UNASSIGNED: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT).
UNASSIGNED: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates.
UNASSIGNED: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035).
UNASSIGNED: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.

OBJECTIVE: The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial.
METHODS: We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid\'s databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included.
RESULTS: The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001).
CONCLUSIONS: PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD.
OBJECTIVE: El efecto de una endoprótesis biliar pre-operatoria sobre las complicaciones después de la pancreaticoduodenectomía sigue siendo controvertido.
UNASSIGNED: Se llevó a cabo un metaanálisis siguiendo las directrices PRISMA y se realizaron búsquedas en PubMed, Web of Science Knowledge y la base de datos de Ovid hasta finales de febrero de 2023. Se incluyeron 35 estudios retrospectivos y 2 ensayos controlados aleatorizados, con un total de 12,641 pacientes.
RESULTS: La tasa global de complicaciones del grupo drenaje biliar pre-operatorio (PBD) fue significativamente mayor que la del grupo no-PBD (odds ratio [OR]: 1.46; intervalo de confianza del 95% [IC 95%]: 1.22-1.74; p < 0.0001), la incidencia de vaciado gástrico retardado posoperatorio fue mayor en los pacientes con PBD en comparación con los de cirugía precoz (OR: 1.21; IC95%: 1.02-1.43; p = 0.03), y hubo un aumento significativo de las infecciones posoperatorias de la herida en los pacientes que recibieron PBD (OR: 2.2; IC 95%: 1.76-2.76; p < 0.00001).
CONCLUSIONS: El drenaje biliar pre-operatorio no tiene ningún efecto beneficioso sobre el resultado posoperatorio. El aumento de las complicaciones posoperatorias globales y de las infecciones de la herida urge a precisar las indicaciones de PBD y a desaconsejar la descompresión biliar pre-operatoria sistemática, en especial en pacientes con bilirrubina total inferior a 250 μmol/l en espera de pancreaticoduodenectomía.

Systemic treatment of resectable non-small cell lung cancer (NSCLC) is evolving with emerging neoadjuvant, perioperative, and adjuvant immunotherapy approaches. Circulating tumor DNA (ctDNA) detection at clinical diagnosis, during neoadjuvant therapy, or after resection may discern high-risk patients who might benefit from therapy escalation or switch. This Review summarizes translational implications of data supporting ctDNA-based risk determination in NSCLC and outstanding questions regarding ctDNA validity/utility as a prognostic biomarker. We discuss emerging ctDNA capabilities to refine clinical tumor-node-metastasis (TNM) staging in lung adenocarcinoma, ctDNA dynamics during neoadjuvant therapy for identifying patients deriving suboptimal benefit, and postoperative molecular residual disease (MRD) detection to escalate systemic therapy. Considering differential relapse characteristics in landmark MRD-negative/MRD-positive patients, we propose how ctDNA might integrate with pathological response data for optimal postoperative risk stratification.

Non-small cell lung cancer, even when diagnosed in early stages, has been linked with poor survival rates and distant recurrence patterns. Novel therapeutic approaches harnessing the immune system have been implemented in early stages, following the designated steps of advanced NSCLC treatment strategies. Immune-checkpoint inhibitor (ICI) regimens as monotherapy, combinational, or alongside chemotherapy have been intensely investigated as adjuvant, neoadjuvant, and, more recently, perioperative therapeutic strategies, representing pivotal milestones in the evolution of early lung cancer management while holding great potential for the future. The subject of current ongoing research is optimizing treatment outcomes for patient subsets with different needs and identifying biomarkers that could be predictive of response while translating the trials\' endpoints to survival rates. The aim of this review is to discuss all current treatment options with the pros and cons of each, persistent challenges, and future perspectives on immunotherapy as illuminating the path to a new era for resectable NSCLC.

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Immune-checkpoint inhibitors (ICIs) have an established role in the treatment of locally advanced and metastatic non-small cell lung cancer (NSCLC). ICIs have now entered the paradigm of early-stage NSCLC. The recent evidence shows that the addition of ICI to neoadjuvant chemotherapy improves the pathological complete response (pCR) rate and survival rate in early-stage resectable NSCLC and is now a standard of care option in this setting. In this regard, stage III NSCLC merits special consideration, as it is heterogenous and requires a multidisciplinary approach to management. As the neoadjuvant approach is being adopted widely, new challenges have emerged and the boundaries for resectability are being re-examined. Consequently, it is ever more important to carefully individualize the treatment strategy for each patient with resectable stage III NSCLC. In this review, we discuss the recent literature in this field with particular focus on evolving definitions of resectability, T4 disease, N2 disease (single and multi-station), and nodal downstaging. We also highlight the controversy around adjuvant treatment in this setting and discuss the selection of patients for adjuvant treatment, options of salvage, and next line treatment in cases of progression on/after neoadjuvant treatment or after R2 resection. We will conclude with a brief discussion of predictive biomarkers, predictive models, ongoing studies, and directions for future research in this space.

