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Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre-induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 10(9) /l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre-induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998-2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 10(9) /l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 10(9) /l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre-induction leucoreduction., (© 2014 John Wiley & Sons Ltd.)

Purpose: To compare the characteristics and prognoses of gastric cancers by tumor location in Korean and U.S. subjects after curative-intent (R0) resection for gastric cancer (GC)., Methods: Data were collected for all patients who had undergone R0 resection at one U.S. institution (n = 567) and one South Korean institution (n = 1,620). Patients with gastroesophageal junction tumors or neoadjuvant therapy were excluded. Patient, surgical, and pathologic variables were compared by tumor location. Factors associated with disease-specific survival (DSS) were determined via multivariate analysis., Results: In the Korean cohort, significantly more upper third GC (UTG) patients had undifferentiated, diffuse type, and advanced stage cancers compared to lower third GC (LTG) and middle third GC (MTG) patients. In the U.S. cohort, however, T stage was relatively evenly distributed among UTG, MTG, and LTG patients. The independent predictors of DSS in the Korean cohort were T stage, tumor size, retrieved and positive lymph node counts, and age, but in the U.S. cohort, the only independent predictors were T stage and positive lymph node count. Tumor size significantly affected DSS of Korean UTG patients but not U.S. UTG patients., Conclusions: There were significant differences in tumor characteristics by tumor location within and between both national cohorts. On the basis of these findings, further study to investigate the biological difference between the two countries is needed.

Background and Purpose: We report a patient with abnormal diffusion tensor imaging (DTI) and tractography of the corticospinal tract caused by mass effect from adjacent enlarged Virchow-Robin spaces., Methods: DTI was performed using 25 noncollinear directions. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated. Region-of-interest measurements of the corticospinal tracts were organized in histograms, and comparisons were made between sides. Statistical analysis consisted of a Wilcoxon rank-sum nonparametric test and a two-sample test of proportions to compare the relative percentage of voxels >.8., Results: The patient had no signs or symptoms of motor weakness. The corticospinal tract adjacent to the enlarged Virchow-Robin spaces showed significant changes in the proportion of FA > .8, distribution of FA and distribution of MD (P < .001)., Conclusions: Diffusion tensor changes may be caused by enlarged Virchow-Robin spaces in the absence of clinical signs or symptoms. We hypothesize that the DTI changes are due to alterations in the extravascular extracellular space. Tensor changes should be interpreted with caution in patients with space occupying mass lesions such as brain tumors., (Copyright © 2011 by the American Society of Neuroimaging.)

Purpose: Determine incidence, clinical presentation, electrographic correlates, and outcome of nonconvulsive status epilepticus (NCSE) in cancer patients on whom an EEG was performed., Methods: Retrospective review of 947 EEG reports on 658 patients in whom any type of EEG was performed at Memorial Sloan-Kettering Cancer Center (July 2006 to March 2008). Using the Epilepsy Research Foundation criteria, patients were classified as definite or probable NCSE. Medical records were reviewed for diagnosis, causes of NCSE, response to treatment, and outcome. Mortality was determined for patients with NCSE., Results: Twenty-six episodes of NCSE were identified in 25 patients (25/658, 4%). Eleven patients had primary brain tumor, 12 patients systemic cancer, and two had both. At diagnostic EEG, 18 were awake, 3 were lethargic, and 5 patients were comatose. EEG revealed a seizure in 62% of the patients, periodic lateralized epileptiform discharges in 42%, and periodic epileptiform discharges in 7.7%. Neuroimaging revealed new intracranial pathology in 54% of the patients. Seventy-seven percent of the patients achieved control; 65% required ≥3 antiepileptic drugs, and 33% required intubation. Three patients died from NCSE., Discussion: In our cohort, awake NCSE was more common than comatose NCSE. Treatment was successful in patients with heterogeneous central nervous system disease. EEG evaluation should be considered in patients with cancer because NCSE is treatable despite a high prevalence of structural brain disease. Nonconvulsive status epilepticus control did not always require intubation and burst suppression, but frequently required three or more antiepileptic drugs.

Purpose: To perform semiautomated quantitative analysis of the background enhancement (BE) in a cohort of patients with newly diagnosed breast cancer and to correlate it with mammographic breast density and menstrual cycle., Materials and Methods: Informed consent was waived after the research ethics board approved this study. Results of 177 consecutive preoperative breast magnetic resonance (MR) examinations performed from February to December 2009 were reviewed; 147 female patients (median age, 48 years; range, 26-86 years) were included. Ordinal values of BE and breast density were described by two independent readers by using the Breast Imaging Reporting and Data System lexicon. The BE coefficient (BEC) was calculated thus: (SI2 · 100/SI1) - 100, where SI is signal intensity, SI2 is the SI enhancement measured in the largest anteroposterior dimension in the axial plane 1 minute after the contrast agent injection, and SI1is the SI before contrast agent injection. BEC was used for the quantitative analysis of BE. Menstrual cycle status was based on the last menstrual period. The Wilcoxon rank-sum or Kruskal-Wallis test was used to compare quantitative assessment groups. Cohen weighted κ was used to evaluate agreement., Results: Of 147 patients, 68 (46%) were premenopausal and 79 (54%) were postmenopausal. The quantitative BEC was associated with the menstrual status (BEC in premenopausal women, 31.48 ± 20.68 [standard deviation]; BEC in postmenopausal women, 25.65 ± 16.74; P = .02). The percentage of overall BE was higher when the MR imaging was performed in women in the inadequate phase of the cycle (<35 days, not 7-14 days; mean BEC, 35.7) compared with women in the postmenopausal group (P = .001). Premenopausal women had significantly higher BEC when compared with postmenopausal women (P = .03). There was no significant difference in the percentage of BE between breast density groups., Conclusion: Premenopausal women with breast cancer, and specifically women in the inadequate phase of the cycle, presented with higher quantitative BE than postmenopausal women. No association was found between BE and breast density.

