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BACKGROUND Mastectomy remains an effective treatment for ductal carcinoma in situ (DCIS) but whether further therapy is warranted for close or positive margins is controversial. We aim to characterize the treatment practices of DCIS throughout the United States in patients who undergo mastectomy with close or positive margins to better understand the use of postmastectomy radiation therapy (PMRT). MATERIALS AND METHODS Using the 2004-2013 National Cancer Database, we identified all female patients with a diagnosis of DCIS who underwent mastectomy. Distributional characteristics were summarized for overall and margin-stratified samples. Characteristic differences were assessed by region and receipt of radiation. Chi-square and independent sample t-tests were used to assess differences for categorical and continuous variables, respectively. RESULTS In 21,591 patients who met inclusion criteria, 470 patients with close/positive margins were identified. Sixteen percent of patients with close/positive margins received PMRT compared to 1.5% with negative margins (P

The NCCN Guidelines for Melanoma have been significantly revised over the past few years in response to emerging data on a number of novel agents and treatment regimens. These NCCN Guidelines Insights summarize the data and rationale supporting extensive changes to the recommendations for systemic therapy in patients with metastatic or unresectable melanoma.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Melanoma focuses on adjuvant therapy and treatment of in-transit disease, because substantial changes were made to the recommendations for the 2016 update. Depending on the stage of the disease, options for adjuvant therapy now include biochemotherapy and high-dose ipilimumab. Treatment options for in-transit disease now include intralesional injection with talimogene laherparepvec (T-VEC), a new immunotherapy. These additions prompted re-assessment of the data supporting older recommended treatment options for adjuvant therapy and in-transit disease, resulting in extensive revisions to the supporting discussion sections.

Purpose The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. Patients and Methods Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma ≥ 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). Results In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. Conclusion No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor-negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.

Team work is the key to successful breast conservation therapy. Patient education and the informed consent process should include a discussion about the importance of margin status. Specimen management is critically important to obtain the highest quality information about margins. Operating technique should avoid trauma to or disruption of the specimen surface. The specimen should be oriented for the pathologist using standard techniques including sutures, clips, or colored inks. Specimen radiography is mandatory to confirm complete resection of the target tissues and can be used to direct additional margin resections during the initial procedure. With a well-designed and oriented specimen, the pathologist can give an accurate description of the margin distance for both the invasive and in situ components of the cancer. In most cases, decision-making about margins will be straightforward. Positive margins should be re-excised or the treatment is converted to mastectomy. Clear margins (>5 mm) require no further surgical therapy. “Close” margins (1–4 mm) will remain a point of controversy because of conflicting reports from clinical series. At UAB, decision for re-excision is made on a case-by-case basis. Routinely 2 mm is considered adequate, however, volume of disease and intraductal component are important considerations when making recommendations.

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.

Background: Triple negative breast cancer (TNBC) comprises 15–20% of newly diagnosed invasive breast cancers and has been associated with an elevated risk of both local-regional recurrence (LRR) as well as distant failure. Bevacizumab (BEV) has been shown to improve pathologic complete response rates in the setting of neoadjuvant chemotherapy (NCT), but its effect on LRR remains undefined. This study reports the impact of adding BEV to standard breast cancer therapy in TNBC patients treated at a single institution. Methods: One hundred and eighty-five consecutive TNBC patients treated at the University of Alabama Birmingham from May 2005 to August 2010 were reviewed. Thirty-one TNBC patients treated with chemotherapy (CT) and BEV on prospective studies were matched (1:2) with 62 TNBC patients treated with CT alone, controlling for age, stage, and use of radiation (RT). The Kaplan-Meier method was used to estimate LRR, distant metastasis-free survival (DMFS), and overall survival (OS), and cohorts were compared using Cox proportional hazards models and the 2-sided log-rank test. Results: Mean age was 47 and 46 years in the cohorts with and without BEV, respectively. Stage in each cohort was as follows: 32% stage I, 61% stage II, and 7% stage III. Use of adjuvant RT was 81% in each cohort (25/31 BEV, 50/62 no BEV). BEV was delivered with NCT in 17 patients (55%) and with adjuvant CT in the remaining 14 patients (45%). Eleven patients (35%) completed an additional 1 year of maintenance therapy with BEV. LRR occurred in 2 (6%) patients treated with BEV vs. 16 (26%) treated with CT alone (HR = 0.25, 95% CI 0.06–1.07, p = 0.04). Distant recurrence occurred in 3 (10%) patients treated with BEV vs. 11 (18%) patients in the CT group HR=0.6, 95% CI 0.2–1.8, p = 0.48). There were 2 (6%) deaths in the BEV group vs. 12 (19%) in the CT alone group (HR = 0.55, 95% CI 0.13–2.3, p = 0.19). Conclusions: In a matched-pair analysis of TNBC patients, the addition of BEV to conventional breast cancer management was associated with a reduction in LRR. Further prospective study is necessary to examine the impact of BEV on local-regional control in TNBC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-17-07.

