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Holcombe E Grier

Publications and source records attributed to Holcombe E Grier.

At least 19 recordsLinked to original sources

Telling children and adolescents about their cancer diagnosis: Cross-cultural comparisons between pediatric oncologists in the US and Japan.

PURPOSE: Over the last 50 years, direct communication about cancer with adults has shifted from an approach of not telling to one of telling. Less is known about communication practices with children. The purpose of this study is to (1) describe patterns of communication at diagnosis between pediatric oncologists and children with cancer and (2) compare cultural differences in these practices in the US and Japan. METHODS: This 2003 survey, developed in English and translated into Japanese was mailed to members of the American Society of Pediatric Hematology/Oncology and the two Japanese Societies of Pediatric Hematology and Oncology; there were 350 US and 362 Japanese respondents. Descriptive statistics and logistic regressions were performed. RESULTS: US physicians had a consistent pattern of telling children (65% always told the child; less than 1% rarely or never told). Japanese physicians had greater variability in their patterns of telling (with only 9.5% always telling, 34.5% rarely or never telling). Direct communication with the child was influenced by personal attitudes, patient factors, and work culture in both countries. Many more variables emerged as influencing Japanese physicians' communication practices than for US physicians. US physicians were influenced by their own sense of responsibility for telling, while Japanese physicians were more influenced by personal attitudes, patient factors, and work culture. CONCLUSIONS: US and Japanese physicians differed when communicating directly with the child about his or her cancer. The impact of these practices on children and their parents should be explored and the parent and child's perspectives elicited. This information will help facilitate culturally sensitive patient and family centered communication.

Adolescent↗

Communication about prognosis between parents and physicians of children with cancer: parent preferences and the impact of prognostic information.

PURPOSE: Concerns about the harms of prognostic information, including distress and loss of hope, cause some physicians to avoid frank disclosure. We aimed to determine parent preferences for prognostic information about their children with cancer and the results of receiving such information. PATIENTS AND METHODS: We surveyed 194 parents of children with cancer (overall response rate, 70%), treated at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) and the children's physicians. Our main outcome measure was parent rating of prognostic information as extremely or very upsetting. RESULTS: The majority of parents desired as much information about prognosis as possible (87%) and wanted it expressed numerically (85%). Although 36% of parents found information about prognosis to be extremely or very upsetting, those parents were more likely to want additional information about prognosis than those who were less upset (P = .01). Parents who found information upsetting were no less likely to say that knowing prognosis was important (P = .39), that knowing prognosis helped in decision making (P = .40), or that hope for a cure kept them going (P = .72). CONCLUSION: Although many parents find prognostic information about their children with cancer upsetting, parents who are upset by prognostic information are no less likely to want it. The upsetting nature of prognostic information does not diminish parents' desire for such information, its importance to decision making, or parents' sense of hope.

Adolescent↗

Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group.

This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.

Acute Disease↗

Local control in pelvic Ewing sarcoma: analysis from INT-0091--a report from the Children's Oncology Group.

PURPOSE: The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091. PATIENTS AND METHODS: Patients < or = 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, > or = 8 cm) and chemotherapy type. RESULTS: Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, > or = 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06). CONCLUSION: There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗

Intensive therapy with growth factor support for patients with Ewing tumor metastatic at diagnosis: Pediatric Oncology Group/Children's Cancer Group Phase II Study 9457--a report from the Children's Oncology Group.

