1. The study aimed to develop a predictive nomogram and dose constraints for hematological toxicity in cervical cancer patients treated with chemoradiation including IMRT.
2. Thirty-seven patients were treated with IMRT and cisplatin, and bone marrow was re-delineated to include the entire marrow volume.
3. Dose-volume histograms were combined with toxicity data to create a nomogram from which hematological toxicity probabilities can be estimated based on bone marrow dosimetry.
This document discusses lung stereotactic body radiotherapy (SBRT) for the treatment of early stage non-small cell lung cancer (NSCLC). It covers treatment indications for SBRT, methods used to account for tumor motion including 4DCT planning and respiratory gating, treatment planning guidelines, evidence from studies showing high rates of local control and survival, and results from RTOG trials of SBRT for lung cancer. In particular, it highlights that SBRT achieves local control rates of 85-95% and overall survival rates of 50-95% at 3-5 years for early stage NSCLC.
Adaptive radiotherapy (ART) can improve treatment for head and neck cancer patients. ART involves modifying the treatment plan based on anatomical changes observed during radiation therapy delivery. For head and neck cancer, target volumes and organs at risk often change significantly over the course of treatment due to factors like weight loss or tumor shrinkage. Studies have shown ART can improve dose distribution by reducing dose to organs at risk while maintaining or improving tumor dose coverage. Clinical benefits of ART include improved local tumor control and fewer treatment toxicities. ART is most beneficial for patients experiencing greater anatomical changes, such as those with more advanced tumors or significant weight loss.
El QUANTEC nos ayuda a los oncólogos radioterápicos a la hora de aprobar un tratamiento con sus tablas con "constraints" de los órganos de riesgo (los límites de dosis que pueden recibir los órganos sanos situados entorno al tumor que queremos tratar).
PD: Las tablas se encuentran en las páginas 15-17
SBRT versus Surgery in Early lung cancer : DebateRuchir Bhandari
This document discusses stereotactic body radiation therapy (SBRT) versus surgery for early stage non-small cell lung cancer (NSCLC). SBRT delivers a high dose of precision radiation to the tumor target in 1-5 fractions. Several studies have shown comparable survival and recurrence rates between lobectomy and sublobar resection for stage I lung cancer. SBRT has comparable or better local tumor control and survival rates than conventional radiation therapy for early stage NSCLC, with fewer side effects. While surgery may remain the standard of care, SBRT has emerged as a viable alternative to surgery for medically inoperable early stage NSCLC patients, with some studies investigating its use in operable patients as well.
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 discusses target volume definitions in radiotherapy planning according to ICRU reports. It defines key volumes including the gross tumor volume (GTV), clinical target volume (CTV), internal target volume (ITV), planning target volume (PTV), treated volume, and irradiated volume. The CTV accounts for subclinical spread around the GTV, while margins are added to the CTV to create the ITV and PTV to account for organ motion and set-up uncertainties respectively. Together these volumes aim to ensure the prescribed dose is delivered to the tumor while minimizing dose to surrounding healthy tissues.
This document summarizes guidelines for radiotherapy planning for lung cancer. It discusses:
- Defining the gross tumor volume (GTV) based on imaging like PET which can help reduce margins.
- Adding margins to the GTV to create the clinical target volume (CTV) accounting for microscopic spread. There is debate around elective nodal irradiation.
- Further expanding the CTV to create the planning target volume (PTV) accounting for set-up uncertainty and tumor motion. Techniques like gating can help reduce this.
- Contouring the lungs as organs at risk and calculating dosimetric parameters like V20 and V5 to quantify lung dose and risk of toxicity. Dose needs to
Radiotherapy in paediatrics - late effects and second malignanciesAshutosh Mukherji
1. Childhood cancer survivors face risks of late sequelae from radiation therapy including growth impairment, cognitive deficits, infertility and cardiac issues.
2. The risks are dependent on factors like radiation dose, age at treatment, and volumes of normal tissues irradiated.
3. Second malignancies are a major concern after radiation therapy, with bone tumors, soft tissue sarcomas and breast cancer being common second cancers seen in survivors.
This document discusses lung stereotactic body radiotherapy (SBRT) for the treatment of early stage non-small cell lung cancer (NSCLC). It covers treatment indications for SBRT, methods used to account for tumor motion including 4DCT planning and respiratory gating, treatment planning guidelines, evidence from studies showing high rates of local control and survival, and results from RTOG trials of SBRT for lung cancer. In particular, it highlights that SBRT achieves local control rates of 85-95% and overall survival rates of 50-95% at 3-5 years for early stage NSCLC.
Adaptive radiotherapy (ART) can improve treatment for head and neck cancer patients. ART involves modifying the treatment plan based on anatomical changes observed during radiation therapy delivery. For head and neck cancer, target volumes and organs at risk often change significantly over the course of treatment due to factors like weight loss or tumor shrinkage. Studies have shown ART can improve dose distribution by reducing dose to organs at risk while maintaining or improving tumor dose coverage. Clinical benefits of ART include improved local tumor control and fewer treatment toxicities. ART is most beneficial for patients experiencing greater anatomical changes, such as those with more advanced tumors or significant weight loss.
El QUANTEC nos ayuda a los oncólogos radioterápicos a la hora de aprobar un tratamiento con sus tablas con "constraints" de los órganos de riesgo (los límites de dosis que pueden recibir los órganos sanos situados entorno al tumor que queremos tratar).
PD: Las tablas se encuentran en las páginas 15-17
SBRT versus Surgery in Early lung cancer : DebateRuchir Bhandari
This document discusses stereotactic body radiation therapy (SBRT) versus surgery for early stage non-small cell lung cancer (NSCLC). SBRT delivers a high dose of precision radiation to the tumor target in 1-5 fractions. Several studies have shown comparable survival and recurrence rates between lobectomy and sublobar resection for stage I lung cancer. SBRT has comparable or better local tumor control and survival rates than conventional radiation therapy for early stage NSCLC, with fewer side effects. While surgery may remain the standard of care, SBRT has emerged as a viable alternative to surgery for medically inoperable early stage NSCLC patients, with some studies investigating its use in operable patients as well.
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 discusses target volume definitions in radiotherapy planning according to ICRU reports. It defines key volumes including the gross tumor volume (GTV), clinical target volume (CTV), internal target volume (ITV), planning target volume (PTV), treated volume, and irradiated volume. The CTV accounts for subclinical spread around the GTV, while margins are added to the CTV to create the ITV and PTV to account for organ motion and set-up uncertainties respectively. Together these volumes aim to ensure the prescribed dose is delivered to the tumor while minimizing dose to surrounding healthy tissues.
This document summarizes guidelines for radiotherapy planning for lung cancer. It discusses:
- Defining the gross tumor volume (GTV) based on imaging like PET which can help reduce margins.
- Adding margins to the GTV to create the clinical target volume (CTV) accounting for microscopic spread. There is debate around elective nodal irradiation.
- Further expanding the CTV to create the planning target volume (PTV) accounting for set-up uncertainty and tumor motion. Techniques like gating can help reduce this.
- Contouring the lungs as organs at risk and calculating dosimetric parameters like V20 and V5 to quantify lung dose and risk of toxicity. Dose needs to
Radiotherapy in paediatrics - late effects and second malignanciesAshutosh Mukherji
1. Childhood cancer survivors face risks of late sequelae from radiation therapy including growth impairment, cognitive deficits, infertility and cardiac issues.
2. The risks are dependent on factors like radiation dose, age at treatment, and volumes of normal tissues irradiated.
3. Second malignancies are a major concern after radiation therapy, with bone tumors, soft tissue sarcomas and breast cancer being common second cancers seen in survivors.