Background and Objectives: Disease-specific survival (DSS) for GC patients differs in Eastern and Western countries. The aim is to compare outcomes of US and Korean patients following resection of early-stage, node-negative gastric carcinoma (GC)., Methods: All patients (1995-2005) with T1N0 gastric carcinoma, excluding gastroesophageal tumors, were evaluated. DSS was compared by adjusting for prognostic variables from an internationally validated GC nomogram., Results: The cohort included 598 Korean patients and 159 US patients. Age and BMI were significantly higher in US patients. Distal tumor location was more frequent in Korea (60% vs. 52%) and proximal location in the US (19% vs. 5%, P < 0.0001). Five-year DSS did not differ significantly between Korea and the US. After multivariate analysis, DSS of Korean patients persisted, with no significant differences when compared to US patients (HR = 1.2, 95% CI: 0.3-5.2, P = 0.83)., Conclusions: Despite widespread speculations that GC differs in the East and West, when we compare similarly staged, node-negative GC patients, survival did not differ significantly between Korea and the US. This suggests that GC is a heterogeneous disease and when similar subtypes of gastric cancer are compared, these differences disappear. This study suggests more similarities than previously hypothesized between US and Korean GC patients., (Copyright © 2012 Wiley Periodicals, Inc.)

The Edmonton Symptom Assessment System (ESAS) is a common screening tool in cancer, although its validity for distress screening is unproven. Here, screening performance of the ESAS anxiety (ESAS-A) and depression (ESAS-D) items were validated against the anxiety [Generalised Anxiety Disorder-7 (GAD-7)] and depression [Patient Health Questionnaire-9 (PHQ-9)] subscales of the PHQ. A total of 1215 cancer patients completed the Distress Assessment and Response Tool (DART), a computerised distress screening instrument. Spearman's rank correlation coefficients and receiver operating characteristic curve analyses were used to evaluate the ability of ESAS-A and ESAS-D to identify moderate distress (GAD-7/PHQ-9 ≥ 10). Spearman's rank correlation coefficients comparing ESAS-A and ESAS-D with GAD-7 and PHQ-9 were 0.74 and 0.72 respectively. Areas under the receiver operating characteristic curves were 0.89 and 0.88 for anxiety and depression respectively. A cut-off of ≥3 on ESAS-A demonstrated a sensitivity of 0.91, specificity of 0.68, positive predictive value of 0.34 and negative predictive value of 0.97. A cut-off of ≥2 on the ESAS-D demonstrated a sensitivity of 0.86, specificity of 0.72, positive predictive value of 0.46 and negative predictive value of 0.95. High sensitivities of ESAS-A and ESAS-D at certain cut-offs suggest they have use in ruling-out distress. However, their low specificities indicate secondary screening is needed to rule-in anxiety or depression for case-finding., (© 2012 Blackwell Publishing Ltd.)

Purpose: To compare contrast material-enhanced computed tomographic (CT) urography 60 seconds after injection of contrast material (urothelial phase [UP]) after intravenous administration of a diuretic with the standard 5-minute delayed excretory phase (EP) in a high-risk population for upper tract tumors., Materials and Methods: Institutional review board approval and informed consent were obtained. Eighty CT urographic examinations in 77 patients known to have or at high risk for urothelial malignancy were included. After intravenous administration of a diuretic, dual-phase CT urography was performed at 60 seconds (UP) and 5 minutes (EP) after intravenous administration of contrast material. Two experienced abdominal radiologists independently interpreted each phase more than 1 month apart to minimize recall bias. Urinary tract distention and location and size of all lesions suspected of being urothelial tumors were recorded. Standard of reference was obtained from prospective study interpretation and surgical histopathologic findings. Generalized estimating equations for logistic regression were used to compare performance measures and adjust for the correlation of repeated measures within patients., Results: There were 23 upper and 61 lower urinary tract tumors confirmed in 15 and 32 patients, respectively. For detection of bladder tumors, there was higher sensitivity for the UP than the EP (89.3% [109 of 122] vs 70.5% [86 of 122], respectively; P<.0001). For detection of upper tract tumors, there was higher sensitivity for the UP than the EP (82.6% [38 of 46] vs 69.6% [32 of 46], respectively; P=.0194). Distention of all upper urinary tract segments was better during the EP than the UP (P<.0001)., Conclusion: UP CT urography after injection of a diuretic has a higher lesion detection rate than the EP for both upper and lower urinary tract tumors, which suggests its possible use as a single-phase protocol for evaluation of the entire urinary tract in patients at high risk for urothelial tumors., (© RSNA, 2012.)

Purpose: To determine the accuracy of secondary magnetic resonance (MR) imaging signs of anterior cruciate ligament (ACL) insufficiency in predicting clinical anterior translational knee laxity, in the presence of an intact graft, after ACL reconstruction., Materials and Methods: Institutional review board approval was obtained, and the requirement to obtain informed consent was waived. Fifty-two patients with ACL reconstruction and no injury to the contralateral knee were included. Three patients with visible ACL graft tears at MR imaging were excluded. All patients underwent MR imaging of the affected knee, functional assessment with use of the International Knee Documentation Committee (IKDC) score, and arthrometric testing of both the affected and uninjured knee. A side-to-side difference of more than 3 mm at 133 N was considered to be indicative of knee laxity. Two radiologists independently evaluated all MR images for seven signs of anterior knee laxity. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were calculated for each MR imaging sign., Results: Ten patients demonstrated knee laxity at arthrometric testing. Patients with knee laxity at arthrometric testing had significantly lower IKDC scores (P < .03). Sensitivities for all signs were low (0%-50%). Anterior translation of the tibia of more than 7 mm, a posterior cruciate ligament (PCL) angle of less than 100°, and a PCL curvature ratio of more than 0.39 demonstrated high specificity (range, 82%-90%). Uncovering of the posterior horn of the lateral meniscus and the posterior femoral line had a specificity of 97%-100% and a sensitivity of 0%. All signs had a low PPV and high NPV for laxity. All MR imaging signs demonstrated near-perfect interobserver agreement., Conclusion: Although MR imaging signs of knee laxity in the presence of an intact ACL graft have a high specificity, the low PPV means that MR imaging is of little value in predicting anterior knee laxity as demonstrated with mechanical testing.

