This randomized controlled trial compared neoadjuvant chemoradiotherapy followed by surgery to upfront surgery followed by adjuvant therapy for patients with borderline resectable pancreatic cancer. It found that the neoadjuvant treatment approach significantly improved 2-year survival rates compared to upfront surgery. Specifically, the 2-year survival rate was 40.7% for the neoadjuvant group versus 26.1% for the upfront surgery group. The neoadjuvant approach also resulted in a higher R0 resection rate and median overall survival of 21 months compared to 12 months for upfront surgery. However, both approaches had similar recurrence rates, with most recurrences being systemic.
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
Overview about evolution of the term Oligometastases,the paradigm and various states of oligometastases,treat options ,clinical trials and relevance in current clinical practice
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Tried to summarise all landmark trials in carcinoma breast in radiation oncology,medical oncology as well in surgical oncology.
References taken from Devita Book,Breast Disease book from Springer,journals like NEJM,JAMA,LANCET,ANNL ONCOLOGY etc,internet,Perez book,Practical Clinical Oncology by Hanna etc textbooks.
Thanks.
Hypofractionation in early breast cancer is no more a research scholars topic. Multiple studies with robust data have proven its utility. It may hold an important role in many countries with constrained resources. This is a short presentation incorporating important completed and ongoing trials. Feel free to use this.
Abstract
OBJECTIVE: Complete surgical resection is the only potentially curative treatment of localized pancreatic neuroendocrine tumors. Unfortunately, a significant proportion of these patients present with unresectable locally advanced tumors or massive metastatic disease. Recently, a new therapeutic approach for this subset of patients has emerged consisting of neoadjuvant therapy followed by surgical exploration in responders.
DESIGN: We searched MEDLINE for the purpose of identifying reports regarding neoadjuvant treatment modalities for advanced pancreatic neuroendocrine tumors.
RESULTS: We identified 12 studies, the vast majority of which were either case reports or small case series. Treatment options included chemotherapy, radiotherapy, peptide receptor radionuclide therapy, biological agents or various combina- tions of them.
CONCLUSIONS: Increasing evidence supports the application of neoadjuvant protocols in advanced pancreatic neuroendocrine tumors aiming at tumor downsizing, thus rendering curative resection feasible. Given that prospective and controlled randomized clini- cal trials from high-volume institutions are not feasible, expert panel consensus is needed to define the optimal treatment algorithm.
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.
Controversies in the management of rectal cancersAjeet Gandhi
Management of rectal cancers have undergone a huge paradigm shift over the last decade. One the one hand, it has opened up new avenues; it also has thrown up new challenges and controversies
Επιλεκτική Ανασκόπηση Βιβλιογραφίας 2017-2019
Consensus, Recommendations, Guidelines
Prospective randomized trials
Meta analysis
Systematic review
Advances in Surgery 2018
Up to date 2019
Comprehensive review of Isolated Axillary lymph nodal metastasis of unknown origin- Clinically unknown primary axilla which includes detailed approach and management of inguinal lymph nodal metastasis also
In Depth review of the Surgical management of esophageal carcinoma including management overview, endoscopic management, Type of surgeries, Open, and minimally invasive, Extent of lymphadenectomy. Literature review of evidence for type of surgery and complications
Detailed Information regarding MSKCC,IMDC score with evidence .
SSIGN Score, Fuhrman's grading described .
Prognostic significance of risk score explained
The Trial Assigning IndividuaLized Options for Treatment (Rx) -TAILORx,TAILORx clinical trial showed that most women with hormone receptor (HR)–positive, HER2-negative, axillary node–negative early-stage breast cancer and a mid-range score on a 21-tumor gene expression assay (Oncotype DX® Breast Recurrence Score) do not need chemotherapy after surgery
Brief Review of Surgical management of Early laryngeal cancer e.g glottic and supraglottic cancer.
This presentation describes latest literature evidence of conservative laryngeal surgery as well as radiotherapy in early glottic cancer
Ca ovary staging(AJCC 8th Edition& FIGO 2014) and classificationDr.Bhavin Vadodariya
Pathological classification of ovary in details.
Principles of Staging in Ca Ovary.
Staging according to AJCC 8th edition & Figo 2014.
Summary of changes in 8th Edition AJCC
Basics about Microcalcifications in mammography of breast as well as Review of Journal article on Residual Microcalcifications after Neoadjuvant Chemotherapy in Carcinoma Breast.
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
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STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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4. DEFINITION
Borderline tumors are best conceptualized as:
Those that involve the mesenteric vasculature to a limited extent. Those for
which resection, while possible, would likely be compromised by positive
surgical margins … in the absence of preoperative therapy.”