Background We found that a computer model developed by the American Joint Committee on Cancer (AJCC) melanoma staging committee had limitations for predicting prognosis of patients staged by sentinel lymph node (SLN) biopsy. We sought to develop a model that more accurately predicts prognosis in this population. Study Design Using a data set obtained from a prospective multi-institutional study of 2,507 patients with clinically node-negative melanomas ≥1.0 mm Breslow thickness, we developed a prognostic model using a Cox regression formula incorporating a number of significant clinicopathologic factors. The AJCC model and our model were used to predict 5-year survival from this test data set. The concordance correlation coefficient (CCC) was determined and chi-square tests were performed. Our new prognostic model was validated using an independent data set of 1,001 patients. Results Using the test data set, the CCC for the AJCC model was 0.875; chi-square tests demonstrated statistically significant differences between observed and predicted survivals for numerous clinicopathologic factors. The CCC for our model was 0.976 and none of the chi-square tests was statistically significant. Our model performed similarly well in SLN-negative patients (CCC 0.929) and SLN-positive patients (CCC 0.889). The AJCC model performed well in SLN-negative patients (CCC 0.854), but not in SLN-positive patients (CCC 0.626). Using the validation data set, similar findings were obtained. Conclusions Our prognostic model provides superior survival estimates compared with the AJCC model for patients undergoing SLN biopsy. This online tool is available at www.melanomacalculator.com, and will provide important information that can be used to guide adjuvant therapy decisions and stratification in clinical trials.

Introduction: Overexpression of vascular endothelial growth factor (VEGF) in breast cancer tumors has been associated with resistance to anti-estrogen adjuvant therapy. We designed a pilot study of neoadjuvant letrozole and bevacizumab (anti-VEGF) to assess feasibility and short term efficacy in post-menopausal women with stage II/III, ER/PR positive breast cancer. Patients and Methods: Patients were treated with a neoadjuvant regimen of letrozole, 2.5 mg/day (PO) and bevacizumab 15 mg/kg every 3 weeks (IV) for a total of 24 weeks prior to surgical treatment of their breast cancer. Patients were followed for toxicity at three week intervals and tumor assessment (physical exam and tumor ultrasound) at six week intervals. Results: Twenty-five evaluable patients were treated. The regimen was well tolerated except for two patients who were taken off-study for difficult to control hypertension. Objective clinical response occurred in 17/25 patients (68%) including 16% CR and 52% PR. The four patients with clinical CR had pathologic CR in their breasts (16%) although one had residual tumor cells in axillary nodes. Two of the 17 responding patients were lost to follow-up; with a median follow-up of 50 months, no relapses have been seen in the 15 responsive patients, including 10 patients who received no adjuvant chemotherapy. Two patients with progressive disease at 9 and 16 weeks received neoadjuvant chemotherapy, surgery and radiation. One of these patients relapsed at 35 months and the other is NED at 44 months. Four patients had stable disease and all received adjuvant chemotherapy; one patient relapsed at 25 months, and the reminder are NED at 44-52 months. Overall, 2 out of 21 patients with adequate follow-up had disease reoccurrence (9.5%) at a median follow-up of 45 months. Conclusion: Combination neoadjuvant therapy with letrozole and bevacizumab was well tolerated and resulted in impressive clinical and pathologic responses. Data suggest that patients having an objective response to neoadjuvant therapy had excellent 4 year disease-free survival (100%) while relapsed occurred in 2 out of 6 patients who failed to have an objective response despite additional neoadjuvant or adjuvant chemotherapy. The Breast Cancer Translational Research Consortium has an ongoing randomized phase II trial of letrozole ± bevacizumab in this patient population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-04.

Background Current recommendations by the National Comprehensive Cancer Network and other groups suggest that follow-up of cutaneous melanoma may include chest radiography (CXR) at 6- to 12-month intervals. The aim of this study was to determine the clinical efficacy of routine CXR for recurrence surveillance in melanoma. Methods Post hoc analysis was performed on data from a prospective, randomized, multi-institutional study on melanoma ≥1.0 mm in Breslow thickness. All patients underwent excision of the primary melanoma and sentinel node biopsy with completion lymphadenectomy for positive sentinel nodes. Yearly CXR and clinical assessments were obtained during follow-up. Results of routine CXR were compared with clinical disease states over the course of the study. Results A total of 1,235 patients were included in the analysis over a median follow-up of 74 months (range, 12–138). Overall, 210 patients (17.0%) had a recurrence, most commonly local or in-transit. Review of CXR results showed that 4,218 CXR were obtained in 1,235 patients either before, or in the absence of, initial recurrence. To date, 88% ( n = 3,722) CXR are associated with no evidence of recurrence. Of CXR associated with recurrence, only 7.7% ( n = 38) of surveillance CXR were read as “abnormal.” Overall, 99% ( n = 4,180) of CXR were read as either “normal” or found to be falsely positive (read as “abnormal,” but without evidence of recurrence on investigation). Only 0.9% ( n = 38) of all CXR obtained were true positives (“abnormal” CXR, with confirmed first known recurrence). Among these 38 patients with true positive CXR, 35 revealed widely disseminated disease (multiorgan or bilateral pulmonary metastases); only 3 (0.2%) had isolated pulmonary metastases amenable to resection. Sensitivity and specificity for surveillance CXR in detecting initial recurrence were 7.7% and 96.5%, respectively. Conclusion The routine use of surveillance CXR provides no clinically useful information in the follow-up of patients with melanoma. CXR does not detect recurrence at levels sufficient to justify its routine use and, therefore, cannot be recommended as part of the standard surveillance regimen for these patients.

To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1–T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4–97.2%). No single gene or combination of study genes was predictive of recurrence. The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.

