Scans and Ovarian Cancer: Everything You Want to Knowbkling
When you’re diagnosed with ovarian cancer, scans become an inevitable part of life. But what are the differences between the imaging tests? When should which scans be used? What about the pros and cons of each test? Join Dr. Kevin Holcomb, Vice-Chair of Gynecology and member of the Division of Gynecologic Oncology at Weill Cornell Medicine, and Dr. Elisabeth O’Dwyer, Instructor in Radiology at Weill Cornell Medicine and Assistant Attending Radiologist at NewYork-Presbyterian Hospital-Weill Cornell Campus, as they help make sense of it all.
Original StudyType of Breast Cancer Diagnosis, Screening,a.docxvannagoforth
Original Study
Type of Breast Cancer Diagnosis, Screening,
and Survival
Carla Cedolini,1 Serena Bertozzi,1 Ambrogio P. Londero,2 Sergio Bernardi,3,4
Luca Seriau,1 Serena Concina,1 Federico Cattin,1 Andrea Risaliti1
Abstract
Organized, invitational breast cancer screening in our population succeeded in detecting early-stage tumors,
which have been consequently treated more frequently with breast and axillary conservative surgery, com-
plementary breast irradiation, and eventual hormonal therapy. The diagnosis of invasive cancer with screening
in our population resulted in a survival gain at 5 years from the diagnosis.
Introduction: Breast cancer screening is known to reduce mortality. In the present study, we analyzed the prevalence
of breast cancers detected through screening, before and after introduction of an organized screening, and we
evaluated the overall survival of these patients in comparison with women with an extrascreening imaging-detected
breast cancer or those with palpable breast cancers. Materials and Methods: We collected data about all women
who underwent a breast operation for cancer in our department between 2001 and 2008, focusing on type of tumor
diagnosis, tumor characteristics, therapies administered, and patient outcome in terms of overall survival, and re-
currences. Data was analyzed by R (version 2.15.2), and P < .05 was considered significant. Results: Among the 2070
cases of invasive breast cancer we considered, 157 were detected by regional mammographic screening (group A),
843 by extrascreening breast imaging (group B: 507 by mammography and 336 by ultrasound), and 1070 by extra-
screening breast objective examination (group C). The 5-year overall survival in groups A, B, and C were, respectively,
99% (95% CI, 98%-100%), 98% (95% CI, 97%-99%), and 91% (95% CI, 90%-93%), with a significant difference
between the first 2 groups and the third (P < .05) and a trend between groups A and B (P ¼ .081). Conclusion: The
diagnosis of invasive breast cancer with screening in our population resulted in a survival gain at 5 years from the
diagnosis, but a longer follow-up is necessary to confirm this data.
Clinical Breast Cancer, Vol. 14, No. 4, 235-40 ª 2014 Elsevier Inc. All rights reserved.
Keywords: Breast cancer, Breast cancer screening, Invasive breast cancer, Mammographic screening, Overall survival
Introduction
Because of the detection of early-stage tumors, breast cancer
screening reduced breast cancer mortality in Europe by 25%-31%
in patients who were invited for screening and by 38%-48% in
those who were actually screened during the last decade of the
twentieth century and the first decade of the twenty-first.1 In our
region of Italy, an organized breast cancer screening was firstly intro-
duced in 2005, but despite the high compliance of invited women
1Clinic of Surgery
2Clinic of Obstetrics and Gynecology
University of Udine, Udine, Italy
3Department of Surgery, Ospedale Civile di Latisana, Udine, Italy
4 ...
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
Breast conserving surgery followed by adjuvant radiotherapy is adopted in the early detected cases and mastectomy followed by radiotherapy or chemotherapy in the advanced cases are the general practices.
A prospective study of breast lump andclinicopathologicalanalysis in relation...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Scans and Ovarian Cancer: Everything You Want to Knowbkling
When you’re diagnosed with ovarian cancer, scans become an inevitable part of life. But what are the differences between the imaging tests? When should which scans be used? What about the pros and cons of each test? Join Dr. Kevin Holcomb, Vice-Chair of Gynecology and member of the Division of Gynecologic Oncology at Weill Cornell Medicine, and Dr. Elisabeth O’Dwyer, Instructor in Radiology at Weill Cornell Medicine and Assistant Attending Radiologist at NewYork-Presbyterian Hospital-Weill Cornell Campus, as they help make sense of it all.
