A gene-based score for the risk stratification of stage IA lung adenocarcinoma.

OBJECTIVE: We aim to molecularly stratify stage IA lung adenocarcinoma (LUAD) for precision medicine. METHODS: Twelve multi-institution datasets (837 cases of IA) were used to classify the high- and low-risk types (based on survival status within 5 years), and the biological differences were compared. Then, a gene-based classifying score (IA score) was trained, tested and validated by several machine learning methods. Furthermore, we estimated the significance of the IA score in the prognostic assessment, chemotherapy prediction and risk stratification of stage IA LUAD. We also developed an R package for the clinical application. The SEER database (15708 IA samples) and TCGA Pan-Cancer (1881 stage I samples) database were used to verify clinical significance. RESULTS: Compared with the low-risk group, the high-risk group of stage IA LUAD has obvious enrichment of the malignant pathway and more driver mutations and copy number variations. The effect of the IA score on the classification of high- and low-risk stage IA LUAD was much better than that of classical clinicopathological factors (training set: AUC = 0.9, validation set: AUC = 0.7). The IA score can significantly predict the prognosis of stage IA LUAD and has a prognostic effect for stage I pancancer. The IA score can effectively predict chemotherapy sensitivity and occult metastasis or invasion in stage IA LUAD. The R package IAExpSuv has a good risk probability prediction effect for both groups and single stages of IA LUAD. CONCLUSIONS: The IA score can effectively stratify the risk of stage IA LUAD, offering good assistance in precision medicine.

Analysis of CDO1, PITX2, and CDH13 Gene Methylation in Early Endometrial Cancer for Prediction of Medical Treatment Outcomes.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AEH), undergoing organ-preserving treatment, was conducted. OBJECTIVE OF THE STUDY: To determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. MATERIALS AND METHODS: A total of 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n = 28) and AEH (n = 13), willing to preserve reproductive function, were studied; 18 specimens of uterine cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. RESULTS: All 13 women with AEH had a complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n = 28), 14 patients had a complete response (EC CR group) and 14 did not (EC non-CR group). It was found that all groups had statistically significant differences in CDO1 gene methylation levels compared to the control group (p < 0.001) except for the EC CR group (p = 0.21). The p-value for the difference between EC CR and EC non-CR groups was <0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p < 0.001), except for the AEH group (p = 0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p < 0.001), and the control and EC comparison groups (p = 0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was <0.001. The simultaneous assessment of CDO1 and CDH13 genes methylation allowed for an accurate distinction between EC CR and EC non-CR groups (AUC = 0.96). CONCLUSION: The assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), scheduled for medical treatment, can predict the treatment outcome.

Estimating the cure proportion of stage IA lung adenocarcinoma: a population-based study.

BACKGROUND: We aimed to investigate the factors influencing the cure, recurrence, and metastasis rates of stage IA lung adenocarcinoma, using a mixed cure model. METHODS: A total of 1,064 patients who underwent video-assisted thoracoscopic pulmonectomy were included. Variable screening was performed using the random forest algorithm and least absolute shrinkage and selection operator approaches. The mixed cure model was used to identify factors affecting patient cure and survival, and a sequential analysis was performed on 5%, 10%, and 20% of the presentational subtype concurrently. A receiver operating characteristics curve was used to determine the best model and construct a nomogram to predict the cure rate. RESULTS: The median follow-up time was 58 (range: 3-115) months. Results from the cure part of the mixed model indicated that the predominant subtype, presentational subtype, and tumor diameter were the main prognostic factors affecting cure rate. Therefore, the nomogram to predict the cure rate was constructed based on these factors. The survival part indicated that the predominant subtype was the only factor that influenced recurrence and metastasis. A sequential analysis of the presentational subtype showed it had no significant effect on survival (P > 0.05). Regardless of the recording mode, no significant improvement was observed in the model's discriminative ability. Only a few postoperative pathological specimens showed lymphovascular invasion (LVI); however, the survival curve suggested a significant effect on patient survival. CONCLUSIONS: After excluding the existence of long-term survivors, the predominant tumor subtype was determined to be the only factor influencing recurrence and metastasis. Although LVI is rare in stage IA lung adenocarcinoma, its significance cannot be discounted in terms of determining patient prognosis.

Clinical and Oncological Outcomes after Uniportal Anatomical Segmentectomy for Stage IA Non-Small Cell Lung Cancer.

