Colorectal Cancer Patients' Reported Frequency, Content, and Satisfaction with Advance Care Planning Discussions.

(1) Background: This observational cohort study describes the frequency, content, and satisfaction with advance care planning (ACP) conversations with healthcare providers (HCPs), as reported by patients with advanced colorectal cancer. (2) Methods: The patients were recruited from two tertiary cancer centers in Alberta, Canada. Using the My Conversations survey with previously validated questions, the patients were asked about specific ACP elements discussed, with which HCPs these elements were discussed, their satisfaction with these conversations, and whether they had a goals of care designation (GCD) order. We surveyed and analyzed data from the following four time points: enrollment, months 1, 2, and 3. (3) Results: In total, 131 patients were recruited. At enrollment, 24% of patients reported discussing at least one ACP topic. From enrollment to month 3, patients reported a high frequency of discussions (80.2% discussed fears, 71.0% discussed prognosis, 54.2% discussed treatment preferences at least once); however, only 44.3% of patients reported discussing what is important to them in considering health care preferences. Patients reported having ACP conversations most often with their oncologists (84.7%) and cancer clinic nurses (61.8%). Patients reported a high level of satisfaction with their ACP conversations, with over 80% of patients reported feeling heard and understood. From enrollment to month 3, there was an increase in the number of patients with a GCD order from 53% to 74%. (4) Conclusions: Patients reported more frequent conversations compared to the literature and clinical documentation. While the satisfaction with these conversations is high, there is room for quality improvement, particularly in eliciting patients' personal goals for their treatment.

Examining the development of information needs assessment tools for use in the cancer context: A scoping and critical review.

BACKGROUND: Information needs are one of the most common unmet supportive care needs of those living with cancer. Little is known about how existing tools for assessing information needs in the cancer context have been created or the role those with lived cancer experience played in their development. OBJECTIVES: This review aimed to characterize the development and intended use of existing cancer specific information needs assessment tools. METHODS: A systematic scoping review was conducted using a peer-reviewed protocol informed by recommendations from the Joanna Briggs Institute and the Prefered Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. RESULTS: Twenty-one information needs assessment tools were included. Most tools were either breast cancer (n = 8) or primary tumor nonspecific (n = 8). Patients and informal carers participated in initial identification of questionnaire items in the minority of cases (n = 6) and were more commonly involved in reviewing the final questionnaire before use or formal psychometric testing (n = 9). Most questionnaires were not assessed for validity or reliability using rigorous quantitative psychometric testing. SIGNIFICANCE OF RESULTS: Existing tools are generally not designed to provide a rigorous assessment of informational needs related to a specific cancer challenge and are limited in how they have been informed by those with lived cancer experience. Tools are needed that both rigirously address information needs for specific cancer challenges and that have been developed in partnership with those who have experienced cancer. Future directions should include understanding barriers and facilitators to developing such tools.

Clinical and metabolomic characterization of Brivanib-Induced hypertension in metastatic colorectal cancer.

BACKGROUND: Trials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome. PATIENTS AND METHODS: Clinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA). RESULTS: In the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R2 Y score = 0.89, Q2 Y score = 0.70, CV-ANOVA = 2.01 e-7). Notable metabolomic features previously reported in pre-eclampsia and associated with vasoconstriction were found. CONCLUSION: TKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.

Navigating the Cancer Journey Using Web-Based Information: Grounded Theory Emerging From the Lived Experience of Cancer Patients and Informal Caregivers With Implications for Web-Based Content Design.

