Individualized Stereotactic Ablative Radiotherapy for Lung Tumors: The iSABR Phase 2 Nonrandomized Controlled Trial.

Importance: Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. Objective: To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. Design, Setting, and Participants: This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Intervention: Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Main outcome: Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. Results: In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). Conclusions and Relevance: The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. Trial Registration: ClinicalTrials.gov Identifier: NCT01463423.

Delays in Care Associated With Non-English-Speaking Patients With Breast Cancer.

BACKGROUND: Breast cancer care requires coordination between multiple diagnostic and treatment modalities. Disparities such as age, race/ethnicity, and socioeconomic status are associated with delays in care. This study investigates whether primary language is associated with delays in breast cancer diagnosis and treatment before and through radiotherapy (RT). PATIENTS AND METHODS: This study was an institutional retrospective matched-cohort analysis of women treated with breast RT over 2 years. A total of 65 non-English-speaking (NES) patients were matched with 195 English-speaking (ES) patients according to stage, age, and chemotherapy delivery. Key time intervals along the breast cancer care path from initial findings through RT were recorded. Data were analyzed in a mixed model with matching as the random effect. The impact of race and insurance status was analyzed in addition to language. RESULTS: Significant delays were found for NES patients, which varied by race. NES Latina patients experienced the longest delay, with a mean total care-path time of 13.53 months (from initial findings to end of RT) versus 8.18 months for all ES patients (P<.0001). Specifically, their mean total care-path time was 5.97 months longer than that of ES Latina patients (P=.001) and 5.80 months longer than that of ES White patients (P<.0001). In addition, NES Latina patients had a significantly longer total care-path time than NES patients of other races/ethnicities (P=.001). Delays were specifically seen between initial clinical or radiographic findings and diagnostic mammogram (P=.001) and between biopsy and resection (P=.044). Beyond language, race/ethnicity was itself associated with delays between resection and start of RT (P=.032) and between start and end of RT (P=.022). CONCLUSIONS: Language is associated with pre-RT delays in breast cancer care, especially for NES Latina patients. Delays are most pronounced before diagnostic mammograms, but they also exist before resection and RT. Future work should target NES patients to assist their progress along the care path.

Impact of Insurance on Stage of Breast Cancer Presentation for Different Races and Ethnicities.

PURPOSE: Survival in breast cancer is largely stage-dependent. Lack of insurance and Medicaid have been associated with later-stage breast cancer, but it is unknown to what degree this association varies by race or ethnicity. METHODS: We conducted a retrospective single-institution cohort analysis of women undergoing breast radiotherapy from 2012 to 2017 (n = 1,019). Patients were categorized as having private insurance (n = 540), Medicare (n = 332), Medicaid (n = 122), or self-pay (n = 25). Ordinal logistic regression analysis identified variables associated with later-stage presentation, including age, race or ethnicity, insurance, the interaction between insurance and race or ethnicity, body mass index, education, and language. RESULTS: The association between insurance and breast cancer stage varied on the basis of a patient's race or ethnicity (P = .0114). White and Asian patients with Medicaid had significantly higher odds of later-stage breast cancer than those with private insurance (White odds ratio [OR], 2.10; 95% CI, 1.02 to 4.34; Asian OR, 3.22; 95% CI, 1.56 to 6.67). However, the inverse was true for Hispanic patients who had lower odds of later-stage disease with Medicaid than private insurance (OR, 0.36; 95% CI, 0.16 to 0.90). Hispanic patients with Medicaid had lower odds than either White or Asian patients with Medicaid. These findings persisted across all ages. CONCLUSION: The association between insurance and later-stage presentation is significantly influenced by race or ethnicity. Medicaid was generally associated with later-stage breast cancer diagnosis, but this was not true across all races and ethnicities. Although White and Asian patients with Medicaid presented with later stage, Hispanic patients fared better with Medicaid than private insurance. Future work should investigate how Medicaid is successfully targeting Hispanic patients in breast cancer care.

Locoregional and Distant Outcomes in Women With cT1-3N1 Breast Cancer Treated With Neoadjuvant Chemotherapy With or Without Adjuvant Radiotherapy.

BACKGROUND: We evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: We retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0. RESULTS: After excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P < .001) and/or lymphovascular invasion (P = .03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P = .04) and/or if they had ypN+ disease (P = .01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n = 98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P = .23). CONCLUSION: Recommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.

