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Zhouyu Zhu, Ying Chai Department of Thoracic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Ying ChaiDepartment of Thoracic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, # 88 Jiefang Road, Hangzhou, 310009, People’s Republic of ChinaTel +86-571-87783642Fax +86-571-87783318Email 2183001@zju.edu.cnBackground: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is an effective treatment for advanced lung cancer harboring EGFR gene mutations, and has improved progression-free survival in several clinical trials.Methods: We investigated 30 stage I non-small-cell lung cancer patients harboring EGFR gene mutations with postoperative intrapulmonary recurrence. Progression-free survival and response rate were analyzed.Results: Partial response was achieved in 23 patients and stable disease was found in 7 patients. The objective response rate was 76.7% and disease control rate was 100%. The median progression-free survival (PFS) time was 24.5 months. The median PFS in patients with only intrapulmonary recurrence was significantly superior to patients with both intrapulmonary recurrence and metastasis (32.0 months vs 14.0 months, P = 0.003). The median PFS observed in patients who underwent icotinib treatment was significantly longer than in patients who underwent gefitinib treatment (30.5 months vs 12.0 months, p = 0.005). There were no statistical differences in median PFS between patients with tumors harboring exon 21 mutation and exon 19 deletion, age < 65 and ≥ 65, male and female, smoker and non-smoker.Conclusion: Our result reveals that first-line EGFR-TKIs treatment for stage I non-small-cell lung cancer patients harboring EGFR gene mutations with postoperative intrapulmonary recurrence is effective and could be a useful option in practical setting.Keywords: EGFR-TKIs, lung cancer, postoperative recurrence, stage I, efficacy

AbstractBackground This study evaluated the correlation between radiation-induced lung injury (RILI) and dosimetric parameters on computed tomography (CT) images of stage I non-small cell lung cancer (NSCLC) patients undergoing intensity-modulated radiotherapy (IMRT).Materials and methods Sixty-three stage I NSLC patients who underwent IMRT were enrolled in the study. The patients underwent CT within 6 months (acute phase) and 1.5 years (late phase) after radiotherapy. These were fused with the planned irradiation CT. The range of RILI was measured from 10% to 100%, with an IC in 10% increments.Results The median interval from completion of radiotherapy to acute and late phase CT was 92 and 440 days, respectively. The median RILI ranges of the acute and late phases were in the 80% (20–100%) and 70% dose regions (20–100%), respectively. The significantly narrower range of RILI when lung V20 in the acute phase was less than 19.2% and that of V5 in the late phase was less than 27.6% at the time of treatment planning.Conclusions This study showed that RILI occurred in a localized range in stage I NSCLC patients who underwent IMRT. The range of RILI was correlated with V20 in the acute phase and V5 in the late phase.KEY MESSAGESRILI correlated with V20 in acute and V5 in late phase.The shadow of RILI occurred in 80% dose region in acute and 70% in late phase.No relationship exists between radiographic changes in RILI and PTV volume.

BackgroundOvarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial ovarian carcinoma (EOC) that is often diagnosed at an earlier stage in younger women. It remains uncertain whether adjuvant chemotherapy improves the prognosis of patients with stage I OCCC.ObjectiveThis systematic review and meta-analysis aimed to assess the impact of adjuvant chemotherapy on survival in patients with stage I OCCC.Search StrategyEligible studies were screened from PubMed, Web of Science, Embase, and the Cochrane Library up to October 10, 2021.Selection CriteriaStudies that compared the oncological outcomes of adjuvant chemotherapy with observation were included.Data Collection and AnalysisSix studies comprising a total of 4553 patients were enrolled in our study, of whom 3320 (72.9%) patients had undergone adjuvant chemotherapy and 1233 (27.1%) had not.Main ResultsThe 5-year disease-free survival (DFS) and 5-year overall survival (OS) of stage I OCCC were 82.7% and 86.3%, respectively. In the overall population, adjuvant chemotherapy did not improve the 5-year DFS (83.2% vs 83.7%, OR 0.77, 95% CI 0.21-2.82, P=0.69) or 5-year OS (87.3% vs 83.6%, OR 1.30, 95% CI 0.86–1.98, P=0.22). Further subgroup analysis on stage IA/IB suggested that adjuvant chemotherapy did not impact 5-year DFS (OR 0.20, 95% CI 0.01-5.29, P=0.34) or 5-year OS (OR 1.52, 95% CI 0.78-2.98, P=0.22). For stage IC including 1798 patients, adjuvant chemotherapy revealed a significant survival benefit for 5-year OS (84.5% vs 83.3%, OR 1.44, 95% CI 1.08-1.94, P=0.01). Furthermore, the administration of adjuvant chemotherapy was found to be associated with a better 5-year OS (OR 4.98, 95% CI 1.12-22.22, P=0.04) in stage IC2/3. But no inferences regarding the effect of AC on stage IC2/3 can be made due to the limited size of the non-AC arm.ConclusionThis study indicated that adjuvant chemotherapy did not improve the prognosis of stage IA and IB OCCC patients. However, for patients with stage IC, due to the retrospective, heterogenous and older data with limited sample size, the pooled results of our study should be interpreted with caution. More prospective studies on the role of adjuvant chemotherapy in stage I OCCC are warranted.Systematic Review RegistrationPROSPERO, CRD42021287749.

BACKGROUND: Combination of different cancer markers is often used for predicting tumor growth, for the response to cancer therapy, and for increase in the positive diagnosis ratio in the malignant tumors. OBJECTIVE: Evaluation of the diagnostic efficacy of CA 15-3 and CA-62 cancer markers combination for early stages of breast cancer (BC) detection. METHODS: This blind study was performed on 2 clinically validated Sets that included serum measurements of CA 15-3 ELISA and CLIA-CA-62 assays in 488 serum samples with TNM classification. A study included 300 BC patients (254 at Stages I and II, 20 with ductal carcinoma in situ (DCIS), and 26 Stages III and IV patients), 47 patients with breast benign diseases, and 141 healthy controls. RESULTS: Sensitivity for DCIS & Stage I breast cancer detection was 75% at 100% Specificity (AUC = 0.895) using a following combination of two antigens: 10 < CA15-3 < 46 U/ml and CA-62 ⩾ 6300 U/ml, which allows eliminating false positive results. CONCLUSIONS: The results obtained in a blind study demonstrate that a combination of CA15-3 with CA-62 yields 75% Sensitivity at 100% Specificity for DCIS and Stage I breast cancer detection, which has a potential to be integrated into existing screening programs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Immune microenvironment changes can occur at very low tumor burden, even in stage I lung cancer. • Lung cancer-associated TCR (LC-aTCR) is a candidate biomarker for early detection of stage I lung cancer with high sensitivity and specificity. Early detection of lung cancer in asymptomatic patients remains challenging, especially for stage I. Considering the substantial interaction with tumor immunogenicity, we hypothesized that lung cancer-associated TCR (LC-aTCR) may serve as potential biomarker in early detection of stage I lung cancer. Individuals who received low-dose computed tomography (LDCT) screening were enrolled in the study. Surgical tissues and peripheral blood specimens were collected and performed with DNA-based T cell repertoire (TCR) sequencing. The motif-based algorithm was used to deconstruct specific lung cancer-associated TCRs (LC-aTCRs). A total of 146 individuals participating in the real-world LDCT screening project were enrolled in this study, including 52 patients with pathologically-confirmed stage I lung cancer and 94 non-cancer controls. We developed a motif-based algorithm to define 80 LC-aTCRs in the training cohort. Moreover, in the validation cohort, high sensitivity and specificity was showed in stage I lung cancer with 72% and 91% respectively, and the AUC of the ROC curve was 0.91 (95% CI: 0.85 ∼ 0.96). This work provides inspiration for stage I lung cancer detection by using blood TCR profiling data. The combination of TCR-based assay and routine screening deserves further testing in larger cohorts. [ABSTRACT FROM AUTHOR]

