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Background: Immunotherapy is emerging as a promising option for certain locally advanced and metastatic cutaneous malignancies. However, the role of neoadjuvant immunotherapy (NIO) in Merkel cell carcinoma (MCC) with clinically detected regional lymph node metastasis (CDRLNM) has not been fully elucidated. Methods: For this study, MCC patients with CDRLNM who underwent surgical excision were selected from the National Cancer Database (NCDB). Those who received NIO were propensity-matched with those who did not, and Kaplan-Meier analysis was used to compare overall survival (OS). Results: Of the 1809 selected patients, 356 (19.7%) received NIO followed by wide excision (n = 352, 98.9%) or amputation (n = 4, 1.1%). The rate of complete pathologic response for the primary tumor (ypT0) was 45.2%. Only 223 patents (63.4%) also underwent lymph node dissection (LND). The complete pathologic nodal response (ypN0) rate for these patients was 17.9%. A pathologic complete response of both the primary tumor and the nodal basin (ypT0 ypN0) was seen in 16 of the 223 patients who underwent both primary tumor surgery and LND. Subsequently, 151 pairs were matched between the NIO and no-NIO groups (including only patients with LND). Kaplan-Meier analysis demonstrated a significant OS improvement with NIO (median not reached vs. 35.0 ± 8.0 months; p = 0.025). The 5-year OS was 57% in the NIO group versus 44% in no-NIO group (p = 0.021). Conclusion: The study suggests that NIO in MCC with CDRLNM provides improved OS in addition to promising rates of primary complete response, which could change the profile of surgical resection. This supports ongoing clinical trials exploring the use of NIO in MCC. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the most prevalent malignant tumors worldwide, characterized by high incidence and mortality rates. At present, comprehensive surgical treatment has enhanced the prognosis of locally advanced gastric cancer patients significantly. However, the postoperative recurrence rate remains high, and the long-term survival for patients is sub-optimal. In recent years, immunotherapy has garnered extensive attention as an innovative approach to the treatment of gastric cancer. Indeed, multiple studies have validated its therapeutic effects in advanced gastric cancer patients, leading to its incorporation into treatment guidelines. Currently, researchers are exploring the application of immunotherapy in the neoadjuvant setting globally in order to further adjust and refine neoadjuvant immunotherapy regimens for gastric cancer. This article summarizes the research progress and controversies associated with neoadjuvant immunotherapy in gastric cancer, aiming to optimize clinical benefits for gastric cancer patients undergoing this treatment approach. The retrieval methods of this study encompassed databases such as PubMed, Google Scholar, Web of Science, clinicaltrials.gov, etc. The retrieved articles included guidelines, consensus, meta-analyses, clinical trials, and reviews related to locally advanced gastric cancer published up to January 2024. [ABSTRACT FROM AUTHOR]

Background: Static tumor features before initiating anti-tumor treatment were insufficient to distinguish responding from non-responding tumors under the selective pressure of immuno-therapy. Herein we investigated the longitudinal dynamics of peripheral blood inflammatory indexes (dPBI) and its value in predicting major pathological response (MPR) in non-small cell lung cancer (NSCLC). Methods: A total of 147 patients with NSCLC who underwent neoadjuvant immunochemotherapy were retrospectively reviewed as training cohort, and 26 NSCLC patients from a phase II trial were included as validation cohort. Peripheral blood inflammatory indexes were collected at baseline and as posttreatment status; their dynamics were calculated as their posttreatment values minus their baseline level. Least absolute shrinkage and selection operator algorithm was utilized to screen out predictors for MPR, and a MPR score was integrated. We constructed a model incorporating this MPR score and clinical predictors for predicting MPR and evaluated its predictive capacity via the area under the curve (AUC) of the receiver operating characteristic and calibration curves. Furthermore, we sought to interpret this MPR score in the context of micro-RNA transcriptomic analysis in plasma exosomes for 12 paired samples (baseline and posttreatment) obtained from the training cohort. Results: Longitudinal dynamics of monocyte-lymphocyte ratio, platelet-tolymphocyte ratio, platelet-to-albumin ratio, and prognostic nutritional index were screened out as significant indicators for MPR and a MPR score was integrated, which was further identified as an independent predictor of MPR. Then, we constructed a predictive model incorporating MPR score, histology, and differentiated degree, which discriminated MPR and non-MPR patients well in both the training and validation cohorts with an AUC value of 0.803 and 0.817, respectively. Furthermore, micro-RNA transcriptomic analysis revealed the association between our MPR score and immune regulation pathways. A significantly better event-free survival was seen in subpopulations with a high MPR score. Conclusion: Our findings suggested that dPBI reflected responses to neoadjuvant immuno-chemotherapy for NSCLC. The MPR score, a noninvasive biomarker integrating their dynamics, captured the miRNA transcriptomic pattern in the tumor microenvironment and distinguished MPR from non-MPR for neoadjuvant immunochemotherapy, which could support the clinical decisions on the utilization of immune checkpoint inhibitor-based treatments in NSCLC patients. [ABSTRACT FROM AUTHOR]

