Favorable Survival Research Articles

Molecular Tumor Boards impact on patients’ health: towards a policy brief in the Can.Heal project

Abstract Background Molecular Tumor Boards (MTBs) are pivotal in the current management of oncological patients, integrating molecular diagnostics with clinical expertise to tailor precise treatments. Within the framework of EU-funded ‘Building EU Cancer and Public Health Genomics platform’ (Can.Heal) project that aims at streamlining genomics implementation in public health, we are developing a policy brief to promote MTBs’ adoption across the EU. Methods A two-step approach was employed to delineate strategies for MTB implementation. Firstly, we conducted a systematic review and meta-analyses (if feasible) up to November 2023, on studies assessing the MTBs’ clinical impact. Secondly, based on the results of the review, we conducted an expert consultation to identify key areas to improve MTBs implementation and impact. Results 48 studies were included, whose results were heterogeneous in terms of organizational aspects and number of experts involved (mean n: 6, range: 2-19). Average implementation rate of the recommendations issued by the MTB was 43.1% (3.2%-92%), with a turnaround time from testing to recommendation of 36 days (15-58). By pooling data from 12 studies (n = 1623), a favorable overall survival [HR = 0.63 (95% CI 0.53-0.76), I2 42.0%] was reported for patients managed in hospitals with MTBs versus not. Similar estimates were reported when the outcome was progression free survival [HR = 0.63 (95% CI 0.54-0.72), I2 = 0.0%], based on 8 studies (n = 1106). The subsequent expert consultation identified 5 key areas for MTB implementation: genetic data sharing, standards for results’ interpretation, equitable access to MTB, optimization of the testing process, and funding and reimbursement. Conclusions The policy brief underscores the significant clinical benefits of MTB-recommended therapy, improving patients’ outcomes. Nevertheless, addressing resource allocation and infrastructure development is essential to optimize MTB utilization and enhance patient outcomes. Key messages • Our results highlight that MTBs-recommended therapy translates into tangible clinical benefits. • More fundings and resources are needed to optimize and fully implement MTBs in clinical practice.

Cardiovascular etiologies and risk factors of survival outcomes after resuscitation for out-of-hospital cardiac arrest: data from the KoCARC registry

Abstract Background The outcomes and characteristics of out-of-hospital cardiac arrest (OHCA) vary across geographic regions. The etiologies and prognoses of OHCA in Asian populations remain less established. This study aimed to investigate the etiologies and clinical characteristics of patients successfully resuscitated after OHCA and identify predictors of survival outcomes. Methods Data were extracted from a South Korean multicenter prospective registry of OHCA that included 64 tertiary hospitals from 2015 to 2018 (n=7577). The primary outcome was in-hospital mortality, and secondary outcome was the grade-1 cerebral performance category (CPC) score at discharge. Results Of the 7577 patients, 2066 achieved return of spontaneous circulation (ROSC) and were hospitalized and 915 (44·2%) presented with ventricular arrhythmia (VA) as their initial rhythm or on admission. The leading cause was obstructive coronary artery disease (n=413; 20·0%). Sudden unexplained death syndrome (SUDS) accounted for 67·5% of survivors, which were significantly lower with VA (82·7% vs. 48·3%, p<0.001). VA was an independent predictor of in-hospital mortality (adjusted hazard ratio [aHR] 0·72, 95% confidence interval 0·60–0·87) and the grade-1 CPC score at discharge (aHR 3·63, 95% CI 2·56–5·15). Other predictors of the primary outcome included age, ROSC on arrival, total arrest time, alertness on admission, extracorporeal membrane oxygenation use, targeted temperature management, implantable cardioverter defibrillator use, and coronary vasospasm. Conclusions SUDS was common in patients with ROSC after OHCA and thus needs to be evaluated comprehensively. VA was independently associated with favorable survival outcomes at discharge. Further management may improve clinical outcomes in patients with OHCA, particularly those with VA.