This study evaluated the correlation between radiation-induced lung injury (RILI) and dosimetric parameters on computed tomography (CT) images of stage I non-small cell lung cancer (NSCLC) patients undergoing intensity-modulated radiotherapy (IMRT). Sixty-three stage I NSLC patients who underwent IMRT were enrolled in the study. The patients underwent CT within 6 months (acute phase) and 1.5 years (late phase) after radiotherapy. These were fused with the planned irradiation CT. The range of RILI was measured from 10% to 100%, with an IC in 10% increments. The median interval from completion of radiotherapy to acute and late phase CT was 92 and 440 days, respectively. The median RILI ranges of the acute and late phases were in the 80% (20–100%) and 70% dose regions (20–100%), respectively. The significantly narrower range of RILI when lung V20 in the acute phase was less than 19.2% and that of V5 in the late phase was less than 27.6% at the time of treatment planning. This study showed that RILI occurred in a localized range in stage I NSCLC patients who underwent IMRT. The range of RILI was correlated with V20 in the acute phase and V5 in the late phase. RILI correlated with V20 in acute and V5 in late phase. The shadow of RILI occurred in 80% dose region in acute and 70% in late phase. No relationship exists between radiographic changes in RILI and PTV volume. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for patients with stage I non-small cell lung cancer (NSCLC)., Materials and Methods: The databases PubMed was searched from inception to November 2023 to identify relevant studies. Statistical analyses were performed with R version 3. 6. 3., Results: Thirty-three studies involving 1400 patients were finally included. According to our study, the incidence of patients with stage I NSCLC who were older than 60 years old was 98 % (95 % CI [94-100 %]); the lesions were mostly located in RUL (Right Upper Lobe) and LUL (Left Upper Lobe), and the incidence of the two sites was 29 % (95 % CI [23-35 %]) and 27 % (95 % CI [21-33 %]), respectively; the types of lung cancers mainly included adenocarcinoma, squamous carcinoma, and large-cell lung cancer, of which adenocarcinoma accounted for the largest proportion of 63 % (95 % CI [56-70 %]); the causes of death were mainly categorized into cancer-related (57 %, 95 %CI[40-74 %]) and noncancer-related (40 %, 95 %CI [23-58 %]); the common complications in the postoperative period were pneumothorax and pain, with the incidence of 33 % (95 %CI[24-44 %]) and 33 % (95 %CI[19-50 %]), and the rate of the postoperative complications in MWA was slightly higher than those in RFA; the local recurrence rate was 23 % (95 %CI[17-29 %]) and the distant recurrence rate was 18 % (95 %CI[7-32 %]); the pooling result showed the rate of 1-, 2-, 3-, and 5-year survival rate were 96 %, 81 %, 68 %, and 42 %, the Cancer-specific survival (CSS) rates at 1, 2, 3, and 5 years were 98 %, 88 %, 75 %, and 58 %, Disease-free survival (DFS) rates at 1, 2, 3, and 5 years were 87 %, 63 %, 57 %, and 42 %, there were no significant differences existed between the RFA group and MWA group in survival rate, CSS and DFS., Conclusion: Ablation therapy is safe and effective for stage I NSCLC patient. MWA and RFA have comparable efficacy, safety, and prognosis, which could be recommended for patients with stageⅠNSCLC, especially for patients who cannot tolerate open surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). Results: A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. Conclusions: Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis. [ABSTRACT FROM AUTHOR]

Purpose: To identify whether chemoradiotherapy improves survival of stage I nasopharyngeal carcinoma (NPC). Materials and Methods: NPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Pathologically confirmed stage T1N0M0 (the 7th edition AJCC) were investigated. Overall survival (OS) and cancer-specific survival (CSS) were compared between the radiotherapy and chemoradiotherapy groups using the Kaplan-Meier method and propensity score matching (PSM) analyses. Results: This study included 91 (40.27%) patients in the chemoradiotherapy group and 135 (59.73%) patients in the radiotherapy group. Before PSM, chemoradiotherapy was associated with worse 3-year OS (74.31 vs 87.23%; P = 0.025) and 5-year OS (64.28 vs 83.12%; P = 0.001) compared to those associated with radiotherapy. Similarly, chemoradiotherapy showed worse 3-year CSS (87.01 vs 96.97%; P = 0.028) and 5-year CSS (80.39 vs. 96.97%; P = 0.002) than those of radiotherapy. After PSM, chemoradiotherapy revealed worse 5-year OS (63.10 vs. 82.49%; P = 0.031) and CSS (80.95 vs. 93.70%; P = 0.016) than radiotherapy. The multivariate regression analysis revealed that chemoradiotherapy was an independent risk prognostic factor for OS and CSS before and after PSM. Conclusion: Radiotherapy alone is recommended for stage I NPC patients. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of lymphadenectomy on the prognosis of women of reproductive age with clinically apparent Stage I epithelial ovarian cancer (EOC). Methods: Data of women of reproductive age with Stage I EOC, diagnosed between 2010 and 2016, were extracted from the Surveillance, Epidemiology, and End Results database. Five‐year cancer‐specific survival (CSS) was evaluated using the Kaplan–Meier method. Multivariate Cox analysis was performed to evaluate the effect of lymph node dissection on survival. Propensity score (PS) matching was conducted to balance various clinicopathologic factors. Results: Of 2222 patients included, 1609 (72.4%) received lymph node dissection. The rate of histopathologically confirmed lymph node metastasis was highest in serous subtype (10.2%) and lowest in mucinous subtype (2.2%). No significant difference between the lymphadenectomy and non‐lymphadenectomy groups in 5‐year CSS was observed in the original cohort (P = 0.364) or in the PS matching cohort (P = 0.248). Nevertheless, there was a significant difference between the lymphadenectomy and non‐lymphadenectomy groups for patients with Stage IC EOC (92.4% vs. 88.1%, P = 0.027). According to the multivariate analysis, performance of the lymphadenectomy was not significantly associated with CSS in the original cohort (P = 0.163) or the PS matching cohort (P = 0.101). Conclusion: Dissection of lymph nodes was not significantly associated with improved prognosis for most Stage I EOC, but, lymphadenectomy may be necessary for women of reproductive age with Stage IC subtype. Synopsis: Performance of lymphadenectomy was necessary for women of reproductive age with Stage IC epithelial ovarian cancer. [ABSTRACT FROM AUTHOR]

BackgroundAmong patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer.MethodsThe current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated.ResultsOf 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens.ConclusionsOver time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

PurposeTo identify whether chemoradiotherapy improves survival of stage I nasopharyngeal carcinoma (NPC).Materials and MethodsNPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. Pathologically confirmed stage T1N0M0 (the 7th edition AJCC) were investigated. Overall survival (OS) and cancer-specific survival (CSS) were compared between the radiotherapy and chemoradiotherapy groups using the Kaplan-Meier method and propensity score matching (PSM) analyses.ResultsThis study included 91 (40.27%) patients in the chemoradiotherapy group and 135 (59.73%) patients in the radiotherapy group. Before PSM, chemoradiotherapy was associated with worse 3-year OS (74.31 vs 87.23%; P = 0.025) and 5-year OS (64.28 vs 83.12%; P = 0.001) compared to those associated with radiotherapy. Similarly, chemoradiotherapy showed worse 3-year CSS (87.01 vs 96.97%; P = 0.028) and 5-year CSS (80.39 vs. 96.97%; P = 0.002) than those of radiotherapy. After PSM, chemoradiotherapy revealed worse 5-year OS (63.10 vs. 82.49%; P = 0.031) and CSS (80.95 vs. 93.70%; P = 0.016) than radiotherapy. The multivariate regression analysis revealed that chemoradiotherapy was an independent risk prognostic factor for OS and CSS before and after PSM.ConclusionRadiotherapy alone is recommended for stage I NPC patients.

