Search

As biologic therapies enter the mainstream for cancer and HIV treatments, clinicians need the knowledge and expertise to safely and competently care for their patients who are undergoing these therapies. This article provides an overview of the immune system, emphasizing the elements that are affected by the biologic agent Interleukin 2 (IL-2). IL-2 has been approved for use in the treatment of metastatic renal cell carcinoma and metastatic melanoma. Clinical trials currently are being conducted to determine its use in treating other cancers. The severity of the side effects of IL-2 varies with the dose, route, and schedule of administration. The most common side effects with all methods of administration are flu-like symptoms. Because the side effects of IL-2 are relatively predictable, clinical pathways offer practical tools for anticipating and managing the toxicities associated with IL-2 administration. [ABSTRACT FROM AUTHOR]

Introduction: Gene expression profiling (GEP) of primary cutaneous melanoma aims to offer prognostic and predictive information to guide clinical care. Despite limited evidence of clinical utility, these tests are increasingly incorporated into clinical care., Methods: A panel of melanoma experts from the Society of Surgical Oncology convened to develop recommendations regarding the use of GEP to guide management of patients with melanoma. The use of currently available GEP tests were evaluated in three clinical scenarios: (1) the utility in patient selection for sentinel lymph node biopsy; (2) the utility to guide surveillance; and (3) the utility to inform adjuvant therapy. As a basis for these recommendations, the panel performed a systematic review of the literature, including articles published from January 2012 until August 2023., Results: After review of 137 articles, 50 met the inclusion criteria. These articles included evidence related to three available GEP tests: 31-GEP, CP-GEP, and 11-GEP. The consensus recommendations were finalized using a modified Delphi process. The panel found that current evidence often fails to account for known clinicopathologic risk factors and lacks high-level data. The panel recognizes that the study of GEP tests is still evolving. The integration of GEP into routine clinical practice for predicting sentinel lymph node status and patient prognosis in melanoma is therefore not currently recommended., Conclusion: At present, GEP should be considered primarily an investigational tool, ideally used in the context of clinical trials or specialized research settings., (© 2024. The Author(s).)

Background: Young women with breast cancer (YWBC; ≤40 years) often have a poorer prognosis than older women with breast cancer (OWBC; ≥65 years). We explored molecular features of tumors from YWBC and OWBC to identify a biologic connection for these patterns., Materials and Methods: We retrospectively analyzed the molecular profiles of 1879 breast tumors. Testing included immunohistochemistry (IHC), in situ hybridization (ISH), and next-generation sequencing. Statistical analyses included Pearson's chi 2 test for comparisons, with significance defined as FDR (false discovery rate)-P < .05., Results: TP53 and BRCA1 somatic mutations were more common in YWBC tumors than in OWBC tumors (53%, 42%; P = .0001, FDR-P = .0025 and 7%, 2%; P = .0001, FDR-P = .0025; respectively). Conversely, OWBC tumors had higher androgen receptor expression (55%, 45%; P = .0002, FDR-P = .0025) higher PD-L1 expression detected by IHC (8%, 5%; P = .0476, FDR-P = .2754), and more frequent PIK3CA mutations (33%, 17%; P = < .0001, FDR-P = < .0001). Among HR+/HER2- samples, YWBC had more gene amplifications in FGF3 (27%, 10%; P = .0353, FDR-P = .2462), FGF4 (27%, 9%; P = .0218, FDR-P = .1668), FGF19 (30%, 12%; P = .034, FDR-P = .2462) and CCND1 (37%, 18%; P = .0344, FDR-P = .2462) than OWBC., Conclusions: Our data suggest distinct molecular aberrations exist between YWBC and OWBC. Exploiting these molecular changes could refine our treatment strategies in YWBC and OWBC., Competing Interests: Disclosure Arielle L. Heeke: consulting (Caris Life Sciences). Wei Sha: no relevant conflicts to disclose. Rebecca Feldman: employee (Caris Life Sciences) Julie Fisher: no relevant conflicts to disclose. Lejla Hadzikadic-Gusic: no relevant conflicts to disclose. James T. Symanowski: no relevant conflicts to disclose. Richard L. White, Jr: no relevant conflicts to disclose. Antoinette R. Tan: meeting travel and accommodations (Caris Life Sciences)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Postmastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and improves overall survival (OS) in patients with breast cancer. Young age has been recognized as a risk factor for LRR. The primary objective of this study was to determine if recommendations for PMRT differed among patients younger than 50 years as compared to women aged 50 years or older., Methods: We reviewed medical records of patients with breast cancer who underwent mastectomy with or without PMRT from 2010 through 2018. Univariable and multivariable models were used to estimate the association of age with PMRT., Results: Of 2471 patients, 839 (34%) were <50 years; 1632 (66%) were ≥50 years. Patients <50 years had a higher percentage of grade 3 tumors, hormone receptor (HR) negative and/or Her-2/neu positive tumors, clinical stage T2/T3 tumors, and nodal involvement. Compared with patients ≥50 years, patients <50 years were more likely to undergo PMRT (OR 1.57; P = .001) and regional node irradiation (RNI) to the internal mammary nodes. Advanced clinical and pathologic stage, invasive tumor histology, the presence of lymphovascular invasion, and treatment with systemic chemotherapy were predictors of PMRT receipt for patients <50 years (P < .05). PMRT was associated with improved OS and recurrence free survival (RFS) among all patients (P < .01)., Conclusion: Patients <50 years were more likely to undergo PMRT and to receive RNI to the internal mammary nodes but were also more likely to have other risk factors for recurrence that would warrant a PMRT recommendation. PMRT improved OS and RFS for all patients., Competing Interests: Disclosure The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Breast cancer, although the second most common malignancy in women in the United States, is rare in patients under the age of 40 y. However, this young patient population has high recurrence and mortality rates, with chemotherapy frequently used as adjuvant treatment. We aimed to determine whether age is an independent predictor of chemotherapy recommendation and subsequent treatment and the relationship to Oncotype Dx (ODX) recurrence score (RS)., Methods: The National Cancer Database was retrospectively reviewed from 2010-2016 to identify women with early-stage (pT1-pT3, pN0-pN1mic, M0), hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer who underwent ODX RS testing., Results: Of 95,382 patients who met the inclusion criteria, risk groups using the traditional ODX RS cutoffs were 59% low, 33% intermediate, and 8% high. Using Trial Assigning Individualized Options for Treatment RS cutoffs, risk groups were 23% low, 62% intermediate, and 15% high. Chemotherapy recommendation decreased as age at diagnosis increased (P < 0.001). Increasing age was associated with decreased odds of chemotherapy recommendation in univariate models both continuously (odds ratio: 0.98, 95% confidence interval 0.97-0.98; P < 0.001) and categorically by decade (P < 0.001). Age by decade remained an independent prognosticator of chemotherapy recommendation (P < 0.001), adjusted for risk groups., Conclusions: Chemotherapy recommendation and treatment differs by age among patients with early-stage hormone receptor positive breast cancer who undergo ODX testing. While molecular profiling has been shown to accurately predict the benefit of chemotherapy, younger age at diagnosis is a risk factor for discordant use of ODX RS for treatment strategies in breast cancer; with patients aged 18-39 disproportionately affected., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study sought to identify β-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRβ), affect these targets to alter natural history or treatment response in patients., Experimental Design: In vitro experiments utilized primary desmoid cell lines to examine regulation of β-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies., Results: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a β-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRβ signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRβ and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRβ/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment., Conclusions: The β-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients., (©2023 The Authors; Published by the American Association for Cancer Research.)

