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BACKGROUND The clinical role of ground glass opacity (GGO) on computed tomography (CT) in stage I pulmonary adenocarcinoma patients currently remains unclear. AIM To explore the prognostic value of GGO on CT in lung adenocarcinoma patients who were pathologically diagnosed with tumor-node-metastasis stage I. METHODS A comprehensive and systematic search was conducted through the PubMed, EMBASE and Web of Science databases up to April 3, 2021. The hazard ratio (HR) and corresponding 95% confidence interval (CI) were combined to assess the association between the presence of GGO and prognosis, representing overall survival and disease-free survival. Subgroup analysis based on the ratio of GGO was also conducted. STATA 12.0 software was used for statistical analysis. RESULTS A total of 12 studies involving 4467 patients were included. The pooled results indicated that the GGO predicted favorable overall survival (HR = 0.44, 95%CI: 0.34-0.59, P < 0.001) and disease-free survival (HR = 0.35, 95%CI: 0.18-0.70, P = 0.003). Subgroup analysis based on the ratio of GGO further demonstrated that the proportion of GGO was a good prognostic indicator in pathological stage I pulmonary adenocarcinoma patients, and patients with a higher ratio of GGO showed better prognosis than patients with a lower GGO ratio did. CONCLUSION This meta-analysis manifested that the presence of GGO on CT predicted favorable prognosis in tumor-node-metastasis stage I lung adenocarcinoma. Patients with a higher GGO ratio were more likely to have a better prognosis than patients with a lower GGO ratio.

Objective: The proportion of patients with stage I lung adenocarcinoma (LUAD) has dramatically increased with the prevalence of low-dose computed tomography use for screening. Up to 30% of patients with stage I LUAD experience recurrence within 5 years after curative surgery. A robust risk stratification tool is urgently needed to identify patients who might benefit from adjuvant treatment. Methods: In this first investigation of the relationship between metabolic reprogramming and recurrence in stage I LUAD, we developed a recurrence-associated metabolic signature (RAMS). This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognoses of patients with stage I LUAD. The clinical significance and immune landscapes of the signature were comprehensively analyzed. Results: Based on a gene expression profile from the GSE31210 database, functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stage I LUAD with relapse from those without relapse. We then identified a metabolic signature (i.e., RAMS) represented by 2 genes (ACADM and RPS8) significantly related to recurrence-free survival and overall survival times of patients with stage I LUAD using transcriptome data analysis of a training set. The training set was well validated in a test set. The discriminatory power of the 2 gene metabolic signature was further validated using protein values in an additional independent cohort. The results indicated a clear association between a high risk score and a very poor patient prognosis. Stratification analysis and multivariate Cox regression analysis showed that the RAMS was an independent prognostic factor. We also found that the risk score was positively correlated with inflammatory response, the antigen-presenting process, and the expression levels of many immunosuppressive checkpoint molecules (e.g., PD-L1, PD-L2, B7-H3, galectin-9, and FGL-1). These results suggested that high risk patients had immune response suppression. Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high risk patients. However, the patients could respond better to chemotherapy. Conclusions: This study is the first to highlight the relationship between metabolic reprogramming and recurrence in stage I LUAD, and is the first to also develop a clinically feasible signature. This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm.

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 $$\alpha{/}\beta$$ α / β = 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.

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.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. 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.

Background 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. Methods 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. Results 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. Conclusion 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.

The purpose of the study was to investigate the association between tumor volume changes during stereotactic body radiation therapy (SBRT) and prognoses in stage I non-small-cell lung cancer (NSCLC). This retrospective review included stage I NSCLC patients in whom SBRT was performed at a total dose of 48.0–50.5 Gy in four or five fractions. The tumor volumes observed on computed tomography (CT) simulation and on the CT performed at the last treatment session using a CT-on-rails system were measured and compared. Then, the tumor volume changes during the SBRT period were measured and assessed for their association with prognoses (overall survival, local control, lymph node metastases and distant metastases). A total of 98 patients with a mean age of 78.6 years were enrolled in the study. The T-stage was T1a in 42%, T1b in 32% and T2a in 26% of the cases. The gross tumor volume (GTV) shrank and increased ≥10% in 23 (23.5%) and 36 (36.7%) of the cases, respectively. The 5-year local control and overall survival rates in the groups with a tumor shrinkage of ≥10% vs the group with a shrinkage of

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.

Background 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. Materials and method 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. Results 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). Conclusion 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.

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

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.