Unlabelled: Study Type--Therapy (practice patterns). Level of Evidence 2b. What's known on the subject? And what does the study add? The treatment of locally advanced prostate cancer varies widely even though there is level one evidence supporting the use of multimodality therapy as compared with monotherapy. This study defines treatment patterns of locally advanced prostate cancer within the United States and identifies predicators of who receives multimodality therapy rather than monotherapy., Objective: • To identify treatment patterns and predictors of receiving multimodality therapy in patients with locally advanced prostate cancer (LAPC)., Patients and Methods: • The cohort comprised patients ≥66 years with clinical stage T3 or T4 non-metastatic prostate cancer diagnosed between 1998 and 2005 identified from the Surveillance, Epidemiology and End Results (SEER) cancer registry records linked with Medicare claims. • Treatments were classified as radical prostatectomy (RP), radiation therapy (RT) and androgen deprivation therapy (ADT) received within 6 and 24 months of diagnosis. • We assessed trends over time and used multivariable logistic regression to identify predictors of multimodality treatment., Results: • Within the first 6 months of diagnosis, 1060 of 3095 patients (34%) were treated with a combination of RT and ADT, 1486 (48%) received monotherapy (RT alone, ADT alone or RP alone), and 461 (15%) received no active treatment. • The proportion of patients who received RP increased, exceeding 10% in 2005. • Use of combined RT and ADT and use of ADT alone fluctuated throughout the study period. • In all 6% of patients received RT alone in 2005. • Multimodality therapy was less common in patients who were older, African American, unmarried, who lived in the south, and who had co-morbidities or stage T4 disease., Conclusions: • Treatment of LAPC varies widely, and treatment patterns shifted during the study period. • The slightly increased use of multimodality therapy since 2003 is encouraging, but further work is needed to increase combination therapy in appropriate patients and to define the role of RP., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Purpose: To compare the postoperative complications after immediate breast reconstruction (IBR) versus mastectomy alone and to examine the impact on the delivery of chemotherapy., Methods: In this prospective series, there were 391 consecutive women who underwent mastectomy (243 mastectomy alone and 148 mastectomy and IBR). The outcome measures were complications (within 3 months after surgery) and time to adjuvant chemotherapy., Results: Compared to the IBR group, patients in the mastectomy alone group were significantly older (P < 0.0001), smokers (P = 0.007) and less likely to have had previous radiation or lumpectomy (P < 0.0001). Overall, the complication rate was significantly greater in the IBR group than mastectomy alone (27.0% vs. 15.6%, P = 0.009). Univariate analyses revealed that mastectomy with IBR [odds ratio (OR) = 2, 95% confidence interval (CI) 1.21-2.30]; bilateral procedure (OR = 1.84, 95% CI 1.07-3.16); previous radiotherapy (OR = 2.4, 95% CI 1.29-4.47); and previous lumpectomy (OR = 1.84, 95% CI 1.11-3.03) were significant predictors of increased complications. With multivariable analysis, none of these variables were significantly associated with increased complications. 106 patients received adjuvant chemotherapy; median time from mastectomy to chemotherapy was 6.8 (0.71-15) weeks in the mastectomy alone group (n = 96) compared to 8.5 (6.3-11) weeks in the IBR group (n = 10) (P = 0.01)., Conclusions: Although the incidence of overall and major postoperative complications was higher after IBR than mastectomy alone, there were no significant relationships in the multivariable analysis. IBR was associated with a modest increase in time to chemotherapy that was statistically but not clinically significant.

Background: The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS., Methods: Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed. The nomogram model was chosen based on the clinical evidence and statistical significance of the predictors, including age at diagnosis, tumor size, histologic grade, uterine cervix involvement, extrauterine spread, distant metastases, and mitotic index. Five-year overall survival (OS) was the predicted endpoint. The concordance probability (CP) was used as a predictive accuracy measure and compared with the CP of current staging systems. The model was internally validated using 200 bootstrap samples to correct for over fitting., Results: One hundred eighty-five of 270 patients were eligible for the nomogram analysis. The median follow-up was 5.4 years, and the median OS was 3.75 years (95% confidence interval, 3-6 years). The CP of the newly developed nomogram was 0.67 (95% confidence interval, 0.63-0.72). This was superior to predictions based on AJCC and FIGO staging. The bootstrap-validated CP was 0.65 with good calibration accuracy., Conclusions: The authors developed and internally validated a uterine LMS-specific nomogram to predict 5-year OS. This novel, individualized prognostic model outperforms traditionally used categorical staging systems and may be useful for patient counseling and for better selection of patients for adjuvant therapy trials., (Copyright © 2011 American Cancer Society.)

