Pressing challenges have forced health care providers to rethink traditional silos and professional boundaries. Communities of practice (cops) have been identified as a means to share knowledge across silos and boundaries. However, clarity sufficient to enable their easy and uniform reproducibility is lacking, leading to a gap between cop conceptualization and implementation. This paper explores a cop structure and outlines a framework that is adaptable, measurable, and implementable across health disciplines in a regional cancer surgery program.
Community of practice; regional collaborations; quality improvement; health care services research; knowledge translation
Anaplastic lymphoma kinase (ALK) rearrangements have been identified as key oncogenic drivers in a small subset of non-small-cell lung cancers (nsclcs). Small-molecule Alk kinase inhibitors such as crizotinib have transformed the natural history of nsclc for this subgroup of patients. Because of the prevalence of nsclc, ALK-positive patients represent an important example of the paradigm for personalized medicine. Although Alk inhibitors such as crizotinib are well tolerated, there is a potential for adverse events to occur. Proactive monitoring, treatment, and education concerning those adverse events will help to optimize the therapeutic index of the drugs. The present review summarizes the management of treatment-related adverse events that can arise with Alk inhibitors such as crizotinib.
Anaplastic lymphoma kinase inhibitors; ALK; crizotinib; adverse events; lung cancer
Patients requiring assessment for cancer surgery encounter a complex series of steps in their cancer journey. Further complicating the process is the fact that care is often delivered in a fragmented, silo-based system. Isolated strategies to improve cancer outcomes within those systems have had inconsistent results.
A regional quality improvement collaborative was developed based on a community of practice (cop) platform, a hub-and-spoke infrastructure, and a regional steering committee linking cop improvement projects with affiliated hospitals and their strategic priorities. The cop provided an avenue for multidisciplinary teams to collect and compare their performance data and to institute regional standards through literature review, discussion, and consensus. Regional interdisciplinary teams developed a set of quality indicators linked to mutually agreed-upon care standards. A limited regional database supported feedback about performance against both provincial and regional standards.
The cop approach helped to develop a multihospital collaboration that facilitated care quality improvements on a regional scale, with clinical outcomes of the improvements able to be measured. The 9 participating hospitals delivered cancer surgery in the specific disease sites according to practitioner-developed and provincially- or regionally-generated care standards and clinical pathways. Compliance with provincial evidence-based clinical guidelines improved (20% increase in 2010–2011 compared with 2006–2007). Other significant improvements included standardization and implementation of regional perioperative pathways in breast, colorectal, and prostate cancer disease sites; rectal cancer surgery centralization; increased use of sentinel lymph node biopsies in breast cancer surgery; and decreased positive surgical margin rates in prostate cancer.
Improved quality is likely a result of diverse confounding factors. The deliberately cultivated multihospital multidisciplinary cops have contributed to positive structural and functional change in cancer surgery in the region. This regional cop model has the potential to play an important role in the development of successful collaborations in care quality improvement.
Community of practice; regional collaboration; quality improvement; cancer care
Although bendamustine has been used to treat lymphoproliferative disorders for decades, it has only recently been approved for use in Canada. Thus, Canadian recommendations on the administration of bendamustine and the management of common adverse events (aes) are needed. This article highlights effective management and assessment strategies recommended by Canadian nurses and pharmacists for the most common aes arising from the use of bendamustine in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Those strategies include administering bendamustine over 60 minutes instead of 30 minutes, administering pre-medications to control infusion-related reactions and nausea, hydrating patients to minimize fatigue, and using free-flowing saline at the closest port to prevent phlebitis.
Bendamustine; adverse events; toxicities; chronic lymphocytic leukemia; indolent non-Hodgkin lymphoma; nhl; cll; inhl; fatigue; nausea
Myelodysplastic syndromes (mdss) constitute a heterogeneous group of malignant hematologic disorders characterized by marrow dysplasia, ineffective hematopoiesis, peripheral blood cytopenias, and pronounced risk of progression to acute myeloid leukemia. Azacitidine has emerged as an important treatment option and is recommended by the Canadian Consortium on Evidence-Based Care in mds as a first-line therapy for intermediate-2 and high-risk patients not eligible for allogeneic stem cell transplant; however, practical guidance on how to manage patients through treatment is limited. This best practice guideline provides recommendations by a panel of experts from Canadian centres of excellence on the selection and clinical management of mds patients with azacitidine. Familiarity with the referral process, treatment protocols, dose scheduling, treatment expectations, response monitoring, management of treatment breaks and adverse events, and multidisciplinary strategies for patient support will improve the opportunity for optimizing treatment outcomes with azacitidine.