Inflammation Mediates the Development of Aggressive Breast Cancer Following Radiotherapy.

PURPOSE: Women treated with radiotherapy before 30 years of age have increased risk of developing breast cancer at an early age. Here, we sought to investigate mechanisms by which radiation promotes aggressive cancer. EXPERIMENTAL DESIGN: The tumor microenvironment (TME) of breast cancers arising in women treated with radiotherapy for Hodgkin lymphoma was compared with that of sporadic breast cancers. To investigate radiation effects on carcinogenesis, we analyzed tumors arising from Trp53-null mammary transplants after irradiation of the target epithelium or host using immunocompetent and incompetent mice, some of which were treated with aspirin. RESULTS: Compared with age-matched specimens of sporadic breast cancer, radiation-preceded breast cancers (RP-BC) were characterized by TME rich in TGFß, cyclooxygenase 2, and myeloid cells, indicative of greater immunosuppression, even when matched for triple-negative status. The mechanism by which radiation impacts TME construction was investigated in carcinomas arising in mice bearing Trp53-null mammary transplants. Immunosuppressive TMEs (iTME) were recapitulated in mice irradiated before transplantation, which implicated systemic immune effects. In nu/nu mice lacking adaptive immunity irradiated before Trp53-null mammary transplantation, cancers also established an iTME, which pointed to a critical role for myeloid cells. Consistent with this, irradiated mammary glands contained more macrophages and human cells cocultured with polarized macrophages underwent dysplastic morphogenesis mediated by IFNγ. Treating mice with low-dose aspirin for 6 months postirradiation prevented establishment of an iTME and resulted in less aggressive tumors. CONCLUSIONS: These data show that radiation acts via nonmutational mechanisms to promote markedly immunosuppressive features of aggressive, RP-BCs.

Development of a Classification Tree to Predict Implant-Based Reconstruction Failure with or without Postmastectomy Radiation Therapy for Breast Cancer.

PURPOSE: The aim of this study was to determine the complications, incidence, and predictors of implant-based reconstruction failure (RF) among patients treated with mastectomy for breast cancer. METHODS: We retrospectively reviewed 108 patients who underwent mastectomy, tissue expander, and implant-based breast reconstruction with or without radiation therapy (RT) at our institution (2000-2014). Descriptive statistics determined complication incidences, with major complications defined as any complications requiring surgical intervention or inpatient management. Chi square and Fisher's exact tests determined differences in RF incidences, defined as implant loss. Logistic regression analyses identified predictors of RF. RESULTS: Median follow-up was 42.5 months. Sixty patients (55.6%) experienced major complications. Overall, 27 patients (25%) experienced RF. Incidences of RF were significantly increased in patients who had any major complication (43.3% vs. 2.1%; p < 0.0001), especially infection (61.3% vs. 10.4%; p < 0.0001), delayed wound healing (83.3% vs. 21.7%; p = 0.004), and implant exposure (80.0% vs. 19.4%; p = 0.0002). Receiving RT, but not timing of RT, significantly predicted RF [odds ratio (OR) 4.00, 95% confidence interval (CI) 1.11-14.47; p = 0.03]. On multivariable analysis, infection (OR 7.69, 95% CI 2.12-27.89; p = 0.002) and delayed wound healing (OR 17.86, 95% CI 1.59-200.48; p = 0.02) independently predicted for RF. Our newly developed classification tree, which includes stepwise assessment of major infection, delayed wound healing, implant exposure, age ≥ 50 years, and total number of lymph nodes removed ≥ 10, accurately predicted 74% of RF events and 75% of non-RF events. CONCLUSIONS: Infection or delayed wound healing requiring surgical intervention or hospitalization and receipt of RT, but not radiation timing, were significant predictors of RF. Our classification tree demonstrated > 70% accuracy for stepwise prediction of RF.

Association Between Patient Education Videos and Knowledge of Radiation Treatment.

