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Biomedical subjects

Eileen Rakovitch

Publications and source records attributed to Eileen Rakovitch.

13 recordsLinked to original sources

The management of ductal carcinoma in situ of the breast: a screened population-based analysis.

BACKGROUND: A recent SEER study identified significant variations in the care of women with DCIS, yet several potential confounding variables were not included. We report a patterns of care study of women with DCIS to better understand the gap between evidence-based knowledge and the management of DCIS. METHODS: We studied all cases of DCIS diagnosed through the Ontario Breast Screening Program from 1991 to 2000. Data was obtained by database linkage and chart abstraction. A logistic regression model using generalized estimating equations to adjust for clustering was used. RESULTS: About 320,236 women were screened and 727 individuals were diagnosed with DCIS. The rate of mastectomy was 30% and was associated with multifocality (OR: 3.5 [1.7, 7.1], P = 0.0005), tumor size (OR: >2 cm vs. 1 cm (OR: 2.4 [1.3, 4.4], P = 0.006). Half of cases with margins <1 cm did not receive XRT. CONCLUSIONS: Our study corroborates previous reports on the persistent rates of mastectomy and axillary nodal dissection and the limited use of XRT in the treatment of DCIS.

Age Distribution↗

The use of complementary and alternative medicines among patients with locally advanced breast cancer--a descriptive study.

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC). METHODS: Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. RESULTS: Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression. CONCLUSION: The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field.

Adult↗

Body radiation exposure in breast cancer radiotherapy: impact of breast IMRT and virtual wedge compensation techniques.

PURPOSE: Recent reports demonstrate a dramatically increased rate of secondary leukemia for breast cancer patients receiving adjuvant high-dose anthracycline and radiotherapy, and that radiation is an independent factor for the development of leukemia. This study aimed to evaluate the radiation body exposure during breast radiotherapy and to characterize the factors associated with an increased exposure. PATIENTS AND METHODS: In a prospective cohort of 120 women, radiation measurements were taken from four sites on the body at the time of adjuvant breast radiotherapy. Multiple regression analysis was performed to analyze patient and treatment factors associated with the amount of scattered radiation. RESULTS: For standard 50 Gy breast radiotherapy, the minimal dose received by abdominal organs is on average 0.45 Gy, ranging from 0.06 to 1.55 Gy. The use of physical wedges as a compensation technique was the most significant factor associated with increased scattered dose (p < 0.001), resulting in approximately three times more exposure compared with breast intensity-modulated radiation therapy (IMRT) and dynamic wedge. CONCLUSIONS: The amount of radiation that is scattered to a patient's body is consistent with exposure reported to be associated with excess of leukemia. In accordance with the As Low As Reasonably Achievable (ALARA) principle, we recommend using breast IMRT or virtual wedging for the radiotherapy of breast cancer receiving high-dose anthracycline chemotherapy.

Body Height↗

First report of a permanent breast 103Pd seed implant as adjuvant radiation treatment for early-stage breast cancer.

PURPOSE: A new technique of adjuvant partial breast irradiation using 103Pd permanent breast seed implants (PBSI) is presented. The procedure is performed in a single 1-hour session under local anesthesia. METHODS AND MATERIALS: Patients referred to a single institution for adjuvant radiotherapy after lumpectomy for an infiltrating ductal carcinoma < or = 3 cm in diameter, surgical margin > or = 2 mm, no extensive in situ carcinoma, no lymphovascular invasion, and minimal or negative lymph node involvement were offered a PBSI. RESULTS: Between May and December 2004, 31 eligible patients underwent CT scan and ultrasound simulations assessing PBSI feasibility. Fifteen were excluded because of feasibility issues, and 16 received PBSI. A minimal peripheral dose of 90 Gy was prescribed to the planning target volume corresponding to the clinical target volume identified on the CT scan plus a margin of 1 cm. The procedure was well tolerated; 56% of the patients reported no pain during the procedure, and 46% of the patients developed National Cancer Institute Common Toxicity Criteria Grade 1 acute reaction. None experienced toxicity Grade 2 or 3. CONCLUSIONS: Permanent breast seed implantation seems feasible and well tolerated on these preliminary clinical data and represents an ultimate step in the reduction of treatment fraction for partial breast irradiation.