Introduction Tumor content or expression of vascular endothelial growth factor (VEGF) is associated with impaired efficacy of antiestrogen adjuvant therapy. We designed a pilot study to assess the feasibility and short-term efficacy of neoadjuvant letrozole and bevacizumab (anti-VEGF) in postmenopausal women with stage II and III estrogen receptor/progesterone receptor—positive breast cancer. Patients and Methods Patients were treated with a neoadjuvant regimen of letrozole orally 2.5 mg/day and bevacizumab intravenously 15 mg/kg every 3 weeks for a total of 24 weeks before the surgical treatment of their breast cancer. Patients were followed for toxicity at 3-week intervals, and tumor assessment (a physical examination and ultrasound) was performed at 6-week intervals. Positron emission tomography (PET) scans were performed before therapy and 6 weeks after the initiation of therapy. Results Twenty-five evaluable patients were treated. The regimen was well-tolerated, except in 2 patients who were taken off the study for difficulties controlling their hypertension. An objective clinical response occurred in 17 of 25 patients (68%), including 16% complete responses (CRs) and 52% partial responses. The 4 patients with clinical CRs manifested pathologic CRs in their breasts (16%), although 1 patient had residual tumor cells in her axillary nodes. Eight of 25 patients (32%) attained stage 0 or 1 status. The PET scan response at 6 weeks correlated with clinical CRs and breast pathologic CRs at 24 weeks ( P Conclusion Combination neoadjuvant therapy with letrozole and bevacizumab was well-tolerated and resulted in impressive clinical and pathologic responses. The Translational Breast Cancer Research Consortium has an ongoing randomized phase II trial of this regimen in this patient population.

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary melanomas. Median follow-up was 66 months. Except in one patient, the subsequent melanomas were thinner (median, 0.32 mm vs 1.50 mm; P < 0.0001). Compared with patients without MPM, patients with MPM were more likely to be older (median age, 54.5 vs 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM) ( P = 0.025), to have negative sentinel lymph nodes ( P = 0.021), or to lack lymphovascular invasion (LVI) ( P = 0.008) with the initial tumor. On multivariate analysis, age ( P = 0.028), LVI ( P = 0.010), and SSM subtype of the original melanoma ( P = 0.024) were associated with MPM. Patients with MPM and patients with single primary melanoma had similar DFS (5-year DFS 88.7 vs 81.3%, P = 0.380), but patients with MPM had better OS (5-year OS 95.3 vs 80.0%, P = 0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing surveillance of patients with melanoma is important given that a significant number will develop additional melanoma and nonmelanoma tumors. With close follow-up, second primary melanomas are usually detected at an early stage.

BACKGROUND: Sentinel lymph node (SLN) biopsy generally is recommended for patients who have melanoma with a Breslow thickness ≥1 mm. Most patients with melanoma between 1 mm and 2 mm thick have tumor-negative SLNs and an excellent long-term prognosis. The objective of the current study was to evaluate prognostic factors in this subset of patients and determine whether all such patients require SLN biopsy. METHODS: Patients with melanoma between 1 mm and 2 mm in Breslow thickness were evaluated from a prospective multi-institutional study of SLN biopsy for melanoma. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis to compare patients with melanoma that measured from 1.0 mm to 1.59 mm (Group A) versus patients with melanoma that measured from ≥1.6 mm to 2.0 mm thick (Group B). Univariate and multivariate analyses were performed to evaluate factors predictive of tumor-positive SLN status, DFS, and OS. RESULTS: The current analysis included 1110 patients with a median follow-up of 69 months. SLN status was tumor-positive in 133 of 1110 patients (12%) including 66 of 762 patients (8.7%) in Group A and 67 of 348 patients (19.3%) in Group B (P < .0001). On multivariate analysis, age, Breslow thickness, and lymphovascular invasion were independently predictive of a tumor-positive SLN (P < .05). DFS (P < .0001) and OS (P = .0001) were significantly better for Group A than for Group B. When tumor thickness was treated as either a continuous variable (P < 0.0001) or a categorical variable (P < .0001), it was significantly predictive of DFS and OS. On multivariate analysis, Breslow thickness, age, ulceration, histologic subtype, regression, Clark level, and SLN status were significant factors predicting DFS; and Breslow thickness, age, primary tumor location, sex, ulceration, and SLN status were significant factors predicting OS (P < .05). A subgroup of patients who had tumors

Introduction Some melanoma patients who undergo sentinel lymph node (SLN) biopsy will have false-negative (FN) results. We sought to determine the factors and outcomes associated with FN SLN biopsy.

Introduction. We sought to evaluate the factors that affect sentinel lymph node (SLN) metastasis and survival among young melanoma patients (≤30 y). Methods. The Sunbelt Melanoma Trial is a multi-institutional prospective randomized trial of patients aged 18 to 70 y. Statistical analyses were performed to determine if patients ≤30 y of age had a significantly different outcome in terms of SLN metastasis, disease-free survival (DFS), and overall survival (OS) compared to older patients. Results. The median age of the 3031 patients in this study was 50 y (range 18 to 77 y); the 315 patients (10.4%) ≤30 y old were compared with those >30 y old. Of the 1944 patients with follow-up, the median follow-up was 48 mo. On univariate analysis, younger patients were more often female (54.7% versus 40.9%, P < 0.0005), with tumors

