HER2 targeted therapy and outcome in HER2-equivocal cases after 2018 ASCO/CAP HER2 guideline modification.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14729-e14729
Author(s):  
James Crespo ◽  
Hongxia Sun ◽  
Jimin Wu ◽  
Qingqing Ding ◽  
Guilin Tang ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Small Sample ◽  
Her2 Status ◽  
Breast Cancers ◽  
Negative Group ◽  
Metastatic Site ◽  
Kaplan Meier ◽  
Md Anderson

e14729 Background: The best targeted therapeutic approach for HER2-equivocal cases remains unclear. New ASCO/CAP HER2 guidelines are intended to decrease this ambiguity by combining immunohistochemistry and in situ hybridization to resolve equivocal cases as positive or negative. However, the benefit of anti-HER2 therapy in HER2-equivocal cases is unknown. Methods: We retrospectively reviewed patients who visited MD Anderson from April 2017 to March 2018 with equivocal HER2 results based on the 2013 ASCO/CAP guidelines. The population was divided into 2 cohorts according to biopsy origin (primary cohort: biopsy from breast or axilla; recurrent/metastatic cohort: biopsy from recurrent or metastatic site). HER2 status was redefined using the 2018 ASCO/CAP guidelines. OS and PFS were calculated (Kaplan-Meier method) based on redefined HER2 status and use of HER2 targeted therapy. Results: A total of 139 equivocal results were found. Primary cohort had 90 patients (33 received neoadjuvant and 57 adjuvant therapy). HER2 IHC results were 0 (6.6%), 1+ (37.7%), 2+ (50%), 3+ (1.1%), and no IHC (4.4%). 94% of HER2-equivocal results became HER2 negative. Only 5 patients received anti-HER2 therapy, all of them in the HER2-negative group. After median follow-up of 1.91 yrs, 3 deaths and 8 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.67) or PFS (p = 0.49). The recurrence/metastatic cohort had 49 cases with equivocal results. HER2 IHC results were 0 (6.1%), 1+ (22.4%), 2+ (26.5%), and no IHC (44.9%). 55% of HER2-equivocal results became HER2 negative, and only 1 patient received anti-HER2 therapy. After median follow-up of 2.96 yrs, 15 deaths and 35 progressions had occurred. There was no statistically significant association between anti-HER2 therapy and OS (p = 0.61) or PFS (p = 0.78). Conclusions: Most HER2-equivocal results were redefined as HER2 negative using the new ASCO/CAP guidelines. Association between anti-HER2 therapy and OS or PFS according to the new HER2 status was not observed. Although this is a small sample with short follow-up, patients with HER2-equivocal breast cancers seem to have clinical behavior similar to HER2-negative breast cancer.

Improved Postoperative Survival for Intraductal- Growth Subtype of Intrahepatic Cholangiocarcinoma

2016 ◽  
Vol 82 (11) ◽  
pp. 1133-1139 ◽  
Author(s):  
Laura L. Dover ◽  
Rojymon Jacob ◽  
Thomas N. Wang ◽  
Joseph H. Richardson ◽  
David T. Redden ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Small Sample Size ◽  
Tumor Stage ◽  
Small Sample ◽  
Postoperative Survival ◽  
Rank Test ◽  
Intraductal Growth ◽  
Kaplan Meier ◽  
Disease Free

Intrahepatic cholangiocarcinoma (ICC) is classified according to the following subtypes: mass-forming (MF), periductal infiltrating (PI), and intraductal growth (IG). The aim of this study is to measure the association between ICC subtypes and patient survival after surgical resection. Data were abstracted on all patients treated with definitive resections of ICC at a single institution between 2000 and 2011 with at least three years follow-up. Survival estimates were quantified using Kaplan-Meier curves and compared using the log-rank test. There were 37 patients with ICC treated with definitive partial hepatectomies with a median survival of 33.5 months. Tumor stage (P < 0.0001), satellitosis (P < 0.001), lymphovascular space invasion (P = 0.003), and macroscopic subtype (P = 0.003) were predictive of postoperative survival. Disease-free survivals for MF, PI, and IG subtypes, respectively, were 30 per cent, 0 per cent, and 57 per cent (P = 0.017). Overall survivals among ICC macroscopic subtypes were as follows: MF 37 per cent, PI 0 per cent, and IG 71 per cent (P = 0.003). Although limited by the small sample size of this rare cancer, this study demonstrates significant differences among macroscopic subtypes of ICC in both disease-free survivals and overall survivals after definitive partial hepatectomy.

