Given the use of tamoxifen as standard treatment for hormone receptor–positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor–positive breast cancer in premenopausal women.
Premenopausal patients with hormone receptor– positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints.
Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025).
In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor–positive breast cancer in premenopausal women were similar.
Tamoxifen; toremifene; breast cancer; adjuvant endocrine therapy; premenopausal
Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage ii, and smaller cancers, as stage i. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage i or a stage ii breast cancer.
Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1–1.9 cm, exactly 2.0 cm, and 2.1–2.9 cm.
In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1–3.0 cm). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.2% for women with 21-mm to 29-mm tumours.
For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis.
Breast cancer; stage; survival
Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada.
Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993–1999, 2000–2005, and 2006–2011.
Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993–1999 to 2006–2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993–1999 vs. 84% in 2006–2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome.
The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.
Human papillomavirus; oropharyngeal cancer; epidemiology; hnscc
This paper summarizes the practical impact of the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology lung cancer biomarkers guidelines on the lung cancer approach in Canada, providing possible practical solutions for other similar health care systems in which scientific reality needs to be constantly balanced against economic reality.
Lung cancer; College of American Pathologists; cap; International Association for the Study of Lung Cancer; iaslc; Association for Molecular Pathology; amp; guidelines
Increased insulin-like growth factor (igf) signalling has been observed in breast cancer, including endocrine-responsive cancers, and has been linked to disease progression and recurrence. In particular, igf-1 has the ability to induce and promote lymphangiogenesis through the induction of vascular endothelial growth factor C (vegfc). In the present study, we analyzed serum and tumour samples from 60 patients with endocrine-positive breast cancer to determine the expression and the possible relationship of circulating igf-1, igf binding protein 3 (igfbp3), and vegfc with the presence of lymphatic metastasis and other immunohistochemical parameters. The analysis revealed a clear and significant correlation between high basal levels of igf-1, igfbp3, and vegfc and lymph node metastasis in endocrine-responsive breast cancer. In addition, expression of those molecules was significantly higher in breast cancer patients than in healthy control subjects. Those findings may enable more accurate prediction of prognosis in patients with breast cancer.
Breast cancer; igf-1; vegfc
In Canada, many diverse models of integrative oncology care have emerged in response to the growing number of cancer patients who combine complementary therapies with their conventional medical treatments. The increasing interest in integrative oncology emphasizes the need to engage stakeholders and to work toward consensus on research priorities and a collaborative research agenda. The Integrative Canadian Oncology Research Initiative initiated a consensus-building process to meet that need and to develop an action plan that will implement a Canadian research agenda.
A two-day consensus workshop was held after completion of a Delphi survey and stakeholder interviews.
Five interrelated priority research areas were identified as the foundation for a Canadian research agenda:
EffectivenessSafetyResource and health services utilizationKnowledge translationDeveloping integrative oncology models
Research is needed within each priority area from a range of different perspectives (for example, patient, practitioner, health system) and in a way that reflects a continuum of integration from the addition of a single complementary intervention within conventional cancer care to systemic change. Strategies to implement a Canadian integrative oncology research agenda were identified, and working groups are actively developing projects in line with those strategic areas. Of note is the intention to develop a national network for integrative oncology research and knowledge translation.
The identified research priorities reflect the needs and perspectives of a spectrum of integrative oncology stakeholders. Ongoing stakeholder consultation, including engagement from new stakeholders, is needed to ensure appropriate uptake and implementation of a Canadian research agenda.
Integrative oncology; research priorities; consensus development; Canada; complementary medicine; cam
The prognosis of patients with brain metastases from non-small-cell lung cancer (nsclc) is poor. However, some reports suggest that patients with brain metastases at the time of initial diagnosis have a more favourable survival than do patients with advanced nsclc without brain metastases.
In a retrospective cohort of all new lung cancer patients seen at a Canadian tertiary centre between July 2005 and June 2007, we examined survival after a diagnosis of brain metastases for patients with brain metastases at initial diagnosis and patients who developed brain metastases later in their illness.
