Biomedical subjects

David J Carlson

Publications and source records attributed to David J Carlson.

12 recordsLinked to original sources

PubMed2006

Predicting patients at low probability of requiring postmastectomy radiation therapy.

BACKGROUND: Postmastectomy radiation therapy (PMRT) is recommended for patients with four or more positive lymph nodes (LN+). Given the ramifications of PMRT for immediate reconstruction, we sought to create a model using preoperative and intraoperative factors to predict which patients with a positive sentinel lymph node will have less than four LN+. METHODS: The database from a prospective multicenter study of 4,131 patients was used for this analysis. Patients with one to three positive sentinel lymph nodes (SLN) and tumors < 5 cm (n = 1,133) in size were randomly divided into a training set (n = 580) and a test set (n = 553). Multivariate logistic regression was used on the training set to create a prediction rule that was subsequently validated in the test set. RESULTS: Median patient age was 57 (range, 27-100) years, and median tumor size was 2.0 (range, 0.2-4.8) cm. In the training set, factors associated with having four or more LN+ on multivariate analysis were: tumor size [odds ratio (OR) = 2.087; 95% confidence interval (CI): 1.307-3.333, P = 0.002), number of positive SLN (P < 0.0005), and proportion of positive SLN (OR = 3.602; 95% CI: 2.100-6.179, P < 0.005). A predictive model was established with a point assigned to each positive SLN, T2 (vs. T1), and if proportion of positive SLN was > 50%, for a maximum of five points. In both the training and test sets, patients with one point had a low probability of having four or more LN+ (3.8% and 3.3%, respectively). CONCLUSION: Tumor size, number of positive SLN, and the proportion of positive SLN influence whether patients will have four or more LN+. A simple model can predict the probability of requiring PMRT.

Adult↗

PubMed2006

Factors associated with surgical options for breast carcinoma.

BACKGROUND: Breast conservation surgery (BCS) and mastectomy have equivalent survival outcomes for women with breast carcinoma, but treatment decisions are affected by many factors. The current study evaluated the impact of patient and physician factors on surgical decision-making. METHODS: Statistical analyses were performed on a prospective multicenter study of patients with invasive breast carcinoma. Patient, physician, and geographic factors were considered. RESULTS: Of 4086 patients, BCS was performed in 2762 (67.6%) and mastectomy was performed in 1324 (32.4%). The median tumor size was 1.5 cm (range, < 0.1-9.0 cm) in patients undergoing BCS and 1.9 cm (range, 0.1-11.0 cm) in patients undergoing mastectomy (P < 0.00001). The median age of patients undergoing BCS was 59 years (range, 27-100 yrs), whereas patients who underwent mastectomy were older (median age of 63 yrs, range, 27-96 yrs [P < 0.00001]). Physicians in academic practices performed more lumpectomies than those who were not in an academic practice (70.9% vs. 65.7%; P = 0.001). More breast conservation procedures were performed by surgeons with a higher percentage of breast practice (P = 0.012). Geographic location was found to be significant, with the Northeast having the highest rate of breast conservation (70.8%) and the Southeast having the lowest (63.2%; P = 0.002). On multivariate analysis, patient age (odds ratio [OR]: 1.455; 95% confidence interval [95% CI], 1.247-1.699 [P < 0.001]), tumor size (P < 0.001), tumor palpability (OR: 0.613; 95% CI, 0.524-0.716 [P < 0.001]), histologic subtype (P = 0.018), tumor location in the breast (P < 0.001), physician academic affiliation (OR: 1.193; 95% CI: 1.021-1.393 [P = 0.026]), and geographic location (P = 0.045) were found to be significant. CONCLUSIONS: Treatment decisions were found to be related to patient clinicopathologic features, surgeon academic affiliation, and geographic location. Future studies will elucidate the communication and psychosocial factors that may influence patient decision-making.

Academic Medical Centers↗

PubMed2006

Prediction of sentinel lymph node-only disease in women with invasive breast cancer.

