Survival Outcomes Research Articles

Targeted Radionuclide Therapy for the Treatment of Metastatic Bone Disease: A Retrospective Analysis in Moscow, Russia

Introduction: Metastatic bone disease (MBD) is a common complication of advanced cancer, causing significant morbidity and negatively impacting patients' quality of life. Targeted radionuclide therapy (TRT) has emerged as a promising treatment modality for MBD, offering targeted delivery of therapeutic radiation to bone metastases while minimizing damage to healthy tissues. Methods: A retrospective cohort study was conducted at leading oncology centers in Moscow, Russia, between 2018 and 2023. Patients with MBD who received TRT with either Strontium-89 or Samarium-153 were included. Data on patient demographics, primary tumor type, number of bone metastases, pre-treatment pain scores, performance status, and survival outcomes were collected. Results: A total of 150 patients were included in the study (mean age 62 years, 55% female). The most common primary tumor types were prostate (35%), breast (25%), and lung (15%). The median number of bone metastases was 5 (range 1-20). Pre-treatment pain scores were high (median 7 on a 0-10 scale). A significant reduction in pain scores was observed post-TRT (median 3, p<0.001). Overall survival at 1 year was 75%, with a median survival of 18 months. Favorable prognostic factors included a lower number of bone metastases, good performance status, and absence of visceral metastases. Conclusion: TRT is a safe and effective treatment option for patients with MBD in Moscow, Russia, offering significant pain palliation and improved quality of life.

Outcomes of lymphoma patients admitted to the ICU are not influenced by HIV status: a retrospective, observational cohort study.

Lymphoma patients may require intensive care (ICU) due to disease- or treatment-related complications. The lymphoma-HIV interaction complicates management, but whether outcomes are worse in these patients, when critically ill, is unclear. A retrospective observational cohort study reviewed outcomes of patients admitted to ICU, subsequent 5-year survival, and prognostic factors. General ICU at the UK National Centre for HIV Malignancy. Records between 2007-2020, identified the following cohorts: HIV lymphoma, lymphoma-alone, HIV-alone and patients without HIV/lymphoma. Patient demographics, lymphoma characteristics, ICU admission data, and survival outcomes were collected. Five-year survival outcomes were analyzed for the lymphoma cohorts. ICU outcomes were analyzed for all cohorts. Descriptive statistics summarized baseline characteristics and outcomes. Multivariate regression identified factors associated with ICU mortality. Of 5929 patients admitted to the ICU, 63 had HIV lymphoma and 43 had lymphoma-alone. Survival to ICU discharge was 71% and 72%, respectively. Adjusted log-odds ratio for ICU survival was significantly better in the comparator cohort. ICU survival between the HIV lymphoma and lymphoma-alone cohorts was not significantly different. Adjusted 5-year survival was not significantly different between lymphoma cohorts. Factors independently associated with a worse ICU survival prognosis were emergency admissions, APACHE II score, initial lactate, and day requiring level 3 support. Mechanical ventilation and higher APACHE II scores were independent risk factors for worse 5-year survival in the lymphoma cohorts. ICU outcomes and 5-year survival rates of lymphoma patients were unaffected by HIV status, revealing favorable outcomes in patients with HIV-related lymphoma admitted to the ICU.

WP3.11 - Emergency laparotomies in the elderly: long term outcomes

Abstract Aims Emergency laparotomy is understood to be high risk in the elderly, but there is limited long term outcome data. This study assesses long term outcomes in the elderly including: survival and functional outcomes. Methods Patients, aged 80 and above, were identified from the prospective National Emergency Laparotomy Audit (NELA) database, who underwent surgery between: January 2020 and August 2023 at Torbay Hospital. Surviving patients were followed up. Results 132 cases were undertaken (22% of total emergency laparotomies performed). Mean age was 85 years. Most common ASA was 3. Preoperatively, the most common clinical frailty score was 6, i.e., moderately frail and 89% were living at home without care. The most common procedure was adhesiolysis. 50% of patients were admitted to intensive care. 5 patients returned to theatre. 17% were readmitted within 30 days of discharge. The most common reason for was fall. 20% of patients did not survive to discharge. 38% did not survive to August 2023. After the procedure 46% of patients were able to return home independently; 5% had care at home; 26% were discharged to community hospital and 2% to care home. By January 2024 61% of survivors were living independently at home with no functional decline. Most commonly, patients needed support with bathing/stairs/dressing (37%). 11% of respondents were completely dependent. Conclusion Emergency laparotomy confers a significant mortality, morbidity and risk to an elderly patient’s long term functional status. We believe this information is essential for surgical decision making and the consent process.

