Modern era systemic therapies: Expanding concepts of cure in early and locally advanced non-small cell lung cancer.

Cure of cancer is a sensitive and multidimensional concept that is challenging to define, difficult to assert at the individual patient level, and often surrounded by controversy. The notion of cure in non-small cell lung cancer (NSCLC) has changed and continues to evolve with improvements in diagnosis and treatment. Targeted and immune therapies have recently entered the treatment landscape of stage I-III NSCLC. While some initial pivotal trials of such agents failed to improve survival, recently approved epidermal growth factor receptor (EGFR) inhibitors (in EGFR-mutated NSCLC) and immune checkpoint inhibitors have shown delays in disease recurrence or progression and unprecedented survival gains compared to previous standards of care. Additional data is now emerging supporting the benefit of treatment strategies based on alternation-matched targeting (anaplastic lymphoma kinase [ALK] inhibition in ALK-altered disease) and immune checkpoint inhibition in stage I-III NSCLC. Similar to previous developments in the treatment of early and locally advanced NSCLC, it is expected that statistically significant and clinically meaningful trial-level benefits will translate into real-world benefits, including improvements in cure measures. Parallel advances in molecular testing (e.g., circulating tumor DNA analyses) are also allowing for a deeper and more comprehensive characterization of disease status and treatment response. Given the impact that curative-intent treatments have on survival, it is critical that various stakeholders, including clinicians and patients, are aware of new opportunities to pursue cure in stage I-III NSCLC.

Atrial septal interventions during and after hybrid stage I palliation of hypoplastic left heart syndrome.

BACKGROUND: Hybrid stage I palliation (HS1P) is an alternative approach for initial palliation in hypoplastic left heart syndrome (HLHS) patients. Unlike surgical stage I palliation where atrial septectomy is routinely performed, atrial septal intervention (ASI) during HS1P is variable. In this study, we described our experience with ASI in single ventricle (SV) patients who underwent HS1P and identified factors associated with need for ASI after HS1P. METHODS: Data were retrospectively collected for all HLHS patients who underwent HS1P at our center over the past 12 years. We evaluated ASIs performed during the HS1P (intra-HS1P ASI) and ASIs performed during the period from HS1P to the subsequent surgical stage, either interval Norwood stage I or comprehensive stage II (post-HS1P ASI). Patient factors and procedural data were compared to identify factors associated with undergoing post-HS1P ASI and the impact of ASI on patient outcomes was evaluated. RESULTS: Of 50 SV patients included, 23 (46%) underwent intra-HS1P ASI and 26 (52%) underwent post-HS1P ASI. Need for post-HS1P ASI was lower among patients who had an intra-HS1P ASI as compared to those who did not (30% vs. 70%; p = 0.005). There were no significant differences in short or Midterm outcomes between patients who underwent intra-HS1P ASI or post-HS1P ASI and their counterparts. CONCLUSIONS: ASI is common both during and after HS1P but is generally well tolerated and type of ASI does not significantly impact overall patient outcomes. Our findings suggest that the current approach of individualizing management of ASI in the HS1P population is effective and safe.

In the patient's shoes: The impact of hospital proximity and volume on stage I endometrial cancer care patterns and outcomes.

