Miller-Oncology Flashcards
Review Bone tumors by patient age
Malignant then benign
what are the 5 common mets to bone
Breast, lungs, thyroid, kidney, and prostate
“BLT and a kosher pickle” and “PT Barnum Likes Kids”) are the five common osteophiles metastatic to bone.
what are some lab tests used in orthopedic oncology?
Laboratory studies: Diagnostic tests for musculoskeletal neoplasms include
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Prostate-specific antigen (PSA) for prostate cancer
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Serum and urine electrophoresis (SPEP and UPEP) for myeloma
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Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for infection
Review the tumor bone interaction table?:
What are Ennekin’s four questions?
Radiographs in two planes should be obtained to establish answers to Enneking’s four questions:
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Location: Epiphyseal, metaphyseal, diaphyseal, etc.
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Tumor-bone interaction
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Bone-tumor interaction; refers to the interplay between the host bone and the tumor, described by Lodwick
Schemata of bone tumors location and cells for patients under 30
Distribution of bone lesions by location and cell type in patients over 30
names of benign and malignant tumors based on cell type
What to think if you see multiple lesions on bone xrays
based on age
List of tumors classified based on their location within the bone
why order advanced imaging in the work up?
A chest radiograph is used to look for primary lung disease and metastases.
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Technetium Tc99m whole-body bone scan is used to look for occult bone involvement. A whole-body bone scan result can be “cold” in patients with myeloma, in whom a radiographic skeletal survey is more sensitive.
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MRI is used to evaluate the primary tumor site.
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CT may be used for three-dimensional imaging if MRI is contraindicated (e.g., by cardiac pacemaker) or to evaluate a suspected osteoid osteoma or mineralization in a mass.
What are the key principles to tumor biopsy?
Biopsy determines tumor type and grade. Clinicians must follow several surgical principles (Table 9.5).
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Longitudinal incision in line with future resection. Longitudinal incision is extensile and allows for excision of the biopsy tract at the definitive surgical resection.
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Biopsy performed through a single compartment.
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Avoidance of critical structures such as major nerves and blood vessels.
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Inclusion of the soft tissue component of a bone tumor in the biopsy specimen. This principle avoids creating a stress riser and fracture in an already compromised bone.
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Culture the biopsy specimen.
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The three general types of biopsy are fine needle aspiration (FNA), core, and open.
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FNA is used to determine whether a mass is cancer or not. A needle is used to draw a few cells from a mass. FNA is the least invasive method but may not collect enough tissue.
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Core biopsy uses a coring device to remove a larger tissue sample and can diagnose the type and grade of the tumor. Ultrasound, CT, or MRI may be used to guide the procedure.
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Open biopsy may be used if the other two mechanisms are not able to render a diagnosis. The two types of open biopsy are excisional and incisional.
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Excisional biopsy is used when a lesion is less than 3 cm; the procedure removes the entire mass with clear margins.
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Incisional biopsy is used when a lesion is more than 3 cm; the procedure removes a small amount of tissue for diagnosis using the principles listed previously.
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Immunohistochemistry (IHC) and molecular testing can aid in the diagnosis of some bone and soft tissue tumors
Review Immunohistochemistry and Molecular Testing for Bone and Soft Tissue Tumors
review key points about genetic and cancer
Chromosomes—sarcoma-associated translocations. The most well known is Ewing sarcoma, which results from balanced translocation of chromosomes 11 and 22. The gene fusion product from this balanced translocation is the EWS-FLI1 gene.
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Oncogenes—genes with sequences that cause cancer. EWS-FLI1 and SSX1-SYT are oncogenes.
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Tumor suppressor genes—genes that inhibit cell proliferation. Mutations allow for unregulated tumor growth. Examples are Rb (retinoblastoma), which is mutated in 35% of osteosarcomas, and p53, which is mutated in 50% of all tumors and 20%–65% of osteosarcomas (Table 9.7).