Purpose: To investigate the accuracy, reproducibility, and reliability of unenhanced magnetic resonance (MR) imaging techniques for detecting metastatic axillary lymph nodes in patients with newly diagnosed breast carcinoma., Materials and Methods: Institutional review board approval and informed consent were obtained. Seventy-four consecutive women with invasive breast carcinoma were recruited to undergo preoperative breast MR imaging. Thirteen patients were excluded, two because they were undergoing preoperative chemotherapy and 11 because of the presence of movement or susceptibility artifacts on images. Thus, 61 patients (mean age, 53 years; range, 33-78 years) were included in this study. Axial T1-weighted MR images without fat saturation and diffusion-weighted (DW) MR images were analyzed by two experienced radiologists, who were blinded to the histopathologic findings. Visual and quantitative analyses of unenhanced MR images were performed. Sensitivity, specificity, and accuracy were calculated. To assess the intraobserver agreement, a second reading was performed. Statistical analysis was conducted on a patient-by-affected side basis., Results: The sensitivity, specificity, and accuracy were 88%, 82%, and 85%, respectively, for axial T1-weighted MR imaging and 84%, 77%, and 80% for DW imaging. Apparent diffusion coefficients (ADCs) were significantly lower in the malignant group (P<.05 for all four readings), with the average of the four readings ranging from 0.333×10(-3) mm2/sec to 2.843×10(-3) mm2/sec. The mean Lin coefficient comparing the mean ADC reading for each observer was 0.959 (95% confidence interval: 0.935, 0.975), suggesting very high interobserver agreement between the two observers in terms of reproducibility of ADCs. The Bland-Altman plot showed good inter- and intraobserver agreement., Conclusion: Unenhanced MR imaging techniques showed high accuracy in the preoperative evaluation of axillary status in patients with invasive breast cancer. Results indicate reliable and reproducible assessment with DW imaging, but it is unlikely to be useful in clinical practice., (© RSNA, 2011)

Background: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays., Methods and Findings: Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment., Conclusions: Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features.

Background: Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted., Methods: Women with ≤ 2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥ 2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods., Results: The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively., Conclusions: Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy., (Copyright © 2011 American Cancer Society.)

Purpose: The purpose of the study was to determine the performance of a 64-row multidetector computed tomography (MDCT) in identifying peritoneal metastases in ovarian cancer patients undergoing surgical staging or cytoreduction., Methods: This retrospective study included 76 patients who underwent surgical staging (n = 11) or cytoreduction (n = 65). Patients had MDCT before surgery (mean, 24 [SD, 16.9] days) as well as correlative surgicopathologic data. For the imaging analysis, the peritoneal cavity was divided to 28 segments, which were assessed for absence or presence of disease. Rate of optimal cytoreduction at the time of surgery was recorded. The standard of reference for this study was surgery, unless there was proof of metastasis as assessed by follow-up imaging. Sensitivity and predictive accuracy of CT and surgery compared with the standard of reference were calculated., Results: The overall sensitivity and accuracy were 81.2% and 94.3% for MDCT and 87.4% and 97.2% for surgery (P = 0.14, P = 0.007), respectively. There was no difference in the detection of lesions 1 cm or greater between MDCT and surgery (89.3% and 84.9%, respectively; P = 0.31); however, MDCT was less sensitive than surgery in detecting disease sites of less than 1 cm (65.5% and 92.3%, respectively; P = 0.001). For the subgroup of patients undergoing cytoreduction after neoadjuvant chemotherapy (NAC) (n = 30), sensitivities for MDCT and surgery were similar (80% and 76.9%, respectively [P = 0.71]). Although sensitivity of CT was not altered by NAC (P = 0.92), there was a significant decrease in sensitivity of surgical assessment after NAC (94% vs 76.9%; P = 0.003)., Conclusions: Multidetector computed tomography (MDCT) has similar sensitivity as surgery for peritoneal metastases of 1 cm or greater. The maintained sensitivity of MDCT in detecting peritoneal disease after NAC, which is underestimated at surgery, may help surgical planning and may improve optimal cytoreduction rate in this group of patients.

Each year there are an estimated 200,000 new breast cancer cases diagnosed in the United States; of these, 1% of cases are in men. Lymphedema can be a devastating complication from breast cancer and its treatment. Currently, almost all lymphedema-related research is based on women and extrapolated to men. We conducted the first population-based study of men with incident breast cancer of any stage, diagnosed from 1998 to 2005, who were 65 years and older in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We utilized claims related to lymphedema and lymphedema treatment in our cohort. We defined 'lymphedema-specific' claims to contain the word 'lymphedema' in the Medicare claim description; similarly, 'lymphedema-related' claims were defined as treatments reimbursed for lymphedema but not necessarily containing the word 'lymphedema' in the Medicare claim description. We identified 628 men with incident breast cancer from 1998 to 2005 who were 65 years and older. The cumulative incidence, censored for deaths, of lymphedema-specific claims at 2, 3, 4, and 5 years was 8.0, 9.2, 10.5, and 10.5%, respectively. The median follow-up was 3.4 years and for those without any event was 4.7 years. The cumulative incidence, censored for deaths, of lymphedema-related claims at 2, 3, 4, and 5 years was 26.9, 32.2, 35.4, and 39.8%. Rates for men were similar to analogous rates for women. Lymphedema is a common complication affecting men with breast cancer as well as women and appropriate treatment and rehabilitation strategies need to be implemented for both genders.

Objective: The purpose of this study was to compare the error rates in breast imaging reports generated with automated speech recognition (ASR) technology as opposed to conventional dictation transcription., Materials and Methods: Breast imaging reports reviewed from January 2009 to April 2010 during multidisciplinary tumor board meetings at two hospitals were scrutinized for minor and major errors., Results: Of 615 reports obtained, 308 were generated with ASR and 307 with conventional dictation transcription. At least one major error was found in 23% of ASR reports, as opposed to 4% of conventional dictation transcription reports (p < 0.01). Major errors were more common in breast MRI reports (35% of ASR and 7% of conventional reports), the lowest error rates occurring in reports of interventional procedures (13% of ASR and 4% of conventional reports) and mammography reports (15% of ASR and no conventional reports) (p < 0.01). The error rates did not differ substantially between reports generated by staff radiologists and trainees or between reports generated by speakers who spoke English as their first language and those whose native language was not English. After adjustment for academic rank, native language, and imaging modality, reports generated with ASR were 8 times as likely as conventional dictation transcription reports to contain major errors (p < 0.01)., Conclusion: Reports generated with ASR are associated with higher error rates than reports generated with conventional dictation transcription. The imaging modality used is a predictor of the occurrence of reporting errors. Conversely, native language and academic rank of the speaker do not have a significant influence on error rate.

