Radiotherapy In Women Research Articles

Abstract S4-4: SECRAB: The Optimal SEquencing of Adjuvant Chemotherapy (CT) and RAdiotherapy (RT) in Early Breast Cancer (EBC), Results of a UK Multicentre Prospective Randomised Trial

Abstract Background: The optimal sequence of CT and RT for women with EBC has yet to be defined. SECRAB aimed to determine i) if synchronous (Syn) CT-RT improves loco-regional relapse rates (LRR) and ii) whether the treatments could be given together without increased toxicity or compromising the dose intensity of either CT or RT. The first endpoint of this study is presented in this abstract. Methods: SECRAB was a prospective, randomised trial comparing sequential (Seq) to Syn CT-RT. Permitted RT schedules included 40Gy/15F over 3 weeks, 45Gy/20F over 4 weeks and 50Gy/25F over 5 weeks. Syn RT was administered between cycles 2 and 3 for CMF or 5 and 6 for anthracycline-CMF. Syn patients treated using 15F were treated predominantly using a sandwich schedule while those receiving >15F were treated concurrently with CT. Seq RT was delivered on CT completion. Key eligibility criteria were completely excised EBC, fit for and requiring adjuvant CT and RT. The trial was powered to produce a definitive event driven analysis: 150 loco-regional relapses having 85% power to detect 4% 2-sided differences in the primary endpoint of overall LRR. Results: Between Jul 98 and Mar 04, 2296 women were randomised. Baseline characteristics were well balanced. 63% of patients were node positive indicating a high risk population. 2 patients did not receive CT and 23 did not receive RT. 5 patients in the latter group had a loco-regional relapse prior to planned RT (Seq n=3). With a median follow-up of 8.8 years there were 93 and 76 loco-regional relapses in the Seq and Syn arms and 5-year LRR were 7.4% (95% CI 5.9-9.1) and 5.4% (95% CI 4.2-7.0) respectively. There was no significant difference in overall LRR (HRSyn 0.82; 95% CI 0.6-1.1; p=0.19). There was a trend for benefit for Syn treatment which was consistent across different subgroups (grade, lymph node status, tumour size, vascular invasion and excision margin). In an unplanned subgroup analysis, a trend for benefit for Syn treatment was seen predominantly in patients with the presence of lymphovascular invasion (LRR 11.9% Seq vs 8.2% Syn) and also in patients with 0 and 1-3 positive nodes (LRR 7.8% Seq vs 5.2% Syn) but not in those with 4 or more positive nodes. Similar rates were observed for distant recurrences (22.2% vs 22.2%), contralateral recurrences (2.9% vs 2.7%), and new primary cancers (2.9% vs 2.6%) in the Seq and Syn arms respectively. There was also no significant difference in overall survival which was 83% and 82% in the Syn and Seq arms respectively at 5-years (HRSyn 0.99; 95% CI 0.8-1.2; p=0.87). Modest differences in acute skin toxicity and telangiectasia were observed between the two study arms. There was no difference in other late toxicities. The second primary endpoint of safety, toxicity and dose intensity is described in detail elsewhere (abstract no 850168). Conclusions: SECRAB is the largest sequencing trial in EBC to date. Delivering Syn CT-RT using CMF or anthracycline-CMF and a 3 weekly RT fractionation shortens the overall treatment time. Although not statistically significant there was a trend to improved locoregional control with Syn treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-4.

Abstract P4-11-05: Acute and Late Toxicity Results from the SECRAB Trial: The Optimal SEquencing of Adjuvant Chemotherapy (CT) and RAdiotherapy (RT) in Early Breast Cancer (EBC)

