head and neck cancer treatment options Flashcards
most types of head and neck cancer begin in what type of cells?
squamous cells that line the moist surface inside the head and neck
what accounts for nearly 90-95% of head and neck cancer tumors?
squamous cell carcinoma
what can cause cancers in the back of the throat?
Oral human papilloma virus (HPV) (most common STD)–> oropharyngeal cancers
what is the key to increasing the survival rate for head and neck cancers?
early detection
head and neck cancers are —- of all cancer
3-5%
are women or men more affected by h & n cancers
men more than women
oral and pharynx cancer is —- of all h&n cancers
85%
chemical carcinogenesis
“multi-step” process
two hit theory–more than one agent for production of a tumor
viral associated etiopathogenesis
HPV types 16 and 18 – significant cause of OSCC in young people
there are about —– strains of HPV and —- are linked with h & n cancer
100 stains and 40-60 are linked with H & N cancer
how does HPV cause caner
HPV oncoproteins E6 and E7 bind and degrade tumor suppressor genes p53 and RB, preventing their protective function against cancer by loss of repair or apoptotic function
evolution of oral-oropharyngeal carcinoma
- tobacco era
- organ preservation
- improvements in radiation
- HPV
- minimally invasive surgery
- immunotherapy
intensity modulated radiation therapy
- shapes the radiation beam to closely fit the area of the cancer
- reduction in injury to surrounding tissue (salivary glands)
radiostic necrosis
an extraction site doesn’t heal in a person after radiation is given
cytotoxic therapy does what?
targets the pathway of tumor growth
TORS and TLM
trans-oral robotic surgery and transoral laser microsurgery
both are minimally invasive surgeries
radiotherapy has traditionally relied on — but now its evolving to use —-
CT and now they use PET scans more
why do they use PET scans more?
it has superior tumor detection capability which will lead to better patient outcomes
is there a difference between PET-CT and neck dissection?
survival is similar with both but doing PET involved less operations and it was more cost effective
acute oral complications of radiation therapy
oral mucositis
infection
salivary gland dysfunction
taste dysfunction
chronic oral complications of radiation therapy
mucosal fibrosis and atrophy xerostomia dental caries soft tissue necrosis osteoradionecrosis taste dysfunction muscular/cutaneous fibrosis infection
LINAC
- standard radiotherapy machine
- multileaf collimator
- form shapes to precisely fit area
- tumor receives a very high dose and normal healthy cells nearby receive a much lower dose
- each beam can vary in intensity so different doses of radiation can be given across a tumor
IMRT can reduce the risk of —
long term side effects and xerostomia
cell cycle specific anti-tumor agents
- work against proliferating cells
- bleomycin (G2)
- antimetabolites (S)
- taxanes (M)
FDA approved cell cycle specific anti-tumor agents
- abitrexate (methotrexate)–antimetabolite
- blenoxane (bleomycin)–antibiotic (G2)
- docetaxel (taxane) (M)
- cetuximab (EGFR inhibitor)
combination therapy
T: docetaxel (taxotere)
P: cisplatin (platinol)
F: fluorouracil (antimetabolite)
cell cycle non-specific
- against resting and proliferative cells
- alkylating agents (cisplatin)
alkylating agents
- cisplatin
- form alkyl radicals which form covalent linkages with nucleophilicmoieties of DNA, RNA, and proteins
- prevent cell division by cross-linking strands of DNA –> make irreversible changes ( destructive to rapidly proliferating cells)
- mutagenic, teratogenic, carcinogenic, radiomimetic, oncolytic
- vary in solubility, mem transport, pharmacokinetics, clinical utility
- **myelosuppression/immunosuppression and susceptibility to infections are common
antibiotics against tumors
- bleomycin, doxorubicin and daunorubicin
- produced by streptomyces species to form irreversible complexes with DNA which then inhibit cell division
- work on different cell cycles as non-specific agents
antimetabolites
- methotrexate
- structural resemblance to folic acid, purines, and pyrimidines (building blocks of DNA)
- effect cell during S phase
- interfere with rapidly growing cells–> oral manifestations prominent
methotrexate
antimetabolite that inhibits conversion of DHF to THF by inhibition of dihydrofolate reductase enzyme
–results in decreased synthesis of thymidylic acid and inosinic acid thereby retarding DNA and RNA synthesis and protein synthesis is also inhibited
what is a noted feature of antimetabolites?
oral manifestations (ulcerative stomatitis, glossitis, mucositis, gingivitis)
taxanes
- docetaxel
- act by binding to cellular beta-tubulin, increase its polymerization and promote microtubule assembly
- inhibits tubulin depolymerization
- cells become arrested in M phase of cell cycle
- sensitize cells to radiation
vinka alkaloids
arrest cell division in metaphase by binding to microtubular protein tubulin that forms the mitotic spindles
direct toxicities of cancer chemo
a. bone marrow–neutropenia, thrombocytopenia, anemia
b. gastrointestinal mucosa–mucositis, N/V/diarrhea, nutritional disturbances
c. oral mucosa
d. skin
e. hair follicles
f. gonads
other toxicities of cancer chemo
heart (doxarubicin) liver (cyclophosphamide) lung (**bleomycin) cns (vincrestine) kidney (methotrexate**)
characteristics of ideal molecular targets
- found on cancer cells
- differentially expressed or differentially functional in tumor vs nontumor host tissues
- specific to cancer cells
- causally related to tumor cell viability, progression, or both
- involved in several aspects of carcinogenesis pathway
- measurable in diagnostic tumor material
potential targets of targeted cancer therapy
- extracellular blockade of HER/EGFR (human epidermal growth factor)
- intracellular blockade of HER/EGFR
- inhibition of growth inhibitory signals
- evasion of programmed cell death and immortalization
- angiogenesis
- tissue invasion and metastasis
options of targeted therapy
- monoclonal antibodies (MAbs) **
- small-molecule inhibitors **
what drug provides an extracellular blockade of HER/EGFR for treatment of H&N cancer
cetuximab
adverse effects of antibodies as cancer therapeutics
- anaphylaxis early in administration
- hematological toxicity
- neutropenia–> increased risk of infection
- cardiac failure and pulmonary complications
