Radiation therapy for bone-only metastases in breast cancer patients: A GOCO survey of current clinical practice.

INTRODUCTION: The role of radiation therapy (RT) for patients with bone-only metastatic (BOM) breast cancer has not been investigated sufficiently. The aim of this survey was to evaluate current clinical practice in treating breast cancer patients with BOM in Radiation Therapy Departments in Catalonia and Occitania within the scope of the GOCO group. MATERIALS AND METHODS: An electronic questionnaire was completed by experienced radiation oncologists from fourteen RT centers. The items surveyed the professional experience, therapeutic approach, technique, dose stereotactic body RT (SBRT) availability. RESULTS: All Radiation Oncology Departments (ROD) in Catalonia (12) and Occitania (2) responded to the survey. Eleven (78.5%) of the RODs advise RT for BOM as initial treatment in the oligometastatic setting. RT to asymptomatic bone oligometastases is more often restricted for "risky lesions". The most inconsistent approaches were the treatment for asymptomatic lesions, when to treat bone metastases with respect to systemic treatment (ST) and the indication for RT after a complete response to ST. CONCLUSION: While BOM breast cancer patients have a relatively good prognosis, there is a lack of consistency in their approach with RT. This can be explained by the absence of evidence-based guidelines and an incomplete availability of SBRT.

Understanding variations in the use of hypofractionated radiotherapy and its specific indications for breast cancer: A mixed-methods study.

BACKGROUND AND PURPOSE: Radiation oncology guidelines favour hypofractionated whole-breast radiotherapy (HWBRT) over more conventional schemes in the conservative treatment of breast cancer, but its adoption still varies in clinical practice. This study assessed the patterns of HWBRT adoption in Catalonia (Spain). MATERIAL AND METHODS: We used a mixed-methods approach based on an explanatory sequential design, first collecting and analysing quantitative data on HWBRT use (>2.5Gy per fraction) in 11 public radiotherapy centres (2005-2015) and then performing 25 semi-structured interviews with all department heads and reference radiation oncologist/s. RESULTS: Of the 34,859 patients fulfiling the study criteria over the study period, just 12% were hypofractionated, reaching a percentage of 29% in 2015 (p<0.001). Our analysis showed a narrowing age gap between patients receiving conventional fractionation and hypofractionation in centres leading adoption. However, there were important differences in clinicians' interpretation of evidence (e.g. regarding the perceived risk of long-term toxicity) and selection of patients for specific indications, both within and between departments. CONCLUSIONS: Differences observed in the rate of adoption of HWBRT could not be tackled only using a rational, evidence-based approach. Factors related to the management of radiotherapy departments play a major role in the diffusion of therapeutic strategies.

Neoadjuvant Systemic Therapy in Breast Cancer: Association of Contrast-enhanced MR Imaging Findings, Diffusion-weighted Imaging Findings, and Tumor Subtype with Tumor Response.

Purpose To investigate the performance of tumor subtype and various magnetic resonance (MR) imaging parameters in the assessment of tumor response to neoadjuvant systemic therapy (NST) in patients with breast cancer and to outline a model of pathologic response, considering pathologic complete response (pCR) as the complete absence of any residual invasive cancer or ductal carcinoma in situ (DCIS). Materials and Methods This was an institutional review board-approved retrospective study, with waiver of the need to obtain informed consent. From November 2009 to December 2014, 111 patients with histopathologically confirmed invasive breast cancer who were undergoing NST were included (mean age, 54 years; range, 27-84 years). Breast MR imaging was performed before and after treatment. Presence of late enhancement was assessed. Apparent diffusion coefficients (ADCs) were obtained by using two different methods. ADC ratio (mean posttreatment ADC/mean pretreatment ADC) was calculated. pCR was defined as absence of any residual invasive cancer or DCIS. Multivariate regression analysis and receiver operating characteristic analysis were performed. Results According to their immunohistochemical (IHC) profile, tumors were classified as human epidermal growth factor receptor 2 (HER2) positive (n = 51), estrogen receptor (ER) positive/HER2 negative (n = 40), and triple negative (n = 20). pCR was achieved in 19% (21 of 111) of cases; 86% of them were triple-negative or HER2-positive subtypes. Absence of late enhancement at posttreatment MR imaging was significantly associated with pCR (area under the curve [AUC], 0.85). Mean ADC ratio significantly increased when pCR was achieved (P < .001). A κ value of 0.479 was found for late enhancement (P < .001), and the intraclass correlation coefficient for ADCs was 0.788 (P < .001). Good correlation of ADCs obtained with the single-value method and those obtained with the mean-value methods was observed. The model combining the IHC subtype, ADC ratio, and late enhancement had the highest association with pathologic response, achieving an AUC of 0.92 (95% confidence interval: 0.86, 0.97). Conclusion Triple-negative or HER2-positive tumors showing absence of late enhancement and high ADC ratio after NST are associated with pCR. © RSNA, 2016 Online supplemental material is available for this article.

