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PURPOSE: The role of mobile health (mHealth) technology in cancer care has evolved alongside the rapid development in digital technology. Its use can come with significant potential benefits; however, such use may also be associated with risks. This paper summarizes the latest developments around mHealth use in cancer care presented by a panel of experts at the 2019 Annual Meeting of the Multinational Association of Supportive Care in Cancer. METHODS: Through lectures, case studies, and panel discussions, speakers and participants (including cancer specialist doctors, nurses, and allied health professionals) evaluated current and emerging mHealth methods for supportive care in cancer survivorship. Focus areas and special considerations were agreed upon by consensus. RESULTS: Three focus areas for the use of mHealth in cancer care were identified: activation and support of self-management, exercise oncology, and enablement of survivorship care delivery. In addition to these focus areas, two special considerations were highlighted: technology-enhanced supportive cancer care for disparate populations, and ethical considerations relevant to the use of technology in supportive care. CONCLUSION: mHealth has the potential to revolutionize and transform cancer care delivery. Future research should guide further advances in the use of technology in supportive cancer care and carefully explore the safety, efficacy, cost-effectiveness, and implementation of interventions delivered through mHealth platforms.

Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.

Background Cancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors. Methods This is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated. Discussion Efficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF. Trial registration number ClinicalTrials.govNCT04104113. Registered on 26 September 2019

Anxiolytics and anticonvulsants generally positively modulate the action of GABA, whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin, bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been shown to negatively modulate the action of GABA at α1β2γ2L GABAA receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not known to cause convulsions. We have assessed the action of bilobalide, ginkgolide B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole, propofol, thiopentone sodium, diazepam, and allopregnanolone), using two-electrode voltage clamp electrophysiology at recombinant α1β2γ2L GABAA receptors expressed in Xenopus oocytes. The results indicate that bilobalide and ginkgolide B differ from picrotoxinin in their ability to inhibit the actions of a range of these structurally diverse GABAA positive modulators consistent with these modulators acting on a multiplicity of active sites associated with GABAA receptors. In the presence GABA, ginkgolide B was more potent than bilobalide in inhibiting the GABA-potentiating effect of propofol, equipotent against loreclezole and allopregnanolone, and less potent against etomidate, diazepam, and thiopentone sodium. This indicates that in comparison to picrotoxinin, bilobalide and ginkgolide B differ in their effects on the different modulators.

This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients’ experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = − 0.722, p

The terpenoid lactones from Ginkgo biloba, bilobalide and ginkgolides, have been shown to act as negative modulators at α1β2γ2L GABAA receptors. They have structural features similar to those of the chloride channel blocker picrotoxinin. Unlike picrotoxinin, however they are not known to produce convulsant effects. Using two-electrode voltage clamp electrophysiology, this study compared the effect of mutation of 2', 6' and 15' pore facing M2 domain residues to cysteine on the action of picrotoxinin, bilobalide and ginkgolides at α1β2γ2L GABAA receptors expressed in Xenopus oocytes. Picrotoxinin was affected by mutation differently from the ginkgo terpenoid lactones. Although some of these compounds were affected by the mutation at same position and/or subunit, the changes in their potency were found to be dissimilar. The results suggest that the intracellular pore binding site for picrotoxinin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C is comprised of 2'β-6'β6'γ, 2'α2'β-6'α6'β, 2'α2'β2'γ-6'β6'γ, 2'α, 2'β2'γ-6'β and 2'α2'β, respectively. Unlike bilobalide and ginkgolides, the inhibitory action of picrotoxinin was not affected by mutations at 15' position. It is proposed that 15'α15'β, 15'β, 15'α15'β and 15'α15'β15'γ forms an extracellular pore binding site for bilobalide, ginkgolide A, ginkgolide B and ginkgolide C, respectively. The lack of convulsant effects of bilobalide, and ginkgolide A and B may be associated in part with their different binding locations within the chloride channel.