Prognostic relevance of sarcopenia and tumor‐infiltrating CD8+ T cells in patients with hepatocellular carcinoma

AbstractAimThe relationship between sarcopenia, tumor‐infiltrating lymphocytes (TILs), and long‐term survival in patients with hepatocellular carcinoma (HCC) has not been investigated. We aimed to evaluate the prognostic relevance of sarcopenia and TILs in patients with HCC.MethodsWe included 351 patients with HCC following liver resection. Sarcopenia was defined based on the skeletal muscle index using computed tomography. Tumor‐infiltrating CD4+ and CD8+ T cells, perforin, and granzyme B were examined in liver resection specimens.ResultsSarcopenia patients had a significantly lower lymphocyte count (p = 0.003), prognostic nutritional index (p = 0.017), and CD4+ and CD8+ T cell counts (p = 0.008 and p = 0.006, respectively). The overall survival (OS) and recurrence‐free survival (RFS) rates of sarcopenia patients were significantly lower than non‐sarcopenia patients (both p < 0.001). Multivariate analysis revealed that sarcopenia and low CD8 levels were strong independent poor prognostic factors for OS and RFS (both p < 0.001). Regardless of sarcopenia, patients with high CD8 levels had significantly better OS and RFS rates and increased expression of perforin and granzyme B. Particularly, sarcopenia patients with high CD8 levels had much better OS and RFS than those with low CD8 levels and were even comparable to non‐sarcopenia patients with high CD8 levels.ConclusionsSarcopenia and low CD8 levels are strong independent poor prognostic factors in patients with HCC. Furthermore, sarcopenia patients with high CD8 levels had favorable survival and activated local immunity, suggesting that tumor‐infiltrating CD8+ T cells may play a functionally important role in sarcopenia patients.

Comparative Analyses of the Outcomes Between Lobectomies and Trisegmentectomies/Lingulectomies in the Surgical Management of Clinical Stage I Left Upper Lobe Non-small Cell Lung Cancer.

Lobectomies are the standard surgical intervention for lung cancer; however, recently, surgeons have considered segmentectomies for smaller tumors, with their potential for favorable survival outcomes while preserving lung function. The surgical outcomes of trisegmentectomies/lingulectomies and lobectomies for clinical stage I left upper lobe (LUL) non-small cell lung cancers (NSCLCs) remain undetermined. Thus, our study aimed to assess the differences between the short-term surgical and long-term survival outcomes in patients with clinical stage I LUL NSCLC who underwent trisegmentectomies/lingulectomies and those who underwent lobectomies. Between 2011 and 2021, we retrospectively reviewed the data of 377 patients with clinical stage I NSCLC who had undergone LUL lobectomies or trisegmentectomies/lingulectomies. Patients were categorized into two subcohorts according to tumor size, i.e. 0-2 and 2-4 cm. To ensure preoperative demographic comparability, 1:1 propensity-score matching (PSM) was performed. This study focused on the 2-4cm subcohort. Post-PSM, patients who underwent trisegmentectomies/lingulectomies had quicker operations and shorter postoperative hospital and intensive care unit lengths of stay than those who underwent lobectomies. Post-PSM, no statistically significant differences in progression-free survival (PFS) or overall survival (OS) were observed between the segmentectomy and lobectomy groups in both the0-2 and 2-4cm subcohorts. The multivariate analysis revealed that different surgical methods were not statistically significant factors for either PFS or OS. Trisegmentectomies/lingulectomies are a feasible option for clinical stage I NSCLC, with better perioperative outcomes and similar survival rates when compared with LUL lobectomies.

Change in Quality of Life in Patients with Advanced Rectal Cancer Between 2010 and 2022.

Advanced rectal cancer is one of the most common cancers worldwide and has a significant impact on public health. Because favorable and long-term survival has been achieved with multimodal therapy, patient quality of life is very important. The intention of this study was to assess patients' quality of life using various functioning and symptom scores from the years 2010 to 2022 and to examine changes over time. Data on health-related quality of life were collected from rectal cancer patients treated at the University Hospital Erlangen in Germany over a period of 13 years. The EORTC QLQ-C30 questionnaire and the rectal cancer-specific module QLQ-CR38 were completed in this study by a total of 516 patients. The questionnaires were collected before, during and at annual follow-up visits after treatment. Statistical significance was defined as p-values < 0.05 as well as a difference of 10 or more percentage points. The deterioration in scores is most pronounced immediately after radiochemotherapy, especially for pain (+19.8 pp), fatigue (+16.1 pp) and diarrhoea (+24.8 pp). One year after the end of therapy, most of the values are again comparable to or better than those of the German general population and only role functioning (-19.8 pp), social functioning (-24.6 pp), diarrhoea (-21.6 pp) and financial difficulties (-16.3 pp) are considerably worse. Some baselines deteriorate clearly over time from 2010 to 2022; these are role functioning (-23.9 pp), social functioning (-17.3 pp), body image (-15.2 pp), fatigue (+13.8 pp) and nausea and vomiting (+10.5 pp). An improvement in therapy in terms of a reduction in side effects and, thus, an improvement in quality of life over time could not be proven. The deterioration in individual scores over time does not appear to be a problem specific to rectal cancer patients, but rather, is associated with social developments or systemic healthcare factors in German society that are not directly related to oncological diseases.