Interstitial lung disease (ILD) is a risk factor both for the development and treatment failure of lung cancer. In this retrospective study, we analyzed the outcome of carbon-ion radiotherapy (CIRT) in 124 patients with clinical stage I non-small cell lung cancer (NSCLC), of whom 26 (21%) had radiological signs of pre-existing ILD. ILD was diagnosed retrospectively by a pulmonologist based on critical review of CT-scans. Ninety-eight patients were assigned to the non-ILD group and 26 patients (21.0%) to the ILD group. There were significant differences in pre-treatment KL-6 values between the two groups. The three year overall survival and cause-specific survival rates were 83.2% and 90.7%, respectively, in the non-ILD group, and 59.7% and 59.7%, respectively, in the ILD group (between-group differences, p = 0.002 and p &lt, 0.001). Radiation pneumonitis worse than Grade 2 was observed in three patients (3.0%) in the non-ILD group and two patients (7.6%) in the ILD group (p = 0.29). There were no cases of acute exacerbation in the ILD group. CIRT for stage I NSCLC was as safe in the ILD group as in the non-ILD group. Coexisting ILD was a poor prognostic factor in CIRT for clinical stage I lung cancer.

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.

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.

We conducted a Phase II study to evaluate the usefulness of compensator-based non-coplanar intensity-modulated radiotherapy (ncIMRT) for patients with surgically inaccessible Stage I non–small-cell lung cancer (NSCLC). Patients with pathologically proven or clinically diagnosed surgically inaccessible Stage I NSCLC were enrolled in this study from May 2011 to April 2014. These patients underwent ncIMRT of 75 Gy in 30 fractions regardless of the tumor location. The primary end point was 3-year overall survival, and the secondary end points were local control rate and treatment-related toxicities. A total of 48 patients (50 tumors) were enrolled in this study. Of the 50 tumors, the Stage T1 to T2 ratio was 31 to 19, and the ratio of tumors located in the central to peripheral areas was 11 to 39. During the median follow-up time of 35.9 months, the 3-year actuarial local progression-free and overall survival rates were 82.6% and 87.1%, respectively. No patients experienced toxicities of Grade 3 or greater. Standard-fractionated ncIMRT was effective and safe for patients with surgically inaccessible stage I NSCLC, regardless of the tumor location.

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.

A considerable number of patients with extranodal marginal zone lymphoma (EMZL) are diagnosed with stage I disease. Information on treatments and survival by primary location remains limited. We extracted data from the Surveillance, Epidemiology, and End Results (SEER) database to assess treatment, primary location, and survival of patients with stage I EMZL. Results show that 7961 patients met inclusion criteria. Observation (no treatment) was the most common approach (31%) followed by radiation therapy (RT, 23%). The median overall survival (OS) was 17.3 years (95%CI 16.3 to 18.3). Shorter survival was observed in patients with stage I EMZL compared to expected survival in a cohort derived from the general U.S. population matched by sex, age, and calendar year at diagnosis. However, similar survival was observed in RT-treated patients. We identified age ≥ 60 years (SHR = 4.00, 95%CI 3.10–5.15, p &lt, 0.001), higher grade transformation (SHR = 4.63, 95%CI 3.29–6.52, 0.001), and primary lung EMZL (SHR = 1.44, 95%CI 1.05–1.96, p = 0.022) as factors associated with shorter lymphoma-specific survival (LSS). Conversely, primary skin location (SHR = 0.50, 95%CI 0.33–0.77, p = 0.002) was associated with longer LSS. Our results support the use of RT as the preferred approach in localized EMZL.

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.

There is a lack of predictive models to determine the prognosis of elderly patients diagnosed with stage I small-cell lung cancer (SCLC). The purpose of this study was to establish a useful nomogram to predict cancer-specific survival (CSS) in this patient population. Based on the Surveillance, Epidemiology, and End Results registry database, patients aged ≥ 65 years with pathological American Joint Committee on Cancer (AJCC) stage I SCLC from 2004 to 2014 were identified. The CSS was evaluated by the Kaplan-Meier method. Patients were randomly split into training and validation sets. In the training cohort, univariate analysis and multivariate analysis using the Cox regression identified risk factors that affected CSS. The results were utilized to construct a nomogram for the prediction of the 1-, 3-, and 5-year CSS rates of elderly patients with stage I SCLC. The effectiveness of the nomogram was validated internally and externally by the bootstrap method. The clinical practicability and accuracy of the nomogram were evaluated by the concordance index (C-index), calibration curve, receiver operating characteristic curve, and decision curve analysis. In total, we extracted 1,623 elderly patients with stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41%. Multivariate analysis revealed that histologic type, tumor size, age, and AJCC stage were significant predictors of CSS. A nomogram was constructed according to the results of multivariate Cox analysis. The C-indices of the nomogram for training and validation sets were 0.68 and 0.62, indicating that the nomogram demonstrated a favorable level of discrimination. The calibration curves exhibited satisfactory agreement between the actual observation and nomogram prediction. The net benefit of the nomogram was better than the AJCC TNM staging. We constructed a practical nomogram to predict the CSS of elderly patients with stage I SCLC. The predictive tool is helpful for patients counseling and treatment decision-making.

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.

