The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoadjuvant
breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response.
From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoadjuvant
chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion
sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of interest
(ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria)
and pathological response (assessed using Mandard’s classification).
Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evaluated
the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values
obtained with the two different methods of ROI placement were 1.11 and 1.02 · 10)3 mm2 ⁄ seconds. Mean post-treatment
ADC values were 1.40 and 1.35 · 10)3 mm2 ⁄ seconds, respectively. A significant inverse correlation between mean ADC
increase and Mandard’s classifications was observed for both the methods of ADC measurements. Diagnostic performance
analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method
(accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides superior
evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological
MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional
works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to
tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from
nonresponder patients.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...cscpconf
Based on pressing need for predictive performance improvement, we explored the value of pretherapy
tumour histology image analysis to predict chemotherapy response. It was shown that
multifractal analysis of breast tumour tissue prior to chemotherapy indeed has the capacity to
distinguish between histological images of the different chemotherapy responder groups with
accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...csandit
Based on pressing need for predictive performance improvement, we explored the value of pretherapy
tumour histology image analysis to predict chemotherapy response. It was shown that
multifractal analysis of breast tumour tissue prior to chemotherapy indeed has the capacity to
distinguish between histological images of the different chemotherapy responder groups with
accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD.
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).
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.
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.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...cscpconf
Based on pressing need for predictive performance improvement, we explored the value of pretherapy
tumour histology image analysis to predict chemotherapy response. It was shown that
multifractal analysis of breast tumour tissue prior to chemotherapy indeed has the capacity to
distinguish between histological images of the different chemotherapy responder groups with
accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD.
MEDICAL IMAGING MUTIFRACTAL ANALYSIS IN PREDICTION OF EFFICIENCY OF CANCER TH...csandit
Based on pressing need for predictive performance improvement, we explored the value of pretherapy
tumour histology image analysis to predict chemotherapy response. It was shown that
multifractal analysis of breast tumour tissue prior to chemotherapy indeed has the capacity to
distinguish between histological images of the different chemotherapy responder groups with
accuracies of 91.4% for pPR, 82.9% for pCR and 82.1% for PD/SD.
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).
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.
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.
Mucopolysaccharidoses (MPS) represent a group of inheritable lysosomal storage diseases caused by mutations in the genes coding for enzymes involved in catabolism of different glycosaminoglycans (GAGs). They are clinically heterogeneous multisystemic diseases, often involving the spine. Bony abnormalities of the spine included in the so-called dysostosis multiplex and GAG deposits in the dura
mater and supporting ligaments can result in spinal cord compression, which can lead to compressive myelopathy.
Spinal involvement is a major cause of morbidity and mortality in some MPS (e.g., MPS IVA, VI, and I), and early radiological diagnosis is critical in preventing or arresting
neurological deterioration and loss of function.
Final Exam of the Course -
The application of the Theory of Science of falsification by Karl Popper and at least one example of the concept of paradigm.
Philosophy of Science and the Concept of Health - 3073 HT23 Karolinska Institutet - oct - nov 2023 - Presented by Gert Helgesson, Tomas Mansson and Annelie Jonsson.
Cancer-associated VTE is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
Cancer-associated Venous Thromboembolism (VTE) is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
Cancer related vascular biology at CCBIO907 Centre for Cancer Biomarkers by Agnete ST Engelsen.
A recent article from the American Heart Association stressed the importance of the histopahological features of cancer-associated Venous Thromboembolism with the presence of Intrathrombus Cancer Cells and Prothrombotic Factors.
Poster from the revised article "Spinal involvement in Mucopolysaccharidoses" (A.Leone, Childs Nerv. Syst., 2015). Reviewd by Russell Oulette and Anna Hildenbrand Michelman I Karolinska Institutet.
Background Mucopolysaccharidoses (MPS) represent a
group of inheritable lysosomal storage diseases caused by
mutations in the genes coding for enzymes involved in catabolism
of different glycosaminoglycans (GAGs). They are
clinically heterogeneous multisystemic diseases, often involving
the spine. Bony abnormalities of the spine included in the
so-called dysostosis multiplex and GAG deposits in the dura
mater and supporting ligaments can result in spinal cord
compression, which can lead to compressive myelopathy.
Spinal involvement is a major cause of morbidity and mortality
in some MPS (e.g., MPS IVA, VI, and I), and early
radiological diagnosis is critical in preventing or arresting
neurological deterioration and loss of function.
Discussion Management of MPS, however, requires a multidisciplinary
approach because of the multiorgan nature of the
disease. Indeed in order to appreciate the relevance and nuances
of each other's specialty, radiologists and clinicians need
to have a background of common knowledge, rather than a
merely compartmentalized point of view. In the interest of the
management of spinal involvement inMPS, this review article
aims on one hand to provide radiologists with important
clinical knowledge and on the other hand to equip clinicians
with relevant radiological semiotics.
The assignment is to describe and review a teaching experience within higher education, reason about the experience based on pedagogical theories/principles and discuss how the teaching session could be developed in order to better facilitate meaningful learning for the students.
Describe the aims, main content, the set-up and who the students are/the student group. The description should also show the context in which the teaching takes place and the learning outcomes in the course syllabus that your teaching session supports the students in achieving.
Review this session based on the pedagogical theories and principles that have been brought up during the course in relation to, for example, meaningful learning, student-centred teaching, the role of the teacher, outcome-related teaching, constructive alignment, etc. Discuss the ways in which the teaching/supervision facilitates the students' learning and what may constitute difficulties/obstacles.
Discuss what you could consider changing or developing in your teaching, describe how you would go about it and justify changes based on relevant pedagogical theories and concepts. Also describe how you could go about following up the students' learning (if you do not already do this). Your reasoning should be supported by references to course literature and/or other literature/research within higher education. Compile the literature you refer to in a list of references according to an accepted referencing system.