OBJECTIVE: To compare the impact of travel burden and hospital volume on care patterns and outcomes in stage I endometrial cancer. METHODS: This retrospective cohort study identified patients from the National Cancer Database with stage I epithelial endometrial carcinoma who underwent hysterectomy between 2012 and 2020. Patients were categorized into: lowest quartiles of travel distance and hospital surgical volume for endometrial cancer (Local) and highest quartiles of distance and volume (Travel). Primary outcome was overall survival. Secondary outcomes were surgery route, lymph node (LN) assessment method, length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. Results were stratified by tumor recurrence risk. Outcomes were compared using propensity-score matching. Propensity-adjusted survival was evaluated using Kaplan-Meier curves and compared using log-rank tests. Cox models estimated hazard ratios for death. Sensitivity analysis using modified Poisson regressions was performed. RESULTS: Among 36,514 patients, 51.4% were Local and 48.6% Travel. The two cohorts differed significantly in demographics and clinicopathologic characteristics. Upon propensity-score matching (p < 0.05 for all), more Travel patients underwent minimally invasive surgery (88.1%vs79.1%) with fewer conversions to laparotomy (2.0%vs2.6%), more sentinel (20.5%vs11.3%) and fewer traditional LN assessments (58.1vs61.7%) versus Local. Travel patients had longer intervals to surgery (≥30 days:56.7%vs50.1%) but shorter LOS (<2 days:76.9%vs59.8%), fewer readmissions (1.9%vs2.7%%), and comparable 30- and 90-day mortality. OS and HR for death remained comparable between the matched groups. CONCLUSIONS: Compared to surgery in nearby low-volume hospitals, patients with stage I epithelial endometrial cancer who travelled longer distances to high-volume centers experienced more favorable short-term outcomes and care patterns with comparable long-term survival.

Development and validation of time-to-event models to predict metastatic recurrence of localized cutaneous melanoma.

BACKGROUND: The recent expansion of immunotherapy for stage IIB/IIC melanoma highlights a growing clinical need to identify patients at high risk of metastatic recurrence and, therefore, most likely to benefit from this therapeutic modality. OBJECTIVE: To develop time-to-event risk prediction models for melanoma metastatic recurrence. METHODS: Patients diagnosed with stage I/II primary cutaneous melanoma between 2000 and 2020 at Mass General Brigham and Dana-Farber Cancer Institute were included. Melanoma recurrence date and type were determined by chart review. Thirty clinicopathologic factors were extracted from electronic health records. Three types of time-to-event machine-learning models were evaluated internally and externally in the distant versus locoregional/nonrecurrence prediction. RESULTS: This study included 954 melanomas (155 distant, 163 locoregional, and 636 1:2 matched nonrecurrences). Distant recurrences were associated with worse survival compared to locoregional/nonrecurrences (HR: 6.21, P < .001) and to locoregional recurrences only (HR: 5.79, P < .001). The Gradient Boosting Survival model achieved the best performance (concordance index: 0.816; time-dependent AUC: 0.842; Brier score: 0.103) in the external validation. LIMITATIONS: Retrospective nature and cohort from one geography. CONCLUSIONS: These results suggest that time-to-event machine-learning models can reliably predict the metastatic recurrence from localized melanoma and help identify high-risk patients who are most likely to benefit from immunotherapy.

EGFR mutation testing, treatment and survival in stage I-III non-small-cell lung cancer: CancerLinQ Discovery database retrospective analysis.

Aim: To describe real-world biomarker testing, treatment and survival in stage IA-IIIC non-small-cell lung cancer (NSCLC). Methods: Electronic records of USA-based patients in the CancerLinQ Discovery® database with stage IA-IIIC NSCLC (diagnosed between 2014 and 2018) were screened; a curated cohort of 14,452 records was identified for further analysis. Results: Of 3121 (21.6%) patients who had EGFR testing, 493 (15.8%) were EGFR-mutation positive. Of 974 patients who underwent surgical resection, 513 (52.7%) received adjuvant therapy. A quarter of patients with EGFR-mutation positive NSCLC received targeted adjuvant therapy. Conclusion: Approximately a fifth of patients underwent EGFR testing; biomarker testing is important to ensure optimal outcomes for patients with stage I-III NSCLC.