Brachytherapy↗

A permanent breast seed implant as partial breast radiation therapy for early-stage patients: a comparison of palladium-103 and iodine-125 isotopes based on radiation safety considerations.

PURPOSE: A permanent breast seed implant (PBSI) technique has been developed as a new form of partial adjuvant radiation therapy for early-stage breast cancer. This study compares iodine-125 ((125)I) and palladium-103 ((103)Pd) isotopes by examining the exposure and effective dose (ED) to a patient's partner. METHODS AND MATERIALS: A low-energy survey meter was used to measure exposure rates as a function of bolus thickness placed over (103)Pd or (125)I seeds. A general mathematical expression for the initial exposure rate at 1 m (x(o,1m)) from the skin surface as a function of the implant size, R, and the distance between the skin surface and the implant, d, was derived. Also, a second general equation is proposed to calculate the ED to the patient's partner. RESULTS: The initial exposure rate at 1 meter and the ED are calculated as follows: x(o,1m) = 3alpha2R(3) ; ;beta(3) [e(-beta(2R+d))(betaR + 1) + e(-betad)(betaR - 1)], and ED = aR(b) [e(-c(2R+d)) (cR + 1) + e(-cd) (cR - 1)]. For (125)I, the parameters are: alpha = 0.154409, beta = 0.388460, a = 197, b = -0.95, and c = 0.38846. For (103)Pd, they are: alpha = 0.06877, beta = 0.421098, a = 18.6, b = -0.78, and c = 0.421098. For implant diameters varying from 2 to 6 cm and skin-to-implant distances varying from 0.7 to 4 cm, the ED is consistently below 2.6 mSv using the (103)Pd isotope, but more than 5 mSv in many instances and possibly up to 20 mSv using (125)I. CONCLUSIONS: PBSI using (103)Pd seeds appears safe because the patient's partner ED is consistently below 5 mSv. The(125)I isotope is not recommended for PBSI.

Algorithms↗

Complementary and alternative medicine use is associated with an increased perception of breast cancer risk and death.

PURPOSE: Complementary and alternative medicines (CAMS) are frequently used by patients with breast cancer and their use may be related to the presence of psychosocial distress. The objective of this study is to assess the presence of anxiety and depression in breast cancer patients who use CAM and assess how they perceive their risks of recurrence and dying from breast cancer compared to non-users. METHODS: Breast cancer patients attending ambulatory clinics at a single cancer center were approached by their oncologist. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM, views of their risks of developing recurrent cancer, and of dying of breast cancer. The presence of anxiety and depression was scored using the Hospital Anxiety and Depression Scale (HADS). Responses were scored and compared between CAM users and non-users. RESULTS: A total of 251 patients completed the survey. CAM usage was reported by 43% of patients. Individuals who used CAM were younger [53.1 versus 63.0 year (p < 0.001)], had higher education (p < 0.001), were more likely to have full time employment [25.7 versus 16.3% (p < 0.001)] and have private insurance for medications (76 versus 60%, p = 0.007) compared to non-users. CAM users perceived their risk of recurrence (p = 0.011) and death from breast cancer (p = 0.0001) as being significantly greater than non-users. There were no significant differences in anxiety or depression scores between CAM and non-users. CONCLUSION: CAM use is associated with an increased perception of breast cancer recurrence and of breast cancer-related death. There was no association between the presence of anxiety or depression and CAM use. Improved patient understanding of actual risks of recurrence and death are required such that women will be able to make more informed decisions about using CAMs.

