oncology *

Primary Induction Chemotherapy

Chemotherapy administered in patients with advanced cancer for which no alternative treatment exists.

Examples of cancers for Primary Induction Chemotherapy

Hodgkin's and non-Hodgkin's Lymphoma.

Neoadjuvant Chemotherapy

Use of chemotherapy in patients who present with localized cancer for which useful local therapies exist but may not be completely effective.

Adjuvant Chemotherapy

Chemotherapy used as an adjuvant to local therapy such as surgery or radiation.

Therapeutic Index

Lethal Dose of a Drug for 50% of the Population divided by the minimum effective dose for 50% of the population (LD50 / ED50).

Why do Disseminated Cancers respond well to Chemotherapy?

Disseminated Cancers generally have a high growth fraction.

Cell Cycle Specific Drugs

Drugs that work at specific phases in the cell cycle, including antimetabolites, taxanes, and vinca alkaloids.

Cell Cycle Nonspecific Drugs

Drugs that affect the cell cycle at any point, such as alkylating agents and anthracyclines.

Alkylating Agents

Chemotherapeutic agents that are cell cycle nonspecific and can cause abnormal base pairing.

Example of Alkylating Agents Adverse Effects

Bone marrow depression, nausea, vomiting.

Cisplatin

A platinum analogue used to treat testicular, ovarian, and solid tumors.

Examples of Antimetabolites

Methotrexate (folate antagonist), 6 Mercaptopurine (purine antagonist), 5 Fluorouracil (pyrimidine antagonist).

How does Methotrexate work?

Inhibits dihydrofolate reductase (DHFR), interfering with the formation of DNA, RNA, and cellular proteins.

Actions of Methotrexate

Cytotoxic (mainly on bone marrow), immunosuppressive, anti-inflammatory.

Mechanism of 6 Mercaptopurine

Requires metabolism to its active form to inhibit purine nucleotide synthesis.

Mechanism of 5 Fluorouracil

Requires activation via enzymatic reactions to interfere with DNA synthesis.

How do Vinca Alkaloids work?

Inhibit tubulin proliferation, disrupting the assembly of microtubules and causing mitotic arrest.

Mechanism of Antitumour Antibiotics

Bind to DNA causing RNA and DNA synthesis blockade and cell replication interference.

Examples of Hormones used in Chemotherapy

Glucocorticoids, Estrogens, Estrogen Antagonists.

Spread of Cancer to Bone

Associated with pain, hypercalcaemia, anaemia, infection risk, spinal cord/compression issues.

How do Bisphosphonates cause gastrointestinal toxicities?

By binding to calcium in the diet and causing nausea, vomiting, and other GI issues.

Purpose of Drug Combination

Maximize cell kill within a tolerated range of toxicity for each drug.

Definition of Efficacy in drugs

Maximal effect a drug can produce.

Definition of Toxicity in drugs

The degree to which a substance is poisonous or can cause injury.

Suspect Head & Neck Cancer when...

There is a non-healing ulcer, red/white patches, loose teeth, or persistent sore throat among other symptoms.

When to carry out Dental Extractions prior to Radiotherapy?

At least 10 days before radiotherapy.

Aims of Pre-Treatment Assessments

To avoid unscheduled interruptions to treatment, plan dental procedures, and assess post-treatment access.

Short Term Dental Implications of Oncology Treatment

Mucositis, infection, xerostomia, taste loss.

Long Term Dental Implications of Oncology Treatment

Altered anatomy, rampant caries, trismus, mastication difficulties, osteoradionecrosis, xerostomia.

Prevention of Dental Implications in Oncology Treatment

Maintain good oral hygiene, dietary advice, fluoride, saliva replacement, and jaw exercises.

Objectives of Obturators in Dental Rehabilitation

Restore partition between oral and nasal cavities, restore contours, replace dentition.

Hematological issues with Chemotherapy

Decreased red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia).

Patients at risk of developing MRONJ

Patients taking bisphosphonates, Denosumab, or anti-angiogenic therapies.

Prognostic Markers for Treatment Pathways

ER in breast cancer, HER2 in breast/gastric cancers, BRAF in melanoma.

Why is Chemotherapy given as Adjuvant Treatment?

To reduce risk of recurrence.

General Side Effects of Chemotherapy

Nausea & vomiting, fatigue, taste changes, bowel disturbances, renal/liver dysfunction.

Interval for Chemotherapy cycles

Given at 3 weekly cycles, usually 4 to 6 cycles.

Patterns in Blood Levels following Chemotherapy

Blood cells drop post Day 1 but gradually recover; risk if infection occurs at low levels.

Maximum Risk point during Chemotherapy Cycle

Between 7-14 days, specifically during Week 2.

Best time for Dental Treatment during Chemotherapy

Just before the next cycle, usually in Week 3.

Targeted Therapy for Cancers

Oral tyrosine kinase inhibitors and IV monoclonal antibodies.

Immunotherapy Definition

Using drugs to stimulate the body's immune response to disease.

Drugs used in Immunotherapy

PDL1 inhibitors like Pembrolizumab and immune checkpoint inhibitors like Nivolumab.

Effects of Drugs in Immunotherapy

Cause organ inflammation ('itis') but can also effectively control cancers.

Purpose of Bone Treatments in Cancers

To reduce risk of skeletal-related events (SREs) or decrease symptoms of SREs.

Examples of Osteoblastic Cancers

Prostate and breast cancers.

Examples of Osteolytic Cancers

Myeloma.

Clinical Consequences of Bone Metastases

Pathologic fractures, surgery or radiotherapy to bone, spinal cord compression.

Tumour Cells Damage Bone through...

Releasing growth factors and cytokines that stimulate osteoclasts for bone resorption.

