Introduction: New treatments for stage IV (adv) NSCLC have emerged this past decade. Recent pharmacoeconomic research has focused on cost of treatment, comparative costs of therapies, and cost/cost effectiveness of adding a biologic to traditional therapy. Drug cost is thought to be a primary driver of cost change in NSCLC, yet to our knowledge, characterization of the direct cost of NSCLC has not been published since the new treatments have emerged in the guidelines. Our primary objective was to characterize the direct and segmented cost of adv NSCLC from 2000-9. We also want to determine cost impact of new therapies, and cost trend from 2000-9. Methods: This PharMetrics claims database study includes diagnosed NSCLC patients [greater than or equal to] 20 yo. Small cell lung cancer was excluded. Claims were divided into disease segments and time periods representative of changes in therapy ("pre" (2000-2), "transition" (2003-5), and "current" (2006-9) periods). Descriptive statistics (median, interquartile range (IQR)), chi-square test (nominal data), and Wilcoxan rank sum tests were performed on the data. To adjust for baseline confounders, multivariate least squares regression models were created. Results: Costs are reported as medians in terms of per patient per month (pppm). Overall monthly cost (n=969) was $10,281 pppm. Diagnosis cost $6,601 pppm, active treatment cost $9,287 pppm, and end-of life cost $12,215 pppm. There was no difference in cost between the “transition” (n=439) and “current” (n=503) periods overall or for any segment of disease. Comorbidities had no effect on cost. For patients receiving at least 5 months of active treatment medication (n=316) total median cost was $144,147 per patient ($9,371 pppm). Discussion: There was no difference in cost between the transition and current periods, in regards to either overall cost or segmented cost. The most expensive segment was end-of-life, with a median cost exceeding $12,000 pppm. Surprisingly, comorbidities had no effect on cost. Newer agents (biologics, TKIs, and pemetrexed) represent only a modest portion of cost, with a majority of cost for stage IV NSCLC comprised of non-drug costs. / text

Bakgrund: I Sverige drabbas årligen ca 7000 kvinnor av bröstcancer. 90 % av dessa överlever sin sjukdom tack vare goda behandlingsmöjligheter. Kvinnor med spridd bröstcancer lever allt längre tid med sin sjukdom. När bröstcancer sprider sig till andra organ än bröstet räknas den inte längre vara botbar. Behandling inriktar sig då till att vara lindrande eller palliativ. Bröstcancer är den vanligaste dödsorsaken för kvinnor i medelålder i Sverige. Syfte: Syftet med denna litteraturstudie är att belysa kvinnors upplevelse av att leva med obotlig bröstcancer. Metod: Åtta kvalitativa empiriska studier har sammanställts och analyserats med hjälp av beskrivande metasyntes. Artikelsökning utfördes i databaserna PubMed och CINAHL. Resultat: Resultatet från de valda artiklarna rörande kvinnors upplevelser av att leva med obotlig bröstcancer, kunde efter analys och konsensusdiskussioner sammanföras i fyra kategorier; Identitet, Relationer, Perspektiv samt Sorg och Förlust. Slutsats: Litteraturstudien visar att när kvinnor drabbas av obotlig bröstcancer förändras hela deras tillvaro drastiskt. Både livsperspektiv och roller hotas och leder till ångest och sorg. Kvinnorna upplever att det brister i bemötandet från vårdpersonal och behov av utvecklad kunskap och förståelse från sjuksköterskor är nödvändigt. Nyckelord: Metastaserad bröstcancer, Upplevelse, Relationer, Sorg, Omvårdnad / Background: In Sweden approximately 7000 women are diagnosed with breast cancer every year. 90% of these survive the disease because of good treatment possibilities. Women with cancer that has spread live longer with their disease. When breast cancer spreads to other organs it is no longer considered curable. Treatment then focuses on mitigation of pain and being palliative. Breast cancer is the most common cause of death for middle-aged women in Sweden.   Purpose: The purpose of this literature study is to shed light on womens experience of living with incurable breast cancer.   