Adult↗

Radiotherapeutic management of brain metastases: a systematic review and meta-analysis.

BACKGROUND: The management of brain metastases is a significant health care problem. An estimated 20-40% of cancer patients will develop metastatic cancer to the brain during the course of their illness. METHODS: A systematic review of randomized trials on adult cancer patients with single or multiple brain metastases from cancer of any histology was conducted. Eligible studies investigated external beam radiotherapy or radiosurgery in one of the study arms. Outcomes of interest included survival, intracranial progression-free duration, response of brain metastases to therapy, quality of life, symptom control, neurological function, and toxicity. RESULTS: Twenty-seven trials were included in this systematic review of the evidence. Pooled results from three randomized trials of surgical excision combined with whole brain radiotherapy (WBRT) showed no improvement in overall survival as compared to WBRT alone in patients with single brain metastasis. One randomized study of postoperative WBRT following excision of a single brain metastasis versus surgery alone detected a significant reduction in intracranial tumour recurrence rates but no corresponding difference in overall survival. Nine trials of altered dose-fractionation schedules compared to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT showed no difference in probability of survival at 6 months. The addition of radiosensitizers, as assessed in five trials, did not confer additional benefit to WBRT in terms of overall survival or the frequency of brain metastases response. Three trials examined the use of WBRT and radiosurgery boost versus WBRT alone in selected patients with brain metastases. Overall survival did not improve for patients with multiple brain metastases. However, one trial reported an improvement in survival for patients with single brain metastasis treated with WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT versus supportive care alone (using oral prednisone). Results were not conclusive. CONCLUSION: For patients with a single brain metastasis, good performance status, and minimal or no evidence of extracranial disease, surgical excision and postoperative WBRT improves survival (as compared to WBRT alone). There may be a small survival advantage associated with the use of radiosurgery boost and WBRT as compared to WBRT alone in selected patients with a single brain metastasis. There is no difference in overall survival or in neurologic function improvement with the use of altered whole brain dose-fractionation schedules as compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000 cGy in 5 fractions). There is no survival benefit associated with the use of radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain metastases. Currently, neither chemotherapy nor radiosensitizers show a clear benefit in the objective parameters of survival and progression-free survival. For patients with poor performance status and active extracranial disease, steroids and supportive care are an option.

Brain Neoplasms↗

Inverse vs. forward breast IMRT planning.

Breast intensity-modulated radiation therapy (IMRT) improves dose distribution homogeneity within the whole breast. Previous publications report the use of inverse or forward dose optimization algorithms. Because the inverse technique is not widely available in commercial treatment planning systems, it is important to compare the 2 algorithms. The goal of this work is to compare them on a prospective cohort of 30 patients. Dose distributions were evaluated on differential dose-volume histograms using the volumes receiving more than 105% (V(105)) and 110% (V(110)) of the prescribed dose, and on the maximum dose (D(max)) or hot spot and the sagittal dose gradient (SDG) being the gradient between the dose on inframammary crease and the dose prescribed. The data were analyzed using Wilcoxon signed rank test. The inverse planning significantly improves the V(105) (mean value 9.7% vs. 14.5%, p=0.002), and the V(110) (mean value 1.4% vs. 3.2%, p=0.006). However, the SDG is not statistically significantly different for either algorithm. Looking at the potential impact on skin acute reaction, although there is a significant reduction of V(110) using an inverse algorithm, it is unlikely this 1.6% volume reduction will present a significant clinical advantage over a forward algorithm. Both algorithms are equivalent in removing the hot spots on the inframammary fold, where acute skin reactions occur more frequently using a conventional wedge technique. Based on these results, we recommend that both forward and inverse algorithms should be considered for breast IMRT planning.

Algorithms↗

Prognostic and predictive molecular markers in DCIS: a review.

