Adjuvant Therapies — MCQs
Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-
What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
Which one of the following is not sensitive to chemotherapy in advanced stage?
Which of the following is an epiphyseal lesion?
Which of the following are features of Gorham's disease (Disappearing Bones)?
Onion peel appearance on radiograph is not seen in which of the following conditions?
Chemotherapy of Ewing's sarcoma includes all except?
Codman's triangle is seen in which of the following conditions?
A child 10 yrs of age presents with a mass on his left thigh. The mass seems to be arising from the diaphysis of the femur and involving the soft tissue of the thigh. The child is having fever also. Give your most probable diagnosis -
A 20-year old male patient presents with pain on movement. X-ray of knee joint shows lytic lesion on the upper end of tibia. What is the likely diagnosis?
Adjuvant Therapies Indian Medical PG Practice Questions and MCQs
Question 1: Many drugs are used as rescue therapy for preventing the adverse effects of anticancer drugs. Folinic acid is used in:-
- A. Cyclophosphamide toxicity
- B. Doxorubicin toxicity
- C. Methotrexate toxicity (Correct Answer)
- D. Cisplatin toxicity
Explanation: ***Methotrexate toxicity*** - **Folinic acid (leucovorin)** is a reduced folate that bypasses the metabolic block caused by **methotrexate** on dihydrofolate reductase. - It replenishes the body's **folate stores** and protects healthy cells from methotrexate's cytotoxic effects, particularly in the bone marrow and gastrointestinal tract. *Cyclophosphamide toxicity* - **Cyclophosphamide** toxicity, primarily hemorrhagic cystitis, is prevented by **mesna** (2-mercaptoethane sulfonate). - Mesna inactivates the urotoxic metabolite **acrolein** in the urine, preventing bladder damage. *Doxorubicin toxicity* - **Doxorubicin** causes cardiotoxicity, which can be mitigated by the iron-chelating agent **dexrazoxane**. - Dexrazoxane reduces the formation of **free radicals** that contribute to doxorubicin-induced myocardial damage. *Cisplatin toxicity* - **Cisplatin** toxicity, especially nephrotoxicity, is largely prevented by **aggressive hydration** and administration of **diuretics**. - **Amifostine** is another agent that can reduce cisplatin-induced nephrotoxicity, neurotoxicity, and ototoxicity by acting as a cytoprotectant.
Question 2: What is the treatment for HER-2 positive trastuzumab resistant breast cancer?
- A. Sorafenib
- B. Lapatinib (Correct Answer)
- C. Vemurafenib
- D. Erlotinib
Explanation: ***Lapatinib*** - Lapatinib is a **dual tyrosine kinase inhibitor** that targets both **HER-2** and **epidermal growth factor receptor (EGFR)**, acting as a **small molecule inhibitor** that binds to the intracellular domain of these receptors. - Unlike trastuzumab (a monoclonal antibody targeting the extracellular domain), Lapatinib's **intracellular mechanism of action** allows it to overcome common mechanisms of trastuzumab resistance, such as receptor truncation or masking of the extracellular epitope. - It is specifically approved for the treatment of **HER-2 positive metastatic breast cancer** in combination with capecitabine after progression on trastuzumab-containing regimens. *Sorafenib* - Sorafenib is a **multi-kinase inhibitor** primarily targeting RAF, VEGFR, and PDGFR, and is used in renal cell carcinoma and hepatocellular carcinoma. - It does not specifically target HER-2 and is **not indicated** for HER-2 positive trastuzumab-resistant breast cancer. *Vemurafenib* - Vemurafenib is a **BRAF inhibitor** used for treating BRAF V600E mutation-positive melanoma. - This drug has no direct indications or demonstrated efficacy for **HER-2 positive breast cancer** and does not address trastuzumab resistance mechanisms. *Erlotinib* - Erlotinib is an **EGFR tyrosine kinase inhibitor** primarily used for non-small cell lung cancer with activating EGFR mutations. - While it targets EGFR, it does **not effectively target HER-2** and lacks the dual inhibition necessary to overcome trastuzumab resistance in HER-2 positive breast cancer.
Question 3: Which one of the following is not sensitive to chemotherapy in advanced stage?