The optimal treatment for stage I squamous cell carcinoma of the anus (SCCA) remains undefined. Recently, wide local excision alone was found to have comparable survival to those treated with chemoradiation (CRT). Given that local excision may be sufficient for the treatment of stage I SCCA, we hypothesized that radiation therapy (RT) alone, compared to CRT would result in equivalent overall survival (OS) in this population. We identified non-surgically treated patients with stage I SCCA from the National Cancer Database from 2004&ndash, 2015. We included only patients treated either with CRT (45&ndash, 59.4 Gy with chemotherapy initiated within 14 days of RT) or RT alone (45&ndash, 59.4 Gy with no chemotherapy). The primary endpoint was OS between CRT and RT patients. Propensity-score matched (PSM) analysis was performed to determine the effect of concurrent chemotherapy on OS using a Cox proportional hazards model with robust standard error to account for clustering in matched pairs. We identified 3552 stage I patients treated with CRT and 287 treated with RT. Compared to patients treated with CRT, those that received RT were more likely to be &ge, 70 years old (33.1% vs. 19.7%, p &lt, 0.001) and less likely to be female (63.1% vs. 71.0%, p &lt, 0.001). The proportion of patients with a Charlson-Deyo score of 0 was similar in both groups (80.8% RT vs. 82.7% CRT, p = 0.164). The PSM cohort consisted of 287 pairs of patients with median follow-up 48.3 months (interquartile range, 24.4&ndash, 85.1 months) and 151 deaths (86 RT, 65 CRT). CRT was associated with a 31% reduction in the risk of death (HR = 0.69, 95% CI 0.50&ndash, 0.95, p = 0.023). We found that CRT was associated with improved OS, compared to RT alone, in patients with non-surgically treated stage I SCCA. These data suggest that de-intensification of therapy in stage I SCCA must be used with caution. However, given the retrospective nature of the data, prospective trials are required.

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.

International audience; Background - 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. Patients and methods - 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. Results - 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

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

Introduction In addition to the highest incidence rate of lung cancer among the Nordic countries, Denmark has the highest mortality rate. Moreover, rates of tobacco and alcohol consumption are among the highest in these countries. Method In a population-based matched case/control study, we aimed to assess the association between one-year all-cause mortality and a number of smoking-related parameters, high-risk alcohol intake, and nutritional status in clinical stage I lung cancer patients. Results We included 221 patients who died within one year after diagnosis (early death) and 410 matched controls who survived more than one year (survivor). The odds ratio (OR) for early death among never-smokers was 0.3 (CI 95%: 0.1–0.9). There was no significant difference between patients who died early and survivors in proportions of current smokers (49 vs. 45%), number of cumulated pack-years (45 vs. 46), daily tobacco consumption (15 vs. 14 cigarettes/day), patients who quit smoking after diagnosis (25 vs. 40%) and the prevalence of chronic obstructive pulmonary disease (COPD) (43 vs. 38%). Patients that died early received more medications for COPD (p = 0.03) and smoked more after diagnosis, 14 vs. 10 cigarettes per day (p = 0.03). The unadjusted OR for high-risk alcohol intake was 2.2 (CI 95% 1.3–3.7) in the early death group vs. the survivors. However, in a treatment-stratified analysis this was observed only for surgically treated patients (OR, 3.2; CI 95% 1.7–6.1). Low nutritional status was associated with early death, unadjusted (OR 2.3; CI 95% 1.4–3.7), while OR was 1.8 (95% CI 1.0–2.3) adjusted for high-risk alcohol intake and COPD. Treatment selection according to and interventions against these factors before and after lung cancer diagnosis may improve outcomes.

Non-small cell lung cancer (NSCLC) is the most common cancer and cause of cancer-related mortality globally. Increasing evidence suggested that the long non-coding RNAs (lncRNAs) were involved in cancer-related death. To explore the possible prognostic lncRNA biomarkers for NSCLC patients, in the present study, we conducted a comprehensive lncRNA profiling analysis based on 1902 patients from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. In the discovery phase, we employed 682 patients from the combination of four GEO datasets (GSE30219, GSE31546, GSE33745 and GSE50081) and conducted a seven-lncRNA formula to predict overall survival (OS). Next, we validated our risk-score formula in two independent datasets, TCGA (n=994) and GSE31210 (n=226). Stratified analysis revealed that the seven-lncRNA signature was significantly associated with OS in stage I patients from both discovery and validation groups (all P

