To assess the proportion of female childhood and adolescent tumor survivors who could benefit from oocyte cryopreservation.
Case series of female childhood and adolescent tumor survivors referred for ...fertility counseling.
A referral cancer center and an infertility unit of an academic hospital.
Young female childhood and adolescent tumor survivors who received gonadotoxic treatments.
Patients were prescribed tests of ovarian reserve and a personalized counseling was given. Oocyte cryopreservation was considered in subjects aged ≥18 years who were diagnosed with diminished ovarian reserve (DOR) (antimüllerian hormone level <2 ng/mL or total antral follicle count ≤10).
Rate of women with DOR who stored their oocytes.
Ninety out of 126 evaluated women completed the assessments. We documented preserved ovarian reserve, DOR, and premature ovarian insufficiency in 36 (40%), 35 (39%), and 19 (21%) cases, respectively. Overall, 13 subjects with DOR were eligible for oocyte cryostorage, of whom 9 (69%) underwent the procedure. Considering the whole cohort of evaluated young women (n = 90), the rate of those who had egg freezing was 10%. Finally, nine women started seeking pregnancy after the counseling (six with DOR), and seven of them became pregnant. When the data were analyzed separately according to most gonadotoxic treatments, considerable differences emerged but the evidence did not support the idea that counseling should be restricted to particular subgroups of women.
Ovarian reserve impairment is common in female childhood and adolescent tumor survivors. Postcancer oocyte cryopreservation may be part of the armamentarium of fertility preservation options.
Preservación de la fertilidad en mujeres supervivientes de tumores en la infancia y la adolescencia.
Evaluar la proporción de mujeres supervivientes de tumores en la infancia y la adolescencia que podrían beneficiarse de la criopreservación de ovocitos.
Serie de casos de mujeres supervivientes de tumores en la infancia y la adolescencia derivadas para recibir asesoramiento sobre fertilidad.
Centro oncológico de referencia y unidad de infertilidad de un hospital académico.
Mujeres jóvenes supervivientes de tumores en la infancia y la adolescencia que recibieron tratamientos gonadotóxicos.
A las pacientes se les prescribieron pruebas de reserva ovárica y se les dio asesoramiento personalizado. La criopreservación de ovocitos fue considerada en sujetos con edad ≥ 18 años que fueron diagnosticadas con reserva ovárica disminuida (DOR) (niveles de la hormona antimulleriana < 2 ng/ml o recuento total de folículos antrales ≤ 10).
Tasa de mujeres con DOR que preservaron sus ovocitos.
Noventa de las 126 mujeres evaluadas completaron las evaluaciones. Documentamos la reserva ovárica preservada, DOR, y insuficiencia ovárica prematura en 36 (40%), 35 (39%) y 19 (21%) de los casos, respectivamente. En general 13 sujetos con DOR fueron elegidas para la criopreservación de los ovocitos, de los cuales 9 (69%) se sometieron al procedimiento. Considerando toda la cohorte de mujeres jóvenes evaluadas (n= 90), la tasa de las que se sometieron a congelación de óvulos fue del 10%. Finalmente, nueve mujeres comenzaron a buscar un embarazo después del asesoramiento (seis con DOR) y siete de ellas quedaron embarazadas. Cuando los datos se analizaron por separado de acuerdo con la mayoría de los tratamientos gonadotóxicos, surgieron diferencias considerables, pero la evidencia no apoyó la idea de que el asesoramiento debería restringirse a subgrupos particulares de mujeres.
El deterioro de la reserva ovárica es común en mujeres supervivientes de tumores en la infancia y la adolescencia. La criopreservación de ovocitos postcancer puede ser parte del conjunto de opciones de preservación de la fertilidad.
EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe.
Survival in 44,129 children ...diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated.
For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms' tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt's lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year.
These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase.
Abstract
Background
Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of ...STS histological subtypes after specific types of childhood cancer.
Methods
We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated.
Results
Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval CI = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma.
