Psychosocial Factors That Influence a Woman's Decision to Enroll in a Clinical Trial: Implications on How to Improve Clinical Trial Enrollment Among Black Women.

PURPOSE: Black women with breast cancer often present with more aggressive disease compared with other races, contributing to an increased risk of cancer mortality. Despite this inequity, Black women remain severely underrepresented in breast cancer clinical trials. We aim to characterize factors that influence a woman's decision to enroll in a clinical trial, with the goal of identifying clinical interventions to aid in the recruitment of vulnerable groups. METHODS AND MATERIALS: A cross-sectional, descriptive study was conducted using a questionnaire adapted from 2 prevalidated surveys investigating factors influencing clinical trial enrollment. The survey was administered to women with curable breast cancer during a single follow-up visit at 4 different sites within a university medical system where all patients are screened for clinical trial eligibility. Chi-square tests and Mann-Whitney U tests were used to assess associations or differences between the populations. RESULTS: One hundred ninety-four out of 209 women completed the survey, giving a compliance rate of 93%. Twenty-six percent of women self-identified as Black, most women were located at community sites (67.1%), most women had diagnoses of early-stage disease (I: 57.7%, II: 29.4%), and 81% of women had some collegiate-level education. Black women were younger at diagnosis (P = .005) and less likely to be married (P = .012) but more often lived with family members (P = .003) and had a lower median income (P < .001). According to the survey, Black women were less likely to trust their care team (P = .032), more likely to believe that research ultimately harms minorities (P < .001), and had a stronger belief in God's will determining illness and wellness (P < .001). Recurring themes of trust in the health care team, patient education, and advancement of cancer treatments were discussed in the focus groups. CONCLUSIONS: Failure to offer clinical trials and mistrust in research institutions may pose the greatest hindrances to the enrollment of Black women in clinical trials. Empowering women through education and fostering trustworthy relationships can encourage greater clinical trial participation.

A study of skin marker alignment using different diamond-shaped light fields for prone breast external-beam radiation therapy.

For breast cancer patients treated in the prone position with tangential fields, a diamond-shaped light field (DSLF) can be used to align with corresponding skin markers for image-guided radiation therapy (IGRT). This study evaluates and compares the benefits of different DSLF setups. Seventy-one patients who underwent daily tangential kilovoltage (kV) IGRT were categorized retrospectively into four groups: (1) DSLF field size (FS) = 10 × 10 cm2 , gantry angle = 90° (right breast)/270° (left breast), with the same isocenter as treatment tangential beams; (2) same as group 1, except DSLF FS = 4 × 4 cm2 ; (3) DSLF FS = 4 × 4-6 × 8 cm2 , gantry angle = tangential treatment beam, off-isocenter so that the DSLF was at the approximate breast center; and (4) No-DSLF. We compared their total setup time (including any DSLF/marker-based alignment and IGRT) and relative kV-based couch shift corrections. For groups 1-3, DSLF-only dose distributions (excluding kV-based correction) were simulated by reversely shifting the couch positions from the computed tomography plans, which were assumed equivalent to the delivered dose when both DSLF and IGRT were used. For patient groups 1-4, the average daily setup time was 2.6, 2.5, 5.0, and 8.3 min, respectively. Their mean and standard deviations of daily kV-based couch shifts were 0.64 ± 0.4, 0.68 ± 0.3, 0.8 ± 0.6, and 1.0 ± 0.6 cm. The average target dose changes after excluding kV-IGRT for groups 1-3 were-0.2%, -0.1%, and +0.4%, respectively, whereas DSLF-1 was most efficient in sparing heart and chest wall, DSLF-2 had lowest lung Dmax ; and DSLF-3 maintained the highest target coverage at the cost of highest OAR dose. In general, the use of DSLF greatly reduces patient setup time and may result in smaller IGRT corrections. If IGRT is limited, different DSLF setups yield different target coverage and OAR dose sparing. Our findings will help DSLF setup optimization in the prone breast treatment setting.

Patterns of Failure Observed in the 2-Step Institution Credentialing Process for NRG Oncology/Radiation Therapy Oncology Group 1005 (NCT01349322) and Lessons Learned.

