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Common metastasis sites for cervical cancer are the lungs, bones, liver, brain, ovaries, and lymph nodes, among other sites. Skin metastasis is very uncommon, and is only observed in approximately 1% of patients. The cancer spreads typically through lymphatic or blood vessels, but a definitive example of lymphatic spread has not been documented thoroughly in the existing literature. Cutaneous metastasis may be confused with cellulitis or a rash; hence, an immediate cutaneous biopsy of any suspicious lesions is recommended. There is no consensus regarding the treatment of this condition. Only one documented case has shown that a combination of paclitaxel, carboplatin, bevacizumab, and zoledronic acid can lead to a complete metabolic response. Our study, which used two cycles of albumin-bound paclitaxel, cisplatin, and bevacizumab, followed by four cycles of the same regimen plus terprelimab for metastases with CPS scores of Programmed death-ligand 1 (PD-L1) over 10, resulted in a stable complete response for over eight months. Our contribution may assist in formulating effective treatment guidelines for the cutaneous metastasis of squamous cervical carcinoma in the future. [ABSTRACT FROM AUTHOR]

Background: To date, there remains a paucity of comparative investigations pertaining to preoperative immunochemotherapy and conventional chemotherapy in the context of limited-stage small-cell lung cancer (LS-SCLC) patients. This study conducted a comprehensive comparative assessment concerning the safety and efficacy profiles of preoperative immunochemotherapy and chemotherapy in individuals diagnosed with stage I–IIIB SCLC. Methods: This investigation collected 53 consecutive patients diagnosed with LS-SCLC spanning stage I to IIIB who underwent preoperative immunochemotherapy or conventional chemotherapy at our hospital from January 2019 to July 2021. Patients were allocated to receive 2–4 cycles of neoadjuvant immunochemotherapy or chemotherapy, with each cycle lasting three weeks. Comprehensive analyses encompassed baseline characteristics, clinical staging, tumor response, intraoperative and postoperative outcomes, and the assessment of treatment-related adverse events (trAEs). The follow-up period is extended for a minimum of one year after surgery. The primary endpoint embraced the evaluation of the pathological response [major pathological response (MPR) and pathological complete remission (pCR)], while secondary endpoints encompassed objective response rate (ORR), trAEs, surgical resection rates, and disease-free survival (DFS). Results: The objective response rate of the immunochemotherapy group was 89.5%, while that of the chemotherapy group was 75.0% (P = 0.206). A total of 19 patients underwent surgery among these 53 patients, with 14 patients in the neoadjuvant chemoimmunotherapy group and 5 patients in the chemotherapy group. And the surgical resection rate of the immunochemotherapy group was 48.3% (14/29), which was higher than the chemotherapy group (20.8%, 5/24, P = 0.038). The rate of MPR in the immunochemotherapy group was 57.1% (8/14) and 40.0% (2/5) in the chemotherapy group (P = 0.891). The rates of pCR in the immunochemotherapy and chemotherapy group were 50.0% (7/14) and 0.0% (0/5), respectively (P = 0.106).The median DFS for both groups were not reached (P = 0.43). The 2-year DFS rate was 21.4% for the immunochemotherapy group versus 40.0% for the chemotherapy group. There was no significant difference in the incidence of grade 3–4 adverse events between the immunochemotherapy group and the chemotherapy group. Conclusions: For patients with stage I–IIIB SCLC, neoadjuvant immunochemotherapy is feasible and safe. Although immunochemotherapy did not significantly associated with longer DFS versus chemotherapy alone in patients with stage I–IIIB SCLC, it can produce significant downstaging and increase the possibility of surgery. [ABSTRACT FROM AUTHOR]

Background: Infections are common complications and causes of death during immunochemotherapy in diffuse large B-cell lymphoma (DLBCL). The gut microbiota plays a significant role in bacterial infection, but its relationship and predictive capacity with infectious complications in DLBCL are unknown. Methods: We performed 16S rRNA gene sequencing of fecal samples collected from 41 patients with newly diagnosed DLBCL at baseline, after every two cycles of standard immunochemotherapy, during infection, and after infection recovery. Analysis of the diversity and species composition of these samples was used to evaluate the relationship between gut microbiota and bacterial infection. Results: Our findings demonstrate the dynamic changes of Enterobacteriaceae in patients with DLBCL during immunochemotherapy. The abundance of Enterobacteriaceae was markedly higher at baseline in patients who subsequently developed bacterial infection during immunochemotherapy than in those who did not (P < 0.0001), and showed a further increase during infection (P < 0.01), after recovery from the infection, the Enterobacteriaceae was significantly decreased (P < 0.001). While there was no significant change in patients who did not develop bacterial infection. The univariate and multivariate analysis showed that baseline abundance of Enterobacteriaceae > 4.5% was independently associated with post-immunochemotherapy bacterial infection. Conclusions: Our findings suggest that the gut microbiota signatures differ between patients with DLBCL who do and do not develop bacterial infection. The baseline abundance of Enterobacteriaceae is associated with the post-immunochemotherapy bacterial infection, and it has certain predictive value. Detecting the changes of gut microbiota can help predict the risk of bacterial infection after immunochemotherapy. [ABSTRACT FROM AUTHOR]

Background: The use of programmed death-1 (PD-1) inhibitors in the neoadjuvant setting for patients with resectable stage III NSCLC has revolutionized this field in recent years. However, there is still 40%-60% of patients do not benefit from this approach. The complex interactions between immune cell subtypes and tertiary lymphoid structures (TLSs) within the tumor microenvironment (TME) may influence prognosis and the response to immunochemotherapy. This study aims to assess the relationship between immune cells subtypes and TLSs to better understand their impact on immunotherapy response. Methods: This study initially compared the tertiary lymphoid structures (TLSs) density among patients who underwent immunochemotherapy, chemotherapy and upfront surgery using 123 tumor samples from stage-matched patients. Multiplex immunohistochemistry (mIHC) was employed to analyze the spatial distribution of PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs. Cytometry by time-of-flight (CyTOF) was used to assess immune cell dynamics in paired biopsy and resection specimens from six patients who underwent immunochemotherapy. Key immune cells were validated in newly collected samples using flow cytometry, mIHC, and in vitro CAR-T cells model. Results: Patients who underwent neoadjuvant chemotherapy or immunochemotherapy exhibited increased TLSs compared to those who opted for upfront surgery. The TLS area-to-tumor area ratio distinguished pCR+MPR and NR patients in the immunochemotherapy group. Spatial analysis revealed variations in the distance between PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs in the immunochemotherapy group. CyTOF analysis revealed an increase in the frequency of key immune cells (CCR7+CD127+CD69+CD4+ and CD38+CD8+ cells) following combined therapy. Treatment responders exhibited an increase in CCR7+CD4+ T cells, whereas CD38+CD8+ T cells were associated with compromised treatment effectiveness. Conclusions: Immunochemotherapy and chemotherapy increase TLSs and granzyme B+ CD8+ T cells in tumors. The TLS area-to-tumor ratio distinguishes responders from non-responders, with PD-L1+ dendritic cells near CD8+PD-1+ T cells linked to efficacy, suggesting that PD-1 inhibitors disrupt harmful interactions. Post-immunochemotherapy, CD8+ T cells increase, but CD38+CD8+ T cells show reduced functionality. These findings highlight the complex immune dynamics and their implications for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Abstract Background: Neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) is a new neoadjuvant treatment approach that has raised concerns regarding potential challenges in surgery and postoperative complications. This study aimed to compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) and NICRT for the treatment of resectable locally advanced esophageal squamous cell carcinoma (ESCC). Methods: We retrospectively analyzed 291 patients with locally advanced ESCC who underwent neoadjuvant therapy and esophagectomy at three centers between January 2019 and September 2023 and added the data from PALACE-1 for the analysis, Among these patients, 248 and 61 patients received NCRT and NICRT, respectively. Propensity score matching (PSM) was used to balance the potential bias. Results: After the PSM,the rate of a pathological complete response (pCR) in the NCRT group was not significantly different from that in the NICRT group (46.90% vs 36.36%, P = 0.180). There were no significant differences in the tumor regression grade (TRG) and positive lymph node pCR rates between the two groups (P = 0.233 and P = 0.354, respectively). Treatment-related toxicities and postoperative complications were not significantly different between the NCRT group and the NICRT group (P = 0.199, P = 0.284). Conclusion: Compared with NCRT, NICRT did not lead to the better treatment efficacy. There were no significant differences was observed in the incidence of treatment-related toxicities and postoperative complications.