Background: Serum carcinoembryonic antigen (CEA), a classic tumour marker, is widely used in lung cancer in clinical practice. Nevertheless, few studies have elucidated the influence of dynamic changes in CEA in the perioperative phases, as a prognostic indicator, on lung cancer prognosis.Methods: This retrospective cohort analysis included consecutive patients with stage I-III lung cancer who underwent curative resection between December 2010 and December 2014. The patients were grouped into three cohorts: group A included patients with normal preoperative CEA, group B included patients with elevated preoperative CEA but normal postoperative CEA, and group C included patients with elevated preoperative and postoperative CEA. Five-year overall survival (OS) was estimated by Kaplan-Meier analysis (log-rank test). Multivariate analyses were performed with Cox proportional hazard regression.Results: A total of 1662 patients with stage I-III lung cancer were enrolled in our study. Patients with normal preoperative CEA had 15.9 and 20.1% better 3- and 5-year OS rates than the cohort with elevated preoperative CEA (p < 0.001). Furthermore, group C had 36.0 and 26.6% lower 5-year OS rates (n = 74, 32.4%) than group A (n = 1188, 68.4%) and group B (n = 139, 59.0%) (p < 0.001). Group B had poorer OS than group A (p = 0.016). For patients with different pathological TNM stages, subgroup analyses showed that group C had the shortest OS in stages I and II (p < 0.05), and patients with a post-preoperative CEA increment had poorer OS than those without an increment (p = 0.029). Multivariate analyses suggested that group C (HR = 2.0, 95% CI, 1.5–2.7, p < 0.001) rather than the group with normalized postoperative CEA (HR = 1.2, 95% CI, 0.9–1.5, p = 0.270) was an independent prognostic factor. In subgroup analysis of adenocarcinoma (ADC), survival analyses suggested that group C predicted a worse prognosis. Multivariate analysis of ADC indicated that group C was an independent adverse prognostic factor (HR = 1.9, 95% CI, 1.4–2.7, p < 0.001).Conclusions: Combined elevated preoperative and postoperative CEA is an independent adverse prognostic factor for stage I-III lung adenocarcinoma. Additionally, routine perioperative detection of serum CEA can yield valuable prognostic information for patients after lung cancer surgery.

Introduction: To investigate the treatment outcomes of passive scattering proton beam therapy using stereotactic ablative radiotherapy (SABR) or hypofractionated radiation therapy (RT) for inoperable patients or those who refused surgery for stage I non-small cell lung cancer (NSCLC).Methods: From January 2016 to December 2019, we retrospectively analyzed 42 patients with stage I NSCLC treated with proton beam therapy. The initially intended dose regimen was 60 cobalt Gray equivalents (CGE) in 4 fractions; however, sequentially modified dose regimens were used when the dose-volume constraints could not be met. The median total dose was 50 CGE (range 50-70 CGE), while the corresponding median biologically effective dose using [Formula: see text]= 10 (BED10) was 112.5 CGE (range 96-150 CGE).Results: The median follow-up time was 40 months (interquartile range 32-48 months). Among the 42 treated patients, 33 had pathologically proven cancers of which most were adenocarcinoma (n = 21, 64%). The 3-year overall survival rate was 71.8%. The estimated rates of local control and progression free survival at 3 years were 91.5% and 66.9%, respectively. Thirteen patients experienced disease progression consisting of three local, six regional, and nine distant failures. No grade 4 or 5 toxicities were observed.Conclusion: Passive scattering proton beam therapy for stage I NSCLC using SABR or hypofractionated RT was safe and showed high LC rates. [ABSTRACT FROM AUTHOR]

• Outcomes after minimally invasive lobectomy (MIL) and stereotactic ablative radiotherapy (SABR) for stage I NSCLC were compared after propensity score weighting. • Overall survival was not significantly different (HR 0.89, 95 % CI 0.65–1.20) • Recurrence-free survival was better after MIL (HR 0.70, 95 % CI 0.49–0.99) • After MIL, less patients developed regional recurrence or distant metastasis. • Future studies should focus on optimization of patient selection for MIL or SABR. The aim of the Early-Stage LUNG cancer (ESLUNG) study was to compare outcomes after minimally invasive lobectomy (MIL) and stereotactic ablative radiotherapy (SABR) in patients with stage I non-small cell lung cancer (NSCLC). In this retrospective cohort study, patients with clinical stage I NSCLC (according to TNM7), treated in 2014–2016 with MIL or SABR, were included. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between patients treated with MIL and a propensity score (PS)-weighted SABR population with characteristics comparable to those of the MIL group. 1211 MIL and 972 SABR patients were included. Nodal upstaging occurred in 13.0 % of operated patients. 30-day mortality was 1.0 % after MIL and 0.2 % after SABR. After SABR, the 5-year regional recurrence rate (18.1 versus 14.2 %; HR 0.74, 95 % CI 0.58–0.94) and distant metastasis rate (26.2 versus 20.2 %; HR 0.72, 95 % CI 0.59–0.88) were significantly higher than after MIL, with similar local recurrence rate (13.1 versus 12.1 %; HR 0.90, 95 % CI 0.68–1.19). Unadjusted 5-year OS and RFS were 70.2 versus 40.3 % and 58.0 versus 25.1 % after MIL and SABR, respectively. PS-weighted, multivariable analyses showed no significant difference in OS (HR 0.89, 95 % CI 0.65–1.20) and better RFS after MIL (HR 0.70, 95 % CI 0.49–0.99). OS was not significantly different between stage I NSCLC patients treated with MIL and the PS-weighted population of patients treated with SABR. For operable patients with stage I NSCLC, SABR could therefore be an alternative treatment option with comparable OS outcome. However, RFS was better after MIL due to fewer regional recurrences and distant metastases. Future studies should focus on optimization of patient selection for MIL or SABR to further reduce postoperative mortality and morbidity after MIL and nodal failures after SABR. [ABSTRACT FROM AUTHOR]

Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy. We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3. A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001). IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients. [ABSTRACT FROM AUTHOR]

Background: The uterus has a complex lymphatic drainage consisting of many groups that are in danger of endometrial cancer (EC) spread. Lymph node metastasis is a genuine pointer of poor prognosis requiring adjuvant therapy. Lymphatic mapping surgically can be done by blue dye labeling and perioperative algorithm. Aim: To assess the role of perioperative sentinel lymph nodes (SLN) mapping algorithm in reducing the necessity of pelvic lymphadenectomy. Methods: Fifty patients with early stage I EC underwent surgical staging. Transcervical injection of methylene blue was used, laparotomy was done and retroperitoneal spaces were opened. All lymph nodes were histopathologically examined and the negative SLN were ultrastaged. Results: Methylene blue dye injection resulted in blue lymph nodes in 20 (40%) cases, suspicious in 2 (4%) and negative in 28 (56%). Histopathological examination of sampled lymph node showed metastases in 18/20 (90%) of blue nodes, 1/2 (50%) of suspicious nodes and 0/28 (0%) of negative nodes. There were no false negative cases in this study and the detection rate was 89%. Conclusion: Perioperative algorithm accuracy and simplicity make it a reliable approach for lymph node assessment in early stage EC.