This document discusses stereotactic body radiotherapy (SBRT) for early stage lung cancer patients who cannot undergo surgery. It describes how SBRT delivers a high radiation dose to the tumor in just 1-5 sessions. Studies show SBRT provides improved tumor control compared to conventional radiotherapy, with surprisingly low toxicity. Early investigations found 3-year tumor control rates of 60-80% with SBRT, similar to surgery. Larger prospective trials of SBRT for medically inoperable early stage lung cancer patients demonstrated 3-year local control of 90-98% and low risks of side effects. SBRT provides an effective non-invasive alternative to surgery for these high-risk patients.
This document discusses stereotactic body radiation therapy (SBRT) for head and neck cancers. It provides an overview of SBRT indications, efficacy, toxicity profiles, quality of life outcomes, fractionation schedules, target definition, constraints, and the role of cetuximab. Several studies on SBRT for recurrent head and neck cancers, primary cancers metastatic to the head and neck region, and target volume delineation are summarized. Toxicities are generally low but carotid blowout syndrome remains a concern, especially for tumors adjacent to carotid arteries.
The document summarizes the experience of using stereotactic body radiation therapy (SBRT) and intensity modulated radiation therapy (IMRT) at SMC for lung cancer. Specifically:
- SBRT provided high local control (90%) and low toxicity for early stage lung cancer with few side effects. IMRT improved target coverage and spared normal tissues compared to 3D-CRT for locally advanced lung cancer.
- A study of 77 patients with stage IIIB N3+ lung cancer treated with chemoradiation found IMRT (used in 29 patients) achieved better lung sparing than 3D-CRT based on dosimetry, with similar treatment outcomes.
This presentation is intended to refer while doing planning of SBRT Prostate for all practical aspects from Simulation - contouring - planning - treatment. I am sure it will be very useful presentation for any radiation oncologist who are willing to start workflow of SBRT Prostate in the department of radiation oncology
The document discusses treatment options for brain metastases including surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). It notes that while WBRT was traditionally used, studies show SRS alone may be preferred for limited brain metastases to avoid cognitive decline risks from WBRT. For larger or multiple tumors, WBRT provides better local and distant tumor control compared to SRS alone. Ongoing research evaluates hippocampal-sparing WBRT and the role of SRS boost after surgery to improve outcomes while preserving cognition. The optimal approach depends on disease factors and emerging evidence favors SRS for limited metastases to balance survival benefits with quality of life.
Indications and rt techniques in liver,gb & pancreasDr.Amrita Rakesh
1. The document discusses the anatomy, staging, and treatment options for pancreatic cancer, liver cancer, and gallbladder cancer including surgery, chemotherapy, radiation therapy, and newer techniques like stereotactic body radiation therapy.
2. Key points include that surgical resection offers the only chance for cure in pancreatic cancer but is only possible in 20% of cases, and adjuvant or neoadjuvant chemoradiation can improve outcomes. For liver cancer, options include resection, transplantation, ablation, embolization, and stereotactic body radiation has shown promise in early studies.
3. Guidelines for contouring targets and organs at risk in radiation therapy for the pancreas and liver are also reviewed.
Stereotactic body radiation therapy (SBRT) is a form of high-precision radiotherapy that delivers large, precise radiation doses to tumors in just a few treatment sessions. Studies have shown SBRT provides excellent local tumor control of early stage non-small cell lung cancer comparable to surgery, with less invasive treatment. Ongoing and completed prospective studies continue to evaluate SBRT's long-term outcomes and toxicities compared to other standard treatments like surgery or conventional radiation therapy. SBRT is becoming an important treatment option for medically inoperable early stage lung cancer patients.
The document discusses key concepts in radiobiology relevant for radiotherapy. It defines important treatment volumes including the gross tumour volume (GTV), clinical target volume (CTV), planning target volume (PTV), treated volume (TV), irradiated volume (IV), and organs at risk (OARs). It also describes biological factors that influence radiation effects on tissues, known as the "5 Rs": repair, repopulation, reoxygenation, redistribution, and radiosensitivity. Fractionated radiotherapy takes advantage of these factors to maximize tumor cell kill while minimizing damage to normal tissues.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
1. IMRT allows more conformal dose distributions compared to 3D-CRT but requires more knowledge of dose-volume effects on tumors and tissues.
2. The increased time needed to deliver fractionated IMRT doses may reduce its biological effectiveness due to tissue repair between fractions.
3. Techniques like VMAT, tomotherapy, flattening filter-free beams, direct aperture optimization, and reducing the number of segments can help shorten fraction delivery times for IMRT.
This document discusses guidelines for evaluating radiotherapy treatment plans for primary brain tumors. It provides indications for radiotherapy based on tumor type and extent of resection. Key factors in treatment planning include: contouring target volumes and organs at risk, optimizing dose distribution to cover the target while sparing organs at risk, and quantitatively evaluating plans using tools like isodose distributions, dose volume histograms and indices like coverage, conformity and homogeneity. Plan evaluation ensures the target receives adequate and uniform dose while respecting organ at risk tolerances.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
La costante tentazione dei trattamenti ipofrazionati: breve cronistoria dei modelli biologici e degli effetti clinici
Role of Post-op Radiotherapy in Head and Neck CancersAshutosh Mukherji
This document discusses the role of adjuvant radiation therapy in head and neck cancers. It begins by outlining the use of radical and palliative treatment for stage III and IV diseases. It then reviews several landmark studies that established the benefits of postoperative radiation therapy (PORT) over surgery alone in improving local control and survival. Key factors that determine the need for adjuvant therapy like extracapsular extension, positive margins, and T3/T4 stage are discussed. The document also addresses optimal radiation dose, timing, use of concurrent chemotherapy and altered fractionation schedules based on evidence from clinical trials. While targeted therapies in the adjuvant setting have not proven beneficial so far, ongoing studies are exploring their potential role.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
21 marzo 2014: Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali
This document provides an overview of the fourth edition of the textbook "Practical Radiotherapy Planning". The textbook is written by four authors who are professors and consultants in clinical oncology in the UK. It aims to provide guidance on radiotherapy treatment planning based on sound pathological and anatomical principles. The textbook covers topics such as radiobiology, organs at risk, brachytherapy, emergency radiotherapy, and treatment planning for many cancer sites. It emphasizes the underlying principles of treatment planning that can be applied to conventional, conformal and novel radiotherapy techniques. The textbook includes many clinical images to illustrate key planning concepts.
Altered Fractionation Radiotherapy in Head-Neck CancerJyotirup Goswami
Altered fractionation radiotherapy has been shown to improve outcomes for head and neck cancer patients compared to conventional fractionation. Meta-analyses demonstrate significant benefits including improved 5-year locoregional control and overall survival. However, most modern trials do not address fractionation. Hypofractionation shows promise with comparable tumor control and toxicity but reduced treatment time. Ongoing research combines altered fractionation with chemotherapy and radiosensitizers to further improve outcomes while minimizing toxicity.
This document discusses reirradiation in recurrent head and neck cancer. It notes that radiation therapy plays a central role in head and neck cancer treatment but recurrence still occurs in 20-35% of patients. Reirradiation presents challenges due to prior radiation exposure and damage to normal tissues. The document discusses treatment options, appropriate patient selection, techniques like IMRT to minimize dose to organs at risk, optimal timing and dosing of reirradiation, and management of toxicities.
The document discusses various aspects of radiation oncology and radiotherapy clinical trial design. It provides an overview of the evolution of radiation therapy techniques from the 1960s to present. It also covers important considerations for radiation oncology trials, including target volume delineation, dose schedules, quality assurance measures, and assessing toxicity. Multidisciplinary collaboration and factors influencing radiation sensitivity are also briefly discussed.
