Relationship between health-related determinants and adherence to breast and colorectal cancer screening: a population-based study in Flanders, Belgium.

BACKGROUND: Despite the recognized benefits of structured cancer screening, tests outside organized screening programs are common. Comprehensive reports on outside program screening in Europe are lacking, but the Flemish breast cancer (BC) and colorectal cancer (CRC) screening programs monitor data on non-organized tests prescribed by GPs and specialists. METHODS: Using data at aggregated level, logistic regression was used to examine the relationship between health care utilization and screening coverage in 308 Flemish municipalities during 2015-18. RESULTS: With regards to BC, municipalities with higher rates of gynecologists' visits had lower odds of coverage inside (-8%) and higher odds of coverage outside (+17%) the program. By contrast, municipalities with higher rates of GP visits, had higher odds of coverage inside (+6%) and lower odds of coverage outside (-7%) the program. As for CRC, municipalities with higher rates of visits gastroenterologists' visits had lower odds of coverage inside (-3%). Instead, municipalities with higher rates of GP visits, had higher odds of coverage both inside (+2%) and outside (+5%) the program. Municipalities with higher percentages of people with chronic conditions had higher odds of coverage within both the BC and CRC programs (+5% and +3%), and lower odds of outside screening (-7% and -6%). Municipalities with higher percentages of people 65+ with dementia and with mood disorders had, respectively, higher odds (+13% and +5%) and lower odds (-3% and -4%) of coverage inside both the BC and CRC programs. CONCLUSION: Our findings underscore the impact of healthcare utilization on cancer screening coverage at the municipal level in Flanders.

A Belgian Population-Based Study Reveals Subgroups of Right-sided Colorectal Cancer with a Better Prognosis Compared to Left-sided Cancer.

BACKGROUND: Patients with left-sided colorectal cancer (L-CRC) are known to have a significantly better prognosis than those with right-sided CRC (R-CRC). It has been hypothesized that RAS, BRAF mutations, or deficient mismatch repair status (MMR) might be responsible for the prognostic effect of primary tumor location (PTL). This study aims to evaluate the prognostic effect of PTL in the Belgian population and to determine the role of biomarkers (MMR, BRAF, and RAS status) in this effect. PATIENTS AND METHODS: We performed a retrospective analysis of Belgian Cancer Registry data. First, we studied the prognostic effect of PTL on 5-year relative survival of 91,946 patients diagnosed with CRC (all stages) from 2004-2015. Second, we investigated the interaction between biomarkers and the prognostic effect of PTL in 1818 patients diagnosed with stage IV CRC in 2014-2015. RESULTS: L-CRC was associated with a significantly better 5-year relative survival compared to R-CRC in all stages and ages combined (68.4%, 95% CI, 67.7-69.1% vs 65.6%, 95% CI, 64.7-66.4%). Also, when stratified by age, sex, and stage, the prognosis of L-CRC was better compared to R-CRC in most subgroups. Only in stage II and certain subgroups of elderly patients, the opposite was observed. Furthermore, our data showed that none of the biomarkers had a significant interaction with the effect of PTL on survival. CONCLUSION: This population-based study confirms that L-CRC is associated with significantly better relative survival compared to R-CRC, in all stages and ages combined. Furthermore, in stage IV L-CRC is associated with a longer survival than R-CRC, regardless of MMR, RAS, and BRAF status.

SB8, an approved bevacizumab biosimilar based on totality of evidence: scientific justification of extrapolation.

SB8 is a biosimilar of bevacizumab based on its similarity demonstrated by physicochemical, functional, non-clinical and clinical studies. Supported by the concept of extrapolation, SB8 was authorized and is used in a similar manner across all types of tumors as reference bevacizumab. Furthermore, SB8 offers convenience with prolonged stability compared with reference bevacizumab in diluted form. Although a biosimilar must demonstrate biosimilarity to a reference product with the 'totality of evidence' in a stringent regulatory process for marketing authorization, some concerns remain among healthcare practitioners, particularly about extrapolation. This review summarizes the concepts of the totality of evidence and extrapolation in biosimilar development and the role of bevacizumab biosimilars in the management of metastatic colorectal cancer as an extrapolated indication.

