Survival Of Patients Research Articles

Atrioventricular Block in the Setting of Immune Myocarditis: A Pragmatic Approach to Diagnosis and Treatment.

Immunotherapy has revolutionized cancer treatment in the last decade and has significantly improved patient survival. However, immunotherapy is associated with serious cardiac adverse events including myocarditis and conduction disturbances. In the literature, the mortality rate in patients with immunotherapy-associated myocarditis and complete AV block is reported to be approximately 60%. Current cardio-oncology guidelines provide a series of recommendations for the management of immune myocarditis (IM). However, there is no recommendation on whether or when pacemaker implantation should be performed in the setting of complete AV block associated with myocarditis. This gap in the literature has led to a trend in cardio-oncology practice to implant permanent pacemakers (PPMs) in a significant proportion of patients without waiting for a response to immunosuppressive therapy. However, in a significant proportion of patients undergoing PPM implantation, complete AV block resolves after immunosuppressive therapy. This suggests that in cases of complete AV block in the setting of IM, more robust clues are needed for PPM implantation. This review aims to present algorithms for the management of myocarditis and complete AV block, one of the most lethal complications of immunotherapy, to help fill this gap in the literature.

CT-defined muscle density as a prognostic factor in multiple myeloma undergoing autologous stem cell therapy: a retrospective single center study.

Skeletal muscle quality assessment can be performed by cross-sectional imaging. Skeletal muscle density (SMD) identified to be of prognostic relevance of several clinically outcomes in patients with hematological diseases. The purpose of the present study was to establish the effect of SMD on overall survival (OS) and progression-free survival (PFS) in patients with multiple myeloma (MM). All patients with MM were retrospectively analyzed between 2009 and 2019. 127 patients were included into the analysis. Whole-body computed tomography (CT) was used to calculate skeletal muscle index (SMI), SMD, albumin-gauge score and intramuscular adipose tissue content (IMAC). Overall, 28 patients (22.0%) of the patient sample died. In the discrimination analysis muscle density was higher in non-survivors compared to survivors (mean 30.8 ± 12.5 versus 24.1 ± 15.8, p = 0.03) and IMAC was lower in non-survivors (-0.66 ± 1.8 versus -0.25 ± 0.21, p = 0.01). These differences, however, were not demonstrated in the logistic regression analysis, which could not show prognostic relevance for the investigated muscle density parameters on PFS or OS. CT-defined muscle density parameters have no prognostic relevance on survival in patients with MM undergoing autologous stem cell therapy, which was demonstrated in a comprehensive analysis. These results corroborate previous smaller studies that body composition might have a limited role in this tumor entity.

Systemic immune-related spleen radiomics predict progression-free survival in patients with locally advanced cervical cancer underwent definitive chemoradiotherapy.

Systemic immunity is essential for driving therapeutically induced antitumor immune responses, and the spleen may reflect alterations in systemic immunity. This study aimed to evaluate the predictive value of contrast-enhanced CT-based spleen radiomics for progression-free survival (PFS) in patients with locally advanced cervical cancer (LACC) who underwent definitive chemoradiotherapy (dCRT). Additionally, we investigated the role of spleen radiomics features and changes in spleen volume in assessing systemic immunity. This retrospective study included 257 patients with LACC who underwent dCRT. The patients were randomly divided into training and validation groups in a 7:3 ratio. Radiomic features were extracted from CT images obtained before and after dCRT. Radiomic scores (Radscore) were calculated using features selected through least absolute shrinkage and selection operator (LASSO) Cox regression. The percentage change in spleen volume was determined from measurements taken before and after treatment. Independent prognostic factors for PFS were identified through multivariate Cox regression analyses. Model performance was evaluated with the receiver operating characteristic (ROC) curve and the C-index. The Radscore cut-off value, determined from the ROC curve, was used to stratify patients into high- and low-risk survival groups. The Wilcoxon test was used to analyze differences in hematological parameters between different survival risk groups and between different spleen volume change groups. Spearman correlation analysis was used to explore the relationship between spleen volume change and hematological parameters. Independent prognostic factors included FIGO stage, pre-treatment neutrophil-to-lymphocyte ratio (pre-NLR), spleen volume change, and Radscore. The radiomics-combined model demonstrated the best predictive performance for PFS in both the training group (AUC: 0.923, C-index: 0.884) and the validation group (AUC: 0.895, C-index: 0.834). Compared to the low-risk group, the high-risk group had higher pre-NLR (p = 0.0054) and post-NLR (p = 0.038). Additionally, compared to the decreased spleen volume group, the increased spleen volume group had lower post-NLR (p = 0.0059) and post-treatment platelet-to-lymphocyte ratio (p < 0.001). Spleen radiomics combined with clinical features can effectively predict PFS in patients with LACC after dCRT. Furthermore, spleen radiomics features and changes in spleen volume can reflect alterations in systemic immunity.