Do breast cups improve breast cancer dosimetry? A comparative study for patients with large or pendulous breasts.

PURPOSE: Treating patients with large or pendulous breasts is challenging. Although brassiere cups are currently in use, no study has yet been carried out to assess their dosimetric impact. The aim of the present study was to evaluate the possible dosimetric advantages of the use of breast cups on patients with large or pendulous breasts. MATERIALS AND METHODS: Two CT studies were carried out on 12 breast cancer patients with large or pendulous breasts, with one study involving the use of breast cups. Radiation plans were developed in accordance with each of the CT studies. The following were compared: planning target volume (PTV), volume irradiated by the 95% isodose, conformity index, homogeneity index, mean lung dose, and mean heart dose was also compared for left breast treatment. The plan involving the use of cups was found to be the best option, leading to all patients being treated with cups. The resulting acute toxicity and cosmesis were also recorded. Both scenarios involved the use of film dosimetry to evaluate the skin doses. RESULTS: The use of breast cups resulted in a significant reduction of the PTV volume (from 1640 cm3 to 1283 cm3), of the irradiated volume (from 2154 cm3 to 1477 cm3) and of the conformity index (from 1383 to 1213). Despite slight improvements in the homogeneity index (from 0.12 to 0.10), statistical significance was not attained. The use of breast cups also led to significant dose reductions in V20 for lung (from 13.7% to 1.7%) and V5 for heart (from 9.8% to 2.7%). No differences in acute toxicity or cosmesis were observed compared to patients treated without cups. CONCLUSIONS: Our results show that the use of brassiere cups during breast radiation therapy leads to improvements in the main dosimetric factors analyzed. Furthermore, modifications to standard irradiation protocols are not required. In summary, we consider the technique of using breast cups with radiation therapy highly appropriate when treating breast cancer patients with large or pendulous breasts.

Dynamic contrast-enhanced MRI reveals the extent and the microvascular pattern of breast ductal carcinoma in situ.

To report the role of magnetic resonance imaging (MRI) in assessing the extent of breast ductal carcinoma in situ (DCIS). To assess whether the microvascularity pattern in DCIS correlates with magnetic resonance enhancement. Eighty-five histologically proven DCIS (77 pure DCIS, eight microinvasive DCIS) were prospectively studied with MRI. The morphology of magnetic resonance enhancement and the kinetic curve was recorded. Histopathologically, intraductal lesions were classified according to Van Nuys score. Tumor microvascularity was immunohistochemically assessed in a subset of 24 DCIS evaluating the number of microvessels, microvascularity area, and microvascularity pattern (diffuse or periductal). On the mammogram, 74% of DCIS appeared as microcalcifications. On MRI, 70% of DCIS showed enhancement. Non-mass-like uptake was observed in 78% of cases. The mean size of nonenhancing carcinomas was significantly lower than that of enhancing carcinomas (p = 0.033). The diffuse pattern was more frequent than the periductal pattern. A significant relationship between the morphology of MR enhancement and the microvascularity pattern was observed (p = 0.036); thus, 90% of DCIS showing segmental enhancement on MRI displayed a diffuse pattern while all DCIS with ductal enhancement showed a periductal pattern. There was a significant relationship between the maximum area of microvascularity and the vascular pattern (p = 0.015); periductal patterns showed larger areas than diffuse patterns. The lesion size was significantly larger as the Van Nuys score increased (p < 0.001) and was also related to the number of microvessels (p = 0.012). The mean area of microvascularity of DCIS was significantly larger as the Van Nuys score increased (p = 0.02). Breast MRI helps depict the extent of DCIS and reveals its microvascular pattern.