There are many things we have to consider when choosing teaching methods and learning activities. As pointed out earlier in the course it is primarily what students DO that influences learning. Teachers and course organizers need to to consider what students are doing in teaching and learning situations as well as what learning activities they can engage in when working interdependently.
Empirical educational research shows that an active, self-directed approach is likely to have a much greater impact on a student’s learning than passive, lecture-based learning. Lectures should be used sparingly and for broad overviews, summaries and difficult topics. Sadly, only about 5 per cent of what is taught in lectures is actually retained, and too many people use lectures for imparting large quantities of detailed information that could easily be picked up, and more effectively, by reading a textbook.
Of course a number of different methods are used in addition to lectures. In this part of the course we want you to choose ANOTHER teaching form/method to learn more about. The aim of reading about and discussing a number of teaching forms like this is to increase your ability to make conscious choices when planning your teaching and to expand your knowledge of some common methods. We are now approaching the concrete aspects of the craft that is the art of teaching, but should for this sake keep in mind what we want to achieve with our teaching.
Together with a peer or a colleague, decide on an occasion in the coming weeks when you will have the chance to observe his/her teaching. Decide also on a time point for when you can provide your colleague with feedback based on your observations. Agree on what the feedback is to focus on: What does your colleague want you to look at? Another option is to form pairs of critical friends within the group who observe each other 's teaching.
After the feedback to your colleague, you describe:
1.Your preparations, how you conducted your observation and the feedback you gave.
2.What did you learn yourself from observing your colleague's teaching?
3.What did you learn yourself through giving feedback?
Choose a teaching situation significant to you in which you were the teacher/supervisor (or if not possible as student). The incident may have been problematic, difficult to handle or surprisingly positive. The situation you experienced should have aroused emotions and contain some form of dilemma that does not have an obvious "right" answer. Prepare a PowerPoint (or similar) where you address the following:
1) Describe the course of events, the various actors involved and the environment in which the situation took place.
2) Describe why the incident was "critical or significant" for you.
3) Describe what you thought and felt when it happened, and afterwards.
4) Define the problem(s)/difficulties alternatively the success factors in the situation.
5) Analyse the incident based on the following questions:
How has it come about that I look at the situation this way?
What assumptions did I make about the students (the target group), the problem or "success", the teaching environment or the situation?
In which other way(s) could the situation have been interpreted (other actors' perspectives)?
How could clarification of e.g., learning outcomes, forms of working or guideline documents have facilitated or clarified the situation?
How do I reach an understanding of what happened?
6) Give suggestion(s) of actions that would have been able to prevent/improve (a problematic/difficult situation) or, alternatively, protect/improve (a positive situation).
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Navigating the Health Insurance Market_ Understanding Trends and Options.pdfEnterprise Wired
From navigating policy options to staying informed about industry trends, this comprehensive guide explores everything you need to know about the health insurance market.
Welcome to Secret Tantric, London’s finest VIP Massage agency. Since we first opened our doors, we have provided the ultimate erotic massage experience to innumerable clients, each one searching for the very best sensual massage in London. We come by this reputation honestly with a dynamic team of the city’s most beautiful masseuses.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Mucopolysaccharidoses (MPS) represent a group of inheritable lysosomal storage diseases caused by mutations in the genes coding for enzymes involved in catabolism of different glycosaminoglycans (GAGs). They are clinically heterogeneous multisystemic diseases, often involving the spine. Bony abnormalities of the spine included in the so-called dysostosis multiplex and GAG deposits in the dura
mater and supporting ligaments can result in spinal cord compression, which can lead to compressive myelopathy.
Spinal involvement is a major cause of morbidity and mortality in some MPS (e.g., MPS IVA, VI, and I), and early radiological diagnosis is critical in preventing or arresting
neurological deterioration and loss of function.
Final Exam of the Course -
The application of the Theory of Science of falsification by Karl Popper and at least one example of the concept of paradigm.
Philosophy of Science and the Concept of Health - 3073 HT23 Karolinska Institutet - oct - nov 2023 - Presented by Gert Helgesson, Tomas Mansson and Annelie Jonsson.
Cancer-associated VTE is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
Cancer-associated Venous Thromboembolism (VTE) is a critical complication in patients with cancer. However the pathological findings of VTE are limited. Here are investigated the histopathological features of cancer-associated VTE in human autopsy cases.
Cancer related vascular biology at CCBIO907 Centre for Cancer Biomarkers by Agnete ST Engelsen.
A recent article from the American Heart Association stressed the importance of the histopahological features of cancer-associated Venous Thromboembolism with the presence of Intrathrombus Cancer Cells and Prothrombotic Factors.
Poster from the revised article "Spinal involvement in Mucopolysaccharidoses" (A.Leone, Childs Nerv. Syst., 2015). Reviewd by Russell Oulette and Anna Hildenbrand Michelman I Karolinska Institutet.
Background Mucopolysaccharidoses (MPS) represent a
group of inheritable lysosomal storage diseases caused by
mutations in the genes coding for enzymes involved in catabolism
of different glycosaminoglycans (GAGs). They are
clinically heterogeneous multisystemic diseases, often involving
the spine. Bony abnormalities of the spine included in the
so-called dysostosis multiplex and GAG deposits in the dura
mater and supporting ligaments can result in spinal cord
compression, which can lead to compressive myelopathy.
Spinal involvement is a major cause of morbidity and mortality
in some MPS (e.g., MPS IVA, VI, and I), and early
radiological diagnosis is critical in preventing or arresting
neurological deterioration and loss of function.
