Search

BackgroundThe emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in the treatment landscape of non-small cell lung cancer (NSCLC). Despite the promising long-term survival outcomes and optimization of pathological complete response (cPR) demonstrated by various studies such as Impower010 and Checkmate-816, the effectiveness of neoadjuvant immunotherapy in advanced resectable NSCLC remains a subject of debate. Although previous research has explored the connection between the efficacy of neoadjuvant therapy and surgical-related safety, limited studies have specifically investigated the surgical-related safety of neoadjuvant immunotherapy. Therefore, our study aims to assess the efficacy and surgical-related safety of neoadjuvant immunotherapy in advanced resectable non-small cell lung cancer.MethodWe conducted a retrospective study on a cohort of 93 patients with stage IIIA-IIIC NSCLC who underwent neoadjuvant therapy and surgical resection. Among them, 53 patients received neoadjuvant immunotherapy, 18 patients underwent neoadjuvant chemotherapy while the remaining 22 underwent neoadjuvant targeted therapy. The patients were separated into further groups according to their pathological type. Data analyses were performed using Mann-Whitney U test, chi-square test.ResultsAll patients were categorized into six distinct groups. Notably, the neoadjuvant immunotherapy squamous carcinoma group exhibited a favorable edge over the neoadjuvant targeted squamous carcinoma group concerning the duration of drainage tube indwelling and the extent of lymph node dissection. Furthermore, the neoadjuvant immunotherapy adenocarcinoma group outperformed neoadjuvant targeted therapy adenocarcinoma counterpart in terms of achieving complete pathological response (cPR). Simultaneously, the neoadjuvant immunotherapy adenocarcinoma group surpassed the neoadjuvant chemotherapy adenocarcinoma group in the incidence of hydrothorax. Nevertheless, no statistically significant disparities were noted between the neoadjuvant immunotherapy squamous carcinoma group and the neoadjuvant chemotherapy carcinoma group.ConclusionRegarding surgical outcomes, neoadjuvant immunotherapy conferred notable advantages compared to conventional neoadjuvant chemotherapy and neoadjuvant targeted therapy for patients diagnosed with adenocarcinoma. In the case of squamous carcinoma, neoadjuvant immunotherapy exhibited superiority over neoadjuvant targeted therapy, although additional evidence is required to conclusively establish its precedence over neoadjuvant chemotherapy.

ABSTRACTThe use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25–30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation – which is a potentially curative strategy unique to HCC management – as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments.

Background: Neoadjuvant chemoimmunotherapy treatment (NCIT) has achieved great success for non-small cell lung cancer (NSCLC); however, the intrinsic mechanism underlying this treatment remains unclear. Methods: Thirty-two patients with stage IIA–IIIC NSCLC who underwent surgery after NCIT were included in this retrospective study. Multiplex immunofluorescence (mIF) staining and image analysis assays were performed on the samples collected before and after NCIT for each patient. RNA analyses was applied to confirm the mIF results. Results: Among the enrolled patients, 14 achieved major pathological response or pathological complete response (pCR) and were defined as the 'response' group, whereas 18 patients did not respond well to NCIT and were defined as the 'nonresponse' group. The results of the mIF assays revealed an overall increase in tumor immune lymphocytes (TILs) after NCIT in the stroma area (p = 0.03) rather than the tumor area (p = 0.86). The percentage of CD8+ T cells and tertiary lymphoid structure counts in both the response and nonresponse groups increased significantly after NCIT compared with before NCIT. CD3+ T cells and FOXP3+ cells decreased significantly in the response group but remained unchanged or increased in the nonresponse group. A comparison of the response and nonresponse groups showed that CD3, FOXP3+ and CD8+/PD-1+ cells before NCIT may serve as predictors of the response to neoadjuvant immunotherapy. The RNA analyses confirmed the mIF results that TILs were elevated after NCIT. Conclusions: The infiltration of immune cells before NCIT was correlated with pathologic complete response, which enhanced the TILs as a promising predictor for selecting patients who were more likely to benefit from NCIT. [ABSTRACT FROM AUTHOR]

Copyright of China Journal of Oral & Maxillofacial Surgery is the property of Shanghai Jiao Tong University, College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immunotherapy has ushered in a new era in cancer treatment, and cancer immunotherapy continues to be rejuvenated. The clinical goal of cancer immunotherapy is to prime host immune system to provide passive or active immunity against malignant tumors. Tumor infiltrating leukocytes (TILs) play an immunomodulatory role in tumor microenvironment (TME) which is closely related to immune escape of tumor cells, thus influence tumor progress. Several cancer immunotherapies, include immune checkpoint inhibitors (ICIs), cancer vaccine, adoptive cell transfer (ACT), have shown great efficacy and promise. In this review, we will summarize the recent research advances in tumor immunotherapy, including the molecular mechanisms and clinical effects as well as limitations of immunotherapy. [ABSTRACT FROM AUTHOR]

Biomarker-driven neoadjuvant treatment regimens may be explored based on multi-omics exploratory analysis in the early-phase studies when longitudinal peripheral blood and tumour specimens are available. Keywords: biomarkers; locally advanced oesophagal squamous cell carcinoma; neoadjuvant immunotherapy EN biomarkers locally advanced oesophagal squamous cell carcinoma neoadjuvant immunotherapy 1 4 4 10/03/23 20230901 NES 230901 MAIN TEXT The emergence of immune checkpoint agents has transformed neoadjuvant therapy into a life-saving treatment with curative promise. The NATION-1907 trial has identified "Interferon/Epithelial-mesenchymal transition (IFN/EMT) score" signature and immune-enriched tumour microenvironment phenotype to stratify for well responders who would benefit from neoadjuvant adebrelimab blockade, highlighting that anti-PD-L1 monotherapy may be sufficient in the immune "inflamed" patients. [Extracted from the article]

Research has shown that neoadjuvant immunotherapy may provide more significant clinical benefits to cancer patients undergoing surgery than adjuvant therapy. This study examines the development of neoadjuvant immunotherapy research using bibliometric analysis. As of 12 February 2023, articles on neoadjuvant immunotherapy in the Web of Science Core Collection were collected. Coauthorship and keyword co-occurrence analyses and visualizations were performed using VOSviewer, while CiteSpace was used to identify bursting keywords and references. The study analyzed a total of 1222 neoadjuvant immunotherapy publications. The top contributors to this field were the United States, China, and Italy, and the journal with the most publications was Frontiers in Oncology. Francesco Montorsi had the highest H-index. The most common keywords were 'immunotherapy' and 'neoadjuvant therapy'. The study conducted a bibliometric analysis of over 20 years of neoadjuvant immunotherapy research, identifying the countries, institutions, authors, journals, and publications involved in this field. The findings provide a comprehensive overview of neoadjuvant immunotherapy research. [ABSTRACT FROM AUTHOR]

