Radiation is commonly used to treat two-thirds of cancer patients and works by damaging the DNA of cancer cells. While it targets cancer cells, radiation can also damage normal tissues. Radiation modifiers aim to increase the tumor's sensitivity to radiation without increasing injury to normal tissues. They work by either sensitizing tumors or protecting normal tissues. The goal is to improve the therapeutic ratio and allow higher, more effective radiation doses to be used. Examples of radiation modifiers discussed in the document include hyperbaric oxygen, carbogen gas with or without nicotinamide, and hyperthermia.
Surface Guided Radiotherapy for Accuracy, Volume Reduction, Real time Trackin...SGRT Community
1) Surface guided radiotherapy uses optical cameras to track the external surface of a patient in real-time during treatment and provides sub-millimeter accuracy for patient positioning and motion management.
2) The technique has been used at MSKCC for several clinical applications including frameless SRS for brain tumors, head and neck cancers, and deep inspiratory breath hold treatments for breast cancers.
3) Preliminary results found surface guided radiotherapy improved patient comfort for frameless SRS over framed SRS and doubled the treatment throughput. Motion tracking also ensured frameless SRS accuracy to within 1mm.
Evolution of Fractionation and Conventional Fractionation in RadiotherapyNikhil Sebastian
The document discusses the evolution of radiation fractionation in cancer treatment. Early radiation machines had low output, so delivering a tumoricidal dose as a single fraction would have caused unacceptable toxicity. Fractionation was used from the beginning. Over the following decades, two schools of thought emerged on fractionation - the Erlangen school believed single large doses were necessary, while the Paris school's experiments on animal models supported fractionation. Clinical results in the 1930s also showed fractionation produced better tumor control with less toxicity. The rationale for fractionation is based on the different cell kinetics of normal and tumor cells, allowing sparing of normal tissues. Mathematical models were later developed to quantify fractionation schedules, incorporating factors like overall time, dose per
1. ICRU Report 83 provides guidelines for prescribing, recording, and reporting intensity-modulated radiation therapy (IMRT). It emphasizes using dose-volume histograms and statistics like median dose to describe dose distributions.
2. The report outlines three levels of prescribing and reporting with increasing complexity. Level 1 involves basic 2D dose distributions while Level 3 incorporates more advanced metrics like tumor control probability.
3. Key volumes discussed include gross tumor volume, clinical target volume, planning target volume, and organs at risk. The report standardized how to account for uncertainties and patient motion when defining these volumes.
The document discusses total body irradiation (TBI), which involves delivering radiation to the entire body to condition patients for stem cell transplantation. It provides an overview of the history, concept, indications, doses, prerequisites, and treatment planning for TBI. Complications of TBI are also reviewed, including both immediate toxicities like nausea and vomiting as well as late effects such as salivary gland dysfunction and pneumonitis.
The document discusses key concepts in radiation oncology including dose fractionation, tumor lethal dose, normal tissue tolerance, and factors that affect radiosensitivity. Fractionating the total radiation dose into smaller daily doses allows time for repair of sublethal damage in normal tissues, improving the therapeutic ratio by reducing side effects while still effectively treating the tumor.
Brachytherapy involves placing radioactive sources inside or near the target tissue. It began in 1898 with radium and has evolved with different radioactive isotopes and delivery methods. Common isotopes used today include iridium-192, cesium-137, palladium-103, iodine-125, and gold-198, which are used for interstitial, intracavitary, or permanent implantation depending on the clinical application and isotope properties.
Icru reports in external beam radiotherapyDeepika Malik
The document summarizes key ICRU reports related to external beam radiotherapy, including ICRU Reports 29, 50, and 62. Report 29 established definitions like target volume, treatment volume, and organs at risk. Report 50 refined definitions and introduced clinical target volume, planning target volume, and treated volume. Report 62 further refined margins and introduced internal margin and setup margin. It also defined planning organ at risk volume and conformity index. The reports provide recommendations for dose reporting including minimum, maximum, and reference doses.
1. The Manchester system was one of the first standardized methods for interstitial brachytherapy implantation using radium sources. It provided rules for determining the amount of radium needed, its distribution, and dose specification based on the treatment area, distance, and desired total dose.
2. The amount of radium was calculated using exposure rates and tables that specified milligram hours of radium per 1000 rads of exposure for different areas and distances. The distribution of radium sources followed the inverse square law to achieve uniform dosing within 10% across the target area.
3. The system defined geometric terms and provided specific rules for distributing radium sources in planar moulds that were circular, square,
Surface Guided Radiotherapy for Accuracy, Volume Reduction, Real time Trackin...SGRT Community
1) Surface guided radiotherapy uses optical cameras to track the external surface of a patient in real-time during treatment and provides sub-millimeter accuracy for patient positioning and motion management.
2) The technique has been used at MSKCC for several clinical applications including frameless SRS for brain tumors, head and neck cancers, and deep inspiratory breath hold treatments for breast cancers.
3) Preliminary results found surface guided radiotherapy improved patient comfort for frameless SRS over framed SRS and doubled the treatment throughput. Motion tracking also ensured frameless SRS accuracy to within 1mm.
Evolution of Fractionation and Conventional Fractionation in RadiotherapyNikhil Sebastian
The document discusses the evolution of radiation fractionation in cancer treatment. Early radiation machines had low output, so delivering a tumoricidal dose as a single fraction would have caused unacceptable toxicity. Fractionation was used from the beginning. Over the following decades, two schools of thought emerged on fractionation - the Erlangen school believed single large doses were necessary, while the Paris school's experiments on animal models supported fractionation. Clinical results in the 1930s also showed fractionation produced better tumor control with less toxicity. The rationale for fractionation is based on the different cell kinetics of normal and tumor cells, allowing sparing of normal tissues. Mathematical models were later developed to quantify fractionation schedules, incorporating factors like overall time, dose per
1. ICRU Report 83 provides guidelines for prescribing, recording, and reporting intensity-modulated radiation therapy (IMRT). It emphasizes using dose-volume histograms and statistics like median dose to describe dose distributions.
2. The report outlines three levels of prescribing and reporting with increasing complexity. Level 1 involves basic 2D dose distributions while Level 3 incorporates more advanced metrics like tumor control probability.
3. Key volumes discussed include gross tumor volume, clinical target volume, planning target volume, and organs at risk. The report standardized how to account for uncertainties and patient motion when defining these volumes.
The document discusses total body irradiation (TBI), which involves delivering radiation to the entire body to condition patients for stem cell transplantation. It provides an overview of the history, concept, indications, doses, prerequisites, and treatment planning for TBI. Complications of TBI are also reviewed, including both immediate toxicities like nausea and vomiting as well as late effects such as salivary gland dysfunction and pneumonitis.
The document discusses key concepts in radiation oncology including dose fractionation, tumor lethal dose, normal tissue tolerance, and factors that affect radiosensitivity. Fractionating the total radiation dose into smaller daily doses allows time for repair of sublethal damage in normal tissues, improving the therapeutic ratio by reducing side effects while still effectively treating the tumor.
Brachytherapy involves placing radioactive sources inside or near the target tissue. It began in 1898 with radium and has evolved with different radioactive isotopes and delivery methods. Common isotopes used today include iridium-192, cesium-137, palladium-103, iodine-125, and gold-198, which are used for interstitial, intracavitary, or permanent implantation depending on the clinical application and isotope properties.
Icru reports in external beam radiotherapyDeepika Malik
The document summarizes key ICRU reports related to external beam radiotherapy, including ICRU Reports 29, 50, and 62. Report 29 established definitions like target volume, treatment volume, and organs at risk. Report 50 refined definitions and introduced clinical target volume, planning target volume, and treated volume. Report 62 further refined margins and introduced internal margin and setup margin. It also defined planning organ at risk volume and conformity index. The reports provide recommendations for dose reporting including minimum, maximum, and reference doses.
1. The Manchester system was one of the first standardized methods for interstitial brachytherapy implantation using radium sources. It provided rules for determining the amount of radium needed, its distribution, and dose specification based on the treatment area, distance, and desired total dose.
2. The amount of radium was calculated using exposure rates and tables that specified milligram hours of radium per 1000 rads of exposure for different areas and distances. The distribution of radium sources followed the inverse square law to achieve uniform dosing within 10% across the target area.
3. The system defined geometric terms and provided specific rules for distributing radium sources in planar moulds that were circular, square,
This document discusses the history and techniques of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). It begins by outlining the early development of SRS by Lars Leksell in the 1950s. It then defines key terms like SRS, SBRT, and fractionated stereotactic radiosurgery. The document goes on to discuss the rationale and advantages of SRS/SBRT, including its ability to deliver high radiation doses with steep dose gradients using multiple beams and image guidance. It also covers topics like tumor oxygenation, cell kill mechanisms, and recent technological advances in the field like VMAT, flattening filter free beams, and 4D
Altered fractionation schedules in radiation oncologyAbhishek Soni
Altered fractionation schedules aim to optimize tumor control and normal tissue sparing by manipulating total dose, dose per fraction, time interval between fractions, dose rate, and overall treatment time based on tumor and tissue radiosensitivity and repair characteristics. Hyperfractionation uses a higher total dose with smaller, more frequent fractions to exploit tumor reoxygenation and cell cycle effects while hypofractionation uses fewer, larger fractions which is more effective for tumors with low α/β ratios. Accelerated fractionation decreases treatment time to limit tumor repopulation at the cost of increased acute toxicity. Phase III trials show hyperfractionation and accelerated fractionation improve local control for head and neck cancers with acceptable toxicity.