Discussion Management of MPS, however, requires a multidisciplinary
approach because of the multiorgan nature of the
disease. Indeed in order to appreciate the relevance and nuances
of each other's specialty, radiologists and clinicians need
to have a background of common knowledge, rather than a
merely compartmentalized point of view. In the interest of the
management of spinal involvement inMPS, this review article
aims on one hand to provide radiologists with important
clinical knowledge and on the other hand to equip clinicians
with relevant radiological semiotics.
The assignment is to describe and review a teaching experience within higher education, reason about the experience based on pedagogical theories/principles and discuss how the teaching session could be developed in order to better facilitate meaningful learning for the students.
Describe the aims, main content, the set-up and who the students are/the student group. The description should also show the context in which the teaching takes place and the learning outcomes in the course syllabus that your teaching session supports the students in achieving.
Review this session based on the pedagogical theories and principles that have been brought up during the course in relation to, for example, meaningful learning, student-centred teaching, the role of the teacher, outcome-related teaching, constructive alignment, etc. Discuss the ways in which the teaching/supervision facilitates the students' learning and what may constitute difficulties/obstacles.
Discuss what you could consider changing or developing in your teaching, describe how you would go about it and justify changes based on relevant pedagogical theories and concepts. Also describe how you could go about following up the students' learning (if you do not already do this). Your reasoning should be supported by references to course literature and/or other literature/research within higher education. Compile the literature you refer to in a list of references according to an accepted referencing system.
There are many things we have to consider when choosing teaching methods and learning activities. As pointed out earlier in the course it is primarily what students DO that influences learning. Teachers and course organizers need to to consider what students are doing in teaching and learning situations as well as what learning activities they can engage in when working interdependently.
Empirical educational research shows that an active, self-directed approach is likely to have a much greater impact on a student’s learning than passive, lecture-based learning. Lectures should be used sparingly and for broad overviews, summaries and difficult topics. Sadly, only about 5 per cent of what is taught in lectures is actually retained, and too many people use lectures for imparting large quantities of detailed information that could easily be picked up, and more effectively, by reading a textbook.
Of course a number of different methods are used in addition to lectures. In this part of the course we want you to choose ANOTHER teaching form/method to learn more about. The aim of reading about and discussing a number of teaching forms like this is to increase your ability to make conscious choices when planning your teaching and to expand your knowledge of some common methods. We are now approaching the concrete aspects of the craft that is the art of teaching, but should for this sake keep in mind what we want to achieve with our teaching.
Together with a peer or a colleague, decide on an occasion in the coming weeks when you will have the chance to observe his/her teaching. Decide also on a time point for when you can provide your colleague with feedback based on your observations. Agree on what the feedback is to focus on: What does your colleague want you to look at? Another option is to form pairs of critical friends within the group who observe each other 's teaching.
After the feedback to your colleague, you describe:
1.Your preparations, how you conducted your observation and the feedback you gave.
2.What did you learn yourself from observing your colleague's teaching?
3.What did you learn yourself through giving feedback?
Choose a teaching situation significant to you in which you were the teacher/supervisor (or if not possible as student). The incident may have been problematic, difficult to handle or surprisingly positive. The situation you experienced should have aroused emotions and contain some form of dilemma that does not have an obvious "right" answer. Prepare a PowerPoint (or similar) where you address the following:
1) Describe the course of events, the various actors involved and the environment in which the situation took place.
2) Describe why the incident was "critical or significant" for you.
3) Describe what you thought and felt when it happened, and afterwards.
4) Define the problem(s)/difficulties alternatively the success factors in the situation.
5) Analyse the incident based on the following questions:
How has it come about that I look at the situation this way?
What assumptions did I make about the students (the target group), the problem or "success", the teaching environment or the situation?
In which other way(s) could the situation have been interpreted (other actors' perspectives)?
How could clarification of e.g., learning outcomes, forms of working or guideline documents have facilitated or clarified the situation?
How do I reach an understanding of what happened?
6) Give suggestion(s) of actions that would have been able to prevent/improve (a problematic/difficult situation) or, alternatively, protect/improve (a positive situation).
More from Karolinska Institutet, University of Bergen, University of Oslo (11)
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Navigating the Health Insurance Market_ Understanding Trends and Options.pdfEnterprise Wired
From navigating policy options to staying informed about industry trends, this comprehensive guide explores everything you need to know about the health insurance market.
Welcome to Secret Tantric, London’s finest VIP Massage agency. Since we first opened our doors, we have provided the ultimate erotic massage experience to innumerable clients, each one searching for the very best sensual massage in London. We come by this reputation honestly with a dynamic team of the city’s most beautiful masseuses.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
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The Breast Journal 2011 Diffusion weighted Imaging in Evaluating the Response to Neoadjuvant Breast Cancer NAD DWI
1. ORIGINAL ARTICLE
Diffusion-weighted Imaging in Evaluating the Response
to Neoadjuvant Breast Cancer Treatment
Paolo Belli, MD,* Melania Costantini, MD,* Carmine Ierardi, MD,*
Enida Bufi, MD,* Daniele Amato, MD,* Antonino Mule’, MD,
Luigia Nardone, MD,à
Daniela Terribile, MD,§
and Lorenzo Bonomo, MD*
*Department of Bio-Sciences and Radiological Imaging, Department of Pathology, à
Department of
Radiotherapy and §
Department of Surgery, Breast Unit, Catholic University, L.go A. Gemelli 8, 00168
Rome, Italy
n Abstract: The aim of this study was to investigate the role of diffusion imaging in the evaluation of response to neoad-
juvant breast cancer treatment by correlating apparent diffusion coefficient (ADC) value changes with pathological response.
