Background: Palliative gemcitabine has been shown to prevent the deterioration of well-being and to prolong survival of patients with pancreatic cancer in phase III randomized controlled trials (RCTs). It is unknown whether the efficacy reported in RCTs has translated into effectiveness in routine clinical practice. Objectives: 1) To describe the characteristics of patients with pancreatic cancer treated with palliative gemcitabine at the regional cancer centres (RCCs) of Ontario, 2) To describe: clinical benefit at two months, defined as stable or improved well-being; time to treatment discontinuation; and overall survival, 3) To identify factors associated with clinical benefit, and 4) To compare the effectiveness of gemcitabine with its reported efficacy in RCTs. Methods: This was a retrospective analysis of prospectively collected data. The study included patients with pancreatic cancer treated with palliative gemcitabine at the RCCs of Ontario between 2008 and 2011. Information about well-being was patient self-reported as captured by the Edmonton Symptom Assessment System (ESAS) at the RCCs. The proportions of patients that achieved clinical benefit were reported. Time to treatment discontinuation and overall survival were calculated using Kaplan –Meier survival analysis. Logistic regression was used to identify factors associated with clinical benefit. iii Results: The study population included 423 patients. Only 168 (39.1%) patients completed a pre-treatment ESAS. Patients completing a pre-treatment ESAS were not different than those that did not. Patients treated at RCCs were not different than those in RCTs. The median age of the study population was 65 years, 50% were male, 57% had stage IV disease and 94% had adenocarcinoma morphology. Thirty-seven percent of patients achieved clinical benefit at two months. Median time to treatment discontinuation and overall survival was 2 and 5.7 months, respectively. Stage and pre-treatment wellbeing were associated with clinical benefit at two months. Similar proportions of patients at RCCs and RCTs experienced clinical benefit. Time to treatment discontinuation and survival were similar as well. Conclusions: Efficacy of gemcitabine in RCTs has translated into effectiveness for patients treated at the RCCs of Ontario. It is unknown if this is true for patients not treated at the RCCs. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-08-01 17:50:00.185

BACKGROUND: Palliative chemotherapy is cancer-directed therapy, which aims at stopping or slowing down the progression of the malignancy even though it may not have any potential for remission or cure. In South Africa, delayed diagnosis of childhood cancer is a common problem for a variety of reasons including lack of health care facilities, transport, information about the disease and delayed presentation due to traditional healer visits or other cultural issues. In patients who present with advanced cancer, or in patients with relapsed cancer without realistic hope of cure, palliative chemotherapy can be offered in an attempt to manage symptoms, improve quality of life and prolong meaningful survival. OBJECTIVES: This research study evaluated South African paediatric oncologists' perspectives and practices regarding the use of chemotherapy in patients with cancer with no realistic hope of cure. The second part of the study described the use of palliative chemotherapy in patients who received treatment at the Steve Biko Academic Hospital Paediatric oncology unit. DESIGN & METHOD: An online survey was conducted among paediatric oncologists in South Africa. The main aims of the questionnaire were to assess paediatric oncologists' considerations around the use of palliative chemotherapy, and then focus on the most recent patients treated with palliative chemotherapy. For the second part of the study, a file review was done of deceased patients who died in the period from January 2012 to December 2018 and who had received palliative chemotherapy as part of their cancer management. We reviewed diagnoses, palliative chemotherapy regimens, timing of initiation and stopping palliative chemotherapy, and whether end of life decisions and discussions were documented. RESULTS: A total of 41 participants completed the survey, giving a response rate of 89%. The majority of the paediatric oncologists were either neutral or agreed that palliative chemotherapy should be considered. The most important treatment aim was to improve quality of life of the patient (92.7% of respondents). The most important considerations when prescribing palliative chemotherapy was to minimise toxicity of the chemotherapy regimen (4.56 mean, SD=0.5 utilising a 5 point scale where 1=not important to 5=very important), and the effectiveness of the chemotherapy (4.37; SD=0.48). Only 19.5% of patients received treatment primarily because parents requested it. According to the oncologists polled, the key considerations were largely achieved in the most recent patient treated with palliative chemotherapy. Individual opinions and preferences concerning recommending palliative chemotherapy differ between paediatric oncologists. Of the 305 patient deaths recorded in the study period, a total of 74 patients had received palliative chemotherapy and were included in the file review. The most common diagnoses were neuroblastoma (18.2%), retinoblastoma (15.6%) and osteosarcoma (14.3%). At the time of diagnosis, the median age of the patients was 6.0 years (range 0.3 to 17.6 years). In 47 patients (63.5%) the disease was deemed incurable at first diagnosis and palliative chemotherapy given from the onset of treatment, while 27 patients (36.5%) were given palliative chemotherapy at relapse. The median time from last palliative chemotherapy to death was 30 days (range 0-742 days). The main documented aim of palliative chemotherapy was to improve symptom control (97.3%) while parents' opinion played an important role in 32.9% of cases. About half of the patients (41 of 74, 55.4%) had documentation of symptomatic improvement. CONCLUSION: Although the overall attitude towards the use of palliative chemotherapy is positive, there is great inter-individual variation between oncologists in opinions and experience. The lack of empirical data to justify recommendations about palliative chemotherapy remains a problem, and the researcher hopes that this study will spark productive discussion and planning towards more structured use of palliative chemotherapy in children with cancer in South Africa. This study shows that many decisions around end of life care and decision-making could be better researched using a quantitative, prospective, interview-based approach. Repeated measurements of the child and family's quality of life and its associations with palliative chemotherapy should be a research priority in future.

