Breast conservation versus mastectomy in patients with T3 breast cancers (> 5 cm): an analysis of 37,268 patients from the National Cancer Database.

PURPOSE: Breast conservation therapy (BCT) is standard for T1-T2 tumors, but early trials excluded breast cancers > 5 cm. This study was performed to assess patterns and outcomes of BCT for T3 tumors. METHODS: We reviewed the National Cancer Database (NCDB) for noninflammatory breast cancers > 5 cm, between 2004 and 2011 who underwent BCT or mastectomy (Mtx) with nodal evaluation. Patients with skin or chest wall involvement were excluded. Patients having clinical T3 tumors were analyzed to determine outcomes based upon presentation, with those having pathologic T3 tumors, subsequently assessed, irrespective of presentation. Overall survival (OS) was analyzed using multivariable Cox proportional hazards models, with adjusted survival curves estimated using inverse probability weighting. RESULTS: After exclusions, 37,268 patients remained. Median age and tumor size for BCT versus Mtx were 53 versus 54 years (p < 0.001) and 6.0 versus 6.7 cm (p < 0.001), respectively. Predictors of BCT included age, race, location, facility type, year of diagnosis, tumor size, grade, histology, nodes examined and positive, and administration of chemotherapy and radiotherapy. OS was similar between Mtx and BCT (p = 0.36). This held true when neoadjuvant chemotherapy patients were excluded (p = 0.39). BCT percentages declined over time (p < 0.001), while tumor sizes remained the same (p = 0.77). Median follow-up was 51.4 months. CONCLUSIONS: OS for patients with T3 breast cancers is similar whether patients received Mtx or BCT, confirming that tumor size should not be an absolute BCT exclusion. Declining use of BCT for tumors > 5 cm in younger patients may be accounted for by recent trends toward mastectomy.

Gromwell (Lithospermum erythrorhizon) root extract protects against glycation and related inflammatory and oxidative stress while offering UV absorption capability.

Glycation and advanced glycation end products (AGE) damage skin which is compounded by AGE-induced oxidative stress and inflammation. Lip and facial skin could be susceptible to glycation damage as they are chronically stressed. As Gromwell (Lithospermum erythrorhizon) root (GR) has an extensive traditional medicine history that includes providing multiple skin benefits, our objective was to determine whether GR extract and its base naphthoquinone, shikonin, might protect skin by inhibiting glycation, increasing oxidative defenses, suppressing inflammatory responses and offering ultraviolet (UV) absorptive potential in lip and facial cosmetic matrices. We show GR extract and shikonin dose-dependently inhibited glycation and enhanced oxidative defenses through nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element activation. Inflammatory targets, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and tumor necrosis factor alpha, were suppressed by GR extract and shikonin. Glyoxalase 1 (GLO1) and glutathione synthesis genes were significantly upregulated by GR extract and shikonin. GR extract boosted higher wavelength UV absorption in select cosmetic matrices. Rationale for the use of GR extract and shikonin are supported by our research. By inhibiting glycation, modulating oxidative stress, suppressing inflammation and UV-absorptive properties, GR extract and shikonin potentially offer multiple skin benefits.

Impact of rheumatoid arthritis on radiation-related toxicity and cosmesis in breast cancer patients: a contemporary matched-pair analysis.