From June 2007 to June 2009, all consecutive patients with histopathologically confirmed breast cancer undergoing neoad-
juvant chemotherapy were enrolled. All patients underwent magnetic resonance imaging (MRI) (including diffusion
sequence) before and after neoadjuvant treatment. The ADC values obtained using two different methods of region of inter-
est (ROI) placement before and after treatment were compared with MRI response (assessed using RECIST 1.1 criteria)
and pathological response (assessed using Mandard’s classification).
Fifty-one women (mean age 48.41 years) were included in this study. Morphological MRI (RECIST classification) well evalu-
ated the responder status after chemotherapy (TRG class; area-under-the-curve 0.865). Mean pretreatment ADC values
obtained with the two different methods of ROI placement were 1.11 and 1.02 · 10)3
mm2
⁄ seconds. Mean post-treatment
ADC values were 1.40 and 1.35 · 10)3
mm2
⁄ seconds, respectively. A significant inverse correlation between mean ADC
increase and Mandard’s classifications was observed for both the methods of ADC measurements. Diagnostic performance
analysis revealed that the single ROI method has a superior diagnostic accuracy compared with the multiple ROIs method
(accuracy: 82% versus 74%). The coupling of the diffusion imaging with the established morphological MRI provides supe-
rior evaluation of response to neoadjuvant chemotherapy treatment in breast cancer patients compared with morphological
MRI alone. There is a potential in the future to optimize patient therapy on the basis of ADC value changes. Additional
works are needed to determine whether these preliminary observed changes in tumor diffusion are a universal response to
tumor cell death, and to more fully delineate the ability of ADC value changes in early recognizing responder from
nonresponder patients. n
Key Words: apparent diffusion coefficient, breast cancer, magnetic resonance imaging, neoadjuvant treatment, response
Neoadjuvant chemotherapy (NAC) is the current
standard of care for both locally advanced breast
cancer patients, including those with both initially
operable and initially not operable breast cancer.
NAC has the aim of improving both breast-conserving
surgery and systemic control of disease (1–8).
Moreover, preoperative chemotherapy provides the
opportunity to assess the in vivo tumor response to
treatment and to tailor individual treatment on the
basis of the degree of response (3–7,9). Finally, the
tumor response to chemotherapy may be considered
an independent prognostic factor. In fact, a complete
pathological response (pCR) (3–30% of patients) has
been associated with significantly improved disease-
free survival and overall survival rates, besides the ini-
tial tumor stage and other prognostic markers. The
aim of clinicians is indeed the adjustment of alterna-
tive preoperative therapeutic regimens in those prob-
lematic patients showing only partial or minor
response (60–80% of the population) (1,3–5,10–14).
Thus, a reliable assessment of tumor response
through non-invasive and reproducible methods is of
pivotal importance. Traditionally, such assessment has
been carried out through physical examination, mam-
mography, and sonography, with supobtimal accuracy
in tumor response detection. The introduction of mag-
Address correspondence and reprint requests to: Enida Bufi, MD,
Department of Bio-Sciences and Radiological Imaging, Catholic University,
L.go A Gemelli 8, 00168 Rome, Italy, or e-mail: reagandus@alice.it.
DOI: 10.1111/j.1524-4741.2011.01160.x
2011 Wiley Periodicals, Inc., 1075-122X/11
The Breast Journal, Volume 17 Number 6, 2011 610–619
2. netic resonance imaging (MRI) has improved the diag-
nostic accuracy of the breast cancer response to che-
motherapy by measuring tumor diameter changes and
by evaluating the vitality of residual tumor areas
(2,3,5,7,8,15–22). However, two major mismatches
have been evidenced between the MRI and the histo-
pathologic results. The first limitation of MRI is repre-
sented by its low power to detect ductal carcinoma in
situ (DCIS) or microscopic disease within multifocal
cancer. Nevertheless, it is has been demonstrated that
this limitation does not influence the long-term dis-
ease-free and overall survival of patients (6). Second,
the MRI can often overestimate the burden of residual
tumor by confounding a fibrotic scar with viable
tumor tissue. During and after NAC, tumor bed
enhancement reflects both the vascularity of residual
tumor and the effects of chemotherapy on tissue. This
makes the dynamic findings difficult to interpret
(1,23–26).
To improve the diagnostic performance of MRI
and to overcome the above limitations, we tested the
use of the diffusion-weighted-imaging (DWI) sequence.
Recent studies have proposed the DWI as an assess-
ment of tumor response to treatment. DWI reflects the
thermally driven motion of water molecules in the tar-
get tissue, thus providing information on the intrinsic
characteristics of tissue microstructure (volume and
arrangement of intracellular and extracellular spaces,
cellular membrane integrity and permeability).
However, the apparent diffusion coefficient (ADC)
quantifies the water diffusion within the tissue.
(4,8,20,25–32). There are few data over the capability
of DWI sequence in evaluating the histopathologic
response to treatment. Additionally, there is no
evidence available over the differential diagnostic
performance of the two different methods of ADC
assessment, namely the single region of interest (ROI)
versus the multiple ROIs method.
The present study was designed to address the
sensitivity, specificity and accuracy of MRI morpho-
logical sequences in evaluating the tumor response
to treatment (in particular, the responder versus the
nonresponder status). Further study objectives were
the depiction of the role of diffusion imaging in the
evaluation of breast cancer response to neoadjuvant
treatment (correlation of ADC value changes with
the pathological response according to a standard-
ized classification). Finally, we addressed the accu-
racy of the two above-mentioned methods of ROI
placement.
MATERIALS AND METHODS
Patients Selection
From June 2007 to June 2009, we prospectively
enrolled consecutive patients with histopathologically
proven invasive breast cancer (core-needle biopsy)
scheduled for NAC at the Breast Unit of our
hospital.
Study design comprised pre-NAC MRI imaging
(within 4 weeks before start of chemotherapy proto-
col), post-NAC MRI imaging, and definitive surgery
within 4 weeks after the completion of chemotherapy.