Background and Objectives: The existing literature comparing sublobar and lobar resection in the treatment of stage IA lung cancer highlights the trend and overall need for further evaluation of minimally invasive, parenchymal-sparing techniques. The role of uniportal minimally invasive segmentectomy in the oncological therapy of early-stage non-small cell lung cancer (NSCLC) remains controversial. The aim of this study was to evaluate the clinical and midterm oncological outcomes of patients who underwent uniportal video-assisted anatomical segmentectomy for pathological stage IA lung cancer. Materials and Methods: We retrospectively analyzed all patients with pathological stage IA lung cancer (8th edition UICC) who underwent uniportal minimally invasive anatomical segmentectomy at our institution from January 2015 to December 2018. Results: 85 patients, 54 of whom were men, were included. The median length of hospital stay was 3 days (1.-3. IQR 3-5), whereas 30-day morbidity was 15.3% (13 patients), and the in-hospital mortality rate was 1.2% (1 patient). The 3-year overall survival rate was 87.9% for the total population. It was 90.5% in the IA1 group, 93.3% in the IA2 group, and 70.1% in the IA3 group, respectively. Conclusions: There were satisfactory short-term clinical outcomes with low 30-day morbidity and mortality and promising midterm oncological survival results following uniportal minimally invasive anatomical segmentectomy for pathological stage IA non-small cell lung cancer.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Assessment of recurrence rate and risk factors of relapse in stage in IA vulvar carcinoma.

OBJECTIVE: To evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. MATERIAL AND METHODS: Population-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011-2017. A central pathology review was performed on tumors from women with recurrent disease. RESULTS: 62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6). Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. CONCLUSION: Pathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC. Resection margins <8 mm and tumor size were associated with relapse of the disease.

Factors predicting recurrence in patients with stage IA endometrioid endometrial cancer: what is the importance of LVSI?

PURPOSE: The aim of this study is to define the clinical and pathological prognostic factors for recurrence and to evaluate the recurrence patterns and adjuvant therapies used in this group of patients with stage IA endometrioid type endometrial cancer (FIGO 2009-International Federation of Gynecology and Obstetrics). METHODS: Among the patients with epithelial endometrial cancer operated between January 1993 and May 2013 in a single institution, 720 patients with stage IA endometrioid endometrial cancer were included. Patients with a tumor type of serous, clear cell, mucinous, undifferentiated, and mixed type and with a tumor containing sarcomatous component and the patients with a secondary primer cancer were excluded from the study. RESULTS: Lympho-vascular space invasion (LVSI) was present in 60 (8.3%) patients. Pelvic and para-aortic lymphadenectomy was performed in 266 (36.9%) patients. Median follow-up time was 48 months (range 3-240). Recurrence occurred in 23 (3.4%) patients and 6 (0.9%) died of disease. The median time-to recurrence (TTR) was 24 months (range 4-52 months) in the patients with recurrence. LVSI was associated with recurrence in the univariate analysis. Five-year disease-free survival (DFS) decreased from 96.8 to 80.1% in the presence of LVSI (p < 0.001). This association could not be shown in patients who had had lymphadenectomy (p = 0.136). Extra-pelvic recurrence occurred in 6.7% and 1% of the patients with and without LVSI, respectively, (p = 0.001). Any independent prognostic factor could not be detected in the multivariate analysis. CONCLUSIONS: Only LVSI and tumor grade were associated with DFS and disease-specific survival (DSS), respectively, in the 686 patients with stage IA endometrial cancer in the univariate analysis, since these associations could not be shown in multivariate analysis.

Local radiation and phototherapy are the most cost-effective treatments for stage IA mycosis fungoides: A comparative decision analysis model in the United States.

