Lung Cancer

LUNG CANCER
The Magnitude of the Problem  The incidence of lung cancer peaks between ages 55 and 65 years  Accounts for 29% of all cancer deaths (31% in men, 26% in women)  More women die each year of lung cancer than of breast cancer  Women started smoking in substantial numbers about 10– 15 years later than men  Smoking cessation efforts need to increase for women Anatomy of the Lungs

Pathology  Tumors arising from the respiratory epithelium (bronchi, bronchioles, and alveoli)  Mesotheliomas, lymphomas, and stromal tumors (sarcomas) are distinct from epithelial lung cancer  Four major cell types make up 88% of all primary lung neoplasms : o Squamous or epidermoid carcinoma, o small cell (also called oat cell) carcinoma, o Adenocarcinoma (including bronchioloalveolar), o Large cell carcinoma Histologic Distinctions between SCLC and NSCLC include the following: SCLC  Scant cytoplasm  Small hyperchromatic nuclei with fine chromatin pattern  Indistinct nucleoli with diffuse sheets of cells NSCLC  Abundant cytoplasm  pleomorphic nuclei with coarse chromatin pattern  prominent nucleoli  glandular or squamous architecture Types of Lung Cancer Small Cell Lung Cancer  Also known as oat cell carcinoma or small cell undifferentiated carcinoma,  Very early metastasis to mediastinum, hilar lymph nodes and other organ sites

Lung Cancer: Risk Factors  Family History of Lung Cancer - inherit defective genes  Smoking & Second-Hand Smoke  Radon  Asbestos Symptoms  Persistent cough  wheeze and stridor  dyspnea  Sputum streaked with blood  Chest or back pain  Voice change  Recurrent pneumonia or bronchitis  Swelling in the neck or face Lung Cancer Staging Procedures Pretreatment Staging Procedures for Patients with Lung Cancer All Patients :  Complete history and physical examination  Determination of performance status and weight loss  Complete blood count with platelet determination  Measurement of serum electrolytes, glucose, and calcium; renal and liver function tests  Electrocardiogram  Skin test for tuberculosis  Chest x-ray  CT scan of chest and abdomen  CT or MRI scan of brain and radionuclide scan of bone if any finding suggests the presence of tumor metastasis in these organs  Fiber optic bronchoscopy with washings, brushings, and biopsy of suspicious lesions unless medically contraindicated or if it would not alter therapy (e.g., very late stage patient)  X-rays of suspicious bony lesions detected by scan or symptom  Barium swallow radiographic examination if esophageal symptoms exist  Pulmonary function studies and arterial blood gas measurements if signs or symptoms of respiratory insufficiency are present  Biopsy of accessible lesions suspicious for cancer if a histologic diagnosis is not yet made or if treatment or staging decisions would be based on whether or not a lesion contained cancer Biopsy  Bronchoscopy combined with biopsy  Pleural biopsy  CT scan directed needle biopsy  Mediastinoscopy with biopsy  Open lung biopsy  Endoscopic esophageal ultrasound with biopsy

Small Cell or Advanced Non-small Cell Lung Cancer  For small cell lung cancer, all the procedures under "All Patients," plus the following: o CT or MRI scan of brain o Bone marrow aspiration and biopsy (if peripheral blood counts abnormal)  For non-small cell lung cancer or cancer of unknown histology, all the procedures under "All Patients," plus the following: o Fiberoptic bronchoscopy if indicated by hemoptysis, obstruction, pneumonitis, or no histologic diagnosis of cancer o Biopsy of accessible lesions suspicious for tumor to obtain a histologic diagnosis or if therapy would be altered by finding of tumor o Transthoracic fine-needle aspiration biopsy or transbronchial forceps biopsy of peripheral lesions if fiberoptic bronchoscopy is negative and no other material exists for a histologic diagnosis o Diagnostic and therapeutic thoracentesis if a pleural effusion is present Treatments/Interventions Chemotherapy & Radiation – To improve local tumour control, and to the brain, to reduce the risk of brain metastases called (prophylactic cranial irradiation, or PCI). Non-Small Cell Lung Cancer  Squamous cell carcinoma (SCC)  Adenocarcinoma  Large Cell Carcinoma

