Adaptive Proton Therapy for Pediatric Parameningeal Rhabdomyosarcoma: On-Treatment Anatomic Changes and Timing to Replanning.

PURPOSE: To characterize on-treatment changes in GTV morphology in children with parameningeal rhabdomyosarcoma receiving upfront proton therapy with concurrent chemotherapy and thereby provide guidance on the timing of on-treatment imaging and adaptive replanning. METHODS AND MATERIALS: GTV was delineated on 86 simulation and weekly MR images of 15 prospectively enrolled patients (aged 1-21 years). Temporal changes from baseline in volume and surface (95% Hausdorff distance) were analyzed in relation to the need for plan verification and the resultant doses with hypothetical no treatment adaptation. RESULTS: The median time was 6 days from the initiation of chemotherapy to CT+MR simulation and 15 days from the simulation to the start of radiotherapy. All but 1 patient showed a continuous decrease in GTV (0.16-1.52%/day) after simulation. At 3 weeks from simulation, 10 of 15 patients exhibited a significant reduction in volume (median, 20%; range, 6-29%). Without replanning, these changes could lead to a reduction in CTV V95 by 7-14% (n = 2) and/or an increase in D0.01 cc/Dmean of adjacent organs at risk by 6-21% of the prescribed target dose (n = 7). Significant dosimetric consequences occurred in cases with (1) a considerable weight gain, (2) shrinkage of the skin surface, or (3) tumor regression in the oral or nasal cavity and sinus that altered air-tissue components in the beam path. The subsequent GTV and dosimetry after 3 weeks from simulation (4 weeks from chemotherapy initiation) demonstrated a relatively stable trend. CONCLUSIONS: On-treatment imaging at 3 weeks after simulation is recommended, if the simulation is performed at 1 week after the initiation of chemotherapy, to detect significant anatomic changes that could result in >5% deviation from planned target coverage and/or organ doses in pediatric patients with parameningeal rhabdomyosarcoma receiving early proton therapy.

Long-term functional outcomes and quality of life in adult survivors of childhood extremity sarcomas: a report from the St. Jude Lifetime Cohort Study.

PURPOSE: This study compared measured physical performance, health-related quality of life (HRQOL), and social role attainment between extremity sarcoma survivors and controls, and evaluated associations between disease and treatment exposures, health conditions, and performance measures. METHODS: Survivors of extremity sarcoma from the St. Jude Lifetime cohort and controls frequency matched by age-, sex-, and race completed physical performance testing and questionnaires. Survivors with Z-scores on outcome measures ≤ -2.0 SD (compared to controls) were categorized with severe impairment/limitation. RESULTS: Among 206 survivors (52.4 % male median age 36 years (range 19-65)), 37 % had low relative lean mass, 9.7 % had an ejection fraction <50 %, 51.5 % had diffusion capacity for carbon monoxide <75 %, 27.7 % had sensory and 25.2 % motor neuropathy, and 78.2 % had musculoskeletal complications. Severe impairments/limitations were present among ≥25 % of survivors on fitness, balance, and physical HRQOL measures, and among ≥15 % on strength and activity of daily living measures. Lower extremity tumor location (OR 8.23, 95 % CI 2.54-26.67, P value 0.0004) and amputation (OR 8.07, 95 % CI 3.06-21.27, P value <0.0001) were associated with poor fitness. Poor fitness was associated with increased odds of scoring <40 on the SF-36 physical component summary (OR 4.83, 95 % CI 1.95-11.99, P value 0.001) and role-physical subscale (OR 3.34, 95 % CI 1.33-8.43, P value 0.01). Survivors and controls had similar rates of marriage, independent living, employment, and college attendance. CONCLUSIONS: Extremity sarcoma survivors experience high rates of physical impairment and report lower than expected physical HRQOL. However, they are as likely as peers to be married, live independently, be employed, and attend college. IMPLICATIONS FOR CANCER SURVIVORS: Follow-up for extremity sarcoma survivors should include assessment of need for further orthopedic care and rehabilitation to address cardiopulmonary and musculoskeletal health.

Long-term outcomes of pediatric and adolescent mediastinal germ cell tumors: a single pediatric oncology institutional experience.

