Vitamin E/beta carotene and lung cancer.
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Aged↗
Biomedical subjects
W Newton
Publications and source records attributed to W Newton.
The Cooperative Human Tissue Network. An update.
BACKGROUND: During the past decade, the National Cancer Institute became aware of a lack of availability of human tissues for research, especially in the fields of molecular biology, genetics, and immunology. METHODS: In 1987, the National Cancer Institute (NCI) established the Cooperative Human Tissue Network (CHTN) by funding three institutions that had extensive experience in the procurement and distribution of tissues for research. RESULTS: Since its inception, the CHTN has been expanded to five member institutions, with the addition of the Columbus Children's Hospital (the Pediatric Division for the procurement of pediatric tissues) and Case Western Reserve University. Each of the five divisions have established regional networks of institutions that supply tissues to the major divisions. From 1987 through 1991, the CHTN has distributed more than 29,000 human tissue samples and supplied approximately 500 researchers throughout the country. CONCLUSIONS: This report describes the development and current status of the CHTN, a valuable resource to the research community.
Containment of Biohazards↗
Ascending myelitis after intensive chemotherapy and radiation therapy in children with cranial parameningeal sarcoma.
In 1977, a program of early, wide-field radiation therapy (RT) to the central nervous system and repeated lumbar intrathecal (IT) medications along with systemic chemotherapy was begun by the Intergroup Rhabdomyosarcoma Study (IRS) for patients younger than 21 years of age with cranial parameningeal sarcoma and a high risk of meningeal extension. From 1977 until 1987, 149 eligible patients with high-risk cranial parameningeal sarcoma were enrolled in IRS trials. None had evidence of lower extremity or sphincter impairment at diagnosis. Five of the 149 (3.4%) had ascending myelitis at 5.5 to 9 months after the initiation of therapy, with loss of sphincter control and inability to walk; this progressed to severe flaccid quadriparesis and necessitated long-term ventilatory support in 4. All five had received vincristine, dactinomycin, cyclophosphamide, and doxorubicin; four also had received cisplatin and three also had received etoposide. All patients received 4770 to 5500 cGy to the primary tumor, and four patients received 3000 cGy of cranial RT. Three patients received cervical RT and two received spinal RT. The patients also received four to seven courses of IT methotrexate, hydrocortisone, and cytosine arabinoside. Three patients died: one after local tumor recurrence with central nervous system extension and two without known recurrence. In one of the latter patients, the results of an autopsy showed necrosis of the cervical spinal cord and caudal medulla. Although the exact cause of this complication is unclear, no additional cases have been reported to the IRS since the protocol was revised in 1987 to reduce the doses of the IT drugs and to limit them to four courses each.
Adolescent↗
There is no such thing as a free lunch. Developing policies on pharmaceutical industry support.
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Drug Industry↗
Soft tissue sarcoma of the perineal region in childhood. A report from the Intergroup Rhabdomyosarcoma Studies I and II, 1972 through 1984.
Thirty-six previously untreated patients younger than 21 years of age with sarcoma arising in the perineal region were entered on the Intergroup Rhabdomyosarcoma Studies (IRS) I and II from 1972 through 1984. The tumor histologic subtype was alveolar rhabdomyosarcoma (RMS) in 20 patients (56%), embryonal RMS in 11 patients (30%), and other types of sarcoma in 5 patients (14%). Fifteen children had grossly complete surgical excision (Clinical Groups I and II), and 15 had localized gross residual tumor (Group III) after initial operative management. Six patients had distant metastases (Group IV) at diagnosis. Twelve patients without distant metastases underwent regional lymph node biopsy; tumor involvement was found in six. Subsequent treatment consisted of chemotherapy with vincristine (VCR) and dactinomycin (AMD) for all patients; patients in Groups III and IV also received cyclophosphamide (CYC) with or without Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). Radiation therapy (RT) was administered to patients in Clinical Groups II, III, and IV. Overall, 28 (78%) patients achieved a complete clinical response. The 3-year disease-free survival rate for these patients was 42%, compared with 52% for all other patients in the combined IRS I and IRS II series (P = 0.44). The overall 3-year survival rate was 59%, compared with 64% for all other patients in IRS I and IRS II (P = 0.48). Aggressive treatment is needed in children with perineal sarcoma to improve their prognosis.
