Potential Survival Benefit Research Articles

MRI-based microvascular invasion prediction in mass-forming intrahepatic cholangiocarcinoma: survival and therapeutic benefit.

To establish an MRI-based model for microvascular invasion (MVI) prediction in mass-forming intrahepatic cholangiocarcinoma (MF-iCCA) and further evaluate its potential survival and therapeutic benefit. One hundred and fifty-six pathologically confirmed MF-iCCAs with traditional surgery (121 in training and 35 in validation cohorts), 33 with neoadjuvant treatment and 57 with first-line systemic therapy were retrospectively included. Univariate and multivariate regression analyses were performed to identify the independent predictors for MVI in the traditional surgery group, and an MVI-predictive model was constructed. Survival analyses were conducted and compared between MRI-predicted MVI-positive and MVI-negative MF-iCCAs in different treatment groups. Tumor multinodularity (odds ratio = 4.498, p < 0.001) and peri-tumor diffusion-weighted hyperintensity (odds ratio = 4.163, p < 0.001) were independently significant variables associated with MVI. AUC values for the predictive model were 0.760 [95% CI 0.674, 0.833] in the training cohort and 0.757 [95% CI 0.583, 0.885] in the validation cohort. Recurrence-free survival or progression-free survival of the MRI-predicted MVI-positive patients was significantly shorter than the MVI-negative patients in all three treatment groups (log-rank p < 0.001 to 0.046). The use of neoadjuvant therapy was not associated with improved postoperative recurrence-free survival for high-risk MF-iCCA patients in both MRI-predicted MVI-positive and MVI-negative groups (log-rank p = 0.79 and 0.27). Advanced MF-iCCA patients of the MRI-predicted MVI-positive group had significantly worse objective response rate than the MVI-negative group with systemic therapy (40.91% vs 76.92%, χ2 = 5.208, p = 0.022). The MRI-based MVI-predictive model could be a potential biomarker for personalized risk stratification and survival prediction in MF-iCCA patients with varied therapies and may aid in candidate selection for systemic therapy. Question Identifying intrahepatic cholangiocarcinoma (iCCA) patients at high risk for microvascular invasion (MVI) may inform prognostic risk stratification and guide clinical treatment decision. Findings We established an MRI-based predictive model for MVI in mass-forming-iCCA, integrating imaging features of tumor multinodularity and peri-tumor diffusion-weighted hyperintensity. Clinical relevance The MRI-based MVI-predictive model could be a potential biomarker for personalized risk stratification and survival prediction across varied therapies and may aid in therapeutic candidate selection for systemic therapy.

Novel Therapies in the Perioperative Management of Localized Gastric Cancer: Current Perspectives and Future Directions

The management of localized gastric cancer has evolved considerably with the advent of novel perioperative treatment strategies with chemotherapy, significantly impacting patient outcomes. Traditionally, surgery has been the cornerstone of treatment, but recurrence rates remained high, necessitating the exploration of additional therapies to enhance long-term survival. The interplay between chemotherapy and radiotherapy is being meticulously studied to define the optimal sequencing and combination that maximizes tumor control while minimizing toxicity. Furthermore, the integration of targeted therapies and immunotherapy into the perioperative setting is gaining momentum with agents targeting HER2, VEGF, and PD-1/PD-L1, pathways have shown promise in advanced gastric cancer and are now being tested in the neoadjuvant and adjuvant settings. Preliminary results from trials investigating these agents, such as pembrolizumab and trastuzumab-deruxtecan, suggest potential survival benefits and warrant further exploration in combination with chemotherapy in the perioperative context. Additionally, the heterogeneity of gastric cancer across different populations and geographic regions necessitates tailored approaches that consider genetic and molecular characteristics of tumors, as well as patient comorbidities. This Comment provides a comprehensive overview of the latest therapeutic advancements in the perioperative setting for localized gastric cancer, emphasizing the critical role of multimodal treatment approaches.

