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J Brierley

Publications and source records attributed to J Brierley.

At least 19 recordsLinked to original sources

Post-operative radiochemotherapy for gastric cancer: adoption and adaptation.

AIMS: Intergroup study 0116 (INT-0116) showed an 11% absolute improvement in 3-year survival with post-operative radiochemotherapy for gastric cancer, but reported 33% severe acute GI toxicity using conventional simulation with large fields. We adapted the treatment using conformal radiotherapy techniques and assessed toxicity and outcome in 20 consecutive patients. METHODS: A conformal radiotherapy technique previously developed for gastric lymphoma was adapted to treat the target volume defined in INT-0116. The five-field plan used a large anterior field, plus asymmetrically matched upper AP:PA fields and lower lateral fields. Consecutive patients with ECOG PS 0-2 and stage IB-IV non-metastatic gastric cancer were treated with 5-FU (425 mg/m2 daily x 5 days) and leucovorin (20 mg/m2 daily x 5 days) for one cycle prior to and two cycles following concurrent radiation (45 Gy/25 fractions) with identical drug dosages on the first 4 and last 3 days of radiation. Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria. Patient charts were reviewed in November 2003 and late toxicity and outcome were recorded. RESULTS: Nineteen of 20 patients completed radiotherapy and 14 completed all chemotherapy cycles. One patient died of neutropenic sepsis. Maximum acute toxicity [grade (number)] was: 5(1), 4(0), 3(4), 2(10), 1(4), 0(1). There were two grade 1 late toxicities. Two-year overall survival is 70% (95% confidence interval: 50-90). CONCLUSIONS: Conformal radiotherapy may improve acute toxicity (25% grade 3 or greater toxicity as compared with 41% reported in INT-0116). Survival is comparable to that achieved in the INT-0116 treatment arm (approximately 60% at 2 years). INT-0116 results can be achieved outside a study setting; however, further efforts to improve treatment efficacy and minimize toxicity are warranted.

Adult↗

Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years.

OBJECTIVES: To assess the prognostic factors and the role of radioactive iodine (RAI) and external beam radiotherapy (RT) in patients with differentiated thyroid cancer. DESIGN: A retrospective review of 729 patients treated between 1958 and 1998. The median follow-up was 11.3 years (range 0.3-39.8 years). Primary outcomes included time to cause-specific survival and time to local-regional relapse. Baseline and treatment variables were assessed for statistical significance using the Cox proportional hazards model. RESULTS: The 10-year cause-specific survival (CSS) was 87.3% and the 10-year local-regional relapse-free rate (LRFR) was 84.9%. In multivariate analysis there was no statistically significant improvement in CSS with more aggressive treatment (i.e. more extensive surgery, the administration of RAI and/or RT). By multivariate analysis the use of RAI resulted in a statistically significant improvement in LRFR (hazard ratio 0.5; 95% confidence interval 0.3-0.8; P = 0.007). In low-risk patients at AJCC stage I < or = 45 years, there was no apparent benefit from RAI. For patients over 60, with extrathyroid extension but no gross residual disease (n = 70), adjuvant external RT resulted in statistically significantly higher CSS (10-year CSS 81.0%vs. 64.6%, P = 0.04) and LRFR (10-year LRFR 86.4%vs. 65.7%, P = 0.01). CONCLUSIONS: The use of RAI was associated with improved LRFR but not in low-risk patients. External beam RT improved LRFR and CSS in high-risk patients.

Adolescent↗

Local excision and postoperative radiotherapy for distal rectal cancer.