The prognostic and therapeutic value of the tumor microenvironment and immune checkpoints in pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms (Pan-NEN) represent a group of highly heterogeneous cancers, characterized by complex and diverse biological behavior. The objective of this study was to systematically investigate the immunological features of the tumor microenvironment (TME) in Pan-NEN, aiming to identify prognostic biomarkers and explore the therapeutic potential of immunotherapy for Pan-NEN. Tumor and adjacent normal tissues were collected from 56 patients with Pan-NEN. Immunohistochemical analysis was conducted on tumor tissues using a panel of monoclonal antibodies targeting key immune markers. The expression levels of these markers were quantitatively assessed and correlated with clinicopathological features and overall survival. Low expression of CD3, CD8, CD4, CD68, CD163, Foxp3, CD56, CD69, GZMB, HLA-1, HLA-II, PD-1, and PD-L1 were observed in the majority of Pan-NEN patient samples. PD-1 expression was positively correlated with CD4 and Foxp3 expression, while PD-L1 expression was positively correlated with CD68, CD163, and Foxp3 expression; HLA-II expression was positively correlated with GZMB expression. Infiltration of lymphocytes (CD3 + or CD8+) and macrophages (CD68 + or CD163+) and expression of PD-1/PD-L1 were more pronounced in poorly differentiated neuroendocrine carcinoma (Pan-NEC) compared to well-differentiated neuroendocrine tumors (Pan-NET), while CD68 and PD-L1 correlated with advanced disease stage. Conversely, HLA-I antigen expression was commonly downregulated in Pan-NEC. Univariate Cox proportional hazard analysis demonstrated that tumor grade, stage; CD4+, CD68+, and CD163 + cell count; and expression of PD-1 and PD-L1 were significantly associated with poor survival outcomes, while the positive expression of HLA-I was correlated with a more favorable survival prognosis. Furthermore, multivariate Cox proportional hazard analyses revealed that tumor grade, stage, and PD-1 expression are independent prognostic factors. The immunological landscape of Pan-NEN offers potential prognostic value and therapeutic targets. The findings suggest that immunotherapy, particularly targeting the PD-1/PD-L1 pathway, may serve as a promising strategy for the treatment of Pan-NEN, especially for Pan-NEC patients.

Immune marker expression and prognosis of early breast cancer expressing HER3

IntroductionThere is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established. MethodsThe main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive. ResultsAmong 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor. ConclusionsThis study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.

Real-world Study of the Safety and Efficacy of Pembrolizumab in the Treatment of Advanced Non-small Cell Lung Cancer

Pembrolizumab (PEM) has been shown to be effective in clinical trials for the treatment of advanced non-small cell lung cancer (NSCLC), but clinical trials were based on cohorts of patients selected on specific criteria, and whether the findings are consistent with real-world patients is debatable. The aim of this study is to evaluate the efficacy and safety of PEM in the treatment of advanced NSCLC based on real-world data. A retrospective collection of real-world data from patients with advanced NSCLC receiving PEM was conducted. Propensity score matching was used to eliminate inter-group differences and assess the efficacy and safety of PEM compared to chemotherapy. Among 450 matched patients, the incidence rates of any-grade adverse events were 79.87% in the PEM group and 86.71% in the chemotherapy group, while the incidence rates of grade ≥3 adverse events were 4.03% and 7.31%, respectively. The objective response rates were 48.63% for PEM and 36.00% for chemotherapy (P=0.011). The median progression-free survival was 15.5 months for PEM and 8.8 months for chemotherapy (P<0.001), and the median overall survival was not reached for PEM and 26.2 months for chemotherapy (P<0.001). PEM treatment for advanced NSCLC demonstrates favorable survival outcomes and acceptable safety in real-world clinical practice.