Abl interactor 1 (Abi1) is an adaptor protein involved in cell migration. Previous in vitro work suggested that Abi1 is a regulator of breast cancer proliferation, migration, and invasion. In the present study, we explore the expression of Abi1 and its downstream effector phospho-Akt (p-Akt) in a series of breast cancers and correlate their expression with clinicopathological and survival data. Using tissue microarrays, 988 patients with invasive breast carcinoma were evaluated by immunohistochemistry. Statistical correlation was performed to determine associations between Abi1 and p-Akt expression and standard breast clinicopathological factors. The prognostic value of Abi1 and p-Akt for disease-free (DFS) and overall survival (OS) was also evaluated. Abi1 expression was demonstrated in 33.7% (314/933) of invasive carcinomas, while p-Akt was expressed in 46.7% (441/944). There was a significant association between Abi1 and p-Akt expression (P=0.001). Abi1 expression showed significant positive correlation with older age at diagnosis and the Ki67 index. Most importantly, it was demonstrated to be an independent predictor of both DFS and OS (HR = 1.6 and 1.5, P<0.001, respectively). There was no association between p-Akt expression and survival. To the best of our knowledge, this is the first study evaluating Abi1 expression in a large group of breast cancers. Our analysis demonstrated that tumors expressing high levels of Abi1 are significantly associated with early recurrence and worse survival on multivariate analysis. This suggests that Abi1 expression has potential as a molecular marker to refine outcome prediction in breast cancer patients.

Purpose: Population-based studies have reported that as many of 35% of black women do not undergo radiotherapy (RT) after breast conservation surgery (BCS). The objective of the present study was to determine whether this trend persisted at a large multidisciplinary cancer center, and to identify the factors that predict for noncompliance with RT and determine the outcomes for this subset of patients., Methods and Materials: Between January 2002 and December 2007, 83 black women underwent BCS at Memorial Sloan-Kettering Cancer Center and were therefore eligible for the present study. Of the 83 women, 38 (46%) had Stage I, 38 (46%) Stage II, and 7 (8%) Stage III disease. Of the study cohort, 31 (37%) had triple hormone receptor-negative tumors. RT was recommended for 81 (98%) of the 83 patients (median dose, 60 Gy)., Results: Of the 81 women, 12 (15%) did not receive the recommended adjuvant breast RT. Nonreceipt of chemotherapy (p = .003) and older age (p = .009) were associated with nonreceipt of RT. With a median follow-up of 70 months, the 3-year local control, locoregional control, recurrence-free survival, disease-free survival, and overall survival rate was 99% (actuarial 5-year rate, 97%), 96% (actuarial 5-year rate, 93%), 95% (actuarial 5-year rate, 92%), 92% (actuarial 5-year rate, 89%), and 95% (actuarial 5-year rate, 91%), respectively., Conclusion: We found a greater rate of utilization adjuvant breast RT (85%) among black women after BCS than has been reported in recent studies, indicating that excellent outcomes are attainable for black women after BCS when care is administered in a multidisciplinary cancer center., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Prostate cancer treatments, including radical prostatectomy (RP) and radiotherapy (RT), may adversely affect erectile function. Penile implant surgery is a well-recognized erectile dysfunction (ED) treatment for prostate cancer survivors who wish to remain sexually active and in whom nonsurgical treatments are ineffective or unpalatable., Aim: To describe the utilization of penile implants after RP or RT for prostate cancer and to identify predictors of such use., Methods: From Surveillance Epidemiology and End Results cancer registry data linked with Medicare claims, we identified men aged ≥66 years diagnosed with prostate cancer in 1998-2005 who were treated with RP or RT. Utilization of penile implants was identified in Medicare claims. Multivariable logistic regression was used to identify demographic and clinical predictors of implant utilization., Main Outcome Measures: Medicare claim for penile implant surgery, impact of demographic and clinical factors on penile implant surgery utilization., Results: The study group comprised 68,558 subjects, including 52,747 who had RT and 15,811 who had RP as primary prostate cancer treatment. The penile implant utilization rate was 0.8% for the entire group, 0.3% for the RT group, and 2.3% for the RP group. Predictors of penile implant utilization were initial treatment modality, younger age, and African American or Hispanic race, being unmarried and residing in the South or West., Conclusions: Penile implant utilization after prostate cancer treatment is relatively uncommon in men over 65. Men who are younger, African American or Hispanic, and those who have an RP are more likely than their peers to receive a penile implant after prostate cancer treatment., (© 2011 International Society for Sexual Medicine.)

Purpose: To retrospectively identify magnetic resonance (MR) imaging findings that are associated with hepatocellular carcinoma (HCC) in 1-2-cm nodules detected at surveillance ultrasonography (US) and to propose newer MR imaging diagnostic criteria., Materials and Methods: Institutional research ethics board approval was obtained, and informed patient consent was waived. Among 145 consecutive patients who had 1-2-cm nodules that were newly detected at surveillance US, 108 patients underwent gadobenate dimeglumine-enhanced MR imaging. After excluding hemangiomas and unconfirmed nodules, the study sample comprised 96 patients with 116 nodules, including 43 HCCs and 73 benign nodules. MR imaging findings were assessed for signal intensity at each sequence. On the basis of the results of univariate and multivariable logistic regression analyses, several diagnostic criteria were developed by using combinations of MR imaging findings, which were then compared with the American Association for the Study of Liver Diseases (AASLD) practice guideline., Results: Univariate analysis revealed four imaging findings associated with HCC, including arterial phase hyperintensity, portal or delayed phase hypointensity (washout), hyperintensity on T2-weighted images, and hepatobiliary phase hypointensity (P < .001 for each). In the multivariable analysis, arterial phase hyperintensity (adjusted odds ratio [OR], 17.1; P = .003) and washout (adjusted OR, 11.7; P = .007) were associated with HCC. Of the developed criteria, the criteria including nodules fitting the AASLD practice guideline (arterial phase hyperintensity and washout) or nodules having three or more findings were considered most reasonable, showing improved sensitivity (77% [33 of 43] versus 67% [29 of 43], P = .048) and comparable specificity (95% [69 of 73] versus 99% [72 of 73], P = .09), as compared with AASLD practice guideline., Conclusion: Alternative MR imaging criteria for diagnosing HCC in 1-2-cm nodules detected at surveillance US that can improve sensitivity compared with the AASLD practice guideline were proposed. A larger study is needed to verify the preliminary criteria in this study., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101549/-/DC1., (RSNA, 2011)