Background Breast cancer survivors (BCS) often experience cancer-related fatigue (CRF), a distressing condition which does not have an effective standardised pharmacological intervention. Xiang Bei Yangrong Tang (XBYRT), a modified herbal traditional Chinese medicine (TCM) decoction, is formulated for the management of CRF in BCS. In this in vitro study, we evaluated the herb-enzyme inhibition for 9 of the herbal TCMs from the XBYRT formulation, on CYP2D6 activity. Methods The XBYRT herbal components evaluated were Radix Astragaliseu Hedysari, Radix Codonopsis Pilosulae, Rhizoma Atractylodis Macrocephalae, Poria cocos, Radix Paeoniae Alba, Fructus Ligustri Lucidi, Rhizoma Cyperi, Radix Polygalae and Bulbus Fritillariae Thunbergii. Varying concentrations of the herbal TCMs were assayed for herb-enzyme inhibition using the Vivid P450 CYP2D6 assay kit. The percentage inhibition for the maximum XBYRT concentration and the half maximal inhibitory concentrations (IC50) were determined. The maximum XBYRT concentration was calculated based on the total dosage of herbal components consumed, without accounting for first pass metabolism. The IC50 was calculated using the non-linear regression from GraphPad Prism 5. Results Assayed at the maximum XBYRT concentration, herbal components exhibiting the highest inhibition levels were Radix Codonopsis Pilosulae (56.8%), Poris cocos (45.0%), Fructus Ligustri Lucidi (42.9%) and Radix Paeoniae Alba (35.5%). The IC50 values of these four herbal components were 481µg/ml, 572 µg/ml, 447 µg/ml and 475 µg/ml respectively. The other 5 herbal components exhibited Conclusions Components of XBYRT display potential CYP2D6 enzymatic inhibition activities. Hence, caution should be taken with the concomitant usage of XBYRT with drugs that are CYP2D6 substrates such as tamoxifen. In vivo and clinical studies are required to ascertain the actual effects of these herbal components on drug metabolism. Legal entity responsible for the study The authors. Funding Ministry of Health Singapore. Disclosure All authors have declared no conflicts of interest.

Anxiolytics and anticonvulsants generally positively modulate the action of GABA, whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABA

Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the majority of NSCLC patients present with advanced disease, cytology and small biopsy specimens are frequently the only tissue available for mutation testing, but can pose challenges due to low tumor content. We aim to better define the suitability of these specimens for mutation testing.NSCLC cases referred to our institution for mutation testing over a 15-month period were retrospectively reviewed. Specimens were tested for mutations including EGFR, KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed on the Agena Bioscience MassARRAY platform.A total of 146 specimens were tested, comprising 53 (36.3%) resection specimens (including 28 lung resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and BRAF mutations in three specimens (2.1%). There was no significant difference in the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%).Our results support the utility of small biopsy and cytology specimens for mutation testing. Careful evaluation of the adequacy of small specimens is required to minimize the risk of false negative or positive results.

Background Many studies have examined specific mutations in patients with resected lung adenocarcinoma across heterogeneous stages, comprising predominantly advanced/metastatic disease, but there is little data regarding the mutation profile of patients with early stage node negative disease. The aim of this study was to identify patterns of mutations in early stage node negative lung adenocarcinoma. Methods A total of 204 patients who underwent resection for stage IB (sixth Ed American Joint Committee on Cancer) lung adenocarcinoma and received no neoadjuvant or adjuvant treatments were identified. Tumors were genotyped using the OncoCarta v1.0 kit (Sequenom, San Diego, CA) on the Sequenom MassARRAY platform. Fluorescence in situ hybridization for ALK rearrangement was also performed. Results A total of 110 (54%) patients' tumors harbored at least one mutation. KRAS, EGFR, PIK3CA, ALK, PDGFRA, AKT1, BRAF, FGFR1, and HRAS mutations were detected in tumors from 77 (37.7%), 29 (14.2%), 9 (4.4%), 2 (1%), 2 (1%), 1 (0.5%), 1 (0.5%), 1 (0.5%), and 1 (0.5%) patients respectively. Synchronous mutations (either comutations or double mutations) were identified in 18 (8.8%) patients. KRAS and PIK3CA mutations were associated with poorly differentiated tumors (p = 0.03; p = 0.02), whereas EGFR mutations were associated with well-differentiated tumors (p = 0.001). Five tumours contained EGFR mutations (one T790M and four exon 20 insertions), which are associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Conclusions Diverse patterns of mutations are seen in resected node-negative lung adenocarcinoma including an unexpectedly low rate of ALK rearrangement, EGFR mutations associated with resistance to EGFR-TKIs and a high rate of synchronous mutations. These data may influence the design of future adjuvant targeted therapy trials.