The Impact of Primary Tumor Volume on Survival of Patients with Non-Surgically Treated Advanced-Stage Hypopharyngeal Cancer– Retrospective Study and Literature Overview

The Impact of Primary Tumor Volume on Survival of Patients with Non-Surgically Treated Advanced-Stage Hypopharyngeal Cancer– Retrospective Study and Literature Overview

Effect of endometriosis on prognosis of ovarian clear cell carcinoma: a 10-year retrospective study

IntroductionEndometriosis is considered as a precancerous lesion for OCCC; however its prognostic significance remains controversial. This study aims to evaluate the prognostic significance of endometriosis in patients with ovarian clear cell carcinoma (OCCC) and analyze the impact of other clinical pathological features on prognosis. Additionally, we also assess the role of laparoscopic surgery and chemotherapy in OCCC, hoping to provide evidence for improving the clinical diagnosis and treatment of OCCC.MethodsA retrospective analysis was conducted on medical records of 105 OCCC patients diagnosed and treated at the Gynecologic Cancer Center of Hubei Cancer Hospital in China from 2013 to 2022. Based on the presence or absence of endometriosis, OCCC patients were divided into two groups: a group with ovarian endometriosis consisting of 44 cases (41.9%) (EC-positive group) and a group without ovarian endometriosis consisting of 61 cases (58.1%)(EC-negative group). Clinical pathological characteristics, progression-free survival (PFS), and overall survival (OS) were compared between the two groups.ResultsThere were no statistically significant differences between the two groups in terms of age, CA125, tumor size, FIGO stage, adjuvant chemotherapy regimen, or chemotherapy efficacy (P&amp;gt;0.05). Residual tumor after surgery, staging, site invasion involvement, presence of ascites, positive cytology in ascitic fluid, lymph node metastasis, and chemotherapy efficacy were predictive factors for recurrence among patients with statistical significance (P&amp;lt;0.10); chemotherapy efficacy remained as independent predictors for recurrence (P&amp;lt;0.05); staging and chemotherapy efficacy remained as independent predictors for survival (P&amp;lt;0.05). There was no statistically significant difference observed between both groups regarding OS or PFS.ConclusionIn this study, co-existing endometriosis was not a prognostic factor for survival in patients with OCCC. The most important predictors of OS and PFS were FIGO stage and chemotherapy sensitivity. The intrinsic link between endometriosis and OCCC requires larger, better-designed prospective studies to draw more definitive conclusions.

Palmitoylation of TIM-3 promotes immune exhaustion and restrains antitumor immunity.

T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is an immune checkpoint that has critical roles in immune exhaustion. However, little is known about the mechanisms that regulate TIM-3 surface expression and turnover. Here, we report that human TIM-3 is palmitoylated by the palmitoyltransferase DHHC9 at residue cysteine 296 (Cys296). Palmitoylation stabilized TIM-3 by preventing binding to E3 ubiquitin ligase HRD1, thereby suppressing its polyubiquitination and degradation. DHHC9 knockdown attenuated chimeric antigen receptor T (CAR-T) cell exhaustion, and a peptidic inhibitor of TIM-3 palmitoylation accelerated TIM-3 degradation and enhanced antitumor immunity mediated by CAR-T cells and natural killer (NK) cells. In hepatocellular carcinoma, DHHC9 expression correlated with TIM-3 expression in CD8+ T cells and NK cells, and high DHHC9 expression was associated with shorter survival in patients with high TIM-3. These findings demonstrate that palmitoylation of TIM-3 catalyzed by DHHC9 promotes its stability, resulting in immune exhaustion and impaired antitumor immunity.

