Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node.

BACKGROUND AND OBJECTIVE: Sentinel lymph node (SLN) metastasis size is an important predictor of non-SLN involvement. The goal of this study was to construct a nomogram incorporating SLN metastasis size to accurately predict non-SLN involvement in patients with SLN-positive disease. METHODS: We identified 509 patients with invasive breast cancer with a positive SLN who underwent completion axillary lymph node dissection (ALND). Clinicopathologic data including age, tumor size, histology, grade, presence of multifocal disease, estrogen and progesterone receptor status, HER2/neu status, presence of lymphovascular invasion (LVI), number of SLN(s) identified, number of positive SLN(s), maximum SLN metastasis size and the presence of extranodal extension were recorded. Univariate and multivariate logistic regression analyses identified factors predictive of positive non-SLNs. Using these variables, a nomogram was constructed and subsequently validated using an external cohort of 464 patients. RESULTS: On univariate analysis, the following factors were predictive of positive non-SLNs: number of SLN identified (P < 0.001), number of positive SLN (P < 0.001), SLN metastasis size (P < 0.001), extranodal extension (P < 0.001), tumor size (P = 0.001), LVI (P = 0.019), and histology (P = 0.034). On multivariate analysis, all factors remained significant except LVI. A nomogram was created using these variables (AUC = 0.80; 95% CI, 0.75-0.84). When applied to an external cohort, the nomogram was accurate and discriminating with an AUC = 0.74 (95% CI, 0.68-0.77). CONCLUSION: SLN metastasis size is an important predictor for identifying non-SLN disease. In this study, we incorporated SLN metastasis size into a nomogram that accurately predicts the likelihood of having additional axillary metastasis and can assist in personalizing surgical management of breast cancer.

Mature results of the M. D. Anderson Cancer Center risk-adapted transplantation strategy in mantle cell lymphoma.

In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.

MRI features of inflammatory breast cancer.

OBJECTIVE: The aim of this study was to evaluate the features of inflammatory breast carcinoma (IBC) on MRI compared with mammography and ultrasound and to better define the role of MRI in patients with this aggressive disease. MATERIALS AND METHODS: A retrospective analysis was performed of patients with newly diagnosed IBC evaluated at a single institution between 2003 and 2008. Baseline MRI examinations were performed on a 1.5- or 3-T scanner using contrast-enhanced 3D T1-weighted gradient-echo sequences with parallel imaging. MRI findings were rated in accordance with the BI-RADS MRI lexicon established by the American College of Radiology. All patients underwent concomitant mammography and ultrasound examinations. RESULTS: Eighty women with a clinical diagnosis of IBC were included in the study (median age, 52 years; age range, 25-78 years). MRI detected a primary breast lesion in 78 of 80 symptomatic breasts (98%) compared with 53 of 78 (68%) with mammography (p < 0.0001) and 75 of 80 (94%) with ultrasound. Of the 78 breasts with a primary lesion, the most common MRI finding was a mass or multiple masses (57/78, 73%). Masses were frequently multiple, small, and confluent (47/57, 82%); mass margins, irregular (43/57, 75%); and internal enhancement pattern, heterogeneous (47/57, 82%). Kinetic analysis revealed a delayed washout pattern in 66 of 78 tumors (85%). MRI showed skin thickening in 74 of 80 breasts (93%), whereas mammography showed skin thickening in 56 of 78 breasts (72%). CONCLUSION: Multiple small, confluent, heterogeneously enhancing masses and global skin thickening are key MRI features of IBC that contribute to improved detection of a primary breast cancer and delineation of disease extent compared with mammography.

Neoadjuvant chemotherapy is associated with prolonged primary treatment intervals in patients with advanced epithelial ovarian cancer.