Original StudyType of Breast Cancer Diagnosis, Screening,a.docxvannagoforth
Original Study
Type of Breast Cancer Diagnosis, Screening,
and Survival
Carla Cedolini,1 Serena Bertozzi,1 Ambrogio P. Londero,2 Sergio Bernardi,3,4
Luca Seriau,1 Serena Concina,1 Federico Cattin,1 Andrea Risaliti1
Abstract
Organized, invitational breast cancer screening in our population succeeded in detecting early-stage tumors,
which have been consequently treated more frequently with breast and axillary conservative surgery, com-
plementary breast irradiation, and eventual hormonal therapy. The diagnosis of invasive cancer with screening
in our population resulted in a survival gain at 5 years from the diagnosis.
Introduction: Breast cancer screening is known to reduce mortality. In the present study, we analyzed the prevalence
of breast cancers detected through screening, before and after introduction of an organized screening, and we
evaluated the overall survival of these patients in comparison with women with an extrascreening imaging-detected
breast cancer or those with palpable breast cancers. Materials and Methods: We collected data about all women
who underwent a breast operation for cancer in our department between 2001 and 2008, focusing on type of tumor
diagnosis, tumor characteristics, therapies administered, and patient outcome in terms of overall survival, and re-
currences. Data was analyzed by R (version 2.15.2), and P < .05 was considered significant. Results: Among the 2070
cases of invasive breast cancer we considered, 157 were detected by regional mammographic screening (group A),
843 by extrascreening breast imaging (group B: 507 by mammography and 336 by ultrasound), and 1070 by extra-
screening breast objective examination (group C). The 5-year overall survival in groups A, B, and C were, respectively,
99% (95% CI, 98%-100%), 98% (95% CI, 97%-99%), and 91% (95% CI, 90%-93%), with a significant difference
between the first 2 groups and the third (P < .05) and a trend between groups A and B (P ¼ .081). Conclusion: The
diagnosis of invasive breast cancer with screening in our population resulted in a survival gain at 5 years from the
diagnosis, but a longer follow-up is necessary to confirm this data.
Clinical Breast Cancer, Vol. 14, No. 4, 235-40 ª 2014 Elsevier Inc. All rights reserved.
Keywords: Breast cancer, Breast cancer screening, Invasive breast cancer, Mammographic screening, Overall survival
Introduction
Because of the detection of early-stage tumors, breast cancer
screening reduced breast cancer mortality in Europe by 25%-31%
in patients who were invited for screening and by 38%-48% in
those who were actually screened during the last decade of the
twentieth century and the first decade of the twenty-first.1 In our
region of Italy, an organized breast cancer screening was firstly intro-
duced in 2005, but despite the high compliance of invited women
1Clinic of Surgery
2Clinic of Obstetrics and Gynecology
University of Udine, Udine, Italy
3Department of Surgery, Ospedale Civile di Latisana, Udine, Italy
4 ...
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
Breast conserving surgery followed by adjuvant radiotherapy is adopted in the early detected cases and mastectomy followed by radiotherapy or chemotherapy in the advanced cases are the general practices.
A prospective study of breast lump andclinicopathologicalanalysis in relation...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Are There Any Natural Remedies To Treat Syphilis.pdf
CaCu localizado.pdf
1. Current Management of Locally
Advanced Cervical Cancer
April 28 th , 2023
Valeria Caceres, M.D., MSc., Ph.D.
Medical Oncology Department Head
Instituto Angel H Roffo
Universidad de Buenos Aires
2. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
DECLARATION OF INTERESTS
Speaker for MDS, Pfizer, Astra Zeneca, Raffo, Roche,GSK.
Advisory board: MSD, Pfizer, GSK, Pint Pharma
Travel expenses: Raffo, Varifarma and Gador
Congress virtual access: Novartis
Valeria Cáceres
3. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
AGENDA
• Epidemiology, Screening and Vaccination
• Locally Advanced Cervical Cancer Definition
• Imaging work-up
• Treatment phases
• New agents
• LACC in Pandemia at IOAR: 2020
• Take Home Messages
• Final thoughts
4. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Epidemiology, Screening and Vaccination
Valeria Caceres
5. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Cancer Today. http://gco.iarc.fr/today/home
Global Incidence And Mortality Rates For Cervical Cancer
Valeria Caceres
6. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Locally advanced and metastatic carcinoma of cervix is predominantly the disease of
LMIC, with about 88% of global burden attributed to the region as per Globocan 2020
Cancer Today. http://gco.iarc.fr/today/home
Global Incidence And Mortality Rates For Cervical Cancer
Valeria Caceres
7. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Missed Opportunities for HPV Screening and Vaccination
Valeria Caceres
Brisson M, Kim JJ, Canfell K, et al: Impact of HPV vaccination and cervical screening on cervical cancer elimination: A comparative modelling analysis in 78 low- income and lower middle-income
countries. Lancet 395:575-590, 2020
8. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Missed Opportunities for HPV Screening and Vaccination
Valeria Caceres
• Girls’ Vaccination reduce the incidence in LMICs from 19.8 to 2.1/ 100,000 women years by the next century,
preventing 61 million between 2059 and 2102.