During the 2-year period, 91 of 878 patients (10.4%) developed brain metastases. Median age in this cohort was 64 years. In 45, brain metastases were present at initial diagnosis, and in 46, brain metastases developed later in the course of the illness. Median survival in the entire cohort was 7.8 months. Survival after the diagnosis of brain metastases was similar for patients with brain metastases at diagnosis and later in the illness (4.8 months vs. 3.7 months, p = 0.53). As a result, patients who developed brain metastases later in their illness had a longer overall survival than did patients with brain metastases at diagnosis (9.8 months vs. 4.8 months). Among patients who received chemotherapy, the survival of patients with brain metastases at diagnosis was still poor (6.2 months).
Our data show limited survival in patients with brain metastases from nsclc. Careful patient selection for more aggressive treatment approaches is necessary.
Early prognosis; late prognosis; whole-brain radiation; chemotherapy
This observational study set out to evaluate the effectiveness of conscious sedation anesthesia for pain control during high-dose-rate (hdr) brachytherapy using a ring-and-tandem applicator system for patients with cervical cancer.
At the time of initiation of the hdr cervical cancer brachytherapy program at our institution, patients received a detailed symptom assessment during the procedures. Brachytherapy was carried out using a Smit sleeve, together with a ring-and-tandem applicator. Midazolam and an opioid—hydromorphone, morphine, or fentanyl—were the main agents used to achieve conscious sedation.
From January 2009 to October 2010, 20 patients (median age: 45 years) underwent 57 procedures. All patients received chemoradiation with curative intent. The median duration of the procedures was 1.4 hours, and no significant cardiovascular events were noted. The total dose of intravenous midazolam used ranged from 0.5 mg to 8.5 mg (median: 2.5 mg). The total dose of intravenous morphine equivalent used ranged from 2.5 mg to 60 mg (median: 8 mg). The mean and median pain scores during the procedures were 1.4 and 1.1 respectively. Brief moments of moderate to severe incidental pain were noted at the time of certain events during the procedure—specifically during insertion of the ring-and-tandem applicator. The maximal pain score during the entire procedure ranged from 0 to 10 (median: 4.7). The period of recovery from conscious sedation was relatively brief (median discharge time: 1 hour).
We were able to demonstrate that patients undergoing hdr brachytherapy for cervical cancer can achieve good pain control with conscious sedation.
Cervical cancer; carcinoma of the cervix; conscious sedation; high-dose-rate brachytherapy; pain and symptom assessment; incidental pain; recovery time
Extramammary Paget disease (empd) is a rare, slow-growing neoplasm, considered to be an adenocarcinoma of the apocrine glands. In men, the penoscrotal region is the most commonly affected area. The disease can present as carcinoma in situ or as invasive disease that can subsequently metastasize to lymph nodes and distant sites. Because of the rarity of empd, the medical literature available to guide management of the disease is limited, particularly in patients with metastases. In addition, metastatic disease may pose a diagnostic challenge, because invasive cancer of the genitourinary or gastrointestinal tract can occur in association with empd. In the present case series, we describe our experience in treating penoscrotal empd with multimodality therapy, and we review the existing literature concerning its diagnosis and management.
Extramammary Paget disease; apocrine carcinoma; case series; treatment; pathology
In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc).
A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools.
Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions.
Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias.
More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population.
Palliation; rehabilitation; systematic review; lungs; exercise; nutrition
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.
In this article, we review the gonadotoxic effects of cancer treatment on young men and women of reproductive age.
The detrimental effects of cancer on fertility can be severe and may vary depending on the chemotherapy, radiotherapy, or surgical treatments involved.
Fertility preservation should be addressed in an effort to mitigate the gonadal damage that may come with cancer therapy.
Oncofertility; fertility preservation; cryopreservation; gonadotoxicity; young adult; adolescent
To evaluate an Aloe vera lotion for prevention of radiation-induced dermatitis, all patients with a prescription of radiotherapy to a minimum dose of 40 Gy were eligible provided that their treatment area could be divided into two symmetrical halves. Patients were given a lotion of Aloe vera to use on one half of the irradiated area, with no medication to be used on the other half. The grade of dermatitis in each half was recorded weekly until 4 weeks after the end of radiotherapy.