PURPOSE: Patient knowledge of radiation therapy (RT) before consult is typically limited, with many having misconceptions or fears. There exists a need to improve patient education in RT. Our purpose was to study the impact of patient education videos on patient-reported knowledge of RT, anxiety/fear, and satisfaction. METHODS AND MATERIALS: At our institution, we created 2 RT educational videos: a general RT video and a breast cancer-specific video. Patients presenting for breast RT who agreed to participate (n = 107) were randomly assigned to receive a link to the videos (video group; n = 58) or not (no-video group; n = 49) before consultation. Pre- and postconsult surveys were administered assessing patient-reported measures on a 5-point Likert-type scale. RESULTS: Patients in the video group reported significantly higher levels of confidence in their knowledge of radiation side effects, with 45.6.% at least somewhat confident versus 21.3% in the no-video group (P = .009; median on a 5-point Likert-type scale, 2 [interquartile range {IQR}, 2-3] versus 2 [IQR, 1-2], respectively [P = .012]). There was a trend toward higher knowledge of the radiation treatment process in the video group (median, 3 [IQR, 2-3] versus 2 [IQR, 2-3] for no-video group; P = .064). There were no significant differences in preconsult anxiety or fear between the groups, but of those who were assigned videos, 46.8% reported decreased anxiety afterward, and 66.0% felt more comfortable coming to a consult. While those in the no-video group hypothesized that a video would be helpful (median, 3; IQR, 3-4), those in the video group found them to be very helpful in real life (median, 4; IQR, 45; P = .0009). After the consult, all patients in both groups were satisfied. CONCLUSIONS: Patient education videos increase patient-reported knowledge of RT and are found to be very helpful.

Lymphopenia and clinical outcomes in patients with residual nodal disease after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Patients with residual nodal disease after neoadjuvant chemotherapy for breast cancer have a poor prognosis. We wanted to evaluate whether lymphopenia after treatment for breast cancer impacted clinical outcomes. MATERIALS AND METHODS: We assessed 99 patients with node-positive disease after neoadjuvant chemotherapy. Absolute lymphocyte count was recorded 1 year after radiation. Dates of local, regional, and distant failure were recorded. Time to event outcomes were evaluated using Kaplan-Meier analysis. Multivariable analysis determined factors predictive for overall survival. RESULTS: Median follow-up was 44 months (range 3-150). Median age was 48 years (range 23-79). Twenty-six patients (26%) had lymphopenia 1 year after RT. Patients with lymphopenia had a greater incidence of regional (p = 0.03) and distant failure (p = 0.009) compared to those with normal lymphocyte counts and had a 6.05 greater risk of death (p = 0.0002). CONCLUSIONS: In patients with residual nodal disease after neoadjuvant chemotherapy, lymphopenia after breast cancer treatment was associated with overall survival. The relationship between lymphopenia and breast cancer outcomes warrants further investigation.

Angiosarcoma of the Breast: Management and Outcomes.

OBJECTIVE: Angiosarcoma of the breast is rare and has a poor prognosis. We reviewed our institution's experience with this disease to characterize presentation, identify management patterns, and report outcomes. METHODS: Fifty-eight patients with nonmetastatic angiosarcoma were identified from 1998 to 2019 and retrospectively reviewed. Overall survival (OS) and recurrence-free survival (RFS) were calculated using the Kaplan-Meier analysis and log-rank test. RESULTS: The median follow-up was 43.4 months (range: 1.8 to 203.3 mo). Twenty-four patients had primary angiosarcoma (PAS) and 34 patients had secondary angiosarcoma (SAS). Patients with PAS were significantly younger than those with SAS (P<0.0001). Mastectomy was the main surgical treatment in our cohort (n=47) and 3 underwent a lumpectomy. The multifocal disease was found in 5/23 patients with PAS and 11/35 patients with SAS. Twenty-eight patients received chemotherapy. Radiation was administered to 13 patients with PAS and 3 patients with SAS. Five-year OS was 73.7% for PAS and 63.5% for SAS. Local recurrence occurred in a greater proportion of patients with margins <5 mm than those with margins ≥5 mm. Chemotherapy did not impact RFS and was not associated with OS in PAS (P=0.35). Those with SAS treated with chemotherapy had significantly greater OS than those who did not receive chemotherapy (P=0.043). Radiation did not significantly influence RFS or OS. CONCLUSIONS: Five-year OS was higher than anticipated. Margins >5 mm appear important for local control. Patients with SAS, but not PAS, may achieve improved survival with chemotherapy. National trials using prespecified agents may be needed to identify an optimal chemotherapy regimen for women with SAS.

Telemedicine in Radiation Oncology: Is It Here to Stay? Impacts on Patient Care and Resident Education.