Shape matters: unsupervised exploration of IDH-wildtype glioma imaging survival predictors

Abstract Objectives This study examines clustering based on shape radiomic features and tumor volume to identify IDH-wildtype glioma phenotypes and assess their impact on overall survival (OS). Materials and methods This retrospective study included 436 consecutive patients diagnosed with IDH-wt glioma who underwent preoperative MR imaging. Alongside the total tumor volume, nine distinct shape radiomic features were extracted using the PyRadiomics framework. Different imaging phenotypes were identified using partition around medoids (PAM) clustering on the training dataset (348/436). The prognostic efficacy of these phenotypes in predicting OS was evaluated on the test dataset (88/436). External validation was performed using the public UCSF glioma dataset (n = 397). A decision-tree algorithm was employed to determine the relevance of features associated with cluster affiliation. Results PAM clustering identified two clusters in the training dataset: Cluster 1 (n = 233) had a higher proportion of patients with higher sphericity and elongation, while Cluster 2 (n = 115) had a higher proportion of patients with higher maximum 3D diameter, surface area, axis lengths, and tumor volume (p < 0.001 for each). OS differed significantly between clusters: Cluster 1 showed a median OS of 23.8 compared to 11.4 months of Cluster 2 in the holdout test dataset (p = 0.002). Multivariate Cox regression showed improved performance with cluster affiliation over clinical data alone (C index 0.67 vs 0.59, p = 0.003). Cluster-based models outperformed the models with tumor volume alone (evidence ratio: 5.16–5.37). Conclusion Data-driven clustering reveals imaging phenotypes, highlighting the improved prognostic power of combining shape-radiomics with tumor volume, thereby outperforming predictions based on tumor volume alone in high-grade glioma survival outcomes. Clinical relevance statement Shape-radiomics and volume-based cluster analyses of preoperative MRI scans can reveal imaging phenotypes that improve the prediction of OS in patients with IDH-wild type gliomas, outperforming currently known models based on tumor size alone or clinical parameters. Key Points Shape radiomics and tumor volume clustering in IDH-wildtype gliomas are investigated for enhanced prognostic accuracy. Two distinct phenotypic clusters were identified with different median OSs. Integrating shape radiomics and volume-based clustering enhances OS prediction in IDH-wildtype glioma patients.

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UPS in conjunction with immune checkpoint-associated proteins, and combining these with other therapeutic approaches, may significantly enhance the efficacy of combination therapies and pave the way for novel cancer treatment strategies. In this review, we first summarize the composition and alterations of the TIME, with a particular emphasis on the role of the UPS in TIME and its interactions with various immune cell types. Finally, we explore the potential of combining UPS-targeted therapies with immunotherapy to substantially improve the effectiveness of immunotherapy and enhance patient survival outcomes.

