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In the US, spouses are a major source of informal care for older adults and, therefore, key to the US national strategy to provide long-term care to the growing population of older adults. Understanding the mental health impacts of spousal caregiving is therefore critically important. Existing studies on the topic have often been limited by methodological limitations, and most overlook the role of caregiving intensity. In this study, we assess the impact of providing different intensities of caregiving to a spouse on mental health outcomes using data from the Health and Retirement Study. We address the endogeneity of the decision to provide different caregiving intensities using an augmented inverse probability weighted (AIPW) estimator adapted to handle multivalued treatments. We check the robustness of our estimates to the AIPW's identifying assumptions by re-estimating the model using a dynamic fixed effects estimator. We find strong evidence that becoming a caregiver is associated with worsened mental health outcomes for women, while the evidence for men is weaker. When disaggregating by caregiving intensity, we find that transitions into high-intensity caregiving lead to large increases in depression symptoms and the probability of exhibiting major depression for both men and women. The overall mental health impact of transiting into caregiving is driven almost exclusively by the negative impact of high-intensity caregiving, as transitions into low- and moderate-intensity caregiving are not associated with worsening mental health in most specifications. This study provides timely insights that can inform the targeting of long-term care policies and programs aimed at supporting family caregivers of older adults., (© 2024 John Wiley & Sons Ltd.)

Background: Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas., Methods: Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021., Results: At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41-74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs., Conclusions: Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas., Plain Language Summary: Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types. Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer. This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins. Over half of patients had a durable response to larotrectinib, with no unexpected side effects. These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Limited data exist on the clinical behavior of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with distant metastases at onset, and a clear standard of care has not yet been defined., Methods: This cohort study reports on pediatric adult-type metastatic NRSTS enrolled in two concurrent prospective European studies, i.e., the randomized BERNIE study and the single-arm MTS 2008 study developed by the European paediatric Soft tissue sarcoma Study Group. Treatment programs were originally designed for patients with metastatic rhabdomyosarcoma, i.e., nine courses of multidrug chemotherapy (with or without bevacizumab in the BERNIE study), followed by 12 cycles of maintenance therapy, whereas radiotherapy and/or surgery (on primary tumor and/or metastases) were delayed until after seven courses of chemotherapy had been administered., Results: The study included 61 patients <21 years old treated from July 2008 to December 2016. The lung was the site of metastases in 75% of the cases. All patients received multi-agent chemotherapy, 44% had local therapy to primary tumor, and 18% had treatment of metastases. Median time to progression/relapse was 6 months. A high rate of tumor progression was observed during the initial part of the chemotherapy program. With a median follow-up of 41.5 months (range, 2-111 months), 3-year event-free survival and overall survival were 15.4% (95% confidence interval [CI], 7.6-25.7) and 34.9% (95% CI, 22.7-47.5), respectively. There were no statistically significant differences in outcome depending on the type of treatment administered., Conclusions: The study confirmed the overall poor outcome for patients with metastatic NRSTS, whose treatment remains a challenge., Plain Language Summary: Pediatric non-rhabdomyosarcoma soft tissue sarcomas form a heterogeneous group of rare tumors. Although recent international studies have defined the standard of care for patients with localized disease, limited data are available on the clinical behavior of patients with distant metastases. This study on 61 metastatic cases treated on two prospective European protocols confirms that the chances of survival of such patients are often dismal and a standard treatment is still lacking., (© 2023 American Cancer Society.)