Adolescent↗
Primary reexcision for patients with 'microscopic residual' tumor following initial excision of sarcomas of trunk and extremity sites.
Among 404 patients with primary tumors of extremity-trunk sites entered in the Intergroup Rhabdomyosarcoma Study (IRS) (1972 to 1984), 154 were placed in clinical group IIa, ie, with negative nodes but with "microscopic residual" (MR) disease, following the initial excisional (not biopsy) procedure. An elective reexcision of the area of the primary tumor (PRE) was performed in 41 of these patients within 35 days (mean interval, 14 days; SE, 0.9) with no intervening therapy. These procedures consisted of wider excision of the tumor "bed," resulting in a technical transfer of these patients from group IIa to group I, ie, complete excision. This reduced intensity of nonsurgical therapy (irradiation and chemotherapy). Among the 41 patients who underwent PRE, the 3-year survival estimate (Kaplan-Meier) was 91% (SE, 4%). This may be compared with the results in 113 patients who remained in group IIa, in which the 3-year survival estimate was 74% (SE, 4%). A second group for comparison consisted of the 73 patients with trunk/extremity tumors who were placed in group I after a single excisional procedure, ie, no PRE, in whom the 3-year survival estimate was 74% (SE, 5%). Recognized prognostic factors influencing survival in these groups were comparable, with the exception of tumor size, ie, the largest tumors (greater than or equal to 10 cm in diameter) were concentrated in groups I and IIa. When patients with tumors greater than or equal to 10 cm in diameter (9.7% of the total) were removed from all three study groups, patients undergoing PRE had longer survival duration estimates than patients in the control groups.
Humans↗
Results of intensive therapy in children with localized alveolar extremity rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study.
Preliminary analyses of treatment results and prognostic factors from the first Intergroup Rhabdomyosarcoma Study (IRS I) suggested that alveolar histology and extremity site were among factors associated with an adverse outcome in clinical group I patients whose tumors had been completely resected. A high incidence of alveolar histology among the extremity tumors compounded the problem. These findings prompted an amendment to IRS II shortly after the study opened. Therapy for patients with alveolar extremity tumors in groups I and II was changed to more intensive repetitive pulse vincristine, dactinomycin, and cyclophosphamide (VAC) for 2 years. The outcome of 44 patients who received intensive therapy on IRS II is compared with a control series of 30 patients who were treated on IRS I. The control patients received standard VAC therapy for 2 years or VA for 1 year. Half of group I control patients received local radiotherapy, whereas none was given to group I intensive therapy patients. In both studies group II patients received radiotherapy to the primary tumor site and to identified positive regional lymph nodes. Compared with the control group, patients given more intensive therapy had a longer disease-free survival (DFS) (69% v 43% at 3 years), but this was of marginal significance (P = .06). The overall survival difference (77% v 57% at 3 years) was not significant (P = .23). Despite the limited statistical evidence, there is some indication that intensive therapy improved the prognosis of children with localized alveolar rhabdomyosarcoma (RMS).
Antineoplastic Combined Chemotherapy Protocols↗
Clinical staging and treatment results in rhabdomyosarcoma of the female genital tract among children and adolescents.
From 1972 to 1984, 47 children and adolescents with primary tumors of the female genital tract were treated with eight different Intergroup Rhabdomyosarcoma Study (IRS I-II) protocols. These included patients with vaginal (28), uterine (ten), or vulval (nine) rhabdomyosarcoma or undifferentiated sarcomas. The mean age of patients with primary vaginal tumors was younger than 2 years. All were of the embryonal histologic subtype. The majority of these patients were treated with initial chemotherapy (vincristine, dactinomycin, +/- cyclophosphamide, +/- Adriamycin [(ADR) doxorubicin]) followed by delayed hysterectomy and/or partial vaginectomy. Among 26 patients with localized vaginal tumors, there have been six relapses resulting in one tumor-related death and one therapy-related death. The five patients with nonfatal relapse have been disease-free for from 2.5 to 6.5 years (mean, 4.4 years) since salvage therapy was commenced. The 19 patients without relapse have been continuously disease-free for 1.5 to 12 years (mean, 5.34 years: median, 6 years). No patient that received ADR initially relapsed. Ten patients, with a mean age greater than 13 years, had primary uterine sarcomas and were treated by the same chemotherapy regimens. Six with polypoid localized lesions, removed before chemotherapy, have remained disease-free for 2.5 to 6.5 years. Four, with more extensive local lesions or disseminated disease, treated with chemotherapy only, died 2 to 11 months from diagnosis. Nine patients with rhabdomyosarcomas of the vulva (age, 1-19 years) were managed by the same chemotherapy regimens +/- radiotherapy. Resection was carried out initially or after chemotherapy. Eight of these have been disease-free from 4 to 10 years (mean, 6.4 years); and one is alive with probable disease at 2.5 years.