This document summarizes key aspects of the International Commission on Radiation Units and Measurements (ICRU) Report 83 from 2010 on prescribing, recording, and reporting photon beam intensity-modulated radiation therapy (IMRT). The ICRU Report 50 from 1993 and Report 62 from 1999 established guidelines for defining target volumes like gross tumor volume, clinical target volume, and planning target volume. ICRU Report 83 aimed to update these guidelines for IMRT, which uses non-uniform fluence and dose distributions compared to earlier conformal radiation techniques. Key changes included separating the planning target volume into internal and setup margins, classifying organs at risk, and defining new metrics like the planning organ at risk volume and conformity index for evaluating IM
1) The linear-quadratic (LQ) model is commonly used in clinical practice to model cell survival patterns after radiation exposure and calculate biologically equivalent doses.
2) While the LQ model reasonably predicts cell survival up to doses of around 10 Gy per fraction, it may overestimate biological effect at higher doses used in stereotactic radiotherapy.
3) Several modifications have been proposed to the LQ model to address its limitations at high doses, such as accounting for non-DNA targets and cell repopulation, but there is currently no clear alternative model.
This document discusses various aspects of fractionation in radiotherapy. It begins by describing early experiments by Regaud showing that fractionated doses achieved tumor sterilization without excessive skin damage, compared to single high doses. It then discusses the four R's of radiobiology - repair, repopulation, redistribution and reoxygenation - which form the basis for fractionated regimens. Various fractionation schedules are described, including conventional, hyperfractionation, accelerated fractionation and hypofractionation. The advantages and disadvantages of different approaches are summarized.
This document discusses various time-dose models used in radiotherapy, including the Strandqvist, Cohen, NSD, and TDF models. It explains the need for these models to optimize treatment regimes for tumor control while sparing normal tissues. The document also covers gap correction factors used when treatment schedules are interrupted and the various factors that can affect tumor control outcomes due to gaps in treatment. Compensatory methods like accelerated scheduling and increased dosing are presented to account for treatment gaps.
This document provides an overview of interstitial brachytherapy principles and concepts. It discusses the history and evolution of brachytherapy sources from radium to modern radioactive sources like iridium-192. Key concepts covered include dose rate calculations, implant systems like the Paris system, and factors that influence dose distribution from a radioactive source like distance, absorption and scattering. The document also describes temporary and permanent brachytherapy sources and different methods of source application including preloading, afterloading and remote afterloading.
1. The document discusses commissioning parameters for flattening filter free (FFF) photon beams from a linear accelerator, including profile normalization methods, dosimetric field size, penumbra, and slope.
2. Profile normalization can be done using the inflection point or renormalization value to compare FFF and flattened beams. Dosimetric field size is measured as the 50% dose width. Penumbra is defined as the 20-80% distance for FFF beams after normalization.
3. Slope describes the peak shape of FFF profiles, and flatness/unflatness parameters are discussed to characterize beam homogeneity for both FFF and flattened beams.
LET, Linear Energy Transfer, Relative Biologic Effectiveness, Oxygen enhancement ratio,
Dr. Vandana, KGMU, CSMMU, Lucknow, Radiation Oncology, Radiotherapy
This document discusses various methods used to evaluate radiotherapy treatment plans, including physical and biological parameters. Physically, plans are evaluated using isodose curves, dose distribution statistics, differential and cumulative dose-volume histograms (DVHs). Target coverage should be within 95-100% of the prescribed dose. Biologically, tumor control probability (TCP) and normal tissue complication probability (NTCP) models are used. The therapeutic ratio and index compare the dose required for tumor control versus normal tissue complications. NTCP models include Lyman-Kutcher-Burman and critical element/volume models. Plan evaluation ensures target doses are adequate while respecting organ tolerance doses.
Evolution of gynaecological brachytherapyRitam Joarder
This document provides a historical overview of brachytherapy and the evolution of radiation sources used. It discusses some of the early discoveries in x-rays and radioactivity in the 1890s. It then describes some of the early uses of radium to treat skin lesions and cervical cancer in the early 1900s. The document outlines several early brachytherapy systems developed between 1913-1953, including the Stockholm, Paris, Manchester, and Paterson-Parker systems. It also discusses the introduction of the Quimby system using radium needles. The document notes the evolution of brachytherapy sources over time from radium to cesium-137 to iridium-192 to improve dosimetry, specific activity,
Electron beam radiotherapy uses megavoltage electron beams ranging from 6-20 MeV to treat superficial tumors within 6 cm of the skin surface. It provides a uniform dose at a specified depth with rapid dose fall-off, sparing deeper tissues. Common tumors treated include skin, lymphomas, and breast cancer. Electrons deposit dose via interactions like collision and scattering. Dose distribution is characterized by a rapid buildup to a maximum within 1 cm followed by a rapid falloff beyond the treatment depth.
Mlc;multi leaf collimators of variuos companieszahramansouri
This document discusses the three basic applications of multileaf collimators (MLCs) in radiation therapy: 1) replacing conventional blocking, 2) matching the beam's eye view to the planning target volume during arc rotation, and 3) achieving beam intensity modulation. It also describes the material properties of tungsten alloy that make it well-suited for MLC leaf construction, including its high density, hardness, low cost, and low coefficient of expansion. Finally, it briefly mentions mini MLCs and the MIMiC system.
This document discusses the clinical implementation of volumetric modulated arc therapy (VMAT) at UT M.D. Anderson Cancer Center. It provides an overview of VMAT, the advantages it offers over other radiation therapy techniques, and the steps taken to configure the accelerator, treatment planning system, and quality assurance processes for VMAT delivery. Key aspects covered include accelerator prerequisites, TPS commissioning, patient-specific quality assurance using films and ion chambers, monthly constancy checks, and tips for rapid arc treatment planning for prostate cases.
The document discusses cell survival curves, which describe the relationship between radiation dose and the proportion of cells that survive. It defines key terms like clonogenic cells and explains the components of in vitro survival curves. It describes exponential and shoulder survival curves based on single-hit and multi-target theories. The mechanisms of cell killing like mitotic death and apoptosis are covered. Factors influencing radiosensitivity like dose rate, oxygen level and genetic mutations are summarized. Comparisons are made between survival curves of different mammalian cell types and microorganisms.
The document discusses various radiation fractionation schedules used in cancer treatment. It begins with an overview of conventional fractionation, which divides the total radiation dose into smaller daily doses to allow healthy cells to repair sublethal damage between fractions. It then explores the radiobiological rationale of the 5 R's of fractionation - repair, redistribution, reoxygenation, repopulation, and radiosensitivity. The document discusses various altered fractionation schedules including hyperfractionation, accelerated fractionation, split-course, and hypofractionation, explaining how each schedule aims to improve the therapeutic ratio for cancer patients.
The document discusses guidelines from the International Commission on Radiation Units and Measurements (ICRU) for prescribing, recording, and reporting intensity-modulated radiation therapy (IMRT). It describes the different target volumes and organs at risk that must be delineated for treatment planning according to ICRU reports 50, 62, and 83. These include the gross tumor volume, clinical target volume, planning target volume, internal target volume, treated volume, and irradiated volume. Factors such as margins for internal motion and patient setup must be considered when defining volumes. Dose specifications, dose-volume histograms, conformity, and homogeneity are also discussed. Proper delineation of volumes and standardization of dose reporting are emphasized.
This document discusses forward intensity-modulated radiation therapy (IMRT) using the field-in-field (FIF) technique for whole breast irradiation. It begins by introducing the goals of treatment planning to deliver a uniform dose to the target volume while minimizing dose to normal tissues. It then describes how the FIF technique uses multiple subfields in addition to the main tangential fields to improve dose homogeneity. Several studies have shown that improved homogeneity decreases skin toxicities. The document evaluates different methods for generating subfields and finds the alternate subfields method provides the best dose distribution. In summary, the FIF forward planning technique improves dose uniformity in the breast compared to conventional techniques.
In 2000 IAEA published another International Code of Practice.
“Absorbed Dose Determination in External Beam Radiotherapy” (Technical Report Series No. 398)
Recommending procedures to obtain the absorbed dose in water from measurements made with an ionisation chamber in external beam radiotherapy (EBRT).
This document discusses various strategies for radiosensitization and radioprotection in radiation oncology. It describes how radiation directly damages DNA and how free radicals generated can be fixed by oxygen, leading to cell death. It then discusses chronic and acute hypoxia in tumors and various mechanisms and agents that can be used for radiosensitization, including hypoxic cell sensitizers like misonidazole and nimorazole, hypoxic cytotoxins like mitomycin C, and strategies like blood transfusion, hyperbaric oxygen, and carbogen inhalation. It also discusses the radioprotector amifostine and its mechanisms of action and administration. Glutamine is mentioned as a potential protector against radiation-induced
Radiosensitizers are agents that increase the lethal effects of radiation when administered with radiotherapy. They work through various mechanisms like increasing DNA damage, inhibiting repair, and modulating biological response. Common types include physical agents like hyperthermia, chemical agents like nitroimidazoles to target hypoxic cells, and biological modifiers like cetuximab. Effective radiosensitizers improve the therapeutic ratio by increasing tumor cell killing while minimizing harm to normal tissues. Combining radiosensitizers with radiotherapy can improve outcomes for many cancer types.