Squamous Cell  Rate of growth: slow  Metastasis: Late metastasis mainly to hilar lymph nodes, chest wall and mediastinum  S/sx: airway obstruction, cough, sputum production  Dx: sputum analysis, biopsy, immunohistochemistry, electron microscopy,bronchoscopy Adenocarcinoma  Rate of growth: moderate  Mestastasis: early to hilar nodes, chest wall and mediastinun  S/sx: pleural effusion, cough  Dx: fiber-optic bronchoscopy, radiography, electron microscopy Large cell carcinoma  Rate of growth: Fast  Metastasis: early, extensive metastasis in the thoracic structures and other organs  S/sx: cough, hemoptysis, chest wall pain, pleural effusion, sputum production, pneumolnia –induced airway obstruction  Dx: bronchoscopy, sputum analysis,electron microscopy Staging (determined after the biopsy and more imaging test) Non-Cell lung cancer is divided into five stages: Stage 0 CA has not spread beyond the inner lining of the lung organ Stage I CA is small and hasn’t spread to the lymph nodes Stage II CA has spread to some lymph nodes near the original tumor Stage III CA has spread to nearby tissue or spread to far away lymph nodes Stage IV CA has spread to other organs of the body such as the other lung, brain or liver Non-small Cell Lung Cancer Who Have No Contraindication to Curative Surgery or Radiotherapy with or without Chemotherapy All the above procedures, plus the following:  PET scan to evaluate mediastinum and detect metastatic disease  Pulmonary function tests and arterial blood gas measurements  Coagulation tests  CT or MRI scan of brain if symptoms suggestive  Cardiopulmonary exercise testing if performance status or pulmonary function tests are borderline  If surgical resection is planned: surgical evaluation of the mediastinum at mediastinoscopy or at thoracotomy  If the patient is a poor surgical risk or a candidate for curative radiotherapy: transthoracic fine-needle aspiration biopsy or transbronchial forceps biopsy of peripheral lesions if material from routine fiberoptic bronchoscopy is negative Treatments/Interventions  Surgery- part or all of the lung is removed  Radiation therapy-uses powerful x-rays or other radiation to kill CA cells  Chemotherapy- uses drugs to kill or to stop new CA cells from growing  Laser therapy- a small beam of light burns and kills CA cells  Photodynamic therapy-uses light to activate a drug in the body, which kills CA cells  Watchful waiting- in rare cases, the person may only be monitored until symptoms change. TREATMENTS DEPEND UPON THE STAGE OF CANCER. RECOMMENDATIONS  Prevention  Access to lung cancer team  Selection of patients for radical treatment  Radiotherapy using CHART  Psycho-educational interventions such as: o Breathing re-training  Palliative approach care  Chemotherapy

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A hormone-dependent disease Women without functioning ovaries who never receive estrogen-replacement therapy do not develop breast cancer The three dates in a woman's life that have a major impact on breast cancer incidence are: o Age of menarche – 16 have only 50-60% o Age at first full-term pregnancy, by age 18 have a 30-40% lower risk o Age at menopause, 10 years before the median age of menopause (52 years)

Risk Factors  Gender: 100 times more frequently in women than in men  Age: Risk increases with age  Family history: the risk doubles  Personal history: atypical hyperplasia ductal or lobular in situ.  Reproductive factors: Nulliparity or having first full-term pregnancy after age 30.  Menstrual factors: Menarche before the age 12 or onset of menopause after age 55  Oral contraceptives  Estrogen /progestin replacement therapy  Dietary factors: alcohol, fat intake  Exposure to radiation – women who received mantle radiation for Hodgkin’s disease at a young age. o Inversely correlated with age (very low risk if exposure occurred after the age of 40.

BREAST CANCER
     Most common CA in women Caucasian women African-American women Asians and Hispanics are at lower risk American Indian women least likely to have breast CA

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Biopsy o o

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Fine needle aspiration (determine Solid and cystic masses) Core needle biopsy (with or without ultrasound/for both palpable or non-palpable breast masses) Stereotactic biopsy (useful in sampling small, non palpable lesions) Open biopsy

