A case of long-term survival of SADDAN treated with growth hormone for marked short stature.

Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is a bone dysplasia caused by a pathogenic variant of fibroblast growth factor receptor 3 (FGFR3). Pathogenic variants in FGFR3 also cause thanatophoric dysplasia (TD) and achondroplasia. Although the findings of SADDAN and TD during the fetal and neonatal periods are similar, they differ in their long-term prognoses. We conducted FGFR3 analysis in one male patient because of the difficulty in differentiating SADDAN from TD during the neonatal period. We found that the patient had a pathogenic variant, p. Lys650Met, which was similar to that previously reported in patients with SADDAN. Reports on long-term survival in patient with SADDAN are scarce, and there have been no reports of treatment with GH. We administered GH therapy for a markedly short stature. After treatment, his height increased by 4 cm each year for 4 years, the frequency of hospitalizations due to respiratory failure decreased, and the health improved. FGFR3 analysis is useful for diagnosing SADDAN during the early neonatal period. GH therapy may have contributed to the patient's long-term survival.

Predicted prosthesis-patient mismatch and long-term clinical outcomes after transcatheter aortic valve replacement: a SWEDEHEART study.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) is uncertain. This study was performed to investigate the risk of all-cause mortality, heart failure hospitalization, and aortic valve reintervention in patients with and without predicted PPM after TAVR. METHODS: This nationwide, population-based cohort study included all patients who underwent transfemoral primary TAVR in Sweden from 2008 to 2022 in the SWEDEHEART register. PPM was defined according to published effective orifice areas for each valve model and size. The patients were divided into those with and without PPM. Additional baseline characteristics and outcome data were obtained from other national health data registers. Regression standardization was used to adjust for intergroup differences. RESULTS: Of 8485 patients, 7879 (93%) had no PPM and 606 (7%) had PPM. The crude cumulative incidence of all-cause mortality at 1, 5, and 10 years in patients with versus without PPM was 7% versus 9%, 40% versus 44%, and 80% versus 85%, respectively. After regression standardization, there was no between-group difference in long-term mortality, and the absolute difference at 10 years was 1.5% (95% confidence interval, -2.9%-6.0%). The mean follow-up was 3.0 years (maximum, 14 years). There was no difference in the risk of heart failure hospitalization or aortic valve reintervention. CONCLUSIONS: The risk of all-cause mortality, heart failure hospitalization, or aortic valve reintervention was not higher in patients with than without predicted PPM following TAVR. Furthermore, PPM was present in only 7% of patients, and severe PPM was almost nonexistent.

Rare tumours of the pancreas: monocentric study.

PURPOSE: The biology of rare pancreatic tumours, which differs from that of ductal pancreatic cancer, requires increased attention. Although the majority of rare pancreatic tumours are benign, it is difficult to decide whether an invasive component exists without complete removal of the lesion, despite considerable progress in diagnosis. We are investigating a large cohort of patients with histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. METHODS: Here we analyze long-term survival from patients, who underwent resection of histologically confirmed epithelial non-ductal non-neuroendocrine neoplasms of the pancreas. At our department between Jan 1st, 1999, and Dec 31st, 2019. The median follow-up was 61 (range 0-168) month. All statistical analyses were performed using SPSS 26.0 (IBM, Chicago, IL, USA) software. RESULTS: 46 patients (48%) were followed up for more than 5 years, 18 patients (19%) for more than 10 years. The 5-year and 10-year survival rates for rare non-invasive pancreatic tumours were 72% and 55% respectively. The proportion of rare tumour entities (non-ductal and non-neuroendocrine) increased continuously and statistically significantly (p = 0.004) from 4.2 to 12.3% in our clinic between 1999 and 2019. If there is no invasive growth yet, there is a varying risk of malignant degeneration in the course of the disease. Therefore, the indication for pancreatic resection is still the subject of discussion. CONCLUSION: The long-term prognosis of rare epithelial pancreatic tumours after R0 resection-even if they are already malignant-is much better than that of ductal pancreatic cancer.

A study predicting long-term survival capacity in postoperative advanced gastric cancer patients based on MAOA and subcutaneous muscle fat characteristics.

BACKGROUND: The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. METHODS: We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model's performance. RESULTS: The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram's good predictive performance and clinical utility. CONCLUSION: Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.