Aims: PD‐1 block was reported to impair opioid‐induced antinociception and affect cognitive function in rodents and non‐human primates. This prospective multicenter cohort study aims to investigate the possible impact of neoadjuvant immunotherapy with PD‐1 antibody on perioperative analgesic effect of opioids and postoperative delirium (POD) for non‐small‐cell lung cancer (NSCLC) patients. Methods: Eighty‐four NSCLC patients from three medical centers with neoadjuvant chemoimmunotherapy (nCIT) or chemotherapy (nCT) were enrolled. The primary outcome is the total perioperative opioid consumption defined as the sum of intraoperative and postoperative opioid use within 3 days after surgery. Secondary outcomes compromise of incidence of POD, pain intensity, and number of analgesic pump press. Tumor prognostic parameters and perioperative change of inflammatory cytokines and soluble PD‐L1 level were also recorded. Results: Eighty‐one patients were included in the final analysis. The total opioid consumption (sufentanil equivalent) perioperatively in the nCIT group was significantly higher than that in the nCT group, with mean difference of 60.39 μg, 95% CI (25.58–95.19), p < 0.001. Multiple linear regression analysis showed that nCIT was correlated with increased total opioid consumption (β = 0.305; 95% CI, 0.152–0.459; p < 0.001). The incidence of moderate‐to‐severe pain and cumulative analgesic pump press within 72 h was significantly higher in subjects with nCIT. There is no statistical difference in incidence of POD between groups within 72 h after surgery. The pathologic complete response rate and perioperative serum IL‐6 level were higher in the nCIT group than in the nCT group. Conclusion: Patients with NSCLC receiving nCIT warrant increased opioid consumption perioperatively and suffered from more postoperative pain. Clinical Trial Registration: NCT05273827. [ABSTRACT FROM AUTHOR]

Background: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). Methods: The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. Results: The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. Conclusion: The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. Trial registration: Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827). [ABSTRACT FROM AUTHOR]

Objectives: Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. Patients and Methods: We investigate the impact of VEGFR2 inhibition on tumor‐infiltrating immune cells in vivo and the activity of the combination of apatinib and anti‐PD‐1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. Results: We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib‐treated tumors. The combined treatment of apatinib and anti‐PD‐1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Conclusion: Our study demonstrated that apatinib therapy synergized with an anti–PD‐1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Esophageal cancer is a severe disease with a high mortality rate. Recent advancements in treatments have improved outcomes, but survival rates remain low. This study investigates the use of immunotherapy, a treatment that helps the immune system fight cancer, in combination with standard chemoradiation and surgery for patients with locally advanced esophageal cancer. By analyzing data from the National Cancer Database, we found that patients who received adjuvant immunotherapy had better survival rates than those who did not receive immunotherapy or who received neoadjuvant immunotherapy. These findings suggest that adjuvant immunotherapy could be a beneficial addition to existing treatment protocols, and further research is needed to confirm these results and optimize patient outcomes. Background: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. Methods: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan–Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. Results: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. Conclusions: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer. [ABSTRACT FROM AUTHOR]

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4–7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post‑operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1–3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC. [ABSTRACT FROM AUTHOR]

