Prospective Evaluation of the Relationship Between Mechanical Stability and Response to Palliative Radiotherapy for Symptomatic Spinal Metastases.

BACKGROUND: A substantial number of patients with spinal metastases experience no treatment effect from palliative radiotherapy. Mechanical spinal instability, due to metastatic disease, could be associated with failed pain control following radiotherapy. This study investigates the relationship between the degree of spinal instability, as defined by the Spinal Instability Neoplastic Score (SINS), and response to radiotherapy in patients with symptomatic spinal metastases in a multi-institutional cohort. METHODS AND MATERIALS: The SINS of 155 patients with painful thoracic, lumbar, or lumbosacral metastases from two tertiary hospitals was calculated using images from radiotherapy planning CT scans. Patient-reported pain response, available for 124 patients, was prospectively assessed. Pain response was categorized, according to international guidelines, as complete, partial, indeterminate, or progression of pain. The association between SINS and pain response was estimated by multivariable logistic regression analysis, correcting for predetermined clinical variables. RESULTS: Of the 124 patients, 16 patients experienced a complete response and 65 patients experienced a partial response. Spinal Instability Neoplastic Score was associated with a complete pain response (adjusted odds-radio [ORadj] 0.78; 95% confidence interval [CI] 0.62-0.98), but not with an overall pain response (ORadj 0.94; 95% CI 0.81-1.10). CONCLUSIONS: A lower SINS, indicating spinal stability, is associated with a complete pain response to radiotherapy. This supports the hypothesis that pain resulting from mechanical spinal instability responds less well to radiotherapy compared with pain from local tumor activity. No association could be determined between SINS and an overall pain response, which might indicate that this referral tool is not yet optimal for prediction of treatment outcome. IMPLICATIONS FOR PRACTICE: Patients with stable painful spinal metastases, as indicated by a Spinal Instability Neoplastic Score (SINS) of 6 or lower, can effectively be treated with palliative external beam radiotherapy. The majority of patients with (impending) spinal instability, as indicated by a SINS score of 7 or higher, will achieve a (partial) response after palliative radiotherapy; however, some patients might require surgical intervention. Therefore, it is recommended to refer patients with a SINS score of 7 or higher to a spine surgeon to evaluate the need for surgical intervention.

Promoting consultation recording practice in oncology: identification of critical implementation factors and determination of patient benefit.

OBJECTIVE: The objectives of this implementation study were to (i) address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice and (ii) follow patients during the first few days following receipt of the consultation recording to document, from the patient's perspective, the benefits realized from listening to the recording. METHODS: Nine medical and nine radiation oncologists from cancer centers in three Canadian cities (Calgary, Vancouver, and Winnipeg) recorded their primary consultations for 228 patients newly diagnosed with breast (n = 174) or prostate cancer (n = 54). The Digital Recording Use Semi-Structured Interview was conducted at 2 days and 1 week postconsultation. Each oncologist was provided a feedback letter summarizing the consultation recording benefits reported by their patients. RESULTS: Sixty-nine percent of patients listened to at least a portion of the recording within the first week following the consultation. Consultation recording favorableness ratings were high: 93.6% rated the intervention between 75 and 100 on a 100-point scale. Four main areas of benefit were reported: (i) anxiety reduction; (ii) enhanced retention of information; (iii) better informed decision making; and (iv) improved communication with family members. Eight fundamental components of successful implementation of consultation recording practice were identified. CONCLUSIONS: Further randomized trials are recommended, using standardized measures of the patient-reported benefit outcomes reported herein, to strengthen the evidence base for consultation recording use in oncology practice.

Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial.