Radiomics analysis of cerebral blood flow suggests a possible link between perfusion homogeneity and poor glioblastoma multiforme prognosis

Objectives. This study investigates the association between cerebral blood flow (CBF) and overall survival (OS) in glioblastoma multiforme (GBM) patients receiving chemoradiation. Identifying CBF biomarkers could help predict patient response to this treatment, facilitating the development of personalized therapeutic strategies. Materials and Methods. This retrospective study analyzed CBF data from dynamic susceptibility contrast (DSC) MRI in 30 newly diagnosed GBM patients (WHO grade IV). Radiomics features were extracted from CBF maps, tested for robustness, and correlated with OS. Kaplan-Meier analysis was used to assess the predictive value of radiomic features significantly associated with OS, aiming to stratify patients into groups with distinct post-treatment survival outcomes. Results. While mean relative CBF and CBV failed to serve as independent prognostic markers for OS, the prognostic potential of radiomic features extracted from CBF maps was explored. Ten out of forty-three radiomic features with highest intraclass correlation coefficients (ICC > 0.9), were selected for characterization. While Correlation and Zone Size Variance (ZSV) features showed significant OS correlations, indicating prognostic potential, Kaplan-Meier analysis did not significantly stratify patients based on these features. Visual analysis of the graphs revealed a predominant association between the identified radiomic features and OS under two years. Focusing on this subgroup, Correlation, ZSV, and Gray-Level Nonuniformity (GLN) emerged as significant, suggesting that a lack of heterogeneity in perfusion patterns may be indicative of a poorer outcome. Kaplan-Meier analysis effectively stratified this cohort based on the features mentioned above. Receiver operating characteristic (ROC) analysis further validated their prognostic value, with ZSV demonstrating the highest sensitivity and specificity (0.75 and 0.85, respectively). Conclusion. Our findings underscored radiomics features sensitive to CBF heterogeneity as pivotal predictors for patient stratification. Our results suggest that these markers may have the potential to identify patients who are unlikely to benefit from standard chemoradiation therapy.

Association of body composition and systemic inflammation for patients with locally advanced cervical cancer following concurrent chemoradiotherapy

Systemic inflammation and body composition are associated with survival outcomes of cancer patients. This study aimed to examine the combined prognostic value of systemic inflammatory markers and body composition parameters in patients with locally advanced cervical cancer (LACC). Patients who underwent concurrent chemoradiotherapy (CCRT) for LACC at a tertiary referral teaching hospital between January 2010 and January 2018 were enrolled. A predictive model was established based on systemic immune-inflammation index (SII) and computer tomography-derived visceral fat-to-muscle ratio (vFMR). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox regression models. The model performance was assessed using discrimination, calibration, and clinical usefulness. In total, 212 patients were enrolled. The SII and vFMR were closely related, and both independently predicted survival (P < 0.05). A predictive model was established based on the above biomarkers and included three subgroups: high-risk [both high SII (>828) and high vFMR (>1.1)], middle-risk (either high SII or high vFMR), and low-risk (neither high SII nor high vFMR). The 3-year OS (PFS) rates for low-, middle-, and high-risk patients were 90.5% (86.0%), 73.9% (58.4%), and 46.8% (36.1%), respectively (P < 0.05). This model demonstrated satisfactory predictive accuracy (area under the curve values for predicting 3-year OS and PFS were 0.704 and 0.718, respectively), good fit (Hosmer-Lemeshow tests: P > 0.05), and clinical usefulness. Systemic inflammatory markers combined with body composition parameters could independently predict the prognosis of patients with LACC, highlighting the utilization of commonly collected indicators in decision-making processes. The SII and vFMR, as well as their composite indices, were promising prognostic factors in patients with LACC who received definitive CCRT. Future studies are needed to explore novel therapies to improve the outcomes in high-risk patients.

Prevalence and outcomes of gastrointestinal manifestations in an Australian Scleroderma cohort.