PURPOSE: To investigate patterns of failure in institutional credentialing submissions to NRG/RTOG 1005 with the aim of improving the quality and consistency for future breast cancer protocols. METHODS AND MATERIALS: NRG/RTOG 1005 allowed the submission of 3-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), and simultaneous integrated boost (SIB) breast plans. Credentialing required institutions to pass a 2-step quality assurance (QA) process: (1) benchmark, requiring institutions to create a plan with no unacceptable deviations and ≤1 acceptable variation among the dose volume (DV) criteria, and (2) rapid review, requiring each institution's first protocol submission to have no unacceptable deviations among the DV criteria or contours. Overall rates, number of resubmissions, and reasons for resubmission were analyzed for each QA step. RESULTS: In total, 352 institutions participated in benchmark QA and 280 patients enrolled had rapid review QA. Benchmark initial failure rates were similar for 3DCRT (18%), IMRT (17%), and SIB (18%) plans. For 3DCRT and IMRT benchmark plans, ipsilateral lung most frequently failed the DV criteria, and SIB DV failures were seen most frequently for the heart. Rapid review contour initial failures (35%) were due to target rather than organs at risk. For 29% of the rapid review initial failures, the planning target volume boost eval volume was deemed an unacceptable deviation. CONCLUSIONS: The review of the benchmark and rapid review QA submissions indicates that acceptable variations or unacceptable deviations for the ipsilateral lung and heart dose constraints were the most commonly observed cause of benchmark QA failure, and unacceptable deviations in target contouring, rather than normal structure contouring, were the most common cause of rapid review QA failure. These findings suggest that a rigorous QA process is necessary for high quality and homogeneity in radiation therapy in multi-institutional trials of breast cancer to ensure that the benefits of radiation therapy far outweigh the risks.

Dosimetric effects of the kV based image-guided radiation therapy of prone breast external beam radiation: Towards the optimized imaging frequency.

PURPOSE: For prone breast treatment, daily image-guided radiation therapy (IGRT) allows couch shifting to correct breast position relative to the treatment field. This work investigates the dosimetric effect of reducing kV imaging frequencies and the feasibility of optimizing the frequency using patient anatomy or their first 3-day shifts. METHOD: Thirty-seven prone breast patients who had been treated with skin marker alignment followed by daily kV were retrospectively analyzed. Three IGRT schemes (daily-kV, weekly-kV, no-kV) were simulated, assuming that fractions with kV imaging deliver a dose distribution equivalent to that in computed tomography (CT) planning, whereas other fractions yield a dose distribution as recreated by shifting the CT plan isocenter back to its position before the couch shift was applied. Treatment dose to targets (breast and lumpectomy cavity [LPC]) and organs at risks (OAR)s (heart, ipsilateral lung) in different schemes were calculated. Patient anatomy information on CT plans and first 3-day couch shift data were analyzed to investigate whether these factors could guide imaging scheme optimization. RESULTS: When kV imaging frequency was reduced, the percentage dose changes (δD) for breast and LPC objectives (average <1%) were smaller than those for heart and lung (average 28%-31% for Dmean ). In general, the δD of no-kV imaging was approximately that of weekly kV imaging × a factor of 1.2-1.4. Although most dose objectives were not affected, the potential higher heart dose may be of concern. No strong correlation was found between δD for different kV frequencies and patient anatomy size/distance or the first 3-day couch shift data. CONCLUSIONS: Despite resulting in lower imaging dose, time, cost, and similar target coverage, a reduction in kV imaging frequency may introduce higher heart complication risk. Daily kVs are needed more in left-sided breast patients. A less frequent imaging schedule, if considered, cannot be individually optimized using CT anatomic features or early shift data.

Utilization of hypofractionated whole-breast radiation therapy in patients receiving chemotherapy: a National Cancer Database analysis.

PURPOSE: Results from four major hypofractionated whole-breast radiotherapy (HF-WBRT) trials have demonstrated equivalence in select patients with early-stage breast cancer when compared with conventionally fractionated WBRT (CF-WBRT). Because relatively little data were available on patients receiving neoadjuvant or adjuvant chemotherapy, consensus guidelines published in 2011 did not endorse the use of HF-WBRT in this population. Our goal is to evaluate trends in utilization of HF-WBRT in patients receiving chemotherapy. METHODS AND MATERIALS: We retrospectively analyzed data from 2004 to 2013 in the National Cancer DataBase on breast cancer patients treated with HF-WBRT who met the clinical criteria proposed by consensus guidelines (i.e., age >0 years, T1-2N0, and breast-conserving surgery), regardless of receipt of chemotherapy. We employed logistic regression to delineate and compare clinical and demographic factors associated with utilization of HF-WBRT and CF-WBRT. RESULTS: A total of 56,836 women were treated with chemotherapy and WBRT (without regional nodal irradiation) from 2004 to 2013; 9.0% (n = 5093) were treated with HF-WBRT. Utilization of HF-WBRT increased from 4.6% in 2004 to 18.2% in 2013 (odds ratio [OR] 1.21/year; P < 0.001). Among patients receiving chemotherapy, factors most dramatically associated with increased odds of receiving HF-WBRT on multivariate analysis were academic facilities (OR 2.07; P < 0.001), age >80 (OR 2.58; P < 0.001), west region (OR 1.91; P < 0.001), and distance >50 miles from cancer reporting facility (OR 1.43; P < 0.001). Factors associated with decreased odds of receiving HF-WBRT included white race, income <$48,000, lack of private insurance, T2 versus T1, and higher grade (all P < 0.02). CONCLUSIONS: Despite the absence of consensus guideline recommendations, the use of HF-WBRT in patients receiving chemotherapy has increased fourfold (absolute = 13.6%) over the last decade. Increased utilization of HF-WBRT should result in institutional reports verifying its safety and efficacy.

Increasing utilization of regional nodal irradiation in elderly node-positive women and declining emphasis on demographic factors.

