Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Development of highly adaptable RT-PCR methods for identifying Delta and BA.1 variants in inactivated COVID-19 vaccines.

Background The emergence and rapid spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), poses a significant threat to human health and public safety. While next-generation sequencing (NGS) is capable of detecting and tracking new COVID-19 variants for disease diagnosis and prevention, its high cost and time-consuming nature limit its widespread use. In this study, our aim was to develop a highly adaptable and accurate RT-PCR method for identifying the Delta or BA.1 variants in inactivated COVID-19 vaccine. We devised three two-plex RT-PCR methods targeting specific mutation sites: S: Δ156-157, S: N211-, L212I, and S: Δ142-144, Y145D. The RT-PCR method targeting the S: Δ156-157 mutation site was able to distinguish the Delta variant from other COVID-19 virus strains, while the RT-PCR methods targeting the S: N211-, L212I or S: Δ142-144, Y145D mutation sites were able to distinguish the BA.1 variant from other COVID-19 virus strains. We separately validated these three two-plex RT-PCR methods, and the results demonstrated good linearity, repeatability, reproducibility, and specificity for each method. Moreover, all three methods can be applied in the production of SARS-CoV-2 variant inactivated vaccines, enabling the identification of Delta or BA.1 variants in virus cultures as well as in inactivated vaccine stocks. This study presents a systematic approach to identify COVID-19 variants using multiple RT-PCR methods. We successfully developed three two-plex RT-PCR methods that can identify Delta and BA.1 variants based on specific mutation sites, and we completed the validation of these three methods.

Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.

BACKGROUND: Wuhan was the epicentre of the COVID-19 outbreak in China. We aimed to determine the seroprevalence and kinetics of anti-SARS-CoV-2 antibodies at population level in Wuhan to inform the development of vaccination strategies. METHODS: In this longitudinal cross-sectional study, we used a multistage, population-stratified, cluster random sampling method to systematically select 100 communities from the 13 districts of Wuhan. Households were systematically selected from each community and all family members were invited to community health-care centres to participate. Eligible individuals were those who had lived in Wuhan for at least 14 days since Dec 1, 2019. All eligible participants who consented to participate completed a standardised electronic questionnaire of demographic and clinical questions and self-reported any symptoms associated with COVID-19 or previous diagnosis of COVID-19. A venous blood sample was taken for immunological testing on April 14-15, 2020. Blood samples were tested for the presence of pan-immunoglobulins, IgM, IgA, and IgG antibodies against SARS-CoV-2 nucleocapsid protein and neutralising antibodies were assessed. We did two successive follow-ups between June 11 and June 13, and between Oct 9 and Dec 5, 2020, at which blood samples were taken. FINDINGS: Of 4600 households randomly selected, 3599 families (78·2%) with 9702 individuals attended the baseline visit. 9542 individuals from 3556 families had sufficient samples for analyses. 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2, with a baseline adjusted seroprevalence of 6·92% (95% CI 6·41-7·43) in the population. 437 (82·1%) of 532 participants who were positive for pan-immunoglobulins were asymptomatic. 69 (13·0%) of 532 individuals were positive for IgM antibodies, 84 (15·8%) were positive for IgA antibodies, 532 (100%) were positive for IgG antibodies, and 212 (39·8%) were positive for neutralising antibodies at baseline. The proportion of individuals who were positive for pan-immunoglobulins who had neutralising antibodies in April remained stable for the two follow-up visits (162 [44·6%] of 363 in June, 2020, and 187 [41·2%] of 454 in October-December, 2020). On the basis of data from 335 individuals who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralising antibody levels did not significantly decrease over the study period (median 1/5·6 [IQR 1/2·0 to 1/14·0] at baseline vs 1/5·6 [1/4·0 to 1/11·2] at first follow-up [p=1·0] and 1/6·3 [1/2·0 to 1/12·6] at second follow-up [p=0·29]). However, neutralising antibody titres were lower in asymptomatic individuals than in confirmed cases and symptomatic individuals. Although titres of IgG decreased over time, the proportion of individuals who had IgG antibodies did not decrease substantially (from 30 [100%] of 30 at baseline to 26 [89·7%] of 29 at second follow-up among confirmed cases, 65 [100%] of 65 at baseline to 58 [92·1%] of 63 at second follow-up among symptomatic individuals, and 437 [100%] of 437 at baseline to 329 [90·9%] of 362 at second follow-up among asymptomatic individuals). INTERPRETATION: 6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. FUNDING: Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Prognostic significance of the skeletal muscle index and systemic inflammatory index in patients with lymph node-positive breast cancer after radical mastectomy.

