Overview of Chemotherapy

Update 2

Treatment aim	Neoadjuvant Treatment(CT or RT) given before a definitive treatment (surgery or RT) to facilitate the procedure (i.e downsize tumor for normal tissue sparing during definite treatment) and/or improve chances of cure Curative Chemotherapy given as the definitive treatment for cure Adjuvant Treatment given after a definitive treatment (surgery or RT) with the aim of increasing the chances of cure by killing any microscopic disease. Palliative Treatment  given to alleviate symptoms hence improve the quality of life and prolong life if possible
Dose intensity	Defines as total amount of drug delivered to the patient over a week. i.e CT given 3 weekly but intensity reflects the actual average dose per week. Maintaining dose intensity breast cancer CT has been shown to improve survival.
Type of drug in cancer	Chemotherapy classes Antimetabolites 5FU, gemcitabine Alkylating agent Cycphophosphamide, cisplatin Natural product Paclitaxel, Vincristine Antitumor antibiotic Epirubicin, Bleomycin Targeted Rx Hormonal tamoxifen, arimidex, goserelin Antibodies rituximab, cetuximab Small molecules imatinib, erlotinib Supportive Rx Bisphosphonates pamidronate, zoledronic acid Antibody denosumab Immunological GCSF, interferon Analgesic pcm, DF118, morphine Anti-emetic serotonin antagonists, steroid  to be continued

FRCR part 1 Sept/2014

Update 1

Autumn FRCR part 1 exam is around the corner. How is your preparation?

Thanks for the compliments and purchasing of the notes & BOFs.

All the best to those having their first attempt as well those clearing the remaining subjects.

Overview of radiotherapy

Type of radiation used	Ionizing radiation: electrons, protons, neutrons & gamma(radioisotope) MOA: Indirect or Direct ionizing Indirect: creating  hydroxyl radicals OH∙ →Double strand DNA breaks Direct: radiation itself →Double strand DNA breaks Type of radiation damage to DNA Lethal irreversible, irreparable leading to cell death. Sublethal under normal circumstances cells can be repaired in a few hours unless additional sublethal damage (another dose of radiation) occurs which makes the damage lethal. Potentially lethal the component of radiation damage can be modified by the post radiation environment.
Fractionation 5’ R	- radiotherapy given in fractions (not a single huge dose of 30Gy) - this will leads to lethal damage of tumor and normal tissues - normal cells still have the integrity of error-checked and repaired   damaged DNA (recover from radiation damage) -cells will be in different phases of cell cycles (G1,S,G2,M) R that facilitate radiotherapy effect to tumor Reoxygenation O2 required to generate radical. Hypoxic cells resistant to RT, fractionation allow Re-oxygenation of hypoxic cells Radiosensitivity- intrinsic factors of cells (non-modifiable) Radiasensitive Radioresistant Cell structure Nucles-DNA Membrane Cell phases M- chromosomes are lined up on the spindle and repair is difficult S- DNA is replicating,  more damaged DNA repaired (plenty enzyme) Cell types -lymphoma -SCC HNC Chordoma, chondrosarcoma, Melanoma Redistribution During fractionation, tumor cell recycle from resistant phase S into sensitive phase M phase. R that against radiotherapy effect to tumor Repopulation tumor cells: repopulate especially when radiation treatment is very prolonged or interrupted normal cells: (repopulate normal tissue leads to recovery) Repaired Sublethal damage melanoma repair radiation damage →radioresistance normal cells repaired sublethal damaged required atleast 6 hrs bet. fraction
Intent of radiotherapy	Curative contributing 25-30% of cure Radical RT-primary treatment (RT±CT±biologic) Adjuvant RT-given after definitive treatment i.e surgery Palliative improve symptoms (e.g. bone pain) & quality of life
Methods of delivery of radiotherapy	A. External beam RT (EBRT)- Radiation given from a distance Kilovoltage x-ray Electron accelerated towards anode by the difference voltage potential and collision with a metal target -X-ray produced by 1. Bremsstrahlung & 2. Characteristic X- rays Superficial 50–150 kVp <0.5cm lesion Deep 150–500 kVp 0.5 - 2cm lesion Megavoltage X-rays(Photons) acceleration of electrons through accelerating waveguide impact on target in a linear accelerators (LINACs)                         Electrons beam Electrons beam are produced when the target is removed from the path of the electron beam Characteristic Photons Electron low surface dose, build up region,depth of maximum dose(dmax) Dmax 6 MV- 1.5cm 10MV- 2.5cm high surface dose relative to photon -definite range- E/2 cm -effective treatment depth- E/3 (target volume should lie within 90% isodose line) ↑ energy, higher penetrating power & Skin sparing effect ↑ energy, surface dose ↓ & lateral constriction of 90% isodose line B. Brachytherapy -Radiation given within a short distance -Rapid fall off of radiation dose follow inverse square law (ISL) -delivery of a high dose radiation to the tumour with sparing of    surrounding normal tissue Type method Clinical used interstitial placing a radiation source into tumour Breast, prostate intracavity Radiation source placed in body cavity containing the tumour Cervical  C. Nonsealed radionuclides -Given IV or orally Example Radioiodine 131I for thyroid cancer Strontium-89 ,Samarium-153, Alpharadin for bone mets 2° prostate ca

  (to be cont)

Happy reading!!