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Within the global head and neck cancer population, there are subgroups of patients with poorer cancer outcomes independent from tumor characteristics. In this article, we review three such groups. The first group comprises patients with nasopharyngeal cancer in low- and middle-income countries where access to high-volume, well-resourced radiotherapy centers is limited. We discuss a recent study that is aiming to improve outcomes through the instigation of a comprehensive radiotherapy quality assurance program. The second group comprises patients with low socioeconomic status in a high-income country who experience substantial financial toxicity, defined as financial hardship for patients due to health care costs. We review causes and consequences of financial toxicity and discuss how it can be mitigated. The third group comprises older patients who may poorly tolerate and not benefit from intensive standard-of-care treatment. We discuss the role of geriatric assessment, particularly in relation to the use of chemotherapy. Through better recognition and understanding of disadvantaged groups within the global head and neck cancer population, we will be better placed to instigate the necessary changes to improve outcomes and quality of life for patients with head and neck cancer.

Background for shared decision-making, it is important to discuss of the patients’ priorities in order to align treatment decisions with these priorities. Objective to assess the most important health outcome for older patients on the verge of making a treatment decision, using the Outcome Prioritization Tool (OPT). Secondary objectives were the feasibility of the OPT and patient variables associated with prioritising different health outcomes. Design retrospective cohort study. Setting and subjects at the University Medical Hospital Groningen, the Netherlands, 350 patients were included who visited the geriatric outpatient clinic during the work-up regarding a complex treatment decision (such as cancer treatment or heart valve replacement). Methods during geriatric assessment, patients prioritised between four health outcomes, using the OPT. Results median age was 78.5 years, 172 (49.1%) were referred regarding a treatment decision for a malignant disease. Cognitive impairment was present in 23.6%. Most patients (55.2%) prioritised maintaining independence as their most important goal, followed by extending life in 21.1%. Only cognitive impairment was significantly associated with prioritising extending life as the most important health outcome. For 107 patients (30.6%), the OPT was not feasible; these patients more often had malnutrition and assisted living. Conclusions the main health outcome of older patients on the verge of making a treatment decision was maintaining independence, followed by extending life. Patients with cognitive impairment more often prioritised extending life. The OPT was feasible as a decision aid for most patients. For optimal shared decision-making, it is crucial to take patient preferences into account.

Objectives Transcatheter aortic valve implantation (TAVI) is an important treatment option for patients with severe aortic stenosis. To improve patient selection, shared decision-making is recommended to elicit patients' treatment expectations and goals. We assessed patients' expectations and goals before TAVI treatment and whether these were met after treatment. Additionally, we evaluated how meeting these goals aligned with quality of life and functional recovery. Design A mixed method study. Setting An academic medical center. Participants Seventy-four patients undergoing TAVI between 2015 and 2017. Measurements Patients' expectations and goals were assessed qualitatively before treatment. Six to twelve months post procedure, quality of life was measured with the EuroQuol-5D and any change in the number of dependencies in (instrumental) activities of daily living was assessed. Results Mean age of patients was 81.5 years, and 37.8% were male. Regaining the ability to engage in a specific hobby or activity was the most important treatment goal (33 patients, 54.1%), followed by reducing symptoms (19 patients 31.1%). 66.2% of patients stated that their treatment goal was met. Quality of life was higher in this group, as compared with patients who had not met their treatment goal. Twenty-three patients (31.1%) showed functional improvement. Conclusion TAVI patients were quite capable of eliciting treatment goals and a majority stated, after treatment, that these had been met patients' experience of treatment benefits regarding these goals had poor alignment with functional outcomes. This raises questions regarding relevant outcome measurements in this population, and could aid in improving shared decision-making and patient selection for TAVI.

OBJECTIVES: For shared decision making, it is crucial to identify patients' priorities regarding health outcomes. Our aim was to study whether healthcare professionals know these priorities.METHODS: In this cross-sectional study we included older patients who had to make a treatment decision, their general practitioners (GPs) and their medical specialists. Agreement between the patients' main health outcome as prioritised by using the Outcome Prioritization Tool (OPT) and the perception of the same outcome by their healthcare professionals.RESULTS: Eighty-seven patients were included. Median age was 76 years, 87.4% of patients presented with malignant disease. The majority prioritised maintaining independence (51.7%), followed by extending life (27.6%). The agreement between patients and healthcare professionals was low (GPs 41.7%, kappa 0.067, p = 0.39), medical specialists 40.3%, kappa 0.074, p = 0.33). Positively related to agreement was patient's age > 75, and a longer relation with their patients (for GPs), and the patient having no partner (for medical specialist). Having a malignant disease, dependent living and functional deficits were negatively related to agreement.CONCLUSIONS: Healthcare professionals have poor perceptions of their patients' priorities.PRACTICE IMPLICATIONS: To realise patient-centered care, it is crucial to discuss priorities explicitly with all patients.