Abstract Objective Whether cycle number influences the subsequent pathological or surgical outcomes remained unclear. This study aimed to assess the efficacy and surgical safety of neoadjuvant immunochemotherapy‐based treatment in the real‐world setting. Methods Clinical data of patients who received neoadjuvant immunochemotherapy for non‐small‐cell lung cancer between 2018 and 2021 were collected. Oncological outcomes such as objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR), and surgical outcomes including operating time, intraoperative bleeding, postoperative drainage, and hospital stay were analyzed. Results In total, 176 patients were included, among whom 102 cases were lung squamous carcinoma (LUSQ). After immunochemotherapy, 98 (56%) of patients achieved ORR. Notably, the ORR (63% vs. 46%, p = 0.039) and pCR (45% vs. 27%, p = 0.022) were significantly higher in patients with LUSQ. For patients who received two, three, four, and five or more cycles, the ORRs were 52%, 67%, 53%, and 50% (p = 0.36). In post hoc analysis, cycle numbers showed no significant association with MPR or pCR (p = 0.14 and p = 0.073). Treatment cycles showed no influence on operating time, postoperative drainage, and hospital stay (p = 0.79, 0.37, and 0.22). Notably, the blood loss index of patients who received more than four cycles was higher than those receiving four or fewer cycles (mean blood loss: two or fewer cycles 153.1, three cycles 113.8, four cycles 137.6, and five or more cycles 293.3, respectively). Conclusions This study indicated that cycles of neoadjuvant immunochemotherapy had no significant effect on the feasibility and safety of surgery. Although not statistically significant, patients who received five or more cycles of treatment experienced higher intraoperative blood loss.

Abstract Background The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified. Methods We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi‐omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry. Results Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1high, odds ratio [95% confidence interval]: 0.31 [0.10–0.97], p = 0.044). Compared with COL19A1low patients, COL19A1high patients benefited more from neoadjuvant immunotherapy (p

Neoadjuvant systemic therapy is emerging as the best medical practice in patients with resectable stage III melanoma. As different regimens are expected to become available in this approach, the improved optimization of treatment strategies is required. Personalization of care in each individual patient—by precisely determining the disease-related risk and the most efficient therapeutic approach—is expected to minimize disease recurrence, but also the incidence of treatment-related adverse events and the extent of surgical intervention. This can be achieved through validation and clinical application of predictive and prognostic biomarkers. For immune checkpoint inhibitors, there are no validated predictive biomarkers until now. Promising predictive molecular biomarkers for neoadjuvant immunotherapy are tumor mutational burden and the interferon-gamma pathway expression signature. Pathological response to neoadjuvant treatment is a biomarker of a favorable prognosis and surrogate endpoint for recurrence-free survival in clinical trials. Despite the reliability of these biomarkers, risk stratification and response prediction in the neoadjuvant setting are still unsatisfactory and represent a critical knowledge gap, limiting the development of optimized personalized strategies in everyday practice.

Neoadjuvant immunotherapy has brought new hope for patients with non-small cell lung cancer (NSCLC). However, limited by the lack of clinically feasible markers, it is still difficult to select NSCLC patients who respond well and to predict patients’ clinical outcomes before the treatment. Before the treatment, we isolated plasma extracellular vesicles (EVs) from three cohorts (discovery, training and validation) of 78 NSCLC patients treated with neoadjuvant immunotherapy. To identify differentially-expressed EV long RNAs (exLRs), we employed RNA-seq in the discovery cohort. And we subsequently used qRT-PCR to establish and validate the predictive signature in the other two cohorts. We have identified 8 candidate exLRs from 27 top-ranked exLRs differentially expressed between responders and non-responders, and tested their expression with qRT-PCR in the training cohort. We finally identified H3C2 (P = 0.029), MALAT1 (P = 0.043) and RPS3 (P = 0.0086) significantly expressed in responders for establishing the predictive signature. Integrated with PD-L1 expression, our signature performed well in predicting immunotherapeutic responses in the training (AUC=0.892) and validation cohorts (AUC=0.747). Furthermore, our signature was proven to be a predictor for favorable prognosis of patients treated with neoadjuvant immunotherapy, which demonstrates the feasibility of our signature in clinical practices (P = 0.048). Our results demonstrate that the exLR-based signature could accurately predict responses to neoadjuvant immunotherapy and prognosis in NSCLC patients.

Treatment of advanced renal cell carcinoma (RCC) typically involves surgery, even in challenging cases (ie, inferior vena cava [IVC] tumor thrombus, stage 3b [T3b] disease). Although tyrosine kinase inhibitor (TKI)-based neoadjuvant therapy shrinks primary tumors for resection, its benefit for T3b disease is limited, and no guidelines recommend it. Immune checkpoint inhibitor (ICI) combinations and TKIs plus ICIs provide new options for unresectable/metastatic RCC, but reports on ICI-based neoadjuvant therapy for T3b disease are scarce, and none describes survival after cytoreductive nephrectomy. In the present study, we have experienced three cases of advanced RCC with level 2 IVC thrombus, in which neoadjuvant therapy with different types of ICI-based combination therapies was utilized. This approach resulted in significant tumor reduction, regression of thrombus, and successful laparoscopic radical nephrectomy. Pathological analysis confirmed complete responses and no residual carcinoma, including metastatic sites. Notably, no recurrence was observed over 1.5 years in all cases. ICI-based neoadjuvant therapy may facilitate curative resection and prolong progression-free survival in advanced RCC. ICI-based neoadjuvant therapy may facilitate curative resection and prolong progression-free survival in advanced RCC.

Purpose: The aim of present study was to investigate the efficiency of 18F-FDG uptake in predicting major pathological response (MPR) in resectable non-small cell lung cancer (NSCLC) patients with neoadjuvant immunotherapy. Methods: A total of 104 patients with stage I-IIIB NSCLC were retrospectively derived from National Cancer Center of China, of which 36 cases received immune checkpoint inhibitors (ICIs) monotherapy (I-M) and 68 cases with ICI combination therapy (I-C). 18F-FDG PET-CT scans were performed at baseline and after neoadjuvant therapy (NAT). Receiver‐operating characteristic (ROC) curve analyses were conducted and area under ROC curve (AUC) was calculated for biomarkers including maximum standardized uptake value (SUVmax), inflammatory biomarkers, tumor mutation burden (TMB), PD-L1 tumor proportion score (TPS) and iRECIST. Results: Fifty-four resected NSCLC tumors achieved MPR (51.9%, 54/104). In both neoadjuvant I-M and I-C cohorts, post-NAT SUVmax and the percentage changes of SUVmax (ΔSUVmax%) were significantly lower in the patients with MPR versus non-MPR (p < 0.01), and were also negatively correlated with the degree of pathological regression (p < 0.01). The AUC of ΔSUVmax% for predicting MPR was respectively 1.00 (95% CI: 1.00–1.00) in neoadjuvant I-M cohort and 0.94 (95% CI: 0.86–1.00) in I-C cohort. Baseline SUVmax had a statistical prediction value for MPR only in I-M cohort, with an AUC up to 0.76 at the threshold of 17.0. ΔSUVmax% showed an obvious advantage in MPR prediction over inflammatory biomarkers, TMB, PD-L1 TPS and iRECIST. Conclusion: 18F-FDG uptake can predict MPR in NSCLC patients with neoadjuvant immunotherapy.