- A. Wilm's tumor
- B. Ovarian carcinoma
- C. Ewing's carcinoma
- D. Pancreatic carcinoma (Correct Answer)
Explanation: ***Pancreatic carcinoma*** - **Pancreatic carcinoma** is notoriously difficult to treat with chemotherapy, especially in advanced stages, due to its **aggressive biology**, inherent resistance mechanisms, and late presentation [1]. - The disease often presents with **metastatic spread** before diagnosis, and the response rates to even combination chemotherapy regimens are typically poor, highlighting its poor sensitivity [1]. *Wilm's tumor* - **Wilm's tumor (nephroblastoma)** is a pediatric kidney cancer that is highly sensitive to chemotherapy, even in advanced stages. - Combination chemotherapy regimens are a cornerstone of treatment, often leading to **excellent prognosis** and cure rates. *Ovarian carcinoma* - **Ovarian carcinoma**, particularly epithelial ovarian cancer, is often initially sensitive to **platinum-based chemotherapy**. - While it frequently recurs, the initial response to chemotherapy, even in advanced stages, can be significant, leading to periods of **remission**. *Ewing's sarcoma* - **Ewing's sarcoma** is a highly aggressive bone and soft tissue tumor that is very sensitive to chemotherapy, which is a critical component of its multidisciplinary treatment. - Modern multidisciplinary approaches, including intensive chemotherapy, have significantly improved survival rates for patients with both localized and **metastatic disease**.
Question 4: Which of the following is an epiphyseal lesion?
- A. Fibrosarcoma
- B. Chondroblastoma (Correct Answer)
- C. Chondrosarcoma
- D. Non-ossifying fibroma
Explanation: **Chondroblastoma** - **Chondroblastoma** is a rare, benign bone tumor that typically arises in the **epiphysis** of long bones before epiphyseal fusion. - It specifically originates from **chondroblasts** within the epiphyseal growth plate region. *Fibrosarcoma* - **Fibrosarcoma** is a malignant tumor of fibrous connective tissue origin, typically found in the **metaphysis** or **diaphysis** of long bones. - It rarely affects the **epiphyseal** region and is characterized by aggressive local invasion and metastases. *Chondrosarcoma* - **Chondrosarcoma** is a malignant tumor of cartilage, commonly arising in the **metaphysis** or **diaphysis** of long bones, particularly the femur, humerus, and pelvis. - While it involves cartilage, its typical location is not primarily **epiphyseal** and it is characterized by malignant cartilaginous matrix. *Non-ossifying fibroma* - A **non-ossifying fibroma** (NOF), also known as a fibrous cortical defect, is a common benign fibrous lesion typically found in the **metaphysis** of long bones. - These lesions are usually asymptomatic and self-limiting, often resolving spontaneously, and do not originate in the **epiphysis**.
Question 5: Which of the following are features of Gorham's disease (Disappearing Bones)?
- A. Progressive disappearance of bone associated with multiple hemangiomatosis or multiple lymphangiectasis
- B. Usually the progression involves contiguous bones, but occasionally multiple sites are affected
- C. Patients present with mild pain or with pathological fracture
- D. All of the above (Correct Answer)
Explanation: **Gorham’s Disease**, also known as **Vanishing Bone Disease** or Phantom Bone Disease, is a rare musculoskeletal condition characterized by the spontaneous, progressive destruction and resorption of bone tissue. ### **Explanation of Options** * **Option A:** The hallmark of Gorham’s disease is the proliferation of thin-walled vascular or lymphatic channels within the bone. This leads to **progressive osteolysis** (bone disappearance) associated with **hemangiomatosis** or **lymphangiectasis**. The bone is replaced by fibrous connective tissue. * **Option B:** The disease typically spreads across joints to involve **contiguous bones** (e.g., spreading from the humerus to the scapula or from one vertebra to the next). While localized, it can occasionally manifest in multiple non-contiguous anatomical sites. * **Option C:** The clinical presentation is often insidious. Patients may experience **dull aching pain**, localized swelling, or a **pathological fracture** following minor trauma. In severe cases involving the ribs or spine, it can lead to chylothorax. Since all statements accurately describe the pathophysiology, progression, and clinical presentation of the disease, **Option D (All of the above)** is the correct answer. ### **High-Yield Clinical Pearls for NEET-PG** * **Radiology:** Characterized by "tapering" of the ends of remaining bone (sucker-stick appearance) and eventual complete disappearance of the bone shadow. * **Key Feature:** Unlike most bone tumors, Gorham’s disease **crosses joint spaces** to involve adjacent bones. * **Biopsy:** Shows non-malignant proliferation of thin-walled vessels; there is a notable **absence of osteoclasts** (the resorption is mediated by the vascular tissue). * **Complication:** **Chylothorax** is a life-threatening complication if the disease involves the thoracic cage.
Question 6: Onion peel appearance on radiograph is not seen in which of the following conditions?