Background: Because of the low rate of lymph node metastasis in stage I rectal cancer (RC), local resection (LR) can achieve high survival benefits and quality of life. However, the indications for postoperative adjuvant therapy (AT) remain controversial.Methods: A retrospective analysis was performed in 6,486 patients with RC (pT1/T2) using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were initially diagnosed from 2004 to 2016; following LR, 967 received AT and 5,519 did not. Propensity score matching (PSM) was used to balance the confounding factors of the two groups; the Kaplan–Meier method and the log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to screen independent prognostic factors and build a nomogram on this basis. X-tile software was used to divide the patients into low-, moderate-, and high-risk groups based on the nomogram risk score.Results: Multivariate analysis found that age, sex, race, marital status, tumor size, T stage, and carcinoembryonic antigen (CEA) in the non-AT group were independent prognostic factors for stage I RC and were included in the nomogram prediction model. The C-index of the model was 0.726 (95% CI, 0.689–0.763). We divided the patients into three risk groups according to the nomogram prediction score and found that patients with low and moderate risks did not show an improved prognosis after AT. However, high-risk patients did benefit from AT.Conclusion: The nomogram of this study can effectively predict the prognosis of patients with stage I RC undergoing LR. Our results indicate that high-risk patients should receive AT after LR; AT is not recommended for low-risk patients.

Introduction: Patients with early-stage NSCLC typically must choose between a surgery with superior local control (lobectomy) or one that preserves lung parenchyma (wedge). Recognizing that many patients with cancer have competing mortality risks unrelated to cancer, we investigated whether an established model of predicting life expectancy could be used to identify patients with stage I NSCLC for whom survival after wedge is not different from lobectomy. Methods: A retrospective cohort study using the National Cancer Institute’s Surveillance Epidemiology and End Results—Medicare was performed to evaluate survival among treatment-naive patients, diagnosed 2005–2015, who underwent lobectomy or wedge for stage I (≤2 cm tumors) NSCLC. Comorbidity-related life expectancy (CR-LE) was estimated using a standard life-table approach based on comorbid conditions, sex, and age. Cox models and perioperative complications were stratified by 5-year CR-LE. Results: A total of 4560 patients (median age 74, interquartile range 70–78) were identified. CR-LE was greater than or equal to 5 years for 4016 patients (wedge = 23%). CR-LE was less than 5 years for 544 patients (wedge = 41%). Among patients with CR-LE greater than or equal to 5, wedge resection was associated with higher risk of mortality than lobectomy (hazard ratio: 1.68, 95% confidence interval: 1.52–1.86, p < 0.001). For those with CR-LE less than 5, there was no significant difference in mortality risk between lobectomy and wedge (hazard ratio: 1.19, 95% confidence interval: 0.96–1.47; p = 0.11). CR-LE less than five patients who underwent a lobectomy had higher 90-day mortality compared with wedge (9% versus 4%, p = 0.04). Conclusion: The survival advantage of lobectomy over wedge for stage I NSCLC seems to dissipate among patients with shorter life expectancy owing to age and comorbidities. Wedge resection may be a reasonable option for patients at high risk of dying from non–cancer-related causes.

Background: Because of the low rate of lymph node metastasis in stage I rectal cancer (RC), local resection (LR) can achieve high survival benefits and quality of life. However, the indications for postoperative adjuvant therapy (AT) remain controversial. Methods: A retrospective analysis was performed in 6,486 patients with RC (pT1/T2) using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were initially diagnosed from 2004 to 2016; following LR, 967 received AT and 5,519 did not. Propensity score matching (PSM) was used to balance the confounding factors of the two groups; the Kaplan–Meier method and the log-rank test were used for survival analysis. Cox proportional hazards regression analysis was used to screen independent prognostic factors and build a nomogram on this basis. X-tile software was used to divide the patients into low-, moderate-, and high-risk groups based on the nomogram risk score. Results: Multivariate analysis found that age, sex, race, marital status, tumor size, T stage, and carcinoembryonic antigen (CEA) in the non-AT group were independent prognostic factors for stage I RC and were included in the nomogram prediction model. The C-index of the model was 0.726 (95% CI, 0.689–0.763). We divided the patients into three risk groups according to the nomogram prediction score and found that patients with low and moderate risks did not show an improved prognosis after AT. However, high-risk patients did benefit from AT. Conclusion: The nomogram of this study can effectively predict the prognosis of patients with stage I RC undergoing LR. Our results indicate that high-risk patients should receive AT after LR; AT is not recommended for low-risk patients. [ABSTRACT FROM AUTHOR]

Background: The recurrent risk of stage I colorectal cancer (CRC) is not clear, and the data regarding appropriate post-operative surveillance schedules in stage I CRC are scarce. Objectives: We aimed to stratify stage I CRC based on the recurrence risk and evaluate optimal post-operative surveillance durations based on this stratification. Methods: We retrospectively analyzed the cases of 6607 stage I CRC patients from 24 institutions. To assess the patients' clinicopathological factors that impact recurrence-free survival (RFS), we performed univariate and multivariate analyses using Cox proportional hazards models. We divided the patients into classes based on their numbers of factors that were associated with poor RFI in the multivariate analysis. Results: Recurrence occurred in 3.9% patients. The multivariate analysis revealed the independent factors for poor RFS: rectal cancer, T2 depth, presence of lymphatic invasion, high level of pre-operative carcinoembryonic antigen, and absence of D2–3 lymphadenectomy. We also divided the patients into three classes based on their numbers of these risk factors; the 3-year and 5-year RFS rates were 99.3% and 99.1% in the no-risk patients, 97.4% and 96.5% in the patients with 1–2 risks, and 92.1% and 90.0% in the patients with 3–5 risks, respectively. In the patients with no risk and in the patients with 1–2 risks after 3 years post-surgery, ≤ 1% recurrence occurred. Thus, post-operative surveillance may be omitted in these populations. Conclusions: Our new classification properly stratified the recurrence risks of stage I CRC patients, and may help reduce unnecessary post-operative surveillance. [ABSTRACT FROM AUTHOR]

BackgroundThe incidence rates of early-stage non-small cell lung cancer (NSCLC) are now increasing, and therapies such as thermal ablation have shown potential therapeutic promise. This study aimed to determine the influence of different surgical methods on overall survival (OS) and cancer-specific survival (CSS) in patients with stage I NSCLC.MethodsPatients diagnosed with stage I NSCLC who had received thermal ablation or wedge resection between 2004 and 2014 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed according to the surgical method. Kaplan–Meier curves and a Cox proportional hazard model were used to evaluate OS and CSS.ResultsIn all, 4,372 patients with stage I NSCLC were included. Before PSM, the respective 3- and 5-year OS rates were 68.9 and 52.7% in the wedge resection group and 68.5 and 47.8% in the thermal ablation group (p < 0.0001); the corresponding CSS rates were 79.1 and 69.4% and 62.6 and 46.0% (p < 0.0001). After PSM, survival analysis showed that wedge resection had better OS (44.5% vs. 30.1%, p = 0.033) and CSS (63.5% vs. 46%, p = 0.038) than thermal ablation. After PSM, Cox regression showed that treatment was not associated with OS or CSS. For patients aged >75 years, thermal ablation showed similar OS and CSS as wedge resection (OS: 30.6% vs. 41.7%, p = 0.470; CSS: 46.4% vs. 64.1%, p = 0.100). After PSM, thermal ablation still had OS (30.6% vs. 41.0%, p = 0.470) and CSS (46.4% vs. 59.8%, p = 0.100) comparable to wedge resection.ConclusionFor patients with stage I NSCLC who are unfit for lobectomy, thermal ablation could be a potential therapeutic option, especially for those >75 years old.