Conclusions
For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
Fertility preservation in prepubertal and young adolescent girls scheduled for chemotherapy is a demanding situation. Despite the recent impressive improvements of ovarian cortex cryopreservation, ...significant limitations persist. The technique remains experimental, it exposes the girl to the risks of surgery and to an iatrogenic insult to the ovarian reserve, and there is no guarantee of use because not all girls will undergo re-implantation. Moreover, it is impossible to respect all the requested conditions for a valid informed consent. The girl is minor, the time for decision is very short, and the prospect of not surviving clouds both the girl and her relatives. An alternative but neglected option is oocyte cryopreservation after the end of cancer treatments, when the girl reaches adulthood. This possibility can overcome some of the limitations of ovarian cortex freezing and may be considered for girls scheduled for a chemotherapy at low or medium risk of ovarian reserve impairment. In this case report, we describe the case of a young female patient with cancer who survived 2 chemotherapies for 2 distinct cancers and who was diagnosed with reduced ovarian reserve. The patient underwent 3 cycles of ovarian hyperstimulation and ultimately stored 19 oocytes. The success obtained in this girl suggests consideration of egg freezing as an alternative fertility-preservation procedure in prepubertal and young adolescent girls scheduled for chemotherapy. However, cryopreservation of ovarian tissue remains the only option for those scheduled for chemotherapies at high risk of ovarian reserve impairment.
Objective To report on our experience with girls and young women who received treatment for Hodgkin lymphoma, underwent prior oophoropexy to preserve their ovarian function, and subsequently gave ...birth. Design Retrospective monoinstitutional evaluation. Setting National Cancer Institute. Patient(s) Eleven girls given treatment for Hodgkin lymphoma and undergoing bilateral ovarian transposition at a median age of 13 years. Intervention(s) The ovaries were positioned behind the uterus by the general surgeon. Main Outcome Measure(s) Fourteen pregnancies were recorded among these 11 women, with 12 live births (1 twin) and 3 miscarriages. Result(s) None of these women needed the ovaries to be relocated, and none of them resorted to artificial insemination. Their median age at the time of first pregnancy was 31 years, and the median time elapsing since ovarian transposition was 14 years. Conclusion(s) This series confirms that oophoropexy can preserve ovarian function and enable future pregnancy. We encourage pediatric oncologists, surgeons, and radiotherapists to bear this option in mind when considering female patients for pelvic irradiation.
Langerhans cell histiocytosis is rare in adults, and most of what we know about its diagnosis and treatment comes from pediatric studies. We report clinical findings and results of treatment in a ...retrospective series of 63 consecutive adult patients (18–76 years old), treated at our pediatric unit from 1990 to 2020 using the same approach as for children. Patients were classified as having single-system disease (SS-LCH) in 41 cases, which was unifocal in 34 of them and multifocal in 7, or multisystem disease (MS-LCH) in 17 and primary pulmonary (pLCH) in 5. Twenty patients also had diabetes insipidus. A “wait and see” strategy was recommended after biopsy/surgery for patients with unifocal SS-LCH. Systemic treatment was proposed for cases of SS-LCH involving “special sites” or with multifocal disease, and in cases of MS-LCH. EFS and OS for the cohort as a whole were 62.2% and 100%, respectively, at 5 years and 52.5% and 97.6% at 10 years. Three patients died due to the damage caused by the multiple therapies administered. The rate of disease reactivation was high (affecting 40% of cases), with several reactivations over the years despite multiple lines of treatment. Though clinical history of LCH may differ between adults and children, in the absence of specific, tailored protocols, clinical approach to adult cases may draw on pediatric experience. Patients with limited disease have a good prognosis without any need for systemic therapy. Potentially greater toxicity in adults of systemic treatments generally used in pediatric setting should be borne in mind.
Secondary osteosarcoma: a challenge indeed Meazza, Cristina; Giovanna, Sironi; Nigro, Olga ...
International journal of clinical oncology,
2023/1, Letnik:
28, Številka:
1
Journal Article
Recenzirano
Background
The risk of survivors developing a secondary bone sarcoma after being treated for pediatric cancers is well established. The aim of this study was to examine the clinical characteristics ...and outcomes of patients with secondary osteosarcoma (SOS).
Methods
The study concerns survivors of childhood and adolescence primary neoplasms (PN) treated with chemotherapy, with or without radiotherapy and surgery, subsequently diagnosed with SOS.
Results
We identified 26 patients (13 females, 13 males) who developed SOS a median 7.3 years after being diagnosed with a PN (5/7 of these patients tested for Li–Fraumeni and found positive for the syndrome). The sample’s median age was 8.0 and 15.0 years when their PN and SOS were diagnosed, respectively. To treat their PN, 24 out of 26 patients had been given radiotherapy, and 19 had received chemotherapy including doxorubicin. A considerable number of SOS occurred at unfavorable sites (nine hip bone, six skull). All but one patient received chemotherapy with tailored schedules, omitting doxorubicin in 19 cases. Eighteen of the 26 patients underwent surgery. The 5- and 10-year overall survival and probabilities after the diagnosis of SOS (95% confidence interval) were 50% (32.7–76.5%) and 38.9% (22.4–67.4%); 5- and 10-year progression-free survival was 47% (29.9–73.7%) and 35.2% (19.3–64.4%), respectively.