Abstract Background: SECRAB is a large multicentre randomised controlled trial designed to determine the optimal sequence of CT and RT for women with EBC. The second objective of this trial was to determine if CT and RT treatment modalities could be given together without increased toxicity or compromising either modality. See abstract no 851519 for details of CT and RT scheduling. Methods: Data on acute skin reaction was collected on completion of RT and graded as mild, moderate or severe. Late toxicity data was collected annually and included lymphoedema, telangiectasia, severe subcutaneous fibrosis, brachial plexopathy, rib fracture, ischaemic heart disease, symptomatic lung fibrosis, and clinical radiation pneumonitis. Results: Between Jul 98 and Mar 04, 2296 women were randomised. Acute toxicity data was collected on 2267 patients who received RT. The distribution of RT schedules was balanced across treatment arms, with the majority of patients (67%) receiving 40Gy/15F (15F). Significantly more patients in the Syn arm experienced a delay of >10 days in CT delivery (11% vs 5%, p < 0.0001). Very few patients experienced a >7 days delay in RT in either arm (Syn n=12 vs Seq n=3). In a sub-set of 880 patients dose intensity of CT was not significantly different between the two arms. Percentage skin toxicities for the Syn and Seq arms respectively were: None 22.9 vs 36.3; Mild 52.4 vs 48.1; Moderate 20.2 vs 13.6; Severe 3.8 vs 1.1. A significantly (p < 0.001) higher proportion of patients on the Syn arm suffered a moderate or severe skin reaction compared to those on the Seq arm. An unplanned exploratory analysis by duration of RT showed that patients receiving >15F (45Gy/20F or 50Gy/25F) had a significantly worse acute skin reaction than those receiving 15F (25% vs 16%, p=<0.001). 5 patients on the Syn arm were admitted to hospital as a result of a severe RT reaction, 3 received >15F. Acute radiation pneumonitis was 0.3% in both arms (n=5 in total). Percentage late toxicities for the Syn and Seq arms respectively were not significantly different for: moderate/severe lymphoedema 6.1 (n=70) vs 5.5 (n=64); severe subcutaneous fibrosis 1.3 (n= 15) vs 0.6 (n=7); brachial plexopathy 0.2 (n=2) vs 0.1 (n=1); rib fracture 0.6 (n=7) vs 0.4 (n=5); ischaemic heart disease 0.4 (n=5) vs 0.4 (n=2); symptomatic lung fibrosis 0.3 (n=15) vs 0.3 (n=7); and late clinical radiation pneumonitis 0.1 (n=1) vs 0.1 (n=1). Howevermoderate/severe telangiectasia was 2.5% vs 1.3% in the Syn and Seq arms respectively (p =0.05). This difference was not seen in patients receiving 15F. Conclusions: The delivery of Syn CT-RT in the adjuvant treatment of EBC is associated with an increase in acute skin toxicity however the percentage of severe reactions is less than 5%. These skin reactions were seen predominantly in patients treated with concurrent RT (>15F). An increase in late skin telangiectasia was also seen in patients receiving >15F. There was no difference in other late toxicities recorded. Syn CT-RT is feasible in the adjuvant treatment of EBC and does not result in a reduction in dose intensity of delivered CT. The optimal schedule is 40Gy/15F which is now the standard regime used in the UK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-05.

Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial

SummaryBackgroundInitial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial.MethodsWomen with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870.FindingsBetween May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9–14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30–0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19–0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22–0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45–1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58–0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51–0·86; p=0·03) and contralateral tumours (0·44, 0·25–0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66–1·38; p=0·8). No data on adverse events except cause of death were collected for this trial.InterpretationThis updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.FundingCancer Research UK and the Australian National Health and Medical Research Council.

Hypofractionated Adjuvant Whole Breast Radiotherapy: Progress and Prospects

Published results of randomised trials involving >7000 women confirm the safety and efficacy of hypofractionated schedules of adjuvant radiotherapy for women with early breast cancer using fraction sizes between 2 and 3 Gy assuming appropriate downward adjustments to total dose. Unnecessary concerns relating to heart tolerance, suboptimal dose distribution and duration of follow up need not discourage the routine adoption of 15- or 16-fraction schedules in women treated by breast conservation surgery for early breast cancer. Regardless of fractionation regimen, dose escalation to the index quadrant in high risk subgroups will result in a greater relative increase in late adverse effects than tumour control, a therapeutic disadvantage that can only be overcome by exploiting a marked dose-volume effect. A 15-fraction schedule of whole breast radiotherapy is unlikely to represent the lower limits of hypofractionation, and the preliminary results of a 5-fraction regimen are encouraging.