Role of molecular alterations in transplantation decisions for patients with primary myelofibrosis

AbstractThe aim of our study was to analyze the potential survival benefit associated with hematopoietic stem cell transplantation (HSCT) according to clinicobiological scores, which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n = 241) and 1 nontransplant cohort (n = 239) were used to test the hypothesis that patients with primary myelofibrosis with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference. Weighted Cox proportional hazard models and logistic regression analyses were performed. Overall, 105 patients who did not receive transplant could be matched to the 239 patients who did receive transplants. Mean age in matched patients who did and did not undergo transplant was 55.5 and 57.9 years, respectively. Blood cell count and Dynamic International Prognostic Scoring System (DIPSS) score distribution were similar in both groups. HSCT was associated with a higher 6-year overall survival rate in intermediate-2 (60.1% vs 41.5%) and high-risk DIPSS patients (44.4% vs 6.55%), high-risk MIPSS70 (46.5% vs 23.9%), high-risk (73.2% vs 39.7%) or very high-risk MIPSS70+V2 (51.8% vs 24%). Patients with intermediate MIPSS70 scores have an advantage of survival with HSCT only when their myelofibrosis transplant scoring system (MTSS) were low or intermediate. Patients who received transplant had an increased mortality risk the first year, but a significant benefit with HSCT after the 1-year landmark was observed in higher risk patients. This study confirms that, similar to DIPSS, MIPSS70 and MIPSS70+V2 risk score in addition to MTSS can be used to determine which patients with primary myelofibrosis have survival benefit from HSCT over non-HSCT strategies.

Survival Benefit of Primary Tumor Treatment in Uveal Melanoma: A Re-Analysis of the Collaborative Ocular Melanoma Study (COMS) and Natural History Study (NHS) Cohorts.

To evaluate whether primary tumor treatment provides a survival benefit in uveal melanoma by comparing patients who declined treatment (Natural History Study, NHS) with those who received treatment in the Collaborative Ocular Melanoma Study (COMS) for medium-sized choroidal melanomas. Individual-level survival data were reverse-engineered from cumulative all-cause mortality curves in the original COMS and NHS publications. Censoring patterns were estimated from numbers at risk and descriptive statistics. A Bonferroni-corrected significance level of 0.017 was applied. Additionally, to ensure a conservative approach, NHS cohort data were iteratively adjusted by reducing the 8-year cumulative mortality by one percentage point if the Cox regression hazard ratio for all-cause mortality, the unadjusted risk ratio for death, and the 95% confidence intervals (CIs) of the Kaplan-Meier curves did not show a smaller survival difference than originally reported. Kaplan-Meier analysis revealed significantly higher cumulative mortality in the NHS cohort compared to the COMS cohort (log-rank p = 0.012). When restricting the analysis to the first 8 years to account for unclear censoring patterns beyond this period, the NHS cohort still demonstrated worse survival (p = 0.008). A sensitivity analysis, varying censoring times by ±25% over 1000 iterations, confirmed worse survival in the NHS cohort in 100% of cases. In this re-evaluation, patients who declined treatment for medium-sized choroidal melanomas had significantly worse survival, suggesting a potential survival benefit of primary tumor treatment.

Immune Checkpoint Inhibitors and Vaccination: Assessing Safety, Efficacy, and Synergistic Potential.

Although immune checkpoint inhibitors (ICIs) have become predominant therapies for cancer, the safety and efficacy of combining ICIs with vaccinations remain areas of needed investigation. As ICIs gain broader clinical application, the relevance of current vaccination guidelines for cancer patients-largely developed in the context of cytotoxic therapies-becomes increasingly uncertain. Although data support the safety of combining inactivated influenza and mRNA SARS-CoV-2 vaccines with ICI therapy, comprehensive data on other infectious disease vaccines remain scarce. Notably, the combination of ICIs with infectious disease vaccines does not appear to exacerbate immune-related adverse events, despite the heightened cytokine activity observed. However, the efficacy of vaccines administered alongside ICIs in preventing infectious diseases remains poorly supported by robust evidence. Preliminary findings suggest a potential survival benefit in cancer patients receiving ICI therapy alongside influenza or SARS-CoV-2 vaccination, though the quality of evidence is currently low. Moreover, the synergistic potential of combining therapeutic cancer vaccines, particularly mRNA-based vaccines, with ICIs indicates promise but with a paucity of phase III data to confirm efficacy. This review critically examines the safety and efficacy of combining ICIs with both infectious disease vaccines and therapeutic cancer vaccines. While vaccination appears safe in patients undergoing ICI therapy, the impact on infectious disease prevention and cancer treatment outcomes warrants further rigorous investigation.

