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Background: Cure proportion represents the proportion of patients who experience the same mortality rate as the general population and can be estimated together with the survival of the proportion experiencing excess mortality (the uncured). The aim was to estimate the cure proportions and survival among uncured stage II–III cutaneous melanoma (CM) patients. Methods: 1- and 5-year relative survival ratios, cure proportions and the median survival times of uncured stage II–III CM patients in Sweden (n = 6466) were calculated based on data from the nationwide population-based Swedish Melanoma Register 2005–2013 with a follow-up through 2018. Results: Stages IIB and IIC showed significant differences in standardized cure proportions vs. stage IIA CM (0.80 (95% CI 0.77–0.83) stage IIA; 0.62 (95% CI 0.59–0.66) stage IIB; 0.42 (95% CI 0.37–0.46) for stage IIC). Significant differences in standardized cure proportions were found for stages IIIB and IIIC-D CM vs. stage IIIA (0.76 (95% CI 0.68–0.84) stage IIIA; 0.52 (95% CI 0.45–0.59) stage IIIB; 0.35 (95% CI 0.30–0.39) for stage IIIC–D). Conclusions: The results are emphasizing the poor prognosis with low proportions cured by surgery only for sub-groups of stage II–III CM, specifically within stages IIB–C CM.

The aim was to define the role of chemotherapy in stage II nasopharyngeal carcinoma (NPC) and to identify the toxicity of chemotherapy for these patients in the era of intensity-modulated radiotherapy (IMRT). Between January 2002 and December 2013, 169 patients with stage II NPC were analyzed. Of these patients, 149 patients treated with chemotherapy were divided into three groups as follows: neoadjuvant chemotherapy followed by IMRT (NCT) group, concurrent chemotherapy with IMRT (CCRT) group, and neoadjuvant chemotherapy followed by CCRT (NC+CCRT) group. In addition, 20 patients received IMRT alone. We retrospectively assessed the 10-year survival and acute adverse effects in the patients using SPSS software. The median follow-up time was 93 months (2-160 months). The 10-year OS of the NCT, CCRT, NC+CCRT groups vs the IMRT alone group was 69.8%, 63.4%, 69.7% vs 72.4%, respectively ( 0.664, 0.940, and 0.998, respectively). Both univariable and multivariable analyses showed that the addition of chemotherapy to IMRT did not significantly improve the 10-year survival outcomes. The hematotoxicity and mucous reaction of patients with chemotherapy were more serious than those with IMRT alone ( =0.007 and 0.049). Distant metastasis for stage II NPC patients mostly occurred within 3 years, which is very different from patients with advanced NPC. Patients with stage II NPC who are treated with IMRT may obtain satisfactory long-term survival outcomes. The additional chemotherapy cannot significantly increase survival; however, it may remarkably increase treatment-associated acute toxic reactions.

Local tumor failure remains a major problem after radiation‐based nonsurgical treatment for unresectable locally advanced nonsmall cell lung cancer (NSCLC）and inoperable stage II NSCLC. The aim of this study was to evaluate the feasibility of simultaneous integrated boost of intensity‐modulated radiation therapy (SIB‐IMRT) to stage II‐III NSCLC with metastatic lymph nodes (ChiCTR 2000029304). Patients were diagnosed by pathology or PET‐CT. PTV was divided into two parts as follows, the PTV of primary tumor (PTVp) and the PTV of metastatic lymph nodes (PTVn). The radiotherapy doses were simultaneously prescripted 78 Gy (BED = 101.48 Gy) for PTVp and 60‐65 Gy (BED = 73.6‐81.25 Gy) for PTVn, 26f/5.2 weeks. Response was scored according to WHO criteria. Radiotherapy toxicity was scored according to RTOG criteria. Hematology and gastrointestinal toxicity were scored according to CTCAE1.0 criteria. A total of 20 patients were enrolled. Seventeen patients were diagnosed by pathology and three patients were diagnosed by PET‐CT. All patients were treated with SIB‐IMRT. The objective response rate (ORR) was 90%, with CR 25%, PR 65%, NC 10%, and PD 0%. Although radiotherapy toxicity was common, there were no grade ≥3, with radiation pneumonitis (10 cases), esophagitis (17 cases), and dermatitis (12 cases). The local control rates at 1, 3, and 5 years were 85%, 75%, and 70%, respectively. The overall survival（OS）and local progression‐free survival (LPFS) rates at 1, 3, and 5 years were 90%, 42.6%, and 35.5% and 84.4%, 35.5%, and 28.4%, respectively. SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety, and satisfactory efficacy. However, due to the limitation of small sample, these findings are needed to confirm by future trials with a larger sample size. The different radiation doses were simultaneously prescripted 78 Gy (PTVp）and 60‐65 Gy (PTVn). SIB‐IMRT can significantly improve ORR and survival for stage II‐III NSCLC with metastatic lymph nodes, with high safety and satisfactory efficacy.

Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non‐cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non‐cachectic early stage breast cancer after major surgery.

This study identified subtypes and prognostic signature of stage I and stage II gastric cancer based on neutrophil extracellular trap (NET)-related genes. The gene expression data associated with stage I and stage II gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. NET-related genes were obtained from previous reference. Differentially expressed NET-related genes were selected by consensus cluster analysis. The differences in immune infiltration between two subtypes were analyzed. Prognosis-related genes were further screened by univariate Cox regression analysis. Gene Set Enrichment Analysis (GSEA) of prognostic signatures was conducted with clusterprofiler. Finally, a miRNA-mRNA-transcription factor (TF) network was constructed. Total 43 differential NET-related genes were obtained and two subtypes were obtained based on these genes. Patients of cluster 2 had a better prognosis compared to cluster 1. Eight types of immune cells were differential in infiltration level between two subtypes. Following univariate Cox regression analysis, two genes of CXC chemokine receptor 4 ( ) and nuclear factor, erythroid 2-like 2 ( ) significantly related to patient survival were selected. GSEA of single gene revealed that was associated with allograft rejection and was associated with drug metabolism-cytochrome P450. A network with 421 miRNA-mRNA-TF regulatory pairs was constructed. The present study identified two subtypes and a prognostic signature for stage I and stage II gastric cancer based on NET-related genes.

Background There is scant evidence‐based information about survival benefits of postoperative chemotherapy in elderly patients with early‐stage non‐small cell lung cancer (NSCLC). The purpose of this study is to compare the overall survival (OS) and cancer‐specific survival (CSS) rates of surgery alone versus postoperative chemotherapy in patients aged ≥70 years with stage I‐II NSCLC. Methods Elderly patients aged ≥70 years diagnosed with stage I‐II NSCLC were selected from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010 to December 31, 2015. OS and CSS were compared between the two groups utilizing overlap weighting analysis, inverse probability of treatment weight (IPTW), and propensity score matching (PSM). Results Of the 7193 included patients with stage I‐II NSCLC who are more than 70 years old, 681 patients (9.5%) received postoperative chemotherapy and 6512 patients (90.5%) received surgery‐alone. Median OS was 77 months in postoperative chemotherapy group versus 79 months in surgery‐alone group (p = 0.89). The result of IPTW analysis showed the similar results. The probability of patients choosing chemotherapy increased with the AJCC stage and Grade increasing (p < 0.001) and decreased with the growth of age (p < 0.001). The results of subgroup analysis showed that the survival rate of stage IA patients decreased significantly after postoperative chemotherapy (p < 0.01) while the survival rate of stage IB‐II patients increased significantly (p < 0.01). At the same time, we found that patients in the postoperative chemotherapy group tended to have better OS than those in the surgery‐alone group with the grade and tumor size increasing. Conclusion The results of this study indicated that postoperative chemotherapy could significantly improve the survival of stage IB‐II NSCLC patients aged ≥70 years, and decrease the survival of stage IA patients. For patients aged ≥70 years, postoperative chemotherapy can improve the survival rate for those with stage IB and II, and decrease the survival rate for stage IA patients. Therefore, when using chemotherapy, it is necessary to prioritizing the patient's staging along with other vital factors such as age, grade, and other variables in formulating a successful treatment scheme.