Myelodysplastic syndrome; mds; 5-azacitidine; Vidaza; clinical outcomes; practical recommendations; guidelines
Since the first introduction of tumour markers, their usefulness for diagnosis has been a challenging question. The aim of the present prospective study was to investigate, in colorectal cancer patients, the relationship between preoperative tumour marker concentrations and various clinical variables.
The study prospectively enrolled 131 consecutive patients with a confirmed diagnosis of colorectal carcinoma and 131 age- and sex-matched control subjects with no malignancy. The relationships of the tumour markers carcinoembryonic antigen (cea) and carbohydrate antigen (ca) 19-9 with disease stage, tumour differentiation (grade), mucus production, liver function tests, T stage, N stage, M stage were investigated.
Serum concentrations of cea were significantly higher in the patient group than in the control group (p = 0.001); they were also significantly higher in stage iii (p = 0.018) and iv disease (p = 0.001) than in stage i. Serum concentrations of cea were significantly elevated in the presence of spread to lymph nodes (p = 0.005) in the patient group. Levels of both tumour markers were significantly elevated in the presence of distant metastasis in the patient group (p = 0.005 for cea; p = 0.004 for ca 19-9).
Preoperative levels of cea and ca 19-9 might provide an estimate of lymph node invasion and distant metastasis in colorectal cancer patients.
Carbohydrate antigen 19-9; carcinoembryonic antigen; colorectal cancer
Breast cancer treatment guidelines state that radiotherapy (rt) can reasonably be omitted in selected women 70 years of age and older if they take adjuvant endocrine therapy (aet) for 5 years. We aimed to assess persistence and adherence to aet in women 70 years of age and older, and to examine differences between rt receivers and non-receivers.
Quebec’s medical service and pharmacy claims databases were used to identify seniors undergoing breast-conserving surgery (1998–2005) and initiating aet. Cox proportional hazards models were used to identify predictors of aet non-persistence.
Of 3180 women who initiated aet (mean age: 77.5 years), 28% did not receive rt. During the subsequent 5 years, 32% of patients who initiated aet did not persist, 2% filled only a single prescription, and 22% switched medications. Compared with rt receivers, non-receivers discontinued more often (35.5% vs. 30.1%) and earlier (1.4 years vs. 1.6 years). They also became nonadherent earlier (medication possession ratio < 80% at year 3 vs. at year 5). Predictors of nonpersistence included rt omission [hazard ratio (hr): 1.26; 95% confidence interval (ci): 1.09 to 1.46]; age (hr per decade increase: 1.15; 95% ci: 1.01 to 1.31); new medications (hr per medication: 1.01; 95% ci: 1.00 to 1.02); and hospitalizations during aet, (hr per hospitalization: 1.08; 95% ci: 1.05 to 1.11). In a subanalysis of rt non-receivers, significant predictors included hospitalizations (hr: 1.07; 95% ci: 1.02 to 1.12) and medications at aet start (hr: 0.94; 95% ci: 0.91 to 0.97).
Suboptimal use of aet was observed in at least one third of women. In rt non-receivers, aet use was worse than it was in rt receivers. Initiation of new medications and hospitalizations increased the risk of non-persistence.
Adjuvant endocrine therapy; persistence; adherence; radiotherapy; breast cancer; seniors
Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy.
In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.
Colorectal metastasis; liver metastasis; review; hepatic artery infusion pump chemotherapy; intra-arterial chemotherapy
In recent years, considerable attention has been paid to the role of neoadjuvant chemotherapy as a pluripotential test bed for the treatment of breast cancer. Although traditionally reserved to render inoperable disease operable, neoadjuvant chemotherapy is increasingly being used to improve the chance for breast-conserving surgery, to gain information on pathologic response rates for a more rapid assessment of new chemotherapy–biologic regimens, and also to study in vivo tumour sensitivity or resistance to the agent being used.
Similarly, use of neoadjuvant endocrine treatment was also traditionally restricted to elderly or frail patients who were felt to be unsuitable for chemotherapy. It is therefore not surprising that, given the increasing realization of the pivotal role of endocrine therapy in patient care, there is enhanced interest in neoadjuvant endocrine therapy not only as a less-toxic alternative to chemotherapy, but also to assess tumour sensitivity or resistance to endocrine agents.