A Follow-Up Study of Childhood Nasopharyngeal Radium Irradiation in Washington County, Maryland

1996 ◽  
Vol 115 (5) ◽  
pp. 415-416
Author(s):  
Hsin-Chieh Yeh ◽  
Genevieve M. Matanoski ◽  
George W. Comstock
Keyword(s):  
Brain Tumors ◽  
Cancer Incidence ◽  
Epidemiologic Study ◽  
Breast Cancers ◽  
Washington County ◽  
Social Security Administration ◽  
Kaplan Meier ◽  
Incidence And Mortality ◽  
Standardized Mortality Ratios

In 1978 an epidemiologic study exploring the health consequences of nasopharyngeal radium irradiation among individuals treated for adenoid enlargement in Washington County, Maryland, found an excess risk of brain tumors and a deficit of female breast cancers. The study population included all persons first seen at the Washington County Clinic for the Prevention of Deafness in Children from 1940 to January 1, 1960. We will continue the follow-up of irradiated and nonirradiated patients to (1) assess the risk of brain tumors and other neoplasms of the head and neck developing during a 40-year period, (2) assess hormone-related disorders resulting from irradiation of the pituitary gland, and (3) compare cancer incidence and mortality rates among exposed and nonexposed groups. Of the 2135 persons eligible for this study, 93.5% have been traced, and 90% have replied to a mailed questionnaire that elicits information on demographic characteristics, reproductive and medical history, infertility, and other sources of radiation exposure. Information on cancer incidence and mortality is being obtained from the Washington County Cancer Registry and death certificate flies from Washington County and the Social Security Administration. Statistical methods to be used in the data analysis include standardized mortality ratios, standardized cancer incidence ratios, and Kaplan-Meier survival analysis.

scholarly journals RADI-40. STEREOTACTIC RADIOSURGERY FOR BRAINSTEM METASTASES: AN ANALYSIS OF SINGLE FRACTION AND MULTI FRACTION TECHNIQUES

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i29-i29
Author(s):  
Elana Nack ◽  
Varun Iyengar ◽  
Esther Yu ◽  
Thomas DiPetrillo ◽  
Timothy Kinsella ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Tumor Volume ◽  
Small Sample Size ◽  
Small Sample ◽  
Single Institution ◽  
Single Fraction ◽  
Whole Brain Radiation ◽  
Kaplan Meier ◽  
Brain Radiation