Long-Term Survival in a Patient with Metastatic Colorectal Cancer Treated with Trifluridine/Tipiracil as Late-Line Chemotherapy: A Case Report.

Introduction: Although long-term survival in patients with metastatic colorectal cancer (mCRC) is limited, treatments for third-line and later treatment are now recommended. We describe a patient who achieved long-term survival when they received third-line treatment with trifluridine/tipiracil (FTD/TPI). Case Presentation: The woman who was 52 years old at diagnosis of adenocarcinoma of the right colon (T3/N0/M1) with metastases to the lung, liver, ovary, and other soft tissues received first-line fluoropyrimidine-based chemotherapy (FOLFOX/FOLFIRI plus bevacizumab) intermittently for approximately 8.5 years with generally stable disease, and second-line FOLFIRI plus radiotherapy. After progression on second-line therapy, the patient initiated treatment with FTD/TPI 35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle. She received a total of 38 cycles of FTD/TPI over a period of 34 months achieving a partial response, maintained performance status, and improved quality of life. Neutropenia was successfully managed with FTD/TPI dose delays or reductions. Conclusion: This heavily pre-treated patient with mCRC demonstrated impressive long-term survival and maintenance of good quality of life with FTD/TPI treatment.

Tumor mutation burden and FAT3 mutation influence long-term survival in surgically resected small cell lung cancer.

Background: Small cell lung cancer (SCLC) is highly malignant and has a higher risk of recurrence even in patients who undergo early surgery. However, a subgroup of patients survived for many years. So far, the factors that determine the long-term survivorship remain largely unknown. To determine the genetic characteristics of long-term survival (LTS) after surgery in SCLC, we performed comprehensive comparative genomic profiling and tumor mutation burden (TMB) analysis of resected tumor tissues from patients with LTS and short-term survival (STS) after surgery. Methods: The present study screened 11 patients from 52 patients with SCLC who underwent surgery at Zhejiang Cancer Hospital from April 2008 to December 2017. A total of six LTS patients (≥4 years) with stage IIB or IIIA SCLC and five STS patients (<2 years) with stage IA or IB SCLC were included in the study. The STS patients were used as a control. All the patients underwent resection without neoadjuvant therapy. We assessed the genomic profiles of the resected tumor tissues and calculated the TMB using next-generation sequencing. We then analyzed and compared the molecular characteristics between the LTS and STS groups. Results: Our data indicated that tumor tissues from patients with LTS harbor a high TMB. The median TMB for LTS patients was high (approximately 16.4 mutations/Mb), while that for STS patients was low (approximately 8.5 mutations/Mb). The median TMB of patients with LTS and STS showed a trend of significant difference (P=0.08). Gene alterations characterized the survival differences between the two groups. The FAT3 mutation was only found in the LTS group, and the P value determined by Fisher's exact test was 0.06. Conclusions: A high non-synonymous TMB and the FAT3 mutation could potentially influence LTS after SCLC resection. This study provides valuable information about the molecular differences between LTS and STS patients. Studies with larger sample sizes need to be conducted to confirm our findings in the future.

Case report: Precise NGS and combined bevacizumab promote durable response in ALK-positive lung adenocarcinoma with multiple-line ALK-TKI resistance.

Liquid biopsies including pleural fluid or plasma are commonly applied for patients with advanced non-small cell lung cancer (NSCLC) and pleural effusion (PE) to guide the treatment. ALK-TKIs are the first options for patients with ALK-positive mutations and combining ALK-TKIs with angiogenic agents may improve survival. We report here one case with ALK-positive lung adenocarcinoma in which the patient achieved a prolonged progression-free survival (PFS) of 97 months after undergoing precise pleural effusion NGS and receiving combined bevacizumab treatment following multiple-line ALK-TKI resistance.

Preoperative Prediction of Long-Term Survival After Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

[Gastroenteropancreatic neuroendocrine neoplasms-Surgery in a multimodal concept]. / Gastroenteropankreatische neuroendokrine Neoplasien ­ Chirurgie im multimodalen Konzept.

