Consistent efficacy outcomes between phase 2 and phase 3 trials in Crohn's disease or ulcerative colitis in adults: a meta-analysis.

INTRODUCTION: The approval of novel biologic agents and small molecules for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) is dependent on phase 3 randomized controlled trials (RCTs). However, these trials sometimes fail to achieve the expected efficacy outcomes observed in phase 2 trials. METHODS: We conducted a systematic review of RCTs that evaluated biologic agents and small molecules using paired regimens in both phase 2 and phase 3. We searched Medline, EMBASE, and Cochrane databases up until February 13, 2024. The revised Cochrane tool was utilized to assess the risk of bias. A generalized linear mixed-effects model (GLMM) was employed to estimate the odds ratios (ORs) for efficacy outcomes in phase 2 trials compared to phase 3. RESULTS: We identified a total of 23 trials with 10 paired regimens for CD and 30 trials with 11 paired regimens for UC. The GLMM analysis revealed that phase 2 CD trials had higher outcomes measured by the Crohn's Disease Activity Index (CDAI) by 9-13% without statistical significance: CDAI-150: OR, 1.12 (95% CI 0.83-1.51, p = 0.41); CDAI-100: OR, 1.09 (95% CI 0.88-1.35, p = 0.40); or CDAI-70: OR, 1.13 (95% CI 0.61-2.08, p = 0.66). For UC, two efficacy outcomes were estimated to be equally reported in phase 2/phase 3 pairs: clinical remission: OR, 1.00 (95% CI 0.83-1.20, p = 0.96); endoscopic improvement: OR, 0.98 (95% CI 0.83-1.15, p = 0.79). However, the rate of clinical response was underestimated in phase 2 by 19%: OR, 0.81 (95% CI 0.70-0.95, p = 0.03). The inclusion criterion for the type of Mayo score for UC had a significant interaction with the study phase to influence the difference in clinical response (p = 0.002). CONCLUSIONS: Our findings suggest that the main efficacy outcomes for CD and UC remain consistent between phase 2 and phase 3 trials, except for UC response rates. The efficacy data obtained from phase 2 trials can be considered reliable for the design of subsequent phase 3 trials. REGISTRATION: PROSPERO (CRD42023407947).

Fragility index analysis for randomized controlled trials of approved biologicals and small molecule drugs in inflammatory bowel diseases.

INTRODUCTION: Biologics and small molecules have been increasingly applied in Crohn's disease (CD) and ulcerative colitis (UC). But the robustness of their trials has not been evaluated. METHODS: We initially collected all the approved biologics or small molecules for CD or UC up to December 1, 2022. Databases were then queried by keywords in chemical name and CD or UC. Randomized controlled trials (RCTs) in the two-arm, 1:1 design were included. Fragility index (FI) and fragility quotient (FQ) were subsequently calculated. RESULTS: We included twenty-eight RCTs, including nine pivotal trials listed in approval labels, nineteen non-pivotal trials not included in the labels. The median sample size was 99 [IQR, 60-262] and the median number of loss-of-follow-up (LFU) was 14 [IQR, 8-43]. Pivotal trials in the labels had the median FI of 8 [IQR, 4-14, n = 6] that was marginally higher than non-pivotal trials (3 [IQR, 2-4], p = 0.08). The median FQ was 0.0330 [IQR, 0.1220-0.0466] and 0.0310 [IQR, 0.0129-0.0540] for pivotal and non-pivotal trials, respectively (p = 1.0). The sample size and FI were significantly correlated (Spearman correlation coefficient [r] = 0.56, 95 %CI 0.21-0.78, p = 0.003). The number of total events was also significantly correlated with FI (r = 0.53, 95 %CI 0.17-0.77, p = 0.006). Study p-values were significantly associated with FI (p = 0.01): trials with p-values < 0.001 had the highest median FI of 10 [IQR, 6-17]. No factor was found strongly correlated with FQ. CONCLUSION: Results from trials assessing administration-approved biologics or small molecules for treating CD or UC were vulnerable to small changes by measuring FI or FQ. Pivotal studies contributing to regulatory approvals exhibited a relatively higher degree of resilience compared to non-pivotal trials.