Method: Eight qualitative empirical studies have been collated and analyzed using descriptive metasynthesis. The article search has been carried out in the PubMed and CINAHL databases.   Result: The results from the chosen articles about women's experience of living with incurable breast cancer, could after a consensus discussion be brought into four categories; Identity, relations, perspective and finally sorrow and loss.   Conclusion: The literature study shows that when women are stricken with terminal breast cancer their lives change drastically. Both perspective on life and roles are threatened and lead to anxiety and sorrow. Women experience that the personal treatment they get from nursing staff is lacking, and that a higher level of knowledge and understanding in the nurses is necessary.   Keywords: Metastatic breast cancer, Experience, Relationship, Grief, Nursing

Comprehensive characterisation of the mutational landscapes of solid tumours is a multistep process involving the collection of suitable samples, the extraction of nucleic acids and the preparation of these materials for mutational analyses. In this thesis, I aimed to develop a streamlined process for the analysis of colorectal cancer (CRC) patient samples in order to identify novel mutations that hallmark the development of advanced disease. Papers I and II outline a technique for serial extraction of nucleic acids from frozen tissue that we developed and subsequently implemented on a robotic platform to enable high-throughput processing. The extracted nucleic acids were validated in downstream processes relevant for genetic analyses, including traditional Sanger and next generation sequencing  techniques. In Paper III, we developed a genotyping method based on multiplex ligation-dependent genome amplification. The method was designed such that InDel polymorphisms of between 30 and 70 % prevalence in a European population were selected and amplified in a multiplex PCR assay. DNA from 24 patient-matched colorectal tumour and normal tissues was genotyped and paired with a high match probability. In Paper IV, we performed targeted resequencing of 107 primary CRCs, of which approximately half developed metastatic disease or had distant metastases at the time of diagnosis. We chose to analyse 676 genes based on their involvement in key signalling pathways in CRC. We found an enrichment of mutations in the Eph receptor tyrosine kinase gene family in metastatic patients, indicating a potential role for these genes in CRC metastasis. This thesis outlines a series of procedures that can be employed in a high-throughput setting for the analysis of solid tumours. We applied these methods to the analysis of colorectal tumours and propose a link between novel somatic mutations and metastatic disease.

Le cancer colorectal métastatique est l’une des premières causes de décès par cancer dans les pays occidentaux, malgré le développement récent de nouveaux traitements ciblés. L’amélioration de la survie des patients passe par une meilleure compréhension des mécanismes moléculaires impliqués dans la progression tumorale et la formation des métastases. Compte tenu de l’importance du rôle des axes mTOR/HIF1α et CXCL12/CXCR4/CXCR7 dans le processus métastatique, nos objectifs ont été : i) d’analyser de façon extensive le statut de CXCL12 dans une collection de polypes et de tumeurs coliques de tous stades et phénotypes en comparaison avec la muqueuse saine, puis de comprendre les mécanismes régulant l’expression de la chimiokine dans les cellules tumorales ; ii) d’étudier in vitro le rôle de l’hypoxie dans la régulation de la signalisation induite par CXCL12 via CXCR4 et CXCR7 et l’intérêt d’une inhibition des axes mTOR/HIF-1α et CXCL12/CXCR4/CXCR7 en particulier sur les capacités migratoires des cellules tumorales.Nous avons montré que l’extinction du gène CXCL12 est un évènement précoce et systématique au cours de la cancérogenèse colique et que cette perte d’expression pourrait être régulée par un mécanisme d’acétylation au niveau des histones. Une expression différentielle de CXCR4 et CXCR7 au sein des tumeurs du colon a été mise en évidence. L’augmentation d’expression de CXCR7 dans les métastases par rapport aux stades précoces montre