Risk of leukemia after chemotherapy and radiation treatment for breast cancer.
ABSTRACT Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail.
We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy).
The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg.
Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia.
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ABSTRACT: Comparative Effectiveness Research (CER) is defined as the generation and synthesis of evidence that compares the ben-efits and harms of different prevention and treatment meth-ods. This is becoming an important field in informing health care providers about the best treatment for individual pa-tients. Currently, the two major approaches in conducting CER are observational studies and randomized clinical tri-als. These approaches, however, often suffer from either scalability or cost issues. In this paper, we propose a third approach of conducting CER by utilizing online personal health messages, e.g., com-ments on online medical forums. The approach is effective in resolving the scalability and cost issues, enabling rapid de-ployment of system to identify treatments of interests, and developing hypotheses for formal CER studies. Moreover, by utilizing the demographic information of the patients, this approach may provide valuable results on the preferences of different demographic groups. Demographic information is extracted using our high precision automated demographic extraction algorithm. This approach is capable of extracting more than 30% of users' age and gender information. We conducted CER by utilizing personal health messages on breast cancer and heart disease. We were able to generate statiatically valid results, many of which have already been validated by clinical trials. Others could become hypothesis to be tested in future CER research.ACM Conference on Bioinformatics, Computational Biology and Biomedical Informatics (BCB 2013); 09/2013
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ABSTRACT: The aim of this research is to check the efficacy of radiotherapy after execution that helps in preserving patients’ rights against the randomized dose that settled statistically and assessed in standard models ignoring patient-specific factors. Based on studying a dose–response relationship, a mathematical model is presented describes the initial tumor energy (E0Tumor) prior therapy after treatment execution -even if it was not predetermined- by monitoring the tumor response along the treatment phases and compared to the applied dose energy (E0Dose). Our model allows mechanic risk predictions to be made at high radiotherapeutic doses as well as at low doses, besides to the second cancer risk prevention. Thus, the administered dose errors could be determined and consequently preserving patients' rights to evaluate the cancer treatment through the provided mathematical model. Reasons of tumor regrowth are either underestimation or overestimation of the administered dose; the safe dose of the successful treatment occurs only in the case of: E0Dose = E0Tumor, where tumor regrowth energy in such a case would be vanished. Dose assessment by ignoring patient-specific factors and using standard models is responsible for wide range of doses that lead to tumor regrowth and second cancer risks. Current approach suggests settling down a new protocol for the proper ranges of radionuclide doses based on a personalized staging system.
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ABSTRACT: Objective: Our goal was to provide health-care providers, patients, and the general public with an assessment of cur- rently available data regarding the use of adjuvant therapy for breast cancer. Participants: The participants included a non-Federal, non-advocate, 14-member panel representing the fields of oncology, radiology, surgery, pathology, statis- tics, public health, and health policy as well as patient rep- resentatives. In addition, 30 experts in medical oncology, radiation oncology, biostatistics, epidemiology, surgical on- cology, and clinical trials presented data to the panel and to a conference audience of 1000. Evidence: The literature was searched with the use of MEDLINE® for January 1995 through July 2000, and an extensive bibliography of 2230 references was provided to the panel. Experts prepared ab- stracts for their conference presentations with relevant cita- tions from the literature. Evidence from randomized clinical trials and evidence from prospective studies were given pre- cedence over clinical anecdotal experience. Consensus Pro- cess: The panel, answering predefined questions, developed its conclusions based on the evidence presented in open fo- rum and the scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the confer- ence. The draft statement was made available on the World Wide Web immediately after its release at the conference and was updated with the panel's final revisions. The state- ment is available at http://consensus.nih.gov. Conclusions: The panel concludes that decisions regarding adjuvant hor- monal therapy should be based on the presence of hormone receptor protein in tumor tissues. Adjuvant hormonal therapy should be offered only to women whose tumors ex- press hormone receptor protein. Because adjuvant polyche- motherapy improves survival, it should be recommended to the majority of women with localized breast cancer regard- less of lymph node, menopausal, or hormone receptor status. The inclusion of anthracyclines in adjuvant chemotherapy regimens produces a small but statistically significant im- provement in survival over non-anthracycline-containing regimens. Available data are currently inconclusive regard- ing the use of taxanes in adjuvant treatment of lymph node- positive breast cancer. The use of adjuvant dose-intensive chemotherapy regimens in high-risk breast cancer and of taxanes in lymph node-negative breast cancer should be re- stricted to randomized trials. Ongoing studies evaluating these treatment strategies should be supported to determine if such strategies have a role in adjuvant treatment. Studies to date have included few patients older than 70 years. There is a critical need for trials to evaluate the role of adjuvant chemotherapy in these women. There is evidence that women with a high risk of locoregional tumor recurrence after mastectomy benefit from postoperative radiotherapy. This high-risk group includes women with four or more positive lymph nodes or an advanced primary cancer. Cur- rently, the role of postmastectomy radiotherapy for patients with one to three positive lymph nodes remains uncertain and should be tested in a randomized controlled trial. Indi- vidual patients differ in the importance they place on the risks and benefits of adjuvant treatments. Quality of life needs to be evaluated in selected randomized clinical trials to examine the impact of the major acute and long-term side effects of adjuvant treatments, particularly premature menopause, weight gain, mild memory loss, and fatigue. Methods to support shared decision-making between pa- tients and their physicians have been successful in trials; they need to be tailored for diverse populations and should be tested for broader dissemination. (J Natl Cancer Inst 2001;93:979-89)