INTRODUCTION: With the accumulating evidence on the added value on prediction of outcomes of geriatric assessment (GA) in older patients with cancer, the question shifts from whether performing a GA is useful, to how to implement this into standard practice in a feasible and effective way. The effect of implementing GA, and assessment of patient preferences on treatment recommendations by an onco-geriatric multidisciplinary team (MDT), was compared to the recommendation previously made by the tumor board (care as usual).METHODS: Patients aged 70 years and older with a solid malignancy who were referred to a tertiary care center for diagnosis and treatment recommendations, as provided by a tumor board, were included. The intervention consisted of: a nurse-led GA and assessment of patient preferences prior to the start of oncological treatment, discussing this in an onco-geriatric MDT, and weighing all this information in a structured, stepwise manner. Treatment recommendations formulated by this onco-geriatric MDT were compared to the treatment recommendations by the tumor board.RESULTS: Of 236 eligible patients, 197 were included. For 27%, treatment recommendations from the onco-geriatric MDT differed from the recommendations formulated by the tumor board. These modifications were mostly towards less intensive curative or palliative treatment. Thirteen percent of patients were subsequently referred to a geriatrician in order to reach a treatment recommendation.DISCUSSION: Implementing an onco-geriatric care trajectory, using GA and assessment of patient preferences, resulted in an adjustment of treatment recommendations for a quarter of patients. Thirteen percent needed subsequent referral to a geriatrician.

Shared decision making can guide patients facing difficult treatment decisions, with a trade-off between risks and benefits, taking patient goals and preferences into account. The Outcome Prioritization Tool (OPT) was developed to facilitate the discussion of goals and preferences with older patients in an encompassing, non-disease-specific way. The OPT is used in both primary and secondary healthcare for several treatment decisions, but data regarding the tool are limited. A concise review yielded two developmental articles, four articles describing three studies using the OPT, and one study protocol. All studies were performed among older patients. In those studies, the majority of patients ranked maintaining independence as most important. The tool has been shown to be feasible for both patients and healthcare providers.

OBJECTIVE: To investigate the impact of frailty and dependence on health-related quality of life (HRQOL) in elderly women diagnosed with epithelial ovarian cancer (EOC).METHODS: Data was gathered from a prospectively collected data biobank, OncoLifeS (Oncological Life Study) at the University Medical Center of Groningen. Women with a diagnosis of EOC, ≥65 years of age, with baseline assessment available from January 2016 to May 2018 were included. HRQOL was determined using the EORTC QLQ-C30 yielding scores on Global Health Status, five functional scales, three symptom scales, and six single items. The summary score was also calculated. Frailty was measured using the Groningen Frailty Indicator (GFI), and dependence using the Instrumental Activities of Daily Living (IADL). To evaluate the impact of frailty and dependence on HRQOL, linear regression was performed. Analyses were adjusted for age and tumor stage.RESULTS: 84 patients were included. Median age was 71 years (IQR: 68-75), 78% had advanced stage and 81% serous histology. Overall, the median global health status was 67 (IQR: 50-83). HRQOL scales with lowest scores were: role functioning (median: 66.7; IQR: 33-100), fatigue (median: 33.3; IQR: 22-56) and insomnia (median: 33.3; IQR: 0-67). Being frail was associated with worse functioning on all HRQOL scales and higher symptom scores (p = .001). Conversely, being independent was associated with better functioning on all HRQOL scales and lower symptom scores. These associations remained significant after adjusting for age and tumor stage.CONCLUSION: In women ≥65 years, diagnosed with EOC, frailty and dependence are associated to reduced HRQOL. These associations remain significant adjusting for age and stage.

