Survival Benefit Research Articles

Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer.

Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS. We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023. Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX. This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial.

Postoperative Radiotherapy in Advanced Stage Squamous Cell Carcinoma Requiring Maxillectomy.

To evaluate whether postoperative radiotherapy (PORT) improves survival among patients who received maxillectomy for pT4aN0 maxillary gingival or hard palate squamous cell carcinoma (SCC) with respect to tumor size. Retrospective analysis. National Cancer Database from 2004 to 2019. Included adult patients who received maxillectomy (partial, subtotal, or total) and neck dissection for treatment-naive margin negative pT4aN0 SCC of the maxillary gingiva or hard palate. Adjusted for age, gender, race, insurance status, income, education, urban/rural, facility type, region, comorbidity index, tumor grade, and tumor extension. Inverse probability weights were incorporated into a multivariable Cox proportional hazards model. A priori post hoc subgroup analysis was performed according to tumor size. We included 416 patients who underwent maxillectomy for pT4aN0 SCC of the maxillary gingiva or hard palate (mean [standard deviation] age, 71.5 [11.3] years; male, 190 [45.7%]; tumor size 2 cm, 362 [87%]). Overall, 49.3% of patients received PORT (205 patients). PORT was associated with a 50% improvement in survival compared to surgery alone (adjusted hazard ratio [aHR], 0.50; 95% confidence interval [95% CI], 0.32-0.81). On subgroup analysis, PORT was associated with improved survival for tumors 2 cm (aHR, 0.47; 95% CI, 0.29-0.77), but not for tumors < 2 cm (aHR, 1.15; 95% CI, 0.33-4.08). The vast majority of patients with pT4aN0 bone-invading SCC of the maxillary gingiva and hard palate benefit from PORT. Patients with tumors < 2 cm did not demonstrate a survival benefit from adjuvant treatment, suggesting that bony invasion alone may not be sufficient criteria for treatment escalation.

Survival benefit associated with screening of patients at elevated risk for pancreatic cancer.

All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma(PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.

Knockdown of swine leukocyte antigen expression in porcine lung transplants enables graft survival without immunosuppression.

Immune rejection remains the major obstacle to long-term survival of allogeneic lung transplants. The expression of major histocompatibility complex molecules and minor histocompatibility antigens triggers allogeneic immune responses that can lead to allograft rejection. Transplant outcomes therefore depend on long-term immunosuppression, which is associated with severe side effects. To address this problem, we investigated the effect of genetically engineered transplants with permanently down-regulated swine leukocyte antigen (SLA) expression to prevent rejection in a porcine allogeneic lung transplantation (LTx) model. Minipig donor lungs with unmodified SLA expression (control group, n = 7) or with modified SLA expression (treatment group, n = 7) were used to evaluate the effects of SLA knockdown on allograft survival and on the nature and strength of immune responses after terminating an initial 4-week period of immunosuppression after LTx. Genetic engineering to down-regulate SLA expression was achieved during ex vivo lung perfusion by lentiviral transduction of short hairpin RNAs targeting mRNAs encoding β2-microglobulin and class II transactivator. Whereas all grafts in the control group were rejected within 3 months, five of seven animals in the treatment group maintained graft survival without immunosuppression during the 2-year monitoring period. Compared with controls, SLA-silenced lung recipients had lower donor-specific antibodies and proinflammatory cytokine concentrations in the serum. Together, these data demonstrate a survival benefit of SLA-down-regulated lung transplants in the absence of immunosuppression.