BACKGROUND: Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment. Previous findings of adjuvant clodronate trials in different populations with operable breast cancer have been mixed. The National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer. METHODS: NSABP B-34 is a multicentre, randomised, double-blind, placebo-controlled study in 3323 women with stage 1-3 breast cancer. After surgery to remove the tumour, patients were stratified by age, axillary nodes, and oestrogen and progesterone receptor status and randomly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years (n=1662) or placebo (1661). The primary endpoint was disease-free survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00009945. FINDINGS: Median follow-up was 90·7 months (IQR 82·7-100·0) and 3311 patients had data for this period. Disease-free survival did not differ between groups (286 events in the clodronate group vs 312 in the placebo group; hazard ratio 0·91, 95% CI 0·78-1·07; p=0·27). Moreover, no differences were recorded for overall survival (0·84, 0·67-1·05; p=0·13), recurrence-free interval (0·83, 0·67-1·04; p=0·10), or bone metastasis-free interval (0·77, 0·55-1·07; p=0·12). Non-bone metastasis-free interval was slightly increased with clodronate (0·74, 0·55-1·00; p=0·047). Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval (0·75, 0·57-0·99; p=0·045), bone metastasis-free interval (0·62, 0·40-0·95; p=0·027), and non-bone metastasis-free interval (0·63, 0·43-0·91; p=0·014), but not for overall survival (0·80, 0·61-1·04, p=0·094). Adherence to treatment at 3 years was 56% for the clodronate group and 60% for the placebo group. Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group; grade 3-4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group. There was one possible case of osteonecrosis of the jaw in the clodronate group. INTERPRETATION: Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. A meta-analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made. FUNDING: National Cancer Institute, Bayer Oy (formerly Schering Oy).

Facilitating the implementation of empirically valid interventions in psychosocial oncology and supportive care.

PURPOSE: Over the past two decades, the fields of psychosocial oncology and supportive care have seen clinically effective tools as underutilized despite proven benefits to cancer patients and their families. The purpose of this paper is to discuss the reasons for the failure of psychosocial and supportive care interventions in oncology to realize broad clinical implementation and to demonstrate how a knowledge management framework offers several advantages for increasing the probability of successful implementation. METHODS: This paper is based on a systematic review of the literature pertaining to efforts to implement psychosocial oncology and supportive care interventions. RESULTS: The struggle to develop, implement, and evaluate promising psychosocial oncology and supportive care innovations has moved academic thought toward the development of models and theories concerning the best ways to move new knowledge into clinical practice. There are critical and common barriers to the successful transfer and implementation of promising interventions, and implementation efforts may be maximized by using knowledge management frameworks to systematically identify and address these barriers. CONCLUSIONS: The successful implementation of empirically promising interventions requires research networks and practice groups to work together in a concerted, theory-guided effort to identify and address the contextual factors most relevant to any particular intervention. The growing support of knowledge implementation activities by research funders, policy-makers, opinion leaders, and advocates of psychosocial and supportive care interventions is a positive move in this direction.

Predictors of distress and quality of life in patients undergoing cancer therapy: impact of treatment type and decisional role.

PURPOSE: The purpose of this secondary investigation was to examine the impact of the type of treatment received and the perceived role in treatment decision making in predicting distress and cancer-specific quality of life in patients newly diagnosed with breast or prostate cancer. METHOD: Participants included 1057 newly diagnosed breast and prostate cancer patients from four Canadian cancer centers who partook in a randomized controlled trial examining the utility of providing patients with an audio-recording of their treatment planning consultation. A MANCOVA was performed to predict distress and cancer-specific quality of life at 12 weeks post-consultation based on control variables (patient age, education, residence, tumor size (breast sample), gleason score (prostate sample), and receipt of an initial treatment consultation recording), predictor variables (treatment type--chemotherapy, hormone therapy, radiation therapy; decisional role--active, collaborative, passive), and interactions between these predictors. RESULTS: Women who received chemotherapy and reported having played a more passive role in treatment decision making had significantly greater distress and lower cancer-specific quality of life at 12-week post-consultation. There were no statistically significant predictors of these outcomes identified for men with prostate cancer. CONCLUSION: Receipt of chemotherapy places women with breast cancer at risk for distress and reduced quality of life, but only for the subset of women who report playing a passive role in treatment decision making. Prospective, longitudinal studies are needed to confirm the present findings and to explicate the antecedents, composition, and consequences of the 'passive' decisional role during the treatment phase of the cancer trajectory.

Behind closed doors: systematic analysis of breast cancer consultation communication and predictors of satisfaction with communication.

OBJECTIVE: The purpose of this investigation was to explicate the content of primary adjuvant treatment consultations in breast oncology and examine the predictive relationships between patient and oncologist consultation factors and patient satisfaction with communication. METHODS: The recorded consultations of 172 newly diagnosed breast cancer patients from four Canadian cancer centers were randomly drawn from a larger subset of 481 recordings and examined by three coders using the Medical Interaction Process System (MIPS); a system that categorizes the content and mode of each distinct utterance. The MIPS findings, independent observer ratings of patient and oncologist affective behavior, and derived consultation ratios of patient centeredness, patient directedness, and psychosocial focus, were used to predict patient satisfaction with communication post-consultation and at 12-weeks post-consultation. RESULTS: Biomedical content categories were predominant in the consultations, accounting for 88% of all utterances, followed by administrative (6%) and psychosocial (6%) utterances. Post-consultation satisfaction with communication was significantly higher for older patients, those with smaller primary tumors and those with longer consultations. Smaller tumor, lack of patient assertiveness during the treatment consultation and having the consultation with a radiation rather than medical oncologist were significantly predictive of greater satisfaction at 12-weeks post-consultation. CONCLUSIONS: Adjuvant treatment consultations are characterized by a high degree of information-giving by the physician, a predominance of biomedical discussion and relatively minimal time addressing patients' psychosocial concerns. Controlled trials are needed to further identify and address the contextual features of these consultations that enhance patient satisfaction.

Hypofractionated Adjuvant Radiation Therapy Is Effective for Patients With Lymph Node-Positive Breast Cancer: A Population-Based Analysis.

PURPOSE: This study evaluated long-term, population-based, breast cancer-specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions). METHODS AND MATERIALS: A prospective provincial database was used to identify patients with lymph node-positive breast cancer treated with curative-intent breast/chest wall + regional nodal RT from 1998 to 2010. The effect of RT fractionation on locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) was assessed for the entire cohort and for high-risk subgroups: grade 3, ER-/HER2-, HER2+, and ≥4 positive nodes. Multivariable analysis and 2:1 case-match comparison of HF versus CF were also performed. RESULTS: A total of 5487 patients met the inclusion criteria (4006 HF and 1481 CF). Median age was 55 years, and median follow-up was 12.7 years. On multivariable analysis, no statistically significant differences were identified in 10-year LRRFS (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.59-1.27; P = .46), DRFS (HR 0.90; 95% CI, 0.76-1.06; P = .19), or BCSS (HR 0.92; 95% CI, 0.76-1.10; P = .36) between the HF and CF cohorts. There was no statistical difference in breast cancer-specific outcomes in the high-risk subgroups. On analysis of 2962 HF cases matched to 1481 CF controls, no statistical difference was observed in LRRFS (HR 0.98; 95% CI, 0.71-1.33; P = .87), DRFS (HR 0.97; 95% CI, 0.85-1.11; P = .68), or BCSS (HR 1.00; 95% CI, 0.87-1.16; P = .92). CONCLUSIONS: This large, population-based analysis with long-term follow-up after locoregional RT demonstrated that modest HF provides similar breast cancer-specific outcomes compared with CF. HF is an effective option for patients with stage I to III breast cancer receiving nodal RT.

Cardiac death after breast radiotherapy and the QUANTEC cardiac guidelines.

BACKGROUND: Breast/chest wall irradiation (RT) increases risk of cardiovascular death. International Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines state for partial heart irradiation a "V25Gy <10% will be associated with a <1% probability of cardiac mortality" in long-term follow-up after RT. We assessed whether women treated with breast/chest wall RT 10-years ago who died of cardiovascular disease (CVD) violated QUANTEC guidelines. MATERIALS/METHODS: A population-based database identified all cardiovascular deaths in women with early-stage breast cancer <80 years, treated with adjuvant breast/chest wall RT from 2002 to 2006. Ten-year rate of cardiovascular death was calculated using a Kaplan-Meier method. Patients were matched on a 2:1 basis with controls that did not die of CVD. For left-sided cases, the heart and left anterior descending (LAD) artery were retrospectively delineated. Dose-volume histograms were calculated, and heart V25Gy compared to QUANTEC guidelines. RESULTS: 5249 eligible patients received breast/chest wall RT from 2002 to 2006: 76 (1.4% at 10-years) died of CVD by June 2015. Forty-two patients received left-sided RT (1.7% CVD death at 10-years), 34 right-sided RT (1.3% at 10-years). Heart V25Gy did not exceed 10% in any left-sided cases. No cardiac dosimetry parameter distinguished left-sided cases from controls. CONCLUSIONS: QUANTEC guidelines were not violated in any patient that died of CVD after left-sided RT. The risk of radiation induced cardiac death at 10-years appears to be very low if MHD is <3.3 Gy and maximum LAD dose (EQD23 Gy) is <45.4 Gy. Further studies are needed to evaluate heart and LAD constraints in the CT-planning era.

Timing of surgery and radiotherapy in the management of metastatic spine disease: expert opinion.

BACKGROUND: Combined surgery and radiotherapy, in the treatment of metastatic disease of the spine, is now emerging as the gold standard of care where there is an indication for spinal stabilization and/or surgical decompression. However potential complications related to wound healing can occur with radiation delivered shortly before or after to surgery. The purpose of this study was to understand the practice of leading radiation oncologists and spine surgeons with regards to the timing of radiation (conventional and stereotactic) and surgery for the management of spinal metastases. METHODS: Questionnaires were sent to leading radiation oncologists and spine surgeons throughout North America and completed via mail, email or internet. RESULTS: Eighty-six responses were received from radiation oncologists and 27 from spine surgeons. A total of 58% recommended waiting either 1 or 2 weeks after radiotherapy before operating on patients with spinal metastases. With radiotherapy administered after surgery, 62% of respondents suggested either a 1 or 2 weeks interval was sufficient. CONCLUSIONS: There appeared to be no significant difference in practice with the use of stereotactic radiotherapy though surgeons tend to accept a shorter interval in this subset of patients. We recommend that the interval between radiotherapy and surgery (and vice versa) should ideally be a minimum of 2 weeks.

Tamoxifen with or without breast irradiation in women 50 years of age or older with early breast cancer.

BACKGROUND: We determined the effect of breast irradiation plus tamoxifen on disease-free survival and local relapse in women 50 years of age or older who had T1 or T2 node-negative breast cancer. METHODS: Between December 1992 and June 2000, 769 women with early breast cancer (tumor diameter, 5 cm or less) were randomly assigned to receive breast irradiation plus tamoxifen (386 women) or tamoxifen alone (383 women). The median follow-up was 5.6 years. RESULTS: The rate of local relapse at five years was 7.7 percent in the tamoxifen group and 0.6 percent in the group given tamoxifen plus irradiation (hazard ratio, 8.3; 95 percent confidence interval, 3.3 to 21.2; P<0.001), with corresponding five-year disease-free survival rates of 84 percent and 91 percent (P=0.004). A planned subgroup analysis of 611 women with T1, receptor-positive tumors indicated a benefit from radiotherapy (five-year rates of local relapse, 0.4 percent with tamoxifen plus radiotherapy and 5.9 percent with tamoxifen alone; P<0.001). Overall, there was a significant difference in the rate of axillary relapse at five years (2.5 percent in the tamoxifen group and 0.5 percent in the group given tamoxifen plus irradiation, P=0.049), but no significant difference in the rates of distant relapse or overall survival. CONCLUSIONS: As compared with tamoxifen alone, radiotherapy plus tamoxifen significantly reduces the risk of breast and axillary recurrence after lumpectomy in women with small, node-negative, hormone-receptor-positive breast cancers.

Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression. RESULTS: Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. CONCLUSIONS: Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Malignant Epithelial Transformation in Phyllodes Tumor: A Population-Based Case Series.

Background Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial neoplasm. Malignant epithelial transformation in PT is rare. This study reports clinicopathologic characteristics and outcomes of patients with malignant epithelial transformation in PT. Methods From an institutional database of 183 patients with newly diagnosed PT referred to a Canadian provincial cancer institution between 1999 and 2014, 11 cases of PT with concomitant in situ or invasive carcinoma were identified. Descriptive analysis was performed to document the characteristics, treatment and outcomes of this cohort. Results Prevalence of malignant epithelial transformation in PT was 6.0%. Median (range) age was 54 (35-75) years. Types of carcinoma were ductal carcinoma in situ (DCIS) (n = 6), lobular carcinoma in situ (n = 4), and invasive ductal carcinoma (IDC) (n = 1). Median PT size was 5 (1-15) cm. Three PTs were classified as benign (27%), five as borderline (45%), and three as malignant (27%). Mastectomy was performed in six (55%) and breast conserving surgery in five (45%) patients. Hormonal therapy was used in two cases: one with a 1 cm, grade 2 DCIS, and one with an 11 cm, grade 1 IDC, the latter also receiving radiotherapy. Mean follow-up duration was 54 (6-175) months. None of the cases showed any evidence of disease after treatment at the time of their last follow-up. Conclusion This case series showed a higher prevalence of malignant epithelial transformation in PT than reported in previous literature. Outcomes were favourable despite the presence of either in situ or invasive carcinoma within PT.

Evolving treatment strategies for inflammatory breast cancer: a population-based survival analysis.

PURPOSE: To determine if mastectomy (Mx) use, chemotherapy (CT) intensity, or treatment sequence of CT, radiation therapy (RT), and Mx have improved outcome for inflammatory breast cancer (IBC). PATIENTS AND METHODS: A retrospective analysis of 485 patients with IBC diagnosed in British Columbia between 1980 and 2000 analyzed locoregional relapse-free survival (LRFS) and breast cancer-specific survival (BCSS) by treatment intent and treatment received. Curative intent was defined as delivery of more than four cycles of anthracycline-based CT plus locoregional RT in patients without distant metastases. RESULTS: Median follow-up among survivors was 6.5 years. Median BCSS was 1.0 and 3.2 years for patients with distant metastases at diagnosis or those who were curatively treated, respectively. Among patients treated curatively (n = 308), there were no significant differences in LRFS or BCSS with timing of Mx before or after CT/RT, time between diagnosis and RT, or the sequence of RT and CT. Patients receiving more intensive CT had improved 10-year BCSS compared with standard CT (43.7% v 26.3%; P = .04). Ten-year LRFS for patients having Mx after CT, Mx before CT, and without Mx was 62.8%, 58.6%, and 34.4%, respectively (P = .0001); the corresponding 10-year BCSS was 36.9%, 19.9%, and 22.5%, respectively (P = .005). On multivariate analysis, Mx was associated with improved LRFS (P = .04). Independent prognostic factors for BCSS were menopausal status (P = .02), estrogen receptor status (P = .02), and CT type (P = .05). CONCLUSION: This retrospective analysis suggested that mastectomy, in conjunction with CT and RT, seemed to enhance locoregional control, whereas modern CT regimens seemed to improve BCSS.

Consistency in seroma contouring for partial breast radiotherapy: impact of guidelines.

PURPOSE: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. METHODS AND MATERIALS: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a "trained" cohort of four radiation oncologists who were provided with these guidelines and an "untrained" cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the "trained" and "untrained" cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. RESULTS: The "untrained" cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the "trained" cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. CONCLUSION: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.

The Global Public Health Intelligence Network and early warning outbreak detection: a Canadian contribution to global public health.

The recent SARS epidemic has renewed widespread concerns about the global transmission of infectious diseases. In this commentary, we explore novel approaches to global infectious disease surveillance through a focus on an important Canadian contribution to the area--the Global Public Health Intelligence Network (GPHIN). GPHIN is a cutting-edge initiative that draws on the capacity of the Internet and newly available 24/7 global news coverage of health events to create a unique form of early warning outbreak detection. This commentary outlines the operation and development of GPHIN and compares it to ProMED-mail, another Internet-based approach to global health surveillance. We argue that GPHIN has created an important shift in the relationship of public health and news information. By exiting the pyramid of official reporting, GPHIN has created a new monitoring technique that has disrupted national boundaries of outbreak notification, while creating new possibilities for global outbreak response. By incorporating news within the emerging apparatus of global infectious disease surveillance, GPHIN has effectively responded to the global media's challenge to official country reporting of outbreak and enhanced the effectiveness and credibility of international public health.

Patient-reported Long-term Cosmetic Outcomes Following Short Fractionation Whole Breast Radiotherapy With Boost.

OBJECTIVES: To evaluate the cosmetic effect of a tumor-bed boost after hypofractionated whole breast irradiation (HF-WBI+B) using a patient-reported questionnaire. MATERIALS AND METHODS: Between 2000 and 2005, 4392 women aged 75 years and younger with unilateral early-stage breast cancer received HF-WBI alone or HF-WBI+B. From each group, 800 randomly sampled surviving and nonrelapsed women were invited to complete the Breast Cancer Treatment Outcomes Scale questionnaire. RESULTS: A total of 312 women completed the questionnaire: 154 received HF-WBI alone and 158 received HF-WBI+B. Median ages of respondents were 57 years for HF-WBI alone and 52 years for HF-WBI+B (P<0.001). Women receiving HF-WBI+B had a shorter follow-up interval, higher T stage, higher grade, and were more likely to have had nodal radiotherapy and chemotherapy. There were similar responses comparing the overall appearance of the treated to untreated breast (42% stating no or slight difference for HF-WBI alone vs. 41% for HF-WBI+B, P=0.87). The HF-WBI+B group was: (a) slightly worse on the cosmetic subscale (2.3 vs. 2.1, P=0.02); (b) worse on the pain subscale (2.0 vs. 1.6, P<0.0001); but (c) better on the functional subscale (1.5 vs. 1.8, P<0.001). When the pain subscale was applied to the area around the scar (a surrogate for the tumor-bed), the 2 groups were similar (2.0 vs. 2.0, P=0.71). CONCLUSIONS: Similar to conventional fractionated whole breast radiotherapy with a tumor-bed boost, women who received short fractionation whole breast radiotherapy with boost self-report only slightly worse long-term cosmetic and pain outcomes compared with women who received short fractionation alone.

Chronic arm morbidity after curative breast cancer treatment: prevalence and impact on quality of life.

PURPOSE: To determine the prevalence of and contributing factors for chronic arm morbidity including lymphedema in breast cancer patients after treatment and to assess the impact of arm morbidity on quality of life (QOL). PATIENTS AND METHODS: A four-question screening questionnaire was developed and mailed to a random sample of 744 breast cancer patients treated curatively in two cancer centers from 1993 to 1997. Patients were without recurrence and at least 2 years from diagnosis. Respondents were classified as with or without arm-related symptoms on the basis of the survey. Stratified random samples from each group were then invited for a detailed assessment of their symptoms and signs, including the presence of lymphedema. Their QOL was assessed by the European Organization for Research and Treatment of Cancer QOL Questionnaire C-30 and by a detailed arm problem questionnaire that assessed various aspects of daily arm functioning. RESULTS: Approximately half of all screened patients were symptomatic and 12.5% of all assessed patients had lymphedema. Axillary dissection (AD) and axillary radiotherapy (RT) after dissection were statistically significantly related to the occurrence of arm symptoms (odds ratio for AD = 3.3, P <.001; odds ratio for RT = 3.1, P <.001). Symptomatic patients and patients with lymphedema both had impaired QOL compared with asymptomatic patients. CONCLUSION: Treatment for breast cancer is associated with considerable arm morbidity, which has a negative impact on QOL. Arm morbidity should be carefully monitored in future studies involving local treatment modalities for breast cancer.

Impact of providing audiotapes of primary adjuvant treatment consultations to women with breast cancer: a multisite, randomized, controlled trial.