Katz MHG et al, Ann Surg Oncol ; E-pub Feb 23, 2013
5.
6.
7.
8.
9. COLLATERALS
Findings with a cavernous collateralization of the PV axis towards the liver
hilus as
well as a distal tumor involvement of the jejunal vein branches are
considered to be technically not resectable and do not fulfil the criteria of
BR‐PDAC, but are included in the LA‐PDAC definition.
These two latter findings (venous collateralization and jejunal branch
infiltration) are very unlikely to be converted into a resectable situation after
neoadjuvant therapy as a recanalization of venous vessels cannot be
generally expected
10. Borderline Resectable Lesions--
Criteria
MDA
2006 (Type
A)
AHPBA/SSAT/SSO
2009
NCCN
2012
Arterial Involvement:
Abutment Celiac axis √
Abutment SMA √ √ √
Abutment or encasement of short segment
CHA, typically at GDA
√ √ √
Venous Involvement:
Abutment SMV/PV with/without
impingement
√ √
Short segment occlusion of SMV, PV, or
SMV/PV confluence if reconstructable
√ √ √
‘Abutment’ <180°
‘Encasement’ >180°
Varadhachary, Ann Surg Onc, 2006
www.nccn.org, 2012 guidelines
Callery, Ann Surg Onc 2009
12. BORDERLINE RESECTABLE PATIENTS
MD ANDERSON CLASSIFICATION
Three Categories:
Anatomy - Borderline Tumors (1/2 cases)
Biology - Equivocal Staging,CEA >500, Nodal
Condition - Marginal Performance Status
Katz MGH et al, JACS, 2008
13. Pancreatic cancer (PDAC) is one of the most aggressive solid tumor entities
and the fourth leading cause for cancer‐associated mortality in Western
countries and shows an increasing incidence which will make it the second
leading cause of cancer‐associated deaths in 2030.
Currently, only 15%–20% of all patients are candidates for upfront surgery at
the time of diagnosis, which offers the chance of long‐term survival, a
proportion that has not significantly changed during the last two decades.
In the remaining 80%–85% of all patients, either a locally advanced or even
metastatic stage of disease is found at the initial presentation
14. AGGRESSIVE SURGERY??
For patients with borderline resectable pancreatic cancer (BRPC) and locally
advanced pancreatic cancer, some surgeons have performed aggressive
surgical treatment including major vessel resection.
However, the role of aggressive surgical treatment is questionable because
of the high morbidity, low R0 resection, and high early systemic recurrence.
16. DISADVANTAGES
Delayed resection can reduce the chance of cure and result in an
exaggerated effect because of selection bias.
Furthermore, significant downstaging after neoadjuvant treatment is limited
and varies among previous reports owing to the lack of highly effective
treatment regimens.7,8
17. CONSENSUS STATEMNT
HACKERT
1.Patients with resectable PDAC should undergo surgical exploration and
radical resection.
2. Patients with LA-PDAC should not be considered for upfront resection,
but neoadjuvant therapy option should be evaluated, when possible included
in a clinical trial protocol.
18. CONSENSUS STATEMNT
HACKERT
In venous BR PDAC, upfront surgery should be performed and, if the
intraoperative finding matches the presumed borderline situation as defined
above, completed as an en bloc tumor removal with venous replacement.
In contrast, when suspected arterial BRPDAC is found intraoperatively to be a
true arterial involvement, no general recommendation for resection is given,
neoadjuvant
treatment with consecutive surgical re-exploration and the option for a
secondary resection is possible, as well as direct arterial resection in
exceptional cases or under study conditions
19. THE NATIONAL
COMPREHENSIVE CANCER
NETWORK (NCCN)
Recommends Neoadjuvant treatment rather than upfront surgery for BRPC,
despite lacking high-level evidence.
Owing to a lack of consensus and evidence, many surgeons still prefer
upfront surgery as a treatment for BRPC.
Therefore, in this study, They compared the outcomes of neoadjuvant
treatment followed by surgical resection with upfront surgery followed by
adjuvant treatment in BRPC.
21. Only Retrospective data ,This is first study- korean
PREOPANC 1 – Yet not published
Data is highly polluted with LA-PDAC
Different clinical practice patterns reflect the wide variety of protocols and
the lack of a standardized approach for neoadjuvant treatment in BR‐PDAC.
22. PRE-OPERATIVE THERAPY FOR BORDERLINE
RESECTABLE PANCREATIC CANCER
Author
Year
Regimen # Patients Resection
Rate
Median
Survival
Resected
Evans
2008
Gem/XRT 84 74% 34 M
Varadhachary
2008
Gem/Cis
Gem/XRT
96 66% 31 M
Katz
2008
Variable 84
(Type A)
38% 40 M
!
