Hematologic toxicity of high-dose iodine-131-metaiodobenzylguanidine therapy for advanced neuroblastoma.

PURPOSE: Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) has been shown to be active against refractory neuroblastoma. The primary toxicity of (131)I-MIBG is myelosuppression, which might necessitate autologous hematopoietic stem-cell transplantation (AHSCT). The goal of this study was to determine risk factors for myelosuppression and the need for AHSCT after (131)I-MIBG treatment. PATIENTS AND METHODS: Fifty-three patients with refractory or relapsed neuroblastoma were treated with 18 mCi/kg (131)I-MIBG on a phase I/II protocol. The median whole-body radiation dose was 2.92 Gy. RESULTS: Almost all patients required at least one platelet (96%) or red cell (91%) transfusion and most patients (79%) developed neutropenia (< 0.5 x 10(3)/microL). Patients reached platelet nadir earlier than neutrophil nadir (P <.0001). Earlier platelet nadir correlated with bone marrow tumor, more extensive bone involvement, higher whole-body radiation dose, and longer time from diagnosis to (131)I-MIBG therapy (P 相似文献   

Radio iodized metaiodobenzylguanidine (MIBG) in the treatment of neuroblastoma: modalities and indications

Neuroblastoma is the most common pediatric extracranial solid cancer. Patients with metastatic disease at initial diagnosis who are greater than 18 months of age and patients with MycN amplified locoregional tumors are treated with intensive multimodal therapy. While this intensive approach has been shown to improve outcome, patients with high-risk disease frequently relapse and fewer than 50% of these patients will be long-term survivors necessitating new approaches for therapy. Derived from the sympathetic nervous system, this tumor typically expresses the norepinephrine transporter. This transporter mediates active intracellular uptake of metaiodobenzylguanidine (MIBG) an analogue of norepinephrine in approximately 90% of patients allowing the use of radiolabeled (metaiodobenzylguanidine) MIBG, for targeted radiotherapy. This article will review the clinical experience of using MIBG as targeted radiotherapy in neuroblastoma. The administration guidelines, toxicity, response and survival are discussed. Recent studies have evaluated combinations of (131)I-MIBG with myeloablative regimens such as chemotherapy agents with radiation sensitizing properties, or with biologic agents. Most of them report a response rate of 30-40% with (131)I-MIBG in patients with relapsed or refractory neuroblastoma. Due to this high response rates and low non-hematologic toxicity, (131)I-MIBG seems to be an interesting agent for incorporation into the upfront management of newly diagnosed patients with high-risk neuroblastoma.     

Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma.

PURPOSE: The survival for children with relapsed or metastatic neuroblastoma remains poor. More effective regimens with acceptable toxicity are required to improve prognosis. Iodine-131-metaiodobenzylguanidine ((131)I-MIBG) selectively targets radiation to catecholamine-producing cells, including neuroblastoma cells. A pilot study was performed to examine the feasibility of a novel regimen combining (131)I-MIBG and myeloablative chemotherapy with autologous stem-cell rescue. PATIENTS AND METHODS: Twelve patients with neuroblastoma were treated after relapse (five patients) or after induction therapy (seven patients). Eight patients had metastatic and four had localized disease at the time of therapy. All patients received (131)I-MIBG 12 mCi/kg on day -21, followed by carboplatin (1,500 mg/m(2)), etoposide (800 mg/m(2)), and melphalan (210 mg/m(2)) administered from day -7 to day -4. Autologous peripheral-blood stem cells or bone marrow were infused on day 0. Engraftment, toxicity, and response rates were evaluated. RESULTS: The (131)I-MIBG infusion and myeloablative chemotherapy were both well tolerated. Grade 2 to 3 oral mucositis was the predominant nonhematopoietic toxicity, occurring in all patients. The median times to neutrophil (> or = 0.5 x 10(3)/microL) and platelet (> or = 20 x 10(3)/microL) engraftment were 10 and 28 days, respectively. For the eight patients treated with metastatic disease, three achieved complete response and two had partial responses by day 100 after transplantation. CONCLUSION: Treatment with (131)I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity. Future study is warranted to examine the efficacy of this novel therapy.     

