Peds Flashcards
In addition to the primary tumor and operative bed, what else should be included in the recommended treatment volume for high-risk neuroblastoma?
A. Prophylactic regional lymph node RT, and MIBG-avid metastases identified at diagnosis
B. Prophylactic regional lymph node RT, and persistent MIBG-avid metastases following induction chemotherapy
C. Persistent MIBG-avid metastases following consolidation chemotherapy
D. Persistent MIBG-avid metastases following induction chemotherapy
D. Persistent MIBG-avid metastases following induction chemotherapy
The post-induction chemotherapy, pre-surgical volume is the most appropriate starting point for defining the Gross Tumor Volume (GTV) in preparation for external beam radiotherapy following transplant. Elective coverage beyond the recommended Clinical Target Volume (CTV) expansion on the targeted disease extent is not recommended as it has not been shown to improve outcomes (PMID: 30968542). The number and extent of metastases identified in most cases of stage 4 high-risk neuroblastoma precludes radiotherapy to all sites of metastatic disease at diagnosis, and this has not been shown to improve outcomes. Historic studies used total-body irradiation as a component of conditioning prior to autologous stem cell transplant, but this approach was abandoned. Modern trial results demonstrate comparable event-free survival with alternative conditioning regimens [Carbo, Etoposide, Melphalan (CEM) or Busulfan, Melphalan (BuMel)] relative to historic studies and a more favorable late-effects profile (PMID: 16427213). Although TBI has no role in high-risk neuroblastoma anymore, analyses of patients treated with and without TBI have shown a reduced likelihood of relapse in metastatic sites identified at diagnosis (PMID: 28068235). Therefore, investigators have begun pursuing radionuclide/unsealed source-based approaches with therapeutic metaiodobenzylguanidine (I-131 as opposed to I-121 MIBG). This approach was first explored in relapse studies (PMID: 22700000, PMID: 21495159, PMID: 17369569) and is now being investigated in the front-line setting during induction chemotherapy as a part of ANBL1531 (NCT03126916).
In which clinical scenario can RT be omitted for the primary site in a patient with non-metastatic rhabdomyosarcoma following a margin negative resection?
A. Alveolar rhabdomyosarcoma without a FOXO1-translocation following GTR at diagnosis
B. Embryonal rhabdomyosarcoma with GTR following chemotherapy
C. Alveolar rhabdomyosarcoma with a FOXO1-translocation following GTR at diagnosis
D. Embryonal rhabdomyosarcoma following GTR at diagnosis
D. Embryonal rhabdomyosarcoma following GTR at diagnosis
Analysis of patients with group 1 alveolar RMS from prior Children’s Oncology Group protocols has demonstrated that routine use of adjuvant radiotherapy is required (PMID: 32124549). Therefore, adjuvant radiotherapy following resection (group 1, 2, or 3) for alveolar rhabdomyosarcoma (RMS) is always required independent of translocation (FOXO1) status. Alveolar RMS may be FOXO1-negative (approximately 20% of the time) and has clinical behavior and molecular characteristics comparable to those of embryonal RMS (PMID: 20351326). As a result, ARST1431 is evaluating whether the omission of radiotherapy in patients with group 1 translocation-negative alveolar RMS is possible when the resection is performed at diagnosis. Omitting radiotherapy following initial chemotherapy has been evaluated in both low- (select patients/sites in ARST0331) and intermediate-(D9803) risk RMS and has been found to result in inferior local control (PMID: 21298768, PMID: 25418440). Although omitting radiotherapy is not permitted following delayed primary excision, dose-de-escalation is acceptable if a gross-total or margin-negative resection is completed. ARST1431 is evaluating whether radiotherapy dose de-escalation following chemotherapy is possible when a complete radiographic response is obtained, and surgery is omitted (NCT02567435). Although response-based dose reduction has been utilized in low-risk orbital group 3 primaries, it has resulted in inferior local control, so use of <50.4 Gy should be discouraged (PMID: 28548706), especially in the context of reduced-dose cyclophosphamide. Concerns regarding cyclophosphamide dosing and its contribution to inferior local control were also been observed in ARST0531 (PMID: 31174239, PMID: 31174230).
What is the appropriate treatment for a pediatric patient whose disease relapsed at a limited number of sites less than 12 months following treatment for classic Hodgkin lymphoma?
