodemographic and clinicopathologic factors and the robotic approach. RESULTS: Among the 226,455 clinical stage I-III NSCLC patients identified, 34,059 (15%) received robotic resections, 78,039 (34.5%) underwent thoracoscopic resections, and 114,357 (50.5%) had open resections. Robotic surgery utilization increased from 3.1% in 2010 to 34% in 2019 (P < 0.001). Despite this, after adjusting by clinical stage, extent of resection, site of tumor, and receipt of neoadjuvant therapy, multivariable analysis revealed various sociodemographic and treatment facility factors that were associated with underutilization of this approach: lack of insurance (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.73-0.93), lower income brackets (aOR 0.93, 95% CI 0.91-0.96), provincial settings (urban aOR 0.79, 95% CI 0.76-0.82; rural aOR 0.57, 95% CI 0.51-0.64), and treatment at community centers (comprehensive community cancer programs aOR 0.73, 95% CI 0.70-0.75; community cancer programs aOR 0.51, 95% CI 0.47-0.55). CONCLUSIONS: This study suggests that disparities in determinants of health influence accessibility to robotic surgery for resectable NSCLC. Identification of these gaps is crucial to target vulnerable sectors of the population in promoting equality and uniformity in surgical treatment.

Circulating tumor DNA to guide diagnosis and treatment of localized and locally advanced non-small cell lung cancer.

Liquid biopsy is a minimally invasive method for biomarkers detection in body fluids, particularly in blood, which offers an elevated and growing number of clinical applications in oncology. As a result of the improvement in the techniques for DNA analysis, above all next-generation sequencing (NGS) assays, circulating tumor DNA (ctDNA) has become the most informing tumor-derived material for most types of cancer, including non-small cell lung cancer (NSCLC). Although ctDNA concentration is higher in patients with advanced tumors, it can be detected even in patients with early-stage disease. Therefore, numerous clinical applications of ctDNA in the management of early-stage lung cancer are emerging, such as lung cancer screening, the identification of minimal residual disease (MRD), and the prediction of relapse before radiologic progression. Moreover, a high number of clinical trials are ongoing to better define the impact of ctDNA evaluation in this setting. Aim of this review is to offer a comprehensive overview of the most relevant implementations in using ctDNA for the management of early-stage lung cancer, addressing available data, technical aspects, limitations, and future perspectives.

The KRAS G12D mutation increases the risk of unresectable recurrence of resectable colorectal liver-only metastasis.

PURPOSE: Unresectable recurrence is a critical predictor of outcomes for colorectal cancer patients. We attempted to identify the prognostic factors, especially for unresectable recurrence-free survival (URFS) as a new endpoint, in patients with resectable colorectal liver-only metastasis (CRLOM). METHODS: We investigated patients with resectable CRLOM, who underwent an R0 resection for both CRC and CRLOM between January, 2014 and March, 2019 at a single institution. The exclusion criteria were patients who received neoadjuvant treatment, the absence of data for genetic analyses, and the presence of multiple cancers, synchronous CRC, or familial adenomatous polyposis. The prognostic factors were examined retrospectively using data on pre-hepatectomy factors, including primary tumor molecular profiling results. RESULTS: We analyzed the data of 101 patients who underwent curative-intent surgery for CRLOM. Multivariate analysis revealed that KRAS G12D mutation-positivity (hazard ratio [HR]: 7.69; p < 0.01), RYR2 mutation-positivity (HR: 4.03; p < 0.01), and KRAS G12S mutation-positivity (HR: 3.96; p = 0.03), CA19-9 > 37 U/ml before hepatectomy (HR: 3.62; p < 0.01), and primary tumor pN2 stage (HR: 3.22; p = 0.03) were significant predictors of the URFS. CONCLUSIONS: This is the first study to show that specific KRAS and RYR2 mutations were associated with the URFS.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Associated With Recurrence and Survival of Resectable Non-Small Cell Lung Cancer (NSCLC): A Retrospective Study.

INTRODUCTION: Curative lung resection remains the key therapeutic strategy for early-stage non-small cell lung cancer (NSCLC). However, a proportion of patients still experience variable outcomes and eventually develop recurrence or die from their disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been identified as a deleterious factor that inhibits tumor cells apoptosis and leads to reduction of lymphocyte infiltration. However, there has been no research on the predicted role of PCSK9 as an immunohistochemical biomarker with survival in resectable NSCLC. METHODS: One hundred sixty-three patients with resectable NSCLC were retrospectively reviewed, and PCSK9 expression of resected NSCLC was analyzed by immunohistochemistry using tissue microarrays. RESULTS: PCSK9 was associated with recurrence (42.1% relapsed in the PCSK9lo group versus 57.9% relapsed in the PCSK9hi group, P = 0.006) and survival status (39.6% dead in PCSK9lo group versus 60.4% dead in PCSK9hi group, P = 0.004) in patients with resectable NSCLC. Moreover, resectable NSCLC patients with higher PCSK9 expression in tumor tissue experienced poorer disease-free survival (median disease-free survival: 10.5 versus 25.2 mo, hazard ratio = 1.620, 95% confidence interval: 1.124-2.334) and overall suvrival (median overall suvrival: 20.0 versus 54.1 mo, hazard ratio = 1.646, 95% confidence interval: 1.101-2.461) compared to those with lower PCSK9 expression. CONCLUSIONS: High PCSK9 expression of tumor was correlated with recurrence and worse survival status of resectable NSCLC in our retrospective study, which indicated that PCSK9 in NSCLC may be an immunohistochemical biomarker of poor prognosis for patients with resectable NSCLC. Further large-scale prospective studies are warranted to establish these results.