COMBINED MODALITY MULTIDISCIPLINARY APPROACH TO CANCER TREATMENT Dr.

Villa January 20, 2014 Group 4 Basic principle in therapy: To cure the disease To control the disease To palliate the patients symptoms with minimum functional and structural impairment Major Disciplines in the Management of Cancer Surgery - qualified surgeons Radiotherapy- qualified radiooncologists Chemotherapy/ Hormonal Therapy/ Immunologic Therapy - qualified internists/medical oncologists (i.e. adult patients) Current Anti-Cancer Approaches Surgery Remove known tumor/masses Chemotherapy Kills rapidly dividing tumor cells Radiation therapy Kills rapidly dividing tumor cells (local treatment, no systemic effect) Targeted therapy Specifically inhibit required process in tumor cell growth SURGERY

Most of the time, lobectomy is done to ensure that the entire tumor and its circulation is out.

In patients who cannot tolerate having a lung removed, no matter how small the tumor is, surgery is not advised. Especially for female nonsmokers. RADIATION THERAPY Destruction of cancer cells using ionizing radiation Supplementary surgery and palliate pain (in bone metastasis) Complications: skin reactions, mucositis, hoarseness of voice, hypothyroidism, low blood counts, lung fibrosis, heart complications, secondary cancers A primary treatment Before surgery to shrink a tumor After surgery to eliminate any remaining cancer cells To treat cancer that has spread to other areas of the body

Types of Radiation External Beam Radiation Therapy (EBRT): delivers high doses of radiation to lung cancer cells from outside the body, using a variety of machine-based technologies. High Dose Rate(HDR) Brachytherapy (Internal Radiation): delivers high doses of radiation from implants placed close to, or inside, the tumor(s) in the body Advantages of EBRT Accurately targets a tumor with higher doses of radiation, while minimizing damage to healthy lung tissue and nearby organs. As a

result, EBRT helps to lower the risk of side effects typically associated with radiation treatment for lung cancer, such as difficulty breathing or heart damage Some additional advantages of external beam radiation therapy include: fast, painless outpatient procedure does not carry the standard risks or complications of surgery, such as surgical bleeding, post-operative pain, or the risk of stroke, heart attack, blood clot and external treatment unlike chemotherapy, which circulates throughout the body, ERBT is targeted to the area being treated

Most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fastdividing cells

Cell Kill Only a percentage of the cancer cells are killed with each course of chemotherapy. Therefore, repeated doses or cycles of chemotherapy must be done. Tumor growth is exponential and kills constant fraction of tumor cells.

CHEMOTHERAPY Drug treatment to kill fast-growing cancer cells acts on DNA, RNA or proteins of signal transduction Examples: Capecitabine(Xeloda), Doxurubicin, Oxaliplatin, Paclitaxel Effects: systemic in nature Side Effects: low blood counts, nausea/vomiting, alopecia, local reactions, mucositis, cardiotoxicity etc.

Sites of Action of Cytotoxic Agents

Cell Cycle

Tumor Growth Kinetics Tumor cell growth is logarithmic Mechanism of Action

Manner of Administration 1. Adjuvant therapy Cure 2. Neoadjuvant therapy R0 resection, Cure 3. Palliative Control, Quality of Life

CLASSIFICATION of CHEMOTHERAPY DRUGS CYCLE SPECIFIC Antimetabolites interfere with nucleic acid synthesis attack during S phase of life cycle Examples: Cytatabine, Floxuridine, Fluorouracil, hydroxyurea, methotrexate, thioguanine Enzymes useful only for leukemias Example: Aspariginase Plant Alkaloids cycle specific to M Phase prevent mitotic spindle formation Examples: Vinblastine, Vincristine Genotype analyzes the pathway involved to identify what part of the growth process has a problem Target drugs are patterned according to the defect in the pattern Can be monitored properly by PET scan and to check for proper response Target Drugs: - improves the outcome of the treatment - Selective and not cytotoxic, patient friendly - Usually infused for 30mins

CYCLE NON-SPECIFIC Alkylating Agents disrupt deoxyribonucleic acid(DNA) Example: Carboplatin, Cisplatin, Cyclophosphamide, Thiotepa Antibiotics bind with DNA to inhibit synthesis of DNA and RNA -Examples: Bleomycin, Doxorubicin, Idarubicin, Mitomycin, Mitoxantrone TARGETED THERAPY Personalized treatment Understanding the biology of the tumor helps the treatment regimen. Treatment is patterned to the behavior of the tumor or to the direct mutation it undergoes.