New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer.

OPINION STATEMENT: One of the great challenges in digestive oncology is choosing the optimal therapy for RAS-mutated metastatic colorectal cancer (mCRC). Even though the RAS genes and accompanying pathway were identified decades ago and extensive knowledge exists on their role in carcinogenesis, it has proven challenging to translate these insights into new therapies and clinical benefit for patients. However, recently, new drugs targeting this pathway (for example, KRASG12C inhibitors) have shown promising results in clinical trials, as monotherapy or in combination regimens. Although resistance remains an important issue, more knowledge on adaptive resistance and feedback loops in the RAS-pathway has led to strategical combination regimens to overcome this problem. In the past year, many encouraging results have been published or presented at conferences. Even though some of the data is still preliminary, these studies may bring practice-changing results and can lead to a clinical benefit for patients over the coming years. Because of these recent developments, the treatment of RAS-mutated mCRC has become a topic of great interest. Therefore, in this review, we will summarize the standard of care and discuss the most important emerging therapies for this patient population.

The Quest for Circulating Biomarkers in Neuroendocrine Neoplasms: a Clinical Perspective.

OPINION STATEMENT: Given the considerable heterogeneity in neuroendocrine neoplasms (NENs), it appears unlikely that a sole biomarker exists capable of fully capturing all useful clinical aspects of these tumors. This is reflected in the abundant number of biomarkers presently available for the diagnosis, prognosis, and monitoring of NEN patients. Although assessment of immunohistochemical and radiological markers remains paramount and often obligatory, there has been a notable surge of interest in circulating biomarkers over the years given the numerous benefits associated with liquid biopsies. Currently, the clinic primarily relies on single-analyte assays such as the chromogranin A assay, but these are far from ideal because of limitations such as compromised sensitivity and specificity as well as a lack of standardization. Consequently, the quest for NEN biomarkers continued with the exploration of multianalyte markers, exemplified by the development of the NETest and ctDNA-based analysis. Here, an extensive panel of markers is simultaneously evaluated to identify distinct signatures that could enhance the accuracy of patient diagnosis, prognosis determination, and response to therapy prediction and monitoring. Given the promising results, the development and implementation of these multianalyte markers are expected to usher in a new era of NEN biomarkers in the clinic. In this review, we will outline both clinically implemented and more experimental circulating markers to provide an update on developments in this rapidly evolving field.

Increasing Adherence to Prophylactic Swallowing Exercises During Head and Neck Radiotherapy: The Multicenter, Randomized Controlled PRESTO-Trial.

BACKGROUND: Prophylactic swallowing exercises (PSE) during radiotherapy can significantly reduce dysphagia after radiotherapy in head and neck cancer (HNC). However, its positive effects are hampered by low adherence rates during the burdensome therapy period. Hence, the main goal of this multicenter randomized controlled trial (RCT) was to investigate the effect of 3 different service-delivery modes on actual patients' adherence. METHODS: A total of 148 oropharyngeal cancer patients treated with primary (chemo)radiotherapy were randomly assigned to a 4 weeks PSE program, either diary-supported (paper group; n = 49), app-supported (app group; n = 49) or therapist-supported (therapist group; n = 50). Participants practiced 5 days/week, daily alternating tongue strengthening exercises with chin tuck against resistance exercises. Adherence was measured as the percentage of completed exercise repetitions per week (%reps). Statistical analysis was performed by means of SPSSv27, using Linear Mixed-effects Models with post hoc pairwise testing and Bonferroni-Holm correction. RESULTS: Adherence and evolution of adherence over time was significantly different between the three groups (p < .001). Adherence rates decreased in all three groups during the 4 training weeks (p < .001). During all 4 weeks, the therapist group achieved the highest adherence rates, whilst the app group showed the lowest adherence rates. CONCLUSIONS: PSE adherence decreased during the first 4 radiotherapy weeks regardless of group, but with a significant difference between groups. The therapist group achieved the highest adherence rates with a rather limited decline, therefore, increasing the face-to-face contact with a speech-language therapist can overcome the well-known problem of low adherence to PSE in this population. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN98243550. Registered December 21, 2018 - retrospectively registered, https://www.isrctn.com/ISRCTN98243550?q=gwen%20van%20nuffelen&filters=&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search .

