Oncology (not done on slide 29)

cancer

“one renegade cell”

“one good cell goes bad”

Genetic but not necessarily inherited

differentiation

normal cells change physically and structurally as they develop to form different body tissues; differentiated cells perform specific physiologic body functions

undifferentiated

malignant cells lose differentiation and may no lnger be recognizable to parent cell

dysplasia

disorganization of cell from its normal size, shape, or organization

benign, mallignant, or premalignant — will reverse itself or progress to cancer

metaplasia

early dysplasia

hyperplasia

increased number of cells resulting in increased tissue mass; presence increases risk of later development of solid tumor cancers

tumors

aka neoplasms

abnormal growth of tissues serves no useful purpose

competes for blood supply and nutrients

primary tumor

normally local ot strucutre

“where it starts”

secondary tumor

arise from cells that have spread from other part of the body (metastasis)

Carcinoma in situ

localized, pre-invasive, possibly premalignant tumor of epithelial tissue; contained within host organ and has not broken through basement membrane

classifications

cell type

tissue of origin

degree of differentiation

anatomic site

benign or malignant

Cell types

epithelium (carcinomas)

Connective and muscle (sarcoma)

nerve (Astrocytoma)

lymphoid (Lymphomas)

Hematopoietic (leukemias, multiple myeloma, myelodysplasia, myeloproliferative syndrome)

benign

relatively harmless and does not spread to or invade other tissue; if large enough may obstruct normal tissues and impair body functions

Staging and Grading

every cancer has its own unique staging system

Staging and Intent of treatment for: Stages I, II, or III

Usually can be surgically removed

higher stage = less likely curable, but still treated with curative intent

surgery, chemotherapy, radiation may be used individually or in combination to maximize potential for cure

treating with Curative intent

Staging and Intent of treatment for: Stage IV

usually cannot be surgically removed

exception: testicular cancer (stage IV does not exist)

surgery, chemotherapy, and radiation used to ensure best quality and quantity of life

treating with Palliative intent

Curative intent

short term toxicity via chemotherapy for long term cure

treatment regimens standardized to maximize opportunity for cure

patients may forego treatment for many reasons

palliative intent

less likely to accept toxicity unless high chance or long-term remission

treatment regimens varied and tailored to patient’s situation

palliative ≠ hospice

Risk factors for cancer

heredity

advancing ages ~50+ years

lifestyle - tobacco/alcohol use, diet/nutrition, and sexual/reproductive behavior

geographic location and environmental variables — exposure to different carcinogens

ethnicity (racial and ethnic minorities suffer disproportionately from cancer

precancerous lesions and some benign tumors may undergo later transformations into cancerous lesions

stress

Pathogenesis

theory of oncogenesis

cancer stem cell hypothesis

tumor biochemistry and pathogenesis

cancer and the immune system

theory of oncogenesis

complex, multi-step process by which normal cells turn into cancer cells

involves genetic changes resulting in cell growth and abnormal behavior

may be activated by carcinogen exposure

anti-oncogenes, aka tumor suppression genes also exist which, when activated, may regulate growth and carcinogenesis

cancer stem cell hypothesis

not all cancer cells are the same

different functional and morphologic cancer cells exist in a single tumor

hierarchical order in which abnormal stem cells from and feed a cancer

tumor or biochemistry and pathogenesis

carcinogenesis is a multi-step process after initial genetic damage or alteration of cellular DNA

Number of genetic events required for cell conversion debated, but for solid tumors may be as high as 7 or 8

cancer and the immune system

cancer immunosurveillance — immune system continuously searches for and destroys potentially cancerous cells

metastases

cells break away from primary tumor and travel via blood or lymphatic system to other parts of the body and become trapped in the capillaries of organs. there they infiltrate the tissue and grow new tumor deposits

5 most common sites of metastases

lymph nodes

liver

lung

Bone (matters most)

brain

incidence of metastasis

30% newly diagnosed cancer have clinically detectable metastasis

30-40% of remaining persons clinically free of metastasis have occult or hidden metastasis

diagnosis

early detection and staging

tissue biopsy

biologic tumor markers

molecular profiling

early detection and staging

Lab values, radiography (x-rays), endoscopy, isotope scans, CT scans, mammography, MRI, and biopsy