• Twice lifetime HPV screening reduce the incidence to 0.7 /100,000 women, preventing 12.1 million cervical
cancer over the same period and thus accelerating elimination by 11 to 31 years.
Brisson M, Kim JJ, Canfell K, et al: Impact of HPV vaccination and cervical screening on cervical cancer elimination: A comparative modelling analysis in 78 low- income and lower middle-income
countries. Lancet 395:575-590, 2020
9. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Locally Advanced Cervical Cancer
Definition (LACC)
Valeria Caceres
10. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Valeria Cáceres
International federation of gynecology and obstetrics (FIGO)
classification)
Grigsby PW, Massad LS, Mutch DG, et al. FIGO 2018 staging criteria for cervical cancer: impact on stage migration and survival. Gynecol Oncol. 2020;157(3):639–643.
Wright JD, Matsuo K, Huang Y, et al. Prognostic performance of the 2018 International federation of gynecology and obstetrics cervical cancer staging guidelines. Obstet Gynecol. 2019;134(1):49–57. Matsuo K,
Machida H, Mandelbaum RS, et al. Validation of the 2018 FIGO cervical cancer staging system. Gynecol Oncol. 2019;152 (1):87–93.
McComas KN, Torgeson AM, Ager BJ, et al. The variable impact of positive lymph nodes in cervical cancer: implications of the new FIGO staging system. Gynecol Oncol. 2020;156(1):85–92.
2018: FIGO updated clinical classification: images and/or pathological findings for staging.
Lateral extension measurement was removed from stage IA, and
Stage IB: three subgroups based on tumor size (in greatest dimension):
Stage IB1 (≤ 20 mm),
Stage IB2 (>20 mm to ≤ 40 mm)
Stage IB3 (>40 mm).
Incorporation of lymph node (LN) status.
N +: IIIC. Pelvic LN: IIIC1. Para-aortic (PAo) LNs +: IIIC2.
Notations ‘r’ (imaging) and ‘p’ (pathology) indicate the method used to stage.
Four large-scale retrospective cohort studies were conducted to validate classification: good discrimination
between the three groups in stage IB. Nodal status clearly impacts survival, with the risk of death nearly 1.5- and
2-fold greater for pelvic and PAo LN involvement, respectively. This effect varies greatly based on local T stage,
leading to survival heterogeneity in patients with stage III subgroups.
11. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
LACC: Summary FIGO Staging
Valeria Caceres
12. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
IMAGING WORK-UP
Valeria Cáceres
13. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Local Diagnostic
Valeria Caceres
• Gynecologic examination with colposcopy-guided biopsy and
pelvic magnetic resonance imaging (MRI) are mandatory for
primary tumor ‘T’ staging.
• Tumor size and parametrial infiltration assessed with MRI.
• Vaginal and pelvic side wall infiltrations: gynecologic
examination.
• Cystoscopy or rectoscopy may be discussed for biopsy if
suspicious lesions in the bladder or rectum on MRI.
Haldorsen IS, Lura N, Blaakær J, et al. What is the role of imaging at primary diagnostic work-up in uterine cervical cancer? Curr Oncol Rep. 2019;21(9):77.
•• This article concerned a major overview that summarized the reported staging performances of conventional and novel ima- ging methods and describe promising novel imaging methods relevant for cervical cancer patient
care.
Thomeer MG, Gerestein C, Spronk S, et al. Clinical examination versus magnetic resonance imaging in the pretreatment staging of cervical carcinoma: systematic review and meta-analysis. Eur Radiol. 2013 Jul;23(7):2005–2018.
Knoth J, Pötter R, Jürgenliemk-Schulz IM, et al. Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study. Gynecol Oncol. 2020 Oct;159(1):136–141.
Shen G, Zhou H, Jia Z, et al. Diagnostic performance of diffusion-weighted MRI for detection of pelvic metastatic lymph nodes in patients with cervical cancer: a systematic review and meta-analysis. Br J Radiol.
2015;88(1052):20150063.
Hameeduddin A, Sahdev A. Diffusion-weighted imaging and dynamic contrast-enhanced MRI in assessing response and recur- rent disease in gynaecological malignancies. Cancer Imaging. 2015;15(1):3.
14. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Nodal Diagnostic: Nodal staging is key for
prognosis and treatment planning
Valeria Cáceres
• PET/CT is clearly superior for LN detection to standard MRI and tomography .
• PAo LN detection: upstaging + modification of treatment planning with extended-field radiotherapy (RT).
• PAo LN involvement increases with tumor ‘T’ stage: 5% in stage I , 23% in stage III.