BACKGROUND: The internet is an important source of information for many informal caregivers and patients living with cancer. A better understanding of how individuals use the internet to meet their informational needs is important for guiding intervention development. OBJECTIVE: The objectives of this study were to develop a theory describing why individuals living with cancer use the internet to find information, characterize the challenges faced with existing web-based content, and provide recommendations for web-based content design. METHODS: Adults (≥18 years) with a history of being patients with cancer or informal caregivers were recruited from Alberta, Canada. After providing informed consent, participants were engaged through digitally recorded one-on-one semistructured interviews, focus groups, a web-based discussion board, and emails. Classic grounded theory guided the study procedures. RESULTS: A total of 21 participants took part in 23 one-on-one interviews and 5 focus groups. The mean age was 53 (SD 15.3) years. Breast, gynecological, and hematological cancers were the most common cancer types (4/21, 19% each). In total, 67% (14/21) of patients, 29% (6/21) of informal caregivers, and 5% (1/21) of individuals reporting both roles participated. Participants experienced many new challenges in their cancer journey and used the internet to become better oriented to them. For each challenge, internet searching attempted to address one or more of 3 key orientation questions: why the challenge was happening, what to expect, and options for managing it. Better orientation resulted in improved physical and psychosocial well-being. Content that was well laid out, concise, free of distractions, and that addressed the key orientation questions was identified as the most helpful in assisting with orientation. Creators of web-based content are encouraged to 1) clearly identify the cancer challenge and population the content is addressing, as well as the presence of any potentially distressing information; 2) provide versions of the content in different formats, including printer-friendly, audio, video, and alternative languages; 3) state who created the content, including the individuals, organizations, and processes involved; 4) place hyperlinks after the key orientation questions have been addressed; and 5) ensure that the content is optimized for discovery by search engines (ie, Google). CONCLUSIONS: Web-based content plays an essential role for many living with cancer. Clinicians are encouraged to take active steps to help patients and informal caregivers find web-based content that meets their informational needs. Content creators also have a responsibility to ensure that the content they create assists and does not hinder those navigating the cancer journey. Research is needed to better understand the many challenges that individuals living with cancer face, including how they are temporally related. In addition, how to optimize web-based content for specific cancer challenges and populations should be considered an important area for future research.

Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma.

Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.

The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma.

Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.

Treatment patterns and survival outcomes of early-onset colorectal cancer patients in Alberta, Canada: a population-based study.

BACKGROUND: The incidence of early-onset (<50) colorectal cancer (eoCRC) has been increasing in Canada. Little is known about treatment patterns and outcomes among this patient population in Canada. PATIENTS AND METHODS: We conducted a retrospective population-based cohort study of CRC patients in Alberta (2010-2018) using electronic medical records and administrative claims data. Treatment patterns and CRC-specific mortality were compared between early-onset age groups (<40 and 40-49) and average age-at-onset (60-70) (aoCRC) patients with multivariable logistic regression and cox proportional hazard models. RESULTS: There were 334 and 935 patients in the early-onset groups and 4606 in the aoCRC group. Compared with aoCRC, patients <40 were more likely to receive chemotherapy in stage II colon (OR 3.41, CI 1.75-6.47) and stage III rectal (OR 3.01, CI 1.18-10.21), and to receive systemic therapy (OR 2.40, CI 1.46-4.12) and radiation in stage IV CRC (OR 2.70, CI 1.48-4.92). The 40-49 age group was more likely to receive chemotherapy in stage II colon (OR 2.13, CI 1.25-3.56), and chemoradiation in stage II rectal (OR 2.16, CI 1.25-3.80) and stage III rectal (OR 1.63, CI 1.13-2.40), as well as systemic therapy in stage IV CRC (OR 2.46, CI 1.75-3.52). Survival did not differ between <40 and 60-70 age groups. Survival was significantly higher for the 40-49 age group, but only in stage IV (HR 0.79, CI 0.67-0.94). CONCLUSIONS: EoCRC patients tended to receive more therapy than average age CRC patients with minimal survival gains. Additional research to identify optimal treatment strategies for eoCRC patients is required.

Patterns of emergency department visits preceding colorectal cancer diagnosis: a population-based study.

Aim: To assess the patterns of emergency department (ED) visits in the 3 months preceding a diagnosis of colorectal cancer (CRC) in a real-world, population-based context. Materials & methods: Linked provincial registries in Alberta, Canada, were accessed and patients with CRC diagnosed between 2004 and 2018 were identified. The National Ambulatory Care reporting system was used to identify patients who visited an ED within 3 months of a diagnosis of CRC. Multivariable logistic regression analysis was used to identify factors associated with any ED visits as well as frequent (≥3) ED visits. Results: A total of 25,310 patients with CRC were included in the current study. These include 10,126 patients (40%) who had at least one visit to the ED in the 3 months before a diagnosis of CRC diagnosis and 613 patients (2.4%) who visited the ED multiple (≥3) times. The following factors were associated with any visit to an ED: older age (odds ratio [OR]: 1.010; 95% CI: 1.008-1.012), female gender (OR: 1.23; 95% CI: 1.16-1.30), higher comorbidity index (OR: 1.38; 95% CI: 1.35-1.41), metastatic disease (OR: 2.37; 95% CI: 2.23-2.53), proximal tumors (OR: 1.59; 95% CI: 1.50-1.68) and North zone (OR vs south zone: 1.75; 95% CI: 1.55-1.98). Conclusion: It is not uncommon for CRC patients to visit the ED at least once in the 3 months prior to having such a diagnosis. Factors associated with frequent pre diagnosis emergency visits included female gender, higher burden of comorbid disease, advanced stage, proximal tumors and living in the North zone of Alberta (where there is limited access to specialist care).

