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Biomedical subjects

A T Meadows

Publications and source records attributed to A T Meadows.

At least 19 recordsLinked to original sources
PubMed2000

Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma.

PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Outcome of CNS disease at diagnosis in disseminated small noncleaved-cell lymphoma and B-cell leukemia: a Children's Cancer Group study.

PURPOSE: To examine the impact of initial CNS involvement on outcome and patterns of failure in patients with disseminated small noncleaved-cell lymphoma and B-cell leukemia who were treated in four successive Children's Cancer Group trials. PATIENTS AND METHODS: Of 462 patients with disseminated disease, 49 (10.6%) had CNS disease at diagnosis (CNS+). CNS disease included meningeal disease or CNS parenchymal masses with or without cranial neuropathies (CSF+/Mass; CNPs) in 36 patients and isolated CNPs in 13. Of the CNS+ patients, 28 had M2 (5% to 25% blasts) or M3 (> 25% blasts) bone marrow involvement. All patients received protocol-based systemic and intrathecal chemotherapy. Thirty-six patients also received CNS irradiation. RESULTS: Relapses occurred in 21 (43%) of 49 patients, predominantly in the CNS (71%) and bone marrow (52%). The 3-year event-free survival +/- SE for all patients with CNS+ disease was 45% +/- 7%. Patients with CSF+/Mass had a nominally higher treatment failure rate compared with patients with CNS- after adjusting for marrow status and lactate dehydrogenase (LDH) diagnosis, with a relative failure rate (RFR) of 1.52 (95% confidence interval [CI], 0.88 to 2.6; P =.15). In comparison, the RFRs for patients with M2 or M3 marrow and for those with LDH levels greater than 500 IU/L after adjusting for CNS disease were 1.4 (95% CI, 0.96 to 2.0; P =.029) and 2.2 (95% CI, 1.5 to 3.0; P <.001), respectively. The RFR for patients with isolated CNPs was 0.87 (95% CI, 0.36 to 2.1; P =.76). CONCLUSION: We conclude that, with the treatments used during the period covered by these studies, the presence of CSF+/Mass CNS disease at diagnosis was associated with a nominally worse outcome independent of initial bone marrow status and LDH level, but the effect was not statistically significant.

Adolescent↗
PubMed2000

The role of renal salvage procedures for bilateral Wilms tumor: a 15-year review.

PURPOSE: We reviewed our experience with renal salvage procedures in patients with bilateral Wilms tumor to determine the clinical outcome. MATERIALS AND METHODS: From 1982 to 1997, 23 children with bilateral Wilms tumor were treated with partial nephrectomy at our institution, including 7 who were also treated with brachytherapy. Medical history, use and response to chemotherapy and brachytherapy, operative records, renal function, pathological results, survival, and techniques for partial and repeat nephrectomy and brachytherapy were reviewed. RESULTS: We treated 8 boys and 15 girls, of whom 21 who presented with synchronous bilateral Wilms tumor underwent primary chemotherapy followed by secondary partial nephrectomy. A total of 44 partial nephrectomies were performed and brachytherapy was done in 7 patients. Ten children have normal renal function and no disease, 10 are dead and 2 have metastatic disease. Anaplasia was the most significant factor associated with an unfavorable outcome (p = 0.003). Of the patients who were cured 60% had a positive response to initial chemotherapy compared with only 25% who had an unfavorable outcome (p = 0.09). No significant differences were noted with respect to gender, age at presentation, highest local tumor stage at presentation or initial nephrectomy. No patient treated with brachytherapy had local recurrence. CONCLUSIONS: Preoperative chemotherapy followed by nephron sparing surgery is indicated in patients with bilateral Wilms tumor, while in those with diffuse anaplasia nephron sparing surgery is contraindicated. Brachytherapy should be considered for treating local disease involving chemoresistant tumors.

Brachytherapy↗
PubMed1999

Late effects of chemotherapy compared to bone marrow transplantation in the treatment of pediatric acute myeloid leukemia and myelodysplasia.