Exclusion criteria were incomplete or non-optimal
MRI study, surgery or definitive pathological diagno-
sis obtained outside, and non-completion of the
planned chemotherapy protocol. The NAC protocol
was managed by clinical oncologists at our Institution.
The final diagnosis of tumor response to neoadju-
vant treatment was classified according to the histo-
pathological Mandard’s TRG (Tumor Regression
Grade) criteria after surgical excision (33). The diag-
nostic performance of MRI imaging (either morpho-
logical or diffusion imaging) was weighted against the
results of TRG classification.
As the study protocol did not entail any additional
diagnostic or therapeutic intervention than routine
clinical management, and as the patients’ data were
treated anonymously, signed informed consent to
enter the present study was not deemed necessary.
Given the prospective nature of the study, IRB
approval of the study protocol was obtained.
MRI Protocol
All patients gave written informed consent to
undergo MRI and the MRI was performed with a 1.5
T unit with 23 mT⁄m gradient intensity (Signa Excite;
GE Medical System, Milwaukee, WI) with women in
the prone position using a dedicated breast coil.
The following sequences were acquired:
1. STIR axial sequence (short time inversion recov-
ery; repetition time [TR] = 5900, echo time [TE] = 68,
echo train length [ETL] = 17, bandwidth 41–67,
512 · 512 matrix, thickness = 4 mm, 0 interval, field-
of-view [FOV] = 32–34 cm, Number of Excitation
[NEX] = 1–2).
2. DWI axial sequence (TR = 5150, TE = min, fre-
quency-phase 96 · 96, 256 · 256 matrix, thick-
ness = 4 mm, 0 interval, FOV = 32–34 cm, NEX = 2).
DWI was acquired before dynamic sequences with a
DWI and Response to Neoadjuvant Chemotherapy • 611
3. spin echo EPI sequence in the axial plane. Sensitizing
diffusion gradients were applied sequentially in the x-, y-,
and z- directions with b values of 0 and 1,000 seconds⁄mm2
,
according to the pertinent literature (34–37).
3. Three-dimensional (3D) FSPGR (fast spoiled gra-
dient echo) fat sat coronal sequence (FA [flip-
angle] = 15, TR 30 ms, TE 5 ms, NEX = 0.5,
thickness = 2–3 mm, 0 interval, 512 · 512 matrix,
FOV = 34–38 cm) before and five times after intrave-
nous administration of 0.1 mmol⁄kg of Gd-DTPA
(Gadopentetate dimeglumine; Bracco Diagnostics,
Milan, Italy). Contrast medium was injected with a
10 seconds of timing delay into the antecubital vein
with a 18–20 G needle at a flow rate of 2 mL⁄seconds
followed by a flush of 20 mL of saline solution.
4. 3D FSPGR sagittal postcontrast fat-suppressed
sequence (TR30, TE5, FA = 15, 512 · 512 matrix,
thickness = 2–3 mm, 0 interval, FOV = 22–26 cm,
NEX = 2).
5. 3D FSPGR axial postcontrast fat-suppressed
sequence (TR30, TE5, FA = 30, 512 · 512 matrix,
thickness = 2–3 mm, 0 interval, FOV = 34–38 cm,
NEX = 2).
Acquisition time of this complete MRI protocol
was 18–20 minutes.
Dynamic and DWI sequences were evaluated using
a dedicated workstation (GE Healthcare
, Advantage
Windows 4.1) by the consensus of two radiologists
(MC and PB authors) experienced in breast imaging.
The tumor response to treatment was assessed
using RECIST 1.1 (Response Evaluation Criteria in
Solid Tumors) classification (38), based on the longest
diameter measure of the target lesion (postcontrast
fat-suppressed 3D FSPGR T1-weighted images). In the
presence of a multifocal or multicentric disease, the
largest lesion was considered as the target one.
Accordingly, we identified four groups:
1. Complete response (CR): complete disappearance
of lesion.
2. Partial response (PR): at least a 30% decrease in
longest diameter.
3. Progressive disease (PD): at least a 20% increase
in tumor size.
4. Stable disease (SD): neither sufficient shrinkage
to qualify for PR nor sufficient increase to qualify for
PD.
For each target lesion, we evaluated the DWI
sequence and measured the ADC values before and
after the chemotherapy according to the following
formula: ADC = (lnS0)lnS)⁄b (where S0 is signal
intensity obtained at b = 0 and S is signal intensity
obtained at b = 1,000), directly applied by the pro-
gram. Two different methods of measure were
recorded for each lesion:
1. A single ROI was positioned on the slice corre-
sponding to the maximum diameter of the lesion
(‘‘Single ROI’’ method);
2. Five small ROIs (100 pixels) were positioned
on different slices within the lesion, to exclude cystic
or necrotic areas. Subsequently, the mean value was
calculated (‘‘Multiple ROIs’’ method).
Previous literature is available over both the single
ROI method (35) and the multiple ROIs method (39).
In case of tumor fragmentation, the single ROI
included the entire area involved by the lesion
together with the interspersed areas without signal hy-
perintensity. However, the five small ROIs were posi-
tioned only in the residual hyperintensity areas. In
case of absence of hyperintensity areas, we measured
the ADC value in the previous site of lesion.
Pathological Examination
Breast surgical specimens were cut into 5-mm slices,
fixed in 10% neutral-buffered formalin, and stained
with hematoxylin and eosin (H E) for evaluation.
Macroscopic inspection of the specimens was used to
identify gross tumor areas for subsequent microscopic
assessment. Whether gross tumor was not macroscopi-
cally evident, each paraffin block was sliced and the
tumor bed was identified by correlation with imaging
findings and radiography of specimens. The size of
tumor bed, the largest focus of contiguous invasive car-
cinoma and the number of invasive foci were recorded.