Types of Breast Cancer Lobular Carcinoma In Situ (LCIS)  Breast cancer that is confined to the milk-producing glands (lobules) of the breast  Will not progress to invasive breast cancer  Referred to as lobular neoplasia (LN)  Premenopausal women between the ages 40 and 50  Not usually found on a mammogram and generally does not produce a lump  May be treated with hormonal therapy (tamoxifen)  Highly treatable There are 3 main approaches to treatment:  Chemoprevention o Tamoxifen (Nolvadex) o Raloxifene (Evista)  Preventive surgery o Prophylactic mastectomy o Removes both breasts not just the affected side o To reduce risk of developing invasive breast cancer o It is an OPTION o Isn’t urgent Ductal Carcinoma In Situ (DCIS)  Breast cancer that is confined to the milk ducts of the breast  Not invasive  Can be detected on a mammogram and usually produce a lump  The most common is breast-conserving surgery with or without radiation. milk-producing glands (lobules), milk ducts, and connective tissue (stroma) Standard treatment options for DCIS include:  Lumpectomy followed by radiation therapy  Mastectomy  Hormonal therapy  Chemotherapy Invasive (or infiltrating) ductal carcinoma (IDC)  Starts in a milk passage (duct) of the breast, breaks through the wall of the duct, and grows into the fatty tissue of the breast.  It may be able to spread (metastasize) to other parts of the body through the lymphatic system and bloodstream The treatments for invasive ductal carcinoma fall into two broad categories:  Local treatment for IDC o Surgery and Radiation Therapy  Systemic Treatment for IDC o Chemotherapy o Hormonal Therapy o Targeted Therapies Invasive (or infiltrating) lobular carcinoma  Starts in the milk-producing glands (lobules)  It can spread (metastasize) to other parts of the body  May be harder to detect by a mammogram than invasive ductal carcinoma The treatments for invasive lobular carcinoma fall into two broad categories:  Local treatment for ILC o Surgery and Radiation Therapy

Blood and lymphatic vessels are found within the stroma surrounding the lobules and duct Signs and Symptoms  Breast CA – found more frequently on the left side in the upper outer quadrant of the breast o Mass may be tender or painless  Features suggestive of a malignant mass include: o Hard, painless mass that may be fixed to the chest wall o Nipple discharge that is unilateral and serosanguinous  Skin dimpling and retraction  Redness, heat, tenderness, and edema  Skin ulceration  Nipple changes : moist eczematous, dry, or psoriatic  Peau d’orange (orange peel)  Palpable lymph nodes Diagnosis  Radiology o o o o

Mammography Ultrasound MRI- magnetic resonance imaging PET- positron emission tomography

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Systemic Treatment for ILC o Chemotherapy o Hormonal Therapy o Targeted Therapies

 Cover your entire breast, using the same hand movements described in before Treatment Plan  Surgery o Breast-conserving therapy (lumpectomy) o Limited removal of the tumor o Radiation therapy is required to complete local treatment o Choice for women without multifocal disease who have adequate tissue for good cosmesis.  Mastectomy o Removal of the entire breast o Performed based on patient preference  Exploration of the axillary nodes o Determines staging  Radiation therapy  Systemic chemotherapy  Systemic hormonal therapy  Immunotherapy  Supportive care Gynecologic Cancer Endometrial /Uterine Cancer

Less common types of breast cancer  Inflammatory breast cancer  Triple-negative breast cancer  Mixed tumors  Medullary carcinoma  Metaplastic carcinoma  Mucinous carcinoma  Paget disease of the nipple  Tubular carcinoma  Papillary carcinoma  Adenoid cystic carcinoma (adenocystic carcinoma)  Phyllodes tumor  Angiosarcoma General Patient Management Risk reduction 1. Chemoprevention  Tamoxifen prevention  Raloxifene –preventive agent  Approved to treat osteoporosis Assessment Screening and early detection 1. Breast self-examination (monthly beginning adolescence 2. Clinical breast examination- annually by skilled health care prof. 3. Annual mammography beginning at age 40 Breast Self Examination  Mirror shoulders straight and your arms on your hips.  Breasts :usual size, shape, and color.  evenly shaped without visible distortion or swelling.  Any changes?  Bring to doctor's attention:  Dimpling, puckering, or bulging of the skin.  nipple changed position or become inverted (pushed inward instead of sticking out).  Redness, soreness, rash, or swelling. Note: Best time to perform BSE is 7th-10th day from the first day of menstruation  Raise your arms and look for the same changes.  While you're at the mirror, gently squeeze each nipple between your finger and thumb and check for nipple discharge (this could be a milky or yellow fluid or blood).  Feel your breasts while lying down, using your right hand to feel your left breast and then your left hand to feel your right breast.  Use a firm, smooth touch with the first few fingers of your hand, keeping the fingers flat and together.  Cover the entire breast from top to bottom, side to side—from your collarbone to the top of your abdomen, and from your armpit to your cleavage.  Finally, feel your breasts while you are standing or sitting. Many women find that the easiest way to feel their breasts is when their skin is wet and slippery, so they like to do this step in the shower.

