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F Perera

Publications and source records attributed to F Perera.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of intra- and inter-fraction motion in breast radiotherapy using electronic portal cine imaging.

Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters. EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD linear accelerator. Depending on the incident dose and the angle of the wedge, between 4 and 16 images could be acquired in one session using an EPI device based on liquid ionization chambers (Varian). The border between lung and chest-wall could be easily detected in all images and quantitative measurements were taken for the amount of lung in the field and the distance of the breast tissue from the field edges. Inter-fraction variability was found to be about twice as large as intra-fraction variability. The largest variability was detected in cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/- 1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm intra- and inter-fraction, respectively. This indicates that the effect of breathing motion on the amount of radiated lung was not of major concern in the patients studied. Of other patient specific parameters such as body weight, breast separation, field size and location of the target, only increasing age was significantly correlated with larger inter-fraction motion. Acquisition of EPI cine loops proved to be a quick and easy technique to establish the amount of patient movement during breast radiotherapy. The relatively small variability found in the present pilot study justifies considerations for more conformal dose delivery.

Aged↗
PubMed2000

The association between glutathione S-transferase M1 genotype and polycyclic aromatic hydrocarbon-DNA adducts in breast tissue.

A major goal in molecular epidemiology is to identify preventable environmental risk factors and susceptible subpopulations. In a hospital-based molecular epidemiological case-control study of breast cancer, we investigated the relationship between DNA damage from exposure to polycyclic aromatic hydrocarbons (PAHs) and susceptibility attributable to inherited deletion of the xenobiotic detoxifying gene, glutathione S-transferase M1 (GSTM1). Prior to breast surgery, women (n = 227) were enrolled and interviewed and donated a blood sample. PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples retrieved from pathology blocks, and GSTM1 genotype was determined by PCR using WBC DNA. The GSTM1 analysis included 95 cases and 87 benign breast disease controls. GSTM1 genotype was not associated with breast cancer case-control status (odds ratio = 0.73; 95% confidence interval, 0.37-1.44). However, the GSTM1 null genotype predicted PAH-DNA adduct levels in malignant (beta = 0.407; P = 0.003) and nonmalignant (beta = 0.243; P = 0.05) breast tissue from cases. This relationship was not seen in tissue from controls (beta = 0.095; P = 0.341). When tissue from controls was compared with tumor tissue from cases, there was a significant case-control difference in PAH-DNA adduct levels among women who were GSTM1 null. There was no such case-control difference among women who were homozygous or heterozygous for GSTM1. There was an interaction between GSTM1 and case-control status on adduct levels in breast tissue (P = 0.002). The results suggest that genetic susceptibility to the formation of PAH-DNA adducts in breast tissue may play a role in breast cancer development.

Adult↗
PubMed1998

Does delay in breast irradiation following conservative breast surgery in node-negative breast cancer patients have an impact on risk of recurrence?

PURPOSE: This retrospective review was conducted to determine if delay in the start of radiotherapy after definitive breast surgery had any detrimental effect on local recurrence or disease-free survival in node-negative breast cancer patients. METHODS AND MATERIALS: A total of 568 patients with T1-T2, N0 breast cancer were treated with breast-conserving surgery and breast irradiation, without adjuvant systemic therapy between January 1, 1985 and December 31, 1992, at the London Regional Cancer Centre. Adjuvant breast irradiation consisted either of 50 Gy in 25 fractions or 40 Gy in 15 or 16 fractions, followed by a boost of 10 Gy or 12.5 Gy to the lumpectomy site. The time intervals from definitive breast surgery to breast irradiation used for analysis were 0-8 weeks (201 patients), > 8-12 weeks (235 patients), > 1216 weeks (91 patients), and > 16 weeks (41 patients). The time intervals of 0-12 weeks (436 patients) and > 12 weeks (132 patients) were also analyzed. Kaplan-Meier estimates of time to local recurrence and disease-free survival rates were calculated. The association between surgery-radiotherapy interval, age (< or = 40, > 40 years), tumor size (< or = 2, > 2cm), Scharf-Bloom-Richardson (SBR) grade, resection margins, lymphatic vessel invasion, extensive intraductal component, and local recurrence and disease-free survival were investigated using Cox regression techniques. RESULTS: Median follow-up was 63.5 months. Patients in all 4 time intervals were similar in terms of age and pathologic features. There was no statistically significant difference between the 4 groups in local recurrence or disease-free survival with surgery-radiotherapy interval (p = 0.189 and p = 0.413, respectively). The 5-year freedom from local relapse was 95.4%. The crude local recurrence rate was 6.9% (7.8% for 436 patients treated within 12 weeks (median follow-up 67 months) and 3.8% for 132 patients treated > 12 weeks from surgery (median follow-up 52 months). In a stepwise multivariable Cox regression model for disease-free survival, allowing for entry of known risk factors, tumour size (p < 0.001), grade (p < 0.001), and age (p = 0.048) entered the model, but the surgery-radiotherapy interval did not enter the model. CONCLUSION: This retrospective study suggests that delay in start of breast irradiation beyond 12 and up to 16 weeks does not increase the risk of recurrence in node-negative breast cancer patients. The certainty of these results are limited by the retrospective nature of this analysis and the lack of information concerning the late local failure rate.