l’importance de cet axe dans le processus métastatique. Le maintien de l’expression à la surface cellulaire de CXCR4 en normoxie pendant au moins 24h après un bref passage en hypoxie n’avait pas encore été décrit. Ceci pourrait expliquer le « homing » des cellules tumorales circulantes dans les niches métastatiques selon un gradient de CXCL12. L’utilisation combinée d’irinotécan et de chalcone permettant d’inhiber la migration des cellules tumorales est une approche originale in vitro. Enfin, nous avons initié le développement de modèles métastatiques de cancer du colon par greffe orthotopique sur le caecum de souris NUDE dans l’objectif de tester de nouvelles approches thérapeutiques ciblées in vivo. / Despite the recent development of new targeted chemotherapies, metastatic colorectal cancer is still one of the leading causes of cancer related deaths in western countries. A better understanding of metastatic process would improve survival. Since the role of mTOR/HIF1α and CXCL12/CXCR4/CXCR7 axes in metastasis formation, our objectives were: i) to analyze extensively CXCL12 status in a collection of polyps and colon tumors whatever stages and phenotypes; ii) to study the role of hypoxia in CXCL12/CXCR4/CXCR7 signaling pathway in vitro and on tumor cells migration. We have shown that the CXCL12 extinction is a systematic early event during colorectal carcinogenesis. CXCL12 loss expression may be regulated by histone acetylation mechanism. There is a differential CXCR4 and CXCR7 expression in colon tumors. Increased CXCR7 expression in metastasis compared to early stages underlines the importance of this axis in metastatic process. We have shown for the first time that CXCR4 expression remained stabilized at the cell membrane 24 hours after a transient passage in hypoxia. It could explain circulating cells are attracted in metastatic niches under CXCL12 gradient. Drug combinations with chalcone and irinotecan are an original approach for inhibiting cell migration in vitro. Finally, we have initiated the development of a metastatic model of colon cancer with orthotopic colon human tumors xenograft in NUDE mice to test new therapeutic approaches in vivo.

Submitted by Talita Mariana Morata Raposo null (talita_raposo@yahoo.com.br) on 2016-08-26T23:53:52Z No. of bitstreams: 1 tese.pdf: 7349096 bytes, checksum: 15c4a9aa3753843c66b8604dad27c6e8 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-08-30T18:12:04Z (GMT) No. of bitstreams: 1 ferreira_tmmr_dr_jabo.pdf: 7349096 bytes, checksum: 15c4a9aa3753843c66b8604dad27c6e8 (MD5) / Made available in DSpace on 2016-08-30T18:12:04Z (GMT). No. of bitstreams: 1 ferreira_tmmr_dr_jabo.pdf: 7349096 bytes, checksum: 15c4a9aa3753843c66b8604dad27c6e8 (MD5) Previous issue date: 2016-08-22 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Os tumores mamários são os principais tumores que acometem as cadelas, sendo também os tumores mais frequentes em mulheres e, entre ambas as espécies, são observadas semelhanças relacionadas ao comportamento biológico e molecular dessa neoplasia. Assim, as cadelas podem ser um excelente modelo comparativo para o entendimento do processo carcinogênico desta neoplasia. A metástase é uma consequência comum e a principal causa de mortalidade em decorrência dessa enfermidade, em ambas as espécies. O perfil de expressão gênica global permite o melhor entendimento do processo de carcinogênese e de metástases, por permitir a identificação de inúmeros genes que possam estar envolvidos com esses processos. Assim, o objetivo desse estudo foi a realização do estudo em larga escala, através da técnica de microarray, em amostras de tecidos mamários caninos, considerando amostras de glândulas mamárias normais, tumores mamários benignos e tumores mamários malignos (carcinomas simples e mistos), além da avaliação de carcinomas mamários metastáticos e não metastáticos, para identificação de genes diferencialmente expressos entre esses grupos e relacionados com a tumorigênese e o desenvolvimento de metástases dos tumores mamários caninos. Observou-se, aproximadamente 1000 genes diferencialmente expressos entre as amostras tumorais e as glândulas mamárias normais e 465 genes diferencialmente expressos