Objectives: Decision-making in older patients with cancer can be complex, as benefits of treatment should be weighed against possible side-effects and life-expectancy. A novel care pathway was set up incorporating geriatric assessment into treatment decision-making for older cancer patients. Treatment decisions could be modified following discussion in an onco-geriatric multidisciplinary team (MDT). We assessed the effect of treatment modifications on outcomes. Materials and methods: This retrospective study was performed in the surgical department of a University Hospital. Patients of 70 years and older with a solid malignancy were included. All patients underwent a nurse-led geriatric assessment (GA) and were discussed in an onco-geriatric MDT. This could result in a modified or an unchanged treatment advice compared to the regular tumor board. Primary outcome was one-year mortality. Secondary outcomes were post-operative complications and days spent in hospital in the first year after inclusion. Results: For the 184 patients in the analyses, the median age was 77.5 years and 41.8% were female. For 46 patients (25%), the treatment advice was modified by the onco-geriatric MDT. There was no significant difference in one-year mortality between the unchanged and modified group (29.7% versus 26.1%, p = 0.7). There were, however, significantly fewer days spent in hospital (median 5 vs 8.5 days p = 0.02) and fewer grade II or higher postoperative complications (13.3% versus 35.5% p = 0.005) in the modified group. Conclusion: Incorporating geriatric assessment in decision-making did not lead to excess one-year mortality, but did result in fewer complications and days spent in hospital. (c) 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Many epigenetically inactivated genes involved in ovarian cancer (OC) development and progression remain to be identified. In this study we undertook an integrated approach that consisted of identification of genome-wide expression patterns of primary OC samples and normal ovarian surface epithelium along with a pharmacologic unmasking strategy using 3 OC and 3 immortalized normal ovarian epithelial cell lines. Our filtering scheme identified 43 OC specific methylated genes and among the 5 top candidates (GULP1, CLIP4, BAMBI, NT5E, TGFβ2), we performed extended studies of GULP1. In a training set, we identified GULP1 methylation in 21/61 (34%) of cases with 100% specificity. In an independent cohort, the observed methylation was 40% (146/365) in OC, 12.5% (2/16) in borderline tumors, 11% (2/18) in cystadenoma and 0% (0/13) in normal ovarian epithelium samples. GULP1 methylation was associated with clinicopathological parameters such as stage III/IV (p = 0.001), poorly differentiated grade (p = 0.033), residual disease (p

Background Advance Care Planning (ACP) and its documentation, accessible to healthcare professionals regardless of where patients are staying, can improve palliative care. ACP is usually performed by trained facilitators. However, ACP conversations would be more tailored to a patient’s specific situation if held by a patient’s clinical healthcare team. This study assesses the feasibility of ACP by a patient’s clinical healthcare team, and analyses the documented information including current and future problems within the palliative care domains. Methods This multicentre study was conducted at the three Groningen Palliative Care Network hospitals in the Netherlands. Patients discharged from hospital with a terminal care indication received an ACP document from clinical staff (non-palliative care trained staff at hospitals I and II; specialist palliative care nurses at hospital III) after they had held ACP conversations. An anonymised copy of this ACP document was analysed. Documentation rates of patient and contact details were investigated, and documentation of current and future problems were analysed both quantitatively and qualitatively. Results One hundred sixty ACP documents were received between April 2013 and December 2014, with numbers increasing for each consecutive 3-month time period. Advance directives were frequently documented (82%). Documentation rates of current problems in the social (24%), psychological (27%) and spiritual (16%) domains were low compared to physical problems (85%) at hospital I and II, but consistently high (> 85%) at hospital III. Of 545 documented anticipated problems, 92% were physical or care related in nature, 2% social, 5% psychological, and

Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract, is usually diagnosed at an advanced stage as obvious symptoms are absent at early stages. This disease is believed to originate from malignant transformation of the ovarian surface epithelium or fallopian tube. Histologically, several subtypes are being recognized, with serous histology accounting for the majority of cases. Serous tumors include serous borderline tumors and serous carcinomas. A better understanding of the tumor biology and molecular mechanisms involved in these tumors is needed, as both patient management and prognosis differ substantially. Previous microarray analysis identified SerpinA5, a uPA inhibitor, as key regulator for indolent borderline behavior. As carcinomas are characterized by loss of SerpinA5 mRNA expression, we hypothesized that SerpinA5 protein expression is reduced or lost in carcinomas when compared with borderline tumors. We performed SerpinA5 immunohistochemical staining on 32 serous borderline tumors, 187 primary serous carcinomas and 62 serous omental metastases. Reduced or absent SerpinA5 protein staining was observed in carcinomas when compared with borderline tumors (P