A study investigating how many patients with early-stage non-small-cell lung cancer (NSCLC) had mutations in a protein called EGFR and which treatments they received in routine clinical practice: The treatment recommended by medical experts for stage IA­IIIA non-small-cell lung cancer (NSCLC) is surgical removal of the growth (tumor). Patients with stage II or III, and some with stage IB disease, are recommended to receive treatment with medications such as chemotherapy or oral cancer treatments after surgery (adjuvant treatment). In some lung cancers, there are mutations in a protein called EGFR. Osimertinib, a drug that blocks the activity of mutated EGFR on cancer cells, reducing their growth and spread, is recommended as an adjuvant treatment for patients with EGFR-mutated, stage IB­IIIA NSCLC. This study aimed to understand how many patients with stage I­III NSCLC have tumors with EGFR mutations, and which treatments patients received in everyday clinical practice, before new medicines such as osimertinib (that treat EGFR-mutated NSCLC) were recommended. We looked at anonymous data from 14,452 patients with stage I­III NSCLC treated at cancer clinics in the USA between 2014 and 2018. We found that 3121 (21.6%) patients had an EGFR mutation test and 493 (15.8%) had EGFR-mutation positive NSCLC. Of patients who had surgery to remove the tumor, 55% received adjuvant therapy (treatment after surgery). It is important to perform EGFR mutation testing in patients with stage IB­IIIA NSCLC so that patients with EGFR-mutation positive NSCLC can receive appropriate treatment.

The effects of scaling and root planing plus home oral hygiene maintenance in Stage I/II periodontitis population: A 24-week randomized clinical trial.

OBJECTIVES: To compare the effects of powered and manual toothbrushing following scaling and root planing on bleeding on probing and other clinical indicators of periodontitis. MATERIALS AND METHODS: This was a randomized, examiner-blind, parallel-design, 24-week clinical study. Eligible subjects were 18-75 years of age with Stage I or II periodontitis. All subjects received scaling and root planing (SRP) within 28 days of enrollment. Thereafter, subjects were randomized to twice daily at-home use of either a powered toothbrush (PTB) or a manual toothbrush (MTB). Randomization was balanced for gender and periodontitis stage. No other oral hygiene aids were permitted. Subjects were evaluated every 4 weeks for the following measures: bleeding on probing (BOP), surface plaque (MPI), probing pocket depth (PPD) and clinical attachment level until Week 24. RESULTS: Of 328 randomized subjects, 299 subjects completed the study. For BOP at Week 24, the Least Squares (LS) Mean, standard error (SE) reduction from baseline was 0.24 (0.01) for the PTB group and 0.02 (0.01) for the MTB group, resulting in a statistically significant treatment difference of 0.22 (0.01), p-value < 0.0001. There were also concomitant reductions in MPI and PPD at Week 24, resulting in statistically significant (p-value < 0.0001) LS Mean (SE) treatment differences of 0.86 (0.04) and 0.24 (0.01), for MPI and PPD, respectively. CONCLUSION: When combined with SRP, daily home oral hygiene maintenance including a powered toothbrush significantly reduced clinical symptoms of periodontitis and surface plaque levels compared to a manual toothbrush in a Stage I/II periodontitis population. (ClinicalTrials.gov Identifier: NCT04254770).

Stage I epithelial or stromal type Wilms tumors are low risk tumors: An analysis of patients treated on the SIOP-WT-2001 protocol in the UK-CCLG and GPOH studies (2001-2020).