Adult↗
PubMed1997

A phase I pilot study of pelvic radiation and alpha-2A interferon in patients with locally advanced or recurrent rectal cancer.

PURPOSE: The purpose of this pilot study was to determine the maximum tolerated dose of alpha-2a interferon given by subcutaneous injection and combined with high dose pelvic radiation for locally advanced or recurrent rectal cancer. METHODS AND MATERIALS: In this Phase I pilot study, patients with locally advanced, unresectable, or recurrent rectal cancer with or without distant metastases received external beam pelvic radiotherapy over 5 to 6 weeks combined with escalating doses of alpha-2a interferon. Interferon was escalated in increments of 3 million units for each patient cohort, starting at 3 million units subcutaneously 3 days weekly during pelvic radiation. Radiotherapy consisted of 44 Gy (2 Gy fractions) to the pelvis followed by a boost of 6 Gy or 16 Gy to gross pelvic tumor, depending on the presence or absence of small bowel in the boost field, respectively. Between 1991 and 1993, 10 patients were treated on this study, five with locally advanced and five with locally recurrent rectal cancer. RESULTS: At 6 million units of interferon, Grade 3 (WHO criteria) toxicities were as follows: diarrhea (one), leukopenia (one), and neutropenia (one). One patient died of a massive GI bleed at this dose level. Death was not felt to be treatment related. The maximum tolerated dose of interferon was 3 million units three times weekly with radiation. Three patients had unusual complications at 4, 6, and 6 months possibly related to treatment. The first had a right distal ureteric stricture with a right urinoma. The second had a sudden left foot drop that has remained stable. The third had sudden onset of bilateral lower extremity paraplegia with spontaneous resolution. CONCLUSIONS: The maximally tolerated dose of interferon alpha-2a given three times weekly during pelvic radiation was 3 million units based on acute side effects. Nevertheless, even at this dose level there were three unusual subacute complications possibly related to treatment. Caution is advised when combining interferon alpha-2a with high dose pelvic radiation, especially in patients with predisposing conditions (such as diabetes) for radiotherapy complications.

Aged↗
PubMed1997

Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study.

BACKGROUND AND OBJECTIVES: The commonest site of local breast recurrence after breast conservation surgery is the primary tumor bed. We have tested the feasibility of outpatient high dose rate brachytherapy to the primary tumor bed as the only radiation. Our technique relies on the placement of surgical clips to mark the tumor bed. METHODS: Between March 1992 and January 1996, 39 patients with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13 patients had intraoperative implantation of the breast. The remaining 26 patients had outpatient postoperative implantation under general anesthesia (2 patients) or local anaesthesia (24 patients). High dose rate brachytherapy was given twice daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7 days. RESULTS: Three patients had mild clinical cellulitis responding to oral antibiotics. One patient had a small sinus in the lumpectomy scar requiring local excision to heal. Four patients developed fat necrosis at the lumpectomy site at 4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy. Patient rated satisfaction with treatment was high. At a median followup of 20 months, one infield local recurrence has been salvaged by wider resection and postoperative conventional external beam radiation. CONCLUSIONS: Except for fat necrosis, which may be associated with this technique, complications have been minimal. Outpatient implantation under local anesthesia is feasible. Longer followup is required to establish the local control rates.

Adult↗
PubMed1995

Tamoxifen with and without radiation after partial mastectomy in patients with involved nodes.

PURPOSE: To determine the effect of tamoxifen on local control after partial mastectomy with and without adjuvant breast irradiation. METHODS AND MATERIALS: A retrospective study of 97 node positive patients identified from the records of the London Regional Cancer Center included 44 patients who received tamoxifen and breast irradiation (40 or 50 Gy plus booster dose) after partial mastectomy, and 53 patients who received tamoxifen only after partial mastectomy. Base line characteristics of the two groups were similar. RESULTS: At 39 months actuarial follow-up there was a breast tumor recurrence (BTR) in 5% vs. 21% of patients when radiation was omitted (p = 0.0388), but there was no difference in the cause-specific mortality of the two treatment groups. Cox Regression analysis (on only 10 BTR) showed age and adjuvant radiation as significant predictors of BTR. In patients not receiving radiation, no BTR was seen in 22 patients > or = 70 years of age at diagnosis vs. 8 BTR in 31 patients < 70 years (p = 0.0130). All BTR occurred while patients were receiving tamoxifen. CONCLUSIONS: Tamoxifen alone with omission of radiation after partial mastectomy provides inferior breast tumor control in node positive patients. This is especially true for patients under 70 years of age. Patients aged 70 years or older at the time of diagnosis of breast cancer who receive tamoxifen have a low rate of breast tumor recurrence when radiation is omitted. These patients represent a group for whom radiation might not be necessary.