Review common chromosome translocations
Review musculosketal genes syndromes and oncology
important slide
Review histologic “Grading”
of tumors
Grading uses the histologic appearance of a tumor and is based on nuclear atypia (extent of loss of structural differentiation), pleomorphism (variations in size and shape), and nuclear hyperchromasia (increased nuclear staining). Grading of tumors covers a morphologic range.
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Most systems use three grades.
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The grade of tumor that is most strongly correlated with the potential for metastasis:
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In bone: Most malignant bone lesions are high grade.
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In soft tissue: Soft tissue tumors manifest with a greater variety of grades (Table 9.9).
Review the treatment regimens for tumors
review the classification of surgical margins
Intralesional margin: The plane of dissection goes directly through the tumor. Used for benign tumors only, such as giant cell tumor (GCT) of bone and aneurysmal bone cyst (ABC).
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Marginal margin: A marginal line of resection goes through the reactive zone of the tumor; the reactive zone contains inflammatory cells, edema, fibrous tissue, and satellites of tumor cells. It is used commonly for atypical lipomas and well-differentiated liposarcomas.
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Wide margin: Also known as wide excision; the entire tumor is removed with a cuff of normal tissue. This is the most common margin for a soft tissue sarcoma.
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Radical margin: A radical margin is achieved when the entire tumor and its compartment (all surrounding muscles, ligaments, and connective tissues) are removed. Examples are amputation and surgery or removal of the entire anterior thigh compartment, vastus intermedius, vastus lateralis, and vastus medialis.
Review the Enneking staging system
Common chemo agents and their side effects
Multiagent chemotherapy has a significant effect on both the efficacy of limb salvage and disease-free survival for bone sarcomas.
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The common mechanism of action of chemotherapy drugs is the induction of programmed cell death (apoptosis).
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Most protocols entail preoperative regimens (neoadjuvant chemotherapy) followed by surgical resection and then postoperative chemotherapy.
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Patients with localized osteosarcoma or Ewing sarcoma have up to a 60%–70% chance for long-term disease-free survival with the combination of multiagent chemotherapy and surgery.
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The role of chemotherapy in soft tissue sarcoma remains more controversial. Chemotherapy is used for rhabdomyosarcoma and synovial sarcoma.
Most Common tumors
Radiation therapy for tumors
External beam irradiation produces free radicals and direct genetic damage and is used in the following scenarios:
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For local control of selected Ewing sarcoma, lymphoma, myeloma, and metastatic bone disease
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As an adjunct in treatment of soft tissue sarcomas, in which it is used in combination with surgery.
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Radiation may be delivered preoperatively (5000 cGy/50 Gy), followed by resection of the lesion with increased risk of wound healing.
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Postoperative external beam irradiation (6600 cGy/66 Gy) yields equal local control rates, with a lower postoperative wound complication rate but a higher incidence of postoperative fibrosis.
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There are several complications of radiation therapy.
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Postradiation sarcoma: A sarcoma sometimes manifests within the field of irradiation for a previous malignancy (e.g., Ewing sarcoma, breast cancer, lymphoma). The histologic appearance is the same as that of a high-grade sarcoma. Postradiation sarcomas are more common in patients who undergo chemotherapy with alkylating agents combined with irradiation.
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Radiation necrosis of bone: Late stress fractures occur in bones in which high-dose irradiation has been applied. It is more common in older women who have undergone periosteal bone stripping.
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Radiation neuritis, arteritis, and lymphedema: Painful scarring of the nerves and/or diminished blood flow to the extremity can occur in areas where the blood vessels and nerves have been irradiated.