BACKGROUND: Patients treated with preoperative chemotherapy with stage I intermediate-risk Wilms tumor (IR-WT) represent the largest group of patients with Wilms tumor (WT), and they have excellent outcomes. METHODS: The authors performed a retrospective analysis of patients with stage I epithelial (ET-WT) or stromal type WT (ST-WT) treated pre- and postoperatively according to the International Society of Paediatric Oncology-WT-2001 protocol in the UK Children's Cancer and Leukaemia Group and Gesellschaft für Pädiatrische Onkologie und Hämatologie groups' participation in the relevant WT trials and studies (2001-2020). RESULTS: There were 880 patients with stage I IR-WT, including 124 with ET-WT, 156 with ST-WT, and 600 with other IR-WT (oIR-WT). Patients with stage I ET-WT or ST-WT were significantly younger than patients with oIR-WT, represented a large proportion of stage I WTs in their groups, and tumors showed poor histologic response to preoperative chemotherapy. The 5-year event-free survival (EFS) estimates for patients with stage I ET-WT (96.8% ± 1.8 SE) or ST-WT (96.8% ± 1.6 SE) were significantly better than for patients with oIR-WT (90.3% ± 1.3 SE) (p = .014 and p = .009, respectively). A multivariate analysis showed that histologic type (ET-WT or ST-WT) remained a significant factor for EFS when adjusted for age and gender (p = .032 and p = .022, respectively). In both groups, relapses occurred in 3.2% of patients, and the overall survival was 99.2%. CONCLUSIONS: The results suggest that stage I ET-WT or ST-WT could be regarded as low-risk WT, for which omission of postoperative chemotherapy should be considered. PLAIN LANGUAGE SUMMARY: Patients with pretreated intermediate-risk Wilms tumor (WT) represent the largest group of patients with WT. This study reports the outcomes of patients with stage I epithelial type (ET-WT) or stromal type WT (ST-WT). These patients were significantly younger and had a larger proportion of stage I cases than patients with other intermediate-risk WT (oIR-WT). The event-free survival for patients with stage I ET-WT and ST-WT was significantly better than for patients with oIR-WT. Rare relapses were curable resulting in 99.2% overall survival.

Analysis of Immune Intratumor Heterogeneity Highlights Immunoregulatory and Coinhibitory Lymphocytes as Hallmarks of Recurrence in Stage I Non-Small Cell Lung Cancer.

Our understanding of the molecular mechanisms underlying postsurgical recurrence of non-small cell lung cancer (NSCLC) is rudimentary. Molecular and T cell repertoire intratumor heterogeneity (ITH) have been reported to be associated with postsurgical relapse; however, how ITH at the cellular level impacts survival is largely unknown. Here we report the analysis of 2880 multispectral images representing 14.2% to 27% of tumor areas from 33 patients with stage I NSCLC, including 17 cases (relapsed within 3 years after surgery) and 16 controls (without recurrence ≥5 years after surgery) using multiplex immunofluorescence. Spatial analysis was conducted to quantify the minimum distance between different cell types and immune cell infiltration around malignant cells. Immune ITH was defined as the variance of immune cells from 3 intratumor regions. We found that tumors from patients having relapsed display different immune biology compared with nonrecurrent tumors, with a higher percentage of tumor cells and macrophages expressing PD-L1 (P =.031 and P =.024, respectively), along with an increase in regulatory T cells (Treg) (P =.018), antigen-experienced T cells (P =.025), and effector-memory T cells (P =.041). Spatial analysis revealed that a higher level of infiltration of PD-L1+ macrophages (CD68+PD-L1+) or antigen-experienced cytotoxic T cells (CD3+CD8+PD-1+) in the tumor was associated with poor overall survival (P =.021 and P =.006, respectively). A higher degree of Treg ITH was associated with inferior recurrence-free survival regardless of tumor mutational burden (P =.022), neoantigen burden (P =.021), genomic ITH (P =.012) and T cell repertoire ITH (P =.001). Using multiregion multiplex immunofluorescence, we characterized ITH at the immune cell level along with whole exome and T cell repertoire sequencing from the same tumor regions. This approach highlights the role of immunoregulatory and coinhibitory signals as well as their spatial distribution and ITH that define the hallmarks of tumor relapse of stage I NSCLC.