The availability of newer endocrine manipulations and increasing evidence that the benefits of chemotherapy are frequently marginal in many hormone-positive patients is making endocrine therapy increasingly important in the clinical setting. The hope is that, one day, instead of preoperative endocrine therapy being restricted to the infirm and the elderly, it will be used in the time between biopsy diagnosis and surgery to predict which patients will or will not benefit from chemotherapy in the adjuvant setting.
Medical oncology; breast cancer; neoadjuvant therapy; endocrine therapy
Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used.
We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements:
haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases.
These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip
Colorectal metastases; liver metastases; unresectable metastases; adjuvant chemotherapy; intraarterial chemotherapy; hepatic arterial infusion pump chemotherapy
Cancer can be a devastating diagnosis. In particular, malignancy and its indicated treatments have profoundly negative effects on the fertility of young cancer patients. Oncofertility has emerged as a new interdisciplinary field to address the issue of gonadotoxicity associated with cancer therapies and to facilitate fertility preservation. In Canada, these fertility issues are often inadequately addressed despite the availability of resources. The goal of this four-part series is to facilitate systemic improvements in fertility preservation for adolescent and young adult Canadians with a new diagnosis of cancer.
This article reviews fertility preservation options that use cryopreservation techniques. It also outlines some of the alternative options for future parenthood.
Cryopreservation of a woman’s gametes and gonadal tissue may involve embryo, oocyte, and ovarian tissue cryopreservation with or without ovarian stimulation. Similarly, male gametes and gonadal tissue may be cryopreserved. Techniques and success rates continue to improve. Third-party assistance through gamete donation, gestational carriers, and adoption are also alternative options for parenthood.
Cryopreservation techniques are especially feasible options for fertility preservation in the newly diagnosed cancer patient.
Oncofertility; fertility preservation; cryopreservation; gonadotoxicity; young adult; adolescent
Bilineal blast transformation of myeloid and T lymphoid type is a rare event in chronic myeloid leukemia. Here, we report a case in which an adult presented with high white cell counts and lymphadenopathy. Bone marrow studies confirmed the presence of 9 and 22 chromosomal translocation, and a diagnosis of chronic myeloid leukemia in chronic phase was made. Examination of a lymph node showed both myeloid and T lymphoblastoid blast crisis. Molecular studies demonstrated the presence of BCR-ABL fusion transcripts in both the myeloid and the T lymphoblastic component, indicating that the myeloid and T lymphoid blast crisis components shared common progenitors. TP53 deletion was demonstrated by fluorescence in situ hybridization.
Chronic myeloid leukemia; blast transformation; T lymphoblastic lymphoma; BCR-ABL; TP53 mutation; myeloid sarcoma
Mismatch-repair–deficient colorectal cancers often contain kinase-activating V600E BRAF mutations, but no clinical utility has yet been demonstrated in this setting for monotherapy using oral braf kinase inhibitors such as vemurafenib or dabrafenib. Recent studies have indicated that tumour resistance to braf inhibition is mediated by upregulated epidermal growth factor receptor (egfr) signalling, disruption of which is a routine treatment strategy in KRAS wild-type colorectal cancer. In this report, we describe the clinical course of a heavily pretreated patient who elected to receive off-label dual-targeted braf- and egfr-inhibitory therapy with good tolerance and apparent clinical benefit.
Colorectal neoplasms; combination drug therapy; personalized oncology; precision medicine; genomic profiling
Pseudomyxoma peritonei (pmp) is a rare clinical condition defined as extensive intraperitoneal spread of mucus associated with a variety of mucinous tumours of varying biologic behavior. Although appendix or ovaries have usually been implicated as the primary site, cases have been reported in association with neoplastic lesions of other sites. Pseudomyxoma peritonei originating from urachal remnants is a unique entity, reported only 18 times in the English literature thus far. Considering the rarity of the lesion, we report the case of a 50-year-old man surgically treated for pmp associated with a low-grade mucinous urachal neoplasm. Unique aspects of case are the low histologic aggressiveness of the causative lesion (reported only twice worldwide) and the early stage of the disease, with a relatively small amount of intraperitoneal free mucin. Review of the literature about pmp in general and a collation of previously reported cases of pmp originating from the urachus are presented and discussed.
Pseudomyxoma peritonei; urachus; mucinous neoplasms; urachal adenocarcinoma
Oncocytoma is an uncommon neoplasm with a characteristic histologic feature of abundant eosinophilic granular cytoplasm. It almost always occurs in kidney, thyroid, or salivary gland. Pulmonary oncocytoma is a rare pulmonary neoplasm, with fewer than 10 cases reported so far in the available English literature. We encountered one such case that was successfully managed by thoracoscopic lobectomy.
