Pathogenic germline
variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) ...and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline
variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors including pineoblastoma and pituitary blastoma. In May 2016, the International PPB Registry convened the inaugural International
Symposium to develop consensus testing and surveillance and treatment recommendations. Attendees from North America, Europe, and Russia provided expert representation from the disciplines of pediatric oncology, endocrinology, genetics, genetic counseling, radiology, pediatric surgery, pathology, and clinical research. Recommendations are provided for genetic testing; prenatal management; and surveillance for
-associated pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, and central nervous system tumors and gastrointestinal polyps. Risk for most
-associated neoplasms is highest in early childhood and decreases in adulthood. Individual and caregiver education and judicious imaging-based surveillance are the primary recommended approaches. These testing and surveillance recommendations reflect a consensus of expert opinion and current literature. As
research expands, guidelines for screening and treatment will continue to be updated.
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Infants (<12 months) with rhabdomyosarcoma have historically had poorer outcome than the older age groups. We present outcomes for infants and young children aged 12–36 months with localised ...rhabdomyosarcoma with a particular emphasis on infants.
All children less than 36 months of age enrolled on the EpSSG RMS 2005 study for localised disease are included. Treatment comprised chemotherapy, local surgery and/or radiation therapy adapted to risk group and age. Main outcome measures were event free survival (EFS) and overall survival (OS).
Outcome data were available for 485/490 patients aged less than 36 months, 110 were infants. Infants received chemotherapy according to the risk group with no toxic deaths. Radiotherapy was delivered to 33.6% of infants and 63.5% of 12–36 months old, with respectively 41.7% and 22.2% receiving brachytherapy. Radical surgery was performed in 62% of infants and 57.1% of 12–36 months old.
Median follow up for patients who are alive (n = 393) was 72.7 months (range 6.9–158.2). Five-year OS for infants was 88.4% (95%CI 80.3–93.2), which is significantly better than the OS in 12–36 months old patients of 78.0% (95%CI 73.2–82.0; p = 0.0204). Five-year EFS for infants was 72.5% (95%CI 62.8–80.0) compared with 66.1% (95%CI 61.0–70.7; p = 0.2663) for 12–36 months old.
Infants treated on RMS 2005 achieved excellent EFS and OS. The EpSSG RMS 2005 chemotherapy regimen, combined with an increase in the application of adequate local therapy, improvements in imaging and supportive care and potentially favourable patients’ characteristics may have contributed to these results.
•Infants (<12 months) with localised RMS achieved improved outcome in this study.•This compares favourably with previous SIOP and European historical Studies.•Age under 12 months does not appear to be negative prognostic factor for survival.•Infants received radiotherapy particularly brachytherapy with increased frequency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary Survival outcomes for adolescent and young adult patients with soft tissue sarcomas lag behind those of children diagnosed with histologically similar tumours. To help understand these ...differences in outcomes, we discuss the following issues with regard to the management of these patients with soft tissue sarcomas: delays in diagnosis, trial availability and participation, aspects of the organisation of care (with an emphasis on age-specific needs), national centralisation of sarcoma care, international consortia, and factors related to tumour biology. Improved understanding of the causes of the survival gap between adolescents and young adults with sarcomas will help drive new initiatives to improve final health outcomes in these populations. In this Review, we specifically focus on embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and adult soft tissue sarcomas diagnosed in adolescents and young adults, and discuss the age-specific needs of these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To determine whether the clinical and molecular biologic characteristics of the alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS) subtypes have relevance independent of the ...presence or absence of the PAX/FOXO1 fusion gene.
The fusion gene status of 210 histopathologically reviewed, clinically annotated rhabdomyosarcoma samples was determined by reverse transcriptase polymerase chain reaction. Kaplan-Meier analysis was used to assess event-free survival and overall survival in fusion gene-negative ARMS (ARMSn; n = 39), fusion gene-positive ARMS (ARMSp; n = 94), and ERMS (n = 77). A total of 101 RMS samples were also profiled for whole-genome expression, and 128 were profiled for genomic copy number imbalances. Profiling data were analyzed by supervised and unsupervised methods to compare features related to histopathology and fusion gene status. Results were also projected by meta-analysis techniques across three separate publically available data sets.
Overall and event-free survival, frequency of metastases, and distribution of site at initial presentation were not significantly different between ARMSn and ERMS. Consistent with this, analysis of gene expression signatures could not reproducibly distinguish ARMSn from ERMS whereas fusion gene-positive cases were distinct. ARMSn and ERMS frequently show whole-chromosome copy number changes, notably gain of chromosome 8 with associated high levels of expression of genes from this chromosome.
The clinical behavior and molecular characteristics of alveolar cases without a fusion gene are indistinguishable from embryonal cases and significantly different from fusion-positive alveolar cases. This implies that fusion gene status irrespective of histology is a critical factor in risk stratification of RMS.
Summary Ovarian transposition was the first procedure proposed to preserve fertility in girls with cancer and is indicated for patients with tumours requiring pelvic radiation at doses of 42·0–58·4 ...Gy, much higher doses than those that can induce loss of ovarian function (4–20 Gy). Ovarian transposition is usually done after neoadjuvant chemotherapy and is completed by minimally invasive surgery or open surgery in case of concomitant resection of the abdominal tumour. According to the type of tumour, the ovaries are moved and placed in the paracolic gutters when the radiation field reaches the midline (for medulloblastoma or urogenital rhabdomyosarcoma), contralaterally to the tumour (for pelvic sarcomas), or in line with the iliac crests (for Hodgkin's lymphoma). However, in 10–14% of cases the procedure can fail to protect the ovaries. Although few long-term results in adults are available, normal hormonal function and pregnancies have been reported in a few long-term follow-up studies. In view of the continued development of fertility preservation techniques, ovarian transposition should be discussed at a multidisciplinary meeting at the time of cancer diagnosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
6.