Residual disease post-NAC was assessed according
to the Mandard’s classification (40) based on grade of
tumor regression. Five classes of pathological response
were recorded:
1. TRG1: complete regression, absence of residual
tumor cells.
2. TRG2: presence of rare residual cancer cells scat-
tered through the fibrosis.
3. TRG3: increase in the number of residual cancer
cells, but fibrosis still predominated.
4. TRG4: residual cancer outgrowing fibrosis.
5. TRG5: absence of regressive changes.
For data analysis, we defined the ‘‘Responder’’
patients those having TRG class 1, 2, or 3, and the
‘‘Nonresponder’’ patients those having TRG class 4 or
5. Similarly, under the profile of morphological MRI,
we defined the ‘‘Responder’’ patients those having
612 • belli et al.
4. Complete Response or Partial Response, and the
‘‘Nonresponder’’ patients those having Stable of Pro-
gressive Disease (RECIST 1.1). Concerning the diag-
nostic performance analysis of diffusion imaging, we
defined the ADC variation as the post-treatment ADC
minus the pretreatment ADC for each lesion. Finally,
we assumed a cutoff value of ‡20% increase in ADC
value after the chemotherapy treatment as indicative
of response to treatment itself. A battery of different
potential cutoff values were tested within our dataset,
and diagnostic accuracy⁄receiver operator characteris-
tic (ROC) curves were determined for each of them.
The ‡20% increase in ADC value was identified as
the cutoff having the best diagnostic performance;
detailed data relative to the excluded cutoff values
were not shown due to space issues.
Statistical Analysis
The statistical analysis was performed using SPSS
version 11.0 for Windows (Statistical Package for Social
Sciences, SPSS, Chicago, IL). Continuous data are pre-
sented as mean ± standard deviation and categorical
variables as percentages. Intergroup mean comparison
was performed using two-tailed Student’s t-test for
paired samples, or using one-way analysis of variance
(ANOVA) for multiple-groups comparison. Kendall’s
rank-correlation coefficient (tau) was used to analyze
the correlation between the Mandard’s classification
and the variation of ADC after versus before the
chemotherapy treatment. Both methods of ADC assess-
ment were evaluated. Subsequently, Kendall’s coeffi-
cient was used to investigate the correlation between
the Mandard’s classification and the RECIST class.
Diagnostic performance of test (value of either method
of ADC assessment in evaluating the response or nonre-
sponse status of a tumor lesion) was performed by cal-
culation of sensitivity, specificity and diagnostic
accuracy. Adequate ROC curves were built. Subse-
quently, the ROC curves obtained with either method
were statistically compared according to the Hanley
and McNeil methodology (41), using the MedCalc soft-
ware for Windows (MedCalc, Broekstraat 52, B-9030
Mariakerke, Belgium). The alpha level was 0.05.
RESULTS
Characteristics of the Population
The study design is summarized in Fig. 1. A total
of 200 patients were initially enrolled and underwent
pretreatment MRI. Of these, 62 were excluded as they
had excision surgery of breast lesion before chemo-
therapy, 30 did not complete their chemotherapy pro-
tocol due to toxicity and 12 refused the
post-treatment MRI. Ninety-six patients had their
post-treatment MRI; of these, 45 had their excision
surgery of breast lesion with histologic exam within
another Institution. Thus, we had complete data for
51 patients. These constituted the final study popula-
tion. Mean age at diagnosis was 48.41 ± 10.18 years
(range: 26–66 years).
Pretreatment core-needle biopsies revealed 40 inva-
sive ductal carcinomas (including two cases of mixed
invasive ⁄in situ ductal carcinomas), seven invasive
lobular carcinomas, and four poorly differentiated
carcinomas.
In 29 cases (56.86%), the left breast was affected.
From these, the external upper quadrants were
involved in 19 cases (65.51%). There were 37 cases
(72.54%) of axillary lymph nodes metastases and
three cases (5.88%) of distant metastases. Conven-
tional MRI showed 34 cases of unifocal disease and
17 cases of multifocal ⁄multicenter disease. Under the
morphological point of view, breast cancer appeared
as a mass in 37 cases and as diffuse enhancement in
14 cases.
Mean pretreatment diameter obtained with MRI
was 50.23 ± 19.98 mm (range: 18–90 mm).
Mean pretreatment ADC value obtained with the
single ROI method was 1.11 ± 0.16 · 10)3
mm2
⁄
Figure 1. Study design.
DWI and Response to Neoadjuvant Chemotherapy • 613
5. seconds (range 0.82–1.55). Mean pretreatment ADC
value obtained with the multiple ROIs method was
1.03 ± 0.15 · 10)3
mm2
⁄seconds (range 0.78–1.42)
(Fig. 2). We observed no statistically significant differ-
ence in mean pretreatment ADC value between
responder and nonresponder patients.
The neoadjuvant regimens used in our patients
were FEC (Fluorouracil + Epirubicin + Cyclophospha-
mide) in six cases, AT (Doxorubicin + Taxanes) in 23
cases, TAC (Taxanes + Doxorubicin + Cyclophospha-
mide) in nine cases, and TC (Taxanes + Cyclophos-
phamide) ± carboplatinum or trastuzumab in 13 cases,
given 3-weekly for 4–6 cycles.
The total treatment period ranged from 56 to
224 days (mean, 132 days).
Mean post-treatment diameter obtained with MRI
measurements was 27.74 ± 23.21 mm (range: 0–
85 mm).
Based on dynamic and morphological changes, con-
ventional MRI (according to RECIST 1.1 criteria)
identified 11 cases of complete response to treatment,
21 cases of partial response, and 19 cases of stable
disease. No patient showed progressive disease. Defini-
tive pathological analysis according to the Mandard’s
classification confirmed five cases of TGR1, nine cases
of TGR2, 11 cases of TGR3, 18 cases of TGR4, and
eight cases of TGR5.