BACKGROUND: Treatments for early-stage mycosis fungoides (MF) include topical steroids, topical nitrogen mustard, topical bexarotene, narrowband ultraviolet B (NBUVB), psoralen plus ultraviolet A (PUVA), and local radiation. The relative cost-effectiveness of each treatment given the differences in treatment failure, disease progression, and therapy escalation is not established. OBJECTIVE: To compare the cost-effectiveness (CE) of treatment options for stage IA MF. METHODS: A state-transition model was constructed with health states of stage IA to stage IV disease, no MF, and death. Treatment-specific remission and relapse rates were obtained from the literature. Lifetime costs were calculated by accounting for medications, office visits, laboratory monitoring, related procedures, work absences, and travel. RESULTS: The order of CE of the study treatments was determined to be as follows: local radiation, $225,399 for 15.40 life-years (LYs); NBUVB, $344,728 for 15.17 LYs; PUVA, $371,741 for 15.07 LYs; topical corticosteroids, $469,354 for 14.65 LYs; topical nitrogen mustard, $951,662 for 14.29 LYs; and topical bexarotene, 11,892,496 for 13.55 LYs. Sensitivity analyses confirmed the CE rankings. LIMITATIONS: We assumed a constant probability of response, relapse rates, and 3-month treatment intervals. CONCLUSIONS: Local radiation is the most cost-effective treatment for limited local disease, whereas phototherapy (NBUVB or PUVA) is cost-effective for generalized disease. Our findings can serve to inform future studies and recommendations regarding selection of therapy for stage IA MF.

Effects of lymphadenectomy among women with stage IA endometrial cancer: a SEER database analysis.

Aim: To determine whether lymphadenectomy is associated with increased survival of women with stage IA endometrial cancer. Methods: Patients diagnosed with endometrial cancer from 2004 to 2013 and whose clinicopathologic data were recorded in the SEER database were examined. Propensity matching paired subjects with similar background variables. Before and after matching, Kaplan-Meier curves were drawn for comparison. Results: In 11,603 patients, cardiovascular disease and diabetes were the most common causes of death. Before matching, lymphadenectomy significantly improved the overall survival of stage IA/grade 3-4 patients (p = 0.013), but after matching, lymphadenectomy did not prolong survival for any grade. Sentinel lymph nodes biopsy can reduce the number of resected lymph nodes (p = 8.387e-10 in Wilcox test) but can't prolong survival. Conclusion: After matching, no significant difference in survival between lymphadenectomy and nonlymphadenectomy was observed for stage IA patients, sentinel lymph nodes group had fewer lymph node removed, but didn't affect survival.

The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer.

PURPOSE: We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. METHODS: We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. RESULTS: The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. CONCLUSIONS: CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

Can reduced field-of-view diffusion sequence help assess microsatellite instability in FIGO stage 1 endometrial cancer?

PURPOSE: To determine if a reduced-field-of-view (rFOV) diffusion intravoxel incoherent motion (IVIM) sequence can differentiate the imaging characteristics of tumors with microsatellite instability (MSI) from those that are microsatellite stable (MSS) in patients with clinical FIGO stage IA endometrial cancer and if MRI can be used to determine MSI status. MATERIALS AND METHODS: Sagittal rFOV diffusion-weighted images were obtained in 12 patients on a 3T scanner using six b-values (0, 50, 100, 150, 200, and 600). These images were used to derive apparent diffusion coefficient (ADC), true diffusion coefficient (Dt ), pseudodiffusion (D*), and perfusion fraction (f). Regions of interest (ROIs) were drawn on the dynamic contrast-enhanced magnetic resonance imaging (MRI) sequence on an Advantage Windows workstation and were copied to the same location on IVIM-derived images. The ROI mean of these images was recorded and compared with the microsatellite status. The depth of myometrial invasion and IVIM-derived parameters were tabulated by microsatellite status. The Wilcoxon rank sum test was used to compare T1 postcontrast images and IVIM-derived images and microsatellite status. RESULTS: Six patients had MSS tumors and six had MSI tumors. MSS tumors had a significantly higher ADC value (P = 0.03) and Dt (P = 0.045) than the MSI tumors. There was no association between < and ≥ 50% depth of myometrial invasion (measured on pathology and MRI analysis) and MSI stability P > 0.99. CONCLUSION: IVIM, ADC and Dt may be able to determine microsatellite status noninvasively in patients with clinical FIGO stage I endometrial cancer. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:1216-1224.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

BACKGROUND: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). METHODS: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. RESULTS: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. CONCLUSIONS: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Impact of adjuvant chemotherapy and pelvic radiation on pattern of recurrence and outcome in stage I non-invasive uterine papillary serous carcinoma. A multi-institution study.