PURPOSE: To evaluate the epidemiologic, demographic, and clinical characteristics, as well as prognostic factors and long-term outcomes of mediastinal germ cell tumors (MGCT) in children. PATIENTS AND METHODS: A retrospective study of pediatric patients diagnosed with a primary MGCT between January 1963 and August of 2014 was performed. RESULTS: Twenty-five patients were identified. Six children with teratomas were treated with resection alone (median age 7.8 years, range newborn to 15 years) and were cured without recurrence or progression. Nineteen children were treated for a malignant MGCT (median age 11.7 years, range 7 months-18 years); 5 year overall survival (OS) was 0.39 ± 0.12. For malignant non-seminomatous mediastinal germ cell tumors, platinum-based chemotherapy regimen (OS 0.56 vs 0.14, p = 0.03), complete surgical resection with negative margins (OS 0.73 vs 0.11, p = 0.03); and localized disease (OS 0.76 vs 0.0, p = 0.004) demonstrated a survival advantage. CONCLUSIONS: Initial surgical resection is appropriate for teratomas. Localized disease, complete resection, and platinum-based chemotherapy are associated with improved survival in malignant non-seminomatous mediastinal germ cell tumors. Neoadjuvant, platinum-based three drug regimens followed by delayed surgical resection is the appropriate treatment modality for malignant mediastinal germ cell tumors.

Pediatric solid tumor genomics and developmental pliancy.

Pediatric solid tumors are remarkably diverse in their cellular origins, developmental timing and clinical features. Over the last 5 years, there have been significant advances in our understanding of the genetic lesions that contribute to the initiation and progression of pediatric solid tumors. To date, over 1000 pediatric solid tumors have been analyzed by Next-Generation Sequencing. These genomic data provide the foundation to launch new research efforts to address one of the fundamental questions in cancer biology-why are some cells more susceptible to malignant transformation by particular genetic lesions at discrete developmental stages than others? Because of their developmental, molecular, cellular and genetic diversity, pediatric solid tumors provide an ideal platform to begin to answer this question. In this review, we highlight the diversity of pediatric solid tumors and provide a new framework for studying the cellular and developmental origins of pediatric cancer. We also introduce a new unifying concept called cellular pliancy as a possible explanation for susceptibility to cancer and the developmental origins of pediatric solid tumors.

The role of inherited TPMT and COMT genetic variation in cisplatin-induced ototoxicity in children with cancer.

Ototoxicity is a debilitating side effect of platinating agents with substantial interpatient variability. We sought to evaluate the association of thiopurine S-methyltransferase (TPMT) and catechol O-methyltransferase (COMT) genetic variations with cisplatin-related hearing damage in the context of frontline pediatric cancer treatment protocols. In 213 children from the St. Jude Medulloblastoma-96 and -03 protocols, hearing loss was related to younger age (P = 0.013) and craniospinal irradiation (P = 0.001), but did not differ by TPMT or COMT variants. Results were similar in an independent cohort of 41 children from solid-tumor frontline protocols. Functional hearing loss or hair cell damage was not different in TPMT knockout vs. wild-type mice following cisplatin treatment, and neither TPMT nor COMT variant was associated with cisplatin cytotoxicity in lymphoblastoid cell lines. In conclusion, our results indicated that TPMT or COMT genetic variation was not related to cisplatin ototoxicity in children with cancer and did not influence cisplatin-induced hearing damage in laboratory models.

Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer. PATIENTS AND METHODS: Among 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, we calculated the cumulative incidence, standardized incidence ratio (SIR), and absolute excess risk (AER) of subsequent melanoma. Potential risk factors were assessed using a cause-specific hazards model. RESULTS: Fifty-seven melanomas (46 invasive, 2 ocular, and 9 in situ) occurred in 51 survivors. The median time to the development of melanoma was 21.0 years (range: 5.6-35.4 years) and the median age at melanoma was 32.3 years (range: 10.9-49.0 years). Initial cancer diagnoses included soft tissue and bone sarcoma (n = 15), leukemia (13), lymphoma (14), central nervous system malignancy (5), Wilms tumor (3), and neuroblastoma (1). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% [95% confidence interval (CI): 0.37-0.73]. The SIR of subsequent invasive malignant melanoma of the skin was 2.42 (95% CI: 1.77-3.23), and the AER was 0.10 (95% CI: 0.05-0.15) per 1,000 person-years. No statistically significant associations were found between melanoma risk and family history of cancer, demographic, or treatment-related factors. CONCLUSION: Survivors of childhood cancer have an approximate 2.5-fold increased risk of melanoma. Early screening and prevention strategies are warranted.