Background: Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort., Methods: Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS)., Results: From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+, DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt + disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt + patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003)., Conclusions: Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt + disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.

Background: Positive peritoneal cytology is a predictor of poor survival in patients with gastric cancer. Our aim is to more clearly define the natural history of this cohort., Methods: Review of a prospectively maintained gastric cancer database of patients who had diagnostic laparoscopy with peritoneal washings. Clinicopathologic and treatment-related variables were obtained. Univariate and multivariate analyses were performed for factors associated with disease-specific survival (DSS)., Results: From January 1993 to April 2009, a total of 1241 patients with gastric cancer underwent laparoscopy with peritoneal washings; 291 (23%) had positive cytology. There were 198 patients (68%) who had visible metastases discovered at laparoscopy (M1), and 93 patients (32%) were without gross evidence of advanced disease (M1 Cyt+). The median DSS for the entire cohort was 1 year; for M1, DSS was 0.8 years, and for M1 Cyt+ , DSS was 1.3 years. At baseline, independent predictors of worse DSS were poor performance status, M1 disease, and diffuse tumors. Among the subset of patients with M1 Cyt+ disease, performance status was the strongest independent predictor of DSS. A total of 48 of the 291 Cyt+ patients had repeat staging laparoscopy after chemotherapy. Compared with patients who had persistently positive cytology (n = 21), those who converted to negative cytology (n = 27) had a significant improvement in DSS (2.5 years vs. 1.4 years, P = 0.0003)., Conclusions: Patients with positive cytology as the only evidence of advanced disease exhibit a poor outcome; however, clearing of Cyt+ disease by chemotherapy is associated with a statistically significant improvement in DSS. The role for gastrectomy in patients with positive peritoneal cytology remains uncertain.

Background: Volume of disease in the sentinel lymph node (SLN) is a significant predictor of additional nodal metastasis. This study assesses incidence of residual non-SLN disease in a large cohort of women with minimal SLN metastases and compares three methods of SLN micrometastasis volume measurement to determine which best predicts residual disease on completion axillary lymph node dissection (cALND)., Methods: A total of 505 patients with invasive breast cancer and minimal SLN metastasis (pN1mi or pN0(i+)) underwent cALND and had complete data. All SLNs were evaluated by three measurement methods for volume of metastasis: (1) method of detection (frozen section, routine hematoxylin and eosin, serial hematoxylin and eosin, immunohistochemistry), (2) American Joint Committee on Cancer's AJCC Cancer Staging Manual, 7th edition, N category, and (3) number of metastatic cells (1-100, 101-999, ≥1000). Multivariable logistic regression models were used to predict the presence of additional non-SLN disease., Results: A total of 251 patients (50%) had pN0(i+) and 254 patients (50%) had pN1mi disease. Twelve percent of those with pN0(i+) and 20% with pN1mi had additional non-SLN disease. On multivariate analyses including eight variables, only lymphovascular invasion (odds ratio >2.2, P < 0.01) and volume of nodal metastasis as assessed by any method of measurement (method of detection, AJCC, and cell count) were significantly correlated with additional non-SLN disease (P = 0.04, 0.03, and 0.02, respectively). All three models had similar goodness of fit and discrimination (Akaike information criterion = 442, 442, 441; -2log likelihood = 416, 420, 417; concordance index = 0.680, 0.675, 0.676, respectively)., Conclusions: A significant proportion of women with minimal SLN metastases have additional non-SLN disease at cALND. Assessments of SLN volume of disease by three different methods of measurement are equivalent for prediction of additional non-SLN metastases.

Purpose: To determine the relationship between breast density, presenting features and molecular subtype of cancer, and surgical treatment received., Methods: Retrospective review of a prospectively maintained database. Eligible patients had stage 1-3 cancer, were treated between 1/2005 and 6/2007, and had estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) measurements and films available for review. Density was classified at presentation as 1-4 using the Breast Imaging Reporting and Data System (BI-RADS) classification., Results: 1,323 patients were included. Significant differences across the four density groups were present in age, race, multicentricity/focality, and presence of an extensive intraductal component (EIC). When density was combined into two groups, after adjustment for age, only an EIC and mammographically occult cancer were significantly more common in the dense groups. Extremely dense breasts (BI-RADS density 4) more commonly had luminal A tumors (p = 0.05), lobular cancers (p = 0.03), multicentricity (p = 0.02), and occult tumors (p < 0.0001). Greater density was associated with increased mastectomy use, with 61% of the extremely dense group having mastectomy versus 43% of those of lesser density (p = 0.01)., Conclusions: Cancers in extremely dense breasts occur in younger women, are more often mammographically occult, and appear to be phenotypically different from those arising in other density groups. The more common use of mastectomy may be related to these features, although density itself is not a selection criterion for mastectomy.