Recent insights in the PI3K/Akt pathway as a promising therapeutic target in combination with EGFR-targeting agents to treat head and neck squamous cell carcinoma.

Resistance to therapies targeting the epidermal growth factor receptor (EGFR), such as cetuximab, remains a major roadblock in the search for effective therapeutic strategies in head and neck squamous cell carcinoma (HNSCC). Due to its close interaction with the EGFR pathway, redundant or compensatory activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway has been proposed as a major driver of resistance to EGFR inhibitors. Understanding the role of each of the main proteins involved in this pathway is utterly important to develop rational combination strategies able to circumvent resistance. Therefore, the current work reviewed the role of PI3K/Akt pathway proteins, including Ras, PI3K, tumor suppressor phosphatase and tensing homolog, Akt and mammalian target of rapamycin in resistance to anti-EGFR treatment in HNSCC. In addition, we summarize PI3K/Akt pathway inhibitors that are currently under (pre)clinical investigation with focus on overcoming resistance to EGFR inhibitors. In conclusion, genomic alterations in and/or overexpression of one or more of these proteins are common in both human papillomavirus (HPV)-positive and HPV-negative HNSCC tumors. Therefore, downstream effectors of the PI3K/Akt pathway serve as promising drug targets in the search for novel therapeutic strategies that are able to overcome resistance to anti-EGFR treatment. Co-targeting EGFR and the PI3K/Akt pathway can lead to synergistic drug interactions, possibly restoring sensitivity to EGFR inhibitors and hereby improving clinical efficacy. Better understanding of the predictive value of PI3K/Akt pathway alterations is needed to allow the identification of patient populations that might benefit most from these combination strategies.

Optimizing the colorectal cancer screening programme using faecal immunochemical test (FIT) in Flanders, Belgium from the "interval cancer" perspective.

BACKGROUND: Interval cancer (IC) is a critical issue in colorectal cancer (CRC) screening. We identified factors associated with ICs after faecal immunochemical test (FIT) screening and explored the impact of lowering FIT cut-off or shortening screening interval on FIT-ICs in Flanders. METHODS: FIT participants diagnosed with a CRC during 2013-2018 were included. Factors associated with FIT-ICs were identified using logistic regression. Distributions of FIT results among FIT-ICs were examined. RESULTS: In total, 10,122 screen-detected CRCs and 1534 FIT-ICs were included (FIT-IC proportion of 13%). FIT-ICs occurred more frequently in women (OR 1.58 [95% CI 1.41-1.76]) and ages 70-74 (OR 1.35 [1.14-1.59]). FIT-ICs were more often right-sided (OR 3.53 [2.98-4.20]), advanced stage (stage IV: OR 7.15 [5.76-8.88]), and high grade (poorly/undifferentiated: OR 2.57 [2.08-3.18]). The majority (83-92%) of FIT-ICs would still be missed if FIT cut-off was lowered from 15 to 10 µg Hb/g or screening interval was shortened from 2 to 1 year. CONCLUSIONS: FIT-ICs were more common in women, older age, right-sided location, advanced stage and high grade. In Flanders, lowering FIT cut-off (to 10 µg Hb/g) or shortening screening interval (to 1 year) would have a minimal impact on FIT-ICs.

Circulating DNA in the neoadjuvant setting of early stage colon cancer.