Tissue biopsy

tissue sample obtained by various techniques to study the tumor (eg. curettage, fluid aspiration, fine needle aspiration, dermal punch, endoscopy, open surgical incision)

biologic tumor markers

substances produced and secreted by tumor cells found in blood stream

not diagnostic itself, but signals malignancies, level of marker often correlates with extent of disease

E.g. CEA (large bowel, stomach, pancreas, lungs, breasts); CA-125 (ovarian); CA-27-29 (breast); PSA (prostate)

may also be used to evaluate response to treatment or detect tumor recurrence

molecular profiling

provides additional information to oncologists related to aggressiveness of tumor, potential response to treatment, and prediction of risk within a family

primary treatment modalities

surgery

irradiation therapy

chemotherapy

immunotherapy

anti-angiogenic therapy

hormonal therapy

complementary and alternative (integrative medicine)

treatment: surgery

once mainstay, now used in conjunction with other therapies

curative (biopsy, removal) or palliative (relieve pain, alleviate pressure)

adjuvant therapy used after eradicates residual cells (micrometastases)

treatment: irradiation therapy

destroys dividing caner cells by breaking hydrogen bonds between DNA strands in cancer cells

advances have improved dose delivery and precision mapping

goal: ablate cancer cells and spare normal tissues

treatment: chemotherapy

chemical agents destroy cancer cells, may also harm normal cells in the process

useful when treating widespread metastatic disease

treatment: immunotherapy

relies on biologic response modifiers to change relationship between tumor and host by boosting the host’s response

targeted therapies “smart drugs”

hematopoietic cell transplantation (including bone marrow transplantation)

targeted therapies “smart drugs”

- interfere with pathway a cell takes to become a cancer

hematopoietic cell transplantation

provides method of rescue from bone marrow destruction while allowing higher doses of chemotherapy

anti-angiogenic therapy

newer strategy under investigation, limited use currently

blocks formation of new blood vessels supplying cancer cells

may serve beneficial as maintenance therapy to control cancer

treatment: hormonal therapy

used for types of cancer affected by specific hormones (breast cancer)

E.g. (breast) blocks estrogen receptors in breast tumor cells that require estrogen to thrive

treatment: complementary and alternative (integrative medicine)

conventional treatment methods do not always relieve pain, fatigue, anxiety, and mood disturbances

some people cannot tolerate side effects of conventional treatment

E.g. acupuncture, reiki, body talk, hypnosis, mind-body techniques, massage, music, tai chi, qi gong, yoga, meditation, etc

Prognosis is influenced by

type of cancer

stage and grade of disease at diagnosis

availability of effective treatment

other factors include lifestyle, diet, nutrition, exercise, etc.

effects of cancer and cancer treatment

Pain

fatigue

paraneoplastic syndromes

nausea

dyspnea

infections

hair loss

changes in taste and appetite

muscle wasting

fluid retention

organ injury

ostomy placement

death

CRF

distress, persistent, and subjective tiredness or exhaustion related to cancer or cancer tx NOT proportional to activity and interferes with usual functioning

Paraneoplastic syndromes

signs and symptoms at a site distant from tumor metastasized sites

remote effects of malignancy

may involve ectopic hormone production by tumor cells

nonspecific symptoms: skin changes, neurologic changes, anorexia, malaise, diarrhea, weight loss, and fever

E.g. MSK manifestations include gradual weakness, specifically affecting proximal muscles

Stiff person syndrome

Clinical Prediction of Outcomes

performance status

Originally used in clinical trials, now commonly used to assess functional level for newly diagnosed cases

comprehensive geriatric assessment

Performance status

Rough measure of capacity for activity

ECOG (eastern Cooperative Oncology Group): 0-4 (normal, unrestricted activity, bedridden, fully dependent)

Karnofsky perfomance scale: 100-0 (normal to dead)

Pros for Perfomance evaluation

accreditation requirement for oncology centers

linked to tolerance to therapy

quick and inexpensive to administer

for many cancers, specifically solid tumors, is linked to prognosis and survival

Cons for Performance Evaluation

designed to determine “fitness” for chemotherapy

does not break out different domains or settings

doesn’t directly address functional abilities and/or limitations

Comprehensive geriatric assessment

age is associated with higher mortality, especially for adults 60 y/o and older

helps identify individuals likely to benefit from cytotoxic treatment

adjustments may be needed related to renal and cardiac function since cardiac and neurotoxicity are common in persons over the age of 65

