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Flashcards in Miller-Oncology Deck (33)
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1

Review Bone tumors by patient age

 

Malignant then benign

2

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.

3

what are some lab tests used in orthopedic oncology?

Laboratory studies: Diagnostic tests for musculoskeletal neoplasms include

Prostate-specific antigen (PSA) for prostate cancer

Serum and urine electrophoresis (SPEP and UPEP) for myeloma

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) for infection

4

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:

Location: Epiphyseal, metaphyseal, diaphyseal, etc.

Tumor-bone interaction

Bone-tumor interaction; refers to the interplay between the host bone and the tumor, described by Lodwick

5

Schemata of bone tumors location and cells for patients under 30

6

Distribution of bone lesions by location and cell type in patients over 30 

7

names of benign and malignant tumors based on cell type

8

What to think if you see multiple lesions on bone xrays 

 

based on age

9

List of tumors classified based on their location within the bone

10

why order advanced imaging in the work up?

A chest radiograph is used to look for primary lung disease and metastases.

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.

MRI is used to evaluate the primary tumor site.

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.

11

What are the key principles to tumor biopsy?

Biopsy determines tumor type and grade. Clinicians must follow several surgical principles (Table 9.5).


 

 

 

Longitudinal incision in line with future resection. Longitudinal incision is extensile and allows for excision of the biopsy tract at the definitive surgical resection.

Biopsy performed through a single compartment.

Avoidance of critical structures such as major nerves and blood vessels.

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.

Culture the biopsy specimen.

The three general types of biopsy are fine needle aspiration (FNA), core, and open.

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.

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.

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.

Excisional biopsy is used when a lesion is less than 3 cm; the procedure removes the entire mass with clear margins.

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.

Immunohistochemistry (IHC) and molecular testing can aid in the diagnosis of some bone and soft tissue tumors

12

Review Immunohistochemistry and Molecular Testing for Bone and Soft Tissue Tumors

13

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.

Oncogenes—genes with sequences that cause cancer. EWS-FLI1 and SSX1-SYT are oncogenes.

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).

14

Review common chromosome translocations

15

Review musculosketal genes syndromes and oncology

 

important slide

16

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.

Most systems use three grades.

The grade of tumor that is most strongly correlated with the potential for metastasis:

In bone: Most malignant bone lesions are high grade.

In soft tissue: Soft tissue tumors manifest with a greater variety of grades (Table 9.9).

17

Review the treatment regimens for tumors

18

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).

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.

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.

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.

19

Review the Enneking staging system

20

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.

The common mechanism of action of chemotherapy drugs is the induction of programmed cell death (apoptosis).

Most protocols entail preoperative regimens (neoadjuvant chemotherapy) followed by surgical resection and then postoperative chemotherapy.

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.

The role of chemotherapy in soft tissue sarcoma remains more controversial. Chemotherapy is used for rhabdomyosarcoma and synovial sarcoma.

21

Most Common tumors

22

Radiation therapy for tumors

External beam irradiation produces free radicals and direct genetic damage and is used in the following scenarios:

For local control of selected Ewing sarcoma, lymphoma, myeloma, and metastatic bone disease

As an adjunct in treatment of soft tissue sarcomas, in which it is used in combination with surgery.

Radiation may be delivered preoperatively (5000 cGy/50 Gy), followed by resection of the lesion with increased risk of wound healing.

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.

There are several complications of radiation therapy.

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.

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.

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.

23

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

24

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. 

25

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

 

26

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

27

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

28

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

 

29

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

 

30

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