A quality improvement project to optimize access to psychosocial care for cancer survivors who experience fear of recurrence.

BACKGROUND: The prevalence of moderate to high levels of fear of cancer recurrence (FCR) in cancer survivors may vary from 22% to 87%, although most are not usually referred to psychosocial support. The After Cancer Treatment Transition (ACTT) clinic in Women's College Hospital (Toronto) provides follow-up care to cancer survivors but in a sample of 2893 patients seen April 2019 to March 2022, only 1.5% were referred to a social worker for psychosocial needs. A single-question screening tool is currently available to screen for FCR. OBJECTIVE: To evaluate the use of the single-question screening tool for FCR among cancer survivors and its impact on social work referrals. RESULTS: Between July and October 2022, 788 patients were seen in the ACTT clinic. Generally, most patients in ACTT are breast cancer survivors (75%), and the remaining survivors are a mix of other cancer types (colorectal cancer, ovarian cancer, thyroid cancer, melanoma). Three hundred thirty (41.9%) ACTT patients completed the single-question screening tool for FCR. Most screened patients were female (96%), the average age was 60 years, and most were diagnosed with breast cancer (90%). Among screened patients, 37 (11%) indicated a moderately severe to high level of FCR and efforts were made to refer these 37 patients to a social worker. In the end, 22 (59.5%) patients with moderately severe/high levels of FCR were offered and accepted referral to a social worker. In comparison to the 1.5% referred to social work (among 2893 patients) prior to FCR screening, referrals increased to 6.7% (among 330 screened). CONCLUSION: Use of a single-question FCR screening tool improved identifying cancer survivors in need of psychosocial support and improved access to a social worker.

Outcomes of Early Transition of Low-Risk Thyroid Cancer Patients from Specialist to Primary Care.

BACKGROUND: Recently published clinical pathways for management of thyroid cancer outlined the criteria for transitioning low-risk patients to primary care within one to five years from diagnosis. However, discharge patterns among endocrinologists remain heterogeneous as there lacks a consensus regarding post-treatment care for thyroid cancer patients. OBJECTIVE: This study described general characteristics and outcomes of thyroid cancer patients who were discharged from specialist care and transitioned to a primary care-based follow-up clinic. METHODS: Thyroid cancer patients seen in the After Cancer Treatment Transition (ACTT) clinic at Women's College Hospital (Toronto, Canada) were included in the study. Electronic medical records were reviewed between May and October 2021 to collect patient characteristics and outcomes. Descriptive statistics were calculated. RESULTS: The study cohort included 148 thyroid cancer patients and 76% were female. All cases were papillary thyroid cancer and most diagnoses were classified as T2 (42%), N0 (55%), M0 (91%), and stage 1 (83%). Nearly all patients (n = 147) had complete thyroidectomy. Levels of thyroglobulin and thyroglobulin antibodies (TgAb) were low overall, with only 5% of the study cohort deemed TgAb positive. Mean levels of thyroid stimulating hormone (TSH) measured at 2 time points (1.37 mIU/L, 1.42 mIU/L) were within normal range. About 91% of the study cohort had normal TSH levels and 82% met target TSH levels. There were 2 cases of recurrence; however, investigation determined that they were not initially appropriate candidates for transition to primary care. Nearly 99% (n = 146) of patients had excellent response to therapy, showed no evidence of disease recurrence, and have not required re-referral to specialist care. CONCLUSIONS: These findings may reassure specialists that low-risk, stable thyroid cancer patients can be safely transitioned to primary care for post-treatment follow-up.

An examination of depression, anxiety, and fear of recurrence among cancer survivors who participated in a virtual cognitive behavioral therapy (CBT)-based telephone coaching program.