We present the results of our experience in the diagnosis of inborn errors of metabolism (IEM) since the Expanded Newborn Screening was implemented in our Region. Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by mass spectrometry (MS)/MS. Newborns with alterations were referred to the clinical centers for follow-up. Biochemical and molecular genetic studies for confirmation of a disease were performed. In the period 2011 to 2019, 592 822 children were screened: 902 of them were referred for abnormal results. An IEM was confirmed in 222 (1/2670): aminoacidopathies: 89 hyperphenylalaninemia (HPA) (51 benign HPA, 32 phenylketonuria, 4 DNAJC12 defect, and 2 primapterinuria), 6 hypermethioninemia, 3 tyrosinemia type 1 (TYR-1), 1 TYR-3, 4 maple syrup urine disease (MSUD), 2 branched-chain amino acid transferase 2 deficiency, 2 homocystinuria, 1 cystinuria, 2 ornithine transcarbamylase (OTC) deficiency, 2 citrullinemia type I (CTLN1); FAO defects: 43 medium-chain acyl-CoA dehydrogenase deficiency (MCADD), 13 very long-chain acyl-CoA dehydrogenase deficiency, 2 long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD), 1 multiple acyl-coA dehydrogenation deficiency, 11 systemic primary carnitine deficiency, 2 carnitine palmitoyltransferase type 2 (CPT-II) deficiency, 1 CPT-I deficiency; organic acidurias: 12 glutaric aciduria type 1 (GA-1), 4 methylmalonic acidemia (MMA), 7 MMA including combined cases with homocystinuria (MMAHC), 6 propionic acidemia (PA), 7 3-methylcrotonyl-CoA carboxylase, 1 3-hydroxy-3-methylglutaryl-CoA lyase deficiency lyase deficiency. Only 19 infants (8.5%) were symptomatic at newborn screening result (1 LCHADD, 5 PA, 1 CPT-II deficiency, 1 MMA, 3 MMAHC, 2 MSUD, 2 OTC deficiency, 1 CTLN1, 1 MCADD, 2 TYR-1). No false negative cases were identified. Genetic diagnosis was conclusive in all biochemically confirmed cases, except for two infants with HPA, identifying pathogenic variants in 32 different genes. The conditions with the highest incidence were HPA (1/6661) and MCAD deficiencies (1/13 787)., Competing Interests: The authors declare no potential conflict of interest., (© 2021 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals., Methods: A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin., Results: Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported., Conclusions: This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes., (Copyright © 2011 American Cancer Society.)

Prospective right hemidiaphragm navigator (NAV) is commonly used in free-breathing coronary MRI. The NAV results in an increase in acquisition time to allow for resampling of the motion-corrupted k-space data. In this study, we are presenting a joint prospective-retrospective NAV motion compensation algorithm called compressed-sensing motion compensation (CosMo). The inner k-space region is acquired using a prospective NAV; for the outer k-space, a NAV is only used to reject the motion-corrupted data without reacquiring them. Subsequently, those unfilled k-space lines are retrospectively estimated using compressed sensing reconstruction. We imaged right coronary artery in nine healthy adult subjects. An undersampling probability map and sidelobe-to-peak ratio were calculated to study the pattern of undersampling, generated by NAV. Right coronary artery images were then retrospectively reconstructed using compressed-sensing motion compensation for gating windows between 3 and 10 mm and compared with the ones fully acquired within the gating windows. Qualitative imaging score and quantitative vessel sharpness were calculated for each reconstruction. The probability map and sidelobe-to-peak ratio show that the NAV generates a random undersampling k-space pattern. There were no statistically significant differences between the vessel sharpness and subjective score of the two reconstructions. Compressed-sensing motion compensation could be an alternative motion compensation technique for free-breathing coronary MRI that can be used to reduce scan time., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: Colorectal cancer is exceedingly rare in children and adolescents. Reports from small series indicate that poor prognostic factors are more common in children than in adults, resulting in worse outcome for the pediatric population., Methods: The Surveillance, Epidemiology, and End Results database was searched for records of children/adolescents with colorectal cancer, and the features and outcomes were compared with those of adults., Results: From January 1973 through December 2005, only 159 children/adolescents (ages 4-20 years) were reported with a diagnosis of colorectal cancer. The most common sites of involvement were the rectum (27%) and the transverse colon (26%). Adenocarcinoma was the most common histotype in both adults and pediatric patients; however, children/adolescents had more unfavorable histotypes (ie, mucinous adenocarcinoma [22%] and signet ring cell carcinoma [18%]) when compared with adults (10% and 1%, respectively; P < .001). Poorly differentiated and undifferentiated tumors (grades III and IV, respectively) and distant stage were more common in children/adolescents (P < .001). The 5-year relative survival estimates in children/adolescents and adults were 40% +/- 4.2% and 60% +/- 0.10%, respectively, confirming a worse outcome in the pediatric age group (P < .001)., Conclusions: Children/adolescents represent a minority of patients with colorectal cancer and have high-risk features and worse outcome than adults. The small number of patients in this age group was an impediment to the development of meaningful clinical trials. Thus, the principles of management for adult colorectal cancer should be used in the treatment of children and adolescents., (Copyright 2009 American Cancer Society.)