Background: Oxidative stress plays pivotal roles in the progression of lung adenocarcinoma (LUAD) through cell signaling related closely to cancer growth. We previously reported that peroxiredoxin 4 (PRDX4), a secretory-type antioxidant enzyme, can protect against the development of various diseases, including potential malignancies. Since many patients with early-stage LUAD develop recurrence, even after curative complete resection, we investigated the association of the PRDX4 expression with the clinicopathological features and recurrence/prognosis using post-surgical samples of stage I-LUAD. Methods: The expression of PRDX4 and MIB-1, a widely accepted Ki67 protein, was immunohistochemically analysed in 206 paraffin-embedded tumour specimens of patients with stage I-LUAD. The PRDX4 expression was considered to be weak when less than 25% of the adenocarcinoma cells showed positive staining. Results: A weak PRDX4+ expression demonstrated a significantly close relationship with pathologically poor differentiation, highly invasive characteristics and recurrence. The decrease in PRDX4-positivity potentially induced cell growth in LUAD, which was correlated significantly with a very high MIB-1 labelling index (≥17.3%). Univariate/multivariate analyses revealed that the subjects with both weak PRDX4+ expression and a very high MIB-1 index had significantly worse disease-free survival rates than other subjects. Conclusions: The combination of weak PRDX4 expression and a very high MIB-1 index can predict high proliferating activity and recurrence with a potential poor prognosis, especially in post-operative stage I-LUAD patients.

// Tianxiang Chen 1,* , Jizhuang Luo 1,* , Rui Wang 1 , Haiyong Gu 1 , Yu Gu 2 , Qingyuan Huang 1 , Yiyang Wang 1 , Jiajie Zheng 1 , Chang Gu 1 , Xufeng Pan 1 , Jun Yang 1 , Yunhai Yang 1 and Heng Zhao 1 1 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 2 Department of Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Yunhai Yang, email: // Heng Zhao, email: // Keywords : invasive lung adenocarcinoma, non-small cell lung cancer, VPI, stage I Received : February 08, 2017 Accepted : March 14, 2017 Published : March 22, 2017 Abstract Introduction: The impact of visceral pleural invasion (VPI) on survival remains controversial for patients with early stage non-small cell lung cancer (NSCLC). This study investigated the survival status of VPI among patients with lymph node-negative lung invasive adenocarcinoma smaller than 3cm. Methods: We retrospectively reviewed 2537 consecutive patients with pathologic stage I lung invasive adenocarcinoma. All patients had received lobectomy and system lymph nodes resection. Patients were classified into 4 groups according to tumor size and visceral pleural invasion status. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these groups. Results: 548 patients with VPI while 1989 patients without VPI were included in this study. For patients with tumor size ≤2cm, patients with VPI had significant worse DFS (HR,4.85; 95% CI, 2.98-7.91; p = .000) and OS(HR,3.52; 95% CI, 1.59-7.78; p = .002) compared with non-VPI group. For patients with tumor size between 2-3cm, patients with VPI had significant worse DFS (HR, 1.72; 95% CI, 1.16-2.55; p = .006) but no significant OS (HR, 1.31; 95% CI, 0.76-2.24; p = .330) compared with non-VPI group. For patients with VPI, there were no survival difference between tumor size 2-3cm group and ≤2cm group for both DFS(HR,1.02; 95% CI, 0.65-1.61; p = .939) and OS(HR,1.45; 95% CI, 0.71-2.97; p = .315). Conclusions: VPI could predict a poor survival even for node-negative invasive lung adenocarcinoma patients with tumor size less than 3cm.

Introduction: Lung cancer screening by low-dose chest computed tomography is currently implemented in the U.S. After implementation of screening, a stage shift may be observed from around 15% stage I non-small cell lung cancers (NSCLCs) in routine clinical practice to up to 70% in screening patients. This indicates a move in treatment options from advanced to early lung cancers, especially in those with small suspected intrapulmonary nodules. Areas covered: We have reviewed the current status of lung cancer screening from the different randomized controlled lung cancer screening studies and the clinical evidence so far for both surgical and non-surgical treatment options for (screen-detected) stage I NSCLC. Furthermore, we provide a step-wise approach for the treatment of stage I NSCLC. Expert Commentary: Recommended treatment for stage I NSCLC remains (VATS) lobectomy in case of a medically operable patient, VATS sublobar resection for subcentimeter nodules, and SBRT otherwise. Currently, there is too limited evidence for the value of ablative techniques in curative treatment of early stage NSCLC. Therefore, these therapies should only be used in expert centers for selected patients in clinical studies.

Objectives: 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.Methods: 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).Results: 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 (1: HR 1.3, 95% confidence interval (CI) 1.1-1.5; II: HR 1.3 95%CI 1.1-1.7).Conclusion: 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. (C) 2019 Elsevier Ltd. All rights reserved.