Abstract Background The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) in older patients with gastric cancer remains controversial. This study aimed to evaluate the safety, and efficacy of MIG for older patients who underwent neoadjuvant chemotherapy and immunotherapy (NICT). Methods The clinical data of 726 older patients aged over 65 years who underwent upfront MIG or MIG after NICT in the Department of General Surgery, Chinese PLA General Hospital First Medical Center between Jan 2020 and Nov 2023 were retrospectively analyzed. Propensity score-matched (PSM) analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables, short- and long-term outcomes were compared between the two groups. Results The baseline characteristics were comparable between 61 patients in the NICT-MIG group and 114 patients in the MIG group after PSM (P > 0.05). The major pathological response (MPR) rate and pathological complete response (pCR) rate were 44.2% and 21.3%, respectively, in the NICT-MIG group. Patients in the NICT-MIG group had longer operation times (P = 0.005) and postoperative days (P = 0.030) than those in the MIG group. No significant differences were found in intraoperative bleeding, number of retrieved lymph nodes, first flatus day, R0 resection rate, overall postoperative complication (POC) morbidity, severe POC morbidity, 2-year overall, and recurrence-free survival between the MIG and NICT-MIG groups (P > 0.05). Multivariate logistic analysis revealed that an estimated blood loss > 200 mL (P = 0.010) and a lymphocyte-to-monocyte ratio (LMR) ≤ 3.25 (P = 0.006) were independent risk factors for POCs after MIG in older patients. Conclusion The safety, and efficacy of NICT-MIG were comparable to those of upfront MIG in older patients with GC. Patients with an estimated blood loss > 200 mL or an LMR ≤ 3.25 should be carefully evaluated for an increased risk of POCs in older patients who undergo MIG. Trial registration Chinese Clinical Trial Registry (Registration Number: ChiCTR2400086827).

Background: Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) and combined with clinical data to predict the major pathological response to NIT in ESCC patients. Methods: This retrospective study included 82 ESCC patients who were randomly divided into the training group (n = 57) and the validation group (n = 25). Radiomic features were derived from the tumor region in enhanced CT images obtained before treatment. After feature reduction and screening, radiomics was established. Logistic regression analysis was conducted to select clinical variables. The predictive model integrating radiomics and clinical data was constructed and presented as a nomogram. Area under curve (AUC) was applied to evaluate the predictive ability of the models, and decision curve analysis (DCA) and calibration curves were performed to test the application of the models. Results: One clinical data (radiotherapy) and 10 radiomic features were identified and applied for the predictive model. The radiomics integrated with clinical data could achieve excellent predictive performance, with AUC values of 0.93 (95% CI 0.87-0.99) and 0.85 (95% CI 0.69-1.00) in the training group and the validation group, respectively. DCA and calibration curves demonstrated a good clinical feasibility and utility of this model. Conclusion: Enhanced CT image-based radiomics could predict the response of ESCC patients to NIT with high accuracy and robustness. The developed predictive model offers a valuable tool for assessing treatment efficacy prior to initiating therapy, thus providing individualized treatment regimens for patients. [ABSTRACT FROM AUTHOR]

Background: Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer. Methods: The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs). Results: Fourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively. Conclusion: In cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a promising cancer treatment method. However, it has previously been centered on adjuvant therapy, often falling short as a preoperative treatment of solid cancers, largely attributed to the hypoxic and immunosuppressive microenvironments of untreated tumors. Herein, we develop a multifunctional nanoagent based on edge-oxidized graphene (EOG) for tumor imaging and neoadjuvant thermal immunotherapy. EOG, readily synthesized from selective oxidation and mechanical exfoliation of graphene flakes, exhibits good biocompatibility and remarkable microwave absorption capabilities owing to its large aromatic domains. Consequently, it has demonstrated utility in both microwave-induced thermoacoustic imaging and thermal therapy in a mouse hepatoma model. Furthermore, EOG-based thermal therapy is combined with immunotherapy, which can significantly reduce tumor volume and inhibit tumor growth. A mechanistic study reveals that microwave thermal energy alleviates tumor hypoxia, promotes immunogenic cell death, and ultimately enhances antitumor immune responses. This work pioneers a microwave-based imaging-guided immunotherapy strategy for neoadjuvant treatment of solid tumors and reveals the cell-level pathway of the involved immune suppression. [ABSTRACT FROM AUTHOR]