Background: Aggressive fibromatosis (AF) is a rare tumor of intermediate malignancy that has a strong potential for local invasiveness and recurrence. To date, there are no general recommendations for the clinical management of pediatric AF., Methods: The authors retrospectively analyzed 94 patients aged < or =21 years, including 23 patients who underwent complete surgery (Group I), 42 patients who underwent incomplete surgery with microscopic residual tumor (Group II), and 29 patients who underwent either biopsy or macroscopically incomplete surgery (Group III)., Results: The 5-year event-free survival (EFS) and overall survival rates were 44% and 99%, respectively. Local recurrences developed in 22% of patients in Group I, in 76% of patients in Group II, and in 76% of patients in Group III. Two of 7 patients with abdominal disease died of tumor progression, whereas none of the patients with extra-abdominal AF died of their disease. Systemic treatment was given to 15 patients as first-line treatment and to 34 patients at time the time they developed recurrent disease: The response rate was 47% in the former patients and 50% in the latter patients. Objective responses were observed in 11 of 19 patients who received combined methotrexate plus vinblastine/vinorelbine, in 7 of 15 patients who received alkylating-agent chemotherapy, and in 4 of 11 patients who received other therapies (tamoxifen, sulindac, interferon alfa)., Conclusions: The current analysis suggested that the clinical course of AF in children may resemble that of AF in adults. Local recurrences did not affect the chance of responding to systemic therapy or the survival rate. The completeness of initial resection was the main factor that influenced EFS, whereas disease control after marginal resection was much the same as that achieved after intralesional surgery/biopsy. Good responses to systemic treatments, and particularly to low-dose chemotherapy, were observed as reported previously in adults., (Copyright 2010 American Cancer Society.)

Background: In a series of 575 patients < or =21 years of age with soft tissue sarcomas (STSs), the authors investigated the association patterns between symptom interval (ie, the period between the onset of the first symptoms or signs of the disease and its definitive diagnosis) and patient/tumor characteristics or disease outcome (in terms of survival)., Methods: The analysis was based on multivariate models (linear for associations with patient/tumor characteristics and Cox's for survival)., Results: The symptom interval ranged between 1 week and 60 months (median, 2 months) and tended to be longer the older the patient (ie, the interval was longer in adolescents than in children) and the larger the tumor's size, and for tumors located at the extremities and for nonrhabdomyosarcoma STSs (as opposed to rhabdomyosarcomas). A longer symptom interval unfavorably influenced survival (P = .002), which was also significantly affected by the patient's age and the size and surgical stage of the tumor. A different pattern of association between symptom interval and survival emerged for different types of STS histology., Conclusions: Our study points to an independent prognostic effect of symptom interval that cannot be explained by its associations with other factors, such as patient's age or the site, size, stage, and histology of the tumor. Future studies should focus more on the possible causes of symptom interval in pediatric STS populations to enable corrective measures to be implemented to reduce the diagnostic delay., (Copyright 2010 American Cancer Society.)

Background: Synovial sarcoma (SS) is a typical soft tissue sarcoma subtype crosswise between the pediatric and the adult age groups. Less satisfactory overall outcome has been recorded in adult series., Methods: This study compares clinical features and outcomes of SS across the different age groups, by analyzing 1268 cases, 213 children/adolescents (