BACKGROUND: Depression, anxiety, and fear of recurrence (FOR) are prevalent among cancer survivors, and it is recommended that they have access to supportive services and resources to address psychosocial needs during follow-up care. This study examined the impact of a virtual cognitive behavioral therapy (CBT)-based telephone coaching program (BounceBack®) on depression, anxiety, and FOR. METHOD: Through the After Cancer Treatment Transition (ACTT) clinic at the Women's College Hospital (Toronto, Canada), eligible participants were identified, consented, and referred to the BounceBack® program. Program participation involved completion of self-selected online workbooks and support from trained telephone coaches. Measures of depression (PHQ-9), anxiety (GAD-7), and FOR (fear of cancer recurrence inventory, FCRI) were collected at pre-intervention (baseline) and post-intervention (6-month and 12-month time points). For each psychosocial measure, paired t-tests compared mean scores between study time points. Participant experiences and perceptions were collected through a survey. RESULTS: Measures of depression and anxiety significantly improved among participants from pre-intervention to post-intervention. Scores for PHQ-9 and GAD-7 decreased from moderate to mild levels. Measure of FOR also significantly improved, while FCRI sub-scale scores significantly improved for 5 of the 7 factors that characterize FOR (triggers, severity, psychological distress, functional impairment, insight). Participants rated the intervention a mean score of 7 (out of 10), indicating a moderate level of satisfaction and usefulness. CONCLUSION: This study suggested that a virtual CBT-based telephone coaching program can be an effective approach to managing depression, anxiety, and fear of recurrence in cancer survivors.

The development and implementation of the After Cancer Treatment Transition (ACTT) Program for survivors of cancer.

Background: The After Cancer Treatment Transition (ACTT) program at Women's College Hospital (Toronto) is a transitional follow-up program for patients, their families, and healthcare providers to address the broad range of post-cancer treatment and survivorship needs. This publication describes the systematic development and implementation of the ACTT program, with a focus on the advanced practice nursing (APN) role. Program Development: ACTT development required the collaboration of an APN, a general practitioner in oncology (GPO), and an inter-professional team. ACTT developers proposed a clinic structure in an ambulatory setting, linking healthcare professionals to provide post-treatment follow-up and ongoing survivorship care. Post-treatment guidelines were developed based on expert oncologist consensus, cancer site group input, and evidence-informed guidelines or best practice recommendations. Program Implementation: Initial challenges and concerns were rooted in the requirements that post-cancer treatment care was maintained and survivor needs were addressed. Cancer site groups and the inter-professional teams provided continuous feedback on processes and protocols. ACTT established a standard approach to transition patients safely and effectively out of tertiary care and, ultimately, to primary care. Current ACTT Program: ACTT delivers comprehensive posttreatment and survivorship care through close collaboration between the GPO and APN. Both roles specialize in managing late or persistent effects, cancer surveillance and prevention, and addressing psychosocial needs prior to discharge to primary care. The survivorship care plan provided by ACTT is an informative tool for both patient and primary care provider to continue post-treatment follow-ups. Future Directions: Next steps for ACTT include expanding to other cancer specialties, exploring new ways to deliver care, optimizing the transition of care, and conducting comprehensive evaluations of patient reported outcomes.

Endocrinologist-Perceived Factors Affecting the Transition of Thyroid Cancer Patients from Specialist to Primary Care Postcancer Treatment in Ontario, Canada.