Primary tumour resection in metastasised adrenocortical carcinoma: a systematic review.

Up to 30% of adrenocortical carcinoma (ACC) patients have metastasised disease upon initial presentation and systemic treatments currently fail to sufficiently improve survival. Palliative primary tumour resection can be considered for symptomatic relief, but its potential survival benefit remains a topic of debate. This systematic review therefore aims to assess the effect of primary tumour resection on overall survival in patients with metastatic ACC. A systematic review was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Relevant databases were searched from 2000-2024 for studies on primary tumour resection in metastatic ACC. Overall survival data were analysed. A total of thirteen studies on primary tumour resection for metastatic ACC were included. All studies were retrospective and assessed as having a high risk of bias. Data regarding adequate patient characteristics and indications for surgery were missing in all studies. Hence, current literature is hampered by both indication and selection bias to draw any conclusions on the survival benefit of primary tumour resection in patients with metastasised ACC. However, twelve out of thirteen studies (92%) demonstrated longer overall survival after primary tumour resection compared to no surgery. Whereas this is in line with retrospective data on other cancers, randomised controlled trials in other tumours, like breast and colorectal cancer, have failed to display survival benefits of primary tumour resection. These cancers are however relatively chemo-sensitive, unlike ACC. Primary tumour resection could therefore only be considered on individual patient basis.

A comprehensive overview of gastric cancer management from a surgical point of view

Despite advancements in medical care, surgical technologies, and the development of novel treatments over the past decade, the prognosis for patients with gastric cancer (GC) has only modestly improved. This is primarily due to the fact that the majority of patients are diagnosed at advanced stages or present with metastatic disease. Radical resection remains the cornerstone of potentially curative treatment, yet the overall 5-year survival rate remains below 35%. The management of GC varies globally, influenced by factors such as geographical disparities, patient comorbidities and performance status, surgical approaches, and available medical resources. Multidisciplinary collaboration and a multimodal treatment approach are essential for optimizing patient outcomes. Surgeons must stay updated on emerging surgical concepts and make informed decisions regarding patient selection, timing of intervention, and the adoption of appropriate surgical techniques to improve both quality of life and prognosis. This review aims to provide a surgical perspective on the management of GC across all stages, highlighting the importance of a comprehensive treatment approach. Endoscopic resection may be a viable option for early GC in patients with minimal risk of lymph node metastasis, particularly in elderly patients with high surgical risk or severe comorbidities. For advanced GC, neoadjuvant therapy followed by surgery could be a promising strategy to improve patient outcomes. Conversion surgery offers a potential survival benefit for patients who respond to treatment with tumor downstaging. The treatment of peritoneal carcinomatosis remains challenging; however, hyperthermic intraperitoneal chemotherapy combined with complete cytoreductive surgery or pressurized intraperitoneal aerosolized chemotherapy may prolong survival or improve quality of life in highly selected patients.

Prognostic Impact of Adjuvant Immunotherapy in Patients With Resectable NSCLC After Neoadjuvant Chemoimmunotherapy: A Brief Report

ObjectiveThe potential survival benefits of adjuvant immunotherapy for resectable NSCLC after neoadjuvant chemoimmunotherapy, and the optimal number of adjuvant immunotherapy cycles, remain uncertain. This study aims to evaluate the prognostic impact of adjuvant immunotherapy and determine the optimal number of cycles. MethodsA total of 438 patients who received neoadjuvant chemoimmunotherapy between August 2019 and June 2022 across four hospitals were enrolled in this study, with a median follow-up time of 31.3 months. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier methods and tested by log-rank test. Unstratified Cox proportional hazards models were fitted to the subgroups. ResultsIn this multi-center cohort, 29.7% of patients (n = 130) achieved a pathologic complete response. Patients who received adjuvant immunotherapy experienced significant survival benefits compared with those who did not (RFS: hazard ratio [HR] = 0.63, 95% confidence interval: 0.41–0.98, p = 0.037; OS: hazard ratio = 0.27, 95% confidence interval: 0.13–0.57, p < 0.001). Subgroup analyses found that patients with a squamous histologic type, positive PD-L1 expression, and those with a major pathologic response particularly benefited from adjuvant immunotherapy. In addition, we found that six cycles of adjuvant immunotherapy served as a threshold for better prognostic differentiation, suggesting that six or more cycles may be more beneficial. ConclusionsOur study found that the addition of adjuvant immunotherapy to neoadjuvant chemoimmunotherapy is significantly associated with improved RFS and OS in patients with resectable NSCLC. We also identified that six cycles of adjuvant immunotherapy may be the optimal regimen for these patients.

Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events

Abstract Background Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe, bempedoic acic, and proprotein convertase subtilisin/kexin type 9 (PCSK-9) (synthase-) inhibitors allow for the reduction in LDL-cholesterol in addition to statin therapy. Purpose We aimed to perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome. In specific, we evaluated the potential influence of duration of follow-up on the association with mortality endpoints. Methods We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe, bempedoic acid, Bococizumab, Alirocumab, Evolocumab, Inclisiran in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of August 2023, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were : "Bempedoic Acid" or "Bococizumab" or "Alirocumab" or "Evolocumab" or "Ezetimibe" or "Inclisiran" and "statin" and "cardiovascular events". Results A total of 123,785 patients from 15 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, ODYSSEY LONG TERM, EWTOPIA 75, PACMAN-AMI, RACING, SIPRE I, SPIRE II, OSLER-1 and OSLER-2, CLEAR HARMONY, CLEAR OUTCOMES, CLEAR SERENITY, CLEAR WISDOM) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 19% risk reduction in cardiovascular events (OR [95%CI]: 0.81 [0.75; 0.86]). Effect sizes were similar for myocardial infarction (0.81 [0.74; 0.89]) and even more pronounced for ischemic stroke (0.77 [0.70; 0.84]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.99 [0.93; 1.04]). Stratifying by follow-up duration of &amp;lt; vs. ≥ 3 years, no improvement in all-cause mortality was observed in both groups (&amp;lt;3 years: 1.04 [0.93; 1.17]; ≥3 years: 0.97 (0.88; 1.06). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Conclusion Intensified LDL-lowering therapy with ezetimibe, bempedoic acic or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. A potential survival benefit was also not observed in studies with follow-up duration of ≥ 3 years.

Liquid biopsy with plasma Epstein-Barr virus DNA characterizes biological relapse for the prediction of cancer recurrence in non-disseminated nasopharyngeal carcinoma

PurposeTo investigate whether a bounce in plasma Epstein-Barr virus (EBV) DNA during posttreatment surveillance of nasopharyngeal carcinoma (NPC) informs the risk of clinical recurrence and its implication for early therapeutic intervention. Methods950 non-disseminated NPC patients with completed remission in 3 months after treatment were retrospectively screened. Detectable EBV DNA with no evidence of clinical relapse during follow-up was deemed as DNA bounce. The diagnostic and prognostic performance of EBV DNA bounce was assessed for subsequent failures. ResultsTumor recurrence occurred in 6.6 %, 10.1 % and 65.8 % in the group with persistently negative EBV DNA, single positive test and ≥ 2 positive tests, respectively. EBV DNA bounce over twice was associated with worse disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) than the other two groups. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the prediction of recurrence were 0.56, 0.95, 0.66, 0.93 and 0.90 using two positive tests, which were hence deemed as biological relapse. Serial cutoffs (EBV DNA 1 ≥ 40 copies/ml or EBV DNA 2 ≥100 copies/ml) further defined a high-risk subgroup with an eventual recurrence rate of 77.9 % and 3-year DFS of merely 20.5 %. Prophylactic medical intervention with capecitabine or S1 significantly improved the 3-year DFS when compared to those with observation. ConclusionsThe earliest two positive tests of EBV DNA represent a biomarker of biological relapse that allows early detection of clinical recurrence in EBV-related NPC. For high-risk biological relapse, preemptive intervention provides potential survival benefits.

Impact on survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis

BackgroundMetastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and targeted therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored.MaterialsA retrospective review was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team discussion. Patient characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a “PTR” group and a “No PTR” group and then further stratified into “4A,” “4B,” and “4C” subgroups based on the initial mCRC stage. Additionally, four subgroups—namely “PTR( +)/RT( +),” “PTR( +)/RT( −),” “PTR( −)/RT( +),” and “PTR( −)/RT( −)”—were formed to assess the combined effects of PTR and RT.ResultsThe median OS for all the patients was 23.8 months (20.5–27.1 months). The “PTR” group exhibited a significantly higher median OS of 25.9 months (21.3–30.5 months) compared with 21.4 months (15.8–27.1 months) in the “No PTR” group (p = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant (p = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates.ConclusionFor asymptomatic mCRC with synchronous unresectable distant metastasis, PTR following first-line therapy with bevacizumab plus FOLFIRI may provide a potential survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.

