Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial.

BACKGROUND: Sacituzumab govitecan (SG), a novel antibody-drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. PATIENTS AND METHODS: Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. RESULTS: From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%. CONCLUSIONS: In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Therapeutic cancer vaccines revamping: technology advancements and pitfalls.

Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen (Ag)-specific T-cell responses and potentially achieve long-term clinical benefit. However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technological advances regarding vaccine delivery platforms, tools for immunogenomic profiling, and Ag/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease-2019 pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the severe acute respiratory syndrome coronavirus 2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology.

The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial.

BACKGROUND: Previous data suggest that the immune microenvironment plays a critical role in human epidermal growth factor receptor 2 (HER2) -positive breast cancer; however, there is little known about the immune profiles of small HER2-positive tumors. In this study, we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer (APT) trial and to correlate the immune markers with pathological and molecular tumor characteristics. PATIENTS AND METHODS: The APT trial was a multicenter, single-arm, phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer. The study included 406 patients with HER2-positive, node-negative breast cancer, measuring up to 3 cm. Exploratory analysis of tumor infiltrating lymphocytes (TIL), programmed death-ligand 1 (PD-L1) expression (by immunohistochemistry), and immune gene signatures using data generated by nCounter PanCancer Pathways Panel (NanoString Technologies, Seattle, WA), and their association with pathological and molecular characteristics was carried out. RESULTS: Of the 406 patients, 328 (81%) had at least one immune assay carried out: 284 cases were evaluated for TIL, 266 for PD-L1, and 213 for immune gene signatures. High TIL (≥60%) were seen with greater frequency in hormone-receptor (HR) negative, histological grades 2 and 3, as well in HER2-enriched and basal-like tumors. Lower stromal PD-L1 (≤1%) expression was seen with greater frequency in HR-positive, histological grade 1, and in luminal tumors. Both TIL and stromal PD-L1 were positively correlated with 10 immune cell signatures, including Th1 and B cell signatures. Luminal B tumors were negatively correlated with those signatures. Significant correlation was seen among these immune markers; however, the magnitude of correlation did not indicate a monotonic relationship between them. CONCLUSION: Immune profiles of small HER2-positive breast cancers differ according to HR status, histological grade, and molecular subtype. Further work is needed to explore the implication of these findings on disease outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00542451.

OncotypeDX Recurrence Score Does Not Predict Nodal Burden in Clinically Node Negative Breast Cancer Patients.

BACKGROUND: OncotypeDX recurrence score (RS)® has been found to predict recurrence and disease-free survival in patients with node negative breast cancer. Whether RS is useful in guiding locoregional therapy decisions is unclear. We sought to evaluate the relationship between RS and lymph node burden. METHODS: Patients with invasive breast cancer who underwent sentinel lymph node dissection from 2010 to 2015 were identified from a prospectively maintained database. Patients were excluded if they were clinically node positive or if they received neoadjuvant chemotherapy. RS was classified as low (< 18), intermediate (18-30), or high (> 30). The association between RS, lymph node burden, and disease recurrence was evaluated. Statistical analyses were performed in R version 3.4.0; p < 0.05 was considered significant. RESULTS: A positive SLN was found in 168 (15%) of 1121 patients. Completion axillary lymph node dissection was performed in 84 (50%) of SLN-positive patients. The remaining 84 (50%) patients had one to two positive SLNs and did not undergo further axillary surgery. RS was low in 58.5%, intermediate in 32.6%, and high in 8.9%. RS was not associated with a positive SLN, number of positive nodes, maximum node metastasis size, or extranodal extension. The median follow-up was 23 months. High RS was not associated with locoregional recurrence (p = 0.07) but was significantly associated with distant recurrence (p = 0.0015). CONCLUSIONS: OncotypeDX RS is not associated with nodal burden in women with clinically node-negative breast cancer, suggesting that RS is not useful to guide decisions regarding extent of axillary surgery for these patients.