Very rare tumors are not so rare in children Orbach, Daniel; Brecht, Ines; Ferrari, Andrea
EJC paediatric oncology,
June 2024, 2024-06-00, 2024-06-01, Volume:
3
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To retrospectively analyze the clinical features and results of treatment in 56 infants with fibrosarcoma enrolled onto cooperative European protocols between 1979 and 2005 and treated with a ...combination of surgery and chemotherapy.
We performed a retrospective case review of infants under the age of 2 years with fibrosarcoma treated between 1979 and 2005 in six European studies. Patients were staged according to the Intergroup Rhabdomyosarcoma Staging System international classification as a function of the type of initial surgery and the extent of disease and were treated with surgery and chemotherapy. Survival was calculated using the Kaplan-Meier method.
Primary tumor site was the limbs in 66% of patients; median tumor diameter was more than 5 cm in 63% of patients; and postoperative staging was as follows: group I, 22%; group II, 27%; group III, 47%; and group IV, 4%. Response rate to chemotherapy was 75%, and the specific response rate to vincristine-dactinomycin was 71%. Local control was obtained in 84% of patients. At the end of follow-up, 45% of survivors had been treated by surgery alone, 6% by chemotherapy alone, 46% by surgery and chemotherapy, and 2% by surgery, chemotherapy, and radiotherapy. The 5-year overall survival (OS) rate was 89%. The 5-year OS and event-free survival rates for localized patients were 89% and 81%, respectively.
Although complete resection is rarely feasible at diagnosis, conservative surgery remains the mainstay treatment for infantile fibrosarcoma. An alkylating agent-free and anthracycline-free regimen is usually effective and should be chosen as first-line chemotherapy for inoperable tumors. Overall prognosis is good, but progression or relapse, mainly local, remains possible.
Hospitalization rates can be used as an indirect indicator of the burden and severity of adverse health outcomes in childhood cancer survivors (CCS). We aimed to determine the long-term risks of ...hospitalization related to renal and urinary diseases among 5-year CCS.
The French Childhood Cancer Survivor Study cohort was linked with data from the French National Healthcare System database, which enabled the identification of hospitalizations related to renal or urinary diseases. Clinical and detailed treatment data were collected from medical records. Dose-volume histograms were estimated for all patients treated with radiotherapy. Standardized Hospitalization Ratios and absolute excess risks (AER) were calculated. Relative risks were estimated using Poisson regression.
A total of 5,498 survivors were followed for 42,118 person-years (PY). Survivors experience 2.9 times more renal hospitalizations than expected in the general population, with an AER of 21.2/10,000 PY. Exposing more than 10% of the kidneys' volume to at least 20 Gray increases the risk of being hospitalized for renal causes by 2.2 (95% confidence interval, 1.3-3.6). Nephrectomized survivors treated with high doses of ifosfamide (>60 g/m²) have an extremely high risk of hospitalization for renal causes. Patients with comorbidities have about a 3-fold higher risk, and nephrectomized patients a 2-fold higher risk of being hospitalized for renal causes compared with other subjects. In the case of hospitalization for urinary causes, treatment by anthracycline administration was found to be associated with an almost 2-fold higher risk of hospitalization compared with the general population.
These results support the need for careful monitoring of long-term renal diseases in survivors who have undergone nephrectomy, those treated with high doses of radiation (≥20 Gy) even to small volumes of the kidneys, and those with predisposing risk factors.
This study provides new evidence with potential impact on surveillance guidelines related to dose-volume indicators associated with renal toxicity.
Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well ...established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.
One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.
CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.
Background
Nuclear protein of the testis (NUT) carcinoma (formerly NUT midline carcinoma) is an aggressive tumor defined by the presence of NUT rearrangement with a poor prognosis. This rare cancer ...is underdiagnosed and poorly treated.
Objective
The primary objective of this study was to describe the clinical, radiologic, and biological features of NUT carcinoma. The secondary objective was to describe the various treatments and assess their efficacy.
Methods
This retrospective multicenter study was based on review of the medical records of children and adults with NUT carcinoma with specific rearrangement or positive anti‐NUT nuclear staining (>50%).
Results
This series of 12 patients had a median age of 18.1 years (ranges: 12.3–49.7 years). The primary tumor was located in the chest in eight patients, the head and neck in three patients, and one patient had a multifocal tumor. Nine patients presented regional lymph node involvement and eight distant metastases. One‐half of patients were initially misdiagnosed. Specific NUT antibody was positive in all cases tested. A transient response to chemotherapy was observed in four of 11 patients. Only two patients were treated by surgery and five received radiotherapy with curative intent. At the end of follow‐up, only one patient was still in remission more than 12 years after the diagnosis. Median overall survival was 4.7 months (95% confidence interval CI: 2.1–17.7).
Conclusion
NUT carcinoma is an aggressive disease refractory to conventional therapy. Early diagnosis by NUT‐specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma to identify the specific rearrangement of NUT gene is useful to propose the optimal therapeutic strategy.
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