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Janice N Cormier

Publications and source records attributed to Janice N Cormier.

33 records · Page 2Linked to original sources
PubMed2006

Polymorphisms in the DNA repair genes XPC, XPD, and XPG and risk of cutaneous melanoma: a case-control analysis.

Sunlight causes DNA damage, including bulky lesions that are removed effectively by the nucleotide-excision repair (NER) pathway. There are at least eight core NER proteins participating in the pathway, and genetic variations in their genes may alter NER functions. We hypothesized that some NER variants are associated with risk of cutaneous melanoma. In a hospital-based case-control study of 602 non-Hispanic White patients with cutaneous melanoma and 603 age- and sex-matched cancer-free controls, we genotyped five common non-synonymous single-nucleotide polymorphisms identified to date and assessed their associations with risk of cutaneous melanoma. We found that a significantly increased risk of cutaneous melanoma was associated with XPD 751Lys/Gln [adjusted odds ratio (OR), 1.55 and 95% confidence interval (95% CI), 1.12-2.16] and XPD 751Gln/Gln (OR, 1.66; 95% CI, 1.03-2.68) genotypes compared with the XPD 751Lys/Lys genotype as well as XPD312Asp/Asn (OR, 1.54; 95% CI, 1.11-2.12) and XPD312Asn/Asn (OR, 1.75; 95% CI, 1.05-2.90) genotypes compared with the XPD 312Asp/Asp genotype. This increased risk was not observed in the other three XPC and XPG single-nucleotide polymorphisms. Moreover, the number of the observed XPD at-risk genotypes (i.e., 312Asn/Asn+Asn/Asp and 751Gln/Gln+Lys/Gln) was associated with cutaneous melanoma risk in a dose-response manner (OR, 1.47; 95% CI, 0.97-2.23 for one at-risk genotype; OR, 1.83; 95% CI, 1.29-2.61 for two at-risk genotypes; P(trend) < 0.001). However, we found no evidence of any interaction between XPD genotypes with XPC and XPG genotypes or the known risk factors. We concluded that genetic variants of the XPD gene might serve as biomarkers for susceptibility to cutaneous melanoma.

Case-Control Studies↗
PubMed2005

In vitro sensitivity to ultraviolet B light and skin cancer risk: a case-control analysis.

BACKGROUND: Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established. METHODS: We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM. CONCLUSIONS: UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.

Adult↗
PubMed2005

Angiosarcoma of the breast.

BACKGROUND: Angiosarcoma of the breast is a rare entity. The objectives of this study were to evaluate prognostic factors and determine outcomes in a large contemporary series of patients. METHODS: Clinical and pathologic factors were analyzed in all patients with angiosarcoma of the breast treated between 1990 and 2003. Overall survival (OS) and disease-free survival (DFS) were estimated using the methods of Kaplan and Meier. Multivariate analyses were performed to evaluate prognostic factors. RESULTS: Fifty-five women with angiosarcoma of the breast were identified. The median age was 49.1 years, and the median follow-up time was 3.7 years. The median OS and DFS were 2.96 years and 2.26 years, respectively. For the 32 patients with primary angiosarcoma of the breast 5-year OS was 59%. Twenty-three (42%) patients had received prior radiation therapy for the treatment of breast cancer. These patients with radiation therapy-associated angiosarcoma were on average 30 years older and less likely to present with distant metastatic disease than patients presenting with radiation-naive angiosarcoma of the breast. Although radiation-naive patients appeared to have had better early DFS and OS, the Kaplan-Meier curves were not statistically different between patients with radiation therapy-associated disease and radiation therapy-naive patients. On multivariate analysis, tumor recurrence (P = 0.006) was the only significant adverse prognostic factor noted for OS. CONCLUSIONS: In this series of 55 patients with angiosarcoma of the breast, radiation therapy-naive angiosarcomas occurred in younger patients, but they behaved similarly to radiation therapy-associated angiosarcomas.

Adult↗
PubMed2005

Combined-modality therapy for patients with regional nodal metastases from melanoma.

PURPOSE: To evaluate the outcome and patterns of failure for patients with nodal metastases from melanoma treated with combined-modality therapy. METHODS AND MATERIALS: Between 1983 and 2003, 466 patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. Surgery was a therapeutic procedure for clinically apparent nodal disease in 434 patients (regionally advanced nodal disease). Adjuvant radiation was generally delivered with a hypofractionated regimen. Adjuvant systemic therapy was delivered to 154 patients. RESULTS: With a median follow-up of 4.2 years, 252 patients relapsed and 203 patients died of progressive disease. The actuarial 5-year disease-specific, disease-free, and distant metastasis-free survival rates were 49%, 42%, and 44%, respectively. By multivariate analysis, increasing number of involved lymph nodes and primary ulceration were associated with an inferior 5-year actuarial disease-specific and distant metastasis-free survival. Also, the number of involved lymph nodes was associated with the development of brain metastases, whereas thickness was associated with lung metastases, and primary ulceration was associated with liver metastases. The actuarial 5-year regional (in-basin) control rate for all patients was 89%, and on multivariate analysis there were no patient or disease characteristics associated with inferior regional control. The risk of lymphedema was highest for those patients with groin lymph node metastases. CONCLUSIONS: Although regional nodal disease can be satisfactorily controlled with lymphadenectomy and radiation, the risk of distant metastases and melanoma death remains high. A management approach to these patients that accounts for the competing risks of distant metastases, regional failure, and long-term toxicity is needed.