Pulmonary neoplasm; oncocytoma; thoracoscopic surgery
Survivorship care plans (scps) have been recommended as a way to ease the transition from active cancer treatment to follow-up care, to reduce uncertainty for survivors in the management of their ongoing health, and to improve continuity of care. The objective of the demonstration project reported here was to assess the value of scps for cancer survivors in western Canada.
The Alberta CancerBridges team developed, implemented, and evaluated scps for 36 breast and 21 head-and-neck cancer survivors. For the evaluation, we interviewed 12 of the survivors, 9 nurses who delivered the scps, and 3 family physicians who received the scps (n = 24 in total). We asked about satisfaction, usefulness, emotional impact, and communication value. We collected written feedback from the three groups about positive aspects of the scps and possible improvements (n = 85). We analyzed the combined data using qualitative thematic analysis.
Survivors, nurses, and family physicians agreed that scps could ease the transition to survivorship partly by enhancing communication between survivors and care providers. Survivors appreciated the individualized attention and the comprehensiveness of the plans. They described positive emotional impacts, but wanted a way to ensure that their physicians received the scps. Nurses and physicians responded positively, but expressed concern about the time required to implement the plans. Suggestions for streamlining the process included providing survivors with scp templates in advance, auto-populating the templates for the nurses, and creating summary pages for physicians.
The results suggest ways in which scps could help to improve the transition to cancer survivorship and provide starting points for larger feasibility studies.
Care plans; survivorship; communication; breast cancer; head-and-neck cancer; qualitative analysis
Our goal was to determine the economic value of azacitidine in Canada compared with conventional care regimens (ccrs), including best supportive care (bsc) and low- or standard-dose chemotherapy plus bsc in the treatment of higher-risk myelodysplastic syndromes (mdss) and acute myeloid leukemia (aml) with 20%–30% blasts.
The cost–utility model is a lifetime probabilistic Markov model with a 35-day cycle length consisting of 3 health states: mds; transformation to aml with more than 30% blasts; and death. A third-party public payer perspective was adopted. Overall survival was extrapolated beyond the time horizon of the aza-001 trial comparing azacitidine with ccr. Resource use was determined through a questionnaire completed by Canadian hematologists. Utility values were obtained from two studies in which EQ-5D health questionnaire values were mapped from the European Organization for Research and Treatment of Cancer qlq-C30 survey, and SF-6D scores were mapped from the Short Form 12, elicited from 191 and 43 patients in two different trials.
In the base case, azacitidine had an incremental cost-effectiveness ratio (icer) of $86,182 (95% confidence limits: $69,920, $107,157) per quality-adjusted life year (qaly) gained relative to ccr. Comparing azacitidine with bsc, low-dose chemotherapy plus bsc, and standard-dose chemotherapy plus bsc, the icers were, respectively, $86,973, $84,829, and $2,152 per qaly gained. Results were most sensitive to the utility for azacitidine after 6 months of treatment and to overall survival.
The prolonged 9-month median overall survival with azacitidine relative to ccr fills a gap w hen treating patients with higher-risk mds and aml with 20%–30% blasts. The economic value of azacitidine is within the threshold of willingness-to-pay for third-party public payers for oncology treatments in Canada.
Azacitidine; economic evaluation; myelodysplastic syndromes; acute myeloid leukemia
The accord 11/0402 trial demonstrated that folfirinox (5-fluorouracil, leucovorin, irinotecan, oxaliplatin) is significantly more efficacious than gemcitabine monotherapy in the first-line treatment of metastatic pancreatic cancer (mpc). The present study assessed the cost-effectiveness of first-line folfirinox compared with first-line gemcitabine for public payers in Canada.
A Markov model simulated the movement of mpc patients from first-line treatment until death. Overall survival (os) and progression-free survival (pfs) data were derived from accord. Published utility data and Canadian costs were applied based on time in each health state and on treatment-related adverse event (ae) rates. Costs included first- and second-line therapy, monitoring, and costs to treat aes. Two separate analyses were performed. Analysis 1 was based on trial data [first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by second-line platinum-based chemotherapy, with use of granulocyte colony–stimulating factor (g-csf) allowed], and analysis 2 used Ontario treatment patterns before folfirinox funding (first-line folfirinox followed by second-line gemcitabine compared with first-line gemcitabine followed by best supportive care, no use of g-csf).
