Candidates For Resection Research Articles

High levels of autotaxin and lysophosphatidic acid predict poor outcome in treatment of resectable gastric carcinoma

BackgroundAlthough early-stage gastric cancer is a candidate for curative surgical resection, the absence of specific early symptoms results in a late diagnosis and consequently most patients present advanced or metastatic disease. Identifying noveland tumor-specific biomarkers is needed to increase early detection and match patients to the appropriate treatment. The present study focused on the possible prognostic role of Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2)/Autotaxin (ATX) and lysophosphatidic acid (LPA) in Gastro-Esophageal Adenocarcinoma (GEA). High levels of ATX/LPA are associated with several malignancies including gastrointestinal tumors. MethodsUsing a bioinformatics analysis, the incidence of ENPP2 mutations together with its expression in the tumor tissues and the correlation between the presence of mutations and the survival rate were examined in databases of GEA patients. Furthermore, circulating levels of ATX and LPA were studied retrospectively and longitudinally both in patients receiving frontal surgery and in patients receiving preoperative chemotherapy. ResultsOverall findings suggested that although ENPP2 mutations occur at low incidence, their presence was associated with a particular poor Overall Survival (OS). Furthermore, removal of the tumour by surgery resulted in a decrease in serum ATX and LPA levels within five days, regardless of any previous chemotherapy. Basal circulating ATX were associated with the aggressive diffuse GEA and could be considered of negative prognostic value, mainly in combination models with circulating Carcino-Embryonic Antigen (CEA). ConclusionsBased on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.

Exploring the role of the immune microenvironment in hepatocellular carcinoma: Implications for immunotherapy and drug resistance.

Hepatocellular carcinoma (HCC), the most common type of liver tumor, is a leading cause of cancer-related deaths, and the incidence of liver cancer is still increasing worldwide. Curative hepatectomy or liver transplantation is only indicated for a small population of patients with early-stage HCC. However, most patients with HCC are not candidates for radical resection due to disease progression, leading to the choice of the conventional tyrosine kinase inhibitor drug sorafenib as first-line treatment. In the past few years, immunotherapy, mainly immune checkpoint inhibitors (ICIs), has revolutionized the clinical strategy for HCC. Combination therapy with ICIs has proven more effective than sorafenib, and clinical trials have been conducted to apply these therapies to patients. Despite significant progress in immunotherapy, the molecular mechanisms behind it remain unclear, and immune resistance is often challenging to overcome. Several studies have pointed out that the complex intercellular communication network in the immune microenvironment of HCC regulates tumor escape and drug resistance to immune response. This underscores the urgent need to analyze the immune microenvironment of HCC. This review describes the immunosuppressive cell populations in the immune microenvironment of HCC, as well as the related clinical trials, aiming to provide insights for the next generation of precision immunotherapy.

Advances in Image-Guided Ablation Therapies for Solid Tumors.

Image-guided solid tumor ablation methods have significantly advanced in their capability to target primary and metastatic tumors. These techniques involve noninvasive or percutaneous insertion of applicators to induce thermal, electrochemical, or mechanical stress on malignant tissue to cause tissue destruction and apoptosis of the tumor margins. Ablation offers substantially lower risks compared to traditional methods. Benefits include shorter recovery periods, reduced bleeding, and greater preservation of organ parenchyma compared to surgical intervention. Due to the reduced morbidity and mortality, image-guided tumor ablation offers new opportunities for treatment in cancer patients who are not candidates for resection. Currently, image-guided ablation techniques are utilized for treating primary and metastatic tumors in various organs with both curative and palliative intent, including the liver, pancreas, kidneys, thyroid, parathyroid, prostate, lung, breast, bone, and soft tissue. The invention of new equipment and techniques is expanding the criteria of eligible patients for therapy, as now larger and more high-risk tumors near critical structures can be ablated. This article provides an overview of the different imaging modalities, noninvasive, and percutaneous ablation techniques available and discusses their applications and associated complications across various organs.