Multidisciplinary Intraoperative Assessment of Breast Specimens Reduces Number of Positive Margins.

BACKGROUND: Successful breast-conserving surgery requires achieving negative margins. At our institution, the whole surgical specimen is imaged and then serially sectioned with repeat imaging. A multidisciplinary discussion then determines need for excision of additional margins. The goal of this study was to determine the benefit of each component of this approach in reducing the number of positive margin. METHODS: This single-institution, prospective study included ten breast surgical oncologists who were surveyed to ascertain whether they would have taken additional margins based their review of whole specimen images (WSI) and review of serially sectioned images (SSI). These results were compared with the multidisciplinary decisions (MDD) and pathology results. Margin status was defined using consensus guidelines. RESULTS: One hundred surveys were completed. Margins on the original specimen were positive or close in 21%. After WSI, surgeons reported that they would have taken additional margins in 26 cases, reducing the number of positive/close margins from 21 to 13% (p < 0.001). After SSI, 52 would have taken additional margins; however, the number of positive/close margins remained 13%. MDD resulted in additional margins taken in 56 cases, reducing the number of positive/close margins to 7% (p < 0.001 compared with SSI). CONCLUSIONS: While surgeon review of specimen radiographs can decrease the number of positive or close margins from 21 to 13%, more rigorous multidisciplinary, intraoperative margin assessment reduces the number of close or positive margins to 7%.

A feasibility study of neoadjuvant talazoparib for operable breast cancer patients with a germline BRCA mutation demonstrates marked activity.

This study was undertaken to determine the feasibility of enrolling breast cancer patients on a single-agent-targeted therapy trial before neoadjuvant chemotherapy. Specifically, we evaluated talazoparib in patients harboring a deleterious BRCA mutation (BRCA+). Patients with a germline BRCA mutation and ≥1 cm, HER2-negative primary tumors were eligible. Study participants underwent a pretreatment biopsy, 2 months of talazoparib, off-study core biopsy, anthracycline, and taxane-based chemotherapy ± carboplatin, followed by surgery. Volumetric changes in tumor size were determined by ultrasound at 1 and 2 months of therapy. Success was defined as 20 patients accrued within 2 years and <33% experienced a grade 4 toxicity. The study was stopped early after 13 patients (BRCA1 + n = 10; BRCA2 + n = 3) were accrued within 8 months with no grade 4 toxicities and only one patient requiring dose reduction due to grade 3 neutropenia. The median age was 40 years (range 25-55) and clinical stage included I (n = 2), II (n = 9), and III (n = 2). Most tumors (n = 9) were hormone receptor-negative, and one of these was metaplastic. Decreases in tumor volume occurred in all patients following 2 months of talazoparib; the median was 88% (range 30-98%). Common toxicities were neutropenia, anemia, thrombocytopenia, nausea, dizziness, and fatigue. Single-agent-targeted therapy trials are feasible in BRCA+ patients. Given the rapid rate of accrual, profound response and favorable toxicity profile, the feasibility study was modified into a phase II study to determine pathologic complete response rates after 4-6 months of single-agent talazoparib.

Clinicopathological and surgical factors associated with long-term survival in patients with HER2-positive metastatic breast cancer.