Hypofractionated Whole Breast Radiation in Women with DCIS or Grade 3 Invasive Breast Cancer

Randomized data supports hypofractionated whole breast radiation as an appropriate, cost-effective approach demonstrating similar local control, survival, and cosmesis when compared with conventional fractionation. Data is relatively scarce regarding management of DCIS with hypofractionated radiation. Recent randomized data also point to local recurrence risk in patients with invasive grade 3 tumors as a potential concern. We review a large, single-institution experience in using hypofractionated radiation to the intact breast, focusing on outcomes in patients with DCIS or grade 3 invasive breast cancer.

Intraoperative radiotherapy in women with early breast cancer treated by breast‐conserving therapy

Previous studies demonstrated the feasibility of intraoperative radiotherapy (IORT) to the primary tumour bed using a miniature electron beam driven X-ray source for early breast cancer. This study aimed to evaluate the feasibility of IORT as a tumour bed boost after whole breast irradiation (WBI) in breast conserving therapy. This was a single-arm prospective trial for women with breast cancer measuring <3 cm. After breast-conserving surgery, a single IORT dose of 5 Gray (Gy) prescribed to 10 mm from the applicator surface was delivered to the breast tissues using 50 kV X-ray followed by standard WBI. The feasibility rate of protocol therapy was defined as the percentage of all women who completed both IORT and WBI. A desirable completion rate was >90%. The protocol therapy would be considered unsuitable for further development if the completion rate was <75% or severe acute toxicity occurred in >15% of women who received IORT. Sixty patients were recruited for the study. IORT and WBI were delivered in 58 and 55 patients, respectively. Thus, the feasibility rates of IORT alone and both IORT and WBI were 97% (95% confidence interval (CI), 89-99%) and 92% (95% CI, 83-97%), respectively. A severe surgical complication or grade 3 or 4 acute radiation toxicity were identified in 10% (6/58) of women who had IORT. Tumour bed boost using IORT in women with early breast cancer treated with conservative surgery and WBI was shown to be feasibly consistent with previous studies.

The use of MRI for selecting patients with endometrial cancer and significant co-morbidities for vaginal hysterectomy

The objective of this study is to ascertain the presence of extrauterine spread in radiologically early stage and grade endometrial cancer. This could be the basis for offering vaginal hysterectomy without salpingo-oophorectomy as an alternative option to primary radical radiotherapy in women with significant medical co-morbidities in whom laparotomy will be contraindicated. A retrospective cohort study assessing patients with clinically early stage endometrioid adenocarcinoma of the endometrium, treated at the Gynaecological Oncology Centre, Norfolk and Norwich University Hospital and James Paget University Hospital between January 2003 and July 2008. The cancer registry was reviewed, and 542 endometrial cancer cases were identified during the study period, of these 439 were endometrioid type. MR is the standard staging investigation unless there are contraindications. Demographic, clinic-pathologic and surveillance data were collected from hospital records, operative notes and histopathology reports. The histology included tumour type, stage and grade. Post-operative histopathological findings served as a reference standard. Sensitivity and specificity of pre-operative MRI scan were assessed. Of the 439 cases treated during the study periods, 415 patients had an MRI pre-operatively imaging and 14% of these cases showed signs of extrauterine spread. MRI staging was then compared with the histopathology staging; the latter was taken as the gold standard. In 8% of the cases where no spread was seen on MRI, the disease was actually spread outside uterine corpus mainly to the cervix and pelvic lymph nodes. The sensitivity, specificity, positive predictive value and negative predictive value for MRI were 56, 93, 60, and 92, respectively, while predicting early stage disease. There were three cases of adnexal metastases, where the tumour had already spread to uterine serosa. Two cases had poorly differentiated and one had moderately differentiated tumour. The risk of adnexal metastasis is less than 1% in clinically early stage disease and highly unlikely if MRI suggests that the disease is confined to the inner half of the myometrium and low-grade disease. MRI has a high specificity and negative predictive value in endometrial cancer staging with reduced sensitivity of detecting cervical, adnexal and lymphatic spread. We suggest that vaginal hysterectomy might be a safe alternative to laparotomy in the treatment of radiological early stage disease in medically compromised elderly patients. The possibility of converting a vaginal approach to an abdominal route should be always taken into consideration.