Vagus Nerve Stimulation for Intractable Focal Epilepsy

Abstract Background Epilepsy is a common neurological condition affecting 0.5-1% of the population. Despite the advances in the medical management of epilepsy 25-35% of patients have poor control of their seizures or have unacceptable side effects from the medication. Aim and Objectives To make up-to-date recommendations for the value of vagus nerve stimulation (VNS) in patients suffering from intractable focal epilepsy and not candidates for surgical resection. Subjects and Methods Eight studies were included in the present meta-analysis. The flow diagram of the study selection processes. The total number of patients in the eight included studies was 266. The follow-up periods ranged from 12–124 months. Because of significant heterogeneity (I2 = 94 %) among the included studies, a sensitivity analysis was performed. Result 59.4% of all the included patients showed a 50% or greater reduction in seizure frequency after VNS. The patients with > 50% reduction in seizure frequency ranged from 25–66% among the eight included studies. Non-significant improvement in seizure frequency after VNS. Conclusion After VNS, the frequency of seizures was reduced by 50% in about 59.4% of the patients with intractable focal seizures. The present study's random effects forest plot, however, indicated that the reduction in seizure frequency following VNS was not statistically significant. The effectiveness of VNS in reducing seizure frequency in the population under study is therefore still unknown,.

Early Diagnosis of Cancer of the Pancreas: A Key Step in Improving Survival Rates

Cancer of the pancreas has a lifetime incidence in the United States of 1.6% [1]. It accounts for 3.2% of all new cancers and is the 12th most common cancer. The survival of those diagnosed with cancer of the pancreas is unfortunately poor. The majority of pancreatic carcinoma patients are diagnosed at advanced stages of disease [2]. Only 15-20% of patients are candidates for surgical resection at diagnosis and the 5 year survival is less than 10% [3,4]. It is expected to become the second leading cause of death from cancer within a decade [5]. Cancer of the pancreas is the only common cancer for which early detection is not universally available.

Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm

Background & AimsRadiation therapy has been refined with the increasing evidence of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤ 5.0 cm. MethodsPatients with a single HCC lesion ≤ 5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate (CLRR/CDRR), progression-free survival (PFS), overall survival (OS), adverse events (AEs) and subsequent treatments after recurrence were analyzed. ResultsA total of 288 patients received RFA (166) or SBRT (122) were enrolled. The baseline characteristics between the two groups were comparable. The CLRR in the SBRT group was significantly lower than that in the RFA group (HR = 0.30, 95%CI = 0.16 – 0.57, P < 0.001), especially for patients with tumors > 2.0 cm (HR = 0.20, 95% CI = 0.08 – 0.50, P < 0.001) or adjacent to major vessels (HR = 0.29, 95% CI = 0.13 – 0.66, P < 0.001). CDRR, PFS and OS showed no significant differences between the two groups (all P > 0.050). AEs were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and TB increase. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (P < 0.001). ConclusionsBoth RFA and SBRT were effective and safe for HCC with a single lesion ≤ 5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumors > 2.0 cm or adjacent to major vessels. Impact and implicationsStereotactic body radiation therapy (SBRT) may be used as an alternative therapy to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumors > 3 cm and those with 1 to 3 tumors. This study focused on HCC patients with specific tumor burden, a single lesion ≤ 5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumors > 2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting for the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.

Walking or breathing: comparing the 6-minute walking distance test to the pulmonary function test for lung resection candidates.

Given the limited use of the 6-minute walking distance (6MWD) test as a replacement for standard tests in thoracic surgery, insufficient research exists on the prognostic value of this test, and further studies are necessary. This study aimed to investigate the correlation between pulmonary function tests (PFT) and the 6MWD test in lung resection patients. This cross-sectional study, conducted in 2021-2022, involved lung resection candidates referred to the thoracic surgery clinic. Demographic data, including age, sex, and body mass index (BMI), were collected, and pulmonary function tests and 6MWD tests were conducted for all patients. The sample size of the study was 31, and all patients received routine treatment during hospitalization. Of the 31 subjects included in the study, 16 were male (51.6%) and 15 (48.4%) were female. The mean age of the patients was 33.45±13.78 years. The median forced expiratory volume in one second (FEV1) and the mean ratio of FEV1/forced vital capacity (FVC) were 2.16 (1.49-2.85) liters and 81.80±7.34%, respectively. No significant correlation was found between the results of 6MWD and PFT, including FVC, FEV1, and FEV1/FVC ratio (P>0.05). The 6MWD test is a more economical and easily accessible test than PFT. However, this study found no correlation between the 6MWD test and spirometry parameters. Therefore, we suggest that surgeons should not rely on the 6MWD test as a predictive value for assessing respiratory function in lung resection candidates. The study's findings have important implications for clinical practice.