This document discusses the history and techniques of stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). It begins by outlining the early development of SRS by Lars Leksell in the 1950s. It then defines key terms like SRS, SBRT, and fractionated stereotactic radiosurgery. The document goes on to discuss the rationale and advantages of SRS/SBRT, including its ability to deliver high radiation doses with steep dose gradients using multiple beams and image guidance. It also covers topics like tumor oxygenation, cell kill mechanisms, and recent technological advances in the field like VMAT, flattening filter free beams, and 4D
Altered fractionation schedules in radiation oncologyAbhishek Soni
Altered fractionation schedules aim to optimize tumor control and normal tissue sparing by manipulating total dose, dose per fraction, time interval between fractions, dose rate, and overall treatment time based on tumor and tissue radiosensitivity and repair characteristics. Hyperfractionation uses a higher total dose with smaller, more frequent fractions to exploit tumor reoxygenation and cell cycle effects while hypofractionation uses fewer, larger fractions which is more effective for tumors with low α/β ratios. Accelerated fractionation decreases treatment time to limit tumor repopulation at the cost of increased acute toxicity. Phase III trials show hyperfractionation and accelerated fractionation improve local control for head and neck cancers with acceptable toxicity.
This document summarizes key aspects of the International Commission on Radiation Units and Measurements (ICRU) Report 83 from 2010 on prescribing, recording, and reporting photon beam intensity-modulated radiation therapy (IMRT). The ICRU Report 50 from 1993 and Report 62 from 1999 established guidelines for defining target volumes like gross tumor volume, clinical target volume, and planning target volume. ICRU Report 83 aimed to update these guidelines for IMRT, which uses non-uniform fluence and dose distributions compared to earlier conformal radiation techniques. Key changes included separating the planning target volume into internal and setup margins, classifying organs at risk, and defining new metrics like the planning organ at risk volume and conformity index for evaluating IM
1) The linear-quadratic (LQ) model is commonly used in clinical practice to model cell survival patterns after radiation exposure and calculate biologically equivalent doses.
2) While the LQ model reasonably predicts cell survival up to doses of around 10 Gy per fraction, it may overestimate biological effect at higher doses used in stereotactic radiotherapy.
3) Several modifications have been proposed to the LQ model to address its limitations at high doses, such as accounting for non-DNA targets and cell repopulation, but there is currently no clear alternative model.
This document discusses various aspects of fractionation in radiotherapy. It begins by describing early experiments by Regaud showing that fractionated doses achieved tumor sterilization without excessive skin damage, compared to single high doses. It then discusses the four R's of radiobiology - repair, repopulation, redistribution and reoxygenation - which form the basis for fractionated regimens. Various fractionation schedules are described, including conventional, hyperfractionation, accelerated fractionation and hypofractionation. The advantages and disadvantages of different approaches are summarized.
This document discusses various time-dose models used in radiotherapy, including the Strandqvist, Cohen, NSD, and TDF models. It explains the need for these models to optimize treatment regimes for tumor control while sparing normal tissues. The document also covers gap correction factors used when treatment schedules are interrupted and the various factors that can affect tumor control outcomes due to gaps in treatment. Compensatory methods like accelerated scheduling and increased dosing are presented to account for treatment gaps.
This document provides an overview of interstitial brachytherapy principles and concepts. It discusses the history and evolution of brachytherapy sources from radium to modern radioactive sources like iridium-192. Key concepts covered include dose rate calculations, implant systems like the Paris system, and factors that influence dose distribution from a radioactive source like distance, absorption and scattering. The document also describes temporary and permanent brachytherapy sources and different methods of source application including preloading, afterloading and remote afterloading.
1. The document discusses commissioning parameters for flattening filter free (FFF) photon beams from a linear accelerator, including profile normalization methods, dosimetric field size, penumbra, and slope.
2. Profile normalization can be done using the inflection point or renormalization value to compare FFF and flattened beams. Dosimetric field size is measured as the 50% dose width. Penumbra is defined as the 20-80% distance for FFF beams after normalization.
3. Slope describes the peak shape of FFF profiles, and flatness/unflatness parameters are discussed to characterize beam homogeneity for both FFF and flattened beams.
LET, Linear Energy Transfer, Relative Biologic Effectiveness, Oxygen enhancement ratio,
Dr. Vandana, KGMU, CSMMU, Lucknow, Radiation Oncology, Radiotherapy
This document discusses various methods used to evaluate radiotherapy treatment plans, including physical and biological parameters. Physically, plans are evaluated using isodose curves, dose distribution statistics, differential and cumulative dose-volume histograms (DVHs). Target coverage should be within 95-100% of the prescribed dose. Biologically, tumor control probability (TCP) and normal tissue complication probability (NTCP) models are used. The therapeutic ratio and index compare the dose required for tumor control versus normal tissue complications. NTCP models include Lyman-Kutcher-Burman and critical element/volume models. Plan evaluation ensures target doses are adequate while respecting organ tolerance doses.
Evolution of gynaecological brachytherapyRitam Joarder
This document provides a historical overview of brachytherapy and the evolution of radiation sources used. It discusses some of the early discoveries in x-rays and radioactivity in the 1890s. It then describes some of the early uses of radium to treat skin lesions and cervical cancer in the early 1900s. The document outlines several early brachytherapy systems developed between 1913-1953, including the Stockholm, Paris, Manchester, and Paterson-Parker systems. It also discusses the introduction of the Quimby system using radium needles. The document notes the evolution of brachytherapy sources over time from radium to cesium-137 to iridium-192 to improve dosimetry, specific activity,
Electron beam radiotherapy uses megavoltage electron beams ranging from 6-20 MeV to treat superficial tumors within 6 cm of the skin surface. It provides a uniform dose at a specified depth with rapid dose fall-off, sparing deeper tissues. Common tumors treated include skin, lymphomas, and breast cancer. Electrons deposit dose via interactions like collision and scattering. Dose distribution is characterized by a rapid buildup to a maximum within 1 cm followed by a rapid falloff beyond the treatment depth.
Mlc;multi leaf collimators of variuos companieszahramansouri
This document discusses the three basic applications of multileaf collimators (MLCs) in radiation therapy: 1) replacing conventional blocking, 2) matching the beam's eye view to the planning target volume during arc rotation, and 3) achieving beam intensity modulation. It also describes the material properties of tungsten alloy that make it well-suited for MLC leaf construction, including its high density, hardness, low cost, and low coefficient of expansion. Finally, it briefly mentions mini MLCs and the MIMiC system.
This document discusses the clinical implementation of volumetric modulated arc therapy (VMAT) at UT M.D. Anderson Cancer Center. It provides an overview of VMAT, the advantages it offers over other radiation therapy techniques, and the steps taken to configure the accelerator, treatment planning system, and quality assurance processes for VMAT delivery. Key aspects covered include accelerator prerequisites, TPS commissioning, patient-specific quality assurance using films and ion chambers, monthly constancy checks, and tips for rapid arc treatment planning for prostate cases.
The document discusses cell survival curves, which describe the relationship between radiation dose and the proportion of cells that survive. It defines key terms like clonogenic cells and explains the components of in vitro survival curves. It describes exponential and shoulder survival curves based on single-hit and multi-target theories. The mechanisms of cell killing like mitotic death and apoptosis are covered. Factors influencing radiosensitivity like dose rate, oxygen level and genetic mutations are summarized. Comparisons are made between survival curves of different mammalian cell types and microorganisms.
The document discusses various radiation fractionation schedules used in cancer treatment. It begins with an overview of conventional fractionation, which divides the total radiation dose into smaller daily doses to allow healthy cells to repair sublethal damage between fractions. It then explores the radiobiological rationale of the 5 R's of fractionation - repair, redistribution, reoxygenation, repopulation, and radiosensitivity. The document discusses various altered fractionation schedules including hyperfractionation, accelerated fractionation, split-course, and hypofractionation, explaining how each schedule aims to improve the therapeutic ratio for cancer patients.
The document discusses guidelines from the International Commission on Radiation Units and Measurements (ICRU) for prescribing, recording, and reporting intensity-modulated radiation therapy (IMRT). It describes the different target volumes and organs at risk that must be delineated for treatment planning according to ICRU reports 50, 62, and 83. These include the gross tumor volume, clinical target volume, planning target volume, internal target volume, treated volume, and irradiated volume. Factors such as margins for internal motion and patient setup must be considered when defining volumes. Dose specifications, dose-volume histograms, conformity, and homogeneity are also discussed. Proper delineation of volumes and standardization of dose reporting are emphasized.
This document discusses forward intensity-modulated radiation therapy (IMRT) using the field-in-field (FIF) technique for whole breast irradiation. It begins by introducing the goals of treatment planning to deliver a uniform dose to the target volume while minimizing dose to normal tissues. It then describes how the FIF technique uses multiple subfields in addition to the main tangential fields to improve dose homogeneity. Several studies have shown that improved homogeneity decreases skin toxicities. The document evaluates different methods for generating subfields and finds the alternate subfields method provides the best dose distribution. In summary, the FIF forward planning technique improves dose uniformity in the breast compared to conventional techniques.
In 2000 IAEA published another International Code of Practice.
“Absorbed Dose Determination in External Beam Radiotherapy” (Technical Report Series No. 398)
Recommending procedures to obtain the absorbed dose in water from measurements made with an ionisation chamber in external beam radiotherapy (EBRT).
This document discusses various strategies for radiosensitization and radioprotection in radiation oncology. It describes how radiation directly damages DNA and how free radicals generated can be fixed by oxygen, leading to cell death. It then discusses chronic and acute hypoxia in tumors and various mechanisms and agents that can be used for radiosensitization, including hypoxic cell sensitizers like misonidazole and nimorazole, hypoxic cytotoxins like mitomycin C, and strategies like blood transfusion, hyperbaric oxygen, and carbogen inhalation. It also discusses the radioprotector amifostine and its mechanisms of action and administration. Glutamine is mentioned as a potential protector against radiation-induced
Radiosensitizers are agents that increase the lethal effects of radiation when administered with radiotherapy. They work through various mechanisms like increasing DNA damage, inhibiting repair, and modulating biological response. Common types include physical agents like hyperthermia, chemical agents like nitroimidazoles to target hypoxic cells, and biological modifiers like cetuximab. Effective radiosensitizers improve the therapeutic ratio by increasing tumor cell killing while minimizing harm to normal tissues. Combining radiosensitizers with radiotherapy can improve outcomes for many cancer types.