• Best strategy for PAo LN detection is controversial : surgical versus radiological approach.
• Two randomized control trials:
• 1-The Lai study was prematurely closed and limited by many methodological biases.
• 2-UTERUS-11 study, median follow-up of 90 mos, compared two methods PAo LN staging in 225
patients FIGO 2009 IIB-IVA with laparoscopic > 95% of cases in the surgical arm. OS and progression-
free survival (PFS) were not statistically different, whereas cancer-specific survival (CSS) favored the
surgical approach. Surgical staging was safe and neither delayed CCRT nor increased complications
• Lymphadenectomy in Locally Advanced Cervical Cancer (LiLACS) phase III trial is pending, (not recruiting)
Atri M, Zhang Z, Dehdashti F, et al. Utility of PET-CT to evaluate retroperitoneal lymph node metastasis in advanced cervical cancer: results of ACRIN6671/GOG0233 trial. Gynecol Oncol. 2016;142 (3):413–419.
Lai CH, Huang KG, Hong JH, et al. Randomized trial of surgical staging (extraperitoneal or laparoscopic) versus clinical staging in locally advanced cervical cancer. Gynecol Oncol. 2003;89 (1):160–167.
Marnitz-Schulze S, Tsunoda A, Martus P, et al. Surgical versus clinical staging prior to primary chemoradiation in patients with cervical cancer FIGO stages IIB-IVA: oncologic results of a pro- spective randomized
international multicenter (Uterus - 11) intergroup study. Int J Gynecol Cancer. 2020 Dec; 30(12): 1855– 1861.
Frumovitz M, Querleu D, Gil-Moreno A, et al. Lymphadenectomy in locally advanced cervical cancer study (LiLACS): phase III clinical trial comparing surgical with radiologic staging in patients with stages IB2-IVA c
15. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Distant Metastases
• PET/CT staging demonstrates 6 to 14% of cases with distant
metastases with a high specificity (98%), positive predictive value
(79%) and a sensitivity of 55%
• It is considered the best imaging modality for this evaluation
Gee MS, Atri M, Bandos AI, et al. Identification of distant metastatic disease in uterine cervical and endometrial cancers with FDG
PET/
CT: analysis from the ACRIN 6671/GOG 0233 multicenter trial. Radiology. 2018;287(1):176–184.
16. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Response Assessment
• PET/CT+ clinical exam + MRI for response assessment 3 months after
completion of CCRT
• MRI interpretation can be difficult: post-therapy inflammation or
scarring, addition of functional MRI sequences can be useful.
• Metabolic response-> predictive of long-term survival.
Schwarz JK, Siegel BA, Dehdashti F, et al. Metabolic response on post-therapy FDG-PET predicts patterns of failure after radiother- apy for cervical cancer. Int J Radiat Oncol Biol Phys. 2012;83 (1):185–190. Lima GM,
Matti A, Vara G, et al. Prognostic value of posttreatment (18)F-FDG PET/CT and predictors of metabolic response to therapy in patients with locally advanced cervical cancer treated with con- comitant chemoradiation
therapy: an analysis of intensity- and volume-based PET parameters. Eur J Nucl Med Mol Imaging. 2018;45(12):2139–2146.
Scher N, Castelli J, Depeursinge A, et al. (18F)-FDG PET/CT para- meters to predict survival and recurrence in patients with locally advanced cervical cancer treated with chemoradiotherapy. Cancer Radiothér.
2018;22(3):229–235.
18. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Imaging in RT planning with the implementation of conformal techniques: sparing the organs at risk
(OAR) and concentrating the therapeutic dose to the primary disease: survival has increased, and
treatment-related morbidity has decreased.
• Intensity-modulated radiation therapy (IMRT): provide additional 10–15 Gy dose to involved pelvic
LNs using sequential or increasingly simultaneous integrated boost (SIB)
• Volumetric arc therapy (VMAT)
• Image-guided radiation therapy (IGRT) : compensating positioning errors and anatomical variations
• Image-guided adaptive brachytherapy (IGABT): 2D-based BT is gradually replaced by IGABT based
on 3D volumetric imaging. IMRT plus IGABT was associated with improved 5-year OS compared to
patients treated with two-dimensional (2D)-RT and BT (61% versus 57%; p = 0.04) and decreased
grade 3–4 late bowel and bladder toxicities (18% vs 11%; p = 0.02)
Major advances in LACC treatment of over the past two decades
Yeung AR, Pugh SL, Klopp AH, et al. Improvement in patient-reported outcomes with intensity-modulated radiotherapy (RT) compared with standard RT: a report from the NRG oncology RTOG 1203 study. J Clin Oncol. 2020;38(15):1685–1692.