Abstract PURPOSE: Utilization of stereotactic radiosurgery (SRS) for brainstem metastases (BSM) is increasing. Multi-fraction SRS (MF-SRS) is a potential means of obtaining therapeutic gain while limiting toxicity. However, most available data assesses only single-fraction SRS (SF-SRS). This study aims to evaluate the efficacy and safety of SF-SRS and MF-SRS for BSM. METHODS: Data was retrospectively collected for patients with BSM treated with SRS between 2003–2018 at a single institution. Kaplan-Meier method was used to evaluate overall survival (OS) and local control (LC). Independent t-test was used for correlations between groups. RESULTS: 29 patients (31 lesions) were identified; 13 patients (15 lesions) underwent SF-SRS and 16 patients (16 lesions) underwent MF-SRS. Median follow-up was 6.8 months (1–80.8 months). Post-SRS MRI was available for 78% of patients. Median dose was 16Gy (12–18 Gy) for SF-SRS and 24 Gy (18–30 Gy) for MF-SRS. MF-SRS was delivered in a median of 3 fractions (3–5). There was a trend toward larger mean tumor volume with MF-SRS (1.297 vs 0.302mL, p=0.055). OS was 64.8% at 6 months and 49.3% at 12 months. LC was 90.9% at 6 months and 69.9% at 12 months. LC was similar between SF-SRS and MF-SRS at 6 months (100% vs 79.5%, p=0.143) and 12 months (50.0% vs 79.5%, p=0.812). Among the 4 patients who experienced local recurrence, 3 received salvage whole brain radiation and median OS was 8.1 months after LF. Distant CNS failures occurred in 40.3% of patients at 6 months and 72.4% at 12 months. Tumor volume &gt;0.5 mL was associated with worse LC at 6 months (64.3% vs 100%, p=0.022). One patient developed symptomatic radiation necrosis (1/29 lesions, 3.4%) after MF-SRS. CONCLUSION: SRS is a safe and effective treatment for small BSM. Outcomes were not different between SF-SRS and MF-SRS but analysis is limited by small sample size.

scholarly journals Impact of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Updates on HER2 Assessment in Breast Cancer With Equivocal HER2 Immunohistochemistry Results With Focus on Cases With HER2/CEP17 Ratio <2.0 and Average HER2 Copy Number ≥4.0 and <6.0

2019 ◽  
Vol 144 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Raza S. Hoda ◽  
Edi Brogi ◽  
Jin Xu ◽  
Katia Ventura ◽  
Dara S. Ross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Clinical Oncology ◽  
Copy Number ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
American Society ◽  
Dual Probe

Context.— The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. Objective.— To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. Design.— We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry–equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. Results.— A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. Conclusions.— The 2018 guideline eliminated HER2 FISH–equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH–negative cases and a slight decrease in HER2 FISH–positive cases.

Clinical significance of ERβ mRNA expression in ERα-negative and triple-negative breast cancers.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 545-545
Author(s):  
Young Choi Kim ◽  
Hadong Kim ◽  
Tae-Hoon Kim
Keyword(s):  
Mrna Expression ◽  
Triple Negative ◽  
Myoepithelial Cells ◽  
P Value ◽  
Breast Cancers ◽  
Chi Square ◽  
Ki 67 ◽  
Kaplan Meier ◽  
Asco Meeting

545 Background: Previously at the 2012 ASCO meeting, we reported significant ERβ mRNA expression in ERα-negative (ERα-) and triple negative breast cancers (TNBC). In this study, we analyzed its clinical outcome and correlation with other clinical parameters. Methods: A total of 141 cases consisted of 69 ERα- BC including 41 TNBC and 72 ERα+ BC were obtained from patients aged 29 to 97 years old between 2003 and 2010. Treatments included surgery, hormone, chemo- or radiotherapy, or any combinations. The follow-up period ranged from 1 to 132 months. ERβ mRNA was analyzed from formalin-fixed tumor tissues by RT-PCR. ERα, PR, Her-2, Ki-67, AIB-1, NFk/p65, p-c-jun, Ki-67, TIF-2, SRC-1, CK5/6 and p53 were tested by immunohistochemistry. The correlation was deemed significant if p value less than 0.05 from Chi-square. Overall survival (SVR) was defined from the date of diagnosis to last follow-up or death attributed to BC and was analyzed by the Kaplan-Meier curves and Wilcoxon rank sum. Results: Single or combination of ERβ isoform(s) was highly expressed in both ERα- and TNBC and ERβ2 was the most frequent (48.8%) and ERβ5, the least (30.2%). In contrast, ERβ5 was the most frequent in ERα+BC. Presence of all or any ERβ isoform was associated with significantly higher SVR in all cases, and in TNBC (ERβ total, Wilcoxon p = 0.0177, ERβ2, p= 0.0329), and also with negative LN (p< 0.0001). ERβ2 and ERβ5 were expressed in 63.2% and 30 %, respectively, in 20 patients died in 1 to 60 months. Over expression of AIB-1, NF-kB/p65 and TIF-2 was associated with ERβ1 and ERβ2 (p<0.05). Ki-67 + cells were mostly ERβ + BC than ERα+. ERα mRNA expression was up-regulated, and ERβ,down- regulated, with the ERα: ERβ+ ratio of 3-1000:1. There was no association between ERβ expression and the stage, age, tumor size, and postmenopausal status. Conclusions: Specific ERβ isoform appears to be a significant discriminating factor for SVR and negative node. ERβ2 is the predominant isoform in ERα- but ERβ5 in ERα+BC, suggesting a distinct role of ERβ isoform in ERα- and ERα+BC. ERβ isoform may be a selective therapeutic target in this cohort. ERβ+/ Ki-67+cells appear to be a sub-population of BC arising from basal-myoepithelial cells in this cohort.

