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Kelly M McMasters

Publications and source records attributed to Kelly M McMasters.

At least 55 records · Page 3Linked to original sources
PubMed2004

Lessons learned from the Sunbelt Melanoma Trial.

The Sunbelt Melanoma Trial is an ongoing multicenter prospective randomized trial that involves 79 centers and over 3600 patients from across the United States and Canada. This is one of the first large randomized studies to incorporate molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR). While the results related to the primary endpoints of the study are not yet available, several analyses have shed light on many aspects of sentinel lymph node (SLN) biopsy and melanoma prognostic factors. In particular, we have developed a practical definition of sentinel nodes based on the degree of radioactivity. We have established the low rate of postoperative complications associated with SLN biopsy as compared to complete lymph node dissection. We have identified factors that predict the presence of SLN metastases. In contrast, we have been unable to identify factors that indicate a low risk of non-sentinel node metastases in patients with a positive sentinel node, suggesting that completion lymphadenectomy is appropriate for such patients. We have further established the value of identifying interval or in-transit sentinel nodes, which can be the only site of nodal metastasis. We have evaluated the particular challenges associated with SLN biopsy of head and neck melanomas, have evaluated the patterns of early recurrence, and have identified an interesting correlation between increasing patient age and a number of prognostic factors. Future analyses will evaluate the benefit of early therapeutic lymphadenectomy and early institution of adjuvant interferon alfa-2b therapy, as well as the validity of molecular staging.

Antineoplastic Agents↗
PubMed2004

Validation of subareolar and periareolar injection techniques for breast sentinel lymph node biopsy.

HYPOTHESIS: Subareolar or periareolar injection of radioactive technetium sulfur colloid is equivalent to other injection techniques for breast cancer sentinel lymph node (SLN) biopsy. DESIGN AND SETTING: Prospective, multicenter clinical trial. PATIENTS: A total of 3961 individuals with clinical stage I and II breast cancer. INTERVENTIONS: All patients underwent attempted SLN biopsy followed by completion axillary dissection. Injection technique was determined by the preference of each participating surgeon. Most surgeons had little or no experience with SLN biopsy before participation in this study. MAIN OUTCOME MEASURES: The SLN identification and false-negative rates. RESULTS: An SLN biopsy was performed in 3961 patients using blue dye alone or radioactive colloid plus blue dye. Subareolar and periareolar radioactive colloid injection techniques were associated with SLN identification rates of 99.3% and 95.6%, respectively, with false-negative rates of 8.3% and 8.9%, respectively. The identification rates were significantly higher for these 2 techniques than for peritumoral injection of radioactive colloid (91.1%) or the use of blue dye alone (88.5%) (P<.001). The false-negative rates were similar for all techniques. CONCLUSIONS: Although many medical centers have adopted subareolar and periareolar radioactive colloid injections because of their simplicity and convenience, a paucity of data from a few single-institutional studies has existed to substantiate the false-negative rates associated with these techniques. The results of this multicenter study establish the validity of subareolar and periareolar radioactive colloid injections and support the hypothesis that the lymphatic drainage of the entire breast is to the same few SLNs.

Adult↗
PubMed2004

Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique.

OBJECTIVE: The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. METHODS: We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. RESULTS: Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P = 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P = 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P = 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P = 0.003). CONCLUSIONS: In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins.

Adult↗
PubMed2004

Morbidity of adjuvant hepatic arterial infusion pump chemotherapy in the management of colorectal cancer metastatic to the liver.

BACKGROUND: Surgical resection remains the treatment of choice for patients with colorectal cancer metastatic to the liver. Hepatic arterial infusion pump (HAIP) chemotherapy in combination with surgical resection has been demonstrated in a recent study to improve disease-free and overall survival for patients with colorectal cancer metastatic to the liver. Other reports, however, have indicated significant toxicity related to HAIP chemotherapy in the form of biliary sclerosis. Thus, the value of adjuvant HAIP chemotherapy following hepatic resection or ablation remains controversial. The aim of this study was to examine the survival and toxicity in a single institutional experience with adjuvant HAIP chemotherapy. METHODS: Review of a prospective hepatobiliary database was performed. HAIP were placed in the standard technique following resection and/or radiofrequency ablation (RFA) of all liver metastases. Patients received floxuridine (FUDR) via the HAIP at standard doses. Complications were graded according to a standard 5-point grading scale. Statistical analysis was performed by chi(2) test. RESULTS: Thirty-four of 86 patients underwent placement of HAIP at the time of hepatic resection or ablation between January 1999 and November 2002. The HAIP group demonstrated a significantly greater (P <0.05) number (median 5 vs. 2) and size (median 5 cm vs. 3 cm) of hepatic lesions compared to the group without HAIP. The HAIP group experienced a greater frequency of complications (53% vs. 33%), with 6 (18%) patients in the HAIP group demonstrating biliary sclerosis. There were no deaths within 30 days of surgery. Median survival was similar in both groups (HAIP 20 months, no HAIP 24 months). CONCLUSIONS: Patients in the HAIP group had significantly worse overall predictors of outcome in metastatic colorectal cancer, yet the median overall survival in both groups was similar. However, adjuvant HAIP chemotherapy was associated with significantly greater morbidity. Given the availability of newer active systemic agents and regimens, the value of adjuvant HAIP chemotherapy remains controversial.