Dr. Thomas Yankeelov: Integrating Advanced Imaging and Biophysical Models to...Dawn Yankeelov
This is a talk from the Technology Association of Louisville Kentucky. Dawn Yankeelov is co-chair of TALK, and Dr. Thomas Yankeelov is the director for the Institute of Imaging Science at Vanderbilt University. He presented his latest research in June 2013, "Integrating Advanced Imaging and Biophysical Models to Predict Tumor Growth."
This document discusses stereotactic body radiotherapy (SBRT) for early stage lung cancer patients who cannot undergo surgery. It describes how SBRT delivers a high radiation dose to the tumor in just 1-5 sessions. Studies show SBRT provides improved tumor control compared to conventional radiotherapy, with surprisingly low toxicity. Early investigations found 3-year tumor control rates of 60-80% with SBRT, similar to surgery. Larger prospective trials of SBRT for medically inoperable early stage lung cancer patients demonstrated 3-year local control of 90-98% and low risks of side effects. SBRT provides an effective non-invasive alternative to surgery for these high-risk patients.
This document discusses stereotactic body radiation therapy (SBRT) for head and neck cancers. It provides an overview of SBRT indications, efficacy, toxicity profiles, quality of life outcomes, fractionation schedules, target definition, constraints, and the role of cetuximab. Several studies on SBRT for recurrent head and neck cancers, primary cancers metastatic to the head and neck region, and target volume delineation are summarized. Toxicities are generally low but carotid blowout syndrome remains a concern, especially for tumors adjacent to carotid arteries.
The document summarizes the experience of using stereotactic body radiation therapy (SBRT) and intensity modulated radiation therapy (IMRT) at SMC for lung cancer. Specifically:
- SBRT provided high local control (90%) and low toxicity for early stage lung cancer with few side effects. IMRT improved target coverage and spared normal tissues compared to 3D-CRT for locally advanced lung cancer.
- A study of 77 patients with stage IIIB N3+ lung cancer treated with chemoradiation found IMRT (used in 29 patients) achieved better lung sparing than 3D-CRT based on dosimetry, with similar treatment outcomes.
This presentation is intended to refer while doing planning of SBRT Prostate for all practical aspects from Simulation - contouring - planning - treatment. I am sure it will be very useful presentation for any radiation oncologist who are willing to start workflow of SBRT Prostate in the department of radiation oncology
The document discusses treatment options for brain metastases including surgery, whole brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). It notes that while WBRT was traditionally used, studies show SRS alone may be preferred for limited brain metastases to avoid cognitive decline risks from WBRT. For larger or multiple tumors, WBRT provides better local and distant tumor control compared to SRS alone. Ongoing research evaluates hippocampal-sparing WBRT and the role of SRS boost after surgery to improve outcomes while preserving cognition. The optimal approach depends on disease factors and emerging evidence favors SRS for limited metastases to balance survival benefits with quality of life.
Indications and rt techniques in liver,gb & pancreasDr.Amrita Rakesh
1. The document discusses the anatomy, staging, and treatment options for pancreatic cancer, liver cancer, and gallbladder cancer including surgery, chemotherapy, radiation therapy, and newer techniques like stereotactic body radiation therapy.
2. Key points include that surgical resection offers the only chance for cure in pancreatic cancer but is only possible in 20% of cases, and adjuvant or neoadjuvant chemoradiation can improve outcomes. For liver cancer, options include resection, transplantation, ablation, embolization, and stereotactic body radiation has shown promise in early studies.
3. Guidelines for contouring targets and organs at risk in radiation therapy for the pancreas and liver are also reviewed.
Stereotactic body radiation therapy (SBRT) is a form of high-precision radiotherapy that delivers large, precise radiation doses to tumors in just a few treatment sessions. Studies have shown SBRT provides excellent local tumor control of early stage non-small cell lung cancer comparable to surgery, with less invasive treatment. Ongoing and completed prospective studies continue to evaluate SBRT's long-term outcomes and toxicities compared to other standard treatments like surgery or conventional radiation therapy. SBRT is becoming an important treatment option for medically inoperable early stage lung cancer patients.
The document discusses key concepts in radiobiology relevant for radiotherapy. It defines important treatment volumes including the gross tumour volume (GTV), clinical target volume (CTV), planning target volume (PTV), treated volume (TV), irradiated volume (IV), and organs at risk (OARs). It also describes biological factors that influence radiation effects on tissues, known as the "5 Rs": repair, repopulation, reoxygenation, redistribution, and radiosensitivity. Fractionated radiotherapy takes advantage of these factors to maximize tumor cell kill while minimizing damage to normal tissues.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: nuove possibilità di prevenzione e trattamento della tossicità acuta e tardiva
1. IMRT allows more conformal dose distributions compared to 3D-CRT but requires more knowledge of dose-volume effects on tumors and tissues.
2. The increased time needed to deliver fractionated IMRT doses may reduce its biological effectiveness due to tissue repair between fractions.
3. Techniques like VMAT, tomotherapy, flattening filter-free beams, direct aperture optimization, and reducing the number of segments can help shorten fraction delivery times for IMRT.
This document discusses guidelines for evaluating radiotherapy treatment plans for primary brain tumors. It provides indications for radiotherapy based on tumor type and extent of resection. Key factors in treatment planning include: contouring target volumes and organs at risk, optimizing dose distribution to cover the target while sparing organs at risk, and quantitatively evaluating plans using tools like isodose distributions, dose volume histograms and indices like coverage, conformity and homogeneity. Plan evaluation ensures the target receives adequate and uniform dose while respecting organ at risk tolerances.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
La costante tentazione dei trattamenti ipofrazionati: breve cronistoria dei modelli biologici e degli effetti clinici
Role of Post-op Radiotherapy in Head and Neck CancersAshutosh Mukherji
This document discusses the role of adjuvant radiation therapy in head and neck cancers. It begins by outlining the use of radical and palliative treatment for stage III and IV diseases. It then reviews several landmark studies that established the benefits of postoperative radiation therapy (PORT) over surgery alone in improving local control and survival. Key factors that determine the need for adjuvant therapy like extracapsular extension, positive margins, and T3/T4 stage are discussed. The document also addresses optimal radiation dose, timing, use of concurrent chemotherapy and altered fractionation schedules based on evidence from clinical trials. While targeted therapies in the adjuvant setting have not proven beneficial so far, ongoing studies are exploring their potential role.
24° CORSO RESIDENZIALE DI AGGIORNAMENTO
con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO)
Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose
21 marzo 2014: Trattamenti stereo-RT e radiochirurgici come opzioni standard di trattamento: stato dell’arte in base a linee guida internazionali
This document provides an overview of the fourth edition of the textbook "Practical Radiotherapy Planning". The textbook is written by four authors who are professors and consultants in clinical oncology in the UK. It aims to provide guidance on radiotherapy treatment planning based on sound pathological and anatomical principles. The textbook covers topics such as radiobiology, organs at risk, brachytherapy, emergency radiotherapy, and treatment planning for many cancer sites. It emphasizes the underlying principles of treatment planning that can be applied to conventional, conformal and novel radiotherapy techniques. The textbook includes many clinical images to illustrate key planning concepts.
