Diapositiva 1

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• Gastric Rectal Cancer
• D. Genovesi
• Radiation Oncology Department CHIETI
• www.radioterapia.unich.it

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GASTRIC CANCER
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GASTRIC CANCER
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GASTRIC CANCER TNM Classifications AJCC
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Gastric Cancer Clinical Case Presentation
PS 100 (Karnofsky) 68 yrs old male
Cardiac stroke 8yrs ago, no other
diseases and no drugs at the moment.
Endoscopy (17/12/2008) ulcer with free bottom
and infiltrated margins at
antropyloric region, increased thickness with non
crossing stenosis. Contrast CT
Thoraxabdomen (01/09) negative lungs, liver
and bones. Increased wall thikcness of
gastric antrum (thickness of 2 cm) compatible
with Eteroplasy. Concomitant small
perivisceral nodes (0.5 cm) Bigger nodes
at celiac region (2.1 cm) interaortocaval region
(2.1 cm), paraortic region (1 cm).
05/01/09 Sub-total gastrectomylimphoadenect
omy D2. Histology Macroscopic vegetant lesion
of 4. 5 cm of antropyloric region at 1 cm from
distal margin Microscopic Carcinoma G3 (70) and
Adenocarcinoma G2 (30) with entire gastric wall
invasion. Free duodenal stump. Free proximal
margin M of Carcinoma G3 in 1/14 lesser
curvature nodes. No M in 22 greater curvature.
No omental tumour. No M in retrocoledocus,
retropancreatic, celiac, and left gastric artery
nodes. PATHOLOGIC STAGE p T2 p N1 M0
STAGE II
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Key Points
Diagnostic Work-up for Staging
Prognostic Factors
Surgical Treatment
Neoadjuvant Treatments
Adjuvant Treatments
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Key Points
Diagnostic Work-up for Staging

• Double Contrast Upper G.I.

• Barium Radiological Studies

• Endoscopy procedure of choice (8-10 biopsies)

• Chest-Abdomen-Pelvic enhanced CT
• sensitivity 23-56 Early Gastric Cancer
  92-95 in advanced tumors
• metastatic lymph node size criterion gt 10 mm

• Endoscopic Ultrasonography (EUS)

• MRI has not achieved clinical importance

• CT-PET investigational procedure

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Key Points
Prognostic Factors

• Tumor Grading

• R0 R1 R2 resection (operating procedure)
  

• T stage

• Lymphadenectomy
• at least 15 lymph nodes removed and analyzed
• Japanese Classification 16 node stations in
  3 groups depending on T

• T location proximal cancer poorer SVV vs
  distal cancer

• Lymphatic, Venous or Perieneural invasion

• High CEA levels preop

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Key Points
Surgical Treatment

• Total Gastrectomy proximal or middle third or
  diffuse T

• Total Gastrectomy vs Subtotal Gastrectomy
• no advantage for distal (antral) Stomach

• 5 cm free is required for resection margins

• D1 perigastric LFN along lesser and greater
  curvatures (1-6)

• D2 plus LFN along left gastric artery (7),
  common hepatic artery (8),
• celiac trunk (9), splenic hilus and
  splenic artery (10, 11)

• D3 plus LFN along hepatoduodenal ligament (12),
  posterior surface
• of head of the pancreas (13) and the
  root of the mesentery (14)

• D4 plus LFN paracolic region and abdominal
  aorta (15, 16)

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Key Points
Neoadjuvant Treatments

• Preop Chemo high risk pts (T3-T4 N0-2 M0)
  feasibility in
• Phase II studies
  (increase R0 rate) improve
• SVV in 4 Random
  Trials (ECF schedule)
• Type 2 Level of Evidence for Stages II-IV

• Preop Radiotherapy (RT) benefit in only one
  random trial
• 40
  GyS vs S
• Further Randomised Trials are required

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Key Points
Adjuvant Treatments

• Postop Chemo results often disappointing poor
  compliance
• with
  multidrugs schedules small-moderate
• benefit
• Type 2 Level of Evidence for Stages II-IV

• Postop Radiotherapy (RT) No Benefit

• Postop ChemoRadiotherapy
• SWOG-INT 116, Stage I-IV, M0 Surgery Obs
  vs CT-RT 5FU/L
• 5yrs OS 40 vs 28.4 (plt0.001)
• 5yrs DFS 31 vs 25 (plt0.001)
• 36 D1 only 10 D2
• Kim et al IJROBP 63, 2005 clinical benefit
  in D2 (SVV DFS)
• Type 2 Level of Evidence for Stages II-IV