Size, but not the number of positive lymph nodes is associated with worse overall survival in patients with small bowel neuroendocrine tumours

Size, but not the number of positive lymph nodes is associated with worse overall survival in patients with small bowel neuroendocrine tumours

The Rising Threat of Mucormycosis: Oman’s Experience Before and During the COVID-19 Pandemic

Mucormycosis is a rare, severe fungal infection mainly affecting immunocompromised individuals. Because of limited data on its epidemiology in Oman, we present this national, multicentric, retrospective review that includes all cases of proven mucormycosis between 2006 and 2022 in Oman. There were 51 cases of mucormycosis reported in Oman. The annual incidence of mucormycosis was 0.38–0.69 cases per million population before COVID-19. During the pandemic, the incidence rose significantly to 1.76 in 2020, 5.31 in 2021, then decreased to 0.87 per million population in 2022. Diabetes was observed in 82.4% (n = 42) of the cases, COVID-19 in 47.1% (n = 24), and other chronic diseases in 72.6%. The use of steroids was reported in 33.3% (n = 17) and many patients (64.7%, n = 33) had multiple risk factors. The overall mortality rate was 41.2% (n = 21) and most deaths occurred within a month of diagnosis. Mortality rate among patients diagnosed with COVID-19 was 58.3% (14/24). Survival analysis showed a statistically significant association between COVID-19 status and patient survival (p = 0.024). Annual incidence of mucormycosis in Oman rose during the pandemic. This study highlights the epidemiological features of mucormycosis and emphasizes the importance of its inclusion in the national notifiable communicable diseases priority list as well as the importance of enhancing diagnostic capacities to detect and improve patient outcomes.

Evaluation of safety criteria for enoxaparin bridging in patients with left ventricular assist devices in an outpatient care setting.

Appropriate anticoagulation is crucial for the success of left ventricular assist device patients. Currently, there is no consensus on the optimal management of their subtherapeutic INR in ambulatory setting. Our goal is to evaluate both the short-term adverse events and long-term outcomes of enoxaparin bridging at a major transplant center, following the implementation of bridging safety criteria. In total, 85 patients' medical records were reviewed between 7/2019 and 5/2022, with 51 patients meeting safety criteria were bridged with enoxaparin and 34 non-bridged. The primary endpoint was the occurrence of major bleeding/thrombosis events within 30 days of bridging. The secondary endpoint was freedom from events 30 days after enoxaparin initiation and overall patient survivability until the last follow-up. Within 30 days, no major bleeding/thrombotic events were noted. After 30 days, the major bleeding rate was 5.8% in bridged vs. 11.8% in non-bridged patients (p = 0.02). Overall, 3-year survival was 78% in the bridged vs. 49% in non-bridged patients (p < 0.001). In patients with no events, 3-year survival was 80% in bridged vs. 58% in non-bridged (p < 0.001). In the patients with bleeding events, 3-year survival was 55% in bridged vs. 51% in non-bridged (p = 0.11). At 1 year, freedom from bleeding in the bridged patients was 81% in patients with no events vs. 0% in those with an event (p < 0.0001). When eligibility criteria for safe bridging were applied, the use of enoxaparin bridging was associated with no major bleeding/thrombotic events during bridging and improved 3-year survival in LVAD patients. Economically, using outpatient enoxaparin resulted in substantial healthcare savings, fewer readmissions, and improved quality of life.

Safety and Effectiveness of Percutaneous Ethanol Injection as a Treatment for Locally Recurrent Papillary Thyroid Carcinoma