PURPOSE: To evaluate the impact of rheumatoid arthritis (RA) on toxicity and cosmesis in women undergoing radiotherapy for breast cancer. METHODS: We queried an institutional database for women with RA treated with external beam radiotherapy for breast cancer between 1981 and 2016. Matching each patient to three controls without RA was attempted. Radiation toxicity was graded using CTCAE 4.0. Cosmesis was graded using the Global Harris Scoring System of Excellent, Good, Fair, or Poor. Grade 2+ (G2+) acute and late toxicities were compared between women with RA and their matched pairs using a generalized estimating equation (GEE). Wilcoxon test and mixed effects model were used to compare the cosmesis between two groups. RESULTS: Forty women with RA at time of radiation were matched to 117 controls. The median radiation dose was 60 Gy (50-66 Gy) and the median follow-up was 94 months (1-354 months). When comparing the women with RA to their matched pairs, there was no significant difference in the rates of G2+ acute toxicity (25.0 vs. 13.7%, O 2.1, CI 0.91-4.9) or G2+ late toxicity (7.5 vs. 4.3%, OR 1.8, CI 0.48-6.8). Mean cosmesis was between Good and Excellent for both groups of patients, although women with RA were less likely to get Excellent cosmesis compared to their matched pairs (OR 0.35, CI 0.15-0.84). CONCLUSIONS: Among women with RA, radiation for breast cancer was well tolerated without significantly increased toxicity. Their cosmesis was generally Good to Excellent, although they might be less likely to get Excellent cosmesis compared to their matched pairs.

Disparities in the Local Management of Breast Cancer in the US according to Health Insurance Status.

Although standard practice guidelines for breast cancer are clear, the interplay between insurance and practice patterns for the US is poorly defined. This study was performed to test for associations between patient insurance status and presentation of breast cancer as well as local therapy patterns in the US, via a large national dataset. We queried the NCI Surveillance, Epidemiology, and End Results data base for breast cancer cases diagnosed from 2007 to 2011 in women aged 18-64 with nonmetastatic ductal/lobular cancers, treated surgically. We tested for associations between insurance status (insured/Medicaid/uninsured) and choice of surgical procedure (mastectomy/breast conserving surgery [BCS]), omission of radiotherapy (RT) following BCS, and administration of post-mastectomy radiation (PMRT). There were 129,565 patients with localized breast cancer analyzed. The health insurance classification included insured (84.5%), Medicaid (11.5%), uninsured (2.1%) and unknown (1.9%). Medicaid or uninsured status was associated with large, node positive tumors, black race, and low income. The BCS rate varied by insurance status: insured (52.2%), uninsured (47.7%), and Medicaid (45.2%), p < 0.001. In multivariable analysis, Medicaid insurance remained significantly associated with receipt of mastectomy (OR [95% CI] = 1.07 [1.03-1.11]), while RT was more frequently omitted after BCS in both Medicaid (OR [95% CI] = 1.14 [1.07-1.21]) and uninsured (OR [95% CI] = 1.29 [1.14-1.47]) patients. Insurance status was associated with significant variations in breast cancer care in the US. Although patient choice cannot be determined from this dataset, departure from standard of care is associated with specific types of insurance coverage. Further investigation into the reasons for these departures is strongly suggested.

Breast conservation versus mastectomy for patients with T3 primary tumors (>5 cm): A review of 5685 medicare patients.

BACKGROUND: Although breast conservation therapy (BCT) is standard for breast cancer treatment, patients with tumors measuring >5 cm have been excluded from clinical trials. Nevertheless, only a few small retrospective series to date have compared BCT with mastectomy for tumors measuring >5 cm. The current study was performed to determine whether survival is equivalent for BCT versus mastectomy using a large national data set. METHODS: Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked cases were identified for patients aged ≥ 66 years undergoing breast conservation for invasive, noninflammatory, nonmetastatic breast cancer between 1992 and 2009. Propensity score-based adjustment was used to account for demographics and tumor and treatment factors. RESULTS: A total of 5685 patients with tumors measuring >5.0 cm underwent breast surgery, with 15.6% receiving BCT. Mean ages of the patients and tumor sizes were similar. Predictors of BCT included neoadjuvant chemotherapy and postoperative radiotherapy use, higher income, breast cancer as a first malignancy, and a higher Charlson Comorbidity Index. Predictors of mastectomy included younger age, nonductal histology, higher grade, numbers of lymph nodes examined and found to be positive, American Joint Committee on Cancer stage III disease, postoperative chemotherapy use, and residential region of the country. Adjusted overall and breast cancer-specific survival were not different between patients treated with BCT and mastectomy (hazard ratio, 0.934; 95% confidence interval, 0.791-1.103 [P = .419] for overall survival; and subdistribution hazard ratio, 1.042; 95% confidence interval, 0.793-1.369 [P = .769] for breast cancer-specific survival), with each improving over time. The median follow-up was 7.0 years. CONCLUSIONS: For Medicare patients with tumors measuring >5 cm, survival is similar between those treated with BCT and mastectomy as for patients with smaller primary tumors. Despite exclusion from randomized trials, BCT may remain an option for patients with larger tumors when deemed clinically and cosmetically amenable to surgical resection.