Altered Fractionation Radiotherapy in Head-Neck CancerJyotirup Goswami
Altered fractionation radiotherapy has been shown to improve outcomes for head and neck cancer patients compared to conventional fractionation. Meta-analyses demonstrate significant benefits including improved 5-year locoregional control and overall survival. However, most modern trials do not address fractionation. Hypofractionation shows promise with comparable tumor control and toxicity but reduced treatment time. Ongoing research combines altered fractionation with chemotherapy and radiosensitizers to further improve outcomes while minimizing toxicity.
This document discusses reirradiation in recurrent head and neck cancer. It notes that radiation therapy plays a central role in head and neck cancer treatment but recurrence still occurs in 20-35% of patients. Reirradiation presents challenges due to prior radiation exposure and damage to normal tissues. The document discusses treatment options, appropriate patient selection, techniques like IMRT to minimize dose to organs at risk, optimal timing and dosing of reirradiation, and management of toxicities.
The document discusses various aspects of radiation oncology and radiotherapy clinical trial design. It provides an overview of the evolution of radiation therapy techniques from the 1960s to present. It also covers important considerations for radiation oncology trials, including target volume delineation, dose schedules, quality assurance measures, and assessing toxicity. Multidisciplinary collaboration and factors influencing radiation sensitivity are also briefly discussed.
Dr. Thomas Yankeelov: Integrating Advanced Imaging and Biophysical Models to...Dawn Yankeelov
This is a talk from the Technology Association of Louisville Kentucky. Dawn Yankeelov is co-chair of TALK, and Dr. Thomas Yankeelov is the director for the Institute of Imaging Science at Vanderbilt University. He presented his latest research in June 2013, "Integrating Advanced Imaging and Biophysical Models to Predict Tumor Growth."
Abstract—Colorectal cancer is leading cancer-related public health problem. This study was conducted to determine the effect of High-Dose-Rate intraluminal brachytherapy (HDR-BT) with or without interstitial brachytherapy during neoadjuvant chemoradiation for locally advanced rectal cancer. This randomized contrial was conducted on 28 patients attended with locally advanced rectal cancer (T3, T4 or N+) treated initially with concurrent capecitabine (800 mg/m2 twice daily for 5 days per week) and pelvic external beam radiation therapy (45Gy in 25 Fractions) after one week MRI for all patients; received intraluminal HDR-BT with 4Gy x 2 Fractions with one week interval for those had gross residual disease within 1cm of rectal wall and receiveed intraluminal and interstitial brachytherapy with 4Gy x 2 Fractions with one week interval for those had gross residual disease far from 1cm of rectal wall. All patients underwent surgery within 4-8 week after completion of neoadjuvant therapy. In the control group which were not randomized, twenty-eight patients underwent neoadjuvant chemoradiation (45Gy in 25 Fraction with concurrent capecitabine 800mg/m2 twice daily for 5 days per week) followed by surgery. It was found that in HDR-BT group pathologic complete response (pCR), pathologic partial response (pPR) and pathologic response rates (pCR+pPR) based on AJCC TNM staging for colorectal cancer were %35.7, %35.7, and %71.4 respectively. The pCR, pPR, and pRR were %25, %17, and %42 in the control group respectively. pCR, pPR, and pRR were improved with HDR-BT. However, only response rate improvement was statistically significant (p=0.031). There was no a statistically significant difference in the complications between the two groups (p > 0.05). So it can be concluded that HDR intraluminal with or without interstitial brachytherapy may be an effective method of dose escalation technique in neoadjuvant chemoradiation therapy of locally advanced rectal cancer with higher response rate and manageable side effects.
The document summarizes highlights from breakout sessions at a conference on predictive models for decision making in prostate cancer. It discusses how the radiation oncologist and technique affect outcomes, and factors that predict toxicity after external beam radiotherapy or brachytherapy for sexual, urinary, and GI dysfunction. Future predictive models need to incorporate dosimetric, clinical, genetic, and molecular factors using standardized toxicity reporting and integrating patient-reported outcomes with dose-volume data.
This document summarizes the use of intensity-modulated radiation therapy (IMRT) for lung cancer. It discusses:
1) Types of IMRT including LINAC-based step-and-shoot, dynamic, and VMAT techniques as well as tomotherapy-based helical IMRT.
2) Retrospective studies show IMRT improves target coverage and reduces toxicity compared to 3DCRT, though results for organ at risks are mixed.
3) Prospective studies demonstrate the safety and efficacy of hypofractionated IMRT schedules.
4) Proton therapy may further improve sparing of organs at risk compared to photon-based IMRT techniques.
Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomized, open-label, phase 3 trial
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...daranisaha
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...JohnJulie1
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...eshaasini
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...semualkaira
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...NainaAnon
Upper rectal cancer management is controversial. The present series reports the outcomes of treatment comparing neoadjuvant chemoradiation (NCRT) versus upfront surgery.
Clinics of Oncology | Oncology Journals | Open Access JournalEditorSara
Clinics of OncologyTM (ISSN 2640-1037) - Impact Factor 1.920* is a medical specialty that focuses on the use of operative techniques to investigate and resolve certain medical conditions caused by disease or traumatic injury.
Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...semualkaira
In this retrospective study we enrolled patients with upper rectal or sigmoid junction locally advanced tumors (stages II-III). At the first Institution patients received NCRT followed by surgery (study group); at the second Institution patients were referred to upfront surgery (control group). Overall survival was the main endpoint of the analysis. Local relapse and other clinical variables were also analyzed.
Precision Radiotherapy: Tailoring Treatment for Individualised Cancer Care.pptxDr. Rituparna Biswas
Precision radiotherapy, also known as precision radiation therapy or targeted radiotherapy, is a cutting-edge approach in the field of radiation oncology that aims to deliver highly focused and accurate doses of radiation to cancerous cells while minimizing damage to surrounding healthy tissues.
Radiobiological aspects of radiotherapy precisionAmin Amin
This document discusses the required accuracy and uncertainties in radiotherapy. It begins by introducing improvements in radiotherapy technologies that allow more precise dose delivery to tumors. It then discusses various modern radiotherapy modalities and the need for precision radiotherapy given technical and scientific advances. While survival improvements have not been conclusively shown, strategies to widen the therapeutic window include improved treatment conformity and personalized biological treatments. Accuracy requirements in radiotherapy are clinically driven and depend on dose-response curves for tumors and normal tissues. Overall uncertainties of 3% or less are recommended to minimize changes to tumor control or normal tissue complications. The document examines sources of uncertainty and accuracy achievable with techniques like 3D conformal radiotherapy and intensity-modulated radiotherapy.
Controversies in the management of rectal cancersAjeet Gandhi
Management of rectal cancers have undergone a huge paradigm shift over the last decade. One the one hand, it has opened up new avenues; it also has thrown up new challenges and controversies
Radiotherapy contouring guideline for non-hodgkin lymphomaketan kalariya
This document provides guidelines for modern radiation therapy for nodal non-Hodgkin lymphoma. It outlines a new concept of involved-site radiation therapy using reduced treatment volumes based on imaging to define target volumes. Guidelines are provided for radiation therapy as primary treatment, as part of combined modality treatment, and for recurrent or refractory disease. Recommended doses and techniques such as IMRT are discussed depending on the clinical situation and disease stage. The goal is to restrict radiation therapy to limited involved sites to reduce normal tissue exposure while maintaining local tumor control.
Intensity-modulated radiotherapy with simultaneous modulated accelerated boos...Enrique Moreno Gonzalez
To present our experience of intensity-modulated radiotherapy (IMRT) with simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC).