OBJECTIVE: Immune checkpoint inhibitors have initiated a new era in hepatocellular carcinoma (HCC) treatment. For improving the prognosis of patients with resectable HCC and reducing postoperative recurrence, immunotherapy is being developed in the neoadjuvant setting. However, the efficacy and safety of neoadjuvant immunotherapy remain unclear. MATERIALS AND METHODS: PubMed, Embase, Medline, and Cochrane Library databases were systematically searched for the clinical trials of neoadjuvant immunotherapy for resectable HCC. A single-arm meta-analysis was conducted to calculate the odds ratio and 95% confidence interval (CI), and statistical transformation was performed to obtain the pooled rate P(t) and its CI. Subgroup analyses were performed according to the type of combination therapy. RESULTS: 81 patients from four studies were included in this meta-analysis. In patients with resectable HCC, the pooled major pathological response (MPR) rate and pathological complete response (pCR) rate for neoadjuvant immunotherapy were 0.23 (95% CI, 0.14-0.36) and 0.19 (95% CI, 0.10-0.30), respectively. The pooled objective response rate (ORR) was 0.18 (95% CI, 0.10-0.28), comparable to the results of immunotherapy for advanced HCC. The overall treatment-related adverse events (TRAE) rate was 0.80 (95% CI, 0.68-0.89), but the grade =3 TRAE rate was low at 0.21 (95% CI, 0.13-0.33). The pooled surgical resection rate and surgical delay rate were 0.95 (95% CI, 0.85-0.98) and 0.05 (95% CI, 0.02-0.16), respectively. Subgroup analyses revealed no significant differences in clinical outcomes between immunotherapy combinations. CONCLUSIONS: This meta-analysis provides preliminary evidence of the efficacy and safety of neoadjuvant immunotherapy for HCC, suggesting that it is a promising perioperative treatment option. Conclusive evidence supporting its use requires additional data from large-scale clinical trials. [ABSTRACT FROM AUTHOR]

Background: Although neoadjuvant immunotherapy is being widely studied, there is no consensus on its efficacy in microsatellite-stable (MSS) or mismatch repair proficient (pMMR) colorectal cancer (CRC). This meta-analysis aimed to evaluate studies on neoadjuvant immunotherapy for advanced CRC to assess its efficacy and provide new clinical guidelines. Methods: We searched literature databases to identify studies that assessed the efficacy of neoadjuvant immunotherapy in advanced CRC. The outcomes evaluated were pathological complete response (pCR), major pathological response (MPR), R0 resection, and anal preservation rates. Heterogeneity among the included studies was assessed by sensitivity analysis, and publication bias was evaluated using Begg and Egger tests. Results: Eleven articles were included in the analysis. The pCR, MPR, R0 resection, and anal preservation rates reported in these studies were 39 and 49, 97, and 76%, respectively. The MSI-H and MSS groups had pooled pCR rates of 70 and 24%, respectively. The pCR rates for the induction, consolidation, and concurrent immuno-chemoradiotherapy (CRT) subgroups were 43, 33, and 27%, respectively, and those for the single and double immunotherapy subgroups were 34 and 40%, respectively. Conclusion: Neoadjuvant immunotherapy combined with CRT is effective in treating MSI-H/dMMR advanced CRC. It could also be a new first-line therapeutic option for MSS/pMMR advanced CRC. [ABSTRACT FROM AUTHOR]

Objective: Examine patients with locally advanced rectal cancer (LARC) with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) who received neoadjuvant immunotherapy (nIT), and compare the outcomes of those who chose a watch-and-wait (WW) approach after achieving clinical complete response (cCR) or near-cCR with those who underwent surgery and were confirmed as pathological complete response (pCR). Methods: LARC patients with dMMR/MSI-H who received nIT were retrospectively examined. The endpoints were 2-year overall survival (OS), 2-year disease-free survival (DFS), local recurrence (LR), and distant metastasis (DM). The efficacy of programmed cell death protein-1 (PD-1) inhibitor, immune-related adverse events (irAEs), surgery-related adverse events (srAEs), and enterostomy were also recorded. Results: Twenty patients who received a PD-1 inhibitor as initial nIT were examined. Eighteen patients (90%) achieved complete response (CR) after a median of 7 nIT cycles, including 11 with pCR after surgery (pCR group), and 7 chose a WW strategy after evaluation as cCR or near-cCR (WW group). Both groups had median follow-up times of 25.0 months. Neither group had a case of LR or DM, and the 2-year DFS and OS in each group was 100%. The two groups had similar incidences of irAEs (P=0.627). In the pCR group, however, 2 patients (18.2%) had permanent colostomy, 3 (27.3%) had temporary ileostomy, and 2 (18.2%) had srAEs. Conclusion: Neoadjuvant PD-1 blockade had high efficacy and led to a high rate of CR in LARC patients with dMMR/MSI-H. A WW strategy appears to be a safe and reliable option for these patients who achieve cCR or near-cCR after nIT. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant immunotherapy combined with chemotherapy has been used to treat locally advanced non–small cell lung cancer (NSCLC). Several systems have been developed for response evaluation. The aim of this study was to evaluate the predictive value of response evaluation criteria in solid tumors (RECIST) and propose modified RECIST (mRECIST). Methods: Eligible patients received chemotherapy combined with personalized neoadjuvant immunotherapy. Radical resection was subsequently performed for potentially resectable tumors evaluated by RECIST. The resected specimens were evaluated to determine the response to neoadjuvant therapy. Results: A total of 59 patients received radical resection following neoadjuvant immunotherapy combined with chemotherapy. According to RECIST, four patients had complete remission, 41 had partial remission, and 14 had progressive disease. Postoperative pathological examination showed 31 patients achieved complete pathological remission, and 13 achieved major pathological remission. The final pathological results were uncorrelated with RECIST assessment (p = 0.086). The ycN stage and pN stage were irrelevant (p < 0.001). When the cutoff of sum of diameters (SoD) is 17%, the Youden's index reached its highest value. A correlation was found between mRECIST and final pathological results. Patients with squamous cell lung cancer showed higher proportions in objective response (OR) (p < 0.001) and complete pathological remission (CPR) (p = 0.001). A shorter time to surgery (TTS) was correlated with a better OR (p = 0.014) and CPR (p = 0.010). The decrease in SoD was correlated with better OR (p = 0.008) and CPR (p = 0.002). Conclusions: mRECIST was effective for patient selection for radical resection after neoadjuvant immunotherapy with advanced NSCLC. Two modifications were suggested for RECIST: (1) the cutoff value was adjusted to 17% for partial remission. (2) Changes in lymph nodes on computed tomography were eliminated. A shorter TTS, a larger decrease in SoD and squamous cell lung cancer (vs. adenocarcinoma) were correlated with better pathological responses. [ABSTRACT FROM AUTHOR]