BACKGROUND: While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial. MATERIAL AND METHODS: Samples were collected at baseline, 2 weeks and surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA, and analysed with ddPCR technology. ROC curves were applied for cut-off points, and outcome measures included 5-year disease-free survival (DFS) and 6-year overall survival (OS). RESULTS: After a median follow-up of 52.5 months, baseline circulating-free (cf) DNA was an independent prognostic factor for DFS (HR 3.35, 95% CI: 1.15-9.77, p = .03), and a trend towards a similar association was observed for relative cfDNA changes between baseline and surgery (HR 2.57, 95% CI: 0.94-7.05, p = .07). Among 60 ctDNA assessable patients, 25 (42%) had detectable ctDNA at baseline. While detection of ctDNA at any pre-operative timepoint was not associated with outcome, patients with ctDNA increase (change of the worst trending methylation marker ≥11%, or mean ctDNA change of NPY and WIF1 ≥ 0%) between baseline and surgery showed a trend towards worse 5-year DFS (HR 3.66, 95% CI: 0.81-16.44, p = .09). CONCLUSION: This is the first study of ctDNA in the neoadjuvant setting of early-stage colon cancer. Results are hypothesis-generating and should be confirmed in larger series.

Evaluation of a new online cognitive assessment tool in breast cancer survivors with cognitive impairment: a prospective cohort study.

INTRODUCTION: Currently cancer-related cognitive impairment (CRCI) is mainly assessed by means of questionnaires, which is very laborious for the patients and the supervising physician. We evaluated a new online cognitive assessment tool, the MyCognition Quotient (MyCQ, Cambridge) in breast cancer survivors with CRCI, and compared the results with a psychometric test measuring cognitive complaints, depression, and anxiety. MATERIALS AND METHODS: In this prospective study, 46 adult patients between 18 and 70 years old with a diagnosis of BC were studied, all complaining of disturbing cognitive impairment. They participated in a physical cognitive rehabilitation program. The patients had an online cognitive assessment (MyCQ Med by MyCognition) every 4 weeks on their home computer. In addition patients were assessed in the outpatient clinic by the principal investigator at baseline, after 3 and 6 months using the following validated neuro-psychological surveys: the Hospital Anxiety and Depression Scale (HADS), Beck Cognitive Insight Scale (BCIS), and Cognitive Failure Questionnaire (CFQ). MyCQ scores were correlated with the results of these surveys. RESULTS: Only weak correlations could be found between overall MyCQ or the MyCQ subtests with the psychometric tests (between - 0.43 and 0.458) at baseline and when combining data at time point 0, 3, and 6 months. Linear mixed models showed there was a significant association between Latency Choice Reaction Time and CFQ (continuous; p = 0.026). An AUC of 0.640 and a cut-off of 481.5 ms in Latency Choice Reaction Time were found to distinguish patients with CFQ below 44 to patients with CFQ above 44 (sensitivity 0.63 and specificity 0.73). In Latency Coding an AUC of 0.788 and a cut-off of 1316 ms were found to distinguish non-depressive patients from patients likely to present with depressive symptoms (sensitivity 0.75 and specificity 0.76). CONCLUSION: MyCQ cannot replace the various psychometric tests. However, abnormal Latency in cognitive tests, Choice Reaction Time and Coding, seems promising to be used as a screening tool to detect specific aspects of abnormal cognitive functioning in patients with cognitive complaints and depressive symptoms.

ESO-ESSO-ESTRO Multidisciplinary Course in Oncology for Medical Students: 4 Years of Experience (2016-2019).

The ESO-ESSO-ESTRO Multidisciplinary Course in Oncology is intended to fill the gap of the undergraduate fragmented oncology education, to provide insight into all theoretical and practical aspects of oncology, and to encourage future professional choices towards an oncology discipline. Students are exposed to (a) preclinical cancer topics; (b) natural history of the disease; (c) laboratory diagnostic tests; (d) medical, radiation, surgical, and palliative treatment; and (e) direct or through multidisciplinary patients' approach. Students are obliged to attend (i) all theoretical lectures, (ii) clinical case presentations, (iii) laboratories and ward visits, and (iv) to prepare and present a specific project under supervision. Participation is limited to 24 medical students who are selected through a competitive application process. Between 2016 and 2019, 96 students from 29 countries have attended. Data analysis derived from a given questionnaire demonstrates that most of the participants have declared that (1) they have achieved their expectations and objectives, (2) they have highly rated both clinical and non-clinical teaching oncological topics, and (3) they have been stimulated in developing a professional career in the field of oncology.