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NTCP MODELLING OF ACUTE TOXICITY IN CARCINOMA CERVIX TREATED WITH CONCURRENT CHEMORADIATION
1. NTCP MODELLING OF ACUTE TOXICITY IN
CARCINOMA CERVIX TREATED WITH
CONCURRENT CHEMORADIATION
MODERATOR: DR. S. CHANDER
SPEAKER: DR. RITUPARNA BISWAS
2. • The aim of radiotherapy is to give sufficient dose to the tumor to achieve tumor
control without introducing severe complications in surrounding normal tissue.
• Modern radiation therapy does very well at shaping dose distributions
• For tumor control, tumor localization + sufficiently high dose (understanding tumor
dose-response) are key
• For each normal tissue of interest, we know the planned dose distribution for the
entire organ volume
• What dosimetric features should be restricted to keep normal tissue complication
risk low?
Grading schemes: 1 is mild → 5 is lethal
‘Low’ is usually ≤ Grade 2 in any grading scheme
INTRODUCTION
3. For some of the most critical organs and sites in radiotherapy, the following problems
are addressed:
The identification of the clinically most relevant signs and symptoms of normal tissue
complications in different organs, i.e. those which cause the most significant
impairment of the quality of life of a patient who has been cured by radiotherapy.
The analysis of the probable pathogenic and pathophysiological mechanisms
involved in the development, progression and compensation of the specific
manifestations of those normal tissue complications which would be relevant to
NTCP modelling.
The investigation of the clinical and experimental evidence for dose and dose-
distribution dependence of the severity and incidence of the different functional
(physiological) and structural (anatomical, pathological) normal tissue damage.
4.
5.
6. Emami et al ( Part of NCI funded CWG on 3D planning: IJROBP 21, 109-122, 1991)
• Literature review up to 1991, 26 complications
– Predates 3D-CRT era; even DVHs were new
• Tabulated estimates of TD50/5 and TD5/5
– Doses for 50% & 5% complication probability at 5 years
– Conventional fractionation: 1.8-2 Gy/Fx
• For many complications, the TD’s increase if less of the organ is irradiated
– Partial irradiation of volume fraction v of organ
– Tabulated TD50/5 and TD5/5 for v=1/3, 2/3 and 1.0
7.
8. 1991 to Now
• CT-simulation is routine
– Plus MRI, PET, 4D-CT
• 3D-CRT is the norm, IMRT explodes
– 3D plan evaluation tools
• Complex dose distributions
• Huge amount of published information
– Some listed in handout bibliography
– Noisy data, various grading schemes, different calculation methods and
plans – tough to sort out
• October 2007: QUANTEC
– AAPM/ASTRO funded workshop on NTCP
– Consensus guidance for clinical use of NTCP studies
9.
10. NTCP models
Mainly based on data from retrospective or prospective clinical studies
These models are more indicative of average trends rather than outcomes on
individual patients
The models are not based on radiobiological concepts of the pathogenesis of
normal tissue damage.
The risk of complications is generally assumed to depend on the mean dose to the
respective organ or the amount of damaged tissue, described as function of local
dose to that tissue.
They also assume that radiation effects are local effects (i.e. the fate of tissue
depends on the dose to that tissue alone) and that the severity of the effects can
be characterised by a dose-volume histogram (DVH), or parameters derived from
the DVH
11. Empirical models
– Equations with parameters fit to outcomes data sets
– No mechanistic foundation (except LQ if used)
– Examples: Lyman model, gEUD
• Semi-mechanistic models
– Tissue architecture, as well as cellular radiosensitivity,determine NTCP
– Parameters chosen to fit clinical data
– Examples: Serial (critical element) model, Parallel (critical volume) model,
Relative seriality model
12. ACUTE TOXICITIES IN CARCINOMA CERVIX TREATED WITH
CONCURRENT CHEMORADIATION ARE:
1. ACUTE HEMATOLOGICAL TOXICITIES
2. ACUTE GASTROINTESTINAL TOXICITIES
3. ACUTE GENITOURINARY TOXICITIES ( BUT Quantitative
mathematic modeling of bladder toxicity is lacking)
13. NTCP MODELING OF ACUTE HEMATOLOGICAL
TOXICITIES IN CARCINOMA CERVIX TREATED
WITH CONCURRENT CHEMORADIATION
14. • In patients receiving pelvic RT alone, HT is rarely a problem, due to compensatory increased
hematopoiesis in unirradiated BM.
• When chemotherapy is given concurrently, however, additional BM injury and
myelosuppression predispose patients to HT, making effects of pelvic BM irradiation a greater
concern.
• The reduction of CRT-associated HT could improve tolerance to more aggressive
chemotherapy, potentially enhancing disease control in patients with pelvic
malignancies.Though reported rates of acute HT vary in the literature, grade ≥ 3 HT occurs in
approximately 27% of women undergoing CRT.
• HT can also lead to delayed or missed chemotherapy cycles and treatment breaks, potentially
compromising disease control. Reduction of HT is, therefore, an important goal
• Understanding the effects of radiation in active BM subregions, and refining efforts to
selectively spare active BM could help optimize BM-sparing radiation techniques.
INTRODUCTION
15. RADIATION-RELATED PREDICTORS OF HEMATOLOGIC TOXICITY AFTER CONCURRENT
CHEMORADIATION FOR CERVICAL CANCER AND IMPLICATIONS FOR BONE MARROW–
SPARING PELVIC IMRT
KEVIN ALBUQUERQUE, M.D., F.R.C.S., DAVID GIANGRECO, M.D., COURTNEY MORRISON, B.S.,
MOHAMMED SIDDIQUI, C.M.D., JIM SINACORE, PH.D., RONALD POTKUL, M.D., AND JOHN ROESKE, PH.D.
Int. J. Radiation Oncology Biol. Phys., Vol. 79, No. 4, pp.1043–1047, 2011
16. Purpose: To determine factors predictive for hematologic toxicity (HT) associated with concurrent
chemoradiation for Stage II through IV cervical cancer.
Methods and Materials:
Patients and radiation planning
• Number of patients: 40
• Archived treatment planning CT scans for these women were recontoured to estimate BM volume
radiated. Bony contours of the following were used as surrogates for BM volume irradiated: (1)
lumbosacral region (L5 and sacrum), (2) ilium (iliac crests to superior border of femoral heads), (3) lower
pelvis (pubis, ischium, acetabulum, and proximal femurs), (4) pelvis including 2 and 3, and (5) whole
pelvis including 1 and 4
• All patients received 45 Gy in 1.8-Gy daily fractions by use of 23-megavolt photons with concurrent
weekly cisplatin( 40mg/m2) for 5 to 6 cycles .
17. Hematologic toxicity parameters/data recording
• Variables predicting for HT: age, body mass index, transfusions, and bone marrow volumes irradiated were
included.
• Dose–volume histograms corresponding to the delivered dose for each contoured BM region were generated
• The volume of each region receiving doses were designated as follows: lumbosacral BM–V10, BM–V20,
BM–V30, and BM–V45 and similarly for ilium, lower pelvis, pelvis, and whole pelvis.
• Hematologic toxicity was graded according to the Common Terminology Criteria for Adverse Events (version
3.0)
• Hematologic toxicity of Grade 2 or greater (HT2+) was noted as an event, and statistical correlation was
performed with the possible predictors
Statistical considerations
• Descriptive statistics for all variables were obtained.
• In addition,multiple logistic regression analysis was performed to correlate the risk of Grade 2 HT and above
(HT2+) with the predictors (age,stage, BMI, and BM volumes) being studied.
• A data partitioning technique, known as optimal data analysis was used to define the cut points for the
significant predictors of HT
18. Logistic regression analysis of potential
predictors: only V20 whole pelvis was nearing
significance for predicting HT (p = 0.08).
None of the other clinical parameters—was a
significant predictor for this toxicity.