Background: The purpose of this study was to evaluate the delay in initiating adjuvant radiation therapy (RT) after breast-conserving surgery (BCS) in patients with early-stage breast cancer who underwent oncoplastic reduction mammoplasty (ORM) following BCS compared with a matched cohort of patients who did not undergo ORM between BCS and RT., Methods: Medical records of 112 women (56 ORMs and 56 matched non-ORMs) with carcinoma in situ or early-stage breast cancer treated with BCS were reviewed. ORM was performed in a delayed manner following BCS, allowing confirmation of negative surgical margins. Time to RT was defined as time from last oncologic surgery to start of RT., Results: The median follow-up time was 6.8 years for the ORM cohort and 6.7 years for the control non-ORM cohort. Patients who underwent ORM following BCS experienced a significant delay in initiating RT (>8 weeks) than matched patients not undergoing ORM (66% vs. 34%; p < 0.001). Wound complications occurred in 44.6% (n = 25) of patients in the ORM cohort, which were mostly minor, including delayed wound healing and/or infection (39%). There was no significant difference in local recurrence between patients in the non-ORM and ORM cohorts (p = 0.32)., Conclusions: This study demonstrates that ORM following BCS has the potential to delay RT >8 weeks, largely as a result of increased risk of wound complications; however, this delay did not impact local control. ORM can be safely considered for appropriately selected patients with breast cancer., (© 2023. Society of Surgical Oncology.)

Background: Tissue expanders in breast reconstruction are traditionally placed retropectoral. Increasingly, patients are undergoing prepectoral placement. The impact of this placement on the initiation of adjuvant treatment is unknown., Methods: A retrospective review was conducted to identify women diagnosed with breast cancer who underwent mastectomy followed by radiation and/or chemotherapy. Women were divided into 3 groups: prepectoral tissue expander placement, retropectoral tissue expander placement, and no immediate reconstruction. A treatment delay was defined as greater than 8 weeks between tissue expander placement and adjuvant therapy., Results: Of 634 women, 205 (32%) underwent tissue expander placement, and 429 (68%) did not have immediate reconstruction. Of those with tissue expanders placed, 84 (41%) had prepectoral placement, and 121 (59%) had retropectoral placement. The median time to adjuvant therapy was 49 days for the entire cohort: no reconstruction, 47 days; prepectoral, 57 days; and retropectoral, 55 days. Treatment delays were observed in 34% of women: no reconstruction, 28%; prepectoral, 51%; and retropectoral, 46% ( P < 0.001). Tissue expander placement was associated with a delay to adjuvant therapy when compared with no reconstruction ( P < 0.001). The location of the tissue expander did not impact the odds of having a delay. On multivariable analysis, having reconstruction, having postoperative infection, not undergoing chemotherapy treatment, and being a current smoker were associated with a delay to adjuvant therapy. A delay to treatment was not associated with worse survival., Conclusions: Placement of a tissue expander delayed adjuvant therapy. The location of tissue expander placement, retropectoral versus prepectoral, did not impact the time to adjuvant treatment., Competing Interests: Conflicts of interest and sources of funding: None declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There are few quality metrics and benchmarks specific to surgical oncology. Development of a surgeon-level performance metrics system based on peer comparisons is hypothesized to positively influence surgical decision-making. This study established a tracking and reporting system comprised of evidence and consensus-based metrics to assess breast care delivered by individual surgeons., Methods: Surgeons' performance is assessed by a surveillance tracking system of metrics pertaining to referrals and surgical elements. This retrospective analysis of prospectively collected breast care data reports on recurring 6-month and cumulative data from nine care locations from 2015 to 2021., Results: Breast care was provided to 6659 patients by 41 surgeons. A total of 27 breast care metrics were evaluated over 7 years. Metrics with consistent, proficient results were retired after 18 months, including the rate of core biopsy, specimen orientation, and referrals to medical oncology, genetics, and fertility, among others. In clinically node-negative, hormone receptor-positive patients 70 years of age or older, the cumulative rate of sentinel lymph node (SLN) biopsy significantly decreased by 40% over 5.5 years (p < .001). The overall breast conservation rate for T0-T2 cancer increased 10% over 7 years. At the surgeon level, improvements were made in the median number of SLNs removed and in operative note documentation., Conclusions: Implementation of a surgeon-specific, peer comparison-based metric and tracking system has yielded substantive changes in breast care management. This process and governance structure can serve as a model for quantification of breast care at other institutions and for other disease sites., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: The residual cancer burden class informs survival outcomes after neoadjuvant chemotherapy. We evaluated the prognostic ability of the RCB for survival outcomes in women with different phenotypic subtypes of breast cancer treated with neoadjuvant chemotherapy. Additional variables were assessed for inclusion with the RCB to further improve the model's discriminative ability., Patients and Methods: We conducted a retrospective review of patients completing at least 75% of the recommended cycles of neoadjuvant chemotherapy between 1 January 2010 and 31 December 2016. Phenotypic subtypes were defined by hormone receptor and human epidermal growth factor receptor 2 (HER2) status at diagnosis, classified as HR+/HER2-, HER2+, or triple-negative breast cancer (TNBC). The RCB class was calculated and survival endpoints of overall survival, recurrence-free survival, and distant recurrence-free survival were analyzed using Kaplan-Meier and Cox proportional hazards methods. The discriminative ability of the models was quantified by Harrell's C-index., Results: Overall, 532 women met the inclusion criteria. Median follow-up was 65 months. In univariate models, RCB was significantly associated with OS, RFS, and DRFS. The RCB class had good discriminative ability for OS, RFS, and DRFS survival, with Harrell's C-indices of 0.68, 0.67, and 0.68, respectively. The RCB class discriminated well for each survival endpoint within HER2+ and TNBC, but did not discriminate well for HR+/HER2- (OS Harrell's C-indices of 0.77, 0.75, and 0.52, respectively)., Conclusions: The RCB class was prognostic for OS, RFS, and DRFS after neoadjuvant chemotherapy, but prognostic discrimination between patients with subtype HR+/HER2- was not observed during the follow-up period for which the overall event rate was low., (© 2022. Society of Surgical Oncology.)