Early detection of treatment futility in patients with metastatic colorectal cancer.

PURPOSE: Chemotherapy options for treating CRC have rapidly expanded in recent years, and few have predictive biomarkers. Oncologists are challenged with evidence-based selection of treatments, and response is evaluated retrospectively based on serial imaging beginning after 2-3 months. As a result, cumulative toxicities may appear in patients who will not benefit. Early recognition of non-benefit would reduce cumulative toxicities. Our objective was to determine treatment-related changes in the circulating metabolome corresponding to treatment futility. METHODS: Metabolomic studies were performed on serial plasma samples from patients with CRC in a randomized controlled trial of cetuximab vs. cetuximab + brivanib (N = 188). GC-MS quantified named 94 metabolites and concentrations were evaluated at baseline, Weeks 1, 4 and 12 after treatment initiation. In a discovery cohort (N = 68), a model distinguishing changes in metabolites associated with radiographic disease progression and response was generated using OPLS-DA. A cohort of 120 patients was used for validation of the model. RESULTS: By one week after treatment, a stable model of 21 metabolites could distinguish between progression and partial response (R2Y = 0.859; Q2Y = 0.605; P = 5e-4). In the validation cohort, patients with the biomarker had a significantly shorter OS (P < 0.0001). In a separate cohort of patients with HCC on axitinib, appearance of the biomarker also signified a shorter PFS (1.7 months vs. 9.2 months, P = 0.001). CONCLUSION: We have identified changes in the metabolome that appear within 1 week of starting treatment associated with treatment futility. The novel approach described is applicable to future efforts in developing a biomarker for early assessment of treatment efficacy.

No evidence of disease versus residual disease in long-term responders to first-line HER2-targeted therapy for metastatic breast cancer.

BACKGROUND: Long-term response to HER2-targeted therapies is infrequent in metastatic breast cancer (MBC). We evaluated clinical characteristics of HER2-positive MBC patients with no evidence of disease (NED) vs residual disease (RES) experiencing long-term response to first-line HER2-targeted therapy. METHODS: Patients receiving first-line chemotherapy-trastuzumab (CT) or taxane-trastuzumab-pertuzumab (THP) with response duration ≥2-fold higher than in phase II/III trials (CT [18.2 months]; THP [40.4 months]) were included. Clinical characteristics and radiographic review for NED or RES was evaluated by Cox-regression (hazard ratio; HR) or Kaplan-Meier (log-rank). Characteristics associated with NED were evaluated by logistic regression (Odds; OR). RESULTS: From 01/2005-01/2016, N = 103 (4.6%) patients were identified. In multivariate analyses, NED (N = 46) showed improved progression-free (PFS) and overall survival (OS) [p < 0.001] versus RES (N = 57), with high 5-year PFS/OS for NED (93.2%/97.4%) relative to RES (10.6%/61.3%). Premenopausal status (p = 0.006), de-novo metastases (p = 0.002), and no palliative radiotherapy (p = 0.01) were associated with NED. Overall, 6/7 (85.7%) patients with NED were alive and disease-free after discontinuing HER2 treatment (≥1 year) versus 1/17 (5.9%) with RES. CONCLUSIONS: Long-term responders with NED have better survival compared to RES. Premenopausal status and de novo metastatic disease are associated with NED. Prospective studies of HER2 therapy discontinuation with NED in MBC are warranted.

The Impact of Chronic Kidney Disease in Patients With Locally Advanced Rectal Cancer Treated With Neoadjuvant Chemoradiation.