Purpose: While the mortality associated with ductal carcinoma in situ (DCIS) is minimal, the risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is relatively high. Radiation therapy (RT) and antiestrogen agents reduce the risk of IBTR and are considered standard treatment options after BCS. However, they have never been proven to improve survival, and in themselves carry rare but serious risks. Individualized estimation of IBTR risk would assist in decision making regarding the various treatment options for women with DCIS., Patients and Methods: From 1991 to 2006, 1,868 consecutive patients treated with BCS for DCIS were identified. A multivariate Cox proportional hazards model was constructed using the 1,681 in whom data were complete. Ten clinical, pathologic, and treatment variables were built into a nomogram estimating probability of IBTR at 5 and 10 years after BCS. The model was validated for discrimination and calibration using bootstrap resampling., Results: The DCIS nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated good calibration and discrimination, with a concordance index of 0.704 (bootstrap corrected, 0.688) and a concordance probability estimate of 0.686. Factors with the greatest influence on risk of IBTR in the model included adjuvant RT or endocrine therapy, age, margin status, number of excisions, and treatment time period., Conclusion: The DCIS nomogram integrates 10 clinicopathologic variables to provide an individualized risk estimate of IBTR in a woman with DCIS treated with BCS. This tool may assist in individual decision making regarding various treatment options and help avoid over- and undertreatment of noninvasive breast cancer.

Background: The objective of this study was to examine the current treatment for liver abscess and to assess the factors associated with failure of percutaneous drainage., Study Design: Records of 58 patients with pyogenic hepatic abscess, from 1998 to 2009, were examined. Clinicopathologic variables were analyzed as predictors of failure of percutaneous drainage using multivariable logistic regression. The results of surgical intervention after failure of percutaneous treatment were also examined., Results: Fifty-one patients (88%) had a history of malignancy including pancreas (36%), cholangiocarcinoma (17%), colon (12%), and gallbladder (10%). Recent hepatic artery embolization or radiofrequency ablation preceded development of abscess in 13 patients (22%). Fifteen patients (26%) had evidence of biliary tract communication, and 14 of 15 (93%) of these patients had concomitant biliary tract obstruction. Percutaneous drainage was successful in 38 patients (66%) with a median drain dwell time of 26 days (range 3 to 319 days). Five patients (9%) required operative intervention and 2 of these patients (3% overall) died postoperatively from septic complications. Fifteen patients (26%) died with percutaneous drains in place; 9 (60%) of these patients died of cancer progression without evidence of sepsis. Independent predictors of failure of percutaneous drainage included abscesses containing yeast (p = 0.003) and communication of the abscess cavity with the biliary tree (p = 0.02)., Conclusions: Pyogenic hepatic abscess was treated successfully in the majority of patients with advanced malignancy, although mortality remained high. The presence of yeast and communication with an untreated obstructed biliary tree were associated with failure of percutaneous drainage. The need for surgical salvage was associated with a high mortality., (Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To compare disease-specific survival (DSS) between the US and Korea following R0 resection for gastric carcinoma (GC)., Summary Background Data: Many studies have described decreased 5-year survival after curative gastrectomy for GC in the West compared with the East. Although clinicopathological presentations of GC are known to vary widely between Eastern and Western countries, including histology, tumor location, and stage at presentation, it remains unclear whether these factors account for differences in survival., Methods: All patients undergoing curative intent resections (R0) for GC (1995-2005) were evaluated in 2 independent, single-institution prospectively maintained databases from the US (711 patients) and Korea (1646 patients). Patients receiving neoadjuvant chemotherapy were excluded from this analysis. Patient, surgical and pathologic variables were compared. DSS was determined via multivariate analysis using prognostic variables from an internationally validated GC nomogram that estimates the probability of 5- and 9-year survival., Results: Age and body mass index were significantly higher in US patients. Location of tumors was more often proximal in the United States (39% vs. 9%, P < 0.0001) and distal in Korea (54% vs. 33%, P < 0.0001). Korean patients had more early stage tumors (42% vs. 28% stage Ia, P < 0.0001) with a higher number of lymph nodes identified (97% vs. 79%, >or=15 lymph nodes, P < 0.0001). The 5-year DSS was higher in Korea than in the United States. After multivariate analysis, applying factors used in the nomogram, DSS of Korean GC patients remained significantly better than that of US patients (HR = 1.3, 95% CI; 1.0-1.6, P = 0.008)., Conclusions: This study demonstrates better survival for GC patients in Korea compared with the US as determined by multivariate analysis with a validated gastric cancer nomogram. Multiple possibilities can explain this difference.

Purpose: Enthusiasm for laparoscopic surgical approaches to prostate cancer treatment has grown despite limited evidence of improved outcomes compared with open radical prostatectomy. We compared laparoscopic prostatectomy with or without robotic assistance vs open radical prostatectomy in terms of postoperative outcomes and subsequent cancer directed therapy., Materials and Methods: Using a population based cancer registry linked with Medicare claims we identified men 66 years old or older with localized prostate cancer who underwent radical prostatectomy from 2003 to 2005. Outcome measures were general medical/surgical complications and mortality within 90 days after surgery, genitourinary/bowel complications within 365 days, radiation therapy and/or androgen deprivation therapy within 365 days and length of hospital stay., Results: Of the 5,923 men 18% underwent laparoscopic radical prostatectomy. Adjusting for patient and tumor characteristics, there were no differences in the rate of general medical/surgical complications (OR 0.93 95% CI 0.77-1.14) or genitourinary/bowel complications (OR 0.96 95% CI 0.76-1.22), or in postoperative radiation and/or androgen deprivation (OR 0.80 95% CI 0.60-1.08). Laparoscopic prostatectomy was associated with a 35% shorter hospital stay (p <0.0001) and a lower bladder neck/urethral obstruction rate (OR 0.74, 95% CI 0.58-0.94). In laparoscopic cases surgeon volume was inversely associated with hospital stay and the odds of any genitourinary/bowel complication., Conclusions: Laparoscopic prostatectomy and open radical prostatectomy have similar rates of postoperative morbidity and additional treatment. Men considering prostate cancer surgery should understand the expected benefits and risks of each technique to facilitate decision making and set realistic expectations., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The Stanford group has reported excellent results with the Stanford V regimen for patients with bulky and/or advanced Hodgkin lymphoma (HL). However, Gobbi reported markedly inferior failure-free survival (FFS) comparing Stanford V to other regimens but included major deviations from the original program. We retrospectively examined whether treatment at our institution carefully following Stanford V guidelines would confirm the original Stanford outcome data., Patients and Methods: From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12-week Stanford V chemotherapy program followed by 36-Gy involved-field radiotherapy to sites initially > or =5 cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and 20% had international prognostic score (IPS) > or =4. Overall survival (OS), disease-specific survival, progression-free survival (PFS), FFS, and freedom from second relapse (FF2R) were determined., Results: The 5- and 7-year OS were 90% and 88%, respectively. The 5-year FFS was 78%. IPS > or =4 was a significant independent predictor of worse OS and PFS. The FF2R was 64% at 3 years., Conclusion: Stanford V with appropriate radiotherapy is a highly effective regimen for locally extensive and advanced HL.