Radiosensitizers and Biological modifiers in RadiotherapySubhash Thakur
This document discusses various agents that can be used as radiosensitizers to increase the lethal effects of radiation therapy on tumor cells. It describes radiosensitization as using a physical, chemical, or pharmacological intervention to differentially increase the effects of radiation on tumor cells over normal tissues. Some key radiosensitizers mentioned include hyperthermia, carbogen with nicotinamide to overcome tumor hypoxia, and chemotherapeutic drugs that inhibit DNA repair pathways in tumor cells. The ideal radiosensitizer lacks toxicity, has a potent sensitizing effect in both normoxic and hypoxic cells, and can be conveniently administered in an outpatient setting.
Oxygen plays an important role in enhancing the effects of radiation therapy. The presence of oxygen "fixes" or makes radiation damage to DNA permanent, whereas in hypoxic conditions without oxygen, this damage can be repaired. Tumors often develop areas of low oxygen, called hypoxia, which makes tumor cells resistant to radiation. Various strategies are used to overcome tumor hypoxia including fractionating radiation doses to allow reoxygenation, increasing oxygen delivery, using hypoxia-targeted drugs, and improving tumor vasculature. Hypoxic tumor cells are associated with more aggressive disease and poorer outcomes from radiation therapy.
- Reirradiation or retreatments after initial radiotherapy is possible for 10% of cancer patients who experience a second cancer. However, if the radiation tolerance of a normal organ or tissue was exceeded in the initial treatment, reirradiation cannot be done safely.
- Early-responding tissues like skin generally recover better than late-responding tissues like fibrosis and can tolerate reirradiation with reduced doses. Spinal cord and lung data from rodent and monkey studies show some reirradiation is possible. Kidney and bladder do not recover from late damage.
- Clinical studies on reirradiation are limited but show it can provide local control and possibly survival for head and neck cancers, though with high risks of toxicity and functional
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This document discusses the rationale for chemoradiation therapy. It explains that chemotherapeutic drugs can act as radiosensitizers by increasing the lethal effects of radiation when administered together. There are multiple exploitable strategies for improving the therapeutic index of chemoradiation, including spatial cooperation between radiation and chemotherapy, independent toxicity profiles, enhancement of tumor response, and protection of normal tissues. The mechanisms of drug-radiation interaction include increasing initial radiation damage, inhibiting cellular repair, cell cycle redistribution, counteracting tumor hypoxia, and inhibiting tumor cell repopulation. Assessment of drug-radiation interactions can be done using clonogenic survival assays and isobologram analysis. Concurrent chemoradiation is now standard of care for
This document summarizes various radiation therapy modalities for treating hepatic malignant tumors. It discusses external beam radiotherapy techniques like conventional radiotherapy, 3D conformal radiotherapy, stereotactic radiotherapy, and proton radiotherapy. It also covers internal radiotherapy techniques like selective internal radiotherapy using yttrium microspheres, metabolic radiotherapy with iodine-131 lipiodol, and brachytherapy. The document provides details on each technique's dosimetry, efficacy, and safety considerations.
1) Hypoxic cell sensitizers are agents that increase the lethal effects of radiation specifically on hypoxic tumor cells. An ideal sensitizer selectively sensitizes hypoxic cells at concentrations that do not greatly increase toxicity to normal tissues.
2) Several hypoxic cell sensitizers have been evaluated clinically including nitroimidazoles like misonidazole, metronidazole, and nimorazole. Nimorazole showed benefit for head and neck cancers with less toxicity.
3) Other approaches to overcoming tumor hypoxia include hyperbaric oxygen, carbogen breathing, blood transfusions, and bioreductive drugs that selectively kill hypoxic cells. A meta-analysis found that
This document discusses radiotherapy (radiation therapy) and its use in treating cancer. It covers the origins and physics of radiotherapy, how radiation affects cells, and methods to improve radiation therapy outcomes. These methods include using radiosensitizers and radioprotectors, hyperbaric oxygen therapy, altered fractionation schedules, and combining radiation with chemotherapy or hyperthermia. The document also addresses complications and dental care considerations related to radiotherapy.
Smart radiotherapy aims to precisely target tumor cells while sparing healthy cells. New techniques described in the document include using hypoxic cell sensitizers to target hypoxic tumor regions, anti-angiogenic agents to inhibit tumor blood vessels, and nanoparticles to enhance radiation dose and selectively deliver drugs. Molecular imaging helps optimize treatment by identifying tumor characteristics. Combining radiotherapy with immunotherapy or targeted depletion of host cells may also improve outcomes. Overall, the document discusses developing more precise radiation approaches through better understanding of tumor biology and microenvironment.
Proton beam therapy in head and neck cancer.pdfAnkit Vishwani
Proton beam therapy offers dosimetric advantages over photon therapies for head and neck cancers by depositing most radiation at the tumor site while reducing dose to surrounding healthy tissues. Studies have shown lower rates of acute toxicities like dysgeusia, mucositis and nausea with proton beam therapy compared to intensity-modulated radiation therapy (IMRT) for oropharyngeal cancers. Proton beam therapy may also achieve better organ sparing and lower toxicity rates than IMRT for nasopharyngeal cancers, salivary gland tumors, and recurrent or skull base tumors near critical structures.
The document discusses various topics related to radiotherapy including oxygenation and reoxygenation effects, time-dose-fractionation relationships, and altered fractionation schemes. Specifically, it covers how oxygen enhances the effects of radiation, the mechanisms of reoxygenation in tumors, factors influencing early and late responding tissues under different fractionation regimens, and approaches like hyperfractionation and accelerated treatment that aim to better separate tumor and normal tissue responses. Large clinical trials on hyperfractionation and accelerated regimens for head and neck cancers are also summarized.
Endobronchial Brachytherapy by Dr.Tinku JosephDr.Tinku Joseph
Endobronchial brachytherapy (EBBT) involves placing a radioactive source near a tumor to deliver high doses of radiation. It is used palliatively to relieve airway symptoms from large central lung tumors. EBBT spares other tissues compared to external beam radiation. It is performed by placing a radioactive Ir-192 source into the airway under bronchoscopy. EBBT is effective at improving symptoms in 70% of patients for at least 6 months and is used for NSCLC, metastases to the lungs, and recurrent tracheal stenosis. Complications are generally less than 5% and include radiation bronchitis, stenosis, and hemorrhage.
Radiotherapy is used in the management of oral cancer for curative and palliative purposes. It can be delivered as primary treatment combined with chemotherapy for organ preservation or after surgery as adjuvant treatment. Newer radiotherapy techniques like IMRT allow higher doses to be delivered to tumors while reducing damage to nearby organs. Side effects depend on treatment dose and area irradiated, and may include mucositis, xerostomia, skin changes, osteoradionecrosis and rare complications like carotid rupture. Ongoing research aims to reduce toxicity through altered fractionation schedules and novel delivery methods.
Reirradiation can provide local tumor control for recurrent head and neck cancer when surgery is not possible. Modern radiation techniques like IMRT allow higher radiation doses to be safely delivered to the tumor while minimizing risks of severe toxicity. Outcomes from reirradiation include a median survival of 10-12 months and 2-year local control rates of 40-64%. Patient selection is important to balance potential benefits of local tumor control against risks of treatment-related side effects.
This document provides an overview of key concepts in radiobiology, including:
1. Ionizing radiation can cause direct and indirect DNA damage. DNA is the main cellular target of radiation.
2. The biological effects of radiation are determined by factors like DNA break type, cell cycle radiosensitivity, and the advantages of dose fractionation such as allowing time for repair between fractions.
3. Fractionation exploits differences in recovery rates between normal and tumor tissues, allowing higher total doses to be delivered to tumors while sparing normal tissues.
This document discusses the history and techniques of radiotherapy in ENT. It begins with the discovery of x-rays in 1895 and progresses to modern technologies like IMRT, IGRT, proton beam therapy and SBRT. It covers the physics, biology and mechanisms of radiation therapy. Key aspects of radiotherapy for head and neck cancers like dosimetry, fractionation schedules, acute and chronic toxicities are summarized. Newer conformal techniques aim to reduce normal tissue damage while adequately treating tumors.
Endobronchial Brachytherapy by Dr.Tinku JosephDr.Tinku Joseph
Endobronchial brachytherapy (EBBT) involves placing a radioactive source near a tumor to deliver high doses of radiation directly to it. EBBT is used palliatively to relieve symptoms from airway tumors by reducing tumor size. It can be performed using high or low dose rate brachytherapy via bronchoscopy. EBBT is effective at improving symptoms like hemoptysis and airway patency in 70% of patients for at least 6 months. It is also used to prevent restenosis in benign airway stenosis. While generally well-tolerated, risks include radiation bronchitis, stenosis, and fistula formation.
A workshop hosted by the South African Journal of Science aimed at postgraduate students and early career researchers with little or no experience in writing and publishing journal articles.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
Odoo provides an option for creating a module by using a single line command. By using this command the user can make a whole structure of a module. It is very easy for a beginner to make a module. There is no need to make each file manually. This slide will show how to create a module using the scaffold method.
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The simplified electron and muon model, Oscillating Spacetime: The Foundation...RitikBhardwaj56
Discover the Simplified Electron and Muon Model: A New Wave-Based Approach to Understanding Particles delves into a groundbreaking theory that presents electrons and muons as rotating soliton waves within oscillating spacetime. Geared towards students, researchers, and science buffs, this book breaks down complex ideas into simple explanations. It covers topics such as electron waves, temporal dynamics, and the implications of this model on particle physics. With clear illustrations and easy-to-follow explanations, readers will gain a new outlook on the universe's fundamental nature.