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Most common gynecologic malignancy Arises from the epithelial lining of the uterus Primarily affects postmenopausal women 55-70 years of age Most present with early stage disease Overall 5-year survival rate about 85%

Risk Factors/Etiology  Obesity  Hypertension  Diabetes  History of infertility, breast or ovarian cancer  Irregular menses or failure to ovulate  Prolonged estrogen replacement therapy  Endometrial hyperplasia Signs and Symptoms  Postmenopausal vaginal bleeding  Irregular or heavy menstrual flow  Pain, particularly in the lumbosacral, hypogastric or pelvic regions, and an enlarging non-pregnant uterus can be signs of advanced disease. Diagnostic Tests 1. Pelvic Exam 2. PAP tests 3. Trans-vaginal ultrasound 4. Biopsy - dilation and curettage (D&C) General management strategies  Total abdominal hysterectomy and bilateral salpingooophorectomy (TAH-BSO) with pelvic and paraaortic lymph node dissection  Intracavitary or external beam radiation therapy Endometrial CA Staging and Treatment  Stages I and II- Tumor confined to the uterus o Surgery  Total abdominal hysterectomy(TAH) and bilateral salpingo-oophorectomy

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(BSO), with pelvic and paraaortic lymph node dissection o Radiation Therapy  Localized  Intracavitary or external beam radiation therapy o Chemotherapy/Hormonal therapy  Not shown to be effective as adjuvant therapy.  May be used in disease recurrence. Stage III- Tumor extends to fallopian tubes, ovaries, vagina, or pelvic lymph nodes; ascites present or positive peritoneal washing. o Surgery - TAH and BSO o Radiation therapy - Intracavitary or external beam radiation therapy o Chemotherapy and Hormonal therapy - Not shown to be effective Stage IV- involvement of bladder, rectum. Or bowel, or distant metastasis, most commonly to lungs, liver, bone or brain; positive inguinal lymph nodes. o Surgery - TAH and BSO, with pelvic and paraaortic lymph node dissection if patient is surgical candidate. o Radiation therapy  Distant  External beam radiation therapy in addition to surgery for local control of disease in pelvis. (if px is not surgical candidate) o Tamoxifen may be used. o Chemotherapy - Doxorubicin or high-dose platinum-based agent/taxol or both for advanced or recurrent disease, with or without surgery. o Hormonal Therapy - Synthetic progestational agents(magestrol acetate or antiestrogen agents

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Pelvic pressure Back ache Loss of appetite GI work up is usually negative Leg ache Anorexia Feeling of fullness even after light meal Rare-Abnormal vaginal bleeding Weight loss or gain with no known reason Ascites Pelvic mass

Ovarian Cancer Screening  Adnexal palpation  Transvaginal ultrasound  Serum CA-125 o Screening can result in invasive diagnostic workup o In one study, 0.6% had an elevated CA-125  Pelvic examination usually reveals a large pelvic mass in latestage disease.  Ultrasound, CT, or MRI evaluates the size and location of pelvic mass and may help diagnose lymph node involvement. Ovarian Cancer Staging and Treatment  Stage I- Tumor o Confined to one or both ovaries o Ascites present or positive peritoneal washings o Surgery - TAH and BSO with pelvic and paraaortic lymph node dissection omentectomy o Radiation Therapy - localized o Chemotherapy and Hormonal therapy - Usually not recommended  Stage II and III- Tumor spread beyond ovaries to the pelvis and other intraperitoneal structures, lymph nodes o Surgery - TAH and BSO with pelvic and paraaortic lymph node dissection , omentectomy o Chemotherapy and Hormonal therapy o Usually not recommended  Stage IV- Distant metastases,most commonly to pleura, lungs or liver parenchyma. o Surgery - TAH and BSO with pelvuic and paraaortic lymph node dissection, possible omentectomy o Radiation therapy – Distant; Possible to the whole abdomen after surgery if residual disease less than 1 cm (significant morbidity) o Chemotherapy  Combination regimens  Cisplatin or carboplatin with cyclophosphamide or paclitaxel  Topotecan active anti-cancer agent. o Hormonal Therapy - Tamoxifen and magestrol acetate CERVICAL CANCER  Lower part of the uterus  Connects the body of the uterus to the vagina (birth canal)  Begins in the lining of the cervix  Cells change from normal to precancer (dysplasia) and then to cancer  Third most common female reproductive cancer Types  Squamous cell cancer - Cancer of flat epithelial cell  Adenocarcinomas - Cancer arising from glandular epithelium  Adenosquamous carcinomas - Features both types Risk Factors  Human papillomavirus infection (HPV)

Ovarian Cancer Arises from the surface epithelium of the ovaries Accounts for about one third of all cancers of the female reproductive tract and a little more than half of all deaths from gynecologic CA