We aimed to investigate the pathological changes, clinicopathological correlation and prognostic factors of neoadjuvant programmed cell death 1 (PD-1) blockade camrelizumab combined with carboplatin and nab-paclitaxel (CCNP) which we have proved its effectiveness in previous research for resectable esophageal squamous cell carcinoma (ESCC). 108 patients of resectable ESCC, with a mean follow-up of 13 m (ranging 1–30 m), treated with neoadjuvant CCNP from March 2020 to October 2022 in the First Affiliated Hospital of Sun Yat-sen University were enrolled. One year overall survival (OS) and disease-free survival (DFS) were 96.4% and 84.7% respectively. Pathological complete response or major pathological response (pCR/MPR) of the primary tumour (T-pCR/T-MPR) and the metastatic lymph node (N-pCR/N-MPR) were 58.3% and 47.5%. Pathological response of both primary tumours (PT) and lymph nodes (LN) metastasis correlated with DFS. LN pathological response was consistent with PT in 70.0% and inconsistent in 30.0% metastatic cases. Higher ratio of CD8+ to FoxP3+ tumour-infiltrating lymphocytes (TILs), earlier ypT stage and PT invasion not beyond circular muscle correlated with better pathological response. Four types of regression patterns of PT and two types of metastatic LN regression were found. A total of 18 (16.7%) out of 108 developed recurrence with a mean time of 6.9 ± 5.3 months. PT pathological response plus ypN and PT invasion beyond circular muscle or not were independent prognostic factors of DFS. This study suggested that camrelizumab plus chemotherapy had a high rate of T-pCR/T-MPR for resectable ESCC. T-pCR/T-MPR plus ypN0 and tumour invasion not beyond circular muscle predicted better DFS. • Neoadjuvant camrelizumab plus chemotherapy is effective for ESCC. • Pathological response of PT was inconsistent with metastatic LN in 30% cases. • Higher ratio of CD8+ to FoxP3+ TILs correlated with better pathological response. • Tumour regression patterns of both PT and metastatic LN were summarised. • PT pathological response and ypN and circular muscle penetration were independent prognostic factors. [ABSTRACT FROM AUTHOR]

Abstract Purpose Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. Methods Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. Results Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10–0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). Conclusion It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study.

The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T]. Summary background data: NCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates. Results: We included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates. Conclusions: Among the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities. [ABSTRACT FROM AUTHOR]

Background: The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified. Methods: We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi‐omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry. Results: Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy (COL19A1high, odds ratio [95% confidence interval]: 0.31 [0.10–0.97], p = 0.044). Compared with COL19A1low patients, COL19A1high patients benefited more from neoadjuvant immunotherapy (p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence‐free survival (p = 0.013), and overall survival (p = 0.056). Moreover, analysis of an immune‐activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy. Conclusions: The findings of this study provide insight into the optimal design of individual treatments for ESCC patients. [ABSTRACT FROM AUTHOR]

Objective: Whether cycle number influences the subsequent pathological or surgical outcomes remained unclear. This study aimed to assess the efficacy and surgical safety of neoadjuvant immunochemotherapy‐based treatment in the real‐world setting. Methods: Clinical data of patients who received neoadjuvant immunochemotherapy for non‐small‐cell lung cancer between 2018 and 2021 were collected. Oncological outcomes such as objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR), and surgical outcomes including operating time, intraoperative bleeding, postoperative drainage, and hospital stay were analyzed. Results: In total, 176 patients were included, among whom 102 cases were lung squamous carcinoma (LUSQ). After immunochemotherapy, 98 (56%) of patients achieved ORR. Notably, the ORR (63% vs. 46%, p = 0.039) and pCR (45% vs. 27%, p = 0.022) were significantly higher in patients with LUSQ. For patients who received two, three, four, and five or more cycles, the ORRs were 52%, 67%, 53%, and 50% (p = 0.36). In post hoc analysis, cycle numbers showed no significant association with MPR or pCR (p = 0.14 and p = 0.073). Treatment cycles showed no influence on operating time, postoperative drainage, and hospital stay (p = 0.79, 0.37, and 0.22). Notably, the blood loss index of patients who received more than four cycles was higher than those receiving four or fewer cycles (mean blood loss: two or fewer cycles 153.1, three cycles 113.8, four cycles 137.6, and five or more cycles 293.3, respectively). Conclusions: This study indicated that cycles of neoadjuvant immunochemotherapy had no significant effect on the feasibility and safety of surgery. Although not statistically significant, patients who received five or more cycles of treatment experienced higher intraoperative blood loss. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated. Methods: Transcriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence. Results: PLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort [PLEK2high, OR (95% CI): 2.15 (1.07–4.33), P = 0.032; IFI6high, OR (95% CI): 2.21 (1.16–4.23), P = 0.016). PLEK2high and IFI6 high ESCC patients (versus low expressed patients) further exhibit higher chance of non-major pathological remissions (90%, P = 0.004) in neoadjuvant immunotherapy cohort and high mortality (78.9%, P = 0.05), poor prognosis in retrospective cohort. PLEK2high/IFI6high ESCC recapitulated mesenchymal phenotype, characterized by extracellular matrix composition and matrix remodeling. In addition, PLEK2high or IFI6high ESCC displayed an immune-unfavored microenvironment, represented by positive correlating with regulatory T cells, Helper 2 T cell as well as less infiltration of B cells, effector T cells and mast cells. Conclusions: PLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment. [ABSTRACT FROM AUTHOR]

Background: Inflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear. Methods: In this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment. Results: In both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67–0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74–0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level. Conclusions: On-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Durvalumab consolidation therapy is the standard treatment after concurrent chemoradiotherapy for patients with surgically unresectable stage IIIA (N2) non-small-cell lung cancer (NSCLC). Neoadjuvant therapy followed by surgery could reduce locoregional and distant recurrence and improve the survival rate for surgically resectable NSCLC. However, the value of neoadjuvant therapy in locally advanced potentially resectable NSCLC remains controversial. Herein, we report a locally advanced potentially resectable NSCLC case with a history of breast cancer who achieved a pathologic complete response (pCR) after preoperative treatment with pembrolizumab and chemotherapy. A 50-year-old woman developed squamous cell carcinoma (SCC) (left lower lobe of the lung, stage IIIA-N2) after two years of chemotherapy and anti-HER2 therapy following a diagnosis of HER2-overexpressing breast cancer. Surgical resection was attempted despite an MDT classification as unamenable to curative surgical resection. After two cycles of neoadjuvant chemotherapy combined with anti-PD1 immunotherapy, the tumor significantly shrank, then the patient underwent a left lower lobectomy. Complete resection with negative margins (R0 resection) was achieved in the patient. The patient experienced grade 1–2 adverse effects and no grade 3 or worse adverse effects occurred. Cardiotoxicity did not occur in the patient despite prior anti-HER2 treatment for breast cancer. Our case study contributes to the existing evidence on the feasibility, efficacy, and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced unresectable NSCLC. Furthermore, future studies are needed to determine which patients can benefit from immunoadjuvant therapy and the duration and course of preoperative and postoperative immunotherapy.