The gastrointestinal tract (GIT) is the most commonly affected internal organ in systemic sclerosis (SSc). We sought to determine the prevalence and impact of GIT symptoms on survival and patient-reported outcomes. 907 consecutive patients from the Australian Scleroderma Cohort Study (ASCS) who had prospectively completed the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 questionnaire (UCLA GIT) between 2015 and 2021 were included. The association between UCLA GIT scores and physical function (SHAQ), QoL (SF-36), mood (PROMIS anxiety and depression domains), fatigue (FACIT-fatigue score) and employment was investigated using multivariable population-averaged panel models using Generalized Estimating Equations (GEE). Kaplan-Meier curves and multivariable Cox proportional hazard regression model were used to evaluate survival according to total UCLA GIT scores. GIT symptoms were reported in 87% of participants with 46-52% reporting moderate to very severe symptoms of reflux, distension, diarrhoea and constipation. Higher total UCLA GIT scores were associated with worse QoL, physical function, fatigue, anxiety and depression (p<0.001). In multivariable GEE analysis, moderate and severe to very severe total scores, reflux and distension scores were associated with worse physical function, QoL, fatigue, anxiety and depression compared to those with mild scores (p<0.05). Patients with severe total scores and diarrhoea scores were more likely to be unemployed compared to those with mild scores (p<0.05). UCLA GIT total scores were not independently associated with mortality in our cohort. GIT manifestations are common in SSc and negatively impact QoL, physical function and employment but are not directly associated with increased mortality.

A Quality Approach to Blinatumomab Delivery in Pediatric Oncology: A Children's Oncology Group Study.

Background: Blinatumomab is a promising immunotherapy agent that has been shown to improve survival outcomes in children diagnosed with relapsed B-lineage acute lymphoblastic leukemia. Expanded use of blinatumomab in the treatment of childhood cancer is expected; however, clinician perspectives regarding administering this agent in healthcare and home settings have not been explored. Method: Semistructured interviews were conducted with clinicians (N = 13) from pediatric institutions across the United States and Canada. Qualitative data were analyzed using a constant comparative analysis three-stage method. Results: Participants were primarily nurses (92%), female (77%), and had greater than 10 years of pediatric oncology experience. The selective code and overarching theme identified was "A quality approach to blinatumomab delivery in pediatric oncology." Clinicians described detailed processes that were created and implemented to promote a common goal of safe blinatumomab administration across the continuum of care. Clinicians shared how they engaged in planning activities and considered a variety of factors prior to and during blinatumomab administration. Clinicians also expressed a need to reflect and evaluate on previous patient experiences to create new or revise existing processes and workflows. Communication was also central to clinicians' work. Clinicians provided recommendations to assist others with blinatumomab administration and offered suggestions for items that could help with implementing future clinical trials containing similar agents. Discussion: Findings suggest nurses are pivotal to establishing processes which support safe administration of immunotherapies, such as blinatumomab, while also considering patient-specific needs and promoting quality of life.

Impact of Facility Volume on Overall Survival in Patients With Head and Neck Cancer Undergoing Palliative Treatment.

Treatment at high-volume facilities (HVF) has been associated with improved prognosis of HNC patients undergoing curative treatment. Whether this systemic factor influences survival outcomes of patients with HNC undergoing palliative treatment is unknown. To investigate the impact of palliative treatment facility volume on overall survival (OS) in patients with head and neck cancer (HNC). The 2004 to 2018 National Cancer Database was queried retrospectively for patients with HNC undergoing palliative treatment. Patients were stratified based on treatment facility volume percentile. Multivariable binary logistic and Cox proportional hazards regression models were implemented. Of 8682 patients included, 1661 (19.1%) underwent palliative therapy at facilities with volume ≥80th percentile. Among 972 facilities included, 643 (66.2%), 182 (18.7%), 85 (8.8%), 44 (4.5%), and 18 (1.9%) had volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentiles, respectively. 5-year OS rates of patients undergoing palliative therapy at facilities with volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentile was 11%, 13%, 11%, 14%, and 23%, respectively (P < .001). Facility volume ≥80th percentile was associated with higher 5-year OS on multivariable Cox regression (aHR 0.34, 95% CI 0.16-0.69, P < .001). Surgical treatment (aOR 1.34, 95% CI 1.07-1.68, P = .012) was associated with undergoing treatment at facilities with volume ≥80th percentile. Undergoing palliative treatment at HVFs is associated with higher OS in HNC. The survival benefit derived from high facility volume should be carefully considered in the context of other patient and facility characteristics in end-of-life management, with specific emphasis on patient-directed goals of care.