Adolescent↗
PubMed2005

Population-based assessment of surgical treatment trends for patients with melanoma in the era of sentinel lymph node biopsy.

PURPOSE: The surgical staging of melanoma dramatically changed with the introduction of sentinel lymph node (SLN) biopsy. In this study, Surveillance, Epidemiology, and End Results (SEER) data were examined to determine how surgical treatment is being carried out and whether SLN biopsy is being performed in melanoma patients in conformance with National Comprehensive Cancer Network (NCCN) guidelines. PATIENTS AND METHODS: The SEER database (1998 to 2001) was searched for all patients with invasive melanoma. NCCN guidelines were used to define optimal stage-specific surgical treatment. Treatment trends in patients with stages I to III disease were summarized, and multivariate analyses were performed to identify factors associated with nonadherence with treatment guidelines. RESULTS: A total of 21,867 melanoma patients were identified; 18,499 of these patients met the inclusion criteria. The number of patients diagnosed with stage III melanoma increased by 55.7% over the study period, and this corresponded to a 53% increase in the number of SLN biopsies performed annually. The odds ratios for nonadherence were 2.32, 2.27, and 1.54 for stages IB, II, and III disease, respectively, compared with stage IA melanoma. Multivariate analyses revealed that age more than 65 years, marital status, minority populations, and primary tumor location were associated with nonadherence with guidelines. Treatment patterns among tumor registries also varied significantly. CONCLUSION: Stage migration is evident in the SEER registries in consort with increasing use of SLN biopsy. Although treatment trends are improving, SLN biopsy continues to be underused, particularly in the elderly and minority populations, in patients with truncal and head/neck melanomas, and also in some geographic regions of the United States.

Adult↗
PubMed2005

Predictors and natural history of in-transit melanoma after sentinel lymphadenectomy.

BACKGROUND: In-transit recurrence is a unique and uncommon pattern of treatment failure in patients with melanoma. Little information exists concerning the incidence, predictors, and natural history of in-transit disease since the introduction of sentinel lymph node biopsy (SLNB). METHODS: Between 1991 and 2001, 1395 patients with primary melanoma underwent SLNB. Univariate and multivariate logistic regression analyses were performed to examine the association among known clinicopathologic factors, in-transit recurrence, and distant metastatic failure after the development of in-transit disease. RESULTS: With a median follow-up of 3.9 years, 241 patients (17.3%) experienced disease recurrence, including 91 (6.6%) who developed in-transit recurrence. Independent predictors of in-transit recurrence included age >50 years, a lower extremity location of the primary tumor, Breslow depth, ulceration, and sentinel lymph node (SLN) status. Of the 69 patients who presented with in-transit disease as the sole site of first recurrence, 39 developed distant disease. By univariate analysis, predictors of distant failure among patients with in-transit disease included SLN status, largest metastatic focus in the SLN >2.5 mm2, subcutaneous location of in-transit disease, in-transit tumor size > or = 2 cm, and a disease-free interval before in-transit recurrence of <12 months. In-transit tumor size remained a significant predictor of distant metastasis by multivariate analysis (odds ratio, 9.69). CONCLUSIONS: The overall incidence of in-transit metastases in patients undergoing SLNB is low and does not seem to have increased since the introduction of the SLNB technique. In-transit recurrence, as well as subsequent distant metastatic failure, can be predicted on the basis of adverse tumor factors and SLN status.

Adolescent↗
PubMed2004

Cohort analysis of patients with localized, high-risk, extremity soft tissue sarcoma treated at two cancer centers: chemotherapy-associated outcomes.