Background: The Ewing sarcoma family of tumors (ESFT) is one of the most common malignant neoplasms of children and adolescents, characterized by nonrandom translocations involving the Ewing sarcoma (EWS) gene. Over the years the adoption of intensive multimodality treatment approaches has led to a gradual improvement in the survival of patients with ESFT. The prognosis is still unsatisfactory for high-risk patients, however, and novel therapeutic approaches are desirable. The aim of the study was to investigate the expression/activation of KIT, PDGFRalpha, and PDGFRbeta receptor tyrosine kinases (RTKs) as potential therapeutic targets in ESFT., Methods: RNA and proteins were extracted from 20 frozen ESFT specimens to ascertain the state activation of KIT, PDGFRalpha, and PDGFRbeta., Results: No mutations were found, whereas the cognate ligands were detected in all cases by polymerase chain reaction (PCR). The expression and activation of KIT, PDGFRalpha, and PDGFRbeta were confirmed by quantitative PCR, immunohistochemistry, and immunoprecipitation and/or Western blot analysis. In particular, when compared with a protein pool obtained from normal adult tissues, PDGFRbeta showed a greater protein expression and/or a stronger phosphorylation signal., Conclusions: The results are consistent with an autocrine/paracrine loop activation of the KIT, PDGFRalpha, and PDGFRbeta receptors and suggest a rationale for the use of RTK inhibitors, either alone or in combination with chemotherapy.

Background: Patients affected by neurofibromatosis type 1 (NF1) are at higher risk of developing soft-tissue sarcomas (STS) than the general population. The clinical findings and outcome in 43 children and adolescents with NF1 treated for STS in the Italian protocols between 1988 and 2004 are reported., Methods: The study included 37 patients with neurogenic sarcomas (36 malignant peripheral nerve sheath tumors [MPNST], 1 triton tumor) and 6 cases of rhabdomyosarcoma (RMS). The prevalence of NF1 observed during the study period was 43% in the MPNST population and 1% in the RMS group., Results: Most patients with neurogenic sarcomas had large, invasive tumors. Five-year event-free and overall survival rates were 19% and 28%, respectively. Two of 16 patients with evaluable disease responded to chemotherapy. All 6 RMS patients were

Background: Epithelioid sarcoma (ES) is an uncommon malignant soft tissue tumor. To the authors' knowledge, little information is available to date concerning its clinical features and management in children and adolescents, particularly with regard to the recently described proximal-type variant. The current study concerns 30 patients age<18 years who were enrolled in the Italian Soft Tissue Sarcoma Committee protocols., Methods: Histopathologic specimens, clinical data, and treatment modalities were reviewed for the current analysis. Nineteen patients had classic ES and 11 had proximal-type ES. Surgery was the mainstay of treatment; radiotherapy was given to six patients considered to be at risk of local disease recurrence due to incomplete resection, and chemotherapy was administered to eight patients., Results: With a median follow-up of 66 months, the 5-year event-free survival (EFS) and overall survival (OS) rates were 61.7% and 92.4%, respectively, but the OS rate dropped to 86.9% and 72.4%, respectively, at 10 years and 15 years. Local disease recurrence was the major cause of treatment failure. The most significant finding influencing both EFS and OS was tumor site, with a tumor location in the extremities predicting a favorable outcome. Initially unfavorable clinical findings and a worse outcome were associated with the proximal-type variant of ES. A response to chemotherapy was noted in three of the seven patients with measurable disease., Conclusions: The current study confirms some typical features of ES (i.e., the peculiar superficial distal location [i.e., the hand, fingers], indolent growth, and a tendency to recur locally). The current study data do not clearly confirm the strong tendency for the lymph node involvement described in adult ES patients. Further studies are needed to better define the clinical behavior and biology of the proximal-type variant of ES., (Copyright (c) 2005 American Cancer Society.)