Abstract Background Immune checkpoint inhibitors (ICIs) had modest advances in the treatment of extensive-stage small cell lung cancer (ES-SCLC) in clinical trials, but there is a lack of biomarkers for prognosis in clinical practice. Methods We retrospectively collected data from ES-SCLC patients who received ICIs combined chemotherapy from two centers in China, integrated clinical and blood parameters, and constructed risk prognostication for immunochemotherapy. The population was divided into high- and low-risk groups, and the performance of the model was assessed separately in the training and validation cohorts. Results Two hundred and twenty and 43 patients were included in the training and validation groups, respectively. The important predictors were screened including body mass index, liver metastases, coefficient variation of red blood cell distribution width, lactate dehydrogenase, albumin, and C-reactive protein. Predicting 1-year overall survival (OS), the AUC values under ROC for the model under training, internal validation, and external validation were 0.760, 0.732, and 0.722, respectively, and the calibration curve and clinical decision curve performed well. Applied the model to divide patients into low-risk and high-risk groups, and the median OS was 23.7 months and 9.1 months, and the median progression-free survival was 8.2 months and 4.8 months, respectively; furthermore, this ability to discriminate survival was also observed in the validation cohort. Conclusions We constructed a novel prognostic model for ES-SCLC to predict survival employing baseline tumor burden, nutritional and inflammatory parameters, it is easily measured to screen high-risk patient populations.

Abstract Objective To evaluate the potential utility of 18F-FDG PET/CT to assess response to neoadjuvant immunochemotherapy in patients with resectable NSCLC, and the ability to screen patients who may benefit from neoadjuvant immunochemotherapy. Methods Fifty one resectable NSCLC (stage IA–IIIB) patients were analyzed, who received two-three cycles neoadjuvant immunochemotherapy.18F-FDG PET/CT was carried out at baseline(scan-1) and prior to radical resection(scan-2). SULmax, SULpeak, MTV, TLG, T/N ratio, ΔSULmax%,ΔSULpeak%, ΔMTV%, ΔTLG%,ΔT/N ratio% were calculated. 18F-FDG PET/CT responses were classified using PERCIST. We then compared the RECIST 1.1 and PERCIST criteria for response assessment.With surgical pathology of primary lesions as the gold standard, the correlation between metabolic parameters of 18F-FDG PET/CT and major pathologic response (MPR) was analyzed. All metabolic parameters were compared to treatment response and correlated to PFS and OS. Results In total of fifty one patients, MPR was achieved in 25(49%, 25/51) patients after neoadjuvant therapy. The metabolic parameters of Scan-1 were not correlated with MPR.The degree of pathological regression was negatively correlated with SULmax, SULpeak, MTV, TLG, T/N ratio of scan-2, and the percentage changes of the ΔSULmax%, ΔSULpeak%, ΔMTV%,ΔTLG%,ΔT/N ratio% after neoadjuvant therapy (p

Follicular lymphoma is one of the most common non-Hodgkin’s lymphomas in adults. One of the rather rare variants of follicular lymphoma is pediatric follicular lymphoma. This variant, despite the name, is diagnosed not only in children, but also among young adults. Pediatric follicular lymphoma is characterized by early (I, II) stages, the absence or weak BCL2 expression, and the predominant absence of t(14;18)(q32;q21) translocation. Treatment tactics vary widely from radical surgical tumor resection with subsequent follow-up to chemoimmunotherapy with rituximab.This article presents a clinical case of advanced pediatric follicular lymphoma (stage III) in a 5-year-old patient. Using a combined treatment approach (surgery followed by immunochemotherapy) allowed to achieve a complete metabolic response which lasts more than a year.

Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p < 0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal‐to‐diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor‐kappa B (NF‐κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal‐to‐diffuse conversion and reprogramming to an immuno‐active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Immunotherapy has been seriously retarded due to inadequate antigen presentation and a tumor cell-dominated immunosuppressive microenvironment (TME). Herein, biodegradable multifunctional mesoporous silica nanoparticles, with dispersed carbon nanodots incorporated into the frameworks, active TKD peptide modification on the surfaces and hydrophobic drug loading in the pores, were prepared for targeted chemotherapy synergized with trans-spatial immunotherapy. The nanoparticles were biodegradable due to nanodot-induced framework swelling, which would (1) kill the in situ tumor cells and promote antigen release by targeted chemotherapy and (2) trigger biodegraded debris involving TKD and CDs to largely adsorb the tumor antigens via π - π conjugation synergized hydrophobic interactions and then massively transport these antigens from the tumor cell-dominated TME to the immune cell-dominated spleen via TKD-mediated small size effects. Thereafter, these antigens can be processed into antigen peptides via TKD-mediated lysosome endocytosis and then activate T cells in the spleen via MHC complex construction and dendritic cell cytomembrane presentation. Therefore, improved immunotherapy with trans-spatial antigen presentation avoided TME immunosuppression, which when synergized with targeted chemotherapy, markedly enhanced the therapeutic outcomes of triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Sleeve and double‐sleeve lobectomies are lung‐sparing techniques for treating central lung cancers. However, if the tumour extends to involve the bronchi and vessels, lung auto‐transplantation may be an alternative to pneumonectomy. Neoadjuvant therapy after surgery is the most common strategy for patients with extensive central lung cancer. Herein, we report a case of central lung cancer in a patient who underwent immunochemotherapy as neoadjuvant therapy following lung auto‐transplantation. A 68‐year‐old man with stage IIIA non‐small cell lung cancer and left upper lobe squamous cell carcinoma underwent neoadjuvant immunochemotherapy. Following partial regression, a multidisciplinary team decided on a back‐table procedure with auto‐lung transplantation after pneumonectomy to preserve pulmonary function. The patient had an uneventful recovery and was discharged after three weeks with no residual tumour or lymph node metastases. Lung auto‐transplantation can be successfully performed in non‐lung transplantation centres, potentially broadening treatment options for patients with central lung cancer. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) had modest advances in the treatment of extensive-stage small cell lung cancer (ES-SCLC) in clinical trials, but there is a lack of biomarkers for prognosis in clinical practice. Methods: We retrospectively collected data from ES-SCLC patients who received ICIs combined chemotherapy from two centers in China, integrated clinical and blood parameters, and constructed risk prognostication for immunochemotherapy. The population was divided into high- and low-risk groups, and the performance of the model was assessed separately in the training and validation cohorts. Results: Two hundred and twenty and 43 patients were included in the training and validation groups, respectively. The important predictors were screened including body mass index, liver metastases, coefficient variation of red blood cell distribution width, lactate dehydrogenase, albumin, and C-reactive protein. Predicting 1-year overall survival (OS), the AUC values under ROC for the model under training, internal validation, and external validation were 0.760, 0.732, and 0.722, respectively, and the calibration curve and clinical decision curve performed well. Applied the model to divide patients into low-risk and high-risk groups, and the median OS was 23.7 months and 9.1 months, and the median progression-free survival was 8.2 months and 4.8 months, respectively; furthermore, this ability to discriminate survival was also observed in the validation cohort. Conclusions: We constructed a novel prognostic model for ES-SCLC to predict survival employing baseline tumor burden, nutritional and inflammatory parameters, it is easily measured to screen high-risk patient populations. [ABSTRACT FROM AUTHOR]