The aim of this study was to systematically review the prognostic and predictive significance of cell biological markers in cervical cancer patients primarily treated with (chemo)radiation. A PubMed, Embase, and Cochrane literature search was performed. Studies describing a relation between a cell biological marker and survival in >/=50 cervical cancer patients primarily treated with (chemo)radiation were selected. Study quality was assessed, and studies with a quality score of 4 or lower were excluded. Cell biological markers were clustered on biological function, and the prognostic and predictive significance of these markers was described. In total, 42 studies concerning 82 cell biological markers were included in this systematic review. In addition to cyclooxygenase-2 (COX-2) and serum squamous cell carcinoma antigen (SCC-ag) levels, markers associated with poor prognosis were involved in epidermal growth factor receptor (EGFR) signaling (EGFR and C-erbB-2) and in angiogenesis and hypoxia (carbonic anhydrase 9 and hypoxia-inducible factor-1alpha). Epidermal growth factor receptor and C-erbB-2 were also associated with poor response to (chemo)radiation. In conclusion, EGFR signaling is associated with poor prognosis and response to therapy in cervical cancer patients primarily treated with (chemo)radiation, whereas markers involved in angiogenesis and hypoxia, COX-2, and serum SCC-ag levels are associated with a poor prognosis. Therefore, targeting these pathways in combination with chemoradiation may improve survival in advanced-stage cervical cancer patients

Objective. Death ligand FasL, its agonistic receptor Fas, tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its agonistic death receptors DR4 and DR5 are implied in carcinogenesis, tumor immune surveillance and response to chemotherapy. TRAIL receptor agonists are evaluated as anti-cancer agents. This study aimed to relate expression of death ligands/receptors and downstream initiator caspase 8 and its antiapoptotic homologue FLICE like inhibitory protein (c-FLIP) in ovarian cancers to chemotherapy response and survival.Methods. Fas, FasL, TRAIL, DR4, DR5, caspase 8 and c-FLIP were determined immunohistochemistry on a tissue microarray containing 382 ovarian cancers. Protein expression profiles were correlated with clinicopathologic variables, chemotherapy response and Survival.Results. Most tumors expressed DR4, DR5, caspase 8 and c-FLIP. High c-FLIP expression was associated with expression of caspase 8 and both TRAIL receptors. TRAIL and Fas were associated with low tumor grade and better progression-free Survival (HR 0.63, p=.018 and HR 0.54, p=.012), respectively, and Fas with disease-specific survival (HR 0.49, p=0.009) in univariate analysis.Conclusions. Fas and TRAIL loss is associated with dedifferentiation and worse prognosis. Expression of DR4, DR5, caspase 8 and c-FLIP by most ovarian cancers does not correlate with survival. High c-FLIP expression should be taken into account for death receptor targeted therapies. (C) 2009 Elsevier Inc. All rights reserved.

The prognosis of epithelial ovarian cancer (EOC), the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%), 173 (68.9%), 208 (90.0%), 129 (56.3%), and 27 (11.0%) of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (over)expressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (over)expression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

Contains fulltext : 70885.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The adaptive immune system seems to play an essential role in the natural course of ovarian cancer. Aim of this study was to establish whether disease-specific survival for patients expressing the tumour antigen p53 is influenced by MHC class I expression or the presence of p53 autoantibodies (p53-Aab). METHODS: P53 and MHC class I expression were analysed in ovarian cancer tissue of 329 patients by immunohistochemistry using tissue microarrays. For 233 patients, pre-treatment serum samples were available to study the presence of p53 autoantibodies by ELISA. Data were linked to clinicopathological parameters and disease-specific survival. RESULTS: P53 overexpression, MHC class I down-regulation in neoplastic cells and serum p53 autoantibodies were observed in 49.4, 38.9 and 15.9% of patients, respectively. MHC class I down-regulation in p53-overexpressing tumours correlated with a 10-month reduced disease-specific survival in univariate analysis (log-rank 4.10; p=0.043). p53-Aab were strongly correlated with p53 overexpression (p

Introduction: Primary human cancers are thought to arise from genetic and epigenetic alterations of tumor suppressor genes and oncogenes. Transcriptional and DNA copy-number studies have improved our understanding and classification of solid tumors. Recent studies have established that like mutation, methylation-mediated gene silencing often leads to tumorigenesis. The aim of this study was to comprehensively explore the “ovarian cancer methylome” and to validate the novel methylation marker AGTR1 in a large independent series of ovarian cancer samples. Patients and methods: Fifteen ovarian cancer samples and 10 normal ovarian surface epithelium brushings were hybridized to Affymetrix U133 plus 2.0 arrays. Furthermore, 3 normal ovarian and 3 isogenic (resistant and sensitive to chemotherapy) ovarian cancer cell lines, with or without treatment with a demethylating agent were hybridized to the same array. Selection of cancer specific methylated genes was based on differential expression between normal and cancer samples, with cancer samples having lower expression than normal samples, and upregulation in cancer cell lines after treatment with a demethylating agent. A number of selected genes that showed low or no expression in primary cancer tissues and re-expressed after treatment with a demethylating agent were then tested for promoter methylation by bisulfite sequencing. Quantitative methylation specific PCR (QMSP) was developed for the AGRT1 gene and tested in a total of 353 ovarian cancer, 17 ovarian cystadenoma and 16 ovarian borderline tumor samples. Results: Fourteen primary ovarian tumor DNA samples were available from the samples that were hybridized for expression array analysis. Twelve out of 14 samples were methylated for AGRT1 which is inversely correlated with expression from our array analysis. We then tested 13 normal ovarian epithelium samples and no methylation was detected in any of the samples. Validation in a large independent set of samples confirmed that ovarian cancer samples (207/353, 53%) were more frequently methylated than ovarian cystadenoma (3/17, 18%; P=0.004). Conclusion: We have identified a set of potential tumor suppressor genes by a comprehensive discovery approach to uncover the cancer methylome. Among these genes, AGTR1 methylation was identified as a potential cancer specific methylated gene that may hold promise for further studies to establish it as a biomarker. Functional studies are warranted to evaluate the biologic role of AGTR1 methylation in the carcinogenic process of solid tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4035. doi:1538-7445.AM2012-4035

