Real-world adjuvant TAC or FEC-D for HER2-negative node-positive breast cancer in women less than 50 years of age.

PURPOSE: We compared the efficacy, toxicity, and use of granulocyte colony-stimulating factor (g-csf) with tac (docetaxel-doxorubicin-cyclophosphamide) and fec-d (5-fluorouracil-epirubicin-cyclophosphamide followed by docetaxel) in women less than 50 years of age. METHODS: The study included all women more than 18 years but less than 50 years of age with her2-negative, node-positive, stage ii or iii breast cancer diagnosed in Alberta between 2008 and 2012 who received tac (n = 198) or fec-d (n = 274). RESULTS: The patient groups were well-balanced, except that radiotherapy use was higher in the tac group (91.9% vs. 79.9%, p < 0.001). At a median follow-up of 49.6 months, disease-free survival was 91.4% for tac and 92.0% for fec-d (p = 0.76). Overall survival (os) was 96% with tac and 95.3% with fec-d (p = 0.86).The incidences of grades 3 and 4 toxicities were similar in the two groups (all p > 0.05). Overall, febrile neutropenia (fn) was reported in 11.6% of tac patients and 15.7% of fec-d patients (p = 0.26). However, use of g-csf was higher in the tac group than in the fec-d group (96.4% vs. 71.5%, p < 0.001). Hospitalization for fn was required in 10.5% of tac patients and 13.0% of fec-d patients (p = 0.41). In g-csf-supported and -unsupported patients receiving tac, fn occurred at rates of 11.1% and 33.3% respectively (p = 0.08); in patients receiving the fec portion of fec-d, those proportions were 2.9% and 8.1% respectively (p = 0.24); and in patients receiving docetaxel after fec, the proportions were 4.1% and 17.6% respectively (p < 0.001). CONCLUSIONS: In women less than 50 years of age receiving adjuvant tac or fec-d, we observed no differences in efficacy or other nonhematologic toxicities. Based on the timing and rates of fn, use of prophylactic g-csf should be routine for the docetaxel-containing portion of treatment; however, prophylactic g-csf could potentially be avoided during the fec portion of fec-d treatment.

Improving access to cancer guidelines: feedback from health care professionals.

PURPOSE: We examined access to locally developed and other available clinical practice guidelines (cpgs) for the management of cancer and evaluated how to improve uptake. METHODS: A 12-question online survey was administered to 772 members of 12 multidisciplinary tumour teams in a Canadian provincial oncology program. The teams are composed of physicians, surgeons, nurses, allied health professionals, and researchers involved in the provision of cancer care across the province. Many of these individuals construct or provide input into the provincial cpgs. The questionnaires were administered online and were completed voluntarily. RESULTS: Responses were received from 232 individuals, a response rate of 30.1%. Most respondents (75.1%) indicated they actively referenced cpgs for cancer treatment. Of the 177 respondents who identified barriers to cpg access, 24.9% said that the cause was being too busy; 24.3% and 22.6% cited the user-unfriendliness of the Web site and a lack of awareness about the cpgs. When asked about innovative changes that could be made to improve access, the creation of cpg summary documents was identified as the most effective change (46.3%). The creation of summary documents was ranked highest by physicians, surgeons, and nurses. CONCLUSIONS: Clinical practice guidelines are important tools for standardizing treatment protocols and improving outcomes in health care systems, but support for their use is variable among health care professionals. We have identified barriers to-and potential mitigating strategies for-more widespread access to cpgs by the various health professions involved in cancer care. Local creation of succinct and easily accessible cpgs was identified as the single most effective way to enhance access by health care professionals.

Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

BACKGROUND: Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. METHODS: The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. RESULTS: Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. SUMMARY: Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases.

Information needs and sources of information for patients during cancer follow-up.

BACKGROUND: Now more than ever, cancer patients want health information. Little has been published to characterize the information needs and preferred sources of that information for patients who have completed cancer treatment. METHODS: We used a nationally validated instrument to prospectively survey patients attending a cancer clinic for a post-treatment follow-up visit. All patients who came to the designated clinics between December 2011 and June 2012 were approached (N = 648), and information was collected only from those who agreed to proceed. RESULTS: The 411 patients who completed the instrument included individuals with a wide range of primary malignancies. Their doctor or health professional was overwhelmingly the most trusted source of cancer information, followed by the Internet, family, and friends. The least trusted sources of information included radio, newspaper, and television. Patients most preferred to receive personalized written information from their health care provider. CONCLUSIONS: Cancer survivors are keenly interested in receiving information about cancer, despite having undergone or finished active therapy. The data indicate that, for patients, their health care provider is the most trusted source of cancer information. Cancer providers should ask patients about the information they want and should direct them to trusted sources.

Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline.

