Novel treatment of endobronchial inflammatory myofibroblastic tumor in a child.

Isolated endobronchial inflammatory myofibroblastic tumors (IMT) are rare, accounting for about 1% of primary endobronchial tumors in children. The mainstay of treatment for this tumor has been surgical resection. Recently, the identification of anaplastic lymphoma kinase (ALK) gene mutations in half of IMTs and promising results of treatment with ALK inhibitors in other ALK-positive tumors have opened the possibility of alternative approaches. We present a 4-year-old child with an ALK-positive endobronchial IMT, treated with endoscopic resection and neoadjuvant therapy with crizotinib, without evidence of tumor recurrence 2 years after the initial resection.

Adolescent and young adult oncology-past, present, and future.

There are nearly 70,000 new cancer diagnoses made annually in adolescents and young adults (AYAs) in the United States. Historically, AYA patients with cancer, aged 15 to 39 years, have not shown the same improved survival as older or younger cohorts. This article reviews the contemporary cancer incidence and survival data through 2015 for the AYA patient population based on the National Cancer Institute's Surveillance, Epidemiology, and End Results registry program and the North American Association of Central Cancer Registries. Mortality data through 2016 from the Centers for Disease Control and Prevention's National Center for Health Statistics are also described. Encouragingly, absolute and relative increases in 5-year survival for AYA cancers have paralleled those of childhood cancers since the year 2000. There has been increasing attention to these vulnerable patients and improved partnerships and collaboration between adult and pediatric oncology; however, obstacles to the care of this population still occur at multiple levels. These vulnerabilities fall into 3 significant categories: research efforts and trial enrollment directed toward AYA malignancies, access to care and insurance coverage, and AYA-specific psychosocial support. It is critical for providers and health care delivery systems to recognize that the AYA population remains vulnerable to provider and societal complacency.

Platinum plus bortezomib for the treatment of pediatric renal medullary carcinoma: Two cases.

Renal medullary carcinoma (RMC) was first described over two decades ago as the seventh sickle nephropathy. Survival after diagnosis with metastatic disease still rarely extends beyond 1 year, with recent reports of median overall survival in patients treated with platinum therapy being just 10 months. We describe our experience using platinum-based chemotherapy plus the proteasome inhibitor bortezomib to treat metastatic RMC in two pediatric patients who had complete responses. One patient passed away 7 years after diagnosis, while another remains disease free nearly 2 years from diagnosis.

Preclinical high-dose acetaminophen with N-acetylcysteine rescue enhances the efficacy of cisplatin chemotherapy in atypical teratoid rhabdoid tumors.

BACKGROUND: Atypical teratoid rhabdoid tumors (AT-RT) are pediatric tumors of the central nervous system with limited treatment options and poor survival rate. We investigated whether enhancing chemotherapy toxicity by depleting intracellular glutathione (GSH; a key molecule in cisplatin resistance) with high dose acetaminophen (AAP), may improve therapeutic efficacy in AT-RT in vitro. PROCEDURE: BT16 (cisplatin-resistant) and BT12 (cisplatin-sensitive) AT-RT cell lines were treated with combinations of AAP, cisplatin, and the anti-oxidant N-acetylcysteine (NAC). Cell viability, GSH and peroxide concentrations, mitochondrial damage, and apoptosis were evaluated in vitro. RESULTS: AAP enhanced cisplatin cytotoxicity in cisplatin-resistant BT16 cells but not cisplatin-sensitive BT12 cells. Baseline GSH levels were elevated in BT16 cells compared to BT12 cells, and AAP decreased GSH to a greater magnitude in BT16 cells than BT12 cells. Unlike BT12 cells, BT16 cells did not have elevated peroxide levels upon treatment with cisplatin alone, but did have elevated levels when treated with AAP + cisplatin. Both cell lines had markedly increased mitochondrial injury when treated with AAP + cisplatin relative to either drug treatment alone. The enhanced toxic effects were partially reversed with concurrent administration of NAC. CONCLUSIONS: Our results suggest that AAP could be used as a chemo-enhancement agent to potentiate cisplatin chemotherapeutic efficacy particularly in cisplatin-resistant AT-RT tumors with high GSH levels in clinical settings.

The use of zoledronic acid in pediatric cancer patients.