Background: Stage I lung cancer is curable with surgery as the treatment of choice. Other effective and curative treatments exist. Nevertheless, some patients only receive palliative treatment and some receive no treatment at all. Materials and methods: Using the Danish Lung Cancer Registry (DLCR), we assessed treatment distribution for a population-based Danish cohort of stage I lung cancer patients diagnosed from 2011 to 2014. We assessed one-year mortality according to treatment. Furthermore, in a nested case-control study based on data from medical records, we assessed the reason for not undergoing treatment among patients in favourable performance status (PS) with no treatment registration in the DLCR. Results: We identified 2985 patients, 68% (n = 2021) were treated surgically and 17% (n = 508) were managed with curative oncological therapy. The unadjusted odds ratio (OR) for death within one year was 2.5 (95% CI, 1.8–3.3) for the oncologically managed vs. the surgically treated. After adjusting for age, lung function and PS, the OR was 1.2 (95% CI, 0.8–1.9). Among 129 patients with a PS of 0–1 and no treatment registration, we established the reason for not undergoing treatment in 122 (95%). The majority (70%) were misclassified and did either not have lung cancer, had more advanced disease or were curatively treated. The 36 (30%) patients that did not undergo treatment, had a lower prevalence of adenocarcinomas (17 vs. 51%, p = 0.003), more comorbidites (median Charlson comorbidity index score 2 vs. 1, p < 0.001) and high alcohol intake (19 vs. 7%, p = 0.04) as compared to surgically treated controls. The primary reasons for no treatment were; comorbidity, patient decision and disease progression. Conclusion: Difference in outcome between the two major treatment groups was confounded by age, lung function and PS. Comorbidity, high alcohol intake and histology were associated with not undergoing curative treatment in spite of a favourable PS.

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.

WOS: 000404154000013, PubMed ID: 27812752, Background Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. Methods A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. Results Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p < 0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p < 0.001). Univariate analysis showed that the presence of LVI (p = 0.01) and treatment option (p < 0.001) were prognostic factors for RFS and pT stage (p = 0.004) and invasion of rete testis (p = 0.004) and the presence of relapse (p < 0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p < 0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p = 0.031), embryonal carcinoma (EC) > 50% (p = 0.013) and tumor diameter (p = 0.016) were found to be independent factors for predicting relapse. Conclusion Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.

Purpose Although numerous studies have demonstrated associations between the preoperative neutrophil-to-lymphocyte ratio (NLR) and long-term outcomes in patients with non-small cell lung cancer (NSCLC), the prognostic significance of postoperative NLR and change in NLR (ΔNLR) is unknown for patients who underwent complete resection of stage I NSCLC. The aim of this retrospective study was to evaluate the prognostic significance of postoperative NLR and ΔNLR in 123 patients with stage I NSCLC. Patients and methods This retrospective study included preoperative and postoperative data of 123 patients who underwent surgical resection for stage I NSCLC. The relationship between disease-free survival (DFS), overall survival (OS), and clinicopathological factors, including NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio, and their changes, was analyzed using both univariate Kaplan–Meier and multivariate Cox regression methods. Results The 5-year DFS and OS rates in our cohort were 60.16% and 67.48%, respectively. Univariate analysis revealed that age (P=0.045), smoking status (P=0.033), preoperative NLR (P=0.032), postoperative NLR (P

Supplemental Digital Content is available in the text, Background: Stereotactic body radiotherapy (SBRT) superseded conventional radiotherapy (CRT) for the treatment of patients with inoperable early stage non-small cell lung cancer (NSCLC) over a decade ago. However, the direct comparisons of the outcomes of SBRT and CRT remain controversial. This meta-analysis was performed to compare the survival and safety of SBRT and CRT in patients with inoperable stage I NSCLC. Methods: We systematically searched the Cochrane Library, Embase, PubMed, Web of Science, Ovid MEDLINE, ScienceDirect, Scopus and Google Scholar for relevant articles. Overall survival (OS), progression-free survival (PFS), lung cancer-specific survival (LCSS), local control rate (LCR) and adverse effects (AEs) were the primary outcomes. Results: We identified 11,110 articles, 17 of which were eventually included in this study; these 17 articles had 17,973 patients (SBRT: 7395; CRT: 10,578). Compared to CRT for the treatment of inoperable stage I NSCLC, SBRT had superior survival in terms of OS (hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.62-0.70, P

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.

To investigate the clinicopathological features and treatment outcomes in patients with stage I, high-risk endometrial cancer. Patients with International Federation of Gynecology and Obstetrics stage I, papillary serous, clear cell, or grade 3 endometrioid carcinoma treated between 2000 and 2012 were analyzed for the clinical and pathological factors in relation to prognosis. A total of 267 patients (stage IA, n = 175, stage IB, n = 92) were included. Among the clinicopathological features, stage and age were significant prognostic factors. The recurrence rate and overall survival for stage IB versus IA were 22.8% versus 9.1% (p = 0.003) and 149.7 months versus 201.8 months (p &lt, 0.001), respectively. The patients &gt, 60 years of age also had a higher recurrence rate (21.7% versus 9.7%, p = 0.008) and poorer survival (102.0 months versus 196.8 months, p = 0.001) than those &le, 60 years of age. Distant recurrence (64.9%) occurred more frequently than local recurrence (24.3%) and local combined with distant recurrence (10.8%) (p &lt, 0.001). The postoperative treatment modality had no impact on tumor recurrence rate, recurrence site, or overall survival. Distant recurrence is a major cause of treatment failure in patients with stage I, high-risk endometrial cancer. However, current adjuvant treatment appeared to have little effect in preventing its occurrence.