Background: The extent of residual disease after neoadjuvant chemotherapy (NAC) can be quantified by the Residual Cancer Burden (RCB), a prognostic tool used to estimate survival outcomes in breast cancer. This study investigated the association between RCB and locoregional recurrence (LRR)., Methods: The study reviewed 532 women with breast cancer who underwent NAC between 2010 and 2016. Relapse in the ipsilateral breast, skin/subcutis at the surgical site, chest wall, pectoralis, or regional lymph nodes defined an LRR. The LRR cumulative incidence (LRCI) was estimated using the Fine and Gray competing-risks model, with death and distant recurrence defined as competing events. The association of LRCI with prognostic variables was evaluated., Results: Overall, 5.5% of the patients experienced an LRR after a median follow-up period of 65 months. The 5-year LRCI rates by RCB were as follows: RCB-0 (0.9%), RCB-1 (3.2%), RCB-2 (6.0%), and RCB-3 (12.9%). In the univariable analysis, LRCI varied significantly by RCB (p = 0.010). The multivariable analysis showed a significant association of LRCI with increasing RCB, and the patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) phenotype were at lower risk for LRR than those with HER2+ and triple-negative cancers (p < 0.032). The patients with RCB-3 were at a higher risk for local relapse than those with RCB-0 (hazard ratio, 13.78; confidence interval, 2.25-84.45; p = 0.04). Type of operation (p = 0.04) and use of adjuvant radiation (p = 0.046) were statistically significant in the multivariable model., Conclusions: The study results demonstrate a significant association between LRCI and increasing RCB, although distant recurrence is a substantial driver of disease outcomes. Future prospective studies should examine the role of RCB in clinical decisions regarding indications for adjuvant therapy., (© 2022. Society of Surgical Oncology.)

Introduction: The National Comprehensive Cancer Network (NCCN) developed clinical practice guidelines for germline pathogenic variants in highly penetrant genes, such as TP53 and PTEN, and in moderately penetrant genes, such as CHEK2, ATM and PALB2. Whether the practice of radiographic surveillance of patients with pathogenic variants in genes other than BRCA1/2 complies with current NCCN guidelines remains unclear., Methods: Retrospective review of patients identified with pathogenic variants in genes other than BRCA1/2 from 2007 through 2017 to determine if radiographic surveillance was in accordance with NCCN guidelines for mammography and consideration of magnetic resonance imaging (MRI). Exclusions included variants of unknown significance, pathogenic variants not associated with an increased risk of breast cancer, and previous breast cancer diagnosis., Results: After exclusions, 35 patients with pathogenic variants in ATM, CDH1, CHEK2, NBN, PALB2, PTEN, and STK11 genes were reviewed to assess whether radiographic surveillance was in accordance with NCCN guidelines. Guidelines for those with variants in ATM, CHEK2 and NBN includes annual mammography with tomosynthesis and consideration of breast MRI at age 40, variants in CDH1 and PALB2 at age 30, variants in PTEN at age 30-35 or 5-10 years before the earliest family breast cancer, and variants in STK11 at age 25. Of these 35 patients, 11 (31%) received mammography only; 11 (31%) received mammography and MRI, and 13 (37%) received no radiographic surveillance. Two of the 35 (6%) patients who received radiographic surveillance were diagnosed with ductal carcinoma in situ or invasive breast cancer., Conclusion: Thirty-one percent of patients with pathogenic variants in genes other than BRCA1/2 received both mammography and MRI. Thirty-seven percent of patients with these highly penetrant and moderately penetrant genes received no radiographic follow-up, clearly demonstrating an opportunity for improvement.

Introduction: The role of sentinel lymph node biopsy (SLNB) when ductal carcinoma in situ with microinvasion (DCISM) is identified on core biopsy is unclear., Objective: Our aim was to assess the upstage rate to invasive cancer and axillary lymph node metastasis in patients diagnosed with DCISM, and whether predictive variables could be identified that may help inform who would most likely benefit from a surgical axillary evaluation., Methods: We performed a retrospective review of 70 patients diagnosed with DCISM on core biopsy. Patients with concomitant or prior invasive cancer were excluded. Demographic, clinical, radiographic, histologic, and treatment data were collected. Fisher's exact test and univariable and multivariable logistic regression were performed to identify variables that may be associated with tumor upstaging and nodal metastasis. Time-to-event distributions were summarized using the Kaplan-Meier method., Results: On final surgical pathology, 49 patients (70%) had a final diagnosis of DCISM or T1mi cancer, whereas 21 patients (30%) were upstaged to measurable invasive cancer (> 1 mm). One of 49 patients (2%) with DCISM on final pathology and 4 of 21 patients (19%) with measurable invasive cancer showed sentinel lymph node metastases., Conclusion: Although the upstage rate to measurable invasive cancer in our cohort of patients with DCISM on core biopsy was 30%, findings of a positive SLNB remain low at 7%. No predictive variables were identified to inform whether the routine practice of SLNB may be omitted in some patients with DCISM.

Some authors report that patients receiving neoadjuvant chemotherapy have fewer lymph nodes harvested during axillary dissection and more dissections with < 10 nodes compared with patients who undergo surgery initially. We sought to determine whether there was a difference between these patient groups in terms of number of nodes harvested and number of dissections with < 10 nodes. Retrospective review of 258 patients diagnosed with breast cancer who underwent an axillary lymph node dissection between July 1, 2015, and December 31, 2017 was performed. Chi-squared test was used to assess differences between patient groups. Of 258 patients undergoing dissection, 48 per cent received neoadjuvant chemotherapy; 52 per cent underwent surgery as first therapeutic intervention. Mean number of nodes resected; 14.3 + 6.3 for patients with no prior chemotherapy versus 14.9 + 6.6 for patients with neoadjuvant chemotherapy ( P = 0.48). For patients undergoing surgery as first intervention, 21 per cent had < 10 nodes harvested. For patients receiving neoadjuvant chemotherapy, 20 per cent had < 10 nodes harvested. Patients who received neoadjuvant chemotherapy showed no statistically significant difference in the number of lymph nodes harvested during axillary dissection compared with patients undergoing surgery as first intervention. Neoadjuvant chemotherapy does not reduce the node harvest at the time of axillary dissection.