P19 A qualitative study related to problems experienced during chemotherapy and radiotherapy in women with breast cancer

P19 A qualitative study related to problems experienced during chemotherapy and radiotherapy in women with breast cancer

The Cochrane Database of Systematic Reviews – Issue 1 of 2010

The Cochrane Database of Systematic Reviews – Issue 1 of 2010

Indication of Radiotherapy for Women With Cervical Cancer in Rio De Janeiro, Brazil

The objective of this article was to analyze the treatment modalities used at the Brazilian National Cancer Institute, with particular emphasis on the use of radiotherapy (RT) and its indications in invasive cervical cancer, considering the staging and clinical epidemiological characteristics of the population. All cases of primary invasive tumors of the cervix (CID C53) registered at the institute and diagnosed between 1999 and 2004 were selected. The following variables were studied: (1) age, (2) year of diagnosis, (3) level of schooling, (4) race, (5) histopathologic subtype, (6) the staging of the tumor on diagnosis, and (7) the treatment modality initially offered. We analyzed 3509 cases of invasive disease, and 79.7% of them received RT. Based on the final logistic model, it was possible to construct a probabilistic model for the indication of RT in the subgroups formed by the combinations of the 3 highlighted variables (stage, age, and histological type). The likelihood varied from 22.5% in those with epidermoid carcinoma, stage I, younger than 55 years up to 100% in those with locally advanced disease and older than 65 years. These results indicate the importance of RT as a modality of treatment of invasive cervical cancer in Brazil, where a substantial proportion of the diagnoses are made in advanced stages. This set of information regarding this important center may help the long-term strategic planning and the allocation of funds that enable the high demand to be met in an optimized manner.

Beneficial Effect of Tamoxifen for Women with DCIS: Long-Term Results from the UK/ANZ DCIS Trial in Women with Locally Excised DCIS.

Abstract Background: Initial results of the UK/ANZ DCIS trial found that adjuvant radiotherapy reduced the recurrence of ipsilateral invasive breast cancer (BC) and ductal carcinoma in situ (DCIS) by 55% and 64% respectively, but the effect of tamoxifen was smaller (Lancet 2003, 362: 95-102). Here, we report an updated analysis of this trial.Methods: 1701 women with completely locally excised DCIS were enrolled in a randomised 2x2 trial of radiotherapy, tamoxifen or both. Elective decision to withhold or provide one of the treatments was also permitted and long-term follow-up was performed by treating hospitals. Seven patients were excluded due to protocol violations leaving 1694 patients available for analysis.Results: After a median follow-up of 12.7 years, a total of 376 breast cancers were diagnosed; 162 invasive (122 ipsilateral; 39 contralateral) and 197 DCIS (173 ipsilateral; 17 contralateral). Radiotherapy continued to reduce the incidence of ipsilateral invasive disease (HR=0.32 (0.19-0.56), P&amp;lt;0.0001) and ipsilateral DCIS (HR=0.38 (0.22-0.63), P&amp;lt;0.0001), but had no significant effect on contralateral breast cancer (HR=0.84 (0.45-1.58)). Tamoxifen significantly reduced all recurrences by 29% (HR=0.71 (0.58-0.88), P=0.002) (Figure 1). This consisted of a 30% (HR=0.70 (0.51-0.86)) reduction in recurrent ipsilateral DCIS, a small 5% (HR=0.95 (0.66-1.38)) reduction in ipsilateral invasive disease, and a 56% (HR=0.44 (0.25-0.77)) reduction in contralateral tumours. Overall, women randomised to radiotherapy and not receiving tamoxifen had a 59% reduction in recurrence (HR=0.41 (0.30-0.57), P&amp;lt;0.0001), whereas those randomised to tamoxifen and not receiving radiotherapy had an overall reduction of 29% (HR=0.71 (0.57-0.87), P=0.001).Conclusion: This updated analysis confirms the long-term benefit of radiotherapy in women with DCIS treated by complete local excision and also established a benefit for tamoxifen. Ongoing work will examine in detail which subsets of tumours (e.g. high grade, oestrogen receptor positive) will benefit most from these treatments. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 34.

