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BACKGROUND: Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study. METHODS: This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n57). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards. RESULTS: After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS. CONCLUSIONS: No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. (C) 2017 American Cancer Society.

Early response to induction chemotherapy is used in current European guidelines to evaluate the efficacy of chemotherapy and subsequently to adapt treatment in pediatric patients with rhabdomyosarcoma (RMS). However, existing literature on the prognostic value of early radiologic response on survival is contradictory; here the prognostic value is analyzed with data from the International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor 95 (MMT-95) study.This study examined 432 Intergroup Rhabdomyosarcoma Study Grouping III (macroscopic residue) patients enrolled in the SIOP MMT-95 study with a response assessment after 3 courses of chemotherapy (a 2-dimensional assessment). Patients with progressive disease (PD) after 3 courses of chemotherapy were excluded (n = 7). Failure-free survival (FFS) and overall survival (OS), calculated with the Kaplan-Meier method, were compared for 3 groups (complete response [CR]/partial response [PR], objective response [OR], and no response [NR]). The prognostic impact of early response was assessed through the calculation of Cox proportional hazards.After 3 courses of chemotherapy, 85.2% of the patients had CR/PR, 8.6% had OR, and 6.3% had NR. For all patients, the 5-year FFS and OS rates were 60% (95% confidence interval [CI], 56%-65%) and 74% (95% CI, 70%-78%), respectively. However, a Cox proportional hazards regression analysis revealed no significant difference in FFS or OS between the response groups. The adjusted hazard ratios for an OR and NR were 1.09 (95% CI, 0.63-1.88) and 0.81 (95% CI, 0.39-1.67), respectively, for FFS and 0.91 (95% CI, 0.47-1.76) and 1.27 (95% CI, 0.61-2.64), respectively, for OS.No evidence was found for the idea that early radiologic response to chemotherapy is prognostic for survival for patients with RMS. Treatment adaptation based on early response (except for patients with PD) should, therefore, no longer be incorporated into future studies. Cancer 2018;124:1016-24. © 2017 American Cancer Society.

BACKGROUND: Central pathology review (CPR) is an important component of multicenter tumor trials. The authors retrospectively analyzed the quality of pathology material submitted to determine the benefits and limitations of rapid CPR. METHODS: Analysis of pathology specimens from previous renal tumors in children trials (1980-2007) included the number of cases submitted, the number of slides per case, discrepancies in diagnosis and staging between institutional pathologists and CPR, and the impact of rapid CPR on treatment. RESULTS: The percentage of cases submitted for CPR increased from 76% in earlier trials to 100% in the current trial. The number of slides submitted rose from a median of 6 (International Pediatric Oncology Society [SIOP] 9301) to 25 for the SIOP-UK Renal Tumors 2001 trial. Discrepancies between the institutional pathologists and CPR were as follows: diagnosis: SIOP 9, 17%; SIOP 93-01, 14%; United Kingdom Wilms Tumour 3 Trial (UKWT3), 3.5%; SIOP-UK 2001, 3.8%; staging: SIOP 6, 9%; SIOP 93-01, 14%; UKWT3, 17%; SIOP-UK 2001, 3.8% of cases. There were clinically significant discrepancies in diagnosis and/or stage in 30 of 152 (20%) cases submitted for delayed CPR in SIOP-UK 2001. CONCLUSIONS: The number and quality of material submitted for CPR has markedly improved over time, predominantly due to the introduction of a simple standard operating procedure. Discrepancies in diagnosis and staging remain, but rapid review CPR allows clinicians to modify treatment if required. Benefits from the CPR system followed in SIOP-UK 2001 have been clearly demonstrated, and similar systems should be considered for future trials of other tumors. Cancer 2009. © 2009 American Cancer Society.

Background. Childhood soft tissue sarcomas are known to occur in a number of genetic syndromes. This study assesses the proportion of soft tissue sarcoma diagnosed in childhood associated with genetic predisposition to cancer. Methods. Information on the occurrence of neoplastic disease was collected for 151 of 179 families of a population-based series of children with soft tissue sarcoma. Results. Considering the index child as the proband, 5 of the 151 families manifested the classic Li–Fraumeni cancer family syndrome according to standard criteria and a further 10 families showed features consistent with the syndrome. One proband had double primary syndrome cancers. One other family had a sibling pair of childhood cancers, seven families had cancer which had occurred in childhood in other relatives, and three families had adult-onset sarcomas in more distant relatives. In another 16 families, one parent or the other had developed a possible syndrome cancer, or had developed cancer when younger than 60 years of age. Two families showed striking clusters of stomach cancer. Five case children were thought to have been affected with neurofibromatosis. Conclusions. Genetic predisposition to cancer was thought to be present in 7% to 33% of families interviewed.

The cancer experience among 754 first-degree relatives (mothers, fathers, and siblings) of a population-based series of 177 children with soft tissue sarcoma is reported. the current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first-degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). the pattern of cancers is consistent with the Li-Fraumeni syndrome. the authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.