Lin Y, Chen K, Lu Z, et al. Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis. Radiat Oncol. 2018;13(1):177. Lin AJ, Kidd E, Dehdashti F, et al. Intensity modulated radiation therapy and image-guided adapted brachytherapy for cervix cancer. Int J Radiat Oncol Biol Phys.
2019;103(5):1088–1097.
Guy JB, Falk AT, Auberdiac P, et al. Dosimetric study of volumetric arc modulation with RapidArc and intensity-modulated radiotherapy in patients with cervical cancer and comparison with 3-dimensional conformal technique for definitive radiotherapy in patients with cervical cancer. Med Dosim. 2016;41(1):9–14.
19. Wang X, Liu R, Ma B, et al. High dose rate versus low dose rate intracavity brachytherapy for locally advanced uterine cervix cancer. Cochrane
Database Syst Rev. 2010;2010(7):CD007563.
Tanderup K, Fokdal LU, Sturdza A, et al. Effect of tumor dose, volume and overall treatment time on local control after radio- chemotherapy
including MRI guided brachytherapy of locally advanced cervical cancer. Radiother Oncol. 2016;120(3):441–446.
Overall Treatment Time (OTT): less than 50 to 55 days.
Significant detrimental effect with loss of local control
probability of approximately 1% per day of treatment
prolongation beyond 7 - 8 weeks
Valeria Cáceres
21. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Concomitant Chemotherapy
• 5 phase III CCRT using cisplatin, 5-FU or hydroxyurea reduced the risk of local and distant
recurrences in LACC and high-risk criteria after hysterectomy
• NCI alert recommending that ‘concomitant (cisplatin-based) chemoradiotherapy should be
considered instead of radiotherapy alone’
• In 2008, a meta-analysis including 13 studies comparing CCRT to RT demonstrated an absolute
benefit of 6% in 5-year OS (from 60 to 66%; HR: 0.81, 95% CI: 0.71–0.9, p < 0.001) for the entire
population but a decreased benefit with increasing stage
• Acute toxicities were more frequent in the CCRT group
• In 2010: Cochrane review: CCRT improved OS and PFS platinum or other agents were used with
absolute benefits of 10% (HR: 0.83, p = 0.017) and 13% (HR: 0.77, p = 0.009)
• Meta-analyses on the benefit of CT were conducted without image-guided or dose escalation
techniques
Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999;340(15):1137–1143.
Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340(15):1144–1153.
Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hys- terectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999;340(15):1154–1161.
Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a gynecologic oncology group and southwest oncology group study. J Clin Oncol. 1999;17 (5):1339–1348.
Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al. Concurrent chemother- apy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol. 2000;18(8):1606–1613.
Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC). Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis. Cochrane Database Syst Rev. 2010 Jan 20;2010(1): CD008285.
22. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Impact of number of cycles of chemotherapy
• Retrospective trial, 189 patients (stages III or IVA or LN+),
• 5 cycles of CT better outcomes vs. 4 cycles:
• 3-year DMFS = 56.3% vs 81.9%; HR 0.35,
• 3-year LC = 77.2% vs 93.9%; HR 0.31,
• 3-year LRC = 62.8% vs 84.6%; HR 0.43
Schmid MP, Franckena M, Kirchheiner K, et al. Distant metastasis in patients with cervical cancer after primary radiotherapy with or without chemotherapy and image guided adaptive brachytherapy. Gynecol Oncol. 2014;133(2):256–262.
Escande A, Khettab M, Bockel S, et al. Interaction between the number of chemotherapy cycles and brachytherapy dose/volume parameters in locally advanced cervical cancer patients. J Clin Med. 2020;9(6):1653.
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Monotherapy versus combination chemotherapy?
• Petrelli: meta-analysis: 1500 patients: CCRT with cisplatin-based doublets significantly
improved OS (OR 0.65; p = 0.0002), PFS (OR 0.71; p = 0.006), and locoregional relapse
(OR 0.64; p = 0.008) compared to weekly cisplatin. Higher toxicities in the doublets
group
• Meta- analysis by Ma: 1503 patients: CCRT with platinum-based doublets significantly
improved OS (HR 0.75; p = 0.01) and PFS (HR 0.78; p = 0.01) vs. cisplatin but increased
toxicities
Petrelli F, De Stefani A, Raspagliesi F, et al. Radiotherapy with concurrent cisplatin-based doublet or weekly cisplatin for cervical cancer: a systematic review and meta-analysis.
Gynecol Oncol. 2014;134(1):166–171.
Ma S, Wang J, Han Y, et al. Platinum single-agent vs. platinum-based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer: a meta-analysis of
randomized controlled trials. Gynecol Oncol. 2019;154(1):246–252.
CCRT with a cisplatin- doublet seems to improve survival at the cost of inducing
higher toxicity, which is probably why this concept is not adopted in daily practice.