Background: Thyroid cancer patient discharge patterns from specialists are heterogeneous, with some specialists following patients for a longer period of time than others. With no well-established transitional plan, such as in breast and colorectal cancer, primary care physicians play a variable role in long-term thyroid cancer care. The objective of this study was to examine endocrinologist-perceived factors affecting the transition of care for thyroid cancer patients through a qualitative and quantitative survey of practicing endocrinologists in Ontario, Canada. Methods: All eligible practicing endocrinologists in Ontario were invited to participate in the study, via an email with an embedded survey link. Consent was assumed if the physician completed the survey. The survey collected physician demographics and asked a series of Likert-scale and open-ended questions on their views regarding transitioning care of their thyroid cancer patients. Quantitative analysis was based on mode and variability. Qualitative analysis was completed using inductive thematic analysis. Results: Seventy physicians completed the survey, with a response rate of 35.5%. Based on the responses to the Likert-scale questions, there was a lack of consensus in terms of discharging criteria for patients who had low-risk papillary thyroid cancer, stable thyrotropin levels, multiple nonthyroid-related comorbidities, and hemithyroidectomy with no disease recurrence. The majority of endocrinologists responded that the main factors affecting discharge included whether the primary care physician was able to follow their recommendations, whether the primary care physician could appropriately adjust levothyroxine doses, and whether the patient was confident that their primary care physician could manage their thyroid cancer follow-up. Themes extracted from the open-ended question also indicated that the main factors affecting the transition of care were related to the primary care physician, the patient, the imaging interpretation, and the discharge guidelines. Conclusion: The lack of consensus among endocrinologists affects the transition of patient care, and there is a need to provide clear and accurate information to primary care physicians and thyroid cancer patients on postcancer treatment care. Efforts should be sought to standardize discharge and long-term care.

Examining Predictors of Fear of Cancer Recurrence Using Leventhal's Commonsense Model: Distinct Implications for Oncology Nurses.

BACKGROUND: Fear of cancer recurrence (FCR) is a common concern for survivors. Oncology nurses have a unique opportunity to identify survivors at increased risk of heightened FCR. Understanding predictors of FCR would be useful for this purpose; however, results about FCR predictors are inconsistent. OBJECTIVE: To examine empirically inconsistent predictors of FCR as guided by Leventhal's Commonsense Model. METHODS: A cross-sectional survey design was used to assess FCR, sociodemographic and clinical characteristics, and characteristics of the self (self-esteem and generalized expectancies) among cancer survivors. Structural equation modeling was used to examine predictors of FCR. RESULTS: Among 1001 participants, the mean time since diagnosis was 9.07 years, and most were diagnosed with breast cancer (65.93%). The strongest predictor of higher FCR was belief that knowing someone with a recurrence affects one's own level of FCR, although knowing someone with a recurrence actually predicted lower FCR. Other significant predictors of higher FCR were having 1 or more symptoms attributed to cancer, lower self-esteem, younger age, female gender, lower pessimism, longer time since diagnosis, and active follow-up at the survivorship clinic. CONCLUSION: Cancer survivors' perceptions are among an important series of variables that may predict higher levels of FCR. Oncology nurses are uniquely situated to identify the subset of cancer survivors with levels of FCR requiring professional intervention. IMPLICATIONS FOR PRACTICE: Oncology nurses can use the predictors indicated in this study to identify survivors with greatest need for coping with FCR to facilitate expedient intervention and/or referral to psychosocial providers.

Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.

Studies have suggested that women with elevated BMI or 25-OH vitamin D levels may derive less benefit from AIs versus tamoxifen. We prospectively investigated whether high BMI or 25-OH vitamin D levels were associated with higher estrogen levels in post-menopausal women receiving standard adjuvant letrozole (2.5 mg/day). Furthermore, we evaluated whether an increased dose of letrozole resulted in lower serum estrogens in women with BMI > 25 kg/m2. Correlation between entry BMI and day 29 serum biomarkers (estrogens, 25-OH vitamin D, insulin, CRP, leptin) was assessed in all patients. On day 29, participants with BMI > 25 kg/m2 switched to letrozole 5 mg/day for 4-weeks and blood was drawn upon completion of the study. The change in serum estrogen levels was assessed in these patients (BMI > 25 kg/m2). 112 patients completed days 1-28. The Pearson correlations of estradiol and estrone with BMI or serum 25-OH vitamin D levels were near zero (-0.04 to 0.07, p = 0.48-0.69). Similar results were obtained for correlation with markers of obesity (insulin, CRP, and leptin) with estradiol and estrone (-0.15 to 0.12; p = 0.11-0.82). Thirty-one patients (BMI > 25 kg/m2) completed the interventional component; Increasing the dose of letrozole did not further reduce estradiol or estrone levels (change 0.1 and 0.4 pmol/L respectively; p = 0.74 and 0.36). There was no observed association between markers of obesity (BMI, insulin, leptin, and CRP), serum 25-OH vitamin D levels and estradiol or estrone levels. Additionally, an increased dose of letrozole did not further reduce estradiol or estrone levels compared to the standard dose.