BACKGROUND: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied. OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer. DESIGN: This is a multi-institutional, retrospective cohort study. SETTINGS: This study was conducted at academic and community cancer centers participating in the Canadian Health Outcomes Research Database Consortium Rectal Cancer Database. PATIENTS: Consecutive patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were selected. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, pathologic complete response, and neoadjuvant chemotherapy/radiotherapy completion rate were the primary outcomes measured. RESULTS: A total of 1254 patients were included. Median age was 62, and 29%/69% had clinical stage II and III disease. Median estimated creatinine clearance was 93 mL/min, with 11% <60 mL/min (n = 136). There was no significant difference in the completion rate of neoadjuvant chemotherapy (82% vs 85%, p = 0.36) or radiotherapy (93% vs 95%, p = 0.45) between patients with and without chronic kidney disease. Patients with chronic kidney disease were less likely to receive adjuvant chemotherapy (63% vs 77%, p < 0.01). On multivariate analysis, patients with chronic kidney disease had decreased disease-free survival (HR, 1.37; 95% CI, 1.03-1.82; p = 0.03) but not overall survival (HR, 1.23; 95% CI, 0.88-1.75; p = 0.23) or pathologic complete response (OR, 0.83; 95% CI, 0.50-1.39; p = 0.71). LIMITATIONS: This study was limited by its retrospective design and by limited events for overall survival analysis. CONCLUSIONS: In patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation, baseline chronic kidney disease was associated with less use of adjuvant chemotherapy and decreased disease-free survival. Chronic kidney disease was not independently associated with neoadjuvant chemotherapy/radiotherapy completion rate, pathologic complete response, or overall survival. These data suggest that patients with locally advanced rectal cancer with chronic kidney disease may have distinct outcomes and, accordingly, the results of landmark clinical trials may not be generalizable to this population. See Video Abstract at http://links.lww.com/DCR/B694. LA REPERCUSIN DE LA ENFERMEDAD RENAL CRNICA EN PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON QUIMIORRADIOTERAPIA NEOADYUVANTE: ANTECEDENTES:Los pacientes con enfermedad renal crónica generalmente se excluyen de los ensayos clínicos. La repercusión de la enfermedad renal crónica en el desenlace en pacientes con cáncer de recto localmente avanzado no se ha estudiado previamente.OBJETIVO:Investigar la repercusión de la enfermedad renal crónica en los desenlaces en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo multiinstitucional.ESCENARIO:Centros oncológicos académicos y comunitarios que participan en la base de datos de cáncer rectal del consorcio CHORD.PACIENTES:Pacientes consecutivos con cáncer de recto localmente avanzado, tratados con quimiorradioterapia neoadyuvante, previa a la cirugía con intención curativa del 2005 al 2013.PRINCIPALES VARIABLES EVALUADAS:Sobrevida libre de enfermedad, sobrevida global, respuesta patológica completa, tasa de conclusión de quimioterapia / radioterapia neoadyuvante.RESULTADOS:Se incluyeron 1254 pacientes. El promedio de edad fue de 62, y el 29% / 69% tenían enfermedad en estadio clínico II y III, respectivamente. El promedio de la depuración de creatinina estimada fue de 93 mililitros / minuto, con un 11% <60 mililitros / minuto (n = 136). No hubo diferencias significativas en la tasa de conclusión de la quimioterapia neoadyuvante (82% vs 85%, p = 0,36) o radioterapia (93% vs 95%, p = 0,45) entre pacientes con y sin enfermedad renal crónica. Los pacientes con enfermedad renal crónica tenían menos probabilidades de recibir quimioterapia adyuvante (63% contra el 77%, p <0,01). En el análisis multivariado, los pacientes con enfermedad renal crónica tenían una sobrevida libre de enfermedad menor (HR 1,37, IC 95% 1,03-1,82, p = 0,03) pero no en la sobrevida global (HR 1,23, IC 95% 0,88-1,75, p = 0,23) o respuesta patológica completa (OR 0,83, IC 95% 0,50-1,39, p = 0,71).LIMITACIONES:Diseño retrospectivo y acontecimientos limitados para el análisis de sobrevida global.CONCLUSIONES:En pacientes con cáncer de recto localmente avanzado tratados con quimiorradioterapia neoadyuvante, la enfermedad renal crónica de base se asoció con un menor uso de quimioterapia adyuvante y una menor sobrevida libre de enfermedad. La enfermedad renal crónica no se asoció de forma independiente con la tasa de conclusión de la quimioterapia / radioterapia neoadyuvante, la respuesta patológica completa o la sobrevida global. Estos datos sugieren que los pacientes con cáncer de recto localmente avanzado con enfermedad renal crónica pueden tener resultados distintos y, en consecuencia, los resultados de los ensayos clínicos de referencia pueden no ser generalizables a esta población. Consulte Video Resumen en http://links.lww.com/DCR/B694.