Disparities in the management and outcome of cervical cancer in the United States according to health insurance status.

INTRODUCTION: Our study sought to characterize the presentation, local management and outcomes of invasive cervical cancer with regard to patient insurance status. METHODS: We queried the NCI-SEER database for invasive cervical cancer cases in patients aged 18-64 from 2007 to 2011. We analyzed clinical and socioeconomic data with regard insurance status (insured, Medicaid, or uninsured). We tested for associations between patient insurance status and treatment with definitive surgery for FIGO IA2-IB1 patients, and treatment with suboptimal radiation therapy (RT) for FIGO IB2-IVA patients (other than combination external beam and brachytherapy). We evaluated overall and cause specific survival according to insurance status. RESULTS: 11,714 cases were analyzed: 60% insured, 31% Medicaid, and 9% uninsured. FIGO III/IV stage at presentation was more frequent with Medicaid (40%) and uninsured (42%) compared to insured patients (28%) (p<0.001). For FIGO IA2-IB1 patients, receipt of definitive surgery was inversely associated with uninsured status (OR [95%CI]=0.65 [0.47-0.90], p<0.001) in univariable analysis; however the relationship lost significance after multivariable adjustment. For FIGO IB2-IVA patients, the use of suboptimal RT was associated with uninsured status (OR [95%CI]=1.33 [1.07-1.65], p=0.011) in adjusted analyses. Among all patients, overall mortality was increased with Medicaid (HR [95%CI]=1.16 [1.05-1.28], p=0.003) and uninsured status (HR [95%CI]=1.17 [1.01-1.34], p=0.031) in multivariable analysis. Cancer specific mortality survival trended towards significance in multivariable analyses for both Medicaid (HR [95%CI]=1.11 [1.00-1.24] and uninsured status (HR [95%CI]=1.14 [0.98-1.33]). CONCLUSIONS: Disparities in cervical cancer treatment with regard to insurance status are apparent in a recent cohort of American patients. Later stage at presentation and differences in management partially account for the inferior prognostic outcomes associated with Medicaid and uninsured status.

The role of adjuvant radiation in lymph node positive endometrial adenocarcinoma.

OBJECTIVES: The purpose of this study was to examine the impact of adjuvant radiation on overall survival (OS) and cancer specific survival (CSS) in patients with lymph node (LN) positive endometrial cancer. METHODS: We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 (n=2177). Patients not undergoing surgery or with missing treatment information were excluded. Chi-squared tests were used to compare predictors of treatment received. Cox proportional hazards model and Kaplan-Meier method were used to assess OS and CSS. RESULTS: The median age was 60 (27-84) and the median follow-up was 31months (2-107). Adjuvant radiation was administered to 1248 (60.3%) patients. A total of 1363 (65.9%) patients had pelvic LN involvement while 658 (31.8%) had para-aortic involvement. The 3-year actuarial OS for patients with and without radiation was 80.5% and 67.6%, respectively (p<0.001). The 3-year actuarial CSS for patients with and without radiation was 83.4% and 73%, respectively (p<0.001). On multivariable analysis, receipt of radiotherapy remained associated with OS (HR 0.61 95% CI 0.51-0.74) and CSS (HR 0.65, 95% CI 0.53-0.80). After propensity matching, radiotherapy continued to be associated with an improved OS (HR 0.65 95% CI 0.54-0.78) and CSS (HR 0.65 95% CI 0.53-0.81). The addition of brachytherapy was not associated with OS or CSS. CONCLUSIONS: In this large population registry analysis, adjuvant radiation was associated with improved OS and CSS in patients with LN positive endometrial cancer. Prospective data is needed to confirm these findings.

