Long‐term follow‐up after proton beam therapy for pediatric tumors: a Japanese national survey

Proton beam therapy (PBT) is a potential new alternative to treatment with photon radiotherapy that may reduce the risk of late toxicity and secondary cancer, especially for pediatric tumors. The goal of this study was to evaluate the long‐term benefits of PBT in cancer survivors. A retrospective observational study of pediatric patients who received PBT was performed at four institutions in Japan. Of 343 patients, 62 were followed up for 5 or more years. These patients included 40 males and 22 females, and had a median age of 10 years (range: 0–19 years) at the time of treatment. The irradiation dose ranged from 10.8 to 81.2 GyE (median: 50.4 GyE). The median follow‐up period was 8.1 years (5.0–31.2 years). The 5‐, 10‐ and 20‐year rates for grade 2 or higher late toxicities were 18%, 35% and 45%, respectively, and those for grade 3 or higher late toxicities were 6%, 17% and 17% respectively. Univariate analysis showed that the irradiated site (head and neck, brain) was significantly associated with late toxicities. No malignant secondary tumors occurred within the irradiated field. The 10‐ and 20‐year cumulative rates for all secondary tumors, malignant secondary tumors, and malignant nonhematologic secondary tumors were 8% and 16%, 5% and 13%, and 3% and 11%, respectively. Our data indicate that PBT has the potential to reduce the risk of late mortality and secondary malignancy. Longer follow‐up is needed to confirm the benefits of PBT for pediatric tumors.     

Familial risk of childhood cancer and tumors in the li‐fraumeni spectrum in the utah population database: Implications for genetic evaluation in pediatric practice

We used the Utah Population Database to examine risk of cancer in relatives of 4,482 pediatric cancer cases (≤18 years old) diagnosed from 1966 to 2009 compared to matched population controls. We quantified cancer risk in relatives of children with cancer to determine evidence of familial aggregation and to inform risk assessment and counseling for families. Odds ratios that reflect risk were obtained using conditional logistic regression models adjusting for number of biological relatives, their degree of genetic relatedness and their person‐years at risk. First‐degree relatives (primarily siblings) of pediatric cases faced a twofold increased risk of a cancer diagnosis before age 19, which extended to their second‐degree relatives (p < 10^?4, respectively). Furthermore, first‐degree relatives of children diagnosed before age 5 had a 3.6‐fold increased risk of developing pediatric cancer (p < 10^?7), second‐degree relatives of very young (under age 5) cases were at 2.5‐fold risk (p < 10^?4) and third‐degree relatives were at twofold risk (P < 10^?3) of childhood cancer. Although first‐degree relatives of pediatric cases have a slight increased risk of adult tumors, when they do develop cancer they have a 1.7‐fold risk of developing a tumor in the Li‐Fraumeni spectrum. Our findings support the hypothesis of familial aggregation in pediatric cancer and suggest that a higher percent of childhood cancers may be related to hereditary syndromes than are adult cancers. We encourage the collection of a family medical history that is routinely updated for all pediatric cancer patients, and that families with early‐onset adult cancers or clusters of several cancers are referred for genetic counseling.     

Immunotherapy of pediatric brain tumor patients should include an immunoprevention strategy: a medical hypothesis paper

Adults diagnosed with Glioblastoma multiforme (GBM) are frequently faced with a 7% chance of surviving 2 years compared with pediatric patients with GBM who have a 26% survival rate. Our recent screen of possible glioma-associated antigen precursor protein (TAPP) profiles displayed from different types of pediatric brain tumors showed that pediatric patients contained a subset of the tumor antigens displayed by adult GBM patients. Adult GBM possess at least 27 tumor antigens that can potentially stimulate T cell immune responses, suggesting that these tumors are quite antigenic. In contrast, pediatric brain tumors only expressed nine tumor antigens with mRNA levels that were equivalent to those displayed by adult GBM. These tumor-associated antigens could be used as possible targets of therapeutic immunization for pediatric brain cancer patients. Children have developing immune systems that peak at puberty. An immune response mounted by these pediatric patients might account for their extended life spans, even though the pediatric brain tumors express far fewer total tumor-associated antigens. Here we present a hypothesis that pediatric brain tumor patients might be the best patients to show that immunotherapy can be used to successfully treat established cancers. We speculate that immunotherapy should include a panel of tumor antigens that might prevent the out-growth of more malignant tumor cells and thereby prevent the brain tumor relapse. Thus, pediatric brain tumor patients might provide an opportunity to prove the concept of immunoprevention.     