Examining the dimensionality of the Fear of Cancer Recurrence Inventory.

OBJECTIVE: Fear of cancer recurrence (FCR) is a common concern among cancer survivors, and the Fear of Cancer Recurrence Inventory (FCRI) is a frequently used measure to assess FCR. Given that the dimensionality of FCR has received recent debate, the overall goal of this secondary analysis was to re-examine the dimensionality of the FCRI using confirmatory factor analyses (CFA) to compare models of FCR, using data from a large sample of cancer survivors. METHODS: Three models of FCR (including unidimensional and multidimensional models of the FCRI) were informed by the literature and proposed a priori. Separate CFAs were conducted to test the fit of each model to the data, and models with acceptable fits were compared. RESULTS: Of all the tested FCR models, a multidimensional first-order model aligned with the originally developed 7-subscale FCRI revealed the best fit to the data (χ2  = 3359.135, P < .0001, df = 795, RMSEA = 0.057 [0.055, 0.059], CFI = 0.897, TLI = 0.888). When this 7-factor structure was loaded onto a single, second-order factor of overall FCR, the model fit statistics were slightly poorer (χ2  = 3459.632, P < .0001, df = 807, RMSEA = 0.058 [0.056, 0.060], CFI = 0.893, TLI = 0.886). However, the difference between the models was significant (chi-square difference = 103.142, P < .0001, df = 12) indicating that the first-order model was a better fit to the data. CONCLUSIONS: These results align with empirical and theoretical literature that supports the use of the FCRI as a multidimensional scale. Implications of results are discussed in light of FCR conceptualization and measurement.

Comparing attitudes of younger and older patients towards cancer clinical trials.

OBJECTIVES: To determine the attitudes of patients towards cancer clinical trials (CCTs) and assess the differences between older and younger patients. MATERIALS AND METHODS: Patients with cancer, receiving treatment or in follow-up in University Hospital Waterford, Ireland were eligible. Patients completed a self-administered questionnaire. To determine attitudes towards CCTs, patients indicated their preference if offered participation in three hypothetical studies (cancer prevention/screening trial; CCT comparing standard to new treatment; a trial of new drug where no standard exists). Patients' reasons to or not to participate in CCTs were explored. RESULTS: From May 2014 to March 2015, 219 patients were accrued, 119 <65years and 100 ≥65years. Twenty-two (18%) younger and 4 (4%) older patients had been/were actively enrolled on a CCT (p=0.0012). No older patient and 5 (4%) of younger patients had enquired about CCT availability. For the CCT questions, 85 (71%) younger vs 57 (57%) older patients would participate in a prevention/screening CCT (p=0.033); 60 (50%) vs 44 (44%) for standard vs new drug (p=0.415), and 83 (69%) vs 78 (78%) for a CCT where no standard exists (p=0.218). The most common reason to participate in a CCT was a recommendation from the oncologist -98% <65years vs 87% ≥65years (p=0.001), with health problems being the leading reason not to participate, 86% vs 72% (p=0.01), respectively. CONCLUSIONS: Older and younger patients in this study gave similar importance to reasons for and against participation in CCTs. Most patients did not actively seek out a CCT, which may reflect a lack of awareness and a need for better education.

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study.

PURPOSE: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). METHODS AND MATERIALS: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. RESULTS: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. CONCLUSIONS: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.

Nomograms to predict serious adverse events in phase II clinical trials of molecularly targeted agents.