Multifocal and multicentric breast cancer is associated with increased local recurrence regardless of surgery type.

Multifocal and multicentric breast cancers have been correlated with poor prognostic factors and worse outcomes versus unifocal disease. We evaluated the impact of multifocal and multicentric disease versus case controls with unifocal disease, matching for age, grade, T-, and N-stage. A total of 110 patients with multifocal (n = 93) or multicentric (n = 17) disease and 263 matched case controls were identified with a median follow-up of 53 months and 64 months, respectively. The actuarial local control rates for the multifocal/multicentric and unifocal group were 88% and 97%, respectively at both 5 and 10 years (p < 0.001). On multivariate analysis, multifocal/multicentric disease remained associated with higher local recurrence after controlling for other covariates including surgery type. The disease-free survival rates in the multifocal/multicentric group at 5 and 10 years were 75% and 71%, respectively, versus 87% and 78% at 10 years (p = 0.01). On multivariate analysis, multifocal/multicentric disease was no longer associated with worse disease-free survival. There was no difference in the cohorts in terms of regional control, overall survival, or cancer specific survival. Our findings suggest that multifocal/multicentric disease may be associated with worse outcomes versus unifocal disease regardless of type of surgery. This suggests a more biologically aggressive cancer and may be an important consideration when managing these patients. Further studies are needed to better understand the impact of multifocal/multicentric breast cancers on outcomes.

Risk of positive nonsentinel nodes in women with 1-2 positive sentinel nodes related to age and molecular subtype approximated by receptor status.

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1-2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1-2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1-10) and 14 (range 6-37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.

Factors Associated with Reconstruction Failure and Major Complications After Postmastectomy Radiation to a Reconstructed Breast.

PURPOSE: Postmastectomy radiation therapy is known to increase risk of complications in the reconstruction setting. We aim to identify the variables associated with reconstruction failure and other major complications. METHODS AND MATERIALS: A prospectively collected institutional database was queried for patients with up to stage IIIC breast cancer treated from 2000 to 2017, undergoing mastectomy, immediate implant or autologous tissue reconstruction, and radiation to the reconstructed breast within 1 year of surgery. Reconstruction failure was defined as complication requiring surgical revision or implant removal. Additional major complications were defined as any infection, contracture, necrosis, or fibrosis. Covariates of interest included age, body mass index, smoking status, stage, hormone receptor and HER2 status, systemic therapy timing, radiation technique, nodal irradiation, and interval between surgery and start of postmastectomy radiation therapy. Differences in complication rates were assessed with χ² or Fisher exact tests. Competing risk regression was used to estimate hazard ratios; covariates were included one at a time to avoid over adjustment. RESULTS: A total of 206 reconstructed breasts in 202 patients resulted from our initial query, with 139 treated with intensity-modulated radiation therapy (IMRT) and 67 treated with conventional radiation therapy (CRT). Median follow-up was 45 months (range, 4-210 months); patient cohorts were generally similar. Eight patients were excluded from toxicity analysis for insufficient follow-up (<2 years). Overall, reconstruction failure and major complication rates were significantly lower in the IMRT group. Reconstruction failure rates were 3.0% for IMRT versus 16.4% for CRT (P = .002), and major complication rates were 6.8% for IMRT versus 24.6% for CRT (P < .001). On univariate analysis, CRT was significantly predictive of implant failure (hazard ratio, 5.54; P = .003) and increased complication rates (hazard ratio, 3.83; P = .001). Significance persisted on multivariable analysis. Survival outcomes were similar, with no difference in 2 year overall survival (P = .12) and local recurrence (P = .41). CONCLUSIONS: Using IMRT may improve reconstruction outcomes over CRT, with significantly lower reconstruction failure and complication rates without compromising local control or survival.