Efficacy and safety of pyrotinib-based regimens in HER2 positive metastatic breast cancer: A retrospective real-world data study

ObjectivePyrotinib is a novel irreversible tyrosine kinase inhibitor that has shown efficacy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). This study explored the efficacy and safety of pyrotinib in the treatment of HER2-positive MBC patients in the real world. MethodsFrom September 2018 to February 2022, 137 female patients with HER2-positive MBC treated in this center were enrolled in this study. The follow-up period ended on January 12, 2023. The primary endpoint of this study was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), central nervous system (CNS)-PFS, CNS-ORR, CNS-CBR, CNS-DCR, and adverse event (AE) were the secondary endpoints. ResultsThe ORR, DCR and CBR were 41.98 % (55/131), 87.79 % (115/131) and 44.27 % (58/131) in this cohort, respectively. The median PFS for this cohort was 10.37 months [95 % confidence interval (CI): 9.205-11.535] and the median OS was 37.53 months (not reached). Univariate and multivariate analyses showed that trastuzumab sensitivity was an independent predictor of improved PFS [hazard ratio (HR): 0.579 (0.371-0.904, p=0.016)] and improved OS [0.410 (0.213-0.790, p=0.008)]. Patients treated with a pyrotinib-based regimen as second-line and third-or-post-line therapy had poorer PFS [second-line: 3.315 (1.832-6.000, p<0.001); third-or-post-line: 3.304 (1.749-6.243, p<0.001)] and OS [second-line: 4.631 (1.033-20.771, p=0.045); third-or-post-line: 5.738 (1.212-27.174, p=0.028)]. There were 38 brain metastases (BM) patients in this study, the CNS-mPFS [14.37 months (7.815-20.925) vs. 7.83 months (7.047-8.613), p=0.375] and mOS [not reached vs. 36.40 months (18.551-54.249), p=0.034] were better in brain radiotherapy (BRT) group than NBRT group. 18.98 % (26/137) of patients experienced grade 3 or higher diarrhea. No AE-related death was reported. ConclusionThis study confirms the promising antitumor activity and acceptable safety of real-world pyrotinib-based regimens for the treatment of HER2-positive MBC patients, particularly those who are trastuzumab-sensitive and who are receiving pyrotinib-based regimens as advanced first-line therapy. It has also been demonstrated that these regimens combined with BRT, provide better intracranial responses and long-term survival benefits for these patients with BM.

Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease.

Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease.

Icotinib in a lung adenocarcinoma patient with acquired EGFR 19del/C797S mutation-mediated resistance to osimertinib: a case report.

Based on the FLAURA and AURA III trials, compared to first- and second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), osimertinib provides a longer overall survival benefit for patients with untreated EGFR mutated non-small cell lung cancer. Similar to other EGFR-TKIs, drug resistance is, however, inevitable. The most common mechanism of acquired resistance to first-line osimertinib therapy is the C797S mutation, which accounts for 6% of cases. In view of the current challenges of the development of the next generation of EGFR inhibitors, the mechanism of third-generation targeted drug resistances and targeted strategies are key for further exploration. Our case report discusses a female patient with advanced lung adenocarcinoma carrying the EGFR exon19 E746_A750delinsIP mutation who received osimertinib as first-line therapy and acquired C797S resistance during treatment. The patient was then treated with icotinib for 8 months until the disease progressed. Icotinib may be effective in patients with the EGFR 19del-C797S resistant mutation acquired after osimertinib treatment.

Survival benefits of propofol-based versus inhalational anesthesia in non-metastatic breast cancer patients: a comprehensive meta-analysis

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78–0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73–0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74–0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87–1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78–0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88–1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61–0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

Immunomic longitudinal profiling of the NeoPembrOv trial identifies drivers of immunoresistance in high-grade ovarian carcinoma

PD-1/PD-L1 blockade has so far shown limited survival benefit for high-grade ovarian carcinomas. By using paired samples from the NeoPembrOv randomized phase II trial (NCT03275506), for which primary outcomes are published, and by combining RNA-seq and multiplexed immunofluorescence staining, we explore the impact of NeoAdjuvant ChemoTherapy (NACT) ± Pembrolizumab (P) on the tumor environment, and identify parameters that correlated with response to immunotherapy as a pre-planned exploratory analysis. Indeed, i) combination therapy results in a significant increase in intraepithelial CD8+PD-1+ T cells, ii) combining endothelial and monocyte gene signatures with the CD8B/FOXP3 expression ratio is predictive of response to NACT + P with an area under the curve of 0.93 (95% CI 0.85-1.00) and iii) high CD8B/FOXP3 and high CD8B/ENTPD1 ratios are significantly associated with positive response to NACT + P, while KDR and VEGFR2 expression are associated with resistance. These results indicate that targeting regulatory T cells and endothelial cells, especially VEGFR2+ endothelial cells, could overcome immune resistance of ovarian cancers.