entre os tumores mamários benignos e malignos, sendo observados genes relacionados com o ciclo celular, desenvolvimento da glândula mamária e supressores tumorais. Em relação aos carcinomas mamários metastáticos e não metastáticos, verificou-se 633 genes diferencialmente expressos. Os genes supressores tumorais, como pertencentes a via de sinalização do ATM e do BRCA1, sugeriram importante papel tanto na progressão tumoral quanto no desenvolvimento de metástases. Outras vias observadas foram as relacionadas com angiogênese e de organização da matriz extracelular. Portanto, a análise do perfil gênico em larga escala permitiu a identificação de inúmeros genes e vias envolvidas tanto no processo de progressão tumoral como envolvidas com o desenvolvimento de metástases, permitindo a realização de estudos futuros em busca de marcadores prognósticos específicos. / Mammary tumors are the main tumors that affect female dogs, as well as in women and in both species, it is observed similarity related to the biological and molecular behavior of this neoplasia. So, female dogs are considered an excellent model for the understanding of carcinogenesis process from mammary tumors. Metastasis occurs frequently and it is the main responsible for the mortality by this neoplasia in both species. Global gene expression profile allows the better understanding of carcinogenesis and metastasis process by the identification of several genes that may be involved with these processes. Therefore, the aim of study was to perform a large-scale study by microarray technique using samples from canine mammary tissues, as normal mammary gland, benign tumors and malignant tumors (simple and mixed carcinomas), beyond metastatic and non-metastatic mammary carcinomas for the identification of differentially expression genes among these groups and related to canine mammary tumors tumorigenesis and metastasis. It was observed next to 1000 differentially expression genes between tumors and normal mammary glands samples and 465 differentially expression genes between benign and malignant mammary tumors mostly related to cell cycle, mammary gland development and tumor suppressors. Related to metastatic and non-metastatic mammary carcinomas was identified 633 differentially expression genes. ATM and BRCA1, associated with tumor suppressor gene pathway, showed to play an important role in both tumor progression and metastasis development. Other networks observed were related to angiogenesis and extracellular matrix organization. Thus, large-scale gene profile analysis allowed the identification of numerous genes and networks involved with both tumor progression and metastasis, allowing new studies in search of specific prognostic markers. / FAPESP: 2013/03940-4 / FAPESP: 2013/25220-3

Introdução: O câncer de próstata metastático resistente à castração apresenta sobrevida inferior a 30% em cinco anos, e o único tratamento disponível para os pacientes até pouco tempo atrás era o docetaxel. Com o maior entendimento dos mecanismos de resistência desse câncer às terapias utilizadas, novas drogas foram desenvolvidas, entre elas a abiraterona, que atua no bloqueio da enzima 17-? desidrogenase-hidroxiesteroide e a enzalutamida que age diretamente nos receptores de androgênios. Foi realizada uma revisão sistemática dos estudos que avaliaram a eficácia e segurança da abiraterona mais prednisona e da enzalutamida em pacientes com CPMRC, tanto previamente quanto posteriormente ao tratamento com docetaxel. Métodos: A pesquisa bibliográfica foi realizada em março de 2016 nas bases da Pubmed, Google Acadêmico e ClinicalTrials.gov. Os seguintes termos de pesquisa foram utilizados \"prostate cancer metastatic resistent\", \"prostate cancer\", \"abiraterone\" e enzalutamide\", restringido a estudos clínicos randomizados fase III, duplo cego e multicêntrico, publicados nos idiomas inglês, espanhol. Os estudos selecionados foram analisados de forma independente por LRM e AAN. Os critérios para análise foram a sobrevida global (SG), sobrevida livre de progressão (SLP) e o tempo até a progressão do PSA (TP PSA), previamente e após o uso de docetaxel. Resultados: Foram identificados 53 estudos. Aplicando os critérios