Comparison of supra-arch in situ fenestration and chimney techniques for aortic dissection involving the left subclavian artery

Vascular ◽  
2018 ◽  
Vol 27 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Ma XiaoHui ◽  
Wei Li ◽  
Guo Wei ◽  
Liu XiaoPing ◽  
Jia Xin ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Subclavian Artery ◽  
Left Subclavian Artery ◽  
Small Sample ◽  
Covered Stents ◽  
Type I ◽  
Type B ◽  
Aortic Dissections

Introduction Endovascular intervention involving the aortic arch, particularly in thoracic aortic dissection, remains challenging and controversial at current time when there is no commercially suitable grafts on most of the international markets. This study compared two endovascular treatments that maintain left subclavian artery perfusion using two modified techniques for type-B aortic dissection patients. Methods Consecutive cases utilizing chimney or in situ fenestration techniques to preserve left subclavian artery in type B AD from 2006 to 2015 in our single institution were retrospectively reviewed. Statistical analyses were performed with Student t-test, Wilcoxon rank sum, and Fisher exact tests when appropriate. Significant statistical differences were determined with p < 0.05. Results A total of 85 cases, including 67 (79.8%) with chimney and 18 (21.2%) with in situ fenestration techniques were identified in this retrospective study. In chimney group, there were 18 (26.9%) acute, 29 (43.3%) sub-acute, and 20 (29.9%) chronic aortic dissections. We implanted 24 Zenith and 43 Talent aortic endografts along with 55 balloon-expandable bare stents and 12 self-expanding covered stents in chimney group. Whereas in in situ fenestration group, there were four (22.2%) acute, six (33.3%) subacute, and eight (44.5%) chronic aortic dissections, all of which received Zenith endografts with 11 balloon-expandable covered and seven self-expanding covered stents, respectively. Demographic variables were similarly distributed with 100% intraoperative technical overall success in both groups. Comparing to in situ fenestration group, chimney group has shorter procedural and fluoroscopy time, less blood loss, and contrast volume used. All patients were followed-up to 52 months (median 38, range 24–52). Overall group mortality is 3.6% (3/84). All deaths were from chimney group. There was no procedure-related stroke observed within the study series. Primary patency was maintained while aortic remodeling with complete false lumen was achieved in all patients except that there were three (4.55%) Type-I endoleak cases in early post-operative period and one (1.5%) stent compression at 3-months follow-up in chimney group. There were no stent-related complications observed in in situ fenestration group. Conclusion Although there were previous studies describing the similar techniques, this study appears to be the first study to compare in situ fenestration and chimney techniques for aortic dissection involving the left subclavian artery according to the MEDLINE search. Although we are unable to establish the superiority between two approaches due to small sample size and relative short period of follow-up, in situ fenestration may represent a more favorable option, especially among aortic dissections with short proximal landing zones in the study.