ObjectiveThis systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T].Summary background dataNCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates.ResultsWe included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates.ConclusionsAmong the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

Background: Immune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment. Methods: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs). Results: A total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%-25.5%] and 44.0% (95% CI, 34.1%-53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%-94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%-66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%-99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)]. Conclusion: This systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has been approved for the treatment of metastatic colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic colorectal cancer remains unclear. We tried to explore clinical effect of neoadjuvant immunotherapy in the treatment of non-metastatic colorectal cancer. Methods: We searched the databases (PubMed, Wanfang Embase, Cochrane Library and China National Knowledge Infrastructure databases) to obtain suitable articles up to September 2022. The primary outcomes of pathological complete response (pCRs), major pathological response (MPR), objective response rate (ORR), R0-resection and anus preserving rate were collected and evaluated. Secordary outcomes (pCRs and MPR) of subgroup analysis between deficient mismatch repair/microsatellite instability-high group (dMMR/MSI-H) and proficient mismatch repair/microsatellite stable group (pMMR/MSS) and outcomes for rectal cancer were analyzed for the final results. Results: We included ten articles and 410 cases of non-metastatic colorectal cancer with neoadjuvant immunotherapy. There were 113 (27.5%) cases with the dMMR/MSI-H status and 167 (40.7%) cases with the pMMR/MSS status. pCRs was found in 167/373 (44.6%) patients (ES: 0.49, 95% CI: 0.36 to 0.62, P<0.01, chi2 = 65.3, P<0.01, I 2 = 86.2%) and MPR was found in 194/304 (63.8%) patients (ES: 0.66, 95% CI: 0.54 to 0.78, P<0.01, chi2 = 42.55, P<0.01, I 2 = 81.2%) with the random-effects model and huge heterogeneity. In the subgroup analysis, pCRs was higher in the dMMR/MSI-H group than the pMMR/MSS group in the fixed-effects model with minimal heterogeneity (OR: 3.55, 95% CI: 1.74 to 7.27, P<0.01, chi2 = 1.86, P=0.6, I 2 = 0%). pCRs was found in 58/172 (33.9%) rectal cancer patients (ES: 0.33, 95% CI: 0.26 to 0.40, P<0.01, chi2 = 3.04, P=0.55, I 2 = 0%) with the fixed-effects model and little heterogeneity. Conclusion: Neoadjuvant immunotherapy could increase pCRs and MPR rate for non-metastatic colorectal cancer. Neoadjuvant immunotherapy could achieve better pCRs rate in dMMR/MSI-H group than in the pMMR/MSS group. Neoadjuvant immunotherapy could be another treatment option for non-metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Despite the poor prognosis of triple-negative breast cancer (TNBC), it has been demonstrated that neoadjuvant immunotherapy in combination with chemotherapy can improve the pathologic complete response (pCR) rate and/or long-term outcome of TNBC. However, there have been no real-world studies reporting on the effectiveness of neoadjuvant checkpoint inhibitors in early TNBC. Methods: Between November 2019 and December 2021, 63 early TNBC patients treated with anti-PD-1 antibodies (pembrolizumab or camrelizumab) or anti-PD-L1 antibody (atezolizumab) in combination with chemotherapy at seven institutions were included. PCR1 defined as ypT0/Tis and ypN0 was the primary endpoint. Secondary endpoints included pCR2 defined as ypT0/Tis, overall response rate (ORR), disease-free survival (DFS), drug-related adverse events (AEs) and biomarkers. Results: Among the patients in the current study, 34.9% of patients were able to achieve pCR1, and 47.6% of patients had achieved pCR2. The ORR was 82.5%. 33 patients with non-pCR2 tumors were found to have a median DFS of 20.7 months (95% CI 16.3 months-not reached). The DFS of patients with pCR2 and non-pCR2 after neoadjuvant therapy was significantly different (HR = 0.28, 95% CI 0.10–0.79; P = 0.038). The most common AEs were nausea (63.4%), fatigue (42.7%), leucopenia (30.0%) and elevated transaminase (11.7%). Conclusion: It is possible to achieve a meaningful pCR rate and DFS by combining neoadjuvant checkpoint blockade with chemotherapy in patients with high-risk TNBC. Compared to clinical trials, however, there was a slightly lower pCR rate in this multicentered real-world study. [ABSTRACT FROM AUTHOR]

Background: While the tumor microenvironment (TME) affects immune checkpoint blockade (ICB) efficacy, ICB also reshapes the characteristics of TME. Thus far, studies have focused on the TME evolution during neoadjuvant or adjuvant ICB therapy in gastric cancer (GC). However, the interaction between TME characteristics and neoadjuvant immunotherapy plus chemotherapy remains to be elucidated. Methods: We performed single-cell RNA sequencing on ten GC specimens pre- and post-neoadjuvant camrelizumab plus mFOLFOX6 to determine the impact of the TME on the efficacy of the combination therapy and the remodeling of TME by the therapy. Results: A high baseline interferon gamma (IFN-γ) signature in CD8+ T cells predicts better responses to the combination therapy. We also observed that the IFN-γ signature significantly decreased in multiple cell types, and the exhausted signature of CD8+ T cells was significantly suppressed during the neoadjuvant therapy. Conclusions: Our data reveal interactions between the TME and neoadjuvant immunotherapy plus chemotherapy in GC. Importantly, it also highlights the signature of CD8+ T cells in predicting response to the combination therapy in GC. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors (ICIs) targeting PD-L1/PD-1 and CTLA-4 has transformed the oncology practice of hepatocellular carcinoma. However, only 25–30% of the patients with advanced HCC treated with atezolizumab-bevacizumab or tremelimumab-durvalumab (STRIDE) respond initially, and mechanistic biomarkers and novel treatment strategies are urgently needed for patients who present with or acquire resistance to first-line ICI-based therapies. The recent approval of the STRIDE regimen has also engendered new questions, such as patient selection factors (e.g. portal hypertension and history of variceal bleed) and biomarkers, and the optimal combination and sequencing of ICI-based regimens. Triumphs in the setting of advanced HCC have also galvanized considerable interest in the broader application of ICIs to early- and intermediate-stage diseases, including clinical combination of ICIs with locoregional therapies. Among these clinical contexts, the role of ICIs in liver transplantation – which is a potentially curative strategy unique to HCC management – as a bridge to liver transplant in potential candidates or in the setting of post-transplant recurrence, warrants investigation in view of the notable theoretical risk of allograft rejection. In this review, we summarize and chart the landscape of seminal immuno-oncology trials in HCC and envision future clinical developments. [ABSTRACT FROM AUTHOR]