Pediatric malignancies in neurofibromatosis type 1: A population-based cohort study

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Persons born in 1987–2011 were included, and 524 persons were followed through the files of the Finnish Cancer Registry from birth up to age 20 years. This amounted to 8,376 person years. Fifty-three patients had cancer <20 years of age, yielding a standardized incidence ratio (SIR) of 35.6. The most frequent location of pediatric cancers was the central nervous system (CNS); there were 45 cases and the SIR was 115.7. Exclusion of 22 optic pathway gliomas (OPGs) gave an SIR of 59.1 for the CNS and 21.6 for all cancers. There were nine malignant peripheral nerve sheath tumors (MPNSTs); their cumulative risk was 2.7% by age 20. No cases of leukemia were observed. NF1 patients showed considerable excess mortality with a standardized mortality ratio (SMR) of 73.1. The survival of NF1 patients with CNS tumors other than OPGs did not differ from that of non-NF1 controls (HR 0.64, 95% CI 0.23 to 1.76). In conclusion, brain tumors in childhood and MPNSTs in adolescence are malignancies of major concern in patients with NF1. The risk for myeloid malignancies may not be as high as suggested in the literature.     

Cancer of the operated stomach as a problem of oncology today

The study was based on the data obtained from a long-term follow-up of 2840 cases of various surgical pathology of the stomach, gastroscopic examination of 1112 surgically-treated patients, experiments on stomach carcinogenesis, clinical and experimental studies on lymph drainage pathways and analysis of the results of 296 radical operations for cancer of the gastric stump. The following aspects of research in cancer of operated stomach were suggested: (1) risk of cancer development in operated stomach; (2) factors contributing to tumorigenesis; (3) biologic peculiarities of growth of gastric stump tumors as well as lymph drainage pathways, and (4) organization of follow-up and development of methods for diagnosis and treatment of the said pathology. The results of the study outlined vistas in prevention of cancer of the gastric stump. Adequate methods of diagnosis and treatment of this grave pathology were developed which was followed by a decrease in postoperative lethality and in increase in 5-year survival rate--to 8.5 and 26.4%, respectively.     

Psychological adjustment of 'surgery-only' pediatric neuro-oncology patients: a retrospective analysis

A recent increase in diagnoses of pediatric neuro-oncology tumors combined with recent advancements in medical treatment of such tumors has resulted in a growing cohort of pediatric brain tumor survivors. These survivors are at risk for short and long-term psychological adjustment problems. Most studies regarding these survivors have focused on children who have received combinations of surgery, radiation, and chemotherapy as medical treatment. The sub-group of pediatric neuro-oncology patients who receive surgery as the only form of medical treatment has not been closely followed for adjustment problems. In this study, data were retrospectively collected from semi-structured clinical interviews with 34 'surgery-only' pediatric neuro-oncology patients who were 2 weeks to 5 years off medical treatment for their tumor. These data suggest that these survivors may be experiencing significant short and long-term mood, behavioral, and academic adjustment problems in comparison to national averages for children regarding these issues. Additional research examining the psychological adjustment process for surgery-only pediatric neuro-oncology patients is needed to validate these preliminary findings and facilitate the development of targeted interventions to address the identified adjustment problems.     