A. 2nd-line chemotherapy -> PET/CT (Deauville 4-5) -> Observation
B. 2nd-line chemotherapy -> PET/CT (Deauville 1-4)-> ASCT +/- RT
C. 2nd-line chemotherapy -> Chemo-refractory -> RT->PET/CT (Deauville 1-4) ->ASCT +/- RT
D. 2nd-line chemotherapy -> PET/CT (Deauville 1-4)->ASCT -> +/- RT -> + Brentuximab
D. 2nd-line chemotherapy -> PET/CT (Deauville 1-4)->ASCT -> +/- RT -> + Brentuximab
Initial response to 2nd-line chemotherapy should drive subsequent treatment options in relapsed/refractory Hodgkin lymphoma (PMID: 20564743). Patients with Deauville 4-5 disease following 2nd-line chemotherapy response evaluation with PET/CT have progressive disease(PMID: 25113771) and should not be observed following 2nd-line chemotherapy, especially in the setting of a short-interval relapse (<12 months)(PMID: 20564743). Instead these patients should proceed to an alternative systemic therapy with consolidation of progressive sites with radiotherapy (PMID: 31005229, PMID: 22398312, PMID: 15632410) if the number of sites is practical. Patients who experience a short-interval relapse (<12 mo) whose disease has a favorable response to 2nd-line chemotherapy on PET/CT should proceed to autologous stem cell transplant (ASCT) followed by consolidative radiotherapy (PMID: 32273588, PMID: 31005229) and brentuximab. The ATHERA trial demonstrated that patients with unfavorable risk factors prior to ASCT experienced a substantial improvement in median progression free survival with the addition of brentuximab maintenance (42.9 vs. 24.1 months (p=0.0013)(PMID: 25796459). Patients whose disease is treatment refractory following initiation of 2nd-line chemotherapy and is, thus, progressive should be strongly considered for consolidative radiotherapy to progressive sites of disease, assuming the disease extent is amenable. The response rate to radiotherapy in the relapse setting is high and should be strongly considered in the setting of chemo-refractory disease. Options B and C are wrong because they omit brentuximab following transplant, despite high-risk features (<12 month relapse and, in the case of option C, chemo-refractory disease). Patients who experience multiple relapses should be considered for immune checkpoint blockade (PMID: 25482239). AHOD1721 recommends the incorporation of consolidative involved-site radiotherapy to doses of 30-36 Gy into salvage programs composed of nivolumab, brentuximab, and bendamustine with or without transplant pending risk and response status (NCT02927769).
Young children with anaplastic rhabdomyosarcoma have a high rate of germline alterations in ________ and should be considered for _______.
A. MYOD1; omission of RT because they have a more favorable prognosis
B. MYCN; dose-escalated RT because they have a higher rate of local failure
C. TP53; screening for cancer predisposition syndromes
D. FOXO1; dose-escalated RT because they have a higher rate of local failure
C. TP53; screening for cancer predisposition syndromes
MYOD1 mutations are typically somatic alterations, are associated with spindle cell or sclerosing rhabdomyosarcoma, and have an aggressive clinical behavior (unfavorable prognosis)(PMID: 27562493, PMID: 30181563). MYCN is amplified in ~25% of alveolar rhabdomyosarcoma tumors (not germline) and has not been directly connected to young children who have anaplastic RMS (PMID: 22065083). PAX3- and PAX7- FOXO1 fusions are found in 80% of alveolar rhabdomyosarcoma tumors (not germline) and are associated with a more aggressive clinical course (PMID: 12039929). Translocation status of FOXO1 has not been shown to be related to anaplastic histology. Germline TP53 alterations are frequent (73%) in young children with anaplastic rhabdomyosarcoma, and nearly all patients screen positive using Chompret criteria (PMID: 16921036). Patients with focal or diffuse anaplasia have inferior failure-free (63% vs. 77% at 5 years) and overall (68% vs. 82% at 5 years) survival (PMID: 18985676). Young patients with anaplastic RMS should be screened using the Chompret criteria (PMID: 26014290) and referred to clinical genetics for appropriate testing. Those found to have Li Fraumeni syndrome should be surveilled for subsequent cancers (PMID: 28572266).
An 8-year-old child has classic medulloblastoma status post GTR with no radiographic evidence of metastatic disease and no tumor cells in the CSF. What is the recommended RT dose and volume?
A. 59.4 Gy to the resection cavity + margin
B. 54 Gy to the resection cavity + margin
C. 23.4 Gy CSI, then 30.6 Gy boost to the resection cavity + margin
D. 36 Gy CSI, then 18 Gy boost to the posterior fossa
C. 23.4 Gy CSI, then 30.6 Gy boost to the resection cavity + margin
As established by Packer et al., the current standard treatment for average (standard) risk medulloblastoma is 23.4 Gy CSI with a focal boost to a total of 54-55.8 Gy. Patients receive concurrent vincristine and adjuvant PCV chemotherapy. COG ACNS0331 demonstrated that the boost may target the involved field (resection cavity + margin), rather than the entire posterior fossa.