Although recent trials started the use of neoadjuvant immunotherapy (NIT) in instability-high (MSI-H) or mismatch repair deficient (dMMR) early-stage or locally advanced colorectal cancer (LACRC), little data on the treatment strategy of NIT has been shown, and whether the tirelizumab mono-immune checkpoint inhibitor (ICI) can be used as NIT for patients with LACRC has not been reported as yet. In this study we report on a locally advanced ascending colon cancer case with a history of incomplete intestinal obstruction which achieved a pathologic complete response (pCR) after treated with Tirelizumab as NIT. A 32-year-old man was diagnosed with locally advanced ascending colon cancer with MSI-H and dMMR. An incomplete intestinal obstruction accompanied with hyperpyrexia occurred unexpectedly and was eased by symptomatic treatment. There was no peritonitis or other acute complications. NIT (three cycles of Tirelizumab) was suggested by the MDT board and partial response was achieved according to CT scanning, and pCR was further revealed by postoperative pathology. A ctDNA clearance confirmed the R0 resection and some immunotherapy related predictors were also detected using the NGS method. Our case study contributes to the evidence on the feasibility, efficacy, and safety of f Tirelizumab as a mono ICI for an optional neoadjuvant therapy in patients with MSI-H/dMMR LACRC. [ABSTRACT FROM AUTHOR]

Background: Pediatric colorectal carcinoma (PCRC) is a rare non-embryonal tumor with an incidence of 0.1% to 1% of adults. Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) have shown significant efficacy in defective mismatch repair/Microsatellite instability-high (dMMR/MSI-H) metastatic CRC (mCRC). Although several studies have reported neoadjuvant immunotherapy (NIT) in MSI-H/dMMR non-mCRC patients, not all patients achieved pathological complete remission (pCR). There are differences between PCRC and adult colorectal carcinoma (CRC), and the role of NIT in PCRC remains to be further defined. Case presentation: We report the case of a 12-year-old child who was admitted to the hospital with abdominal pain and vomiting for more than 3 months. The child’s diagnosis was difficult and complex. He was initially diagnosed with intestinal obstruction, eventually diagnosed with a rare PCRC and identified as locally advanced colorectal cancer (LACRC) with genetic sequencing results showing MSI-H. After a thorough evaluation by clinicians, he received 4 cycles of Camrelizumab (anti-PD-1 antibody) + CapeOx (capecitabine and oxaliplatin) NIT combination chemotherapy. Repeat imaging and all tumor markers were unremarkable, and R0 resection was achieved. Postoperative pathology showed a tumor regression grade (TRG) of 0 grade determined as pCR. Postoperative review has not shown any recurrence or metastasis to date and the prognosis is good. Conclusion: PCRC should improve the diagnostic efficiency to prevent misdiagnosis and miss the best time for treatment. NIT and or chemotherapy can be a reasonable and effective treatment option for dMMR/MSI-H locally advanced PCRC. Our report provides some support and evidence for neoadjuvant immunotherapy for locally advanced PCRC, while highlighting the importance of preoperative detection of microsatellite status for locally advanced PCRC. [ABSTRACT FROM AUTHOR]

Abstract Background Neoadjuvant immunotherapy is emerging as novel effective intervention in lung cancer, but study to unearth effective surrogates indicating its therapeutic outcomes is limited. We investigated the genetic changes between non-small cell lung cancer (NSCLC) patients with varied response to neoadjuvant immunotherapy and discovered highly potential biomarkers with indicative capability in predicting outcomes. Methods In this study, 3 adenocarcinoma and 11 squamous cell carcinoma NSCLC patients were treated by neoadjuvant immunotherapy with variated regimens followed by surgical resection. Treatment-naive FFPE or fresh tissues and blood samples were subjected to whole-exome sequencing (WES). Genetic alternations were compared between differently-responded patients. Findings were further validated in multiple public cohorts. Results DNA damage repair (DDR)-related InDel signatures and DDR-related gene mutations were enriched in better-responded patients, i.e., major pathological response (MPR) group. Besides, MPR patients exhibited provoked genome instability and unique homologous recombination deficiency (HRD) events. By further inspecting alternation status of homology-dependent recombination (HR) pathway genes, the clonal alternations were exclusively enriched in MPR group. Additionally, associations between HR gene alternations, percentage of viable tumor cells and HRD event were identified, which orchestrated tumor mutational burden (TMB), mutational intratumor heterogeneity (ITH), somatic copy number alteration (SCNA) ITH and clonal neoantigen load in patients. Validations in public cohorts further supported the generality of our findings. Conclusions We reported for the first time the association between HRD event and enhanced neoadjuvant immunotherapy response in lung cancer. The power of HRD event in patient therapeutic stratification persisted in multifaceted public cohorts. We propose that HR pathway gene status could serve as novel and additional indicators guiding immune-neoadjuvant and immunotherapy treatment decisions for NSCLC patients.

Background and objective Immunoneoadjuvant therapy opens a new prospect for local advanced lung cancer. The aim of our study was to explore the safety and feasibility of robotic-assisted bronchial sleeve resection in patients with locally advanced non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy. Methods Data of 13 patients with locally advanced NSCLC that underwent bronchial sleeve resection after neoadjuvant chemoimmunotherapy during August 2020 and February 2021 were retrospectively included. According to the surgical methods, patients were divided into thoracotomy bronchial sleeve resection (TBSR) group and robot-assisted bronchial sleeve resection (RABSR) group. Oncology, intraoperative, and postoperative data in the two groups were compared. Results The two groups of patients operated smoothly, the postoperative pathology confirmed that all the tumor lesions achieved R0 resection, and RABSR group no patient was transferred to thoracotomy during surgery. Partial remission (PR) rate and major pathological remissions (MPR) rate of patients in the TBSR group were 71.43% and 42.86%, respectively. Complete pathological response (pCR) was 28.57%. They were 66.67%, 50.00% and 33.33% in RABSR group, respectively. There were no significant differences in operative duration, number of lymph nodes dissected, intraoperative blood loss, postoperative drainage time and postoperative hospital stay between the two groups, but the bronchial anastomosis time of RABSR group was relatively short. Both groups of patients had a good prognosis. Successfully discharged from the hospital and post-operative 90-d mortality rate was 0. Conclusion In patients with locally advanced central NSCLC after neoadjuvant chemoimmunotherapy can achieve the tumor reduction, tumor stage decline and increase the R0 resection rate, bronchial sleeve resection is safe and feasible. Under the premise of following the two principles of surgical safety and realizing the tumor R0 resection, robot-assisted bronchial sleeve resection can be preferred.