PurposeTo evaluate the prognostic significance of molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR) in detecting occult melanoma cells in sentinel lymph nodes (SLNs) and circulating bloodstream.Patients and MethodsIn this multicenter study, eligibility criteria included patient age 18 to 71 years, invasive melanoma ≥ 1.0 mm Breslow thickness, and no clinical evidence of metastasis. SLN biopsy and wide excision of the primary tumor were performed. SLNs were examined by serial-section histopathology and S-100 immunohistochemistry. A portion of each SLN was frozen for RT-PCR. In addition, RT-PCR was performed on peripheral-blood mononuclear cells (PBMCs). RT-PCR analysis was performed using four markers: tyrosinase, MART1, MAGE3, and GP-100. Disease-free survival (DFS), distant–DFS (DDFS), and overall survival (OS) were analyzed.ResultsA total of 1,446 patients with histologically negative SLNs underwent RT-PCR analysis. At a median follow-up of 30 months, there was no difference in DFS, DDFS, or OS between the RT-PCR–positive (n = 620) and RT-PCR–negative (n = 826) patients. Analysis of PBMC from 820 patients revealed significant differences in DFS and DDFS, but not OS, for patients with detection of more than one RT-PCR marker in peripheral blood.ConclusionIn this large, prospective, multi-institutional study, RT-PCR analysis on SLNs and PBMCs provides no additional prognostic information beyond standard histopathologic analysis of SLNs. Detection of more than one marker in PBMC is associated with a worse prognosis. RT-PCR remains investigational and should not be used to direct adjuvant therapy at this time.

Objective: To better understand the factors associated with the well-established gender difference in survival for patients with melanoma. Background Data: Gender is an important factor in patients with cutaneous melanoma. Male patients have a worse outcome when compared with females. The reasons for this difference are poorly understood. Methods: This prospective multi-institutional study included patients aged 18 to 70 years with melanomas ≥1.0 mm Breslow thickness. Wide excision and sentinel lymph node (SLN) biopsy was performed in all patients. Clinicopathologic factors, including gender, were assessed and correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results: A total of 3324 patients were included in the covariate analyses; 1829 patients had follow-up data available and were included in the survival analyses. Median follow-up was 30 months. On univariate analysis, men (n = 1906) were more likely than women to be older than 60 years (P < 0.0001), have thicker melanomas (P < 0.0001), have primary tumor regression (P = 0.0054), ulceration (P < 0.0001), and axial primary tumor location (P < 0.0001). On multivariate analysis, age (P = 0.0002), thickness (P < 0.0001), ulceration (P = 0.015), and location (P < 0.0001) remained significant in the model. There was no difference in the rate of SLN metastasis between men and women (P = 0.37) on multivariate analysis. When factors affecting survival were considered, the prognosis was worse for men as validated by lower DFS (P = 0.0005), DDFS (P < 0.0001), and OS (P < 0.0001). Conclusions: Male gender is associated with a greater incidence of unfavorable primary tumor characteristics without an increased risk for nodal metastasis. Nonetheless, gender is an independent factor affecting survival.

Objective: To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. Background Data: The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. Methods: Effect of celecoxib in cell culture: The effect of 40 μmol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean ± SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80°C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. Results: Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase inl5-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 ± 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 ± 0.4 and 5.0 ± 0.1 cm, respectively. Expression of 15-LOX-1 relative to S9 was 30 in normal mucosa and significantly down-regulated to 11 in adenomas and 16 in carcinomas (P < 0.05). Conclusions: 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and associated with decreased survival. Administration of celecoxib restores 15-LOX-1 protein expression and induces apoptosis. Down-regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence, and reversal with celecoxib may represent one mechanism for chemoprevention of polyps or treatment of carcinomas.

Studies suggest the expression of cyclooxygenase-2 (COX-2) and matrilysin (MMP-7) increase in the early stages of colorectal carcinogenesis, however their interaction with other molecular markers is poorly understood. Results from cell line studies and mouse models suggest polyomavirus enhancer activator 3 (PEA3) may play a role in the activation of COX-2 and MMP-7 promoters. However, the role of E1A-F, the human homolog of murine PEA3, in colorectal cancer (CRC) development has not been elucidated. In this study, we used real-time reverse transcription (RT)-polymerase chain reaction (PCR) to measure the levels of E1A-F, COX-2, and MMP-7 in matched normal mucosa, adenomas, and/or carcinomas from 128 patients. Our results demonstrate significant overexpression of E1A-F and MMP-7 in adenomas and E1A-F, COX-2, and MMP-7 in carcinomas. In carcinomas, E1A-F expression was significantly associated with both COX-2 and MMP-7 overexpression. These results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7.