Background: In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. Methods: A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta‐analyses were performed using Stata BE17 software. Results: For these meta‐analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36–0.54; pCR: ES = 0.26; 95% CI: 0.21–0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48–0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR < 30%; pCR: ES = 3%–17%; nodal downstage to ypN0 rate: ES = 21%–29%). Safety was assessed using the treatment‐related adverse events (trAEs) incidence rate, surgical delay rate, surgical complications incidence rate, and surgical resection rate. In conclusion, the incidence of trAEs, incidence of surgical complications, and surgical delay rate had ES values of 0.66, 0.48, and 0.09, respectively. These rates were comparable to those from nCT or nCRT (95% CI: 0.60–0.70; 0.15–0.51; and 0, respectively). The reported resection rates of 85%–95% with nCT or nCRT were comparable to the mean surgical resection rate of 90%. Conclusion: NAIT is an effective treatment for resectable GEJC; additionally, the level of NAIT toxicity is acceptable. The long‐term effects of NAIT require further study. [ABSTRACT FROM AUTHOR]

Approximately one half of patients with non-small cell lung cancer (NSCLC) are diagnosed at resectable tumor stages (I-IIIA), which can potentially be curatively treated. In the early tumor stages (tumor diameter ≤2 cm) sublobar resection (segmentectomy or atypical wedge resection) leads to a 5‑year long-term survival comparable to lobectomy. The use of immunotherapy, especially within the framework of neoadjuvant treatment, is anticipated to change the surgical treatment of NSCLC in the future. With the introduction of lung cancer screening for certain risk groups in Germany planned for 2024, lung tumors can be expected to be diagnosed at earlier stages and more frequently curatively treated. This article provides an overview of the potential impact of lung cancer screening, modern minimally invasive surgical techniques and neoadjuvant treatment concepts for the surgical treatment of NSCLC. [ABSTRACT FROM AUTHOR]

BackgroundImmune checkpoint inhibitors have demonstrated promising therapeutic outcomes in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC), prompting numerous clinical trials to investigate the safety and efficacy of this approach in neoadjuvant therapy. This systematic review aims to consolidate and analyze the findings from various clinical trials combining neoadjuvant immunotherapy for HNSCC, with the goal of identifying the most effective neoadjuvant immunotherapy regimen.MethodsThe system conducted searches across electronic databases including PubMed, Embase, the Cochrane Library and Web of science from their inception to July 1, 2024. The primary focus was on evaluating efficacy (particularly pathological complete response (pCR), major pathological response (MPR), and overall response rate (ORR)) and safety (primarily assessed by grade 3-4 treatment-related adverse reactions).ResultsA total of 1943 patients from 32 studies were analyzed. Combining neoadjuvant immunotherapy with chemotherapy or radiotherapy demonstrated superiority over neoadjuvant immunotherapy alone in terms of the MPR rate, while showing no statistically significant difference in the pCR rate. Furthermore, the combination of neoadjuvant immunotherapy with chemotherapy or radiotherapy exhibited a lower CR rate compared to neoadjuvant immunotherapy with radiotherapy alone, but a higher PR rate and SD rate. Apart from the neoadjuvant immunotherapy group in isolation, there were no statistically significant differences in grade ≥3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) among the other three combination therapy groups.ConclusionThis systematic review and meta-analysis indicate that patients with locally advanced HNSCC might benefit from neoadjuvant immunotherapy, particularly when used in conjunction with chemotherapy or radiotherapy. Nonetheless, additional data is required to definitively confirm its efficacy.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=553753, identifier CRD42024553753.

Abstract Background Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy’s effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228).

Objective To evaluate the clinical efficacy and safety of platinum-containing neoadjuvant immunotherapy for triple-negative breast cancer. Methods Sixty-four patients with PD-L1 positive triple-negative breast cancer were enrolled and randomly divided into the control（n = 32）and observation groups（n = 32）. In the control group，preoperative chemotherapy regimen of albumin-bound paclitaxel plus cisplatin（TP）was given，while the observation group received platinum-containing neoadjuvant immunotherapy--combined with programmed death receptor-1（PD-1）inhibitor carrilizumab on the basis of TP chemotherapy regimen of control group. At 4 weeks post-neoadjuvant chemotherapy，whether modified radical surgery or breast-conserving surgery was chosen based on surgical indications，and whether axillary lymph node dissection was performed according to intraoperative sentinel lymph node biopsy results. The objective response rate，disease control rate，pathological complete response rate，breast conservation rate，axillary lymph node exemption rate，T lymphocyte subset levels，hypoxia-inducible factor-1αlevels，vascular endothelial growth factor levels，and the incidence of adverse reactions were compared between two groups. Results After 6 cycles of neoadjuvant chemotherapy，the objective remission rate，pathological complete remission rate，and elevated level of CD4+ T lymphocytes in the observation group were higher than those in the control group（all P < 0.05）. The levels of hypoxia-inducible factor-1α and vascular endothelial growth factor in the observation group were lower than those in the control group（all P < 0.05）. Although the disease control rate，breast conservation rate and exemption rate of axillary lymph node dissection were relatively high in the observation group，the difference was not significant when compared with that in the control group（P > 0.05）. There was no significant difference in the incidence of adverse reactions between two groups（P > 0.05）. Conclusion Platinum-containing neoadjuvant immunotherapy is efficacious and safe for triple-negative breast cancer，which reduces the tumor load and improves clinical prognosis of the patients.