Mortality after radiotherapy or surgery in the treatment of early-stage non-small-cell lung cancer: a population-based data analysis in the clinical cancer registry of Brandenburg-Berlin.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an established treatment method with favorable toxicity for inoperable early-stage non-small-cell lung cancer (NSCLC) patients. This paper aims to evaluate the importance of SBRT in the treatment of early-stage lung cancer patients compared to surgery as standard of care. METHODS: The German clinical cancer register of Berlin-Brandenburg was assessed. Cases of lung cancer were considered if they had a TNM stage (clinical or pathological) of T1-T2a and N0/x and M0/x, corresponding to UICC stages I and II. In our analyses, cases diagnosed between 2000 and 2015 were included. We adjusted our models with propensity score matching. We compared patients treated with SBRT or surgery regarding age, Karnofsky performance status (KPS), sex, histological grade, and TNM classification. Further, we assessed the association of cancer-related parameters with mortality; hazard ratios (HR) from Cox proportional hazards models were computed. RESULTS: A total of 558 patients with UICC stages I and II NSCLC were analyzed. In univariate survival models, we found similar survival rates in patients who underwent radiotherapy compared with surgery (HR 1.2, 95% confidence interval [CI] 0.92-1.56; p = 0.2). Our univariate subgroup analyses of patients > 75 years showed a statistically nonsignificant survival benefit for patients treated with SBRT (HR 0.86, 95% CI 0.54-1.35; p = 0.5). Likewise, in our T1 subanalysis, survival rates were similar between the two treatment groups regarding overall survival (HR 1.12, 95% CI 0.57-2.19; p = 0.7). The availability of histological data might be slightly beneficial in terms of survival (HR 0.89, 95% CI 0.68-1.15; p = 0.4). This effect was also not significant. Regarding the availability of histological status in our subgroup analyses of elderly patients, we could show similar survival rates as well (HR 0.70, 95% CI 0.44-1.23; p = 0.14). T1-staged patients also had a statistically nonsignificant survival benefit if histological grading was available (HR 0.75, 95% CI 0.39-1.44; p = 0.4). Concerning adjusted covariates, better KPS scores were associated with better survival in our matched univariate Cox regression models. Further, higher histological grades and TNM stages were related to a higher mortality risk. CONCLUSION: Using population-based data, we observed an almost equal survival of patients treated with SBRT compared to surgery in stage I and II lung cancer. The availability of histological status might not be decisive in treatment planning. SBRT is comparable to surgery in terms of survival.

Adjuvant cytokine-induced killer cell immunotherapy improves long-term survival in patients with stage I-II non-small cell lung cancer after curative surgery.

BACKGROUND AIMS: Non-small cell lung cancer (NSCLC) remains the most common cancer worldwide, with an annual incidence of around 1.3 million. Surgery represents the standard treatment in early-stage NSCLC when feasible. However, because of cancer recurrence, only approximately 53% of patients with stage I and II NSCLC survive 5 years after radical surgery. The authors performed a retrospective study to investigate the impact of cytokine-induced killer (CIK) cell immunotherapy on the long-term survival of patients with stage I-II NSCLC after curative resection. METHODS: Fifty-seven patients with NSCLC were included in the study, with 41 and 16 in the control and CIK groups, respectively. Clinical characteristics were compared using a t-test and χ2 test. Survival analysis of patients with NSCLC was performed using the Kaplan-Meier method. The phenotypes and anti-tumor functions of CIK cells were evaluated by flow cytometry. RESULTS: Patients in the CIK group exhibited significantly longer overall survival (OS) and better disease-free survival (DFS) than those in the control group. Subgroup analysis indicated that patients with a higher risk of recurrence benefited more from CIK treatment and attained longer OS and DFS compared with those in the control group. No severe adverse events related to CIK treatment occurred. CIK cells contained a higher proportion of CD3+CD56+ natural killer (NK) T cells and CD3+ and CD8+ T cells and a lower proportion of CD3-CD56+ NK cells compared with peripheral blood mononuclear cells. CIK cells exhibited potent tumor-killing ability, with longer contact times with tumor cells and a greater number of cells exposed to tumor cells. CONCLUSIONS: The authors' data suggest that adjuvant CIK cell therapy is a safe and effective therapeutic strategy for improving OS and DFS in patients with stage I-II NSCLC after curative resection.

Excellent survival in relapsed stage I testicular cancer.