To further test the association between whole-
pelvis BM dose and HT2+ = Pearson
correlation test.
The correlation between V20 whole pelvis and
the proportion of patients exhibiting HT2+ is
0.8 (p < 0.0001).
A partitioning analysis showed if the V20 of
the whole pelvis exceeds 80%, the risk of
HT2+ developing increases by a factor (odds
ratio) of 4.5 (95%, confidence interval, 1.08–
18.69) (p < 0.05).
19. NORMAL TISSUE COMPLICATION PROBABILITY MODELING OF ACUTE
HEMATOLOGIC TOXICITY IN CERVICAL CANCER PATIENTS TREATED WITH
CHEMORADIOTHERAPY
Brent S. Rose, B.S., Bulent Aydogan, Ph.D., Yun Liang, Ph.D., Mete Yeginer, Ph.D.,
Michael D. Hasselle, M.D., Virag Dandekar, B.S., Rounak Bafana, B.S., Catheryn M.
Yashar, M.D., Arno J. Mundt, M.D., John C. Roeske, Ph.D., and Loren K. Mell, M.D
Int J Radiat Oncol Biol Phys. 2011 March 1; 79(3): 800–807. doi:10.1016/j.ijrobp.2009.11.010
20. PURPOSE—
To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic
toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy (CRT), and to develop a normal tissue
complication probability (NTCP) model for HT.
METHODS AND MATERIALS
Patients and Study Design
Biopsy-proven clinical stage I-IVA or recurrent cervical carcinoma, and no prior history of chemotherapy
or pelvic irradiation.
Patients treated with extended field (para-aortic) RT (EFRT) were excluded.
The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic
radiotherapy.
Pooled with 37 identically treated patients from a prior study, forming a cohort of 81 patients for NTCP analysis.
Chemotherapy Delivery
Chemotherapy consisted of weekly cisplatin(40 mg/m2;maximum:80 mg) delivered concurrently with external
beam RT.
21. Radiation Simulation, Planning and Delivery, Bone Marrow Delineation
• The majority of patients (41 of 44, 94%) received pelvic IMRT.
• Pelvic radiation dose was 39.6-50.4 Gy in 1.8 Gy daily fractions.
• For each patient, the external contour of all bones within the pelvis was delineated on the planning CT using
bone windows
• Bone marrow was not routinely used as an avoidance structure.
• BM volumes receiving ≥10, 20, 30, and 40 Gy (V10, V20, etc.) were quantified.
Hematologic Toxicity
• All patients had complete blood counts (CBC) with differentials weekly during CRT.
• Endpoints of interest
White blood cell count (WBC), absolute neutrophil count (ANC),and hemoglobin (HGB) nadirs
(during or within two weeks of the end of CRT)
• Hematologic toxicity was graded according to the Radiation Therapy Oncology Group acute
radiation toxicity scoring criteria
.
22. Statistical analysis
• For analysis on the validation cohort, hematologic nadirs were associated
with V10 and V20 using least squares regression.
• Univariate analyses on potential confounders: body mass index (BMI),
age(median centered), race,comorbidity, and clinical stage
• Secondary analyses on the association of hematologic nadirs and other
potentially predictive dosimetric parameters including V30, V40, and mean
BM dose.
• Generalized linear modeling was used to test associations between
hematologic nadirs and dosimetric parameters in the combined cohort,
adjusting for body mass index.
• Receiver operating characteristic curves were used to derive optimal
dosimetric planning constraints
24. RESULTS
Validation Study
In the subgroup of patients treated with IMRT, univariate β estimates for WBC nadir as a function of
V10,V20, V30, V40, and mean BM dose were −0.055 (p=0.019), −0.055 (p=0.012), −0.029
(p=0.10), −0.025 (p=0.20), and −0.11 (p=0.032), respectively.
27. Receiver Operating Characteristic curves for grade ≥ 3 toxicity as a function of V10 .The
sensitivity and specificity corresponding to the optimal choice of cutoff is indicated by the
intersection of the left-most diagonal line and the ROC curve.
• The optimal V10 cutoff, indicated by
the upper-left-most point of the ROC
curve, was 95%.
• Patients with V10 ≥ 95% were more
Likely to experience grade ≥ 3 toxicity
(68.8% vs. 24.6%,p<0.001).
• Sensitivity - 44.4%
• Specificity-90.7%
• Positive predictive value for V10 ≥ 95%
were 68.8% (95%CI:58.6%,79.0%)
• Negative predictive value-75.4% (95%
CI:66.0%,84.8%),
• Relative risk - 2.79 (95% CI:1.63,4.79).
28. Receiver Operating Characteristic curves for grade ≥ 3 toxicity as a function of V20
.The sensitivity and specificity corresponding to the optimal choice of cutoff is
indicated by the intersection of the left-most diagonal line and the ROC curve.
• The optimal V20cutoff, indicated by
the upper-left-most point of the ROC
curve, was 76%.
• Patients with V20 ≥ 76% were more
Likely to experience grade ≥ 3 toxicity
(57.7% vs. 21.8%, p=0.001)
• Sensitivity - 55.6%
• Specificity-79.6%
• Positive predictive value for V20 ≥
95% 57.7% (95% CI:46.9%,68.5%)
• Negative predictive value-75.4%
(95% CI:66.0%,84.8%),
• Relative risk -2.64 (95% CI:1.45,4.81)
29. Associations between Dosimetric Parameters and Chemotherapy Delivery
• No significant associations between BM dosimetric parameters and them probability of having ≥ 1
cycle of chemotherapy held.
• The number of cycles of chemotherapy held, however, was significantly associated with V20 on
univariate (β=0.018;95% CI:0.005,0.036, p=.047) but not multivariate (β=0.017; 95%CI:−0.001,0.035,
p=0.066) analysis
In summary, this study lends strong support to the hypothesis that V10 and V20 of pelvic
BM are important predictors of HT in cervical cancer patients undergoing CRT. Efforts to
maintain V10 < 95% and V20 < 76% could significantly reduce HT, but further research is
needed to optimize and determine the clinical significance of BM-sparing techniques.
30.
31.
32. Dose Constraint Recommendations and a Predictive Nomogram of Incidence of
Hematological Toxicity for Cervix Cancer Patients Treated with Concurrent Cisplatin
and Intensity Modulated Radiation Therapy(IMRT)
S. Mutyala et al.
33. • Purpose/Objective(s): To report a predictive complication probability nomogram for HT and propose BM dose
constraint recommendations for IMRT planning for the treatment of cervical cancer.
• Materials/Methods:
Thirty-seven patients with cervical cancer were treated with IMRT and concurrent cisplatin (40mg/m2/wk).
Of these pts,18 received extended fieldRT to include paraaortic nodes,29 received a parametrial RT boost,and
35 received HDR brachytherapy.
Toxicities were scored by RTOG criteria.
For analysis, BM was re-delineated to include the entire marrow of the lumbosacral (to the superior border of
L1), high pelvic, low pelvic and femoral head regions.
Resulting dose volume histograms were combined with patient HT data to create a cumulative dose-volume HT
nomogram, from which toxicity prediction isoprobability curves can be generated.
BM volumes receiving 10 - 50 Gy (V10 -V50) and dose received by 5 - 75% of the total marrow volume (D5 -
D75) were statistically analyzed for associations with HT.
34. Results:
The distribution of HT was: grade 0 - 4 pts; grade 1 - 4 pts; grade 2 - 9 pts; grade 3 -14 pts; and grade 4 - 6pts.
Total marrow mean dose (p = 0.018), V10 (p = 0.005), V20 (p = 0.002), V30 (p = 0.026) and D75 (p = 0.005)
were all positively correlated with increasingly severe HT.