BACKGROUND: The purpose of this study was to create a model that predicts which breast cancer patients will have sentinel lymph node (SLN)-only metastasis. METHODS: SLN-positive breast cancer patients (N = 1,253) were analyzed. Multivariate analysis was performed to identify factors predicting SLN-only disease; a prediction rule was created. RESULTS: Median tumor size was 2 cm. The median number of SLNs removed was 2; the median number of positive SLNs was 1. Multivariate analysis found tumor size, number of positive SLN, and proportion of SLN positive were significant predictors of SLN-only disease (P < .001). A prediction rule with 1 point being given for >1 positive SLN, 1 point for >50% of SLN positive, and up to 4 points for tumor size (T1a = 1, T1b or T1c = 2, T2 = 3, and T3 = 4) was established. Ninety-five percent of patients with 1 point had SLN-only disease (P < .0001). CONCLUSION: An integer-based model may predict SLN-only disease and may be useful in determining whether completion axillary lymph node dissection is required.

Adult↗

PubMed2006

Effects of oxygen on intrinsic radiation sensitivity: A test of the relationship between aerobic and hypoxic linear-quadratic (LQ) model parameters.

The poor treatment prognosis for tumors with high levels of hypoxia is usually attributed to the decreased sensitivity of hypoxic cells to ionizing radiation. Mechanistic considerations suggest that linear quadratic (LQ) survival model radiosensitivity parameters for hypoxic (H) and aerobic (A) cells are related by alphaH = alphaA/oxygen enhancement ratio (OER) and (alpha/beta)H=OER(alpha/beta)A. The OER parameter may be interpreted as the ratio of the dose to the hypoxic cells to the dose to the aerobic cells required to produce the same number of DSBs per cell. The validity of these expressions is tested against survival data for mammalian cells irradiated in vitro with low- and high-LET radiation. Estimates of hypoxic and aerobic radiosensitivity parameters are derived from independent and simultaneous least-squares fits to the survival data. An external bootstrap procedure is used to test whether independent fits to the survival data give significantly better predictions than simultaneous fits to the aerobic and hypoxic data. For low-LET radiation, estimates of the OER derived from the in vitro data are between 2.3 and 3.3 for extreme levels of hypoxia. The estimated range for the OER is similar to the oxygen enhancement ratios reported in the literature for the initial yield of DSBs. The half-time for sublethal damage repair was found to be independent of oxygen concentration. Analysis of patient survival data for cervix cancer suggests an average OER less than or equal to 1.5, which corresponds to a pO2 of 5 mm Hg (0.66%) in the in vitro experiments. Because the OER derived from the cervix cancer data is averaged over cells at all oxygen levels, cells irradiated in vivo under extreme levels of hypoxia (<0.5 mm Hg) may have an OER substantially higher than 1.5. The reported analyses of in vitro data, as well as mechanistic considerations, provide strong support for the expressions relating hypoxic and aerobic radiosensitivity parameters. The formulas are also useful for the analysis of clinical data because the number of radiosensitivity parameters that need to be determined is reduced from four to three without a substantial decrease in the ability of the LQ to accurately predict the surviving faction. The relationships among radiosensitivity parameters imply that the dose to the hypoxic subvolume of the tumor needs to be escalated by a factor of the OER to achieve the same level of tumor control as in well oxygenated tumor regions.

Apoptosis↗

PubMed2005

Biopsy type does not influence sentinel lymph node status.

BACKGROUND: This study sought to determine whether the type of biopsy examination independently affects sentinel lymph node (SLN) status in breast cancer patients. METHODS: A prospective multicenter study of patients who had SLN biopsy examination followed by axillary node dissection was analyzed to determine whether the type of biopsy examination influenced SLN status. RESULTS: Of the 3853 patients studied, 32% had a positive SLN. Patients were diagnosed by fine-needle (N = 293), core-needle (N = 2154), excisional (N = 1386), or incisional (N = 20) biopsy procedures. The rates of SLN positivity for these groups were 45%, 32%, 29%, and 65%, respectively (P < .001). Other factors predictive of SLN status included: patient age (P < .001), tumor size (P < .001), tumor palpability (P < .001), number of SLN removed (P < .001), type of surgery (mastectomy vs. lumpectomy) (P < .001), histologic subtype (P = .048), and the use of immunohistochemistry (P < .001). All of these factors remained significant in the multivariate model except for histologic subtype and biopsy examination type. CONCLUSIONS: Biopsy examination type does not independently influence the risk for nodal metastasis.