Comparison of efficacy discrepancy between early-phase clinical trials and phase III trials of PD-1/PD-L1 inhibitors.

BACKGROUND: Phase III clinical trials are pivotal for evaluating therapeutics, yet a concerning failure rate has been documented, particularly impacting oncology where accelerated approvals of immunotherapies are common. These failures are predominantly attributed to a lack of therapeutic efficacy, indicating overestimation of results from phase II studies. Our research aims to systematically assess overestimation in early-phase trials involving programmed cell death-1 (PD-1)/programmed cell death-ligand 1(PD-L1) inhibitors compared with phase III trials and identify contributing factors. METHODS: We matched 51 pairs of early-phase and phase III clinical trials from a pool of over 9,600 PD-1/PD-L1 inhibitor trials. The matching criteria included identical treatment regimens, cancer types, treatment lines, and biomarker enrichment strategies. To assess overestimation, we compared the overall response rates (ORR) between early-phase and phase III trials. We established independent variables related to eligibility criteria, and trial design features of participants to analyze the factors influencing the observed discrepancy in efficacy between the two phases through univariable and multivariable logistic analyses. RESULT: Early-phase trial outcomes systematically overestimated the subsequent phase III results, yielding an odds ratio (OR) comparing ORR in early-phase versus phase III: 1.66 (95% CI: 1.43 to 1.92, p<0.05). This trend of inflated ORR was consistent across trials testing PD-1/PD-L1 monotherapies and combination therapies involving PD-1/PD-L1. Among the examined factors, the exclusion of patients with autoimmune diseases was significantly associated with the disparity in efficacy between early-phase trials and phase III trials (p=0.023). We calculated a Ward statistic of 2.27 to validate the effectiveness of the model. CONCLUSION: These findings underscore the tendency of overestimation of efficacy in early-phase trials involving immunotherapies. The observed differences could be attributed to variations in the inclusion of patients with autoimmune disorders in early-phase trials. These insights have the potential to inform stakeholders in the future development of cancer immunotherapies.

Utilization and outcomes of the 21-gene recurrence score in de novo metastatic breast cancer.

BACKGROUND: Limited data exist regarding the utility and validity of the 21-gene recurrence score (RS) in patients with de novo metastatic breast cancer (dnMBC). This study aimed to investigate the practice patterns as well as associated survival outcomes based on 21-gene RS in dnMBC. RESEARCH DESIGN AND METHODS: The Surveillance, Epidemiology, and End Results Oncotype database was queried for women with hormone receptor-positive and Her2-negative dnMBC. RESULTS: A total of 153 patients were identified, including 62.7% and 37.3% of patients who had RS < 26 and ≥ 26, respectively. Patients with RS ≥ 26 were more likely to receive chemotherapy compared to those with RS < 26 (61.4% vs. 28.1%, p < 0.001). Patients with RS ≥ 26 had an inferior breast cancer-specific survival (BCSS) (2-year BCSS: 84.3% vs. 89.5, p = 0.067) and overall survival (OS) compared to those with RS < 26 (2-year OS: 76.9% vs. 87.4%, p = 0.018). The multivariate Cox proportional hazard models showed that those with RS ≥ 26 had a significantly inferior BCSS (hazard ratio [HR] 2.251, 95% confidence interval [CI] 1.056-4.799, p = 0.036) and OS (HR 2.151, 95%CI 1.123-4.120, p = 0.021) compared to those with RS < 26. CONCLUSIONS: The 21-gene RS assay is an important prognostic factor in patients with dnMBC.

Analysis of patient-reported outcomes in the approval of novel oncology drugs in the United States, 2017-2022.