Boosting Immunogenicity of a Recombinant Mycobacterium smegmatis Strain via Zinc-Dependent Ribosomal Proteins

Tuberculosis (TB) continues to be a major global health burden and kills over a million people annually. New immunization strategies are required for the development of an efficacious TB vaccine that can potentially induce sterilizing immunity. In this study, we first confirmed that a live vaccine strain of Mycobacterium smegmatis, previously designated as IKEPLUS, conferred a higher survival benefit than the Bacillus Calmette-Guerin (BCG) in a murine model of intravenous Mycobacterium tuberculosis (Mtb) infection. We have shown that there was a significant increase in the expression of the Rv0282 gene, which is encoded in the esx-3 locus, which played an important role in iron uptake when IKEPLUS was grown in both low zinc and iron-containing Sauton medium. We then confirmed using in vitro assays of biofilm formation that zinc plays a vital role in the growth and formation of M. smegmatis biofilms. IKEPLUS grown in low zinc media led to the better protection of mice after intravenous challenge with a very high dosage of Mtb. We also showed that various variants of IKEPLUS induced apoptotic cell-death of infected macrophages at a higher rate than wild-type M. smegmatis. We next attempted to determine if zinc containing ribosomal proteins such as rpmb2 could contribute to protective efficacy against Mtb infection. Since BCG has an established role in anti-mycobacterial efficacy, we boosted BCG vaccinated mice with rmpb2, but this did not lead to an increment in the protection mediated by BCG.

Role of elective neck dissection in cT2N0 maxillary sinus squamous cell carcinoma

Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17–2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.

Intraoperative Ultrasound guided Palliative Radiofrequency Ablation of Unresectable Nonmetastatic Pancreatic Malignancies: A Pilot Observational Study.

Radiofrequency ablation of unresectable pancreatic tumors represents a palliative method in selected patients. The lack of standardization of the technique used as well as the non-homogeneous immediate and long-term results from the reports in the literature made us evaluate in a pilot study the application of a standardized technique through a surgical approach, with the evaluation of the immediate and long-term results. Ten consecutive patients diagnosed with unresectable nonmetastatic pancreatic adenocarcinoma were referred for radio-frequency ablation by surgical approach. For that, a UniBlate (AngioDinamics®) internal cooled electrode was used, under intraoperative ultrasound guidance. We analysed the morbidity, mortality and survival associated with this procedure. The median follow-up period was 12 months. Intraoperative ultrasound was essential for guiding the procedure. No mortality and no major postoperative complications after intraoperative tumoral ablations were noted. The median survival after the procedure was 7.5 months. Radiofrequency intraoperative ablation of unresectable pancreatic tumors is a feasible procedure, with low morbidity and mortality if standardized, being noninferior to palliative chemotherapy alone in regards with survival. A larger study is necessary to demonstrate the potential benefits in survival, the role of multidisciplinary selection being also mandatory.

High early mortality following percutaneous nephrostomy in metastatic cancer: a national analysis of outcomes

ObjectivesTo assess the outcomes of percutaneous nephrostomy in England for renal decompression, in the context of metastatic cancer.MethodsRetrospective observational study of all patients undergoing nephrostomy with a diagnosis of metastatic...

Perioperative outcomes in patients who undergo neoadjuvant chemoradiotherapy versus chemotherapy versus up-front surgery in patients with oesophageal cancer.