Objective: To improve current screening modalities, additional molecular markers that allow detection of ovarian cancer at an early stage are needed. The aim of the current study was to identify novel methylation-based biomarkers for ovarian cancer. Methods: Genes frequently expressed at low levels were identified by comparing global expression levels from 232 primary ovarian cancers to Universal Reference RNA. Ten genes possessing a CpG island in the promoter region that showed frequent low expression in serous cancers and at least one other histological subtype were selected. The methylation status of candidate genes was verified in 50 sporadic ovarian cancers, 11 hereditary cancers, 13 borderline cancers and 12 cystadenomas using methylation specific PCR (MSP). Results: Three candidate genes (IGFBP1, LIN28 and ZNF582) showed frequent methylation in cancers and were unmethylated in normal leukocyte DNA and human ovarian surface epithelial cells. Promoter methylation of any of the three candidate genes was observed in 88% of stage III/IV cancers and 72% of stage I/II cancers. In contrast, only 9% of hereditary cancers showed evidence of methylation for any of the three genes (p Conclusions: Using oligonucleotide microarray data, three novel methylation-based biomarkers for sporadic epithelial ovarian cancer were discovered. Further studies should elucidate the methylation status of these genes in larger cohorts of ovarian cancers and investigate their methylation status in serum. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 161.

Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. GULP1, a molecule not previously related to cancer, is a cytoplasmic adaptor protein with a phosphotyrosine binding domain that plays a role in one of two partially redundant pathways that lead to the engulfment and clearance of apoptotic cells, according to several genetic studies performed in Caenorhabditis elegans. Performing a pharmacologic unmasking technique we observed that this molecule is downregulated in ovarian tumor tissues when compared to normal ovary. Ovarian cancer is the leading cause of death among gynaecological cancers worldwide, this due to the fact that women are diagnosed with advanced stage disease and because of the lack of truly sensitive/specific screening techniques and unavailability of individualized therapy. We performed an expression microarray on 15 ovarian tumor samples, 10 ovarian normal surface epithelium, 3 ovarian cancer cell lines and 3 normal cell lines. All cells have been treated with a demethylating agent which comprehensively uncovers genes silenced by promoter hypermethylation. The selection of the best candidates was based upon the differential expression between normal and tumor samples (or cell lines), them being downregulated in cancer when compared to normal, and finally the re-activation after the treatment with the demethylating agent. One of these promising genes was GULP1, which expression pattern was then assessed by Reverse Transcriptase PCR and Western Blot and compared to its methylation status in the same six ovarian cell lines and showed correlation between absence of expression and presence of methylation (or the opposite situation). We developed quantitative fluorogenic methylation specific PCR (QMSP) for GULP1 and profiled 437 ovarian tumor samples, 17 borderline tumors, 19 cystadenoma samples and 13 normal ovarian samples, finding 34.7% (151/437), 11.7% (2/17), 10.5% (2/19) and 0% (0/13) of methylation frequency, respectively, (establishing an empiric cutoff). Using fisher's exact test, we observe a significant increase in methylation when comparing tumors with cystadenomas and normals (p=0.0439 and p=0.0131, respectively). Late stage tumors also showed a higher frequency of methylation versus early stage (p=0.004). So far, we have demonstrated reduced log growth rates after transiently overexpressing GULP1 in one ovarian cell line (IGROVCP). To assess its potential as a TSG, we have ongoing experiments to assess its biological function as ectopic overexpression of this gene in ovarian cancer cell lines as well as creating knock downs using shRNAs. These preliminary data indicate that GULP1 may be an ovarian cancer biomarker. Further studies on the biology of this gene are needed to evaluate its potential as a TSG and its role in ovarian cancer carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4891.