Background Sublobar resection (SLR) and radiofrequency ablation (RFA) are the two minimally invasive procedures performed for treating stage I non-small cell lung cancer (NSCLC). This study aimed to compare SLR and RFA for the treatment of stage I NSCLC using the meta-analytical method. Methods We searched PubMed and Embase for articles published till December 2019 to evaluate the comparative studies and assess the survival and progression-free survival rates and postoperative complications (PROSPERO registration number: CRD42018087587). A meta-analysis was performed by combining the outcomes of the reported incidences of short-term morbidity and long-term mortality. The fixed or random effects model was utilized to calculate the pooled odds ratios (OR) and the 95% confidence intervals. Results Four retrospective studies were considered in the course of this study. The studies included a total of 309 participants; 154 were assigned to the SLR group, and 155 were assigned to the RFA group. Moreover, there were statistically significant differences between the one- and three-year survival rates and one- and three-year progression-free survival rates for the two groups, which were in favor of the SLR group. Among the post-surgical complications, pneumothorax and pleural effusion were more common for the SLR group, while cardiac abnormalities were prevalent in the RFA group. There was no difference in prevalence of hemoptysis between SLR and RFA groups, which might be attributed to the limited study sample size. Conclusion Considering the higher survival rates and disease control in the evaluated cases, surgical resection is the preferred treatment method for stage I NSCLC. RFA can be considered a valid alternative in patients not eligible for surgery and in high-risk patients as it is less invasive and requires shorter hospital stay.

Lung cancer is a leading cause of death worldwide, claiming nearly 1.80 million lives in 2020. Screening with low-dose computed tomography (LDCT) reduces lung cancer mortality by about 20% compared to standard chest X-rays among current or heavy smokers. However, several reports indicate that LDCT has a high false-positive rate. In this regard, methods based on biomarker detection offer excellent potential for developing noninvasive cancer diagnostic tests to complement LDCT for detecting stage 0∼IV lung cancers. Herein, we have developed a method for detecting and quantifying a p53-anti-p53 autoantibody complex and the total p53 antigen (wild and mutant). The LOD for detecting Tp53 and PIC were 7.41 pg/mL and 5.74 pg/mL, respectively. The detection ranges for both biomarkers were 0–7500 pg/mL. The known interfering agents in immunoassays such as biotin, bilirubin, intra-lipid, and hemoglobin did not detect Tp53 and PIC, even at levels that were several folds higher levels than their normal levels. Furthermore, the present study provides a unique report on this preliminary investigation using the PIC/Tp53 ratio to detect stage I–IV lung cancers. The presented method detects lung cancers with 81.6% sensitivity and 93.3% specificity. These results indicate that the presented method has high applicability for the identification of lung cancer patients from the healthy population.

Paul Aridgides,1 Tamara Nsouli,1 Rishabh Chaudhari,1 Russell Kincaid,1 Paula F Rosenbaum,2 Sean Tanny,1 Michael Mix,1 Jeffrey Bogart1 1Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, NY 13210, USA; 2Department of Public Health and Preventive Medicine, SUNY Upstate Medical University, Syracuse, NY 13210, USA Purpose: To report the outcomes of stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) according to respiratory motion management method. Methods: Patients with stage I NSCLC who received SBRT from 2007 to 2015 were reviewed. Computed tomography (CT) simulation with four-dimensional CT was performed for respiratory motion assessment. Tumor motion >1 cm in the craniocaudal direction was selectively treated with advanced respiratory management: either respiratory gating to a pre-specified portion of the respiratory cycle or dynamic tracking of an implanted fiducial marker. Comparisons were made with internal target volume approach, which treated all phases of respiratory motion. Results: Of 297 patients treated with SBRT at our institution, 51 underwent advanced respiratory management (48 with respiratory gating and three with tumor tracking) and 246 underwent all-phase treatment. Groups were similarly balanced with regard to mean age (P=0.242), tumor size (P=0.315), and histology (P=0.715). Tumor location in the lower lung lobes, as compared to middle or upper lobes, was more common in those treated with advanced respiratory management (78.4%) compared to all-phase treatment (25.6%, P

Background: The incidence rates of early-stage non-small cell lung cancer (NSCLC) are now increasing, and therapies such as thermal ablation have shown potential therapeutic promise. This study aimed to determine the influence of different surgical methods on overall survival (OS) and cancer-specific survival (CSS) in patients with stage I NSCLC. Methods: Patients diagnosed with stage I NSCLC who had received thermal ablation or wedge resection between 2004 and 2014 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed according to the surgical method. Kaplan–Meier curves and a Cox proportional hazard model were used to evaluate OS and CSS. Results: In all, 4,372 patients with stage I NSCLC were included. Before PSM, the respective 3- and 5-year OS rates were 68.9 and 52.7% in the wedge resection group and 68.5 and 47.8% in the thermal ablation group (p < 0.0001); the corresponding CSS rates were 79.1 and 69.4% and 62.6 and 46.0% (p < 0.0001). After PSM, survival analysis showed that wedge resection had better OS (44.5% vs. 30.1%, p = 0.033) and CSS (63.5% vs. 46%, p = 0.038) than thermal ablation. After PSM, Cox regression showed that treatment was not associated with OS or CSS. For patients aged >75 years, thermal ablation showed similar OS and CSS as wedge resection (OS: 30.6% vs. 41.7%, p = 0.470; CSS: 46.4% vs. 64.1%, p = 0.100). After PSM, thermal ablation still had OS (30.6% vs. 41.0%, p = 0.470) and CSS (46.4% vs. 59.8%, p = 0.100) comparable to wedge resection. Conclusion: For patients with stage I NSCLC who are unfit for lobectomy, thermal ablation could be a potential therapeutic option, especially for those >75 years old. [ABSTRACT FROM AUTHOR]

The role of surveillance after surgery for stage IA-C grade 2 (G2) or grade 3 (G3) immature teratomas (ITs) is controversial with many guidelines advocating adjuvant chemotherapy. Here, we investigate the safety of surveillance in stage IA-C G1-3 ITs. Clinicopathological data were analysed on postpubertal patients with stage I pure ITs in Multicenter Italian Trials in Ovarian Cancer centres and at Charing Cross Hospital, UK, between January 1985 and January 2018. Of 108 stage I patients, 66 (61.1%), 3 (2.8%) and 39 (36.1%) were International Federation of Gynecology and Obstetrics IA, IB, IC, respectively, with 31 (28.7%), 41 (38%) and 36 (33.3%) having grade 1 (G1), 2 and 3 disease, respectively. After surgery, 27 patients (25%) had adjuvant chemotherapy and 81 (75%) surveillance. There was no significant increase in the risk of malignant (G2-3 IT) relapse (9/81 vs 2/27; p = 0.72) or in disease-free survival (DFS) or overall survival in the surveillance vs chemotherapy groups. The median time to relapse was 17.8 months (range: 3–47) with no significant difference between surveillance or chemotherapy groups. The median follow-up was 64.3 months (Interquartile range (IQR) 22.2–101.7). Chemotherapy induced cures in all except for one patient who did not follow the surveillance protocol due to pregnancy and died of disease. Univariate and multivariate analyses revealed that only tumour grade (hazard ratio [HR] = 3.11; p = 0.02) and complete surgical staging (HR = 0.2; p = 0.01) were independent prognostic factors for decreased DFS. The present study suggests that in the adult setting careful surveillance appears to be an acceptable alternative to adjuvant chemotherapy for stage IA-C ITs of any grade, properly staged and with negative postoperative tumour markers. • Surveillance does not worsen prognosis of postpubertal stage I ovarian immature teratomas. • When suspecting a recurrence, surgery is recommended to assess the presence of immature disease. • Adjuvant chemotherapy should be reserved for the treatment of recurrent immature grade 2-3 disease. [ABSTRACT FROM AUTHOR]