Background: Reoperation for recurrent papillary thyroid cancer (PTC) is associated with a high risk of complications and limited success in achieving sustained remission. Percutaneous ethanol injection (PEI) presents a potential non-surgical alternative for managing locally recurrent PTC. Objectives: This study aimed to evaluate the safety and effectiveness of PEI in treating recurrent PTC. Methods: From October 2017 to September 2021, PEI was administered to 39 recurrent lesions (23 lateral and 16 central) in 17 patients with PTC. The median follow-up duration was 21.4 months (range, 4.1 - 37.9), with ethanol injections delivered every 3 months under ultrasound (US) guidance as needed. Results: Most patients tolerated the treatment well, experiencing only mild local pain, though one patient reported Horner syndrome following the procedure. In terms of treatment frequency, 31 lesions required 3 or fewer injections, while the remaining lesions required more. The mean initial volume of the lesions decreased from 0.12 mm³ (range: 0.06 - 0.34 mm³) to 0.03 mm³ (range: 0.0 - 0.14 mm³), representing an average reduction of 72.6% (range: 20.0 - 100.0%). Of the 39 lymph nodes treated in 17 patients, 21 lymph nodes (54%) were completely resolved. Seven lymph nodes remain under ongoing ethanol treatment, while 11 lymph nodes in 4 patients were addressed with alternative treatments, including surgery. Conclusions: Percutaneous ethanol injection appears to be a safe and effective treatment option for managing locally recurrent thyroid carcinomas in select patients. However, further comparative, prospective, long-term studies are needed to evaluate PEI’s impact on patient survival and recurrence rates.

Blood CD45+/CD3+ lymphocyte-released extracellular vesicles and mortality in hospitalized patients with coronavirus disease 2019.

The global pandemic of coronavirus disease 2019 (COVID-19) represented a major public health concern. Growing evidence shows that plasma of COVID-19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID-19 patients during hospitalization and its relation to mortality risk. cEVs were quantitatively and phenotypically analysed in hospitalized non-surviving COVID-19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation. Levels of cEV subtypes differed between patients with severe COVID-19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan-leukocyte, and lung epithelial cell-shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2-positive eEVs were significantly increased before death compared to admission whereas endoglin and E-selectin-containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell-derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+-ℓEVs were significantly associated to the patient's survival time. An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell-derived EVs in COVID-19 pathogenesis.

Lfng-expressing centroacinar cell is a unique cell-of-origin for p53 deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with limited understanding of etiology. Studies in mice showed that both acinar and ductal cells of the pancreas can be targeted by combination of oncogenic Kras and p53 mutations to form PDAC. How the transforming capacities of pancreatic cells are constrained, and whether a subset of cells could serve as a prime target for oncogenic transformation, remain obscure. Here we report that expression of a Notch modulator, Lunatic Fringe (Lfng), is restricted to a limited number of cells with centroacinar location and morphology in the adult pancreas. Lfng-expressing cells are preferentially targeted by oncogenic Kras along with p53 deletion to form PDAC, and deletion of Lfng blocks tumor initiation from these cells. Notch3 is a functional Notch receptor for PDAC initiation and progression in this context. Lfng is upregulated in acinar- and ductal-derived PDAC and its deletion suppresses these tumors. Finally, high LFNG expression is associated with high grade and poor survival in human patients. Taken together, Lfng marks a centroacinar subpopulation that is uniquely susceptible to oncogenic transformation when p53 is lost, and Lfng functions as an oncogene in all three lineages of the exocrine pancreas.

Medicaid Expansion and Overall Survival of Lower Gastrointestinal Cancer Patients After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy.

In the United States, often only tertiary centers offer cytoreductive surgery and heated intraperitoneal chemotherapy (CRS+HIPEC) for peritoneal metastases in advanced lower gastrointestinal malignancies. Growing evidence shows that Medicaid expansion under the Affordable Care Act (ACA) of 2010 enhanced healthcare access and outcomes. We sought to determine whether Medicaid expansion was associated with decreased all-cause mortality of lower gastrointestinal cancer patients following CRS+HIPEC. We analyzed data from the National Cancer Database (2010-2019) on lower gastrointestinal cancer patients who underwent CRS+HIPEC. Medicaid expansion, introduced under the ACA in 2010, extends health insurance to low-income adults. We categorized states by expansion timing: early (2010-2013), immediate (January 2014), late (after January 2014), or no expansion to assess the impact of Medicaid expansion on mortality using a multivariable Cox regression model. Of the 1001 study patients, 671 (67%) were diagnosed in Medicaid expansion states. Grade and Medicaid expansion status were the only factors independently associated with overall survival on multivariable analysis. On average, patients in Medicaid expansion states experienced a 4% increase in annual survival compared with those in non-expansion states who had a 1% decrease in annual survival over the study period. Patients from states that had an early expansion of Medicaid and patients with lower-grade tumors had significantly better overall survival. Our study findings suggest that improved access to healthcare through Medicaid expansion was associated with increased survival rates of lower gastrointestinal cancer patients who undergo CRS+HIPEC for the treatment of peritoneal metastases.

