From presentation to paper: Gender disparities in oncological research.

Gender disparities in scientific publications have been identified in oncological research. Oral research presentations at major conferences enhance visibility of presenters. The share of women presenting at such podia is unknown. We aim to identify gender-based differences in contributions to presentations at two major oncological conferences. Abstracts presented at plenary sessions of the American Society of Clinical Oncology (ASCO) Annual Meetings and European Society for Medical Oncology (ESMO) Congresses were collected. Trend analyses were used to analyze female contribution over time. The association between presenter's sex, study outcome (positive/negative) and journals' impact factors (IFs) of subsequently published papers was assessed using Chi-square and Mann-Whitney U tests. Of 166 consecutive abstracts presented at ASCO in 2011-2018 (n = 34) and ESMO in 2008-2018 (n = 132), 21% had female presenters, all originating from Northern America (n = 17) or Europe (n = 18). The distribution of presenter's sex was similar over time (p = 0.70). Of 2,425 contributing authors to these presented abstracts, 28% were women. The proportion of female abstract authors increased over time (p < 0.05) and was higher in abstracts with female (34%) compared to male presenters (26%; p < 0.01). Presenter's sex was not associated with study outcome (p = 0.82). Median journals' IFs were lower in papers with a female first author (p < 0.05). In conclusion, there is a clear gender disparity in research presentations at two major oncological conferences, with 28% of authors and 21% of presenters of these studies being female. Lack of visibility of female presenters could impair acknowledgement for their research, opportunities in their academic career and even hamper heterogeneity in research.

Effect of limitation of iron and manganese on microalgae growth in fresh water.

Eutrophication is caused by the rapid growth of microalgae. Iron and manganese are important micronutrients for microalgae growth. However, the effect of the limitation of iron and manganese on microalgae growth in fresh water has not been well understood. In this study, natural mixed algae, Anabaena flosaquae and Scenedesmus quadricanda, were cultivated under different quotas of iron and manganese to reveal the effect of the limitation of iron and manganese on the growth of microalgae in fresh water. The results showed that the growth rate of algae is influenced more by iron than by manganese. However, the effect of manganese cannot be overlooked: when the initial manganese quota was replete, i.e. 0.6-0.8 mg l-1, manganese was able to relieve the effect of iron limitation on microalgae growth in fresh water. We further found that the microalgae showed an uptake preference for iron over manganese. Iron had a competitive effect on manganese uptake, while manganese had less impact on iron uptake by microalgae. The information obtained in the current study is useful for the provision of water quality warnings and for the control of microalgae bloom in fresh water.

Influence of afatinib dose on outcomes of advanced EGFR-mutant NSCLC patients with brain metastases.

BACKGROUND: Afatinib is an oral irreversible epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor (TKI) indicated in first-line treatment of advanced EGFR-mutant (EGFRm+) non-small cell lung cancer (NSCLC). Dose dependent side effects can limit drug exposure, which may impact on extracranial and central nervous system (CNS) disease control. METHODS: We performed a retrospective study of 125 patients diagnosed with advanced EGFRm+ NSCLC treated with first-line afatinib at a tertiary Asian cancer center, exploring clinicopathological factors that may influence survival outcomes. Median progression free survival (PFS) was estimated using the Kaplan-Meier method. Comparison of PFS between subgroups of patients was done using log-rank tests and Cox proportional hazards models. RESULTS: Out of 125 patients, 62 (49.6%) started on 40 mg once daily (OD) afatinib, 61 (48.8%) on 30 mg OD and 1 (0.8%) on 20 mg OD. After median follow-up of 13.8 months from afatinib initiation, the observed response rate was 70.4% and median PFS 11.9 months (95% CI 10.3-19.3). 42 (33.6%) patients had baseline brain metastases (BM) and PFS of those who started on 40 mg OD (n = 17) vs. 30 mg OD (n = 25) was 13.3 months vs. 5.3 months (HR 0.39, 95% CI 0.15-0.99). BM+ patients who started on 40 mg had similar PFS to patients with no BM (13.3 months vs. 15.0 months; HR 0.79, 95% CI 0.34-1.80). CONCLUSION: In patients with advanced EGFRm+ NSCLC with BM+, initiating patients on afatinib 40 mg OD was associated with improved PFS compared to 30 mg OD, underscoring the potential importance of dose intensity in control of CNS disease.

Correction to: Influence of afatinib dose on outcomes of advanced EGFR-mutant NSCLC patients with brain metastases.

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Novel therapeutic targets on the horizon for lung cancer.

Lung cancer is a leading cause of cancer-related mortality worldwide, and is classically divided into two major histological subtypes: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although NSCLC and SCLC are considered distinct entities with different genomic landscapes, emerging evidence highlights a convergence in therapeutically relevant targets for both histologies. In adenocarcinomas with defined alterations such as EGFR mutations and ALK translocations, targeted therapies are now first-line standard of care. By contrast, many experimental and targeted agents remain largely unsuccessful for SCLC. Intense preclinical research and clinical trials are underway to exploit unique traits of lung cancer, such as oncogene dependency, DNA damage response, angiogenesis, and cellular plasticity arising from presence of cancer stem cell lineages. In addition, the promising clinical activity observed in NSCLC in response to immune checkpoint blockade has spurred great interest in the field of immunooncology, with the scope to develop a diverse repertoire of synergistic and personalised immunotherapeutics. In this Review, we discuss novel therapeutic agents for lung cancer that are in early-stage development, and how prospective clinical trials and drug development may be shaped by a deeper understanding of this heterogeneous disease.

Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC.

OBJECTIVES: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. MATERIALS AND METHODS: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis. CONCLUSIONS: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.

Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma.

Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC.

Advances in systemic treatment for nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches.