Patient preferences for timing and access to radiation therapy.

PURPOSE: Patient preferences for radiation therapy (rt) access were investigated. METHODS: Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded. RESULTS: Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%-15% preferred 07h30-08h00 or 16h30-17h00; 10% preferred 17h00-18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively. CONCLUSIONS: An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%-20% of rt capacity on weekends and during 07h30-08h00 and 16h30-18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.

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.

Does HER2 status influence locoregional failure rates in breast cancer patients treated with mastectomy for pT1-2pN0 disease?

BACKGROUND: The impact of HER2 overexpression on the locoregional control of breast cancer is controversial. PATIENTS AND METHODS: Data on 906 women diagnosed with pT(1-2)pN(0) breast cancer from 1986 to 1992 with known HER2 status and treated with a modified radical mastectomy without adjuvant radiotherapy or adjuvant trastuzumab were analyzed with respect to local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant relapse-free survival (DRFS). Log-rank statistics were used to compare 10-year Kaplan-Meier curves of LRFS, RRFS and DRFS in HER2+ and HER2- patients. RESULTS: Median follow-up was 12.8 years. HER2+ patients had a worse DRFS (P = 0.028) but there was no statistically significant difference in LRFS or RRFS between HER2+ and HER2- patients (P = 0.32 and 0.24 for LRFS and RRFS, respectively). Ten-year LRFS estimates among HER2+ patients was 91.3% and 86.9% for HER2- patients. Ten-year RRFS estimates for HER2+ and HER2- patients were 88.0% and 93.0%, respectively. CONCLUSION: HER2 overexpression was not associated with higher local or regional recurrence risk in subjects with pT(1-2)pN(0) breast cancer following mastectomy and nodal dissection after a median follow-up of >12 years.

A pan-Canadian prospective study of young women with breast cancer: the rationale and protocol design for the RUBY study.

Introduction: The understanding of the biology and epidemiology of, and the optimal therapeutic strategies for, breast cancer (bca) in younger women is limited. We present the rationale, design, and initial recruitment of Reducing the Burden of Breast Cancer in Young Women (ruby), a unique national prospective cohort study designed to examine the diagnosis, treatment, quality of life, and outcomes from the time of diagnosis for young women with bca. Methods: Over a 4-year period at 33 sites across Canada, the ruby study will use a local and virtual recruitment model to enrol 1200 women with bca who are 40 years of age or younger at the time of diagnosis, before initiation of any treatment. At a minimum, comprehensive patient, tumour, and treatment data will be collected to evaluate recurrence and survival. Patients may opt to complete patient-reported questionnaires, to provide blood and tumour samples, and to be contacted for future research, forming the core dataset from which 4 subprojects evaluating genetics, lifestyle factors, fertility, and local management or delivery of care will be performed. Summary: The ruby study will be the most comprehensive repository of data, biospecimens, and patient-reported outcomes ever collected with respect to young women with bca from the time of diagnosis, enabling research unique to that population now and into the future. This research model could be used for other oncology settings in Canada.

Survival outcome and cost-effectiveness with docetaxel and paclitaxel in patients with metastatic breast cancer: a population-based evaluation.

BACKGROUND: A randomized controlled trial showed longer overall survival (OS) with docetaxel compared with paclitaxel in metastatic breast cancer patients with prior exposure to anthracycline. We report a similar comparison using population-based data. METHODS: Data on patients treated with single-agent paclitaxel or docetaxel were retrospectively reviewed. OS was compared using a two-tailed log-rank test and expressed as Kaplan-Meier plots. A cost-effectiveness analysis was carried out using cost/patient and OS. RESULTS: Four hundred and thirty-five patients met eligibility criteria. Prognostic factors were balanced between docetaxel and paclitaxel groups. Median OS was significantly longer for docetaxel versus paclitaxel [10.9 versus 8.3 months; hazard ratio 0.76; 95% confidence interval (CI), 0.62-0.92; P = 0.006]. The median number of cycles administered were four (docetaxel) and three (paclitaxel). The incremental cost-effectiveness ratio was $2434/per month of median survival gained. In the sensitivity analysis, the results were robust except that paclitaxel dominated when the low end of the 95% CI of survival for docetaxel was compared with the high end for paclitaxel. CONCLUSION: This population-based study corroborated the randomized trial's conclusion that for patients with metastatic breast cancer, docetaxel provided superior survival compared with paclitaxel. Each additional month of survival had an incremental cost of $2434.

Medical assistance in dying for cancer patients one year after legalization: a collaborative approach at a comprehensive cancer centre.

Medical assistance in dying (maid) is a new medical service in Canada. Access to maid for patients with advanced cancer can be daunting during periods of declining health near the end of life. In this report, we describe a collaborative approach between the centralized coordination service and a regional cancer centre as an effective strategy for enabling interdisciplinary care delivery and enhancing patient-centred care at the end of the patient's cancer journey.

Rates of cannabis use in patients with cancer.

Background: A comprehensive assessment of cannabis use by patients with cancer has not previously been reported. In this study, we aimed to characterize patient perspectives about cannabis and its use. Methods: An anonymous survey about cannabis use was offered to patients 18 years of age and older attending 2 comprehensive and 2 community cancer centres, comprising an entire provincial health care jurisdiction in Canada (ethics id: hreba-17011). Results: Of 3138 surveys distributed, 2040 surveys were returned (65%), with 1987 being sufficiently complete for analysis (response rate: 63%). Of the respondents, 812 (41%) were less than 60 years of age; 45% identified as male, and 55% as female; and 44% had completed college or higher education.Of respondents overall, 43% reported any lifetime cannabis use. That finding was independent of age, sex, education level, and cancer histology. Cannabis was acquired through friends (80%), regulated medical dispensaries (10%), and other means (6%). Of patients with any use, 81% had used dried leaves.Of the 356 patients who reported cannabis use within the 6 months preceding the survey (18% of respondents with sufficiently complete surveys), 36% were new users. Their reasons for use included cancer-related pain (46%), nausea (34%), other cancer symptoms (31%), and non-cancer-related reasons (56%). Conclusions: The survey demonstrated that prior cannabis use was widespread among patients with cancer (43%). One in eight respondents identified at least 1 cancer-related symptom for which they were using cannabis.

Anemia is a common but neglected complication of adjuvant chemotherapy for early breast cancer.

In this study, we set out to determine the frequency and severity of anemia and the corrective interventions used during adjuvant chemotherapy for breast cancer.We conducted a retrospective electronic chart review of 702 patients who received adjuvant breast cancer chemotherapy at four BC Cancer Agency centres in 2002 and 2003. For these patients, we recorded the initial hemoglobin reading and the date of the first hemoglobin reading in the ranges 110-119 g/L, 100-109 g/L, 90-99 g/L, and <90 g/L. We also recorded any discussion about, or delivery of, interventions for anemia [transfusion, epoetin (epo) or both].Median age of the study population was 51 years, and it varied with chemotherapy type. Among the patients, 12% had a hemoglobin reading <120 g/L before the start of chemotherapy. Overall, the proportion of patients with at least one hemoglobin reading <120 g/L was 78%; <110 g/L, 54%; <100 g/L, 31%; and <90 g/L, 14%. Depending on chemotherapy type, a hemoglobin reading <100 g/L occurred in 5% to 54% of patients. Intervention rates increased as hemoglobin declined. For 99 patients with a hemoglobin reading <90 g/L, a discussion of anemia was documented in the treatment chart in 49% of cases, a transfusion was delivered in 23%, epo was used in 11%, and transfusion and epo were both delivered in 5%.Anemia was relatively common and varied with chemotherapy type. Documentation of a discussion of anemia occurred in fewer than 20% of the patients with a hemoglobin reading of 90-99 g/L and in only half the patients with a hemoglobin reading <90 g/L. Intervention rates were low at hemoglobin readings for which randomized trials have shown that intervention can improve quality of life.

Gel electrophoresis of individual cells to quantify hypoxic fraction in human breast cancers.

A new gel electrophoresis method has been used to quantify hypoxic fraction in human tumors. Radiation-induced DNA damage was measured in individual tumor cells, where the radiobiologically hypoxic cells were observed as a subpopulation showing a 3-fold reduction in DNA strand breaks. Patients receiving palliative radiotherapy for breast cancers were given a single dose of 5-10 Gy, and a fine needle aspiration biopsy was taken immediately after irradiation. Hypoxic cells were detected in seven of eight tumors. In four tumors, bivariate analyses of DNA content versus DNA damage to individual cells allowed distinction between the response of diploid normal cells and aneuploid tumor cells. These early results indicate that "comet assay" shows considerable promise for resolving the extent and significance of hypoxia in human tumors.

Peer Review of Radiotherapy Planning: Quantifying Outcomes and a Proposal for Prospective Data Collection.

AIMS: The Canadian Partnership for Quality Radiotherapy quality assurance guidelines recommend that radiation oncologist peer review of curative radiotherapy plans takes place ideally before the first fraction of treatment is delivered. This study documented and evaluated the outcomes of weekly, disease site-specific, radiotherapy peer review, quality assurance rounds at the Tom Baker Cancer Centre in Calgary, Canada with a view to making recommendations about the optimal timing and documentation of peer review during the radiotherapy planning processes. MATERIALS AND METHODS: Outcomes of each case reviewed at (i) breast, (ii) head and neck (including thyroid and cutaneous cases) and (iii) lung team quality assurance rounds from 6 January to 5 May 2015 were recorded prospectively. Each radiotherapy plan was assigned an outcome: A for plans with no suggested changes; B for satisfactory, but where issues were raised to consider for future patients; or C when a change was recommended before the first or next fraction. The B outcomes were further subdivided into B1 for a case-specific concern and B2 for a policy gap. Plans were assessed after contour definition and before the plan was formulated (post-contouring reviews) and/or assessed when the plan was complete (post-planning reviews). RESULTS: 209 radiotherapy plans prescribed by 20 radiation oncologists were peer reviewed at 43 quality assurance meetings. 93% were curative-intent and 7% were palliative. 83% of plans were reviewed before delivery of the first treatment fraction. There were a total of 257 case reviews: 60 at the post-contouring stage, 197 at the post-planning stage, including 46 patients reviewed at both time points. Overall rates of A, B1, B2 and C outcomes were 78%, 9%, 4% and 9%, respectively. The most common reason for a B or C outcome was related to target volume definition. Only 56% of C outcomes at the post-planning stage would have been detected at the post-contouring stage. Results varied between tumour site groups. CONCLUSIONS: 9% of radiotherapy plans reviewed had changes suggested before delivery to the patient. Review at the post-planning stage after plan completion was necessary to detect all suggested changes, but for head and neck cases, all C outcomes could have been detected at the post-contouring stage. More widespread implementation of radiotherapy peer review in the UK is recommended.

Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer.

PURPOSE: The objective of the study was to evaluate the association between the number of lymph nodes removed at axillary dissection and recurrence and survival for patients with node-negative invasive breast cancer. PATIENTS AND METHODS: Subjects were 2,278 women with pathologically node-negative invasive breast cancer, diagnosed from 1989 to 1993 in British Columbia, Canada. Women aged > or = 90 years, with pure in-situ, bilateral invasive breast cancer or T4, N1, N2, or M1 stage, or who had axillary radiation were excluded. Two groups were defined for analysis: node-negative with no systemic therapy (n = 1,468) and node-negative with systemic therapy (n = 810). Median follow-up was 7.5 years. Prognostic variables assessed were age at diagnosis, tumor size, tumor grade, invasion of lymphatics, veins, or nerves, estrogen receptor status, and number of nodes removed. RESULTS: For patients not receiving systemic therapy, regional relapse was significantly increased with smaller numbers of nodes removed (P =.03). There was a trend toward shorter overall survival with fewer nodes removed (P =.06). Node-negative patients who received systemic therapy did not have a higher regional relapse rate or shorter overall survival when fewer nodes were recovered. CONCLUSION: Recovery of a small number of negative lymph nodes at axillary dissection likely understages patients and leads to undertreatment, resulting in an increased regional relapse rate and poorer survival. The use of systemic therapy may overcome this effect. The number of nodes removed, in conjunction with other prognostic factors, may be useful in selecting node-negative patients for systemic therapy.

Relationship between tumor location and relapse in 6,781 women with early invasive breast cancer.

PURPOSE: To explore the independent prognostic impact of medial hemisphere tumor location in early breast cancer. PATIENTS AND METHODS: A comprehensive database was used to review patients referred to the British Columbia Cancer Agency from 1989 to 1995 with early breast cancer. Patients were grouped according to relapse risk (high or nonhigh) and adjuvant systemic therapy received. Multiple regression analysis was used to determine whether the significance of primary tumor location (medial v lateral hemisphere) was independent of known prognostic factors and treatment. RESULTS: In the adjuvant systemic therapy groups, medial location was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral location. Five-year systemic disease-free survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions, respectively (P <.005). Corresponding 5-year disease-specific survival rates were 75.7% and 80.8%, respectively (P <.03). No significant differences were observed between medial and lateral location for low-risk disease regardless of adjuvant therapy or for high-risk disease with no adjuvant therapy. Local recurrence rates were similar for all risk and therapy groups. CONCLUSION: The two-fold risk of relapse and breast cancer death associated with high-risk medial breast tumors may be due to occult spread to internal mammary nodes (IMNs). Enhanced local control, such as with irradiation of the IMN chain, may be one way to reduce the excess risk. Ongoing randomized controlled trials may provide prospective answers to the question of the optimal volume of radiotherapy.

Short communication: Setup variations in locoregional radiotherapy for breast cancer: an electronic portal imaging study.

Recent trials demonstrating a survival benefit with locoregional radiotherapy (LRRT) to the chest wall and regional nodes in women with node-positive breast cancer have led to increased use of complex techniques to match three or more radiation fields, but information on setup reproducibility with LRRT for breast cancer is scarce. This study reports the magnitude and directions of random and systematic deviations in LRRT for breast cancer using an offline electronic portal imaging verification protocol. Electronic portal images (EPIs) of 46 consecutive women treated with LRRT for breast cancer from March 2001 to February 2002 with LRRT were analysed. Comparisons of EPIs to the corresponding digitally reconstructed radiographs were performed offline with anatomy matching. Displacements in mm were recorded in the superior-inferior (SI), medial-lateral (ML), and anterior-posterior (AP) directions. Random errors ranged from 2.0 mm to 2.5 mm for the breast/chest wall tangential treatments and 2.3 mm to 3.9 mm for the supraclavicular nodal treatments. Systematic errors occurred to a greater degree in the AP direction for the tangential fields and in the ML direction for the supraclavicular field. Displacements of > or =10 mm were found in 1.2% of breast/chest wall tangential treatments and in 6.2% of supraclavicular nodal treatments. These data demonstrate that EPI is a useful tool to verify setup reproducibility in LRRT for breast cancer.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Supervoltage radiotherapy for Graves' ophthalmopathy: CCABC technique and results.