The Ugly: Metastatic Colon Cancer—Surgical Options

AbstractOver 50% of patients with colorectal cancer develop metastatic disease. Although systemic therapy remains the backbone of palliative treatment, select patients may be candidates for surgical resection with curative intent. Given increasing evidence of the association between metastasectomy and prolonged survival, surgery has acquired an increasingly central role in the management of liver, lung, and peritoneal metastases. This is compounded by accumulating advances in local and systemic treatments that have allowed for expansion of the resectability pool, bringing the potential for curative surgical treatment to increasing numbers of patients with stage IV disease. However, as the boundaries of resectability are pushed, patient selection and consideration of tumor-related and technical factors are imperative to the identification of patients for whom surgery would be of the greatest benefit.

A phase I/II open-label clinical trial of CPI-613 in combination with modified FOLFIRINOX in patients with locally advanced (LAPC) or borderline resectable pancreatic cancer (BRPC).

4172 Background: Pancreatic ductal adenocarcinoma (PDA) carries a poor prognosis with a 5-year relative survival rate of 13%. Surgical resection is the only curative treatment option, but less than 20% of patients are eligible at diagnosis. A subset of patients with locally advanced disease can become candidates for resection with neoadjuvant (NA) therapy. mFOLFIRINOX is the standard of care in the adjuvant setting, with extrapolated data supporting its use in the NA setting. CPI-613/Devimistat (D) is a small molecule that targets mitochondrial metabolism in tumor cells leading to ROS-mediated apoptosis. A phase III trial of mFOLFIRINOX + D at 500 mg/m2 in metastatic PDA did not meet primary endpoint of overall survival (OS). Here we present the results of the combination’s use at standard and escalated doses in LAPC and BRPC. Methods: In this investigator-initiated, single-center, phase I/II, open-label trial treatment-naïve patients with investigator assessed LAPC or BRPC were treated with mFOLFIRINOX in 14 day cycles + D. In the standard dosing (SD) cohort, patients received D at 500mg/m2 while in the dose escalation (DE) cohort; D at 750 mg/m2 or 1000 mg/m2 was used. Radiographic response was assessed every 8 weeks. Patients who remained unresectable after 12 cycles could receive additional standard treatments, including chemoradiotherapy. The primary endpoint was median overall survival (mOS), with the study powered to show a mOS improvement from the historical standard of 14 months to 28 months with mFOLFIRINOX + D. Secondary endpoints were median progression free survival (mPFS), percent resected, and safety outcomes. NCT03699319 Results: Between Dec 2018 and Mar 2022, 37 patients and 11 patients enrolled in the SD and DE cohorts. Median age 69 years (range 47-78), male/female (27/21), Caucasian (83%), LAPC/BRPC (34/14). One patient (2%) withdrew, 4 patients (8%) discontinued treatment due to toxicity, 9 patients (19%) had progressive disease prior to completion of 12 cycles. In all patients mOS was 16.3 months and mPFS was 10.7 months. By cohort: SD/DE mOS: 16.2/17.6 months (p=0.56). Fourteen patients (29%) had partial response by RECIST 1.1. Twenty patients (41.7%) had resection; mOS 29.7 months. In the SD cohort, 78% and 24% of patients had grade 3 and/or 4 AEs. There were no dose limiting toxicities (DLT) in the DE cohort, and eight patients received the maximum dose of 1000 mg/m2 of D. After the DLT period, 100% patients in DE cohort had grade 3 toxicity and 55% had grade 4 toxicity. For all the most common toxicities (gr3,4) were neutropenia (27%,25%), diarrhea (25%,0), anorexia wt. loss (23%,0), nausea/vomiting (23%,0). Conclusions: The combination of mFOLFIRINOX and D is feasible in the LAPC/BRPC population at increased dose levels of D; however, it did not meet the primary endpoint of doubling OS compared to historical controls. Clinical trial information: NCT03699319 .