Introduction Recently, perioperative use of immune checkpoint inhibitors has improved the prognosis of muscle‐invasive bladder cancer. It is unclear whether radical cystectomy or systemic pembrolizumab is the optimal next treatment in patients with muscle‐invasive bladder cancer and progressive disease in the pelvic lymph node following neoadjuvant chemotherapy (NAC). Case presentation A 62‐year‐old woman with cT3N0M0 bladder cancer and high programmed death‐ligand 1 expression developed solitary obturator lymph node metastasis following 5 cycles of neoadjuvant chemotherapy. Six subsequent cycles of pembrolizumab shrank the lymph node significantly, and conversion radical cystectomy was planned. Pathologically, only carcinoma in situ around the scar of transurethral resection of bladder tumor remained in the primary tumor, and the accumulation of foamy macrophages and fibrosis without viable tumor cells was observed in the dissected lymph node. Eighteen months passed without a recurrence following radical cystectomy. Conclusion Pembrolizumab administration before radical cystectomy achieved a good response in a patient with obturator lymph node metastasis following neoadjuvant chemotherapy.

Background: Emerging data suggested a favorable outcome in advanced non-small cell lung cancer (NSCLC) with chronic obstructive pulmonary disease (COPD) patients treated by immunotherapy. The objective of this study was to investigate the effectiveness of neoadjuvant immunotherapy among NSCLC with COPD versus NSCLC without COPD and explore the potential mechanistic links. Patients and methods: Patients with NSCLC receiving neoadjuvant immunotherapy and surgery at Shanghai Pulmonary Hospital between November 2020 and January 2023 were reviewed. The assessment of neoadjuvant immunotherapy's effectiveness was conducted based on the major pathologic response (MPR). The gene expression profile was investigated by RNA sequencing data. Immune cell proportions were examined using flow cytometry. The association between gene expression, immune cells, and pathologic response was validated by immunohistochemistry and single-cell data. Results: A total of 230 NSCLC patients who received neoadjuvant immunotherapy were analyzed, including 60 (26.1%) with COPD. Multivariate logistic regression demonstrated that COPD was a predictor for MPR after neoadjuvant immunotherapy [odds ratio (OR), 2.490; 95% confidence interval (CI), 1.295–4.912; P = 0.007]. NSCLC with COPD showed a down-regulation of HERV–H LTR-associating protein 2 (HHLA2), which was an immune checkpoint molecule, and the HHLA2low group demonstrated the enrichment of CD8+CD103+ tissue-resident memory T cells (TRM) compared to the HHLA2high group (11.9% vs. 4.2%, P = 0.013). Single-cell analysis revealed TRM enrichment in the MPR group. Similarly, NSCLC with COPD exhibited a higher proportion of CD8+CD103+TRM compared to NSCLC without COPD (11.9% vs. 4.6%, P = 0.040). Conclusions: The study identified NSCLC with COPD as a favorable lung cancer type for neoadjuvant immunotherapy, offering a new perspective on the multimodality treatment of this patient population. Down-regulated HHLA2 in NSCLC with COPD might improve the MPR rate to neoadjuvant immunotherapy owing to the enrichment of CD8+CD103+TRM. Trial registration: Approval for the collection and utilization of clinical samples was granted by the Ethics Committee of Shanghai Pulmonary Hospital (Approval number: K23-228). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Lung cancer remains the leading cause of cancer-related mortality, with 1.8 million deaths per year. Small cell lung cancer and non-small cell lung cancer (NSCLC) are the main cancer types. Approximately 85% of cases are NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In this reported treatment case, the tumor histological type changed after targeted therapy, which has not been previously well documented. The patient was a 67-year-old woman diagnosed with squamous cell carcinoma via bronchoscopy. She received five neoadjuvant immune monotherapies. The lesion shrank but then progressed, with a diagnosis of small cell carcinoma via bronchoscopy. This finding suggests that tumor acquisition of resistance as manifested by cancer-type changes needs consideration and study in the application of this particular type of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy for advanced gastric cancer/gastroesophageal junction tumors has made great progress, the efficacy and safety of neoadjuvant immunotherapy for locally resectable gastric cancer/gastroesophageal junction tumors have not been clearly demonstrated. Here, we conducted a systematic review and meta-analysis to assess the efficacy and safety of neoadjuvant immunotherapy and advance the current research. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy for resectable gastric cancer/gastroesophageal junction tumors published up until October 15, 2023 were retrieved from PubMed, Embase, the Cochrane Library, and other major databases. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated for heterogeneity and subgroup analysis. Results: A total of 1074 patients from 33 studies were included. The effectiveness of neoadjuvant immunotherapy was mainly evaluated using pathological complete remission (PCR), major pathological remission (MPR), and tumor regression grade (TRG). Among the included patients, 1015 underwent surgical treatment and 847 achieved R0 resection. Of the patients treated with neoadjuvant immunotherapy, 24% (95% CI: 19%-28%) achieved PCR and 49% (95% CI: 38%-61%) achieved MPR. Safety was assessed by a surgical resection rate of 0.89 (95% CI: 85%-93%), incidence of = 3 treatment-related adverse events (TRAEs) of 28% (95% CI: 17%-40%), and incidence of = 3 immune-related adverse events (irAEs) of 19% (95% CI: 11%-27%). Conclusion: Neoadjuvant immunotherapy, especially neoadjuvant dualimmunotherapy combinations, is effective and safe for resectable gastric/gastroesophageal junction tumors in the short term. Nevertheless, further multicenter randomized trials are required to demonstrate which combination model is more beneficial. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Results: Sixteen studies involving 501 patients were included in the metaanalysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any-grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. Conclusion: This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: The benefit of neoadjuvant chemoimmunotherapy was compared with chemotherapy for localized NSCLC in several trials. We conducted a systematic review and meta-analysis to evaluate the benefit of adding immunotherapy to neoadjuvant chemotherapy in patients with localized NSCLC. We observed that neoadjuvant immunotherapy significantly improves EFS, OS, and pCR rates with a slight increase in high-grade toxicities. The subgroup analyses demonstrated a consistent benefit with neoadjuvant immunotherapy independent of age, ECOG status, smoking status, and stage, while the benefit of neoadjuvant immunotherapy was lower in patients with PD-L1-negative tumors than patients with moderate or high levels of PD-L1 expression. Further research is needed to define the optimal duration of immunotherapy after surgery and the overall survival benefit of neoadjuvant immunotherapy with longer follow-ups. Background: After the success of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), the benefit of neoadjuvant chemoimmunotherapy was compared with chemotherapy for localized NSCLC in several trials. However, the available studies had variable study designs, and study cohorts had limited follow-up times. Therefore, we conducted a systematic review and meta-analysis to evaluate the benefit of adding immunotherapy to neoadjuvant chemotherapy in patients with localized NSCLC. Methods: We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until 5 December 2023. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a fixed effects model. Results: Overall, 7 studies encompassing 2993 patients were included in the analyses. The use of neoadjuvant chemoimmunotherapy was associated with a 41% reduction in the risk of progression or death compared to neoadjuvant chemotherapy (HR: 0.59, 95% CI: 0.52–0.66, p < 0.0001) and a lower risk of death (HR: 0.67, 95% CI: 0.55–0.82, p < 0.0001). The neoadjuvant chemoimmunotherapy improved pCR rates compared to chemotherapy (21.8% vs. 3.8%, OR: 7.04, 95% CI: 5.23–9.47, p < 0.0001), while high-grade adverse events were higher with neoadjuvant chemoimmunotherapy (OR: 1.18, 95% CI: 1.02–1.36, p = 0.0300). Conclusions: The available evidence demonstrates a statistically significant and clinically meaningful event-free survival benefit and possibly an overall survival benefit with neoadjuvant chemoimmunotherapy with a slight increase in high-grade toxicities. [ABSTRACT FROM AUTHOR]

