Surgical lessons from the Intergroup Rhabdomyosarcoma Study (IRS) pertaining to extremity tumors.
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Extremities↗
Biomedical subjects
R Heyn
Publications and source records attributed to R Heyn.
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↗
Intensive chemotherapy including cisplatin with or without etoposide for children with soft-tissue sarcomas.
Forty-two children, 6 months to 17 years of age with newly diagnosed soft-tissue sarcomas (gross residual or metastatic), were treated according to either of two pilot protocols that included intensive chemotherapy before irradiation. Vincristine, actinomycin D, cyclophosphamide, and doxorubicin were used in various combinations with cisplatin alone (regimen 35) or with cisplatin plus etoposide (regimen 36) in a 20-week induction treatment; irradiation (4,000 cGy) was delayed until week 6. Fourteen (82%) of the 17 patients on regimen 35 and 15 (60%) of the 25 on regimen 36 had a complete response. Although severe leukopenia was frequent in both groups (88% and 84% of patients), there were only two fatal infections and no early deaths. Other potentially serious toxicity included a greater than 10% weight loss in 52% of the patients and hypomagnesemia in 74%. An average of 75-100% of the prescribed drug doses were administered during the induction phase of therapy. We conclude that this intensified treatment is toxic but feasible to deliver. The higher overall response rate compared to that in the preceding Intergroup Rhabdomyosarcoma Study (69% vs 53%) suggests improved therapeutic efficacy that warrants further evaluation of both regimens.
Adolescent↗
Localized orbital rhabdomyosarcoma. An interim report of the Intergroup Rhabdomyosarcoma Study Committee.
Children with rhabdomyosarcoma (RMS) (1461 total cases) were included in two prospective, randomized protocols conducted by the Intergroup Rhabdomyosarcoma Study (IRS) Committee from November 1972 to June 1983. Treatment assignment was determined by extent of tumor at diagnosis (clinicopathologic group) and not by primary site. Accordingly, 127 patients with RMS confined to the region of the eyelid and orbit were treated by a variety of regimens characterized by initial partial tumor resection followed by concurrent multiagent chemotherapy and orbital radiation therapy. Recurrent tumor developed in ten patients. Seven relapsed initially in the orbit (of whom 4 were salvaged) and three in regional nodes. In addition to the six patients who died of tumor, three died of other causes for a 93% 3-year actuarial survival rate. In 89 children who had subtotal resection or biopsy only, the local control rate with radiotherapy and chemotherapy was 94%.
Adolescent↗
Infants younger than 1 year of age with rhabdomyosarcoma.
Of a total of 1561 patients registered in the Intergroup Rhabdomyosarcoma Study (IRS) as of May 1983, 78 patients (5%) were younger than 1 year of age. These infants did not differ from the older children (1-20 years of age) in male/female ratio, clinical grouping, or survival rates. Infants younger than 1 year of age had a significantly greater frequency of undifferentiated sarcoma, 18% versus 7% in older children (P less than 0.005). Infants also had a significantly greater proportion of cancers with botryoid pathology, 10% versus 4% in older children (P less than 0.005). When reviewed by the newly proposed IRS cytopathologic classification, there was no difference in pathologic types between the two age groups. Infants younger than 1 year of age had a higher rate of bladder-prostate-vagina primary tumor sites than older children, 24% versus 10% (P less than 0.05). In addition, infants tended to receive less of the prescribed doses of chemotherapy and radiation therapy than older children, and to develop more toxicity to treatment than older children. Despite these differences, the overall survival curve for the two age groups appears to be similar. In contrast to Wilms' tumor and neuroblastoma, in which age (less than 1 year) is a favorable prognostic factor, age does not appear to be an important prognostic factor in rhabdomyosarcoma.
Antineoplastic Agents↗
Late effects of therapy in orbital rhabdomyosarcoma in children. A report from the Intergroup Rhabdomyosarcoma Study.
Late effects of therapy were evaluated in 50 children surviving orbital rhabdomyosarcoma following treatment on Intergroup Rhabdomyosarcoma Study I. All patients had microscopic or gross tumor present following surgery and subsequently received radiotherapy and various combinations of chemotherapeutic agents. Problems in the eye included infections and functional and structural changes. Decreased vision in the treated eye was the most common functional problem and in most patients related to cataract formation, which occurred in 90% of eyes. Changes in the cornea and retina were also seen. Bony hypoplasia of the orbit and facial asymmetry were present in one half of the children. Gonadal development was normal. Statural growth was retarded in 61% of the patients. All children were in school, with five having learning or behavioral problems. One child developed acute myeloblastic leukemia. The excellent survival in patients with orbital rhabdomyosarcoma provides support for treatment programs that use multiple-agent chemotherapy and radiotherapy and do not include orbital exenteration initially.
Antineoplastic Combined Chemotherapy Protocols↗
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↗
Hypergammaglobulinemia in histiocytosis X.
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Adolescent↗
Significance of X granules in histiocytosis X: an ultrastructural study.
Histiocytosis X is characterized by the presence of cytoplasmic rod structures called Langerhans' cell granules or X granules (XG). It has been speculated that histiocytosis X is a Langerhans' cell disorder. This ultrastructural study was performed to quantitate the number of XG containing histiocytes in the histiocytosis X lesions. Twenty-four specimens from 22 patients with histiocytosis X were studied: 4 from skin, 5 from lymph node, 11 from bone, 2 from lung, 1 from gingiva, and 1 from cheek. The majority of the histiocytes in histiocytosis X lesions do not contain X granules. The majority of the histiocytes in histiocytosis X lesions do not contain X granules. The percentage of histiocytes with XG in a lesion has no relation to the age of the patient or the organ from which it was obtained, except for skin, where they were quite numerous. The relative percent-age of histiocytes with granules does not correlate significantly with the prognosis of these patients.