PURPOSE: Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) have high risks of distant recurrence and death. The role of chemotherapy for these patients remains controversial despite several randomized trials and a meta-analysis. METHODS: We reviewed the treatments and outcomes of 674 consecutive adult patients presenting with primary stage III extremity STS between 1984 and 1999. Pre- or postoperative doxorubicin-based chemotherapy was used in a nonrandomized fashion in approximately half of this high-risk population. The objective of this review was to evaluate the impact of chemotherapy while accounting for known prognostic variables. RESULTS: Among 674 patients, 338 (50%) were treated with local therapy only, and 336 (50%) were treated with local therapy plus chemotherapy. The median follow-up for survivors was 6.1 years. Five-year local and distant recurrence-free interval probabilities were 83% and 56%, respectively, for the two groups combined. The 5-year disease-specific survival (DSS) rate was 61%. Cox regression analyses showed a time-varying effect associated with chemotherapy. During the first year, the hazard ratio associated with DSS for patients treated with chemotherapy versus no chemotherapy was 0.37 (95% CI, 0.20 to 0.69; P = .002). Thereafter, this hazard ratio was 1.36 (95% CI, 1.02 to 1.81; P = .04). CONCLUSION: It seems that the clinical benefits associated with doxorubicin-based chemotherapy in patients with high-risk extremity STS are not sustained beyond 1 year. These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up.

Adult↗
PubMed2004

Interval between surgery and radiotherapy: effect on local control of soft tissue sarcoma.

PURPOSE: To evaluate the clinical significance of the interval between surgery and postoperative radiotherapy (RT) for patients with soft tissue sarcoma. METHODS AND MATERIALS: The records of 799 patients who underwent postoperative RT for soft tissue sarcoma between 1960 and 2000 were retrospectively reviewed. Univariate and multivariate analyses were used to evaluate the potential impact of the timing of postoperative RT on the rate of local control (LC). RESULTS: The actuarial overall LC rate was 79% at 10 years and 78% at 15 years. Univariate analysis indicated that the factors associated with an inferior 10-year LC rate were positive resection margins (p <0.0001); treatment for recurrent disease (p <0.0001); primary location in the head and neck or deep trunk (p <0.0001); age >64 years (p <0.0001); histopathologic subtype of malignant fibrous histiocytoma, neurogenic sarcoma, or epithelioid sarcoma (p = 0.01); tumor size >10 cm (p = 0.02); postoperative radiation dose <64 Gy (p = 0.03); and high histologic grade (p = 0.05). On multivariate analysis, all these factors remained statistically significant, except for high histologic grade and large size. A delay between surgery and the start of RT of >30 days was associated with a decreased 10-year LC rate, but this association was not statistically significant (76% vs. 83%, p = 0.07). The potential association between RT delay and inferior LC could be explained by an imbalance in the distribution of other prognostic factors. CONCLUSION: The interval between surgery and RT did not significantly impact the 10-year LC rate. These findings indicate that an RT delay should not be viewed as an independent adverse factor for LC and that treatment intensification may not be necessary for patients in whom a treatment delay has already occurred.

Adolescent↗
PubMed2004

Sentinel lymph node biopsy following neoadjuvant chemotherapy: review of the literature and recommendations for use in patient management.

Breast cancer is a significant health problem worldwide and is one of the leading causes of cancer-related mortality in women. Preoperative chemotherapy has become the standard of care for patients with locally advanced disease and is being used more frequently in patients with early-stage breast cancer. Sentinel lymph node biopsy has shown great promise in the surgical management of breast cancer patients, but its use following preoperative chemotherapy is yet to be determined. Eleven studies have been published with respect to the accuracy of sentinel lymph node biopsy following neoadjuvant chemotherapy. Ten studies showed favourable results, with the ability to identify a sentinel lymph node in 84% to 98% of cases, and reported false negative rates ranging from 0% to 20%. The accuracy of sentinel lymph node biopsy following preoperative chemotherapy for breast cancer ranges from 88% to 100%, with higher rates when specific techniques and inclusion criteria are applied. The published literature supports the use of sentinel lymph node biopsy for assessment of the axilla in patients with clinically node-negative disease following preoperative chemotherapy.

Antineoplastic Agents↗
PubMed2003

Is there a role for surgery in patients with "unresectable" cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?