Background: With the growing notion of patient-focused drug development, the quality of life and other patient-reported outcomes (PROs) of cancer patients are gaining considerable attention. Several drug regulatory agencies, including the U.S. Food and Drug Administration (FDA), are calling attention to PROs. This review aims to comprehensively characterise the application of PROs and regulatory considerations for PROs in the FDA-approved novel oncology drugs. Methods: The FDA review documents and labels for novel oncology drugs approved from July 2017 to July 2022 were retrieved. We collected and analysed drug approval information, types of endpoints for PROs, PRO measures, designs of trials including PROs, and regulatory comments on PRO-related contents. Findings: Results demonstrated that PROs were used more commonly for solid tumours than hematologic malignancies, which might be correlated with the disease characteristics. We further categorised and analysed existing PRO measures, providing insight for tool selection in future oncology trial design. Our findings also indicated that PROs currently do not play a significant role in oncology drug approvals. The major deficiencies related to PROs commented on by FDA reviewers were analysed, followed by recommendations for improvements. Interpretation: This review demonstrates that PROs currently do not play a significant role in oncology drug marketing review, and how they can be used to support the approval of new oncology drugs is still in the exploratory stage. This current situation is not only related to the deficiencies in the design and implementation of PRO-related contents in oncology trials, but more importantly, it is a reminder that we should pay more attention to patient experience in the development of oncology drugs. Funding: This study was not supported by any funding.

Impact of the 21-gene expression assay on treatment decisions and clinical outcomes in breast cancer with one to three positive lymph nodes.

Background: To assess the practice patterns of the recurrence score (RS) based on the 21-gene expression assay on adjuvant chemotherapy recommendations and survival outcomes in estrogen receptor-positive (ER+)/HER2- breast cancer (BC) with one to three positive lymph nodes (N1). Methods: We included patients with T1-2N1M0 and ER+/HER2- BC diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results Oncotype DX Database. Breast cancer-specific survival (BCSS) and overall survival (OS) were assessed. Results: We included 35,137 patients in this study. There were 21.2% of patients who had RS testing in 2010, which was significantly increased to 36.8% in 2015 (P < 0.001). Performance of the 21-gene testing was associated with older age, lower tumor grade, T1 stage, lower number of positive lymph nodes, and progesterone receptor-positive disease (all P < 0.05). In those without 21-gene testing, age was the main factor significantly related to the receipt of chemotherapy, whereas RS was the main factor significantly related to chemotherapy receipt in those with 21-gene testing. The probability of chemotherapy receipt in those without 21-gene testing was 64.1% and was decreased to 30.8% in those with 21-gene testing. On multivariate prognostic analysis, the performance of 21-gene testing was associated with better BCSS (P < 0.001) and OS (P < 0.001) compared with those without 21-gene testing. Similar results were found after propensity score matching. Conclusions: The 21-gene expression assay is frequently and increasingly used for chemotherapy decision-making in ER+/HER2- BC with N1 disease. Performance of the 21-gene testing is associated with improved survival outcomes. Our study supports the routine use of 21-gene testing in the clinical practice of this population.

Genomic characterization of Bacillus cereus isolated from food poisoning cases revealed the mechanism of toxin production.

Introduction: Bacillus cereus is a ubiquitous opportunistic human pathogen that causes food intoxications worldwide. However, the genomic characteristics and pathogenic mechanisms of B. cereus are still unclear. Methods: Here, we isolated and purified nine strains of B. cereus (LY01-LY09) that caused vomiting, diarrhea and other symptoms from four foodborne outbreaks happened in Guizhou Province in southwest China from June to September 2021. After colony observation, Gram staining, microscopic examination and biochemical test, they were identified as B. cereus. The genomic characteristics, phylogenetic relationships and virulence factors of the isolated strains were analyzed at the genome level. Genome sequencing, comparative genomic analysis, secondary metabolite analysis and quantitative PCR were utilized to give a thorough exploration of the strains. Results: We obtained the genome maps of LY01-LY09 and found that LY01-LY09 had a complex interspecific relationship with B. anthracis and B. thuringiensis. We also observed a contraction of gene families in LY01-LY09, and the contracted families were mainly associated with prophage, which contributed to the species diversity of B. cereus. The Hsp20 gene family underwent a rapid evolution in LY01-LY09, which facilitated the adaptation of the strains to adverse environmental conditions. Moreover, the LY01-LY09 strains exhibited a higher copy number in the non-ribosomal polypeptide synthetase (NRPS) genes and carried the complete cereulide synthetase (ces) gene cluster sequences. Considering that the NRPS system is a classical regulatory mechanism for emetic toxin synthesis, we hypothesized that LY01-LY09 could synthesize emetic toxins through the regulation of ces gene clusters by the NRPS system. Discussion: These findings are important for further investigation into the evolutionary relationship between B. cereus and their related species, as well as the underlying mechanisms governing the synthesis and secretion of bacterial toxins.