BACKGROUND: We evaluated the impact of neoadjuvant chemotherapy (NC) relative to primary surgery (PS) to determine if there was a difference in the total time and number of chemotherapy cycles given in patients with advanced epithelial ovarian cancer. METHODS: We identified 263 consecutive women meeting eligibility from 1993 to 2005 for this institutional review board-approved study. Eligible patients in this analysis were those women with advanced disease (stage IIIC-IV) in whom a maximal cytoreductive effort was planned either at PS or after NC. Time to start chemotherapy was defined as follows: (1) NC group: confirmation of diagnosis through biopsy, cytological diagnosis from ascites, and pleural effusion; (2) PS group: confirmation of diagnosis from the date of surgery that confirmed the diagnosis of epithelial ovarian cancer. Total chemotherapy cycles: (1) NC group: NC chemotherapy cycles plus postoperative cycles; (2) PS group: chemotherapy after primary tumor debulking surgery. Clinical information evaluated included chemotherapy type, chemotherapy cycle number, total time to administer frontline chemotherapy, and survival. RESULTS: Median chemotherapy cycles were greater in the NC group compared with the PS group (9 [range, 4-30] vs 6 [range, 3-19]; P < 0.01). The PS group was also more likely to undergo chemotherapy regimens involving platinum and taxane treatment compared with the NC group (79% vs 65%; P = 0.017). Total time undergoing primary chemotherapy from initial diagnosis was greater in the NC group compared with PS (223 vs 151 days; P < 0.01). No significant difference was observed in overall survival and progression-free survival in the 2 groups. CONCLUSIONS: In patients with advanced ovarian cancer, NC followed by abdominal hysterectomy is associated with improved perioperative outcomes including optimal cytoreduction, decreased blood loss, and decreased inpatient hospitalization. In this cohort, NC was also associated with prolonged chemotherapy treatment intervals and increased chemotherapy cycles without improvement in survival.

Clinical characteristics of patients with prolonged disease-free survival after primary treatment in advanced ovarian cancer: a brief report.

OBJECTIVE: Optimal cytoreduction and response to chemotherapy have been associated with prolonged disease-free survival (DFS), but there are limited data regarding the clinical characteristics of those patients with optimal 5-year DFS (5YrDFS) outcomes. METHODS: A case-control study was performed on 32 patients who were progression-free and alive at 5 years with advanced ovarian cancer 5YrDFS from 1993 to 2005 for this institutional review board-approved study. Matching controls were identified from the subset of patients who died or experienced disease progression before 5 years. RESULTS: One hundred sixty patients were evaluated. There was no statistical difference between cases and controls in regard to neoadjuvant chemotherapy, grade, race, preoperative cancer antigen-125 level, optimal cytoreduction, operating room time, length of hospital stay, or total chemotherapy cycles in regard to 5YrDFS. If a patient achieved complete response after primary treatment, the likelihood of progression-free survival 5 years or longer is 7 times more likely, (odds ratio = 7.2 [95% confidence interval = 2.3-22.4]; P = 0.0006). CONCLUSION: In this matched case-control analysis, complete response after primary treatment was the only significant factor associated with 5YrDFS. Further study is needed in patient and tumor characteristics to identify those patients who may have poor or favorable outcomes before treatment completion.

Imaging characteristics of hyperfunctioning parathyroid adenomas using multiphase multidectector computed tomography: a quantitative and qualitative approach.