PURPOSE: Women with breast cancer were provided with an audiotape of their primary adjuvant treatment consultation, and the following patient outcomes were measured at 12 weeks postconsultation: perceived degree of information provision, audiotape satisfaction and use, communication satisfaction with oncologist, mood state, and cancer-specific quality of life. PATIENTS AND METHODS: Participants included 628 women newly diagnosed with breast cancer and 40 oncologists from six cancer centers in Canada. The patients were block randomized to one of four consultation groups: standard care control, not audiotaped; audiotaped, no audiotape given; audiotaped, patient given audiotape; and audiotaped, patient offered choice of receiving audiotape or not. RESULTS: Patients receiving the consultation audiotape had significantly better recall of having discussed side effects of treatment than patients who did not receive the audiotape. Audiotape benefit was not significantly related to patient satisfaction with communication, mood state, or quality of life at 12 weeks postconsultation, and was not significantly affected by choice of receiving the audiotape. Patients rated the audiotape intervention positively, with an average score of 83.9 of 100. CONCLUSION: Audiotape provision benefits patients by facilitating their perception of being informed about treatment side effects, but does not significantly influence patient satisfaction with communication, mood state, or quality of life.

Identification of a Low-Risk Luminal A Breast Cancer Cohort That May Not Benefit From Breast Radiotherapy.

PURPOSE: To determine the prognostic and predictive value of intrinsic subtyping by using immunohistochemical (IHC) biomarkers for ipsilateral breast relapse (IBR) in participants in an early breast cancer randomized trial of tamoxifen with or without breast radiotherapy (RT). PATIENTS AND METHODS: IHC analysis of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67 was conducted on 501 of 769 available blocks. Patients were classified as luminal A (n = 265), luminal B (n = 165), or high-risk subtype (luminal HER2, n = 22; HER2 enriched, n = 13; basal like, n = 30; or triple-negative nonbasal, n = 6). Median follow-up was 10 years. RESULTS: Classification by subtype was prognostic for IBR (10-year estimates: luminal A, 5.2%; luminal B, 10.5%; high-risk subtypes, 21.3%; P < .001). Luminal subtypes seemed to derive less benefit from RT (luminal A hazard ratio [HR], 0.40; luminal B HR, 0.51) than high-risk subtypes (HR, 0.13); however, the overall subtype-treatment interaction term was not significant (P = .26). In an exploratory analysis of women with clinical low-risk (age older than 60 years, T1, grade 1 or 2) luminal A tumors (n = 151), 10-year IBR was 3.1% versus 11.8% for the high-risk cohort (n = 341; P = .0063). Clinical low-risk luminal A patients had a 10-year IBR of 1.3% with tamoxifen versus 5.0% with tamoxifen plus RT (P = .42). Multivariable analysis showed that RT (HR, 0.31; P < .001), clinical risk group (HR, 2.2; P = .025), and luminal A subtype (HR, 0.25; P < .001) were significantly associated with IBR. CONCLUSION: IHC subtyping was prognostic for IBR but was not predictive of benefit from RT. Further studies may validate the exploratory finding of a low-risk luminal A group who may be spared breast RT.

The problem of evidence-based medicine: directions for social science.

Evidence-based medicine (EBM) is arguably the most important contemporary initiative committed to reshaping biomedical reason and practice. The move to establish scientific research as a fundamental ground of medical decision making has met with an enthusiastic reception within academic medicine, but has also generated considerable controversy. EBM and the broader forms of evidence-based decision making it has occasioned raise provocative questions about the relation of scientific knowledge to social action across a variety of domains. Social science inquiry about EBM has not yet reached the scale one might expect, given the breadth and significance of the phenomenon. This paper contributes reflections, critique and analysis aimed at helping to build a more robust social science investigation of EBM. The paper begins with a "diagnostics" of the existing social science literature on EBM, emphasizing the possibilities and limitations of its two central organizing analytic perspectives: political economy and humanism. We further explore emerging trends in the literature including a turn to original empirical investigation and the embrace of "newer" theoretical resources such as postmodern critique. We argue for the need to move the social inquiry of EBM beyond concerns about rationalization and the potential erasure of the patient and, to this end, suggest new avenues of exploration. The latter include analysis of clinical epidemiology and clinical reason as the discursive preconditions of EBM, the role of the patient as a site for the production of evidence, and the textually mediated character of EBM.