Evolution of drug regulations and regulatory innovation for anticancer drugs in China.

Over the past two decades, China has introduced significant changes to drug regulations through regulatory innovations to accelerate drug review and approvals, keeping in line with the rapidly growing scientific innovation in drug research and development (R&D). In this study, we outlined the revolution of drug regulation in China since the establishment of the State Drug Administration in 1998. More particularly, we performed a comprehensive analysis of newly approved anticancer drugs in China from the year 2005 to May 2021, as a powerful illustration of how the revolution has changed the drug R&D landscape. Innovative drug development in China has boomed, benefiting in particular from pro-innovation policies as well as expedited program designations by the authority. We found a significant increase in the number of both imported and domestic new anticancer drugs from 2005 to 2021, with the emergence of drugs with novel mechanisms of action, including immune checkpoint inhibitors and cell therapy products. Drug lag has also been dramatically shortened by more than 70% for imported drugs in years 2016-2020 compared to years 2006-2010. Furthermore, we provide an insight into the potential approaches to further optimize the science-based and clinical value-based regulatory and R&D drug ecosystem in China. This review provides evidence of significant impacts of regulations and policies on drug R&D and suggests that the constantly adapting regulatory ecosystem will speed up drug development in China and worldwide.

Gene and cell therapies in China: booming landscape under dual-track regulation.

The booming of gene and cell therapy (GCT) worldwide in recent years has been observed, especially in the field of cancers. In order to provide the comprehensive GCT landscape in China with a focus on differential development pathways under the current dual-track regulation mode, we analyzed 953 clinical trials initiated by March 2021 including Investigational New Drugs (IND) registered trials and investigator-initiated trials (IITs). We classified GCT products into three categories and analyzed the clinical development by phases and regulation tracks, disease areas, indications, and targets. We found that CAR-T therapies from ex vivo category and stem and somatic cells from non-gene category are two most studied therapy types and GCT mostly focused on cancers. The number of IITs far exceeded IND-registered trials except for in vivo category. After 2017, when the cell therapy guideline issued, products of all categories boomed, especially the ex vivo categories. These data showed that current dual regulation tracks in China complemented each other and together facilitated the GCT development, especially after 2017. More consistent technical standards and risk-based regulation will help bring more GCT products to patients.

Serologic response and safety of COVID-19 vaccination in HSCT or CAR T-cell recipients: a systematic review and meta-analysis.