BACKGROUND: As more pediatric patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) survive, comparison of the late effects of various therapies becomes increasingly important. This study of survivors of AML is the largest to date comparing the late effects of patients treated with chemotherapy (CT) with or without irradiation (RT) or CT followed by bone marrow transplantation (BMT). PROCEDURE: In a retrospective review of 228 patients with AML or MDS from 1970 to 1995, 62 survived and had follow-up data available more than 1 year following completion of therapy. Ten patients with Down syndrome were excluded. Twenty-six received CT and 26 underwent BMT. Weight and height Z scores, endocrine, ophthalmologic, renal, and cardiac function following CT +/- RT or BMT +/- total body irradiation (TBI) were compared at a mean follow-up of 7.4 and 5.6 years, respectively. RESULTS: Both groups experienced a decrement in height and increase in weight. The mean height Z score in the CT group fell from -0.29 to -0.72 (P = 0.02) and mean weight Z score rose from -0.06 at diagnosis (T0) to 0.51 at last follow-up (T2) (P = 0.02), a finding no longer significant when patients who received RT were excluded. The mean height Z score in the BMT group fell from -0.17 at TO to -0.65 at T2 (P = 0.02), while the mean weight rose from 0.29 at T0 to 0.84 at T2, (P = 0.07). Six of 9 BMT adolescent girls experienced ovarian failure versus 0 of 11 girls treated with CT (P = 0.002). Seven adolescent CT males and seven BMT males showed normal pubertal progression. Two BMT patients require thyroid hormone supplementation, and one receives growth hormone. Six BMT patients and one CT patient developed cataracts, all of whom received irradiation (P = 0.10). Serum creatinine level, hypertension, or left ventricular shortening fraction were not different in the two groups. One BMT patient has chronic graft versus host disease. CONCLUSIONS: Growth, renal, and cardiac functions were similar in the two groups. The need for estrogen supplementation was more frequent following BMT. Recommendations concerning therapy for AML should depend on the probability of cure.

Acute Disease↗
PubMed1998

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

OBJECTIVE: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. METHODS: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed. Median follow-up was 28 months. RESULTS: There were 16 eyes in the 2-cycle chemoreduction treatment group and 11 eyes in the 6-cycle chemoreduction treatment group. No significant difference was noted between the 2 groups with respect to baseline patient and eye findings. After chemoreduction treatment, external beam irradiation was necessary in 12 (75%) of 16 eyes in the 2-cycle chemoreduction treatment group and in 4 (36%) of 11 eyes in the 6-cycle chemoreduction treatment group. There was no statistical difference between the 2- and 6-cycle chemoreduction treatment groups with respect to necessity for external beam irradiation (logistic regression analysis). All 4 eyes in the 2-cycle chemoreduction treatment group and 3 of 12 eyes in the 2-cycle chemoreduction treatment and irradiation group were eventually enucleated, the globe salvage rates being 0% and 75%, respectively. Two of 7 eyes in the 6-cycle chemoreduction treatment group and 1 of 4 eyes in the 6-cycle chemoreduction treatment and irradiation group were enucleated, the globe salvage rates being 71% and 75%, respectively. Except for the 2-cycle chemoreduction treatment group, in which the globe salvage rate was significantly lower (P = .03), there was no difference among the other 3 groups (2-cycle chemoreduction treatment and irradiation, 6-cycle chemoreduction treatment, and 6-cycle chemoreduction treatment and irradiation) with respect to globe salvage (logistic regression analysis). CONCLUSIONS: Local tumor control of group V retinoblastoma is possible with 6-cycle chemoreduction and focal therapy when external beam irradiation is not used. A larger sample size is necessary to determine how often external beam irradiation can be avoided.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Predicting posttraumatic stress symptoms in mothers and fathers of survivors of childhood cancers.

OBJECTIVE: To predict posttraumatic stress symptoms in parents of survivors of childhood cancer, using as predictors the following: personality (trait anxiety); current family and individual variables (perceived life threat, perceived treatment intensity, life events, family functioning, and social support); posttreatment variables (time since treatment ended, child anxiety, medical sequelae); and treatment events (age at diagnosis, radiation therapy, intensity of treatment). METHOD: Mothers and fathers of 6- to 20-year-old survivors of childhood cancer (n = 331 families) completed a questionnaire battery in this two-site study. The outcome variable was the Posttraumatic Stress Disorder Reaction Index. Multiple regressions and path analyses were used to test the model. RESULTS: For both mothers and fathers, anxiety was the strongest predictor of posttraumatic stress symptoms. The current family and individual variables also contributed significantly, particularly with respect to the individual contributions of perceived life threat, perceived treatment intensity, and social support. Objective medical data did not contribute to posttraumatic stress symptoms. CONCLUSIONS: Parental anxiety warrants attention throughout the course of treatment for childhood cancer and after treatment ends. Beliefs about past and present life threats associated with cancer treatment and family and social support are other important targets for intervention.

Adolescent↗
PubMed1997

Familial neuroblastoma: a three-generation pedigree and a further association with Hirschsprung disease.