Melanoma in children and adolescents.

Childhood and adolescent melanoma is rare, accounting for only 1.3% for all cases of cancer in patients under the age of 20 years. However, in 15-19 year olds, melanoma accounts for up to 7% of all cancers. Review of reported cases in this age group reveals that predisposing 'paediatric' conditions such as a giant congenital melanocytic naevi or xeroderma pigmentosum are rarely present. Furthermore, inactivating germ-line mutations of the gene CDKN2A have only been reported in 1.5% of cases of early onset melanoma. Epidemiological studies suggest that interactions between solar exposure, development of naevi, pigmentary traits, and a family history of melanoma are the main determinants of melanoma development during the first 20 years of life. As yet, there are no available staging or treatment strategies for this group of patients so treatment recommendations are based on the adult experience. To improve our understanding of the natural history of melanoma and to identify the most appropriate therapies for young patients with this disease, practising physicians are encouraged to enroll their patients, especially those with advanced stage disease, in cooperative group trials which incorporate newer staging systems and promising therapies.

Is reexcision in pediatric nonrhabdomyosarcoma soft tissue sarcoma necessary after an initial unplanned resection?

PURPOSE: The aim of this study was to determine the importance of pretreatment reexcision (PRE) of pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) after initial unplanned resection. METHODS: The authors retrospectively reviewed the records of 116 consecutive patients with surgically resected NRSTS treated at their institution between February 1978 and September 1999. Ninety-four (81.0%) patients had undergone unplanned resections before referral to their institution for further therapy. Demographic data, tumor characteristics, treatment administered, and outcomes were recorded. RESULTS: Sixty-nine patients (73.4%) underwent PRE at a median interval after the initial unplanned resection of 29 days. Twenty-five patients were thought unsuitable for PRE because of the proximity to vital neurovascular bundles. Tumors deemed not feasible for PRE were more likely to be greater than 5 cm (P =.0094) and high grade (P =.0200). Tumor was found in 33 (47.8%) of the PRE specimens, and 24 of these patients (72.7%) were deemed disease free after achieving negative surgical margins. Residual tumor was more likely to be found after PRE in head and neck primary tumors than in trunk wall or extremity primary tumors (P =.0128). There were no local failures in the 60 PRE patients who achieved clear margins. The estimated 5-year event-free and 5-year overall survival rates in these 60 patients were 98.3% +/- 2.0% and 98.2% +/- 2.1%, respectively. CONCLUSIONS: Pretreatment reexcision should be performed whenever feasible in pediatric patients with NRSTS who had an initial unplanned resection. The proportion of patients with residual tumor in the PRE specimen is high, and negative microscopic margins can be achieved after PRE in most patients with residual tumor. Despite delay in obtaining a complete surgical resection, no local recurrences were seen. The possibility of NRSTS should be considered when resecting a soft tissue mass in children, and diagnostic incisional biopsy followed by wide local excision with negative microscopic margins should be the surgical goal.

Brain metastases in paediatric solid tumours.

Brain metastases in children with cancer are rare and their incidence is significantly lower (5-10%) than that reported in adults. The development of metastatic brain tumours in children is usually a manifestation of advanced disease and commonly occur after, or at the time of progression at other sites. This review summarises the salient clinical features of the most common paediatric solid tumours that metastasize to the brain including neuroblastoma, musculoskeletal sarcomas, germ cell tumours and melanoma.

Neonatal alveolar rhabdomyosarcoma with skin and brain metastases.