Adolescent↗
Necrotizing lymphoid vasculitis in X-linked lymphoproliferative syndrome.
An 8-year-old maternally related relative of three boys who had developed agammaglobulinemia associated with Epstein-Barr virus (EBV)-induced infectious mononucleosis was studied for X-linked lymphoproliferative syndrome (XLP) in 1979. At that time, he demonstrated no striking immunologic aberrations and was seronegative for EBV. Subsequently, immunologic abnormalities including failure to switch from IgM to IgG antibody synthesis after secondary immunization with bacteriophage phi X174 were detected. In 1983, he experienced episodic intracerebral hemorrhages, with the second being fatal. At autopsy, necrotizing vasculitis and aneurysms involving arteries of the central nervous system were observed. Studies of blood obtained immediately before and after death failed to show antibodies to EBV. However, EBV genome was demonstrated in tissues obtained at autopsy by DNA hybridization studies. Fatal lymphoid vasculitis in this patient is unique among boys with XLP in the registry. These findings probably extend the phenotypic expressions of XLP.
Antibodies, Viral↗
Occult abdominal involvement with apparently isolated testicular relapse in children with acute lymphocytic leukemia.
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Abdominal Neoplasms↗
Evaluation of azapicyl in soft tissue sarcomas in children: a report from the Children's Cancer Study Group.
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Adolescent↗
Differences in prognosis for boys and girls with acute lymphoblastic leukaemia.
In the period 1968--78, 3161 children were enrolled in six studies of acute lymphoblastic leukaemia by participating institutions of the Childrens Cancer Study Group. In the first two studies, which did not include central-nervous-system (CNS) prophylaxis in the treatment programme, the outcome for male and female patients was very similar. In the following four studies, which included radiation prophylaxis to the CNS, a difference in outcome favouring females appeared consistently. This difference began about 6--12 months after initial remission and was further accentuated by withdrawal of therapy. Some of these studies also included a randomised trial of duration of therapy, studying 3 versus 5 years of maintenance treatment. Analysis of these studies suggests that sex group has implications both for duration of treatment and for optimum central-nervous-system prophylaxis.
Adolescent↗
Inhibition of adenosine deaminase activity results in cytotoxicity to T lymphoblasts in vivo.
We have treated a patient with refractory T-cell acute lymphoblastic leukemia with 2'-deoxycoformycin, a potent inhibitor of the enzyme adenosine deaminase. Inhibition of adenosine deaminase activity resulted in (1) an abrupt rise in plasma deoxyadenosine, but not adenosine, concentrations; (2) accumulation of deoxyadenosine triphosphate by lymphoblasts; (3) inhibition of the enzyme S-adenoylhomocysteine hydrolase; and (4) rapid lysis of the leukemic cells. The patient died suddenly 3 days after therapy was discontinued, and postmortem examination revealed a complete absence of leukemic cells in all organs. Pharmacologic inhibition of adenosine deaminase activity can result in the lysis of T lymphoblasts in vivo, and this effect appears to be mediated by deoxyadenosine.
Adenosine↗
Treatment of rhabdomyosarcoma in children with surgery, radiotherapy and chemotherapy.
From May, 1970 through December, 1972, Children's Cancer Study Group entered 112 patients on an amended treatment program for rhabdomyosarcoma and undifferentiated sarcoma in children. These patients had Group II disease with residual tumor remaining after surgery, or metastatic disease at onset. Another group consisted of patients who previously had treatment with surgery and radiotherapy and had recurrent disease. Cyclophosphamide was added to a previously used drug regimen which consisted of actinomycin D and vincristine. The drugs were given sequentially in repeated cycles for 18 months. Of 97 evaluable patients, there were 24 with microscopic residual disease, 37 with gross residual disease, 22 with metastatic disease at onset, and 14 patients who were treated with chemotherapy for the first time with recurrent or metastatic disease. All patients have been followed for 3 or more years. Survival in each group was 70.8%, 43.2%, 27.2%, and 28.2%, respectively. Although the number of complete remissions was greater than with two-drug therapy, survival with three-drug therapy was not significantly different than that seen in the earlier study.
Adolescent↗
[Needle biopsies of areas suspicious of recurrence in patients with gynaecological tumors (author's transl)].
With the biopsy needle of Franzén, 403 needle biopsies were carried out in 263 patients with gynaecological malignant tumors. In 152 cases the results of the aspiration cytology were compared with microscopic examinations or with the clinical course for at least 6 months. In 88 cases with probable recurrence the needle biospy showed a positive or suspicious result in 73 cases. A positive needle biopsy result was confirmation of recurrent tumor whereas a negative result did not rule out a recurrence. Aspiration cytology is a valuable ancillary method in the diagnosis of the recurrence of gynaecological tumors.
Biopsy, Needle↗
Acute and chronic effects of methotrexate on hepatic, pulmonary, and skeletal systems.
With the progressive improvement in the survival of children with acute lymphocytic leukemia, the question of late effects of therapy on normal tissue becomes a more significant problem. In a review of a large number of children who have received long-term treatment with chemotherapy, especially methotrexate, a significant increase in the serious effects on hepatic, pulmonary, and skeletal tissue was noted. A review of the methotrexate-induced acute and chronic changes seen in these tissues is the basis for this report.
Bone and Bones↗