Introduction BRAF is a proto-oncogene encoding a serine/ threonine protein kinase which is a downstream effector of RAS and transduces signals through the MAPK pathway to promote cell proliferation and survival. Although BRAF mutations are commonly seen in melanoma and papillary thyroid cancer, other cancers may also harbour BRAF mutations. We aimed to investigate the prevalence and clin-icopathological features of BRAF mutations in non-small cell lung cancer (NSCLC). Methods Tumours were genotyped using the Sequenom Mas-sARRAY platform with the OncoCarta panel v1.0. Results 224 cases of NSCLC were tested and four (1.8%) were found to have BRAF mutations. All four cases (3 males and 1 female, age range 70-76, all smokers) were adenocarcinomas that were wild type for EGFR and KRAS. V600E was identified in two cases and the others were K601N and L597Q mutations. Discussion Other studies have reported BRAF mutation prevalence between 2% and 5% in NSCLC. The spectrum of mutations is also similar with 50% of mutations being non-V600E (compared to predominant V600E mutations in melanoma). Novel RAF inhibitors are being used to treat melanoma and may potentially be therapeutic to the small subset of NSCLC patients with BRAF mutations. However, the significance of the different mutation spectrum remains unknown.

Aims Phyllodes tumours (PT) are rare fibro-epithelial lesions of the breast for which clinical behaviour is not reliably predicted by the pathological features. They have an unpredictable risk of recurrence and potential for metastatic spread, with no effective therapies if surgical control is not possible. New therapeutics that target specific mutant tyrosine kinase receptors have been developed and used successfully in a range of malignancies. We assessed 30 PT for the presence of common, actionable mutations using a sensitive, high-throughput mass spectrometry based assay which detects a panel of 238 specific mutations in 19 oncogenes. Methods DNA was extracted from four fibroadenomas (FA), 18 benign (low grade), six borderline and six malignant PT, prepared using the Oncocarta v1.0 kit and processed on the Sequenom compact MassARRAY platform. Results Analysis of four FA and 30 PT revealed that there were no targeted mutations, including within a malignant PT with heter-ologous differentiation, and two recurrent tumours (one borderline and one malignant PT). Conclusions This study highlights the ongoing complexity in understanding the pathogenesis of PT, which lack common, actionable mutations. We are currently undertaking further studies utilising more comprehensive next generation mutation panels on this group of tumours.

Introduction Inhibitors of the epidermal growth factor receptor (EGFR) show impressive response rates in selected lung cancer patients with activating EGFR gene mutations. Newer targeted agents are also in development with a pressing need to accurately identify the presence of ‘actionable’ mutations in patients with this poor prognosis cancer. We describe our experience with a sensitive, high throughput mass spectrometry based assay which detects a panel of 238 specific mutations in 19 oncogenes identified as biologically significant through literature review including KRAS, EGFR, BRAF, PIK3CA, MET, AKT1 and ERBB2. Methods DNA was extracted from resected tumours of 160 patients with lung adenocarcinoma, prepared using the Oncocarta v1.0 kit and processed on the Sequenom compact MassARRAY platform. Results We identified 101 mutations in 160 patients, with eight patients (5%) showing a mutation in two different genes concurrently. KRAS gene mutations were the most prevalent, seen in 40.6% of patients while EGFR mutations were seen in 13.1%. Rarer mutations were detected in PIK3CA (3.8%), MET (3.1%) and AKT1 (1 case only). Conclusions We detected at least one potentially clinically relevant mutation in the tumours of over half of our patients. We suggest this accurate and high throughput method may offer significant advantages over traditional Sanger sequencing.