Prognostic Significance of Disease Control at 12 Weeks in Patients With Advanced Pancreatic Cancer Receiving FOLFIRINOX as First-line Chemotherapy.

OBJECTIVES: The POLO (Pancreas Cancer Olaparib Ongoing) trial demonstrated improvement in progression-free survival (PFS) with olaparib maintenance in advanced pancreatic cancer (APC) patients with germline BRCA1/2 mutations who had disease control after 16 weeks of platinum-based first-line therapy. However, in the real-world, the first assessment is usually performed at 12 weeks. Therefore, this study aimed to identify the proportion of real-world patients with APC that have disease control at 12 weeks (DC12) after FOLFIRINOX, assess any associations of baseline variables with DC12, and to determine the effect of DC12 on PFS and overall survival (OS). METHODS: APC patients treated with first-line FOLFIRINOX from 2011 to 2018 in Alberta, Canada, were identified. We conducted an analysis of baseline characteristics to identify factors associated with DC12 and to compare the PFS and OS of patients with DC12 to those with earlier disease progression. RESULTS: We identified 165 APC patients treated with FOLFIRINOX with unknown BRCA1/2 status, of which 56% were men, and the median age at diagnosis was 59 years (interquartile range, 38 to 75 y). Of these, 72 (44%) had DC12. Lower serum carbohydrate antigen 19.9 and normal serum albumin were associated with a higher likelihood of DC12. The PFS and OS of patients with DC12 was significantly higher than those with earlier progression (9.3 vs. 2.5 mo; hazard ratio, 0.22; 95% confidence interval, 0.15-0.32; P<0.001; 21.6 vs. 8.9 mo; hazard ratio, 0.35; 95% confidence interval, 0.25-0.49; P<0.0001). CONCLUSION: Less than half of real-world patients treated with first-line FOLFIRINOX have DC12. Patients with APC who have higher carbohydrate antigen 19.9 and low albumin are less likely to have DC12. DC12 is significantly associated with longer PFS and OS.

Hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy: a real-world study.

OBJECTIVE: To assess the patterns of hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy and to identify high-risk groups that may benefit from more careful monitoring in a real-world, population-based context. METHODS: This is a population-based study using linked administrative databases from the province of Alberta, Canada. Any events of hospitalization among patients with non-metastatic colon cancer undergoing upfront surgery followed by adjuvant chemotherapy were reviewed. Multivariable logistic regression analysis was used to examine factors associated with risk of hospitalization, and the impact of hospitalization on overall survival was assessed through Kaplan-Meier estimates and Multivariable Cox regression analysis. RESULTS: A total of 2257 patients were considered eligible and were included in the current analysis, including 483 patients (21.4%) who were hospitalized within 6 months of the start of adjuvant chemotherapy, and 1774 patients (78.6%) who were not. The following factors were associated with a higher hospitalization risk: older age (OR: 1.02; 95% CI 1.01-1.03), higher comorbidity (OR: 1.48; 95% CI 1.31-1.67), women (OR for men versus women: 0.79; 95% CI 0.64-0.98), living in the North zone (OR for Edmonton zone versus North zone: 0.60; 95% CI 0.42-0.87), and CAPOX chemotherapy (OR for CAPOX versus FOLFOX: 1.50; 95% CI 1.12-2.00). Patients with a history of hospitalization during adjuvant chemotherapy had a worse overall survival compared to patients who were not hospitalized (P < 0.001). CONCLUSION: In this study, one out of five colon cancer patients were hospitalized during adjuvant chemotherapy. Older individuals, women, those with higher comorbidity, and those receiving adjuvant CAPOX were more likely to be hospitalized.

Real-World Outcomes of Oxaliplatin-Based Chemotherapy on R0 Resected Colonic Liver Metastasis.