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are mainly found in the small intestine and pancreas. The course of the disease in patients is highly variable and depends on the degree of differentiation (G1-G3) of the neoplasm. The potential for metastasis formation of GEP-NEN is high even with good differentiation (G1). Lymph node metastases and, in many cases, liver metastases are also often found. Less common are bone metastases or peritoneal carcinomas. The treatment of these GEP-NENs is surgical, whenever possible. If an R0 resection with removal of all lymph node and liver metastases is successful, the prognosis of the patients is excellent. Patients with diffuse liver or bone metastases can no longer be cured by surgery alone. The long-term survival of these patients is nowadays possible due to the availability of drugs (e.g., somatostatin analogues, tyrosine kinase inhibitors), peptide receptor radionuclide therapy (PRRT) and liver-directed procedures, with a good quality of life.

Long-term survival following out-of-hospital cardiac arrest in women and men: Influence of comorbidities, social characteristics, and resuscitation characteristics.

AIM: We aimed to study sex differences in long-term survival following out-of-hospital cardiac arrest (OHCA) compared to the general population, and determined associations for comorbidities, social characteristics, and resuscitation characteristics with survival in women and men separately. METHODS: We followed 2,452 Danish (530 women and 1,922 men) and 1,255 Dutch (259 women and 996 men) individuals aged ≥25 years, who survived 30 days post-OHCA in 2009-2015, until 2019. Using Poisson regression analyses we assessed sex differences in long-term survival and sex-specific associations of characteristics mutually adjusted, and compared survival with an age- and sex-matched general population. The potential predictive value was assessed with the Concordance-index. RESULTS: Post-OHCA survival was longer in women than men (adjusted incidence rate ratio (IRR) for mortality 0.74, 95%CI 0.61-0.89 in Denmark; 0.86, 95%CI 0.65-1.15 in the Netherlands). Both sexes had a shorter survival than the general population (e.g., IRR for mortality 3.07, 95%CI 2.55-3.70 and IRR 2.15, 95%CI 1.95-2.37 in Danish women and men). Higher age, glucose lowering medication, no dyslipidaemia medication, unemployment, and a non-shockable initial rhythm were associated with shorter survival in both sexes. Cardiovascular medication, depression/anxiety medication, living alone, low household income, and residential OHCA location were associated with shorter survival in men. Not living with children and bystander cardiopulmonary resuscitation provision were associated with shorter survival in women. The Concordance-indexes ranged from 0.51 to 0.63. CONCLUSIONS: Women survived longer than men post-OHCA. Several characteristics were associated with long-term post-OHCA survival, with some sex-specific characteristics. In both sexes, these characteristics had low predictive potential.

A novel methylation signature predicts extreme long-term survival in glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival. METHODS: GBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database. RESULTS: We identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM. CONCLUSION: In conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients.

Clinical Factors Affecting Survival in Patients with Congenitally Corrected Transposition of the Great Arteries: A Systematic Review and Meta-Analysis.

Background: Congenitally corrected transposition of the great arteries (cc-TGA) is a defect characterized by arterio-ventricular and atrioventricular disconcordance. Most patients have co-existing cardiac abnormalities that warrant further treatment. Some patients do not require surgical intervention, but most undergo physiological repair or anatomical surgery, which enables them to reach adulthood. Aims: We aimed to evaluate mortality risk factors in patients with cc-TGA. Results: We searched the PubMed database and included 10 retrospective cohort studies with at least a 5-year follow-up time with an end-point of cardiovascular death a minimum of 30 days after surgery. We enrolled 532 patients, and 83 met the end-point of cardiovascular death or equivalent event. As a risk factor for long-term mortality, we identified New York Heart Association (NYHA) class ≥III/heart failure hospitalization (OR = 10.53; 95% CI, 3.17-34.98) and systemic ventricle dysfunction (SVD; OR = 4.95; 95% CI, 2.55-9.64). We did not show history of supraventricular arrhythmia (OR = 2.78; 95% CI, 0.94-8.24), systemic valve regurgitation ≥moderate (SVR; OR = 4.02; 95% Cl, 0.84-19.18), and pacemaker implantation (OR = 1.48; 95% Cl, 0.12-18.82) to affect the long-term survival. In operated patients only, SVD (OR = 4.69; 95% CI, 2.06-10.71) and SVR (OR = 3.85; 95% CI, 1.5-9.85) showed a statistically significant impact on survival. Conclusions: The risk factors for long-term mortality for the entire cc-TGA population are NYHA class ≥III/heart failure hospitalization and systemic ventricle dysfunction. In operated patients, systemic ventricle dysfunction and at least moderate systemic valve regurgitation were found to affect survival.