PURPOSE: Prognosis is poor for Ewing sarcoma patients with metastasis at diagnosis. We intensified a five-drug therapy (ifosfamide, etoposide alternated with vincristine, doxorubicin, and cyclophosphamide) using filgrastim but not stem-cell support. We studied topotecan alone and combined with cyclophosphamide in therapeutic windows before the five-drug therapy. A randomly assigned proportion of patients received amifostine as a cytoprotective agent. PATIENTS AND METHODS: Eligible patients were < or = 30 years old and had histologically proven Ewing sarcoma or primitive neuroectodermal tumor (PNET) and metastasis at diagnosis. Chemotherapeutic cycles began every 21 days, after recovery from toxicities. RESULTS: One hundred ten of the 117 patients enrolled were eligible. Thirty-six patients received initial topotecan. Three had partial responses (PRs), and 17 had progressive disease (PD). Thirty-seven patients were administered topotecan and cyclophosphamide; 21 of these patients achieved PR, and one patient had PD. In a randomly assigned group of 69 patients, amifostine did not provide myeloprotection, which was measured by absolute neutrophil count, platelet count, or cycle intervals. The best responses to the overall therapy included 45 complete responses, 41 PRs, stable disease in 14 patients, and PD in five patients. For all patients, the 2-year event-free survival (EFS) rate was 24% (+/- 4%), and the overall survival rate was 46% (+/- 5%). For the 39 patients with isolated pulmonary metastases, the 2-year EFS rate was 31% (+/- 7%) compared with 20% (+/- 5%) for patients with more widespread disease. CONCLUSION: Topotecan had limited activity in patients with Ewing sarcoma or PNET metastatic at diagnosis. The topotecan-cyclophosphamide combination was active. Amifostine was not myeloprotective. Overall results showed no improvement compared with previous studies.

Adolescent↗

Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience.

OBJECTIVE: To determine the presentation, pathologic features, treatment outcome, and prognosis of mucoepidermoid carcinoma of the parotid gland in children. DESIGN: Retrospective clinical and histopathologic study with institutional review board approval. SETTING: Tertiary pediatric medical center. PATIENTS: Seven children (4 girls and 3 boys) presented with mucoepidermoid carcinoma of the parotid gland between 1994 and 2004. MAIN OUTCOME MEASURES: Clinical presentation, pathologic features, treatment outcome, complications, local recurrence, distant metastasis, and overall survival. RESULTS: All patients presented with an asymptomatic parotid mass. Initial treatment in 7 patients included total parotidectomy (n = 3), superficial parotidectomy (n = 3), transoral enucleation (n = 1), and supraomohyoid neck dissection (n = 1). Four patients required additional surgical procedures because of a close and/or positive margin, including revision parotidectomy (n = 2), total parotidectomy (n = 1), superficial parotidectomy (n = 1), and supraomohyoid neck dissection (n = 1). One patient required postoperative radiation therapy. No evidence of local recurrence or distant metastasis was noted with a mean follow-up of 3.4 years. CONCLUSIONS: Mucoepidermoid carcinoma of the parotid gland is very rare in children. Clinical stage and histologic grade are the main prognostic factors. Complete excision (superficial or total parotidectomy) with preservation of facial nerve is the treatment of choice. Neck dissection should be considered when there is clinical evidence of regional metastasis, high TNM stage, high histologic grade, and involvement of regional nodes. Because of the possibility of long-term adverse effects in pediatric patients, radiotherapy should be used only in selected cases. Long-term follow-up is essential to rule out late recurrence.

Adolescent↗

Parent and physician perspectives on quality of care at the end of life in children with cancer.

PURPOSE: To ascertain parents' and physicians' assessments of quality of end-of-life care for children with cancer and to determine factors associated with high-quality care as perceived by parents and physicians. METHODS: A survey was conducted between 1997 and 2001 of 144 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital (Boston, MA) or Children's Hospitals and Clinics of St Paul and Minneapolis, MN, between 1990 and 1999 (65% of those located and eligible) and 52 pediatric oncologists. RESULTS: In multivariable models, higher parent ratings of physician care were associated with physicians giving clear information about what to expect in the end-of-life period (odds ratio [OR] = 19.90, P = .02), communicating with care and sensitivity (OR = 7.67, P < .01), communicating directly with the child when appropriate (OR = 11.18, P < .01), and preparing the parent for circumstances surrounding the child's death (OR = 4.84, P = .03). Parent reports of the child's pain and suffering were not significant correlates of parental ratings of care (P = .93 and .35, respectively). Oncologists' ratings of care were inversely associated with the parent's report of the child's experience of pain (OR = 0.15, P = .01) and more than 10 hospital days in the last month of life (OR = 0.24, P < .01). Parent-rated communication factors were not correlates of oncologist-rated care. No association was found between parent and physician care ratings (P = .88). CONCLUSION: For parents of children who die of cancer, doctor-patient communication is the principal determinant of high-quality physician care. In contrast, physicians' care ratings depend on biomedical rather than relational aspects of care.