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

Introduction Although the protocol of 48 Gy in four fractions over 4 days has been most often employed in stereotactic body radiotherapy (SBRT) for stage I non–small-cell lung cancer in Japan, higher doses are necessary to control larger tumors, and interfraction intervals should be longer than 24 hours to take advantage of reoxygenation. We report the final results of our study testing the following regimen: for tumors less than 1.5, 1.5–3, and greater than 3 cm in diameter, 44, 48, and 52 Gy, respectively, were given in four fractions with interfraction intervals of greater than or equal to 3 days. Methods Among 180 histologically proven patients entered, 120 were medically inoperable and 60 were operable. The median patient age was 77 years (range, 29–89). SBRT was performed with 6-MV photons using four noncoplanar and three coplanar beams. Isocenter doses of 44, 48, and 52 Gy were given to four, 124, and 52 patients, respectively. Results The 5-year overall survival rate was 52.2% for all 180 patients and 66% for 60 operable patients. The 5-year local control rate was 86% for tumors less than or equal to 3 cm (44/48 Gy) and 73% for tumors greater than 3 cm (52 Gy; p = 0.076). Grade greater than or equal to 2 radiation pneumonitis developed in 13% (10% for the 44/48-Gy group and 21% for the 52-Gy group; p = 0.056). Other grade 2 toxicities were all less than 4%. Conclusions Our first prospective SBRT study yielded reasonable local control and overall survival rates and acceptable toxicity. Refinement of the protocol including dose escalation may lead to better outcome.

Background Patients unable to receive surgery for stage I non-small cell lung cancer (NSCLC) can undergo conventional radiotherapy (ConvRT), stereotactic body radiotherapy (SBRT), or no treatment (NoTx). This study assessed patterns of care and disparities in the receipt of each of these treatments. Methods The study included patients in the National Cancer Database from 2003 to 2011 with T1-T2N0M0 inoperable lung cancer (n = 39,822). Logistic regressions were performed to determine predictors of receiving any radiation versus NoTx and for receiving SBRT versus ConvRT. Results Treatment with radiation was significantly less likely in blacks (odds ratio, OR 0.65) and Hispanics (OR 0.42) compared with whites. Treatment with SBRT versus ConvRT was more likely in an academic research program (OR 2.62) and a high-volume facility (OR 7.00) compared with community cancer programs or low-volume facilities. In 2011, use of SBRT, ConvRT, and NoTx was 25%, 28%, and 46% for patients in a community cancer center versus 68%, 11%, and 21%, respectively, in an academic center (p Conclusion There were marked institutional and socioeconomic variations in the treatment of inoperable stage I NSCLC. These results suggest that removal of barriers to receive radiation therapy and particularly improved access to SBRT may meaningfully improve survival in this disease.

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

Adjuvant treatment options for Stage I seminoma include active surveillance, chemotherapy, and radiotherapy. Active surveillance may not be ideal for the average Indian patient. Of the two accepted adjuvant therapy options, namely single-dose carboplatin chemotherapy and radiotherapy to the retroperitoneal nodes, though it intuitively appears more appealing, a deeper review reveals the potential drawbacks of chemotherapy. This article highlights the misconceptions regarding carboplatin and provides reasons for an argument why radiotherapy is better when a patient with Stage I seminoma chooses to undergo adjuvant treatment.

Introduction Circulating tumor microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early-stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I non–small-cell lung cancer (NSCLC) patients undergoing imaging evaluation. Methods First, we prospectively enrolled patients during 18F-FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking, and cancer history) and imaging (tumor diameter, location in lung, and maximum standard uptake value [SUV max ]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group. Results We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p value=0.001) and for stage I patients alone (AUC = 0.87, p value=0.002). Conclusion CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

Background: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined. Methods: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings. Results: Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6–99.6%). Conclusions: The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.

ObjectiveWe propose a new staging system for stage I endometrial cancer and compare its performance to the 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) systems.MethodsWe analyzed patients with 1988 FIGO stage I endometrial cancer from January 1993 to August 2011. Low-grade carcinoma consisted of endometrioid grade 1 to grade 2 lesions. High-grade carcinoma consisted of endometrioid grade 3 or nonendometrioid carcinomas (serous, clear cell, and carcinosarcoma). The proposed system is as follows:IA. Low-grade carcinoma with less than half myometrial invasionIA1: Negative nodesIA2: No nodes removedIB. High-grade carcinoma with no myometrial invasionIB1: Negative nodesIB2: No nodes removedIC. Low-grade carcinoma with half or greater myometrial invasionIC1: Negative nodesIC2: No nodes removedID. High-grade carcinoma with any myometrial invasionID1: Negative nodesID2: No nodes removedResultsData from 1843 patients were analyzed. When patients were restaged with our proposed system, the 5-year overall survival significantly differed (P < 0.001): IA1, 96.7%; IA2, 92.2%; IB1, 92.2%; IB2, 76.4%; IC1, 83.9%; IC2, 78.6%; ID1, 81.1%; and ID2, 68.8%. The bootstrap-corrected concordance probability estimate for the proposed system was 0.627 (95% confidence interval, 0.590–0.664) and was superior to the concordance probability estimate of 0.530 (95% confidence interval, 0.516–0.544) for the 2009 FIGO system.ConclusionsBy incorporating histological subtype, grade, myometrial invasion, and whether lymph nodes were removed, our proposed system for stage I endometrial cancer has a superior predictive ability over the 2009 FIGO staging system and provides a novel binary grading system (low-grade including endometrioid grade 1–2 lesions; high-grade carcinoma consisting of endometrioid grade 3 carcinomas and nonendometrioid carcinomas).