BACKGROUND: Approximately 5-10% of patients with rhabdomyosarcomas (RMS) are diagnosed during the first year of life, and their clinical characteristics have been well documented. However, because RMS rarely occurs during the neonatal period, little is known about neonatal RMS. METHODS: Four patients with neonatal RMS were treated at St. Jude Children's Research Hospital between 1962 and 1999. The authors report the results of a review of these patients and of cases described in the literature. Clinical, radiologic, and pathologic features of these patients and their outcomes were evaluated. RESULTS: One patient with embryonal RMS was treated successfully with a combination of systemic chemotherapy and local control measures. The other three patients had alveolar RMS. Two of them had multiple skin and subcutaneous metastatic nodules at the time of diagnosis and developed brain metastases early in their course. In one of these patients, the PAX3-FKHR fusion transcript was detected. Three other similar cases of neonatal alveolar RMS with metastases to the skin and brain have been reported in the literature. CONCLUSIONS: A distinct syndrome of neonatal RMS is described. This syndrome is characterized by alveolar histology, multiple skin and subcutaneous metastases, and fatal outcome as the result of early brain metastasis.

Rhabdomyosarcoma of the parotid region occurring in childhood and adolescence. A report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: Rhabdomyosarcoma (RMS) of the parotid region is rare and to the authors' knowledge little information is available regarding the site of tumor origin, clinical presentation, and outcome in these patients. Therefore, the authors reviewed the files of all patients with RMS of the parotid region who were registered on the Intergroup Rhabdomyosarcoma Studies (IRS) I-IV. METHODS: Patient charts and the Intergroup Rhabdomyosarcoma Study Group (IRSG) database were reviewed. RESULTS: Sixty-two patients presenting with a mass in the parotid region were identified. None of the tumors was localized exclusively to the parotid gland, so the primary site was referred to as the "parotid region." The tumor invaded a parameningeal site in 30 patients. These cases have been designated as parameningeal-parotid tumors to distinguish them from 32 cases that did not invade a parameningeal site and were designated as nonparameningeal-parotid tumors. The majority of patients had Group III tumors in both the nonparameningeal-parotid and parameningeal-parotid subgroups. However, although there were 16 patients with Group I or II tumors in the nonparameningeal-parotid subgroup, no patients with Group I or II tumors were found in the parameningeal-parotid subgroup (P = 0.001). Fifty-six of 62 patients (90%) received radiotherapy. The parameningeal primary site designation resulted in intensification of both chemotherapy and radiotherapy for patients with parameningeal-parotid RMS. The 5-year failure-free survival rate was 81% and the 5-year survival rate was 84%. There were no deaths reported among patients with Group I or II tumors. The 5-year failure-free survival did not appear to differ when comparing patients with parameningeal-parotid tumors with patients with nonparameningeal-parotid tumors (P = 0.21). CONCLUSIONS: Treatment as defined by the IRS protocols has been reported to be highly effective for patients with RMS of the parotid region. Outcome for the more aggressively treated patients with parameningeal-parotid RMS appears similar to that for patients with nonparameningeal-parotid RMS.

Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. PATIENTS AND METHODS: Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). RESULTS: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. CONCLUSION: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

Tumor volume or dynamic contrast-enhanced MRI for prediction of clinical outcome of Ewing sarcoma family of tumors.

BACKGROUND: The identification of risk factors that predict poor clinical outcome at the time of diagnosis could lead to intensified early therapy and improved outcome for pediatric patients with Ewing sarcoma family of tumors (ESFT). OBJECTIVE: To compare the effectiveness of static magnetic resonance (MR) imaging measurements of tumor volume with variables obtained by dynamic contrast-enhanced MR imaging (DEMRI) in predicting ESFT outcome. METHODS: MR examinations that included DEMRI were retrospectively reviewed. The analyses included 45 examinations of 21 patients with ESFT (performed from 1992 to 1996). Tumor volumes were measured on the static MR images, and the regions of interest were selected for DEMRI analysis. The relationships of static MR imaging and DEMRI variables with the probability of progression-free survival (PFS) and disease-free survival (DFS) were determined. RESULTS: Larger tumor volume at the time of diagnosis predicted poorer PFS and DFS estimates. No DEMRI variable predicted outcome. CONCLUSION: Determination of tumor volume by static MR imaging at the time of diagnosis is a simple and reliable method of predicting the clinical outcome of patients with ESFT. DEMRI is not as reliable a technique as static MR imaging for predicting the outcome of these patients.