BACKGROUND: The third generation bisphosphonate zoledronic acid has demonstrated efficacy in reducing skeletal-related events in adult patients with multiple cancer types that have skeletal disease. The use of zoledronic acid in pediatric oncology patients with bone metastases for the purpose of reducing pain, improving bone strength and altering the progression of metastatic disease has not been thoroughly evaluated. PROCEDURE: From October 2005 to December 2008, 19 patients at the Aflac Cancer Center received one or more doses of zoledronic acid as part of their therapy. A retrospective review of these patients was performed and information was collected including indication for treatment, toxicities, and outcomes. RESULTS: Most patients (n = 15) received zoledronic acid following relapse of their malignancy with metastatic disease present in one or more bony sites. Hypocalcemia and hypophosphatemia were frequent, but did not result in clinical symptoms. More significant toxicities associated with zoledronic acid, including clinically apparent renal insufficiency and osteonecrosis of the jaw, were not seen. Overall, zoledronic acid was well tolerated in this population. CONCLUSIONS: The benefits of zoledronic acid seen in randomized trials of adults with bone metastases have sparked interest in its use for children with metastatic cancer. The administration of zoledronic acid in pediatric oncology appears safe, and may result in improved bone strength and pain control. Further evaluation is warranted to prospectively evaluate its efficacy and long-term safety in pediatric patients with cancer and skeletal metastases.

Sentinel lymph node biopsy in the pediatric population.

BACKGROUND: Sentinel lymph node biopsy (SLNB) has only been recently used for childhood neoplasms. METHODS: We reviewed all patients younger than 19 years who underwent SLNB for 5 years. RESULTS: Twenty patients were identified (11 male, 9 female). Sentinel lymph node biopsy was performed for 10 sarcomas (5 synovial, 3 rhabdomyosarcoma, 1 epitheliod, 1 other); 9 skin neoplasms (4 melanomas, 3 Spitz nevi, 2 melanocytomas); and 1 acinic cell carcinoma. All patients underwent Technetium 99m sulfur microcolloid injection and 4-quadrant subdermal injection with Lymphazurin 1% (Autosuture, Norwalk, Conn). Six patients required either sedation for lymphoscintigraphy. Intraoperative gamma probe was used. Primary lesions were found in lower extremity (n = 8), upper extremity (n = 6), trunk (n = 3), and head and neck (n = 3). The lymphatic basins were inguinal (n = 8), axilla (n = 8), neck (n = 3), and both inguinal and axilla (n = 1). At least one lymph node was identified in each procedure. Of 20 patients, 5 (25%) had metastatic disease (4 skin neoplasms and 1 sarcoma). There were no complications in our series, and all patients are alive with no recurrence at an average follow-up of 2.2 years. CONCLUSIONS: Sentinel lymph node biopsy allows for an accurate biopsy in children. However, some younger patients may require sedation, and it may be more challenging to isolate the sentinel node.

Intensity-modulated radiotherapy with use of cone-down boost for pediatric head-and-neck rhabdomyosarcoma.

PURPOSE: To report our initial experience using intensity-modulated radiotherapy (IMRT) with a cone-down boost for pediatric head-and-neck rhabdomyosarcoma (RMS). METHODS AND MATERIALS: A review of institutional treatment records identified children treated with IMRT for head-and-neck RMS between January 2000 and February 2007. All patients had undergone chemotherapy according to cooperative group RMS protocols. The initial planning target volume (PTV) covered the prechemotherapy tumor extent with variable margins, generally 1-2 cm. The boost PTV covered the postchemotherapy tumor volume, usually with a margin of 0.5-1 cm. RESULTS: A total of 20 patients were treated with IMRT for head-and-neck RMS. Of these 20 patients, 4 had Group II, 15 Group III, and 1 Group IV disease. The site was parameningeal in 12, nonparameningeal in 6, and orbit primary in 2. Of the 20 patients, 14 were treated with a cone-down boost after a median dose of 36 Gy (range, 30-45.6). The mean initial PTV was 213.5 cm(3), and the mean boost PTV was 76.9 cm(3). Patients received a median total dose of 50.4 Gy. The median follow-up time was 29 months. The 3-year Kaplan-Meier local control rate was 100%, although 1 patient developed an in-field recurrence 50 months after IMRT. The 3-year event-free survival rate, overall survival rate, and risk of central nervous system failure was 74%, 76%, and 7%, respectively. CONCLUSIONS: Our preliminary follow-up of pediatric head-and-neck RMS patients treated with IMRT revealed excellent local control. The initial targeting of the prechemotherapy tumor volume with 1-2-cm margin to 30.6 or 36 Gy followed by a cone-down boost to the postchemotherapy tumor volume with a 0.5-1-cm margin allowed for significant sparing of normal tissues and provided good local control.

Melanoma in children and adolescents.

Melanoma is rarely described in the pediatric population. However, recent studies show that the incidence may be increasing. The diagnosis of melanoma presents unique challenges in this age group. There may be predisposing factors that affect children more than adults. A high index of suspicion is necessary in order to make a timely diagnosis. Prompt surgical treatment by individuals with expertise in care of patients with melanoma with potentially curative excision and appropriate lymph node evaluation is important to optimize survival. Careful review of all specimens by an experienced dermatopathologist is important. Through cooperation with adult trials and potential inclusion of pediatric patients in evaluations of new therapies, further progress against this disease can hopefully be addressed in all age groups.