BACKGROUND: Patients receiving hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cell (CAR T-cell) therapy are immunocompromised and at high risk of viral infection, including SAR2-CoV-2 infection. However, the effectiveness and safety of COVID-19 vaccines in these recipients is not well characterized. The present meta-analysis evaluated the serologic response and safety of COVID-19 vaccines in these population. METHODS: Literature databases (MEDLINE, EMBASE, Web of Science, MedRvix and BioRvix) were searched for original studies with serologic response post COVID-19 vaccination in HSCT or CAR T-cell recipients published until July 14, 2022. The analysis included 27 observational studies with a total of 2899 patients receiving allogeneic HSCT (2506), autologous HSCT (286) or CAR T-cell therapy (107), and 683 healthy participants with serologic response data. Random effects models were used to pool the rate of serologic response to COVID-19 vaccination in HSCT or CAR T-cell recipients and odds ratio comparing with healthy controls. RESULTS: The pooled seropositivity rates in HSCT and CAR T-cell recipients were 0.624 [0.506-0.729] for one dose, 0.745 [0.712-0.776] for two doses. The rates were significantly lower than those in healthy controls (nearly 100%). In subgroup analysis, CAR T-cell recipients exhibited an even lower seroconversion rate (one dose: 0.204 [0.094-0.386]; two doses: 0.277 [0.190-0.386]) than HSCT counterparts (one dose: 0.779 [0.666-0.862]; two doses: 0.793 [0.762-0.821]). The rates were comparable between autologous and allogeneic HSCT recipients. Other possible impact factors related to seropositivity were time interval between therapy and vaccination, use of immunosuppressive drugs and immune cell counts. Most vaccine-related adverse effects were mild and resolvable, comparable to general population. CONCLUSIONS: This analysis revealed a diminished response to COVID-19 vaccines in HSCT or CAR T-cell recipients. Our findings may inform regular COVID-19 vaccination at appropriate intervals after HSCT or CAR T-cell therapy.

Impact of AJCC prognostic staging on prognosis and postmastectomy radiotherapy decision-making in hormone receptor-positive and HER2-positive breast cancer.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in patients with node-positive hormone receptor-positive (HoR) and HER2-positive breast cancer (BC) regarding AJCC pathological prognostic staging (PPS) has not been fully determined. This study aimed to validate PPS in patients with node-positive HoR+/HER2+ BC after mastectomy and to investigate the role of PPS on PMRT decision-making in this patient subset. METHODS: Patients diagnosed with BC from the Surveillance, Epidemiology, and End Results database were included. Patients were classified based on the anatomical staging (AS) and PPS. Breast cancer-specific survival (BCSS) was calculated. RESULTS: In total, 6862 patients were included: 4306 (62.8 per cent) patients received PMRT and 2556 (37.2 per cent) patients had not. Compared to AS, PPS downstaged 5260 patients (76.7 per cent) and no patients were upstaged. The C-index was similar between PPS and AS (0.690 versus 0.682; P = 0.346). Regarding AS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.017) and stage IIIC (P < 0.001) disease, but not in stage IB (P = 0.675), IIA (P = 0.677), IIB (P = 0.100), and IIIB (P = 0.747) disease. Regarding PPS, patients who received PMRT had significantly better BCSS than those who had not in stage IIIA (P = 0.038) and stage IIIB (P = 0.017) disease, but not in stage IA (P = 0.336), IB (P = 0.893), IIA (P = 0.815), and IIB (P = 0.120) disease. PPS might allow approximately 1390 stage III patients (45.0 per cent) in the AS criterion to avoid PMRT. CONCLUSION: PPS does not provide better risk discriminatory ability in predicting prognosis than AS in patients with node-positive HoR+/HER2+ BC after mastectomy. However, PPS is valuable in providing prognostic counselling to patients and may also guide PMRT decision-making.

lnc­MICAL2­1 sponges miR­25 to regulate DKK3 expression and inhibits activation of the Wnt/ß­catenin signaling pathway in breast cancer.