Evans DB, et al. JCO, 2008.
Varadhachary GR, et al. JCO, 2008.Katz MH, et al. J Am Coll Surg, 2008.
25. PROGRESSIVE DISEASE-17%
Patients with aggressive an unfavorable tumor biology. In this subgroup of
patients, a resection could have been performed at the time of diagnosis due
to the BR
stage of the tumor
However, they may not have had a benefit of the operation and may have
suffered from very early recurrence postoperatively, which underlines the
importance of considering the B category of the IAP consensus
26. In the case of stable disease or response, a resection was possible in two out
of three patients, including approximately 60% of R0 resections and a
median survival
time of 25.9 months,
Which is comparable to the outcome after upfront resection.
Because of the large data heterogeneity, the overall small number of
patients, and the fact that all results are based on observational studies
alone, it is not valid to draw a conclusion or give recommendation for
neoadjuvant treatment in BR‐PDAC
27. SPECIAL SITUATION
when tumors of the pancreatic body involve the basis of the CA and
do not extend towards the common hepatic artery beyond the
offspring of the gastroduodenal
artery (GDA).
In these situations, a distal pancreatectomy with CA resection under
preservation of the GDA (DP‐CAR, modified Appleby procedure) is
technically feasible.
28.
29.
30. A recent systematic review on 19 studies included 240 patients and
confirmed that, despite a considerable morbidity, this procedure can be
performed with a low mortality of 3.5% and results in 15 months median
survival, which increases to
18 months if resection is embedded in a multimodal therapy approach.
34. STUDY DESIGN
This randomized controlled parallel-group trial
Group 1- NACT RT f/b Surgery
Group 2- Upfront Surgery f/b Adjuvant Therapy
35. INCLUSION CRITERIA
Between 18 and 75 years of age and providing written informed consent
Radiologic evidence of BRPC according to the 2012 NCCN guidelines,
Histologically or cytologically proven pancreatic cancer
No history of previous chemoradiation therapy
Adequate bone marrow, hepatic, and renal function according to laboratory
test results.
36. EXCLUSION CRITERIA
Had undergone concomitant unplanned antitumor therapy (eg,
chemotherapy, radiotherapy, immunotherapy)
Had a concomitant or previous malignancy (except cancer that had been in
complete remission for >5 years)
Had uncontrolled systemic disease (eg, infectious disease and cardiovascular
disease).
38. NEOADJUVANT
CHEMOTHERAPY
In the neoadjuvant group, a 3-dimensional treatment plan was established
using radiotherapy-planning computed tomography (CT) before starting
chemoradiation.
Chemoradiotherapy consisted of
45 gray (Gy) in 25 fractions and 9 Gy in 5 fractions (5 times a week for a
total of 6 weeks),
plus
Intravenous gemcitabine (at 400 mg/m2 with 150 mL) of normal saline
39. NEOADJUVANT
CHEMOTHERAPY
After chemoradiation, patients underwent a 4- to 6-week rest period.
CT, PET,MRI were performed to reassess the extent of disease before
determination of surgery according to the RECIST version 1.1.
Surgery with curative intent was performed if no distant metastasis or
progression was observed.
The assessment was carried out at 3-month intervals, along with an
evaluation of tumor markers, including carbohydrate antigen.
40. UPFRONT SURGERY
In the upfront surgery group, surgery was performed according to the
participating surgeons’ guidelines regarding dissection of the nerve plexus
of major vessels and D2 lymph node dissection (including station 16 nodes).
The surgical extent was identical to the neoadjuvant group.
According to the depth and length of adjacent vessel invasions, the
surgeons used their discretion to decide on the optimal methods of
resection and anastomosis of vessels to achieve R0 resection.
41. UPFRONT SURGERY
After surgery, chemoradiation was performed within 8 weeks using
the same protocol as the neoadjuvant group, provided the patients’
condition was acceptable.
42. MAINTENANCE
CHEMOTHERAPY
Maintenance chemotherapy was performed within 4 t 6 weeks after
completion of surgery and chemoradiation regardless order of treatment in
both groups.
Gemcitabine at 1000 mg/m2 was administered as an intravenous infusion
over 30 to 40 minutes on days 1, 8, and 15, followed by 1 week of rest,
every 4 weeks for 4 cycles
50. R0,R1
Pathologically, an R1-positive margin is defined as 1 cancer
cells within 1 mm of any surface or margin (R1 <1 mm).
A clear (R0) resection margin is then defined as tumor cells 1 mm away from
any
margin or surface (R0 >1 mm).
51.