Stage IIIA-N2 non-small cell lung cancer (NSCLC) is a heterogeneous group with different potential therapeutic approaches. Treatment is typically multimodal with either surgical resection after neoadjuvant chemotherapy and/or radiation or concurrent chemotherapy and radiation if unresectable. Despite the multimodal treatment and early stage, cure rates have traditionally been low. The introduction of immunotherapy changed the treatment landscape for NSCLC in all stages, and the introduction of immunotherapy in early-stage lung cancer has improved event free survival and overall survival. Tyrosine Kinase inhibitors (TKIs) have also improved outcomes in early-stage mutation-driven NSCLC. Optimal treatment choice and sequence is increasingly becoming based upon personalized factors including clinical characteristics, comorbidities, programmed death-ligand 1 (PD-L1) score, and the presence of targetable mutations. Despite encouraging data from multiple trials, the optimal multimodal sequence of stage IIIA-N2 NSCLC treatment remains unresolved and warrants further investigation. This review article summarizes recent major clinical trials of neoadjuvant and adjuvant treatment including stage IIIA-N2 NSCLC with a focus on immunotherapy and TKIs.

OBJECTIVE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer.
METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted.
RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group.
CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.

UNASSIGNED: Identification of unsuspected nodal metastasis may occur at the time of operation for a stage I non-small cell lung cancer. Guidelines for this scenario are unclear. Our goal was to assess the cost-effectiveness of aborting the operation in an attempt to first provide neoadjuvant systemic therapy compared with upfront resection.
UNASSIGNED: A computer simulation Markov model with a lifetime horizon was constructed to compare the costs and clinical outcomes, as measured by quality-adjusted life-years (QALYs), of upfront resection at the time of identification of unsuspected N2 mediastinal disease vs. aborting initial resection and continuing with neoadjuvant therapy prior to resection. Input parameters for the model were derived from published literature with costs measured from the healthcare perspective. The incremental cost-effectiveness ratio (ICER) was evaluated with a willingness-to-pay (WTP) threshold of $150,000/QALY. Both deterministic (one-, two-, and three-way) and probabilistic sensitivity analysis (PSA) were performed to assess the impact of variation in input parameter values on model results.
UNASSIGNED: Aborting initial resection in favor of neoadjuvant therapy resulted in both higher costs ($40,415 vs. $29,873) and more QALYs (3.95 vs. 2.84) relative to upfront resection, yielding an ICER of $9,526/QALY. While variation in overall survival had a significant impact on the ICER, perioperative variables did not. As the annual mortality of best-case therapy in the abort group increased from a base-case estimate of 11% to 15%, the ICER exceeded the WTP threshold of $150,000/QALY. Subsequent one- and two-way sensitivity analyses did not find substantially alter the overall results. PSA resulted in aborting resection to be cost-effective in 99.7% of samples, with 13% of samples dominating upfront resection.
UNASSIGNED: Treatment of stage IIIa lung cancer requires the input of a multidisciplinary team who must consider cost, quality of life, and overall survival. As new treatments are developed, further analyses should be performed to determine optimal therapy.

Neoadjuvant immunotherapy has demonstrated beneficial outcomes in various cancer types; however, standardized protocols for neoadjuvant immunotherapy in hepatocellular carcinoma (HCC) are currently lacking. This systematic review and meta-analysis aims to investigate the reliability of neoadjuvant immunotherapy\'s efficacy and safety in the context of HCC.
A systematic search was conducted across PubMed (MEDLINE), EMBASE, the Web of Science, the Cochrane Library, and conference proceedings to identify clinical trials involving resectable HCC and neoadjuvant immunotherapy. Single-arm meta-analyses were employed to compute odds ratios and 95% confidence intervals (CIs). Heterogeneity analysis, data quality assessment, and subgroup analyses based on the type of immunotherapy drugs and combination therapies were performed. This meta-analysis is registered in PROSPERO (identifier CRD42023474276).
This meta-analysis included 255 patients from 11 studies. Among resectable HCC patients, neoadjuvant immunotherapy exhibited an overall major pathological response (MPR) rate of 0.47 (95% CI 0.31-0.70) and a pathological complete response (pCR) rate of 0.22 (95% CI 0.14-0.36). The overall objective response rate (ORR) was 0.37 (95% CI 0.20-0.69), with a grade 3-4 treatment-related adverse event (TRAE) incidence rate of 0.35 (95% CI 0.24-0.51). Furthermore, the combined surgical resection rate was 3.08 (95% CI 1.66-5.72). Subgroup analysis shows no significant differences in the efficacy and safety of different single-agent immunotherapies; the efficacy of dual ICIs (Immune Checkpoint Inhibitors) combination therapy is superior to targeted combined immunotherapy and monotherapy, while the reverse is observed in terms of safety.
Neoadjuvant immunotherapy presents beneficial outcomes in the treatment of resectable HCC. However, large-scale, high-quality experiments are warranted in the future to provide robust data support.