Background: Treatment of initially unresectable nonrhabdo soft tissue sarcomas (NRSTS) in pediatric age is debated, due to their different chemosensitivity. The authors objective was to evaluate clinical features and treatment results observed in a series of Italian patients over a 24-year period., Methods: Fifty-two patients age 8-18 years (median 8 years) were observed (1979-2002). Primary sites were on the lower limbs in 41 and on the upper limbs in 11 cases. Clinical TNM and surgical Intergroup Rhabdomyosarcoma Staging systems were adopted. Therapeutic guidelines recommended an initial biopsy plus neoadjuvant chemotherapy. Aggressive delayed surgery of residual disease, including compartmental resections, was recommended. Radiotherapy was suggested only for patients age > 3 years when surgery was incomplete or not feasible., Results: The evaluation was performed dividing the patients into two categories according to their chemosensitivity. Chemosensitive (CTs) sarcomas, 21: synovial sarcoma, 11; extraosseous Ewing sarcomas, 5; primitive peripheral neuroectodermic tumors, 5. Nonchemosensitive (CTns) sarcomas, 31: fibrosarcoma, 11; malignant peripheral nerve sheet tumors, 10; liposarcoma, 2; hemangiopericitoma adult type, 2; epithelioid sarcoma, 2; and alveolar soft part sarcoma, leiomyosarcoma, clear cell sarcoma, and sarcoma NOS, each 1. Nineteen of 21 patients with CTs-NRSTS were alive without disease: the 5-year overall survival (OS) and progression-free survival (PFS) were 94.4% and 79.3%, respectively; 23 of 31 patients with CTns-NRSTS were alive without disease: 5-year OS and PFS were 75.3% and 68.3%, respectively. Response to neoadjuvant chemotherapy was complete or partial in 10 of 20 evaluable CTs and in 8 of 26 evaluable CTns tumors. The achievement of complete delayed resection was particularly important for CTns-NRSTS. Tumor size < 5 cm, distal site, and tumor grading for CTns sarcomas were often linked to a favorable outcome; no conclusive results were detected concerning age of the patients or T status of the tumor., Conclusions: Multidisciplinary treatment without mutilating procedures allowed the cure of most patients with CTs and CTns-NRSTS. Relapses were cured in several cases of CTs tumors, whereas almost all patients with relapsed CTns tumors died due to the high rate of metastatic spread., ((c) 2005 American Cancer Society.)

Background: The role of doxorubicin (Doxo) as part of multidrug regimens used to treat children with soft tissue sarcoma (STS) is controversial. To evaluate the feasibility of combining Doxo with the well established ifosfamide, vincristine, and actinomycin D (IVA) regimen, the Italian STS Committee performed a pilot study on a series of children with metastatic STS., Methods: Between July 2002 and February 2004, 29 evaluable patients were enrolled in this study; 19 patients had rhabdomyosarcoma, 5 patients had peripheral neuroectodermal tumor, and 5 patients had other types of STS. The IVA-Doxo (IVADo) regimen included ifosfamide 3 g/m(2) on Days 1 and 2, vincristine 1.5 mg/m(2) on Day 1, actinomycin D 1.5 mg/m(2) on Day 1, and Doxo 30 mg/m(2) on Days 1 and 2. Three courses of IVADo were to be administered in the initial part of treatment and analyzed for toxicity and tumor response., Results: Overall, 92 cycles were delivered. Major regimen-related toxicity was myelosuppression, with Grade 4 neutropenia in 67% of cycles and fever and neutropenia in 37% of cycles. Nonhematologic toxicity included Grade 3-4 mucositis (6.5% of cycles), constipation (9.7%), and peripheral neuropathy (6.5%). Other manifestations of major toxicity were venoocclusive disease and seizures, which occurred in one patient each. All but 1 patient with a malignant schwannoma showed some degree of tumor volume reduction; however, considering only complete and partial remissions, the response rate was 76% (+/- 7.9%)., Conclusions: The intensive IVADo regimen was effective against pediatric STS with acceptable toxicity. This combination will be investigated in high-risk patients with rhabdomyosarcoma in a randomized trial launched by the European pediatric Soft tissue sarcoma Study Group., ((c) 2005 American Cancer Society.)

Background: Following their previous report on the activity of vinorelbine in the treatment of rhabdomyosarcoma, the authors report the results of a pilot study aimed at defining the optimal dose of vinorelbine when this agent is used in conjunction with continuous, orally administered low-dose cyclophosphamide to treat patients with refractory or recurrent sarcoma. It is hoped that the combination of vinorelbine and low-dose cyclophosphamide can be used as a maintenance regimen in an upcoming European trial involving high-risk patients with rhabdomyosarcoma., Methods: In the current pilot study, the cyclophosphamide dose was fixed at 25 mg/m2 per day for 28 days. Vinorelbine was administered intravenously on Days 1, 8, and 15, with trial doses escalated from an initial level of 15 mg/m2 in steps of 5 mg/m2; intrapatient dose escalation was not allowed., Results: Between April 2002 and November 2003, 18 patients ages 2-23 years were treated with the study regimen after having received 1-4 (median, 2) other regimens previously. Ninety cycles were administered in total (median, 5 cycles per patient; range, 1-10 cycles per patient). Two cases of dose-limiting toxicity (Grade 4 neutropenia in both cases) were observed among the 5 patients who received vinorelbine at a dose of 30 mg/m2. Of the 41 cycles in which vinorelbine was administered at a dose of 25 mg/m2, Grade > or = 3 neutropenia was observed in 15 (37%); no other major toxicity was documented in association with these cycles. One complete remission and 6 partial remissions were noted among the 17 patients who had measurable disease. Three of the eight assessable patients with rhabdomyosarcoma (which was embryonal in two cases and alveolar in one) had responses to treatment., Conclusions: Combination therapy involving vinorelbine and low-dose cyclophosphamide was found to be feasible and to possess activity against recurrent sarcomas. The maintenance therapy doses recommended for use in the upcoming European trial are cyclophosphamide 25 mg/m2 per day for 28 days and vinorelbine 25 mg/m2 on Days 1, 8, and 15., ((c) 2004 American Cancer Society.)