OBJECTIVES: To determine the impact of adjuvant chemotherapy or pelvic radiation on risk of recurrence and outcome in stage IA non-invasive uterine papillary serous carcinoma (UPSC). METHODS: This is a multi-institutional retrospective study for 115 patients with stage IA non-invasive UPSC (confined to endometrium) treated between 2000 and 2012. Kaplan-Meier and multivariable Cox proportional hazards regression modeling were used. RESULTS: Staging lymphadenectomy and omentectomy were performed in 84% and 57% respectively. Recurrence was seen in 26% (30/115). Sites of recurrences were vaginal in 7.8% (9/115), pelvic in 3.5% (4/115) and extra-pelvic in 14.7% (17/115). Adjuvant chemotherapy did not impact risk of recurrence (25.5% vs. 26.9%, p=0.85) even in subset of patients who underwent lymphadenectomy (20% vs. 23.5%, p=0.80). These findings were consistent for pattern of recurrence. Among those who underwent lymphadenectomy, adjuvant chemotherapy did not impact progression-free survival (p=0.34) and overall survival (p=0.12). However among patients who did not have lymphadenectomy, adjuvant chemotherapy or pelvic radiation was associated with longer progression-free survival (p=0.04) and overall survival (p=0.025). In multivariable analysis, only staging lymphadenectomy was associated with improved progression-free survival (HR 0.34, 95% CI 0.12-0.95, p=0.04) and overall survival (HR 0.35, 95% CI 0.12-1.0, p=0.05). Neither adjuvant chemotherapy nor pelvic radiation were predictors of progression-free or overall survivals. CONCLUSION: In stage IA non-invasive UPSC, staging lymphadenectomy was significantly associated with recurrence and outcome and therefore, should be performed in all patients. Adjuvant chemotherapy or pelvic radiation had no impact on outcome in surgically staged patients but was associated with improved outcome in unstaged patients.

Safety of less aggressive surgery for stage IA1 squamous cell carcinoma of the cervix.

AIM: To determine the risk of extracervical disease in patients with stage IA1 squamous cell carcinoma of the cervix. METHODS: A retrospective analysis was performed of 169 patients who had stage IA1 cervical cancer after conization at Seoul National University Hospital between 1997 and 2007. RESULTS: During the study period, 18 patients had conization as a definite treatment and 151 underwent subsequent surgery ranging from simple hysterectomy to radical hysterectomy with lymphadenectomy. Of the 151 patients who underwent subsequent surgery following conization, 35 (23.3%) patients underwent a simple hysterectomy, 20 (13.1%) a simple hysterectomy with pelvic lymphadenectomy and 96 (63.6%) radical surgery with lymphadenectomy. No parametrial involvement or lymph node metastasis was noted in any of the patients who underwent parametrial resection and/or lymphadenectomy. Of the 62 patients who had negative resection margins in conization specimens, only one presented with residual tumor in subsequent surgery. One recurrence of the disease was identified in the total sample (169 patients) with a median follow-up time of 99 months. CONCLUSION: The risk of extracervical disease following conization is negligible, even for patients with positive resection margins in conization specimens. A more conservative and less aggressive approach may be possible for this patient subset.

Preoperative respiratory assessment predicts post-operative survival in stage IA non-small cell lung cancer.

Background: Respiratory impairment can lead to pulmonary complications after surgery; therefore, it should be considered when determining the choice of surgical procedure. Several studies have examined the relationship between preoperative respiratory function and postoperative mortality and morbidity after lung resection; however, there are no indicators for limited surgical procedure selection. The aim of this study was to examine the association between preoperative respiratory function and postoperative early and late complications, recurrence-free survival (RFS), and overall survival (OS) in patients undergoing pulmonary resection for stage I lung cancer. Methods: We performed a retrospective analysis of data from 192 patients undergoing pulmonary resection for primary pathological stage IA non-small cell lung cancer (NSCLC) at the Iwakuni Clinical Center in Japan between 2012 and 2015. We reviewed clinicopathological characteristics including preoperative pulmonary function and elucidated the relationship between them and postoperative survival. Results: Obstructive ventilatory impairment was present in 55 patients (28.6%), and restrictive ventilatory impairment was present in 31 patients (16.1%). Seven patients (3.6%) had both ventilatory impairment. Obstructive ventilatory impairment did not affect the 5-year RFS (P=0.08) or OS (P=0.21). However, restrictive ventilatory impairment reduced the 5-year RFS (P=0.002) and OS (P=0.009). The rates of early and late complications were not significantly different based on the preoperative respiratory function. Conclusions: In patients with preoperative restrictive ventilatory impairment in whom lobectomy or segmentectomy cannot be performed, careful consideration is needed for surgical indications.