BACKGROUND: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population. METHODS: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model. RESULTS: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36). CONCLUSIONS: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study.

A follow-up study shows that recovered patients with re-positive PCR test in Wuhan may not be infectious.

BACKGROUND: Previous studies showed that recovered coronavirus disease 2019 (COVID-19) patients can have a subsequent positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after they are discharged from the hospital. Understanding the epidemiological characteristics of recovered COVID-19 patients who have a re-positive test is vital for preventing a second wave of COVID-19. METHODS: This retrospective study analyzed the epidemiological and clinical features of 20,280 COVID-19 patients from multiple centers in Wuhan who had a positive PCR test between December 31, 2019, and August 4, 2020. The RT-PCR test results for 4079 individuals who had close contact with the re-positive cases were also obtained. RESULTS: In total, 2466 (12.16%) of the 20,280 patients had a re-positive SARS-CoV-2 PCR test after they were discharged from the hospital, and 4079 individuals had close contact with members of this patient group. All of these 4079 individuals had a negative SARS-CoV-2 PCR test. CONCLUSIONS: This retrospective study in Wuhan analyzed the basic characteristics of recovered COVID-19 patients with re-positive PCR test and found that these cases may not be infectious.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Three-Dimensional Nanoscale Flexible Memristor Networks with Ultralow Power for Information Transmission and Processing Application.

To construct an artificial intelligence system with high efficient information integration and computing capability like the human brain, it is necessary to realize the biological neurotransmission and information processing in artificial neural network (ANN), rather than a single electronic synapse as most reports. Because the power consumption of single synaptic event is ∼10 fJ in biology, designing an intelligent memristors-based 3D ANN with energy consumption lower than femtojoule-level (e.g., attojoule-level) and faster operating speed than millisecond-level makes it possible for constructing a higher energy efficient and higher speed computing system than the human brain. In this paper, a flexible 3D crossbar memristor array is presented, exhibiting the multilevel information transmission functionality with the power consumption of 4.28 aJ and the response speed of 50 ns per synaptic event. This work is a significant step toward the development of an ultrahigh efficient and ultrahigh-speed wearable 3D neuromorphic computing system.

The effect of postmastectomy radiotherapy in node-positive triple-negative breast cancer.

BACKGROUND: The value of postmastectomy radiotherapy (PMRT) for pathological node-positive triple-negative breast cancers (TNBC) remains debatable. The aim of this population-based retrospective study was to evaluate the effect of PMRT on survival outcomes in this population. METHODS: Patients diagnosed with stage T1-4N1-N3M0 TNBC between 2010 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used univariate and multivariate Cox regression hazards method to determine the independent prognostic factors associated with 3-year breast cancer-specific survival (BCSS). The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. RESULTS: Of the 4398 patients included in this study, 2649 (60.2%) received PMRT. Younger age, black ethnicity, and advanced tumor (T) and nodal (N) stage were the independent predictors associated with PMRT receipt (all P < 0.05). Patients who received PMRT showed better 3-year BCSS (OR = 0.720, 95% CI = 0.642-0.808, P < 0.001) than those that did not. The effect of PMRT on 3-year BCSS was analyzed after stratification by pathological staging of groups. The results showed that PMRT was associated with better 3-year BCSS in patients with stage T3-4N1 (P = 0.042), T1-4N2 (P < 0.001), and T1-4N3 (P < 0.001), while comparable 3-year BCSS was found between the PMRT and non-PMRT cohorts with T1-2N1 disease (P = 0.191). CONCLUSIONS: Radiotherapy achieved better 3-year BCSS in TNBC patients with stage T3-4N1 and T1-4N2-3 disease. However, no survival benefit was found with the addition of PMRT in patients with T1-2N1 TNBC.

Histological Tumor Type is Associated with One-Year Cause-Specific Survival in Women with Stage III-IV Epithelial Ovarian Cancer: A Surveillance, Epidemiology, and End Results (SEER) Database Population Study, 2004-2014.