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Platinum versus non-platinum-based chemotherapy?
• In the Vale et al. and Cochrane meta-analyses, a survival benefit was
observed for both groups of trials using platinum and non-platinum-
based CCRT.
• Nevertheless, no trials with direct comparison have been published.
Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemor- adiotherapy for cervical cancer: a systematic review and meta-analysis of
individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802–5812.
•• This meta-analysis provides an unconfounded estimate of the effect of chemoradiotherapy compared with radiotherapy. There is also the potential to use both platinum and nonplati- num
regimens and to investigate whether additional che- motherapy offers additional benefits.
Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC). Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-
analysis. Cochrane Database Syst Rev. 2010 Jan 20;2010(1): CD008285.
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Carboplatin?
• No phase III randomized studies have compared carboplatin to cisplatin during
CCRT.
• The use of carboplatin is supported by small phase I and II studies and pre-clinical
evidence of synergism of this drug with RT
• A meta-analysis of 12 studies and 1698 patients suggested poorer complete
response (OR 0.53) and a trend toward inferior survival (3-year OS = OR 0.70) with
weekly carboplatin
Nam EJ, Lee M, Yim GW, et al. Comparison of carboplatin- and cisplatin-based concurrent chemoradiotherapy in locally advanced cervical cancer patients with morbidity risks.
Oncologist. 2013;18 (7):843–849.
Xue R, Cai X, Xu H, et al. The efficacy of concurrent weekly carbo- platin with radiotherapy in the treatment of cervical cancer: a meta-analysis. Gynecol Oncol. 2018;150(3):412–419.
Carboplatin (AUC 2) an alternative in patients unfit for cisplatin
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Adjuvant Chemotherapy?
Dueñas-González A, Zarbá JJ, Patel F, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cispla- tin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29(13):1678–1685. Dueňas-González A, Orlando M,
Zhou Y, et al. Efficacy in high burden locally advanced cervical cancer with concurrent gemcita- bine and cisplatin chemoradiotherapy plus adjuvant gemcitabine and cisplatin: prognostic and predictive factors and the impact of disease stage on outcomes from a prospective randomized phase III trial. Gynecol Oncol. 2012;126(3):334–340.
Tangjitgamol S, Katanyoo K, Laopaiboon M, et al. Adjuvant che- motherapy after concurrent chemoradiation for locally advanced cervical cancer. Cochrane Database Syst Rev. 2014 Dec 3;2014(12): CD010401.
Tang J, Tang Y, Yang J, et al. Chemoradiation and adjuvant che- motherapy in advanced cervical adenocarcinoma. Gynecol Oncol. 2012;125(2):297–302.
Tangjitgamol S, Tharavichitkul E, Tovanabutra C, et al. A randomized controlled trial comparing concurrent chemoradia- tion versus concurrent chemoradiation followed by adjuvant che- motherapy in locally advanced cervical cancer patients: ACTLACC trial. J Gynecol Oncol. 2019;30(4):e82.
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OUTBACK: International, randomized phase III trial (median follow-up: 5 yr):
compared efficacy and safety of standard cisplatin-based CRT followed by adjuvant
carboplatin/paclitaxel vs CRT alone in women with LACC
Mileshkin. ASCO 2021. Abstr LBA3. NCT01414608.
Patients with cervical cancer
suitable for CRT with curative intent;
FIGO 2008 stage IB1 + LN, IB2, II-IVA;
squamous cell carcinoma,
adenocarcinoma, or
adenosquamous carcinoma; no
nodal disease > L3/L4; ECOG PS 0-2
(N = 926)
Concurrent CRT*
(n = 461; n = 456 in survival
analyses)
Concurrent CRT*
(n = 465; n = 463 in survival
analyses).
Stratified by pelvic or common iliac node involvement;
requirement for extended-field RT; FIGO 2008 stage (IB/IIA vs IIB
vs IIIB/IVA); age (< vs ≥60 yrs); hospital/site
Carboplatin AUC 5 +
Paclitaxel 155 mg/m2 Q3W
x 4 cycles
(n = 361)
*40-45 Gy of external beam XRT in 20-25 fractions including nodal
boost + brachytherapy with cisplatin 40 mg/m2 weekly during XRT.