Corticosteroids for hospitalized patients with severe/critical COVID-19: a retrospective study in Chongqing, China

Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis.

Beyond Dialysis: Reshaping CKD Paradigms in Developing Nations.

Dear Sir / Madam, Respected Editor, I am writing to bring attention to the critical need for increased research on conservative kidney management (CKM) in the context of patients with advanced chronic kidney disease (CKD). The recent advancements in developed nations have demonstrated that CKM is a novel and effective approach to caring for CKD patients, particularly those who choose not to pursue maintenance dialysis. Historically, medical care for individuals with CKD has adhered to a paternalistic model, where clinicians make treatment decisions independent of patient preferences. JS Scherer et al observed that a provider's assessment of a patient's frailty and response exerted a more substantial influence on the treatment provided than the patient’s comorbidities, functional status, and stated preferences. 2 Furthermore, another study showed that some individuals exhibited a preference for conservative care after shared-decision making, irrespective of the potential survival benefits offered by dialysis if it entailed frequent hospital visits or travel restrictions. 3 This underscores the significance of patient autonomy, where the pursuit of freedom can sometimes outweigh the emphasis on clinical outcomes. However, contemporary CKD management in the 21st century emphasizes shared decision-making and patient empowerment. While research suggests CKM can improve quality of life, reduce hospitalizations, and minimize invasive procedures, offering a valuable alternative to dialysis, its impact on survival becomes less clear for patients over 80 or those with multiple comorbidities.4 Additionally, the inclusion of patients and their families in collaborative decision-making processes has proven advantageous, supported by specialized decision aids that promote well-informed discussions regarding CKM with healthcare providers.5 Nephrologists face significant challenges in implementing effective conservative kidney management (CKM) due to a lack of clinical guidelines, training, evidence, and system-level infrastructure. This has resulted in limited awareness and discussion of CKM among patients and healthcare providers, hindering its adoption. With the global burden of chronic kidney disease (CKD) increasing significantly over the past three decades, particularly affecting low- and middle-income countries, there is a pressing need for innovative, cost-effective solutions. CKM emerges as a viable alternative where dialysis is often inaccessible or unaffordable, with the potential to significantly impact CKD management, especially in resource-limited settings such as Pakistan. I urge the scientific community and policymakers to recognize the importance of supporting and conducting research on conservative kidney management. ---Continue

Heparin therapy in sepsis and sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis

BackgroundSepsis is a life-threatening condition that affects 49 million people annually. Managing sepsis-associated coagulopathy poses a significant challenge due to its high mortality rates in intensive care. Recent reports suggest that administering heparin may offer potential survival benefits in sepsis and coronavirus disease cases. However, there is currently no established evidence supporting the use of heparin for sepsis. Thus, in this study, we aimed to assess the efficacy of heparin administration in patients with sepsis.MethodsA systematic review was conducted following the PRISMA guidelines. The searches included MEDLINE, Cochrane, and Japanese databases up to January 2023. The inclusion criteria consisted of randomized control trials (RCTs) involving adult sepsis patients receiving heparin. The risk of bias was assessed using RoB2, and the data extraction included 28-day mortality and bleeding complications.ResultsOut of 1733 initial articles, only three studies met the inclusion criteria. The analysis, which included 426 patients, showed no significant difference in 28-day and in-hospital mortality between the heparin and control groups (risk ratio [RR] = 0.86, 95% confidence interval [CI]: 0.60–1.24). Subgroup analysis of sepsis-associated disseminated intravascular coagulation (DIC) patients (n = 109) also did not show a significant reduction in mortality (RR = 0.84, 95% CI: 0.51–1.38). Heterogeneity was zero, and no publication bias was observed. Additionally, there was significant difference in bleeding complications (RR = 0.49, 95% CI: 0.24–0.99, p = 0.047).ConclusionsThis meta-analysis did not demonstrate a survival benefit of heparin administration in patients with sepsis and sepsis-associated DIC. Further investigation into the potential benefits of heparin is warranted. Moreover, the analysis revealed no increase in bleeding risks with heparin administration; instead, a significant reduction in the risk of bleeding was noted.Trial registrationThis review was preregistered with PROSPERO (registration: CRD42023385091).

Assessing the Impact of Hyperthermic Intraperitoneal Chemotherapy on Anastomotic Integrity after Cytoreductive Surgery in Gastrointestinal Malignancies

Peritoneal carcinomatosis (PC) from gastrointestinal malignancies, particularly colorectal and gastric cancers, represents a significant therapeutic challenge due to the diffuse nature of tumor spread. The combination of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a promising treatment modality, offering potential survival benefits by targeting residual microscopic disease. However, this aggressive approach is associated with a heightened risk of gastrointestinal anastomotic leaks, one of the most severe complications of gastrointestinal surgery. These leaks result from a complex interplay of factors, including hyperthermia-induced ischemia, chemotherapy-induced cytotoxicity, and a pro-inflammatory cytokine cascade involving IL-6, TNF-α, and IL-1β, which impair tissue healing. Furthermore, dysbiosis of the intestinal microbiota induced by HIPEC contributes to local inflammation and an increased risk of infection, exacerbating the likelihood of anastomotic failure. The duration and temperature of the HIPEC procedure, the extent of surgery, and the patient’s performance status and tumor burden further influence the risk of leaks. Preventive strategies such as preoperative nutritional optimization, meticulous surgical technique, intraoperative reinforcement of anastomoses, and selective use of protective ileostomies are critical for minimizing these risks. Early detection and prompt management of leaks are essential for reducing morbidity and mortality, improving both short-term and long-term outcomes. This review comprehensively examines the multifactorial causes of anastomotic leaks in the setting of CRS and HIPEC and highlights potential strategies for prevention and improved management.

Renin angiotensin system inhibitors and outcome in patients with takotsubo syndrome: A propensity score analysis of the GEIST registry

BackgroundFew data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). MethodsTTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. Registrationclinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 ResultsOf the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71±11 vs 69±13 years, p=0.01), with higher prevalence of hypertension (74%vs53%, p<0.01) and diabetes (19%vs15%, p=0.01), higher admission left ventricular ejection fraction (LVEF) (41±11% vs 39±12%, p<0.01) and lower rates of in-hospital complications (18.9% vs 29.6%, p<0.01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95%CI 0.45-0.87, p<0.01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank p=0.001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank p=0.168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in two subgroups: patients with admission LVEF ≤40% (HR 0.54 95%CI 0.38-0.78, p=0.001; HR 0.59, 95%CI 0.37-0.95, p=0.030) and diabetes (HR 0.41, 95%CI 0.23-0.73, p= 0.002; HR 0.41, 95%CI 0.21-0.82, p=0.011). ConclusionsLong-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤40% or diabetes.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Patient- vs Physician-Initiated Response to Symptom Monitoring and Health-Related Quality of Life