de inclusão foram selecionados quatro estudos que juntos somaram uma população de 5.199 (2.394 pacientes após docetaxel e 2.805 pacientes previamente ao uso do docetaxel). Em relação a SG, a abiraterona reduziu o risco de morte em 26% após docetaxel (HR 0,74 95% IC 0,64-0,86) e 19% no pré-docetaxel (HR 0,81 95% IC 0,70-0,93), e a enzalutamida reduziu em 37% após (HR 0,63 95% IC, 0,53-0,75) e 23% no pré-docetaxel (HR 0,77 95% IC 0,67-0,88). Em relação a SLPr, abiraterona retardou a progressão da doença em 34% após (HR 0,66 95% IC 0,58-0,76) e 48% na pré-quimio (HR 0,52 95% IC 0,45-0,61), e a enzalutamida em 60% após quimio (HR 0,40 95% IC 0,35-0,47) e 68% na pré-quimio (HR 0,32 95% IC 0,28-0,36). Abiraterona aumentou o tempo até a progressão do PSA em 64% após quimio (HR 0,36 95% IC 0,52-0,78) e 50% na pré-quimio (HR 0,50 95% IC 0,43- 0,58), e a enzalutamida em 75% após quimio (HR 0,25 95% IC 0,20-0,30) e 83% na pré- quimio (HR 0,17 95% IC 0,15-0,20). Conclusão: Tanto abiraterona quanto enzalutamida demonstraram melhores resultados no aumento da SG, da SLPr e do TP PSA no tratamento de pacientes com CPMRC. Não há um estudo comparativo direto e devido a diferenças nos critérios de inclusão e dos grupos comparadores entre esses estudos clínicos, não é possível uma análise indireta entre tais medicamentos. Assim, questões como qual a melhor estratégia de tratamento na pré e pós-quimio e o sequenciamento ideal para enfrentamento do CPMRC não podem ser respondidas. / Introduction: Castrate-resistant metastatic prostate cancer presents survival less than 30% in five years, and the only treatment available to patients until recently was docetaxel. With the greater understanding of the mechanisms of resistance of this cancer to the therapies used, new drugs have been developed, among them abiraterone, which acts in the blockade of the enzyme 17-? dehydrogenase-hydroxysteroid and the enzyme that acts directly on the androgen receptors. A systematic review was made of studies evaluating the efficacy and safety of abiraterone plus prednisone and of enzyme adduct in patients with CPMRC both before and after docetaxel treatment. Methods: The literature search was prepared in March 2016 based on Pubmed, Google Scholar and ClinicalTrials.gov. The following search terms were used \"prostate cancer metastatic resistant\", \"prostate cancer\", \"abiraterone\" and \"enzyme\", restricted to phase III, double blind and multicenter clinical trials published in English, Spanish, Italian and Portuguese. The selected studies were analyze by LRM and AAN. The criteria for analysis were overall survival (OS), progression-free survival (PSA) and time to PSA progression (PS PSA), before and after docetaxel use. Results: Fifty-three studies were identified and, according to the inclusion criteria, four studies were selected that together added a population of 5,199 (2,394 patients after docetaxel and 2,805 patients prior to docetaxel use). In relation to SG, abiraterone reduced the risk of death by 26% after docetaxel (HR 0.74 95% CI 0.64-0.86) and 19% in predocetaxel (HR 0.81 95% CI 0.70- 0.93), and enzyme reductase reduced by 37% (HR 0.63 95% CI, 0.53-0.75) and 23% in pre docetaxel (HR 0.77 95% CI 0.67-0, 88). In relation to SLPr abiraterone delayed disease progression by 34% (HR 0.66 95% CI 0.58-0.76) and 48% in pre-chemotherapy (HR 0.52 95% CI 0.45-0, 61), and enzyme-alpha 60% after chemo (HR 0.40 95% CI 0.35-0.47) and 68% in pre-chemo (HR 0.32 95% CI 0.28-0.36). Abiraterone increased the time until PSA progression by 64% after chemo (HR 0.36 95% CI 0.52-0.78) and 50% in pre-chemo (HR 0.50 95% CI 0.43-0, 58), and enzyme-alpha in 75% after chemo (HR 0.25 95% CI 0.20-0.30) and 83% in pre-chemo (HR 0.17 95% CI 0.15-0.20). Conclusion: Both abiraterone and enzalutamide showed better results in increasing SG, SLPr and TP PSA in the treatment of patients with CPMRC. There is no direct comparative study and, because of differences in inclusion criteria and comparator groups between these clinical studies, indirect analysis of such drugs is not possible. Thus, questions such as the best pre and post chemo treatment strategy and the optimal sequencing for CPMRC coping cannot be answered.

