Principles of Adjuvant Therapy in Childhood Cancer Flashcards
Which of the following is the most common malignancy found in childhood?
A. Lymphoma B. Leukemia C. Neuroblastoma D. Nephroblastoma E. Rhabdomyosarcoma
ANSWER: B
COMMENTS: Malignancy is second only to trauma as the leading cause of childhood death. In infants, it is the third most frequent cause of death after prematurity and congenital anomalies.
Approximately 40% of childhood malignancies are leukemia.
The most common solid tumor in children younger than 2 years is neuroblastoma, which accounts for 6%–10% of all childhood cancers.
In children older than 2 years, the most common solid tumor is Wilms tumor.
Which of the following is associated with a good prognosis in neuroblastoma?
A. MYC-N amplification B. Age > 13 years C. Age < 1 year D. Stromal poor tumor cells on histology E. High mitotis–karyorrhexis index (MKI)
ANSWER: C
COMMENTS: Neuroblastoma is the most common solid extracranial tumor in the pediatric population.
The tumor arises from neural crest cells and is most commonly found in the adrenal medulla. However, it may also be found anywhere along the sympathetic chain.
The presentation is generally insidious. Commonly, a large abdominal mass is found. Masses within the thoracic cavity can present with Horner syndrome (miosis, ptosis, anhidrosis, and occasionally enophthalmos).
Workup should include evaluating urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA).
CT scans most frequently demonstrate a mass with calcifications.
Metaiodobenzylguanidine (MIBG) scanning may be used to help identify the metastatic disease.
The tumor should be biopsied. Unfavorable findings associated with a poor prognosis include stroma-poor tumors, MYC-N amplification, and high MKI.
Patients diagnosed at less than 1 year of age have significantly improved outcomes compared with older children.
Survival is largely based on age at diagnosis, histologic subtype, MYC-N status, and extent of the disease.
Management is often multimodal and includes surgical excision, systemic chemotherapy, and occasional immunotherapy.
Stage 4S is a unique group of patients <18 months of age with a small primary tumor and metastatic disease limited to the liver, skin, or bone marrow, but not the lymph nodes.
Many of these patients experience spontaneous regression of their disease.
Some require aggressive therapy, but the overall survival rates are fairly high.
Regarding pediatric oncology, all of the following are true, except:
A. Lymphoma is the commonest malignancy.
B. Viral oncogene is pathogen.
C. Carcinogenesis occurs either through activation of growth-promoting oncogene or the loss of growth regulating tumour suppressor gene.
D. Diploid chromosomes show good prognosis, while hyperlipoid chromosomes show bad prognosis.
E. Cancer can result from genetic effects that alter a single cell.
A
Cancers in children, from common to rare, are leukemia, brain tumor, lymphoma, neuroblastoma, sarcoma, Wilms tumor, osteosarcoma, and liver tumors.
Syed/MCQ
All of the following are principles of radiation therapy, except:
A. Radiosensitivity of the tumour cells should be more than the surrounding normal cells.
B. The higher the energy, the deeper the ionizing radiation penetration.
C. The lesser the mitotic activity, the more the sensitivity to radiation.
D. Oxygenated tissues are much more sensitive to radiation than hypoxic tissues.
E. Minimise the exposure of normal tissues to radiation.
C
The higher the mitotic activity, the more sensitivity to radiation. Other principles include total cumulative dose depends primarily in the type of tumor being treated, not the age or weight of the child.
Maximize the irradiated normal tissues to repair by use of hyperfractioned radiation therapy.
Syed/MCQ
Regarding side effects of chemotherapeutic drugs, all of the following are correct except:
A. Cisplatin is nephrotoxic.
B. Methotrexate causes restrictive lung disease.
C. Anthramycin is cardiotoxic.
D. Dactinomycin causes GIT mucositis and diarrhoea.
E. Bone marrow is affected by most of chemotherapeutic drugs.
B.
Busulfan and bleomycin cause restrictive lung disease.