Harringtons criteria for prophylatic impending fracture fixation
Harington’s criteria
> 50% destruction of diaphyseal cortices
> 50-75% destruction of metaphysis (> 2.5 cm)
Permeative destruction of the subtrochanteric femoral region
Persistent pain following irradiation
Review Mirel’s criteria for impending fracture
Mirels scoring for metastatic disease assigns points for pain (1: mild, 2: moderate, 3: functional3), lesional composition (1: blastic, 2: mixed, 3: lytic), lesional extent (1: <1/3, 2: 1/3 - 2/3, 3: >2/3 ), and lesional location (1: upper extremity, 2: lower extremity, 3: peritrochanteric). In patients with a Mirels score of 8 or higher, prophylactic fixation should be performed.
For patients with Mirels’ scores of 8 or higher, surgical options depend on the location of the lesion: For proximal humerus (Bickel’s Type I) lesions, endoprosthetic replacement is recommended; for diaphyseal (Type II) lesions, intramedullary rods, intercalary spacers, or plates and screws may be used; and for distal lesions (Type III), flexible nails or elbow replacement can be used.
Mirels proposed a scoring system for diagnosing impending fractures. He found that the risk of fracture was 33% at 6 months for a score of 9. He proposed that lesions with scores of 8 or higher require prophylactic internal fixation.
Review treatment protocol for pathologic fracture treatment
Obtain tissue diagnosis unless patient has a known primary neoplasm with bone biopsy proven skeletal metastasis, the treating surgeon should biopsy the lesion in question
biopsy may require separate incision than the incision used for IM nailing of bone
if biopsy suggests primary neoplasm of bone (like sarcoma) that may benefit from neoadjuvant chemo/radiotherapy then close wound and refer to local sarcoma center prior to surgical stabilization
surgical treatment of primary sarcoma will contaminate entire bone with sarcoma and affect ability to perform limb-salvage surgery
Radiation therapyindications
low Mirels’ score
Surgical fixation
do not proceed with fixation until primary neoplasm of bone has been ruled out with biopsy
goals of fixation
maximize ability for immediate mobilization and weight-bearing
protect the entire bone in setting of systemic or metastatic disease
optimize implant choice in the context of the patient’s overall prognosis
type of fixation depends on location of lesion and type of diseasehumerus proximal humerus lesions
endoprosthesis
diaphysis
intramedullary nail
resection and intercalary spacer
plates and screws (less preferred)
distal humerus lesions
flexible nails
elbow replacement
femur peritrochanteric lesions
intramedullary nail
femoral neck and head lesions
hemiarthroplasty
Postoperative radiation following surgery refer the patient to radiation oncology for post-operative radiotherapy treatment to
decrease pain
slow progression
treat remaining tumor burden not removed at surgery
what are the different ways to biopsy
Fine Needle Aspiration (FNA)
provides cytologic (cellular) specimen
frequently used for carcinoma
not typically used for sarcoma
Core biopsy (Tru-cut) allow for tumor structural examination
can evaluate both the cytologic and stromal elements of the tumor
frequently used for sarcoma
Incisional biopsy
small surgical incision carefully placed to access tumor without contamination of critical structures
Excisional biopsy
select indications: small, superficial soft tissue masses
what are the principals of open biopsy?