Eighteen percent of all new breast cancers detected on screening mammography are ductal carcinoma in situ (DCIS), a preinvasive lesion that is highly curable. However, some women with DCIS will develop life-threatening invasive breast cancer. Because the determinants of invasive recurrence are unknown, all women with DCIS require the same treatment (usually with surgery and radiation). Therefore, there is a need to identify biologic markers and create a profile that will provide prognostic information that is more accurate than the currently used van Nuys Index to predict invasive recurrence. In the present review, we examined the many biologic markers studied in breast cancer, describe their main biologic role and their expression in DCIS, and review the various studies regarding their ability to serve as prognostic factors in breast cancer with an emphasis on predicting invasive recurrence in patients with DCIS. This review covers established markers, namely, ER, PR and HER2/neu, that are used routinely to make treatment decisions as well as investigative biologic factors involved in cell proliferation, cell cycle regulation, extracellular molecules, factors involved in extracellular matrix degradation, and angiogenesis. However, controversies exist regarding the value of these prognostic factors, their interrelationship, and their advantages over morphologic evaluation.

Biomarkers, Tumor↗

Comparison of the efficacy and acute toxicity of weekly versus daily chemoradiotherapy for non-small-cell lung cancer: a meta-analysis.

PURPOSE: Recent studies have reported improved survival with concurrent chemoradiotherapy (ChRT) for inoperable non-small-cell lung cancer (NSCLC). ChRT includes the delivery of low-dose chemotherapy given daily during radiotherapy (RT) or higher doses administered weekly. It remains unknown whether a difference in efficacy or toxicity exists between these approaches. A systematic review was performed to compare the efficacy and toxicity of weekly vs. daily ChRT. METHODS AND MATERIALS: The results from randomized studies comparing ChRT to RT for NSCLC were pooled using meta-analyses. The relative risk (RR) of death at 1, 2, and 3 years and of acute esophagitis, pneumonitis, or neutropenia (World Health Organization Grade 3 or greater) were determined. RESULTS: Ten studies involving 1802 patients were included. No significant difference in mortality or toxicity was observed between the weekly and daily regimens: RR of death at 2 years-weekly 0.93, 95% confidence interval [CI] 0.87-0.99; daily 0.92, 95% CI 0.85-1.00; RR of death at 3 years-weekly 0.93, 95% CI 0.89-0.98; daily 0.90, 95% CI 0.81-1.01; RR of esophagitis-weekly 2.07, 95% CI 0.96-4.46; daily 1.70, 95% CI 1.17-2.48; RR of pneumonitis-weekly 1.52, 95% CI 0.93-2.48; daily 1.17, 95% CI 0.65-2.09; and RR of neutropenia-weekly 8.57, 95% CI 3.75-19.58; daily 11.93, 95% CI 1.55-92.12. CONCLUSION: No statistically significant difference in efficacy or acute toxicity was observed to suggest the superiority of daily vs. weekly ChRT regimens for NSCLC.

Antineoplastic Agents↗

Is expert breast pathology assessment necessary for the management of ductal carcinoma in situ ?

BACKGROUND: Current guidelines include a recommendation that a pathologist with expertise in breast disease review all ductal carcinoma in situ (DCIS) specimens due to the presence of significant variability in pathologic reporting of DCIS. The objective of this study was to evaluate the completeness and accuracy of pathologic reporting of DCIS over the past decade and to determine the current impact of expert breast pathology assessment on the management of DCIS. METHODS: All patients with a diagnosis of DCIS referred to a single regional cancer centre between 1982 and 2000 have been reviewed. Inter-observer variability between initial and secondary reports has been evaluated using kappa statistics. For each case, the Van Nuys Prognostic Index (VNPI) using pathologic data obtained from the initial and reviewed pathology reports were compared. The impact of expert breast pathology on risk assessment and treatment was determined. RESULTS: 481 individuals with DCIS were referred and pathology review was performed on 350 patients (73%). Inter-observer agreement was high for the main pathologic features of DCIS. From 1996 to 2000, secondary pathology assessments lead to a change in the assessment of local recurrence risk in 100 cases (29%) and contributed to a change in treatment recommendation in 93 (43%) cases. CONCLUSION: Expert breast pathology assessments continue to be necessary in the management of DCIS.