Adolescent↗

Phase II trial of neoadjuvant vincristine, ifosfamide, and doxorubicin with granulocyte colony-stimulating factor support in children and adolescents with advanced-stage nonrhabdomyosarcomatous soft tissue sarcomas: a Pediatric Oncology Group Study.

PURPOSE: To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. PATIENTS AND METHODS: Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m(2) weekly for 13 doses), ifosfamide (3 g/m(2) daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m(2) daily for 2 days for six cycles), and mesna (750 mg/m(2) for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 mug/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. RESULTS: The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (+/- standard deviation) for eligible patients were 59% +/- 8.2% and 43.6% +/- 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. CONCLUSION: The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.

Adolescent↗

Outcome for children with group III rhabdomyosarcoma treated with or without radiotherapy.

PURPOSE: To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT). METHODS AND MATERIALS: The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy. RESULTS: Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival. CONCLUSION: The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy.

Adolescent↗

The Day One Talk.

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Attitude to Death↗

Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651.

PURPOSE: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. PATIENTS AND METHODS: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. RESULTS: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P =.8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). CONCLUSION: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy.

Adolescent↗

Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone.

BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. METHODS: Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. RESULTS: A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01). CONCLUSIONS: The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone.

Adolescent↗

BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma.

The poorly differentiated carcinoma with t(15;19)(q13, p13.1) is characterized by its highly aggressive, invariably lethal clinical course. The chromosome 19 translocation breakpoint targets the BRD4 double bromodomain-containing gene, which functions in regulation of cell cycle progression. Herein we demonstrate that BRD4 is fused with nearly the entire transcript of the novel 15q13 gene, NUT (nuclear protein in testis), forming a 6.4-kb fusion oncogene, BRD4-NUT. NUT, like BRD4, is predicted to encode a nuclear protein but, unlike the ubiquitous BRD4 transcript, is expressed only in testis. These findings establish a model to elucidate the oncogenic consequences of unscheduled NUT expression and altered BRD4 function. Very few fusion oncogenes have been identified in epithelial tumors, and BRD4-NUT is the first fusion oncogene mechanism identified in a highly lethal form of carcinoma.

Amino Acid Sequence↗

The role of chromosomal translocation (15;19) in the carcinoma of the upper aerodigestive tract in children.

OBJECTIVE: To further evaluate the role of chromosomal translocation (15;19) in the presentation of the carcinoma (CA) of the upper aerodigestive tract. STUDY DESIGN AND SETTING: A retrospective study at a tertiary care pediatric medical center. RESULTS: Seven patients with a mean age of 12 years presented with CA of nasopharynx (N = 2), sinonasal region (N = I), parotid gland (N = 2), or larynx (N = 2). Treatments included combinations of surgery (N = 5), chemotherapy (N = 5), and radiation therapy (N = 4). One patient with sinonasal CA and one patient with laryngeal CA had chromosomal translocation (15;19); these patients both died of their disease with a mean survival of 6 months. The 5 patients without translocation (15;19) responded well to treatment and are disease-free with a mean follow-up of 47 months. CONCLUSION: The preliminary results appear to indicate poor prognosis associated with the presentation of chromosomal translocation (15;19) despite aggressive multi-modality treatment. Further investigation is needed to better understand the cause and relationship of the translocation (15;19) and aggressive behavior of these tumors.

Adolescent↗

Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants.

OBJECTIVE: To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. METHODS: Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation. RESULTS: Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. CONCLUSIONS: The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.

Adolescent↗

Ewing sarcoma/primitive neuroectodermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy.