An accurate prediction of negative lymph node metastasis with consideration of glucose metabolism in early-stage non-small cell lung cancer.

OBJECTIVE: We aimed to identify risk factors in lymph node metastasis in early-stage non-small cell lung cancer (NSCLC) and predict lymph node metastasis. METHODS: A total of 416 patients with clinical stage IA2-3 NSCLC who underwent lobectomy and lymph node dissection between July 2016 and December 2020 at National Cancer Center Hospital East were included. Multivariable logistic regression was performed to develop a model for predicting lymph node metastasis. Leave-one-out cross-validation was performed to evaluate the developing prediction model, and sensitivity, specificity, and concordance statistics were calculated to evaluate its diagnostic performance. RESULTS: The formula for calculating the probability of pathological lymph node metastasis included SUVmax of the primary tumor and serum CEA level. The concordance statistics was 0.7452. When the cutoff value associated with the risk of incorrectly predicting pathological lymph node metastasis was 7.2%, the diagnostic sensitivity and specificity for predicting metastasis were 96.4% and 38.6%, respectively. CONCLUSIONS: We created a prediction model for lymph node metastasis in NSCLC by combining the SUVmax of the primary tumor and serum CEA levels, which showed a particularly strong association. This model is clinically useful as it successfully predicts negative lymph node metastasis in patients with clinical stage IA2-3 NSCLC.

Survival analysis and clinicopathological features of patients with stage IA lung adenocarcinoma.

Background: With the development of medical technology and change of life habits, early-stage lung adenocarcinoma (LUAD) has become more common. This study aimed to systematically analyzed clinicopathological factors associated to the overall survival (OS) of patients with Stage IA LUAD. Methods: A total of 5942 Stage IA LUAD patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier methods and log-rank tests were used to compare the differences in OS. A nomogram constructed based on the Cox regression was evaluated by Concordance index (C index), calibration curve, decision curve analysis (DCA) and area under curve (AUC). And 136 patients were recruited from Shandong Province Hospital for external validation. Results: Cox analysis regression indicated that 12 factors, such as Diagnosis to Treatment Interval (DTI) and Income Level, were independent prognostic factors and were included to establish the nomogram. The C-index of our novel model was 0.702, 0.724 and 0.872 in the training, internal and external validation cohorts, respectively. The 3-year and 5-year survival AUCs and calibration curves showed excellent agreement in each cohort. Some new factors in the SEER database, including DTI and Income Level, were firstly confirmed as independent prognostic factors of Stage IA LUAD patients. The distribution of these factors in the T1a, T1b, and T1c subgroups differed and had different effects on survival. Conclusion: We summarized 12 factors that affect prognosis and constructed a nomogram to predict OS of Stage IA LUAD patients who underwent operation. For the first time, new SEER database parameters, including DTI and Income Level, were proved to be survival-related.

Low-grade endometrioid endometrial cancer with adnexal only metastasis: Evaluation of de-escalation of adjuvant therapy.

OBJECTIVE: To assess survival outcomes of stage IA3 endometrial cancer and the association of adjuvant therapy and survival. METHODS: The National Cancer Database was retrospectively queried to examine 594 and 1455 patients with stage IA3 and IIIA1 endometrial cancer, respectively, from 2010-2015. Overall survival (OS) was examined based on adjuvant therapy: multimodal combination chemotherapy and external beam radiotherapy, chemotherapy alone, external beam radiotherapy alone, and none. RESULTS: For stage IA3 disease, 109 (18.4%) patients did not receive adjuvant therapy. The 5-year OS rates for the no adjuvant therapy group and the combination group were 86.3% and 91.4%, respectively (adjusted-hazard ratio [aHR] 1.23, 95% confidence interval [CI] 0.70-2.18). This survival association was consistent when compared to chemotherapy alone (5-year OS rates 86.3% vs 86.3%, aHR 1.11, 95%CI 0.67-1.83). The results were similar among those who underwent nodal evaluation (5-year OS rates, 92.6%, 86.6%, and 89.4% for combination therapy, chemotherapy alone, and no adjuvant therapy), including grade 1 lesions (96.2%, 89.4%, and 100%, respectively). In grade 2 lesions, 5-year OR rates was modestly lower for no adjuvant therapy than combination therapy (89.4%, 84.0%, and 82.7% for combination, chemotherapy alone, and no adjuvant therapy, P = 0.03). For stage IIIA1 disease, omission of adjuvant therapy was associated with decreased OS compared to combination therapy (43.2% vs 73.1%, aHR 1.65, 95%CI 1.30-2.11) or chemotherapy alone (43.2% vs 67.1%, aHR 1.62, 95%CI 1.32-1.99). CONCLUSION: The results of this investigation suggest that survival effects of adjuvant therapy differ for stage IA3 and IIIA1 diseases. Patients with stage IA3 disease have overall good prognosis regardless of adjuvant therapy particularly grade 1 lesions, partly supporting the FIGO committee suggestion for adjuvant therapy de-escalation in stage IA3 endometrial cancer.

