False negatives from nasopharyngeal swabs (NPS) using reverse transcriptase PCR (RT-PCR) in SARS-CoV-2 are high. Exhaled breath condensate (EBC) contains lower respiratory droplets that may improve ...detection. We performed EBC RT-PCR for SARS-CoV-2 genes (E, S, N, ORF1ab) on NPS-positive (n=16) and NPS-negative/clinically positive COVID-19 patients (n=15) using two commercial assays. EBC detected SARS-CoV-2 in 93.5% (29/31) using the four genes. Pre-SARS-CoV-2 era controls (n=14) were negative. EBC was positive in NPS negative/clinically positive patients in 66.6% (10/15) using the identical E and S (E/S) gene assay used for NPS, 73.3% (11/15) using the N/ORF1ab assay and 14/15 (93.3%) combined.
Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased ...hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer. The purpose of this study was to assess the use of lipegfilgrastim in the treatment of early breast cancer and to examine the incidence of treatment-related neutropenia during the dose dense AC phase and subsequent paclitaxel treatment.
This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of < 1.0 × 10
/L, during four cycles of dose dense AC with lipegfilgrastim support. The secondary endpoints were the incidence of febrile neutropenia, (temperature > 38 °C and ANC < 1.0 × 10
/L), treatment delays, premature treatment cessation and toxicity.
Forty-one participants were included in the study. Of the 160 planned dose dense AC treatments, 157 were administered, and 95% (152/160) of these were given on time. The rate of treatment delay was 5% (95% CI 2.2 to 9.9%) due to infection (4) and mucositis (1). Four (10%) patients developed febrile neutropenia. The most frequently occurring adverse event was grade 1 bone pain.
Lipegfilgrastim is an effective option in the prophylaxis of chemotherapy-induced neutropenia, and its use in everyday anti-cancer treatment can be considered.
Following optimal local therapy, adjuvant Procarbazine, Lomustine and Vincristine (PCV) improves overall survival (OS) in low-grade glioma (LGG). However, 1 year of PCV is associated with significant ...toxicities. In the pivotal RTOG 9802 randomised control trial, approximately half of the patients discontinued treatment after 6 months. As patients on clinical trials may be fitter, we aimed to further explore the tolerability of PCV chemotherapy in routine clinical practice.
We conducted a retrospective study between 2014 and 2018 at a National Neuro-Oncology centre. Patients who had received PCV during this time period were included. The primary objective was to assess tolerability of treatment. Secondary objectives included evaluation of treatment delays, dose modifications and toxicities.
Overall, 41 patients were included, 24 (58%) were male and 21 (51%) aged ≥40 years. 38 (93%) underwent surgical resection and all patients received adjuvant radiotherapy prior to chemotherapy. The median number of cycles completed was 3,2,4 for procarbazine, lomustine and vincristine respectively. Only 4 (10%) completed all 6 cycles of PCV without dose modifications. There was a universal decline in dose intensity as cycles of chemotherapy progressed. Dose intensity for cycle 1 versus cycle 6 respectively: procarbazine (98% versus 46%), lomustine (94% versus 48%) and vincristine (93% versus 50%). Haematological toxicities were common. Six (14%) patients experienced Grade III-IV thrombocytopaenia and 13 (31%) experienced Grade III-IV neutropaenia.
Toxicities are frequently observed with the PCV regimen in clinical practice. It might be preferable to adjust doses from the start of chemotherapy to improve tolerability or consider alternative chemotherapy, particularly in older patients with LGG.
•Exhaled Breath (EBC) and plasma were analysed for 5 genetic alterations using ultrasensitive PCR in lung cancer patients.•Results were compared to corresponding diagnostic tissue samples analysed ...using targeted NextGeneration Sequencing (NGS).•Higher failure rates owing to unamplifiable DNA were noted in tissue NGS compared to EBC and Plasma.•Significantly higher numbers of mutations in EGFR, KRAS and PIK3CA were identified in EBC and plasma than tissue NGS.•Overlap and divergence was noted in the mutation profiles between EBC and plasma.
Small diagnostic tissue samples can be inadequate in testing an expanding list of validated oncogenic driver alterations and fail to reflect intratumour heterogeneity (ITGH) in lung cancer. Liquid biopsies are non-invasive and may better reflect ITGH. Most liquid biopsies are performed in the context of circulating tumour DNA (ctDNA) in plasma but Exhaled Breath Condensate (EBC) shows promise as a lung-specific liquid biopsy.
In this prospective, proof-of-concept study we carried out targeted Next Generation Sequencing (NGS) on diagnostic tissue samples from 125 patients with lung cancer and compared results to plasma and EBC for 5 oncogenic driver mutations (EGFR, KRAS, PIK3CA, ERBB2, BRAF) using an ultrasensitive PCR technique (UltraSEEK™ Lung Panel on the MassARRAY® System, Agena Bioscience, San Diego, CA, USA).