Brain Metastases as Inaugural Sign of Non-Small Cell Lung Carcinoma: Case Series and Review of Literature.

In the era of immune checkpoint inhibitors (ICI), managing non-oncogene driven non-small cell lung cancer (NSCLC) with brain metastases (BM) is challenging, especially when brain involvement is the initial sign. Patients with newly diagnosed brain metastatic NSCLC without epidermal growth factor receptor (EFGR) nor anaplastic lymphoma kinase (ALK) alterations were retrospectively included. Twenty-five patients were analyzed; 15 (60%) had symptomatic BM as the first sign (group 1), while 10 (40%) had BM discovered during complementary examinations (group 2). Fourteen patients (56%) had concomitant extracerebral metastases, primarily in group 2. Eight (32%) had oligometastatic disease, with seven in group 1. Over half received chemotherapy and pembrolizumab as first-line treatment. BM surgical resection occurred in twelve (80%) patients in group 1 and one in group 2. Median cerebral progression-free survival was 10 months: 12 in group 1 and 5 in group 2. Median overall survival was 25 months: not reached in group 1 and 6 months in group 2. This case series highlights survival outcomes for patients with inaugural BM, a demographic underrepresented in pivotal trials. Oligometastatic disease and symptomatic BM as initial signs seem associated with better prognosis due to increased use of multimodal local approaches. Combining local approaches with first-line ICI+/- chemotherapy appears to improve survival in brain metastatic NSCLC. A literature review was conducted to explore key questions regarding upfront ICI alone or in combination with systemic drugs or local approaches in brain metastatic NSCLC.

Familial adenomatous polyposis: a case report

BackgroundFamilial adenomatous polyposis is characterized by the presence of multiple colorectal adenomatous polyps and caused by germline mutations in the tumor suppressor gene and adenomatous polyposis coli, located on chromosome 5q21–q22. Familial adenomatous polyposis occurs in approximately 1/10,000 to 1/30,000 live births, and accounts for less than 1% of all colorectal cancers in the USA. It affects both sexes equally and has a worldwide distribution. The incidence of colon cancer in low- and middle-income countries is rising. In addition to the increasing incidence, lack of early detection and impeded access to optimal multidisciplinary treatment may worsen survival outcomes. Developing quality diagnostic services in the proper health context is crucial for early diagnosis and successful therapy of patients with colorectal cancer, and applying a resource-sensitive approach to prioritize essential treatments on the basis of effectiveness and cost-effectiveness is key to overcoming barriers in low- and middle-income countries. We report a case of familial adenomatous polyposis presenting as adenocarcinoma with multiple colorectal adenomatous polyps. The diagnosis of familial adenomatous polyposis was made by the presence of numerous colorectal adenomatous polyps and family history of colonic adenocarcinoma. Due to its rarity, we decided to report it.Case presentationA 22-year-old Ethiopian female patient presented to Addis Ababa University College of Health science, Addis Ababa, Ethiopia with rectal bleeding. Abdominopelvic computed tomography scan was done and showed distal rectal asymmetric anterior wall thickening in keeping with rectal tumor. Colonoscopy was done and she was diagnosed to have familial adenomatous polyposis with severe dysplasia. In the meantime, colonoscopy guided biopsy was taken and the diagnosis of adenocarcinoma with familial adenomatous polyposis was rendered. For this, total proctocolectomy was carried out. On laparotomy there was also incidental finding of left ovarian deposition for which left salpingo-oophorectomy was done, and 4 weeks after surgical resection, the patient was started on oxaliplatin, leucovorin, fluorouracil chemotherapy regimen.ConclusionIn the clinical evaluation of a patient with rectal bleeding, familial adenomatous polyposis must be considered as a differential diagnosis in subjects having family history of colonic adenocarcinoma for early diagnostic workup, management, family genetic counseling, and testing.

Mitochondria and Acute Leukemia: A Clinician's Perspective.