The trial enrolled 60 patients (mean age: 52 years; 67% women). Most patients had breast cancer (38%), followed by pelvic (32%), head-and-neck (22%), and other cancers (8%). Field size was 80–320 cm2 (mean: 177 cm2), and the dose of radiotherapy was 40–70 Gy (mean: 54 Gy). Concurrent chemotherapy was administered in 20 patients. From week 4 to week 6 of radiotherapy and then at weeks 2 and 4 after radiotherapy, the mean grade of dermatitis with and without Aloe vera was 0.81 and 1.10 (p < 0.001), 0.96 and 1.28 (p < 0.001), 1.00 and 1.57 (p = 0.006), 0.59 and 0.79 (p = 0.003), and 0.05 and 0.21 (p = 0.002) respectively. Age and radiation field size had a significant effect on the grade of dermatitis. Based on these results, we conclude that the prophylactic use of Aloe vera reduces the intensity of radiationinduced dermatitis.
Aloe vera; radiation-induced dermatitis; radiotherapy; prevention
Mastocytosis is an uncommon disorder defined by increased and abnormal mast cells in one or more tissues. Cutaneous mastocytosis (cm) is limited to the skin, with varying degrees of rash, pruritus, and disfigurement. Systemic mastocytosis (sm) typically involves the bone marrow, sometimes in association with other bone marrow disorders, including chronic myelomonocytic leukemia (cmml). Mastocytosis has been associated with somatic mutations in the gene encoding the tyrosine kinase Kit, leading to identification of Kit as a therapeutic target. The Kit inhibitor imatinib mesylate is approved for aggressive sm. We present an unusual patient with disabling pruritus from telangiectasia macularis eruptiva perstans, a subtype of cm, and cmml, but with no evidence of systemic mast cell disease. She was treated with imatinib and experienced marked improvement in her pruritus. Concomitant cm and cmml have not previously been reported, and the present report is the first of successful imatinib therapy in an adult patient with cm.
Mastocytosis; chronic myelomonocytic leukemia; imatinib; pruritus; cutaneous; tyrosine kinase inhibitor; tmep
Parotid metastases from non–head-and-neck cancers are rare and may represent a diagnostic and therapeutic challenge. A late metastasis to the parotid gland from a seminoma is an unusual manifestation of disease. A 45-year-old man with a history of testicular seminoma 5 years earlier presented with a rapidly progressing parotid mass. Ultrasonography and computed tomography showed a space-occupying lesion at the angle of the right jaw. The mass was infiltrating into the parotid gland and into the parapharyngeal space. A primary parotid neoplasm was suspected, and panendoscopy combined with open biopsy was performed. Histology examination confirmed a seminoma metastatic to the parotid gland, and comparison with the primary tumour showed identical histology. The patient received chemotherapy for recurrent seminoma in accordance with the pei (cisplatin, etoposide, ifosfamide) protocol. After 4 courses of chemotherapy, salvage radical parotidectomy with removal of all suspicious residual tumour tissue was performed.
This case illustrates the difficulties that may be encountered in the differential diagnosis of parotid gland masses and underlines the necessity for a detailed clinical history and for strong interdisciplinary collaboration between oncologists and pathologists to correctly diagnose cases with such unusual presentations.
Seminoma; parotid gland; late metastasis
Most lung cancer patients experience multiple symptoms related either to the disease or its treatment. The commonly reported symptoms are pain, depression, anxiety, nausea, and poor well-being. The aim of the present study was to evaluate the effect of acupuncture as a potential treatment modality in symptomatic lung cancer patients.
This prospective observational study enrolled 33 lung cancer patients from the Peter Brojde Lung Cancer Centre between August 2010 and May 2012. All patients received 45-minute sessions of acupuncture, 1–2 times weekly for a minimum of 4 sessions. Symptom severity was assessed using the Edmonton Symptom Assessment System (esas) before and after completion of acupuncture.
The study cohort included 30 patients with non-small- cell lung cancer and 3 with small-cell lung cancer. Mean age was 62 years (range: 36–88 years); 17 of the patients were women. Most of the patients had advanced-stage cancer (73%) and good performance status (Eastern Cooperative Oncology Group 0–1: 88%). Of these patients, 67% received anticancer treatment (chemotherapy or radiotherapy, or both) with acupuncture. Of the remaining 10 patients, 8 received acupuncture after a complete surgical resection of their tumour, and because of their advanced age, 2 received acupuncture and best supportive care. The median number of acupuncture sessions was 7 (interquartile range: 4–13 sessions). Statistically significant improvements in pain, appetite, nausea, nervousness, and well-being were observed. A clinically important improvement (2 points on the esas) was reported by 61% of patients for pain and by 33% for well-being.