BackgroundThe therapeutic efficacy of neoadjuvant immunotherapy combined with chemotherapy (Io+Chemo) is superior than chemotherapy alone (Chemo). However, the mechanism of Io+Chemo superiority remains to be further elucidated.MethodsThe study included 128 patients with resectable stage II-III gastric cancer, in which 63 were given neoadjuvant Io+Chemo, and 65 Chemo alone. Patients given Io+Chemo were treated with 2-4 cycles of PD-(L)1 inhibitor (Pembrolizumab, Sintililimab or Nivolumab) with S-1 and oxaliplatin (SOX) or capecitabine and oxaliplatin (XELOX) before surgical resection. Patients given Chemo were treated with 2-4 cycles of SOX or XELOX before surgical resection. Tumor tissues were evaluated for tumor-infiltrating immune cells (TIICs) using immunohistochemistry and QuPath software quantitative analysis, for detecting T, B, NK, plasma cells, and macrophages. The relationship between TIICs and different neoadjuvant treatment regimens and pathological responses was also explored.ResultsCompared with Chemo, Io+Chemo induced higher rates of pathological complete response (33.3 vs. 9.2%, p=0.001) and major pathological response (MPR) (49.2 vs. 30.8%, p=0.033). Compared with Chemo group, density of CD4+(1904.8 vs. 1530), CD8+(1982.9 vs. 1124.4), CD20+(1115.6 vs. 574), CD38+(1580.4 vs. 1128), CD138+(1237.2 vs. 496.4), and CD56+ (596.8 vs. 159) cells was increased 24.5%, 76.4%, 94.4%, 40.1%, and 149.2% respectively, whereas CD163+ macrophages (994.4 vs. 1706) was decreased 41.7% in Io+Chemo group.ConclusionsOur study favors neoadjuvant Io+Chemo over Chemo and reveals Io+Chemo can induce the formation of an immune-activated microenvironment that make Io+Chemo superior to Chemo.

Common metastasis sites for cervical cancer are the lungs, bones, liver, brain, ovaries, and lymph nodes, among other sites. Skin metastasis is very uncommon, and is only observed in approximately 1% of patients. The cancer spreads typically through lymphatic or blood vessels, but a definitive example of lymphatic spread has not been documented thoroughly in the existing literature. Cutaneous metastasis may be confused with cellulitis or a rash; hence, an immediate cutaneous biopsy of any suspicious lesions is recommended. There is no consensus regarding the treatment of this condition. Only one documented case has shown that a combination of paclitaxel, carboplatin, bevacizumab, and zoledronic acid can lead to a complete metabolic response. Our study, which used two cycles of albumin-bound paclitaxel, cisplatin, and bevacizumab, followed by four cycles of the same regimen plus terprelimab for metastases with CPS scores of Programmed death-ligand 1 (PD-L1) over 10, resulted in a stable complete response for over eight months. Our contribution may assist in formulating effective treatment guidelines for the cutaneous metastasis of squamous cervical carcinoma in the future.

BackgroundThe use of programmed death-1 (PD-1) inhibitors in the neoadjuvant setting for patients with resectable stage III NSCLC has revolutionized this field in recent years. However, there is still 40%-60% of patients do not benefit from this approach. The complex interactions between immune cell subtypes and tertiary lymphoid structures (TLSs) within the tumor microenvironment (TME) may influence prognosis and the response to immunochemotherapy. This study aims to assess the relationship between immune cells subtypes and TLSs to better understand their impact on immunotherapy response.MethodsThis study initially compared the tertiary lymphoid structures (TLSs) density among patients who underwent immunochemotherapy, chemotherapy and upfront surgery using 123 tumor samples from stage-matched patients. Multiplex immunohistochemistry (mIHC) was employed to analyze the spatial distribution of PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs. Cytometry by time-of-flight (CyTOF) was used to assess immune cell dynamics in paired biopsy and resection specimens from six patients who underwent immunochemotherapy. Key immune cells were validated in newly collected samples using flow cytometry, mIHC, and in vitro CAR-T cells model.ResultsPatients who underwent neoadjuvant chemotherapy or immunochemotherapy exhibited increased TLSs compared to those who opted for upfront surgery. The TLS area-to-tumor area ratio distinguished pCR+MPR and NR patients in the immunochemotherapy group. Spatial analysis revealed variations in the distance between PD-L1+CD11c+ cells and PD1+CD8+ T cells within TLSs in the immunochemotherapy group. CyTOF analysis revealed an increase in the frequency of key immune cells (CCR7+CD127+CD69+CD4+ and CD38+CD8+ cells) following combined therapy. Treatment responders exhibited an increase in CCR7+CD4+ T cells, whereas CD38+CD8+ T cells were associated with compromised treatment effectiveness.ConclusionsImmunochemotherapy and chemotherapy increase TLSs and granzyme B+ CD8+ T cells in tumors. The TLS area-to-tumor ratio distinguishes responders from non-responders, with PD-L1+ dendritic cells near CD8+PD-1+ T cells linked to efficacy, suggesting that PD-1 inhibitors disrupt harmful interactions. Post-immunochemotherapy, CD8+ T cells increase, but CD38+CD8+ T cells show reduced functionality. These findings highlight the complex immune dynamics and their implications for NSCLC treatment.