Correlation between clinical findings and magnetic resonance imaging for the assessment of local response after standard treatment in cervical cancer.

BACKGROUND: The aim of our study is to evaluate the correlation between gynecological examination and magnetic resonance (MRI) findings for the assessment of local response in cervical cancer patients treated with radiotherapy/chemotherapy (RT/ChT). PATIENTS AND METHODS: This study is a retrospective review of 75 consecutive cervical cancer patients from April 2004 to November 2009 treated with RT/ChT. Clinical and radiological data were subsequently analyzed. Patient's median age was 51 with a FIGO stage from Ib to IVb. Individualized RT/ChT was administered with a median dose of 45 Gy. Sixty-three patients received a complementary brachytherapy. Seventy-one patients received chemotherapy on a weekly basis. Gynecological exam was performed 3 months and 6 months after treatment and these findings were compared to MRI results at the same time. STATISTIC ANALYSIS: We used the Spearman's Rho test to determine the correlation level between the clinical and radiological methods. RESULTS: A correlation of 0.68 (60%) was observed between the clinical and MRI findings at 3 months with a further increase of up to 0.86 (82.6%) at 6 months. In the few cases with a poor correlation, the subsequent assessment and the natural history of the disease showed a greater value of the clinical exam as compared with the MRI findings. CONCLUSIONS: Physical exam remains an essential tool to evaluate the local response to RT/ChT for cervical cancer. The optimal clinical radiological correlation found at 6 months after treatment suggests that the combination of gynecological examination and MRI are probably adequate in patient monitoring.

Solid cancer, antiphospholipid antibodies, and venous thromboembolism.

The pathogenic role of antiphospholipid antibodies (aPL) in the development of venous thromboembolism (VTE) in patients with malignancies has not been established. From May 2006 to April 2008, 258 consecutive patients with solid-organ malignancies who developed VTE (VTE+) were recruited. A group of 142 patients matched for age, sex and tumor type cancer patients without VTE (VTE-) and an age-and-sex matched group of 258 healthy subjects were also included. A second blood sample was taken in positive aPL patients at least 12 weeks later. Twenty-one (8.1%) VTE+ patients, 2 (1.4%) VTE- patients (p=0.006) and 2 (0.8%) healthy subjects (p<0.001) were positive for aPL. Persistent aPL positivity was observed in only 4 out of 15 available VTE+ patients. No differences in demographic characteristics, clinical pattern and outcome were observed in VTE+ patients according to aPL status. The low prevalence and transience of aPL positivity in patients with solid-organ malignancies with VTE argues against a pathogenic role in the development of thrombosis in this setting. The published evidence of the relationship between cancer, aPL, and thrombosis is reviewed.

Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer.

BACKGROUND: The utility of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) as prognostic factors in primary breast cancer is unclear. METHODS: We prospectively studied CEA and CA 15.3 in the sera of 2062 patients with untreated primary breast cancer diagnosed between 1984 and 2008. RESULTS: Increased CEA (>5 microg/L) and CA 15.3 (>30 kU/L) concentrations were found in 12.7% and 19.6% of the patients, respectively, and 1 or both tumor markers were increased in 28% (570 of 2062). Increases in each tumor marker correlated with larger tumor sizes and nodal involvement. Tumor size, estrogen receptor (ER), and CEA were independent prognostic factors by multivariate analysis in the total group [disease free survival (DFS) and overall survival (OS)] as well as in node-positive (NP) and node-negative (NN) patients. Nodal involvement and histological grade were independent prognostic factors in the total group as well as in NP patients. By contrast, adjuvant treatment and CA 15.3 were independent prognostic factors only in NN patients (DFS and OS). All patients with CEA >7.5 microg/L had recurrence during follow-up. Use of both tumor markers allowed discrimination of the groups of risk in T1 NN patients: 56.3% of recurrences were seen when 1 or both tumor markers were increased, whereas only 9.4% of recurrences were seen in T1 NN patients without increases of either marker. CONCLUSIONS: CEA and CA 15.3 are useful prognostic factors in NP and NN breast cancer patients. CEA >7.5 microg/L is associated with a high probability of subclinical metastases.

Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value.

Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p < 0.0001). CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER-) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer.

Radiologic and pathologic findings in breast tumors with high signal intensity on T2-weighted MR images.

Various histopathologic components in benign and malignant breast lesions may generate hyperintense signal at T2-weighted magnetic resonance (MR) imaging. A comparison of the specific histologic features found in breast lesions with a high-signal-intensity appearance on unenhanced T2-weighted turbo spin-echo MR images obtained without spectral fat suppression shows that this MR imaging characteristic is often suggestive of the differential diagnosis. Histopathologic features that may produce high signal intensity in breast lesions include extensive necrosis, a cystic or microcystic component, an adipose or sebaceous component, mucinous stroma, loose myxoid stroma, stromal edema, and hemorrhagic changes. A more nuanced understanding of the correlation between the MR imaging appearance and specific pathologic findings may help radiologists achieve earlier and more accurate differentiation among this group of breast lesions.

Predicting non-sentinel lymph node status in breast cancer patients with sentinel lymph node involvement: evaluation of two scoring systems.

The aim of this study was to validate a nomogram and a scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph node biopsy at our institution from January 2001 to August 2006. A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. A total of 114 patients were identified. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and an axilla scoring system from Paris (Hôpital Tenon) were used to predict the probability of having non-SLN involvement. One hundred fourteen patients were included in the study. The areas under the receiver operating characteristics (ROC) curves were 0.671 (95% CI: 0.552-0.790) for the MSKCC nomogram and 0.703 (95% CI: 0.596-0.811) for the Tenon score. The univariate analysis shows that size of SLN metastases, the number of positive and negative SLN and the proportion of positive SLN were statistically significant. On multivariate logistic regression analysis, the size of SLN metastases and the proportion of positive SLN were statistically significant. The two scoring systems are similar according to their area under ROC curves, but should be improved to be valid and determinant to the general population. Meanwhile, the use of scoring systems could be applied in an individual manner in some patients.

Whole abdominal radiotherapy in ovarian cancer.

OBJECTIVES: The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer. MATERIAL AND METHODS: Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40-70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42-45 Gy in the pelvis. RESULTS: The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery. CONCLUSIONS: Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.

Brain nodules with lung mass: are they always metastases?

In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

Preoperative MRI of pure intraductal breast carcinoma--a valuable adjunct to mammography in assessing cancer extent.

The aim of the study was to evaluate the contribution of preoperative breast magnetic resonance imaging (MRM) as an adjunct to mammography in assessing extent of pure ductal carcinoma in situ (DCIS) and to relate magnetic resonance imaging (MRI) findings to histopathological features. A retrospective analysis was conducted of 86 histologically proven cases of pure DCIS of the breast. Two experienced radiologists with knowledge of clinical and histopathological findings at the time of the review evaluated mammographic and preoperative MRI results by consensus. Compared to histopathology, mammography or MRM alone underestimated DCIS extent in 18.6% and 31.4% of cases, respectively. When both imaging modalities were considered, DCIS extent was underestimated in 8% of cases. Combined use of mammography and MRM revealed good agreement with histopathology to assess DCIS extent (kappa=0.439; P<0.001). MR enhancement of DCIS was related to histologic size (P=0.011). Mammography is more accurate than MRM in assessing cancer extent of pure DCIS, but combined use of both imaging techniques leads to improved accuracy.

A randomized trial of the effect of training in relaxation and guided imagery techniques in improving psychological and quality-of-life indices for gynecologic and breast brachytherapy patients.

PURPOSE: The randomized study aimed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization. METHODS AND MATERIALS: Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona (Spain) were included in this study. The patients were randomly allocated to either the study group (n=32) or the control group (n=34). Patients in both groups received training regarding brachytherapy, but only study group patients received training in relaxation and guided imagery. After collection of sociodemographic data, all patients were given a set of questionnaires on anxiety and depression: the Hospital Anxiety and Depression Scale (HADS), and on quality of life: Cuestionario de Calidad de Vida QL-CA-AFex (CCV), prior to, during and after brachytherapy. RESULTS: The study group demonstrated a statistically significant reduction in anxiety (p=0.008), depression (p=0.03) and body discomfort (p=0.04) compared with the control group. CONCLUSIONS: The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety, depression and body discomfort in patients who must remain isolated while undergoing brachytherapy. This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy.State: This study has passed Ethical Committee review.