OBJECTIVE: To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. METHODS: Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. RESULTS: Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). CONCLUSION: The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.

Adult↗

Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial.

PURPOSE: The objectives of this trial were to estimate the response rate, progression-free survival, and overall survival of patients who received therapy with etoposide and high-dose ifosfamide, and to define the toxicity of this combination when provided with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma. PATIENTS AND METHODS: Eligible patients received infusions of 100 mg/m(2) per day of etoposide and 3.5 g/m(2) per day of ifosfamide for 5 days. Therapy with granulocyte colony-stimulating factor was begun on day 6. This was repeated 3 weeks after therapy was begun. Response was determined at week 6 by both standard World Health Organization response criteria and by pathologic determination of tumor necrosis of the primary tumor. RESULTS: Forty-three patients were registered; 39 were assessable for response and 41 for toxicity and survival. Twenty-eight (68%) of 41 had metastatic sites only in the lung; 12 (29%) had metastatic sites in other bones with or without lung involvement. Four patients (10%) experienced complete response, and 19 patients (49%) experienced partial response, for an overall response rate of 59% +/- 8%. The projected 2-year progression-free survival (PFS) for the 28 patients with metastases to lungs was 39% +/- 11%. The projected 2-year PFS for the 12 patients with metastases to other bones (with or without pulmonary metastases) was 58% +/- 17%. Two patients died as a result of therapy toxicity. Eighty-three percent of patients had grade 4 neutropenia, and 29% had grade 4 thrombocytopenia. Ten patients (24%) had sepsis. Fanconi's syndrome was observed in five patients. CONCLUSION: The combination of etoposide and high-dose ifosfamide is effective induction chemotherapy for patients with metastatic osteosarcoma, despite significant associated myelosuppression sometimes complicated by infection and renal toxicity.

Adolescent↗

Treatment of infantile fibrosarcoma with chemotherapy and surgery: results from the Dana-Farber Cancer Institute and Children's Hospital, Boston.

PURPOSE: To retrospectively evaluate the treatment and outcome of patients diagnosed with infantile fibrosarcoma at the Dana-Farber Cancer Institute and Children's Hospital, Boston. PATIENTS AND METHODS: Between 1982 and 1998, a total of 11 infants were diagnosed pathologically with infantile fibrosarcoma. A retrospective chart review was conducted to determine the extent of surgical therapy and chemotherapy required for a favorable clinical outcome. Cytogenetic findings were reviewed and archived tumor specimens were analyzed, when available, for the presence of the TEL/TRKC fusion gene. RESULTS: Three patients had primary surgical resection with negative pathologic margins and have been lost to follow-up. Two patients received chemotherapy only after limited biopsy or subtotal resection and are alive with no evidence of disease 8 and 18 years from diagnosis. Four patients had limited biopsies followed by chemotherapy with delayed resection. One of these four patients had negative margins and received no further chemotherapy. The other three of these patients had positive microscopic margins; two of them received postoperative chemotherapy while the third did not. All four are currently alive with no evidence of disease. Two patients had progressive disease within 7 and 10 months of diagnosis while on chemotherapy after subtotal resections. One of these two patients is dead of disease; the other is alive after palliative radiotherapy. Seven patients had archived or frozen tissue available for molecular analysis. All seven had evidence of TEL gene rearrangement; six exhibited the TEL/TRKC fusion. Six patients had characteristic trisomies previously reported to be associated with infantile fibrosarcoma. CONCLUSIONS: Previously reported series of treatment outcomes in infantile fibrosarcoma have been limited to very few patients due to the rare occurrence of this tumor. In our experience, initial chemotherapy combined with surgery has been successful for most cases. When disease progression occurred, it was within one year of diagnosis. There was no development of distant metastases in the patients with progressive disease. The role of additional chemotherapy for microscopic margins after local control is not clear. We found a high incidence of the TEL/TRKC fusion gene, confirming its utility in diagnosis. We propose a uniform approach to treatment to gather clinical and biologic information about this rare and curable disease.

Boston↗