Fertility preservation before and after cancer treatment in children,adolescents, and young adults

Fertility is a top concern for many survivors of cancer diagnosed as children, adolescents and young adults (CAYA). Fertility preservation (FP) treatments are effective, evidence-based interventions to support their family building goals. Fertility discussions are a part of quality oncology care throughout the cancer care continuum. For nearly 2 decades, clinical guidelines recommend counseling patients about the possibility of infertility promptly at diagnosis and offering FP options and referrals as indicated. Multiple guidelines now recommend post-treatment counseling. Infertility risks differ by cancer treatments and age, rendering risk stratification a central part of FP care. To support FP decision-making, online tools for female risk estimation are available. At diagnosis, females can engage in mature oocyte/embryo cryopreservation, ovarian tissue cryopreservation, ovarian suppression with GnRH agonists, in vitro oocyte maturation, and/or conservative management for gynecologic cancers. Post-treatment, several populations may consider undergoing oocyte/embryo cryopreservation. Male survivors’ standard of care FP treatments center on sperm cryopreservation before cancer treatment and do not have the same post-treatment indication for additional gamete cryopreservation. In practice, FP care requires systemized processes to routinely screen for FP needs, bridge oncology referrals to fertility, offer timely fertility consultations and access to FP treatments, and support financial navigation. Sixteen US states passed laws requiring health insurers to provide insurance benefits for FP treatments, but variation among the laws and downstream implementation are barriers to accessing FP treatments. To preserve the reproductive futures of CAYA survivors, research is needed to improve risk stratification, FP options, and delivery of FP care.     

Cancer of unknown primary: Incidence rates,risk factors and survival among adolescents and young adults

Cancer of unknown primary (CUP) is a clinical challenge especially when it occurs in adolescents and young adults (AYA), aged 15–39 years, due to the sparse data in this population. The available data has not described the population-based epidemiological features of CUP among AYA. Therefore, we collected patient information from the Surveillance, Epidemiology and End Results (SEER) registry, 1990–2015. Age, gender, ethnic, five pathological classification groups were assessed along with an aggregate level socioeconomic status (SES) index and population density at the county level. Incidence rates, modeled relative risks and survival of AYA patients with CUP were assessed. Among 2,480 AYA patients, 907 met the definition of standard pathology classifications. The majority of AYA patients with CUP had a neuroendocrine, squamous cell and poorly differentiated carcinomas with 0.4 cases per 1,000,000 population. AYA living in areas with the highest SES level had the highest risks of CUP; adjusted relative risks (ARR) of 1.17 (95% CI 1.0–1.4) and 1.99 (95% CI 1.5–2.6), respectively. AYA living in nonmetropolitan areas had a lower risk of CUP (ARR = 0.16; 95% CI 0.1–0.2). The incidence of differentiated neoplasms has been decreasing slower than undifferentiated neoplasms since the early 1990s. The median overall survival (OS) was 11 months (95% CI 9–13 months) with squamous CUP having the longest median OS 16 years (95% CI 3–24 years). In conclusion, this analysis answers several gaps in the knowledge of CUP among AYA and provides a platform to better understand this disease and its management within this group.     

Incidence and risk factors for secondary malignancy in patients with neuroblastoma after treatment with 131I-metaiodobenzylguanidine

Several reports of second malignant neoplasm (SMN) in patients with relapsed neuroblastoma after treatment with ¹³¹I-MIBG suggest the possibility of increased risk. Incidence of and risk factors for SMN after ¹³¹I-MIBG have not been defined.This is a multi-institutional retrospective review of patients with neuroblastoma treated with ¹³¹I-MIBG therapy. A competing risk approach was used to calculate the cumulative incidence of SMN from time of first exposure to ¹³¹I-MIBG. A competing risk regression was used to identify potential risk factors for SMN.The analytical cohort included 644 patients treated with ¹³¹I-MIBG. The cumulative incidence of SMN was 7.6% (95% confidence interval [CI], 4.4–13.0%) and 14.3% (95% CI, 8.3–23.9%) at 5 and 10 years from first ¹³¹I-MIBG, respectively. No increase in SMN risk was found with increased number of ¹³¹I-MIBG treatments or higher cumulative activity per kilogram of ¹³¹I-MIBG received (p = 0.72 and p = 0.84, respectively). Thirteen of the 19 reported SMN were haematologic. In a multivariate analysis controlling for variables with p < 0.1 (stage, age at first ¹³¹I-MIBG, bone disease, disease status at time of first ¹³¹I-MIBG), patients with relapsed/progressive disease had significantly lower risk of SMN (subdistribution hazard ratio 0.3, 95% CI, 0.1–0.8, p = 0.023) compared to patients with persistent/refractory neuroblastoma.The cumulative risk of SMN after ¹³¹I-MIBG therapy for patients with relapsed or refractory neuroblastoma is similar to the greatest published incidence for high-risk neuroblastoma after myeloablative therapy, with no dose-dependent increase. As the number of patients treated and length of follow-up time increase, it will be important to reassess this risk.     