PURPOSE: A tool that quantifies the risk of treatment-related toxicity based on individual patient characteristics can augment the informed consent process and safety monitoring in the setting of phase II cancer treatment trials of molecularly targeted agents (MTAs). METHODS: A regression model was constructed to predict the risk of a serious adverse event (SAE) with an MTA and presented as a nomogram. Estimation of risk can be performed by integrating risk estimates from the nomogram and from a reference or average patient. Internal validation was performed using bootstrapping techniques. RESULTS: A total of 578 patients were treated with one of 14 MTAs given alone or in combination on one of 27 clinical trials performed by the Princess Margaret Hospital Drug Development Program between 2001 and 2006. Approximately 50% and 24% of patients experienced an SAE and an attributable SAE (SAEatt) during cycle 1, respectively. Albumin, lactate dehydrogenase (LDH), number of target lesions, prior radiotherapy, Charlson score, age, and performance status were included in the optimal model as predictors of a cycle 1 SAE, whereas the number of prior chemotherapy regimens, baseline creatinine, LDH, prior radiotherapy, Charlson score, body-surface area, and performance status were included as predictors of an SAEatt. Moderate-good internal validity was demonstrated, with area under the curve estimates ranging from 56.7% to 86.1% for all SAEs and 63.0% to 89.7% for SAEatts. CONCLUSION: A regression model was constructed that predicts the SAE and SAEatt risk for an individual patient during cycle 1 of phase II trial treatment with moderate to good internal validity. External validation is still required.

The influence of mentorship on research productivity in oncology.

BACKGROUND: This study evaluates the impact of mentors in research productivity in oncology. METHODS: Two electronic surveys were sent out to 1009 oncologists who attended educational workshops between 1996 and 2004. RESULTS: Response rate was 41.4% (339 of 818). Respondents with mentors are more currently engaged in academic research than those without mentors. Mentorship status did not influence on self-reported publication record or on becoming principal investigators, even when adjusted for other factors. CONCLUSIONS: Mentorship is valuable to oncologists in enhancing their research experiences. In this selected group, mentorship has effects on current involvement in academic research but not on self-reported publication.

Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer.

BACKGROUND: A phase 2 trial of gemcitabine and capecitabine (GemCap) in patients with advanced biliary cancer led to an objective response in approximately 30% of patients and a median survival of 14 months. In the current study, the authors report further efficacy data of a larger cohort of such patients treated with the GemCap regimen. METHODS: Patients aged >18 years and who had a diagnosis of locally advanced biliary cancer received first-line treatment with capecitabine at a dose of 650 mg/m(2) twice daily for 14 days and gemcitabine at a dose of 1,000 mg/m(2) on Day 1 and Day 8, every 3 weeks until disease progression. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Between July 2001 and January 2005, 75 patients were enrolled in the study. At a median follow-up of 9.5 months, the overall response rate was 29% (95% confidence interval [95% CI], 19.4-41%), with a median duration of 9.7 months (range, 3-36 months). Three patients achieved complete responses, with a median duration of 17 months (range, 9-27 months). The median progression-free survival and overall survivals were 6.2 months (95% CI, 4.4-8.3 months) and 12.7 months (95% CI, 9.5-31 months), respectively. CONCLUSIONS: The GemCap regimen is active in patients with biliary cancer. Randomized trials are warranted to define the impact of such a regimen on patient survival and quality of life.

Concurrent gemcitabine and radiotherapy with and without neoadjuvant gemcitabine for locally advanced unresectable or resected pancreatic cancer: a phase I-II study.