52. ITT ANALYSIS
NACT RT Upfront SX
1 year Survival Rate 74.1% 47.8%
2 year Survival Rate 40.7% 26.1% (P=0.028)
Median Overall Survival 21 months 12 months
56. There was no difference in the recurrence pattern between the
2 arms (P= 1.000).
The recurrence rate was 88.2% in Arm 1 and 88.9% in Arm 2.
Most recurrences were systemic with the liver being the most
frequent site of recurrence in both groups (41.2% in Arm 1 vs 66.7%
in Arm 2)
57. DSB
The safety monitoring committee decided on early termination of this
study on the basis of the statistical significance of neoadjuvant
treatment efficacy, in consideration of patient safety.
58.
59.
60.
61.
62.
63. CONCLUSION PREOPANC 1
Preoperative chemoradiotherapy significantly improves outcome in
(borderline) resectable pancreatic cancer compared to immediate
surgery.
64. Patient Korean Trial PREOPANC 1
NACT Upfront
Surgery
P Value NACT Upfront
Surgery
P Value
Overall
Survival
21 months 12 months 0.028 17.1 months 13.5 months 0.047
Resection
Rate
70 % 78% 62% 72%
R0 Rate 82.4% 33.3% 0.010 65% 31% 0.010
Actual OS 22 months 19.5 months 0.337 29.9 months 16.8 months 0.001
ADE No difference No difference
Recurrence
rate
88.2% 88.9% 1.000 NA NA
DFS 11.2 months 7.9 months 0.010
DMFI 17.1 months 10.2 months 0.012
LRFI Not reached 11.8 months <0.001
66. WHY NACT IMPROVED OS
Early systemic treatment for undetected micrometastasis
R0 resection rate increment (51 vs 26 %)
Optimal selection of patients for surgery.
Aggressive resection doesn’t improve OS because of margin positivity
69. A recent prospective randomized clinical
trial showed that only 57% of patients
underwent surgery after neoadjuvant
therapy and only 21% finished the entire
treatment protocol, even in patients with
initially resectable pancreatic cancer.
In this study, 62.9% of BRPC patients
underwent resection after neoadjuvant
treatment and 52.2% underwent
chemoradiation after surgical resection (P
¼ 0.59), whereas 28% completed
maintenance chemotherapy.
70. DIFFICULTY
Events such as drug toxicity or disease progression can hinder the
completion of the initial treatment in pancreatic cancer.
These results illustrate the difficulties faced by clinical trials in pancreatic
cancer and thepossibility of selection bias when interpreting outcomes of
neoadjuvant treatment, especially in the retrospective study setting.
71. MORE EFFECTIVE SYSTEMIC
THERAPY
There was no difference in recurrence patterns.
The recurrence rate was 88.2% in the neoadjuvant treatment group and
88.9% in the upfront surgery group.
Most recurrences were systemic with the liver as the most common site.
More effective systemic therapy, to reduce metastasis and recurrence even
after neoadjuvant treatment followed by resection, must be investigated to
improve long-term survival.
72. DIFFERENCE IN SURVIVAL –
EXTENT OF TUMOUR
INVOLVEMENT
The survival outcome can differ markedly according to the extent of tumor
involvement and types of vessels involved.
Therefore, BRPC should not be regarded as a single entity but rather as a
spectrum of disease that needs further clarification and a standardized
definition.
Yamada et al19 reported that the median disease-free survival durations in
patients with pancreatic cancer and portal vein, hepatic artery, and superior
mesenteric artery invasion were 12.0, 7.4, and 6.7 months, respectively (P <
0. 05).
73. STANDARD RADIOLOGY
FORMAT
To overcome the heterogeneity of BRPC, several radiologic organizations
have
attempted to introduce a standardized reporting system.
Standardization can help facilitate research by using consistent staging with
respect to resectability status and allowing for comparison among
different institutions.
74.
75.
76.
77.
78.
79. OPTIMAL TREATMENT
REGIMEN
Although the use of neoadjuvant therapy results in a higher R0 resection
rate than surgery and provides treatment for subclinical metastases, no
standardized regimen is available at this time.
Currently, the chemotherapy such as FOLFIRINOX and gemcitabine combined
with protein-bound paclitaxel (nab-paclitaxel, Abraxane) regimens are
widely used due to the relatively high response rate.
More high-level evidence is needed in selecting the appropriate treatment
regimen.
80. TAKE HOME MESSAGE
The first randomized clinical trial to investigate the oncological
benefits of neoadjuvant treatment in BRPC.
Neoadjuvant treatment, rather than upfront surgery, should be
considered for patients with BRPC.
Future studies are needed to identify more effective systemic
treatments that control local disease and reduce systemic metastasis
after treatment.