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বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
তাই একজন নাগরিক হিসাবে এই তথ্য গুলো আপনার জানা প্রয়োজন ...।
বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
2. INTRODUCTION
■ Radiation is a loco-regional therapeutic modality used in definitive or palliative
management of approximately two third of cancer patients
■ Cellular DNA molecule of cancer cells or normal tissues is the target for radiation
■ DNA damage to cancer cells via:
• Direct damage photon electron damage the DNA.
• Indirect damage photon electron generate free radical damage the
DNA.
● Single broken strand can usually be repaired by the cell while two broken strand
commonly results in cell death
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4. Therapeutic Ratio
Ratio of Tumor lethal dose /Normal tissue
toxicity
TR is a indicates if a tumor is radio-curable
TLD> NTT then radical dose of radiation
cannot be delivered radioresistant
The optimum choice of radiation dose delivery
technique is one of the maximizes the TCP &
simultaneously minimize the NTCP
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5. How to achieve tumor
control ?
1. Dose escalation
2. Reduce the dose to
normal tissue
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6. Dose escalation
■ Physical &Technological techniques: Conformal radiotherapy
■ Exploiting Radiobiological advantages: fractionation & Quality of radiation
■ Chemical agents- radiosensitizers & chemical radioprotectors
■ Others- stem cell therapy, gene therapy
Protection of
normal tissue
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7. To deliver sufficient
dose to the tumor
To induce minimal damage
to the in the surrounding
normal tissue
Probability of
cure
Risk of
toxicity
Need of Radiation Modifiers
The tolerance of normal tissue continues to limit the maximum dose that can
be delivered safely to the tumor
e n -
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8. Radiation modifiers
• Agents that can modify the sensitivity of tumor or normal tissue to
radiation are collectively called as radiation modifiers
• They should increase possibility of tumor control without increasing the
normal tissue injury
● Radiation sensitizer increase the effect of RT, selectively on the tumor
● Radiation protector spares Normal tissue from effects of RT
● Radiation mitigators Prevent occurrence of detrimental effects of RT on
normal tissues
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9. Therapeutic ratio with radiation sensitizer
RS Shifts the tumor control curve to the left
Resulting in higher chances of cure for an equivalent
toxicity
Selective uptake in tumor leaky tumor vasculature or
pathways targeted by the radiation sensitizer or
receptors affected by the RS may have
higher/preferential expression in tumor
-
-
-
-
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10. Therapeutic ratio with radiation protector
Radioprotector reduces the probability of normal
tissue toxicity for a given dose of radiation
Pushing the toxicity curve to the right
Allows higher dose to be delivered
Higher rate of cure with less or equivalent normal
tissue injury
Selective uptake of RP in normal tissue through
enhanced delivery, uptake or retention compared with
tumor and this give greater protective effective in
normal tissue
- -
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--
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11. Expresses the response of the tumor to irradiation
BERGONIE & TRIBONDAEU’S LAW:
Tissue is considered radiosensitive when
● The cells are undifferentiated
● High metabolic activity
● Higher proliferative capacity and high growth rate
Radio-curability- is the ability of radiotherapy to cause the local eradication of a malignancy
E.g. : Leukemias- these are radio sensitive tumor but not radio-curable
RADIOSENSITIVITY
Exquisitely RS - Small cell lung cancer,
Germ cell tumor, Lymphoma
Moderately RS –Breast cancer, Non small
cell lung cancer, Breast cancer
Radioresistant – Malignant melanoma,
Renal cell carcinoma, adenocarcinoma
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13. Cell cycle phase & Radiosensitivity
M>G2>G1>EARLY S>LATE S
G1
S
G2
M
G0
G0
MITOSIS
DNA
SYNTHESIS
2nd
GAP
1st GAP
RADIORESISTANT
MOD
RADIOSENSITIVE
HIGHLY RADIOSENISTIVE
G1
S
G2 M
Checkpoint inhibitors
CDK2/ CYCLIN
CYCLINE/CDK
2
CYCLIND/
CDK4
CYCLIN
B/CDK1
15. Oxygen effect in Radiotherapy
● After absorption of radiation interaction
with water molecules free radical
production occurs
● passing through biological material these
induce SSBs and DSBs however short
lived
● O2 causes oxidation fixation of these
breaks causing unrepairable DNA damage
This is called “damage fixation” by oxygen
16. Oxygen Enhancement Ratio
OER- Dose to produce a given effect with no O2 present
Dose to produce the same effect with 1 atm of air
■ Oxygen is the best known most general radiation sensitizer
■ Well oxygenated cells- approximately 2.5 times more sensitive to a given dose of
ionizing radiation
■ Its value close to 3.5 at high doses but may have lower value of about 2.5 at x-ray
less than about 2 to 3 Gy
17. HYPOXIA
● CHRONIC HYPOXIA- Limited diffusion
distance of O2 through tissue
● ACUTE HYPOXIA- Temporary closing of a
tumor blood vessel owing to the malformed
vasculature of the tumor due to lack of
smooth muscle, incomplete endothelial lining
and incomplete basement membrane
● Leads to slow rate of proliferation which
decreases the sensitivity to chemotherapy and
radiotherapy
● The concentration of anticancer drugs lesser
in cells away from the blood vessels leads to
COP-
22mmhg
COPi- 20
mmhg
PP- 0
mmhg
70um
18. IDEAL RADIOSENSITISER
■ Non-cell cycle specific
■ Potent radio sensitizing effect
■ Lack of toxicity
■ Adaptable to convenient out-patient administration
To be clinically effective they should improve the therapeutic ratio i.e.
TCP/NTCP, because if it equally increases the effect and side effect
then it is not useful
-
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-
- -
19. CHEMICAL
●Modifiers of HB
●Hypoxic cell and non hypoxic
cells radiosensitizer
●Hypoxic cytotoxins– non hypoxic
cell
●Biologic modifiers
●Chemotherapeutic drugs
PHYSICAL
●Hyperbaric oxygen
●Carbogen with or without
nicotinamide
●Arcon
●Hyperthermia
TYPES OF RADIOSENSITIZATION
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e
~
~
W
W
21. HYPERBARIC OXYGEN
■ HBO therapy- an increase in
barometric pressure of the gas breathed
by the patient during radiotherapy is
termed as hyperbaric oxygen therapy
■ Pioneered by Churchill-Davidson in
1958 at St. Thomas hospital in London.
■ Patients were sealed in chambers filled
with pure oxygen raised to a pressure at
3 atm
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22. ■ M.O.A.- enhances the amount of dissolved oxygen in plasma, thereby increasing
O2 delivery independent of hemoglobin
■ Elevation of the tumor oxygen pressure has ben shown to be preserved clinically
after 30 min after HBO exposure
■ Tissue damage is dependent on the cell type, concentration of O2 and duration of
exposure
■ Two different application in combination with radiotherapy
● As a radiosensitizer
● As a therapeutic agent for treating late radiation injury
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~
23. BOHR EFFECT
Hyperbaric oxygen shift the graph to the
right side , so more unloading at the
metabolizing site ( tumor site) due to low Ph
in the environment
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24. PROBLEMS
● Feeling of claustrophobia from being sealed in narrow tube
● Cumbersome logistics associated with delivery- unconventional hypo-fractionated schemes
SIDE EFFECTS
● Barotrauma to ears ,sinuses and lungs
● temporary worsening of myopia
● Acute CNS oxygen toxicity
Recent Cochrane review- For H&N cancer, HBOT improved local tumour
control and tumour related mortality; No benefit in other subsites, rather
increased risk of severe radiation tissue injury observed
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25. CARBOGEN = 95% O2 + 5% CO2
● Pure oxygen if breathed vasoconstriction defeats the objective of increasing O2
availability
● RATIONALE addition of co2 to gas breathing mixture shift the oxygen-HB CURVE to
right which facilitate oxygen unloading into the tissue
● Corrects Chronic hypoxia
■ Advantages Can be given under normo-baric condition
Can be given with or without concurrent administration of nicotinamide
■ Clinically failed to provide significant therapeutic gain ( Horseman et al-2007)
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&
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26. NICOTINAMIDE
■ Vitamin B3
■ Prevents the transient fluctuations in tumor blood flow corrects acute hypoxia
■ Nicotinamide administered 1 to 1.5 hrs prior to radiotherapy at 60-80 mg/kg
■ Acts as PARP inhibitor inhibits DNA repair
Synergistic effect seen in combination with
1. Hyperthermia
2. Perfluorochemical emulsion
3. Pentoxifylline
4. High oxygen content gas breathing
BCON- Study shows continued a benefit from hypoxia
modification using a carbogen and nicotinamide with
radiation therapy in bladder cancer in presence of necrosis, a
high hypoxia gene score and the basal type
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27. ARCON
Combination of altered fractionation and radiosensitisation using carbogen and nicotinamide
● Accelerated- to overcome proliferation
● Hyper-fractionated - to spare late responding normal tissues
● Carbogen breathing- to overcome chronic hypoxia
● Nicotinamide- to overcome acute hypoxia
RESULT INDICATE THAT ADVANCED LARYNGEAL CANCER WHEN COMBINED
WITH
ARCON HAS A LOCOREGIONAL CONTROL RATE 92% AND EXCELLENT
POSSIBILITIES FOR LARYNGEAL PRESERVATION
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28. HYPERTHERMIA
■ Definition : Elevation of temperature to a supra-physiologic level in the
range of 39 C TO 45 C
■ Hippocrates (470-377 BC) states- “ What medicines do not heal, the lance
will; what the lance does not heal, fire will. Those who cannot be cured by
fire, they are indeed incurable”
■ Biological basis of hyperthermia is based on : Classic radiobiology,
molecular biology and tumor physiology
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29. Hyperthermia induced Cytotoxicity
■ Log linear cell kill very similar to ionizing
radiation cell kill
■ Shoulder region followed by steep slope
■ Lower temperatures, a tail is seen suggestive
of resistant fraction of cells– Thermotolerance
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30. THERMAL ISOEFFECT DOSE:THE ARRHENIUS
RELATIONSHIP
■ Temperature dependence of the rate of cell killing by
heat portrayed by Arrhenius plots
■ Plots the log of the slope (1/Do) of cell survival
curves as a function of temperature
■ Biphasic curves with slope changes at the BREAK
POINT (43 degree for human cells)
■ Above this temperature, an increase of 1 C double the
rate of cell killing
■ Below the breakpoint, the rate of cell killing by heat
drops by a factor of 2 to 4 for each drop of 1 C
■ Cumulative equivalent minutes at 43* C (thermal
dose)
CEM 43 = tR(43-T)
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e
31. THERMOTOLERANCE
■ Development of a transient and
nonhereditary resistance to subsequent
heating by an initial HT
■ Begins a few hours after the first treatment