Laparoscopic central hepatectomy: Feasibility and safety.

Anatomical liver resection is the gold standard for hepatocellular carcinoma (HCC), enhancing survival and disease-free outcomes. For centrally located tumors, major resections are necessary but risky, especially for patients with liver disease. Central hepatectomy (CH) offers a parenchymal-sparing alternative to extended or hemihepatectomy (HH), reducing postoperative liver failure risk. However, its complexity and the large transection area make it challenging, especially with laparoscopic techniques. This study evaluates the feasibility and safety of laparoscopic CH for centrally located HCC, comparing surgical outcomes with those of the HH group. A total of 1592 laparoscopic hepatectomy cases from January 2011 to April 2023 were reviewed in a single institution. Patients undergoing laparoscopic CH were compared to those receiving HH during the same period. Exclusion criteria included non-HCC diagnosis, non-central tumors, and cases involving combined procedures. 70 cases of laparoscopic CH and 32 cases of laparoscopic HH were included. The CH and HH groups showed similar estimated blood loss (median 400ml vs. 290ml, p = 0.187) and intraoperative blood transfusion rates (10% vs. 15%, p = 0.413). Operation time did not significantly differ (median 330min vs. 360min, p = 0.862). Postoperative hospital stay was shorter in CH (median 6days vs. 9days, p = 0.018), with fewer ICU transfers (19% vs. 44%, p = 0.014) and lower 90-day mortality (1% vs. 9%, p = 0.055) compared to HH. Complication rates were similar overall (26% vs. 41%, p = 0.069), but HH had more Clavien-Dindo class I and II complications (13% vs. 19%, p = 0.040). Long-term survival did not significantly differ, but tended to favor the CH group. Despite the complexity, laparoscopic CH offers comparable perioperative outcomes and favorable long-term survival compared to HH. It can be considered a viable option for centrally located HCC, preserving liver function.

Comprehensive analysis of the expression level, prognostic value, and immune infiltration of cuproptosis-related genes in human breast cancer.

As a novel cell death form, cuproptosis results from copper combining with lipidated proteins in the tricarboxylic acid cycle. To the best of our knowledge no study has yet comprehensively analyzed the relationship between cuproptosis-related genes and breast cancer. The expression, prognostic value, mutations, chemosensitivity, and immune infiltration of cuproptosis-related genes in breast carcinoma patients were analyzed, PPI networks were constructed, and enrichment analyses were performed based on these genes. TIMER, UALCAN, Kaplan-Meier plotter, Human Protein Atlas, cBioPortal, STRING, GeneMANIA, DAVID, and R program v4.0.3 were used to accomplish the analyses above. Compared to normal breast tissues, FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, MTF1, and GLS were down-regulated in breast cancer tissues, while CDKN2A was up-regulated. High expression of FDX1, LIAS, DLD, DLAT, MTF1, GLS, and CDKN2A were associated with favorable overall survival. Cuproptosis-related genes showed a high alteration rate (51.3%) in breast cancer, contributing to worse clinical outcomes. The expression levels of FDX1, LIPT1, DLD, DLAT, PDHA1, PDHB, MTF1, GLS, and CDKN2A were associated positively with 1 or more immune cell infiltrations in breast cancer. Patients with high levels of B cell, CD4+ T cell, CD8+ T cell, and dendritic cell infiltration had a higher survival rate at 10 years. This study comprehensively investigated relationships between cuproptosis and breast cancer by bioinformatic analyses. We found that cuproptosis-related genes were generally lowly expressed in breast carcinoma tissue. As the critical gene of cuproptosis, high expression of FDX1 was related to favorable prognoses in breast cancer patients; thus, it might be a potential prognostic marker. Moreover, genes associated with cuproptosis were linked to immune infiltration in breast cancer and this relationship affected the prognosis of breast cancer.

Effects of Perfusion, Coronary Artery Disease Burden, and Revascularization in Establishing Organized Cardiac Rhythm During Extracorporeal Cardiopulmonary Resuscitation for Shockable Refractory Out-of-Hospital Cardiac Arrest.

