Intro to Clinical Oncology Flashcards
Most common malignancies and most common causes of death
Most common malignancies:
- Prostate/breast
- Lung/Bronchus
- Colon
Most common causes of death
- Lung/bronchus
- Prostate/breast
- Colon
How does cancer present?
- Local symptoms of disease:
- Interference with normal organ function –> bowel obstruction, cough
- Direct extension into adjacent organ/structures –> chest wall pain - Symptoms of metastatic disease:
- Pain or organ dysfunction from disease that has pread to other organs –> bone pain, seizures, headache - Paraneoplast:
- Abnormal hormone production - Incidental or screening
Presentations of hematologic malignancies
- Bone marrow failure
- anemia –> weakness, fatigue, dyspnea
- thrombocytopenia –> bleeding, bruising
- leucopenia –> infection - Bone marrow proliferation
- erythrocytosis (PCRV) –> headache, plethora
- thrombocytosis –> thrombosis, bleeding
- leukocytosis –> dyspnea, confusion
- splenomegaly - Lymphadenopathy
- B-symptoms: fever, night sweats, weight loss
- due to elaboration of cytokines - Thrombosis
Signs (physical findings) and symptoms (what the patient reports)
Local symptoms:
- pain
- mass
- organ dysfunction –> symptoms depend on the organ
- direct extension to adjacent organs –> e.g. difficulty swallowing due to a tumor in the bronchus obstructing the esophagus
Metastatic disease:
- lumps, bumps
- pain
- symptoms referable to disruption of normal organ function –> obstruction, seizure, paralysis, fracture
Paraneoplastic symptoms
Symptoms that result from various substances secreted by the tumor or as a response to the tumor –> not a direct effect of malignancy
- weight loss without GI tract obstruction
- hypercalcemia
- hyponatremia
- “clubbing”
DVT and pulmonary embolism = common presentation and/or complication due to hypercoagulability
- requires immediate diagnosis and anticoagulation
- potentially fatal
Clubbing
Cutaneous signs of malignancy –> can be direct extension, paraneoplastic or metastatic
- cutaneous metastases generally associated with poor prognosis
Cancer anorexia and cachexia –> weight loss is common (>10%)
- frequent presenting sign
- usually associated with advanced disease
- etiology is controversial
Difference between incidental finding and screening
Incidental = patient evaluated for another reason
- frequently, an unsuspected radiologic finding
- major source of medicolegal problems
Screening
- recommended for breast, colon, cervical, lung in certain patients (sprial CT)
- prostate (PSA blood test) is controversial
- more complex than most appreciate
Screening for cancer
Detecting cancer before symptoms and signs
- basic premise is that smaller/earlier is better –> proven to be true in some disease, but not in others
- level of benefit varies –> best where the site of tumor is directly sampled (e.g. pap smear or colonoscopy); less effective when radiologic imaging is used (e.g. mammography or CT scan)
Current recommended screening for standard risk population
- Breast cancer –> mammography after age 50
- Colon cancer –> colonoscopy after age 50
- Cervical cancer –> pap smears
- Head and neck cancer –> evaluation during dental exam
- Prostate cancer –> PSA testing in males >50 (controversial)
- Lung cancer (as of 2011) –> low dose helical CT for patients with significant smoking history, >55, only at institutions with substantial expertise
Diagnosis of cancer
There must be histologic or cytologic proof of disease –> rare exceptions
- biopsy should be from the most accessible, least dangerous place –> generally, if you prove a cancer from a distant site, you do not need to biopsy the primary tumor unless curable approaches to both sites would be changed
- the biopsy should come before the rest of the evaluation, however a certain degree of radiographic evaluation is frequently performed simultaneously
Example of biopsy dilemmas:
1 41 y.o female presents with a breast lump and a single bony swelling in the distal femur. Biopsy of breast = infiltrating ductal cancer
- should the leg also be biopsied? –> YES! if low grade chondrosarcoma, patient could have two ultimately curable neoplasms
2. 50 y.o. male smoker presents with pancytopenia and a lung mass apparent on chest x ray. Bone marrow biopsy = diagnostic of small cell lung cancer
- can proceed with tx for small cell lung cancer
The diagnostic biopsy
- need a diagnosis –> “suspicious” and “possible” are not good enough, need the definitive proof for diagnosis
- need enough tissue to perform special stains and other analysis –> FNA usually not enough
- immunohistochemistry –> can distinguish tissue of origin in difficult cases
- molecular analysis –> for therapeutic decisions (Her2/neu, EGFR, k-ras, etc.)
Staging
- clinical vs. pathological staging
How extensive is the cancer?