and takes up to a week to decay
■ Shift the Arrhenius curve to the right and
downward, reflect great thermal resistance
to heat
■ Clonogenic assays reveal that although one
dose of heat kills a substantial fraction of
~
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-
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32. MECHANISM OF ACTION
DIRECT EFFECTS
■ Target for hyperthermia is protein
■ Denaturation of other proteins takes place with HT
■ Heat shock protein upregulation occurs with HT
■ Cytoskeleton of cell i.e., membranes disrupted and signaling pathways are impaired
■ DNA repair proteins are damaged
■ Centrioles are denatured leading to chromosome aberrations
TUMOR CELL DEATH
1. APOPTOSIS reoxygenation due to cell loss
2. NECROSIS
- >
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~
33. Physiology of HT
EFFECT on pH
Tumor cells
Decrease in extracellular PH
Cannot increase proton pumping
Increase in intracellular PH and lead
increase in cyto-toxicity
IMMUNOLOGICAL
EFFECT
■ Heat shock proteins are expressed in cell
surface after hyperthermia
■ Antigen presentation to dendritic cells
■ HSP70 as a cytokine produce
proinflammatory cytokines via binding to
CD14
■ So monoclonal antibodies can be made
for monitoring these proteins non
invasively
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C
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~
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34. EFFECT ON
PERFUSION
Increased tissue perfusion (41-41.5 C)
Changes in vascular permeability
Vascular stasis and hemorrhage (42-44C)
EFFECT OF HYPOXIA
Hypoxic cells are not resistant to
hyperthermia as opposed to X rays
which are not effective against
Hypoxic cells
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35. Based on mode of delivery of hyperthermia, classified as
● Local hypothermia
● Regional hyperthermia
● Whole body hyperthermia
Clinical hyperthermia achieved by exposing tissue to-
■ Conductive heat sources
■ Non-ionizing radiation e.g.- electromagnetic or ultrasonic waves
Can be administered using-
■ Invasive sources-radiofrequency antennas, RF electrodes, ferromagnetic metals & US
I
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37. RATIONALE FOR COMBINATION WITH
EXTERNAL RADIOTHERAPY
● Sensitizes the cells in S phase to RT
● No difference in sensitivity to aerobic and anaerobic cells
● HT can lead to reoxygenation which will improve RT response
● HT inhibits the repair of both sub lethal and potentially lethal damage via
its effects in inactivating crucial DNA repair pathways
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38. RATIONALE IN CHEMOTHERAPY
● Increased oxygen radical production
● Hypoxia and pH changes reverse drug resistance
● increased cellular uptake of drug damaged cell membranes enable perfusion independent
drug uptake into tumor tissue
● Temperature sensitive liposome used to selectively deliver drug to tumors because
hyperthermia increases drug delivery and efficacy. E.g. doxorubicin liposomes low
temperature sensitive formulation that exhibits very rapid release of drug ( 50% of drug
release when temperature reaches at 40 degree C
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e - -
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39. THERMAL ENHANCEMENT RATIO
■ Is defined as the ratio of doses of X-
rays required to produce a given level
if biological damage with and without
the application of heat.
■ TER decreases with increasing time
interval between heat and RT
■ TER increases with increasing heat
dose
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~
-
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-
40. ■ Typical TER values applied for 1 hour
● 1.4 at 41 degree
● 2.7 at 42.5 degree
● 4.3 at 43 degree
■ When RT precedes HT,sensitization no longer detectable 2-3 hrs after RT
■ When HT precedes RT, cells can be sensitized for upto several hours
THERAPEUTIC GAIN FACTOR
Ratio of the TER in the tumor to the TER in normal tissues
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41. ADVERSE EFFECTS
■ External application of heat may cause surface burns
■ Whole body hyperthermia can cause swelling , blood clots and bleeding
■ Systemic shock
42. ●META ANAYLYSIS- Showed small but significant benefit of
sensitizer in local control and overall survival which was
shown in head & neck ,bladder & rectal cancer but non-
significant benefit in prostate & breast cancers
-
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-
-
43. CHEMICAL RADIOSENSITISERS
●Modifiers of HB
● Non hypoxic cell radiosensitizer
●Hypoxic cell radiosensitizer
●Hypoxic cytotoxins
●Biologic modifiers
●Chemotherapy
44. BLOOD
TRANFUSION
■ Anemia, powerful adverse prognostic
factor in pts of ca cervix, H & N cancers &
lung cancer
■ 1ST clinical investigation- in advanced
cervical cancer
■ Transfusion to HB level of 11 mg/dl or
higher- improved survival
■ Transfusion to HB level of 11g/dl or
higher- improved survival
■ Transfusion to pts with low Hb levels lead
to increased oxygen tension within tumor
In a study of Denmark, the patients with low
hemoglobin level had a significant reduced
probability of locoregional control, disease-
specific and overall survival. In the low
hemoglobin group, transfusion did not
improve the outcome in locoregional control,
disease specific or overall survival
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~
-
-
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45. ERYTHROPOETIN
It is an alternating means of raising hemoglobin during radiotherapy
● Dose- 200 micro/kg/day * 5 days/week
● Not cost effective(vs. transfusion)
● Induces prompt reticulocyte count
● Two studies conducted in head & neck cancer failed to show any benefit
PERFLUROCARBONS
● Artificial blood substances
● Small particles capable of carrying more oxygen or manipulating the oxygen
unloading capacity of blood
E.g. Perfluorotributylamine
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e
~
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46. NON-HYPOXIC CELL SENSITIZERS
● Halogenated pyrimidines
● Since rapidly dividing tumor cells require nucleotide metabolites for DNA synthesis, selective
uptake occurs compared to normal tissue
● MOA- Incorporates into DNA in place of thymidine faulty DNA more sensitive to U.V. Rays
and X-rays cell kill at attempted repair
● Cell cycle specific radiosensitizers
1. 5- bromodeoxyuridine
2. 5-iododeoxyuridine
● Tumor responses are good, but normal tissue toxicity was unacceptable because ofsusceptibility
of rapidly dividing cells like mucosa , skin , bone marrow which lead to more normal tissue
toxicity
~
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-
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-
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-
-
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-
- -
47. HYPOXIC CELL RADIOSENSITIZERS
● Electrophilic agents enhances the tissue response to standard radiation,
generally by mimicking the effects of oxygen, which induces the
formation and stabilization of toxic DNA radicals
● These are the nitroimidazole group of compounds and acts as electron
donors and reacts with DNA to form adducts with increased free radicals
and increased DNA damage
● Forms DNA adducts and increased free radicals
● Selectively activated in the hypoxic tumor cells causing
radiosensitisation with acceptable normal tissue toxicity
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48. PROPERTIES OF HYPOXIC CELL SENSITIZER
■ Should be chemically stable & not subject to rapid metabolic break down
■ Highly soluble in water or lipids & must be capable of diffusing a considerable
distance through a non vascularized cell mass to reach the hypoxic cell
■ It should be effective at relatively low daily dose/fraction used in conventional
fractionated radiotherapy
~ -
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49. DOSE MODIFICATION
FACTOR
Defined as the dose of radiation required
to produce an effect without and with a
dose of radiation required to produce an
effect without and with a drug
DMF=
If DMF, =1 no drug effect
>1 enhancement
Dose (radiation)
Dose ( radiation+ drug)
SENSITIZER
ENHANCEMENT RATIO
■ The magnitude of sensitizing effect
is usually expressed as sensitizer
enhancement ratio for the same
biological effect
● None of the hypoxic sensitizers
developed to date can create more
SER= Radiation dose without sensitizer
Radiation dose with sensitizer
-
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-
50. than SER of 1.3 at tolerable doses
METRONIDAZOLE
■ 1st generation 5-nitroimidazole
■ Sensitizer enhancement ratio 1.2
■ Dose-oral 500mg tablets
■ Half life-9.8hrs
■ Total cumulative dose should not exceed
54gm/m2
■ Optimal time for administration – 4hr
before radiation
■ Dose limiting toxicity-
1. Gastrointestinal
2. Sensory peripheral neuropathy
MISONIDAZOL
E
● 2ND generation 2-nitroimidazole
● Higher electron affinity
● Sensitizer enhancement ratio
1.4 with multiple dose of 2gm/m2
1.15 with 0.5mg/m2
● Formulations 500 and 100 mg tab and
capsules
● Once or twice a week for 5-6 weeks
● Total cumulative dose not to exceed
12gm/m2
● Optimal dose for administration- 4hr
before radiation
51. ETANIDAZOLE
● 3RD generation analog of misonidazole
● SER- 2.5-3 with dose of 12 gm/m2
● 1000mg/19.4ml saline solution
● Total dose -40.8 g/m2 3 times/week for
6 weeks
● 30 min before radiation
● Arthralgia seen more often with 48 hr
continuous infusion
● Lesser neurotoxicity due to shorter half
life and lower lipid solubility( less
rapidly taken by the neural tissue)
PIMONIDAZOLE
● 4- Nitroimidazole
● More potent than
Misonidazole
● Several- fold increase in
tumor concentration
● Maximum tolerated dose-
750mg/m2
● Dose limiting toxicity-
CNS manifesting as
disorientation & malaise
52. NIMORAZOLE
● A5-nitroimidazole of same structural class as metronidazole
● Administered in form of gelatin-coated capsules containing 500mg active
drug
● Given orally 90 min prior to irradiation
● Daily dose 1200mg/m2 body surface
● Total dose not exceed 40gm/m2
● Less effective radiosensitizer than misonidazole or etanidazole
● Less toxic, no cumulative neuropathy
● Large dose can be given
53. In Denmark, Nimorazole has become the part of the
standard RT in Head & Cancer quote study locally
advanced pharynx and supraglottic cancer RT vs RT with
nimorazole showed local control 49% vs 33 % and can
be given without major side effects
NEWER NITROIMIDAZOLES ARE:
C
- -
- -
-
-
54. • Doranidazole
HYPOXIC CYTOTOXINS- Bio reductive Drugs
■ Killing of radioresistant hypoxic cells by selective undergoing intracellular
activation in low oxygen tensions
■ Overcome major cause of resistance of solid tumors – inadequate
oxygenation & drug delivery to tumor cells distant to blood vessel
QUINIONE
ANTIBIOTICS
➢ MMC
➢ PORIFIROMYCIN
➢ E09
BENZOTRIAZINE
DI-N-OXIDES
➢ TIRAPIZAMINE
➢ CHLORAMBUCIL N-
OXIDE
NITROAROMATIC
➢ MISONDIAZOLE
➢ Nicq-1
➢ Pr-104
-
- -
-
- -
- -
-
- u
-
~
~
55. MITOMYCIN-C
■ Chemotherapy drug alkylating agent inhibits DNA-DNA cross linking
■ Cytotoxic to radioresistant hypoxic cells
■ Differential cytotoxicity between hypoxic and oxygenated cells
■ Dose limiting toxicity-cumulative myelosuppression
■ Clinical application backbone of definitive chemoradiation protocols
in squamous cell ca of the anal canal in conjunction with 5 FU (1000
mg/m2) C.I.