BACKGROUND: Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard management. However, 15-50% of patients eventually relapse with metastatic disease after AS. Relapses need to be detected early in order to achieve cure and avoid overtreatment. METHODS: We retrospectively analyzed consecutive GCC patients treated at two Swiss academic centers between 2010 and 2020. Patients with stage IS and extragonadal primaries were excluded. We compared disease characteristics and survival outcomes of patients relapsed from initial CSI to patients with de novo metastatic disease. Primary endpoint was the IGCCCG category at the time of relapse. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 360 GCC patients with initial CSI and 245 de novo metastatic patients. After a median follow-up of 47 months, 81 of 360 (22.5%) CSI patients relapsed: 41 seminoma (Sem) and 40 non-seminoma (NSem) patients. All Sems relapsed in the IGCCCG good prognosis group. NSem relapsed with good 29/40 (72.5%) and intermediate 11/40 (27.5%) prognostic features; 95.1% of relapses occurred within five years post-orchiectomy. Only 3 relapsed NSem patients died from metastatic disease. Five-year OS for relapsed CSI patients was 100% for Sem and 87% (95% CI: 61-96%) for NSem patients; five-year PFS was 92% (95% CI: 77-97) and 78% (95% CI: 56-90) for Sem and NSem, respectively. When stratified by IGCCCG prognostic groups, good risk relapsed patients had a trend towards better OS and PFS as compared to de novo metastatic patients. CONCLUSIONS: GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival.

Cumulative incidence of first recurrence after curative treatment of stage I-III colorectal cancer. Competing risk analyses of temporal and anatomic patterns.

BACKGROUND: Updated knowledge about the rates of recurrence and time to recurrence following curative treatment of colorectal cancer is essential to secure better patient information on prognosis, to serve as a premise in the discussion on adjuvant chemotherapy, and help to properly scale the intensity and length of follow-up. METHODS: This is a population-based study investigating aspects on first recurrence after radical treatment of clinical stages I-III of colorectal cancer in Central-Norway during 2001-2015. To reveal any time-trends, data were stratified by the time periods 2001-2005, 2006-2010 and 2011-2015. The cumulative incidence of first recurrence was calculated, treating death of unrelated causes as a competing event. Multivariable Cox analyses were done to calculate cause specific hazard ratios (HR) for risk of recurrence. RESULTS: At a minimum follow-up of six years, a first recurrence was detected in 1,113/5,556 patients at risk (20.0%). The recurrence rate was reduced from 23.6% in the first time period, through 20.0% in the second, and to 17.2% in the last, p < 0.001. The reduction applied to all tumor locations, to pathological disease stages II and III, to both gender, across different tumor differentiations, and to both elective and emergency surgery. In multivariable analyses time period, gender, disease stage, and tumor differentiation were significant determinants for risk of recurrence. CONCLUSIONS: The rate of first recurrence after curative surgery for colorectal cancer was substantially reduced from 2001 to 2015. The reason for the reduction could not be attributed to a single factor only. A combined effect of several incremental improvements, such as an increased use of preoperative radiation for rectal cancers, improved adjuvant chemotherapy for colon cancer, and a reduced proportion of emergency surgery, is suggested.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

MRI-based radiomics model for distinguishing Stage I endometrial carcinoma from endometrial polyp: a multicenter study.