Mean post-treatment ADC value obtained with the
single ROI method and the multiple ROIs method
was 1.40 ± 0.30 · 10)3
mm2
⁄seconds (range 0.69–
2.00) and 1.35 ± 0.28 · 10)3
mm2
⁄seconds (range
0.73–1.99), respectively (Fig. 3).
At the end of the neoadjuvant treatment, we
observed a statistically significant increase in mean
ADC value assessed by either methodology (p 0.001
for both the single ROI method and the multiple ROIs
method) (Fig. 4).
Diagnostic Performance
We assessed the diagnostic performance of both the
morphological MRI imaging and the DWI sequence.
Our data confirm previous findings that the morpho-
logical MRI imaging according to the RECIST classifi-
cations well evaluates the TRG histologic response
(sensitivity 96%, specificity 73%, diagnostic accuracy
84% in our series). Such concept is supported even by
the ROC curve for our data (area-under-the-curve
0.865) (graph not shown).
(a)
(c) (d)
(b)
Figure 2. Pre-NAC DWI images and ADC
maps for the multiple ROIs method (a and b)
and the single ROI method (c and d).
614 • belli et al.
6. Concerning the DWI sequence, mean ADC varia-
tion after neoadjuvant treatment was maximal among
patients having TRG class 1, and progressively
decreased in class 2 toward class 5 for both the single
ROI and the multiple ROIs methods (Table 1). Such
variation was statistically significant according to the
ANOVA analysis (p = 0.001 for the single ROI
method and p 0.001 for the multiple ROIs method).
We observed a statistically significant inverse
correlation between the percentage variation of ADC
(single ROI method) and the TRG class
(tau = )0.415, p 0.001). Similarly, an inverse corre-
lation exists between the percentage ADC variation
obtained by the multiple ROIs method and the TRG
class (tau = )0.445, p 0.001).
Subsequently, we compared the diagnostic perfor-
mance of the single ROI versus the multiple ROIs
method. For this purpose, we grouped the TRG
(a)
(c) (d)
(b)
Figure 3. Post-NAC DWI images and ADC
maps for the multiple ROIs method (a and b)
and the single ROI method (c and d).
(a) (b)
Figure 4. Box plot for mean ADC value comparison: pre-NAC versus post-NAC mean ADC values for the Single ROI method (a) and the
Multiple ROIs method (b).
DWI and Response to Neoadjuvant Chemotherapy • 615
7. classes according to the responder (TRG class 1, 2,
and 3) or nonresponder (TRG class 4 and 5) status,
and corresponding ROC curves were built. For the
single ROI method, we observed a 0.804 area-under-
the-curve (evaluation of the responder status by ADC
variation) (Fig. 5a). However, a 0.746 area-under-the-
curve was calculated for the multiple ROIs method
(Fig. 5b). Accordingly, the two ROI placement meth-
ods displayed similar sensitivity (80% both), but supe-
rior specificity was observed for the single ROI
method (84% versus 69%). Thus, the single ROI
method displayed a higher overall diagnostic accuracy
(82% versus 74%). However, when comparing the
two ROC curves according to the Hanley and McNeil
methodology, there appeared to be no statistically sig-
nificant difference (p = 0.74, z statistic = 0.32).
DISCUSSION
Dynamic contrast-enhanced RMI and more recently
DWI have demonstrated relevant abilities in assessing
tumor progression and⁄or responses to chemotherapy.
However, it has been suggested that the morphologi-
cal MRI imaging alone has suboptimal capability to
differentiate among the scar tissue and the viable
tumor tissue, and may overestimate or underestimate
the residual tumor size (2–8,15–25). This potentially
generates false positive results and leads to misrecog-
nize a proportion of responder patients, with ensuing
suboptimal clinical management. Our data indicate
that the DWI sequence can be proficiently used to
fill such diagnostic gap. In our series, we confirm
the above limitation of DCE-MRI. In fact, the mor-
phological MRI imaging showed an excellent sensitiv-
ity (96%) coupled with a fairly lower specificity
(73%) in evaluating the histologic response to NAC
(TRG classification). Overall diagnostic accuracy was
84%.
When taking the DWI imaging into analysis, we
found that the mean ADC values significantly
increased after the NAC treatment. The effects of che-
motherapy are registered as an increase in ADC value,
in consequence of cellular damage (25–32,42–48).
Changes in ADC may be a generalized measure of
cytotoxic response to chemotherapy. The nature of
the cytological changes that gives rise to these ADC
changes is not well defined. Current models indicate
that increases in ADC are consistent with an increase
in tissue water mobility, which can be achieved
through cell shrinkage, breakdown of the plasma
membrane, or increase in the nuclear⁄cytoplasmic
ratio (8,9).
Table 1. Mean Increase of ADC Value in Relation
to Pathological Response
Mandard’s
classifications
Mean ADC difference
for single ROI method
Mean ADC difference
for multiple ROIs method
TRG1 0.63 0.68
TRG2 0.42 0.47
TRG3 0.36 0.38
TRG4 0.17 0.2
TRG5 0.09 0.16
(a) (b)
Figure 5. Diagnostic performance of ADC increase after NAC (20% increase as cutoff value for responder status) for the Single ROI
method (a) and the Multiple ROIs method (b).
616 • belli et al.
8. Our findings of increased ADC value after chemo-
therapy confirm previous results (4,8,20,25,39). The
referenced studies, however, while evaluating the DWI
sequence as a predictor of tumor response, did not use
a formal classification of histopathologic response to
address this point. As such, several investigations are
limited by little sample size (8) or poor definition of
histopathologic response outcome measurement (4).