BACKGROUND The prognosis of epithelial ovarian cancer (EOC) remains poor. Cause-specific survival (CSS) is an overall survival measure of cancer survival that excludes other causes of death. This retrospective population study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors associated with one-year CSS in women with stage III-IV EOC between 2004-2014. MATERIAL AND METHODS Data from the SEER program included a cohort of patients with stage III-IV EOC between 2004-2014. Binomial logistic regression analysis, Kaplan-Meier survival curves, and multivariate Cox proportional hazards models were used for analysis of patient outcome, including the one-year CSS. RESULTS There were 14,798 patients with stage III-IV EOC identified from SEER between 2004-2014, including 13,134 (88.8%), 892 (6.0%), 448 (3.0%), and 324 (2.2%) patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively. The overall one-year CSS was 91.2%. One-year CSS was 92.5%, 92.2%, 74.0%, and 62.5% in patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively (P<0.001). Histological tumor type was an independent prognostic factor of one-year CSS. Patients with mucinous EOC (HR, 8.807; 95% CI, 6.563-9.965; P<0.001) and clear cell EOC (HR, 4.581; 95% CI, 3.774-5.560; P<0.001) had a significantly lower one-year CSS compared with patients with endometrioid and serous EOC who had comparable one-year CSS (HR, 1.247; 95% CI, 0.978-1.590; P=0.075). CONCLUSIONS A retrospective population study of the SEER database between 2004-2014 identified that histological tumor type was associated with one-year CSS in women with stage III-IV EOC.

An investigation of changes in water quality throughout the drinking water production/distribution chain using toxicological and fluorescence analyses.

Changes in water quality from source water to finished water and tap water at two conventional drinking water treatment plants (DWTPs) were monitored. Beside the routine water quality testing, Caenorhabditis elegans-based toxicity assays and the fluorescence excitation-emission matrices technique were also applied. Both DWTPs supplied drinking water that met government standards. Under current test conditions, both the investigated finished water and tap water samples exhibited stronger lethal, genotoxic and reprotoxic potential than the relative source water sample, and the tap water sample was more lethal but tended to be less genotoxic than the corresponding finished water sample. Meanwhile, the nearly complete removal of tryptophan-like substances and newly generated tyrosine-like substances were observed after the treatment of drinking water, and humic-like substances were identified in the tap water. Based on these findings, toxic pollutants, including genotoxic/reproductive toxicants, are produced in the drinking water treatment and/or distribution processes. Moreover, further studies are needed to clarify the potentially important roles of tyrosine-like and humic-like substances in mediating drinking water toxicity and to identify the potential sources of these contaminants. Additionally, tryptophan-like fluorescence may be adopted as a useful parameter to monitor the treatment performance of DWTPs. Our observations provided insights into the importance of utilizing biotoxicity assays and fluorescence spectroscopy as tools to complement the routine evaluation of drinking water.

The 1-year mortality after radiotherapy for nasopharyngeal carcinoma: a population-based analysis.

Aim: To assess the incidence and predictors of nasopharyngeal carcinoma (NPC)-specific mortality in the first year among NPC patients. Methods: We identified 2714 patients in the SEER program. Results: Of the patients, 151 (5.6%) patients who died as NPC-related disease within 1 year of diagnosis. Specifically, 67.5% of the NPC-related deaths were attributed to keratinizing tumors, while 67.6% were attributed to advanced T stage. Older age, keratinizing squamous tumors and stage T3-4 disease were independent predictors of 1-year NPC-related death. Conclusion: The 1-year mortality rate is low among NPC patients after radiotherapy. Older age, keratinizing tumor and advanced T stage are predictors of high-mortality risk within 1 year in NPC patients.

The 21-gene recurrence score and effects of adjuvant radiotherapy after breast conserving surgery in early-stage breast cancer.

Aim: To investigate the associations with the 21-gene recurrence score (RS) and effect of adjuvant radiotherapy (RT) for early-stage breast cancer after breast conserving surgery. Methods: We included 13,246 patients in the SEER database. Results: Patients with a higher RS were independently related to nonreceipt of RT (p < 0.001). In both the traditional and Trial Assigning Individualized Options for Treatment (TAILORx) RS cut-offs, the receipt of RT was not related to better breast cancer-specific survival in low- and high-risk RS groups, but was independently related to better breast cancer-specific survival in intermediate-risk RS group before (p = 0.029) and after (p = 0.001) propensity score matching. Conclusion: The 21-gene-RS may impact the decision-making of adjuvant RT in early-stage breast cancer after breast conserving surgery. The survival benefit of adjuvant RT may be limited to patients with intermediate-risk RS.

Inflammatory breast cancer outcomes by breast cancer subtype: a population-based study.