Association of human interpretable features derived from pancreatic ductal adenocarcinoma pathology slides with disease-free survival.

e16368 Background: Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second cause of cancer death in the US by 2040. For the minority of patients who are candidates for curative-intent surgical resection, a neoadjuvant approach with chemotherapy or chemotherapy followed by chemoradiotherapy (chemoRT) has become the standard of care. The tumor microenvironment (TME) has been recognized as a key factor in therapeutic resistance and disease progression. This study aims to explore the prognostic value of human-interpretable machine learning image features (HIFs) derived from whole-slide H&amp;E images. Methods: Consecutive PDAC patients who underwent neoadjuvant therapy followed by surgical resection were studied in this single-institution retrospective study. Clinical variables collected include tumor site (head/body/tail), surgery extent, histology, sex, age at diagnosis, grade, treatment response (4-point scale), LVI, PNI, resection margin status, pathological TNM staging, number of lymph nodes removed/positive, neoadjuvant strategy (chemotherapy vs chemoRT), and number of neoadjuvant chemo cycles. These factors were analyzed with a multivariable Cox proportional hazards model for disease-free survival (DFS) after surgery. Additionally, 420 human-interpretable image features (HIFs) derived from a commercial machine learning software were analyzed with a univariable Cox model on a binary outcome of 1-yr DFS, applying a Bonferroni correction for multiple comparisons to identify significant predictors. Results: Increased neoadjuvant chemotherapy cycles (HR = 0.62, p = 0.001, [median: 8, IQR: 6-12]) and receipt of combination neoadjuvant therapy (HR = 0.15, p = 0.020, [29% chemo, 71% +chemoRT]) exhibited a protective effect in the multivariable DFS model. 3 HIFs quantifying immune cells and macrophages within the cancerous tissue and its stroma were associated with an improved probability of 1-year DFS. Conclusions: In addition to clinical factors, HIFs may offer valuable insights into the tumor microenvironment's influence on PDAC progression, paving the way for improved prognostic models and therapeutic strategies. Future work will integrate clinical predictors with HIFs in a combined model.

A phase 2/3 study of fianlimab plus cemiplimab versus cemiplimab in patients with advanced non-small cell lung cancer with tumors expressing PD-L1 ≥50%.

TPS8663 Background: Fianlimab (anti–lymphocyte activation gene 3 [LAG-3]) and cemiplimab (anti–programmed cell death-1 [PD-1]) are high-affinity, fully human, IgG4 monoclonal antibodies. In patients (pts) with advanced non-small cell lung cancer (aNSCLC) and programmed cell death-ligand 1 (PD-L1) expression ≥50% with no actionable mutations, first-line cemiplimab monotherapy showed significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy, with a safety profile consistent with previous reports for cemiplimab monotherapy. Despite pts’ selection by PD-L1 expression, only ~50% of pts respond to PD-1 therapy, thus there is a need for immune-oncology combinations like anti–LAG-3 plus anti–PD-1 to potentially improve outcomes. Methods: This is a randomized, double-blind, Phase 2/3 study (NCT05785767) to evaluate fianlimab + cemiplimab versus cemiplimab monotherapy as first-line treatment in pts with aNSCLC and tumors expressing PD-L1 ≥50%. The study will be conducted globally at ~210 sites. Key inclusion criteria: ≥18 years old; histologically confirmed squamous or non-squamous stage IIIB/C (not candidates for surgical resection or definitive chemoradiation) or stage IV NSCLC (no prior systemic treatment for recurrent or metastatic NSCLC); PD-L1 expression in ≥50% of tumor cells; ≥1 radiographically measurable lesion per Response Evaluation Criteria in Solid Tumors v1.1; Eastern Cooperative Oncology Group performance status ≤1; adequate organ and bone marrow function. This study has Phase 2 and Phase 3 parts and is expected to enroll ~850 pts. Pts will be treated for up to 108 weeks. In Phase 2, 150 patients will be randomized 1:1:1 into three treatment arms (Q3W IV): Arm A, fianlimab high dose + cemiplimab 350 mg; Arm B, fianlimab low dose + cemiplimab 350 mg; Arm C, cemiplimab 350 mg + saline/dextrose placebo. Based on findings from Phase 2, the dose of fianlimab (low or high) will be selected for Phase 3. In Phase 3, 700 patients will be randomized 1:1 into either experimental Arm A or B, and comparator Arm C (cemiplimab + placebo). In Phase 2, the primary endpoint is objective response rate (ORR) per blinded independent central review (BICR). The secondary endpoints are safety, ORR per investigator assessment, disease control rate (DCR), time to tumor response (TTR), duration of response (DOR), PFS, OS, patient-reported outcomes, pharmacokinetics, and immunogenicity. In Phase 3, the primary endpoint is OS in patients receiving fianlimab + cemiplimab versus cemiplimab monotherapy. Secondary endpoints are safety, ORR, DCR, TTR, DOR, and PFS, per BICR and investigator assessment, patient-reported outcomes, pharmacokinetics, and immunogenicity. This study is open for enrollment along with a second study of fianlimab + cemiplimab + chemotherapy in aNSCLC. Clinical trial information: NCT05785767 .