Background: The optimal treatment strategy for synovial sarcoma (SS) is subject to debate, and different strategies have been used for pediatric and adult patients. The current retrospective analysis examined a large group of patients of all ages who were treated at a single institution over a 30-year period., Methods: The study included 271 patients who ranged in age from 5 years to 87 years; 255 had localized disease, which was macroscopically resected in 215 cases and deemed unresectable at diagnosis in 40 cases. Chemotherapy was administered to 41% of patients, corresponding to 76% of patients age or 16 years and < 20% of older patients; 28% of patients with macroscopically resected disease received chemotherapy on an adjuvant basis., Results: The 5-year event-free survival rate for the study cohort as a whole was 37%, although this rate varied with age (66%, 40%, and 31% for patients age < or = 16 years, 17-30 years, and > 30 years, respectively). Chemotherapy was used more commonly for children than for adults. Among patients with surgically resected disease, the 5-year metastasis-free survival (MFS) rate was 60% for those who were treated with chemotherapy and 48% for those who were not; the benefit associated with chemotherapy use appeared to be greatest for patients age > or = 17 years who had tumors measuring > 5 cm (MFS, 47% [chemotherapy] vs. 27% [no chemotherapy]). In the subgroup of patients with measurable disease, the rate of tumor response to chemotherapy was approximately 48%., Conclusions: Although the authors await more convincing proof of the efficacy of adjuvant chemotherapy in the treatment of adult soft tissue sarcoma, they recommend that patients with high-risk SS (tumor size > 5 cm) be the first to be considered for this type of treatment.

Background: The authors reviewed their institutional experience regarding adult patients with Wilms' tumor (WT) to assess their clinical characteristics and compliance with respect to children's treatment guidelines., Methods: A total of 17 adult patients (median age at the time of diagnosis of 17.5 years; range, 16-29 years) were referred to the study institute between 1983 and 2001 and were followed for a median of 131 months. The treatment modality was planned according to the two consecutive Italian protocols for WT that were active during the referral years. The patients were staged according to the National Wilms Tumor Study-4 (NWTS) staging system as follows: eight patients had Stage II disease, four patients had Stage III disease, and five patients had Stage IV disease., Results: All the patients but one underwent nephrectomy, with three incomplete surgeries performed. Two patients with Stage II disease were treated elsewhere with nephrectomy only and they were admitted to the study institution at the time of disease recurrence. Anaplasia was found to be present in only one patient with Stage IV disease. The authors noted 9 cases of disease recurrence or progression occurring during treatment and 6 of these 9 patients died of their disease, with an overall survival rate of 62.4% at 5 years., Conclusions: Compared with children, adults with WT are reported to have a worse prognosis. In the current study, the authors found that poor compliance with specific therapeutic guidelines may contribute to this poorer outcome. Because of the rarity of this disease, adults with WT are at a risk of either undertreatment or incorrect treatment., (Copyright 2004 American Cancer Society.)