PURPOSE: To determine the safety, efficacy, and tolerability of biweekly gemcitabine with concurrent radiotherapy (RT) for resected and locally advanced (LA) pancreatic cancer. METHODS AND MATERIALS: Eligible patients had either LA or resected pancreatic cancer. Between March 1999 and July 2001, 63 patients (31 with LA and 32 with resected disease) were treated. Of the 63 patients, 28 were enrolled in a Phase I study of increasing radiation doses (35 Gy [n = 7], 43.75 Gy [n = 11], and 52.5 Gy [n = 10] given within 4, 5, or 6 weeks, respectively, in 1.75-Gy fractions) concurrently with 40 mg/m(2) gemcitabine biweekly. Subsequently, 35 were enrolled in a Phase II study with the addition of induction gemcitabine 1000 mg/m(2) within 7 or 8 weeks to concurrent biweekly gemcitabine (40 mg/m(2)) and 52.5 Gy RT within 6 weeks. RESULTS: In the LA population, the best response observed was a complete response in 1, partial response in 3, stable disease in 10, and progressive disease in 17. In the phase II trial, gemcitabine plus RT was not delivered to 8 patients because of progression with induction gemcitabine alone (n = 5) or by patient request (n = 3). On intent-to-treat analysis, the median survival in the LA patients was 13.9 months and the 2-year survival rate was 16.1%. In the resected population, the median progression-free survival was 8.3 months, the median survival was 18.4 months, and the 2- and 5-year survival rate was 36% and 19.4%, respectively. The treatment was well tolerated; the median gemcitabine dose intensity was 96% of the planned dose in the neoadjuvant and concurrent portions of the Phase II study. No treatment-related deaths occurred. CONCLUSION: Biweekly gemcitabine (40 mg/m(2)) concurrently with RT (52.5 Gy in 30 fractions of 1.75 Gy) with or without induction gemcitabine is safe and tolerable and shows efficacy in patients with LA and resected pancreatic cancer.

Evaluation of adverse events experienced by older patients participating in studies of molecularly targeted agents alone or in combination.

BACKGROUND: The tolerability of molecularly targeted agents in older patients has not been specifically examined. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium database were analyzed to address this question. METHODS: The Consortium database collects trial information on all patients treated with either a molecularly targeted agent alone or in combination since 2001. The frequency of adverse events was determined and analyzed by two different age groups, <65 years and >/=65 years. Toxicity indices (TI) and frequencies of dose-limiting toxicities (DLT), based on adverse events of all causalities (TI(ALL) and DLT(ALL)), and on adverse events that were at least possibly related to the molecularly targeted agent (TI(MTA) and DLT(MTA)), were calculated for both age groups. RESULTS: Four hundred and one patients who received 1,252 treatment cycles were analyzed from 19 different studies. Baseline performance status was similar between both age groups, but fewer older patients have had multiple prior regimens of chemotherapy or prior radiation therapy. A comparison of the proportions of younger and older patients experiencing DLT(ALL) and DLT(MTA) showed similar results. The TI(MTA) values were comparable between the two age groups in both single agent (3.25 versus 3.00, for <65 versus >/=65 years) and multi-agent (3.65 versus 3.00, for <65 versus >/=65 years) trials. CONCLUSIONS: Older patients seem to tolerate molecularly targeted therapies either alone or in combination with chemotherapy as well as younger patients. Age alone should not be a barrier in the administration of targeted agents.

Understanding the attitudes of the elderly towards enrolment into cancer clinical trials.

BACKGROUND: The optimal cancer treatment for an older population is largely unknown because of the low numbers of elderly patients accrued into clinical trials. This project focuses on the attitudes of the elderly about participation in clinical trials to determine if this is one of the barriers to the involvement of this population in clinical trials. METHODS: The first phase of this study was a self-administered questionnaire mailed to 425 elderly persons with cancer, selected from Princess Margaret Hospital oncology clinics. The second phase consisted of individual semi-structured interviews with cancer patients to assess their attitudes towards cancer, its management and enrolment into cancer clinical trials. RESULTS: Ninety-four patients responded to the survey giving a response rate of 22.1%. Three quarters of respondents stated that they would be willing to participate in a clinical trial. The factors that most influenced older patients' willingness to participate in a cancer study were recommendations from a cancer doctor and the chance that the study treatment may help them feel better. Seventeen survey responders participated in interviews. Common themes from these interviews included patient-physician communication, the referral process, and the role of age in cancer care decision-making. CONCLUSION: Most elderly people, who responded to this survey, are willing to consider participation in cancer clinical trials however, elderly patients do not appear to actively seek clinical trials and few were informed of the availability of clinical trials. Physician barriers and availability of appropriate clinical trials may play a bigger role in preventing accrual of elderly cancer patients into trials.