Breast cancer is the most common cancer among Canadian women and 14-20% will develop lethal metastases within 5 years. A potential novel therapeutic target is Focal Adhesion Kinase (FAK), a cytoplasmic tyrosine kinase. FAK’s expression is inversely correlated with survival and is known to regulate cell migration, proliferation and invasion. While tyrosine kinase inhibitors are historically ineffective as single agents, they are commonly used as part of combination therapies. Therefore, given its central role in tumor cell biology and cell signaling, we hypothesized that inhibiting FAK in combination with pharmacological agents commonly used to treat metastatic breast cancer patients will result in enhanced anti-tumor activity. We combined a commercial FAK inhibitor (PF-562271) with a range of chemotherapeutic agents commonly used to treat metastatic breast cancer and searched for synergistic partners. Only DNA topoisomerase inhibitors showed potential to synergistically reduce cell viability when paired with low doses of the FAK inhibitor. However, the combination does not induce an increase in cell death or apoptosis. It was then discovered that both agents in isolation and in combination produce increased levels of ROS, a toxic metabolite. This, along with other more preliminary data, provides clues for a novel proposed mechanism of action for this interaction.

Notre objectif était d’analyser l’implication potentielle des voies associées aux récepteurs de chimiokines CXCR2 et CXCR4 dans le cancer colorectal métastatique au foie. Les niveaux d’expression de CXCR2, CXCR4 et de leurs chimiokines étaient évalués dans les métastases hépatiques de cancers colorectaux dans le but d’étudier leurs corrélations avec la survie globale et la survie sans récidive de patients ayant reçu, ou non, une chimiothérapie néoadjuvante. Des analyses d’expression pour RT-PCR quantitative et immunohistochimie étaient réalisées en utilisant des prélèvements humains de métastases hépatiques de cancers colorectaux. Les niveaux d’expression de CXCR2, CXCR4 et de leurs ligands étaient statistiquement analysés en fonction des traitements par chimiothérapie néoadjuvante administrés ou non, et en fonction du suivi des patients. Des modèles murins de xénogreffes sous-cutanées et orthotopiques intracaecales ont été mis au point et utilisés pour étudier l’expression de CXCR2, CXCR4 et CXCL7 en relation avec le traitement des souris par chimiothérapie.Nous avons montré que la surexpression de CXCR2 et CXCL7 était corrélée à de plus courtes survies globales et sans récidive de nos patients. En analyse multivariée, l’expression de CXCR2 et de CXCL7 étaient des facteurs indépendants de survie globale et sans récidive. La chimiothérapie néoadjuvante augmentait significativement l’expression de CXCR2, et de CXCL7 de façon proche de la significativité. Les résultats de nos modèles murins ont montré une tendance à la surexpression de nos gènes d’intérêts dans les tissus tumoraux des souris traités. En conclusion, ces résultats suggèrent l’implication de la voie de signalisation CXCL7/CXCR2 comme facteur prédictif de mauvais pronostic dans le cancer colorectal métastatique. Les chimiothérapies à base de 5 Fluoro-uracile augmentent l’expression de ces gènes dans les métastases hépatiques, fournissant une explication sur l’agressivité des tumeurs métastatiques en échappement thérapeutique. Un blocage sélectif de l’axe CXCR2/CXL7 pourrait fournir de nouvelles opportunités thérapeutiques. / Our aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. Expression levels of CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen.Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using human CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients ' outcome. Murine models of subcutaneous and orthotopic intracaecal xenografts have been developed and used to study the expression of CXCR2, CXCR4 and CXCL7 in connection with the treatment of mice with chemotherapy.We showed that CXCR2 and CXCL7 overexpression are correlated to patient’s shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2 and CXCL7 was overexpressed close to significance. Results of our mouse models have shown a trend over-expression of our interest genes in tumor tissues of the treated mice.In conclusion, we show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities.

