Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 ...vaccines is unclear.
To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls.
This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel).
Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL.
The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses.
The analysis included 180 participants, which comprised 102 patients with cancer (median interquartile range (IQR) age, 66 56-72 years; 58 men 57%) and 78 healthy controls (median IQR age, 62 49-70 years; 25 men 32%). The most common tumor type was gastrointestinal (29 28%). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 IQR, 509-4386 AU/mL vs 7160 IQR, 3129-11 241 AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, -3.5; 95% CI, -5.6 to -1.5).
In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.
Gastric cancer is the third most lethal cancer worldwide, and evaluation of the genomic status of gastric cancer cells has not translated into effective prognostic or therapeutic strategies. We ...therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), in particular, cancer-associated fibroblasts (CAF). However, very little is known about the role of CAFs in gastric cancer. To address this, we mapped the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from patients with gastric cancer. A stromal gene signature was associated with poor disease outcome, and the transcription factor heat shock factor 1 (HSF1) regulated the signature. HSF1 upregulated inhibin subunit beta A and thrombospondin 2, which were secreted in CAF-derived extracellular vesicles to the TME to promote cancer. Together, our work provides the first transcriptional map of human gastric cancer stroma and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment. SIGNIFICANCE: This study shows how HSF1 regulates a stromal transcriptional program associated with aggressive gastric cancer and identifies multiple proteins within this program as candidates for therapeutic intervention. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/7/1639/F1.large.jpg.
Gastric cancer (GC) is a leading cause of cancer death, occurs predominantly in older age, with increasing incidence in young patients. The Cancer Genome Atlas indicates four subtypes for GC among ...which Epstein-Barr virus (EBV) subtype is estimated at 8.7%. We aim to determine the prevalence of EBV subtype in young GC patients (≤45 years) compared with an average-onset cohort (≥55 years) and characterize the clinicopathologic pattern of young-onset GC.
Gastric cancer samples of patients of both cohorts were screened for EBV by qPCR. Additional staining was done for Human epidermal growth factor receptor 2 (HER2), microsatellite instability (MSI) status and Programmed death-ligand 1 (PD-L1). Demographics and clinical data were retrieved from the medical records.
Thirty-nine young-onset and 35 average-onset GC patients were reviewed. There was no apparent difference in tumor location, family history, histology and HER2 status between the cohorts. More young-onset patients were diagnosed with metastatic disease (27% vs 9%, p = 0.0498). EBV was significantly more prevalent in the young-onset cohort (33% vs 11%, p = 0.025). 15/17 EBV positive patients were under the median age of diagnosis for GC in the US (68 years). MSI-H was found only in the average-onset cohort 0% vs 27%, p = 0.001). PD-L1 positivity was higher in the young-onset cohort (31% vs 3%, p = 0.002).
Our study indicates that EBV subtype is more prevalent in young-onset GC and may play a key role in the pathogenesis. Higher rate of PD-L1 positivity in young-onset GC could change treatment strategies. We are currently evaluating these findings in a prospective trial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Smoking is associated with an increased incidence of hormone receptor positive breast cancer. Data regarding worse breast cancer outcome in smokers are accumulating. Current literature regarding the ...impact of smoking on breast cancer characteristics is limited. We evaluated the impact of smoking on breast cancer characteristics and outcome.
This was a retrospective single center study. All women diagnosed from 4/2005 through 3/2012 and treated in our institute for early, estrogen receptor positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer, whose tumors were sent for Oncotype DX analysis were included. Medical records were reviewed for demographics, clinico-pathological parameters, treatment and outcome. Data regarding smoking were retrieved according to patients' history at the first visit in the oncology clinic. Patients were grouped and compared according to smoking history (ever smokers vs. never smokers), smoking status (current vs. former and never smokers) and smoking intensity (pack years ≥30 vs. the rest of the cohort). Outcomes were adjusted in multivariate analyses and included age, menopausal status, ethnicity, tumor size, nodal status and grade.
A total of 662 women were included. 28.2% had a history of smoking, 16.6% were current smokers and 11.3% were heavy smokers. Smoking had no impact on tumor size, nodal involvement and Oncotype DX recurrence score. Angiolymphatic and perineural invasion rates were higher in current smokers than in the rest of the cohort (10.4% vs. 5.1%, p = 0.045, 8.3% vs. 3.5%, p = 0.031, respectively). Smoking had no other impact on histological characteristics. Five-year disease free survival and overall survival rates were 95.7% and 98.5%, respectively. Smoking had no impact on outcomes. Adjusted disease free survival and overall survival did not influence the results.
Smoking had no clinically significant influence on tumor characteristics and outcome among women with estrogen receptor positive, HER2 negative, early breast cancer. As the study was limited to a specific subgroup of the breast cancer population in this heterogeneous disease and since smoking is a modifiable risk factor for the disease, further research is required to clarify the possible impact of smoking on breast cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Colorectal carcinoma is one of the most common cancers in the world, and more than 50% of these patients develop liver metastases. Despite recent advances, systemic chemotherapy for metastatic ...disease without the use of surgery is considered palliative, as there are rarely long-term survivors. However, patients who are candidates for surgical resection of their liver metastases can have a prolonged survival or possibly a cure. Consensus guidelines on criteria for resection and prognostic scores help facilitate patient selection, yet only 25% of patients with liver metastases are considered to have resectable metastases. Neoadjuvant chemotherapy has been explored in an attempt to render more patients candidates for resection. First reports using neoadjuvant systemic chemotherapy in patients with unresectable disease found that 13% to 16% of patients could be rendered resectable. Efforts to increase response rates using hepatic arterial infusion or biologic agents may increase resection rates. This review summarizes the current data on neoadjuvant chemotherapy, the rationale for this approach, potential complications, and future prospects.