Adult↗
PubMed2004

Sentinel lymph node biopsy in juvenile secretory carcinoma.

A 9-year-old girl presented with a 3-year history of a right breast mass. Excisional biopsy showed a secretory carcinoma. A treatment plan of simple mastectomy and axillary sentinel lymph node biopsy was chosen. She remains free of disease at 3-year follow-up. Sentinel lymph node biopsy offers an approach to stage the axillary lymphatic basin with a lower complication rate than formal dissection. The authors advocate its use in the treatment of pediatric breast cancer.

Breast Neoplasms↗
PubMed2004

E1A-induced apoptosis does not prevent replication of adenoviruses with deletion of E1b in majority of infected cancer cells.

Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both E1B19K and E1B55K resulted in cellular DNA degradation. However, less than 20% of human lung cancer cells infected with a virus deleted for both E1B19K and E1B55 K had evidence of chromatin condensation and multiple-micronuclei formation (apoptotic hallmarks); these cells could not produce infectious viral particles. The majority of cancer cells infected with viruses deleted for the entire E1b gene did not undergo extended apoptosis and produced abundant viral progeny. Thus, only a fraction of cancer cells underwent apoptosis and did not allow E1b-deleted viruses to replicate, while the majority of cancer cells were resistant to E1A-induced apoptosis and could support virus-selective replication. The results of this study imply that, in addition to inhibiting E1A-induced apoptosis, E1B proteins may contribute other important roles in the viral life cycle. Our results also suggest that combining virus-induced apoptosis and selective viral replication into one vector will be a novel approach to destroy cancer cells.

Adenoviridae Infections↗
PubMed2004

Correlation between prognostic factors and increasing age in melanoma.

BACKGROUND: Age of patients with melanoma varies directly with mortality and inversely with the presence of sentinel lymph node (SLN) metastasis. To gain further insight into this apparent paradox, we analyzed the relationship between age and other major prognostic factors. METHODS: The Sunbelt Melanoma Trial is a prospective, randomized study with 79 institutions involving SLN biopsy for melanoma. Eligible patients were 18 to 70 years old with melanoma of > or = 1.0-mm Breslow thickness and clinically N0 regional lymph nodes. SLNs were evaluated by serial histological sections and immunohistochemistry for S-100 protein. RESULTS: A total of 3076 patients were enrolled in the study, with a median follow-up of 19 months. Five age groups were examined: 18 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years. Trends between age and several key prognostic factors was identified: as age group increased, so did Breslow thickness (analysis of variance; P <.001), the incidence of ulceration and regression, and the proportion of male patients (each variable: chi2, P <.001). The incidence of SLN metastasis, however, declined with increasing age (chi2; P <.001). CONCLUSIONS: As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients-all poor prognostic factors. However, the frequency of SLN metastasis declines with increasing age. It is not known whether this represents a decreased sensitivity (higher false-negative rate) of the SLN procedure in older patients or a different biological behavior (hematogenous spread) of melanomas in older patients.

Adolescent↗
PubMed2004

Sentinel lymph node biopsy for breast cancer: from investigational procedure to standard practice.

Sentinel lymph node biopsy, popularized in melanoma, has revolutionized the management of breast cancer. While the morbidity associated with axillary node dissection was once thought to be a requisite risk in order to appropriately stage the axilla, large validation studies have demonstrated that sentinel lymph node biopsy is a minimally invasive technique that can accurately predict nodal status. This technique has become an accepted practice in many centers, but there remain many controversies surrounding the technique itself, the pathologic evaluation of the sentinel node and the optimal management of patients with minimal nodal disease. The historic roots of this technique are discussed, along with the controversial issues surrounding the technique and the clinical trials that are currently ongoing.

Breast Neoplasms↗
PubMed2004

Intraoperative frozen section of sentinel nodes: a formal decision analysis.