Abstract Context Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. Objective This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. Methods A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. Results We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Conclusion Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

Background Precise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk. Methods From September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care. Results Preoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72; P  < 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19; P  < 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08; P  < 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months. Conclusions Postoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.

Accurate risk stratification for patients with stage II/III colon cancer is pivotal for postoperative treatment decisions. Here, we aimed to identify and validate a circRNA‐based signature that could improve postoperative prognostic stratification for these patients. In current retrospective analysis, we included 667 patients with R0 resected stage II/III colon cancer. Using RNA‐seq analysis of 20 paired frozen tissues collected postoperation, we profiled differential circRNA expression between patients with and without recurrence, followed by quantitative validation. With clinical information, we generated a four‐circRNA‐based cirScore to classify patients into high‐risk and low‐risk groups in the training cohort. The patients with high cirScores in the training cohort had a shorter disease‐free survival (DFS) and overall survival (OS) than patients with low cirScores. The prognostic capacity of the classifier was validated in the internal and external cohorts. Loss‐of‐function assays indicated that the selected circRNAs played functional roles in colon cancer progression. Overall, our four‐circRNA‐based classifier is a reliable prognostic tool for postoperative disease recurrence in patients with stage II/III colon cancer. Synopsis Novel molecular biomarkers allowing for better prognostic stratification of patients with stage II/III colon cancer are urgently needed. In this study, a circRNA‐based signature (cirScore) was identified and validated to improve postoperative risk‐stratification for these patients. Dysregulated circRNAs showed strong classification capacities in distinguishing between recurrent and nonrecurrent colon cancer patients. The proposed four‐cirRNA‐based cirScore can effectively classify patients with stage II/III colon cancer into groups with low and high risks of disease recurrence. The loss‐of‐function assay indicated that the representative circRNAs plays functional roles in the sophisticated regulation of colon cancer progression. Nomograms incorporating the cirScore with existing risk factors achieved excellent accuracy for predicting disease‐free and overall survival for patients with stage II/III colon cancer. Graphical Abstract Novel molecular biomarkers allowing for better prognostic stratification of patients with stage II/III colon cancer are urgently needed. In this study, a circRNA‐based signature (cirScore) was identified and validated to improve postoperative risk‐stratification for these patients.

Background In the current era of effective adjuvant therapies and de-escalation of surgery, distinguishing which patients with high-risk stage II melanoma are at increased risk of recurrence after excision of the primary lesion is essential to determining appropriate treatment and surveillance plans. Methods A single-center retrospective study analyzed patients with stage IIB or IIC melanoma. Demographic and tumor data were collected, and genomic analysis of formalin-fixed, paraffin-embedded tissue samples was performed via an internal next-generation sequencing (NGS) platform (SNaPshot). The end points examined were relapse-free survival (RFS), distant metastasis-free survival (DMFS), overall survival (OS), and melanoma-specific survival (MSS). Uni- and multivariable Cox regressions were performed to calculate the hazard ratios. Results The study included 92 patients with a median age of 69 years and a male/female ratio of 2:1. A Breslow depth greater than 4 mm, a higher mitotic rate, an advanced T stage, and a KIT mutation had a negative impact on RFS. A primary lesion in the head and neck, a mitotic rate exceeding 10 mitoses per mm 2 , a CDH1 mutation, or a KIT mutation was significantly associated with a shorter DMFS. Overall survival was significantly lower with older age at diagnosis and a higher mitotic rate. An older age at diagnosis also had a negative impact on MSS. Conclusion Traditional histopathologic factors and specific tumor mutations displayed a significant correlation with disease recurrence and survival for patients with high-risk stage II melanoma. This study supported the use of genomic testing of high-risk stage II melanomas for prognostic prediction and risk stratification.