Preoperatively predicting survival outcome for clinical stage IA pure-solid non-small cell lung cancer by radiomics-based machine learning.

OBJECTIVE: Clinical stage IA non-small cell lung cancer (NSCLC) showing a pure-solid appearance on computed tomography is associated with a worse prognosis. This study aimed to develop and validate machine-learning models using preoperative clinical and radiomic features to predict overall survival (OS) in clinical stage IA pure-solid NSCLC. METHODS: Patients who underwent lung resection for NSCLC between January 2012 and December 2020 were reviewed. The radiomic features were extracted from the intratumoral and peritumoral regions on computed tomography. The machine-learning models were developed using random survival forest and eXtreme Gradient Boosting (XGBoost) algorithms, whereas the Cox regression model was set as a benchmark. Model performance was assessed using the integrated time-dependent area under the curve (iAUC) and validated by 5-fold cross-validation. RESULTS: In total, 642 patients with clinical stage IA pure-solid NSCLC were included. Among 3748 radiomic and 34 preoperative clinical features, 42 features were selected. Both machine-learning models outperformed the Cox regression model (iAUC, 0.753; 95% confidence interval [CI], 0.629-0.829). The XGBoost model showed a better performance (iAUC, 0.832; 95% CI, 0.779-0.880) than the random survival forest model (iAUC, 0.795; 95% CI, 0.734-0.856). The XGBoost model showed an excellent survival stratification performance with a significant OS difference among the low-risk (5-year OS, 100.0%), moderate low-risk (5-year OS, 88.5%), moderate high-risk (5-year OS, 75.6%), and high-risk (5-year OS, 41.7%) groups (P < .0001). CONCLUSIONS: A radiomics-based machine-learning model can preoperatively and accurately predict OS and improve survival stratification in clinical stage IA pure-solid NSCLC.

Evaluation of the preoperative neutrophil-to-lymphocyte ratio as a predictor of the micropapillary component of stage IA lung adenocarcinoma.

OBJECTIVE: To assess the ability of markers of inflammation to identify the solid or micropapillary components of stage IA lung adenocarcinoma and their effects on prognosis. METHODS: We performed a retrospective study of clinicopathologic data from 654 patients with stage IA lung adenocarcinoma collected between 2013 and 2019. Logistic regression analysis was used to identify independent predictors of these components, and we also evaluated the relationship between markers of inflammation and recurrence. RESULTS: Micropapillary-positive participants had high preoperative neutrophil-to-lymphocyte ratios. There were no significant differences in the levels of markers of systemic inflammation between the participants with or without a solid component. Multivariate analysis showed that preoperative neutrophil-to-lymphocyte ratio (odds ratio [OR] = 2.094; 95% confidence interval [CI], 1.668-2.628), tumor size (OR = 1.386; 95% CI, 1.044-1.842), and carcinoembryonic antigen concentration (OR = 1.067; 95% CI, 1.017-1.119) were independent predictors of a micropapillary component. There were no significant correlations between markers of systemic inflammation and the recurrence of stage IA lung adenocarcinoma. CONCLUSIONS: Preoperative neutrophil-to-lymphocyte ratio independently predicts a micropapillary component of stage IA lung adenocarcinoma. Therefore, the potential use of preoperative neutrophil-to-lymphocyte ratio in the optimization of surgical strategies for the treatment of stage IA lung adenocarcinoma should be further studied.