Trastuzumab-based treatment has dramatically improved the outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC) patients, with some patients achieving prolonged survival times. In this study, we aim to identify factors that are associated with long-term survival. Patients with HER2+ MBC treated with anti-HER2 target therapy were identified. Patients were grouped according to overall survival (OS) and categorized as long-term survivors (LTS, OS ≥ 5 years), or non-long-term survivors (non-LTS, OS < 5 years). Descriptive statistics and multivariable logistic regression modeling were used. A sensitivity analysis was carried out, including only patients diagnosed before 2007; therefore, 5 years of potential follow-up was possible. 1063 patients with HER2+ MBC diagnosed between 1994 and 2012 and treated with anti-HER2 therapy were identified. Among them, 154 (14.5 %) patients were categorized as LTS (median OS 92.2 months). Among LTS, 63.4 % were HR-positive and 32 % had de novo stage IV disease. Hormone receptor positivity (OR) 1.69; 95 % CI 1.17-2.44), resection of metastases (OR 2.38; 95 % CI 1.53-3.69), and primary breast surgery in patients with de novo stage IV (OR 2.88; 95 % CI 1.47-5.66) were associated with improved long-term survival. Greater number of metastatic sites (≥3 vs. 1, OR 0.41; 95 % CI 0.23-0.72) and visceral metastases (OR 0.61; 95 % CI 0.4-0.91) were associated with poor survival. Hormone receptor positivity, low burden of disease, metastasis to soft and bone tissues, and surgical management with resection of the metastatic site and the primary tumor were associated with long-term survival in patients with MBC who received anti-HER2 treatment.

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence.

BACKGROUND: AE37 is the Ii-Key hybrid of the MHC class II peptide, AE36 (HER2 aa:776-790). Phase I studies showed AE37 administered with granulocyte macrophage colony-stimulating factor (GM-CSF) to be safe and highly immunogenic. A prospective, randomized, multicenter phase II adjuvant trial was conducted to evaluate the vaccine's efficacy. METHODS: Clinically disease-free node-positive and high-risk node-negative breast cancer patients with tumors expressing any degree of HER2 [immunohistochemistry (IHC) 1-3+] were enrolled. Patients were randomized to AE37 + GM-CSF versus GM-CSF alone. Toxicity was monitored. Clinical recurrences were documented and disease-free survival (DFS) analyzed. RESULTS: The trial enrolled 298 patients; 153 received AE37 + GM-CSF and 145 received GM-CSF alone. The groups were well matched for clinicopathologic characteristics. Toxicities have been minimal. At the time of the primary analysis, the recurrence rate in the vaccinated group was 12.4% versus 13.8% in the control group [relative risk reduction 12%, HR 0.885, 95% confidence interval (CI) 0.472-1.659, P = 0.70]. The Kaplan-Meier estimated 5-year DFS rate was 80.8% in vaccinated versus 79.5% in control patients. In planned subset analyses of patients with IHC 1+/2+ HER2-expressing tumors, 5-year DFS was 77.2% in vaccinated patients (n = 76) versus 65.7% in control patients (n = 78) (P = 0.21). In patients with triple-negative breast cancer (HER2 IHC 1+/2+ and hormone receptor negative) DFS was 77.7% in vaccinated patients (n = 25) versus 49.0% in control patients (n = 25) (P = 0.12). CONCLUSION: The overall intention-to-treat analysis demonstrates no benefit to vaccination. However, the results confirm that the vaccine is safe and suggest that vaccination may have clinical benefit in patients with low HER2-expressing tumors, specifically TNBC. Further evaluation in a randomized trial enrolling TNBC patients is warranted.

Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy.

PURPOSE: To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST). PATIENTS AND METHODS: Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan-Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed. FINDINGS: Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively). CONCLUSIONS: In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.

Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients.

BACKGROUND: E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses. PATIENTS AND METHODS: The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests. RESULTS: Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%). CONCLUSION: The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated. CLINICAL TRIALS: NCT00841399, NCT00584789.

Which threshold for ER positivity? a retrospective study based on 9639 patients.