Malignant ovarian germ cell tumors are rare tumors, affecting young women with a generally favorable prognosis. The French reference network for Rare Malignant Gynecological Tumors (TMRG) aims to improve their management. The purpose of this study is to report clinicopathological features and long-term outcomes, to explore prognostic parameters and to help in considering adjuvant strategy for stage I patients. Data from patients with MOGCT registered among 13 of the largest centers of the TMRG network were analyzed. We report clinicopathological features, estimated 5-year event-free survival (5y-EFS) and 5-year overall survival (5y-OS) of MOGCT patients. We collected data from 147 patients including 101 (68.7%) FIGO stage I patients. Histology identifies 40 dysgerminomas, 52 immature teratomas, 32 yolk sac tumors, 2 choriocarcinomas and 21 mixed tumors. Surgery was performed in 140 (95.2%) patients and 106 (72.1%) received first line chemotherapy. Twenty-two stage I patients did not receive chemotherapy. Relapse occurred in 24 patients: 13 were exclusively treated with upfront surgery and 11 received surgery and chemotherapy. 5y-EFS was 82% and 5y-OS was 92.4%. Stage I patients who underwent surgery alone had an estimated 5y-EFS of 54.6% and patients receiving adjuvant chemotherapy 94.4% (P <.001). However, no impact on estimated 5y-OS was observed: 96.3% versus 97.8% respectively (P =.62). FIGO stage, complete primary surgery and post-operative alpha fetoprotein level significantly correlated with survival. Adjuvant chemotherapy does not seem to improve survival in stage I patients. Active surveillance can be proposed for selected patients with a complete surgical staging. • Malignant ovarian germ cell tumors are rare tumors. • French Rare Malignant Gynecological Tumors Network collect data about these tumors. • Adjuvant chemotherapy for stage I does not seem to improve survival. • Active surveillance can be proposed for selected patients. • Risk-adapted treatment should be assessed on a prospective basis at European level. [ABSTRACT FROM AUTHOR]

Purpose: Evidence on risk factors for postoperative recurrence in patients with colorectal cancer (CRC) confined to pathological stage I is limited. Therefore, this study aimed to identify the risk factors for recurrence in patients with stage I CRC. Methods: Data on clinicopathological factors and blood tests of patients diagnosed with pathological stage I CRC at Hiroshima University Hospital between April 1, 2010, and December 31, 2018, were retrospectively obtained. The statistical significance between the clinical factors and postoperative recurrence was also investigated. Results: A total of 244 patients were included. The median observation period was 45 months. There were 17 patients (6.6%) with a postoperative recurrence (8 local and 9 distant recurrences). In the log-lank test, rectal cancer (p = 0.004), pT2 (p = 0.020) and organ/space surgical site infection (SSI) (p = 0.008) were significantly associated with postoperative recurrence. In a multivariate analysis, rectal cancer (hazard ratio [HR] 3.678, 95% confidence interval [CI] 1.184–11.425, p = 0.024) and organ/space SSI (HR 3.137, 95% CI 1.013–9.713, p = 0.047) were independently associated with a higher recurrence rate. Among 18 patients with organ/space SSI, 4 recurrences occurred, all of which were distant metastases. Conclusion: Organ/space SSI significantly affects the postoperative recurrence in patients with stage I CRC. [ABSTRACT FROM AUTHOR]

Clinical factors, such as tumor thickness, ulceration and growth phase have a role as prognostic factors for stage I melanoma. However, it is still under debate whether these variables influence the related direct costs. We aimed to investigate which clinical factors represent direct health care "cost drivers" for stage I melanoma. Analyses were conducted on a cohort of patients diagnosed with stage I melanoma. Differences in the costs incurred by different groups of patients were examined using Mann-Whitney or Kruskal-Wallis non-parametric tests. Log linear multivariate analysis was used to identify the clinical drivers of the total direct costs one and two years after diagnosis. The study was conducted from the perspective of Italy's National Health care System. One year after diagnosis, patients whose melanomas had a Breslow thickness ≥0.8 mmin (compared with those with lower thickness) and a vertical growth phase (compared with those with radial growth) incurred higher costs for hospitalization, as well as higher overall costs. One year after their diagnosis, treatment of patients with stage I melanoma in the vertical growth phase costs 50% more (95% CI: 22–85%) than their counterparts with a radial growth pattern, resulting in an estimated absolute increase of € 256.23. Having a tumor thicker than 0.8 mm prompted an increase of 91% (95% CI: 43–155%) in the costs (€955.24 in absolute terms). Our data indicate a heterogeneity in the direct costs of stage I melanoma patients during the first year after diagnosis, which can be partly explained by clinical prognostic factors, like tumor thickness and growth pattern. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component <50% in diameter of the tumor and no metastases were studied. Concerning histology, 32 tumors were adenocarcinoma, 1 was squamous cell carcinoma, 2 were unclassified carcinoma and 49 cases were histology-unproven but increased in size or had a positive finding in 18F-FDG positron emission tomography (PET) examination. The median tumor size was 20 mm (range, 10–41 mm). All of the patients were treated with SBRT, and the total prescribed dose at the isocenter ranged between 48 Gy in four fractions and 84 Gy in ten fractions. Median follow-up duration was 33 months. No patient had local failure nor regional lymph node failure. The 3-year rate of distant failure was 2.6%. Two patients who experienced distant metastases had a past surgical history of initial lung cancer before SBRT. The rates of cause-specific and overall survival at 3 years were 98.2 and 94.6%, respectively. Treatment-related adverse events of ≥grade 4 were not reported. Although more cases and longer follow-ups are mandatory, SBRT may be one of the radical treatment options for patients with GGN. [ABSTRACT FROM AUTHOR]

Purpose of Review: To summarize the current available treatments for stage I rectal cancer and the evidence that supports them. Recent Findings: Radical surgery, or total mesorectal excision (TME) without neoadjuvant therapy, reports excellent oncologic outcomes, with 5-year disease-free survival of approximately 95%. Alternative therapies include local excision, which has acceptable long-term outcomes in some low-risk T1 tumors; but overall local excision, with or without additional chemotherapy or radiation, generally reports 5-year disease-free survival less than TME alone. New research is showing complete clinical response rates of 67% with chemoradiation combined with additional consolidation chemotherapy in T2 lesions, making watch and wait a potential strategy for stage I tumors. Summary: Owing to its superior oncologic outcomes, radical surgery remains the mainstay of treatment for stage I tumors. Both local excision and watch and wait have advantages that may make them useful in individual patients and should be considered under the right circumstances. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the oncologic safety and reproductive outcome in patients with stage I epithelial ovarian cancer (EOC) treated with fertility-sparing surgery (FSS). Women aged ≤40 years with stage I EOC who had undergone FSS between 2000 and 2010 were retrospectively reviewed. Survival was examined using the Kaplan-Meier method and statistical significance was analyzed using the log-rank test. A total of 29 EOC patients (stage IA, n=14; stage IC1 n=6; stage IC3, n=9) from seven participating institutions belonging to the Tohoku Gynecologic Cancer Unit were enrolled. After a median follow-up duration of 60.6 months (range, 6–135 months), five patients (17.2%) experienced tumor recurrence. The respective five-year relapse-free survival (RFS) and overall survival (OS) rates were 90.9 and 100% for stage IA/IC1, and 43.8 and 87.5% for stage IC3. Significant differences in RFS were observed between stage IA/IC1 and IC3 patients (P=0.026). However, there was no significant difference in OS between patients with 1A/1C1 and those with 1C3 (P=0.712). After FSS, seven pregnancies occurred in five patients, which resulted in the birth of six healthy children. The results of the present study confirmed that FSS may be an acceptable treatment method for stage IA and IC1 EOC, exhibiting a favorable reproductive outcome. However, the safety of FSS for treating stage IC3 EOC is uncertain and warrants further investigation. [ABSTRACT FROM AUTHOR]

The occurrence of intranodal salivary gland neoplasm is uncommon; squamous cell carcinoma (SCC) of the external auditory canal (EAC) is another rare occurrence. Clinically, SCC of EAC presents with symptoms similar to other benign otologic conditions. A case of Stage I SCC in EAC region is presented here in a 60-year-old male patient with incidental intranodal Warthin tumor along with the histological differential diagnosis. The patient is being followed up. There is no evidence of recurrence 1 year and 11 months after surgery. [ABSTRACT FROM AUTHOR]