Like the other embryonal cancers of childhood, neuroblastoma occasionally occurs within families. We now provide an update on a nuclear family in which seven individuals are affected with neuroblastoma, inherited in an autosomal dominant fashion over three generations. In addition, two of these individuals are also affected with Hirschsprung disease. This family may lend insight into the molecular pathogenesis of familial neuroblastoma.

Child↗
PubMed1997

Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma.

OBJECTIVE: The purpose of the study is to investigate chemoreduction and adjuvant treatment (AT) for retinoblastoma and its effect on complete retinal tumor control, vitreous seed control, and subretinal seed control. DESIGN: The study design was a prospective, nonrandomized clinical trial. PARTICIPANTS: There were 130 intraocular retinoblastomas in 52 eyes of 32 consecutive patients observed for at least 1 year after initiation of treatment. INTERVENTION: Treatment with chemoreduction using vincristine, etoposide, and carboplatin (VEC) and adjuvant treatment (+ AT) (cryotherapy, laser photocoagulation, thermotherapy, chemothermotherapy, plaque radiation therapy, or external beam radiation therapy) were assessed. MAIN OUTCOME MEASURES: The effect of chemoreduction for 6 cycles (VEC x 6) versus fewer than 6 cycles (VEC x <6) on retinoblastoma control was analyzed. Furthermore, the impact of adjuvant treatment (+ AT) versus no adjuvant treatment (no AT) on retinoblastoma control was analyzed. RESULTS: Retinal tumors showed favorable initial regression with chemoreduction. Adjuvant treatment was applied to 93% of the retinal tumors after chemoreduction and only 2% recurred over the mean follow-up of 17 months (range 13-27 months). Vitreous seeds and subretinal seeds showed initial regression and often complete disappearance with chemoreduction. In those eyes with seeds before treatment, the addition of AT to VEC for 6 cycles decreased the vitreous seed recurrence from 75% to 0% (P = 0.04) and also decreased the subretinal seed recurrence from 67% to 0% (P = 0.003). More important, when considering that enucleation or external beam radiation therapy was the only other treatment option for these 52 eyes, the authors were successful in avoiding these methods in 42% of cases. Of the 36 eyes classified as Reese-Ellsworth group 5, there was 78% ocular salvage, and external beam radiation therapy was avoided in 25% of these eyes. There was a 100% ocular salvage in the group 5 eyes that received VEC for 6 cycles + AT to retinal tumors and seeds. CONCLUSIONS: Chemoreduction and AT to intraocular retinoblastoma and its seeds provides good retinal tumor control, even in eyes with advanced disease. Chemoreduction alone generally is not adequate to achieve complete tumor seed control. Cautious follow-up of affected patients is recommended because the risk for recurrent vitreous and subretinal seeds is substantial and proper treatment is critical for salvaging the eye.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Posttraumatic stress, family functioning, and social support in survivors of childhood leukemia and their mothers and fathers.

Psychological sequelae are examined in 130 former childhood leukemia patients and 155 comparison participants and their parents. The major dependent variables are symptoms of anxiety and posttraumatic stress, family functioning, and social support. Multivariate analyses of covariance indicated significantly more posttraumatic stress symptoms in mothers and fathers of childhood leukemia survivors (p < .001) and no differences between survivors and peers. There were no significant group differences for family functioning or social support, although they were associated with anxiety and posttraumatic stress outcomes. Current child age, age at diagnosis, and months off treatment were not significantly correlated with outcome. These findings document the long-term impact of childhood cancer treatment on parents. The lack of significant differences for survivors argues for further attention to the relevance of posttraumatic stress disorder for childhood cancer survivors. The clinical implications are that psychological interventions are needed during and after cancer treatment.

Adolescent↗
PubMed1997

Families surviving childhood cancer: a comparison of posttraumatic stress symptoms with families of healthy children.

Compared posttraumatic stress symptoms in 309 8- to 20-year-old survivors of childhood cancer and their parents with healthy children and their parents who responded to child-related stressors. The relationship of child demographic, cancer and treatment, and family and social support factors with posttraumatic stress symptoms was analyzed also. Results indicate that mothers and fathers of childhood cancer survivors showed significantly higher levels of posttraumatic stress symptoms than comparison parents. The survivors themselves did not differ from their healthy counterparts. Past perceived life threat and family and social support resources contributed to posttraumatic stress symptoms in survivors and their parents. Survivor mother and child and survivor father and child symptoms were associated. Implications for the long-term functioning of families of survivors and suggestions for preventive interventions are discussed.