Adjuvant radiotherapy of women with breast cancer – Information, support and side-effects

The aim of this study was to 1) examine the occurrence and burden of side effects over time in the period after post surgical adjuvant radiotherapy in women with breast cancer and 2) explore the women's experiences of given information and need of support to handle side effects. Material and method 171 women with breast cancer receiving post-surgical adjuvant radiotherapy completed a questionnaire on radiotherapy-related side effects (Treatment Toxicity Assessment Tool OTTAT) at four times between the start of radiotherapy and six months after completion. Comparisons were made between women with breast conservative surgery (group A) and women with modified mastectomy (group B), and for having chemotherapy or not (C+ and C−). Questions regarding the experience of delivered information and support were added. Results Fatigue was the single most prevalent side effect and, together with skin reactions and pain, it also had the highest mean score over the study period and the largest score increase during treatment. The largest increase during the six months was seen for skin reaction, pain, and dyspnoea. The average score for skin reaction was significantly higher in group B than in group A. A majority of the women experienced the given information and support as satisfying and a need for follow-up of the side-effects was expressed. Conclusion Nursing for women with breast cancer receiving adjuvant radiotherapy should focus on preventing and treating side effects, and also include the period post treatment. There is a need for developing evidence based guidelines including guidelines for follow-up.

Racial Disparities in the Use of Radiation Therapy in Women with Early-stage Breast Cancer after Lumpectomy

Breast conservation surgery (BCS) with radiation therapy is considered standard of care for patients with early-stage breast cancer. The purpose of this study is to assess racial disparities in women who do not receive radiation therapy after BCS.

Outcomes After Breast Conservation Treatment with Radiation in Women with Ductal Carcinoma In Situ and Prior Nonbreast Malignancy

Management of ductal carcinoma in situ (DCIS) of the breast is controversial, as not all patients progress to invasive carcinoma. This report analyzes the outcomes after breast conservation treatment (BCT) with radiation in patients with DCIS following prior malignancy at another anatomic site. The study cohort was comprised of 14 women with DCIS who were treated between 1978 and 2003. The median age at diagnosis of DCIS was 54 years (mean 56; range 37-78) and for the prior nonbreast malignancy was 44 years (mean 47; range 27-76). All patients underwent breast conservation surgery followed by whole breast radiation and tumor bed boost. The median and mean follow-up times after treatment of DCIS were 8.0 and 9.1 years, respectively (range 2-18). The median and mean interval period between the prior malignancy and DCIS was 6.0 and 8.2 years, respectively (range 1-30). There was one (7%) local failure, two (14%) contralateral breast cancers, and one (7%) death from breast cancer that occurred 7 years after BCT following contralateral invasive breast cancer. In this cohort of 14 patients treated for DCIS of the breast after a prior nonbreast malignancy, treatment for DCIS resulted in a high rate of local control and should be considered for curative intent.