The Target Epidermal Growth Factor Receptor

HER1/EGFR signalling increases VEGF ( Vascular Endothelium Growth Factor) and matrix metalloproteinase levels

Lung Cancer Mutation Consortium: Single Driver Mutations in NSCLC

The most common side effect of Tarceva is rash. Advise patient to use sunblock and protective devices. The more rash there is, the better the response to the drug. Any tumor beyond 3mm cannot grow without a blood supply. They make their own blood vessels by secreting VEGF (Strong compound produced by the tumor that encourages the formation of new blood vessels). This is the target of Bevacizumab and Avastin (anti-VEGF). HANDLING COMPLICATIONS of CHEMOTHERAPY Alopecia hair loss that occurs as chemotherapeutic drugs destroy the rapidly growing cells of hair follicles may be minimal or severe occurs 2 to 3 weeks after treatment begins almost always temporary Signs & Symptoms: - hair loss that may include eyebrows, lashes, and body hair Interventions minimize shock and distress by warning the patient of this possibility discuss with the patient why it occurs describe to the patient how much hair loss to expect emphasize to the patient the need for appropriate head protection against sunburn *very sensitive inform the patient that new hair may be a different texture or color give the patients sufficient time to decide whether to order a wig or to opt for other measures inform the patient that his scalp will become sore at times due to follicles swelling Anemia occurs as chemo drugs destroy healthy cells and cancer cells RBCs are destroyed and cant be replaced by the bone marrow not able to recover

Mutation found in 54% of tumors completely tested. EGFR Expression

Immunohistochemical staining is used to check for EGFR expression. Targeted Agents Drug Targeted Agent Classification Tyrosine Gefitinib Kinase (Iressa) Inhibitor Eriotinib (Tarceva)

Target Receptor TKI

TKI

The patient must be positive for mutation to use these two drugs. They are very expensive.

Signs & Symptoms: dizziness, fatigue, pallor, and shortness of breath after minimal exertion low hemoglobin level and hematocrit may develop slowly over several courses of treatment not automatic Interventions: monitor hemoglobin level, hematocrit, RBC count; report dropping values be prepared to administer a blood transfusion or erythropoietin (usually for patients who do not want to receive blood products eg Jehovahs witnesses) Preventive Measures: instruct the patient to take frequent rests, increase his intake of iron-rich food, and take a multivitamin with iron as prescribed if the patient has been prescribed a drug such as epoetin, make sure he understands how to take the drug and what adverse effects he should watch for and report Diarrhea occurs because the rapidly dividing cells of the intestinal mucosa are killed Complications: weight loss, F & E imbalance, malnutrition Signs & Symptoms: increase in the volume of stool compared with the patients normal bowel habits Interventions: assess frequency, color and consistency of stool encourage fluids; give IV fluids and potassium supplements as ordered advise patients not to take any medications like Loperamide. We have to remember that the patient has just been given chemotherapy and sometimes it is just an infectious diarrhea. Extravasation inadvertent leakage of a vesicant solution into the surrounding tissue capable of burning or causing necrosis of skin and surrounding tissues.

Signs & Symptoms: initial signs and symptoms may resemble those of infiltration: blanching, pain, and swelling symptoms possibly progressing to blisters; to skin, muscle, tissue and fat necrosis; and to tissue sloughing

Blood return is an INCONCLUSIVE test & shouldnt be used to determine if IV catheter is correctly seated in the peripheral vein. To assess peripheral IV placement, flush the vein with NSS and observe site for swelling. Ex. Extravasation of Doxorubicin Interventions: stop the infusion check your facilitys policy to determine if the IV catheter is to be removed or left in place to infuse corticosteroids or a specific antidote notify the physician We usually do not remove the line automatically. We have to flush it and aspirate as much amount of drug that has been infiltrated and give steroids. instill the appropriate antidote according to facility policy, usually youll give the antidote for extravasation either by instilling it through the existing IV catheter or by using a 1ml syringe to inject small amounts subcutaneously in a circle around the extravasated area after the antidote has been given, remove the IV catheter instruct how to be managed at home Preventive Measures: verify IV line patency and placement by flushing with normal saline solution remember, When in doubt, take it out! use a transparent, semi permeable dressing for inspection of site

Leukopenia reduced leukocytes or WBCs occurs as WBCs and cancer cells are destroyed by chemo drugs Signs & Symptoms: susceptibility to infections neutropenia Interventions: watch for nadir, the point of lowest blood cell count be prepared to administer colony-stimulating factors institute neutropenic precautions teach the patient & caregiver about: o good hygiene practices o signs and symptoms of infection o importance of checking the patients temperature regularly o how to prepare low-microbe diet (avoid fresh food) o how to care for vascular access devices Instruct the patient to avoid: o crowds o people with colds or respiratory infections o fresh flowers/plants o fresh fruit maybe the carriers of some microorganisms Nausea and Vomiting can appear in 3 different patterns o Anticipatory o Acute o Delayed Anticipatory Nausea & Vomiting nausea and vomiting thats a learned response from prior nausea and vomiting after a dose of chemotherapy high anxiety levels (acts as trigger) Interventions: post-treatment control of nausea and vomiting may prevent future anticipatory episodes