Adolescent↗
The Intergroup Rhabdomyosarcoma Study-I. A final report.
The results of treatment of 686, previously untreated patients younger than 21 years with rhabdomyosarcoma or undifferentiated sarcoma, who were entered on Intergroup Rhabdomyosarcoma Study-I (IRS-I) were analyzed after a minimum potential follow-up time of 7 years. Patients in Clinical Group I (localized disease, completely resected) were randomized to receive either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC + radiation. At 5 years, approximately 80% of patients given either treatment were still disease-free and there was no significant difference between treatments in the overall percentages of patients surviving of 93% and 81%, respectively (P = 0.67). Patients in Clinical Group II (regional disease, grossly resected) were randomized to receive either vincristine and dactinomycin (VA) + radiation or VAC + radiation. At 5 years, 72% and 65% of the patients, respectively, were disease-free and there was no evidence of a difference between treatments (P = 0.46). The overall survival percentage at 5 years was approximately 72% for both treatments. Patients in Clinical Groups III (gross residual disease after surgery) and IV (metastatic disease) were randomized to receive either "pulse" VAC + radiation or "pulse" VAC + Adriamycin (doxorubicin) + radiation. The complete remission (CR) rate was 69% in Clinical Group III and 50% in IV, with no statistically significant difference in CR rates between treatments in either group. Those who achieved a CR had a nearly 60% chance of staying in remission for 5 years in Clinical Group III compared with approximately 30% in Clinical Group IV. The overall survival percentage at 5 years was 52% in Clinical Group III compared to 20% in Clinical Group IV (P less than 0.0001). The 5-year survival percentage for the entire cohort of 686 patients was 55%. Survival after relapse was poor, being 32% at 1 year and 17% at 2 years. The risk of distant metastasis was much greater than the risk of local recurrence within each clinical group, and there was no evidence of differing types of relapses between treatments. Primary tumors of the orbit and genitourinary tract carried the best prognosis, whereas tumors of the retroperitoneum had the worst prognosis. The authors conclude that for the therapeutic regimens evaluated there was no therapeutic advantage to including radiation in the treatment of Clinical Group I disease, or cyclophosphamide given as a daily low-dose oral regimen in the treatment of Clinical Group II disease or Adriamycin in the treatment of Clinical Groups III and IV diseases.
Adolescent↗
Bone sarcomas linked to radiotherapy and chemotherapy in children.
We estimated the risk of subsequent bone cancer among 9170 patients who had survived two or more years after the diagnosis of a cancer in childhood. As compared with the general population, the patients had a relative risk of 133 (95 percent confidence interval, 98 to 176) and a mean (+/- SE) 20-year cumulative risk of 2.8 +/- 0.7 percent. Detailed data on treatment were obtained on 64 patients in whom bone cancer developed after childhood cancer. As compared with 209 matched controls who had survived cancer in childhood but who did not have bone cancer later, patients who had had radiation therapy had a 2.7-fold risk (95 percent confidence interval, 1.0 to 7.7) and a sharp dose-response gradient reaching a 40-fold risk after doses to the bone of more than 6000 rad. The relative dose-response effect among patients who had been treated for retinoblastoma resembled that among patients with all other types of initial tumors, although the cumulative risk of bone cancer in the retinoblastoma group was higher. Similar numbers of patients were treated with orthovoltage and megavoltage; the patterns of risk among categories of doses did not differ according to the type of voltage. After adjustment for radiation therapy, treatment with alkylating agents was also linked to bone cancer (relative risk, 4.7; 95 percent confidence interval, 1.0 to 22.3), with the risk increasing as cumulative drug exposure rose. We conclude that both radiotherapy and chemotherapy with alkylating agents for childhood cancer increase the subsequent risk of bone cancer.