BACKGROUND: Patients with early endometrial carcinoma (EC) have a good prognosis, but it is difficult to distinguish from endometrial polyps (EPs). PURPOSE: To develop and assess magnetic resonance imaging (MRI)-based radiomics models for discriminating Stage I EC from EP in a multicenter setting. MATERIAL AND METHODS: Patients with Stage I EC (n = 202) and EP (n = 99) who underwent preoperative MRI scans were collected in three centers (seven devices). The images from devices 1-3 were utilized for training and validation, and the images from devices 4-7 were utilized for testing, leading to three models. They were evaluated by the area under the receiver operating characteristic curve (AUC) and metrics including accuracy, sensitivity, and specificity. Two radiologists evaluated the endometrial lesions and compared them with the three models. RESULTS: The AUCs of device 1, 2_ada, device 1, 3_ada, and device 2, 3_ada for discriminating Stage I EC from EP were 0.951, 0.912, and 0.896 for the training set, 0.755, 0.928, and 1.000 for the validation set, and 0.883, 0.956, and 0.878 for the external validation set, respectively. The specificity of the three models was higher, but the accuracy and sensitivity were lower than those of radiologists. CONCLUSION: Our MRI-based models showed good potential in differentiating Stage I EC from EP and had been validated in multiple centers. Their specificity was higher than that of radiologists and may be used for computer-aided diagnosis in the future to assist clinical diagnosis.

Postoperative tegafur-uracil for stage I lung adenocarcinoma: first real-world data with an exploratory subgroup analysis.

PURPOSE: The effect of postoperative tegafur-uracil on overall survival (OS) after resection of stage I adenocarcinoma has been shown in clinical trials. The purpose of this study was to investigate whether findings from randomized trials of adjuvant tegafur-uracil are reproducible in a real-world setting. METHODS: A retrospective cohort study was performed using a multi-institutional database that included all patients who underwent complete resection of pathological stage I adenocarcinoma between 2014 and 2016. Survival outcomes for patients managed with and without tegafur-uracil were analyzed using the Kaplan-Meier method and a Cox proportional hazards model for the whole patient cohort and in a selected cohort based on eligibility criteria of a previous randomized trial. Propensity score matching was used to adjust for confounding effects. RESULTS: After propensity score matching, the hazard ratios for OS were 0.57 (95% confidence interval (CI) 0.29-1.14, P = 0.11) in the whole cohort and 0.69 (95% CI 0.32-1.50, P = 0.35) in the selected cohort. CONCLUSIONS: The effects of tegafur-uracil in this retrospective study appear to be consistent with those found in randomized clinical trials. These effects may be maximized in patients aged from 45 to 75 years.

A preoperative predictive model for stage IV endometriosis.

This was a retrospective study that evaluated a total of 280 patients who underwent surgery for complete removal of endometriosis to develop and validate the predictive model for stage IV endometriosis. The differences between stage I-III and stage IV endometriosis were performed by logistic regression. A model for the prediction of stage IV endometriosis was constructed, which was subsequently validated. The independent variables were visual analogue scale (VAS)≥4 [3.855, 95% confidence interval (CI): 1.675-8.871, p = 0.002], painful nodularity on uterosacral ligaments (13.954, 95% CI: 1.658-117.423, p = 0.015), and bilateral endometriosis (5.933, 95% CI: 1.931-18.225, p = 0.002). The AUC of the model was 0.777, with a sensitivity of 71.9% and specificity of 76.3% for stage IV endometriosis. Therefore, a complete collection of patient information prior to surgery, asking about pain and VAS scores, careful completion of pelvic examinations, and application of imaging techniques are conducive to better diagnosis and prediction of advanced endometriosis.IMPACT STATEMENTWhat is already known on this subject? Endometriosis, a chronic disease causing pain and infertility, is characterised by endometrial-like tissue outside the uterine cavity, which is often treated via surgery at present. Considering the risks of surgery, it is necessary to identify patients with stage IV endometriosis through non-invasive predictive models for adequate preparation for surgery. However, there is no reliable non-invasive predictive model now, despite utilisation of patient medical history, symptoms especially pain-related ones, pelvic examinations, laboratory examinations, and images in the preoperative diagnosis of endometriosis in the clinic.What do the results of this study add? A model developed based on three simple, accessible and non-invasive indicators displays good performance in predicting stage IV endometriosis.What are the implications of these findings for clinical practice and/or further research? It is conducive to diagnosing and predicting advanced endometriosis before surgery, so as to reduce the difficulty and improve the safety of surgery.