Introduction: The introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs). Methods: We enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature). Results: In the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort. Discussion: This study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC. [ABSTRACT FROM AUTHOR]

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. Patients with hemophagocytic lymphohistiocytosis (HLH)-associated IVLBCL variants exhibit significantly poor survival. Cytokines play pivotal roles in malignancy-associated HLH as well as in capillary leak syndrome (CLS). The pathogenesis of CLS involves hyperpermeability and transient endothelial dysfunction. Here, we report the first case of HLH-associated IVLBCL variant complicated with CLS. The patient presented with fever, refractory hypoproteinemia, hypotension and severe edema, followed by telangiectasias. Treatment with etoposide and dexamethasone and hydroxyethyl starch-based artificial colloid led to transient improvement. The diagnosis of IVLBCL was confirmed after the sixth bone marrow biopsy. Subsequently, the R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone) regimen was administered and resulted in prompt alleviation of CLS and HLH symptoms. The patient has survived for more than 6 years after combination of immunochemotherapy and autologous peripheral stem-cell transplantation. This case provides some insights into the mechanism and clinical management of IVLBCL complicated with HLH and CLS. Similar cases concerning lymphoma-associated CLSs were also reviewed. [ABSTRACT FROM AUTHOR]

Most patients with diffuse large B-cell lymphoma (DLBCL) are >65 years of age, with the number of patients expected to increase in the coming years. A comprehensive geriatric assessment that carefully evaluates fitness status and comorbidities is essential for selecting the appropriate treatment intensity. Although generally healthy patients or those <80 years of age may benefit from standard immunochemotherapy, unfit/frail patients or patients >80 years old may require reduced-intensity chemotherapy or less-toxic drugs. Some new drugs are currently being tested as single or combined agents for first-line treatment, aiming to improve the outcomes of conventional chemotherapy. This review systematically collates and discusses the outcomes associated with the use of immunochemotherapy in older patients with DLBCL, as well as considering the impact of full-dose immunochemotherapy on quality of life in older and frail patients, summarizing the rationale for reduced dosing in the older population, and presenting recommendations for selecting patients likely to benefit from reduced dosing. If preliminary efficacy and safety data are confirmed in future clinical trials, non-chemotherapy-based immunotherapy approaches could become an alternative potentially curative option in frail patients and those >80 years of age with DLBCL. [ABSTRACT FROM AUTHOR]

Abstract Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment‐naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25% vs. 4%, p

Abstract Background Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC_Percentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions.

Aim. To study the glomerular filtration rate (GFR) dynamics calculated by creatinine and cystatin C during induction immunochemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma in order to objectify the method for estimation.Materials and methods. The open longitudinal study included 39 patients with newly diagnosed diffuse large B-cell lymphoma who received specialized treatment at the Oncohematology Department of National Medical Research Centre for Oncology (Rostov-on-Don) in 2021. Patients received induction immunochemotherapy according to the R-CHOP regimen (rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone) in combination with accompanying therapy (allopurinol 300 mg/day). Blood sampling was carried out at 0, 24, 48, 72, 120 hours and on 21st day of the 1st therapy cycle. Patients were divided into 2 groups depending on the GFR level, calculated by creatinine, before treatment: group A – 27 (69 %) patients with GFR >90 ml/min/1.73 m2, group B – 12 (31 %) patients with GFR

Abstract Until now, there are still few comparisons between neoadjuvant immunochemotherapy and chemotherapy as first-line treatment for patients with stage IB-IIIB lung squamous cell carcinoma (LUSC). In addition, the ability of pathologic response to predict long-term survival has still not been established. In this retrospective, controlled clinical trial, we ultimately enrolled 231 patients with stage IB to IIIB LUSC who received 2–4 cycles perioperative immunochemotherapy or chemotherapy alone, followed by resection. The primary endpoint of this study was pathological response. Secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), surgical resection rate and adverse events (AEs). The rates of major pathologic response (MPR) and pathologic complete response (pCR) in the immunochemotherapy group were 66.7% and 41.9%, respectively, which were both higher than that in the other group (MPR: 25.0%, pCR: 20.8%) (P

Simple Summary: Classical Hodgkin Lymphoma is a blood cancer, accounting for 0.5% of all new cancer diagnoses. Despite high cure chances, approximately 20% of patients are refractory to frontline treatment or relapse thereafter. Treatment strategies for relapsed/refractory patients have progressively lower chances of inducing a persistent complete remission. Therefore, great efforts are being made to further improve rates of response of frontline therapy, as well as to explore the efficacy of new compounds and different drug combinations. The present review aims to summarize these efforts, offering an overview of recent advances and future perspectives in the field. Classical Hodgkin Lymphoma (cHL) is a highly curable disease, but around 20% of patients experience progression or relapse after standard frontline chemotherapy regimens. Salvage regimens followed by autologous stem cell transplants represent the historical treatment approach for these cases. In the last decade, with the increasing understanding of cHL biology and tumor microenvironment role in disease course, novel molecules have been introduced in clinical practice, improving outcomes in the relapsed/refractory setting. The anti-CD30 antibody-drug conjugated brentuximab vedotin and PD-1/PD-L1 checkpoint inhibitors represent nowadays curative options for chemorefractory patients, and randomized trials recently demonstrated their efficacy in frontline immune-chemo-combined modalities. Several drugs able to modulate the patients' T-lymphocytes and NK cell activity are under development, as well as many anti-CD30 chimeric antigen receptor T-cell products. Multiple tumor aberrant epigenetic mechanisms are being investigated as targets for antineoplastic compounds such as histone deacetylase inhibitors and hypomethylating agents. Moreover, JAK2 inhibition combined with anti-PD1 blockade revealed a potential complementary therapeutic pathway in cHL. In this review, we will summarize recent findings on cHL biology and novel treatment options clinically available, as well as promising future perspectives in the field. [ABSTRACT FROM AUTHOR]

UICC stage IV small-cell lung cancer (SCLC) is a highly aggressive malignancy without curative treatment options. Several randomized trials have demonstrated improved survival rates through the addition of checkpoint inhibitors to first-line platin-based chemotherapy. Consequently, a combination of chemo- and immunotherapy has become standard palliative treatment. However, no reliable predictive biomarkers for treatment response exist. Neither PD-L1 expression nor tumor mutational burden have proven to be effective predictive biomarkers. In this study, we compared the cellular immune statuses of SCLC patients to a healthy control cohort and investigated changes in peripheral blood B, T, and NK lymphocytes, as well as several of their respective subsets, during treatment with immunochemotherapy (ICT) using flow cytometry. Our findings revealed a significant decrease in B cells, while T cells showed a trend to increase throughout ICT. Notably, high levels of exhausted CD4+ and CD8+ cells, alongside NK subsets, increased significantly during treatment. Furthermore, we correlated decreases/increases in subsets after two cycles of ICT with survival. Specifically, a decrease in Th17 cells indicated a better overall survival. Based on these findings, we suggest conducting further investigation into Th17 cells as a potential early predictive biomarkers for response in patients receiving palliative ICT for stage IV SCLC. [ABSTRACT FROM AUTHOR]

Background: Elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergoing reduced intensity R-CHOP therapy are at a heightened risk of acquiring infections, notably coronavirus disease 2019 (COVID-19) infection. This study aimed to evaluate the efficacy of intravenous immunoglobulin (IVIG) as prophylaxis against COVID-19 in this vulnerable population. Methods: A total of 125 elderly patients with DLBCL undergoing reduced intensity R-CHOP therapy were analyzed in this prospective, multicenter study. Patients with hypogammaglobulinemia were categorized into IVIG and non-IVIG groups, while those with normal immunoglobulin levels constituted the observation group. The study evaluated COVID-19 infection rates, therapy response, and safety outcomes. Results: Among the enrolled patients (median age: 77 years), 89 patients (71.2%) presented with hypogammaglobulinemia at diagnosis, and 56 patients enrolled in the IVIG administration group. IVIG administration remarkably reduced COVID-19 infection rates compared to non-IVIG recipients (8.9% vs. 24.6%; p =0.040). Notably, patients over 80 years old were more susceptible to COVID-19. Patients on IVIG exhibited good tolerance with manageable adverse events. Among patients with hypogammaglobulinemia who received IVIG, 40.5% of patients developed additional immunoglobulin deficiencies during chemotherapy. One or more new hypogammaglobulinemia occurred during chemotherapy in 72% of patients with hypogammaglobulinemia who did not receive IVIG, and in 61.3% of patients who did not have hypogammaglobulinemia at diagnosis. Conclusion: IVIG showed promise in reducing COVID-19 infections among elderly patients with DLBCL receiving reduced intensity R-CHOP therapy. This highlights IVIG's potential as a prophylactic measure, necessitating further investigation to optimize dosing, administration schedules, and potential interactions with vaccination strategies. [ABSTRACT FROM AUTHOR]