POORLY DIFFERENTIATED CLUSTERS IN COLORECTAL CARCINOMA: ASSOCIATION WITH OTHER HISTOPATHOLOGICAL PROGNOSTIC PARAMETERS INCLUDING TUMOUR BUDDING

Objective: In India, colorectal carcinoma (CRC) ranks third in terms of cancer incidence. Pathologists are essential when it comes to determining the stage, examining surgical margins, and recording the histopathologic prognostic factors. A new prognostic grading system is proposed named poorly differentiated clusters (PDCs), which are defined by neoplastic clusters of 5 cells lacking glandular structure in the invasive front of the stroma. It is significant for cancer-specific and recurrence-free survival in CRC patients, reflecting the biological aggressiveness of the tumor. Aim of the study was to analyse of PDCs in colorectal carcinomas and association with other histopathological prognostic factors. Methods: The Hematoxylin and Eosin (HandE)-stained slides of 76 histopathologically diagnosed CRC resection specimens were reviewed. Poorly differentiated clusters (PDC) were assessed into under 200x power. The correlation of PDC with other histopathological prognostic parameters like tumor size, site, grade, laterality, lymphovascular invasion, perineural invasion, T stage, N stage, and tumor budding was analyzed using descriptive statistics and the Chi-square test with SPSS version 26.0. Results: There was no significant association between PDC and age, tumor location, tumor size, histological grade, LVI, PNI, or lymphnode status. Where a significant association was noted between the sex and PDC grade (P value = 0.035), T stage and PDC grade (P value = 0.045), and N stage and PDC grade is significant (P value = 0.001). Conclusion: PDCs may be considered, along with other clinical-pathological parameters, a promising prognostic factor for the management of patients with CRC and should be included in pathological reports, but it still needs standardization and further validation. At the same time, tumor budding can become an irreplaceable histological indicator for identifying a high malignant potential carcinoma and poor prognosis in CRCS, thus indicating the need for aggressive postoperative management to improve the prognosis of the patient. PDC is important for the survival of CRC patients, indicating the aggressiveness of the tumor both in terms of cancer-specific survival and freedom from recurrence. PDC may help to identify patients who need a more intensive postoperative follow-up and the possibility of adjuvant therapy.

Multidisciplinary tumor boards in oral cavity cancer: survival effect due to balancing guideline adherence and treatment delays

ObjectivesThe purpose of the study was to assess the impact of a pretherapeutic Multidisciplinary Tumor Board (MTB) presentation on the prognosis and treatment outcomes in patients with primary oral cavity carcinoma.Materials and methodsThis single-center study included 630 patients diagnosed with oral cavity carcinoma treated between 2010 and 2020. The study cohort was divided in a group with and without pretherapeutic MTB presentation. Data on patient demographics, tumor characteristics, treatment and the time to treatment initiation (TTI) were collected retrospectively.ResultsPrimary findings revealed no significant difference in 3-year survival rate (3-YSR) and 3-year disease-free survival rate (3-YDFSR) for the non-MTB and MTB group. The 3-YSR was 73.1% in the non-MTB group and 67.1% in the MTB group (p = 0.112). The 3-YDFSR was 73.8% in the non-MTB group and 76.5% in the MTB group (p = 0.447). Estimated mean 5-year survival (5-YS) and 5-year disease-free survival in (5-YDFS) did not differ significantly between both groups, across the UICC stages I-IV, as well as for the entire cohort. The TTI was significantly longer in the MTB group (33.5 days, CI: 31.3;35.7) compared to the non-MTB group (20.1 days, CI: 17.9;22.4, p &amp;lt; 0.001). The MTB group adhered more frequently to the national guidelines (68% vs. 79.6%, p &amp;lt; 0.01).ConclusionThe results demonstrate both positive and negative side effects of the MTB presentation in patients with oral cavity cancer. Further multicenter studies will be required to assess the impact of TTI and adherence to guidelines on the survival of oral cavity cancer patients.