Incidence and Predictors of Thyroid Dysfunction following Three-Dimensional Conformal Radiation Therapy (3D-CRT) to Low Neck as Component of Adjuvant Radiation in Women with Breast Cancer: Prospective Long Term Follow-Up

Incidence and Predictors of Thyroid Dysfunction following Three-Dimensional Conformal Radiation Therapy (3D-CRT) to Low Neck as Component of Adjuvant Radiation in Women with Breast Cancer: Prospective Long Term Follow-Up

Outcome After Breast Conservation Treatment with Radiation for Women with Triple-Negative Early-Stage Invasive Breast Carcinoma

Background Triple-negative breast carcinoma is defined by a primary tumor that is estrogen receptor negative, progesterone receptor negative, and HER2 negative. The current study was performed to determine the relationship of triple-negative tumor status to outcome after breast conservation treatment with radiation. Patients and Methods A total of 519 women with early-stage invasive breast carcinoma underwent breast conservation treatment with radiation. Of the 519 primary breast carcinomas, 90 (17%) were triple negative and 429 (83%) were not triple negative. The median follow-up after treatment was 3.9 years. Results Compared with the patients without a triple-negative tumor, the patients with a triple-negative tumor had a higher 8-year rate of any local failure (8% vs. 4%, respectively; P = .041) and a lower 8-year rate of freedom from distant metastases (81% vs. 92%, respectively; P = .0066). There were no differences between the 2 groups for local-only first failure, overall survival, or contralateral breast cancer (all P ≥ .3). On multivariate analysis, triple-negative tumors had an increased risk for any local failure (hazard ratio, 2.58), although this difference was not statistically significant ( P = .097). Conclusion After breast conservation treatment with radiation, women with a triple-negative tumor had a higher rate of local failure compared with women without a triple-negative tumor. However, the absolute difference in local failure between the 2 groups was relatively small and therefore does not preclude breast conservation treatment with radiation for triple-negative early-stage invasive breast carcinoma.

Accelerated Partial Breast Irradiation: Where Do We Stand?

Accelerated partial breast irradiation (APBI) is a new form of postlumpectomy radiotherapy delivered over 1 to 5 days. Early trials showed high local recurrence rates. More recent single and multiinstitutional studies, as well as a single phase III trial, have shown local control more comparable to whole breast radiotherapy. Patient selection and surgical technique are important variables preparatory to irradiation, which is delivered using 1 of 4 accelerated radiotherapy methods. Phase I/II studies have produced most of the information currently available regarding APBI. Additional phase III studies are underway to determine whether any or all of these accelerated radiotherapy approaches may safely substitute for whole breast radiotherapy in women seeking breast conservation.