BACKGROUND: Guidelines for the use of chemotherapy and endocrine therapy recently recommended that estrogen receptor (ER) status be considered positive if ≥1% of tumor cells demonstrate positive nuclear staining by immunohistochemistry. In clinical practice, a range of thresholds are used; a common one is 10% positivity. Data addressing the optimal threshold with regard to the efficacy of endocrine therapy are lacking. In this study, we compared patient, tumor, treatment and survival differences among breast cancer patients using ER-positivity thresholds of 1% and 10%. METHODS: The study population consisted of patients with primary breast carcinoma treated at our center from January 1990 to December 2011 and whose records included complete data on ER status. Patients were separated into three groups: ≥10% positive staining for ER (ER-positive ≥10%), 1%-9% positive staining for ER (ER-positive 1%-9%) and <1% positive staining (ER-negative). RESULTS: Of 9639 patients included, 80.5% had tumors that were ER-positive ≥10%, 2.6% had tumors that were ER-positive 1%-9% and 16.9% had tumors that were ER-negative. Patients with ER-positive 1%-9% tumors were younger with more advanced disease compared with patients with ER-positive ≥10% tumors. At a median follow-up of 5.1 years, patients with ER-positive 1%-9% tumors had worse survival rates than did patients with ER-positive ≥10% tumors, with and without adjustment for clinical stage and grade. Survival rates did not differ significantly between patients with ER-positive 1%-9% and ER-negative tumors. CONCLUSIONS: Patients with tumors that are ER-positive 1%-9% have clinical and pathologic characteristics different from those with tumors that are ER-positive ≥10%. Similar to patients with ER-negative tumors, those with ER-positive 1%-9% disease do not appear to benefit from endocrine therapy; further study of its clinical benefit in this group is warranted. Also, there is a need to better define which patients of this group belong to basal or luminal subtypes.

Comparison of clinicopathologic features and survival in young American women aged 18-39 years in different ethnic groups with breast cancer.

BACKGROUND: Ethnic disparities in breast cancer diagnoses and disease-specific survival (DSS) rates in the United States are well known. However, few studies have assessed differences specifically between Asians American(s) and other ethnic groups, particularly among Asian American(s) subgroups, in women aged 18-39 years. METHODS: The Surveillance, Epidemiology, and End Results database was used to identify women aged 18-39 years diagnosed with breast cancer from 1973 to 2009. Incidence rates, clinicopathologic features, and survival among broad ethnic groups and among Asian subgroups. RESULTS: A total of 55,153 breast cancer women aged 18-39 years were identified: 63.6% non-Hispanic white (NHW), 14.9% black, 12.8% Hispanic-white (HW), and 8.7% Asian. The overall incidence rates were stable from 1992 to 2009. Asian patients had the least advanced disease at presentation and the lowest risk of death compared with the other groups. All the Asian subgroups except the Hawaiian/Pacific Islander subgroup had better DSS than NHW, black, and HW patients. Advanced tumour stage was associated with poorer DSS in all the ethnic groups. High tumour grade was associated with poorer DSS in the NHW, black, HW, and Chinese groups. Younger age at diagnosis was associated with poorer DSS in the NHW and black groups. CONCLUSION: The presenting clinical and pathologic features of breast cancer differ by ethnicity in the United States, and these differences impact survival in women younger than 40 years.

Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer.

BACKGROUND: We sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab. PATIENTS AND METHODS: Two hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (

A novel interaction between HER2/neu and cyclin E in breast cancer.

HER2/neu (HER2) and cyclin E are important prognostic indicators in breast cancer. As both are involved in cell cycle regulation we analyzed whether there was a direct interaction between the two. HER2 and cyclin E expression levels were determined in 395 breast cancer patients. Patients with HER2-overexpression and high levels of cyclin E had decreased 5-year disease-specific survival compared with low levels of cyclin E (14% versus 89%, P<0.0001). In vitro studies were performed in which HER2-mediated activity in HER2-overexpressing breast cancer cell lines was downregulated by transfection with HER2 small interfering RNA or treatment with trastuzumab. Cyclin E expression levels were determined by western blot analysis, and functional effects analyzed using kinase assays, MTT assays were used to assess cell viability as a marker of proliferation and fluorescence-activated cell sorting analysis was used to determine cell cycle profiles. Decreased HER2-mediated signaling resulted in decreased expression of cyclin E, particularly the low molecular weight (LMW) isoforms. Decreased HER2 and LMW cyclin E expression had functional consequences, including decreased cyclin E-associated kinase activity and decreased proliferation, because of increased apoptosis and an increased accumulation of cells in the G1 phase. In vivo studies performed in a HER2-overexpressing breast cancer xenograft model confirmed the effects of trastuzumab on cyclin E expression. Given the relationship between HER2 and cyclin E, in vitro clonogenic assays were performed to assess combination therapy targeting both proteins. Isobologram analysis showed a synergistic interaction between the two agents (trastuzumab targeting HER2 and roscovitine targeting cyclin E). Taken together, these studies show that HER2-mediated signaling effects LMW cyclin E expression, which in turn deregulates the cell cycle. LMW cyclin E has prognostic and predictive roles in HER2-overexpressing breast cancer, warranting further study of its potential as a therapeutic target.