Lymphatic space invasion is not an independent predictor of outcomes in early stage breast cancer treated by breast-conserving surgery and radiation.

To study the prognostic importance of lymphovascular invasion (LVI) in early stage breast cancer after conservative surgery and radiation. From 2/80 to 8/07, 1,478 patients were treated with breast-conserving surgery and radiation with or without systemic therapy. Study eligibility included breast conservation, whole breast postoperative radiation, T1-T2 disease, and known LVI status. Endpoints were 5- and 10-year actuarial outcomes for local control and survival. LVI was present in 427 patients and absent in 1,051 patients. Median follow-up was 68 and 69 months, respectively. Patients with LVI had a younger median age, were more often pre- or perimenopausal, T2, physically palpable, invasive ductal, node positive, grade 3, and treated with chemotherapy compared with patients without LVI. The 5- and 10-year local-regional recurrence was 4.5% and 9.6% with LVI compared with 1.6% and 5.6% without LVI (p = 0.01). The 5- and 10-year overall survival was 83% and 68% for LVI and 91% and 80% for no LVI, respectively (p < 0.0001). Multivariate analysis showed that LVI was not an independent predictor of local-regional control (p = 0.0697) or survival (p = 0.1184). LVI in breast cancer is found in association with other worse prognostic factors for outcome, is associated with a modest increase in local-regional recurrence, but is not an independent predictor of local-regional recurrence or survival on multivariate analysis.

Health states of women after conservative surgery and radiation for breast cancer.

The aim of the study is to use the EQ-5D instrument to evaluate the long-term health states of women with early stage breast cancer treated by breast-conserving surgery and radiation. A total of 1,050 women treated with conservative surgery and radiation with or without systemic therapy completed 2,480 questionnaires during follow-up visits. The EQ-5D is a standardized and validated instrument for measuring quality of life outcomes. The descriptive system uses 5 dimensions of health with three possible levels of response that combine into 243 (3(5)) possible unique health states that are each assigned a values-based index score from 0 to 1. The visual analog scale (VAS) rates health on a simple vertical line from 0 to 100. Higher scores correspond to better health status. The mean index scores were 0.89 (95% CI: 0.87-0.91) at 5 years, 0.9 (95% CI: 0.86-0.94) at 10 years, and 0.9 (95% CI: 0.83-1.0) at 15 years. There were no significant differences in health states between patients by age when compared with U.S. controls. There was a statistically significant positive correlation between the results of the VAS and descriptive system. Significant trends in health dimensions over 15 years were increased problems with self-care and decreased problems with anxiety/depression, pain/discomfort, and performing usual activities. This study of EQ-5D is unique and demonstrates very high quality of life in patients long-term after breast-conserving surgery and radiation. These health states are comparable to the adult female U.S. population. These data will provide valuable patient utility information for informing decision analyses investigating new treatments in women with breast cancer.

History of smoking is associated with younger age at diagnosis of breast cancer.

Smoking tobacco has been associated with incidence, response and outcomes after treatment of some cancers. We hypothesized that tobacco use could result in an observable effect on breast cancer stage and characteristics at diagnosis. There were 6,000 patients with Tis-4, N0-3 breast cancers who presented to a comprehensive cancer center at initial diagnosis between 1970 and 2006. Patients were included who had a known smoking history, and subdivided into any tobacco use 2683 (45%) or never tobacco use 3317 (55%). Analyses were performed to evaluate the association of smoking with clinical, pathologic and treatment-related factors at cancer presentation. Median age at diagnosis for all breast cancers was 55 years, for nonsmokers was 56 years, for any smoking history was 55 years, and the subgroup of current smokers was 52 years. The difference in median age for current smokers versus nonsmokers was statistically significant (p < 0.0001). The probability of age <55 years at breast cancer diagnosis for any smoking history compared to nonsmokers was 1.2 for white patients (p < 0.0003) but 0.81 for black patients (p = 0.25). There was no statistically significant association between smoking and T stage, N stage, ER/PR status, or Her-2/neu status, although smokers were less likely to utilize breast-conserving treatment. Smoking was associated with a younger age at diagnosis and lower utilization of breast conservation, and observed in the subgroup of white patients but not black patients. Further efforts to clarify potential reasons for any racial differences and lower utilization of breast conservation with smoking are warranted.

Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast: The NRG Oncology/RTOG 1014 Phase 2 Clinical Trial.

IMPORTANCE: Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. OBJECTIVES: To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. DESIGN, SETTING, AND PARTICIPANTS: The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. INTERVENTIONS: Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. MAIN OUTCOMES AND MEASURES: The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis-free survival, overall survival, and circulating tumor cell incidence. RESULTS: A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) for ERBB2 (formerly HER2 or HER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis-free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. CONCLUSIONS AND RELEVANCE: For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

Young age is not associated with increased local recurrence for DCIS treated by breast-conserving surgery and radiation.

BACKGROUND: We report local recurrence (LR) after breast-conserving surgery and radiation (BCS + RT) for ductal carcinoma in situ (DCIS) to determine outcomes for patients aged

Phase III Trial: Adjuvant Pelvic Radiation Therapy Versus Vaginal Brachytherapy Plus Paclitaxel/Carboplatin in High-Intermediate and High-Risk Early Stage Endometrial Cancer.

PURPOSE: The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS: A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS: The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION: Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy in postoperative treatment of endometrial and cervical cancer.

PURPOSE: To develop an atlas of the clinical target volume (CTV) definitions for postoperative radiotherapy of endometrial and cervical cancer to be used for planning pelvic intensity-modulated radiotherapy. METHODS AND MATERIALS: The Radiation Therapy Oncology Group led an international collaboration of cooperative groups in the development of the atlas. The groups included the Radiation Therapy Oncology Group, Gynecologic Oncology Group, National Cancer Institute of Canada, European Society of Therapeutic Radiology and Oncology, and American College of Radiology Imaging Network. The members of the group were asked by questionnaire to define the areas that were to be included in the CTV and to outline theses areas on individual computed tomography images. The initial formulation of the group began in late 2004 and culminated with a formal consensus conference in June 2005. RESULTS: The committee achieved a consensus CTV definition for postoperative therapy for endometrial and cervical cancer. The CTV should include the common, external, and internal iliac lymph node regions. The upper 3.0 cm of the vagina and paravaginal soft tissue lateral to the vagina should also be included. For patients with cervical cancer, or endometrial cancer with cervical stromal invasion, it is also recommended that the CTV include the presacral lymph node region. CONCLUSION: This report serves as an international template for the definition of the CTV for postoperative intensity-modulated radiotherapy for endometrial and cervical cancer.

Four-week course of radiation for breast cancer using hypofractionated intensity modulated radiation therapy with an incorporated boost.

PURPOSE: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. METHODS AND MATERIALS: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age >or=18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31-81 years). Of the patients, 15% had ductal carcinoma in situ, 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. RESULTS: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. CONCLUSIONS: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules.

Health and housing among low-income adults with physical disabilities.

The purpose of this study was to understand the impact of living environment on the health and access to health care of low-income working-age adults with physical disabilities. We conducted focus groups of participants with physical disabilities in the District of Columbia living in each of three housing situations (a homeless shelter, a nursing home, and an inaccessible house or apartment). Twenty-eight people participated in the focus groups. Most were male (79%) and African American (93%). Participants from a homeless shelter expressed concerns about accessibility and sanitation at the shelter. Nursing home participants expressed a need for privacy and autonomy that would foster consumer-directed care. Participants living in inaccessible apartments or houses worried about their ability to maintain daily living and social activities. Participants perceived barrier-free housing conditions to be a prerequisite for independent living and for ensuring their basic health and well-being.