Incision
use longitudinal incision in the extremities
allows for extension of the incision for definitive management
Approachdo not expose neurovascular structures
all tissue exposed during the biopsy is considered contaminated with tumor
maintain meticulous hemostasis
post-operative hematomas are considered contaminated with tumor
release tourniquet prior to wound closure
Biopsy
perform through the involved compartment of the tumor
for bone lesions with a soft tissue mass, it is ok to perform the biopsy using the soft tissue mass
Closure if using a drain, bring drain out of the skin in line with surgical incision
allows drain site to be removed with definitive surgical extensile incision
Orthobullets
Chemotherapy
Mechanism
induces apoptosis
may target specific proteins over-expressed in cancer cells e.g. tyrosine kinase inhibitors
imatinib (Gleevec) for chronic myelogenous leukemia
gefitinib (EGFR inhibitor, Iressa) for lung, breast cancer
erlotinib (EGFR inhibitor, Tarceva) for NSCLC and pancreatic cancer
eliminates micrometastasis in lungs
>98% necrosis with chemotherapy is good prognostic sign
Resistance expression of multi-drug resistance (MDR) gene portends very poor prognosis
cells can pump chemotherapy out of cell
present in 25% of primary lesions and 50% of metastatic lesions
Indications
Integral component of treatment along with surgical resection in
osteosarcoma (intramedullary and periosteal)
Ewing’s sarcoma/primative neuroectodermal tumor
malignant fibrous histiocytoma
dedifferentiated chondrosarcoma
chemotherapy for soft tissue sarcoma is controversial
Administration
Preoperative chemotherapy given for 8-12 weeks
Maintenance chemotherapy for 6-12 months
Specific Agents & Antidotes
Doxorubicin (Adriamycin)
mechanism
doxorubicin is an anthracycline antibiotic commonly used in oncological protocols
functions as a cytostatic agent
side effectscardiac toxicity
leads to congestive heart failure
dexrazoxane used to mitigate toxicity
Agents and Antidotes
mechlorethamine/cisplatin - give sodium thiosulfate
doxorubicin/epirubicin - give dexrazoxane
vinca alkaloids (vincristine/vinblastine) - give hot compress and hyaluronidase
give cold compress for all other vesicants
Radiation from orthobullets
Mechanism
induces apoptosis
may target specific proteins over-expressed in cancer cells e.g. tyrosine kinase inhibitors
imatinib (Gleevec) for chronic myelogenous leukemia
gefitinib (EGFR inhibitor, Iressa) for lung, breast cancer
erlotinib (EGFR inhibitor, Tarceva) for NSCLC and pancreatic cancer
eliminates micrometastasis in lungs
>98% necrosis with chemotherapy is good prognostic sign
Resistance expression of multi-drug resistance (MDR) gene portends very poor prognosis
cells can pump chemotherapy out of cell
present in 25% of primary lesions and 50% of metastatic lesions
Indications
Integral component of treatment along with surgical resection in
osteosarcoma (intramedullary and periosteal)
Ewing’s sarcoma/primative neuroectodermal tumor
malignant fibrous histiocytoma
dedifferentiated chondrosarcoma
chemotherapy for soft tissue sarcoma is controversial
Administration
Preoperative chemotherapy given for 8-12 weeks
Maintenance chemotherapy for 6-12 months
Specific Agents & Antidotes
Doxorubicin (Adriamycin)
mechanism
doxorubicin is an anthracycline antibiotic commonly used in oncological protocols
functions as a cytostatic agent
side effectscardiac toxicity
leads to congestive heart failure
dexrazoxane used to mitigate toxicity
Agents and Antidotes
mechlorethamine/cisplatin - give sodium thiosulfate
doxorubicin/epirubicin - give dexrazoxane
vinca alkaloids (vincristine/vinblastine) - give hot compress and hyaluronidase
give cold compress for all other vesicants
when do you use chemotherapy in ortho onc?
Integral component of treatment along with surgical resection in
osteosarcoma (intramedullary and periosteal)
Ewing’s sarcoma/primative neuroectodermal tumor
malignant fibrous histiocytoma
dedifferentiated chondrosarcoma
chemotherapy for soft tissue sarcoma is controversia
what are tyrosine kinase inhibitors?
Tyrosine kinase inhibitors are currently being used for cancer chemotherapy. Tyrosine kinase receptors are a family of receptors which naturally occur in nature and are often over-expressed in neoplastic cancer cells. They each have a tyrosine kinase domain (which phosphorylates proteins on tyrosine residues), a hormone binding domain, and a carboxyl terminal segment with multiple tyrosines for autophosphorylation.
Two examples of tyrosine kinase inhibitors, as described in the review by Shawver et al. are: herceptin for the treatment of breast cancer and gleevec for chronic myelogenous leukemia and gastrointestinal stromal tumors.
what is the major side effect to doxirubicin?
cardiac toxity