AIM: To assess the outcomes of breast cancer subtype in inflammatory breast cancer (IBC). METHODS: We retrospectively assessed IBC patients from the SEER program. RESULTS: We identified 626 patients, including 230 (36.7%),100 (17.6%), 113 (18.1%), and 173 (27.6%) patients with HoR+/HER2-, HoR+/HER2+, HoR-/HER2+, and HoR-/HER2- subtype disease, respectively. Multivariate analysis demonstrated that, using HoR+/HER2- subtype as reference, patients with HoR+/HER2+ subtype had better breast cancer-specific survival (BCSS) and overall survival (OS), and patients with HoR-/HER2- subtype had worse BCSS and OS, while BCSS and OS were comparable for HoR-/HER2+ subtype. Similar trends were observed in patients who received surgery, radiotherapy, chemotherapy or trimodality therapy. CONCLUSION: Breast cancer subtype is clinically useful for predicting survival outcome in IBC. The HoR+/HER2- subtype shows poorer survival outcome than HoR+/HER2+ subtype.

Efficacy of controlled-release oxycodone for reducing pain due to oral mucositis in nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy: a prospective clinical trial.

BACKGROUND: Pain due to oral mucositis (OM) is a major problem during concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients. METHODS: We enrolled 56 NPC patients receiving CCRT and allocated them into two groups: moderate pain group (n = 27) and a severe pain group (n = 29) according to the degree of pain reported (moderate = numerical rating scale (NRS) score 4-6 or severe = NRS score 7-10) at initiation of controlled-release oxycodone (CRO) treatment. RESULTS: Total dose of CRO was significantly higher in severe pain patients than in moderate pain patients (791.60 ± 332.449 mg vs. 587.27 ± 194.940 mg; P = 0.015). Moderate pain patients had significantly better quality of life (P = 0.037), lower weight loss (P = 0.030) and more active CCRT response (90.9% vs. 64.0%; P = 0.041). Although 24-h pain control rate was comparable in the two groups (85.2% vs. 86.2%; P = 0.508), the moderate pain group score eventually stabilized at ~ 2 vs. 3 in the severe pain group (P < 0.001); the titration time to reach bearable pain (NRS ≤ 3) was also significantly shorter in moderate pain patients (2.45 ± 0.60 days vs. 3.60 ± 1.98 days; P = 0.012). Incidence of adverse events was comparable in both groups. CONCLUSIONS: The study findings suggest that early introduction of low-dose CRO at the moderate pain stage could help reduce the total dose required, provide better pain control, improve quality of life, and enhance CCRT response.

The Role of Axillary Lymph Node Dissection in Tubular Carcinoma of the Breast: A Population Database Study.

BACKGROUND The aim of this study was to investigate the role of axillary lymph node dissection on the outcome of patients with tubular carcinoma of the breast. MATERIAL AND METHODS Patients diagnosed with tubular carcinoma of the breast between 2000-2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analysis of the data was undertaken, including analysis of breast cancer-specific survival (BCSS). RESULTS Of the 5,645 patients identified on the SEER database with tubular carcinoma of the breast, 5,032 (89.4%) patients had undergone axillary lymph node dissection, with significantly increased rates after 2002 compared with rates between 2000-2001 (p <0.001), which stabilized between 2002-2013 (p=0.330). Axillary lymph node metastases were present in 6.1% of all patients and in 5.3% of patients with a tumor size ≤2 cm. Lymph node-positive disease was associated with patient age ≤65 years, intermediate-grade or high-grade tumors, and tumor size >2.0 cm. Axillary lymph node dissection was an independent prognostic indicator. The 10-year BCSS was 97.3% and 96.6% in patients with and without axillary lymph node dissection, respectively (p=0.002). The number of removed lymph nodes was not related to breast cancer-specific survival. CONCLUSIONS In patients with tubular carcinoma of the breast, lymph node status was not associated with significant breast cancer-specific survival. However, axillary lymph node dissection may still be considered for patients with for tubular carcinoma of the breast even in patients with a small tumor size.

Survival benefits with the addition of adjuvant hysterectomy to radiochemotherapy for treatment of stage I-II adenocarcinoma of the uterine cervix.

BACKGROUND AND OBJECTIVES: To determine the survival benefits of additional adjuvant hysterectomy in the International Federation of Gynecology and Obstetrics (FIGO) stage I-II cervical adenocarcinoma patients treated with radiochemotherapy. METHODS: Patients with FIGO stage I-II cervical adenocarcinoma were selected from the Surveillance, Epidemiology, and End Results 18 Regs research database. Propensity score matching (PSM) was used to balance patient baseline characteristics. Patient characteristics and outcomes were compared between the two groups. RESULTS: A total of 530 patients were included, 389 (73.4%) underwent definitive radiochemotherapy and 141 (26.6%) underwent an additional adjuvant hysterectomy. The multivariate Cox analysis surgery was shown to be an independent predictor of survival. Before PSM, the hazard ratios for cause-specific survival and overall survival in the surgery group were 0.632 (P = 0.036) and 0.674 (P = 0.041), respectively. After PSM, the respective hazard ratios were 0.392 (P < 0.001) and 0.465 (P = 0.001). The surgery group had significantly better 5-year cause-specific survival (80.5% vs 59.1%; P = 0.001) and overall survival than the nonsurgery group (76.3% vs 56.0%; P = 0.002). CONCLUSIONS: Additional adjuvant hysterectomy after radiochemotherapy may improve survival outcomes in patients with FIGO stage I-II cervical adenocarcinoma.