Compared with first-line gemcitabine, first-line folfirinox resulted in more life-years and quality adjusted life-years (qalys). Probabilistic sensitivity analysis results showed that, for analyses 1 and 2 respectively, folfirinox has a greater than 85% probability and an approximately 80% probability of being cost-effective at the $100,000 threshold.
Compared with gemcitabine, first-line folfirinox significantly prolongs median os. Given the favourable cost per qaly, the improvement in clinical efficacy, and the limited available treatment options, folfirinox represents an attractive cost-effective treatment for mpc.
folfirinox; gemcitabine; cost-effectiveness; pancreatic cancer; accord trial; chemotherapy; quality-adjusted life year; qaly
Delays in chemotherapy because of neutropenia may be associated with poorer outcomes. The purpose of the present study was to examine the effect that granulocyte colony–stimulating factors (g-csfs) have on survival.
We conducted a chart review of all outpatients diagnosed with metastatic colorectal cancer and treated with folfiri chemotherapy (irinotecan, 5-fluorouracil, leucovorin) with or without bevacizumab at Mount Sinai Hospital between 2007 and 2012. Multivariable Cox proportional hazards models were used to compare survival in neutropenic patients treated with g-csf, in neutropenic patients not so treated, and in patients without neutropenia.
The review identified 93 patients, 31 of whom did not experience a neutropenic event. Of the 62 who experienced neutropenia, 18 were managed with g-csf support, and 44, with reductions or delays in dose. Compared with patients experiencing a neutropenic episode not treated with g-csf, those treated with g-csf experienced a nonsignificant increase in time to event [progression or death: hazard ratio (hr): 1.37; 95% confidence limits (cl): 0.72, 2.61], but compared with patients not having a neutropenic episode, the same patients experienced a significant increase in time to event (hr: 2.07; 95% cl: 1.03, 4.15).
In patients who experienced neutropenia, g-csf did not have a statistically significant impact on survival. Time to event was prolonged in g-csf–treated patients compared with patients who did not experience neutropenia.
Colorectal cancer; g-csf; metastasis; neutropenia; progression; survival
The ratio of extracellular mass to body cell mass (ecm/bcm), determined by bioelectrical impedance analysis, has been found to be a potentially useful indicator of nutrition status. Subjective global assessment (sga) is a subjective method of evaluating nutrition status in head-and-neck cancer. The present study was conducted to investigate the association between ecm/bcm and sga in head-and-neck cancer.
Patients were classified as either well-nourished or malnourished by sga. Bioelectrical impedance analysis was conducted on a population of 75 patients with histologically confirmed head-and-neck cancer, and the ecm/bcm was calculated. Receiver operating characteristic curves were estimated using the nonparametric method to determine an optimal cut-off value of the ecm/bcm.
Compared with malnourished patients, those who were well-nourished had a statistically significantly lower ecm/bcm (1.11 vs. 1.28, p = 0.005). An ecm/bcm cut-off of 1.194 was 76% sensitive and 63% specific in detecting malnutrition.
The ecm/bcm can be an indicator that detects malnutrition in patients with head-and-neck cancer. Further observations are needed to validate the significance of the ecm/bcm and to monitor nutrition interventions.
Head-and-neck cancer; bioelectrical impedance analysis; extracellular–to–body cell mass ratio; subjective global assessment
Cervical cancer is a major cause of mortality in Uighur women compared with Han women in the Xinjiang region of China. Although a reduction in the class i major histocompatibility complex (mhc-i) antigen processing machinery (apm) is associated with the development of cervical cancer, the mhc-i apm has not been studied in this particular group of women, who have the highest incidence rate of cervical cancer in China.
We used immunohistochemical staining and polymerase chain reaction amplification of viral dna from infection with the human papilloma virus (hpv) to study the expression of members of the mhc-i apm in cervical cancer sections collected from Uighur and Han women and in cervicitis samples from age-matched counterparts.
Expression of the molecules of interest was compared between two ethnic groups, and expression of transporter associated with antigen processing 1 and 2, heat shock protein 90, and calnexin were found to be reduced even more significantly in Han women with cervical cancer than in Uighur women with same disease. However, compared with Han women, Uighur women had a higher rate of infection with hpv 16.
The mhc-i apm were reduced in cervical cancer, with heterogeneity in the two ethnic groups. The reduction was more pronounced in Han women, who less frequently had hpv 16 infection, suggesting possible differences in the roles of members of the mhc-i apm and in the mechanisms of cervical cancer development in these two ethnic groups despite residence in the same region of China.
tap-1; tap-2; β2-microglobulin; Hsp70; calnexin; Hsp90; Grp94; hpv 16