Surveillance for Breast Cancer After Childhood Cancer

BREAST CANCER IS A RECOGNIZED COMPLICATION OF chest irradiation for childhood cancer, and surveillance for breast cancer with regular clinical examination and annual screening mammography starting at age 25 years or 8 years after radiation is recommended. However, uptake of screening mammograms in this high-risk group is suboptimal, as shown in the report by Oeffinger and colleagues in this issue of JAMA. The authors examined breast cancer surveillance practices in a survey of 625 female survivors of pediatric cancer who were between 25 and 50 years and participants in the longitudinal Childhood Cancer Survivor Study (CCSS). These survivors were at a significantly increased risk of breast cancer as a result of treatment they received in the form of moderateto high-dose ( 20 Gy) irradiation to the chest for treatment of a childhood cancer (chest RT group). The women in the chest RT group were compared with 639 similarly aged CCSS participants who did not receive chest irradiation and with 712 siblings in the CCSS siblings cohort. Oeffinger et al found that 55% of the women in the chest RT group reported having a screening mammogram within the previous 2 years. Rates of screening mammography varied by age at the time of the survey, with 23.3% of women aged 25 through 39 years and 53.6% of women aged 40 through 50 years reporting a screening mammogram in the previous year. Among women in the younger group, those who reported a physician recommendation for screening were 3 times as likely to have had screening in the previous 2 years when compared with those whose physician did not recommend that they have a mammogram. In light of a recognized increased risk of breast cancer following radiation to the chest, chest irradiation is now used less frequently for the curative treatment of some pediatric cancers, which include different types of childhood cancer including Hodgkin disease, Wilms tumor, neuroblastoma, and non-Hodgkin lymphoma; however, there are an estimated 20 000 to 25 000 adult survivors of pediatric cancer older than 25 years in the United States who are in this risk category. Current Childhood Oncology Group (COG) guidelines for breast cancer surveillance after pediatric cancer in the United States recommend yearly clinical breast examination from the age of puberty until age 25 years, and then every 6 months if the survivor was treated with irradiation of at least20 Gy to mantle, minimantle, mediastinal, chest (thoracic), or axillary fields. In addition, it is recommended that these survivors have annual mammography and an adjunct breast magnetic resonance imaging (MRI) starting at age 25 years or 8 years after radiation, whichever is last. The effectiveness of the standard mammogram in detecting preinvasive and invasive breast cancer is known to be relatively poor in young women due to the density of breast tissue in this age group, increasing the importance of MRI in the detection and diagnosis of breast cancer in younger women with dense breast tissue. The estimated dose of radiation from a standard 2-view screening mammogram is approximately 3.85 mGy per mammogram. Although it is accepted that the additional dose is small compared with the higher therapeutic dose already received, it is not known to what extent repeated exposure to small doses of breast irradiation in women already at an increased risk of breast cancer may result in a significantly increased risk of second primary breast cancer. This is an important question that needs to be addressed in future studies. The generally low uptake rate of screening mammogram in a high-risk population of pediatric cancer survivors has also been highlighted in a previous study of adult survivors. Some factors associated with the uptake of breast screening including age and race/ethnicity, physician recommendation, health beliefs, and personal understanding of breast cancer risk were explored by Oeffinger et al, but economic factors were not. Thus, whether the cost of annual breast cancer screening was a factor in this cohort is not known. In comparison, among a population of 461 Australian women at an increased risk of developing hereditary breast cancer, uptake of breast screening was 89% overall, although it decreased to 77% among those

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis

SummaryBackgroundEarly endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer.MethodsBetween July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40–46 Gy in 20–25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5).FindingsAfter a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1·05 (95% CI 0·75–1·48; p=0·77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1·04; 95% CI 0·84–1·29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6·1%.InterpretationAdjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.FundingMedical Research Council, National Cancer Research Network, National Cancer Institute of Canada, with funds from the Canadian Cancer Society.

A phase I/II study of extended field radiation therapy with concomitant paclitaxel and cisplatin chemotherapy in patients with cervical carcinoma metastatic to the para-aortic lymph nodes: A gynecologic oncology group study

Objectives To determine the maximum tolerated dose (MTD) of weekly paclitaxel and cisplatin chemotherapy concurrent with extended field irradiation in women with cervical cancer metastatic to the para-aortic nodes. Methods Patients with carcinoma of the cervix and histologically documented para-aortic node metastases were eligible for this phase I/II trial. Chemotherapy agents were administered weekly concurrent with extended field radiation with escalating doses of paclitaxel from 30–50 mg/m 2 in each of three cohorts of three patients each. A phase II cohort was then evaluated at the selected maximum tolerated dose (MTD). Results The MTD was determined to be cisplatin 40 mg/m 2 (maximum dose of 70 mg) and paclitaxel 40 mg/m 2 administered weekly for six cycles concurrent with extended field radiation therapy. There were 19 evaluable patients for the phase II analysis of toxicity and efficacy. Grade three and four gastrointestinal toxicity was seen in 6 and neutropenia in 7. Radiation therapy was successfully completed in 36.8% of patients at eight weeks and in 68.4% of patients at nine weeks, with a median time to completion was 56 days. A total of 27 evaluable patients were enrolled, twelve are dead (mean survival of those deceased is 25 months), and 15 (56%) are alive, and have been followed for a mean of 48 months (range 25–68; median of 46 months). Conclusions Paclitaxel and cisplatin combination chemotherapy concurrent with extended field pelvic para-aortic irradiation can be administered at the described MTD and shows a higher than previously reported disease-free survival in relation to historical data. The 56% survival to date, and 50% estimated 48 month survival, warrants validation in a larger prospective cohort. Central radiation dose reduction is being considered in the next trial to decrease late toxicity of regimen.