PURPOSE: Telemedicine was rapidly and ubiquitously adopted during the COVID-19 pandemic. However, there are growing discussions as to its role postpandemic. METHODS AND MATERIALS: We surveyed patients, radiation oncology (RO) attendings, and RO residents to assess their experience with telemedicine. Surveys addressed quality of patient care and utility of telemedicine for teaching and learning core competencies. Satisfaction was rated on a 6-point Likert-type scale. The quality of teaching and learning was graded on a 5-point Likert-type scale, with overall scores calculated by the average rating of each core competency required by the Accreditation Council for Graduate Medical Education (range, 1-5). RESULTS: Responses were collected from 56 patients, 12 RO attendings, and 13 RO residents. Patient feedback was collected at 17 new-patient, 22 on-treatment, and 17 follow-up video visits. Overall, 88% of patients were satisfied with virtual visits. A lower proportion of on-treatment patients rated their virtual visit as "very satisfactory" (68.2% vs 76.5% for new patients and 82.4% for follow-ups). Only 5.9% of the new patients and none of the follow-up patients were dissatisfied, and 27% of on-treatment patients were dissatisfied. The large majority of patients (88%) indicated that they would continue to use virtual visits as long as a physical examination was not needed. Overall scores for medical training were 4.1 out of 5 (range, 2.8-5.0) by RO residents and 3.2 (range, 2.0-4.0) by RO attendings. All residents and 92% of attendings indicated they would use telemedicine again; however, most indicated that telemedicine is best for follow-up visits. CONCLUSIONS: Telemedicine is a convenient means of delivering care to patients, with some limitations demonstrated for on-treatment patients. The majority of both patients and providers are interested in using telemedicine again, and it will likely continue to supplement patient care.

Impact of mastectomy for breast cancer on spinal curvature: Considerations when treating patients with scoliosis.

OBJECTIVE: Mastectomy has been shown to influence body posture in women; however, there are limited data outlining changes in spine curvature after mastectomy in patients with scoliosis. We sought to quantify changes in spine curvature after mastectomy for breast cancer. METHODS: We conducted a retrospective review of 62 patients with scoliosis who underwent mastectomy for breast cancer at a single institution between 1995 and 2018. Preoperative and postoperative radiographs were used to measure Cobb angles to assess lateral spinal curvature. Changes in Cobb angle were compared using paired two-tailed t-tests. The relationship between mass of breast removed and changes in Cobb angle was modeled using a linear regression. RESULTS: The median follow-up after mastectomy was 7.9 years (range 0.9-21.5). Median age was 62 years (range 30-85). Of 62 patients, 10 (16%) expressed that their back pain became worse after mastectomy. Nineteen patients had evaluable radiographs before and after mastectomy. In these patients, the average change in Cobb angle was 4.7° (range -0.2-12.2). Cobb angle significantly increased after mastectomy (P < .0001). Although not statistically significant, average Cobb angle was greater for patients who underwent unilateral compared to bilateral mastectomy (P = .09). Mass of breast removed significantly correlated with the difference in Cobb angle for patients who underwent unilateral mastectomy (P = .0006), but not for bilateral mastectomy (P = .55). CONCLUSIONS: In this understudied patient population, mastectomy significantly increased the change in spine curvature. Further care should be taken to assess patient-reported pain and quality of life in patients with spine morbidity who undergo mastectomy for breast cancer.

Importance of a Culture Committee for Boosting Morale and Maintaining a Healthy Work Environment in Radiation Oncology.

During the unprecedented workplace disruption from the corona virus disease 2019 (COVID-19) pandemic, health care workers have been particularly vulnerable to increased work-related stress and anxiety. This may have a negative effect on job performance and personal well-being. Personal safety, job security, and childcare needs are essential concerns that must be addressed by health care organizations to ensure stability of its workforce. In addition, workplace morale is also damaged by the many daily changes brought about by social distancing. Thus, opportunities exist for departments to address the loss of social bonding and cohesiveness needed for successful team building. In this report, we describe the efforts of our departmental workplace culture committee during this pandemic.

Patterns of Failure in Women Who Have Residual Nodal Disease After Neoadjuvant Chemotherapy for Breast Cancer According to Extent of Lymph Node Surgery.