Purpose: Radial scars (RS) commonly present mammographically as architectural distortions, but these lesions may be associated with non-invasive and invasive breast cancer. Digital breast tomosynthesis (DBT) has resulted in higher detection rates of architectural distortion particularly in patients with dense breast tissue. We hypothesized that rates of clinically relevant lesions confirmed surgically would be lower in patients who received DBT imaging compared with those who received standard digital breast imaging., Methods: We performed a retrospective review of 223 patients diagnosed with pure RS by core biopsy and surgical excision before and after DBT was introduced. The rate of upgrading to malignancy or high-risk lesion was evaluated. Demographics, biopsy type, and histologic data were analyzed. Univariable logistic regression analysis was used to identify variables that may be associated with upgrading., Results: The rate of identifying RS increased from 0.04-.13% (P < 0.0001) with DBT imaging. The upgrade rate on surgical specimen to invasive or non-invasive cancer was similar before and after DBT; 6% versus 3%, as were findings of a high-risk lesion; 12% versus 22%. No predictive factors were identified for patients upgraded to malignant neoplasms or high-risk lesions., Conclusions: The likelihood of identifying RS has increased with DBT imaging, but rates of upgrading to a malignant neoplasm or high-risk lesion were similar to those before DBT. Although the rate of upgrading to malignancy after DBT was low, an excisional biopsy should be considered as 22% of patients were upgraded to high-risk lesions. These patients are candidates for chemoprevention and/or high-risk surveillance.

Background: The ACOSOG (American College of Surgeons Oncology Group) Z1071 assessed the feasibility of performing sentinel lymph node biopsy (SLNB) in node-positive patients who completed neoadjuvant chemotherapy (NACT). Historically, adoption of clinical research into practice takes years. The goal of this study was to determine the effect of Z1071 on our practice., Materials and Methods: This is a retrospective review of Z1071's influence on a single institution's practice. Patients with biopsy-proven positive axillary lymph nodes before NACT were eligible for the study. After NACT, patients with nodal response according to imaging and exam were candidates for SLNB. Two cohorts were stratified according to diagnosis date before and after Z1071 results were presented on December 5, 2012 at the San Antonio Breast Cancer Symposium. Fisher exact tests and nonparametric rank tests were used to compare cohorts., Results: The pre-Z1071 cohort included 74 patients and the post-Z1071 cohort 56 for a total of 130 patients. Post-Z1071, 73% (41/56) underwent a SLNB with an average of 4 nodes removed. Moreover, 27% (15/56) of patients had an axillary lymph node dissection as first intervention post-Z1071, compared with 99% (73/74) pre-Z1071. Axillary pathologic complete response pre-Z1071 was 35% (26/74) and post-Z1071 was 27% (15/56) (P = .35)., Conclusion: This report shows that meaningful practice changes can be implemented rapidly. Changes in practice generated by clinical trial results should be monitored and outcomes followed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neoadjuvant chemotherapy (NAC) reduces tumor size, facilitating the use of breast conservation surgery (BCS). However, mastectomy remains the surgical outcome for certain women. The goal of this study was to determine the rationale for mastectomy after NAC, particularly in women eligible for BCS. Retrospective data were reviewed on patients who received NAC between February 2006 and August 2010 at our institution. Demographics and tumor characteristics were compared between patients who received BCS and mastectomy after NAC. Of 149 patients meeting inclusion criteria, 102 (68%) underwent BCS and 47 (32%) underwent mastectomy. Patient preference was the most common rationale for mastectomy (n = 19; 40%), followed by extent of disease (n = 13; 28%), presence of a breast cancer susceptibility gene (BRCA) mutation (n = 9; 19%), persistent positive margins (n = 5; 11%), and wound complications (n = 1; 2%). Of the 47 patients who underwent mastectomy, 37 (79%) were eligible for BCS after NAC. Larger pathologic tumor size (2.05 vs 1.25 cm, P = 0.04) and lobular histology [invasive lobular carcinomas, n = 12/17 (70%) vs invasive ductal carcinomas, n = 36/133 (27%); P < 0.01] were associated with increased rate of mastectomy. After NAC, patient preference, extent of disease, and the presence of a BRCA mutation account for the vast majority of mastectomies. Interestingly, most of these patients were shown to be candidates for breast conservation. This highlights the importance of educating patients about their surgical choice and the lack of evidence, showing a benefit to more extensive surgery.

Genetic testing is important for comprehensive cancer care. Commercial analysis of the BRCA1/2 genes has been available since 1996, and testing for hereditary breast and ovarian cancer syndrome is well established. The National Comprehensive Cancer Network (NCCN) guidelines identify individuals for whom BRCA1/2 analysis is appropriate and define management recommendations for mutation carriers. Despite recommendations, not all who meet NCCN criteria undergo genetic testing. We assess the frequency that individuals meeting NCCN criteria decline BRCA1/2 analysis, as well as factors that affect the decision-making process. A retrospective chart review was performed from September 2013 through August 2014 of individuals who received genetic counseling at the Levine Cancer Institute. A total of 1082 individuals identified through the retrospective chart review met NCCN criteria for BRCA1/2 analysis. Of these, 267 (24.7%) did not pursue genetic testing. Of the Nontested cohort, 59 (22.1%) were disinterested in testing and 108 (40.4%) were advised to gather additional genetic or medical information about their relatives before testing. The remaining 100 (37.5%) individuals were insured and desired to undergo genetic testing but were prohibited by the expense. Eighty five of these 100 patients were responsible for the total cost of the test, whereas the remaining 15 faced a prohibitive copay expense. Financial concerns are a major deterrent to the pursuit of BRCA1/2 analysis among those who meet NCNN criteria, especially in patients diagnosed with breast or ovarian cancer. These findings highlight the need to address financial concerns for genetic testing in this high-risk population.

Introduction: Prior to the "no ink on tumor" SSO/ASTRO consensus guideline, approximately 20% of women with stage I/II breast cancers undergoing breast conservation surgery at our institution underwent margin re-excision. On May 20, 2013, our institution changed the definition of negative margins from 2 mm to "no ink on tumor.", Methods: A retrospective review was conducted of patients who had surgery at our institution with clinical stage I/II breast cancers between June 1, 2011 and May 1, 2015. In the pre-guideline cohort (pre) and post-guideline cohort (post), negative margins were 2 mm and "no ink on tumor," respectively., Results: Implementation of the guideline resulted in a significant decrease in the positive/close margin rate (29.6% pre vs 10.1% post; P < 0.001) and numerical decrease in re-excision rate (20.4% pre vs 16.3% post; P = 0.104). No significant difference was found in local recurrence between the cohorts with limited follow-up (1.2% pre vs 1.5% post; P = 0.787)., Conclusion: The implementation of the "no ink on tumor" guideline at our institution has resulted in a significant decrease in positive margin rates and a numerical decrease in margin re-excisions. In addition to margin status, surgeons continue to use individual patient and histologic factors to decide for or against margin re-excision., (© 2017 Wiley Periodicals, Inc.)

Objective: We hypothesized that the Oncotype Dx ® 21-gene Recurrence Score (RS) could guide neoadjuvant systemic therapy (NST) to facilitate breast conserving surgery (BCS) for hormone receptor positive (HR+) breast cancers., Methods: This study enrolled patients with HR+, HER2-negative, invasive breast cancers not suitable for BCS (size ≥ 2 cm). Core needle biopsy blocks were tested. For tumors with RS < 11, patients received hormonal therapy (NHT); patients with RS > 25 tumors received chemotherapy (NCT); patients with RS 11-25 were randomized to NHT or NCT. Primary endpoint was whether 1/3 or more of randomized patients refused assigned treatment., Results: Sixty-four patients were enrolled. Of 33 patients with RS 11-25, 5 (15%) refused assignment to NCT. This was significantly lower than the 33% target (binomial test, P = 0.0292). Results for clinical outcomes (according to treatment received for 55 subjects) included successful BCS for 75% of tumors with RS < 11 receiving NHT, 72% for RS 11-25 receiving NHT, 64% for RS 11-25 receiving NCT, and 57% for RS > 25 receiving NCT., Conclusions: Using the RS to guide NST is feasible. These results suggest that for patients with RS < 25 NHT is a potentially effective strategy., (© 2017 Wiley Periodicals, Inc.)

Background: The seventh edition of the American Joint Commission on Cancer staging manual (AJCC7, published 2009), updated thin cutaneous melanoma staging protocols with the incorporation of mitotic rate (MR). In these patients, higher MR is associated with decreased survival. This study utilizes the National Cancer Data Base (NCDB) to evaluate MR reporting since AJCC7., Methods: The NCDB was queried for patients with primary cutaneous melanoma from 1998 to 2013. Because MR reporting was infrequent prior to implementing AJCC7, records from 2010 to 2013 were analyzed. Categorical variables were compared with chi-square tests; univariate and multivariate logistic regression models were constructed to determine the effects of covariates on MR reporting., Results: A total of 107,134 patients met inclusion criteria. From 2010 to 2013, MR reporting increased dramatically (64.3-80.9%). On multivariate analysis, factors significantly related to increased MR reporting include later diagnosis year, T-classification (T1a and b vs. T1), facility type (academic vs. other specified types of cancer programs), facility volume, patient income, level of education, and county population (metropolitan vs. urban and rural)., Conclusions: MR reporting increased dramatically after the introduction of AJCC7; however, disparities in reporting remain across facility types. Further investigation of procedures performed in academic settings that may influence reporting of MR is warranted. J. Surg. Oncol. 2017;115:281-286. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM., (© 2015 Wiley Periodicals, Inc.)

Background: SSO-ASTRO recently published guidelines defining adequate margins in breast conservation therapy (BCT) as no tumor on ink based on studies demonstrating little difference in local recurrence (LR) with wider margins. We hypothesize that not routinely re-excising close margins results in decreased costs without compromising care., Methods: A decision tree model was developed for the management of margins after BCT for invasive cancer. Patients were compared among three margin status groups: positive, close (≤2 mm) and negative (>2 mm). Ten publications provided re-excision rates (RER) and LR rates. The model assumed 140,000 BCT/year. Sensitivity analyses determined the most cost-effective strategy. Surgical costs were estimated using 2013 Medicare reimbursement rates., Results: Re-excising close margins was significantly more costly than the alternative, $233.1 million versus $214.3 million, per year in the United States. Total surgical cost was most sensitive to re-excision of close margins-increasing the RER from 0% to 100% resulted in an $18.8 million cost difference., Conclusions: The strategy of re-excising close margins resulted in a predicted cost of $18.8 million per year. This does not include hospital costs, the cost of surgical complications after re-excision, and underestimates the potential savings by using Medicare reimbursement rates., (© 2015 Wiley Periodicals, Inc.)

At Carolinas Medical Center, before 2008, axillary sentinel lymph nodes (SLNs) from breast cancer patients were evaluated with a single hematoxylin and eosin-stained slide. In 2008, the protocol changed to include a limited step sectioning at 500 μm. In this study, we compared the intraoperative and permanent section pathologic findings for SLN biopsies from 2006 to 2007 to those from 2009 to 2010. We hypothesized that evaluating 2 slides would increase the detection of micrometastases and isolated tumor cells (ITCs) on permanent sections and correspondingly decrease the sensitivity of intraoperative touch preparation cytology (IOTPC). From 2006 to 2007, 140 (23.5%) of 597 of SLN permanent sections contained tumor cells: 92 macrometastases (65.7%), 36 micrometastases (25.7%), and 12 ITCs 0.2 mm or less (8.6%). The sensitivity of IOTPC for 2006 to 2007 was 51.4% for any tumor cells and 71.7% for macrometastases. From 2009 to 2010, 160 (21.9%) of 730 SLN permanent sections were positive for any tumor cells: 76 macrometastases (47.5%), 55 micrometastases (34.4%), and 29 ITCs (18.1%). The sensitivity of IOTPC for 2009 to 2010 was 39.4% for any tumor cells and 76.3% for macrometastases. With limited step sectioning, we observed an approximately 10% increase in the detection of both micrometastases and ITCs in SLN. The increased detection of ITCs on permanent sections reached statistical significance (P = .018). However, under current clinical guidelines, patients with limited SLN involvement may not be required to undergo completion axillary lymph node dissection. The ability to detect SLN tumor deposits less than 2 mm must be balanced with the clinical utility of doing so., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Immunotherapy with interleukin-2 (IL-2) has been the mainstay of systemic therapy for advanced kidney cancer and melanoma. Although IL-2 treatment is limited to healthy patients, a select group of these patients have derived substantial, durable benefit from it-in some translating into cures with no ongoing therapy or chronic toxicity. Over the past 10 years, insights into the biology of renal cell carcinoma and into key signaling mechanisms in melanoma, and growth in our understanding of immune checkpoints, have led to the development and approval of targeted and immune-modulatory therapeutic options with clinically relevant benefit. Our improved understanding of the relationship between the host environment, immune system, and malignancy has helped identify compounds and therapies that are changing the way we think about cancer and our approach to cancer therapeutics. While the newer options may be applicable to most patients, durable responses measured in years are rare. In this review, we examine the currently approved options available for these disease processes, including the newer agents and selected combinatorial approaches under investigation, and we attempt to identify the role of high-dose IL-2 in the context of current clinical practice.