Pros to Comprehensive assessment

multiple domains are included

provides a very detailed and robust picture of pt’s condition

Cons to comprehensive assessment

only validated in geriatric population

appropriate referral services may not be available to treat some of the conditions discovered

no component related to patients goals or wishes

expensive and time consuming

only represents one point in time

Domains of concern for persons with cancer

pain

loss of independence

inability to speak or eat

changes in continence or ostomy placement

financial impact

burden to others

anxiety and depression

no longer trusting one’s body

“the tyranny of positive thinking”

Breast Cancer categories

ductal carcinoma in situe (DCIS) (most common type of in situ cancer)

Invasive ductal carcinoma (IDC) (most common invasive breast cancer)

medullary, tubular, mucinous, papillary, and cribriform — less common subtypes of ductal carcinoma

invasive lobular carcinoma (2nd most common type of invasive cancer)

inflammatory breast cancer (rare)

Paget disease of breast cancer (rare form of ductal carcinoma)

male breast cancer

Risk factors of Breast cancer in women

gender and hormone exposure

age

race and ethnicity

personal history, family history, and heredity

diet, weight gain, obesity

radiation exposure

alcohol

other environmental factors

Risk factors of Breast Cancer in men

age

heredity

stage at diagnosis (early stage at diagnosis has 83% survival)

high estrogen exposure

kinefelter syndrome

chest radiation

Protective factors (breast cancer)

younger age at first live birth, more than two births, breastfeeding, and regular weekly physical activity

What can happen in persons treated with curative intent with breast cancer

phantom pain following mastectomy

skin and soft tissue changes related to surgery and/or radiation therapy

joint and tendon pain related to hormonal blocking agents

lymphedema, especially pts with axillary lymph node involvement

types of lung cancer

small cell lung cancer (SCLC) - 10-15%; small cell carcinoma

Non-small cell lung cell (NSCLC) - 80-85%

• Squamous cell carcinoma

• adenocarcinoma

• large cell carcinoma

Risk factors for Lung Cancer

cigarette smoking

marijuana

environmental tobacco smoke

occupational exposure

links between COPD, emphysema, and lung cancer

nutrition

genetics

What happens in persons treated with curative intent with lung cancer

phantom pain after lung surgery

skin and soft tissues changes related to surgery and/or radiation therapy

decreased reserve

rapid desaturation with activity

metastases with lung cancer

most common because of venous drainage; lungs are first organ to filter malignant cells

dry, persistent cough often first symptom

pleural pain often indicates pleural invasion and SOB occurs with a malignant pleural effusion

bronchial invasion often presents as hemoptysis with primary lung cancer of metastatic disease

Etiology of colorectal cancer

cause unknwon

environmental familial factors

• genetic syndrome occur < age 40

• 75% occur in persons with no known predisposing factors

Risk factors for colorectal cancer

age

male gender

personal histroy of adenomatous polyps

inflammatory bowel disease — ulcerative colitis and Crohn’s disease

family history of colon cancer

obesity and inactivity

cigarette smoking and excessive alcohol use may increase risk

geographic distributions — diets in low fiber and high in animal fat, sugar, and protein; large amounts of red, processed meat over a long period of time

What happens in persons treated with curative intent with colorectal cancer

continence issues

possible ostomy placement

pain syndromes (referred pain), specifically rectal cancer, may mimic sciatica

nutritional issues

Soft Tissue Sarcomas

e.g. rhabdomyosarcoma, striated muscle

predominantly identified in adults

osteosarcoma

e.g. ewing bone sarcoma

generally diagnosed in children or adolescents or older adults >60 linked to longstanding bone disease

risk factors soft tissue sarcoma

radiation to treat other cancers

familial cancer syndromes - e.g. neurofibromatosis, gardner syndrome, etc

damaged lymph system

chemical exposure

risk factors for osteosarcoma

age

heigh

sex

race and ethnicity

radiation to bones

certain bone diseases - Paget’s disease of bone, hereditary multiple ostochondromas, fibrous dysplasias

inherited cancer syndromes — e.g. hereditary retinoblastoma, Li Fraumeni syndrome, etc