Efficacy and Safety of Atezolizumab and Bevacizumab in Appendiceal Adenocarcinoma.

Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously. We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA. Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041). In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted. AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study.

Epileptic encephalopathies secondary to hypothalamic hamartomas treated with radiosurgery: A case series.

Hypothalamic hamartomas are congenital lesions that typically present with gelastic seizures, refractory epilepsy, neurodevelopmental delay, and severe cognitive impairment. Surgical procedures have been reported to be effective in removing the hamartomas, however, they are associated with significant morbidity. Therefore, it is not considered a safe therapeutic modality. Image-guided robotic radiosurgery (CyberKnife® Radiosurgery System) has been shown to provide good outcomes without lasting complications. This series of cases describes the clinical, radiological, radiotherapeutic, and postsurgical outcomes of five patients with epileptic encephalopathies secondary to hypothalamic hamartomas who were treated with CyberKnife®. All patients exhibited refractory epilepsy with gelastic seizures and were unsuitable candidates for surgical resection The prescribed dose ranged between 16 and 25 Gy, delivered in a single fraction for four patients and five fractions for one patient while adhering strictly to visual pathway constraints. After radiosurgery, four patients maintained seizure control (one with an Engel class Ia, three with an Engel class 1d), and another presented sporadic, nondisabling gelastic seizures (with an Engel class IIa). After 24-26 months of follow-up, in three patients, their intelligence quotient scores increased. No complications were reported. This report suggests that Cyberknife may be a good option for treating hypothalamic hamartoma, particularly in cases where other noninvasive alternatives are unavailable. Nevertheless, additional studies are essential in order to evaluate the effectiveness of the technique in these cases.

Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

Radiotherapy for pediatric low-grade glioma.

Radiotherapy is a highly effective treatment for pediatric low-grade glioma, serving as the standard for evaluating progression-free and overall survival, as well as vision preservation. Despite its proven efficacy, concerns about treatment complications have led to increased use of chemotherapy and targeted therapy, which are associated with poorer progression-free survival outcomes. This review by Indu Bansal and Thomas E. Merchant examines the indications, timing, and results of radiotherapy for pediatric low-grade glioma. The authors provide a comprehensive analysis of clinical management strategies, addressing the controversies surrounding the use and timing of radiotherapy compared to other therapies. The review highlights that while radiotherapy is essential for certain patients, particularly those who are not candidates for complete resection due to the tumor's infiltrative nature or location, it is often deferred in favor of systemic therapies. This deferral can lead to significant morbidity, including poor visual outcomes. Reports indicate that systemic therapy negatively impacts progression-free survival in patients who eventually undergo radiotherapy. Newer radiotherapy techniques have been developed to minimize complications, offering potential benefits over traditional methods. The evolving clinical management of pediatric low-grade glioma involves balancing the benefits of radiotherapy with concerns about its side effects. Although systemic therapies are increasingly favored, their associated inferior progression-free survival and potential for significant morbidity underscore the need for careful consideration of radiotherapy, particularly in older children, adolescents, or those with progressive disease post-systemic therapy. The emerging role of targeted therapy presents additional challenges, including uncertainties about long-term side effects and its interaction with radiotherapy. Further research is needed to optimize treatment strategies and improve outcomes for pediatric patients with low-grade glioma.