A phase II trial with pharmacodynamic endpoints of the proteasome inhibitor bortezomib in patients with metastatic colorectal cancer.

PURPOSE: To evaluate the effects of the proteasome inhibitor bortezomib on tumor growth in patients with advanced colorectal cancer, and to explore the relationship between correlative studies and clinical outcome. DESIGN: Bortezomib (1.3 mg/m(2)) was administered i.v. on days 1, 4, 8, and 11 of a 21-day cycle. Tumor response was assessed after every two cycles. Tumor biopsies were done prior to treatment and on day 9 of the first treatment cycle. Biopsies were examined for Ser(32/36)-IkappaB, Ser(276)-nuclear factor kappaB (NFkappaB), hypoxia-inducible factor-1alpha (HIF-1alpha), carbonic anhydrase IX (CAIX), p53, and microvessel density using immunohistochemistry. RESULTS: Nineteen patients received 42 cycles (range 1-4) of bortezomib. No objective response was seen; three patients had stable disease at cycle 2, two patients had progressive disease after cycle 1, and 11 patients had progressive disease at cycle 2. Of the three patients with stable disease, one had progressive disease after cycle 4, and two were withdrawn due to toxicity. The median time to progression was 5.1 weeks (95% confidence interval, 5.1-11.1 weeks). There was a significant increase in the expression of HIF-1alpha relative to its transcriptional target CAIX following bortezomib, and a similar effect was also observed in a companion study using a human tumor xenograft model. Expression of p53, Ser(276)-NFkappaB, and Ser(32/36)-IkappaB was unchanged. CONCLUSION: Single agent bortezomib is inactive in metastatic colorectal cancer. Using this regimen, there was no detectable effect on NFkappaB, but a significant accumulation of HIF-1alpha was seen relative to CAIX. This suggests that proteasome inhibition alters the response to tumor hypoxia, and further investigation of this effect is indicated.

Analysis of treatment practices for elderly cancer patients in Ontario, Canada.

PURPOSE: Older patients are underrepresented in many areas of cancer services utilization and in clinical trial enrollment. This study evaluates whether age, when adjusted for sex, comorbidity, stage, tumor site, geography, and time period, is predictive of cancer treatment practice. METHODS: First, we used the Ontario Cancer Registry (OCR) to examine for any apparent differences in treatment practices between elderly (> or = 70 years) and younger patients in the last three decades. Second, we performed a chart review of 1,505 patients with lung, breast, and colorectal cancers seen in Ontario either at an urban center, the Princess Margaret Hospital, or at a rural center, the Northwestern Regional Cancer Centre. Patients were randomly selected from two time periods, 1977 to 1978 and 1997; and the study population was to comprise at least 50% elderly patients. RESULTS: OCR data demonstrated that, in some settings, such as colorectal cancer, the proportions of elderly cancer patients who were referred to cancer centers and who received any cancer treatment were lower than their younger counterparts. The chart review data showed that increasing age was a significant negative predictor for receiving any cancer treatment (P < .001, multivariate analysis) and for having a clinical trial discussion with the treating specialist (P < .001, multivariate analysis). CONCLUSION: Independent of other factors, older age is consistently a cause of disparity in cancer treatment practice and in clinical trial discussion with patients. By increasing the accrual rate of elderly cancer patients in clinical trials, a better understanding of appropriate therapies for this patient population can be obtained and may, thereby, impact on their cancer-related morbidity and mortality.

Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials.

PURPOSE: Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies. METHODS: A systematic literature search was undertaken using several different strategies to identify relevant articles. RESULTS: Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials. CONCLUSION: Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.