Purpose: Recurrence risk management of patients with small (≤ 2 cm), node-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains challenging. We studied the effects of adjuvant chemotherapy and/or trastuzumab and survival outcomes among these patients, using data from the population-based Japanese National Clinical Database (NCD). Methods: We identified a cohort of 2736 breast cancer patients with HER2+ pT1N0 disease: 489 pT1a, 642 pT1b, and 1623 pT1c. The median observation period was 76 months, and the 5-year follow-up rate was 48.2%. The number of events was 212 for disease-free survival (DFS), 40 for breast cancer-specific survival, and 84 for overall survival (OS). Results: There were 24.5% of pT1a, 51.9% of pT1b, and 63.3% of pT1c patients who were treated systemically after surgery. OS in pT1b (logrank test; p = 0.03) and DFS in pT1c (logrank test; p < 0.001) were significantly improved in treated compared with untreated patients. In the Cox proportional hazards model, treated patients had significantly longer OS than untreated patients in pT1b (hazard ratio (HR) 0.20) and pT1c (HR 0.54) groups. Estrogen receptor-negative tumors was also a significant predictor of survival in pT1c (HR 2.01) but not pT1ab patients. Furthermore, HR was greater in patients aged ≤ 35 years (3.18) compared to that in patients aged 50–69 years in the pT1b group. Conclusions: NCD data revealed that systemic treatment improved OS in pT1bc but not in pT1a node-negative HER2+ breast cancer patients. Future observational research using big-sized data is expected to play an important role in optimizing treatment for patients with early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Lung cancer continues to be one of the leading causes of cancer-related mortality worldwide and its incidence is still increasing. With aging population and development in imaging technology, many more elderly with early-stage lung cancers are being diagnosed than in the past. Lobectomy and sub-lobar resection are two main surgical approach for the treatment for this kind of patients. This review aimed to compare these two methods for this hot issue.

Abstract Background Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC). Methods Overall, 108 patients of reproductive age (≤ 40 years) diagnosed with stage I EOC who were treated at Peking Union Medical College Hospital between 1999 and 2013 were included in the study. The Kaplan-Meier model and Cox regression analyses were used for the survival analysis. Results The type of surgery included fertility-sparing surgery (FSS) (48.1%) and radical surgery (RS) (51.9%). After a median follow-up of 83 months, we observed that grade 3 or clear-cell carcinoma was the only independent risk factor for disease-free survival and tumor-specific survival in the multivariate analysis. Patients with grade 3 or clear-cell carcinoma tended to be older than 30 years, have endometriosis, and undergo RS (p

Background and objective Surgical resection is the best choice for early lung cancer, but the prognosis of early postoperative lung cancer is still very different, whether or not to apply adjuvant chemotherapy is controversial. This study examines the role of postoperative adjuvant chemotherapy in patients with stage I non-small cell lung cancer (NSCLC), particularly in high-risk groups. Methods Patients with pathologic stage Ia and stage Ib NSCLC who underwent complete (R0) resection between January 2009 and June 2013 were identified from Peking University People's Hospital and classified into two groups based on postoperative chemotherapy or not. Kaplan-Meier and Log-rank tests were used to compare disease free survival (DFS). Scored according to the number of risk factors, all patients were divided into three groups. Kaplan-Meier and Log-rank tests were used to compare DFS between them. The effect of postoperative chemotherapy on high-risk group was observed individually. Results A total of 465 patients including 284 cases of stage Ia and 181 cases of stage Ib were enrolled in this study. For stage Ia there was no significant difference between the chemotherapy group and the control group in DFS (P=0.171), but the survival curve of the chemotherapy group was located below the control group. For stage Ib there was no significant difference between the two groups either (P=0.630). But there were significant differences on DFS between the three groups according to the number of risk factors (P

Background: The objective of the present study was to identify patients with pathologic stage I lung adenocarcinoma (LUAD) who are at high risk of recurrence and assess the efficacy of adjuvant chemotherapy (ACT) in these individuals., Methods: A retrospective study was conducted on 1504 patients with pathologic stage I LUAD who underwent surgical resection at Shanghai Pulmonary Hospital and Sun Yat-sen University Cancer Center. Cox proportional hazard regression analyses were performed to identify indicators associated with a high risk of recurrence, while the Kaplan-Meier method and Log-rank test were employed to compare recurrence-free survival (RFS) and overall survival (OS) between patients with ACT and those without it., Results: Four independent indicators, including age (≥62 years), visceral pleural invasion (VPI), predominant pattern (micropapillary/solid), and lymphovascular invasion (LVI), were identified to be significantly related with RFS. Subsequently, patients were classified into high-risk and low-risk groups by LVI, VPI, and predominant pattern. The administration of ACT significantly increased both RFS (P < 0.001) and OS (P = 0.03) in the high-risk group (n = 250). Conversely, no significant difference was observed in either RFS (P = 0.45) or OS (P = 0.063) between ACT and non-ACT patients in the low-risk group (n = 1254)., Conclusions: Postoperative patients with stage I LUAD with factors such as LVI, VPI, and micropapillary/solid predominant pattern may benefit from ACT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Stereotactic body radiotherapy (SBRT) can achieve high tumour control with limited toxicity for inoperable early stage non-small-cell lung cancer (NSCLC) patients. Patients and methods: The German Epidemiologic Cancer Registries from the Robert-Koch Institute were assessed. Periods according to the availability of SBRT were: (1) 2000–2003 (pre-SBRT); (2) 2004–2007 (interim); and (3) 2007–2014 (broad availability of SBRT). To assess the association of cancer-related parameters with mortality, hazard ratios (HR) from Cox proportional hazards models were computed. To evaluate the change of treatment-related mortality, we performed interaction analyses and the relative excess risk due to interaction (RERI, additive scale) was computed. Results: A total of 16,292 patients with UICC stage I NSCLC diagnosed between 2000 and 2014 were analysed. Radiotherapy utilization increased from 5% in pre-SBRT era to 8.8% after 2007. In univariate analyses, survival in the whole cohort improved only marginally when 2000–2003 is compared to 2004–2007 (HR 0.92, 95% CI 0.85–1.01) or 2008–2014 (HR 0.93, 95% CI 0.86–1.01). Comparing surgery/radiotherapy, mortality in the radiotherapy group started from a 3.5-fold risk in 2000–2003 to 2.6 after 2007. The interaction analysis revealed a stronger improvement for radiotherapy (multiplicative scale for 2000–2003 vs. > 2007: 0.74, 95% CI 0.58–0.94). On an additive scale, treatment × period interaction revealed an RERI for 2000–2003 vs. > 2007 of − 1.18 (95% CI − 1.8, − 0.55). Conclusions: Using population-based data, we observed a survival improvement in stage I lung cancer over time. With an increasing utilization of radiotherapy, a stronger improvement occurred in patients treated with radiotherapy when compared to surgery. [ABSTRACT FROM AUTHOR]

As the proportion of women diagnosed with early stage breast cancer increases, the role of imaging for staging and surveillance purposes is considered. National and international guidelines discourage the use of staging imaging for asymptomatic patients newly diagnosed with stage 0 to II breast cancer, even if there is nodal involvement, as unnecessary imaging can delay care and affect outcomes. In asymptomatic patients with a history of stage I breast cancer that received treatment for curative intent, there is no role for imaging to screen for distant recurrences. However, routine surveillance with an annual mammogram is the only imaging test that should be performed to detect an in-breast recurrence or a new primary breast cancer in women with a history of stage I breast cancer. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