Challenges in the recruitment of adolescents and young adults to cancer clinical trials

The adolescent and young adult (AYA) oncology population has seen inferior progress in cancer survival compared with younger children and older adults over the past 25 years. Previously, AYAs had the best survival rates due to the prevalence of highly curable diseases including Hodgkin lymphoma and germ cell tumors, yet today AYAs have inferior survival rates to children and some adult cohorts. Survival rates are particularly poor for AYA-specific diseases such as sarcomas. Research involving children and adults diagnosed with common malignancies such as acute lymphoblastic leukemia has resulted in improved survival rates. However, AYAs have not directly benefited from such research due to low rates of access to and accrual on clinical trials. AYAs are less likely to have insurance or access to healthcare, are more likely to see providers who are not part of research institutions, and are less likely to be referred to or to join clinical trials, all of which may contribute to worse outcomes. Few clinical trials target AYA-specific diseases, leading to little information regarding how these diseases behave and what role the host plays. Tumor samples for this population are underrepresented in national tumor banks. Coupled with the need for more clinical trials that focus on AYA-specific cancers, better collaboration between adult and pediatric cooperative groups as well as increased education among community oncologists and primary care providers will be needed to enhance participation in clinical trials with the goal to increase survival and improve quality of that survival.     

Effects of mass screening for neuroblastoma on incidence, mortality, and survival rates in Osaka, Japan

Objectives: To evaluate the effects of mass screening for neuroblastoma, time trends of incidence, mortality, and survival of neuroblastoma in Osaka Prefecture were analyzed.Methods: Data for this analysis was obtained from the population-based Osaka Cancer Registry. Time trends of incidence and mortality rates were analyzed by calendar year and by birth cohort. Survival was compared between before and after the introduction of systematic screening.Results: From 1970-94, 457 cases of neuroblastoma and 182 deaths from neuroblastoma were observed in Osaka. The annual age- standardized incidence rate per million children increased from 7.5 in 1970-84 to 20.5 in 1985-94, while the mortality rates did not differ between these two periods. Analysis by birth cohort showed that the incidence rate at 0 year of age per 100,000 live births increased from 2.30 in 1970-79 (unscreened) to 19.80 in 1988-89 (screening by high-performance liquid chromatography, HPLC). The incidence rate in children 1 and 2-4 years of age also increased according to the introduction of HPLC. The mortality rate in children 1-4 years of age per 100,000 live births slightly decreased from 3.87 in 1970-79 to 3.30 in 1988-89, which was presumed to be derived from the improvement in survival due to the progress in treatment.Conclusions: It is strongly suggested that mass screening for neuroblastoma causes harm because of overdiagnosis, and it has little effect on decreasing the incidence and the mortality of neuroblastoma at 1-4 years of age.     

Cancer statistics for adolescents and young adults, 2020

Cancer statistics for adolescents and young adults (AYAs) (aged 15-39 years) are often presented in aggregate, masking important heterogeneity. The authors analyzed population-based cancer incidence and mortality for AYAs in the United States by age group (ages 15-19, 20-29, and 30-39 years), sex, and race/ethnicity. In 2020, there will be approximately 89,500 new cancer cases and 9270 cancer deaths in AYAs. Overall cancer incidence increased in all AYA age groups during the most recent decade (2007-2016), largely driven by thyroid cancer, which rose by approximately 3% annually among those aged 20 to 39 years and 4% among those aged 15 to 19 years. Incidence also increased in most age groups for several cancers linked to obesity, including kidney (3% annually across all age groups), uterine corpus (3% in the group aged 20-39 years), and colorectum (0.9%-1.5% in the group aged 20-39 years). Rates declined dramatically for melanoma in the group aged 15 to 29 years (4%-6% annually) but remained stable among those aged 30 to 39 years. Overall cancer mortality declined during 2008 through 2017 by 1% annually across age and sex groups, except for women aged 30 to 39 years, among whom rates were stable because of a flattening of declines in female breast cancer. Rates increased for cancers of the colorectum and uterine corpus in the group aged 30 to 39 years, mirroring incidence trends. Five-year relative survival in AYAs is similar across age groups for all cancers combined (range, 83%-86%) but varies widely for some cancers, such as acute lymphocytic leukemia (74% in the group aged 15-19 years vs 51% in the group aged 30-39 years) and brain tumors (77% vs 66%), reflecting differences in histologic subtype distribution and treatment. Progress in reducing cancer morbidity and mortality among AYAs could be addressed through more equitable access to health care, increasing clinical trial enrollment, expanding research, and greater alertness among clinicians and patients for early symptoms and signs of cancer. Further progress could be accelerated with increased disaggregation by age in research on surveillance, etiology, basic biology, and survivorship.