Adult↗

PubMed2005

Effect of lymphoscintigraphy drainage patterns on sentinel lymph node biopsy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy examination is an accepted method of staging breast cancer patients. SLN biopsy examination in patients with drainage to the internal mammary chain (IMC) nodes is controversial. METHODS: A prospective study of SLN biopsy examination followed by axillary dissection was analyzed to determine how surgeons manage patients with IMC drainage and the rates of axillary SLN identification and positivity in these cases. RESULTS: Lymphoscintigraphy was performed in 2196 (53.2%) of the 4131 patients in this study. IMC drainage was noted in 80 patients (3.6%). An axillary SLN was identified in 29 of the 40 patients with IMC drainage alone (72.5%). The rate of finding a positive axillary lymph node did not differ based on the lymphoscintigraphic pattern (P = .470). CONCLUSIONS: Most surgeons do not perform IMC SLN biopsy procedures. Even when lymphoscintigraphy shows isolated drainage to IMC nodes, axillary SLNs usually are identified. Lymphoscintigraphy therefore has limited usefulness.

Adult↗

PubMed2005

Surgeon and community factors affecting breast cancer sentinel lymph node biopsy.

BACKGROUND: We sought to determine whether the results of sentinel lymph node (SLN) biopsy are related to practice and community factors. METHODS: This prospective study included more than 300 surgeons from a variety of practice environments. Most surgeons had minimal experience with SLN biopsy prior to this study. Patients underwent attempted SLN biopsy, followed by completion axillary dissection. Univariate and multivariate analyses were performed to assess factors related to the SLN identification rate and the false negative rate. RESULTS: A total of 4131 patients were enrolled. SLN identification rate was 93%; the false negative (FN) rate was 7.9%. The only factor that was significantly associated with improved SLN identification rate (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.12 to 2.36, P = .0126) and FN rate (OR 2.39, 95% CI 1.32 to 4.79, P = .0073) was surgeon experience (>20 SLN cases). CONCLUSIONS: Surgeon experience is the major factor that contributes to improved SLN biopsy results. SLN biopsy can be performed equally well by community and academic surgeons.

Adult↗

PubMed2005

Factors predicting failure to identify a sentinel lymph node in breast cancer.

BACKGROUND: Although sentinel lymph node (SLN) biopsy is widely accepted as a minimally invasive method of nodal staging, failure to identify an SLN mandates a level I/II axillary node dissection. The purpose of this study was to elucidate factors that independently predict failure to identify an SLN. METHODS: Using a large multicenter prospective study of SLN biopsy for patients with invasive breast cancer, we performed univariate and multivariate regression analyses to determine clinicopathologic factors predictive of failure to identify an SLN. RESULTS: Of the total 4131 patients in the study, an SLN was not identified in 249 (6.0%). Tumor location (P = .409), biopsy type (P = .079), surgery type (P = .380), and histologic subtype (P = .999) were not significant predictors of failure to identify an SLN. On multivariate analysis, age greater than 60 years (OR = 1.469; 95% CI, 1.116-1.934, P = .006), nonpalpable tumors (OR = 0.639; 95% CI, 0.479-0.852, P = .002), injection technique with blue dye alone (OR = 0.389, 95% CI, 0.259-5.86, P < .001), and surgical experience of less than 10 SLN biopsy cases (OR = 1.886; 1.428-2.492, P < .001) were significant independent predictors of failure to identify an SLN. Optimal SLN biopsy technique using an intradermal and/or subareolar injection of radioactive colloid and blue dye can improve SLN identification rates regardless of patient and tumor characteristics. CONCLUSIONS: Patient age and tumor palpability significantly affect the ability to identify an SLN in patients with breast cancer. Optimal injection technique can significantly improve sentinel node identification rate regardless of these factors.

Adult↗

PubMed2004

Comparison of in vitro and in vivo alpha/beta ratios for prostate cancer.

Parallel in vitro and in vivo studies provide insight into the relationship between clinical response and intrinsic cellular radiosensitivity and may aid in the development of predictive assays. Compilations of radiosensitivity parameters from in vitro experiments can also be used to examine the potential effectiveness of alternative or new treatment plan designs until enough clinical data become available to directly estimate the requisite radiosensitivity parameters. In this work, survival data for six prostate cancer cell lines (ten datasets total) have been extracted from the literature and re-analysed using the linear-quadratic (LQ) survival model. The paired bootstrap technique for regression is used to compute 95% confidence intervals for the estimated radiosensitivity parameters. LQ radiosensitivity parameters derived from the in vitro data are then compared to radiosensitivity parameters derived from clinical data for prostate cancer. Estimates of alpha range from 0.09 to 0.35 Gy(-1) (all cell lines), and the alpha/beta ratio ranges from 1.09 to 6.29 Gy (all cell lines). Point estimates of the repair half-time (PPC-1, TSU-Pr1, PC-3 and DU-145 cell lines) range from 5.7 to 8.9 h (95% confidence interval from 0.26 h to 10.7 h). Differences in the radiosensitivity parameters determined from the data reported by different laboratories are as large as or larger than the differences in radiosensitivity parameters observed among the various prostate cell lines. The reported studies demonstrate that even seemingly small corrections for dose rate effects, such as those expected in high dose rate (HDR) experiments, can sometimes have a significant impact on estimates of alpha and alpha/beta. By neglecting dose rate effects in the analysis of HDR experiments, estimates of the alpha/beta, ratio may be too high by factors as large as 1.3 to 6.2. The half-time for repair derived from the in vitro experiments appears significantly larger (slower repair rate) than estimates derived from the clinical data. However, the prostate radiosensitivity parameters alpha and alpha/beta may be approximately the same in vitro and in vivo. Most of the in vitro data are consistent with an alpha/beta ratio for prostate cancer less than 3 or 4 Gy.