A treatment technique employing retrobulbar supervoltage radiotherapy (XRT) in Graves' ophthalmopathy is described. Twenty-eight patients have been treated and followed between 1980-1983. Twenty-six of 28 patients (93%) showed some response, with 19/28 (68%) having a good to excellent response. Four of 28 (14%) had recurrent symptoms post-XRT. Soft tissue signs and symptoms were relieved and disease progression arrested in the majority of patients, but proptosis and ophthalmoplegia responded poorly. High dose corticosteroids have generally been the alternative form of therapy for this disease. Post-XRT, 24/28 (86%) of patients have had no further steroid requirements, and been spared the associated complications. Treatment was well tolerated, with only five patients (18%) demonstrating a transient worsening of symptoms which settled entirely within 2 weeks. No long-term complications have been encountered. Eleven patients had post-XRT CT scans which were compared to pre-treatment scans and clinical response. Nine of 11 patients (82%) had CT changes in general agreement with the observed clinical response, but the degree of involvement seen on the initial CT scan was not predictive of response nor the risk of relapse. XRT with the described technique is felt to be an effective, safe, and practical approach to the disabling and disfiguring complications of severe Graves' ophthalmopathy.

Effect of time interval between breast-conserving surgery and radiation therapy on ipsilateral breast recurrence.

PURPOSE: To examine the effect of the time interval (interval) between breast-conserving surgery (BCS) and the start of radiation therapy (RT) on the subsequent risk of ipsilateral breast cancer recurrence (IBR). METHODS AND MATERIALS: We reviewed interval and a number of prognostic and treatment factors among 1,962 women treated with BCS and RT for invasive breast cancer diagnosed between January 1, 1989 and December 31, 1993 in British Columbia, Canada. Subjects were female, less than 90 years old at diagnosis, not treated with chemotherapy, not stage T4 or M1, and had survived more than 30 days from diagnosis. The cumulative incidence of IBR was estimated in four interval groups: 0-5, 6-8, 9-12, and 13+ weeks. Only 23 women had an interval of greater than 20 weeks between BCS and start of RT. To assess whether an imbalance of prognostic and treatment factors could be obscuring real differences between the interval groups, Cox proportional hazards regression analyses were conducted. RESULTS: Median follow-up was 71 months. The crude incidence of IBR for the entire sample was 3.9%. The cumulative incidence of IBR in the 6-8, 9-12, and 13+ week groups was not statistically significantly different from the cumulative incidence of IBR in the 0-5 week group. Multivariate analyses demonstrated that patients not using tamoxifen p = 0.027) and those with grade 3 histology (p = 0.003) were more likely to recur in the breast. Interval between BCS and RT was not a statistically significant predictor of breast recurrence when entered into a model incorporating tamoxifen use and tumor grade (0-5 vs. 6-8 weeks, p = 0.872; 0-5 vs. 9-12 weeks, p = 0.665; 0-5 vs. 13+ weeks, p = 0.573). CONCLUSIONS: We found no univariate or multivariate difference in ipsilateral breast cancer recurrence between intervals of 0 to 20 weeks from breast conserving surgery to start of radiation therapy, in a population-based, low risk group of women not receiving adjuvant chemotherapy, after controlling for other factors important in predicting ipsilateral breast cancer recurrence.

Late cosmetic outcome after conservative surgery and radiotherapy: analysis of causes of cosmetic failure.

Although the majority of patients with early breast cancer treated with conservative surgery and radiotherapy have acceptable cosmetic outcomes, the specific causes of a less-than-acceptable result are not well known. To assess the technical factors associated with late cosmetic failure, we reviewed the records of 593 patients treated with conservative surgery and radiotherapy at the Joint Center for Radiation Therapy, Boston, between 1968 and 1981. Median follow-up was 76 months with a range of 37-186 months. Using a 4-point scoring system (excellent, good, fair, poor) patients were noted to have cosmetic "failure" if scored as either fair or poor. Cosmetic results were similar at 3, 5, and 7 years with excellent or good scores seen in 88%, 90%, and 78% of patients, respectively. Three technical factors were associated with a significant worsening of the cosmetic results. The resection of 70 cm3 or more of breast tissue was more common among the failed patients than among matched patients with good or excellent results (p = 0.03). Eighty-nine percent of patients treated with a tangent pair technique had excellent results at 5 years compared to 69% of patients treated with a three-field technique (p = 0.004). The use of a larger volume implant was associated with a greater risk of a fair or poor cosmetic result compared to the use of a smaller volume implant. We conclude that overall cosmesis has been acceptable in this series, but there are technical (surgery and radiotherapy) factors which can be modified to optimize the cosmetic result without compromising local tumor control.