Two hundred eighty-nine consecutive patients in refractory shockable OHCA were placed on ECMO followed by coronary angiogram (n=289) and PCI (n=165). Patients were grouped based on the extracorporeal cardiopulmonary resuscitation stage where a sustained organized rhythm was achieved. Survival outcomes were evaluated by using the Cerebral Performance Category. Logistic regression analysis was performed to determine the relationship between Cerebral Performance Category and timing of organized rhythm. Standard advanced cardiac life support before hospital arrival resulted in 148 of 289 (51%) patients attaining an organized rhythm while 87 of 289 (30%) achieved an organized rhythm post ECMO cannulation but before PCI, and 37 of 289 (13%) achieved an organized rhythm following PCI. Obstructive coronary artery disease was observed in 192 of 289 (66%) patients. A total of 144 of 192 (75%) patients with obstructive coronary artery disease converted to an organized rhythm before PCI and 37 of 192 (19%) following PCI. Cerebral Performance Category score 1 or 2 was significantly more likely in patients with cardiac arrest and obstructive coronary artery disease who achieved an organized rhythm before PCI (odds ratio [OR], 3.9 [95% CI, 1.2-12.0], P=0.024). Most patients undergoing extracorporeal cardiopulmonary resuscitation for refractory OHCA due to shockable rhythms achieved an organized rhythm before PCI independent of coronary artery disease burden. Also, neurologically favorable survival was more prevalent in those attaining an organized rhythm before PCI.

Second-Line Fluoropyrimidine-Based Chemotherapy in Advanced Biliary Tract Cancer: A Meta-Analysis Based on Individual Patient-Level Data of Randomized Trials.

While fluoropyrimidine-based chemotherapy regimens are recommended second-line treatment for patients with advanced biliary tract cancer (BTC), there have been no studies comparing different regimens head-to-head. We performed individual patient-level meta-analysis based on data from the intention-to-treat population of the phase 2b NIFTY trial (liposomal irinotecan [nal-IRI] plus fluorouracil and leucovorin [5-FU/LV] vs. 5-FU/LV; NCT03542508) and the phase 2 FIReFOX trial (modified oxaliplatin plus 5-FU/LV [mFOLFOX] vs. modified irinotecan plus 5-FU/LV [mFOLFIRI]; NCT03464968). Pairwise log-rank tests and multivariable analysis using Cox proportional hazards modeling with shared frailty to account for the trial's effect were used to compare overall survival (OS) between regimens. A total of 277 patients were included. The nal-IRI plus 5-FU/LV group (n=88) showed significantly better OS compared to the mFOLFOX group (n=49, pairwise log-rank, p=0.02), and mFOLFIRI group (n=50, p =0.03). Multivariable analysis showed consistent trends in OS with adjusted hazard ratios of 1.39 (mFOLFOX vs nal-IRI plus 5-FU/LV, 95% CI 0.93-2.07, p=0.11) and 1.36 (mFOLFIRI vs nal-IRI plus 5-FU/LV, 95% CI 0.92-2.03, p=0.13), respectively. Compared to the 5-FU/LV group, the mFOLFOX group and the mFOLFIRI group did not show differences in terms of OS (pairwise log-rank p=0.83 and p=0.58, respectively). The nal-IRI plus 5-FU/LV group experienced more frequent diarrhea, while the mFOLFOX group experienced peripheral neuropathy. Nal-IRI plus 5-FU/LV showed favorable survival outcomes compared to mFOLFOX, mFOLFIRI, or 5-FU/LV. The safety profiles of these regimens should be considered along with efficacy.

Heart rhythm at hospital admission: A factor for survival and neurological outcome among ECPR recipients?

BackgroundThe initial rhythm is a known predictor of survival in extracorporeal cardiopulmonary resuscitation (ECPR) patients. However, the effect of the rhythm at hospital admission on outcomes in these patients is less clear. MethodsThis observational, single-center study assessed the influence of the rhythm at hospital admission on 30-day survival and neurological outcomes at discharge in patients who underwent ECPR for out-of-hospital cardiac arrest (OHCA). ResultsBetween January 2012 and December 2023, 1,219 OHCA patients were admitted, and 210 received ECPR. Of these, 196 patients were analyzed. The average age was 52.9 years (±13), with 80.6 % male. The median time to ECPR initiation was 61 min (IQR 54–72). Patients with ventricular fibrillation as both the initial and admission rhythm had the highest 30-day survival rate (52 %: 35/67), while those with asystole in both instances had the lowest (6 %: 1/17, log-rank p < 0.00001). After adjusting for age, sex, initial rhythm, resuscitation time, location, bystander, and witnessed status, asystole at admission was linked to higher 30-day mortality (OR 4.03, 95 % CI 1.49–12.38, p = 0.009) and worse neurological outcomes (Cerebral Performance Category 3–5) at discharge (OR 4.61, 95 % CI 1.49–17.62, p = 0.013). ConclusionsThe rhythm at hospital admission affects ECPR outcomes. Patients presenting with and maintaining ventricular fibrillation have a higher chance of favorable neurological survival, whereas those presenting with or converting to asystole have poor outcomes. The rhythm at hospital admission appears to be a valuable criterion for deciding on ECPR initiation.