Alpha Particles↗

PubMed2002

The effect of prior breast biopsy method and concurrent definitive breast procedure on success and accuracy of sentinel lymph node biopsy.

BACKGROUND: It has been suggested that sentinel lymph node (SLN) biopsy for breast cancer may be less accurate after excisional biopsy of the primary tumor compared with core needle biopsy. Furthermore, some have suggested an improved ability to identify the SLN when total mastectomy is performed compared with lumpectomy. This analysis was performed to determine the impact of the type of breast biopsy (needle vs. excisional) or definitive surgical procedure (lumpectomy vs. mastectomy) on the accuracy of SLN biopsy. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible. All patients underwent SLN biopsy and completion level I/II axillary dissection. Statistical comparison was performed by chi(2) analysis. RESULTS: A total of 2206 patients were enrolled in the study. There were no statistically significant differences in SLN identification rate or false-negative rate between patients undergoing excisional versus needle biopsy. The SLN identification and false-negative rates also were not statistically different between patients who had total mastectomy compared with those who had a lumpectomy. CONCLUSIONS: Excisional biopsy does not significantly affect the accuracy of SLN biopsy, nor does the type of definitive surgical procedure.

Adult↗

PubMed2002

Frequency of sentinel lymph node metastases in patients with favorable breast cancer histologic subtypes.

BACKGROUND: The need for axillary nodal staging in favorable histologic subtypes of breast cancer is controversial. METHODS: Patients with clinical stage T1-2, N0 breast cancer were enrolled in a prospective, multi-institutional study. All patients underwent sentinel lymph node (SLN) biopsy followed by completion level I/II axillary dissection. RESULTS: SLN were identified in 3,106 of 3,324 patients (93%). Axillary metastases were found in 35% and 40% of patients with infiltrating ductal carcinoma and infiltrating lobular carcinoma, respectively. Among tumor subtypes, positive nodes were found in 17% of patients with pure tubular carcinoma, 7% of patients with papillary cancer, 6% of patients with colloid (mucinous) carcinoma, 21% of patients with medullary carcinoma, and 8% of patients with DCIS with microinvasion. CONCLUSIONS: Patients with favorable breast cancer subtypes have a significant rate of axillary nodal metastasis. Axillary nodal staging remains important in such patients; SLN biopsy is an ideal method to obtain this staging information.

Adenocarcinoma↗

PubMedDate not supplied

Sentinel lymph node biopsy for breast cancer: improvement in results over time.

Many modifications in the technique of sentinel lymph node (SLN) biopsy for breast cancer have taken place since it was first introduced. This analysis was undertaken to determine, in a large multi-institutional study, whether SLN biopsy results have improved over time. Patients with clinical stage T1-2, N0 breast cancer were enrolled in this prospective study between August 1997 and February 2002. SLN biopsy was performed using blue dye and/or radioactive colloid along with completion level I/II axillary dissection in all patients. The majority of subjects included in this study represent the surgeons' initial experience with SLN biopsy for breast cancer. Statistical comparison of the SLN identification (ID) rate and false-negative (FN) rate were performed by chi-squared analysis. A total of 3370 subjects from 300 surgeons were enrolled in the study. Collectively the SLN ID rate, as well as the mean number of SLNs removed per patient has improved, while the FN rate has remained fairly constant over time. The improved ID rate may be related to improved technical details, while the FN rate has not changed significantly. This highlights the ongoing need for surgeons to perform backup axillary dissection during their initial learning phase.

Adult↗