- TMN system
- other factors –> tumor markers
- therapy is stage directed but not mandated
- staging systems do not incorporate all known variables –> therefore, therapy is determined by stage in addition to other factors (physiology, patient preferences, local expertise)
- staging does not incorporate performance status
Clinical vs. pathological staging
- clinical stage = stage determined after complete clinical assessment (physical exam, laboratory, radiologic, biopsy, mediastinoscopy, etc.) –> clinical stage frequently underestimates the extent of disease
- pathological stage = stage determined after resection (or attempted resection) OR pathological determination of metastatic disease
Tumor board
Organized meeting of internal medicine, surgical, and radiation oncologists –> include radiologists and pathologists
- review all evidence and assign clinical and/or pathologic stage
- recommend treatment approaches
- OK to use staging manuals –> guidelines change frequently
- important to have in mid the clear staging criteria for curative intent in each tumor type
Performance status
Considers the general ability of a patient to do things –> 2 major scales
- Karnofsky –> percentage score, more detailed
- Eastern Cooperative Oncology Group
- -> 0 = no limitations
- -> 1 = OOB all day, capable of a full day of work
- -> 2 = OOB > 50% of the day, limited ability to work
- -> 3 = OOB < 50% of day –> capable of self care
- -> 4 = requires nursing assistance with ADL
- ->5 = dead
How is staging accomplished?
- History and physical
- Radiographic studies
- Laboratory evaluation
- Invasive and surgical
- Clinical vs. surgical staging
Radiographic studies in cancer diagnosis
- Plain films = chest X ray –> easy, inexpensive, useful for initial assessment and follow up
- CT = best method for many disease –> excellent imaging of most organs
- need IV contrast (iodinated) for best assessment usually
- easy and relatively inexpensive - MRI = best method for imaging the brain and spinal cord
- useful in certain special situation in chest and liver
- cannot use in patients with ferrous metals in the body
- slightly more difficult to obtain and more expensive than CT - PET scans = assessment of undiagnosed masses to determine malignant potential
- useful as part of staging evaluation for lung and other cancers
- requires 18FluoroDeoxyGlucose isotope
- expensive, limited availability
- may ultimately prove valuable in follow up
- currently overutilized –> PET avidity and value in each cancer has yet to be established - PET/CT
- Ultrasound
Surgical staging
Occurs prior to definitive procedure
- provides information regarding lymph node status (primarily in lung cancer)
- mediastinoscopy
- other methods are gaining favor –> e.g. endoscopic bronchial ultrasound
Treatment of cancer
Stage directed
Goals of therapy –> vary depending upon disease, extent, and patient
For solid tumors –> must control both the local disease (i.e. primary disease) and the systemic disease
Local therapy for local disease:
- surgery
- radiation
- adjuvant therapy
- others –> radiofrequency ablation, cryotherapy
Locally advanced disease –> combined modality therapy
Advanced disease:
- chemotherapy
- hormonal therapy –> breast/prostate cancer
- immunotherapy
Stage directed therapy –> localized disease
Confined to tissue or origin, no invasion of adjacent structures, at most local lymph node
- treat with localized therapy –> surgery or radiation
- adjuvant chemotherapy
Stage directed therapy –> locally advanced disease
Regional lymph node involvement, large tumors, invades adjacent structures
- treat with combined modality therapy –> chemotherapy, radiation, surgery
Stage directed therapy –> advanced diseases = metastases
Distant spread
- treat with systemic therapy –> chemo, hormonal
- radiation + surgery to relive/prevent specific local complications, occasionally to remove residual disease for cure (e.g. testicular cancer)
Surgical treatment
Can you operate vs. should you operate
Various goals of surgery:
- diagnostic
- curative
- staging procedures –> e.g. mediastinoscopy
- “debulking” to optimize use of other treatments
- palliative –> treatment and prevention of complications
For cure, goal should be complete removal of the tumor with clear margins in an anatomically appropriate fashion
- potentially curative procedure should not be undertaken until after completion of non-surgical staging
Resectable vs. operable
Principles of radiation therapy
Maximize dose to the target (tumor or areas at risk) while minimizing exposure to normal cells
- precise target localization
- reliable target immobilization
- conformal treatment delivery
Use a fractionated dose that causes lethal damage to cancer cells but only sublethal damage to nearby normal cell populations
Radiation biology
Photons
- gamma rays = photons produced from radiation decay –> cobalt-60, cesium-137, iridium-192, etc.