Background: Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database., Methods: Seventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma. Multiple demographic and tumor factors were analyzed for correlation with a positive SLN. Univariate and multivariate statistical analyses were performed., Results: Of 3445 analyzable patients, 561 (16.3%) had a positive SLN biopsy. In multivariate analysis of 1526 patients with complete records for 10 variables, increasing Breslow thickness, lymphovascular invasion, ulceration, younger age, the absence of regression, and tumor location on the trunk were statistically significant predictors of a positive SLN., Conclusions: These results confirm the predictive significance of the well-established variables of Breslow thickness, ulceration, age, and location, as well as consistently reported but less well-established variables such as lymphovascular invasion. In addition, the presence of regression was associated with a lower likelihood of a positive SLN. Consideration of multiple tumor parameters should influence the decision for SLN biopsy and the estimation of nodal metastatic disease risk.

Immune-based therapies for cancer are now commonplace. Cytokine therapy, including interferon and interleukin-2, is safe in the community setting. The US Food and Drug Administration has recently approved sipuleucel-T for the treatment of advanced prostate cancer, the first therapeutic cancer vaccine to meet this level of efficacy. The therapeutic use of monoclonal antibodies directed against proteins controlling various cell functions, including growth and modulation of immune response, has become so pervasive that the oncologist, whether surgeon or medical oncologist, must be familiar with indications, contraindications, and the associated toxicities., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The timing of sentinel node biopsy in the setting of neo-adjuvant chemotherapy for breast cancer is controversial. Sentinel node biopsy performed after neo-adjuvant chemotherapy may save patients with a nodal response the morbidity of an axillary lymph node dissection. A retrospective review of prospectively collected data compared sentinel node biopsies performed after patients had received neo-adjuvant chemotherapy with patients who had not received neo-adjuvant chemotherapy. Demographic factors, tumor characteristics, and the results of the sentinel node biopsies and completion lymph node dissections (when applicable) were compared. A total of 231 axillary procedures (224 patients) were evaluated. The patients who received neo-adjuvant chemotherapy (NEO; N=52) were younger, had higher grade tumors, were more likely to have a mastectomy, and were more likely to have ER-negative and HER-2/neu positive tumors than the patients who did not receive neo-adjuvant chemotherapy (NON; N=179). The mean clinical tumor size in the neo-adjuvant group was 4.5cm (±1.8) prior to chemotherapy; the post-chemotherapy pathologic size was 1.4cm (±1.3). A sentinel node was identified in all cases. There were no significant differences between the groups in the mean number of sentinel nodes removed (NEO=3.3; NON=3.1; p=0.545), the percentage of positive axillae (NEO=24%; NON=21%; p=0.776) or the mean number of positive sentinel nodes (NEO=1.3; NON=1.5; p=0.627). There was no difference in the percentage of completion lymph node dissections with additional positive nodes (NEO=20%; NON=35%; p=0.462); there was a difference in the number of nodes removed in the completion lymph node dissections (mean NEO=12.0; NON=16.4; p=0.047). Sentinel node biopsy performed after neo-adjuvant chemotherapy appears to be an oncologically sound procedure and may save some patients the morbidity of a complete lymph node dissection., (© 2010 Wiley Periodicals, Inc.)

Background: Preoperative injection of radiocolloid before a sentinel lymph node (SLN) biopsy is painful for patients with breast cancer. Injection after anesthesia eliminates this discomfort but allows less time for radiocolloid migration. Our goal was to validate the efficacy of intraoperative injection., Methods: In this retrospective study of prospectively collected data, patients underwent periareolar dermal injection of technetium sulfur colloid. Patients in the preoperative injection (PO) group were injected by radiologists in the breast imaging center. Patients in the intraoperative injection (IO) group were injected by surgeons after induction of anesthesia. Consecutive cases were evaluated for radioactive "hotspots," time elapsed before incision, number of SLNs removed, number of positive SLNs, and percentage of positive biopsies., Results: Two hundred fourteen breasts were evaluated (PO = 102; IO = 112). The mean time from injection to incision was significantly shorter by 107 minutes for the IO group. There were no differences in the percentage of positive biopsies (PO: 20.6%; IO: 19.6%; P = 0.863), the number of SLNs removed (PO: 3.3; IO: 3.0; P = 0.091), or the number of positive SLNs (PO: 1.4; IO: 1.4; P = 0.657)., Conclusions: There are no significant differences in the principal results of SLN biopsy between PO and IO injection methods. Dermal radiocolloid injection after induction of anesthesia seems to be an oncologically sound procedure and may be a preferable technique.

The results of non-surgical treatment of advanced stage melanoma are disappointing. Carefully selected stage IV melanoma patients can profit from an aggressive surgical approach. The possibilities of surgical treatment of solitary and single-organ metastasis of melanoma are discussed for most common metastatic sites.

We describe our experience in a patient with a congenital solitary kidney encased by a perirenal liposarcoma managed by nephron-sparing excision. The best predictor of survival with liposarcoma is complete resection of the tumor. Generally a diffuse peri-renal liposarcoma arising within Gerota's fascia would necessitate a radical nephrectomy. Having a congenitally solitary kidney, this patient refused nephrectomy, therefore a kidney-sparing excision of his liposarcoma was attempted. To obtain negative margins and to provide a nephron-sparing excision, the capsule of the kidney was resected with the mass. Direct extension into the diaphragm necessitated an en bloc resection of 4 x 6 cm of the left hemidiaphragm. The defect was reconstructed with a Gortex patch graft. Pathology revealed a 32 x 22 x 8-cm liposarcoma with areas of sclerosing liposarcoma and poorly differentiated spindle cell sarcoma, focally Grade 3 of 3, with the remaining tumor being Grade 1. There was diaphragmatic invasion, but all surgical margins were negative. At 22 months CT follow-up, the patient has no radiographic evidence of disease. Excision of this mass with the renal capsule allowed our patient to be margin negative and maintain normal renal function. This is the only report in the literature describing nephron-sparing resection of a giant perirenal liposarcoma involving a solitary kidney.