Risk Factors  Family history o One 1st degree relative → 5% risk o Two 1st degree relatives → 10x more likely o No relatives → 1.5% risk  Reproductive history o Early menses o Never given birth o First child after age 30 o Menopause after age 50  Use of fertility drugs  Estrogen - only Hormonal Replacement Therapy  Genetic syndromes o Breast-ovarian syndrome o Hereditary non-polyposis colon cancer syndrome  Age  High-fat diet  Exposure to asbestos or talc Clinical Manifestations  Bloating sensation  Abdominal swelling  Long-term stomach pain or gas pain

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Sexual behavior (SEXUAL INTERCOURSE BEFORE AGE 17) MULTIPLE SEX PARTNERS Smoking HIV infection Chlamydia infection Diet Oral contraceptives Multiple pregnancies Low socioeconomic status Maternal use of Diethylstilbestrol (DES) Family history

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Radical hysterectomy and pelvic lymph node dissection - Removal of entire uterus, surrounding tissue, upper part of the vagina, and lymph nodes from the cervix.

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Radiation Chemotherapy

Signs and symptoms  Thin watery vaginal discharge - Seen after intercourse or douching, may go unnoticed  Abnormal vaginal bleeding  Increased vaginal discharge  Pelvic pain  Pain during sexual intercourse Diagnostic Test  Cervical Cytology  (Pap Test) o Cells are removed from the cervix and examined under the microscope. o Can detect epithelial cell abnormalities o Atypical squamous cells o Squamous intraepithelial lesions o Squamous cell carcinoma (likely to be invasive)  Colposcopy - cervix is viewed through a colposcope and the surface of the cervix can be seen close and clear.  Cervical Biopsies o Colposcopic biopsy – removal of small section of the abnormal area of the surface. o Endocervical curettage – removing some tissue lining from the endocervical canal.  Coning – cone-shaped piece of tissue is removed from the cervix

PRECURSOR or PREINVASIVE LESIONS - mild to moderate dysplasia (stage I and II) 1. Cryotherapy 2. Laser therapy 3. LEEP 4. Cone biopsy or Conization

INVASIVE CANCER 1. Surgery  Total hysterectomy  Radical hysterectomy  Radical vaginal hysterectomy  Bilateral pelvic lymphadenectomy  Pelvic exentration  Radical trachelectomy 2. Radiation  External radiation  Internal radiation o Intracavity o Brachytherapy 3. Chemotherapy  Cisplatin (Platinol)  5-Fluorouracil (Efudex)  Paclitaxel (Taxol)  Ifosfamide (Ifex) VULVAR CANCER Risk Facors  Age >60 years  Chronic vulvar irritation  History of lower genital tract malignancy  History of infection HPV, or other STDs  Exposure to coal tar derivatives Signs and symptoms  Mass /growth in the vulvar area  Some are asymptomatric  Vulvar bleeding may occur due to the irritation by the tumor  Pain Diagnostic tests  PE of external genitalia  Vulvar biopsy of a palpable mass  Observable lesion  Colposcopy  Pap smear of the cervix  Chest x-ray – to R/O metastatic dse. In the pleural cavity  Cystoscopy- to R/O bladder or renal involvement  CT scan or MRI- disease spread General Management  Surgical removal o Vulvectomy o Total pelvic exenteration  Radiotherapy – treat groin or pelvic lymph node disease. Stage I and II  Tumor confined to vulvar region/perineum  SURGERY - Radical vulvectomy  RADIATION THERAPY o Localized o Not indicated as primary treatment  CHEMO/HORMONAL therapy - Not shown to be effective Stage III

Staging FIGO System (International Federation Of Gynecology and Obstetrics) Has five stages – 0 to 4 Stage 0 Carcinoma in situ Stage 1 Invaded cervix, but has not spread. Stage 2 Has spread to nearby areas, not leaving pelvic area. Stage 3 Cancer has spread to the lower part of the vagina. Stage 4 Cancer has spread to nearby organs; metastasis. Treatment  Surgery o Preinvasive cervical cancer  Cryosurgery  Laser surgery  Conization o Invasive cervical cancer  Simple hysterectomy - Removal of the body of the uterus and cervix

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Tumor spread to lower urethra, anus, vagina, or unilateral regional lymph node metastasis. SURGERY - Radical vulvectomy RADIATION THERAPY o Regional o Useful for patient who is a poor surgical risk Chemo/Hormonal Therapy – not effective

Stage IV  Metastases to upper urethra, bladder, rectal mucosa, pelvic bone, regional or distal lymph nodes or distant metastatic disease.  SURGERY o Radical vulvectomy o Total pelvic exenteration  RADIATION THERAPY o Distant o May be used to shrink non resectable tumor  CHEMOTHERAPY o Used as palliation o Active agents include: o Bleomycin o Methotrexate  HORMONAL therapy - Not shown to be effective