Oesophagectomy is the mainstay of curative treatment for oesophageal cancer. The role of neoadjuvant therapy has evolved over time as evidence for its survival benefit comes to hand. Clinician reluctance to offer patients neoadjuvant therapy may be based on the perception that patients receiving treatment before surgery may be exposed to a greater risk of perioperative complications. The aim of this study was to examine short-term outcomes in patients who undergo neoadjuvant therapy versus up-front surgery in patients with oesophageal cancer. This was a retrospective cohort study of prospectively collated data from 2001 to 2020 of patients undergoing resection for oesophageal cancer. Patients who had neoadjuvant chemoradiotherapy, chemotherapy and up-front surgery were compared for perioperative morbidity (via the Clavien-Dindo classification), length of stay, unplanned readmission, and 30- and 90-day mortality. Logistic regression was performed to predict perioperative morbidity following surgery. In total, 284 patients underwent an oesophagectomy. Most patients received neoadjuvant treatment (41% received chemoradiotherapy (117/284), 33% received chemotherapy (93/284)), and 26% of patients received up-front surgery (74/284). Patients who received neoadjuvant chemoradiotherapy or up-front surgery were more likely to have a complication (57%, 67/117 and 57%, 43/74) than patients who received neoadjuvant chemotherapy only (38%, 35/93, P = 0.009). The 30- and 90-day mortality rates were 1.4% (n = 4) and 2.8% (n = 8), respectively, with no difference between the use of neoadjuvant therapy. In this series, we found that patients who received neoadjuvant treatment could undergo oesophagectomy with curative intent with acceptable postoperative morbidity and mortality.

Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease.

We sought to define the survival benefit of kidney transplantation versus long-term dialysis relative to waitlist time on dialysis, social vulnerability, and age among end-stage renal transplant candidates. End-stage renal disease patients who were candidates for their first deceased donor kidney transplantation between 2008 and 2020 were identified using the US Renal Data System. Survival probabilities for patient survival were compared using the restricted mean survival times (RMSTs) across different age and social vulnerability index (SVI) ranges. Among 149 923 patients, 68 795 (45.9%) patients underwent a kidney transplant and 81 128 (54.1%) remained on dialysis. After propensity-score matching (n = 58 035 in each cohort), the 5-y RMST difference between kidney transplant and dialysis demonstrated an increasing trend in mean life-years gained within 5 y of follow-up relative to advancing age (<30 y: 0.40 y, 95% confidence interval, 0.36-0.44 y versus >70 y: 0.75 y, 95% confidence interval, 0.70-0.80 y). Conversely, disparities in 5-y RMSTs remained consistent relative to social vulnerability (median 5-y RMST difference: 0.62 y comparing low versus high SVI). When considering waitlist duration, stratified analyses demonstrated increasing trends across different age groups with the largest RMST differences observed among older patients aged ≥70 y. Notably, longer waitlist durations (>3 y) yielded more pronounced RMST differences compared with shorter durations (<1 y). These data underscore the survival benefit associated with kidney transplantation over long-term dialysis across various age and SVI ranges. Transplantation demonstrated a greater advantage among older patients who had a longer waitlist duration.

Recent Advances of Neoadjuvant Immunotherapy for Urothelial Bladder Cancer.

Urothelial bladder cancer is one of the most common malignant tumors of the urinary system, which accounts for 90~95% of urothelial carcinoma. Despite the current standard neoadjuvant management for localized urothelial MIBC (T2-4cN0M0) is cisplatin-based chemotherapy before radical cystectomy, there still had poor performances and less overall survival benefits in patients with localized urothelial MIBC. Moreover, nearly half of MIBC patients were ineligible for receiving cisplatin because of chronic kidney disease and performance status. Although immunotherapy, immune checkpoint inhibitors (ICIs) has been identified as first or second-line treatments for localized and metastasis bladder cancer based on less adverse reactions and favorable outcomes, neoadjuvant immunotherapy had rarely used for the treatment of these patients because of less large-scale clinical randomized studies and limited outcomes. Therefore, we reviewed the advances of efficacy and safety with neoadjuvant immunotherapy for urothelial bladder cancer depended on published articles and clinical studies, which could provide more theoretical evidences and promising strategy for clinical therapeutic development.