Background: The staging of patients with primary melanoma is dependent on adequate sampling of the tumor thickness. Initial biopsies with a positive deep margin suggest inadequate sampling, potentially limiting accurate staging and affecting treatment decisions., Methods: To determine the efficacy of shave biopsy to adequately sample the tumor, we retrospectively reviewed our pathology database for original pathology reports of primary melanomas accessioned between 01/01/04 and 6/30/05. The biopsies were evaluated by technique, the presence of tumor at the margins of the specimen, and specimen thickness., Results: We identified 240 cases of primary melanoma; 223/240 were analyzable. The specimens were divided by biopsy technique (excisional, n = 51; punch, n = 44; and shave, n = 128). Shave and punch specimens had a significantly higher percentage of positive margins than excisional specimens (50, 68, and 16%, respectively; P < 0.0001). Shave specimens had a significantly higher percentage of positive deep margins than punch or excisional specimens (22, 7, and 2%, respectively; P = 0.0009). For melanomas

Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma., Patients and Methods: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status., Results: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively)., Conclusion: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Objective: To determine the impact of sentinel lymph node (SLN) status and other risk factors on recurrence and overall survival in head and neck melanoma patients., Design: The SLN Working Group, based in San Francisco, Calif, with its 11 member centers, the John Wayne Cancer Institute, and The University of Texas M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma patients who had selective sentinel lymphadenectomy. A total of 614 subjects were analyzable. All centers obtained internal review board approval and adhered to the Health Insurance Portability and Accountability Act of 1996 regulations. A Cox proportional hazards model was used to identify factors associated with overall and disease-free survival., Setting: Tertiary care medical centers., Main Outcome Measure: Clinical outcome of head and neck melanoma patients undergoing selective sentinel lymphadenectomy., Results: Overall, 10.1% (n = 62) of the subjects had at least 1 positive node. Subjects with positive SLN status had significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were more likely to have ulcerated tumors (P = .004). During the median follow-up of 3.3 years, the overall mortality from head and neck melanoma was 10%, with more than 20% experiencing at least 1 recurrence. Multivariate analysis showed that tumor site was an independent predictor of mortality; location on the scalp had a more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor thickness was also an independent predictor of overall survival, and SLN status was the most important predictor of disease-free survival in the multivariate model (P < .001). Tumors on the scalp had the highest rate of recurrence, while those on the neck had the lowest. Tumor ulceration was the significant predictor of time to recurrence or disease-free survival (P < .001)., Conclusion: In this multicenter study, SLN status and other risk factors have an effect on recurrence and/or overall survival.

Background: Columnar alteration with prominent snouts and secretions (CAPSS) is routinely described on breast core needle biopsies (CNBs); however, its significance and appropriate treatment is unknown. This study evaluated the incidence of cancer (in situ/invasive) in core biopsies and in subsequent surgical biopsy specimens after an initial core biopsy identifying CAPSS., Methods: Using our medical center's pathology database, we retrospectively identified lesions described as CAPSS on breast core needle biopsies performed between January 1998 and August 2003. The specimens were subdivided into CAPSS lesions with and without atypical features. We also identified lesions described as atypical ductal hyperplasia., Results: Overall, 10 cancers were associated with 135 (7.4%) CAPSS lesions without atypia, and 11 (18.3%) were associated with 60 CAPSS lesions with atypia (P = 0.023). CAPSS lesions with atypical features had a slightly higher rate of coexisting cancer on initial biopsy than CAPSS without atypical features (7% vs 12%, P = 0.320). Specimens showing atypical ductal hyperplasia on initial biopsy had a greater rate of coexisting cancer than CAPSS with or without atypical features (P <0.0001)., Conclusion: We support the existing recommendation that a patient with a CNB showing CAPSS with atypical features undergo surgical biopsy.

Purpose: We evaluate the role of fluorodeoxyglucose F 18 positron emission tomography (PET) in patients with renal cell carcinoma (RCC) by retrospective review. To our knowledge this series is the largest reviewing the use of PET in patients with RCC., Materials and Methods: A total of 66 patients who underwent 90 PET scans for suspected or known RCC were identified. Dictated reports of PET, chest computerized tomography (CT), abdominal/pelvic CT and bone scan were examined with confirmation of results by histopathology or followup of at least 1 year. The accuracies of PET and conventional imaging modalities were compared., Results: PET exhibited a sensitivity of 60% and specificity of 100% for primary RCC tumors (abdominal CT demonstrated 91.7% sensitivity and 100% specificity). For retroperitoneal lymph node metastases and/or renal bed recurrence, PET was 75.0% sensitive and 100.0% specific (92.6% sensitivity and 98.1% specificity for abdominal CT). PET had a sensitivity of 75.0% and a specificity of 97.1% for metastases to the lung parenchyma compared to 91.1% and 73.1%, respectively, for chest CT. PET had a sensitivity of 77.3% and specificity of 100.0% for bone metastases, compared to 93.8% and 87.2% for combined CT and bone scan. In 39 scans (32 patients) PET failed to detect RCC lesions identified by conventional imaging., Conclusions: The role of fluorodeoxyglucose F 18 PET in the detection of RCC is limited by low sensitivity. With superior specificity PET may have a complementary role as a problem solving tool in cases that are equivocal on conventional imaging.

Sentinel lymph node biopsy in women with breast cancer has become routine in many surgical practices; yet basic questions regarding the procedure remain unanswered. The National Surgical Adjuvant Bowel and Breast Project (NSABP) and the American College of Surgeons Oncology Group (ACOSOG) trials address the issues of morbidity, efficacy, safety, and the significance of low-volume disease. NSABP B-32 randomizes women to sentinel lymph node biopsy followed by a standard level I and II axillary dissection or sentinel lymph node biopsy without dissection unless metastatic disease is noted by H&E examination. Overall survival, disease-free survival, and morbidity serve as end points. Further pathologic evaluation of the lymph nodes with immunohistochemistry will be performed by the study center. This study is nearing its anticipated accrual goal. Patients enrolled in the now-closed ACOSOG Z0010 trial underwent bone marrow aspiration just prior to sentinel node biopsy. Immunocytochemical analysis of the marrow will be compared to sentinel lymph node (SLN) biopsy to determine prognostic accuracy. ACOSOG Z0011 randomizes women undergoing breast-conserving therapy with low-volume axillary disease to completion axillary dissection or observation. Overall survival, disease-free survival, local regional control, and morbidity serve as end points. This trial is currently enrolling patients.