- X-rays = man made
- –> diagnostic radiology = kilovoltage energy
- –> radiation oncology = megavoltage energy
Electrons, protons, neutrons, etc
Radiation dose
Uses radiation of a certain type (ionizing) to cause tissue damage by ions release from target molecules and from DNA
- gray = gy: a unit of energy delivered per mass of tissue (cGy = 1 rad)
Fractionated dosing:
- 1.25 - 8 Gy daily fraction x a total dose dictated by organ tolerance
- 1.8 - 2 Gy for curative cases
- palliative cases usually 3 gy per day –> can be 8 Gy for those with very poor performance status
Total dose = a complex balance between giving enough radiation to kill the primary and subclinical tumor and avoiding normal tissues
- stage I seminoma: 25 Gy in 1.25 Gy fxn
- high risk prostate cancer: 75.6-84.4 Gy
Systemic cancer treatment = chemotherapy/biological therapy
Chemotherapy:
- cytotoxic “small molecule” drugs
- targeted “small molecule”
Biological therapy:
- antibodies/antibody drug complexes
- ligand directed proteins
- cytokines
- cellular therapies
- gene therapies
Principles of chemotherapy
- drug sensitivity is specific to disease
- log-kill hypothesis = fractional kill
- growth kinetics –> small tumors are more sensitive to chemo
- overlapping toxicities are additive
- cytotoxicity is usually dose dependent
Combination chemotherapy principles
- individual drugs should be effective
- combinations should “make sense” –> be synergistic, etc.
- repeated dosing > single high doses
- low stage disease responds better
- avoid cross resistant combinations
- toxicities should not overlap
- use each drug at optimum dose
Utilization of antineoplastic agents
Increase life expectancy/palliative treatment in advanced disease –> breast, colon, lung, prostate, bladder, pancreas
Curative therapy of advanced disease
- hematologic malignancies –> hodgkins, NHL, acute myelogenous leukemia, acute lymphoblastic leukemia
- solid tumors –> testicular cancer + choriocarcinoma
Chemoradiotherapy for curative treatment of locally advanced disease –> bulky hodgkins, stage III NSCLC, limited SCLC, rectal cancer
Preservation of organ function –> laryngeal cancer, lung cancer, anal carcinoma
Adjuvant therapy in early stage disease –> breast, colon, lung, prostate, bladder
The decision to use chemotherapy
- should be evidence based
- drug/regiment to be utilized should be employed in a patient who could have been enroled in a trial which demonstrated a positive outcome for that particular treatment plan
- decisions require that the patient be carefully staged
Stage I and II disease - the decision to utilize adjuvant chemotherapy
Adjuvant treatment: therapy administered after all known disease is removed because there is a statistical possibility of relapse
- requires large studies to prove benefit
- must balance the risks of exposing cured patients to potentially toxic agents
- proven benefit in all major solid tumors –> lung, breast, colon, prostate
Decision to use chemo as part of multimodality treatment
Locally advanced disease is frequently unresectable or has poor long term outcome due to both local and systemic relapse
- chemo can improve the outcomes of radiotherapy
- risk of increased toxicity
Decision to utilize chemo in advanced cancer
With a few notable exceptions, most metastatic cancers are incurable
- chemo can improve both quality and quantity of life in many patients
- factors beyond classic staging frequently come into play –> performance status, co-morbidities, patient attitude
Future of chemotherapy
Improved understanding of the molecular basis of cancer will lead to better therapy –> “targeted agents”
- more narrowly targeted agents will result in fewer side effects
- patient selection –> prognostic and predictive markers
Individualization of therapy
Not a new concept –> we have individualized based upon patient factors including performance status, organ function, toxicity, etc. for a long time
New examples:
- Bcr-abl –> imatinib
- ER –> tamoxifen
- Her2-neu –> trasztusumab, lapatanib
- RAR alpha –> all trans retinoic acid
- Ras mutation –> cetuximab
Prognostic vs. predictive
Prognostic –> marker that indicates how the patient will do irrespective of therapy (unless specifically directed)
Predictive –> marker that indicates how a patient will respond to treatment
Examples:
- ER is a positive prognostic and positive predictive marker (tamoxifen) in breast cancer
- Her 2-neu is a negative prognostic and positive predictive marker (trastuzumab) in breast cancer
- Ras is a negative prognostic and negative predictive marker (cetuximab) in colon cancer
- ERCC1 is a positive prognostic and negative predictive (cisplatin) marker in lung cancer
Important points of lecture
- Cancer can present in a myriad of ways.
- Symptoms can be a direct or indirect effect of the malignancy.
- Screening for asymptomatic disease has been demonstrated to improve survival in some cancers.
- Diagnosis requires tissue.
- Staging is the extent of the cancer and is based upon history, exam, labs and radiologic studies (depending upon the malignancy).
- Treatment is stage directed