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34–52 %) with two cycles and 33 % (95%CI, 22–45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28–50 %) and 56 % (95%CI, 44–68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21–50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15–35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

Abstract Background In recent years, neoadjuvant immunotherapy (NAIT) has developed rapidly in patients with gastroesophageal junction cancer (GEJC). The suggested neoadjuvant treatment regimens for patients with GEJC may vary in light of the efficacy and safety results. Methods A search of the Cochrane Library, PubMed, Embase, and Web of Science was completed to locate studies examining the safety and effectiveness of NAIT for resectable GEJC. We analyzed the effect sizes (ES) and 95% confidence intervals (CI) in addition to subgroups and heterogeneity. Meta‐analyses were performed using Stata BE17 software. Results For these meta‐analyses, 753 patients were chosen from 21 studies. The effectiveness of NAIT was assessed using the pathological complete response (pCR), major pathological response (MPR), and nodal downstage to ypN0 rate. The MPR, pCR, and nodal downstage to ypN0 rate values in NAIT were noticeably higher (MPR: ES = 0.45; 95% CI: 0.36–0.54; pCR: ES = 0.26; 95% CI: 0.21–0.32; nodal downstage to ypN0 rate: ES = 0.60; 95% CI: 0.48–0.72) than those of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) (MPR

Junfeng Zhao,1,&ast; Shaoyu Hao,2,&ast; Ying Li,3 Xiaoman Liu,4 Zhaoxuan Liu,5 Chunhui Zheng,6 Dan Han1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 4Department of Oncology, BinZhou Medical University Affiliated Hospital, BinZhou Medical University, Binzhou, Shandong, People’s Republic of China; 5Department of Oncology, Zibo Centre Hospital, BinZhou Medical University, Zibo, Shandong, People’s Republic of China; 6Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dan Han, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Huayin District, Jinan, Shandong, People’s Republic of China, Tel +86-17862893373, Email echohandan@163.comPurpose: This study aimed to compare the efficacy and safety of neoadjuvant chemotherapy (NCT) and neoadjuvant immunotherapy combined with chemotherapy (NICT) combined with radical lung cancer resection for the treatment of patients with resectable non-small cell lung cancer (NSCLC). To adjust for confounding factors, we innovatively adopted two matching methods: propensity score (PS) and inverse probability of treatment weighting (IPTW).Patients and Methods: We conducted a retrospective analysis of the clinicopathological features and prognosis of patients with resectable NSCLC treated with NCT or NICT combined with radical lung cancer resection using propensity score matching (PSM) at a ratio of 1:1 and IPTW to balance potential bias.Results: After PSM, 116 pairs of patients who had undergone NCT or NICT were selected for the final analysis. The pathological complete remission (pCR) and major pathological remission (MPR) rates were significantly better in the NICT group than in the NCT group (pCR rate of 44.8% vs 2.6%, P< 0.001; MPR rate of 66.4% vs 20.7%, P< 0.001). No significant difference was seen between the NICT and NCT groups in terms of postoperative complications (12.1% vs 9.5%, P=0.182). Patients in the NICT group had significantly better disease-free survival (DFS) and overall survival(OS) than those in the NCT group ([3-year DFS: 75.2% vs 43.3%, P< 0.001] and [3-year OS: 91.5% vs 58.0%, P< 0.001]). Among all patients, those with postoperative pathology of pCR had better DFS (P< 0.001) and OS (P= 0.009). Patients with postoperative pathology of MPR had better DFS (P< 0.001) and OS (P< 0.001). The IPTW method yielded similar pathologic and prognostic results.Conclusion: Patients with resectable NSCLC treated with NICT had better pathological responses and prognosis, than those treated with NCT, and the safety profiles of NICT and NCT were similar.Keywords: neoadjuvant immunotherapy, neoadjuvant chemotherapy, non-small cell lung cancer, propensity score matching, inverse probability of treatment weighting, lung cancer resection, immune checkpoint inhibitor