Comparative efficacy of six programmed cell death Protein-1 inhibitors as first-line treatment for advanced non-small cell lung cancer: a multicenter retrospective cohort study.

The purpose of this study was to assess the comparative efficacy of six programmed cell death-1 inhibitors (nivolumab, pembrolizumab, sintilimab, tislelizumab, toripalimab, and camrelizumab) that have been used as first-line therapy for Chinese patients with advanced non-small cell lung cancer (NSCLC), which remains unclear. We determined the differences in efficacy by observing patient survival data, with the goal of informing future treatment options. Retrospective data analysis from June 2015 to April 2023 included 913 patients across six groups: nivolumab (123%, 13.5%), pembrolizumab (421%, 46.1%), sintilimab (239%, 26.1%), tislelizumab (64%, 7.0%), toripalimab (39%, 4.3%), and camrelizumab (27%, 3.0%). The median progression-free survival (PFS) for each group was 16.0, 16.1, 18.4, 16.9, 23.7, and 12.8 months, and the median overall survival (OS) was 33.7, 36.1, 32.5, not reached, 30.9 and 46.0 months for the nivolumab, sintilimab, pembrolizumab, tislelizumab, toripalimab, and camrelizumab groups, respectively. While differences existed in the objective response rates among groups (p < 0.05), there were no significant differences (all p > 0.05) in PFS or OS. The findings suggest comparable efficacy among these PD-1 inhibitors for NSCLC treatment, underscoring their collective suitability and aiding treatment decisions.

Sarcopenic obesity predicts short- and long-term outcomes after neoadjuvant chemotherapy and surgery for gastric cancer.

BACKGROUND: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival. METHODS: Data from 207 patients with LAGC, who underwent NAC followed by radical gastrectomy between January 2010 and October 2019, were reviewed. Skeletal muscle mass and visceral fat area were measured pre- and post-NAC using computed tomography to define sarcopenia and obesity, the coexistence of which was defined as SO. RESULTS: Among the patients, 52 (25.1%) and 38 (18.4%) developed SO before and after NAC, respectively. Both pre- (34.6%) and post- (47.4%) NAC SO were associated with the highest postoperative morbidity rates; however, only post-NAC SO was an independent risk factor for postoperative morbidity [hazard ratio (HR) = 9.550, 95% confidence interval (CI) = 2.818-32.369; P < .001]. Pre-NAC SO was independently associated with poorer 3-year overall [46.2% vs. 61.3%; HR = 1.258 (95% CI = 1.023-1.547); P = .049] and recurrence-free [39.3% vs. 55.4%; HR 1.285 (95% CI 1.045-1.579); P = .017] survival. CONCLUSIONS: Pre-NAC SO was an independent prognostic factor in patients with LAGC undergoing NAC; post-NAC SO independently predicted postoperative morbidity.

Reduced 30-day in-hospital but increased long-term mortality for weekend vs weekday acute medical admission.

BACKGROUND: Acute medical admission at the weekend has been reported to be associated with increased mortality. We aimed to assess 30-day in-hospital mortality and subsequent follow-up of all community deaths following discharge for acute medical admission to our institution over 21 years. METHODS: We employed a database of all acute medical admissions to our institution over 21 years (2002-2023). We compared 30-day in-hospital mortality by weekend (Saturday/Sunday) or weekday (Tuesday/Wednesday) admission. Outcome post-discharge was determined from the National Death Register to December 2021. Predictors of 30-day in-hospital and long-term mortality were analysed by logistic regression or Cox proportional hazards models. RESULTS: The study population consisted of 109,232 admissions in 57,059 patients. A weekend admission was associated with a reduced 30-day in-hospital mortality, odds ratio (OR) 0.70 (95%CI 0.65, 0.76). Major predictors of 30-day in-hospital mortality were acute illness severity score (AISS) OR 6.9 (95%CI 5.5, 8.6) and comorbidity score OR 2.4 (95%CI 1.2, 4.6). At a median follow-up of 5.9 years post-discharge, 19.0% had died. The strongest long-term predictor of mortality was admission AISS OR 6.7 (95%CI 4.6, 9.9). The overall survival half-life after hospital discharge was 16.6 years. Survival was significantly worse for weekend admissions at 20.8 years compared to weekday admissions at 13.3 years. CONCLUSION: Weekend admission of acute medical patients is associated with reduced 30-day in-hospital mortality but reduced long-term survival.