Background: Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of a medical treatment. However, the efficacy demonstrated by trials does not automatically translate into a comparable level of effectiveness in the real world. RCTs may vary from routine clinical practice in several ways; the patients themselves, the delivery of the treatment, and the collateral care provided during treatment. Phase IV studies that assess outcomes of a treatment in the real-world provide a mechanism for assessing treatment effectiveness. Objectives: The objectives of this study were to: describe the characteristics of patients receiving standard, first-line, palliative, platinum-doublet chemotherapy (PPDC) for non-small cell lung cancer (NSCLC) in routine care; describe the effectiveness of PPDC in terms of wellbeing and symptom control; identify patient characteristics associated with change in wellbeing with treatment; and compare reported treatment efficacy to the effectiveness observed in the current study. Methods: This study was a retrospective cohort study of patients treated at Ontario’s Regional Cancer Centres (RCCs). Patients’ Edmonton Symptom Assessment System (ESAS) scores were used to describe patients’ symptomatic status and wellbeing. The proportions of patients whose wellbeing improved, remained stable or deteriorated at two months were calculated. Using logistic regression, patient and disease characteristics were assessed for association with change in wellbeing at two months (dichotomized as improved/stable and deteriorated). In comparing trial results to this study, adjustments were made for differences in case mix. Results: Patients’ median age was 65, 55% were male and the majority had stage IV disease and adenocarcinoma histology. Patients’ baseline wellbeing and symptomatic status varied widely. 61.3% (95% CI: 55.8 – 66.6%) of patients had improved or stable wellbeing at two months. Histology and baseline wellbeing score were associated with change in wellbeing at two months. The case mix adjusted estimates of the proportion of improved/stable patients (60.0% (95% CI 54.5 – 65.3) and 60.5% (95% CI 54.9 – 65.6)) were consistent with the proportion of patients achieving general quality of life improvement or stabilization in RCTs (55% and 63%). Conclusion: The effectiveness of PPDC delivered in Ontario’s RCCs is consistent with that expected based on the results of RCTs. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2012-04-23 11:53:33.491