■ Dose – 10mg/m2 on Day 1 and 30
PORFIROMYCIN - A mitomycin C derivative
■ Provides greater differential cytotoxicity between hypoxic and
-
-
~ - -
~
56. TIRAPAZAMINE (sr 4233)
● Highly selective toxicity against hypoxic cells both in vivo & vitro
● MOA causes ds DNA breaks via the active compound which is a drug is reduced by intracellular
reductases to form highly reactive material produces both double & single strand break in DNA
● 25-200 times more drug is required to cause same amount of cell kill in aerobic conditions compared to
anaerobic conditions
● Dose-290mg/m2/d on day 2 of weeks 1.4. and 7 weeks with cisplatin 75mg/m2
● Tirapazamine can also enhance the cytotoxicity of the cisplatin
● S/E- nausea & muscle cramping
● Unlike the oxygen-mimetic sensitizers, tirapazamine mediated therapeutic enhancement occur both
when the drug is given before or after irradiation
- -
- - - -
- - -
-
-
-
-
-
58. GOALS IN COMBINING CT WITH RT
■ Improving local-regional tumor control
■ Decreasing or eliminating distant metastases
■ Preserving organ or tissue integrity and function
■ To have independent toxicity
■ To enhance tumor radio response
59. Enhancement of tumor radio-response
● Induces cell death by causing direct DNA Damage
● Increases cell DNA susceptibility to radiation by altering SLD repair/PLD repair
Cell cycle redistribution & synchronization
● Moves cells into more sensitive phases of cell cycle (G2M)
● Blocks transition of cells and accumulates in G-2 to M TAXANES
● Kill radioresistant S phase cells E.g. Gemcitabine
Counteracting Hypoxia-associated tumor radio-resistance
Chemotherapy cell kill leads to lowering of the interstitial pressure the reopening of
previously closed capillaries reestablishment of blood supply Previously hypoxic cells
are closer to capillaries hypoxia negated
Prevents repopulation of tumor cells that occurs during the course of radiation when used
concurently
CHEMOTHERAPY &RADIATION INTERACTION
MECHANISMS
60. Four Strategies to improve Therapeutic Index
Steel and Peckham classified into four
groups
■ A spatial cooperation
■ Independent toxicity
■ Enhancement of tumor response
■ Protection of normal tissue
61. SPATIAL COOPERATION
■ Action of RT and CT drugs occurs at different anatomical sites
■ No interaction between the two modalities
■ Independent action of the two agents Localized tumors are treated radiation therapy, while
chemotherapeutic drugs are given to eliminate disseminated micro metastases
E.g., Early-stage breast cancer
INDEPENDENT TOXICITY
■ Combination of radiation and CT is better tolerated if drug with non-overlapping toxicities are
used
■ Two modalities can both be given at full dose.
E.g., avoiding MTX with brain RT/ or bleomycin with lung irradiation
PROTECTION OF NORMAL TISSUES
■ Technical improvement in radiation delivery
■ Administration of chemical or biological agents that selectively or preferentially protect normal
62. tissue against the damage by radiation or drugs e.g. Amifostine, which is radical scavenging agent
Enhancement of tumor response(Cytotoxic
Enhancement)
Interaction between drugs and radiation at the molecular ,
cellular or pathophysiologic level, resulting in antitumor
effect greater than would be expected on the basis of
additive actions
Can be explained by iso-bologram
➢ Between mode1 and mode 2 above ( additive
interaction)
➢ Above mode 1 – infra-additive interactiojn
➢ Below mode 2- supra-additive interaction
Mode 1
Mode 1
-
-
-
-
- - -
-
-
-
~ -
63. Biological Cooperation
■ Independent targeting if subpopulations of cells within the tumor itself, as
some portion of the actual radiation target is resistant to radiation
■ So more prominent example for biological cooperation is hypoxic cell
cytotoxins such as tirapazamine which is most potent in anoxic conditions
Temporal Modulation
■ Drugs that impact tumor response in between fractions targeting repair,
reoxygenation, repopulation and redistribution
■ For e.g.- antiproliferative therapies could prevent accelerated repopulation
between fractions , conversely although DNA damage repair blockade may
66. STRATEGY ADVANTAGES DISADVANTAGES
SEQUENTIAL
CHEMORADIATION
• Least toxic
• Maximizes systemic
therapy
• Smaller radiation fields if
induction shrinks tumor
• Increased treatment time
• Lack of local synergy
CONCURRENT
CHEMORADIATION
• Shorter treatment time
• Radiation enhancement
• Compromised systemic
therapy
• Increased toxicity
• No cytoreduction of tumor
CONCURRENT
CHEMORADIATION
AND ADJUVANT
CHEMOTHERAPY
• Maximizes systemic
therapy
• Radiation enhancement
• Both local and distant
therapy delivered up front
• Increased toxicity
• Increased treatment time
• Difficult to complete
chemotherapy after
chemoradiation
INDUCTION
CHEMOTHERAPY AND
CONCURRENT
CHEMORADIATION
• Maximizes systemic
therapy
• Radiation enhancement
• Increased toxicity
• Increased treatment time
• Difficult to complete
chemoradiation after induction
ADVANTAGES & DISADVANTAGES OF DIFFERENT CHEMORADIATION
SEQUENCING
67. Platinum Compounds (Cisplatinum)
● MOA- Inhibition of DNA synthesis and transcription
-inhibition of repair of radiation induced DNA damage
● Cell cycle- nonspecific
● More toxic to hypoxic than aerated cells
● Also, radiation induces increased cellular cisplatin uptake
● Concurrent with radiation
Head & neck cancer(100mg/m2) three weekly regimen
Carcinoma cervix (40mg/m2) weekly regimen, lung cancer and esophageal cancer
Carboplatin
Dose- AUC-2 weekly regimen with paclitaxel in esophageal cancer and high risk
medulloblastoma
68. TOPOISOMERASE-1
INHIBITORS
■ Camptothecin (irinotecan, topotecan)
■ Inhibition of repair of radiation
induced DNA strand breaks
■ Redistribution into G-2 phase of the
cell
■ Conversion of radiation induces SSB
to DSB
■ Used in SCLC @ doses sequential-
200mg/m2 + cisplatin 80mg/m2
● Cell cycle – specific arrest in G2/M phase
which is highly radiosensitive
● Microtubule inhibitors
● Induction of apoptosis leads to
reoxygenation
● Used in esophageal cancer – paclitaxel
50mg/m2 weekly regimen with carboplatin
TAXANES
69. ANTIMETABOLITES (5-FLUROURACIL)
■ Incorporates into RNA disruption of RNA function
■ Inhibition of thymidylate synthetase function- inhibits DNA synthesis and results in
accumulation of cells in early phase
■ Direct incorporation of the drug into DNA
■ The combination of these effects underlie its radio-sensitizing effect
■ The combination of continuous infusion 5-FU and radiation is a mainstay of treatment
for GI tumors, anal cancer and bladder cancers
■ Also, along with RT in combination with Leucovorin weekly(375 mg/m2)
70. CAPECITABINE
■ Oral Fluoropyrimidine carbamate prodrug form of 5- fluorouracil
■ Antimetabolite and cytotoxic since thymidine phosphorylase is
overexpressed in tumor tissues
■ Capecitabine was shown to be safe to replace 5-FU in chemoradiotherapy
regimen for rectal cancer
■ Dose- 825 mg/m2 b.d.