This study aimed to investigate the clinical outcomes of intensity-modulated radiotherapy (IMRT)-based stereotactic body radiotherapy (SBRT) for patients with stage I non-small cell lung cancer (NSCLC). A prospective database of 16 consecutive patients receiving SBRT for pathologically-proven and peripherally-located stage I NSCLC was reviewed. Fifteen patients were medically inoperable and one patient refused to undergo surgery. The median age of the patients was 76 years (range, 69–86). Treatment planning used four-dimensional computed tomography and fixed-field IMRT (n=11) or volumetric-modulated arc therapy (VMAT; n=5). The SBRT scheme was 48 Gy in four fractions (n=9) or 55 Gy in five fractions (n=7), delivered on consecutive days. The overall response rate at 6 months was 78.6%, including a complete response in three (21.4%) patients and a partial response in eight (57.1%). Three patients (21.4%) demonstrated a stable disease status. The median follow-up time was 14 months (range, 6–20) for the surviving patients. One patient developed local failure at 11 months, while another suffered from regional failure in a subcarinal lymph node at 4 months. Two patients did not survive within the first 6 months; one patient died during salvage chemotherapy for mediastinal lymph node metastasis and the other succumbed to a cause unrelated to lung cancer. The Kaplan-Meier estimates of local failure-free, progression-free and overall survival rates at 18 months were 91.0, 85.2 and 87.5%, respectively. The toxicity was mild; no severe (grade ≥3) toxicity was identified. IMRT-based (including VMAT) delivery of SBRT for patients with stage I NSCLC demonstrated favorable responses and local control without severe toxicity.

Background: Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures. Methods: A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining. Results: There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68–0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20–0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15–1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29–12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Conclusions: For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.

// Jizhuang Luo 1,* , Rui Wang 1,* , Baohui Han 2 , Jie Zhang 3 , Heng Zhao 1 , Wentao Fang 1 , Qingquan Luo 4 , Jun Yang 1 , Yunhai Yang 1 , Lei Zhu 3 , Tianxiang Chen 1 , Xinghua Cheng 5 , Qingyuan Huang 1 , Yiyang Wang 1 , Jiajie Zheng 1 and Haiquan Chen 1,5,6,7 1 Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 2 Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 3 Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 4 Department of Shanghai Lung Tumor Clinic Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 5 Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 6 Institutes of Biomedical Sciences, Fudan University, Shanghai, China 7 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Haiquan Chen, email: // Keywords : invasive lung adenocarcinoma; non-small cell lung cancer; postrecurrence survival; solid; stage I Received : July 25, 2016 Accepted : September 22, 2016 Published : October 09, 2016 Abstract Introduction: This study investigated the correlation between histologic predominant pattern and postrecurrence survival (PRS), and identified the clinicopathologic factors influencing PRS in patients with completely resected stage I lung adenocarcinoma. Methods: A total of 136 stage I lung adenocarcinoma patients who experienced tumor recurrence after completely resection were included in this study. To analysis the association between histologic predominant pattern and PRS, invasive adenocarcinomas with mixed histologic components were divided into 2 groups: solid and nonsolid group (including lepidic, acinar, papillary, micropapillary) based on the histologic predominant pattern. PRS was analyzed to identify the prognostic predictors using the Kaplan-Meier approach and multivariable Cox models. Results: For all stage I invasive adenocarcinoma patients, the majority of postsurgical recurrences occurred within 2 years. Patients with solid predominant histological pattern were associated with unfavorable PRS (HR, 2.40; 95%CI 1.13-5.08, p =.022). There was a significant difference for poor PRS for patients who diagnosed tumor recurrence shorter than 12 months after surgery (HR, 2.34; 95%CI 1.12-4.90, p =.024). Extrathoracic metastasis was associated with poor media PRS in univariable analysis ( p =.011), however, there was no significant PRS difference in multivariable analysis (HR, 1.56; 95%CI 0.65-3.73, p =.322) compared with intrathoracic metastasis. Conclusions: Solid predominant histologic subtype and recurrence free interval less than 12 months predict worse PRS in patients with stage I lung adenocarcinoma.