MRI of metaplastic carcinoma of the breast.

OBJECTIVE: The purpose of our study was to describe the MRI findings of metaplastic carcinoma of the breast and to compare those findings with underlying histopathologic features. CONCLUSION: Metaplastic carcinoma of the breast shows high signal intensity on T2-weighted MRI. This finding is related to the necrotic component of the tumor and may be useful for preoperative diagnosis of metaplastic carcinoma of the breast, although it must be differentiated from mucinous carcinoma and, less frequently, necrotic infiltrating ductal carcinoma.

Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan.

PURPOSE: To analyze the frequency in determining pathologically proven metastatic involvement of internal mammary nodes (IMN) after sentinel lymph node (SLN) technique in breast cancer and to evaluate the implications for radiotherapy (RT) management of patients. METHODS AND MATERIALS: Two hundred and twenty-five patients who underwent lymphatic mapping for early breast cancer treated with breast-conserving surgery and radiation (80%) or mastectomy (20%) were evaluated. There were two phases in the study: the validation phase (105 patients, 52 T1, 53 T2 < or = 4 cm), and the application phase (120 patients, 70 T1, 50 T2 < or = 2.5 cm). In the validation, if a drainage pathway to the IMN was identified, no biopsy was performed in this phase. In the application, if the study showed metastases in the IMNs, biopsy was performed. When histologically proven IMN metastases were detected, RT was included on the IMN chain planned with a 3D treatment system using conformal techniques. At the beginning of the study the injection site was subdermal and subsequently, the injection site was changed to peritumoral and intratumoral to search for IMN. RESULTS: In 31 patients of 225 (14%) hot spots were observed in the internal mammary chain (11.5% and 17.2% in the validation and application phases, respectively). In the validation phase, in 11 cases (11.5%) IMN drainage was observed, and in the application phase, in 20 cases (17.2%). Sampling of the internal mammary basin based on lymphoscintigraphy results was successful in 69% of the cases (14 of 20) and revealed metastatic involvement in 14% (2 of 14). This represents incidence of only 1.7% (2 of 116) in early breast cancer patients with SLN study in the application phase. In both cases the axillary SLN was also positive. Both patients with metastatic involvement of the IMN area received RT on the IMN chain next to the remaining breast after conservative surgery. CONCLUSIONS: We can conclude that 14% of the patients with intraoperative drainage into the IMN surgical examination of the lymph nodes had pathologically positive metastases. The percentage in pathologically proven metastatic involvement of IMN after the SLN technique in early breast cancer is low, but it is not negligible. Moreover, it is expected to increase since the international recommendations have established a 3-cm cutoff for practicing the SLN technique. Although the real value of IMN irradiation in early breast cancer is not known, including this chain in postoperative radiotherapy is not recommended unless pathologically proven IMNs have been produced by the SLN technique. To avoid overdosage or underdosage in the joint between the medial tangential and IMN fields, an individualized 3D dosimetry study is mandatory to enhance dose distribution and reduce the heart volume to lessen side effects.

Improvement in performance status after erythropoietin treatment in lung cancer patients undergoing concurrent chemoradiotherapy.

PURPOSE: A prospective Phase II trial was carried out to evaluate the effectiveness of erythropoietin in improving or maintaining performance status as determined by the Karnofsky performance status (KPS) score and hemoglobin (Hb) levels in lung cancer patients treated with concurrent chemoradiation (CH-RT). METHODS AND MATERIALS: A total of 51 patients with lung cancer (11 with small-cell, limited stage and 40 with non-small-cell disease, 17 with Stage IIIA and 23 with Stage IIIB), who underwent three different concurrent CH-RT protocols were enrolled. Baseline Hb and KPS values were recorded, as were the nadir Hb and KPS values before concurrent CH-RT. The final Hb and KPS values were recorded the last week of concurrent CH-RT. An Hb level of