Background
In response to the prioritization of healthcare resources towards the COVID-19 pandemic, routine cancer screening and diagnostic have been disrupted, potentially explaining the apparent ...COVID-era decline in cancer cases and mortality. In this study, we identified temporal trends in public interest in cancer-related health information using the nowcasting tool Google Trends.
Methods
We used Google Trends to query search terms related to cancer types for short-term (September 2019–September 2020) and long-term (September 2016–September 2020) trends in the US. We compared average relative search volumes (RSV) for specified time ranges to detect recent and seasonal variation.
Results
General search interest declined for all cancer types beginning in March 2020, with changes in search interest for “Breast cancer,” “Colorectal cancer,” and “Melanoma” of − 30.6%, − 28.2%, and − 26.7%, respectively, and compared with the mean RSV of the two previous months. In the same time range, search interest for “Telemedicine” has increased by + 907.1% and has reached a 4-year peak with a sustained increased level of search interest. Absolute cancer mortality has declined and is presently at a 4-year low; however, search interest in cancer has been recuperating since July 2020.
Conclusion
We observed a marked decline in searches for cancer-related health information that mirrors the reduction in new cancer diagnoses and cancer mortality during the COVID-19 pandemic. Health professions need to be prepared for the coming demand for cancer-related healthcare, foreshadowed by recovering interest in cancer-related information on Google Trends.
Abstract
While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at ...relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While
TP53
and
CCND3
mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in
ID3
,
DDX3X, ARID1A
and
SMARCA4
, while several genes such as
BCL2
and
YY1AP1
are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that
TP53
mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials.
The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine - receptor interaction between neoplastic cells and their ...microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues.
We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro.
Unexpectedly, plerixafor led to an increase in cell viability and proliferation in standard cell growth conditions, and to chemotactic migration towards plerixafor. Exploring potential molecular mechanisms underlying this effect, we found that Ewing sarcoma cell lines divided into classes of high- and low-level CXCR4 surface expression. Proliferative plerixafor responses were observed in both groups, maintained despite significant CXCR4 down-regulation or inhibition of Gαi-protein signal transduction, and involved activation of multiple receptor tyrosine kinases (DDR2, MERTK, MST1R, NTRK1, RET), the most prominent being platelet-derived growth factor receptor beta (PDGFRB). PDGFRB was activated in response to inhibition of the CXCL12-CXCR4 axis by plerixafor and/or pertussis toxin (Gαi-protein inhibitor). Dasatinib, a multi-kinase inhibitor of both PDGFRB and the CXCR4 downstream kinase SRC, counteracted this activation in some but not all cell lines.
These data suggest a feedback interaction between the CXCR4 chemokine receptor and RTK signaling cascades that elicits compensatory cell survival signaling and can shift the net effect of plerixafor towards proliferation. PDGFRB was identified as a candidate driver RTK and potential therapeutic co-target for CXCR4 in Ewing sarcoma. Although as yet limited to in vitro studies, these findings call for further investigation in the cancer - microenvironment interplay in vivo.
Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable ...remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0–163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34
+
cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.
Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding ...vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman's rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 - 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 - 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns.
The treatment options for systemically progressed hepatocellular carcinoma (HCC) have significantly expanded in recent years. In this study, we aimed to evaluate the potential of Google searches as a ...reflection of prescription rates for HCC drugs in the United States (US).
We conducted an in-depth analysis of US prescription data obtained from the IQVIA National Prescription Audit (NPA) and corresponding Google Trends data from January 2017 to December 2022. We focused on drugs used in the first line and second or later treatment lines for HCC, collecting data on their prescriptions and search rates. Search volumes were collected as aggregated search queries for both generic drugs and their respective brand names.
During the study period from Q1 2017 to Q4 2022, monthly prescriptions for drugs used in HCC treatment showed an 173% increase (from 1253 to 3422). Conversely online searches increased by 3.5% (from 173 to 179 per 10 million searches). Notably, strong correlations were observed between search interest and prescriptions for newer drugs, which indicates increasing usage, while older drugs with declining usage displayed limited correlation. Our findings suggest a growing role of non-physician professions in managing systemically progressed HCC within the US healthcare system, although oncologists remained primarily responsible for drug prescriptions.
In conclusion, online search monitoring can offer the potential to reflect prescription trends specifically related to the treatment of HCC. This approach provides a swift and accessible means of evaluating the evolving landscape of HCC treatment.
Background
Despite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the ...anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.
Methods
Antibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in
in vitro
and
in vivo
models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).
Results
Three different sensitivity profiles to antibody monotherapy or combination treatment were observed in
in vitro
models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model.
Conclusion
This study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma
in vitro
and
in vivo
.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous diagnostic category comprising distinct molecular subtypes characterized by diverse genetic aberrations that dictate patient outcome. As ...roughly one-third of patients with DLBCL are not cured by current standard chemoimmunotherapy, a better understanding of the molecular pathogenesis is warranted to improve outcome. B-cell receptor (BCR) signaling is crucial for the development, growth, and survival of normal B cells and a substantial fraction of malignant B cells. Various analyses revealed genetic alterations of central components of the BCR or its downstream signaling effectors in some subtypes of DLBCL. Thus, BCR signaling and the downstream NF-κB and phosphatidylinositol 3-kinase (PI3K) cascades have been proposed as potential targets for the treatment of patients with DLBCL. As one of the main effectors of BCR activation, PI3K-mediated signals play a crucial role in the pathogenesis and survival of DLBCL. In this review, we summarize our current understanding of BCR signaling with a special focus on the PI3K pathway in DLBCL and how to use this knowledge therapeutically.
Display omitted
Deregulated phosphatidylinositide 3-kinase (PI3K) signaling plays a crucial role in the biology of different lymphoma entities leading to the proliferation and survival of the malignant cells. Due to ...novel treatment options and modern supportive care, the outcome of patients with lymphomas has significantly improved in the past years. However, patients with relapsed or refractory disease still have a limited prognosis. PI3K inhibitors represent a modern and effective therapeutic option for patients with different types of lymphoma. However, the efficacy of PI3K inhibitors varies among lymphoma entities. Additionally, severe toxicity including infectious and autoimmune complications leading to therapy-related deaths has been observed. Next-generation PI3K inhibitors show promising efficacy and manageable toxicity profiles. Future research might identify effective combinatorial therapy approaches for PI3K inhibitors to further improve response rates. This review discusses the most recent developments in the field of PI3K inhibition in different subtypes of lymphoma.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
CD19‐directed chimeric antigen receptor (CAR)‐T cell therapy has become a standard treatment for relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). While the benefits of CAR‐T cell ...treatment are clear in the general patient population, there remains a relative scarcity of real‐world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR‐T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR‐T infusion (<70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged <70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow‐up of 8.3 months, median progression‐free survival was 10.2 months (95% confidence interval CI: 6.5–21.8) and 11.1 months (95% CI: 4.9–NR) (p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8–NR) and 34.4 months (95% CI: 10.1–NR) (p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome (p = 0.53) or grade ≥3 neurotoxicity (p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR‐T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR‐T cell therapy should be not withheld for elderly patients with r/r DLBCL.
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