Background: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. Methods: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan–Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. Results: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. Conclusions: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Background: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. Study design and endpoints: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. Patients and interventions: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant immunotherapy has been demonstrated to be effective and safe in resectable non-small cell lung cancer (NSCLC) patients. However, the presence of different oncogenic driver mutations may affect the tumor microenvironment and consequently influence the clinical benefit from immunotherapy. Methods: This retrospective study included consecutive NSCLC patients (stage IIA to IIIB) who underwent radical surgery after receiving neoadjuvant immunotherapy at a single high-volume center between December 2019 and August 2022. Pathological response and long-term outcomes were compared based on the driver oncogene status, and RNA sequencing analysis was conducted to investigate the transcriptomic characteristics before and after treatment. Results: Of the 167 patients included in this study, 47 had oncogenic driver mutations. KRAS driver mutations were identified in 28 patients, representing 59.6% of oncogenic driver mutations. Of these, 17 patients had a major pathological response, which was significantly higher than in the non-KRAS driver mutation group (60.7% vs. 31.6%, P = 0.049). Multivariate Cox regression analysis further revealed that the KRAS driver mutation group was an independent prognostic factor for prolonged disease-free survival (hazard ratio: 0.10, P = 0.032). The median proportion of CD8+ T cells was significantly higher in the KRAS driver mutation NSCLCs than in the non-driver mutation group (18% vs. 13%, P = 0.030). Furthermore, immune-related pathways were enriched in the KRAS driver mutation NSCLCs and activated after immunotherapy. Conclusion: Our study suggests that NSCLC patients with KRAS driver mutations have a superior response to neoadjuvant immunotherapy, possibly due to their higher immunogenicity. The findings highlight the importance of considering oncogenic driver mutations in selecting neoadjuvant treatment strategies for NSCLC patients. [ABSTRACT FROM AUTHOR]

Neoadjuvant immunotherapy has significantly changed the therapeutic approach for treating patients with surgically resectable non‐small cell lung cancer (NSCLC). Here, peripheral blood inflammation‐based biomarkers as well as previously less focused eosinophil fraction, modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) were systematically included to comprehensively analyze their potential in predicting neoadjuvant immunotherapy efficacy and prognosis. We enrolled 189 patients (94 in training and 95 in validation cohorts) with stage I–III B surgically resectable NSCLC treated with neoadjuvant immunotherapy from the National Cancer Center of China. Baseline and post‐treatment eosinophils fraction, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), systemic immune‐inflammation index (SII), monocyte‐to‐lymphocyte ratio (MLR), PNI, mGPS, and their changes were calculated and analyzed for correlation with neoadjuvant immunotherapy efficacy and prognosis. In patients in the major pathological response (MPR) group, the post‐treatment eosinophil fraction was significantly high, and NLR, PLR, SII, and MLR were significantly lower compared to the non‐MPR group in both the training and validation cohorts. The receiver operating characteristic curve showed that post‐treatment, eosinophil fraction and SII and their changing were two of the most important factors. Univariate and multivariate logistic regression analyses showed that post‐treatment eosinophil fraction, SII, mGPS, and ΔSII could independently predict MPR in patients treated with neoadjuvant immunotherapy. Survival analysis showed a significant correlation between high post‐treatment NLR, PLR, SII, mGPS, and their changes in ΔNLR and ΔSII elevation with poor overall survival and event‐free survival of patients. Our results suggest that inflammatory biomarkers could predict the patient's response to neoadjuvant immunotherapy and prognosis. [ABSTRACT FROM AUTHOR]

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]

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Purpose of reviewIn this review, we summarized recent findings that highlight the progress for checkpoint blockade immunotherapy in glioblastoma (GBM) patients.Recent findingsWe reviewed new data from our group and others that suggest that the timing of when immunotherapy is applied can impact the antitumor immune response and, potentially, the ultimate clinical benefit of patients.SummaryThe neoadjuvant priming and expansion of exhausted T cells within the GBM microenvironment, followed by the removal of an immune suppressive tumor microenvironment through surgical resection, may lead to enhanced antitumor immune responses that are beneficial clinically. As such, neoadjuvant immunotherapeutic approaches and rational combinations may be helpful scientifically to understand how immunotherapeutic interventions influence the tumor microenvironment, as well benefit the patients.

Abstract 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

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

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.

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]

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]