Second malignancies

The secondary development of malignant tumors after the treatment of Hodgkin's disease has been termed the price of success, but is relevant also to other types of cancer and gives an opportunity to study mechanisms of carcinogenesis and tumor induction. The authors review here their experience with second malignant neoplasms (SMN) as well as the result of an extensive search of the recent literature. The primary malignancies discussed in this article include Hodgkin's disease, pediatric cancer, breast cancer, lung cancer and other types of tumors. The international literature was searched (Medline 1989-1995) for reports of SMN with special emphasis on risk factors and the molecular mechanisms of tumor induction. In Hodgkin's disease, a 3 to 5-fold elevated risk for SMN was recognized, with a 15-year cumulative incidence in the range of 11-18%. All types of malignancies have a statistically increased risk (leukemias, non-Hodgkin's lymphomas, solid tumors). The risk for leukemia is related to the intensity of treatment with alkylating agents. Some solid tumors like lung cancer or breast cancer are related to radiation therapy. Present-day treatments may carry a lower risk of inducing secondary malignancies than treatments in the past. For non-Hodgkin's lymphoma as primary malignancy, fewer data exist on SMN. In pediatric cancer, no general risk estimate can be given and the genetic influence is greater as a cause of SMN. The improved prognosis for acute lymphoblastic leukemia has led to a changing pattern of pediatric SMN. In head and neck- and in lung cancer, the same etiologic factors which cause the primary tumor may also cause SMN. SMN occur as part of familial cancer syndromes. Two types of treatment related leukemias (mostly AMLs) exist and can be recognized by cytogenetic and molecular analysis. A complete follow-up is necessary to fully appreciate the risk of second malignancy. The goal to prevent SMN must be reached without decreasing the cure rates of the primary tumor. New treatment approaches need to be carefully monitored for SMN. Improved tests of mutagenesis and molecular screening may help to recognize patients prone to develop SMN and permit to estimate certain types of risk. Screening and prevention strategies are useful in high-risk situations.     

Preclinical testing of a peptide-based, HER2/neu vaccine for prostate cancer

The HER2/neu protein is over-expressed in multiple epithelial tumors and the source of immunogenic peptides currently under investigation in vaccine trials in ovarian and breast cancers. We sought to define the correlation between HER2/neu expression and risk for prostate cancer recurrence and then determine the potential efficacy of anti-HER2/neu vaccination in prostate cancer patients at risk for recurrence. The risk for prostate-specific antigen (PSA) recurrence in 95 patients undergoing prostatectomy at the Walter Reed Army Medical Center (WRAMC) was calculated and correlated to HER2/neu expression, as determined by immunohistochemical staining. Peripheral blood lymphocytes (PBL) were then isolated from six consecutive human leukocyte antigen (HLA) A2+ patients with HER2/neu+ prostate tumors. These PBL were grown in parallel cultures and stimulated either with no peptide, HER2/neu E75 peptide, or control peptide. The cultures were compared for stimulated proliferation, induced peptide-specific cytotoxicity and tumor-specific cytotoxicity. When assessed by risk group, 69% of the high risk patients' tumors over-expressed HER2/neu compared to 47% of the intermediate risk group (p<0.05). Evaluation of the in vitro immune response of PBL isolated from six consecutive prostate cancer patients revealed a statistically significant increase in E75-stimulated lymphocytic proliferation. E75-stimulated lymphocytes demonstrated an E75-specific cytolytic response in 6/6 prostate cancer patients that increased with successive stimulations. Moreover, these E75-specific lymphocytes also demonstrated tumor-specific lysis against HER2/neu-expressing prostate cancer cell lines. The majority of prostate cancer patients at high risk for recurrence have HER2/neu expressing tumors. Hence, HER2/neu is a viable target for immunotherapeutics such as preventative immunization strategies with HER2/neu peptide vaccines.     

A "wrapping-up" gastrointestinal anastomosis

Formation of "wrapping" gastrointestinal anastomosis is suggested to reduce lethality after subtotal resection of the stomach for cancer in patients at high risk for pyo-septic complications. The procedure allows to completely avoid anastomotic leakage and thus decreases lethality by half.     

Can mouse models for brain tumors inform treatment in pediatric patients?

Brain tumors represent the most common solid tumor of childhood. Although the histology of many pediatric brain tumors is similar to that of their adult counterparts, significant differences exist with regard to tumor location and response to therapy. The biological and genetic basis for this difference is poorly understood, as tumor tissue is generally unavailable for such studies. While targeted therapies directed against specific molecules active in cancer represents a new arsenal of agents for treating these tumors, such agents are generally not being developed for pediatric cancer in particular. Therefore, new agents for treatment of pediatric glioma must be obtained from compounds being tested against tumors of comparable histology in adult patients. Compounding this problem, although brain tumors are among the most lethal tumors of childhood, their absolute number is relatively small. As a consequence, trials with new agents must be prioritized based on the likelihood that a particular agent or combination of agents will have efficacy in pediatric cancer. Mouse models for brain tumors may help to identify targeted agents, and combinations of agents, effective against these tumors. Such data can be used to prioritize therapies for clinical trials in children with these tumors.     