Abstract Background Immune checkpoint inhibitors were used for patients with advanced non-small cell lung cancer (NSCLC) more and more frequently and the effects were thrilling. Toripalimab as a new immune checkpoint inhibitor has been shown to be effective in patients with advanced NSCLC. However, data regarding the safety and feasibility of surgical resection after treatment with toripalimab for NSCLC remain scarce. Here, we present a case with locally advanced NSCLC that received video-assisted thoracic surgery (VATS) lobectomy after treatment with toripalimab in combination with chemotherapy. Case presentation A 62-year-old male patient with a history of coronary artery stenting operation for two times was found a 3.4 × 3.2 cm cavity mass in the upper lobe of the left lung and enlarged left hilar and mediastinal lymph nodes. Pathological results identified squamous cell carcinoma. The patient was diagnosed with a locally advanced NSCLC and received VATS left upper lobectomy and lymph node dissection after neoadjuvant chemotherapy plus toripalimab for 3 cycles. The postoperative pathological results showed complete tumor remission. Short-term follow-up results were excellent, and long-term results remain to be revealed. Conclusions Our preliminary results showed that the use of neoadjuvant toripalimab and chemotherapy for the locally advanced NSCLC before surgical resection is safe and feasible.

ObjectiveThis systematic review and meta-analysis aimed to explore the efficacy and safety of neoadjuvant immunotherapy in patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC).BackgroundSeveral studies have reported the outcomes of neoadjuvant immunotherapy in patients with ESCC. However, phase 3 randomized controlled trials (RCTs) with long-term outcomes and the comparison of different therapeutic strategies are lacking.MethodsStudies involving patients with advanced ESCC treated with preoperative neoadjuvant immune checkpoint inhibitors (ICIs) were searched through PubMed, Embase, and Cochrane Library up to July 1, 2022. The outcomes were presented as proportions and pooled respectively by fixed or random effect model depending on the heterogeneity between studies. All analyses were performed using the R packages meta 5.5-0 and meta-for 3.4-0.ResultsThirty trials involving 1406 patients were included in the meta-analysis. The pooled pathological complete response (pCR) rate for neoadjuvant immunotherapy was 0.30 (95% confidence interval [CI]: 0.26–0.33). The pCR rate of neoadjuvant immunotherapy combined with chemoradiotherapy (nICRT) was significantly higher than that of neoadjuvant immunotherapy combined with chemotherapy (nICT) (nICRT: 0.48, 95% CI: 0.31–0.65; nICT: 0.29, 95% CI: 0.26–0.33; p=0.03). No significant difference in efficacy was observed between the different chemotherapy agents and treatment cycles. The incidences of grade 1–2 and 3–4 treatment-related adverse events (TRAEs) were 0.71 (95% CI: 0.56–0.84) and 0.16 (95% CI: 0.09–0.25), respectively. Patients treated with nICRT and carboplatin had a higher incidence of grade 3–4 TRAEs compared with those treated with nICT (nICRT: 0.46, 95% CI: 0.17–0.77; nICT: 0.14, 95% CI: 0.07–0.22; p=0.03) and cisplatin (carboplatin: 0.33, 95% CI: 0.15–0.53; cisplatin: 0.04, 95% CI: 0.01–0.09; p

BackgroundWhile the tumor microenvironment (TME) affects immune checkpoint blockade (ICB) efficacy, ICB also reshapes the characteristics of TME. Thus far, studies have focused on the TME evolution during neoadjuvant or adjuvant ICB therapy in gastric cancer (GC). However, the interaction between TME characteristics and neoadjuvant immunotherapy plus chemotherapy remains to be elucidated.MethodsWe performed single-cell RNA sequencing on ten GC specimens pre- and post-neoadjuvant camrelizumab plus mFOLFOX6 to determine the impact of the TME on the efficacy of the combination therapy and the remodeling of TME by the therapy.ResultsA high baseline interferon gamma (IFN-γ) signature in CD8+ T cells predicts better responses to the combination therapy. We also observed that the IFN-γ signature significantly decreased in multiple cell types, and the exhausted signature of CD8+ T cells was significantly suppressed during the neoadjuvant therapy.ConclusionsOur data reveal interactions between the TME and neoadjuvant immunotherapy plus chemotherapy in GC. Importantly, it also highlights the signature of CD8+ T cells in predicting response to the combination therapy in GC.

The morbidity and mortality of lung cancer rank higher, which seriously threatens public health. Recently, the emergence of immune checkpoint inhibitors has brought bright light for the treatment of advanced non-small cell lung cancer (NSCLC). Based on the theoretical basis, it is speculated that NSCLC may benefit from neoadjuvant immunotherapy. With the development of various studies, it is demonstrated that neoadjuvant immunotherapy for NSCLC is safe and feasible, and can contribute greatly to the exciting outcome of pathological response. However, current results do not contain long-term prognosis, distinguish potential beneficiaries, develop a rational therapeutic regimen and course, and so on. In this review, we will conclude the development processes, molecular mechanisms, current research status and treatment-related challenges of neoadjuvant immunotherapy for NSCLC.

Background: Previously reported results have shown promising efficacy of neoadjuvant immunotherapy for resectable non–small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemotherapy have yet been reported. The aim of the present study was to evaluate the superiority of neoadjuvant immunotherapy compared with standard neoadjuvant chemotherapy in resectable NSCLC in terms of short-term clinical outcomes and surgical outcomes. Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov database, Web of Science, and abstracts derived from multiple major cancer meetings up to March 1, 2020. Short-term clinical outcomes (including objective response rate [ORR], major pathologic response, and pathologic complete response [pCR]) and surgical outcomes (including surgical resection rate and R0 resection rate) were reported. Data were summarized as the estimated pooled value of each evaluated index. The risk of bias of included studies was assessed using standard methods. Results: This systematic review and meta-analysis of 21 trials on neoadjuvant immunotherapy and neoadjuvant chemotherapy for NSCLC included 1795 patients. Patients who received Programmed death ligand 1 (PD-1/PD-L1) inhibitors (NeoIO) alone (13.3%; 95% confidence interval [CI], 9.0%-19.3%) had the lowest ORR compared with those who received NeoIO plus chemotherapy (CT) (62.5%; 95% CI, 54.4%-70.0%) or CT alone (41.6%; 95% CI, 36.8%-46.7%) (NeoIO vs CT, P

BackgroundImmune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported.MethodsThe computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed.ResultsOf the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm2/m2, p=0.042), SAI (from 34.7 to 32.9 cm2/m2, p=0.01) and VAI (from 32.4 to 26.8 cm2/m2, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm2/m2, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06–9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20–3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35–20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73–112.7, p=0.013).ConclusionLow SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs.