Background: The goal of the current study was to clarify treatment outcomes for adult patients with rhabdomyosarcoma (RMS). Published series have reported definitively worse results for adults with RMS compared with children with RMS. This finding casts doubt on whether RMS is the same disease in adults as it is in children., Methods: Of 190 patients with RMS who were age 18 years or older and whose cases were recorded over a 25-year span in the pathology database of the Istituto Nazionale Tumori (Milan, Italy), 171 could be analyzed retrospectively for treatment outcome. The authors attempted to stratify patients according to the degree to which they had been treated appropriately, based on current treatment guidelines for childhood RMS., Results: The overall rate of response to chemotherapy was 85%. For the entire series, 5-year event-free survival and 5-year overall survival (OS) were 28% and 40%, respectively. Among the 110 patients with embryonal, alveolar, or 'not otherwise specified' RMS, 5-year OS was 46%; however, 5-year OS was 61% for patients within this group (39% of the total) who had high scores for appropriate treatment., Conclusions: The current series parallels other published series in that it confirms the finding of a relatively poor long-term outcome for adult patients with RMS. However, for patients whose treatment adhered to the current guidelines for treatment of children, outcome was similar to what has been reported in pediatric series. In addition, the rate of response to chemotherapy for the entire series was similar to the rate typically observed among children. These findings suggest that adults and children with RMS should receive similar treatment. Treatment protocols adopted from pediatric programs but tailored to adults could increase adults' chances of receiving appropriate treatment; prospective studies are needed to test this idea., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11550)

Background: The management of rhabdomyosarcoma (RMS) in patients age < 1 year is particularly problematic and requires a tailored therapeutic approach. We report on the Italian Cooperative Group's 20-year study of 50 children with RMS who were age < 1 year at diagnosis., Methods: Patients were treated using multimodality therapeutic approaches that were based on three consecutive protocols. Chemotherapy was administered to all patients, with dosages calculated according to body weight; calculated doses subsequently were reduced by 33-50%. Radiotherapy was administered to 10 patients., Results: With a median follow-up of 76 months, 5-year event-free survival and overall survival rates were 42.3% and 61.7%, respectively. Local recurrence was the major reason for treatment failure. In particular, the local recurrence rate was high in patients who warranted radiotherapy but received none due to their age. Completeness of surgery and nodal involvement were the most significant prognostic factors. After a suitable reduction in dosage was made, acute toxicity was no different from what has been observed in older children. The most relevant toxic event was cardiotoxic death in a newborn (n = 1)., Conclusions: The current study confirmed that the outcome for infants with RMS is less satisfactory than for older children and that infants with RMS require more careful monitoring and specific treatment guidelines. The absence of local control is the major cause of treatment failure; aggressive conservative surgery should be encouraged, but more radiotherapy may be advisable in selected cases. Intensive chemotherapy is essential; a 33% dose reduction may ensure adequate tolerance. In addition, patients age < 3 months should not receive anthracyclines., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11357)

Background: In the current study, the authors aim to evaluate clinical features and treatment results observed in patients from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS)., Methods: One hundred sixty-one patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the Italian studies between April 1975 and December 1995. The age range of the patients was 0-18 years (median, 4 yrs). The distribution of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal, 34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40-44 Gy); 133 Group III patients underwent neoadjuvant CT +/- surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not recommended for patients age < 3 years., Results: The 10-year overall survival (OS) and progression-free survival (PFS) were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4% vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (> 5 cm, 42.1% vs. < 5 cm, 81% [P = 0.005]), age (< 10 yrs, 51.4% vs. >or= 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (+/-RT) (70.4% vs. 34.4% without it [P = 0.0015]). Most patients who achieved the delayed local control had responded well to neoadjuvant CT., Conclusions: Tumor size, histology, age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable outcomes., (Copyright 2003 American Cancer Society.)