Acute leukemia is a group of aggressive hematological malignancies, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the most common types. The biology of acute leukemia involves complex genetic and epigenetic alterations that lead to uncontrolled cell proliferation and resistance to apoptosis. Mitochondrial dysfunction is a feature of acute leukemia that results in altered energy production, unregulated cell death pathways, and increased cancer cell survival. Apoptosis, particularly via the mitochondrial pathway, is crucial for cellular homeostasis and cancer prevention. In acute leukemia, disruption of apoptosis is pivotal in disease development and progression, with elevated levels of anti-apoptotic proteins conferring a survival advantage to leukemia cells and promoting resistance to conventional therapies. Targeting mitochondrial apoptosis using BH3 mimetics and anti-apoptotic protein inhibitors is a viable therapeutic strategy. Alterations in the mitochondrial membrane potential, metabolism, and dynamics also contribute to the pathogenesis of acute leukemia. Continued research is vital for developing novel therapies and enhancing survival outcomes in patients with acute leukemia while minimizing the long-term adverse effects of treatment. In this narrative review, we provide a birds-eye view of the available scientific literature on the importance of mitochondria in acute leukemia, and discuss the role of BH3 mimetics in targeting the mitochondrial internal apoptotic machinery.

Association between Levetiracetam Use and Survival in Patients with Glioblastoma: A Nationwide Population-Based Study.

This study aimed to investigate whether levetiracetam (LEV), the most used antiepileptic drug, influences survival in patients with glioblastoma (GBM), using a national database. This study used data from the Korea Health Insurance Review and Assessment database. Patients diagnosed with GBM between 2007-2018 treated with standard therapy were included. The study population was divided into long-term (≥60 days) and short-term (<30 days) LEV groups. A separate long-term valproic acid (VPA) group (≥60 days) was identified for comparison. Demographics, disease characteristics, and treatment parameters were collected. Kaplan-Meier method and Cox regression were used to compare survival outcomes between the groups. Overall, 2,971 patients were included, with 1,319 and 1,652 in the short-term and long-term LEV groups, respectively. The median overall survival (OS) for the entire population was 19.15 months post-surgery. Kaplan-Meier analysis revealed a significantly longer median OS in the long-term LEV group versus the short-term LEV group. After adjusting for confounders, Cox proportional hazard analysis revealed an association of long-term LEV use with improved survival, which was also observed in a subgroup analysis of patients without preoperative seizure history. The long-term LEV group demonstrated longer median OS, compared with the long-term VPA group. Our nationwide population-based study found an association between long-term LEV use and improved survival in patients with GBM, regardless of preoperative seizure history. Prospective studies are needed to validate these findings and investigate the potential impact of LEV on the survival outcomes of patients with GBM.

Ventilatory pressure parameters impact the association between acute gastrointestinal injury and all-cause mortality in mechanically ventilated patients