BACKGROUND: Imatinib mesylate (Gleevec) is being studied as adjuvant chemotherapy for the treatment of cKIT+ gastrointestinal stromal tumors (GISTs). Early reports using Gleevec for the treatment of unresectable GISTs have shown 50% to 60% partial response rates based on radiographic evaluation alone. No study has yet correlated radiographic response with pathologic findings. This retrospective review of patients with cKIT+ GISTs who received Gleevec prior to surgical resection examines the pathologic response to therapy and the feasibility of surgical resection after treatment. METHODS: Patients with cKIT+ GISTs were identified from the institutional sarcoma database. Patients were included if they had pathologic confirmation of cKIT mutation and therapy with Gleevec. The pretreatment and preoperative radiographs, surgeons' operative notes, and pathology reports were reviewed for documentation of the extent of disease. RESULTS: Between January 2001 and Octorber 2002, 126 patients with unresectable cKIT + GISTs treated with Gleevec were identified. Of these 126 patients, 17 have subsequently undergone surgical resection after a median of 10 months (range 2 to 16) of treatment with Gleevec. Based on computed tomographic (CT) scanning, 1 (6%) patient had evidence of a complete tumor response, 12 (70%) patients had a partial response, 3 (24%) patients had stable disease, and 1 (6%) patient had progressive disease. Posttreatment/preoperative CT imaging documented an overall response rate of 76%. The pathologic review of the operative specimens showed that 2 (12%) patients had a complete response to therapy, 11 (65%) had a partial response to therapy, 3 (18%) patients had no evidence of treatment effect on the excised tumor, 1 patient had progressive disease. Sixteen patients (94%) underwent complete surgical resection of disease, including 3 patients with no pathologic evidence of response to therapy. One patient had progression of disease and was unresectable at surgical exploration. CONCLUSIONS: This series is the first to present pathologic data after the treatment of cKIT+ GISTs with Gleevec. In this series, the majority of responses were limited to partial responses, indicating that surgical resection remains a vital component of the treatment plan for patients with cKIT+ GISTs. This series is consistent with previous reports indicating that complete responses are extremely rare in response to treatment with Gleevec. Patients with advanced disease may benefit from a course of neoadjuvant therapy with Gleevec followed by resection, even when there is evidence of multifocal disease. A prospective evaluation of neoadjuvant Gleevec therapy for advanced cKIT+ GISTs is warranted.

Adult↗
PubMed2002

Gastrointestinal stromal tumors: rationale for surgical adjuvant trials with imatinib.

Gastrointestinal stromal tumors (GISTs) constitute the majority of mesenchymal tumors involving the gastrointestinal tract. Over the past decade, it has been recognized that these tumors have distinctive immunohistochemical and genetic features. The expression of c-Kit (CD117), a transmembrane growth factor receptor, has emerged as an important defining feature of GISTs, and the pathogenesis of these tumors may be related to c-Kit mutations. Promising preclinical results have provided the driving force for the rapid clinical development of imatinib mesylate, a selective tyrosine kinase inhibitor of c-Kit. This novel molecularly targeted therapy has produced impressive clinical responses in a large proportion of patients with advanced GISTs and is under study as an adjuvant therapy in patients with localized resectable GISTs.

Animals↗
PubMedDate not supplied

Soft tissue sarcomas.

Sarcomas are a heterogeneous group of rare tumors that arise predominantly from the embryonic mesoderm. They present most commonly as an asymptomatic mass originating in an extremity but can occur anywhere in the body, particularly the trunk, retroperitoneum, or the head and neck. Pretreatment radiologic imaging is critical for defining the local extent of a tumor, staging the disease, guiding biopsies, and aiding in diagnosis. Core-needle biopsy is the preferred biopsy technique for diagnosing soft tissue sarcomas. The American Joint Committee on Cancer (AJCC) staging system for soft tissue sarcomas is based on histologic grade, the tumor size and depth, and the presence of distant or nodal metastases. Despite improvements in local control rates with wide local resections and radiation therapy, metastasis and death remain a significant problem in 50% of patients who present with high-risk soft tissue sarcomas. The most common site of metastasis is the lungs, and metastasis generally occurs within two to three years after the completion of therapy. Progress in the molecular characteristics of these tumors should in the near future translate into molecularly based therapies that can be incorporated into standard treatment strategies.

Gastrointestinal Neoplasms↗
PubMedDate not supplied

Measuring quality of life in patients with melanoma: development of the FACT-melanoma subscale.

A systematic review of the literature on quality of life (QOL) in melanoma patients suggested an overwhelming need for a disease-specific subscale. A melanoma subscale for the Functional Assessment of Cancer Therapy (FACT-Melanoma) was developed to meet this need. This instrument was developed in three stages. In stage I, the literature was comprehensively reviewed, and over 300 cancer-specific items from the Functional Assessment of Chronic Illness Therapy (FACIT) item bank were examined to identify questions of potential relevance to melanoma patients. In stage II, 20 melanoma experts identified questions that were relevant to melanoma patients and that were to be included in a pilot questionnaire. In stage III, the pilot questionnaire and a semistructured interview to assess item comprehension, relevance, and overall content were administered to 40 patients with various stages of melanoma. In all, 97 items were culled from the literature and the FACIT item bank; after items were reviewed and evaluated, 25 questions were retained. Most patients considered the content of the pilot questionnaire to be relevant (95%), comprehensive (60%), and easy to understand (88%). After final revisions were made, the FACT-Melanoma tool included 24 items encompassing three QOL domains: 20 items relate to physical well-being, 3 to emotional well-being,and 1 to social well-being. The face and content validity of the FACT-Melanoma assessment tool has been confirmed in melanoma patients and by professionals. Formal validation and reliability testing of the questionnaire is being determined in a prospective cohort of melanoma patients.

Adult↗