- A. Garre's osteomyelitis
- B. Ewing's sarcoma
- C. Osteogenic sarcoma
- D. Fibrous dysplasia (Correct Answer)
Explanation: **Explanation:** The "onion peel" appearance (lamellated periosteal reaction) is a radiographic sign caused by the rhythmic or episodic lifting of the periosteum, leading to the deposition of multiple concentric layers of new bone. **1. Why Fibrous Dysplasia is the Correct Answer:** Fibrous dysplasia is a benign fibro-osseous lesion where normal bone is replaced by fibrous tissue and immature trabeculae. It is an **intramedullary** process that does not typically involve the periosteum. Therefore, it does not produce a periosteal reaction. Its classic radiographic appearance is described as **"Ground-glass opacification"** with a well-defined "rind" of sclerotic bone. **2. Analysis of Incorrect Options:** * **Ewing’s Sarcoma:** This is the classic association for onion peel appearance. The aggressive nature of this tumor causes rapid, successive layers of periosteal bone formation. * **Garre’s Osteomyelitis:** Also known as Chronic Sclerosing Osteomyelitis with proliferative periostitis. It is a low-grade chronic infection (often in the mandible) that stimulates the periosteum to form reactive peripheral bone in a lamellated pattern. * **Osteogenic Sarcoma (Osteosarcoma):** While "Sunburst" and "Codman’s triangle" are more common, Osteosarcoma is a highly aggressive tumor that can occasionally present with a lamellated (onion peel) appearance depending on the rate of tumor growth. **Clinical Pearls for NEET-PG:** * **Onion Peel Appearance:** Seen in Ewing’s sarcoma, Garre’s osteomyelitis, Osteosarcoma, and sometimes Langerhans Cell Histiocytosis (LCH). * **Ground Glass Appearance:** Pathognomonic for Fibrous Dysplasia. * **Sunburst/Sunray Appearance:** Highly suggestive of Osteosarcoma. * **Codman’s Triangle:** Indicates an aggressive process (malignancy or subperiosteal abscess) lifting the periosteum rapidly.
Question 7: Chemotherapy of Ewing's sarcoma includes all except?
- A. Doxorubicin
- B. Dactinomycin
- C. Topotecan
- D. 5-Fluorouracil (Correct Answer)
Explanation: **Explanation:** Ewing’s Sarcoma is a highly malignant, small round blue cell tumor that is exquisitely sensitive to chemotherapy. The standard of care involves a multimodal approach (Chemotherapy + Surgery/Radiotherapy). **Why 5-Fluorouracil (5-FU) is the correct answer:** 5-Fluorouracil is an antimetabolite primarily used in the treatment of epithelial malignancies (GI tract, breast, and head/neck cancers). It has **no established role** in the management of Ewing’s Sarcoma. **Analysis of other options (The VAC-IE Regimen):** The current standard chemotherapy for Ewing's Sarcoma follows the **VAC-IE** protocol, which includes: * **Vincristine** * **Actinomycin D (Dactinomycin):** An antitumor antibiotic that inhibits RNA synthesis (Option B). * **Cyclophosphamide** * **Ifosfamide** * **Etoposide** * **Doxorubicin (Adriamycin):** An anthracycline that is a cornerstone in treating both Ewing’s and Osteosarcoma (Option A). * **Topotecan:** A Topoisomerase I inhibitor often used in second-line or salvage therapy for recurrent/refractory Ewing’s Sarcoma (Option C). **High-Yield Clinical Pearls for NEET-PG:** * **Genetics:** Characterized by the **t(11;22)** translocation, leading to the **EWS-FLI1** fusion gene. * **Radiology:** Classic **"Onion-peel"** periosteal reaction. * **Histology:** Small round blue cells that are **PAS positive** (due to cytoplasmic glycogen) and express **CD99 (MIC-2).** * **Site:** Most common in the diaphysis of long bones (Femur is most common). * **Prognosis:** The most important prognostic factor is the presence of metastasis at the time of diagnosis (Lungs and Bone marrow are common sites).
Question 8: Codman's triangle is seen in which of the following conditions?