Ovarian Cancer-Self Assessment: An Innovation for Early Detection and Risk Assessment of Ovarian Cancer

Objective: The modality to detect ovarian cancer at an early stage is very limited. Early diagnosis determines the prognosis. This study aimed to develop a risk assessment tool for early detection of ovarian cancer using artificial intelligence. To accomplish this, the presence of ten signs and symptoms reported by patients with ovarian cancer was assessed. Methods: This study was carried out as a cohort study of patients diagnosed with suspected ovarian tumors undergoing cytoreduction operation at Hasan Sadikin Hospital, Bandung, from December 2019 to September 2020. Compared to ovarian cancer self-assessment through questionnaire, postoperative histopathology in patients with suspected ovarian tumors. The questionnaire proceeded by artificial intelligence is grouped into risk and no risk. Statistical analyses were done using Chi-Square and Exact Fisher Test. Result: In total, 115 patients included in this study. The differences were statistically significant in terms of the six variables (abdominal bloating, nausea/vomiting, decreased of appetite, fullness, menstrual disturbance, and weight loss) ovarian cancer self-assessment compared to postoperative histopathology with a tendency towards benign ovarian tumors (p<0.05), while there was no statistically significant difference in the four variables (abdominal enlargement, abdominal pain, urinating disturbance, and defecation disturbance)  (p>0.05).  According to the artificial intelligence grouping, fifty-five patients were at risk, and sixty patients were not at risk. The Fifty-five risk patients were related  with postoperative histopathology diagnosis (with RR 0.682 and CI 95% 0.519-0.895). Conclusion: Risk assessments based on ovarian cancer self-assessment unfortunately were not comparable to postoperative histopathology as a single predictor. Ten variables in ovarian cancer artificial intelligence self-assessment for early detection needs improvement in adding another variable like tumor marker and ultrasonography assessment.     

Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell

Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of the cell responsible for propagating neuroblastomas is essential to understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells from 16 tumors and bone marrow metastases from patients in all neuroblastoma risk groups. Dissociated cells from tumors or bone marrow grew as spheres in conditions used to culture neural crest stem cells, were capable of self-renewal, and exhibited chromosomal aberrations typical of neuroblastoma. Primary spheres from all tumor risk groups differentiated under neurogenic conditions to form neurons. Tumor spheres from low-risk tumors frequently formed large neuronal networks, whereas those from high-risk tumors rarely did. As few as 10 passaged tumor sphere cells from aggressive neuroblastoma injected orthotopically into severe combined immunodeficient/Beige mice formed large neuroblastoma tumors that metastasized to liver, spleen, contralateral adrenal and kidney, and lung. Furthermore, highly tumorigenic tumor spheres were isolated from the bone marrow of patients in clinical remission, suggesting that this population of cells may predict clinical behavior and serve as a biomarker for minimal residual disease in high-risk patients. Our data indicate that high-risk neuroblastoma contains a cell with cancer stem cell properties that is enriched in tumor-initiating capacity. These cells may serve as a model system to identify the molecular determinants of neuroblastoma and to develop new therapeutic strategies for this tumor.     

Results of therapy in different groups of risk for superficial bladder cancer

Approximately 10.0% of tumors occurs in the lower urinary tract and morbidity and lethality are constantly on the rise. Over 90% of such tumors registered in Europe and the USA is transitional cell carcinoma. Primary bladder cancer morbidity in Russian males rose by 4.0-4.6% in 1990-1997 while the share of patients with superficial bladder cancer (SBC) went up by 1.5% for the same period. According to the National Bladder Cancer Group, the rising incidence of relapsing SBC is associated with urothelial dysplasia, positive test for urinary sediment after therapy and occurrence of four or more tumors larger than 5 cm. Prevention of muscular invasion is vital in management of SBC. Sometimes, such aggressive modalities as early cystectomy or radiotherapy are recommended in cases of high risk for this pathology. Conversely, certain palliative measures, short of transurethral resection of the bladder and adjuvant intravesical therapy, are regarded as sufficient.     