INTRODUCTION: In resected colonic liver metastasis (CLM), randomized studies of oxaliplatin-based chemotherapy have demonstrated improvements in disease-free survival (DFS), but not overall survival (OS). Additionally, oxaliplatin regimens have not been compared to non-oxaliplatin chemotherapy. Despite limited evidence, perioperative chemotherapy is often used in the management of CLM. The primary aim of this study was to assess the impact of oxaliplatin chemotherapy regimens on OS in patients who have undergone resection of CLM in a real-world setting. PATIENTS AND METHODS: Patients who underwent resection of CLM in the provinces of Alberta and British Columbia, Canada, were identified from 1996 to 2016. Perioperative (pre- and/or post-) systemic therapy was categorized as oxaliplatin or non-oxaliplatin-based chemotherapy or no chemotherapy. The primary and secondary outcomes were OS and DFS, respectively. RESULTS: We identified 511 patients who underwent R0 resection of CLM. A significant difference in median OS was identified among the oxaliplatin, non-oxaliplatin, and no-chemotherapy groups of 100, 60, and 59 months, respectively (P = .009). In multivariate analysis, patients who received oxaliplatin regimens had a lower risk of death (hazard ratio, 0.68; 95% confidence interval, 0.51-0.92; P = .012), whereas the non-oxaliplatin chemotherapy group did not (hazard ratio, 0.88; 95% confidence interval, 0.65-1.20; P = .422) compared with no chemotherapy. CONCLUSIONS: In this multicenter, retrospective, population-based study, perioperative oxaliplatin-based chemotherapy was associated with improved OS in conjunction with R0 resection of CLM. Further studies should evaluate the optimal duration and sequencing of perioperative chemotherapy in relation to curative-intent surgical resection of CLM.

Oncology Clinicians' Challenges to Providing Palliative Cancer Care-A Theoretical Domains Framework, Pan-Cancer System Survey.

Despite the known benefits, healthcare systems struggle to provide early, integrated palliative care (PC) for advanced cancer patients. Understanding the barriers to providing PC from the perspective of oncology clinicians is an important first step in improving care. A 33-item online survey was emailed to all oncology clinicians working with all cancer types in Alberta, Canada, from November 2017 to January 2018. Questions were informed by Michie's Theoretical Domains Framework and Behaviour Change Wheel (BCW) and queried (a) PC provision in oncology clinics, (b) specialist PC consultation referrals, and (c) working with PC consultants and home care. Respondents (n = 263) were nurses (41%), physicians (25%), and allied healthcare professionals (18%). Barriers most frequently identified were "clinicians' limited time/competing priorities" (64%), "patients' negative perceptions of PC" (63%), and clinicians' capability to manage patients' social issues (63%). These factors mapped to all three BCW domains: motivation, opportunity, and capability. In contrast, the least frequently identified barriers were clinician motivation and perceived PC benefits. Oncology clinicians' perceptions of barriers to early PC were comparable across tumour types and specialties but varied by professional role. The main challenges to early integrated PC include all three BCW domains. Notably, motivation is not a barrier for oncology clinicians; however, opportunity and capability barriers were identified. Multifaceted interventions using these findings have been developed, such as tip sheets to enhance capability, reframing PC with patients, and earlier specialist PC nursing access, to enhance clinicians' use of and patients' benefits from an early PC approach.

Delving into Early-onset Pancreatic Ductal Adenocarcinoma: How Does Age Fit In?

PURPOSE: With the rising incidence of early-onset pancreatic cancer (EOPC), molecular characteristics that distinguish early-onset pancreatic ductal adenocarcinoma (PDAC) tumors from those arising at a later age are not well understood. EXPERIMENTAL DESIGN: We performed bioinformatic analysis of genomic and transcriptomic data generated from 269 advanced (metastatic or locally advanced) and 277 resectable PDAC tumor samples. Patient samples were stratified into EOPC (age of onset ≤55 years; n = 117), intermediate (age of onset 55-70 years; n = 264), and average (age of onset ≥70 years; n = 165) groups. Frequency of somatic mutations affecting genes commonly implicated in PDAC, as well as gene expression patterns, were compared between EOPC and all other groups. RESULTS: EOPC tumors showed significantly lower frequency of somatic single-nucleotide variant (SNV)/insertions/deletions (indel) in CDKN2A (P = 0.0017), and were more likely to achieve biallelic mutation of CDKN2A through homozygous copy loss as opposed to heterozygous copy loss coupled with a loss-of-function SNV/indel mutation, the latter of which was more common for tumors with later ages of onset (P = 1.5e-4). Transcription factor forkhead box protein C2 (FOXC2) was significantly upregulated in EOPC tumors (P = 0.032). Genes significantly correlated with FOXC2 in PDAC samples were enriched for gene sets related to epithelial-to-mesenchymal transition (EMT) and included VIM (P = 1.8e-8), CDH11 (P = 6.5e-5), and CDH2 (P = 2.4e-2). CONCLUSIONS: Our comprehensive analysis of sequencing data generated from a large cohort of PDAC patient samples highlights a distinctive pattern of biallelic CDKN2A mutation in EOPC tumors. Increased expression of FOXC2 in EOPC, with the correlation between FOXC2 and EMT pathways, represents novel molecular characteristics of EOPC.See related commentary by Lou, p. 8.