Acute gastrointestinal injury (AGI) is common in mechanically ventilated (MV) patients, but the potential association between ventilatory pressure parameters and AGI grade and their impact on mortality remains unclear. This study aimed to explore the association between ventilatory pressure parameters and AGI grade, and their interaction on all-cause mortality in MV patients. This study was a secondary analysis of a multicenter, prospective, observational study that enrolled adult patients with an expected duration of mechanical ventilation ≥ 48 h from 14 general intensive care units in Zhejiang Province between March and August 2014. The AGI grade was assessed daily on the basis of gastrointestinal symptoms, intra-abdominal pressures, and feeding intolerance in the first week of admission to the ICU. This study included 331 patients (69.2% men; mean age, 64.6 ± 18.9 years). Multivariate regression analysis showed that plateau pressure (Pplat) (OR 1.044, 95% CI 1.009–1.081, P = 0.013), serum creatinine (OR 1.003, 95% CI 1.001–1.006, P = 0.042) and APACHE II score (OR 1.035, 95% CI 1.021–1.072, P = 0.045) were independently associated with global AGI grade III/IV within 7 days of ICU admission. Moreover, global AGI grade (HR 2.228, 95% CI 1.561–3.182, P < 0.001), serum creatinine (HR 1.002, 95% CI 1.001–1.003, P = 0.012) and APACHE II score (HR 1.039, 95% CI 1.015–1.063, P = 0.001) were independently associated with 60-day mortality. In addition, there were significant (Pint ≤ 0.028) interactions of Pplat and DP with AGI grade in relation to 60-days mortality, whereas no interaction (Pint = 0.061) between PEEP and AGI grade on 60-days mortality was observed. In the presence of Pplat ≥ 19 cmH2O, the patients with AGI grade III/IV had 60-day mortality rate of 72.2%, significantly higher than those with AGI grade I/II (48.7%, P = 0.018), whereas there were no significant differences (27.9% vs. 33.7%, P = 0.39) in 60-days mortality between AGI grade I/II and III/IV among the patients with Pplat < 19 cmH2O. In comparison with Pplat, DP had a similar interaction (Pint = 0.028) with AGI grade on 60-day mortality. Ventilatory pressure parameters (Pplat and DP) are independent risk factors of AGI grade III/IV. Pplat and DP interact with AGI grade on 60-days mortality, highlighting the importance of optimizing ventilatory pressure parameters to improve gastrointestinal function and survival outcomes of MV patients.Trial registration: ChiCTR-OCS-13003824.

Efficacy of PARP inhibitor therapy after targeted BRAF/MEK failure in advanced melanoma

Modern advancements in targeted therapy and immunotherapy have significantly improved survival outcomes for advanced melanoma; however, there remains a need for novel approaches to overcome disease progression and treatment resistance. In recent years, PARPi therapy has shown great promise both as a single regimen and in combination with other therapeutics in melanoma. Here, we describe three unique cases of advanced BRAF V600 mutated melanoma that progressed on targeted BRAF/MEK agents that subsequently exhibited partial to near-complete responses to combinatory PARPi and BRAF/MEK inhibitors. This highlights both a potential synergy underlying this combinatory approach and its efficacy as a treatment option for patients with advanced melanoma refractory to targeted and/or immunotherapies. Prospective clinical trials are needed to explore this synergic effect in larger melanoma cohorts to investigate this combination for treating refractory advanced melanoma.

A Contrastive-Learning-Based Deep Neural Network for Cancer Subtyping by Integrating Multi-Omics Data.

Accurate identification of cancer subtypes is crucial for disease prognosis evaluation and personalized patient management. Recent advances in computational methods have demonstrated that multi-omics data provides valuable insights into tumor molecular subtyping. However, the high dimensionality and small sample size of the data may result in ambiguous and overlapping cancer subtypes during clustering. In this study, we propose a novel contrastive-learning-based approach to address this issue. The proposed end-to-end deep learning method can extract crucial information from the multi-omics features by self-supervised learning for patient clustering. By applying our method to nine public cancer datasets, we have demonstrated superior performance compared to existing methods in separating patients with different survival outcomes (p < 0.05). To further evaluate the impact of various omics data on cancer survival, we developed an XGBoost classification model and found that mRNA had the highest importance score, followed by DNA methylation and miRNA. In the presented case study, our method successfully clustered subtypes and identified 14 cancer-related genes, of which 12 (85.7%) were validated through literature review. Our findings demonstrate that our method is capable of identifying cancer subtypes that are both statistically and biologically significant. The code about COLCS is given at: https://github.com/Mercuriiio/COLCS .

Dietary Counseling Outcomes in Patients with Lung Cancer in an Upper-Middle-Income Country: An Open-Label Randomized Controlled Trial.