Routine brain imaging is unwarranted in asymptomatic patients with rhabdomyosarcoma arising outside of the head and neck region that is metastatic at diagnosis: a report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: To the authors' knowledge, the incidence of brain metastases at the time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising outside the head and neck region is unknown, and routine imaging to identify metastatic brain involvement is costly. METHODS: The authors retrospectively reviewed the results of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the head, which was mandated by protocol, in patients with metastatic RMS arising outside the head and neck region who were enrolled on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997). RESULTS: Of 100 eligible patients with metastatic RMS arising outside the head and neck region, 56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56 patients (12.5%) had abnormal scans. Three patients with physical findings suggesting head or neck pathology underwent imaging that confirmed the presence of metastases in bone (one patient), orbit (one patient), or lymph nodes (one patient). One patient who presented with seizures had imaging findings consistent with cerebral embolic infarctions. Of three asymptomatic patients, one had bone metastases that also were identified on skeletal survey and one had bone metastases in the base of the skull that were not identified on bone scan. The remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal canal extension and subsequently developed leptomeningeal disease dissemination. CONCLUSIONS: Brain metastases are uncommon at the time of initial diagnosis of metastatic RMS arising outside the head and neck region, and the majority of abnormalities detected on head CT or MRI scans are evident clinically or on other imaging studies. Patients with clinical findings suggesting intracranial pathology and those with paraspinal tumors may benefit from brain imaging, but cost savings may be realized by foregoing imaging in patients without these features.

Primary Ewing tumor of the vertebrae: clinical characteristics, prognostic factors, and outcome.

BACKGROUND: Fewer than 10% of Ewing family of tumors (EFT) arise in the vertebrae. Little information is available regarding the clinical presentation and outcome of these tumors. PROCEDURE: We reviewed the clinical features, prognostic factors, and outcome of EFT of the spine identified at our institution between 1962 and 1999. RESULTS: Thirty-three (10%) of 344 patients with EFT had a primary vertebral tumor. There were 21 (64%) males. Median age at diagnosis was 13.3 years. Six patients had metastatic disease and 10 had tumors > or = 8 cm in diameter. Primary sites were sacral (13), thoracic (10), lumbar (8), and cervical (2) vertebrae. We found no association between the affected spinal region and outcome, although sacral tumors were associated with delayed diagnosis (4 vs. 2 months after onset of symptoms, P = 0.076). Pain (n = 32) and neurologic deficits (n = 31; 82% motor, 58% sensory, 42% bladder, 27% bowel) were the most common presenting features. All patients received combination chemotherapy and local radiotherapy. With a median follow up of 9.7 years, 5-year survival and event-free survival ( +/- SD) estimates were 48.1% (8.9%) and 35.6% (8.6%), respectively, comparable to those of other patients with EFT. Outcome was better for patients with tumor size < 8 cm (P = 0.008) or localized disease (P = 0.084). Treatment era and specific tumor site did not affect outcome. CONCLUSIONS: Outcomes are similar for primary EFT of the spine and primary EFT in other sites. Unlike others, we found that patients with sacral tumors did not fare worse than patients with tumors at other spinal sites.

Improved outcome for patients with middle ear rhabdomyosarcoma: a children's oncology group study.

PURPOSE: The goal of this study was to define the clinical features and optimal therapy for children and adolescents with middle ear (ME) rhabdomyosarcoma (RMS). PATIENTS AND METHODS: We reviewed demographic data, clinical features, therapy (including chemotherapy, surgery, and radiation), and outcome for the 179 eligible patients with ME RMS who were enrolled onto Intergroup Rhabdomyosarcoma Studies (IRS) I through IV or pilot studies between November 1972 and December 1997. RESULTS: Most patients were younger than 10 years old (90%), and 63% were male. Because of the parameningeal location, most tumors were not resected before chemotherapy (group I, < 1%; group II, 4%; group III, 84%; group IV, 12%). Although most tumors were locally invasive (T2, 89%), the majority were small (< or = 5 cm, 66%), lacked nodal metastases (N0, 86%), and had embryonal histology (85%). The 5-year failure-free survival (FFS) and overall survival (OS) estimates were 67% and 72%, respectively. Both FFS and OS improved significantly over the course of IRS I through IV (3-year FFS and OS: IRS-I, 42% and 42%; IRS-II, 70% and 74%; IRS-III, 65% and 72%; IRS-IV pilot, 81% and 96%; IRS-IV, 88% and 88%, P <.001). Lower clinical group or stage and smaller tumor size were associated with better outcome. Age, sex, tumor invasiveness, and nodal metastases were not predictive of outcome. CONCLUSION: Patients with ME RMS generally present with small, unresectable, invasive tumors at a site traditionally considered prognostically unfavorable. Nevertheless, such patients have benefited markedly from improvements in multimodal, risk-based therapy during the course of IRS I through IV, and with contemporary therapy, most are cured.