OBJECTIVE: The objective of the study was to characterize the enhancement pattern of hyperfunctioning parathyroid adenomas on multiphase multidetector computed tomography (CT) or 4-dimensional CT. METHODS: We retrospectively studied the enhancement patterns of 48 pathologically confirmed parathyroid adenomas with 4-dimensional CT, compliant with institutional review and the Health Insurance Portability and Accountability Act. Region-of-interest analysis was done at baseline and at arterial (25 seconds), venous (55 seconds), and delayed (85 seconds) enhancement phases over the adenoma and adjacent normal thyroid tissue. Qualitative and quantitative analysis was done. Discriminant functions were calculated using a multivariate logistic regression model, and receiver operating characteristic curves were measured. RESULTS: Adenomas are lower than thyroid in density, demonstrate avid early contrast enhancement, and show rapid wash-out of contrast. Adenomas and thyroid had baseline Hounsfield unit attenuations of 35 ± 11 and 94 ± 21 and enhancement percentage change from baseline to arterial of 493% ± 328% and 132% ± 148%, respectively (P < 0.0001 both). Quantitative analysis showed that these 2 measures of baseline density and the percentage change from baseline to arterial were the most powerful discriminatory features, with contrast wash-out from arterial peak to venous phase being a less powerful discriminator. Several discriminant functions were derived, the best of which was: X = 13.74 - (0.207 × baseline Hounsfield unit) - (0.006 × percent density change from baseline to arterial). X > 0.2 classifies tissue as parathyroid with high certainty (area under the receiver operating characteristic curve = 0.98; specificity, 0.938; sensitivity, 0.999). CONCLUSIONS: Parathyroid adenomas have a characteristic enhancement pattern that can be distinguished from thyroid tissue: the key diagnostic discriminators are baseline density, percentage change in density from baseline to arterial enhancement, and percentage decrease in density from arterial to venous phases.

Comparison of half-dose and full-dose gadolinium MR contrast on the enhancement of bone and soft tissue tumors.

OBJECTIVE: To evaluate the effect of half-dose intravenous gadolinium contrast on the enhancement of bone and soft tissue tumors. MATERIALS AND METHODS: This study is HIPAA compliant and informed consent was waived by the institutional review board. An institutional database search was performed over a 1-year period for patients with full- and half-dose MR examinations performed for musculoskeletal oncologic indications. Examination pairs that were identical with regard to field strength and presence or absence of fat saturation were included, resulting in 29 paired examinations. When multiple, the lesion that was best delineated and enhanced well on the first examination in the pair was chosen, yielding 17 bone and 12 soft tissue. Five musculoskeletal radiologists blinded to dosages were asked to assess for a difference in enhancement when comparing the lesion on both examinations and to rate the degree of difference on a three-point scale. They were also asked to identify the examination on which the lesion enhanced less (tallied as low dose). Results were analyzed with the exact binomial test. RESULTS: The readers perceived an enhancement difference in 41% (59/145) of studies (p = 0.03) and the majority were rated as "mild" (66%, 39/59). The readers did not accurately identify the low-dose examinations (54% correctly identified, 32/59, p = 0.60). CONCLUSIONS: Half-dose gadolinium enhancement of lesions could not be accurately distinguished from full-dose enhancement upon review of the same lesion imaged at both concentrations.

Tumor necrosis in osteosarcoma: inclusion of the point of greatest metabolic activity from F-18 FDG PET/CT in the histopathologic analysis.

OBJECTIVE: To determine if the location of the point of maximum standardized uptake value (SUVmax) being included in or not included in the histopathologic slab section corresponded to tumor necrosis or survival. MATERIALS AND METHODS: Twenty-nine osteosarcoma patients underwent post-chemotherapy [fluorine-18]-fluoro-2-deoxy-D: -glucose (FDG) positron-emission tomography-computed tomography (PET/CT) prior to resection. PET/CT images were correlated with slab-section location as determined by photographs or knowledge of specimen processing. The location of the point of SUVmax was then assigned as being 'in' or 'out' of the slab section. Cox's proportional hazard regression was used to evaluate relationships between the location and value of SUVmax and survival. Logistic regression was employed to evaluate tumor necrosis. RESULTS: No correlation was found between the SUVmax location and survival or tumor necrosis. High SUVmax correlated to poor survival. CONCLUSION: High SUVmax value correlated to poor survival. Minimal viable tumor (> 10%) following chemotherapy is a known indicator of poor survival. No correlation was found between the location of SUVmax and survival or tumor necrosis. Therefore, the SUVmax value either does not correspond to a sufficient number of tumor cells to influence tumor necrosis measurement or it was included in the out-of-slab samples that were directed to viable-appearing areas of the gross specimen. Since high SUVmax has been previously found to correspond to poor tumor necrosis, and tumor necrosis is simply an estimate of the amount of viable tumor, SUVmax likely represents many viable tumor cells. Therefore, when not in the slab section, SUVmax was likely included in the tumor necrosis measurement through directed sampling, validating our current method of osteosarcoma specimen analysis.

