Postradiotherapy pelvic fractures: cause for concern or opportunity for future research?
Explore the source record for details and available documents.
Fractures, Bone↗
Biomedical subjects
Lisa Kachnic
Publications and source records attributed to Lisa Kachnic.
Palliative single-fraction radiation therapy: how much more evidence is needed?
Explore the source record for details and available documents.
Analgesics↗
Outcome results of the 1996-1999 patterns of care survey of the national practice for patients receiving radiation therapy for carcinoma of the esophagus.
PURPOSE: A Patterns of Care Study of patients treated from 1996 to 1999 evaluated the national practice for patients receiving radiation therapy for carcinoma of the esophagus in the United States. METHODS: A national survey was conducted at 59 institutions in a stratified random sample selected from a master list of radiation therapy facilities throughout the United States. Patient, tumor, and treatment characteristics were evaluated. Multivariate comparisons of survival times were made using the Cox proportional hazards model. RESULTS: Adenocarcinoma was diagnosed in 51% of patients and squamous cell carcinoma in 49% of patients. Sixteen percent of patients were clinical stage (CS) I (using the 1983 American Joint Committee on Cancer system), 39% were CS II, and 33% were CS III. Significant variables in the multivariate analysis of survival times included clinical stage, treatment approach, and facility size. Patients with CS III disease had a higher hazard risk of death as compared with CS I patients (hazard ratio [HR], 2.01; P = .001), whereas those treated with chemoradiotherapy followed by surgery (HR, 0.32; P < .0001) had a decreased risk of death compared with chemoradiotherapy-only patients. Patients at small centers had a higher risk of death (HR, 1.32; P = .03) compared with patients treated at larger facilities. CONCLUSION: Concurrent chemoradiotherapy continued to be the most commonly utilized treatment approach during the time period studied. The observation that patients undergoing surgical resection following chemoradiation have a decreased HR or chance of death compared with other treatment schemes supports the need for a randomized trial comparing these strategies.
Adenocarcinoma↗
Radiotherapy for invasive breast cancer in North America and Europe: results of a survey.
PURPOSE: To document and explain the current radiotherapeutic management of invasive breast cancer in North America and Europe. We also identified a number of areas of agreement, as well as controversy, toward which additional clinical research should be directed. METHODS AND MATERIALS: An original survey questionnaire was developed to assess radiation oncologists' self-reported management of breast cancer. The questionnaire was administered to physician members of the American Society for Therapeutic Radiology and Oncology and the European Society for Therapeutic Radiology and Oncology. We present the results of the comparative analysis of 702 responses from North America and 435 responses from Europe. RESULTS: Several areas of national and international controversy were identified, including the selection of appropriate candidates for postmastectomy radiation therapy (RT) and the appropriate management of the regional lymph nodes after mastectomy, as well as after lumpectomy. Only 40.7% and 36.1% of respondents would use postmastectomy RT in patients with 1-3 positive lymph nodes in North America and Europe, respectively. Sentinel lymph node biopsy was offered more frequently by North American than European respondents (p <0.0001) and more frequently by academic than nonacademic respondents in North America (p < 0.05). The average radiation fraction size was larger in Europe than in North America (p < 0.01). European respondents offered RT to the internal mammary chain more often than did the North American respondents (p < 0.001). North American respondents were more likely to offer RT to the supraclavicular fossa (p < 0.001) and axilla (p < 0.01). CONCLUSION: Marked differences were found in physician opinions regarding the management of breast cancer, with statistically significant international differences in patterns of care. This survey highlighted areas of controversy, providing support for international randomized trials to optimize the RT management of invasive breast cancer.
Breast Neoplasms↗
The management of ductal carcinoma in situ in North America and Europe. Results of a survey.
BACKGROUND: The goal of the current study was to understand and document contemporary treatment approaches in the management of ductal carcinoma in situ (DCIS). METHODS: An original questionnaire was designed to assess radiation oncologists' management of breast carcinoma, including 26 questions specifically addressing DCIS. A postal survey was conducted of members of the American and European Societies of Therapeutic Radiology and Oncology. The results of 702 responses from North America were compared with 435 responses from Europe, to determine treatment recommendations and variability by type of institution and geographic region. RESULTS: There were strong correlations between the grade of DCIS and/or the margin status and the use of radiotherapy (RT; P < 0.0001). For Grade 3 DCIS, RT was recommended regardless of the margin status. Opinions were split in the treatment of low-grade DCIS with 10-mm margins. North American respondents were more likely to recommend RT for low-grade DCIS than their European counterparts (P < 0.0001). Within the United States, there were significant regional variations in physician recommendations for tamoxifen (P < 0.001), but not in the tendency to recommend RT. North American academic physicians were less likely to recommend RT for favorable DCIS than nonacademic physicians (P < 0.01). CONCLUSIONS: There were marked differences in physician opinions regarding the management of DCIS, with significant international differences in patterns of care. The survey quantified and highlighted areas of agreement and controversy regarding the use of RT and tamoxifen in the management of DCIS. It provided support for large international trials to evaluate the optimal management of DCIS in the areas identified as most controversial.
Breast Neoplasms↗
DNA damage induces p53-dependent BRCA1 nuclear export.
The tumor suppressor gene BRCA1 plays an important role in the response to DNA damage. BRCA1 function is regulated by a variety of mechanisms including transcriptional control, phosphorylation, and protein-protein interactions. Recent studies have shown that BRCA1 is a nuclear-cytoplasmic shuttle protein. Its subcellular localization is controlled by a nuclear localization signal-mediated nuclear import via the importin receptor pathway and a nuclear export signal-facilitated nuclear export through a CRM1-dependent pathway. Using the human breast cancer cell line, MCF7, the subcellular distribution of BRCA1 was assessed by immunohistochemical staining and Western blotting analyses of fractionated subcellullar extracts. Ionizing radiation stimulated BRCA1 nuclear export in a dose-dependent manner. This DNA damage-induced BRCA1 nuclear export utilized a CRM1-dependent mechanism and also required wild-type p53, whose function was abrogated by the E6 protein in MCF7 cells. In addition, the dependence on p53 was confirmed using a second cell type operating a tetracycline-inducible system. The effect of ionizing radiation on BRCA1 export was observed in every phase of the cell cycle, although BRCA1 localization did vary between the G(1), S, and G(2)/M phases. These results imply that, in addition to ATM-, ATR-, and Chk2-dependent phosphorylations, cytoplasmic relocalization of BRCA1 protein is a mechanism whereby BRCA1 function is regulated in response to DNA damage.
Active Transport, Cell Nucleus↗
The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study.
PURPOSE: A Patterns of Care Study (PCS) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. METHODS: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCS. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. RESULTS: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was >or=80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). CONCLUSIONS: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen.
Adenocarcinoma↗