Monitoring circulating tumor cells in cancer vaccine trials.

The presence of circulating tumor cells (CTC) from various cancers has provided a wealth of information and possibilities. As the role of CTC detection in the treatment assessment of metastatic breast cancer becomes standard, there is interest in applying this tool in cancer vaccine development and clinical trial monitoring. Since we lack a proven immunologic assay that correlates with clinical response, CTC detection, quantification and phenotypic characterization may be a useful surrogate for clinical outcome. The Cancer Vaccine Development Program is involved in the development of HER2/neu peptide based vaccine development for the prevention of recurrence in HER2/neu expressing cancers like breast cancer. The CellSearch System (Veridex, LLC Warren, NJ) has been used by our lab in conjunction with in vivo and/or in vitro immunologic measurements to define a monitoring tool that could predict clinical response. Once validated, this assay could significantly shorten clinical trials and lead to more efficient assessment of potentially promising cancer vaccines.

Utility of intraoperative endoscopy: implications for surgical education.

BACKGROUND: The use of intraoperative endoscopy by surgeons can identify pathology and help determine the appropriate procedure to perform. However, residency training in endoscopy is often variable and unstructured. The purpose of this study was to determine the indications for and impact of intraoperative endoscopy performed at the time of general surgical procedures. METHODS: The records of all patients who underwent intraoperative endoscopy from January 1998 to December 1999 were reviewed. The indications for endoscopy, endoscopic findings, the impact of these findings on the operation performed, complications, and whether the patient was spared from undergoing a second procedure on a separate date were noted. RESULTS: A total of 107 intraoperative endoscopic procedures were performed in 103 patients. Excluding breast, endocrine, central line, and peritoneal dialysis catheter cases, endoscopy was utilized in 5.1% of all general surgery procedures performed during this time period. In 91 patients (88%), the endoscopic procedure was planned preoperatively; in 13 (12%), intraoperative findings dictated its use. The most common indications for endoscopy were identification of lesions and determination of extent of resection (n = 27); evaluation of rectal bleeding (n = 21); colonic evaluation in patients with perianal infections (n = 13); evaluation of extent of injury in trauma cases (n = 8); evaluation of pain (n = 6); evaluation of intestinal tract hemorrhage (n = 6); performance of procedures such as placement of a biliary stent, placement of a nasojejunal tube, or polypectomy (n = 5); and surveillance of chronic disease (n = 5). In 37 patients (36%), the endoscopic findings affected the operation performed. Sixty-nine patients (67%) were spared an endoscopic procedure at a second date, which would have required additional sedation or anesthesia. There were no complications related to endoscopy. CONCLUSION: Intraoperative endoscopy is a valuable tool that can be performed safely for multiple indications and is frequently of value in determining the operation to be performed. Surgical residents should be trained in the indications for endoscopic evaluation as well as the competent performance of such procedures.

Thyroidectomy for selected patients with thyrotoxicosis.