18F-FDG PET/CT as an indicator of progression-free and overall survival in osteosarcoma.

UNLABELLED: The aim of our study was to retrospectively evaluate whether maximum standardized uptake value (SUV(max)), total lesion glycolysis (TLG), or change therein using (18)F-FDG PET/CT performed before and after initial chemotherapy were indicators of patient outcome. METHODS: Thirty-one consecutive patients who underwent (18)F-FDG PET/CT before and after chemotherapy, followed by tumor resection, were retrospectively reviewed. Univariate Cox regression was used to analyze for relationships between covariates of interest (SUV(max) before and after chemotherapy, change in SUV(max), TLG before and after chemotherapy, change in TLG, and tumor necrosis) and progression-free and overall survival. Logistic regression was used to evaluate tumor necrosis. RESULTS: High SUV(max) before and after chemotherapy (P = 0.008 and P = 0.009, respectively) was associated with worse progression-free survival. The cut point for SUV(max) before chemotherapy was greater than 15 g/mL* (P = 0.015), and after chemotherapy it was greater than 5 g/mL* (P = 0.006), as measured at our institution and using lean body mass. Increase in TLG after chemotherapy was associated with worse progression-free survival (P = 0.016). High SUV(max) after chemotherapy was associated with poor overall survival (P = 0.035). The cut point was above the median of 3.3 g/mL* (P = 0.043). High TLG before chemotherapy was associated with poor overall survival (P = 0.021). Good overall and progression-free survival was associated with a tumor necrosis greater than 90% (P = 0.018 and 0.08, respectively). A tumor necrosis greater than 90% was most strongly associated with a decrease in SUV(max) (P = 0.015). CONCLUSION: (18)F-FDG PET/CT can be used as a prognostic indicator for progression-free survival, overall survival, and tumor necrosis in osteosarcoma.

Immunohistochemical detection of lymphovascular invasion with D2-40 in melanoma correlates with sentinel lymph node status, metastasis and survival.

Using immunohistochemistry with anti-D2-40 for the detection of lymphovascular invasion (LVI-IHC) in 74 cases of invasive melanoma, we found LVI in 23% (16/74) of the tumors. Data on sentinel lymph node (SLN) biopsy were available for 36 patients. Sixty-seven percent (6/9) of patients with LVI-IHC and 19% (5/27) without LVI-IHC had positive SLN. Follow-up data were available for 60 patients. Data on recurrence/metastasis were available for 60 patients. Twenty-five percent (15/60) had LVI with immunohistochemistry. Fifty-three percent (8/15) of these patients had "distant" metastasis or regional recurrence compared with 11% (5/45) in those without LVI-IHC. Overall and disease-specific survival was shorter for patients with LVI. In both the univariate and multivariate Cox proportional hazards regression models, LVI-IHC in addition to ulceration was statistically significant with respect to overall survival. Specifically, in the reduced multivariate model, compared with patients with no LVI, patients with intratumoral LVI had a hazard ratio (HR) of 5.4 (95% CI 1.6-18.4), while patients with peritumoral LVI had a HR of 3.8 (95% CI 0.7-20.9). In addition, patients with ulceration had an increased hazard of 4.4 (95% CI 1.2-16.8). For the first time, we herein show a positive correlation with LVI in melanoma detected with immunohistochemistry and distant metastasis, overall survival and disease-free survival.

Opening the black box: the impact of an oncology management program consisting of level I pathways and an outbound nurse call system.