There was a significantly higher failure rate due to unamplifiable DNA in tissue NGS (57/125, 45.6%) compared to plasma (27/125, 21.6%, p < 0.001 and EBC (26/125,20.8%, p ≤ 0.001. Consequently, both plasma and EBC identified higher number of mutations compared to tissue NGS. Specifically, there were significantly higher numbers of mutations detected in EGFR, KRAS and PIK3CA in plasma (p = 9.82 × 10−3, p = 3.14 × 10−5, p = 1.95 × 10−3) and EBC (p = 2.18 × 10−3, p = 2.28 × 10−4,p = 0.016) compared to tissue NGS. There was considerable divergence in mutation profiles between plasma and EBC with 34/76 (44%) mutations detected in plasma and 37/74 (41.89%) in EBC unique to their respective liquid biopsy.
The results suggest that EBC is effective in identifying clinically relevant alterations in patients with lung cancer using UltraSEEK™ and has a potential role as an adjunct to plasma testing.
Aberrant PI3K signalling is implicated in trastuzumab resistance in HER2-positive gastric cancer (GC). The role of PI3K or MEK inhibitors in sensitising HER2-positive GCs to trastuzumab or in ...overcoming trastuzumab resistance is unclear.
Using mass spectrometry-based genotyping we analysed 105 hotspot, non-synonymous somatic mutations in PIK3CA and ERBB-family (EGFR, ERBB2, ERBB3 and ERBB4) genes in gastric tumour samples from 69 patients. A panel of gastric cell lines (N87, OE19, ESO26, SNU16, KATOIII) were profiled for anti-proliferative response to the PI3K inhibitor copanlisib and the MEK1/2 inhibitor refametinib alone and in combination with anti-HER2 therapies.
Patients with HER2-positive GC had significantly poorer overall survival compared to HER2-negative patients (15.9 months vs. 35.7 months). Mutations in PIK3CA were only identified in HER2-negative tumours, while ERBB-family mutations were identified in HER2-positive and HER2-negative tumours. Copanlisib had anti-proliferative effects in 4/5 cell lines, with IC50s ranging from 23.4 (N87) to 93.8 nM (SNU16). All HER2-positive cell lines except SNU16 were sensitive to lapatinib (IC50s 0.04 µM-1.5 µM). OE19 cells were resistant to trastuzumab. The combination of lapatinib and copanlisib was synergistic in ESO-26 and OE-19 cells (ED50: 0.83 ± 0.19 and 0.88 ± 0.13, respectively) and additive in NCI-N87 cells (ED50:1.01 ± 0.55). The combination of copanlisib and trastuzumab significantly improved growth inhibition compared to either therapy alone in NCI-N87, ESO26 and OE19 cells (p < 0.05).
PI3K or MEK inhibition alone or in combination with anti-HER2 therapy may represent an improved treatment strategy for some patients with HER2-positive GC, and warrants further investigation in a clinical trial setting.
The EGFR T790M somatic mutation is the most common mechanism of resistance to tyrosine kinase inhibitors in NSCLC. Patients with advanced disease are not always amenable to repeat biopsy for further ...molecular analysis. Developing noninvasive methods to detect T790M in cell-free DNA in the absence of tissue is being actively investigated. Unfortunately, the low sensitivity of plasma for detection of T790M has limited its clinical use. Exhaled breath condensate (EBC) is an easily collected sample that is known to harbor cell-free DNA, including lung cancer mutations. This report details the potential utility of exhaled breath condensate in the detection of the EGFR T790M mutation.
Background
Clinical trials are often considered the gold standard in cancer care. However, patients face barriers in trial participation including distances to cancer centres and personal costs ...including changing employment status, cost of medications, inpatient admissions, and parking tariffs.
Aim
Our aim was to compare the distances patients travelled for clinical trials compared to those receiving standard systemic anticancer therapy (SACT). We also investigated the additional costs associated with this.
Methods
This was a retrospective review of electronic patient medical records. The distance from the patients’ home address to Beaumont was calculated as a one-way journey in kilometres. Patients attending for clinical trials were compared to those receiving standard of care SACT.
Results
A total of 271 patients receiving standard SACT over a 5-day period and 111 patients enrolled on 24 clinical trials were included. The median one-way distance travelled by patients enrolled in clinical trials was 41.4 km, compared to 14 km in those patients’ receiving standard of care SACT. The median estimated cost was €13 vs €4.20 for those enrolled on clinical trials compared to those receiving standard of care treatment, respectively.
Conclusion
Patients enrolled on clinical trials often travel more than twice as far to receive their anti-cancer treatment compared to those receiving standard of care SACT and incur an increased cost of travel expenses.
To determine the changes in clinical trials and outcomes of patients with advanced-stage non-small-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 ...to 1994.
Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute's Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time.
Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P <.001). Five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months).
Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed.
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