In the absence of data from randomized trials, a formal decision analysis was undertaken to quantify the relative value of the patients' quality of life with regard to performing intraoperative frozen section (FS) versus permanent section (PS) analysis of the sentinel lymph node (SLN) for breast cancer. Assumptions for this analysis were based on data from 203 nodal basins where the prevalence of nodal metastasis was 26.1 per cent; the FS sensitivity was 68 per cent and FS false-positive rate was 0.7 per cent. DATA 4.0 was used to model the decision analysis. The two branches of the tree represent the two surgical options of either FS analysis intraoperatively, accompanied by immediate axillary dissection for positive nodes versus PS analysis followed by reoperative axillary dissection. The expected utility (EU) with the FS strategy is 0.9736; the EU for PS is 0.9732, suggesting no definite preference for either procedure. Overall, the toss-up is very robust. The decision to choose FS versus PS should be based on individual patient risk and preference because the decision analysis indicated that these two options are equivalent with respect to patient quality of life.

Adult↗
PubMed2003

Adjuvant chemotherapy for breast cancer: how presentation of recurrence risk influences decision-making.

PURPOSE: The purpose of this study was to examine the impact of four methods of communicating survival benefits on chemotherapy decisions. We hypothesized that the four methods of communicating mathematically equivalent risk information would lead to different chemotherapy decisions. METHODS: Each participant received two hypothetical scenarios regarding their mother (a postmenopausal woman with an invasive, lymph node-negative, hormone receptor-positive breast cancer) and was asked to decide whether they would encourage their mother to take chemotherapy in addition to surgery and tamoxifen. In the part 1, participants received one of four methods of describing the chemotherapy survival benefit: (1) relative risk reduction, (2) absolute risk reduction, (3) absolute survival benefit, or (4) number needed to treat. In part 2, each participant received all four methods. Following each decision, participants were asked to rate their confidence and confusion regarding their decision. RESULTS: Participants included 203 preclinical medical students. In part 1, participants who received relative risk reduction information were significantly more likely to endorse chemotherapy. In part 2, there were no treatment decision differences when participants received all four methods of communicating survival benefits of chemotherapy. However, receiving all four methods led to significantly higher ratings of confusion. In deciding on endorsing chemotherapy, participants understood the information best when presented with data in the absolute survival benefit format. CONCLUSION: These results support the hypothesis that the method used to present information about chemotherapy influences treatment decisions. Absolute survival benefit is the most easily understood method of conveying the information regarding benefit of treatment.

Adult↗
PubMed2003

Adenovirus with insertion-mutated E1A selectively propagates in liver cancer cells and destroys tumors in vivo.

The adenovirus E1A proteins are involved in the transcriptional activation of viral and cellular genes needed for controlling cell cycle and virus replication. Undifferentiated embryonic carcinoma cells have the ability to produce an E1A-like activity that can induce the expression of E1A-targeted adenoviral and cellular genes in the absence of the E1A products. Differentiated embryonic carcinoma cells lose the ability to produce the E1A-like activity. In this study, we investigated the E1A-like activity in cancer cells with an adenovirus having a mutated E1a gene. The mutation is generated by the insertion of a large DNA fragment in the E1a gene and interrupts the COOH-terminal region of both the E1A 12S and 13S proteins. The E1a-mutated virus can efficiently replicate in HepG2 and Hep3B liver cancer cells and produce high titers of virus. Replication of the E1a-mutated virus inhibits tumor formation and destroys tumors in vivo. The results obtained in this study imply that cancer cells may produce an E1A-like activity to support the selective replication of mutated virus in cancer cells. In addition, we found that although the E1a-mutated virus could not replicate in Huh1.cl2 liver cells, the viral DNA could amplify in the cells. This result suggests that replication of adenoviral DNA is necessary, but not sufficient, for generating infectious viral progeny and destroying tumor cells.

Adenovirus E1A Proteins↗
PubMed2003

Current management of melanoma: benefits of surgical staging and adjuvant therapy.

Issues regarding appropriate management of stage I to III melanoma are addressed. Accurate surgical staging is critical to identifying patients who can benefit from therapeutic lymph node dissection and adjuvant therapy. Patients with primary tumors > or = 1 mm thick are appropriate candidates for sentinel lymph node biopsy, and node-positive patients benefit from therapeutic lymphadenectomy. Although the overall survival benefit of high-dose interferon has been questioned, the weight of evidence supports the use of adjuvant therapy in patients with stage IIB and III disease.

Antineoplastic Agents↗
PubMed2003

New TNM melanoma staging system: linking biology and natural history to clinical outcomes.

The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.

Clinical Trials as Topic↗