The Janeway lecture. Hodgkin's disease--finding the balance between cure and late effects

PURPOSE: The purpose of this review is to summarize the Stanford experience in Hodgkin's disease, the late effects of treatment, and strategies to improve management to maximize cure and decrease late effects in these patients. PATIENTS AND METHODS: Between 1960 and 1999, 2617 consecutive patients with Hodgkin's disease have been seen, treated, and rigorously followed at Stanford. This population includes patients of all ages and stages of disease. The database summarizing this experience serves as the source of survival and mortality data over 4 decades. Two thousand two hundred thirty-two of the population comprise the group evaluated for secondary cardiac disease. Two thousand one hundred sixty-two patients have been evaluated for risk of secondary leukemia, non-Hodgkin's lymphoma, and solid tumors. Eight hundred eighty-five women were evaluated for secondary breast cancer, prompting a subsequent analysis of risk of secondary cancer among 694 pediatric patients. RESULTS: The probability of cure of Hodgkin's disease has dramatically improved over the past 40 years. Today, 94% of patients are expected to survive. Among those who do not survive, approximately half die of Hodgkin's disease, 20% of new cancers, and 14% of cardiovascular complications. Modifications in patient management and treatment have greatly reduced the serious late effects observed from prior therapy. With current combined-modality therapy using moderate doses of involved field of radiation and limited cycles of multiagent, risk adapted chemotherapy, serious cardiac complications and development of secondary cancers are expected to be greatly reduced. The Stanford 25-year pediatric Hodgkin's disease experience reveals that survival in favorable early-stage disease exceeds 95%. Newer protocols for children with advanced-stage disease continue to show these excellent survival rates and promise less late morbidity. Adult protocols using the risk-adapted Stanford V combined-modality program now parallel the pediatric experience, with greater than 90% survival in these patients. DISCUSSION: Thus today the likelihood of cure of Hodgkin's disease greatly exceeds the risk of late effects, a goal both Dr. Henry Janeway and Madame Marie Curie emphasized and taught from first-hand experience.     

Risk estimation of radiation-induced thyroid cancer from treatment of brain tumors in adults and children

The purpose of this study was to estimate the risk of thyroid cancer induction attributable to brain radiation therapy in adult and pediatric patients. An anthropomorphic phantom was used to simulate treatment of brain tumors with two lateral opposed fields. Thyroid dose was measured using thermoluminescent dosimeters. Phantom measurements were performed for all possible field sizes that may be applied during brain radiotherapy in adults and children. The dependence of the thyroid dose on the distance from the irradiation field and on the presence of beam modifiers in the primary beam was investigated. All phantom exposures were generated with a 6 MV photon beam. Thyroid dose was found to vary from 9.6 to 89.4 cGy and from 8.0 to 194.0 cGy depending upon the field size used and the thyroid location in respect to the field edge for adults and children respectively. The excess relative risk of thyroid cancer induction for exposed children was estimated to be 0.6-14.9. The corresponding excess relative risk for adults was 0.1-1.1. The introduction of lead blocks or wedges into the primary beam may result in a considerable increase of the risk of thyroid cancer due to the increase of the thyroid dose. This study shows that brain radiotherapy during childhood may be associated with an increased risk of secondary thyroid cancer while the risk in adult patients is much smaller.     

晚期肿瘤患者营养风险及影响因素的研究

目的:探讨晚期肿瘤患者的营养风险及可能的影响因素。方法:收集2018年1月到2020年6月我院肿瘤内科收治的94例晚期肿瘤患者的临床资料，采用KPS评分评估患者的体力状况，采用营养风险筛查量表（NRS2002）筛查患者的营养风险，采用疼痛视觉模拟评分法(VAS)评估患者的疼痛程度，分析患者的营养风险情况及其可能的影响因素。结果:94例晚期肿瘤患者中有营养风险的患者(NRS2002评分≥3分的患者)共53例，占56.4%；年龄＞70岁患者共34例，有营养风险患者占70.6%，与年龄≤70岁患者具有显著统计学差异；KPS评分≤60分患者有37例，有73.0%患者存在营养风险，与KPS＞60分患者有显著统计学差异；不同BMI指数及疼痛程度的患者间有显著的统计学差异。消化系统肿瘤共有59例，有营养风险者占43例，总营养风险发生率达72.9%(43/59)。结论:晚期肿瘤患者营养风险的发生率较高，消化道肿瘤更显著，年龄、KPS评分、BMI指数、疼痛是其重要的影响因素。     

Circulating tumor DNA analysis enables molecular characterization of pediatric renal tumors at diagnosis