BACKGROUND: Optimal surgical management of limited axillary nodal disease following neoadjuvant chemotherapy (NAC) for breast cancer is evolving. Concerns exist with respect to leaving residual disease in the axilla when omitting axillary lymph node dissection (ALND) in this setting. We sought to determine whether extent of nodal surgery altered patterns of failure and patient outcomes. PATIENTS AND METHODS: We identified 70 patients with breast cancer who were confirmed cN0 after NAC yet had residual nodal disease (ypN1) on sentinel lymph node biopsy (SLNB). Twenty-eight patients underwent SLNB alone and 42 underwent SLNB+completion (c)ALND in a non-randomized fashion. Most (n = 65) patients underwent adjuvant regional nodal irradiation (RNI). Detailed patterns of failure data were obtained for each patient. RESULTS: The median follow-up was 43.5 months. There were 30 (43%) recurrences. Of these, 5 were isolated locoregional failures, and 24 were distant failures. There were no significant differences in local (P = .13), regional (P = .62), or distant (P = .47) failure between patients who underwent SLNB alone versus SLNB+cALND. Seventeen (24%) patients died. Overall survival was similar in both groups with median overall survival not reached for those who underwent SLNB and 109 months for those who underwent SLNB+cALND (P = .45). CONCLUSIONS: There were no differences in patterns of recurrence among patients with 1 to 3 involved lymph nodes after NAC who underwent SLNB alone versus SLNB+cALND in the setting of RNI. We await the results of ongoing, prospective clinical trials to confirm the relative merits of RNI in lieu of cALND in these patients.

Erythema of the skin after breast radiotherapy: It is not always recurrence.

Recurrence of breast cancer is a predominant fear for patients who were treated for breast cancer. Acute and late dermatologic effects of radiotherapy are not uncommon and could have similar characteristics to breast cancer recurrence. Thus, it is important to highlight key differences between the clinical and histologic presentations of radiation effects and recurrence. Herein, we present two patients who presented with late dermatologic effects of radiotherapy months to years after treatment, neither of whom had workup consistent with cancer recurrence. We provide clinical and microscopic descriptions of each case and provide a review to differentiate various dermatologic conditions. This report aims to outline potential late dermatologic effects of radiation treatment and emphasise that changes in the breast do not always signal breast cancer recurrence.

Adjuvant treatment and survival in older women with triple negative breast cancer: A Surveillance, Epidemiology, and End Results analysis.

Patients with triple negative breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Competing risks analysis was used to assess the cumulative incidence of breast cancer-specific mortality (BCSM). Multivariable Fine-Gray regression was used to identify predictors of BCSM. Women age 70+ (n = 4221) were less likely to receive chemotherapy and radiation treatment (P < 0.0001) and had higher BCSM compared to younger women (P < 0.0001). There were no differences in BCSM in patients who received adjuvant treatment (P = 0.10). Stage II patients derived the greatest relative and absolute benefit from adjuvant treatment. Age was not a significant predictor of BCSM.

Association between primary language, a lack of mammographic screening, and later stage breast cancer presentation.

BACKGROUND: Health determinants are known to influence the stage of breast cancer presentation, but it is unclear to what extent language affects stage. This study investigates whether non-English-speaking (NES) patients present at a later stage than their English-speaking (ES) counterparts and whether language is associated with mammographic screening. METHODS: This study was a retrospective, single-institution cohort analysis of women undergoing breast radiotherapy from 2012 to 2017 (n = 1057). Patients were categorized as ES (n = 904) or NES (n = 153). Ordinal logistic regression analysis identified variables associated with later stage presentation, including language, race/ethnicity, and age. A subcohort analysis investigated the influence of mammographic screening on stage for NES patients. RESULTS: NES patients had greater odds of later stage disease than ES patients (odds ratio, 1.47; 95% confidence, 1.001-2.150). This association persisted across all races/ethnicities. An additional analysis examined age categories associated with mammographic screening. For women eligible for screening (ie, those 40-50 years old or older than 50 years), there was a significant association between language and stage. NES patients older than 50 years were twice as likely to present at an advanced stage in comparison with ES patients (16.19% vs 8.11%; P = .0082). An additional subset analysis accounted for mammograms. NES patients who did not undergo screening had a higher probability of stage III disease (40.3% of NES patients vs 12.7% of ES patients). There was no difference in stage between NES and ES patients who did undergo screening. CONCLUSIONS: Language is independently associated with later stage breast cancer for NES patients, regardless of race/ethnicity. NES patients may have difficulty in accessing the health care system. Future interventions should seek to reduce language barriers for mammographic screening and diagnosis.