Solid Tumor Malignancies

Tumor Markers

Several tumor markers are utilized in clinical practice

• Carcinoembryonic antigen (CEA) (determines response to colon CA treatment/surrogate marker to identify recurrence)

• Epidermal growth factor receptor (EGFR) (determines if targeted drug therapy is appropriate in lung CA)

• Estrogen receptor/progesterone receptor (ER/PR) (determines if hormonal drug therapy is appropriate in breast CA)

• Human epidermal growth factor receptor 2 (HER2/neu) (determines if targeted drug therapy is appropriate in breast CA)

• KRAS mutation (determines if targeted drug therapy is appropriate in colon CA)

What percentage of chronic cigarette smokers develop lung cancer?

• <20%

Pathogenesis

• Lung carcinomas arise from normal bronchial epithelial cells that have acquired multiple genetic lesions caused by carcinogens. This chronic inflammation eventually leads to cytogenetic changes and transformation -> malignancy. Many of these molecular genetic changes result in impairment of normal cellular regulators and growth control pathways.

  • Activation of oncogenes

  • inhibition or mutation of tumor suppressor genes

  • production of autoceone (self-stimulatory) growth factors—> cellualr proliferation and malignant transformation

Lung CA: non-small cell and small cell

• Staging- lung cancer

  • Staging: non-small cell lung cancer (80%)

    • Tumor size

    • nodal involvement

    • metastasis

  • Staging small-cell lung cancer (~15%)

    • limited stage

    • extended stage

  • Metastatic sites: adrenal glands, brain, bone, liver

    • Prognosis:

      • Localized disease versus metastatic disease

• Non-small cell lung cancer histology

  • Adenocarcinoma ( non-squamous):

    • Most common subtype overall

    • most common in non-smokers

    • peripheral lung portion

  • Large cell (non-squamous)

    • poor prognosis

    • peripheral lung portion

  • Squamous cell

    • closely linked with smoking

    • central bronchial origin

• What is the biggest risk factor for developing lung cancer?

  • Cigarette smoking

    • Tobacco smoke contains tumor promoters, carcinogens, and cocarcinogenRisksk increases with the quantity and duration of cigarette consumption

  • cessation of of msoking for >5 years is associated with a gradual decrease in cancer risk

    • Quitting smoking for 10-15 years, lung cancer is still 2X that of a non-smoker

• Additional risk factors: lung cancer

  • Occupational or environmental exposure

    • Environmental respiratory carcinogens: radon gas released from soil and building materials, environmental exposure to secondhand smoke, air, pollution, and diesel exhaust

    • Occupational respiratory carcinogens: asbestos, rubber manufacturing, paving, roofing, painting, and chimney sweeping

  • Comorbodidties

    • Emphysema, COPD, Asthma, TB

  • Genetic predisposition

    • First-degree relative with lung cancer

• Signs and symptoms

  • Most common local symptomes

    • Cough, purulent sputum, dyspnea/wheezing, hoarseness

    • hemoptysis

    • localized chest pain, shoulder/arm pain

    • recurrent bronchititis or pneumonia

  • Metastatic disease-symptoms consistent with organ involvement

  • systamic symptomes -anorexia, unexplained weight loss

  • Paraneoplastic syndromes: A phenomenon mediated by humoral factors hormones) excreted by tumor cells or against tumor cells

    • SIADH (syndrome of inappropriate anti-diuretic hormone). ADH helps the kidneys control the amount of water your body loses through the urine. SIADH causes the body to retain too much water, which leads to low serum sodium

    • Hypercalcemia - increased calcium

    • Pleural effusion

Screening recommendation: Lung CA

• Increased risk:

  • May undergo testing for early lung cancer detection

    • Anual survelance (low dost CAT scan of the lungs)

  • Discuss potential benefits/harms and importance of multidisciplinary expertise in workup/therapy

    • treails evaluing the efficacy of lung cancer screening demonstrated some benefit in heavy smokers (> 20 packs years smoning history)

Diagnostic workup

• history and physical

• imagining studies: Chest x-ray, CT scans (chest, abdomen, and pelvis)

• Biopsy/cytology

  • Tumor biopsy for pathology review

  • cytology of pleural effusion

• Selective tumor marker

  • EGFR

  • PDL-1

Colorectal cancer

pathogenesis

Risk factors: non-modifiable

• age > 45 yo

• Personal history of colorectal polyps

• chronic inflammatory bowel diseases

  • uulcerativecolitis

  • Crohn’s disease

• genetic predisposition (significantly increase risk for colon CA)

  • FAP(familial adenomatous polyposis)

  • HNPCC (hereditary nonpolyposis colorectal cancer)

Risk factors: modifiable

• Diet:

  • High fat/ high red meat/ low fruits, veggies

  • Low fiber

• Obesity

  • Increased BMI

  • Physical inactivity

• Excessive alcohol intake

• chronic tobacco use

Signs and symptoms

• most common presenting symptoms

  • Asymptomatic at the early stage

  • change in bowel habits

  • melena or rectal bleeding

  • abdominal pain, discomfort, or distention

  • weight loss

• Metastatic disease

  • symptoms consitant with organ involvement

    • right upper quadrant pain or discomfort (lve metastasis)

• Screening tests

  • Fecal testing -once annually

    • Fecal immunochemical test (FIT)

    • Guaiac-based fecal occult blood test (gFOBT)

  • Flexible sigmoidoscopy -every 5 years or

  • Colonoscopy-every 10 years

• Screening recommendations:

• AAveragerisk 45 years of age

• Increased/ high risk

  • Early and more frequent screening

    • Start based on family history

      • First-degreeelative with Colon cancer- screening begins at 35 or 10 years earlier than the diagnosis age of the affected relative

    • Start based on personal history

      • FAP-screening begins at adolescence

      • Ulcerative colitis - screening begins 8 years after diagnosis

Diagnosis workup

• History and physical

• imaging status: colonoscopy

• Pathology:t tumourbiopsy foophthalmologygy review

• Carcinoembryonic antigen (CEA) tumor marker:

• KRAS testing:

  • tumot maker

  • identification in the biopsy sample