AIM：To compare the microRNA （miR） profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS：The study group included 45 patients who underwent curative ...gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction （qRT-PCR）.Findings were compared between patients who had a recurrence within 36 mo of surgery （bad-prognosis group,n=14,31%） and those who did not （good-prognosis group,n=31,69%）.RESULTS：Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis （P0.0002,0.0027 and 0.0046 respectively）.High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% （13/13）.The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION：This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.
We present here a new, classification-based screening method for anti-cancer botanical combinations. Using this method, we discovered that the combination of
and
(AV) has strong synergic ...anti-proliferative and killing effects on cancer cells. We showed that AV induces the hyper activation of proliferation and survival pathways (Akt and ERK1/2) and strongly downregulates the cell cycle control proteins p21 and p27. Moreover, FACS analyses revealed that AV induces accumulation of cells in G2/M phase, supported by accumulation of cyclin A. Taken together, our results suggest that AV interferes with the cell cycle in cancer cells, leading to accumulation in G2/M and apoptosis. Further studies are needed to validate the generalizability of the anti-cancer effect of the AV combination, to fully understand its mechanism of action and to evaluate its potential as a new anti-cancer treatment.
The success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.
...We report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.
In contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.
These features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges.
Background
Efficacy of immune checkpoint inhibitors (ICIs) in metastatic gastric/gastroesophageal junction (GEJ) adenocarcinoma is inconsistent. Whether the efficacy of ICIs is comparable across ...different subgroups remains unknown.
Methods
We identified randomized controlled trials (RCTs) that compared standard treatment for metastatic gastric/GEJ adenocarcinoma to ICIs. Hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) were extracted and pooled in a meta‐analysis. Prespecified subgroups were included as follows: age at randomization (</≤65 vs ≥/>65 years), gender (female vs male), ethnicity (Asians vs non‐Asians), performance‐status (0 vs 1), tumor location (gastric vs GEJ), and histological subtype (diffuse vs others). OS in patients with programmed death ligand (PD‐L1) positive and with microsatellite instability‐high (MSI‐H) were also extracted and pooled in a meta‐analysis.
Results
Five RCTs comprising 2,264 patients were analyzed. Compared to standard therapy, ICIs did not improve OS (HR = 0.86, 95% CI 0.71‐1.03, P = .10) and the effect of ICIs on OS was similar in all subgroups. Nonsignificantly greater effect sizes were seen in older patients (HR = 0.85 vs 0.88, P = .81), male (HR = 0.82 vs 0.99, P = .16), Asians (HR = 0.86 vs 0.96, P = .55), performance‐status 0 (HR = 0.84 vs 0.88, P = .81), GEJ tumors (HR = 0.78 vs 0.90, P = .37), and nondiffuse subtype (HR = 0.71 vs 0.79, P = .62). ICIs were associated with significantly improved OS in patients with MSI‐H (HR = 0.33, P = .001), but not in PD‐L1 positive disease (HR = 0.86, P = .06).
Conclusions
Compared to standard treatment, ICIs in metastatic gastric/GEJ adenocarcinoma did not improve OS. None of the evaluated subgroups has shown increased magnitude of effect to ICIs, aside of the small group with MSI‐H tumors.
Compared to standard treatment, ICIs in metastatic gastric/GEJ adenocarcinoma did not improve OS. None of the evaluated subgroups including, age, gender, ethnicity, performance status, primary tumor location, and histological subtype, has shown increased magnitude of effect from ICIs. In exploratory analysis for small group with MSI‐H tumors, treatment with ICIs was associated with significant OS improvement compared to the control group.
Background
The incidence of colorectal cancer in young patients is increasing. It remains unclear if the disease has unique features in this age group.
Methods
This was a single-center, retrospective ...cohort study which included patients diagnosed with colorectal cancer at age ≤40 years in 1997–2013 matched 1:2 by year of diagnosis with consecutive colorectal cancer patients diagnosed at age >50 years during the same period. Patients aged 41–50 years were not included in the study, to accentuate potential age-related differences. Clinicopathological characteristics, treatment, and outcome were compared between groups.
Results
The cohort included 330 patients, followed for a median time of 65.9 months (range 4.7–211). Several significant differences were noted. The younger group had a different ethnic composition. They had higher rates of family history of colorectal cancer (
p
= 0.003), hereditary colorectal cancer syndromes (
p
< 0.0001), and inflammatory bowel disease (
p
= 0.007), and a lower rate of polyps (
p
< 0.0001). They were more likely to present with stage III or IV disease (
p
= 0.001), angiolymphatic invasion, signet cell ring adenocarcinoma, and rectal tumors (
p
= 0.02). Younger patients more frequently received treatment. Young patients had a worse estimated 5-year disease-free survival rate (57.6 vs. 70 %,
p
= 0.039), but this did not retain significance when analyzed by stage (
p
= 0.092). Estimated 5-year overall survival rates were 59.1 and 62.1 % in the younger and the control group, respectively (
p
= 0.565).
Conclusions
Colorectal cancer among young patients may constitute a distinct clinical entity. Further research is needed to validate our findings and define the optimal approach in this population.
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