- A. Chondroblastoma
- B. Osteosarcoma (Correct Answer)
- C. Chondrosarcoma
- D. Giant Cell Tumor
Explanation: ### Explanation **Codman’s Triangle** is a classic radiological sign representing an aggressive **periosteal reaction**. It occurs when a rapidly growing lesion (usually a tumor) lifts the periosteum away from the bone, leaving a triangular area of new subperiosteal bone at the margin where the periosteum is still attached. #### Why Osteosarcoma is Correct: **Osteosarcoma** is the most common primary malignant bone tumor in adolescents. Because it is highly aggressive and grows rapidly, it frequently breaches the cortex and elevates the periosteum. This results in characteristic periosteal reactions: **Codman’s Triangle** and the **Sunburst (Spiculated) appearance**. #### Why Other Options are Incorrect: * **Chondroblastoma:** A benign, epiphyseal tumor typically seen in young patients. It usually presents as a well-defined lytic lesion with a "fluffy" or "popcorn" calcification, but lacks aggressive periosteal reactions. * **Chondrosarcoma:** While malignant, it often presents in older adults with "endosteal scalloping" and "ring-and-arc" calcifications. While it can show periosteal changes, it is less classically associated with Codman’s Triangle than Osteosarcoma. * **Giant Cell Tumor (GCT):** A "benign but locally aggressive" tumor located in the epiphysis (extending to the subchondral bone). It typically shows a **"Soap-bubble appearance"** and lacks a periosteal reaction because it expands the bone rather than lifting the periosteum abruptly. #### NEET-PG High-Yield Pearls: * **Codman’s Triangle** is not pathognomonic for Osteosarcoma; it can also be seen in **Ewing’s Sarcoma**, subacute osteomyelitis, and active hematomas. * **Ewing’s Sarcoma** is more classically associated with an **"Onion-skin"** (lamellated) periosteal reaction. * **Osteosarcoma** most commonly occurs around the knee (distal femur/proximal tibia) and is associated with a rise in **Serum Alkaline Phosphatase**.
Question 9: A child 10 yrs of age presents with a mass on his left thigh. The mass seems to be arising from the diaphysis of the femur and involving the soft tissue of the thigh. The child is having fever also. Give your most probable diagnosis -
- A. Osteosarcoma
- B. Chondrosarcoma
- C. Ewing's sarcoma (Correct Answer)
- D. Malignant fibrous histiocytoma
Explanation: ***Ewing's sarcoma*** - **Ewing's sarcoma** commonly presents in children and adolescents, often involving the **diaphysis of long bones** like the femur. - The presence of a **soft tissue mass** and **fever** are characteristic systemic symptoms due to its aggressive nature and rapid growth. *Osteosarcoma* - While it is a common pediatric bone tumor, **osteosarcoma** typically arises in the **metaphysis** of long bones, not the diaphysis. - Systemic symptoms like fever are less common at presentation compared to Ewing's sarcoma unless there's significant metastatic disease. *Chondrosarcoma* - **Chondrosarcoma** is a malignant tumor of cartilage that usually affects older adults and rarely occurs in children. - It typically affects the **pelvis, shoulder, or long bones**, but a fever and involvement of the soft tissue with a diaphyseal origin are less classic presentation. *Malignant fibrous histiocytoma* - **Malignant fibrous histiocytoma** (now often termed undifferentiated pleomorphic sarcoma) is a tumor of adulthood, primarily affecting individuals over 40 years of age. - While it can involve deep soft tissues and bone, it is an extremely rare diagnosis in a 10-year-old child.
Question 10: A 20-year old male patient presents with pain on movement. X-ray of knee joint shows lytic lesion on the upper end of tibia. What is the likely diagnosis?
- A. Simple bone cyst
- B. Osteoclastoma (Correct Answer)
- C. Multiple myeloma
- D. Adamantinoma
Explanation: **Osteoclastoma** - An **osteoclastoma**, also known as a **giant cell tumor of bone**, typically presents in young adults (20-40 years old) and is characterized by a **lytic lesion** often located in the **epiphysis or metaphysis** of long bones, particularly around the knee joint (distal femur or proximal tibia). - These tumors are locally aggressive and can cause pain and swelling. *Simple bone cyst* - A **simple bone cyst (unicameral bone cyst)** is usually found in younger individuals (under 20) and is a **fluid-filled lesion** that often appears as a **central, expansile lytic lesion** in the **metaphysis** of long bones, commonly the proximal humerus or femur, not typically the epiphysis. - These are often painless and discovered incidentally or due to a pathological fracture. *Multiple myeloma* - **Multiple myeloma** is a plasma cell malignancy primarily affecting older adults (typically >50 years old) and presents with **multiple "punched-out" lytic lesions** in various bones (skull, spine, ribs, pelvis), rather than a solitary lytic lesion in a young adult. - It is associated with systemic symptoms such as anemia, hypercalcemia, renal failure, and abnormal immunoglobulins. *Adamantinoma* - An **adamantinoma** is a rare, malignant bone tumor that almost exclusively occurs in the **tibia**, but it typically presents as a **lytic, often eccentric lesion with sclerotic margins** and occasionally a "soap bubble" appearance, and while it occurs in young adults, it is a very rare diagnosis compared to osteoclastoma for a knee lytic lesion. - It often has a characteristic histological appearance resembling epithelial tissue.
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