Low anterior resection and abdominoperineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. It is our hypothesis that selected patients with early T stage, well or moderate grade of differentiation, and small tumor size are good candidates for transanal excision in terms of minimal morbidity, low recurrence rate, and sphincter preservation. From January 1993 until August 2001 30 patients underwent transanal excision; three patients were excluded because they had histology other than adenocarcinoma. Factors analyzed included those related to the patient [age (years), gender, race, body mass index, and anal tone], tumor [size (cm), distance from the anal verge (cm), differentiation, and American Joint Committee on Cancer stage], and additional treatment. Median follow-up of the group was 40.7 months (range 0.6–99) and the primary end points were local and distant recurrence. Data are presented as mean (range). The median age of the group was 58.9 years (range 27–94); 52 per cent were female and 48 per cent were male. The mean body mass index was 25.9 (range 22.7–36.7). Preoperatively 81, 11, and 4 per cent of the patients had stage I, II, and III/IV cancer, respectively. Preoperative size of the tumor was 2.0 cm (1–3 cm), and distance from the anal verge was 5.0 cm (3–15 cm). Blood loss was 50 cm3(5–200 cm3), and there were no operative complications. Tumor differentiation levels were well (37%) and moderate (63%). All patients had negative margins. Additional treatment consisted of radiation therapy in seven patients (six postoperative and one preoperative). Chemotherapy was given to seven patients (six postoperative and one preoperative). The local recurrence rate was 7.4 per cent (two patients), and 3.7 per cent recurred distantly (one patient). Transanal excision of low rectal cancer in selected patients is an acceptable alternative to formal resection. Important selection criteria include early T stage, well or moderate differentiation, relatively small tumor size, and negative microscopic margins. The roles of radiation and chemotherapy remain controversial.

The proposed benefits of laparoscopy for certain surgical procedures have been decreased postoperative pain and hospital stay balanced against the proposed deficits of increased costs. We have reviewed our data to evaluate factors associated with patient, procedure, and hospital charges for patients undergoing open versus laparoscopic adrenalectomy and splenectomy during the same time period. Eighty-seven patients underwent adrenalectomy (n = 47) or splenectomy (n = 40) from October 30, 1995 to June 6, 2001 and were retrospectively reviewed. Patient and operative factors were analyzed by intent to treat; the major endpoints were operating room (OR) time in minutes, blood loss in cm3, length of hospital stay in days, and charges broken down by anesthesia/operation [OR/recovery room (RR)] and total charges in dollars x 1000. Comparisons of means were analyzed by unpaired t test; data are presented as mean ± SEM, and significance is defined as P < 0.05. Median age of the group was 47 years (range 20–77). Forty-five patients underwent a laparoscopic approach of which two were converted to open (4%) as compared with 42 undergoing an open operation; one patient from each group was excluded from outcome analyses because of prolonged hospitalization (>3 weeks). Operative mortality of the whole group was one per cent. There were no differences between the groups with respect to age, gender, or comorbidity. The laparoscopic group had significantly longer operative times and OR/RR charges. However, the length of hospital stay and the total charges for the patient undergoing a laparoscopic approach were significantly less ( P < 0.05). We conclude that a laparoscopic approach for adrenalectomy or splenectomy can be accomplished in approximately 95 per cent of patients selected for this procedure. Despite prolonged OR time and increased OR/RR charges the laparoscopic procedures resulted in significantly decreased length of hospital stay and overall patient charges. Laparoscopy is a safe and cost-effective approach and should be strongly considered in patients requiring adrenalectomy or splenectomy.

Background In recent years there has been a dramatic increase in the use of breast conservation therapy for patients with cancer. There are several factors associated with local recurrence but none are considered absolute contraindication for breast conserving therapy except multifocal carcinoma. This single-institution series investigates the effects of multiple factors on local relapse-free survival after breast-conserving therapy for women with invasive cancer.

To examine the incidence of local recurrence (LR) and factors associated with it in a population of patients who underwent skin-sparing mastectomy (SSM) and immediate reconstruction for invasive carcinoma.The efficacy of SSM has been challenged by concerns about increased risks of LR.A consecutive series of 173 patients (176 cancers) with invasive carcinoma underwent SSM and immediate breast reconstruction (June 1986 to December 1997). Data were analyzed by the Kaplan-Meier method, the log-rank statistic test, and the Cox proportional hazards model.Mean patient age was 47 +/- 9 years (27% were 40 or younger). The AJCC stages were 1 = 43%, 2 = 52%, and 3 = 5%. Thirty percent of tumors were poorly differentiated. With a median follow-up of 73 months, the LR rate was 4.5%. The mean local relapse-free interval was 26 months. Seventy-five percent of patients who presented with LR developed distant metastases and died of disease within a mean of 21 months. On univariate analysis, factors associated with higher LR rate were tumor stage 2 or 3, tumor size larger than 2 cm, node-positive disease, and poor tumor differentiation. Actuarial 1-, 3-, and 5-year overall survival rates were 98%, 94%, and 88%, respectively. On multivariate analysis, factors associated with decreased survival were advanced stage, presence of LR, and absence of hormone therapy. LR was a highly significant predictor of tumor-related death.There is a low incidence of LR after SSM, and it is associated with advanced disease at presentation. LR is an independent risk factor for tumor-related death.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including orthotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham from January 1990 through December 1999. Clinicopathologic and treatment factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or IV tumors. The median follow-up for survivors was 22 months. The 1-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial 1-, 3-, and 5-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.