A significant positive correlation between improved well-being and the number of acupuncture sessions was observed. This correlation remained significant even after controlling for treatment and narcotic use. Receiver operating characteristic analysis demonstrated that a minimum of 6 acupuncture sessions are required for a 70% chance of a clinically important improvement in well-being.
The present study is the first to demonstrate that acupuncture may be an effective approach for improving symptoms—in particular, pain and well–being—in lung cancer patients. Acupuncture is a safe and minimally invasive procedure, and it is potentially useful even in patients undergoing anticancer treatment.
Acupuncture; lung cancer; Edmonton Symptom Assessment System; esas; pain; integrative oncology clinics; narcotics
Cancer patients face substantial care-related out-of-pocket (oop) costs that may influence treatment decisions, attitudes, and use of drug- or appointment-related cost-saving strategies. We examined the relationship between oop costs and care-related responses by patients.
We surveyed 170 prostate and 131 breast cancer patients presenting at clinics or support groups, or listed on the cancer registry in Newfoundland and Labrador.
In the 3-month period before the survey, 18.8% of prostate and 25.2% of breast cancer patients had oop costs greater than $500. Those oop costs consumed more than 7.5% of quarterly household income for 15.9% of prostate and 19.1% of breast cancer patients. Few patients (8.8% prostate, 15.3% breast) ever adopted any drug- or appointment-related cost-saving strategy. Few patients (7.2% prostate, 9.6% breast) said oop costs influenced treatment decisions, told their physicians about their oop costs (27.0% prostate, 21.1% breast), or were aware of available financial assistance programs (27.3% prostate, 36.9% breast). Compared with patients having low or moderate oop costs (22.9% prostate, 16.7% breast, and 25.7% prostate, 58.3% breast respectively), a larger proportion of prostate (56.0%) and breast (58.3%) cancer patients with high oop costs said that those costs created stress. Among prostate cancer patients, a larger proportion of those having high oop costs (compared with low or moderate costs) used drug-related (22.2% vs. 3.3% and 9.6% respectively) and appointment-related (11.1% vs. 1.1% and 3.8% respectively) cost-saving strategies, said oop costs created an unusual amount of stress (48.0% vs. 18.4% and 10.4%), and had difficulty paying those costs (29.2% vs. 6.2% and 10.4%).
For a small group of breast and prostate cancer patients, oop costs are high, but rarely lead to the use of care-related cost-saving strategies or influence care decisions.
Out-of-pocket costs; financial barriers; patient responses
In rectal cancer, decisions about the use of adjuvant and neoadjuvant treatment rely on clinical information from a variety of sources. Currently, the quality and accuracy of the aggregate of this clinical information is unclear. The objectives of the present study were to evaluate the completeness and quality of clinical information available to oncologists managing rectal cancer.
All patients diagnosed with rectal cancer in Nova Scotia between 2001 and 2005 were identified through the provincial cancer registry. The registry was linked to other administrative databases to obtain demographic, diagnostic, and treatment data. Patients undergoing radiation oncology consultation were identified, and a standardized review of the cancer centre chart was performed on a random sample, stratified by year.
For the 222 patients reviewed, the relevant endoscopy report was present in 113 cases (51%). The level of the tumour was documented in 75% of those reports, and colonoscopy completeness, in 81%. The relevant operative report was available in 192 cases (87%). Tumour level was described in 59% of those reports, and local extension, in 73%. Elements of total mesorectal excision were partially described in 97%. In pathology reports (10% of which were synoptic), we observed significant variability in the presence of important elements. Reporting of those elements was significantly better in the synoptic pathology reports.
Clinical information related to adjuvant and neoadjuvant therapy decision-making in rectal cancer is often not available or incomplete. A synoptic reporting system in endoscopy, surgery, and pathology could potentially be a beneficial tool in rectal cancer care.
Synoptic reporting; rectal cancer; surgery; pathology; endoscopy; radiotherapy