BackgroundImmune checkpoint inhibitors (ICIs) have been increasingly used for the treatment of advanced gastric cancer (AGC). However, the safety and the short-term outcomes of laparoscopic gastrectomy for patients with AGC after neoadjuvant immunotherapy (NAI) remain unknown.MethodsWe retrospectively analyzed the patients with AGC who underwent laparoscopic surgery after neoadjuvant therapy between 1 January 2019 and 31 October 2021. We further compared the differences in postoperative complications, overall response rate, adverse events, surgical parameters, and postoperative recovery between two cohorts: the NAI group (NAI plus chemotherapy) and the neoadjuvant chemotherapy (NAC) group. Multivariable regression analyses were used to determine the risk factors for the overall response rate.ResultsOverall, 80 patients were enrolled, of whom 30 cases were included in the NAI cohort and 50 were included in the NAC cohort. The overall rate of postoperative complications was 30.0% in both groups (p = 1.000). The overall response rate was 70.0% in the NAI cohort and 40% in the NAC cohort (p = 0.012). The adverse effects were found in 16 cases (53.3%) of the NAI cohort and 23 cases (46.0%) of the NAC cohort (p = 0.645). There was no statistical difference in intraoperative bleeding (50 ml vs. 50 ml, p = 0.983), operation time (320.9 min vs. 303.5 min, p = 0.382), dissected lymph node count (43.5 vs. 40.0, p = 0.364), first postoperative anal aerofluxus (3 days vs. 3 days, p = 0.091), first liquid diet (4 days vs. 5 days, p = 0.213), and postoperative length of stay in the hospital (8 days vs. 7 days, p = 0.508) between the two groups. NAI was estimated to be the independent protective factor [odds ratio (OR) 4.931, 95% confidence interval (CI) (1.385–17.559), p = 0.014] for odds to overall response rate, whereas vessel invasion was found to be the significant risk factor [OR 0.113, 95% CI (0.027–0.475), p = 0.003].ConclusionsLaparoscopic surgery after NAI combined with chemotherapy is a safe therapeutic choice for AGC and may bring better short-term outcomes due to a higher overall response rate.

Background: Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Methods: Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. Results: After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). Conclusion: For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs. [ABSTRACT FROM AUTHOR]

Tissue-resident memory T (TRM) cells have emerged as key players in the immune control of melanoma. These specialized cells are identified by expression of tissue retention markers such as CD69, CD103 and CD49a with downregulation of egress molecules such as Sphingosine-1-Phosphate Receptor-1 (S1PR1) and the lymphoid homing receptor, CD62L. TRM have been shown to be integral in controlling infections such as herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV) and influenza. More recently, robust pre-clinical models have also demonstrated TRM are able to maintain melanoma in a dormant state without progression to macroscopic disease reminiscent of their ability to control viral infections. The discovery of the role these cells play in anti-melanoma immunity has coincided with the advent of immune checkpoint inhibitor (ICI) therapy which has revolutionized the treatment of cancers. ICIs that target programmed death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) have led to substantial improvements in outcomes for patients with metastatic melanoma and have been rapidly employed to reduce recurrences in the resected stage III setting. While ICIs mediate anti-tumor activity via CD8+ T cells, the specific subsets that facilitate this response is unclear. TRM invariably exhibit high expression of immune checkpoints such as PD-1, CTLA-4 and lymphocyte activating gene-3 (LAG-3) which strongly implicates this CD8+ T cell subset as a crucial mediator of ICI activity. In this review, we present pre-clinical and translational studies that highlight the critical role of TRM in both immune control of primary melanoma and as a key CD8+ T cell subset that mediates anti-tumor activity of ICIs for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Purpose of Review : To review and update surgeons about the evolving complexities in the surgical management of melanoma including lymph node staging and treatment. Recent Findings: Primary resection with adequate margins continues to be the standard of care for localized cutaneous melanoma. Sentinel lymph node biopsy is confirmed to be a powerful tool due to its prognostic value and informative guidance for adjuvant treatments and surveillance. Due to the lack of benefit in melanoma-specific survival and distant metastasis-free survival, completion lymph node dissection is not performed routinely after a positive sentinel lymph node biopsy. Neoadjuvant systemic treatment approaches for advanced loco-regional disease show promise in phase I and II clinical trial data, and phase III studies. Summary: The surgical management of cutaneous melanoma continues to evolve with further de-escalation of the extent of excision of primary melanomas and the management of lymph node disease. [ABSTRACT FROM AUTHOR]

Background: Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC. Methods: We retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared. Results: A total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally Frontiers in Oncology 01 frontiersin.org OPEN ACCESS EDITED BY Helmut H. Popper, Medical University of Graz, Austria REVIEWED BY Haiyu Zhou, Guangdong Provincial People's Hospital, China Song Xu, Tianjin Medical University General Hospital, China *CORRESPONDENCE Wei Guo gyguowei@hotmail.com These authors have contributed equally to this work and share first authorship SPECIALTY SECTION This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology RECEIVED 18 August 2022 ACCEPTED 07 October 2022 PUBLISHED 24 October 2022 CITATION Dai F, Wu X, Wang X, Li K, Wang Y, Shen C, Zhou J, Niu H, Deng B, Tan Q, Wang R and Guo W (2022) Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients' overall survival when compared with neoadjuvant chemotherapy in nonsmall cell lung cancer: A cohort study. Front. Oncol. 12:1022123. doi: 10.3389/fonc.2022.1022123 COPYRIGHT © 2022 Dai, Wu, Wang, Li, Wang, Shen, Zhou, Niu, Deng, Tan, Wang and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Original Research PUBLISHED 24 October 2022 DOI 10.3389/fonc.2022.1022123 invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P<0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P<0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group. Conclusions: In conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors. [ABSTRACT FROM AUTHOR]

The treatment of lung cancer has fully entered the era of immunotherapy, which has significantly elevated the survival rate of patients with advanced nonsmall cell lung cancer (NSCLC), thus shedding light on resectable NSCLC. Previous clinical trial data suggested that neoadjuvant immuno-chemotherapy obtained a significant objective response rate (ORR) and disease control rate (DCR). Here, a case that achieved an excellent outcome following neoadjuvant immuno-chemotherapy was reported. The patient admitted to our hospital was 58 years old, female, with a rare case of stage IB lung squamous cell carcinoma (LUSC) harboring both epidermal growth factor receptor (EGFR) p.L858R mutations and high expression of programmed death ligand-1 (PD-L1) (tumor proportion score (TPS)=80%). Her tumor substantially shrunk following two cycles of neoadjuvant immuno-chemotherapy. The patient successively received single-port right upper thoracoscopic lobectomy + mediastinal lymph node dissection, which attained pathologic complete response (pCR). Additionally, the patient had grade 2 myelosuppression during the two cycles, which was treated with polyethylene glycol recombinant human granulocyte colony-stimulating factor (rhG-CSF). The patient was discharged uneventfully without any procedure-related complications. Two courses of adjuvant immuno-chemotherapy were administered postoperatively, leaving the patient in good physical condition at the 5-month follow-up visit. This case provided evidence for the feasibility and effectiveness of neoadjuvant immunochemotherapy in treating early-stage LUSC with EGFR mutations and high expression of PD-L1. However, randomized and multi-center controlled trials are required to validate the findings. [ABSTRACT FROM AUTHOR]