Background: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area. Methods: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fisher’s exact test was used for comparisons. Significance was defined as P < .05. Results: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%. Conclusions: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

PURPOSE: The American Joint Committee on Cancer (AJCC) recently proposed major revisions of the tumor-node-metastases (TNM) categories and stage groupings for cutaneous melanoma. Thirteen cancer centers and cancer cooperative groups contributed staging and survival data from a total of 30,450 melanoma patients from their databases in order to validate this staging proposal. PATIENTS AND METHODS: There were 17,600 melanoma patients with complete clinical, pathologic, and follow-up information. Factors predicting melanoma-specific survival rates were analyzed using the Cox proportional hazards regression model. Follow-up survival data for 5 years or longer were available for 73% of the patients. RESULTS: This analysis demonstrated that (1) in the T category, tumor thickness and ulceration were the most powerful predictors of survival, and the level of invasion had a significant impact only within the subgroup of thin (≤ 1 mm) melanomas; (2) in the N category, the following three independent factors were identified: the number of metastatic nodes, whether nodal metastases were clinically occult or clinically apparent, and the presence or absence of primary tumor ulceration; and (3) in the M category, nonvisceral metastases was associated with a better survival compared with visceral metastases. A marked diversity in the natural history of pathologic stage III melanoma was demonstrated by five-fold differences in 5-year survival rates for defined subgroups. This analysis also demonstrated that large and complex data sets could be used effectively to examine prognosis and survival outcome in melanoma patients. CONCLUSION: The results of this evidence-based methodology were incorporated into the AJCC melanoma staging as described in the companion publication.

Gastrointestinal (GI) sarcomas are uncommon tumors with the majority of previous studies performed over long time intervals. The purpose of this review is to analyze our single-institution experience with primary GI sarcomas. Between January 1990 and June 1998,27 adult patients with primary GI sarcomas were identified in the tumor registry at the University Hospital, School of Medicine of University of Alabama at Birmingham and retrospectively reviewed. Patient, tumor, and treatment factors as well as expression of p53 and Ki-67 were analyzed with overall survival as the main outcome variable. Statistical analysis was performed by log rank test and Cox regression. Significance was defined as P < 0.05. Median age was 55 years (range 36–80 years). The stomach was the most common site of presentation (59%) followed by small bowel (29%). The average tumor size was 15 cm (range 2–46 cm). A complete resection was performed in 22 patients (81.5%). Fifteen tumors were classified as low grade (55.5%). Actuarial 3-year survival was 43 per cent with a median follow-up of 16 months. Overexpression of p53 and Ki-67 correlated with a trend to decreased survival but it did not reach statistical significance. Multivariate analysis found incomplete resection ( P = 0.00001) and high grade ( P = 0.003) to be significant negative prognostic factors. We conclude that GI sarcomas tend to be large tumors with most arising in the stomach and proximal GI tract. Complete surgical resection is associated with prolonged survival and despite the large size of these tumors should be attempted whenever possible.

BACKGROUND Ten- to 15-year survival results were analyzed from a prospective multi-institutional randomized surgical trial that involved 740 stages I and II melanoma patients with intermediate thickness melanomas (1.0 to 4.0 mm) and compared elective (immediate) lymph node dissection (ELND) with clinical observation of the lymph nodes as well as prognostic factors that independently predict outcomes. METHODS Eligible patients were stratified according to tumor thickness, anatomical site, and ulceration, and then prerandomized to either ELND or nodal observation. By using Cox stepwise multivariate regression analysis, the independent predictors of outcome were tumor thickness (P < .001), the presence of tumor ulceration (P < .001), trunk site (P = .003), and patient age more than 60 years (P = .01). RESULTS Overall 10-year survival was not significantly different for patients who received ELND or nodal observation (77% vs. 73%; P = .12). Among the prospectively stratified subgroups of patients, 10-year survival rates favored those patients with ELND, with a 30% reduction in mortality rate for the 543 patients with nonulcerated melanomas (84% vs. 77%; P = .03), a 30% reduction in mortality rate for the 446 patients with tumor thickness of 1.0 to 2.0 mm (86% vs. 80%; P = .03), and a 27% reduction in mortality rate for 385 patients with limb melanomas (84% vs. 78%; P = .05). Of these subgroups, the presence or absence of ulceration should be the key factor for making treatment recommendations with regard to ELND for patients with intermediate thickness melanomas. CONCLUSIONS These long-term survival rates from patients treated at 77 institutions demonstrate that ulceration and tumor thickness are dominant predictive factors that should be used in the staging of stages I and II melanomas, and confer a survival advantage for these subgroups of prospectively defined melanoma patients.

Methods of assigning patients with papillary or follicular thyroid cancer (well-differentiated thyroid cancer) to risk groups for the purpose of determining appropriate therapy have been developed. Despite these efforts, the optimal extent of surgery for intermediate-risk patients remains controversial.A retrospective study was conducted of 208 patients with well-differentiated thyroid cancer (DTC) from two institutions. Univariate and multivariate analysis of patient- and tumor-related variables was performed. A regression model was obtained, three risk groups (low, intermediate, and high) were defined, and survival curves were generated.Prognostic variables were age (P0.001), distant metastases (P0.001), tumor size (P0.001) and an aggressive growth pattern (P = 0.03) by univariate analysis and age (P0.001) and distant metastases (P0.001) by multivariate analysis. Tumor size (P = 0.07) was included in the regression model. Total thyroidectomy appeared to provide a survival advantage for intermediate risk patients. High-risk patients treated by lobectomy had a poorer prognosis.Total thyroidectomy may provide a survival advantage for intermediate-risk patients with DTC. A prospective randomized trial with 200 such patients is required to confirm this finding.