Background: In order to improve survival outcomes in resectable non‐small cell lung cancer (NSCLC), strategies for neoadjuvant therapy need to be revisited. We evaluated and compared the efficacy of different neoadjuvant therapeutic modalities in a real‐world setting. Methods: A total of 258 patients with clinical stage IIA to IIIB NSCLC was included. All the patients underwent surgical resection after one to four cycles of neoadjuvant treatment consisting of chemotherapy (83), immunotherapy (23), and immunotherapy plus chemotherapy (152). Results: The radiologic response rate in the combined immunochemotherapy group was 67.8%, higher than that of 48.2% in the chemotherapy group and 4.3% in the immunotherapy group (p < 0.001). An improved major pathological response (MPR) was also achieved in the combined therapy group compared with the chemotherapy group and the immunotherapy group (53.9% vs. 10.8% vs. 8.7%, p < 0.001). Patients in the combined therapy group had a significant trend toward longer disease‐free survival than those in the chemotherapy alone group (3‐year disease‐free survival [DFS] of 68.79% vs. 50.81%; hazard ratio [HR] for progression or death, 0.477; p = 0.003). Multivariate Cox analysis identified radical surgery (HR, 0.328; p = 0.033), ypN0–1 stage (HR, 0.591; p = 0.038) and MPR result (HR, 0.362; p = 0.007) to be independent prognostic factors for DFS. Conclusions: Neoadjuvant treatment with a combination of immunotherapy plus chemotherapy appears to achieve higher radiological and pathological responses than monotherapy for IIA‐IIIB NSCLC. Log‐rank analysis showed that a better outcome could be expected in patients with the addition of immunotherapy to neoadjuvant chemotherapy if compared with patients with chemotherapy alone in terms of DFS. [ABSTRACT FROM AUTHOR]

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare extranodal type of non-Hodgkin's lymphoma. Diffuse large B cell lymphoma (DLBCL) is most often histopathologically confirmed. Modern PCNSL therapy should include an induction and a consolidation phase. Treatment regimens are based on high doses of methotrexate, and the intensity of therapy is adapted to the age of patients and their biological condition. Material and methods: The aim of this study was a retrospective analysis of the effectiveness and toxicity of therapy used in patients diagnosed with DLBCL of the central nervous system (CNS), treated at the Department of Hematology, Blood Neoplasms and Bone Marrow Transplantation in Wroclaw, Poland, between 2015 and 2022. The analyzed population included 46 patients with a median age of 64.5 years (range: 27-80). Patients were treated according to the R-MATRix, R-MPV, or R-HD-MTX-ARA-C regimen. Results: After the first-line treatment, complete remission (CR) was achieved in 11 patients, partial remission (PR) in 15, and seven did not respond to the therapy. 11 patients died and two were not qualified for chemotherapy due to their poor general condition. The effectiveness of R-MATRix and R-MPV was similar. Conclusions: We have shown that the use of the MATRix regimen is associated with greater toxicity and prolonged neutropenia. [ABSTRACT FROM AUTHOR]

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middleaged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant therapy followed by surgery has become the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC) and accurate pathological response assessment is critical to assess the therapeutic efficacy. However, it can be laborious and inconsistency between different observers may occur. Hence, we aim to develop an interpretable deep-learning model for efficient pathological response assessment following neoadjuvant therapy in ESCC. Methods: This retrospective study analyzed 337 ESCC resection specimens from 2020–2021 at the Pudong-Branch (Cohort 1) and 114 from 2021–2022 at the Puxi-Branch (External Cohort 2) of Fudan University Shanghai Cancer Center. Whole slide images (WSIs) from these two cohorts were generated using different scanning machines to test the ability of the model in handling color variations. Four pathologists independently assessed the pathological response. The senior pathologists annotated tumor beds and residual tumor percentages on WSIs to determine consensus labels. Furthermore, 1850 image patches were randomly extracted from Cohort 1 WSIs and binarily classified for tumor viability. A deep-learning model employing knowledge distillation was developed to automatically classify positive patches for each WSI and estimate the viable residual tumor percentages. Spatial heatmaps were output for model explanations and visualizations. Results: The approach achieved high concordance with pathologist consensus, with an R^2 of 0.8437, a RAcc_0.1 of 0.7586, a RAcc_0.3 of 0.9885, which were comparable to two senior pathologists (R^2 of 0.9202/0.9619, RAcc_0.1 of 8506/0.9425, RAcc_0.3 of 1.000/1.000) and surpassing two junior pathologists (R^2 of 0.5592/0.5474, RAcc_0.1 of 0.5287/0.5287, RAcc_0.3 of 0.9080/0.9310). Visualizations enabled the localization of residual viable tumor to augment microscopic assessment. Conclusion: This work illustrates deep learning's potential for assisting pathological response assessment. Spatial heatmaps and patch examples provide intuitive explanations of model predictions, engendering clinical trust and adoption (Code and data will be available at https://github.com/WinnieLaugh/ESCC%5fPercentage once the paper has been conditionally accepted). Integrating interpretable computational pathology could help enhance the efficiency and consistency of tumor response assessment and empower precise oncology treatment decisions. [ABSTRACT FROM AUTHOR]