Adolescent↗
PubMed1997

Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a cooperative Children's Cancer Group and National Institutes of Health study.

PURPOSE: To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood. PATIENTS AND METHODS: Adult survivors (n = 580), aged > or = 18 years, who were treated before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state. RESULTS: Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P<.01) and reported more tension (P< .01), depression (P<.01), anger (P<.01), and confusion (P<.01), but not more fatigue or less vigor. Female, minority, and unemployed survivors reported the highest total mood disturbance. Overall, survivors were more likely to be unemployed (P<.05) or working less than half-time (P<.01) compared with controls. CONCLUSION: This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention.

Adult↗
PubMed1996

Birth defects in offspring of adult survivors of childhood acute lymphoblastic leukemia. A Childrens Cancer Group/National Institutes of Health Report.

BACKGROUND: It is not known if therapy for acute lymphoblastic leukemia (ALL) during childhood increases the risk of birth defects in the offspring of adult survivors. The Childrens Cancer Group (CCG), in collaboration with the National Institutes of Health (NIH), conducted a retrospective cohort study of adults successfully treated for childhood ALL to determine if their offspring had an increased incidence of birth defects compared with the offspring of their sibling controls. METHODS: Study subjects were patients who had been enrolled on CCG ALL protocols, who were treated for ALL prior to age 20, who survived at least 2 years, and who were at least age 18. Survivors (N=593) and sibling controls (N=409) were interviewed by telephone. RESULTS: The mean age of survivors was 22.6 years; the mean age of controls was 25.2 years. Among survivors, 93 (15.7%) had given birth to or fathered a total of 140 live-born offspring, (mean age, 3.4 years), and 122 (29.8%) sibling controls had given birth to or fathered a total of 228 live-born offspring (mean age, 5.9 years). There was no difference in the rate of birth defects between offspring of survivors and offspring of controls (3.6% [5 of 140] vs. 3.5% [8 of 228]; relative risk, 1.02; 95% confidence interval, 0.34, 3.05). No specific ALL therapy was associated with an increased rate of birth defects. Only female survivors reported offspring with birth defects (P=0.0735). CONCLUSIONS: Adult survivors of childhood ALL in our study were not at greater risk for having offspring with birth defects compared with sibling controls. Although this is the largest group of ALL survivors studied to date, the number of offspring is still not large enough to detect small but significant differences in rare events such as birth defects. Studies following this cohort into later adulthood and studies of additional ALL survivors are necessary to adequately quantify the risks.

Adult↗
PubMed1996

Breast cancer and other second neoplasms after childhood Hodgkin's disease.

BACKGROUND: Patients who survive Hodgkin's disease are at increased risk for second neoplasms. As survival times increase, solid tumors are emerging as a serious long-term complication. METHODS: The Late Effects Study Group followed a cohort of 1380 children with Hodgkin's disease to determine the incidence of second neoplasms and the risk factors associated with them. RESULTS: In this cohort, there were 88 second neoplasms as compared with 4.4 expected in the general population (standardized incidence ratio, 18.1; 95 percent confidence interval, 14.3 to 22.3). The estimated actuarial incidence of any second neoplasm 15 years after the diagnosis of Hodgkin's disease was 7.0 percent (95 percent confidence interval, 5.2 to 8.8 percent); the incidence of solid tumors was 3.9 percent (95 percent confidence interval, 2.3 to 5.5 percent). Breast cancer was the most common solid tumor (standardized incidence ratio 75.3; 95 percent confidence interval, 44.9 to 118.4), with an estimated actuarial incidence in women that approached 35 percent (95 percent confidence interval, 17.4 to 52.6 percent) by 40 years of age. Older age (10 to 16 vs. <10 years) at the time of radiation treatment (relative risk, 1.9) and a higher dose (2000 to 4000 vs. <2000 cGy) of radiation (relative risk, 5.9) were associated with significantly increased risk of breast cancer. The estimated actuarial incidence of leukemia reached a plateau of 2.8 percent (95 percent confidence interval, 0.8 to 4.8 percent) 14 years after diagnosis. Treatment with alkylating agents, older age at the diagnosis of Hodgkin's disease, recurrence of Hodgkin's disease, and a late stage of disease at diagnosis were risk factors for leukemia. CONCLUSIONS: The risk of solid tumors, especially breast cancer, is high among women who were treated with radiation for childhood Hodgkin's disease. Systematic screening for breast cancer could be important in the health care of such women.

Actuarial Analysis↗