Adult↗
PubMed1995

Method of localization and implantation of the lumpectomy site for high dose rate brachytherapy after conservative surgery for T1 and T2 breast cancer.

PURPOSE: This article describes our technique of localization and implantation of the lumpectomy site of patients with T1 and T2 breast cancer. Our method was developed as part of our Phase I/II pilot study of high dose rate (HDR) brachytherapy alone after conservative surgery for early breast cancer. METHODS AND MATERIALS: In March 1992, we started a pilot study of HDR brachytherapy to the lumpectomy site as the sole radiotherapy after conservative surgery for clinical T1 or T2 invasive breast cancer. Initially, the protocol required intraoperative placement of the interstitial needles at the time of definitive surgery to the breast. The protocol was then generalized to allow the implantation of the lumpectomy site after definitive surgery to the breast, either at the time of subsequent axillary nodal dissection or postoperatively. To date, five patients have been implanted intraoperatively at the time of definitive breast surgery. Twelve patients were implanted after definitive breast surgery, with 7 patients being done at the time of axillary nodal dissection and 5 patients postoperatively. We devised a method of accurately localizing and implanting the lumpectomy site after definitive breast surgery. The method relies on the previous placement of surgical clips by the referring surgeon to mark the lumpectomy site. For each patient, a breast mold is made with radio-opaque angiocatheters taped onto the mold in the supero-inferior direction. A planning CT scan is then obtained through the lumpectomy site. The volume of the lumpectomy site, the number of implant planes necessary, and the orientation of the implants are then determined from the CT scan. The angiocatheters provide a reference grid on the CT films to locate the entry and exit points of the interstitial needles on the plastic mold. The entry and exit points for reference needles are then transferred onto the patient's skin enabling implantation of the lumpectomy site. Needle positions with respect to the lumpectomy site are then verified using simulator radiographs. RESULTS: Eight double plane implants and four single plane implants have been done using this method. Five implants were done using direct visualization. It has not been necessary to reorient the implant in any of the patients. If not for the presence of surgical clips, the size of the lumpectomy site cannot be separated from the surrounding normal breast tissue. CONCLUSION: This technique is an accurate way to localize the lumpectomy site for HDR brachytherapy.

Adult↗
PubMed1994

Platinum-DNA adducts assayed in leukocytes of patients with germ cell tumors measured by atomic absorbance spectrometry and enzyme-linked immunosorbent assay.

BACKGROUND: Platinum-DNA adducts can be measured in peripheral blood cells, and high adduct levels have previously been correlated with favorable clinical response to platinum-based therapy in patients with germ cell tumors and ovarian cancer. METHODS: To evaluate the relationship between platinum-DNA adducts and clinical response to chemotherapy, 36 patients with germ cell tumors treated with cisplatin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin [VAB-6] with or without high dose carboplatin plus etoposide plus autologous bone marrow rescue (Regimen C). Blood samples were drawn before and after each cycle of chemotherapy. RESULTS: One hundred ninety-two blood samples were assayed by AAS and 137 by ELISA: DNA adducts measured by AAS and ELISA increased immediately after treatment and decreased during the intervening time before the next treatment. DNA adducts were measurable by both methods 4-8 weeks after the last cycle of therapy. The peak and mean adduct levels measured in samples drawn immediately after Cycles 1 and 2 and after all cycles were analyzed in terms of their relationship to clinical response. In contrast to numerous prior studies, a positive correlation was not observed between DNA adduct formation as determined by either AAS or ELISA and favorable clinical responses. CONCLUSIONS: This study demonstrated that peak and mean platinum-DNA adduct levels were influenced by the dose and schedule of the platinum analogue. For example, treatment with VAB-6 with or without high dose carboplatin and etoposide (Regimen C) resulted in significantly higher adduct levels when measured by AAS compared with Regimen A or B. Inconsistencies between studies regarding observed correlations of DNA adducts and treatment outcome may be attributable to differences in platinum analogue, dose, schedule, and timing of sample procurement. These factors must be considered in future studies.