The Dickkopf 3 (DKK3) protein antagonizes the Wnt receptor complex in the Wnt signaling pathway; however, to date, there have been no relevant studies investigating its upstream regulatory mechanism in breast cancer (BC), to the best of our knowledge. The present study aimed to explore whether long non­coding RNA MICAL2­1 (lnc­MICAL2­1) sponged microRNA (miR)­25 to regulate DKK3 and inhibit activation of the Wnt/ß­catenin signaling pathway. The Atlas of non­coding RNA in Cancer database was used to measure the expression levels of lnc­MICAL2­1 and their correlation with DKK3 expression levels. In addition, cell proliferation, invasion and migration were determined following the silencing or overexpression of lnc­MICAL2­1. The binding between lnc­MICAL2­1 and miR­25, or miR­25 and DKK3 was verified using RNA pull­down and dual­luciferase reporter assays. The effects of overexpression or knockdown of lnc­MICAL2­1 on DKK3 expression and the Wnt signaling pathway were further evaluated in a nude mouse xenograft model. The results revealed that, compared with in adjacent normal tissue, the expression levels of lnc­MICAL2­1 were downregulated in BC tissues, and the expression levels of lnc­MICAL2­1 were found to be positively correlated with DKK3 expression. The overexpression of lnc­MICAL2­1 in BC cells upregulated the mRNA expression levels of DKK3 and inhibited their proliferation. Results from the RNA pull­down and dual luciferase reporter assays validated that lnc­MICAL2­1 could bind to miR­25, which targets DKK3. The in vivo experimental data demonstrated that lnc­MICAL2­1 inhibited tumor growth via regulating the Wnt signaling pathway. In conclusion, the findings of the present study highlighted a novel molecular mechanism through which lnc­MICAL2­1 may regulate the DKK3­mediated Wnt signaling pathway in BC, highlighting potential targets for the treatment of the disease.

Distribution, Chemotherapy Use, and Outcome of the 21-Gene Recurrence Score Between Chinese and White breast Cancer in the United States.

PURPOSE: To compare the distribution, chemotherapy-decision making, and prognosis of the 21-gene recurrence score (RS) between Chinese breast cancer (BC) in the United States and White American (WA) BC. METHODS: We identified early-stage and estrogen receptor-positive BC patients diagnosed between 2004 and 2015. Multivariate logistic regression, Kaplan-Meier analysis, and multivariate Cox proportional hazards models were used for statistical analyses. RESULTS: A total of 67,486 patients were identified, including 66,215 (98.1%) WA patients and 1271 (1.9%) Chinese patients. Regarding the RS, 38,894 (57.6%) had low RS, 23,882 (35.4%) had intermediate RS, and 4710 (7.0%) had high RS. A similar distribution of RS was found between WA and Chinese BC (P = .280). The race was not the predictor associated with high RS. Similar trends of chemotherapy use were found in Chinese and WA BC. In WA BC, there were 4.1%, 31.5%, and 72.2% of patients receiving chemotherapy in low, intermediate, and high RS cohorts, respectively (P < .001). The proportion of chemotherapy use was 6.8%, 30.9%, and 74.0% in Chinese BC with low, intermediate, and high RS cohorts, respectively (P < 0.001). The multivariate prognostic analyses indicated that a higher RS was independently associated with an inferior breast cancer-specific survival. Similar trends were found among those with Chinese and WA BC. CONCLUSION: Our results demonstrate similar distribution, chemotherapy use, and outcome of the 21-gene RS between Chinese and WA BC in the United States.

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, immune-related adverse events (irAEs) in the gastrointestinal (GI) system commonly occur. In this study, data were obtained from the US Food and Drug Administration adverse event reporting system between July 2014 and December 2020. Colitis, hepatobiliary disorders, and pancreatitis were identified as irAEs in our study. Reporting odds ratio (ROR) with information components (IC) was adopted for disproportionate analysis. A total of 70,330 adverse events were reported during the selected period, 4,075 records of which were associated with ICIs. GI toxicities have been reportedly increased with ICI, with ROR025 of 17.2, 6.7, and 2.3 for colitis, hepatobiliary disorders, and pancreatitis, respectively. The risks of colitis, hepatobiliary disorders, and pancreatitis were higher with anti-CTLA-4 treatment than that with anti-PD-1 (ROR025 2.6, 1.3, and 1.1, respectively) or anti-PD-L1 treatment (ROR025 4.8, 1.3, and 1.3, respectively). Logistic analysis indicated that hepatobiliary disorders and pancreatitis more frequently occurred in female patients (adjusted odds ratio, 1.16 and 1.52; both p < 0.05). Consistently, polytherapy was a strong risk factor for colitis (adjusted odds ratio 2.52, p < 0.001), hepatobiliary disorders (adjusted odds ratio 2.50, p < 0.001), and pancreatitis (adjusted odds ratio 2.29, p < 0.001) according to multivariate logistic analysis. This pharmacovigilance analysis demonstrated an increased risk of all three GI irAEs associated with ICI therapies. The comparative analysis offered supportive insights on selecting GI irAEs for patients treated with ICIs.