A trauma expert consensus: Capabilities are required early to improve survivability from traumatic injury.

Mortality reviews examine US military fatalities resulting from traumatic injuries during combat operations. These reviews are essential to the evolution of the military trauma system to improve individual, unit, and system-level trauma care delivery and inform trauma system protocols and guidelines. This study identifies specific prehospital and hospital interventions with the potential to provide survival benefits. US Special Operations Command fatalities with battle injuries deemed potentially survivable (2001-2021) were extracted from previous mortality reviews. A military trauma review panel consisting of trauma surgeons, forensic pathologists, and prehospital and emergency medicine specialists conducted a methodical review to identify prehospital, hospital, and resuscitation interventions (e.g., laparotomy, blood transfusion) with the potential to have provided a survival benefit. Of 388 US Special Operations Command battle-injured fatalities, 100 were deemed potentially survivable. Of these (median age, 29 years; all male), 76.0% were injured in Afghanistan, and 75% died prehospital. Gunshot wounds were in 62.0%, followed by blast injury (37%), and blunt force injury (1.0%). Most had a Maximum Abbreviated Injury Scale severity classified as 4 (severe) (55.0%) and 5 (critical) (41.0%). The panel recommended 433 interventions (prehospital, 188; hospital, 315). The most recommended prehospital intervention was blood transfusion (95%), followed by finger/tube thoracostomy (47%). The most common hospital recommendations were thoracotomy and definitive vascular repair. Whole blood transfusion was assessed for each fatality: 74% would have required ≥10 U of blood, 20% would have required 5 to 10 U, 1% would have required 1 to 4 U, and 5% would not have required blood products to impact survival. Five may have benefited from a prehospital laparotomy. This study systematically identified capabilities needed to provide a survival benefit and examined interventions needed to inform trauma system efforts along the continuum of care. The determination was that blood transfusion and massive transfusion shortly after traumatic injury would impact survival the most. Expert Opinion; Level V.

Differential inflammatory conditioning of the bone marrow by acute myeloid leukemia and its impact on progression.

Inflammation promotes solid tumor progression, but how regulatory mechanisms of inflammation may impact leukemia is less well studied. Using annexin A5 (ANXA 5), a calcium-binding protein known for apoptosis, which we discovered to be differentially expressed in the bone marrow microenvironment (BMM) of mice with acute myeloid (AML) versus chronic myeloid leukemia, as a model system, we unravel here a circuit in which AML-derived tumor necrosis factor (TNF)α dose-dependently reduces ANXA5 in the BMM. This creates an inflammatory BMM via elevated levels of prostaglandin E2 (PGE2). Via binding to its EP4 receptor, PGE2 increases -catenin and hypoxia-inducible factor (HIF) 1 α signaling in AML cells, thereby accelerating PGE2-sensitive AML. Human trephine biopsies may show lower ANXA5 expression and higher PGE2 expression in AML compared to other hematological malignancies. Further, syngeneic and xenogeneic transplantation models suggest a survival benefit after treatment with the inhibitor of prostaglandin-endoperoxide synthase 2 (cyclooxygenase 2 (COX2)), celecoxib, plus cytarabine in those AML types highly sensitive to PGE2 compared to cytarabine alone. Taken together, TNFα/ANXA5/NF-kB/COX2/PGE2-mediated inflammation influences AML course in a highly differential and circular manner, and AML patients with 'inflammatory AML' may benefit from antiphlogistic agents as adjunct therapy.

Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer

ObjectiveThe aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables.MethodsPatients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model.ResultsA total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36–4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17–3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT.ConclusionAdjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors.

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6low and IL-10low cases (P<0.05), whereas ABCA1-mediated CE was increased in IL-10high patients (P=0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6low (HR 2.13 and 2.97, respectively) and IL-10low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy.