BACKGROUND: Adjuvant nivolumab reduces recurrence in patients with locoregional esophageal cancer who had pathological residual disease after neoadjuvant chemoradiotherapy and R0 resection. However, the efficacy of adjuvant anti-PD-1 therapy in patients at higher risk of recurrence remains unclear.
METHODS: This phase II trial (ClinicalTrials.gov identifier: NCT03322267) enrolled patients with locally advanced esophageal squamous cell carcinoma (ESCC) received neoadjuvant chemoradiotherapy plus esophagectomy but still had various risk factors for recurrence, such as involved or close margins (≤ 1 mm), extranodal extension of the involved lymph nodes, and the ypN2-3 stage. Patients received adjuvant therapy composed of a course of cisplatin-based chemoradiotherapy and pembrolizumab (200 mg, IV every 3 weeks) for 18 cycles. The primary endpoint was 1-year relapse-free survival (RFS) rate.
RESULTS: Twenty-five patients were enrolled. The risk factors were tumor margins of ≤ 1 mm (18 patients), extranodal extension of the involved lymph nodes (9 patients), and the ypN2-3 stage (9 patients). The median follow-up duration was 21.6 months (95% CI: 18.7-33.2). The rate of 1-year RFS was 60.0%. The median duration of RFS and overall survival was 14.3 (95% CI: 9.0-19.5) and 21.6 (95% CI: 0.0-45.5) months, respectively. Treatment-emergent adverse events of any grade and those of ≥ 3 grade occurred in 56% and 8% of all patients receiving cisplatin-based chemoradiotherapy and in 79.2% and 12.5% of those receiving pembrolizumab.
CONCLUSIONS: Adjuvant chemoradiotherapy followed by pembrolizumab is feasible and may be associated with improved 1-year RFS rate in patients at high risk of recurrence after trimodality therapy for locally advanced ESCC. Trial registration number ClinicalTrials.gov (No. NCT03322267).

OBJECTIVE: To determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC).
METHODS: We conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation.
RESULTS: Of 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94).
CONCLUSIONS: Receipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated.

BACKGROUND: The administration of adjuvant imatinib during three years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards.
METHODS: IMADGIST (NCT02260505) was a multicenter open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-years arm) compared to Interruption (3-years arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to treat disease-free survival (DFS). Secondary endpoints include overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, safety.
RESULTS: From December 24th 2014 to April 4th 2023; 136 patients aged ≥18, ECOG PS ≤2, with a localized GIST with a R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to NCCN risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-Years arm vs. 71 in the 6-Years arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients respectively. Respectively 52 (38%) and 71 (52%) of patients had a risk of relapse of 35-70% and >70%.. With a median follow-up of 55 (IQR=46-59) months post randomization, DFS was significantly superior in the 6-Years arm (HR: 0.40 [0.20-0.69], p=0.0008). Time to imatinib resistance, survival, adverse events and quality of life are not different in the 2 arms.
CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

BACKGROUND: Micropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components.
METHODS: We retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination.
RESULTS: Overall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P < 0.001), and MPP pathological subtype (P < 0.001) were more frequent in the TPM-positive (TPMP) group than in the TPM-negative (TPMN) group. Five-year disease-free survival (DFS) rates were significantly lower in the TPMP group than in the TPMN group (84.5% vs. 93.4%, P = 0.006). In addition, patients with high proportions (greater than 10%) of MPP components had worse overall survival (OS) (91.0% vs. 98.9%, P = 0.025) than those with low proportions (5%≤ TPM ≤ 10%). However, postoperative EGFR tyrosine kinase inhibitors (TKIs) or adjuvant chemotherapy (ACT) cannot improve DFS and OS between EGFR-mutated patients with different proportions of MPP components.
CONCLUSIONS: MPP was related to earlier recurrence and shortened survival time, even in stage IA. Further research needs a larger sample size to clarify that EGFR-mutated stage IA patients with MPP components obtain survival benefits from adjuvant therapy.

UNASSIGNED: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF.
UNASSIGNED: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed.
UNASSIGNED: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group.
UNASSIGNED: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control.
UNASSIGNED: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

暂无摘要。

On April 18, 2024, the Food and Drug Administration approved alectinib as an adjuvant treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) after tumor resection. This approval was grounded in the outcomes of the ALINA trial, which demonstrated that alectinib significantly enhances disease-free survival compared to traditional platinum-based chemotherapy in the adjuvant setting. The ALINA trial is notable not just for advancing ALK tyrosine kinase inhibitors (TKIs) into the adjuvant setting but also for its innovative approach of comparing them to adjuvant chemotherapy, distinguishing it from other landmark trials.

OBJECTIVE: To evaluate the outcomes of adjuvant radiotherapy in patients with esophageal cancer (EC) who underwent esophagectomy following neoadjuvant chemoradiotherapy (NCRT).
METHODS: The data of EC patients who received adjuvant therapy after NCRT between 2004 to 2019 was retrieved from the SEER database. The patients were split into the adjuvant radiotherapy with or without chemotherapy (RT±CT) and the adjuvant chemotherapy (CT) groups. The process of propensity score matching (PSM) was employed.
RESULTS: Following PSM, 157 patients in total were recruited in each treatment group. There were no significant variations in either overall survival (OS) or cancer-specific survival (CSS) between the RT±CT and CT groups (median OS: 28 months versus. 51 months, p=0.063; median CSS: 31 months versus. 52 months, p=0.16). Within the CT group, patients with ypI/II or cI/II tumor stage, positive lymph node ratio (LNR) ≤0.1, and tumor size ≥50 mm (p<0.05) had higher OS compared to the RT±CT groups. Among patients with cT3-4 tumors in N-stage downstaging group, the OS and CSS were significantly greater for those underwent RT±CT as opposed to the CT group (5-year OS:56.6% versus 19.4%, p=0.042; 5-year CSS:67.9% versus. 19.4%, p=0.023). Multivariate Cox regression analysis identified the tumor histology grade as an independent prognostic factor of OS and CSS.
CONCLUSIONS: Radiotherapy-based adjuvant therapy does not significantly improve the prognosis of EC patients after NCRT, although it may provide a survival benefit for patients with cT3-4 tumors in N-stage downstaging.

BACKGROUND: Recently, the PORT-C and LUNG-ART trials, which evaluated the role of postoperative radiation therapy (PORT), have significantly altered the treatment landscape for NSCLC pN2 patients who previously underwent surgery. In response, the Italian Association of Radiotherapy and Oncology Thoracic Oncology study group has initiated an observational multicenter trial to assess both acute and late toxicities of PORT in pN2 NSCLC patients treated with modern techniques.
METHODS: Data on NSCLC patients submitted to PORT after radical surgery treated between 2015 and 2020 in six Italian Centers were collected. Heart, lung, and esophageal acute and late toxicities have been retrospectively analyzed and related to radiation therapy dosimetric parameters. Furthermore, loco-regional control, distant metastasis and overall survival have been analyzed.
RESULTS: A total of 212 patients with a median age of 68 years from six different centers were included in this analysis (142 males and 70 females). Prior to undergoing PORT, 96 patients (45.8%) had a history of heart disease, 110 patients (51.9%) had hypertension, and 51 patients (24%) had COPD. Acute toxicity was observed in 147 patients (69.3%), with lung toxicity occurring in 93 patients (G1 in 70 patients, G2 in 17 patients, and G3 in 4 patients), esophageal toxicity in 114 patients (G1 in 89 patients, G2 in 23 patients, and G3 in 1 patient), and cardiac toxicity in 4 patients (G1 in 2 patients and G3 in 2 patients). Late side effects were found in 60 patients (28.3%), predominantly involving the lungs (51 patients: 32 G1, 11 G2, and 1 G3) and the esophagus (11 patients: 8 G1 and 3 G2), with no reported late cardiac side effects. Various clinical and dosimetric parameters were found to correlate with both acute and chronic toxicities. Over a median follow-up period of 54 months, 48 patients (22.6%) showed locoregional disease relapse, 106 patients (50%) developed distant metastases, and 66 patients (31.1%) died.
CONCLUSIONS: RAC-TAC retrospective multicentric study showed the low toxicity of PORT when advanced technology is used. At the same time, it\'s noteworthy to underline that 50% of the patients develop distant recurrences in the follow up.

Streptococcus pneumoniae is a common pathogen associated with community-acquired bacterial meningitis, characterized by high morbidity and mortality rates. While vaccination reduces the incidence of meningitis, many survivors experience severe brain damage and corresponding sequelae. The pathogenesis of pneumococcal meningitis has not been fully elucidated. Currently, meningitis requires bacterial disruption of the blood - brain barrier, a process that involves the interaction of bacterial surface components with host cells and various inflammatory responses. This review delineates the global prevalence, pathogenesis, and treatment strategies of pneumococcal meningitis. The objective is to enhance the thorough comprehension of the clinical manifestations and biological mechanisms of the disease, thereby enabling more efficient prevention, diagnosis, and therapeutic interventions.