Background: Gene expression profiling of breast cancers identifies distinct molecular subtypes that affect prognosis. Our goal was to determine whether presenting features of tumors differ among molecular subtypes., Methods: Subtypes were classified by immunohistochemical surrogates as luminal A (estrogen receptor [ER] and/or progesterone receptor [PR] positive, HER-2-), luminal B (ER and/or PR+, HER-2+), HER-2 (ER and PR-, HER-2+), or basal (ER, PR, HER-2-). Data were obtained from an established, registered database of patients with invasive breast cancer treated at our institution between January 1998 and June 2007. A total of 6,072 tumors were classifiable into molecular subtypes. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between subtype and clinicopathologic variables., Results: The distribution of subtypes was luminal A, 71%; luminal B, 8%; HER-2, 6%; and basal, 15%. Marked differences in age, tumor size, extent of lymph node involvement, nuclear grade, multicentric/multifocal disease, lymphovascular invasion (LVI), and extensive intraductal component were observed among subtypes. When compared with luminal A tumors, those overexpressing HER-2 (luminal B, HER-2) were significantly more likely to manifest nodal involvement, multifocal, extensive intraductal component, and LVI (P < 0.0001). On multivariate analysis, after controlling for patient age, tumor size, LVI, and nuclear grade, HER-2 subtype tumors were 2.0 times more likely to have four or more metastatic lymph nodes (P < 0.0001) and 1.6 times more likely to have multifocal disease (P < 0.0001) compared with patients with luminal A., Conclusions: Tumor presentation varies among molecular subtypes; this information may be useful in selecting local therapy. Neoadjuvant therapy and lymph nodes evaluation before surgery or neoadjuvant therapy are likely to be beneficial in HER-2-overexpressing tumors.

Purpose: In breast cancer, somatic mutations in the PIK3CA gene are common. The prognostic implication of these activating mutations remains uncertain as moderately sized studies have yielded variable outcomes. Our aim was to determine the prognostic implications of PIK3CA mutations in breast cancer., Experimental Design: Archival formalin-fixed paraffin-embedded primary breast tumors, from 590 patients selected for known vital status with a median follow-up of 12.8 years and a tumor >1 cm, were genotyped for PIK3CA mutations. Mutation rates and associations between mutation site and clinicopathologic characteristics were assessed. Progression-free survival, overall survival, and breast cancer-specific survival were examined using Kaplan-Meier or competing risk methodology., Results: PIK3CA mutation is identified in 32.5% of breast cancers. PIK3CA mutation significantly associates with older age at diagnosis, hormone receptor positivity, HER2 negativity, lower tumor grade and stage, and lymph node negativity. Patients with PIK3CA mutated tumors have significant improvement in overall survival (P = 0.03) and breast cancer-specific survival (P = 0.004). Analysis for PIK3CA mutation site-specific associations reveals that the H1047R kinase domain mutation highly associates with node negativity (P = 0.007), whereas helical domain hotspot mutations associate with older age at diagnosis (P = 0.004)., Conclusion: This study defines the positive prognostic significance of PIK3CA mutations. This work is clinically relevant, as it will significantly affect the design of clinical trials planned for phosphatidylinositol 3-kinase-targeted therapy. Future work may define a population of older age breast cancer patients in whom therapy can be minimized.

Purpose: Uterine leiomyosarcoma (LMS) is staged by the modified International Federation of Gynecology and Obstetrics (FIGO) staging system for uterine cancer. We aimed to determine whether the American Joint Committee on Cancer (AJCC) soft tissue sarcoma (STS) staging system is more accurate in predicting progression-free survival (PFS) and overall survival (OS)., Patients and Methods: Patients with uterine LMS who presented at our institution from 1982 to 2005 were staged retrospectively according to a modified FIGO staging system and the AJCC STS staging system. The predictive accuracy of the two staging systems was compared using concordance estimation., Results: Two hundred nineteen patients had sufficient clinical and pathologic information to be staged under both systems; 132 patients were upstaged using the AJCC staging system, whereas only four were downstaged. Stage-specific PFS and OS rates for stages I, II, and III differed substantially between the two staging systems. In both systems, there was prognostic overlap between stages II and III. Thus, despite the marked stage-specific differences in 5-year PFS and OS rates for stages I, II, and III, both systems had similar concordance indices., Conclusion: Estimates of stage-specific PFS and OS for uterine LMS were altered substantially when using the AJCC versus FIGO staging system. Adjuvant treatment strategies should be tested in patients at substantial risk for disease progression and death. Neither the FIGO nor AJCC staging system is ideal for identifying such patients, suggesting a need for a uterine LMS-specific staging system to better target patients for trials of adjuvant therapies.