Mammographically detected ductal carcinoma in situ of the breast treated with breast-conserving surgery and definitive breast irradiation: long-term outcome and prognostic significance of patient age and margin status.

PURPOSE: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast treated with breast-conserving surgery followed by definitive breast irradiation. METHODS AND MATERIALS: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1-19.8 years). RESULTS: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0-15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age < or = 39 years, 13% for age 40-49 years, 8% for age 50-59 years, and 6% for age > or = 60 years (p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (p = 0.030). Patient age < or = 39 years and positive margins of resection were both independently associated with an increased risk of local failure (p = 0.0006 and p = 0.023, respectively) in the multivariable Cox regression model. CONCLUSIONS: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma in situ of the breast.

Effect of acetylsalicylic acid on radiation and cosmetic results after conservative surgery for early breast cancer: a randomized trial.

BACKGROUND AND PURPOSE: Acetylsalicylic acid (ASA) can reduce the incidence of stroke and myocardial infarction by inhibiting platelet-fibrin thrombi in small blood vessels. To determine if ASA could reduce late effects of radiation therapy mediated by damage to small blood vessels, a prospective, placebo-controlled, double-blind trial was conducted in women with early breast cancer, receiving radiotherapy to the conserved breast. MATERIALS AND METHODS: Cosmetic outcome and late radiotherapy effects were recorded prospectively for 186 women with T1 or T2, pathologically node-negative breast cancer treated with breast conservation and randomized to receive ASA (325 mg daily) or placebo for 1 year from the start of radiation therapy. Radiation was a tangent pair to the breast alone delivering a modal dose of 44 Gy in 16 daily fractions in 22-25 days. RESULTS: Median follow-up is 6.5 years. The use of ASA has not had any effect on the acute (erythema, edema or discomfort) or late (induration, telangiectasia) effects of radiotherapy (all P > 0.10), the patients' or physicians' assessment of the cosmetic outcome (all P > 0.25) or rates of breast recurrence (P > 0.25). CONCLUSION: ASA cannot be recommended to improve the outcome of radiotherapy complementing breast conserving surgery.

Late cosmetic results of short fractionation for breast conservation.

BACKGROUND AND PURPOSE: The number of fractions of radiation therapy (RT) used after breast conserving surgery varies widely and accounts for a significant proportion of the workload in a modern radiotherapy department. Internationally, 'standard' therapy ranges from 3 to 7 weeks of daily treatment with or without a boost. Short RT schedules have the attraction of reducing workload but raise concern about an increased risk of late effects and poorer cosmetic outcome. MATERIALS AND METHODS: In a randomized trial, 186 women with T1 or T2, pathologically node-negative breast cancer had cosmetic and various normal tissue effects data collected prospectively. The breast RT prescription was 44 Gy in 16 daily fractions to a tangent pair. RESULTS: Median follow-up is 6.7 years. Actuarial 5-year breast recurrence was 6%. Overall cosmetic results at 5 years were good or excellent in 89% and 96% as reported by physicians and patients, respectively, and were stable between 2 and 5 years. Breast discomfort, erythema, edema and induration were related to both surgery and RT. At 5 years, 20% had breast discomfort, 18% had induration, 6% had erythema and 3% had some degree of breast edema. Fewer patients had these effects at 5 years than immediately after primary surgery. The presence of induration prior to starting RT was associated with a greater likelihood of breast induration 3 or more years following RT (P = 0.02). Thirteen percent of patients, generally those with large breasts, developed mild inframammary telangiectasia by 5 years. CONCLUSIONS: Results are comparable to those reported from centers employing more conventional fractionation. Short fractionation produces acceptable cosmetic results for the majority of women if there are no contraindications to RT and in the absence of significant post-operative breast induration.