From the dose-volume atlas of HT, several significant dose points that were highly predictive of severe (grade
3 or worse) HT were identified.
These were V10 ≥95% (complication probability [CP] = 87.5%, p = 0.048), V20≥ 80% (CP = 80%, p = 0.018),
V30 ≥64% (relative risk 2.06, CI 1.45 to 2.93), and D75 ≥ 24.5 Gy (CP = 100%, p = 0.020).
Radiation of extended paraaortic field (CP = 77.8%, p = 0.008) and several lumbosacral marrow dosevolume
parameters (p <0.05) were also predictive of severe HT.
Conclusions:
The use of marrow sparing IMRT using total bone marrow dose constraints of V10 <95%, V20<80%,
V30<64%, and D75<24.5 Gy to minimize incidence of HT in patients receiving concurrent Cisplatin and RT for
cervical cancer were recommended.
Furthermore, this nomogram can be used to predict the risk of HT for an IMRT plan, identify high-risk patients,
and prophylactically prevent HT when possible.
35. NTCP MODELING OF ACUTE GASTROINTESTINAL
TOXICITIES IN CARCINOMA CERVIX TREATED WITH
CONCURRENT CHEMORADIATION
36. Acute gastrointestinal (GI) toxicity is a common problem for cervical patients undergoing concurrent
chemoradiotherapy
Clinically significant acute GI toxicity occurs in approximately one third of patients adversely
impacting quality of life and potentially posing an important impediment to treatment with concurrent
multiagent chemotherapy
Validated normal tissue complication probability (NTCP) models of GI toxicity are needed to provide
evidence for dosimetric guidelines in treatment planning and protocols
However, validated NTCP models of GI toxicity in cervical cancer, particularly in patients undergoing
chemoradiation, are lacking
INTRODUCTION
37. THE DIFFERENT VOLUME EFFECTS OF SMALL-BOWEL TOXICITY DURING
PELVIC IRRADIATION BETWEEN GYNECOLOGIC PATIENTS WITH AND WITHOUT
ABDOMINAL SURGERY: A PROSPECTIVE STUDY WITH COMPUTED
TOMOGRAPHY-BASED DOSIMETRY
ENG-YEN HUANG, M.D., CHIEN-CHENG SUNG, B.S., SHEUNG-FAT KO, M.D.,
CHONG-JONG WANG, M.D.AND KUENDER D. YANG, M.D., PH.D.
38. • Purpose:
To evaluate the effect of abdominal surgery on the volume effects of small-
bowel toxicity during wholepelvic irradiation in patients with gynecologic
malignancies.
• Methods and Materials:
80 gynecologic patients without (Group I) or with (Group II) prior abdominal
surgery were analyzed.
Computed Tomography (CT) planning system was used to measure the small-
bowel volume and dosimetry.(10% (V10) to 100% (V100) of dose, at 10%
intervals)
The onset and grade of diarrhea during whole-pelvic irradiation were recorded
as small-bowel toxicity.
39.
40.
41. A dosimetric analysis of acute gastrointestinal toxicity in women receiving
intensity-modulated whole-pelvic radiation therapy
John C. Roeske, Dacian Bontaa, Loren K. Mella, Anthony E. Lujana, Arno J. Mundta
Radiotherapy and Oncology 69 (2003) 201–207
42. • Purpose: To identify dosimetric factors correlated with acute gastrointestinal (GI) toxicity in gynecology
patients undergoing intensity modulated whole pelvic radiation therapy (IM-WPRT)
• Material and methods:
50 patients with cervical (29), endometrial (18) or other (3) gynecologic malignancies received IM-
WPRT (45–1.8 Gy/fraction) between 2/00 and 3/02. T
26 women (all with cervical cancer) received concomitant chemotherapy (cisplatin, 40 mg/m2/weekly).
Grade 2 acute GI toxicity requiring frequent medications and grade 3–5 toxicities were designated as
clinically significant and analyzed as a function of patient and dosimetric variables.
In addition to the absolute PTV, the SB and rectal volumes receiving 25, 50, 75, 90, 100 and 110% of
the prescription dose were also evaluated.
Comparison of proportions was performed using the Pearson chi-square test or Fisher exact test
whenever appropriate.
Logistic regression analysis (multivariate) was performed on all significant factors from the univariate
analysis.
The most significant volumetric factors were fit to a normal tissue complication probability (NTCP)
function.
43.
44. A multivariate analysis (logistic
regression) was performed
which included the most
significant factors from the
univariate analysis. The sole
factor that reached statistical
significance in terms of acute
GI toxicity was Vol(SB,100)
P=0.012
45. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical
Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin
Daniel R. Simpson, M.D.,* William Y. Song, Ph.D.,* Vitali Moiseenko, Ph.D.,Brent S. Rose, M.D.,* Catheryn M. Yashar,
M.D.,* Arno J. Mundt, M.D.,* and Loren K. Mell, M.D.
46. Purpose:
To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in
cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT),
using a previously derived normal tissue complication probability (NTCP) model
Methods:
• FIGO Stage IB-IIIB cervical cancer treated with IMRT and concurrent chemotherapy (consisting of weekly
cisplatin [40 mg/m2]) at the UCSD between July 2006 and February 2010.
• IMRT plans consisted of seven to nine coplanar fields using 6-MV photons. The prescription dose ranged
between 45 and 50.4 Gy (median, 45 Gy)
• An external beam boost of 9.0-14.4 Gy was given after pelvic IMRT in patients with gross nodal disease. Only 2
patients received a simultaneous integrated boost.
• The remainder of patients received a sequential boost after the completion of pelvic external beam RT.
• Patients with intact cervical cancer were treated with a high-dose-rate brachytherapy boost of five fractions of
5.5-6.0 Gy prescribed to point A.
• Toxicity during treatment was graded using the Radiation Therapy Oncology Group Acute Radiation Morbidity
Scoring Criteria(weekly for toxicity from the beginning to the end of external beam RT.)
• Only lower GI events (e.g., diarrhea, bleeding, abdominal pain, distension, etc.) were included as events for
analysis
47. Statistical analysis
• The volume of bowel receiving 5, 10, 15, 20, 25, 30, 35, 40, and 45 Gy (V5-V45) were
included separately in the NTCP models as dosimetric predictors (explanatory variables).
• Model covariates included the log of the body mass index (BMI) as a continuous variable,
Stage IIB as a dichotomous variable, treatment intent (definitive vs. postoperative) as a
dichotomous variable, and field volume (pelvic vs. pelvic para-aortic [extended field]) as a
dichotomous variable.
• Correlations between acute GI toxicity and dosimetric predictors and covariates were tested
using univariable and multivariable logistic regression. Toxicity and dosimetric data were
then fit to a logistic NTCP function:
where V is the volume of bowel receiving a given dose level, V50 is the volume corresponding
to 50% incidence of complications, and g is the normalized slope of the volume-response
curve.
• Fisher’s exact test was used as a nonparametric test of the significance of 2x2 tables of
Grade 2 GI toxicity versus varying dose volume cutoffs.
z
50. Comparison of average dose-volume histograms for patients with and without acute
Grade 2 gastrointestinal toxicity.
51. Univariable analysis of factors associated with acute gastrointestinal toxicity
NTCP modeling
52. Plot of Fisher’s exact p values from 2x2 tables of the probability of
acute gastrointestinal toxicity versus varying dose-volume
cutoffs.