Function of Radiopharmaceuticals

Bone targeted agents that bind to bone surface and cause local cancer cell damage.

Structure of Bisphosphonates

Composed of R1 and R2 chains; R1 binds to bone and R2 provides anti-resorptive properties.

Half Life of Bisphosphonates

0.5-2 hours with 50% uptake by skeleton; can remain in bone for 1-10 years.

Mechanism of Denosumab

Blocks interaction between RANKL and RANK receptor on osteoclasts to prevent their formation.

Denosumab vs. Bisphosphonates

Denosumab is subcutaneously administered, has no renal safety concerns, but can cause ONJ.

Dentists' Rule for Managing ONJ

Suspend or stop treatment immediately; consider restarting after 6 weeks if no ONJ is found.

Sources of Radiation in Radiotherapy

Linear accelerators.

General Principles of Curative Radiotherapy

Complex planning with accurate localization and longer treatment courses with early side effects.

Radiotherapy Treatment Modalities

Include X-rays, electron treatment, and brachytherapy.

Gender Affected by Head & Neck Cancers

Commonly affect males at a ratio of 2:1 over females.

Common HPV type in Cervical and Oropharyngeal Cancers

Type 16.

Percentage of HPV Positive Head and Neck Cancers

25%.

Correlation between HPV Positive Cancers and Chemotherapy Response

They respond well and have better prognosis when HPV positive.

Advantages of Non-Surgical Oncology Treatment

Facilitates organ preservation.

Late Side Effects of Radiotherapy

Xerostomia, altered taste, osteoradionecrosis, alopecia, hypothyroidism, second malignancy.

Dose of Radiotherapy to Target Cancer Areas

High Dose of 70Gy.

Dose of Radiotherapy for Areas at Risk

Elective Dose of 57Gy.

Osteoradionecrosis Definition

Death of bone due to damage to blood vessels from radiotherapy.

Concurrent Chemoradiotherapy Drug for Head & Neck Cancers

Cisplatin, given every 3 weeks during radiotherapy.

Drugs used in Palliative Chemotherapy

Cisplatin & 5FU given every 4 weeks.

Selective Toxicity Definition

Ability of a drug to kill pathogens while minimizing damage to the host.

Disc Diffusion Test for Antibiotics

Bacteria grown on agar with antibiotic discs; clear zones indicate sensitivity.

MIC Definition

Minimum Inhibitory Concentration—the lowest concentration needed to stop bacterial growth.

MBC Definition

Minimum Bactericidal Concentration—the lowest concentration needed to kill bacteria.

Liquid Testing of Antibiotics Process

Bacteria in tubes with decreasing antibiotic concentrations to find MIC and then MBC.

Main targets for Antibiotics

Cell wall, protein synthesis, metabolic pathways, bacterial DNA, membranes, bacterial enzymes.

Structure of Peptidoglycan

Repeating chains of NAG-NAM with tetrapeptide side chains and peptide cross-links.

Amino Acids forming Peptide Crosslinks in Peptidoglycan

D-Alanine and D-Glutamate.

Antibiotics inhibiting peptidoglycan synthesis

Beta Lactams (Penicillin, Cephalosporins), Glycopeptides (Vancomycin), Cycloserine.

Beta Lactam Antibiotics Definition

Bactericidal compounds containing a beta-lactam ring that inhibit cell wall formation.

Beta Lactam Antibiotics Examples

Penicillin and Cephalosporins.

PBPs Definition

Penicillin Binding Proteins that are involved in peptidoglycan synthesis.

Binding site of Beta Lactam Antibiotics

Beta Lactam Antibiotics bind to PBPs to inhibit peptidoglycan synthesis.

Cycloserines Mechanism of Action

Analog of alanine that interferes with cross-linking in peptidoglycan.

Penicillin vs. D-alanyl-D-alanine Structure

Structurally analogous; D-Ala-D-Ala is part of peptidoglycan crosslinking.

Penicillin vs. Vancomycin Mechanism of Action

Vancomycin blocks D-Ala-D-Ala binding; Penicillin prevents PBPs from binding to D-Ala-D-Ala.

Antibiotics affecting Bacterial Protein Synthesis

Aminoglycosides, tetracyclines, erythromycin, fusidic acid.

Difference in Bacterial vs. Mammalian Ribosomes

Bacterial have 30s and 50s; mammalian have 40s and 60s.

Aminoglycosides Mechanism of Action

Act on the 30s ribosomal subunit, causing misreading of the genetic code.

Examples of Aminoglycosides

Gentamicin and streptomycin.

Microorganisms effective against Aminoglycosides

Aerobes and facultative anaerobes.

Aminoglycosides Administration Route

IV or IM; not absorbed from the gut.

Tetracyclines Mechanism of Action

Inhibit tRNA binding to the 50s ribosomal subunit, preventing protein synthesis.

Erythromycin Usage

Used for penicillin-allergic patients; penetrates mammalian cells.

Antimicrobial Agents affecting Bacterial DNA

Quinolones, rifamycins, metronidazole.

Quinolones Mechanism of Action

Inhibit DNA gyrase.

Rifamycins Effect on Bacterial DNA

Act on DNA-dependent RNA polymerases to affect mRNA synthesis.

Metronidazole Effect on Bacterial DNA

Directly damages bacterial DNA, effective only against anaerobic organisms.

Antibiotics affecting Metabolic Pathways

Sulfonamides disrupt folic acid synthesis.

Sulfonamides Activity Spectrum

Effective against gram-positive and gram-negative bacteria.

Sulfonamides Mechanism of Action

Compete with PABA for binding to dihydropteroate synthetase, inhibiting folic acid synthesis.