Until now, there are still few comparisons between neoadjuvant immunochemotherapy and chemotherapy as first-line treatment for patients with stage IB-IIIB lung squamous cell carcinoma (LUSC). In addition, the ability of pathologic response to predict long-term survival has still not been established. In this retrospective, controlled clinical trial, we ultimately enrolled 231 patients with stage IB to IIIB LUSC who received 2–4 cycles perioperative immunochemotherapy or chemotherapy alone, followed by resection. The primary endpoint of this study was pathological response. Secondary endpoints were disease-free survival (DFS), overall survival (OS), objective response rate (ORR), surgical resection rate and adverse events (AEs). The rates of major pathologic response (MPR) and pathologic complete response (pCR) in the immunochemotherapy group were 66.7% and 41.9%, respectively, which were both higher than that in the other group (MPR: 25.0%, pCR: 20.8%) (P < 0.001). The median DFS in the chemotherapy group was 33.1 months (95% CI 8.4 to 57.8) and not reached in the immunochemotherapy group (hazard ratio [HR] for disease progression, disease recurrence, or death, 0.543; 95% CI 0.303 to 0.974; P = 0.038). The median OS of the immunochemotherapy group was not achieved (HR for death, 0.747; 95% CI 0.373 to 1.495; P = 0.41), with the chemotherapy group 64.8 months (95% CI not reached to not reached). The objective response rate (ORR) of immunochemotherapy regimen was higher than that of the chemotherapy regimen (immunochemotherapy: 74.5%, chemotherapy: 42.3%, P < 0.001). About 60.8% in the immunochemotherapy group and 61.5% in the chemotherapy group eventually underwent surgery. The incidence of grade3 and 4 adverse events was 18.3% in the immunochemotherapy group and 2.6% in the chemotherapy group. MPR was significantly associated with DFS and OS (HR, 0.325; 95% CI 0.127 to 0.833; P = 0.019; and HR, 0. 906; 95% CI 0.092 to 1.008; P = 0.051, respectively). The C-index of MPR (0.730 for DFS, 0.722 for OS) was higher than the C-index of cPR (0.672 for DFS, 0.659 for OS) and clinical response (0.426 for DFS, 0.542 for OS). Therapeutic regimen (P < 0.001; OR = 7.406; 95% CI 3.054 to 17.960) was significantly correlated with MPR. In patients with stage IB to IIIB LUSC, neoadjuvant treatment with immunochemotherapy can produce a higher percentage of patients with a MPR and longer survival than chemotherapy alone. MPR may serve as a surrogate endpoint of survival to evaluate neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Introduction: The proportion of older patients diagnosed with advanced-stage non-small cell lung cancer (NSCLC) has been increasing. Immune checkpoint inhibitor (ICI) monotherapy (MONO) and combination therapy of ICI and chemotherapy (COMBO) are standard treatments for patients with NSCLC and programmed cell death ligand-1 (PD-L1) tumor proportion scores (TPS) ≥ 50%. However, evidence from the clinical trials specifically for older patients is limited. Thus, it is unclear which older patients benefit more from COMBO than MONO. Methods: We retrospectively analyzed 199 older NSCLC patients of Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and PD-L1 TPS ≥ 50% who were treated with MONO or COMBO. We analyzed the association between treatment outcomes and baseline patient characteristics in each group, using propensity score matching. Results: Of the 199 patients, 131 received MONO, and 68 received COMBO. The median overall survival (OS; MONO: 25.2 vs. COMBO: 42.2 months, P = 0.116) and median progression-free survival (PFS; 10.9 vs. 11.8 months, P = 0.231) did not significantly differ between MONO and COMBO group. In the MONO group, OS was significantly shorter in patients without smoking history compared to those with smoking history [HR for smoking history against non-smoking history: 0.36 (95% CI: 0.16-0.78), P = 0.010]. In the COMBO group, OS was significantly shorter in patients with PS 1 than those with PS 0 [HR for PS 0 against PS 1: 3.84 (95% CI: 1.44-10.20), P = 0.007] and for patients with squamous cell carcinoma (SQ) compared to non-squamous cell carcinoma (non-SQ) [HR for SQ against non-SQ: 0.17 (95% CI: 0.06-0.44), P < 0.001]. For patients with ECOG PS 0 (OS: 26.1 months vs. not reached, P = 0.0031, PFS: 6.5 vs. 21.7 months, P = 0.0436) or non-SQ (OS: 23.8 months vs. not reached, P = 0.0038, PFS: 10.9 vs. 17.3 months, P = 0.0383), PFS and OS were significantly longer in the COMBO group. Conclusions: ECOG PS and histological type should be considered when choosing MONO or COMBO treatment in older patients with NSCLC and PDL1 TPS ≥ 50%. [ABSTRACT FROM AUTHOR]

Primary bone lymphoma of the scapula is a rare tumor that usually causes local pain. The presented patient suffered for two years from paresthesia, tingling, numbness, and edema of the little and ring fingers. The 45-year-old man underwent several radiological and neurological assessments of the palm, elbow, and neck before radiographs revealed a tumor of the left shoulder. Once diffuse large B-cell lymphoma was confirmed, immunochemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and methylprednisolone (R-CHOP) started. The treatment was accompanied by antiviral treatment with lamivudine due to positive hepatitis B virus serology, specifically anti-HBs (hepatitis B surface) antibody, total anti-HBc (hepatitis B core) antibody, and anti-HBe (hepatitis B e antigen) antibody, together with bisphosphonate treatment for the prevention of bone resorption. Once immunochemotherapy was finished, the treatment was supplemented by radiotherapy of the shoulder. After more than three years of remission, the patient had an ischemic stroke manifesting with right-sided hemiparesis. Following physical therapy, the patient is currently in the process of evaluation for thrombophilia, as well as further cardiac assessment due to the positive transcranial Doppler bubble test, setting high suspicion for the presence of patent foramen ovale. [ABSTRACT FROM AUTHOR]

Richter's transformation (RT) is defined as the development of an aggressive lymphoma in 2-10% of patients with chronic lymphocytic leukemia (CLL). Despite significant advances in the last decade, there is currently no established standard of care for RT, making its management a significant challenge. Questions regarding patients' treatment management in the era of novel agents and targeted therapies have yet to be answered. Nevertheless, several retrospective studies and clinical trials have emphasized the use of novel targeted agents to address this problem. In this review, we provide a summary of potential therapeutic options for RT. [ABSTRACT FROM AUTHOR]

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient’s demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time.

Background: EGFR and ERBB2 exon 20 insertion (Ex20ins) account for a small fraction of patients with EGFR mutations. The efficacy of immune checkpoint inhibitors (ICIs) for these patients was still controversial. Methods: This retrospective study enrolled lung cancer patients harboring either EGFR or ERBB2 Ex20ins mutations. All the patients were treated with platinum-based chemotherapy plus ICIs, or platinum-based chemotherapy. The demographic features and clinical outcome of each patient were reviewed and analyzed. Results: When treated with immunochemotherapy, patients with EGFR/ERBB2 Ex20ins mutations (n = 31) had poor PFS compared with those without EGFR mutations (n = 141, 5.0 mon and 11.2 mon, p < 0.001). When compared with those with EGFR classic mutations who received immunotherapy as the salvage therapy (n = 24), these patients with EGFR/ERBB2 Ex20ins mutations had similar PFS (5.0 mon and 4.1 mon, p = 0.625), ORR (37.5% vs. 48.4%), and DCR (70.8% vs. 77.4%). In the patients with EGFR/ERBB2 Ex20ins mutations, the PFS of those treated with chemotherapy (n = 54) and those treated with immunochemotherapy (n = 31) was 6.5 mon vs. 5.0 mon (p = 0.066). In the EGFR Ex20ins subgroup, the PFS of addition of bevacizumab to chemotherapy (n = 20) and chemotherapy alone (n = 16) was 8.8 mon and 5.2 mon, respectively (p = 0.082) or immunochemotherapy (n = 15, 8.8 mon and 5.0 mon, p = 0.097). Similarly, in the ERBB2 subgroup, the combination of bevacizumab and chemotherapy achieved a numerically longer PFS over chemotherapy alone (9.1 mon and 4.5 mon, p = 0.253), but there was no statistical significance. Conclusions: This study showed that platinum-based chemotherapy plus ICIs had limited efficiency compared to platinum-based chemotherapy for patients with EGFR/ERBB2 Ex20ins. Chemotherapy plus bevacizumab may be a potential scheme for these patients.