A 5 year-old child has medulloblastoma. The surgeon reports that a GTR has been performed. What study should be performed to confirm that all disease has been resected?
A. CT scan intraoperatively
B. CT scan within 1-3 days postoperatively
C. MRI scan within 1-3 days postoperatively
D. MRI scan within 1-3 weeks postoperatively
C. MRI scan within 1-3 days postoperatively
An MRI scan of the brain should be performed within 24-72 hours postoperatively to evaluate the degree of resection. If the MRI is performed later, blood products may complicate the interpretation of the images.
A 12-year-old child presents with headaches and an MRI reveals a pineal mass. AFP is markedly elevated in the serum and CSF. These findings are consistent with which diagnosis?
A. Intracranial pure germinoma
B. Intracranial non-germinomatous germ cell tumor
C. Ependymoma
D. Pineoblastoma
B. Intracranial non-germinomatous germ cell tumor
The most common locations for intracranial germ cell tumors are the pineal and suprasellar regions. An elevated AFP level in the serum and/or CSF is consistent with a non-germinomatous germ cell tumor.
What is the typical initial treatment of a 4 year-old child with a posterior fossa ependymoma?
A. Chemotherapy
B. Maximal safe resection
C. Craniospinal irradiation
D. Focal RT to the tumor
B. Maximal safe resection
The standard treatment of posterior fossa ependymoma involves maximal safe resection, followed by conformal radiation therapy.
A 16 year-old has localized Ewing sarcoma of the sacrum and is receiving standard chemotherapy and definitive RT for local control. What dose should be given to the gross disease?
A. 40 Gy
B. 50.4 Gy
C. 55.8 Gy
D. 72 Gy
C. 55.8 Gy
The standard definitive radiation therapy dose for non-vertebral Ewing sarcoma is 55.8 Gy (45 Gy to the initial volume, followed by a 10.8 Gy boost to the pre-chemotherapy bone/post-chemotherapy soft tissue volume).
Which late effect is expected after a single dose 6 Gy of radiation?
A. Sterility after radiation to the testes
B. Necrosis after radiation to the brain
C. Pericarditis after radiation to the heart
D. Myelopathy after radiation to the spinal cord
A. Sterility after radiation to the testes
The TD5 and TD50 for sterility are 1 Gy and 2 Gy to the testes, respectively. The other listed complications may be seen after higher doses.
Which factor is typically considered a CONTRAINDICATION to CSI for medulloblastoma?
A. Anaplastic histology
B. Complete surgical resection
C. Diagnosis as an infant
D. Lack of malignant cells in the CSF
C. Diagnosis as an infant
Craniospinal irradiation is typically avoided in infants because it causes significant neurotoxicity. To delay or eliminate the need for craniospinal irradiation, these patients are typically treated with intensive chemotherapy.
Which diagnosis has the poorest survival outcomes in children?
A. Diffuse intrinsic pontine glioma
B. Intracranial germinoma
C. Juvenile pilocytic astrocytoma
D. Medulloblastoma
A. Diffuse intrinsic pontine glioma
Patients with diffuse intrinsic pontine glioma have a poor prognosis. Median survival is typically 8-12 months. The other listed diagnoses are associated with significantly more favorable outcomes.
A child with high risk neuroblastoma undergoes conventional therapy and at the time of RT has a 2 cc of residual disease at the primary site. In addition to receiving 21.6 Gy in 12 Fx to the extent of disease at the time of surgery, what boost dose should be prescribed to the residual disease?
A. 0 Gy
B. 10.8 Gy in 6 Fx
C. 14.4 Gy in 8 Fx
D. 21.6 Gy in 12 Fx
A. 0 Gy
Children’s Oncology Group study ANBL found that boosting residual disease (with 14.4 Gy) did not improve local control compared to prior studies without boosts beyond 21.6 Gy
A 2-year-old with poorly differentiated high-risk neuroblastoma is treated according to Children’s Oncology Group trial ANBL0532. What is the patient’s approximate 3-year DFS if she received tandem autologous stem cell transplants as part of her course?
A. 25%
B. 45%
C. 65%
D. 85%
C. 65%
The Children’s Oncology Group Study ANBL0532 showed patients had a 3 year DFS of 62% with tandem transplant compared to 48% with single transplant, establishing tandem transplant as the new standard of care for most patients with high risk neuroblastoma.
Which imaging study is a necessary component of the workup for a pediatric patient with high risk neuroblastoma?
A. Bone scan
B. SPECT MRI
C. Gallium scan
D. MIBG scan
D. MIBG scan
MIBG scans help identify metastases of neuroblastoma. In addition, I-Metaiodobenzylguanidine (MIBG) can be used for therapeutic purposes in neuroblastoma.