Introduktion: Den palliativa behandlingsfasen vid obotlig cancersjukdom har blivit längre. Cancerpatienters upplevelser och hantering av att leva med en obotlig sjukdom är relativt väl undersökt men för den som lever med en obotlig sjukdom och får palliativ cytostatika- behandlingen behöver upplevelsen av livssituationen belysas mer.  Syfte: Att beskriva patienters upplevelse av sin livssituation under palliativ cytostatika-behandling.   Metod: Detta är en systematisk litteraturöversikt av kvalitativa forskningsresultat som utgick ifrån intervjuer. De delar av studiernas resultat som mötte syftet analyserades med tematisk analys där både det latenta och manifesta innehållet tolkades.   Resultat: Sammanlagt analyserades 13 artiklar. I dessa deltog 213 personer, åldern 28-86 år med 20 olika cancerdiagnoser och relativt jämn könsfördelning. Resultatet inordnades under fyra teman: den fysiska, psykiska, sociala och existentiella/andliga dimensionen. Palliativ cytostatikabehandling, trots de problem den medförde, stod för hopp liksom förlängd överlevnad och kunde kontrasteras mot palliativ vård som förknippades med döden. Livet  omorganiserades, omvärderades och deltagarna fokuserade på att leva det liv som fanns kvar och befinna sig i nuet.   Slutsats:  Litteraturöversikten ger en inblick i hur patienter upplever och hanterar sin livssituation; betydelsen som cytostatikabehandlingen har, hur förloppet påverkar patienten liksom dennes starka fokusering på livet och nuet, vilket också inkluderar ett undvikande av att tänka eller samtala om döden eller att anslutas till palliativ vård. Resultatet kan ge stöd i samtalet med patienten och i kontakten med dennes livsvärld, då en förutsättning för god  patientcentrerad vård är att utgå ifrån patientens förutsättningar och prioriteringar. / Introduction: The palliative treatment phase for incurable cancer has become longer. Cancer patients' experiences and ways of living with incurable cancer are relatively well studied, but for those living with an incurable disease and receiving palliative chemotherapy treatment, their own experience of their life situation needs to be elucidated more. Aim: To describe patients' experience of their life situation during palliative chemotherapy. Method: This is a systematic literature review of qualitative research results that were based on interviews. A thematic analysis were used, both the latent and manifest content were interpreted. Result: A total of 13 articles were analyzed. These included 213 persons, aged 28-86 with 20 different types of cancer, men and women were fairly evenly represented. The result was organized into four themes: the physical, psychological, social and existential/spiritual dimension. Palliative chemotherapy, despite the problems it caused, stands for hope as well as extended survival in comparison with palliative care that they associated with death. Life was reorganized, re-evaluated and they focused on appreciating life. Conclusions: The literature review provides an insight into how these patients experience and manage their life; the importance of chemotherapy, how the current situation affects the patient, as well as their focus on life and the present, which also includes the avoidance of thinking or talking about death or being connected to a palliative care unit. The result can provide support in the conversation with the patient and in contact with his or her lifeworld.

There is evidence that kinetics of tumour markers (TMs) CEA, CA15-3 and CA19-9 provide valuable information about disease state over time in patients with advanced breast and colorectal cancer but the literature contains differences in methodology so comparing findings is difficult. By modifying criteria developed by Rustin and colleagues [1-5] in ovarian carcinoma we have retrospectively identified a subset of patients (those with progressive (P) TMs) where survival is significantly reduced compared with those with responsive (R) TMs. This is true for CEA, CA15-3 and CA19-9 at the first chemotherapy given in advanced disease (chem1) (Hazard ratios (HR) = 9.99, 8.89, 5.75, P ¿ 0.001 in all cases) and CEA and CA19-9 at the second chemotherapy (chem2) (HR = 7.95, 9.00, P = 0.001 and 0.002 respectively) in patients with breast cancer. It is also true for CEA at chem1 in patients with colorectal cancer (HR = 2.51, P <0.001). Further studies are necessary to see if treatment directed by these criteria can influence survival. CEA and CA19-9 Rustin category in colorectal patients and CA15-3 Rustin category in breast patients correlated significantly with radiological category at chem1 and chem2 (CEA rs = 0.45 and 0.43, CA19-9 rs = 0.26 and 0.35, CA15-3 rs = 0.28 and 0.44). CA19-9 also correlates with radiological category at chem2 (rs = 0.38) in breast patients. This provides valuable information because RECIST criteria can delay radiological identification of disease progression compared with WHO criteria [6, 7] and new therapies may act to stabilise tumour growth rather than reduce it [8]. / Oncology Research Trust Fund at Airedale NHS Trust

Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients’ median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy.

Background: The landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE). Methods: For this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival. Results: Subgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen. Conclusion: This retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making.