Despite randomized prospective studies and National Institutes of Health recommendations, surgeons especially in the southern United States have been slow to adopt breast conservation surgery (BCS). Data were analyzed regarding 3,349 cases of stage 0, I, and II breast cancer (1991-1998) from Charlotte-Mecklenburg County, NC; 1057 cases from six surrounding rural counties (1995-1997); and 90,398 cases (1995) from the National Cancer Data Base. During 1995 through 1997 Charlotte-Mecklenburg County had statistically significantly higher rates of BCS compared with six surrounding rural counties for stage I (59% and 42% respectively, P = 0.001) and stage II (37% and 19%, respectively, P = 0.001) breast cancer. The BCS rates in Charlotte-Mecklenburg County (1991-1998) showed the following: Stage 0 rate increased from 17 per cent in 1991 to 78 per cent in 1998 (P = 0.001), stage I rate increased from 31 per cent in 1991 to 65 per cent in 1998 (P = 0.001), and stage II rate increased from 18 per cent in 1991 to 42 per cent in 1998 (P = 0.001). BCS rates for early-stage breast cancer in Charlotte-Mecklenburg County have increased over the last 8 years and now equal national rates; however, patients in surrounding rural counties are not receiving BCS as frequently. There is a need for more widespread education of surgeons, other health care providers, and the general public to increase the use of BCS.

Patients with cancer provide a unique challenge for critical care nurses. Outcomes of clinical trials, new surgical modalities, and pioneering cancer treatments have helped prolong lives. The patient with cancer can require surgical and critical care intervention at the time of diagnosis, at the point of definitive therapy, or in the later stages of disease. Treatment is individual and sometimes aggressive. Surgical intervention is undertaken with a view toward the patient's ultimate outcome, quality of life, and potential cure. Multimodality cancer therapy will continue to flourish, demanding astute assessment skills by the critical care nurse. The critical care nurse must be able to integrate knowledge of the patient's type of cancer, treatment history, comorbid conditions, and surgical interventions into routine postoperative critical care.

Objective: The purpose of this study was to determine the sensitivity, specificity, and clinical utility of 18F 2-fluoro-2-deoxy-D-glucose (FDG) total-body positron emission tomography (PET) scanning for the detection of metastases in patients with malignant melanoma., Summary Background Data: Recent preliminary reports suggest that PET using FDG may be more sensitive and specific for detection of metastatic melanoma than standard radiologic imaging studies using computed tomography (CT). PET technology is showing utility in the detection of metastatic tumors from multiple primary sites including breast, lung, lymphoma, and melanoma. However, little information is available concerning the general utility, sensitivity, and specificity of PET scanning of patients with metastatic melanoma., Methods: One hundred three PET scans done on 76 nonrandomized patients having AJCC stage II to IV melanoma were prospectively evaluated. Patients were derived from two groups. Group 1 (63 patients) had PET, CT (chest and abdomen), and magnetic resonance imaging (MRI; brain) scans as a part of staging requirements for immunotherapy protocols. Group 2 (13 nonprotocol patients) had PET, CT, and MRI scans as in group 1, but for clinical evaluation only. PET scans were done using 12 to 20 mCi of FDG given intravenously. Results of PET scans were compared to CT scans and biopsy or cytology results., Results: PET scanning for the detection of melanoma metastases had a sensitivity of 94.2% and a specificity of 83.3% compared to 55.3% and 84.4%, respectively, for CT scanning. Factors that produced false-positive PET scans were papillary carcinoma of the thyroid (1), bronchogenic carcinoma (1), inflamed epidermal cyst (1), Warthin's tumor of the parotid gland (1), surgical wound inflammation (2), leiomyoma of the uterus (1), suture granuloma (1), and endometriosis (1). The four false-negative scans were thought to be due to smaller (<0.3 to 0.5 cm) and diffuse areas of melanoma without a mass effect., Conclusions: PET scanning is extremely sensitive (94.2%) and very specific (83.3%) for identifying metastatic melanoma, particularly in soft tissues, lymph nodes, and the liver. A number of second primary or metastatic tumors and an inflammatory response can also be localized by PET. This observation mandates a close clinical correlation with positive PET and emphasizes the importance of establishing a tissue diagnosis. False-negative scans in the presence of metastases are rare (4% of scans). Metastases < or =5 mm in diameter may not image well. PET is superior to CT in detecting melanoma metastases and has a role as a primary strategy in the staging of melanoma.

Background: High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed., Methods: One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD)., Results: Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia ( < 1,000 leukocytes/mm3) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia ( < 30,000 platelets/mm3) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common: abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths., Conclusions: During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy.

Background: Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed., Methods: The treatment courses of all patients receiving high dose intravenous bolus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity., Results: One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P2 = 0.037)., Conclusions: Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible.

The nucleus raphe obscurus (NRO) has recently emerged as an important nucleus for excitation of gastric motor activity through projections to the dorsal motor nucleus of the vagus (DMV) [P. J. Hornby, C. D. Rossiter, R. L. White, W. P. Norman, D. H. Kuhn, and R. A. Gillis. Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G91-G96, 1990; and M. J. McCann, G. E. Herman, and R. C. Rogers. Brain Res. 486: 181-184, 1989]. A neurotransmitter thought to be involved in this NRO-DMV pathway is thyrotropin-releasing hormone (TRH), a peptide that excites gastric activity when microinjected into the DMV. The purpose of the present study was to determine whether gastric acid and pepsin secretion were altered by 1) activation of neurons in the NRO by microinjection of kainic cid and 2) microinjection of TRH into the DMV in chloralose-anesthetized cats. Microinjection of kainic acid into the NRO increased gastric acid secretion [baseline was 6 +/- 2 (mu eq) H+/15 min (n = 7) and increased to 8 +/- 2, 26 +/- 11 (P less than 0.05), and 21 +/- 7 mu eq/15 min (P less than 0.05) during the first, second, and third 15-min periods after microinjection, respectively]. Pepsin output also increased from a baseline of 287 +/- 67 pepsin units (PU) (n = 4) to 507 +/- 126 PU 15 min postinjection, 541 +/- 118 PU 30 min after injection (P less than 0.05), 608 +/- 92 PU 45 min after injection (P less than 0.05), and 700 +/- 156 PU 60 min postinjection (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)