The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic.

BACKGROUND: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance. METHODS: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available. RESULTS: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive. CONCLUSIONS: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.

Management of small bowel adenocarcinoma: making the most of the available evidence to inform routine practice.

PURPOSE OF REVIEW: Small bowel adenocarcinoma (SBA) is a rare disease, for which few studies have been conducted so far. Therefore, most treatment recommendations have been extrapolated from trials in colorectal cancer. In this review, we revise available data that could improve the management of SBA, with a particular focus on systemic therapy. RECENT FINDINGS: For advanced/irresectable disease, first-line doublet chemotherapy remains standard of care. It is uncertain whether extending treatment to triplet chemotherapy brings added benefit. Pembrolizumab is an accepted treatment modality for mismatch repair-deficient tumors, yet might also be active in microsatellite stable tumors. More trials with immunotherapy are underway. Although there is no place for anti-EGFR monotherapy, the addition of cetuximab to chemotherapy should be investigated further. Two trials suggest an added value of bevacizumab to chemotherapy, yet larger trials are needed to confirm these data. For localized disease, the role of (neo)adjuvant chemotherapy is under investigation. SUMMARY: For decades, patients with SBA have probably been treated suboptimal by basing treatment recommendations on data from colorectal cancer. An effort for SBA-specific trials and/or inclusion of SBA patients in basket trials is of utmost importance in order to improve outcome for these patients.

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

Meeting the Challenges in Cancer Care Management During the SARS-Cov-2 Pandemic: A Retrospective Analysis.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has overwhelmed the capacity of healthcare systems worldwide. Cancer patients, in particular, are vulnerable and oncology departments drastically needed to modify their care systems and established new priorities. We evaluated the impact of SARS-CoV-2 on the activity of a single cancer center. METHODS: We performed a retrospective analysis of (i) volumes of oncological activities (2020 vs 2019), (ii) patients' perception rate of the preventive measures, (iii) patients' SARS-CoV-2 infections, clinical signs thereof, and (iv) new diagnoses made during the SARS-CoV-2 pandemic. RESULTS: As compared with a similar time frame in 2019, the overall activity in total numbers of outpatient chemotherapy administrations and specialist visits was not statistically different (P = .961 and P = .252), while inpatient admissions decreased for both medical oncology and thoracic oncology (18% (P = .0018) and 44% (P < .0001), respectively). Cancer diagnosis plummeted (-34%), but no stage shift could be demonstrated.Acceptance and adoption of hygienic measures was high, as measured by a targeted questionnaire (>85%). However, only 46.2% of responding patients regarded telemedicine, although widely deployed, as an efficient surrogate to a consultation.Thirty-three patients developed SARS-CoV-2, 27 were hospitalized, and 11 died within this time frame. These infected patients were younger, current smokers, and suffered more comorbidities. CONCLUSIONS: This retrospective cohort analysis adds to the evidence that continuation of active cancer therapy and specialist visits is feasible and safe with the implementation of telemedicine. These data further confirm the impact of SARS-CoV-2 on cancer care management, cancer diagnosis, and impact of infection on cancer patients.

Biosimilars in an era of rising oncology treatment options.

New diagnostic technologies, including molecular profiling, have enabled advances in treatments of various cancers; this has significantly improved clinical outcomes, including overall survival. However, the high cost of biologic drugs may prevent patients from having access to optimal treatment. Introduction of lower priced biosimilar agents into the therapeutic armamentarium brings the potential to ease the burden on healthcare expenditure and facilitate better access to effective cancer treatments. Oncology biosimilars have shown comparable efficacy and safety based on clinical evidence and physicochemical quality data as well as in real-world settings. This paper aims to review changes in the management of oncology treatment and their implication with respect to biosimilars.

AMTRA: a multicentered experience of a web-based monitoring and tailored toxicity management system for cancer patients.

