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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"Some comparative studies have been done for both heart disease   and breast cancer   . Some studies compared the effectiveness of drugs      without examining the demographic information of the sample . In our work, these types of studies correspond to population effectiveness study. "
[Show abstract][Hide abstract] 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.
"A good cancer treatment should ideally prolong survival while preserving a high quality of life cost-effectively, which suggests the necessity for long-term follow up. Nevertheless prolonged survival in a clinical trial in some more slowly progressing cancers can take 5–10 years or longer . Such trials are expensive, not only in cost but in time. "
[Show abstract][Hide abstract] 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.
"Although considered rare long-term sequelae, there are many reports in the literature of radiation-induced tumors following cranial irradiation.[12–142224556263] The oncogenic risk of radiation exposure has been examined in several populations, including atomic bomb survivors, high levels of radiation from extensive diagnostic radiographic procedures, environmental or work-related exposure, or radiotherapy to treat benign and malignant disease. "
[Show abstract][Hide abstract] ABSTRACT: A serious, albeit rare, sequel of therapeutic ionizing radiotherapy is delayed development of a new, histologically distinct neoplasm within the radiation field.
We identified 27 cases, from a 10-year period, of intracranial tumors arising after cranial irradiation. The original lesions for which cranial radiation was used for treatment included: tinea capitis (1), acute lymphoblastic leukemia (ALL; 5), sarcoma (1), scalp hemangioma (1), cranial nerve schwannoma (1) and primary (13) and metastatic (1) brain tumors, pituitary tumor (1), germinoma (1), pinealoma (1), and unknown histology (1). Dose of cranial irradiation ranged from 1800 to 6500 cGy, with a mean of 4596 cGy. Age at cranial irradiation ranged from 1 month to 43 years, with a mean of 13.4 years.
Latency between radiotherapy and diagnosis of a radiation-induced neoplasm ranged from 4 to 47 years (mean 18.8 years). Radiation-induced tumors included: meningiomas (14), sarcomas (7), malignant astrocytomas (4), and medulloblastomas (2). Data were analyzed to evaluate possible correlations between gender, age at irradiation, dose of irradiation, latency, use of chemotherapy, and radiation-induced neoplasm histology. Significant correlations existed between age at cranial irradiation and development of either a benign neoplasm (mean age 8.5 years) versus a malignant neoplasm (mean age 20.3; P = 0.012), and development of either a meningioma (mean age 7.0 years) or a sarcoma (mean age 27.4 years; P = 0.0001). There was also a significant positive correlation between latency and development of either a meningioma (mean latency 21.8 years) or a sarcoma (mean latency 7.7 years; P = 0.001). The correlation between dose of cranial irradiation and development of either a meningioma (mean dose 4128 cGy) or a sarcoma (mean dose 5631 cGy) approached significance (P = 0.059).
Our study is the first to show that younger patients had a longer latency period and were more likely to have lower-grade lesions (e.g. meningiomas) as a secondary neoplasm, while older patients had a shorter latency period and were more likely to have higher-grade lesions (e.g. sarcomas).
No preview · Article · May 2012 · Surgical Neurology International