Syed/MCQ
A 40-year-old female with known colorectal cancer has been diagnosed with an APC gene mutation. Which of the following is the most appropriate recommendation for thyroid cancer screening in her son?
Choices:
1. Annual thyroid ultrasound, and thyroid function test beginning at age 12
2. Annual thyroid exam beginning at age 12
3. Annual thyroid ultrasound, and T3 resin uptake (T3 RU) beginning at age 25
4. Annual thyroid exam beginning at age 25
Answer: 4 - Annual thyroid exam beginning at age 25
Explanations:
• A mutation of the APC gene is associated with familial adenomatous polyposis (FAP). FAP is associated with a nearly 100% risk of developing colorectal cancer. It is also associated with an increased risk of other tumors/malignancies, including thyroid cancer, gastric and duodenal polyps, desmoid tumors, and hepatoblastoma.
•Patients with a family history of FAP should undergo sigmoidoscopy at age 12 to evaluate for polyposis. Surgical resection is performed when the polyp burden is no longer manageable with endoscopy resection.
• Other screening exams include an annual thyroid exam beginning at the age of 25 with consideration of annual thyroid ultrasound.
• Annual esophagogastoduodenoscopy should begin at twenty years of age to evaluate for gastric and duodenal polyps.
StatPearls
What are the phases of clinical trials for developing anticancer agents?
In the clinical development of promising anticancer agents, phase I clinical trials are designed as dose-escalation studies to determine the maximally tolerated dose of a new drug.
Phase II studies explore the efficacy of a drug to establish the spectrum of activity of the agent.
Phase III trials use a prospective randomized control design to compare established effective chemotherapy combinations to new treatment regimens.
H&A
What is the mainstay of medical treatment for childhood cancer?
Combination chemotherapy remains the mainstay of the medical treatment of childhood cancer.
In the 1960s the benefit of combining several drugs together was demonstrated first for ALL.
Complete remission by using single agents could be expected in only about half of the patients, whereas the combination of four or five drugs produced remission rates of more than 95%.
The principle of designing combination chemotherapy regimens by using non-cross-resistant agents with nonoverlapping toxicities has been successfully used for childhood solid tumor treatment for the past 25 years.
The improvement in survival rates over this period for neuroblastoma, Ewing sarcoma, anaplastic Wilms tumor, and osteosarcoma can be directly linked to effective combination chemotherapy treatment.
H&A
Which of the following is not a characteristic of phase I clinical trials in paediatric oncology?
A They are offered to patients for whom no known curative treatment is available.
B They assess whether a new agent is sufficiently efficacious to warrant further study.
C Small numbers of patients are required.
D They use a dose-escalating design.
E They are conducted in large individual institutions or small consortia of institutions.
B
Phase I trials are designed to evaluate the toxicity of new therapeutic agents. They typically use a dose-escalating trial design.
Each cohort is monitored for toxicity before the next cohort is given a higher dose.
The end point is either the determination of the safety of the agent or the maximum tolerated dose.
Phase II trials are designed to determine if a new therapy is sufficiently active in a specific disease to warrant its further study.
SPSE 1
Which of the following is not a cause of graft vs. host disease?
A umbilical cord blood transplantation
B T-cell-depleted allogeneic haematopoietic stem cell transplantation
C matched unrelated donor haematopoietic stem cell transplantation
D purged autologous haematopoietic stem cell transplantation
E sibling donor haematopoietic stem cell transplantation
D
The source of stem cells used in haematopoietic stem cell transplantation is denoted by the descriptions autologous (from the patient themselves) and allogeneic (from someone else).
Graft vs. host disease refers to the clinicopathologic process of enteritis, hepatitis and dermatitis. It is mediated by donor T-cells that recognise antigenic disparities between donor and recipient.
This is therefore not a problem of autologous haematopoietic stem cell transplants.
‘Purged’ refers to techniques to remove tumour cells that might be present in the stem cell collection from the patient, before reinfusion.
SPSE 1
Which of the following is true regarding acute graft vs. host disease?
A It is often the first sign of graft failure.
B It requires lifelong immunosuppression.
C It manifests as lichen planus.
