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.
Novel inhaled therapeutics including antibiotics, vaccines and anti-hypertensives, have led to innovations in designing suitable delivery systems. These emerging design technologies are in urgent ...demand to ensure high aerosolisation performance, consistent efficacy and satisfactory patient adherence. Recent vibrating-mesh and software technologies have resulted in nebulisers that have remarkably accurate dosing and portability. Alternatively, dry powder inhalers (DPIs) have become highly favourable for delivering high-dose and single-dose drugs with the aid of advanced particle engineering. In contrast, innovations are needed to overcome the technical constrains in drug–propellant incompatibility and delivering high-dose drugs with pressurised metered dose inhalers (pMDIs). This review discusses recent and emerging trends in pulmonary drug delivery systems.
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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.
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.
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.
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.
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 standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline ...neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC.
We reviewed patients with LARC undergoing nCRT followed by surgery from 2005 to 2013 across 8 Canadian cancer centres. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for associations between baseline hematologic variables and outcomes.
Of 1527 identified patients, 1237 (81%) were included in the DFS/OS analysis. Median age was 62 (range 23-88), 69% were male, and 80% had performance status (PS) 0-1. Twenty-six percent had elevated NLR (≥ 4), and 66% had elevated PLR (≥ 150). Ninety-seven percent of patients received FP-based nCRT, with 96% receiving ≥44 Gy. 81% completed neoadjuvant chemotherapy and 95% completed neoadjuvant radiotherapy, with a pCR rate of 18%. After a median follow-up time of 71 months, 8% developed local recurrence, 22% developed distant recurrence and 24% died. 5-year DFS and OS were 69% (95% CI 66-72%) and 79% (95% CI 77-82%), respectively. In multivariate analyses, elevated baseline NLR and PLR were neither prognostic for DFS and OS nor predictive of pCR.
NLR and PLR were not found to be independently prognostic for DFS or OS and did not predict for pCR in patients with LARC undergoing nCRT followed by surgery.
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.
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l-Leucine (LL) has been widely used to enhance the dispersion performance of powders for inhalation. LL can also protect powders against moisture, but this effect is much less ...studied. The aim of this study was to investigate whether LL could prevent moisture-induced deterioration in in vitro aerosolization performances of highly hygroscopic spray-dried powders. Disodium cromoglycate (DSCG) was chosen as a model drug and different amounts of LL (2–40% w/w) were added to the formulation, with the aim to explore the relationship between powder dispersion, moisture protection and physicochemical properties of the powders. The powder formulations were prepared by spray drying of aqueous solutions containing known concentrations of DSCG and LL. The particle sizes were measured by laser diffraction. The physicochemical properties of fine particles were characterized by X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic vapor sorption (DVS). The surface morphology and chemistry of fine particles were analyzed by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). In vitro aerosolization performances were evaluated by a next generation impactor (NGI) after the powders were stored at 60% or 75% relative humidity (RH), and 25°C for 24h. Spray-dried (SD) DSCG powders were amorphous and absorbed 30–45% (w/w) water at 70–80% RH, resulting in deterioration in the aerosolization performance of the powders. LL did not decrease the water uptake of DSCG powders, but it could significantly reduce the effect of moisture on aerosolization performances. This is due to enrichment of crystalline LL on the surface of the composite particles. The effect was directly related to the percentage of LL coverage on the surface of particles. Formulations having 61–73% (molar percent) of LL on the particle surface (which correspond to 10–20% (w/w) of LL in the bulk powders) could minimize moisture-induced deterioration in the aerosol performance. In conclusion, particle surface coverage of LL can offer short-term protection against moisture on dispersion of hygroscopic powders.
Our aims were to determine the correlations between progression-free survival (PFS), time to progression (TTP), and response rate (RR) with overall survival (OS) in the first-line treatment of ...metastatic colorectal cancer (MCRC), and to identify a potential surrogate for OS.
Randomized trials of first-line chemotherapy in MCRC were identified, and statistical analyses were undertaken to evaluate the correlations between the end points.
Thirty-nine randomized controlled trials were identified containing a total of 87 treatment arms. Among trials, the nonparametric Spearman rank correlation coefficient (r(s)) between differences (Delta) in surrogate end points (DeltaPFS, DeltaTTP, and DeltaRR) and DeltaOS were 0.74 (95% CI, 0.47 to 0.88), 0.52 (95% CI, 0.004 to 0.81), 0.39 (95% CI, 0.08 to 0.63), respectively. The r(s) for DeltaPFS was not significantly different from the r(s) DeltaTTP (P = .28). Linear regression analysis was performed using hazard ratios for PFS and OS. There was a strong relationship between hazard ratios for PFS and OS; the slope of the regression line was 0.54 +/- 0.10, indicating that a novel therapy producing a 10% risk reduction for PFS will yield an estimated 5.4% +/- 1% risk reduction for OS.
In first-line chemotherapy trials for MCRC, improvements in PFS are strongly associated with improvements in OS. In this patient population, PFS may be an appropriate surrogate for OS. As a clinical end point, PFS offers increased statistical power at a given time of analysis and a significant lead time advantage compared with OS.
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).
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.
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).
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.
(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
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.
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