To identify predictors of unsuccessful sentinel lymph node (SLN) mapping in patients with apparent early-stage endometrial cancer (EC) undergoing surgical staging with cervical injection of indocyanine green and SLN biopsy. We retrospectively identified consecutive patients with EC with attempted SLN biopsy between June 2014 and June 2016 at our institution. Patients were grouped according to whether they had a successful procedure, defined as the bilateral identification of SLNs, or an unsuccessful procedure, defined as unilateral or no SLN mapping. Logistic regression was used to evaluate predictors of an unsuccessful procedure. Among 327 patients included in the analysis, 256 (78.3%) had a successful procedure and 71 (21.7%) had an unsuccessful procedure (15.0% unilateral SLN mapping, 6.7% no mapping). The rate of successful procedure increased from 57.7% to 83.3% between the first and last quarters of the 2-year study period, which represented the learning curve for the technique. The mean (SD) operative time decreased from 164 (55) to 137 (37) minutes. By multivariable analysis, lysis of adhesions at the beginning of surgery (odds ratio, 3.07; 95% CI, 1.56–6.07) and the presence of enlarged lymph nodes (odds ratio, 4.69; 95% CI, 1.82–12.11) were independently associated with an unsuccessful procedure. Lysis of adhesions at the beginning of surgery and the presence of enlarged lymph nodes independently affect the bilateral detection of SLNs. • The rate of failed unilateral or bilateral sentinel lymph node mapping is 21.7%. • The presence of enlarged lymph nodes and lysis of adhesions are independently associated with an unsuccessful procedure. • The expertise of the surgeon is associated with a successful procedure and consequent decreases in operative time [ABSTRACT FROM AUTHOR]

In the fifth National Wilms Tumor Study (NWTS-5), the 4-year event-free survival (EFS) and overall survival (OS) estimates for 29 patients with stage I focal (n = 10) or diffuse (n = 19) anaplastic Wilms' tumour (AWT) treated with vincristine and dactinomycin without flank radiation were 69.5% and 82.6%, respectively. The Children's Oncology Group AREN0321 study evaluated whether adding doxorubicin and flank radiation improves survival for these patients. Tumour histology and stage were confirmed by real-time central pathology, surgery and radiology review. The patients received 25 weeks of vincristine, dactinomycin and doxorubicin (cumulative dose 150 mg/m2) with flank radiation (1080 cGy). We retrospectively analysed outcomes of all patients with stage I AWT enrolled in NWTSs 1–5 and AREN0321 with respect to treatment regimens. Eighteen patients with stage I AWT (8 focal and 10 diffuse) were enrolled on AREN0321. With a median follow-up of 4.6 years, the 4-year EFS and OS were 100%. One patient with diffuse AWT had pulmonary relapse 4.12 years after diagnosis. In the 112 patients with stage I AWT treated in NWTSs 1–5 and AREN0321, the EFS was significantly improved with doxorubicin treatment (p = 0.01; 4-year EFS: 97.2% [95% confidence interval {CI}: 91.3–100] vs. 77.5% [95% CI: 67.6–87.4]) but not by flank radiation (p = 0.15). Treatment of stage I AWT with vincristine, dactinomycin, doxorubicin and flank radiation in AREN0321 yielded excellent survival outcomes. Retrospective analysis of AREN0321 and NWTS patients suggests that doxorubicin had a greater contribution to the excellent outcomes than radiation. • Vincristine, dactinomycin, doxorubicin and radiation in stage I anaplastic Wilms' tumour. • Three-drug chemotherapy and radiation yielded 100% 4-year event-free survival. • Doxorubicin had a greater contribution to the excellent outcome than radiation. [ABSTRACT FROM AUTHOR]

Background: Sublobar resection for lung cancer is associated with a higher risk of recurrence than that of lobectomy; we evaluated the factors considered to be predictors of recurrence. Methods: By analyzing multicenter prospective studies of sublobar resection for patients with c-stage I non-small lung cancer who were unable to undergo lobectomy (KLSG-0801), we investigated the relationship between (1) tumor location (TL) and margin distance from the stump (MD), (2) the MD/tumor size (TS) ratio and prognosis, (3) and the margin cytology (MC) and prognosis. Results: The correlation between TS and MD was statistically significant in cases of easily resectable regions defined by Lewis' classification (n = 18). However, there was no correlation in difficult-to-resect regions (n = 14). Among cases of recurrence, the MD/TS ratio was less than 1. The 3-year survival rate was 100% for patients with MD/TS > 1 (n = 12), 59.7% for patients with MD/TS ≤ 1 (n = 20) (p = 0.06), 88.1% in cases of negative MC (n = 18), and 20% in cases of positive MC (n = 5) (p = 0.001). Conclusion: Cases with positive MC had a significantly worse prognosis than those with negative MC. It may be difficult to secure an MD greater than the TS in a difficult-to-resect region according to Lewis' classification. [ABSTRACT FROM AUTHOR]

Insights regarding utilization and survival of surgery and radiotherapy (stereotactic body radiotherapy (SBRT) or conventional radiotherapy (RT)) are lacking for older patients with stage I and II non-small cell lung cancer (NSCLC) in clinical practice. Data from the Netherlands Cancer Registry were retrieved for patients ≥65 years with clinical stage I-II NSCLC in 2010–2015. Descriptive analyses, overall survival (OS), and cox regression were stratified for stage I (n = 8742) and II (n = 3439) and compared age groups (65–74 years vs ≥75 years). Patients aged 65–74 underwent surgery significantly more often compared to those aged ≥75 (stage I 55% vs 27%; stage II: 65% vs 35%), and received SBRT less often (I: 29% vs 42%; II: 5% vs 11%), conventional RT less often (I: 6% vs 11%; II 10% vs 24%) and best supportive care alone less often (BSC, I: 8% vs 19%; II: 9% vs 25%). One-year OS was significantly higher in patients aged 65–74 compared to those aged ≥75 (I: 87% vs 78%; II: 74% vs 60%); as was five-year OS (I: 49% vs 31%; II: 36% vs 18%). After adjustment for gender, histology, stage, treatment, and comorbidity, hazard ratio (HR) of death was higher for patients aged ≥75 compared to those aged 65–74 (I: HR 1.3, 95% confidence interval (CI) 1.1–1.5; II: HR 1.3 95%CI 1.1–1.7). Patients aged ≥75 with stage I-II NSCLC had poorer OS, underwent surgery less often, and received SBRT, conventional RT, and BSC more often than patients aged 65–74. In both stages, one-year OS within age groups was similar for surgery and SBRT. However, long-term OS adjusted for prognostic factors was superior for surgery compared to SBRT and remained poorer for those aged ≥75. Prospective research should focus on predictive characteristics for treatment selection and patient-centered outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the implications of preoperative serum carcinoembryonic antigen (CEA) elevation in cause-specific survival (CSS) of patients diagnosed with stage I (T1N0M0 and T2N0M0) colon cancer. Methods: Eligible patients diagnosed with stage I colon cancer from the Surveillance, Epidemiology, and End Results (SEER) database from January 2004 to December 2010 were included in this respective and propensity score–matched (PSM) study. Some Cox proportional hazards models were constructed to identify prognostic factors associated with oncologic outcomes of colon cancer. Pearson's chi-squared tests and Kaplan–Meier methods were performed. Results: The median follow-up time of the whole cohort was 79 months. A total of 16,659 patients diagnosed with stage I colon cancer were identified from the SEER database. Multivariate Cox analyses showed that stage T1N0M0 in the context of serum CEA elevation (T1, CEA+) presented up to 158.4% increased risk of colon cancer-specific mortality compared with stage T1N0M0 in the context of normal serum CEA [hazard ratio (HR) = 2.584, 95% confidence interval (CI) = 2.167–3.082, P < 0.001]. After PSM, Kaplan–Meier survival curves of stage T1N0M0 colon cancer showed that 5-year CSS rates of normal and elevated CEA were 94.8% and 96.6% (P < 0.001). Conclusions: This large population-based and propensity score–matched study with long follow-up time provides the first evidence that stage T1N0M0 colon cancer with the elevation of preoperative serum CEA would be a surrogate of aggressive tumor biology and predict poor prognosis. In addition, this subgroup of colon cancer might need to be paid more attention of clinicians. [ABSTRACT FROM AUTHOR]