To overcome such limitations, we adopted the formal
TRG histopathologic classification as the outcome
measure of our study for tumor response. We dis-
carded all patients without complete in-house evalua-
tion, to increase the homogeneity of outcome measure
data and the reliability of the conclusions, and to
reduce the selection bias. For our analysis, we calcu-
lated the variation of ADC value prior versus post-
NAC in each patient, and the mean variation value
was made available. Our ANOVA model disclosed a
statistically significant increase in the mean ADC vari-
ation value across the five TRG classes, with class 1
(complete response) showing the larger mean variation
(i.e., larger post-NAC mean ADC increase) and class
5 (stable disease) showing the lesser mean variation
(i.e., lesser post-NAC ADC increase or almost no
increase) (p = 0.001). The mean variation of ADC
decreased linearly with increase in the TRG class
(Table 1). The finding of a statistically significant
inverse correlation (Kendall’s tau) between the ADC
variation and the TRG classes supports this concept.
We did not find a statistically significant difference in
pretreatment ADC value among the responder versus
the nonresponder patients. This finding is in contrast
with previous evidence (4). Such discrepancy may be
attributed to a different definition of the responder sta-
tus, which, in the above-referenced study, was based on
the variation in tumor size after NAC (DCE-MRI).
Conversely, we defined the response to NAC on the
basis of histopathologic assessment: patients having
TRG classes 1, 2, and 3 were defined as responders;
otherwise, patients having TRG class 4 or 5 were
defined as nonresponders. We believed that the histo-
pathologic classification should be considered as the
true standard for the outcome measure in our study.
Under the profile of assessment of the ADC value,
two alternative methods are currently available (the
Single ROI versus the Multiple ROIs method). These
methods have been variably employed in the studies
published so far; however, a direct benchmark compari-
son of their differential performance in the same popu-
lation is required. For this purpose, for each patient
included in our study, we measured the ADC value
using both methods at each time point, and conducted a
formal diagnostic performance analysis for both of
them. Both methodologies disclosed a statistically sig-
nificant difference in pre-NAC versus post-NAC mean
ADC value (p 0.001 for both Single ROI and Multi-
ple ROIs method). In addition, the inverse correlation
between ADC value variation and TRG class was statis-
tically significant for both methods, showing similar tau
coefficients ()0.415 and )0.445, Single ROI versus
Multiple ROIs method). However, when introducing
more refined tests of diagnostic performance (ROC
curves), it emerges that the Single ROI method has a
fairly better diagnostic performance in evaluating the
responder status (TRG classification). We adopted a
20% increase in ADC value (post-NAC versus pre-
NAC) as a cutoff measurement to define the responder
status on the basis of the DWI sequence, and compared
the DWI status findings with the histopathologic
responder⁄nonresponder status (TRG). Based on such
definitions, the Single method showed a 0.804 area
under the curve, 80% sensitivity, 84% specificity, and
82% accuracy. Conversely, the Multiple ROIs method
was characterized by a 0.746 area under the curve,
80% sensitivity, 69% specificity and 74% diagnostic
accuracy. Thus, the better diagnostic performance of
the Single ROI method can be attributed essentially to a
superior specificity than the Multiple ROIs method.
Actually, in the Multiple ROIs method, five ROIs are
manually selected by each individual examiner in the
context of the hyperintensity areas, with the scope of
avoiding measurement bias due to central necrotic
areas. Despite this methodology should ideally confine
the analysis to the only viable areas of the tumor, our
findings actually indicate that the Single ROI method
displays a better diagnostic performance for the histo-
pathologic response to treatment. Nonetheless, we
failed to demonstrate a statistically significant differ-
ence among ROC curves obtained for either method,
possibly due to scarce sample size. While the two meth-
ods may be regarded as essentially equivalent to evalu-
ate the response to NAC, the Single ROI method can be
proposed for routine use in the evaluation of breast can-
cer in consideration of its performance, reproducibility,
and rapidity. The above-mentioned cutoff for ADC
value increase (20%) provided the better diagnostic
performance among a battery of potential cutoff values
(data not shown).
Conventional MRI is the current gold-standard for
the reassessment of breast cancer during treatment
DWI and Response to Neoadjuvant Chemotherapy • 617
9. protocols; however, it is limited by the need to admin-
ister contrast agent. Our data indicate that the single
ROI method may be comparable to conventional MRI
in terms of diagnostic accuracy. As the DWI sequence
requires no injection of contrast agent, it is reasonable
to foresee its expanding role during the NAC cycles
and after surgery. Patients with contrast medium
intolerance and renal failure may particularly benefit
from this strategy.
We acknowledge the lack of mid-term data for his-
topathology, DCE-MRI, and DWI as a potential study
limitation. However, our purpose was limited to the
assessment of the diagnostic value of DWI at the end
of the entire NAC treatment. Other studies performed
complete reassessment of the lesions between each
NAC cycle (25,39,41); further investigations of these
points are encouraged. In addition, our patients under-
went a number of different NAC protocols, which
may theoretically represent a confounder. However, in
our global analysis, we disclosed evident results over
the variation of mean ADC values and their potential
to evaluate the tumor response; as such, studies with
larger sample sizes are required to perform an assess-
ment of DWI performance in different NAC protocol
subgroups.
CONCLUSION
The significant changes that occurred in ADC val-
ues after NAC suggest that this parameter could be a
useful biomarker for assessing response to therapy in
breast tumors.
The relationship between ADC changes and the
degree of response is of particular interest due to the
current paucity of data existing in the literature.
Determination of ADC is time-saving, requires
no injection of contrast agents, and may be considered
an addition tool to tailor the individual patients’ treat-
ment.
There is a potential in the future to optimize
patient therapy on the basis of the application of DWI
to monitor effective response at an early stage of
treatment.
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