Acute Nausea and Vomiting Nausea and vomiting occurring within the first 24 hours of treatment Interventions: - Treat the patient with acute nausea and vomiting with antiemetic drugs like: Dexamethasone Granisetron Lorazepam Metoclopramide Ondansetron Delayed Nausea and Vomiting Nausea or vomiting starting or continuing beyond 24 hours after chemo has began Interventions: - The administration of serotonin antagonists, corticosteroids, various antihistamines, benzodiapines, and metoclopramide are usually effective in treating patients Stomatitis Inflammation of the lining of the oral mucosa Can spread into the esophagus and pharynx Signs and symptoms: - Painful mouth ulcers that range from mild to severe appearing 3-7 days after certain chemo drugs are given; usually due to antimetabolites chemo drugs like 5-FU (5-Flourouracil) Interventions: - Instruct the patient to perform meticulous oral hygiene - Administer topical anesthetic mixtures as appropriate - If pain is severe, opioid analgesics may be prescribed until the ulcers heal Preventive Measures: - Instruct the patient to suck on dry ice chips while receiving certain drugs that can cause stomatitis;

this decreases the blood supply to the mouth, thus decreasing ulcer formation Thrombocytopenia Decrease platelet count, prone to bleeding Signs and symptoms: - Bleeding gums - Coffee-ground emesis - Hematuria - Hypermnorrhea - Increased bruising - Petechiae - Tarry stools Interventions: - Monitor patients platelet count, critical point: 20,000 cell/mm - Avoid unnecessary IM injections or venipuncture - If an IM injection is necessary, apply pressure to the site for at least 5mins, pressure dressing - Instruct the patient to: Avoid cuts and bruises Shave with electric razor Avoid blowing his nose Stay away from irritants that would trigger sneezing Avoid using rectal thermometers - Instruct the patient to report sudden headaches (which could indicate potentially fatal intracranial bleed) PALLIATIVE CARE An approach that improves the quality of life of patients and family facing the problem associated with life threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychological and spiritual. Is applicable early in the course of illness, in conjunction with other therapies that are

intended to prolong life such as chemo or radiation therapy Palliative Management 1. Medical management 2. Pain Management 3. Nutritional management 4. Lung cancer counseling and support groups 5. Issues on death and dying Performance Status - Basis for the Palliative management, needs to be identified before you treat the patient for palliative care 0 Fully active without restriction 1 activity restricted; ambulatory; light work only 2 Ambulatory; all self-care; no work activities; up >50% waking hours 3 limited self-care; confined to bed >60% of the time 4 Completely disable

Medical Management Stage IV M1a (Pleural effusion, pericardial effusion)

Positive pleural fluid

WHO Pain Management

Thoracentesis Pericardiocentesis
Step 3. SEVERE PAIN morphine hydromorphone methadone levorphanol fentanyl oxycodone +/- nonopoid analgesics +/- adjuvants Step 2. MODERATE PAIN Acet or ASA + codeine hydrocodone dihydrocodeine tramadol (not available with ASA or Acet) +/- adjuvants

Chemotherapy for stage IV Pleurodesis Pericardial window Surgical resection followed by WBRT

Stage IV B - Brain

Stage IV B Adrenals

Palliative chemotherapy

Bone metastasis

Palliative radiation therapy Bisphosphonate infusion

Step 1.

Superior Vena Cava obstruction

Radiation therapy Stent

MILD PAIN Aspirin (ASA) Acetaminophen (Acet) Nonsteroidal anti-inflam drugs (NSAIDs) +/- adjuvants

Severe Hemoptysis

EBRT Laser

Pain Management Lung cancer pain may result from: - A tumor putting pressure on tissues, bones, nerves, organs - Poor blood circulation - Infection or inflammation in the lungs - Side effects of surgery, radiation therapy, chemotherapy, other cancer treatments - Metastasis, or cancer cells that have spread to other sites in the body - Stiffness from inactivity - Pain that is completely independent from cancer or cancer treatment (e.g. headaches, backaches, muscle strains, arthritis or other common pain)

These may be given in the form of: Pills Injections Skin Patches Implanted pain pumps that automatically deliver a predetermined dose of pain medicine to the spine Remember to discuss any of the side effects, like nausea, drowsiness, constipation, dry mouth and itching. Nutritional Management Malnutrition results from: - Depression, denial, loss of hope - Lack of family support - Cancer cachexia

Signs and symptoms of lung cancer Side of effects of treatment

Modes of Nutrition: o Enteral o Parenteral o Feeding tubes Death and Dying Grief Stage Denial Anger Bargaining Depression Acceptance Terminally Ill Patient Response This cant be happening to me! Why is this happening to me? I promise Ill be a better person if I dont care anymore. Im ready for whatever comes.

Months to year/years 1. Encourage designation of health care 2. Explore fears about dying and address 3. Assess decision making capacity and surrogate decision maker 4. Initiate discussion of personal values and preference for end of life care 5. Initiate discussion of palliative care option Days to weeks 1. Implement and ensure compliance with advance care plan 2. Clarify and confirm patients decision about life sustaining treatment including CPR

Notes by: Catague R, Dizor J, Sameon N