Adult↗

Clinical significance of atomic inner shell ionization (ISI) and Auger cascade for radiosensitization using IUdR, BUdR, platinum salts, or gadolinium porphyrin compounds.

PURPOSE: Halogenated pyrimidines (iododeoxyuridine [IUdR] and bromodeoxyuridine [BUdR]), platinum salts, and gadolinium porphyrins are heavy atom compounds used as radiosensitizers. For IUdR, it has been hypothesized that iodine inner shell ionizations (ISI) and Auger cascades could be one of the primary radiosensitization mechanisms. The purpose of this paper is to estimate the number of ISI produced per tumor cell and per 2 Gy irradiation in clinically relevant modelings. MATERIALS AND METHODS: ISI were evaluated using a two-step method. Photon-induced ISI were calculated using the MCNP-4C Monte Carlo code, heavy atom concentrations from clinical data published in the literature, and at various depths in a water phantom irradiated with 6-MV, (60)Co, (137)Cs, or (192)Ir sources. Electron knock-on induced ISI on K, L, and M atomic shells were evaluated with an hybrid method, using simulated electron spectra and cross-sections derived from the Møller formalism. Using a biological dose equivalence of 0.05 Gy per cell ISI, relative biological effectiveness (RBE) values were calculated for each situation. RESULTS: For platinum and gadolinium, ISI occurs in far less than 0.1% of the cell, whichever is the configuration. For IUdR and BUdR, ISI occurs in between 45% to 483% of the cell. Due to spectrum degradation, about 3 times more photoelectric ISI are generated at greater than shallower depths, and 10 times more for (192)Ir compared with (60)Co or 6-MV X-rays. Photoelectric ISI are about 3 times more frequent for iodine than bromine, but electron knock-on ISI are more frequent on bromine, and at the end about the same number of ISI are generated for both elements. RBEs were found to be between 1.01 and 1.12 for clinically relevant irradiation settings. CONCLUSIONS: The mechanisms of radiosensitization for platinum and gadolinium are clearly not related to an Auger cascade. For halogenated pyrimidines, however, clinically relevant numbers of ISI are generated within each cell. For IUdR, ISI appears to be strongly tied to the photon spectra. Halogenated pyrimidines should be evaluated again clinically, but using lower energy photons like a (192)Ir implant.

Bromodeoxyuridine↗

A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer.

PURPOSE: To assess how women with ductal carcinoma in situ (DCIS) perceive their risks of recurrence, dying from breast cancer, and psychological distress compared to women with early stage invasive breast cancer (EIBC). PATIENTS AND METHODS: Eligible patients included those with DCIS or EIBC (T1 or T2, N0) referred to one cancer center between November 1998 and June 1999. Participants completed a self-administered survey regarding their views of their risks of developing recurrent cancer, of dying of breast cancer and the presence of psychological symptoms of distress. Responses were scored and compared between the two groups. RESULTS: In total, 495 patients were screened, 240 found ineligible, 228 patients who agreed to participate. No significant difference between the two groups was observed in perceptions of risk related to the likelihood of developing local recurrence (DCIS: 53%, EIBC 45%, P = 0.14), distant recurrence (DCIS: 36%; EIBC: 39%, P = 0.35) or dying of breast cancer (DCIS: 27%, EIBC 27%, P = 0.5). Both groups expressed similar levels of psychological distress (anxiety, DCIS: 56%, EIBC 54%, P = 0.38; depression, DCIS: 41%, EIBC, 48%, P = 0.17). CONCLUSIONS: Despite the excellent prognosis, women with DCIS express serious concerns and report similar psychological morbidity as women with invasive cancer.

Adult↗