© 2016 Elsevier Ltd. All rights reserved., Background: A contemporary US study showed an increase in the use of chemotherapy in the last decade for some patients with stage-I breast cancer; with a rise in more intensive regimens, and declining use of anthracyclines. Nevertheless, there is still uncertainty on the absolute benefit of chemotherapy for these patients and the optimal regimen. In this study we compare those findings with the patterns of care among a Portuguese cohort of stage-I breast cancers. Methods: Retrospective cohort study of patients with stage-I breast cancer diagnosed from 2006 to 2008 at four Portuguese institutions. The use and type of chemotherapy was evaluated. Results: Among patients with stage I-III breast cancer 39.4% (n = 682) had stage I disease. Of the 595 eligible patients, 22.4% were treated with chemotherapy, 33.9% aged 65 years (p < 0.001). Thirteen percent of patients with hormone receptor (HR)+/HER2- tumors, 52.7% of patients with HER2+ and 66.0% of patients with HR-/HER2- received chemotherapy (p < 0.001). In addition, we found inter-institutional variability, with the use of chemotherapy ranging from 0.0% to 43.4% (p < 0.001). Eighty-five percent of patients treated with chemotherapy received less-intensive regimens with anthracycline-based regimens, such as doxorubicin and cyclophosphamide, being the most frequently used, while docetaxel and cyclophosphamide was only used in 1.5% of cases. Conclusions: Overall, almost one-quarter of patients received chemotherapy with institutional variability. When treated, mostly less-intensive associations including anthracyclines were used, which contrasts with contemporary US practice. This study highlights the need for health-services research to understand local practices and tailor quality improvement interventions., Fundação para a Ciência e a Tecnologia (FCT) grants HMSP-ICS/0004/201 to IVL and HMSP-ICJ/0007/2013 to ARF.

Background Stage I pulmonary adenocarcinoma (PA) can offer an unfavorable prognosis. The aim of this study was to classify the prognosis of stage I PA on the basis of the lepidic component and to confirm whether the lepidic component can be used as a criterion for predicting the prognosis of stage I PA. Methods We conducted a retrospective study of patients who underwent curative surgery for stage I and IIA PA. Stage I disease was divided into three groups on the basis of the lepidic component: group 1, ≤10 %; group 2, >10 to 50 %; and group 3, >50 %. We compared recurrence-free survival (RFS) rates among groups 1, 2, and 3, and stage IIA disease. We also evaluated risk factors for disease recurrence with multivariate analysis. Results A total of 224 patients were included in our study; most patients (n = 201) had stage I disease. Three-year RFS rates in group 1 (n = 73), group 2 (n = 75), and group 3 (n = 53) were 74.1, 90.4, and 90.0 %, respectively. There was a significant difference in RFS between group 1 and group 2 (p = 0.009). The 3-year RFS rate in stage IIA disease was 61.4 %. There were no significant differences in RFS between group 1 and stage IIA disease (p = 0.163). In multivariate analysis, group 1 had the highest risk of recurrence (HR 5.806, p = 0.006) in stage I PA. Conclusions Stage I PA with a lepidic component ≤10 % was associated with an unfavorable prognosis that was similar to the prognosis of stage IIA disease. The prognosis for stage I PA should not be based on general criteria, but instead, the lepidic component should be evaluated and considered when determining disease prognosis.

PURPOSE In recent years, the incidence of early-stage colorectal cancer (CRC) has markedly increased in the population within the Republic of Korea. The aim of this study was to evaluate the clinicopathologic features of adenomatous polyps in TNM stage I CRC patients and in the general population. METHODS Between March 2003 and September 2009, 168 patients with stage I CRC were enrolled in this study. In addition, the records of 4,315 members of the general population without CRC, as determined by colonoscopy during a health check-up, were reviewed. RESULTS Of the 168 patients with stage I CRC, 68 (40.5%) had coexisting colorectal adenomatous polyps and of the 4,315 members of the general population, 1,112 (26.0%) had coexisting adenomatous polyps (P = 0.006). The prevalences of adenomatous polyp multiplicity in early CRC and in the general population were 32% and 15%, respectively (P = 0.023). Patients with coexisting adenomatous polyps had a higher frequency of tubulovillous or villous adenomas than members of the general population with polyps (7.5% vs. 2.0%, P = 0.037). Furthermore, a subgroup analysis showed that the occurrence (44% vs. 34%, P = 0.006) and the multiplicity (32% vs. 15%, P = 0.023) of adenomatous polyps were greater for T2 than T1 cancer. CONCLUSION The prevalence and the multiplicity of adenomatous polyps in TNM stage I CRC is higher than it is in the general population. The findings of this study suggest that depth of invasion of early stage CRC affects the prevalence and the number of adenomatous polyps in the remaining colon and rectum.