Circulating tumor DNA (ctDNA) is a powerful tool for the molecular characterization of cancer. The most frequent pediatric kidney tumors (KT) are Wilms’ tumors (WT), but other diagnoses may occur. According to the SIOP strategy, in most countries pediatric KT have a presumptive diagnosis of WT if they are clinically and radiologically compatible. The histologic confirmation is established after post-chemotherapy nephrectomy. Thus, there is a risk for a small fraction of patients to receive neoadjuvant chemotherapy that is not adapted to the disease. The aim of this work is to perform molecular diagnosis of pediatric KT by tumor genetic characterization based on the analysis of ctDNA. We analyzed ctDNA extracted from plasma samples of 18 pediatric patients with KT by whole-exome sequencing and compared the results to their matched tumor and germline DNA. Copy number alterations (CNAs) and single nucleotide variations (SNVs) were analyzed. We were able to detect tumor cell specific genetic alterations—CNAs, SNVs or both—in ctDNA in all patients except in one (for whom the plasma sample was obtained long after nephrectomy). These results open the door to new applications for the study of ctDNA with regards to the molecular diagnosis of KT, with a possibility of its usefulness for adapting the treatment early after diagnosis, but also for disease monitoring and follow up.     

A risk stratification by hormonal receptors (ER, PgR) and HER-2 status in small (≤1 cm) invasive breast cancer: who might be possible candidates for adjuvant treatment?

As the use of screening mammography expands, the proportion of invasive breast cancer ≤1 cm is increasing. The aims of this study were: (1) to identify risk factors for systemic metastases in patients with ≤1 cm invasive breast cancer and (2) to investigate the patient groups at the greatest risk for metastases with such small tumors. Data were collected retrospectively from the breast cancer registry of our institution for patients with invasive breast cancer from October 1994 to December 2004. Of 4,036 patients who received curative breast cancer surgery, we identified 427 patients who had T1a or T1b breast cancer excluding 39 patients who received neoadjuvant chemotherapy. Ipsilateral axillary lymph node involvement was found in 13% (57/427) of patients at the time of surgery. A multivariate analysis was conducted in 370 (T1aN0, T1bN0) patients without lymph node involvement. In a Cox-regression model, HER-2 positive and triple negative (TN) groups were identified as independent risk factors to predict distant relapse-free survival (DRFS) [Hazard ratio (HR) 8.8, P = 0.003 for HER-2 positive group; HR 5.1, P = 0.026 for TN group] in T1bN0 tumors. Statistical significance was not maintained when the analysis was limited to T1aN0 tumors. Even though T1aN0 and T1bN0 tumors have a relatively low risk of systemic failure, anti-HER-2-directed therapy for HER-2 group and new innovative adjuvant systemic treatment for TNBC patients with T1bN0 tumors should be considered. Prospective adjuvant trials are warranted in these subgroups of patients.     

Whole body magnetic resonance imaging (WB-MRI) and brain MRI baseline surveillance in <Emphasis Type="Italic">TP53</Emphasis> germline mutation carriers: experience from the Li-Fraumeni Syndrome Education and Early Detection (LEAD) clinic

Individuals with Li-Fraumeni syndrome (LFS) have a significantly increased lifetime cancer risk affecting multiple organ sites. Therefore, novel comprehensive screening approaches are necessary to improve cancer detection and survival in this population. The objective of this study was to determine the diagnostic performance of whole body MRI (WB-MRI) and dedicated brain MRI screening as part of a comprehensive screening clinic called Li-Fraumeni Education and Early Detection (LEAD) at MD Anderson Cancer Center. Adult (≥21 year old) and pediatric (<21 year old) patients were referred to the LEAD clinic by healthcare providers or self-referred and screened at 6 month intervals. During the study period, 63 LFS individuals were seen in the LEAD clinic including 49 adults (11 male, 38 female) and 14 children (7 male, 7 female). Fifty-three of 63 potentially eligible individuals underwent baseline WB-MRI (41 adults and 12 children) with primary tumors detected in six patients, tumor recurrence in one patient and cancer metastases in one patient. Thirty-five of 63 patients (24 adults and 11 children) underwent baseline brain MRI with primary brain tumors detected in three individuals, also noted on subsequent WB-MRI scans. Three additional tumors were diagnosed that in retrospect review were missed on the initial scan (false negatives) and one tumor noted, but not followed up clinically, was prospectively found to be malignant. The high incidence of asymptomatic tumors identified in this initial screening (13%), supports the inclusion of WB-MRI and brain MRI in the clinical management of individuals with LFS.