Background The management of micrometastatic disease from squamous cell carcinoma (SCC) of the oral tongue remains controversial. This study describes prognostic factors in the disease and reviews the role of elective neck dissection (END). Methods A retrospective analysis of all patients undergoing definitive surgical treatment of T1 and T2 SCC of the oral tongue between 1956 and 1994 at the University of Alabama at Birmingham was performed. Results Patient, disease, and treatment variables were compiled for 169 patients. Multivariate analysis showed age (p = .02), sex (p = .02), disease differentiation (p = .0003), and palpable lymphadenopathy (p = .02) to be significant prognostic variables. Fifteen patients underwent END and 6 were shown to have micrometastatic disease (40.0%). There were no neck recurrences in these patients, but END was not shown to improve survival. Conclusions The presence of poorly differentiated disease gave the worst prognosis in this population of patients with T1 and T2 SCC of the oral tongue. A high incidence of nodal micrometastatic disease and the absence of recurrent disease after END suggest that END is appropriate therapy for these patients. © 1999 John Wiley & Sons, Inc. Head Neck 21: 124–130, 1999.

The controversy over whether melanoma of the foot has a poorer prognosis than melanoma of the leg remains unresolved. This investigation used a case-control design to address this issue. This design consisted of a survival analysis of 119 cases with localized melanoma of the foot and 238 controls with localized melanoma of the leg that were matched on prognostic factors including tumor thickness, ulceration, surgical treatment, gender, year of diagnosis, and age. There was a statistically significant difference between the survival rates of cases and controls. The 5-year survival rate for cases was 74.3% compared to 85.2% for controls. At 10 years, the survival rate was 63.6% for cases and 77.2% for controls. Cases experienced a higher percentage of distant recurrences than controls. These results imply that patients with melanoma of the foot have a poorer survival than patients with melanoma of the leg after controlling for prognostic factors.

Background: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets—men aged 44–57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease—showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 199 6 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. Study Design: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 × 10 6 melanoma cells and 10 5.6 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10 5.4 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. Results: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44–57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). Conclusions: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.

Background and Objectives: Approximately one third of all melanoma patients will experience disease recurrence. Factors that affect patient survival following local, regional, or distant first recurrences of localized melanoma are the subject of this investigation. Methods: Survival times for a total of 1,085 first recurrences from 4,568 localized melanoma patients were examined in relationship to patient and disease factors by Cox regression. Nearly half (48.8%) of all first recurrences were regional, 21.8% were local, and 29.4% were distant recurrences. Results: Survival following recurrence differed significantly by site of recurrence (local, regional, or distant; P < 0.0001). Within each site, the median survival time did not differ by time of recurrence following diagnosis. Significant tumor factors for survival following local recurrence included tumor thickness (P = 0.0263) and lesion location (P < 0.0001). For regional recurrences, survival was significantly related to ulceration (P = 0.0105) and whether the recurrence was combined with a local recurrence (P = 0.0429). Survival following distant metastasis was related to number of distant sites (P < 0.0001) and whether a visceral site was involved (P < 0.0001). Conclusions: Patient and tumor characteristics predict survival following recurrence. Regardless of disease-free interval, long-term follow-up of melanoma patients is necessary. Patients experiencing distant metastasis have the shortest median survival time compared to patients experiencing local or regional recurrences.

BACKGROUND Over the past 2 decades, remarkable progress has been made in the identification of clinical and pathologic factors that affect the survival of patients with melanoma. Through the use of multivariate regression methods, key prognostic factors, such as tumor thickness, tumor ulceration, invasion level, and lesion location, have been identified. Clinical investigators are often interested in developing criteria to classify melanoma patients into different risk groups based on the key prognostic factors identified. However, classical multivariate regression models are generally less efficient in accomplishing this task than newly developed tree-based methods. METHODS In this study, the authors applied the exponential survival trees method to analyze a combined data set (n = 4568) from the University of Alabama at Birmingham and the Sydney Melanoma Unit in Camperdown, Australia. A survival tree was created according to prognostic factors that classified patients into homogeneous subgroups by survival. Six clinical and pathologic factors were included in the analysis. This tree-based method provided a superior means of prognostic classification and was shown to have greater ability to detect interactions among the variables than regression models. RESULTS Tumor thickness was found to be the most important prognostic factor, followed by tumor ulceration and primary lesion site. Some important interactions among these prognostic factors were identified. Five distinct risk groups, defined by tumor thickness, ulceration, and primary lesion site, were created. Patients who had tumor thickness less than or equal to 0.75 mm and lesions on their arms or legs had the best prognosis. Patients who had ulcerated tumors with thickness greater than 4.50 mm had the poorest prognosis. CONCLUSIONS The authors' analysis, based on exponential survival trees, provides a comprehensive, easy-to-use risk grouping system for classifying patients with localized melanoma. This grouping system would be useful in the clinical management of melanoma patients and in designing and analyzing clinical trials. Cancer 1997; 79:1122-8. © 1997 American Cancer Society.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