The Survival Effect of Chest Wall With or Without Regional Lymphatic Radiotherapy for Breast Cancer Patients With T3~4N0M0.

BACKGROUND: Peripheral lymphatic radiotherapy in patients with pT3N0M0 and pT4N0M0 breast cancer has been a matter of considerable debate among radiation oncologists. This is the first report in a non-Caucasian population. PATIENTS AND METHODS: The study included 165 pT3N0M0 and pT4N0M0 patients. Univariate, multivariate, propensity score matching (PSM), and Kaplan-Meier analyses were conducted to evaluate the survival of patients. We also review all the literature about regional lymph nodes radiation in T3-4N0M0 patients and summarize them with tables to compare with the present study. RESULTS: The median follow-up duration was 58.7 months. Multivariate analyses showed that advance T stage and grade were dependent poor prognostic factors for OS, DMFS, LRFS, and DFS between group A (chest wall radiation) and group B (chest wall and regional lymph nodes radiation). The overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were not significantly different between group A and group B. The 5-year OS rate was 92.3% vs 89.7% for group A and group B, respectively (P=0.819). The 5-year LRFS rate was 94.9% vs 94.3% for group A and group B, respectively (P=0.852). Fifty-four pairs of patients were selected after propensity score matching (PSM) analysis was conducted. There was also no significant difference between group A and group B in regard to the OS, DFS, LRFS, and DMFS rates after PSM. The patients included in previous studies were all Caucasians, and our study was focused on non-Caucasians. The cases of previous studies were 10 to 20 years ago, but our study has more recent cases. The radiotherapy techniques of previous studies were conventional, and the techniques used in our study were three-dimensional conformal radiotherapy (3DCRT) or intensity modulated radiotherapy (IMRT). CONCLUSION: Both our study and previous studies suggested that regional lymph nodes radiation cannot improve the survival rate for breast cancer patients with T3-4N0M0 in non-Caucasian population. Advance T stage and grade were the dependent poor prognostic factors for T3-4N0M0 patients.

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making.

PURPOSE: To investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease. METHODS: Patients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model. RESULTS: We identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC. CONCLUSION: The 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

Anonymous Linkage Between College Students and Human Immunodeficiency Virus (HIV) Facilities: Systematic Evaluation of Urine Self-Collection for HIV Testing Initiative in China.

BACKGROUND: Identifying young individuals living with human immunodeficiency virus (HIV) who are unaware of their status is a major challenge for HIV control in China. To address this, an innovative, anonymous vending machine-based urine self-collection for HIV testing (USCT) program was implemented in 2016 in colleges across China. METHODS: From June 2016 to December 2019, 146 vending machines stocked with urine self-collection kits were distributed on 73 college campuses across 11 provinces of China. Urine samples were collected, delivered, and tested in an anonymous manner. We analyzed the returned rate, reactive rate (likelihood of HIV screening positive), testing effectiveness (the annual number of college students living with HIV screened by USCT or other testing methods), and the spatiotemporal relationship between USCT usage and student activity per college generated from the usage of a social networking application. RESULTS: Among the 5178 kits sold, 3109 (60%) samples were returned; of these, 2933 (94%) were eligible for testing. The HIV reactive rate was 2.3% (66 of 2933). The average effectiveness ratio among the 34 participating Beijing colleges was 0.39 (12:31) between USCT and conventional testing methods. A strong spatiotemporal correlation between USCT numbers and online student activity was observed during school semesters in Beijing. CONCLUSIONS: USCT is a powerful complement to current interventions that target at-risk students and promote HIV testing. The social networking-based evaluation framework can be a guide in prioritizing at-risk target populations.