BACKGROUND: Dexamethasone is the corticosteroid most commonly used for the management of vasogenic edema and increased intracranial pressure in patients with brain tumours. It is also used after surgery (before embarking on radiotherapy), particularly in patients whose tumours exert significant mass effect. Few prospective clinical trials have set out to determine the optimal dose and schedule for dexamethasone in patients with primary brain tumours, and subsequently, fewer clinical practice guideline recommendations have been formulated. METHODS: A review of the scientific literature published to November 2012 considered all publications that addressed dexamethasone use in adult patients with brain tumours. Evidence was selected and reviewed by a working group comprising 3 clinicians and 1 methodologist. The resulting draft guideline underwent internal review by members of the Alberta Provincial cns Tumour Team, and feedback was incorporated into the final version of the guideline. RECOMMENDATIONS: Based on the evidence available to date, the Alberta Provincial cns Tumour Team makes these recommendations: Treatment with dexamethasone is recommended for symptom relief in adult patients with primary high-grade glioma and cerebral edema.After surgery, a maximum dose of 16 mg daily, administered in 4 equal doses, is recommended for symptomatic patients. This protocol should ideally be started by the neurosurgeon.A rapid dexamethasone tapering schedule should be considered where appropriate.Patients who have high-grade tumours, are symptomatic, or have poor life expectancy, can be maintained on a 0.5-1.0 mg dose of dexamethasone daily.Side effects with dexamethasone are common, and they increase in frequency and severity with increased dose and duration of therapy. Patients should be carefully monitored for endocrine, muscular, skeletal, gastrointestinal, psychiatric, and hematologic complications, and for infections and other general side effects.

Paroxetine levels in postpartum depressed women, breast milk, and infant serum.

BACKGROUND: The purpose of this study was to determine the concentrations of paroxetine in maternal serum, breast milk, and infant serum samples and to estimate infant exposure through breastfeeding. METHOD: A total of 25 sample sets was obtained: I sample set each from 23 mother-infant dyads and 2 sample sets from 1 mother-infant dyad. All mothers met DSM-IV criteria for major depressive disorder. The maternal fixed dosage of paroxetine was 10, 20, or 40 mg/day for a minimum of 30 days before the samples were drawn. Samples were collected 6 hours after dose intake, and the concentration of paroxetine in each sample was determined using gas chromatography/mass spectrometry. The analytic method employed in this study is the most sensitive to date, with the ability to detect drug concentrations as low as 0.1 ng/mL. RESULTS: Detectable levels of paroxetine were present in all maternal serum samples and in 24 of the 25 breast milk samples. In all of the infant serum samples, the paroxetine concentrations were below the lower limit of quantification. No unusual adverse effects were reported in any of the infants. CONCLUSION: The results of this study demonstrate that paroxetine, like the other selective serotonin reuptake inhibitors studied to date, is excreted into the breast milk of nursing mothers. The mean infant dose of paroxetine was 1. 1% of the maternal dose. Although no short-term adverse effects were reported in any of the infants in this study, future studies are needed to address a more systematic method for observing and recording any adverse effects. In addition, future studies should incorporate follow-up studies in order to evaluate possible long-term effects of paroxetine exposure.

The impact of partner support in the treatment of postpartum depression.

OBJECTIVE: To determine the impact of partner support in the treatment of mothers suffering from postpartum depression (PPD). METHOD: Patients underwent a comprehensive psychiatric assessment and were enrolled in the study only if they met the DSM-IV criteria for major depressive disorder with postpartum onset. Patients with PPD (n = 29) were assigned randomly to 2 treatment groups: group 1 (control group) consisted of patients only (n = 13), while group 2 (support group) consisted of patients (n = 16) and their partners. The patients in both groups were seen for 7 psychoeducational visits each. In group 2, partners participated in 4 of the 7 visits. Patients in both groups were administered a set of questionnaires that included the Edinburgh Postnatal Depression Scale (EPDS), the Kellner Symptom Questionnaire, the Dyadic Adjustment Scale (DAS), and the Parental Bonding Instrument (PBI). In addition, during visits 1 and 7, all patients underwent assessment using the Mini International Neuropsychiatric Instrument (MINI), section A (major depressive episode). The partners in both groups completed the DAS and the General Health Questionnaire (GHQ). RESULTS: Relative to the control-group patients, the support-group patients displayed a significant decrease in depressive symptoms and other psychiatric conditions. Relative to the support group, the general health of the partners in the control group deteriorated. CONCLUSION: Partner support has a measurable effect on women experiencing PPD.

The use of selective serotonin reuptake inhibitors during pregnancy and lactation: current knowledge.

This article reviews the effects of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants in pregnant and lactating women for the treatment of depression and anxiety disorders. An examination of the literature was conducted using Medline (1966 to present). Despite methodological concerns and the scarcity of data on this important subject, the majority of recent investigations demonstrate safety of the fetus exposed to SSRIs during pregnancy. All of the SSRIs reported in the studies are excreted into breast milk, and low levels have been found in infant serum. The implications of this for practice include identifying the effects of treatment versus nontreatment on the mother-infant dyad. Further research must examine long-term neurobehavioural teratogenicity in exposed infants.

Spatial working memory and hippocampal size across pregnancy in rats.

The present experiments investigated the effects of pregnancy on performance in the Morris water maze and on hippocampal volume. In the first study, pregnant rats (in between the first and second trimester) outperformed nonpregnant rats on the Morris water maze on 1 day of testing. In the second study, rats were tested in a working memory variation of the maze in which the spatial location of the platform varied. Pregnant females traveled shorter distances than nonpregnant females during the first two trimesters, but performed worse than nonpregnant females during the third trimester. Latency measures showed a similar profile. Group differences in performance were not related to changes in swim speed. However, changes in performance in pregnant females may be related to estrogen, progesterone, and/or corticosterone levels during pregnancy, with low levels of estradiol and high levels of progesterone being associated with better performance. There were no significant differences between pregnant and nonpregnant animals on any of the brain measures, although pregnant animals tended to have a smaller hippocampus than nonpregnant animals. These results indicate that pregnancy can affect performance, possibly related to the hormonal changes that accompany pregnancy.