In the logistic regression model adjusting for age, BMI,
and postoperative status, the associations between
Grade ≥2 GI toxicity and V35, V40, and V45 remained
statistically significant (OR 1.59, 95% CI 1.04-2.43;OR
1.88, 95% CI 1.08-3.30; and OR 2.40, 95% CI 1.10-
5.21,respectively).
The smallest volume cutoff values for doses 45 and 40
Gy showing statistically significant association with the
incidence of Grade 2 toxicity were 100 and 170 mL,
respectively.
The incidence of complications was 60% (18/30) in
patients with V45 >100 mL or V40 >170 mL and 25%
(5/20) in patients whose DVHs were below these cutoff
values (p =0.021).
53. • Increased doses of bowel irradiation are associated with acute GI toxicity
in cervical cancer patients undergoing concurrent pelvic IMRT and
cisplatin
• The odds of acute toxicity increased approximately twofold for every 100
mL of small bowel receiving 45 Gy or more.The V45 =100 mL cutoff was
also associated with increased incidence of toxicity (p=0.021).
• In addition, lower dose-volume metrics (e.g., V35 and V40) may also be
useful in NTCP models.
Conclusion
54.
55. TAKE HOME MESSAGE
The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy
delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.
Increased doses of bowel irradiation are associated with acute GI toxicity in cervical cancer
patients undergoing concurrent pelvic IMRT and cisplatin
volume effects are different between patients with and without abdominal surgery. Low-dose
rather than full-dose volume correlates with acute diarrhea in patients without abdominal
surgery. Full-dose volume can predict acute diarrhea in patients with abdominal surgery
Validated normal tissue complication probability (NTCP) models of acute toxicities are needed
in optimizing IMRT dosimetric planning, plan evaluation, and for clinical research protocols.
Tolerance doses for normal tissue complications may be determined with reasonable accuracy in animal experiments. The question of whether these data also apply to humans, however, remains an intrinsic problem, and tolerance doses from animal experiments are generally not believed to be directly transferable to humans. In humans, on the other hand, the parameter D50 usually cannot be determined as such high complication rates are usually prevented by clinical experience. For clinical applications, quantities such as D5 (dose leading to 5% complication probability) are more relevant. From such low complication probabilities, however, it is nearly impossible to determine the slope of the curve.
The EUD – a semi-biological approach“The concept of equivalent uniform dose (EUD) assumes that any two dose distributions are equivalent if they cause the same radiobiological effect.”
The idea based on a law by Weber-Fechner-Stevens: R Sa
Biophysical models assume that the function of an organ is related to the inactivation probability of the organs functional sub units - FSU – and their functional organization.An organ consists of a number of identical functional subunits (FSU; Withers et al. 1988), each of them responding independently to radiation.
Among patients experiencing diarrhea or loose stools after pelvic radiotherapy, rectal toxicity becomes difficult to differentiate from small bowel toxicity. IN MOST STUDIES ACUTE gastrointestinal toxicity was correlated with small bowel dose but not rectum
Pelvic BM was not contoured as a critical structure at the time of
planning
, including BMI, age, and transfusions, as well as other dosimetric parameters—namely, different dose levels (V10 to V45) to subsections of the pelvis (lumbosacral, lower pelvis) or whole pelvis (all not significant except V20)
This indicates a statistically significant, strong, and positive correlation between these variables, such that, as the proportion of the whole pelvis irradiated to 20 Gy increases, so too does the proportion of patients exhibiting HT2+, as shown in
Fig. 1
The median age and BMI were similar in the training and validation cohorts (Table 1). More patients were Hispanic and fewer were white in the validation cohort compared to the training cohort (p<0.01). Fewer patients in the validation cohort had stage I-IIA disease(32% vs. 59%, p=0.01, respectively).
Univariate analysis identified statistically significant relationships between decreasing WBC nadir and increasing V10, V20, V30, V40, and mean BM dose .
We observed a trend towards an association between log(BMI) and WBC nadir (p=0.068). No other covariate was significantly associated with WBC nadir.
In the combined cohort, increasing V10, V20, V30, and mean BM dose were associated with significantly decreased log(WBC nadir) on univariate analysis (Table 5). Of the covariates tested, only log(BMI) was significantly associated with decreasing log(WBC nadir). There was a non-significant association between advanced stage and decreased log(WBC nadir)(p=0.056).
Multiple regression analysis adjusting for log(BMI) was performed on the combined cohort.Increasing V10, V20, V30, and mean BM dose were associated with significantly decreased log(WBC nadir) and log(ANC nadir) (Table 6). We observed a non-significant association between V40 and ANC nadir (p=0.069). There was an association between increasing V20 and a decreasing HGB nadir (β=−0.053,95% CI:−0.10,−0.01, p=0.016).
We found weak evidence supporting an association between increasing pelvic BM V20 and poorer chemotherapy delivery
Volume effect of Grade 2–3 diarrhea existed from V10 to V100 in Group I patients and from V60 to V100 in Group II patients on univariate analyses. The V40 of Group I and the V100 of Group II achieved most statistical significance.
Possible predisposing factors, such as age, hypertension, diabetes, concurrent chemotherapy, and different dose-level
volumes were considered in the multivariate analysis of Grade 2–3 diarrhea (Table 6). In Group I patients, V40
(OR, 1.008; 95% CI, 1.003–1.013) (p = 0.001) was a single mindependent factor for Grade 2–3 diarrhea. V100 (OR,
1.023; 95% CI, 1.002–1.043) (p = 0.027) and BMI (OR, 0.498; 95% CI, 0.293–0.848) (p = 0.010) were independent
factors for Grade 2–3 diarrhea in Group II patients
If we
pooled Group I and II patients for analysis, abdominal surgery (OR, 8.465; 95% CI, 2.038–35.157) (p = 0.003), V40
(OR, 1.007; 95% CI, 1.004–1.011) (p < 0.001), chemotherapy (OR, 4.898; 95% CI, 1.304–18.396) (p = 0.019), and
BMI (OR, 0.818; 95% CI, 0.706–0.947) (p = 0.007) were
independent factors for Grade 2–3 diarrhea
As shown in Table 4, none of the patient factors analyzed (age, prior surgery, stage, chemotherapy, and PTV volume)
were correlated with the risk of clinically significant acute GI toxicity in the univariate analysis. Of note, patients age
50 or younger had a lower incidence of acute GI toxicity (16 vs. 40%) compared to older patients; however, this
difference not reach statistical significance p =0.06
The analysis of rectal and SB volumes are summarized in. None of the rectal volumetric factors were correlated with acute GI toxicity. The best correlation was seen in terms of VolR,110 ðp ¼ 0:06Þ: In contrast, a correlation was seen between the volume of SB irradiated to various doses and acute GI toxicity. This correlation was most significant at the 90% (VolSB,90) and 100% (VolSB,100) dose levels (p ¼ 0:009 and p ¼ 0:009; respectively)
shows mean doseevolume histograms for patients with
and without Grade <2 GI toxicity, indicating that, on average,
patients with Grade >=2 GI toxicity had increased bowel dose.
None of the covariates tested was statistically associated with Grade 2 GI toxicity. Extended field treatment and Stage IIB were associated with nonsignificant increases in the odds of Grade >=2 GI toxicity (odds ratio [OR] 3.47 per 100 mL of bowel;95% confidence interval (CI), 0.61e20.0 and OR 2.20; 95% CI,0.50e10.5, respectively). On univariable analysis, V15, V20, V35,V40, and V45 were each significantly associated with Grade >=2 GI toxicity (p < 0.05 for all).
Extended field treatment and Stage IIB were strongly associated with increased bowel dose. Because of concerns for collinearity between bowel dose and both field volume and tumor stage, these covariates were excluded from the multivariable model.