PURPOSE: The Innovent Oncology Program aims to improve the value of cancer care delivered to patients. McKesson Specialty Health and Texas Oncology (TXO) collaborated with Aetna to launch a pilot program. The study objectives were to evaluate the impact of Innovent on Level I Pathway compliance, implement the Patient Support Services program, and measure the rate and costs associated with chemotherapy-related emergency room (ER) visits and hospital admissions. PATIENTS AND METHODS: This was a prospective, nonrandomized evaluation of patients enrolled in Innovent from June 1, 2010, through May 31, 2012. Data from the iKnowMed electronic health record, the McKesson Specialty Health financial data warehouse, and Aetna claims data warehouse were analyzed. RESULTS: A total of 221 patients were included and stratified according to disease and age groups; 76% of ordered regimens were on pathway; 24% were off pathway. Pathway adherence improved from TXO baseline adherence of 63%. Of the 221 patients, 81% enrolled in PSS. Within the breast, colorectal, and lung cancer groups, 14% and 24% of patients had an ER visit and in-patient admission (IPA; baseline) versus 10% and 18% in Innovent, respectively; average in-patient days decreased from 2.1 to 1.2 days, respectively. Total savings combined for the program was $506,481. CONCLUSION: Implementation of Innovent positively affected patient care in several ways: Fewer ER visits and IPAs occurred, in-patient days decreased, cancer-related use costs were reduced, and on-pathway adherence increased.

Conspicuity of bone metastases on fast Dixon-based multisequence whole-body MRI: clinical utility per sequence.

PURPOSE: The purpose of the study was to evaluate the conspicuity of bone metastases on each of the numerous sequences produced by fast Dixon-based multisequence whole-body (WB) magnetic resonance imaging (MRI) scanning in order to determine the most clinically useful sequences overall and per anatomic region. MATERIALS AND METHODS: Twenty-seven breast cancer patients with bone metastases were prospectively studied with fast Dixon-based WB MRI including head/neck, chest, abdominal, pelvic, thigh, calf/feet and either cervical, thoracic and lumbar or cervical/thoracic and thoracic/lumbar regions. Sequences included coronal T2, axial T1 without and with intravenous gadolinium (+C), sagittal T1 spine+C, each associated fat-only (FO) and fat-saturated (FS) sequence, axial diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR). Blinded reviewers evaluated lesion conspicuity, a surrogate of clinical utility, on a five-point scale per anatomic region. Sequences were compared using analysis of variance, differences were detected with Tukey's honestly significant difference test, and the four sequences with highest mean conspicuity were compared to the remainder overall and per anatomic region. RESULTS: Overall, a significant lesion conspicuity difference was found (P<.0001), and lesion conspicuity was significantly higher on FS T1+C, FO T1+C, T1+C sagittal and FS T1+C axial sequences (P<.0001). Per-region results were the same in the head/neck. Other sequences overlapped with these and included the following: chest/abdomen - FO T2, DWI; pelvis - DWI, FO T2; thigh - FS T2, FO T2, FO T1+C; calf/feet - FS T2, DWI, FO T2, STIR. CONCLUSION: Overall, bone lesions were most conspicuous on FS T1+C sagittal, FO T1+C sagittal, T1+C sagittal and FS T1+C axial fast Dixon WB MRI sequences.

Tissue-based predictors of germ-line BRCA1 mutations: implications for triaging of genetic testing.

BRCA testing of patients with breast cancer considered at high risk for having a germ-line BRCA mutation usually consists of comprehensive mutational analysis of both BRCA1 and BRCA2. A more cost-effective strategy of triaging patients for analysis of a single gene could be adopted if tissue-based predictors indicated a high risk specifically for either BRCA1 or BRCA2. To identify potentially useful tissue-based predictors of BRCA mutation status in breast cancer, we evaluated multiple histopathologic features of invasive breast carcinoma on archival tissue sections from 196 high-risk patients who had undergone BRCA testing, and we analyzed which individual or combination of features was most associated with BRCA mutations. Of the 196 patients with invasive breast carcinoma, there were 44 (22%) with a deleterious BRCA1 mutation and 27 (14%) with a deleterious BRCA2 mutation. For patients with available untreated surgical resection specimens for evaluation (n=172), estrogen receptor-positive phenotype was inversely associated with the presence of a BRCA1 mutation (odds ratio, 0.243; 95% confidence interval, 0.070-0.840; P=.025), and high mitotic activity (≥25 mitotic figures per 10 high-power fields) was directly associated with the presence of a BRCA1 mutation (odds ratio, 4.222; 95% confidence interval, 1.353-13.18; P=.013). The combination of estrogen receptor-negative phenotype and high mitotic rate had high specificity (99%; 95% confidence interval, 95%-100%) but low sensitivity (43%; 95% confidence interval, 26%-61%) for identifying a deleterious BRCA1 mutation. In patients with breast cancer at high risk for carrying a BRCA mutation, those with estrogen receptor-negative phenotype and high mitotic rate could be triaged specifically for BRCA1 testing instead of initially performing mutational analysis for both BRCA1 and BRCA2.

Correlation of NRAS mutations with clinical response to high-dose IL-2 in patients with advanced melanoma.

The purpose of this study is to identify clinical and molecular characteristics of melanoma patients that predict response to high-dose interleukin-2 (HD IL-2) to improve patient selection for this approved but toxic therapy. We reviewed the records of 208 patients with unresectable stage III/IV melanoma treated with HD IL-2 at the University of Texas M.D. Anderson Cancer Center (n=100) and the Beth Israel Deaconess Medical Center (n=108) between 2003 and 2009. The BRAF and NRAS mutation status of the tumors was determined for patients with available tissue samples and the mutation status and clinical characteristics were compared with clinical outcomes. Pretreatment serum lactate dehydrogenase levels were available for most patients (n=194). Tissue was available for mutational analysis on a subset of patients (n=103) and the prevalence of mutations was as follows: BRAF 60%, NRAS 15%, WT/WT 25%. In the subset of patients for which mutational analysis was available, there was a significant difference in the response rate based on the mutation status: NRAS 47%, BRAF 23%, and WT/WT 12% (P=0.05). Patients with NRAS mutations had nonstatistically longer overall survival (5.3 vs. 2.4 y, P=0.30) and progression-free survival (214 vs. 70 d, P=0.13). Patients with an elevated lactate dehydrogenase level had a decreased progression-free survival (46 vs. 76 d, P<0.0001), decreased overall survival (0.56 vs. 1.97 y, P<0.0001), and trended toward a decreased response rate (7% vs. 21%, P=0.08). NRAS mutational status is a new candidate biomarkers for selecting patients with melanoma for HD IL-2 treatment.

Pleomorphic ductal carcinoma of the breast: predictors of decreased overall survival.

The World Health Organization classification of tumors of the breast includes a rare variant of invasive ductal carcinoma termed pleomorphic carcinoma. This variant has marked nuclear pleomorphism (>6-fold variation in nuclear size by definition, but often>10-fold) and characteristically contains multinucleated tumor giant cells. Approximately one-third of the cases in the initial series contained a focal spindle cell metaplastic component. The tumors are reported to have an aggressive behavior, but because some contain a spindle cell metaplastic component, it is unclear whether the metaplastic component or other clinicopathologic features account for the poor clinical outcome. We identified 37 cases of pleomorphic carcinoma of the breast and evaluated the association between clinical outcome and multiple clinicopathologic features. Patients with invasive pleomorphic lobular carcinoma and those without at least a tissue biopsy before chemotherapy were excluded. Patients ranged in age from 23 to 78 years (median, 49 y). Tumor size was >5 cm in 12 cases and <5 cm in 22. A focal spindle cell component (<25% of the tumor) was present in 14 tumors (38%). Clinical follow-up was available for 36 patients (median, 17 mo). In multivariate analysis, when the 2 stage-IV patients were excluded, the presence of a spindle cell component and tumor size >5 cm were each independently associated with decreased overall survival. The actuarial 5-year overall survival for patients with and without a metaplastic spindle cell component was 38%+/-15% and 89%+/-7%, respectively. Poor clinical outcome, therefore, is associated with the subset of pleomorphic carcinomas with a spindle cell metaplastic component. As the morphologic features of pleomorphic carcinoma can be seen in primary tumors from other sites, it is important to recognize this tumor as a rare variant of invasive breast carcinoma.