D It manifests as cirrhosis.
E None of the above.
E
The appearance of acute graft vs. host disease symptoms often accompanies evidence of successful engraftment (recovering blood counts).
It is mediated by donor T-cells and therefore is not a feature of a failing donor haematopoietic stem cell graft.
Acute graft vs. host disease can usually be controlled by a course of immunosuppression which can then be gradually withdrawn completely.
Acute graft vs. host disease develops within the first 100 days after haematopoietic stem cell transplantation and is characterised by enteritis, hepatitis and dermatitis.
lichen planus, ocular sicca, dry mouth and cirrhosis are manifestations of chronic graft vs. host disease.
SPSE 1
Radiation forms part of multimodal therapy for all of the following except:
A large B-cell lymphoma
B Hodgkin’s lymphoma
C alveolar rhabdomyosarcoma
D neuroblastoma
E nephroblastoma.
A
large B-cell lymphoma makes up 10% of non-Hodgkin’s lymphoma in children.
Burkitt’s lymphoma makes up 50%, lymphoblastic lymphoma 30% and anaplastic large cell lymphoma 10%.
The treatment of non-Hodgkin’s lymphoma in children is multidrug chemotherapy.
large B-cell and Burkitt’s non-Hodgkin’s lymphoma are treated with intensive pulsed chemotherapy with the most important drugs being cyclophosphamide, high-dose methotrexate and cytarabine.
The role of targeted B- cell antibody therapy (anti-CD20, rituximab) has not yet been established in children.
SPSE 1
Which of the following drugs is not a vesicant?
A doxorubicin
B cytarabine
C dactinomycin
D vincristine
E daunorubicin
B
A vesicant is a chemical that, if it escapes from the vein, causes extensive tissue damage with vesicle formation or blistering.
The widespread use of central lines reduces the risk of this complication in paediatric oncology.
Chemotherapy agents are classified according to their risk of causing tissue damage if extravasated.
Vesicants are the highest risk group.
Cytarabine is in the lowest risk group (neutrals) and can be given subcutaneously as well as intravenously.
SPSE 1
Adjuvant therapy is based on risk stratification in:
A localised rhabdomyosarcoma
B precursor B-cell acute lymphoblastic leukaemia
C Burkitt’s lymphoma
D childhood medulloblastoma
E all of the above.
E
Risk stratification is widely used in paediatric oncology to ensure that patients at lower risk of recurrence receive less intensive treatment and those at higher risk of recurrence receive more intensive treatment.
Risk factors were identified and risk-based treatment stratification validated in large multicentre trials for several diseases.
Risk stratification varies between different treatment protocols but risk factors include:
● localised rhabdomyosarcoma – age, size of tumour, presence of spread to local lymph nodes, site of primary, post-surgical stage (Intergroup Rhabdomyosarcoma Study Group), pathology
● precursor B-cell acute lymphoblastic leukaemia – age, white blood cell count, cytogenetic features, rate of response to induction treatment
● Burkitt’s lymphoma – modified murphy staging system
● Childhood medulloblastoma – clinical, pathologic and molecular variables.
SPSE 1
Which of the following biochemical changes is not a manifestation of acute tumour lysis syndrome?
A hypercalcaemia
B hypophosphataemia
C hypokalaemia
D hypocalcaemia
E none of the above
D
Acute tumour lysis syndrome is the result of the rapid release of large quantities of intracellular metabolites (uric acid, potassium and phosphate) from dying cells.
This is mainly a feature of rapidly growing tumours that are also very sensitive to chemotherapy (Burkitt’s lymphoma, T-cell leukaemia/lymphoma and leukaemia patients with very high white cell counts).
It usually occurs during the first 5 days after commencement of chemotherapy but may start even before treatment begins (spontaneous tumour necrosis).
The serum biochemical features are high uric acid, high potassium, high phosphate and low calcium.
The low calcium is secondary to the hyperphosphataemia).
Acute renal failure may result.
Preventive measures and careful monitoring and management of electrolyte abnormalities are essential.
SPSE 1