Venetoclax plus low intensity chemotherapy for adults with acute lymphoblastic leukemia.

In acute lymphoblastic leukemia (ALL), the BCL2 inhibitor venetoclax may enhance the efficacy of chemotherapy allowing dose reductions that reduce toxicity. We designed a phase 1b study of venetoclax plus attenuated chemotherapy to determine the recommended phase 2 dose (RP2D) of venetoclax. The study enrolled 19 patients with ALL either newly diagnosed (≥60 years, n=11 [B-cell, n=8; T-cell, n=3]) or R/R (≥18 years, n=8 [B-cell, n=3; T-cell, n=5]). Venetoclax was given for 21 days with each cycle of mini-hyper-CVD (cyclophosphamide, vincristine, dexamethasone alternating with methotrexate and cytarabine). There were no dose limiting toxicities at dose level (DL) 1 (n=3, 400 mg/day) or DL2 (n=6, 600 mg/day); DL2 was the RP2D and explored further (n=10). The most common non-hematologic adverse events were grade 3+ infections. There were no deaths within 60 days and no patients discontinued therapy for toxicity. There was no tumor lysis syndrome, hepatotoxicity, or prolonged cytopenias. Among patients with newly diagnosed ALL, 10/11 (90.9%) achieved a measurable residual disease-negative (<0.01% sensitivity) complete remission (CR) including 6 patients with hypodiploid TP53 mutated ALL. All patients in CR bridged to hematopoietic stem cell transplant (n=9) or completed protocol (n=1). With a median follow-up of 60.0 months, median disease-free survival (DFS) for patients with newly diagnosed ALL was 54.6 months (95% CI: 35.5 months - NA) with a 2-year DFS rate of 90% (95% CI, 71% - 100%). Among patients with R/R ALL, 3/8 (37.5%) achieved CR. In summary, for patients with newly diagnosed ALL, venetoclax plus mini-HCVD is well-tolerated with promising efficacy. NCT03319901.

Textbook oncological outcome of locally advanced gastric cancer patients with preoperative sarcopenia: a multicenter clinical study.

The impact of postoperative sarcopenia on the Textbook Oncological Outcome (TOO) in locally advanced gastric cancer (LAGC) remains uncertain. This study investigates the relationship between sarcopenia and TOO, explores its long-term prognostic value, and develops a prognostic model incorporating sarcopenia and TOO for survival prediction. We performed a retrospective analysis of clinical and pathological data from patients with LAGC who underwent radical surgery at two Chinese tertiary referral hospitals. Sarcopenia was defined as an SMI < 36.4 cm2/m2 in males and < 28.4 cm2/m2 in females. TOO was defined as the addition of perioperative chemotherapy to the textbook outcomes (TO). A nomogram was developed to predict postoperative overall survival (OS) and recurrence-free survival (RFS) in LAGC patients. The study included 972 patients with LAGC. The overall TOO achievement rate was 67.1%. The TOO achievement rate was significantly higher in patients non-sarcopenia compared to those with sarcopenia (68.9% vs. 61.1%, P = 0.031). Logistic regression revealed that age ≥ 65, high ASA score, and sarcopenia were independent risk factors for TOO failure. Cox regression analysis identified TOO, sarcopenia, tumor size, differentiation, vascular invasion, pT stage, and pN stage as independent predictors of OS and RFS. Nomogram models based on sarcopenia and TOO accurately predicted the 3-year and 5-year OS and RFS. Preoperative sarcopenia was an independent predictor of TOO implementation. A prognostic prediction model that integrates preoperative sarcopenia and TOO, which outperforms the current staging system, can aid clinicians in effectively assessing the prognosis of patients with LAGC.