The Cemented Custom Femoral Stem - a 10 Year Review

2007 ◽  
Vol 17 (4) ◽  
pp. 194-204 ◽  
Author(s):  
S. O'brien ◽  
R.K. Wilson ◽  
B.M. Hanratty ◽  
N.W. Thompson ◽  
M.E. Wallace ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Median Survival ◽  
Revision Surgery ◽  
Hip Replacement ◽  
Femoral Stem ◽  
Kaplan Meier ◽  
Custom Made ◽  
Titanium Stem

We report a series of 706 patients (759 hip implants) with an average follow up of 10.5 years (range, 10 - 11 years) following total hip replacement (THR) using a cemented custom-made femoral stem and a cemented HDP acetabular component. The fate of every implant is known. One hundred and seventy-four patients (23%) were deceased at the time of their 10-year review - all died with a functioning THR in situ. Four hundred and sixty-two patients (61%) were subsequently reviewed. One hundred and twenty three patients (16%) were assessed by telephone review, as they were too ill or unwilling to attend. Kaplan-Meier survival analysis (all components) demonstrated a median survival at 10 years of 96.05% or 95% Confidence Intervals (CI) for median survival of (94.41% to 97.22%). Revision surgery occurred in 30 cases (3.9%). Seventeen had full revisions (2.2%) and 13 (1.7%) socket revisions only. Twenty-one out of 30 revisions were for infection or dislocation. There were 2 cases (0.3%) of revision for aseptic loosening of the stem. The 10-year results of the custom femoral titanium stem are encouraging and compare well with other cemented systems.

scholarly journals Gamma knife stereotactic radiosurgery in the treatment of brainstem metastases: The MD Anderson experience

2015 ◽  
Vol 2 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Khinh Ranh Voong ◽  
Benjamin Farnia ◽  
Qianghu Wang ◽  
Dershan Luo ◽  
Mary F. McAleer ◽  
...  
Keyword(s):  
Stereotactic Radiosurgery ◽  
Gamma Knife ◽  
Progression Free Survival ◽  
Lesion Size ◽  
Significant Treatment ◽  
Kaplan Meier ◽  
Treatment Dose ◽  
Md Anderson ◽  
Gamma Knife Stereotactic Radiosurgery

Abstract Background Brainstem metastases (BSMs) represent a significant treatment challenge. Stereotactic radiosurgery (SRS) is often used to treat BSM. We report our experience in the treatment of BSM with Gamma Knife SRS (GK_SRS). Methods The records of 1962 patients with brain metastases treated with GK_SRS between 2009 and 2013 were retrospectively reviewed. Seventy-four patients with 77 BSMs and follow-up brain imaging were identified. Local control (LC), overall survival (OS), progression-free survival (PFS), and toxicity were assessed. Results Median follow-up was 5.5 months (range, 0.2–48.5 months). Median tumor volume was 0.13 cm3 (range, 0.003–5.58 cm3). Median treatment dose was 16 Gy (range, 10–20 Gy) prescribed to 50% isodose line (range, 40%–86%). Crude LC was 94% (72/77). Kaplan-Meier estimate of median OS was 8.5 months (95% CI, 5.6–9.4 months). Symptomatic lesions and larger lesions, especially size ≥2 cm3, were associated with worse LC (HR = 8.70, P = .05; HR = 14.55, P = .02; HR = 62.81, P &lt; .001) and worse OS (HR = 2.00, P = .02; HR = 2.14, P = .03; HR = 2.81, P = .008). Thirty-six percent of BSMs were symptomatic, of which 36% (10/28) resolved after SRS and 50% (14/28) had stable or improved symptoms. Actuarial median PFS was 3.9 months (95% CI, 2.7–4.9 months). Midbrain location was significant for worse PFS (HR = 2.29, P = .03). Toxicity was low (8%, 6/74), with size and midbrain location associated with increased toxicity (HR 1.57, P = .05; HR = 5.25, P = .045). Conclusions GK_SRS is associated with high LC (94%) and low toxicity (8%) for BSMs. Presence of symptoms or lesion size ≥ 2 cm3 was predictive of worse LC and OS.

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