Adjuvant CT (ACT)
Primary endpoint: OS
‒ Study protocol amended in 2016 to increase sample size from N = 780 to 900 due to nonadherence with adjuvant CT
and lower event rate than anticipated (80% power and 2-sided α = 0.05 to detect 8% absolute improvement in OS at
5 yr [72% to 80%])
Secondary endpoints: PFS, patterns of disease recurrence, radiation protocol compliance, PROs, safety
Valeria Cáceres
28. Treatment effects consistent across subgroups except
for those aged < vs ≥60 yr, where younger patients
had greater OS and PFS benefit with CRT + ACT
(interaction P = .01 and .03, respectively)
OUTBACK: OS and PFS
No significant improvement in 5-yr rates for OS or
PFS with CRT + ACT vs CRT alone
Sensitivity analyses found no significant differences
in OS or PFS in CRT + ACT arm for those who did vs
did not complete CRT
Mileshkin. ASCO 2021. Abstr LBA3. Reproduced with permission.
Proportion
Alive
Proportion
Alive
and
Progression-Free
Mos From Randomization
OS PFS
Patients at Risk, n
CRT Alone CRT + ACT
5-yr OS, % 71 72
HR (95% CI) 0.90 (0.70-1.17; P = .8)
CRT Alone CRT + ACT
5-yr PFS, % 61 63
HR (95% CI) 0.86 (0.69-1.07; P = .6)
100
80
60
40
20
0
0 12 24 36 48 60
463
456
403
417
347
343
307
306
245
244
149
164
Mos From Randomization
Patients at Risk, n
100
80
60
40
20
0
0 12 24 36 48 60
463
456
351
335
302
275
366
255
215
210
134
137
Valeria Cáceres
30. OUTBACK: Conclusions
In this analysis of the phase III OUTBACK trial, the addition of
adjuvant carboplatin/paclitaxel following concurrent CRT did not
improve OS or PFS vs CRT alone in patients with locally advanced
cervical cancer
Investigators indicate that results do not support addition of adjuvant
carboplatin/paclitaxel after CRT with weekly cisplatin in this setting
‒ Recommend further research into identifying other adjuvant therapies
with greater potential efficacy and tolerability after standard CRT
Mileshkin. ASCO 2021. Abstr LBA3.
Investigators conclude that pelvic CRT with concurrent weekly cisplatin remains the
standard of care
Valeria Cáceres
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Neoadjuvant CMT Followed by Surgery vs CCRT
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Because of a slower-than-anticipated accrual over a 10-year period, the study
was closed at 87% of the planned sample size
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71% received surgery in
NACT
69.3 vs 76.7%
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NACT followed by surgery versus CCRT
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NACT followed by surgery versus CCRT
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New agents
• Current optimal treatment: high recurrence: 65-70% disease-free long term.
• Bevacizumab: phase II study, patients with stage IB to IIIB were treated with weekly
cisplatin during CCRT followed by BT. Patients also received 3 cycles of bevacizumab
during CCRT. The regimen was well tolerated, with grades 3 and 4 toxicity of 26.5% and
10.2%, respectively. OS, DFS, and local relapse-free rate at 3 years were 81.3%, 68.7%, and
23.2%, respectively.
• Immune checkpoint receptors inhibitors: CALLA: durvalumab was negative. Waiting for
pembrolizumab resuls.
• Therapeutic live vaccines targeting HPV have also been developed using bacterial vectors.
Adoptive cell therapy with tumor-infiltrating lymphocytes, activated and expanded ex vivo
is another potential strategy.
• Triapine, a ribonucleotide reductase inhibitor, showed preliminary interesting results in a
phase II trial, in combination with CCRT. A phase III trial is currently ongoing .
Yang W, Lu YP, Yang YZ, et al. Expressions of programmed death (PD)-1 and PD-1 ligand (PD-L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status. J Obstet Gynaecol Res. 2017;43(10):1602–1612.
Mayadev J, Nunes AT, Li M, et al. CALLA: efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy ver- sus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study. Int J Gynecol Cancer.
2020;30(7):1065–1070.
Basu P, Mehta A, Jain M, et al. A randomized phase 2 study of ADXS11-001 listeria monocytogenes-listeriolysin o immunotherapy with or without cisplatin in treatment of advanced cervical cancer. Int J Gynecol Cancer. 2018;28(4):764–772.
Mayor P, Starbuck K, Zsiros E. Adoptive cell transfer using auto- logous tumor infiltrating lymphocytes in gynecologic malignancies. Gynecol Oncol. 2018;150(2):361–369.
Jazaeri AA, Zsiros E, Amaria RN, et al. Safety and efficacy of adop- tive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervi- cal carcinoma. J Clin Oncol. 2019;37(15):2538.
Kunos CA, Andrews SJ, Moore KN, et al. Randomized phase II trial of triapine- cisplatin-radiotherapy for locally advanced stage uterine cervix or vaginal cancers. Front Oncol. 2019;9:1067.
50. Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
New agents
• Current optimal treatment: high recurrence: 65-70% disease-free long term.