Conclusions
The survival rates after SOS are lower than in patients with primary osteosarcoma, but not negligible. It is therefore mandatory to discuss the best choice of treatment for such patients at a referral center, in terms of their chances of cure and quality of life.
Although pediatric malignant extracranial germ-cell tumors (meGCTs) are among the most chemosensitive solid tumors, a group of patients relapse and die of disease. To identify new markers predicting ...clinical outcome, we examined the prognostic relevance of tumor-infiltrating T lymphocytes (TILs) and the expression of PD-1 and PD-L1 in a cohort of pediatric meGCTs by in situ immunohistochemistry. MeGCTs were variously infiltrated by T cell-subtypes according to the tumor subtype, tumor location and age at diagnosis. We distinguished three different phenotypes: i) tumors not infiltrated by T cells (immature teratomas and half of the yolk sac tumors), ii) tumors highly infiltrated by CD8
+
T cells expressing PD-1, which identifies activated tumor-reactive T cells (seminomas and dysgerminomas), iii) tumors highly infiltrated by CD8
+
T cells within an immunosuppressive tumor microenvironment characterized by CD4
+
FOXP3
+
Treg cells and PD-L1-expressing tumor cells (embryonal carcinomas, choriocarcinomas and the remaining yolk sac tumors). Tumor subtypes belonging mixed meGCTs were variously infiltrated, suggesting the coexistence of multiple immune microenvironments either facilitating or precluding the entry of T cells.
These findings support the hypothesis that TILs influence the development of meGCTs and might be of clinical relevance to improve risk stratification and the treatment of pediatric patients.
With a view to improving the prognosis for patients with metastatic medulloblastoma, we tested the efficacy and toxicity of a hyperfractionated accelerated radiotherapy (HART) regimen delivered after ...intensive sequential chemotherapy.
Between 1998 and 2007, 33 consecutive patients received postoperative methotrexate (8 g/m(2)), etoposide (2.4 g/m(2)), cyclophosphamide (4 g/m(2)), and carboplatin (0.8 g/m(2)) in a 2-month schedule, then HART with a maximal dose to the neuraxis of 39 Gy (1.3 Gy/fraction, 2 fractions/d) and a posterior fossa boost up to 60 Gy (1.5 Gy/fraction,2 fractions/d). Patients with persistent disseminated disease before HART were consolidated with two myeloablative courses and circulating progenitor cell rescue.
Patients were classified as having M1 (n = 9), M2 (n = 6), M3 (n = 17), and M4 (n = 1) disease. Seven patients younger than 10 years old who achieved complete response after chemotherapy received a lower dose to the neuraxis (31.2 Gy). Twenty-two of the 32 assessable patients responded to chemotherapy; disease was stable in five patients and progressed in five patients. One septic death occurred before radiotherapy. Eight patients experienced relapse after a median of 12 months. Fourteen of the 33 patients underwent consolidation therapy after HART. With a median 82-month survivor follow-up, the 5-year event-free, progression-free, and overall survival rates were 70%, 72%, and 73%, respectively. No severe clinical complications of HART have emerged so far.
HART after intensive postoperative chemotherapy, followed by myeloablative chemotherapy in selected cases, proved feasible in children with metastatic medulloblastoma. The results of our treatment compare favorably with other series treated using conventional therapies.
To improve the poor prognosis for children with metastatic osteosarcoma (OS), interleukin-2 (IL-2) was added to the standard treatment due to its capacity to activate lymphocytes and differentiate ...lymphocyte subsets into lymphokine-activated killer (LAK) cells that are capable of recognizing and killing various tumor cells. This study concerns a cohort of unselected patients aged < 18 years with metastatic OS, who were treated with IL-2, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, LAK reinfusion, and surgery, between 1995 and 2010. Thirty-five patients aged 4–17 years were involved. Thirty-two of the 35 patients underwent surgery on their primary tumor, and 25 had surgery on lung metastases too. Twenty-seven patients received IL-2 plus LAK reinfusion. The median follow-up was 130 months (77–228), and the 3-year event-free and overall survival rates were 34.3 and 45.0%, respectively. Eleven patients remained alive, all of whom achieved a complete surgical removal of the primary tumor and lung metastases (1 patient did not receive lung resections due to complete lung metastases remission). Patients who had a complete surgical remission of the primary and metastatic sites and who responded well to chemotherapy had a better event-free survival. These results confirm the importance of complete surgical remission and point to a noteworthy (though still be ameliorate) survival rate in our series of patients, underling a potential role for immunotherapy with IL-2 and LAK/NK cell activation.
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