The cases reported in this paper were treated at 7 different clinical centers and present clinical and histologic observations from 15 patients and 21 human biopsies. The biopsies were taken from extraction sockets or dental implant sites which were grafted with either autologous intra-oral bone (6 sites), demineralized freeze-dried bone (DFDBA) (7 sites), or mineralized freeze-dried bone (MFDBA) (7 sites), or a combination of autologous bone, DFDBA and a barrier membrane (1 site). Six sites were grafted with DFDBA and augmented with expanded polytetrafluoroethylene (ePTFE) barrier membranes. Biopsies for histological evaluation were taken 4 to 13 months after implantation. A bone scoring system of 0 to 4 was used to evaluate the sections for dead implanted particles or the presence of vital bone. A bone score of 3 indicated the presence of dead implant material, blood vessels, islands of cartilage, osteoblasts, and new bone formation. A score of 4 indicated total replacement of the implanted material by the host bone. The average bone score for sites which received autologous bone was 2.33; for DFDBA sites, 0.98; and MFDBA was 0.18. The over-riding histologic characteristic of sites implanted with DFDBA or MFDBA was retention of non-vital graft particles within fibrous connective tissue. Biopsies taken adjacent to the host bed demonstrated incorporation of the allografts (osteoconduction). Sites grafted with autologous bone chips also demonstrated non-vital bone chips surrounded by vital host bone (osteoconduction). Sites which received barrier membranes did not appear to improve or impair bone healing of the augmented sites. Autologous bone chips harvested from within the oral cavity as well as allografts may serve as biologic fillers, but do not apparently contribute to osteoinduction. Autologous bone will eventually be resorbed and replaced by the host. DFDBA and MFDBA are resorbed very slowly and apparently do not contribute to osteoinduction. Allografts apparently are not resorbed by osteoclasts and therefore their continued use around dental implants is questioned.

PURPOSE: To determine the effect of a selective core biopsy program on the yield at needle-localization biopsy (NLB) of nonpalpable lesions. MATERIALS AND METHODS: Two hundred consecutive core biopsy samples of the breast were evaluated in an ongoing consecutive series of 1,172 NLB samples. RESULTS: Before implementation of the core biopsy program, the yield at NLB improved from 21% at 100 cases to 35% just before the introduction of core biopsy. After implementation, the yield increased gradually to 55% at 200 cases. The yield in masses increased from 21% at 100 cases to 43% just before the initiation of the core biopsy program and then increased dramatically to 72% at 200 cases. The percentage of small lesions detected did not change with implementation: 88% of invasive cancers measured less than 1.5 cm and 60% measured less than 1 cm in the last 100 cases. CONCLUSION: Appropriate selection of cases for core biopsy can more than double the yield of cancer in NLB samples without a decrease in the percent...

Background. In a Phase II trial, surgical adjuvant active specific immunotherapy using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate, vaccinia melanoma oncolysate (VMO), produced a significant disease free interval (DFI) in patients with International Union Against Cancer Stage II melanoma with positive lymph nodes. Therefore, a Phase III randomized prospective, double-blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine the efficacy of VMO to increase the DFI and the overall survival in this group of patients with Stage II disease. Methods. Two hundred and fifty patients with Stage II melanoma were divided into two postsurgical groups. One group received VMO (total protein equals 2 mg/ml) and the other received the placebo of live vaccinia vaccine virus (V) (105.4 TCID50/ml), an adjuvant component of the VMO. Patients initially received these biologies once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. All surviving patients have been followed for at least 30 months. Results. Statistical analysis of survival data (n = 217) for this first interim analysis shows that there is no statistically significant (P = 0.99) increase in DFI of patients treated with VMO (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for patients treated with VMO and 37.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66 and 36%, respectively, of patients treated with V were free of melanoma. The median overall survival is not available because the pa-tients treated with VMO have not yet reached the 50% mark and the median overall survival is 45.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of VMO-treated patients survived when compared with 66 and 36%, respectively, of pa-tients treated with V. Although the overall survival of pa-tients treated with VMO is not statistically significant (P = 0.88) at this point, there is an increasing trend in the overall survival of patients treated with VMO; a 10% increase at the 4-year time point. Moreover, in the subset analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival at 4-year time point when compared with male patients treated with V (n = 67) (P = 0.19) at the same time point and male patients (n = 20) between the ages of 44 and 57 having 1-5 positive lymph nodes showed a 37% difference in overall survival at the 4-year time point when compared with those patients treated with V (n = 18) (P = 0.13) at the same time point. Conclusion. In this first interim analysis, active specific immunotherapy with VMO vs. V showed no difference in the disease free interval or overall survival. Subset analyses likewise showed no significant differences in outcome but the data suggest a potential difference in immunoreactivity between male and female patients with melanoma that awaits further follow up and may merit further investigation.

Background: Trends in the care of patients with cancer are monitored annually by the Commission on Cancer of the American College of Surgeons. In 1991 a patient care evaluation study of breast cancer was conducted, which among other questions examined the correlation of health insurance with type or quality of care delivered for breast cancer on a national basis. Methods: The tumor registry system of the American College of Surgeons was used to obtain data on patients with breast cancer diagnosed in 1983 and 1990. Trends in diagnosis and treatment were correlated with the type of insurance or lack of insurance. Results: Data were obtained from hospitals in 50 states on a total of 41,651 patients. The largest number of patients were covered by Medicare. Fewer than 5% were considered medically indigent. Medically indigent patients presented with higher stage disease and did not participate in a trend toward downstaging, which occurred between the two study years. The treatment of medically indigent patients appeared to be appropriate and comparable with better insured patients. Insurance type (health maintenance organization vs. private) did not affect stage, treatment, or outcome. Decisions to use controversial therapies, such as chemotherapy for stage I disease, did not appear to be financially driven. Conclusion: A nationwide pattern of care study for breast cancer indicates that medically indigent patients present with more advanced disease compared with better insured patients, but once the diagnosis is made, treatment and outcome have little to do with insurance type.