Adolescent↗
PubMed1994

Peripheral thrombocytopenia, accessory spleen and Hodgkin's disease: an unusual combination.

A 32-year-old male developed severe autoimmune thrombocytopenia refractory to conventional immunosuppression. He had been treated with radiotherapy for stage I-A Hodgkin's disease (HD) 2 years earlier after a staging laparotomy and splenectomy. A 3-cm accessory spleen was detected using computed tomography scan and 99mTc scintigraphy. Resection resulted in normalization of the platelet counts. Two years later the patient remains in remission of both diseases. Immune thrombocytopenia is rarely associated with HD and its remission following resection of an accessory spleen is an unusual finding.

Adult↗
PubMed1992

Genetic monitoring of human polymorphic cancer susceptibility genes by polymerase chain reaction: application to glutathione transferase mu.

Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human populations and are associated with increased risk of cancer at some sites. This study focuses on the polymorphic enzyme glutathione transferase mu (GT mu). Smokers with low lymphocyte GT mu activity are at an approximately 2-fold higher risk for lung cancer and an approximately 3-fold higher risk for stomach and colon adenocarcinomas. Recent cloning and sequencing of the GST1 gene has allowed the development of convenient genotyping methods based on restriction fragment length polymorphisms (RFLP) or the polymerase chain reaction (PCR). The GST1 polymorphism has been shown to be a deletion of the gene locus. To detect the presence or absence of the gene we amplified exons 4-5 and/or exons 6-7 of the GST1 gene by PCR. PCR amplification produced bands of 215-bp or 273-bp from individuals with one or two copies of the GST1 allele and no band if the individual was homozygously deleted (0/0). In the exon 6-7 PCR, we co-amplified a 268-bp portion of the beta-globin gene as an internal reference standard for quantitative analysis of product yield. This allowed homozygote individuals (+/+) to be distinguished from heterozygotes (+/0). We have compared the GST1 genotype to lymphocyte GT mu activity measured on trans-stilbene oxide (TSO) in the lymphocytes of 45 individuals. Low GT mu activity (< 67 pmole/min/10(7) cells) was strongly associated (24/24) with the GST1 0/0 genotype. With the exception of one individual, activities greater than 67 pmole/min/10(7) were associated with the presence of the GST1 allele (20/21). Individuals with the highest GT-TSO activity were found to be homozygous for GST1. (+/+), while heterozygotes (+/0) generally had lower activity, suggesting a gene dosage effect in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene Deletion↗
PubMed1992

DNA adducts and related biomarkers in populations exposed to environmental carcinogens.

Prevention of environmentally related cancer will be enhanced by the availability of sensitive early warning systems and by improvements in quantitative assessment of human risks. Accordingly, we have carried out a series of molecular epidemiologic studies aimed at validating a panel of biologic markers, including carcinogen-DNA and -protein adducts, sister chromatid exchange, micronucleus formation, DNA strand breaks, and DNA repair capacity. Results from three such studies illustrate the usefulness of these biomarkers in elucidating low-dose-response relationships, correlations between biomarkers, and the range of variation in biomarkers between individuals exposed to similar concentrations of carcinogens. Low-level workplace or ambient exposures to styrene, ethylene oxide, and polycyclic aromatic hydrocarbons (PAH) were associated with significant increases in both molecular dose of carcinogens (adducts) and various markers of preclinical effects. Correlations between biomarkers varied by exposure. For example, in the styrene study, sister chromatid exchange frequency was not correlated with any of the markers, in contrast to the studies of ethylene oxide and PAH. Significant molecular effects were observed not only in occupationally exposed people but also in residents of an area in Poland characterized by high levels of air pollution. For example, the mean PAH-DNA level in exposed residents (winter sample) was 30.4 adducts per 10(8) nucleotides. This level was significantly higher than that of adducts seen in summer samples from the same area (4.2/10(8), or in winter samples from residents of a rural area (11.01/10(8). Significant seasonal variation in PAH-DNA adduct formation in this group was consistent with recorded fluctuations in air pollution levels. Striking interindividual variation was observed in all three exposed populations.

Biomarkers↗
PubMed1991

Biologic markers in risk assessment for environmental carcinogens.

The potential of biologic markers to provide more timely and precise risk assessments for environmental carcinogens is viewed against the current state-of-the-art in biological monitoring/molecular epidemiology. Biologic markers such as carcinogen-DNA adducts and oncogene activation are currently considered valid qualitative indicators of potential risk, but for most chemical exposures research is needed to establish their validity as quantitative predictors of cancer risk. Biologic markers have, however, already provided valuable insights into the magnitude of interindividual variation in response to carcinogenic exposures, with major implications for risk assessment.

Bias↗