Class of 2017 Abstract / Objectives: To determine the efficacy and toxicity of fluorouracil/leucovorin/oxaliplatin (FOLFOX) versus capecitabine/oxaliplatin (XELOX) in the treatment of colorectal cancer (CRC) in the adjuvant (aCRC) and metastatic (mCRC) setting in Veterans at the Southern Arizona Veteran Affairs Health Care System (SAVAHCS). Methods: A retrospective chart review was conducted to collect efficacy and toxicity data. Subjects were included based on age, treatment setting and regimen in the preset 5-year period, and appropriate diagnosis via International Classification of Diseases-Revision 9 (ICD-9) codes. Efficacy was measured via 1-year disease-free survival (DFS) for aCRC, progression-free survival (PFS) for mCRC, and overall survival (OS) for both settings. Results: A total of 79 subjects were initially enrolled with 51 and 54 all-male subjects included in the efficacy and toxicity analysis, respectively. Mean range of age was 63-72 years old. Subjects were divided into four groups: FOLFOX aCRC (17) and mCRC (19), XELOX aCRC (10) and mCRC (8). No difference was found in 1-year DFS and OS between aCRC groups, and PFS between mCRC groups; a higher incidence of 1-year OS with FOLFOX in the mCRC setting was noted (p = 0.03). No difference was found in toxicity between FOLFOX and XELOX, except a higher incidence of hand-foot syndrome in XELOX (p = 0.0007). Conclusions: Efficacy between FOLFOX and XELOX in aCRC and mCRC is similar, while toxicity is slightly more prevalent in XELOX due to increased hand-foot syndrome incidence. These findings agreed with the results reported by prospective clinical trials.

Stage IV cancer is characterized by a cancer’s ability to metastasize, or spread throughout the body. Metastatic disease in bone is a devastating condition affecting hundreds of thousands of people each year. Stage IV cancer patients suffering from metastatic disease in the proximal femur are at high risk of catastrophic pathologic fracture, an event which severely impacts patient health. Although metrics have been created to assess the risk of impending fracture, they lack specificity in the proximal femoral region. Shortcomings of these metrics further complicate clinical decision making related to prophylactic fixation in these medically compromised individuals. Fortunately, by using computational modeling to study this at-risk patient population, the likelihood of fracture due to metastatic lesions in the proximal femur can be more accurately assessed to improve clinical decision making. Finite element analysis (FEA) is a computational modeling technique that can non-invasively provide mechanics information to better assess true fracture risk of a given metastatic lesion. Although FEA has previously been utilized to study metastatic disease, lesions were always modeled as spheres or ellipsoids, while true lesion shapes are far more amorphous. It was the focus of this study to validate FEA’s ability to predict fracture location in cadaveric femora with realistically shaped experimental metastatic lesions. Off-set torsion, or load applied off-set from the fixed long bone axis, was applied to cadaveric specimens with mechanically induced metastatic lesions, and the resultant fracture location was compared to specimen-specific FEA models replicating the mechanical test. FEA was able to correctly predict fracture locations in five models. Determining fracture risk based on objective mechanical data may more accurate and effective in this patient population.