Subtype-Discordant Pancreatic Ductal Adenocarcinoma Tumors Show Intermediate Clinical and Molecular Characteristics.

PURPOSE: RNA-sequencing-based subtyping of pancreatic ductal adenocarcinoma (PDAC) has been reported by multiple research groups, each using different methodologies and patient cohorts. "Classical" and "basal-like" PDAC subtypes are associated with survival differences, with basal-like tumors associated with worse prognosis. We amalgamated various PDAC subtyping tools to evaluate the potential of such tools to be reliable in clinical practice. EXPERIMENTAL DESIGN: Sequencing data for 574 PDAC tumors was obtained from prospective trials and retrospective public databases. Six published PDAC subtyping strategies (Moffitt regression tools, clustering-based Moffitt, Collisson, Bailey, and Karasinska subtypes) were used on each sample, and results were tested for subtype call consistency and association with survival. RESULTS: Basal-like and classical subtype calls were concordant in 88% of patient samples, and survival outcomes were significantly different (P < 0.05) between prognostic subtypes. Twelve percent of tumors had subtype-discordant calls across the different methods, showing intermediate survival in univariate and multivariate survival analyses. Transcriptional profiles compatible with that of a hybrid subtype signature were observed for subtype-discordant tumors, in which classical and basal-like genes were concomitantly expressed. Subtype-discordant tumors showed intermediate molecular characteristics, including subtyping gene expression (P < 0.0001) and mutant KRAS allelic imbalance (P < 0.001). CONCLUSIONS: Nearly 1 in 6 patients with PDAC have tumors that fail to reliably fall into the classical or basal-like PDAC subtype categories, based on two regression tools aimed toward clinical practice. Rather, these patient tumors show intermediate prognostic and molecular traits. We propose close consideration of the non-binary nature of PDAC subtypes for future incorporation of subtyping into clinical practice.

Information Access and Use by Patients With Cancer and Their Friends and Family: Development of a Grounded Theory.

BACKGROUND: Information has been identified as a commonly unmet supportive care need for those living with cancer (ie, patients and their friends and family). The information needed to help individuals plan their lives around the consequences of cancer, such as the receipt of health care, is an example of an important informational need. A suitable theory to guide the development of interventions designed to meet this informational need has not been identified by the authors. OBJECTIVE: The aim of this study is to generate a grounded theory capable of guiding the development of interventions designed to assist those living with cancer in meeting their informational needs. METHODS: Classic grounded theory was used to analyze data collected through digitally recorded one-on-one audio interviews with 31 patients with cancer and 29 friends and family members. These interviews focused on how the participants had accessed and used information to plan their lives and what barriers they faced in obtaining and using this information. RESULTS: The theory that emerged consisted of 4 variables: personal projects, cancer as a source of disruption to personal projects, information as the process of accessing and interpreting cancer-related data (CRD) to inform action, and CRD quality as defined by accessibility, credibility, applicability, and framing. CRD quality as a moderator of personal project disruption by cancer is the core concept of this theory. CONCLUSIONS: Informational resources providing accessible, credible, applicable, and positively framed CRD are likely key to meeting the information needs of those affected by cancer. Web-based informational resources delivering high-quality CRD focused on assisting individuals living with cancer in maintaining and planning their personal projects are predicted to improve quality of life. Research is needed to develop and integrate resources informed by this theoretical framework into clinical practice.

A Smartphone App-Based Mindfulness Intervention for Cancer Survivors: Protocol for a Randomized Controlled Trial.