PURPOSE: To assess the outcome following local excision and postoperative radiotherapy (RT) for distal rectal carcinoma. MATERIALS AND METHODS: Seventy-three patients received postoperative radiotherapy following local surgery for primary rectal carcinoma at Princess Margaret Hospital from 1983 to 1998. Selection factors for postoperative RT were patient preference, poor operative risks, and "elective" where conservative therapy was regarded as optimal therapy. Median distance of the primary lesion from the anal verge was 4 cm (range, 1--8 cm). There were 24 T1, 36 T2, and 8 T3 lesions. The T category could not be determined in 5. Of 55 tumor specimens in which margins could be adequately assessed, they were positive in 18. RT was delivered using multiple fields by 6- to 25-MV photons. Median tumor dose was 50 Gy (range, 38--60 Gy), and 62 patients received 50 Gy in 2.5-Gy daily fractions. The tumor volume included the primary with 3--5 cm margins. No patients received adjuvant chemotherapy. Median follow-up was 48 months (range, 10--165 months). RESULTS: Overall 5-year survival and disease-free survival were 67% and 55%, respectively. Tumor recurrence was observed in 23 patients. There were 14 isolated local relapses; 6 patients developed local and distant disease; and 3 relapsed distantly only. For patients with T1, T2, and T3 lesions, 5-year local relapse-free rates were 61%, 75%, and 78%, respectively, and 5-year survival rates were 76%, 58%, and 33%, respectively. The 5-year local relapse-free rate was lower in the presence of lymphovascular invasion (LVI) compared to no LVI, 52% vs. 89%, p = 0.03, or where tumor fragmentation occurred during local excision compared to no fragmentation, 51% vs. 76%, p = 0.02. Eleven of 14 patients with local relapse only underwent abdominoperineal resection, 8 achieved local control, and 4 remained cancer free. The ultimate local control, including salvage surgery, was 86% at 5 and 10 years. The 5-year colostomy-free rate was 82%. There were 2 patients who experienced RTOG Grade 3 late complications, and 1 with Grade 4 complication (bowel obstruction requiring surgery). CONCLUSION: The local relapse rate for patients with T1 disease was high compared to other series of local excision and postoperative RT. Patients with LVI or tumor fragmentation during excision have high local relapse rates and may not be good candidates for conservative surgery and postoperative RT.

Adenocarcinoma↗

Squamous cell carcinoma of the oesophagus treated with radiation and 5-fluorouracil, with and without mitomycin C.

A retrospective analysis was performed of patients with squamous cell carcinoma of the oesophagus without evidence of distant metastases, who were treated with radical intent. Between 1981 and 1984, and 1989 and 1991, 98 patients were treated with radiation, 5-fluorouracil (5-FU) and mitomycin C; and between 1984 and 1989, 133 patients were treated with radiation and 5-FU without mitomycin C. Actuarial survival and local control were assessed, and prognostic factors were identified for both endpoints. The standard dose of radiation prescribed was 52 Gy to the 95% isodose in 20 fractions over 4 weeks. 5-FU was given by continuous infusion as 1 g/m2 (maximum 1.5 g)/day, for 4 days. Patients who received mitomycin C were given 10 mg/m2 (maximum 18 mg) on day 1. Survival and local relapse-free rates were estimated using the method of Kaplan and Meier, and the Cox proportional hazards model was used to evaluate possible prognostic factors, including the effect of mitomycin C administration. The median survival was 15.4 months (95% confidence interval 12.7-17.2) with 31% 2-year survival (standard error (SE) 3%), and 13% 5-year survival (SE 2%). In the multivariate analysis, lower radiation dose and younger age were the only statistically significant prognostic factors for reduced overall survival and reduced relapse-free rate respectively. There was no difference in survival (chi(2) = 0.07, 1 degree of freedom (df), P=0.79) or local relapse-free rate (chi2 = 0.39, 1 df, P = 0.53) between patients treated with or without mitomycin C. The treatment was well tolerated. Further studies are required to determine the most effective combination of radiation and chemotherapy or other radiation sensitizers for squamous cell carcinoma of the oesophagus.

Aged↗

Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study.

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2-47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.

Adolescent↗

Iron overload in paediatrics undergoing cardiopulmonary bypass.

Pathological changes in iron status are known to occur during bypass and will be superimposed upon physiological abnormalities in iron distribution, characteristic of the neonatal period. We have sought to define the severity of iron overload in these patients. Plasma samples from 65 paediatric patients undergoing cardiopulmonary bypass (CPB) were analysed for non-haem iron, total iron binding capacity, transferrin and bleomycin-detectable iron. Patients were divided into four age groups for analysis. Within each age group, patients who were in iron overload at any time point were statistically compared to those who were not. The most significant changes in iron chemistry were seen in the plasma of neonates, with 25% in a state of plasma iron overload. 18.5% of infants and 14.3% of children at 1-5 years were also in iron overload at some time point during CPB. No children over 5 years, however, went into iron overload. Increased iron saturation of transferrin eliminates its ability to bind reactive forms of iron and to act as an antioxidant. When transferrin is fully saturated with iron, reactive forms of iron are present in the plasma which can stimulate iron-driven oxidative reactions. Our data suggest that paediatric patients are at greater risk of iron overload during CPB, and that some form of iron chelation therapy may be advantageous to decrease oxidative stress.