Online symptom monitoring through patient-reported outcomes can enhance health-related quality of life and survival. However, widespread adoption in clinical care remains limited due to various barriers including the need to reduce health care practitioners' workload. To report the effects of patient-reported outcome (PRO) symptom monitoring on HRQOL and survival up to 1 year after initiation of any treatment in patients with lung cancer. SYMPRO-Lung is a multicenter stepped-wedge cluster randomized trial including patients with stage I to IV lung cancer. The inclusion period was from October 24, 2019, until September 16, 2021, and data collection ended October 8, 2022. Data analysis was conducted from November 9, 2023, until March 18, 2024. Patients in the intervention group reported PRO symptoms weekly using the Patient Reported Outcomes version of the Common Toxicity Criteria for Adverse Events lung cancer subset. If symptoms exceeded a validated threshold, an alert was sent to the health care practitioner (active intervention subgroup) or to the patient (reactive intervention subgroup). Patients in the control group received standard care. Health-related quality of life was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at baseline, 15 weeks (T1), 6 months (T2), and 1 year (T3), with the summary score (SS) and physical functioning (PF) as primary end points. Linear mixed-effects modeling was used to assess mean differences over time. Effect size (ES) of 0.40 or greater was considered clinically relevant. Cox proportional hazards regression survival analyses were performed to estimate the effect of the intervention on progression-free survival and overall survival (OS). Data were analyzed on an intention-to-treat basis. A total of 515 patients (266 [51.7%] men; mean [SD] age, 65.4 [9.4] years) were included in the study (266 in the control group; 249 in the pooled intervention group). Most baseline characteristics were balanced between groups; however, the most notable exception was the distribution in cancer staging: the intervention group had a higher proportion of patients with stage IV cancer compared with the control group (139 [56%] vs 118 [44%]). The pooled intervention group had a significantly better SS (mean difference T1, 5.22; 95% CI, 2.72-7.73; P < .001; ES = 0.33; mean difference T2, 6.28; 95% CI, 3.65-8.92; P < .001; ES = 0.40; mean difference T3, 3.97; 95% CI, 1.15-6.80; P = .006; ES = 0.25) compared with the control group. Group differences improved more in PF but did not meet the ES greater than or equal to 0.40 threshold (mean difference T1, 7.00; 95% CI, 3.65-10.35; P < .001; ES = 0.27; mean difference T2, 6.79; 95% CI, 3.26-10.31; P < .001; ES = 0.26; mean difference T3, 5.01; 95% CI, 1.23-8.79; P = .009; ES = 0.19). No significant differences in HRQOL were observed between the reactive (n = 89) and active (n = 160) intervention groups. The HR for progression-free survival for the active intervention group compared with the control group was 0.78 (95% CI, 0.58-1.04); the finding was not statistically significant. The HR for overall survival for both interventions groups compared with the control group were not statistically significant.(active: HR, 0.80; 95% CI, 0.55-1.15; reactive: HR, 0.69; 95% CI, 0.42-1.15). In this 1-year follow-up of a stepped-wedge cluster randomized trial, PRO symptom monitoring yielded improvements in long-term HRQOL in patients with lung cancer. The reactive approach proved equally effective as the active approach. A nonsignificant potential survival benefit was observed for the intervention group. These positive results provide further evidence for the usefulness of routine PRO symptom monitoring in lung cancer care. The Netherlands trial register Identifier: NL7897.

Radiotherapy and Systemic Treatment for Leptomeningeal Disease.

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2-4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches.

Cost of ovarian cancer by the phase of care in the United States

BackgroundOvarian cancer is associated with delayed diagnosis and poor survival; thus, interest is high in identifying predictive and prognostic biomarkers and novel therapeutic agents.Although the costs of ovarian cancer care are likely to increase as newer, more effective, but more expensive treatment regimens become available, information on the current costs of care for ovarian cancer—across the care continuum from diagnosis to the end of life—are lacking. ObjectiveThis study aimed to estimate real-world mean and median costs of ovarian cancer care within the first 5 years after diagnosis by patients’ phase of care, age, race/ethnicity, and geographic region. Study DesignWe performed a retrospective cohort study of ovarian cancer patients diagnosed between January 1, 2015 and December 31, 2020. We used claims data from Optum’s de-identified Clinformatics® Data Mart database, which includes inpatient, outpatient, and prescription claims for commercial insurance and Medicare beneficiaries nationwide. Cost of ovarian cancer care were calculated for the start of care (ie, the first 6 months), continuing care (ie, period between the initial and end-of-life care), and end-of-life care (ie, the last 6 months) phases and reported in 2021 U.S. dollar amounts. Ovarian cancer care costs were stratified by age, race/ethnicity, and geographic region. Due to the skewed nature of cost data, the mean cost data were log-transformed for modelling. Ordinary least-squares regression was conducted on the log costs, adjusting for patient categorical age, race/ethnicity, and geographic region. ResultsA total of 7913 patients were included in the analysis. The mean cost per year for ovarian cancer care was >$200,000 during the start of care, between $26,000 and $88,000 during the continuing care phase, and >$129,000 during the end-of-life care phase. There were statistically significant associations between age and costs during each phase of care. Compared to younger patients, older patients incurred higher costs during the continuing care phase and lower costs during the end-of-life care phase. Geographic differences in the costs of ovarian cancer care were also noted regardless of the phase of care. There were no associations between cost and race/ethnicity in our cohort. ConclusionsOvarian cancer care costs are substantial and vary by the phase of care, age category, and geographic region. As more effective but expensive treatment options for ovarian cancer become available with potential survival benefit, sustainable interventions to reduce the cost of care for ovarian cancer will be needed throughout the cancer care continuum.