BACKGROUND: Cancer patients transitioning to survivorship after completing cancer treatments need psychosocial interventions to manage stressors such as anxiety, depression, and fear of cancer recurrence. Mindfulness-based interventions (MBIs) are effective for treating these symptoms; however, cancer survivors are often unable to participate in face-to-face interventions because of difficulties such as work and family commitments, treatment-related side-effects, scheduling conflicts, and geography. Smartphone app-based MBIs are an innovative way to deliver psychosocial cancer care and can overcome several such difficulties, since patients can participate at their own convenience. OBJECTIVE: The SEAMLESS (Smartphone App-Based Mindfulness Intervention for Cancer Survivors) study aims to evaluate the efficacy of a tailored app-based mindfulness intervention for cancer survivors (the Am Mindfulness-Based Cancer Survivorship-MBCS-Journey) for treating (1) symptoms of stress (primary outcome), as well as (2) fear of cancer recurrence, anxiety, depression, fatigue, and overall physical functioning (secondary outcomes). This is the first Canadian efficacy trial of a tailored mindfulness app intervention in cancer survivors. METHODS: This is a randomized waitlist-controlled trial, which will evaluate the effectiveness of Am MBCS for impacting the primary and secondary outcomes in cancer survivors who have completed all their cancer treatments. Outcomes will be assessed using web-based surveys with validated psychometric instruments at (1) baseline, (2) mid-intervention (2 weeks later), (3) immediately postintervention (4 weeks), (4) 3 months postbaseline, (5) 6 months postbaseline, and (6) 12 months postbaseline. The waitlist group will complete all assessments and will cross over to the intervention condition after the 3-month assessment. In addition, data will be obtained by the smartphone app itself, which includes users' engagement with the app-based intervention, their emotional state (eg, angry and elated) from a user-inputted digital emotion-mapping board, and psychobiometric data using photoplethysmography technology. RESULTS: The study received ethics approval in September 2018 and recruitment commenced in January 2019. Participants are being recruited through a provincial cancer registry, and the majority of participants currently enrolled are breast (44/83, 53%) or colorectal (17/83, 20%) cancer survivors, although some survivors of other cancer are also present. Data collection for analysis of the primary outcome time-point will be complete by September 2019, and the follow-up data will be collected and analyzed by September 2020. Data will be analyzed to determine group differences using linear mixed modelling statistical techniques. CONCLUSIONS: Cancer care providers are uncertain about the efficacy of app-based mindfulness interventions for patients, which are available in great supply in today's digital world. This study will provide rigorously evaluated efficacy data for an app-based mindfulness intervention for cancer survivors, which if helpful, could be made available for psychosocial care at cancer centers worldwide. TRIAL REGISTRATION: ClinicalTrials.gov NCT03484000; https://clinicaltrials.gov/ct2/show/NCT03484000. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15178.

The impact of driving time, distance, and socioeconomic factors on outcomes of patients with locally advanced rectal cancer.

Objectives: Cancer patients experience disparities due to socioeconomic status (SES) factors. We assessed the impact of SES factors on outcomes in patients with locally advanced rectal cancer (LARC) who received neoadjuvant chemoradiation (nCRT) and surgery (Sx) in 3 Canadian provinces. Study design: This study was a multi-institutional retrospective chart review. Methods: Associations among community characteristics (2016 Canadian Census data), distance and time to the cancer center (mapping software), and outcomes were evaluated using the CHORD multi-institutional database. Results: 1,064 patients were included. Median age 62, 68% male, 15% lived in a rural community, 19% with median community household income >$50,000 CAD, median community proportion with post-secondary education 66%, 12% lived >100km away, and 18% lived >1 â€‹h away.Factors predictive of worse disease-free survival (DFS) and overall survival (OS) in univariate analysis included driving time >1 â€‹h, median community income ≤$50,000 CAD, driving distance >100km, and lower median community proportion with post-secondary education. Driving time >1 â€‹h remained significant in multivariate analysis for worse DFS (HR 1.47; 95% CI 1.14-1.90; p â€‹= â€‹0.003) and OS (HR 1.60, 95% CI 1.19-2.16; p â€‹= â€‹0.002). Conclusion: Outcomes of patients with LARC undergoing nCRT are negatively associated with increased driving time to the cancer centre.