A Prospective Longitudinal Study to Demonstrate the Utility of the Palliative Prognostic Index in Forecasting the Short-term Survival of Patients with Advanced Cancer in India

Objectives: In this study, our primary objectives were to validate the palliative prognostic index (PPI) tool in the context of palliative care for patients with advanced cancer. Specifically, we aimed to assess the accuracy of the PPI in predicting actual survival in these patients through prospective validation. Materials and Methods: To achieve our objectives, we enrolled a cohort of 227 advanced cancer patients receiving palliative care. The study population comprised 132 (58.1%) men and 95 (41.9%) women, with a median age of 52 years (Range: 20–81). Among them, 56 (24.7%) underwent chemotherapy, and 26 (11.5%) underwent palliative radiotherapy. We utilised the PPI score to categorise patients into three prognostic groups: (a) PPI score &lt;4 indicating likely survival of more than 6 weeks; (b) PPI score 4–6 indicating likely survival shorter than 6 weeks; and (c) PPI score &gt;6 indicating likely survival &lt;3 weeks. Results: Through our analysis, we found that the PPI demonstrated limited predictive capabilities, particularly for short-term survival (&lt;3 weeks). The PPI’s performance metrics included a positive predictive value of 45.24%, a negative predictive value of 100%, a sensitivity of 100.00% and a specificity of 88.94%. Conclusion: In conclusion, our study establishes the limited reliability of the PPI in predicting short-term survival (&lt;3 weeks) among patients in palliative care with advanced cancer. These findings underscore the PPI’s potential as a valuable tool for healthcare professionals, aiding in the development of treatment plans and facilitating discussions on end-of-life care options with patients and their families. In addition, the PPI may assist healthcare professionals in identifying individuals who could benefit from more aggressive interventions or those approaching the end of life, thereby guiding the provision of additional support and care.

MCRS1 sensitizes T cell-dependent immunotherapy by augmenting MHC-I expression in solid tumors.

Dampened antigen presentation underscores the resistance of pancreatic cancer to T cell-mediated anti-tumor immunity, rendering immunotherapy largely ineffective. By high-throughput CRISPR activation perturbation, we discovered that the transcriptional regulator MCRS1 significantly augmented the sensitivity of mouse pancreatic cancer cells to T cell immunity in vitro and in vivo. Mechanistically, MCRS1 interacted with the transcription factor and genome organizer YY1 to coordinately increase the chromatin accessibility and expression of MHC-I genes. Elevated MCRS1 subverted MHC-I suppression and activated anti-tumor T cells, which sensitized mouse pancreatic cancer to α-PD-1 therapy. Remarkably, high MCRS1 expression was associated with increased T cell infiltration and extended survival of patients with pancreatic cancer and was predictive of favorable responses to α-PD-1 therapy in patients with lung cancer. Together, our study uncovers that MCRS1 sensitizes cancer cells to T cell immunity by transcriptionally subverting MHC-I suppression, which enhances the effectiveness of α-PD-1 therapy in mice and humans, paving the way to further improve immunotherapy against solid tumors.

Radiotherapy in patients with brain metastases with and without concomitant immunotherapy: comparison of patient outcome and neurotoxicity.

Recently, immune checkpoint inhibitors (ICI) have been added to the treatment of brain metastases. While combining radiotherapy and ICI can enhance therapeutic effects, it might also increase the risk of severe autoimmune adverse events. This retrospective study aims to compare treatment responses and neurotoxicity in patients treated with radiotherapy alone versus those receiving a combination of radiotherapy and ICI. All patients with brain metastases who received radiotherapy at Hannover Medical School from 2017 to 2019 were included. The medical reports of all study participants were evaluated. Patients who received radiotherapy alone and those who received a combination of radiation and ICI were compared. A total of 248 patients were analyzed, with the most common tumor types being non-small cell lung cancer (NSCLC) and malignant melanoma. Half of the patients received whole-brain radiotherapy (WBRT) and the other half stereotactic radiotherapy (SRT). Of these, 29 patients received concurrent immunotherapy and radiotherapy, 30 completed immunotherapy before radiotherapy, and 29 started ICI after completing radiotherapy. Two cases lacked information on the duration of immunotherapy. Overall survival post-initial tumor diagnosis within the total cohort was 52months, with significantly worse survival for patients with multiple brain metastases (p = 0.020). No significant differences in survival or incidence of neurological adverse events were observed between patients with or without ICI. Combining radiotherapy and ICI did not significantly increase neurotoxicity or improve survival in this cohort, though the heterogeneity of the subgroups limits the generalizability of these findings.