OBJECTIVE: To examine the indications for operation and the frequency, efficacy, and outcome of surgical therapy for thyrotoxicosis. METHODS: The medical records of all patients who underwent thyroidectomy between 1990 and 1998 were reviewed. Operative indications, laboratory evaluations, extent of thyroidectomy, pathologic findings, and morbidity and mortality were determined for patients with thyrotoxicosis. RESULTS: Of the 347 patients who underwent thyroidectomy, 54 (16%) had thyrotoxicosis, secondary to Graves' disease (32 patients), toxic multinodular goiter (18 patients), thyroiditis (2 patients), or amiodarone (2 patients). The indications for operation were compressive symptoms or substernal extension or both (35 patients), patient preference (12 patients), thyrotoxicosis (4 patients), or a dominant nodule (3 patients). Most patients received pharmacological preparation, followed by total (32 patients), near-total (13 patients), subtotal (8 patients), or unilateral (1 patient) thyroidectomy. The initial 8 patients with Graves' disease underwent subtotal thyroidectomy, and after a mean 28-month follow-up, 1 was euthyroid; 2, hyperthyroid; and 5, hypothyroid. Associated carcinoma was present in 4 (7%) of the 54 patients. Symptomatic hypocalcemia occurred in 10 patients (19%), with a mean free thyroxine level of 60.49 +/- 16.09 pmol/L vs 40.41 +/- 19.56 pmol/L (4.70 +/- 1.25 ng/dL vs 3.14 +/- 1.52 ng/dL) in 25 patients (46%) with asymptomatic hypocalcemia (P<.05). Vocal cord paresis and a hematoma requiring operative evacuation occurred in 1 patient each. There was 1 mortality in a patient with amiodarone-induced thyrotoxicosis. CONCLUSIONS: Massive thyroid enlargement with compressive symptoms, a dominant nodule, and patient preference are indications for surgical treatment of thyrotoxicosis. Near-total or total thyroidectomy is safe and more effective than subtotal thyroidectomy in preventing recurrence and should be considered in most patients referred for surgical treatment of thyrotoxicosis. Transient postoperative hypocalcemia is common and is related to the severity of thyrotoxicosis.

Endoscopic placement of nasojejunal feeding tubes in ICU patients.

BACKGROUND: Enteral nutrition is an important component in the management of critically ill patients, but it may be limited by gastric ileus and unreliable positioning of standard feeding tubes. The purpose of this study was to determine the risk, utility, and outcome of endoscopically placed nasojejunal feeding tubes (NJT) in intensive care unit (ICU) patients. METHODS: We reviewed the records of all ICU patients who underwent endoscopic NJT placement from May 1995 to May 1997. A through-the-scope method was used with placement of either an 8-Fr or 10-Fr 240-cm tube. Comparison was made between tubes secured to a nasopharyngeal bridle and tubes secured without bridling. RESULTS: A total of 66 NJT were placed in 56 patients. Previous gastric feeds had been attempted in 39 patients (70%) an average of 8.4 days prior to placing the NJT. Fifty tubes (76%) were placed in the ICU and 16 (34%) in the OR at the time of additional procedures. Procedure time ranged from 7 to 28 mins (mean, 15.2), and bridling was used in 24 of 66 placements (36%). Full caloric goal rates were achieved via 56 of 66 tubes (85%) at an average of 26.1 h after placement (range, 1-144). Goal rates were not achieved in 10 cases due to inadequate tube positioning in six, ileus in three, and early dislodgement in one. A procedure complication, consisting of aspiration, occurred in one case (1.5%). Length of tube use averaged 18.5 days (range, 1-74). Accidental tube dislodgement or migration occurred in 16 of 42 (38%) nonbridled tubes vs one of 24 (4%) bridled tubes (p <.05). CONCLUSIONS: Endoscopic placement of nasojejunal feeding tubes in critically ill patients is a safe, quick, and reliable option for enteral nutrition. Full caloric goal rates can be achieved rapidly in a high percentage of patients, even in cases where previous gastric feeds have not been tolerated. Use of a nasopharyngeal bridling system for tube security significantly decreases the risk of migration or accidental tube dislodgement.