Retroperitoneal Sarcoma Requiring Abdominal Aortic Replacement With Long-Term Survival: A Case Report.

Retroperitoneal sarcoma (RPS) is a rare disease. RPS invading the abdominal aorta is exceedingly rare and has a poor prognosis. There have been scattered cases of RPS treated with combined abdominal aortic replacement. However, the average survival time for these cases was only 8 months, with a 2-year survival rate of 21%, indicating a poor prognosis. In this case study, a 44-year-old man presented to our hospital complaining of abdominal pain. Multiple imaging findings suggested a retroperitoneal mass that was diagnosed as a malignant tumor. The patient underwent tumor resection with abdominal aortic replacement due to an RPS tumor invading the abdominal aorta. The histopathological grade was determined to be grade 3, the most malignant grade tumor, according to the Fédération Nationale des Centres de Lutte Contre le Cancer grading system. Postoperative chemotherapy with doxorubicin and ifosfamide was administered for five cycles. The patient has been alive for over 8 years after the operation without any recurrence. This case presents a long-term survival of RPS requiring abdominal aortic replacement.

Loss of copy numbers of retrotransposons (HERVK) on chromosome 7p11.2 impacts EGFR (Epidermal Growth Factor Receptor)-induced phenotypes for platinum sensitivity and long-term survival in ovarian cancer-A study from the OVCAD consortium.

We analyzed variations in the epidermal growth factor receptor (EGFR) gene and 5'-upstream region to identify potential molecular predictors of treatment response in primary epithelial ovarian cancer. Tumor tissues collected during debulking surgery from the prospective multicenter OVCAD study were investigated. Copy number variations in the human endogenous retrovirus sequence human endogenous retrovirus K9 (HERVK9) and EGFR Exons 7 and 9, as well as repeat length and loss of heterozygosity of polymorphic CA-SSR I and relative EGFR mRNA expression were determined quantitatively. At least one EGFR variation was observed in 94% of the patients. Among the 30 combinations of variations discovered, enhanced platinum sensitivity (n = 151) was found dominantly with HERVK9 haploidy and Exon 7 tetraploidy, overrepresented among patients with survival ≥120 months (24/29, p = .0212). EGFR overexpression (≥80 percentile) was significantly less likely in the responders (17% vs. 32%, p = .044). Multivariate Cox regression analysis, including age, FIGO stage, and grade, indicated that the patients' subgroup was prognostically significant for CA-SSR I repeat length <18 CA for both alleles (HR 0.276, 95% confidence interval 0.109-0.655, p = .001). Although EGFR variations occur in ovarian cancer, the mRNA levels remain low compared to other EGFR-mutated cancers. Notably, the inherited length of the CA-SSR I repeat, HERVK9 haploidy, and Exon 7 tetraploidy conferred three times higher odds ratio to survive for more than 10 years under therapy. This may add value in guiding therapies if determined during follow-up in circulating tumor cells or circulating tumor DNA and offers HERVK9 as a potential therapeutic target.

Estimating the long-term survival of unresectable stage III non-small cell lung cancer based on cure model analysis.

BACKGROUND: The predictors of long-term survival and appropriate surrogate endpoints in unresectable stage III non-small cell lung cancer (NSCLC) treated with radiotherapy remain unclear, especially in the immune therapy era. METHODS: This study retrospectively analyzed a prospective cohort of 822 patients treated at the Chinese National Cancer Center from 2013 to 2022. Cure fractions, surrogates for long-term survival, and associated factors were assessed using a mixture cure model, with validation against a matched Surveillance, Epidemiology, and End Results (SEER) dataset. RESULTS: 27.3% of patients with unresectable stage III NSCLC can achieve long-term survival after treated by radiotherapy. 4-year PFS and 5-year OS, when 80% of patients were considered cured, showed significant correlations with cure rates based on background mortality-adjusted PFS and relative survival, with R-squared values exceeding 0.85. Independent predictors of long-term survival included non-squamous cell carcinoma (non-SCC) pathological type, N category, gross tumor volume, and treatment combination with immune checkpoint inhibitors (ICIs). CONCLUSIONS: Radiotherapy, especially when combined with ICIs, offers a potential cure for a proportion of patients with unresectable stage III NSCLC. Tumor burden and ICIs are key predictors of long-term survival. The study suggested 4-year PFS and 5-year OS as surrogate endpoints for cure and long-term survival assessment.