PCV ALONE IN GRADE 2 AND GRADE 3 OLIGODENDROGLIOMA – LONG-TERM RESULTS FROM A UK TERTIARY CARE CENTRE

Abstract AIMS Oligodendroglioma is a subgroup of gliomas which affects young adults and has a favourable overall survival (OS) ranging between 31.5 to 56.6.% at 10 years. Standard management of these tumours is maximal safe resection followed by adjuvant radiotherapy and systemic chemotherapy with Procarbazine, Lomustine and Vincristine (PCV), or surveillance where appropriate. PCV alone is an option that helps defer or avoid radiotherapy and its neurocognitive side effects in a selected group of patients. Our retrospective study analyses outcomes with PCV alone in Oligodendroglioma. METHOD We screened patient records between 1999 to 2021 and identified 31 patients who had a histological diagnosis of grade 2/3 oligodendroglioma (with confirmation of 1p19qcodeletion on molecular testing) and received PCV alone after surgery (biopsy/ tumour resection). RESULTS Out of 31 patients, twenty-six patients were grade 2 and five patients were grade 3 oligodendroglioma. Median age was 44 years and male: female was 15:16. Median follow up was 9.5 years. Twenty-five patients (80%) presented with seizures. 80% of patients had tumour resection &amp; twenty four patients received 5 or more cycles of PCV alone as first-line oncological treatment. There was no significant difference in outcomes for grade2/3 tumours. Eighteen patients (58%) had local tumour relapse. Fourteen patients (45%) underwent salvage radiotherapy. Median time to radiotherapy was 7 years. Median OS was 19.4 years and median progression free survival (PFS) was 13.3 years. 9 deaths were reported. CONCLUSION PCV chemotherapy alone is an effective adjuvant treatment option for selected patients with oligodendroglioma, with a favourable PFS and OS shown in our series. Its use may allow deferral of radiotherapy and avoidance of associated neurocognitive side effects which can have a detrimental effect of quality of life for these young patients.

Quality of life in disease-free survived patients with early-stage extranodal nasal-type NK/T-cell lymphoma after definitive intensity-modulated radiotherapy: a cross-sectional study of 310 cases

PurposeRadiotherapy is a critical treatment for early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTL) and has yielded favorable survival outcomes. However, their postradiotherapy quality of life (QOL) has not been investigated. Here, we conducted a cross-sectional study to assess the QOL of ENKTL patients with disease-free survival after definitive radiotherapy and to identify factors associated with QOL and treatment optimization.MethodsThis cross-sectional study included 310 patients with stage I–II ENKTL of the upper aerodigestive tract (UADT) who had received simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) with a consistent design and achieved disease-free survival. The median postradiotherapy time was 47.2 months (range, 3.1–115.7). The EORTC QLQ-H&N35 questionnaire was used to assess symptom-related QOL, and nine additional items were added to incorporate nasal, optical, and aural-related symptoms. The scores indicate the severity of the symptoms.ResultsThe most common postradiotherapy symptoms among patients with ENKTL were nose problems (49.7%), dry mouth (44.8%), tooth problems (41.3%), sensory problems (32.6%), and less sexuality (25.8%). Tooth problems had the highest average score of 18.6, which is still acceptable. The severity of these symptoms decreased over time and reached a plateau in the second year after radiotherapy. Multivariable regression analysis showed that whole-neck irradiation was an independent predictive factor for xerostomia (P = 0.013, OR = 1.114), while age > 60 years was a predictive factor for lower sexuality (P < 0.001, OR = 1.32).ConclusionThe QOL of patients with early-stage ENKTL after radiotherapy was favorable, and most symptoms improved over time. Radiotherapy was correlated with specific symptoms, which may suggest a direction for further improvement in SIB-IMRT.

Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.

Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.

Immunotherapeutic Potential of Mutated NPM1 for the Treatment of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one-third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with AML NPM1mut may be better suited to immunogenic strategies that are based on the inhibition of the PD-1 immune checkpoint pathway than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PD-1 inhibitors.

Radiotherapy with 15 × 2.633 Gy vs. 20 × 2.0 Gy in Patients with Malignant Spinal Cord Compression and Favorable Survival Prognoses: A Secondary Analysis of the RAMSES-01 Trial.

Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.

Factors behind favorable long-term lung cancer survival in Norway compared to Denmark: a retrospective cohort study

ABSTRACT Background Long-term survival of patients with non-small cell lung cancer (NSCLC) is considerably higher in Norway compared to Denmark, even though diagnostic work-up, treatment, and follow-up are comparable. We aim to explore factors behind favorable long-term survival for lung cancer patients in Norway compared to Denmark. Method A retrospective cohort study of patients with NSCLC diagnosed between 2014 and 2016. From the Danish Lung Cancer Registry, 1000 patients were randomly selected, and 974 patients were included. From the Norwegian Vestfold Hospital Trust, 220 patients were randomly selected, and 218 were included. Data from medical records were obtained for all patients. The Danish and Norwegian cohorts were compared using the Pearson chi squared test and multivariate logistic regression analysis. Results The two cohorts were comparable in terms of age, sex, and smoking history. However, the Danish patients had a higher number of pack-years (43.5 vs 34.5 p < 0.001) and more comorbidities. The Norwegian patients had less advanced disease stage (p < 0.001), and a larger proportion was treated with curative intent (90 (41.3%) vs 343 (35.2%), p = 0.063). One-year survival was similar, but the 5-year survival was superior in the Norwegian cohort (58 (26.6%) vs 177 (18.2%), p = 0.005). In a multivariate logistic regression model, adjusted for sex, smoking history, performance status, TNM stage and comorbidity, the odds ratio of being a five-year survivor in Norway was 1.81 (95% CI: 1.11–2.94) compared to Denmark. Conclusions We found a higher proportion of Norwegian patients diagnosed at potential curable stage and fewer heavy smokers compared to Danish patients. This could contribute to the superior long-term survival found in Norwegian NSCLC patients.

Impact of systemic steroids on the efficacy of first line imatinib treatment of patients with advanced gastrointestinal stromal tumors (GISTs).

Effective management of adverse events is required to maintain sufficient imatinib dosing when treating patients with gastrointestinal stromal tumors (GISTs). Skin rash is a common adverse event of imatinib, which can be effectively controlled by systemic steroid treatment without imatinib dose modification or interruption. However, the impact of the use of systemic steroids on the efficacy of imatinib treatment remains unclear. Between October 2014 and February 2022, 277 consecutive patients from a prospective registry of GIST patients were included as the study population. Patients who started systemic steroids due to grade ≥ 3 skin rash or grade 2 skin rash with grade 2 pruritis were classified as the steroid group, whereas patients who did not develop a skin rash or those who did not require steroids for a mild skin rash were classified as the control group. Efficacy outcomes were compared between the two groups. Among the 277 patients, 30 (10.8%) were treated with systemic steroids for skin rash. There was no significant difference in progression free survival (PFS) or overall survival (OS) between the steroid and control groups (3-year PFS, 67.7% vs. 65.1%, p = 0.53; 3-year OS, 91% vs. 89.9%, p = 0.67, respectively). The use of systemic steroids was not an independent factor associated with PFS (hazard ratio 0.73, 95% confidence interval 0.36-1.49, p = 0.39) and OS (hazard ratio 0.37, 95% confidence interval 0.12-1.18, p = 0.09). In the steroid group, patients who successfully maintained the imatinib dosage showed a trend toward more favorable survival outcomes than those who did not (3-year PFS, 73.3% vs. 44.4%, p = 0.34; 3-year OS, 95.8% vs. 75.0%, p = 0.15, respectively). The use of systemic steroids for the control of imatinib induced severe skin rash did not adversely affect the efficacy outcomes of imatinib in patients with advanced GIST.