Background: Vinca alkaloids have proved active against a number of pediatric malignancies. The aim of this study was to assess the feasibility and effectiveness of using vinorelbine in previously treated pediatric patients with advanced sarcomas., Methods: From September 1998 to August 2001, 33 previously treated patients with progressive sarcoma were treated: 13 had rhabdomyosarcomas, 5 had other soft tissue sarcomas, 9 had Ewing sarcomas, and 6 had osteosarcomas. Vinorelbine was given intravenously on Days 1 and 8 of a 21-day treatment cycle. Four patients with uncontrolled pain or central nervous system invasion received concurrent radiotherapy and were only evaluated for toxicity., Results: One hundred seventy-eight treatment cycles were administered (median of four per patient, range 1-20). Grade 3 to 4 neutropenia occurred in 63% of patients, Grade 3 anemia in 9%, and Grade 3 thrombocytopenia in 3%. Nonhematological toxicity was mild or moderate, i.e., always lower than Grade 3, with the exception of one child who experienced paralytic ileus. Twenty-eight patients were assessable for response. Eight patients had a partial response, one patient had a minor response, and nine patients had stable disease. Objective responses were observed in 6 of 12 patients with rhadbomyosarcomas (five of six of the alveolar subtype), in one of five patients with osteosarcomas, and in one of seven patients with Ewing sarcomas. The median duration of response was 10 months (range, 3+ to 20)., Conclusions: Vinorelbine has a favorable toxicity profile with evidence of biological activity in already heavily treated pediatric patients with sarcomas. In particular, the objective response rate obtained for patients with alveolar rhabdomyosarcoma seems very promising. Due to the few cases considered here, further Phase II studies are needed to establish a potential role of vinorelbine in the treatment of these tumors., (Copyright 2002 American Cancer Society.)

Background: Clear cell sarcoma (CCS) of tendons and aponeuroses is extremely rare in childhood and little information is available on its clinical management. Originally believed to be a type of melanoma of soft tissue origin, CCS is now considered a distinct clinicopathologic entity that behaves like a high-grade soft tissue sarcoma. We report on a series of 28 pediatric patients treated from 1980 to 2000 by the Soft Tissue Sarcoma Italian Cooperative Group and the German Cooperative Group., Methods: Patients were treated with a multimodality therapeutic approach. Surgical resection was complete in 17 patients (mutilating in 3), radiotherapy was administered to 8 patients, and 20 patients received chemotherapy., Results: After a median follow-up of 102 months (range, 19-238 months), the 5-year and event-free survival rates were 66.4% and 63.3%, respectively. Seventeen patients were alive in first remission, two were alive in second remission, and nine had died of disease. The response to chemotherapy in the 7 evaluable patients included one partial remission, one minor response, and five no responses. Radiotherapy contributed to achieving local control in four of six Intergroup Rhabdomyosarcoma Study (IRS) Group II patients. Statistically significant differences in outcome were evident according to IRS group, tumor size, and site., Conclusions: Our study confirms the aggressive behavior of CCS. Complete surgical resection represents the mainstay of treatment, and even the only treatment for patients with small tumors. Radiotherapy may control microscopic residual disease after surgery. Chemotherapy is ineffective and the prognosis is unfavorable for patients with unresectable and large tumors., (Copyright 2002 American Cancer Society.)

Background: Hemangiopericytoma (HPC) is very uncommon in childhood and comprises two different clinical entities, the adult type and the infantile type, occurring in the first year of age. We report on a series of 27 pediatric patients treated from 1978 to 1999 by the Italian and German Soft Tissue Sarcoma Cooperative Group., Methods: Seven patients had infantile HPC; complete resection was achieved in the tumors of five patients and chemotherapy was given to four patients. Twenty children had adult type HPC; nine received complete tumor resection (four patients at diagnosis and five at delayed surgery). Post-operative radiotherapy was administered to 15 patients, chemotherapy to 19., Results: Six of seven patients with infantile HPC were alive in first remission; one patient died of disease. Chemotherapy achieved an objective response in four of four patients. Among the adult type HPC cases, 5-year event free survival was 64% (median follow-up 125 months); 12 patients were alive in first remission, eight patients relapsed and died of disease. Seven of 10 evaluable patients showed good response to chemotherapy. Statistically significant differences in outcome were observed in relation to Intergroup Rhabdomyosarcoma Study grouping, size, local invasiveness, and gender., Conclusions: Infantile HPC is a unique entity probably related to infantile myofibroblastic lesions and characterized by a high response to chemotherapy, which is required in case of unresectable, life-threatening tumors. In children over 1 year of age, HPC behaves like its adult counterpart; complete surgical resection remains the mainstay of treatment, but chemotherapy and radiotherapy seem effective and are recommended in all patients with incomplete tumor resection and/or locally invasive, large tumors., (Copyright 2001 American Cancer Society.)