Background. In recent decades, a course of chemotherapy with etoposide (EP) and platinum preparations (сarboplatinum, CP) has been recommended as a standard first-line treatment option in patients with advanced small cell lung cancer (SCLC), but with the advent of new immunological drugs, immune checkpoint inhibitors, approaches to therapy have changed. Based on randomized clinical trials, courses combining traditional platinum-containing chemotherapy with inhibitors of programmed death-ligand 1 (PD-L1) atezolizumab (ATZ) or durvalumab (Durv) have been included in many clinical recommendations for oncologists.Objective: to evaluate the clinical and cost-effectiveness of using ATZ and Durv as first-line therapy in advanced SCLC adult patients within the Russian healthcare system.Material and methods. The model of treatment of advanced SCLC adult patients in conditions of the healthcare system of the Russian Federation included the most popular options for first-line immunochemotherapy: CP/EP + ATZ and CP/EP + Durv courses. Pharmacoeconomic cost-effectiveness analysis, sensitivity analysis of the selected model to changes in its initial parameters, budget impact analysis were carried out.Results. The total medical costs for CP/EP + ATZ course (2,310,546.07 rubles) were significantly lower than for the CP/EP + Durv course (4,081,833.98 rubles). With comparable costs for the treatment of complications (426,175.17 and 407,704.50 rubles, respectively), the cost of Durv exceeded ATZ by 94.8%. When conducting a cost-effectiveness analysis, the advantage was retained by the CP/EP + ATZ course, the cost-effectiveness ratios for which amounted to 187,849.27 rubles per month of patient's life and 444,335.78 rubles per month of patient's life without progression (for CP/EP + Durv, 316,421.24 and 800,359.60 rubles, respectively). When choosing the CP/ET + ATZ strategy, the savings will be 128,571.96 rubles per month of life and 356,023.82 rubles per month of life without progression. Sensitivity analysis demonstrated the stability of the developed model: to increase in the price of the CP/EP + ATZ course up to +68%; to decrease in overall survival with the course of CP/EP + ATZ up to –40%; to decrease in progression-free survival with the course of CP/EP + ATZ to –44%. Budget impact analysis showed that with a possible cohort size of 4,448 people an increase in the proportion of patients receiving CP/EP + ATZ course from 70% to 90% will reduce budget costs by 1,575,737,725.38 rubles per year, which will allow additional treatment of 681.9 advanced SCLC patients per year (+15.3%).Conclusion. The use of ATZ combined with standard platinum-containing chemotherapy in advanced SCLC adult patients as the first-line therapy is clinically and cost-effective strategy within the Russian healthcare system, as it allows to reduce therapy costs compared to Durv and treat more SCLC patients, which fully corresponds to the target indicators of the federal program “Oncology”.

Background: It is still uncertainwhetherNanoparticle albumin-bound paclitaxel (nabpaclitaxel) and programmed cell death protein 1 (PD-1) inhibitor have synergistic effects on metastatic soft tissue sarcomas (STSs). The purpose of this study was to evaluate the safety and activity of nab-paclitaxel plus camrelizumab (a PD-1 inhibitor) in patients with advanced STS who had previously failed chemotherapy. Methods: In this single-center, open-label, single-arm phase II clinical trial, patients with advanced (unresectable or metastatic) STS who had previously failed chemotherapy received up to six cycles of nab-paclitaxel plus camrelizumab, whereas camrelizumab treatment was continued for up to 1 year. The median progression-free survival (PFS), objective response rate (ORR) and safety were collected and evaluated. Results: This trial included 40 patients (28 men and 12 women). The overall ORR was 22.5%, and the median PFS was 1.65 months (95% confidence interval [CI], 1.3-2.0 months). Patients with epithelioid sarcoma demonstrated a longer PFS compared with those with other histological subtypes (2.3 months vs. 1.5 months, respectively); however, this difference was not significant. Patients who had received only one line of previous chemotherapy had a significantly longer PFS compared with those who had undergone two or more lines of previous chemotherapy (2.8 months vs. 1.3 months, respectively, p = 0.046). In terms of safety, the toxicity of this combination therapy is mild and no serious adverse events have occurred. Conclusion: Nab-paclitaxel plus camrelizumab exhibited modest activity and mild toxicity in treating epithelioid sarcoma, angiosarcoma, and fibrosarcoma. The overall effectiveness of this treatment regimen for advanced STS is relatively low. Further research on combining nab-paclitaxel with effective drugs, including chemotherapy and targeted agents, for these specific STS subtypes is needed. [ABSTRACT FROM AUTHOR]

Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PDL1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) accounts for 3-10% of non-Hodgkin's lymphomas (NHL). We identified 14 patients with mantle cell lymphoma, with an average number of 3.5 new cases/year. A male predominance was observed with a sex ratio equal to 6. The average age of our patients was 64.4±14.1 years, with an average diagnostic delay of 6.57 months. Regarding the clinical presentation, adenopathy was the most reported physical sign (78.6%) followed by B symptoms (57.1%). Disseminated stages were the most frequent in our series: stages IV (78.5%) and III (7.1%) versus stages I (0%) and II (7.1%). The extra-ganglionic localizations observed were hepatic 5 cases (31.1%), pulmonary 04 cases (25%), medullary 4 cases (25%), pleural 2 cases (12.5%) and prostate 1 case (6.2%). All diagnosed cases are mantle cell lymphomas, of which 12 cases (85.7%) are classical and 2 cases (14.3%) indolent. The high-risk group is, according to international prognostic index (MIPI) MCL prognostic score, the most represented in our series: 0-3 = 6 cases (42.9%), 6-11 = 8 cases (57.1%). The therapeutic protocol chosen 1st line: 9 patients treated with R-DHAP, three with R-CHOP, one with DHAOX and one with R-CVP. Second line: two patients treated with R-DHAP, one after R-CHOP and the other after R-CVP. Two patients received autologous hematopoietic stem cell transplant at the end of the treatment. The evolution was marked by the death of 7 patients, 3 lost to follow-up and 4 still followed. Additionally, the study highlights characteristics and treatment patterns of mantle cell lymphoma, emphasizing its predominance in males, delayed diagnosis, frequent dissemination, and high-risk classification, with chemotherapy as the primary treatment modality and a challenging prognosis contributing to a comprehensive understanding of mantle cell lymphoma presentation and management. [ABSTRACT FROM AUTHOR]

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the triallevel. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r=0.765) or HRPFS (r=0.534) and HROS was observed at the trial- level. Two-year EFS (r=0.918) or 2-year PFS (r=0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The polaR-CHP regimen is expected to improve 5-year OS. [ABSTRACT FROM AUTHOR]

Abstract Background There is no standard first‐line immunochemotherapy regimen for transplant‐ineligible patients with mantle cell lymphoma (MCL) currently, and the efficacy of various treatment remains unclear. Methods We conducted a Bayesian network meta‐analysis (NMA) of all eligible randomized controlled trials. Pairwise comparisons and ranking of different first‐line treatment options were performed. Results Nine studies were included in the NMA, involving a total of 2897 MCL patients. The BR‐Ibrutinib+R regimen showed the best progression‐free survival (PFS), with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69%. The VR‐CAP regimen was the most potential intervention to improve overall survival (OS), with a SUCRA of 0.89 and PbBT of 63%. Compared with the R‐CHOP regimen, the BR regimen achieved a better PFS (hazard ratio [HR] 0.45 [95% credible interval 0.2–0.96]). The BR‐Ibrutinib+R regimen (HR 0.14 [0.02–0.99]), BR+R regimen (HR 0.19 [0.034–0.99]), and BR regimen (HR 0.3 [0.08–1.03]) were superior to CHOP regimen with better PFS. The R‐FC regimen (HR 2.27 [1.01–5.21]) or FC regimen (HR 3.17 [1.15–8.71]) was inferior to the VR‐CAP regimen with a worse OS. Conclusions Our study presents the most promising first‐line treatment strategy for transplant‐ineligible MCL patients in terms of PFS and OS, which provides innovative treatment strategy for MCL treatment.

IntroductionPembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in 3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS.ConclusionsIn the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

Background: The role of neoadjuvant immunochemotherapy (NICT) has gradually attracted attention in recent years. To date, sensitive and reliable blood indicators to forecast the therapeutic response are still lacking. This study aimed to conduct a novel predictive score based on a variety of peripheral hematological immune-nutritional indicators to predict the therapeutic response in esophageal squamous cell carcinoma (ESCC) receiving NICT. Methods: There were 206 ESCC patients receiving NICT retrospectively recruited. With pathological complete response (pCR) as the dependent variable, independent risk variables of various peripheral blood immune-nutritional indexes were screened by logistic regression analyses to establish an integrative score. Results: By logical regression analyses, lymphocyte to monocyte ratio (LMR) and body mass index (BMI) were independent risk factors among all immunenutritional indices. Then, an integrative score named BMI-LMR score (BLS) was established. Compared with BMI or LMR, BLS was related to complications, especially for respiratory complication (P=0.012) and vocal cord paralysis (P=0.021). Among all patients, 61 patients (29.6%) achieved pCR after NICT. BLS was significantly related to pCR [odds ratio (OR)=0.269, P<0.001)]. Patients in high BLS cohort demonstrated higher 3-year overall survival (OS) (89.9% vs. 67.9%, P=0.001) and disease-free survival (DFS) (81.2% vs. 62.1%, P=0.001). BLS served as an independent factor of DFS [hazard ratio (HR) =2.044, P =0.020) and OS (HR =2.960, P =0.019). Conclusion: The BLS, based on immune-nutritional indicators of BMI and LMR, employed as a straightforward, accurate, and useful indicator of pCR and prognostic prediction in ESCC patients undergoing NICT. [ABSTRACT FROM AUTHOR]

Background: EGFR and ERBB2 exon 20 insertion (Ex20ins) account for a small fraction of patients with EGFR mutations. The efficacy of immune checkpoint inhibitors (ICIs) for these patients was still controversial. Methods: This retrospective study enrolled lung cancer patients harboring either EGFR or ERBB2 Ex20ins mutations. All the patients were treated with platinum-based chemotherapy plus ICIs, or platinum-based chemotherapy. The demographic features and clinical outcome of each patient were reviewed and analyzed. Results: When treated with immunochemotherapy, patients with EGFR/ERBB2 Ex20ins mutations (n = 31) had poor PFS compared with those without EGFR mutations (n = 141, 5.0 mon and 11.2 mon, p < 0.001). When compared with those with EGFR classic mutations who received immunotherapy as the salvage therapy (n = 24), these patients with EGFR/ERBB2 Ex20ins mutations had similar PFS (5.0 mon and 4.1 mon, p = 0.625), ORR (37.5% vs. 48.4%), and DCR (70.8% vs. 77.4%). In the patients with EGFR/ERBB2 Ex20ins mutations, the PFS of those treated with chemotherapy (n = 54) and those treated with immunochemotherapy (n = 31) was 6.5 mon vs. 5.0 mon (p = 0.066). In the EGFR Ex20ins subgroup, the PFS of addition of bevacizumab to chemotherapy (n = 20) and chemotherapy alone (n = 16) was 8.8 mon and 5.2 mon, respectively (p = 0.082) or immunochemotherapy (n = 15, 8.8 mon and 5.0 mon, p = 0.097). Similarly, in the ERBB2 subgroup, the combination of bevacizumab and chemotherapy achieved a numerically longer PFS over chemotherapy alone (9.1 mon and 4.5 mon, p = 0.253), but there was no statistical significance. Conclusions: This study showed that platinum-based chemotherapy plus ICIs had limited efficiency compared to platinum-based chemotherapy for patients with EGFR/ERBB2 Ex20ins. Chemotherapy plus bevacizumab may be a potential scheme for these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to assess clinical outcomes, determine survival predictors, and compare responses between different primary therapeutic modalities in a large real-world cohort of patients with mantle cell lymphoma (MCL), with a focus on assessing the impact of intensified immunochemotherapy regimens based on high doses of cytarabine (HDAC) on outcomes in ASCT-eligible patients. A total of 165 Brazilian patients with biopsy-proven MCL were included from 2010 to 2022. After a long follow-up, our results demonstrated that patients treated with (R)-HDAC-based regimens had higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those treated with (R)-CHOP, as well as lower rates of early relapses (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, enhanced induction regimens employing (R)-HDAC were not associated with a real overall survival benefit in MCL patients undergoing ASCT (2-year OS: 88.7% for (R)-HDAC plus ASCT vs. 78.8% for (R)-CHOP plus ASCT, p = 0.289). Additionally, up-front ASCT was independently associated with improvement in OS (p < 0.001), EFS (p = 0.005), and POD-24 (p < 0.001) in MCL. In conclusion, in the largest real-world Latin American study involving MCL patients, we were able to ratify the benefit of up-front ASCT in young and physically fit patients regardless of the intensity of the induction immunochemotherapy regimen used. Although HDAC-based induction regimens were not associated with improved survival in ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses in the whole cohort. These findings can decisively impact the therapeutic management of MCL patients in different clinical settings. Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38–89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort. [ABSTRACT FROM AUTHOR]

Background: The rapid development of multiple myeloma (MM) management underscores the value of real-world data. In our study we examined 509 adult MM patients treated with immunochemotherapy (ICT) with/without stem cell transplantation (SCT) from 2013 to 2019 in the Hospital District of Helsinki and Uusimaa, Finland. Materials & methods: Our study was based on computational analyses of data integrated into the hospital data lake. Results: After 2017, treatment pattern diversity increased with improved access to novel treatments. 5-year survivals were 74.4% (95% CI: 65.5–84.5) in SCT-eligible and 44.0% (95% CI: 37.6–51.4) in non-SCT subgroups. In the SCT-eligible subgroup, high first-year hospitalization costs were followed by stable resource requirements. Conclusion: Hospital data lakes can be adapted to carry out complex analysis of large MM cohorts. To better understand how multiple myeloma (a type of blood cancer) is clinically managed, we examined 509 adult patients using advanced computer analysis and data stored in the Hospital District of Helsinki and Uusimaa information system. Our study found that after 2017, there was more variety in treatments due to better access to new therapies. Compared with a nontransplant group (44.0%), patients eligible for stem cell transplantation had a better 5-year survival rate (74.4%) and used higher levels of healthcare resources. Our study highlights the potential of hospital data systems to study large groups of multiple myeloma patients and inform strategies to tackle the burden associated with the treatment costs of multiple myeloma. Treatment patterns in multiple myeloma patients are heterogeneous, and have extended in duration in recent years following the adoption of novel modalities – study of >500 multiple myeloma patients with the Helsinki (Finland) data lake @oscarbruck @RaijaSilvennoi1 @kporkka @HUS_fi @medaffcon. [ABSTRACT FROM AUTHOR]