BACKGROUND: Technology-based interventions are increasingly being introduced in routine clinical cancer care. There is a need for reliable systems to monitor treatment-related toxicity in a standardized manner. Such electronic tools bridge the gap in providing quality home-based monitoring. METHODS: From July 2017 to December 2017, we performed a multicentered, non-randomized prospective cohort analysis with patients who were receiving routine chemotherapy for various solid tumors, using a web-based patient-reported toxicity registration, management, and intervention system called AMTRA (ambulatory Monitoring of cancer Therapy using an interactive Application) linked to the homecare nursing organization Remedus®. Twelve common toxicities plus pain and two biometrics could be registered daily or more frequently as required. These were processed centrally to generate tailored advice for lesser symptoms or a phone call from a dedicated nurse in case of severe or prolonged toxicity. A compliance tool to monitor oral therapies was incorporated in the system. RESULTS: One hundred sixty-eight patients (92%) were enrolled, with 31,514 registrations analyzed. One hundred eight patients reported severe toxicity (> 1461 registrations), resulting in 102 clinical interventions ranging from self-management advice, supplemental consultations to hospitalizations. Compliance to oral chemotherapy was high using AMTRA with a median of 98.7% (95 confidence interval (CI) [93.5-100.0%]). Seventy-nine percent of patients stated that the availability of AMTRA self-reports was useful in communication with the care provider, while 75% felt more in control while managing their treatment. CONCLUSIONS: The application of an interactive PRO-system in routine symptom management of cancer patients allowed standardized documentation of toxicities and recorded a high compliance with oral treatment. It allows for rapid interaction for toxicities and cancer-related symptoms experienced at home.

Cetuximab-induced natural killer cell cytotoxicity in head and neck squamous cell carcinoma cell lines: investigation of the role of cetuximab sensitivity and HPV status.

BACKGROUND: The epidermal growth factor receptor (EGFR) is overexpressed by 80-90% of squamous cell carcinoma of head and neck (HNSCC). In addition to inhibiting EGFR signal transduction, cetuximab, a monoclonal antibody targeting EGFR can also bind to fragment crystallisable domain of immunoglobulins G1 present on natural killer (NK), causing antibody-dependent cellular cytotoxicity (ADCC). However, presence of cetuximab resistance limits effective clinical management of HNSCC. METHODS: In this study, differences in induction of ADCC were investigated in a panel of ten HNSCC cell lines. Tumour cells were co-cultured with NK cells and monitored using the xCELLigence RTCA. RESULTS: While ADCC was not influenced by HPV status, hypoxia and cetuximab resistance did affect ADCC differentially. Intrinsic cetuximab-resistant cell lines showed an increased ADCC induction, whereas exposure to hypoxia reduced ADCC. Baseline EGFR expression was not correlated with ADCC. In contrast, EGFR internalisation following cetuximab treatment was positively correlated with ADCC. CONCLUSION: These findings support the possibility that resistance against cetuximab can be overcome by NK cell-based immune reactions. As such, it provides an incentive to combine cetuximab with immunotherapeutic approaches, thereby possibly enhancing the anti-tumoural immune responses and achieving greater clinical effectiveness of EGFR-targeting agents.

The Oncology Data Network (ODN): A Collaborative European Data-Sharing Platform to Inform Cancer Care.

The rise of precision oncology has made clinical decision making more complex than ever before. The Oncology Data Network was established to enable the clinical community to efficiently access potentially practice­changing insights from an extended network of cancer centers. This article describes the progress to date and calls for greater collaboration.

Pisces: an accurate and versatile variant caller for somatic and germline next-generation sequencing data.

MOTIVATION: Next-generation sequencing technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants. RESULTS: We have developed Pisces, a rapid, versatile and accurate small-variant calling suite designed for somatic and germline amplicon sequencing applications. Accuracy is achieved by four distinct modules, each incorporating a number of novel algorithmic strategies. AVAILABILITY AND IMPLEMENTATION: Pisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces. Pisces is available on the BaseSpace™ SequenceHub. It is distributed on Illumina sequencing platforms such as the MiSeq™ and is included in the Praxis™ Extended RAS Panel test which was recently approved by the FDA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.