• Bevacizumab: phase II study, patients with stage IB to IIIB were treated with weekly
cisplatin during CCRT followed by BT. Patients also received 3 cycles of bevacizumab
during CCRT. The regimen was well tolerated, with grades 3 and 4 toxicity of 26.5% and
10.2%, respectively. OS, DFS, and local relapse-free rate at 3 years were 81.3%, 68.7%, and
23.2%, respectively.
• Immune checkpoint receptors inhibitors: CALLA: durvalumab was negative. Waiting for
pembrolizumab resuls.
• Therapeutic live vaccines targeting HPV have also been developed using bacterial vectors.
Adoptive cell therapy with tumor-infiltrating lymphocytes, activated and expanded ex vivo
is another potential strategy.
• Triapine, a ribonucleotide reductase inhibitor, showed preliminary interesting results in a
phase II trial, in combination with CCRT. A phase III trial is currently ongoing .
Yang W, Lu YP, Yang YZ, et al. Expressions of programmed death (PD)-1 and PD-1 ligand (PD-L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status. J Obstet Gynaecol Res. 2017;43(10):1602–1612.
Mayadev J, Nunes AT, Li M, et al. CALLA: efficacy and safety of concurrent and adjuvant durvalumab with chemoradiotherapy ver- sus chemoradiotherapy alone in women with locally advanced cervical cancer: a phase III, randomized, double-blind, multicenter study. Int J Gynecol Cancer.
2020;30(7):1065–1070.
Basu P, Mehta A, Jain M, et al. A randomized phase 2 study of ADXS11-001 listeria monocytogenes-listeriolysin o immunotherapy with or without cisplatin in treatment of advanced cervical cancer. Int J Gynecol Cancer. 2018;28(4):764–772.
Mayor P, Starbuck K, Zsiros E. Adoptive cell transfer using auto- logous tumor infiltrating lymphocytes in gynecologic malignancies. Gynecol Oncol. 2018;150(2):361–369.
Jazaeri AA, Zsiros E, Amaria RN, et al. Safety and efficacy of adop- tive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervi- cal carcinoma. J Clin Oncol. 2019;37(15):2538.
Kunos CA, Andrews SJ, Moore KN, et al. Randomized phase II trial of triapine- cisplatin-radiotherapy for locally advanced stage uterine cervix or vaginal cancers. Front Oncol. 2019;9:1067.
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LACC in PANDEMIA at IOAR: 2020
• 146 pts: EI: 14 pts, EII: 53 pts (36%), EIII: 72 pts (49%), EIVA: 7 pts
• Treatment: 130 pts (89%) CCRT + BT : CDDP: 102 pts (78%), Carbo: 15 pts , No
CMT: 13 pts. 16 pts NOT completed due to progression
• OTT: 92 pts (70%): 7,3 weeks, 28 pts (21.5%): 8,2 weeks and 10 pts: 9 weeks
• Toxicity: Neutropenia G2: 32 pts 24,6 %, G3:17 pts 13%, G4: 6 pts. 4,6%
Gastrointestinal: GI: 40 pts: 30%, GII: 35 pts : 27%, GIII:15 pts; 11,5 %
No fistula were reported
Acknowledgment : Dra Guadalupe Sanchez
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Take Home Messages I
• Major progresses in LACC: OS at 5 years: 65-70%, 40% will recur
• 2018 FIGO classification: three subgroups of stage IB and LN inclusion
Nevertheless, survival remains heterogeneous among stage III
• Imaging: initial workup + post-treatment evaluation + RT planning: conformal
radiation techniques: increase LC, OS and decrease toxicities
• Cisplatin-based CCRT: 40 mg/m2/week x 5 cycles : SOC
• Weekly carboplatin (AUC 2): alternative unfit for cisplatin
• OTT < 55 days
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Take Home Messages II
• EBRT: 1.8 Gy/day for 25 days: 45 Gy to the entire pelvis
• Tumor boosted, using image-guided BT, with 30 to 40 Gy: total dose of 85
Gy. Bulky nodes: additional 10 to 15 Gy
• Positive PAo LN : RT field is extended up to the level of the 10th dorsal
vertebrae
• Treatment-related morbidity and QoL.: vaginal stenosis and dryness and
rectitis
• Risk for radiation-induced secondary neoplasms: colon, rectum/anus, and
bladder
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FINAL THOUGHTS
The optimal care of CC patients should be done by a
multidisciplinary expert team
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Muchas gracias!!!!!
IOAR Female Tumor Unit
valeriacaceres@yahoo.com
vcaceres@institutoroffo.uba.ar
Declaración de Respeto de Propiedad intelectual
“Manifiesto que, durante la elaboración de las diapositivas para la actual presentación se consultaron y respetaron los derechos de propiedad intelectual de los autores originales de los conceptos, gráficas y tablas
usadas como respaldo científico”.