Limb-sparing therapy (for sarcoma)

combination of chemo and radiation followed by surgery

not always effective

may leave non-functioning limb if unsuccessful

amputation (tx for sarcoma)

can be used after limb-sparing attempt or as primary tx

often younger pts

some pts may decline amputation even if curative

Types of skin cancers

benign tumors

precancerous lesions

non-melanoma

melanoma

benign tumors with skin cancer

seborrheic keratosis

nevi (moles)

precancerous lesions (skin cancer)

actinic keratosis

non-melanoma (skin cancer)

basal cell carcinoma

squamous cell carcinoma

risk factors for non-melanoma

older age

fair complexion

males

inability to tan

prolonged redness after sun exposure

Caucasian race

residence near equator

prolonged sun exposure

family hz

immunosuppresion

pre-malignant conditions, such as chronic skin irritation

radiation therapy

exposure to local carcinogens like tar and oil

previous hx of basal cell carcinoma increases risk by 50%

Risk factors melanoma

>15 years old

fair complexion (blond/red hair, fair skin, blue eyes)

Caucasian race

sun sensitivity and excessive sun exposure

+ family hx

presence of many moles, especially atypical moles

previous hx of melanoma

medical hx including chronic osteomyelitis, burn scars, chronic skin ulcers

residence near equator

Previous hx of basal cell carcinoma increases risk of developing melanoma 3x

Clinical Manifestations of Skin Cancer

more than 80% squamous cell carcinomas occur in head and neck region

more than 65% basal cell carcinomas occur in head and neck region

symptoms of metastasis include: malaise, weakness, fatigue, anorexia, and pain

Skin cancer diagnosis

contingent upon biopsy and study of tissues

Skin cancer treatment

depends on size, location and depth, but may include curettage, electrodesiccation, chemotherapy, surgical excision, and irradiation

melanomas — surgical resection, possible lymphadenectomy, chemotherapy, radiation therapy

Skin cancer Prognosis

all major tx methods have excellent rates of cure, however, prognosis is better with well differentiated lesion

melanoma - 5 year survival rate if depth of lesion is < .76 mm

Role of the PT with cancer tx

generalized strengthening, mobility, and promotion of well-being

• ability to walk (2 min walk test)

• gait and balance

• fatigue

• depression

• ADLs

Select malignancy interventions

Malignancy interventions: sarcoma

limb loss interventions, prosthetic training

malignancy interventions: lung cancer

loss of functional lung capacity, endurance training

malignancy interventions: breast and ovarian cancer

lymphedema, manual lymph drainage, wrapping

malignancy interventions: CNS tumors

specific deficits based on anatomic location, vestibular therapy, balance therapy, etc

malignancy interventions: treatment specific toxicities

nerve damage or neuropathy, etc from chemotherapy and radiation

PT implications general overview

involved in all phases of care (prevention, restoration, support, palliative care, hospice)

therapists treats the disease as well as the effects of the medical interventions implemented

therapists should advocate for pt access prior to surgery or impairment to anticipate and prevent complications

as medical interventions improve and survival rate increases, shift from searching for a cure to management of cancer as a chronic condition

recognizing psychosocial and spiritual status and cultural beliefs may be a driving factor for successful outcomes

PT implications for benign tumors

may be asked by client to examine unusual skin lesions or aberrant tissue (see skin cancer screening)

refer pt to medical professional for thorough examination, especially those with additional risk factors ( DO NOT MEDICALLY DIAGNOSE)

Cancer, physical activity, and Exercise Training with Cancer prevention

evidence supports moderate levels of physcial activity may affect cancer risk (moderate = 30-60 minutes at leas 5 days per week)

being sedentary is a risk factor for several of the most common types of cancer

being overweight or obese also increases cancer risk, possibly due to inflammation and abnormalities in immune function

research is ongoing in this area

Exercise for cancer survivors

beneficial throughout continuum of care, especially during early stages

survivors often decrease physical activity levels, especially if sedentary prior to diagnosis

individualized exercise program tailored to the individual is recommended

education regarding benefit may be needed