Tubular carcinomas of the breast: an epidemiologic study.

AIM: We explored the clinicopathologic characteristics, prognostic factors and outcomes in tubular carcinoma (TC) of the breast. METHODS: We retrospectively assessed 8091 TC patients using the SEER database from 2000 to 2013. RESULTS: Most patients were non-Hispanic white, well-differentiated disease, tumor size ≤2 cm, node-negative, nonmetastatic, hormone receptor-positive and HER2-negative status. The 10-year breast cancer-specific survival and overall survival were 98.1 and 82.0%, respectively. Multivariate analysis indicated that age, ethnicity, surgery procedures, radiotherapy and chemotherapy were independent predictors affecting survival outcomes. There was comparable breast cancer-specific survival between surgery and nonsurgery groups. CONCLUSION: The patients with TC has excellent survival outcomes, which may in part be due to the favorable tumor characteristics.

Widowed status increases the risk of death in vulvar cancer.

AIM: To evaluate the effect of marital status on survival of patients with vulvar cancer. MATERIALS & METHODS: A total of 4001 patients with vulvar cancer were included from the SEER database. Statistical analyses were performed using χ2 test, Kaplan-Meier method, Cox regression proportional hazards and a 1:1 propensity score-matching. RESULTS: The 8-year vulvar cancer-related survival in married, divorced, single and widowed patients were 78.6, 82.2, 78.9 and 61.6%, respectively (p < 0.001). In multivariate analysis, widows patients had significantly worse vulvar cancer survival than the nonwidowed counterparts in unmatched and matched populations. CONCLUSION: Being widowed is associated with greater risk of vulvar cancer mortality than the nonwidowed counterparts.

Lymph node ratio has prognostic value related to the number of positive lymph nodes in patients with vulvar cancer.

AIM: We investigated the value of the number of positive lymph nodes (PLNs) and lymph node ratio (LNR) on survival of vulvar cancer patients. METHODS: A total of 2332 patients with vulvar squamous cell carcinoma were included from the SEER program. RESULTS: In multivariate analysis, the number of PLNs and LNR were independent prognostic indictors of survival outcomes, a higher number of PLNs and a higher LNR had poorer survival outcomes. An LNR >0.2 was associated with poor survival outcomes according to the number of PLNs. CONCLUSION: The LNR has prognostic value related to the number of PLNs and may allow a more accurate determination of the lymph node status of vulvar cancer patients.

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer.

BACKGROUND: Thymosin beta 10 (TMSB10) has been demonstrated to be involved in the malignant process of many cancers. The purpose of this study was to determine the biological roles and clinical significance of TMSB10 in breast cancer and to identify whether TMSB10 might be used as a serum marker for the diagnosis of breast cancer. METHODS: TMSB10 expression was evaluated by immunohistochemical analysis (IHC) of 253 breast tumors and ELISA of serum from 80 patients with breast cancer. Statistical analysis was performed to explore the correlation between TMSB10 expression and clinicopathological features in breast cancer. Univariate and multivariate Cox regression analysis were performed to examine the association between TMSB10 expression and overall survival and metastatic status. In vitro and in vivo assays were performed to assess the biological roles of TMSB10 in breast cancer. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the tumor-promoting role of TMSB10. RESULTS: We found TMSB10 was upregulated in breast cancer cells and tissues. Univariate and multivariate analysis demonstrated that high TMSB10 expression significantly correlated with clinicopathological features, poor prognosis and distant metastases in patients with breast cancer. Overexpression of TMSB10 promotes, while silencing of TMSB10 inhibits, proliferation, invasion and migration of breast cancer cells in vitro and in vivo. Our results further reveal that TMSB10 promotes the proliferation, invasion and migration of breast cancer cells via AKT/FOXO signaling, which is antagonized by the AKT kinase inhibitor perifosine. Importantly, the expression of TMSB10 is significantly elevated in the serum of patients with breast cancer and is positively associated with clinical stages of breast cancer. CONCLUSION: TMSB10 may hold promise as a minimally invasive serum cancer biomarker for the diagnosis of breast cancer and a potential therapeutic target which will facilitate the development of a novel therapeutic strategy against breast cancer.