Alkylating Agents↗
Lymphatic metastases with childhood rhabdomyosarcoma. A report from the Intergroup Rhabdomyosarcoma Study.
A review of 1415 patients without distant metastasis from the Intergroup Rhabdomyosarcoma Study (IRS) I and II revealed an overall 10% incidence of identified lymphatic spread at diagnosis, whereas 81 of 592 children with localized rhabdomyosarcoma who had grossly complete resection (and therefore with more complete pathologic data) had histologically proven lymphatic spread (14%). The percentage of patients in this latter group with nodal metastases was highest for the prostate (41%), paratesticular sites (26%), and genitourinary sites overall (24%). Sites with a small percentage of proven lymphatic involvement were the orbit (0%), nonorbital head and neck sites (7%), and truncal sites (3%), whereas the percentage of patients with nodal metastases from extremity lesions was 12%. The primary tumor mean diameter was significantly larger in the group with nodal metastases, but there was no evidence of a relationship between lymphatic spread and age, sex, or histologic subtype. Patients with lymph node metastases who had resection had a poorer survival rate (logrank P value = 0.001), with a 3-year survival estimate of 54%, compared with 78% for patients without lymphatic metastases. Patients with extremity lesions and positive lymph nodes also did poorly when compared with patients with normal nodes (P = 0.006), and a similar observation was made for patients with paratesticular sarcoma (P = 0.06).
Actuarial Analysis↗
Cost analysis of a mucoadhesive foam versus conventional treatment for postepisiotomy patients.
The cost of treating postepisiotomy pain and edema with foam containing 1% hydrocortisone acetate and 1% pramoxine hydrochloride and a spray with 20% benzocaine was compared in 200 postpartum patients. Treatment with foam was demonstrated to be more effective than benzocaine spray with greater pain relief and reduction of edema as shown by lower patient need of supplemental pain-relief measures. Treatment with foam was also determined to be less expensive than benzocaine spray when the cost of the supplemental pain-relief measures for benzocaine-treated patients were assessed. Methods used to determine actual hospital costs are presented, and supplemental pain relief treatments are discussed. Use of this type of cost analysis may be useful to the P & T Committee when determining actual cost-effectiveness of different treatment modalities.
Aerosols↗
Soft tissue sarcomas arising in the retroperitoneal space in children. A report from the Intergroup Rhabdomyosarcoma Study (IRS) Committee.
One hundred one eligible children with soft-tissue sarcomas arising within the retroperitoneal space have been registered on Intergroup Rhabdomyosarcoma Study Committee (IRS) studies I and II and followed for at least 2 years or until death. The most common presenting symptoms and signs were pain in the abdomen or lower extremities, and/or an abdominal mass, usually noted by a parent or a physician seeing the child for other complaints. The median age at diagnosis was 6.5 years and the sex ratio (M/F) 1.7:1. Histologic types were embryonal or botryoid rhabdomyosarcoma (RMS) in 58 patients, alveolar RMS in 8, pleomorphic RMS in 2, undifferentiated sarcoma in 20, extraosseous Ewing's sarcoma in 4 and unspecified sarcoma in 9. Median tumor size was 10 cm, significantly larger than the 7.5 cm noted in the IRS studies as a whole (P less than 0.05). One patient had complete tumor removal (Group I); 12 had grossly complete removal with microscopic residual tumor (Group II). Fifty-one patients had residual local tumor after biopsy or partial resection (Group III) and 37 patients had distant metastases at diagnosis (Group IV). Treatment included surgery, radiation therapy (RT) and combination chemotherapy with vincristine and actinomycin D with or without cyclophosphamide and Adriamycin (doxorubicin) according to protocol. Thirty-nine of 99 patients (39%) had major difficulties in the delivery of specified RT. Seventy patients received sufficient therapy to be evaluable for treatment response. Forty-one (58%) achieved a complete remission and 16 (23%) achieved partial remission. Twenty-four of 41 children (59%) achieving a CR have relapsed. The proportion of children who remained relapse-free at 2 and 3 years of follow-up was 44% or 42%, respectively. Overall, 40 children have developed recurrent sarcoma and the median disease-free interval and overall survival times were 54 and 88 weeks, respectively. Most children experienced severe myelosuppression; there were three early deaths from infection which occurred during granulocytopenic periods. One third of the patients experienced cystitis. Children with soft-tissue sarcomas arising in the retroperitoneal space have a poor prognosis associated with large tumors which, because of location and/or extent (Groups III or IV), are unresectable and difficult to treat.
Antineoplastic Combined Chemotherapy Protocols↗
Sarcomas of the vagina and uterus: the Intergroup Rhabdomyosarcoma Study.
During a 12-year period (1972-1984), 43 patients with sarcomas of the female genital tract were admitted to the Intergroup Rhabdomyosarcoma Study (IRS), including 31 with primary tumors of the vagina; and 12 with tumors of the uterus, including the cervix. Thirty-four of these can be evaluated on the basis of periods of observation from 18 months to 12 years. Primary tumors of the uterus were a distinct group, distinguished from those arising in the vagina by patient age-range and probably by prognosis, as well as site. Patients with vaginal tumors, with a mean age of 1.8 years, responded to a multimodality approach employing combinations of chemotherapy (vincristine sulfate and actinomycin D, or the aforementioned two drugs with cyclophosphamide +/- doxorubicin hydrochloride), irradiation, and/or surgery, with only one tumor-related death, among 24 evaluable patients. In contrast, among the patients with primary uterine tumors, in which the mean age was greater than 14 years, four of ten evaluable patients died secondary to tumor relapse or progression.
Adolescent↗
Hypergammaglobulinemia in histiocytosis X.
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Adolescent↗
Second malignant neoplasms in children: an update from the Late Effects Study Group.
This paper presents an update from the Late Effects Study Group on 292 cases of second malignant neoplasms (SMN) occurring in individuals who were diagnosed with their first neoplasm in childhood. Data are presented regarding the types of first and second neoplasm, the therapy administered, and the predisposing factors. Of the 292 cases (308 SMN), the most common primary was retinoblastoma followed by Hodgkin's disease, soft-tissue sarcomas, and Wilms' tumor. This is not similar to the relative frequency of these cancers in children but rather reflects specific risk factors. Bone sarcomas were the most common SMN among the 208 SMN developing in previously irradiated sites while acute leukemia was the most common SMN unassociated with radiation. Known predisposing conditions to cancer were present in 73 cases; retinoblastoma was the most common of these, followed by neurofibromatosis. There were ten patients with three and three patients with four malignant neoplasms. In 14 patients, the cause of SMN was not suggested by known risk factors as these patients had negative family histories and received no radiation or chemotherapy. We note, therefore, that although most cases of SMN in survivors of childhood cancer can be attributed to radiation, genetic disease, chemotherapy, or combinations of these, unrecognized predisposition or chance may also play a role.
Antineoplastic Combined Chemotherapy Protocols↗
Role of sexual behavior in the development of pelvic inflammatory disease.
The role of sexual behavior in the development of pelvic inflammatory disease (PID) is not well understood. In general the literature is limited and flawed in the methods used to assess sexual behavior. Good evidence suggests that PID in Western society is a sexually transmitted disease. For number of partners, frequency of intercourse, time of intercourse and sexual life-style the evidence suggests that those variables have a significant role in the development of PID. It is important to assess PID in the context of all its risk factors, including sexual behavior, race, prior history of PID and IUD use.
Adolescent↗
The Northwestern University multihospital twin study. IV. Duration of gestation according to fetal sex.
Recently MacGillivray has observed that the average duration of male twin gestations is shorter than that of either female twin or male/female twin gestations. The data from 562 twin gestations from the Northwestern University multihospital twin study were used to test this observation. Male twin gestations were slightly but significantly shorter than other twin gestations as measured by pediatric examination (p less than 0.005). Approaching significance at the 0.05 level were findings that male twin gestations were shorter than other twin gestations when measured by dates, and that the male twins were slightly shorter and lighter than other twins. No significant differences were found between male/female twin gestations and female twin gestations. No relationship could be found between twin sex combinations and a variety of maternal and obstetric factors. Taken together, the results suggest that male twin gestations differ in some distinctive biologic sense from other twin gestations.
Adult↗