A Systematic Review Investigating the Difference between 1 Cycle versus 2 Cycles of Adjuvant Chemotherapy in Stage I Testicular Germ Cell Cancers.

Standard care for stage I testicular germ cell cancers (seminomatous-STC or non-seminomatous-NSTC) is orchiectomy followed by active surveillance, 1 or 2 cycles of adjuvant chemotherapy, surgery or radiotherapy. The decision on the adjuvant therapeutic approach is guided by the associated risk factors of the patient and the potential related toxicity of the treatment. Currently, there is no consensus regarding the optimal number of adjuvant chemotherapy cycles. Although in terms of overall survival, there is no proven inconsistency regarding the number of cycles of adjuvant chemotherapy, and the rate of relapse may vary.

Cyclin D1 Serves as a Poor Prognostic Biomarker in Stage I Gastric Cancer.

TNM stage still serves as the best prognostic marker in gastric cancer (GC). The next step is to find prognostic biomarkers that detect subgroups with different prognoses in the same TNM stage. In this study, the expression levels of epidermal growth factor receptor (EGFR) and cyclin D1 were assessed in 96 tissue samples, including non-tumorous tissue, adenoma, and carcinoma. Then, the prognostic impact of EGFR and cyclin D1 was retrospectively investigated in 316 patients who underwent R0 resection for GC. EGFR positivity increased as gastric tissue became malignant, and cyclin D1 positivity was increased in all the tumorous tissues. However, there was no survival difference caused by the EGFR positivity, while the cyclin D1-postive group had worse overall survival (OS) than the cyclin D1-negative group in stage I GC (10-year survival rate (10-YSR): 62.8% vs. 86.5%, p = 0.010). In subgroup analyses for the propensity score-matched (PSM) cohort, there were also significant differences in the OS according to the cyclin D1 positivity in stage I GC but not in stage II and III GC. Upon multivariate analysis, cyclin D1 positivity was an independent prognostic factor in stage I GC. In conclusion, cyclin D1 may be a useful biomarker for predicting prognosis in stage I GC.

Prognostic biomarker study in patients with clinical stage I esophageal squamous cell carcinoma: JCOG0502-A1.

We undertook genomic analyses of Japanese patients with stage I esophageal squamous cell carcinoma (ESCC) to investigate the frequency of genomic alterations and the association with survival outcomes. Biomarker analysis was carried out for patients with clinical stage T1bN0M0 ESCC enrolled in JCOG0502 (UMIN000000551). Whole-exome sequencing (WES) was performed using DNA extracted from formalin-fixed, paraffin-embedded tissue of ESCC and normal tissue or blood sample. Single nucleotide variants (SNVs), insertions/deletions (indels), and copy number alterations (CNAs) were identified. We then evaluated the associations between each gene alteration with a frequency of 10% or more and progression-free survival (PFS) using a Cox regression model. We controlled for family-wise errors at 0.05 using the Bonferroni method. Among the 379 patients who were enrolled in JCOG0502, 127 patients were successfully analyzed using WES. The median patient age was 63 years (interquartile range, 57-67 years), and 78.0% of the patients ultimately underwent surgery. The 3-year PFS probability was 76.3%. We detected 20 genes with SNVs, indels, or amplifications with a frequency of 10% or more. Genomic alterations in FGF19 showed the strongest association with PFS with a borderline level of statistical significance of P = .00252 (Bonferroni-adjusted significance level is .0025). Genomic alterations in FGF4, MYEOV, CTTN, and ORAOV1 showed a marginal association with PFS (P < .05). These genomic alterations were all CNAs at chromosome 11q13.3. We have identified new genomic alterations associated with the poor efficacy of ESCC (T1bN0M0). These findings open avenues for the development of new potential treatments for patients with ESCC.

An integrated analysis of the competing endogenous RNA network associated of prognosis of stage I lung adenocarcinoma.

BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.