Background: Malnutrition harms treatment outcomes, QoL, and survival in lung cancer patients. Effective dietary counseling can improve nutrition, but few randomized controlled trials have focused on lung cancer patients. The objective of this study was to determine if dietary counseling improves nutritional and treatment outcomes when compared to routine care. Methods: This open-label parallel RCT was conducted at Maharaj Nakorn Chiang Mai Hospital in Thailand. The investigators used computer-generated blocked randomization to assign patients to dietary counseling by a nutritionist or routine care. The nutritionist sessions occurred before treatment, with follow-ups at 3-4 weeks and 12 weeks. The primary outcome was the mean percentage change in the body weight of patients at 12 weeks. Secondary outcomes included changes in the BMI, nutrition score, QoL, serum albumin level, lymphocyte count, energy and protein intake, treatment response, PFS, and OS. Results: Between April 2020 and May 2022, after completing recruitment, 80 lung cancer patients were randomized: 43 to dietary counseling and 37 to routine care. The dietary counseling group showed significant benefits, with smaller decreases in body weight at 3-4 weeks (-0.8% vs. -2.6%, p = 0.05) and 12 weeks (-1.1% vs. -4.3%, p = 0.05). They also had higher energy and protein intake levels and better treatment response rates. The secondary outcomes and significant adverse events did not differ significantly between the groups. Conclusions: Dietary counseling helps to maintain body weight, maintain dietary intake, and enhance treatment responses in lung cancer patients. Although not all nutritional markers or survival outcomes were affected, these findings highlight the importance of early nutritional interventions.

Role of midline raphe in compartmental surgery for squamous cell carcinoma of the tongue.

In the present study, we investigated how tumor distance from midline (TDFM) and depth of invasion (DOI) may affect survival outcomes after compartmental tongue surgery (CTS) for oral tongue squamous cell carcinoma (OTSCC). A retrospective series of cT2-T3 OTSCC treated with upfront CTS at our Department from 2010 to 2021 was evaluated. Radiological and pathological DOI and TDFM were correlated. The main outcomes were overall (OS) and loco-regional recurrence free survival (LRRFS). The linear relationship between DOI and TDFM with 2-year OS and LRRFS was tested. Survival estimates were obtained by the Kaplan-Meier method. Univariate analysis was performed for variables of interest, and results expressed in terms of hazard ratios and 95% confidence intervals. A total of 64 patients underwent CTS and neck dissection. No significant difference was found between pathological (pDOI) and radiological DOI (rDOI) (p = 0.321) or between pathological (pTDFM) and radiological TDFM (p = 0.435). Two- and 5-year OS and LRRFS were 85.7% and 70.4%, 84.3% and 76.1%, respectively. A linear and significant relationship with OS (p = 0.020) and LRRFS (p = 0.013) was found for pDOI; although linear, the relationship between pTDFM was not statistically significant for either survival outcomes. Once categorized, the ideal cut-off for pDOI according to OS was set at 10mm (p = 0.023). In patients undergoing CTS for primary OTSCC, magnetic resonance-derived rDOI represents an accurate estimate of pDOI, In contrast, TDFM was not associated with OS suggesting that the median raphe is a safe deep margin for CTS. BS/231,009 retrospectively registered.

Rethinking Surgical Margins: A New Approach to Predict Outcomes in Oral Squamous Cell Carcinoma.

The traditional categorical division of surgical margins using a 5 mm cutoff in oral cavity squamous cell carcinoma (OCSCC) is controversial. The primary aim of this study was to investigate the presence of an optimal cutoff point or, alternatively, assess the potential improvement in predictive value by considering the surgical margins as a continuum. Retrospective analysis of OCSCC patients at a tertiary medical center in 1995-2020. Clinical, pathological, and surgical data were evaluated for effect on survivability by regression analyses. The cohort included 266 patients (48.1% male, mean age 65.4 ± 17.7). Patient stratification by categorical margin status yielded no significant between-group differences in survival (p = 0.54). Significance was achieved when margin distance was reevaluated as a continuous variable (p = 0.0018). Similar results were shown in local control (categorical p = 0.59 vs. continuous p = 0.06). Multivariate model excluded possible confounders. A predictive model was created to provide a more accurate prediction of survival. The continuum spectrum of margin distance better predicts survival outcomes and locoregional control in OCSCC. 3 Laryngoscope, 2024.