Bleomycin↗

Antioxidant protection against iron toxicity: plasma changes during cardiopulmonary bypass in neonates, infants, and children.

Cardiopulmonary bypass surgery is associated with the release of low molecular mass iron, which increases the saturation of plasma transferrin to over 50% in all adult patients treated. In a significant minority, however plasma transferrin becomes 100% iron saturated and non-transferrin bound iron can be detected in the plasma. An iron-saturated transferrin is also a common physiological finding in normal term and pre-term infants at a time when their plasma antioxidants, which protect against iron toxicity and radical scavenging, are profoundly different from those seen in adults. This study was conducted to assess the extent to which antioxidants, which protect against iron toxicity, are altered in neonates, infants, and children undergoing cardiopulmonary bypass surgery.

Antioxidants↗

Outcome after treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.

BACKGROUND: Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial. OBJECTIVE: To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma. DESIGN: Analysis of data from a multicenter study. SETTING: 14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry. PATIENT: 385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma). MEASUREMENTS: Death, disease progression, and disease-free survival. RESULTS: Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival. CONCLUSIONS: This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.

Adenocarcinoma, Follicular↗

Medullary thyroid cancer: analyses of survival and prognostic factors and the role of radiation therapy in local control.

Records of 73 patients with medullary thyroid cancer were reviewed to assess prognostic factors and the role of external beam radiation therapy. Patients were treated between 1954 and 1992. The median age was 49 years (range 15-85), M:F ratio 1.6:1, and the median follow-up was 7.9 years. (2.5-34.6). The primary tumor size was < 1 cm in 10%, 1-4 cm in 53%, and > 4 cm in 37%. Multifocality was noted in 32%, and 23% had metastasis at presentation. Eight patients presented with inoperable tumors, 40% had gross, and 37% microscopic residual disease postthyroidectomy. Extraglandular extension was present in 56%, and 74% had pathologically involved lymph nodes. Treatment was by total or near total thyroidectomy in 41 patients; 37 had a lymph node dissection. Forty-six patients were irradiated, the dose of radiation ranging from 20 to 75.5 Gy; median was 40 Gy, treatment time median was 28 days and the median number of fractions was 20. The overall cause specific survival (CSS) was 70% and 57% at 5 and 10 years, respectively. In a univariate analysis, the following factors predicted for lower CSS: age as a continuous variable (p = 0.003), male gender (p = 0.008), presence of distant metastasis (p < 0.0001), lymph node involvement (p = 0.03), gross residual disease (p < 0.0001), tumor size > 4 cm (p = 0.05), extraglandular invasion (p < 0.004), vascular invasion (p = 0.007), diarrhea (p < .0007), and abnormal postoperative calcitonin (p = 0.02). On multivariate analysis only two factors were significant: the presence of extraglandular invasion, and postoperative gross residual disease. There was no difference in local/regional relapse free rate between patients receiving external radiation and those that did not, but in 40 high risk patients (microscopic residual disease, extraglandular invasion, or lymph node involvement), the local/regional relapse free rate was 86% at 10 years with postoperative external beam radiation (25 patients), and 52% for those with no postoperative external radiation (p = 0.049). To optimize local/regional tumor control, we therefore continue to advise external beam radiation in patients at high risk of local/regional relapse.

Adolescent↗

Glioma arising after radiation therapy for pituitary adenoma. A report of four patients and estimation of risk.