■ Used in rectal cancer, esophageal cancer and gastric cancer
71. GEMCITABINE
■ Another nucleoside analog that
acts as a potent radiosensitizer
■ M.O.A- direct incorporation into
DNA and drug induced apoptosis
are underlie its cytotoxicity
■ S- phase specific and selective
toxic to proliferative cells
■ DOSE- 300-400mg/m2 weekly
in pancreatic cancer with RT
PEMETREXED
■ It is not cell cycle phase
specific,
■ Simultaneous inhibition of
multiple folate-requiring
enzymes including
thymidylate synthase
synergistic activity with
radiation seen because of
interference with DNA
synthesis
72. TEMOZOLAMID
E
● Alkylating agent
and cell cycle
nonspecific agent
● Metabolic
activation to the
VINCRISTINE
M-Phase specific drug
MOA- antitumor activity is due to primary to
inhibition of mitosis at metaphase through its
interaction with tubulin
Dose- 1.5 mg/m2 weekly regimen with
radiation in medulloblastoma
74. Activation leads to Enhancement of
proliferation ,tumor survival, and DNA
repair and further signalling is activated
after irradiation and has been
implicated in accelerated repopulation
EGFR blockade leads to reduction of
tumor cell repopulation by modulation
of cellular proliferation &
enhancement of tumor radio response
EGFR
pathways
75. CETUXIMAB
■ Specifically targets EGFR with high affinity and blocks ligand binding
■ Enhances antitumor activity of cisplatin / radiotherapy
■ Intravenous given one week before radiotherapy with loading dose of 400 mg per square
meter over a period of 120 mins f/b weekly 60 min infusion of 250mg/m2 for the duration of
radiotherapy
■ Side effects- angioedema , urticaria , hypotension , bronchospasm, Rash
■ Dose limiting side effect- Infusion related toxicity
Bonner et al showed treatment of locoregional H&N cancer with
concomitant high dose radiotherapy plus cetuximab improves
locoregional control and reduced mortality without increasing side
effects.
77. Protection Mitigation Treatment
measure applied before the
threshold dose for the
specific side effect is
reached
in the symptomatic phase to
reduce the side effects
Strategies used before the
manifestation of clinical
symptoms
78. IDEAL RADIOPROTECTOR
■ High therapeutic ratio
■ Easy and comfortable administration
■ Reasonable and cost-effectiveness
■ Should preserve of the anti-tumor efficacy of radiation
■ High efficacy /toxicity profile
80. HISTORICALLY
CYSTEINE
● a free SH group at one end
● strong basic function i.e., amine or guanidine at
other
■ Free radical scavenging
■ Hydrogen atom donation to facilitate direct
chemical repair at sites of DNA
■ The toxicity of the compound could be greatly
S-CH2-CHH
NH2
COOH
81. DOSE REDUCTION FACTOR
■ DRF- Dose of radiation in the presence of the drug/ dose of radiation in the
absence of the drug
■ Animals injected with cysteamine to concentrations of about 150mg/kg
require doses of x-rays 1.8 times larger than control animals to produce the
same mortality rate. This factor of 1.8 is called the DOSE REDUCTION
FACTOR, defined as to produce a given level of lethality
82. Two Radioprotectors in Practical Use
COMPOUND DOSE
(MG/KG)
DRF
7DAYS (GI)
DRF
30DAYS
(HEMATOP
OETIC)
USE
WR-638
CYSTAPHOS
500 1.6 2.1 Carried in field
pack by Russian
army
WR-2721
AMIFOSTINE
900 1.8 2.7 Protector in
radiotherapy and
carried by US on
lunar trips
83. AMIFOSTINE (WR-2721)
Walter Reed Army Research Institute, USA
AMIFOSTINE
( Phosphorothioate prodrug –inactive,
does not readily permeate cells)
ACTIVE THIOL
(WR 1065)
ENTER IN CELL BY FACILIATED
OXIDATION
DIFFUSION
WR- 33278 ( Polyamine like
disulphide metabolite)
84. WR-33278 ( ANTIMUTAGENIC)
A.RADIOPROTECTION B. ACCELERATED RECOVERY
1. Prevention of DNA damage a. upregulates the expression of proteins
➢ Condensation of DNA, thereby involved with DNA repair
limiting potential target sites b. Inhibits apoptosis, by Bcl-2 and
for free-radical attack hypoxia-inducible factor-1
➢ Anoxia c. Enhanced cellular proliferation
Rapid consumption of O2 levels
to induction of cellular anoxia
85. WHY SELECTIVE
CYTOPROTECTIO
N?
Extensive uptake is seen in:
1. Salivary glands
2. Kidneys
3. Intestinal mucosa
Markedly lower uptake is seen in
■ Tumor tissue
■ Amifostine and metabolites
do not cross the blood-brain
barrier
Differential expression of
alkaline phosphatase in tumor
tissue
Hypo vascularity & hypoxia
Low pH the tumor
100 folds decreased
concentration in
tumor tissue
86. ■ Not orally bioavailable
● Rapidly cleared from plasma; t1/2 < 1min and >90% drug cleared plasma 6 min
after administration
● Once Amifostine enters the plasma, it is rapidly metabolized and distributed in
tissues, whereas the excretion of the metabolic products is very low
■ Timely administration of amifostine is necessary
■ Amifostine before 30 min of RT provide optimal benefit for cytoprotection of
normal tissue.
■ Single morning dose of amifostine provides superior radioprotection than with a
single afternoon dose
87. ROUTES OF
ADMINISTRATION
■ At a dose of 200mg/m2 daily, given as a slow i.v. push over 3 mins,15-30 mins
before each fraction of radiation therapy after premedication
■ B.P. should be measured before and immediately after the 3 mins Amifostine
infusion
■ S/c injection of 500mg of amifostine
■ 1500 mg intra rectally 20-30 mins before each radiotherapy session Useful for
pelvic irradiation
■ Side effects : Nausea,Fever/rash reaction,Hypotension
88. SIDE EFFECTS
■ Nausea, vomiting & other GI effects
■ Transient hypotension-
■ Infusion related- flushing and feeling warmth, chills , dizziness,
somnolence, hiccups
& sneezing.
■ Hypocalcemia in <1%
■ Metallic taste during infusion
■ Allergic reactions include rash, fever and anaphylactic shock
89. GLUTAMINE
■ Glutamine is a neutral amino acid that acts as a substrate for nucleotide synthesis in most
dividing cells
■ It is the most abundant amino acid in free blood and constitutes 60% of the total free
amino acid pool in skeletal muscle
■ Glutamine metabolism regulated by glutaminase and glutamine synthetase which occur
primarily in skeletal muscle and brain.
■ States of physiologic stress, including those resulting from the treatment of malignant
disease , are characterized by a relative deficiency of glutamine
■ Supplementation with this inexpensive dietary supplement may have an important in
prevention GI, neurologic, and decreases mucosal membrane injury
90. MEMANTINE
■ NMDA receptor antagonist , open channel blocker that shown to be
neuroprotective and improve cognitive function in patients receiving WBRT
■ MOA- it binds to NMDA receptor and prevents the influx of calcium , thus
preventing the disruption of synaptic plasticity.
■ Dose-started within 3 days of initiation of WBRT and continued for 24 weeks
with gradual escalation from 5mg to 20 mg per day.
■ Side effects- fatigue, alopecia, nausea ,headache , dizziness, constipation
91. NITROXIDES
■ Are Antioxidants that convert between the
oxidized and reduced form
■ In, oxidized form, it exist as a stable free radical
that can undergo hydrogen reductions to
hydroxylamines
92. ■ Both are antioxidants functions, only nitroxides
RADIATION MITIGATORS
Alternatively, radiation mitigators can be delivered
during or shortly after exposure to repopulate a
critical cell compartment such as mucosa or bone
marrow
In this instance, the mitigator is used to prevent acute
toxicity
Radiation induce late normal toxicity
Events include mitotic cell death, active cytokines
cascades and extracellular matrix cell deposition
Mitigators aim to interrupt these cascades to prevent
the perpetuation of damage
Reduce the expression of toxicity
93. PALIFERMIN- Radiation Mitigator
■ Recombinant human keratinocyte growth (FIBROBLAST GROWTH
FACTOR 7)factor used to prevent and treat oral mucositis following
radiation or chemotherapy
■ Stimulates cell proliferation and differentiation in. mucosa of alimentary
tract, salivary glands, and type II pneumocytes
■ Enhances glutathione mediated cell protection too
■ Preclinical trials have shown requirement of increase in RT doses to cause
ulcerative mucositis
■ Predominant use till date has been for stem cell transplant with TBI
94. regimens before and after TBI at doses of 60mcg/Kg/day
CONCLUSION
■ Radiation as solo modality is not sufficient in majority of instances to cure cancers
mainly due to NTT
■ Cell hypoxia is one of the most correctable & exploited situation in clinic that has led to
important improvements in treatment outcomes
■ Newer molecular pathways are being studied for understanding mechanisms which can
increase radiosensitivity
■ Chemo-radiation continues to be the most significant radiosensitizer
■ Effective and feasible radiation protectors and mitigators have mostly been of
theoretical importance and their routine use in clinic is still a distant reality in day to day
practice