Cemiplimab (Libtayo)

CADTH recommends that Libtayo in combination with platinum-based chemotherapy be reimbursed by public drug plans for the first-line treatment of adults with non–small cell lung cancer (NSCLC) whose tumours have no EGFR, ALK, or ROS1 aberrations and is locally advanced where patients are not candidates for surgical resection or definitive chemoradiation, or for those with metastatic NSCLC, if certain conditions are met. Libtayo in combination with platinum-based chemotherapy should only be covered to treat adults who have stage IIIB or IIIC NSCLC and are not suitable for curative surgery or definitive chemoradiation or have stage IV NSCLC and have not received prior systemic treatment. Patients’ tumours should have no EGFR, ALK, or ROS1 Patients should have a good performance status. Libtayo should only be reimbursed in combination with platinum-based chemotherapy if prescribed by clinicians with expertise and experience in treating NSCLC. The treatment should be delivered in outpatient specialized oncology clinics with expertise in systemic therapy delivery and management of immunotherapy-related side effects. The price of Libtayo should be negotiated so that its use in combination with platinum-based chemotherapy does not exceed the total drug cost of treatment with the least costly immunotherapy reimbursed in the first-line setting.

New models for prediction of postoperative pulmonary complications in lung resection candidates.

In recent years, ventilatory efficiency (minute ventilation (V'E)/carbon dioxide production (V'CO2 ) slope) and partial pressure of end-tidal carbon dioxide (P ETCO2 ) have emerged as independent predictors of postoperative pulmonary complications (PPC). Single parameters may give only partial information regarding periprocedural hazards. Accordingly, our aim was to create prediction models with improved ability to stratify PPC risk in patients scheduled for elective lung resection surgery. This post hoc analysis was comprised of consecutive lung resection candidates from two prior prospective trials. All individuals completed pulmonary function tests and cardiopulmonary exercise testing (CPET). Logistic regression analyses were used for identification of risk factors for PPC that were entered into the final risk prediction models. Two risk models were developed; the first used rest P ETCO2 (for patients with no available CPET data), the second used V'E/ V'CO2 slope (for patients with available CPET data). Receiver operating characteristic analysis with the De-Long test and area under the curve (AUC) were used for comparison of models. The dataset from 423 patients was randomly split into the derivation (n=310) and validation (n=113) cohorts. Two final models were developed, both including sex, thoracotomy, "atypical" resection and forced expiratory volume in 1 s/forced vital capacity ratio as risk factors. In addition, the first model also included rest P ETCO2 , while the second model used V'E/V'CO2 slope from CPET. AUCs of risk scores were 0.795 (95% CI: 0.739-0.851) and 0.793 (95% CI: 0.737-0.849); both p<0.001. No differences in AUCs were found between the derivation and validation cohorts. We created two multicomponental models for PPC risk prediction, both having excellent predictive properties.

Risk factors for lymph node metastasis in T2 colorectal cancer: a systematic review and meta-analysis.