Selective use of whole-lung irradiation for patients with Ewing sarcoma family tumors and pulmonary metastases at the time of diagnosis.

PURPOSE: The benefit of whole-lung irradiation (WLI) for patients who have pulmonary metastases (PM) of Ewing sarcoma family tumors (ESFT) is unclear. At our institution, WLI is reserved for patients with PM that do not respond completely to induction chemotherapy. We reviewed our experience to assess the impact of WLI on clinical outcome. PATIENTS AND METHODS: Twenty-eight patients with ESFT and PM were treated in three consecutive institutional trials (1979-1996). Extent of pulmonary involvement at diagnosis, response of PM after induction chemotherapy, local treatment of PM thereafter, and clinical outcome were recorded. Treatment included primary tumor surgery and/or radiotherapy and 42 to 58 weeks of multiagent chemotherapy. RESULTS: Only eight patients (29%) received WLI. For the entire study group, the estimated 5-year event-free survival was 22.9% +/- 9.0%; the 5-year survival was 37.3% +/- 9.8%. Complete resolution of PM after induction chemotherapy was not correlated with survival (P = 0.53), nor was treatment with WLI (P = 0.87). CONCLUSIONS: The comparable survival of patients with poor and good response of PM to induction chemotherapy suggests that WLI may benefit poor responders. The use of WLI in good responders may provide similar benefit and merits further study.

Use of reverse transcriptase polymerase chain reaction for diagnosis and staging of alveolar rhabdomyosarcoma, Ewing sarcoma family of tumors, and desmoplastic small round cell tumor.

PURPOSE: To compare the use of reverse transcriptase polymerase chain reaction (RT-PCR) with that of morphology-based methods for diagnosis, staging, and detection of metastatic disease in pediatric alveolar rhabdomyosarcoma (ARMS), Ewing sarcoma family of tumors (ESFT), and desmoplastic small round cell tumors (DSRCT). MATERIALS AND METHODS: RT-PCR assays for the EWS-FLII, EWS-ERG, PAX3-FKHR, PAX7-FKHR, and EWS-WTI fusion transcripts were performed on RNA extracted from the primary tumor tissue, bone marrow, and body fluids obtained at initial presentation and relapse. Molecular findings were compared with original histologic diagnoses and results of staging procedures. RESULTS: Eighty-eight samples from 47 patients with ARMS (n = 13), ESFT (n = 31), or DSRCT (n = 3) were analyzed. The detection rate of metastatic disease was significantly higher with RT-PCR (95%) as compared with the morphologic methods (70%) for the three pediatric sarcomas studied. In primary tumors with characteristic fusion transcript, RT-PCR was positive in all cases with morphologic evidence of metastatic disease. Moreover, in six patients (3 with ARMS, 2 with DSRCT, and 1 with ESFT) with metastatic disease, micrometastases in bone marrow (4) and other sites (2) were detected by RT-PCR alone. Importantly, none of the patients with localized disease diagnosed had micrometastases detected by RT-PCR in bone marrow. CONCLUSIONS: The high sensitivity and specificity of RT-PCR for the characteristic fusion transcripts of pediatric sarcomas make it an ideal method to aid in the routine staging of these patients. In addition, the 100% sensitivity of RT-PCR in detection of micrometastasis makes it useful for follow-up and detection of minimal residual disease. However, the clinical significance of molecularly-detectable disease remains unknown. Further studies should aim to elucidate the therapeutic and prognostic implications of micrometastases detected by RT-PCR alone.