PURPOSE: To evaluate the practice patterns for the use of regional nodal irradiation (RNI) in treatment of elderly women with low volume node-positive breast cancer in the setting of breast conservation surgery (BCS). METHODS: Women aged 70-89 diagnosed with unilateral, pathologic T1-2N1M0 breast cancer from 2004 to 2013, who underwent BCS and received radiotherapy were identified from the National Cancer Database. In 2011, two major trials were presented that helped define indications for RNI. Patients were dichotomized into "early", i.e. diagnosed up to 2010, and "late" cohorts. Patient and treatment characteristics were compared between the cohorts and logistic regression used to determine independent factors associated with the receipt of RNI. RESULTS: 7228 women met inclusion criteria; 4330 (59.9%) in early and 2898 (40.1%) in late cohorts. Utilization of RNI increased from 33.9% in early to 42.5% in late cohorts (P ≤ 0.001) and was independent of a general increase in RNI utilization. RNI in the early and late cohorts was not different between the study population and younger women (P > 0.05). RNI utilization increased in both cohorts with increasing number of positive lymph nodes. In the early cohort, RNI was also associated with higher grade, white race and lower income. In the late cohort, RNI increased with the presence of multiple, predefined risk factors. CONCLUSIONS: There was an increase in utilization of RNI for elderly patients from 2004 to 2013. In more recent years, the primary factors associated with receipt of RNI were tumor related with declining importance of demographic factors.

Increasing national mastectomy rates for the treatment of early stage breast cancer.

BACKGROUND: To study national trends in the mastectomy rate for treatment of early stage breast cancer. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results database, including 256,081 women diagnosed with T1-2 N0-3 M0 breast cancer from 2000 to 2008. We evaluated therapeutic mastectomy rates by the year of diagnosis and performed a multivariable logistic regression analyses to determine predictors of mastectomy as the treatment choice. RESULTS: The proportion of women treated with mastectomy decreased from 40.1 to 35.6 % between 2000 and 2005. Subsequently, the mastectomy rate increased to 38.4 % in 2008 (p < 0.0001). Simple logistic regression models demonstrated that mastectomy rates between 2005 and 2008 were moderated by age (p < 0.0001), marital status (p = 0.0230), and geographic location (p < 0.0001). Multivariate logistic regression analysis found that age, race, marital status, geographic location, involvement of multiple regions of the breast, lobular histology, increasing T stage, lymph node positivity, increasing grade, and negative hormone receptor status were independent predictors of mastectomy. Additionally, multivariate analysis confirmed that women diagnosed in 2008 were more likely to undergo mastectomy than women diagnosed in 2005 (odds ratio 1.17, 95 % confidence interval 1.13 to 1.21, p < 0.0001). CONCLUSIONS: There is evidence of a reversal in the previously declining national mastectomy rates, with the mastectomy rate reaching a nadir in 2005 and subsequently rising. Further follow-up to confirm this trend and investigation to determine the underlying cause of this trend and its effect on outcomes may be warranted.

Preoperative radiation therapy significantly increases patient eligibility for accelerated partial breast irradiation using 3D-conformal radiotherapy.

INTRODUCTION: Three-dimensional-conformal radiation (3D-CRT) is the most common approach used in National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39 for accelerated partial breast irradiation (APBI). Administration of APBI-3D-CRT in the preoperative (preop) setting has been shown to decrease the planning target volume. The impact of this decrease on patient eligibility for APBI has not been evaluated in a comparative manner. MATERIALS AND METHODS: Forty patients with 41 previously treated breast cancers (≤4 cm) were analyzed. A spherical preop tumor volume was created using the largest reported radiographic dimension and centered within the contoured lumpectomy cavity. Plans were created and optimized using the preop tumor volume and postoperative lumpectomy cavity using NSABP B-39 guidelines. The primary end point was to evaluate for differences in patient eligibility and normal tissue exposure. RESULTS: Thirty-five tumors (85%) in the preop versus 19 tumors (46%) in the postoperative setting were eligible for 3D-CRT-APBI using NSABP B-39 criteria (P=0.0002). The most common reason for ineligibility was due to >60% of the ipsilateral breast volume receiving 50% of the dose. Other reasons included dose to the contralateral breast, heart, and ipsilateral lung. Preop 3D-CRT-APBI was associated with statistically significant improvements in dose sparing to the heart, ipsilateral normal breast tissue, contralateral breast, chest wall, ipsilateral lung, and skin. CONCLUSIONS: Dosimetrically, the use of preop radiation would increase patient eligibility for 3D-CRT-APBI and decrease dose to normal tissues, which will potentially decrease toxicity and improve cosmesis. These results provide the basis for a recently activated prospective study of preop 3D-CRT-APBI.

Repeat computed tomography simulation to assess lumpectomy cavity volume during whole-breast irradiation.

PURPOSE: To determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease. PATIENTS AND METHODS: Forty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2. RESULTS: The median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume. CONCLUSIONS: Patients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.