Lymph node metastasis (LNM) occurs in 20-25% of patients with T2 colorectal cancer (CRC). Identification of risk factors for LNM in T2 CRC may help identify patients who are at low risk and thereby potential candidates for endoscopic full-thickness resection. We examined risk factors for LNM in T2 CRC with the goal of establishing further criteria of the indications for endoscopic resection. MEDLINE, CENTRAL, and EMBASE were systematically searched from inception to November 2023. Studies that investigated the association between the presence of LNM and the clinical and pathological factors of T2 CRC were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Certainty of evidence (CoE) was assessed using the GRADE approach. Fourteen studies (8349 patients) were included. Overall, the proportion of LNM was 22%. The meta-analysis revealed that the presence of lymphovascular invasion (OR, 5.5; 95% CI 3.7-8.3; high CoE), high-grade tumor budding (OR, 2.4; 95% CI 1.5-3.7; moderate CoE), poor differentiation (OR, 2.2; 95% CI 1.8-2.7; moderate CoE), and female sex (OR, 1.3; 95% CI 1.1-1.7; high CoE) were associated with LNM in T2 CRC. Lymphatic invasion (OR, 5.0; 95% CI 3.3-7.6) was a stronger predictor of LNM than vascular invasion (OR, 2.4; 95% CI 2.1-2.8). Lymphovascular invasion, high-grade tumor budding, poor differentiation, and female sex were risk factors for LNM in T2 CRC. Endoscopic resection of T2 CRC in patients with very low risk for LNM may become an alternative to conventional surgical resection. PROSPERO, CRD42022316545.

Identifying Optimal Candidates for Primary Tumor Resection Among Metastatic Pancreatic Cancer Patients: A Population-Based Predictive Model

Background There is a controversy about whether surgery should proceed among metastatic pancreatic cancer (mPC) patients. A survival benefit was observed in mPC patients who underwent primary tumor resection; however, determining which patients would benefit from surgery is complex. For this purpose, we created a model to identify mPC patients who may benefit from primary tumor excision. Methods Patients with mPC were extracted from the Surveillance, Epidemiology, and End Results database, and separated into surgery and nonsurgery groups based on whether the primary tumor was resected. Propensity score matching (PSM) was applied to balance confounding factors between the two groups. A nomogram was developed using multivariable logistic regression to estimate surgical benefit. Our model is evaluated using multiple methods. Results About 662 of 14,183 mPC patients had primary tumor surgery. Kaplan–Meier analyses showed that the surgery group had a better prognosis. After PSM, a survival benefit was still observed in the surgery group. Among the surgery cohort, 202 patients survived longer than 4 months (surgery-beneficial group). The nomogram discriminated better in training and validation sets under the receiver operating characteristic (ROC) curve (AUC), and calibration curves were consistent. Decision curve analysis (DCA) revealed that it was clinically valuable. This model is better at identifying candidates for primary tumor excision. Conclusion A helpful prediction model was developed and validated to identify ideal candidates who may benefit from primary tumor resection in mPC.

An assessment of risk factors for recurrence and survival for patients undergoing liver resection for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with increasing rates of incidence and mortality. Surgical resection is curative for patients who are diagnosed at early stages of iCCA. Limited data exist regarding risk factors for postresection recurrence and overall survival as iCCA is rare, and majority of patients are diagnosed at an advanced stage and thus not candidates for resection. We aimed to analyze clinical and laboratory characteristics, tumor histology, locoregional invasion, recurrence and survival in patients undergoing curative resection for iCCA. All patients who underwent curative resection for iCCA between 2006 and 2023 at our institution were included in the study. Clinical characteristics, laboratory, histological and follow-up data were collected. The 1-, 3-, and, 5-year survival rates were 90.9%, 65.9% and 44.2%, respectively. About 65.6% of patients had recurrence in a median of 1.2 years after liver resection. Positive surgical margins were present in 20.73% of patients. Notably, 80.51% had solitary tumor and the remaining 19.48% had multifocal tumor. A total of 64.51% of patients received adjuvant chemotherapy after resection. A total of 26 (31.3%) patients had died during the follow-up period. Duration from liver resection to last follow-up or death was 1.6 years (0.8-3.2). Overall median survival was 4.6 years. The presence of lymph node metastases, vascular invasion, positive surgical margin and advanced tumor stage at diagnosis were associated with significantly worse overall survival, which remained significant in multivariable model for advanced tumor stage and positive surgical margin. Despite curative resection, recurrence rate is high and overall survival is poor in patients with iCCA. Real-world data regarding patient characteristics and longitudinal follow-up remain important as iCCA is a rare malignancy.