BACKGROUND: Many case reports in the literature associate cranial radiation therapy with the development of brain tumors. Quantitation of the risk of second brain tumors after irradiation in childhood is available, but it is seldom reported for those treated by radiation therapy as adults. METHODS: A retrospective review was made of 367 patient records registered at the Princess Margaret Hospital with a diagnosis of pituitary adenoma from 1972 to 1986. Three hundred five patients treated with megavoltage radiation therapy form the basis of this report. Second brain tumors were identified and the patient case histories described. The risk of second brain tumor after irradiation was estimated by calculating the observed/expected (O/E) ratio, age- and sex-adjusted to the Ontario population. RESULTS: Of the 305 patients in this study, 4 had glioma of the brain. All gliomas arose within the previous radiation field(s), with a latency of 8-15 years after radiation therapy. Additional treatment was compromised by the location of the glioma and the moderately high doses of radiation received previously; all four patients died of their gliomas. Our cohort of patients had a relative risk of malignant brain tumor 16 times greater than that of the general population in Ontario (P < 0.001; 95% confidence interval, 4.4-41). The cumulative actuarial risk of secondary glioma after radiation therapy was 1.7% at 10 years and 2.7% at 15 years. CONCLUSIONS: There was a clinically significant increased risk of malignant brain tumor developing after radiation therapy for pituitary adenoma. Because there is no reported association between pituitary adenomas and gliomas of brain, this excess risk is attributed to irradiation. Before advising radiation therapy for pituitary adenoma, the risk:benefit ratio, including the risk of secondary brain tumors, should be carefully considered.

Adenoma↗

Hormone-induced preimplantation Lyt 2+ murine uterine suppressor cells persist after implantation and may reduce the spontaneous abortion rate in CBA/J mice.

Immunoregulatory cells in the maternal uterine endometrium and decidua are thought to play an important role in ensuring the success of the semiallogeneic conceptus. Two phases of suppression have been described in pregnant mice. Prior to implantation, the hormonal changes triggered by mating activate or recruit a population of nonspecific Lyt 2+ suppressor cells that inhibit cytotoxic T lymphocyte generation: this suppression appears to wane at the time or implantation and 4-5 days after implantation, a non-T suppressor cell population activated or recruited by fetal trophoblast cells develops. In this paper we confirm the non-major histocompatibility complex specificity of the hormone-regulated preimplantation suppressor cell. We show that this activity persists in the uterus during the early postimplantation period where its suppressive activity is masked by an Fc-receptor-positive cell population recruited by the implanting embryo. The potential importance of the persisting suppressor cells is suggested by an increase in the rate of spontaneous abortion of DBA2-mated CBA/J mice following injection of monoclonal anti-Lyt 2+ antibody in the early postimplantation period.

Abortion, Veterinary↗

Characterization of hormone-dependent suppressor cells in the uterus of mated and pseudopregnant mice.

The survival of the implanted "fetal allograft" has been attributed to the action of local decidua-associated suppressor cells. These suppressor cells are Fc-receptor positive small lymphocytic cells lacking T-cell markers which arise following implantation, are localized at the implantation site, and block the action of IL-2 that stimulates NK and T effector cells. Kinetic studies have demonstrated the occurrence of an earlier peak of suppressive activity occurring 2-3 days after mating prior to implantation. The cells associated with pre-implantation suppression differs significantly from post-implantation suppressor cells. Velocity sedimentation studies show that early suppression is associated with large cells sedimenting at a modal velocity of 6-7 mm/hr. Suppressive activity from cells of similar size is also present in the uterine lining of hormonally-treated, pseudopregnant mice. In addition, suppressor cells can be demonstrated in the non-pregnant uterus at the time of estrus. These observations suggest suppressor cell activity may be hormonally regulated. The suppressor cell(s) in pseudopregnant mice bears Lyt 2.1 and Thy 1.2 surface antigens and suppressor(s) present in the pregnant animals bears Lyt 2.1 and Lyt 1.1. Although the suppressor cell was large, it did not appear to be a macrophage because it was resistant to antibodies to Mac-1 and FcR cell surface markers but susceptible to anti-T cell reagents. Furthermore, suppression was not mediated by a soluble factor that has been associated with the small lymphocytic suppressor. Thus, the suppressor activity present in the pre-implantation uterine lining appears to differ significantly from the suppressor cell activity found after implantation. The possible role of a hormone-activated suppressor T cell in the success of the pregnancy is discussed.

Animals↗