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Type II Level of Evidence
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RESULTS
3 yr OS
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48
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Macdonald JS et Al New Eng J Med -2001
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Type III Level of Evidence
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Kim IJROBP, 2005
Results
DFS
OS
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GASTRIC CANCER EBM for Radiotherapy
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Gastric Cancer Clinical Case Presentation
PS 100 (Karnofsky) 68 yrs old male
Cardiac stroke 8yrs ago, no other
diseases and no drugs at the moment.
Endoscopy (17/12/2008) ulcer with free bottom
and infiltrated margins at
antropyloric region, increased thickness with non
crossing stenosis. Contrast CT
Thoraxabdomen (01/09) negative lungs, liver
and bones. Increased wall thikcness of
gastric antrum (thickness of 2 cm) compatible
with Eteroplasy. Concomitant small
perivisceral nodes (0.5 cm) Bigger nodes
at celiac region (2.1 cm) interaortocaval region
(2.1 cm), paraortic region (1 cm).
05/01/09 Sub-total gastrectomylimphoadenect
omy D2. Histology Macroscopic vegetant lesion
of 4. 5 cm of antropyloric region at 1 cm from
distal margin Microscopic Carcinoma G3 (70) and
Adenocarcinoma G2 (30) with entire gastric wall
invasion. Free duodenal stump. Free proximal
margin M of Carcinoma G3 in 1/14 lesser
curvature nodes. No M in 22 greater curvature.
No omental tumour. No M in retrocoledocus,
retropancreatic, celiac, and left gastric artery
nodes. PATHOLOGIC STAGE p T2 p N1 M0
STAGE II
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GASTRIC CANCER Management of our Clinical
Case
Day 1- Day 28-31 Day 56-58
Day 84-98 Day 112-6
FU-FA (5 gg)
FU-FA (5 gg)
FU-FA (3 gg)
FU-FA (4 gg)
FU-FA (5 gg)
Radiotherapy
INT-0116
Macdonald JS et Al New Eng J Med -2001
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Why preoperative treatments ?
pCR
R0 vs R
Ajani JA et Al JCO - 2005
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RECTAL CANCER
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RECTAL CANCER
11.000 12.000 new cases/year in Italy
De Carli A., La Vecchia C. 2002 Verdecchia A.,
Micheli A., Gatta G. 2002
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RECTAL CANCER
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RECTAL CANCER
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Rectal Cancer Clinical Case Presentation
PS 100 (Karnofsky) 62
yrs old male no other diseases.
Endoscopy (13/01/2006) ulcerated and vegetant
lesion of 6 cm very near to internal
anal sphincter HISTOLOGY
Adenocarcinoma G2. Contrast CT
Thoraxabdomen (20/01/06) negative lungs and
liver. Neoplastic lesion which makes
the lumen substenotic, presence of some
lesions in perirectal adipous tissue.Two nodes
of 1 cm in perirectal adipous
tissue. CLINICAL STAGE c T3 c
N1 M0 IIIB STAGE
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Key Points
Diagnostic Work-up for Staging
Pathology
Surgical Treatment
Radiotherapy and Chemotherapy
Ongoing Research
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Key Points
Diagnostic Work-up for Staging

• Endoscopy with biopsies

• Endorectal ultrasound T1 vs T2 tumors vs
  borderline T3

• Multislice-CT is not sufficiently accurate for
  low tumors
• CT cannot accurately distinguish LFN vs LFN-

Phased Array MRI is highly accurate in
Staging Difficulty in differentiation T1 vs T2 vs
borderline T3

• Circumferential Resection Margin (CRM) MRI is
  highly
• accurate for the prediction of CRM

• MRI with specific contrast enhanced
  (USPIO)promising

• FDG-PETdisappointing results on N role in
  response evaluation

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The Circumferential Resection Margin
predictivity MRI
Sensitivity 60-80 Specificity 73-100
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T3 with involved mesorectal fascia
Beets-Tan et al. Lancet 2001 357 (9255) 497 - 504
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The Value of CRM
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Macroscopic assessment of Mesorectal excision

• CRM ( cm ) incomplete
• lt 0.1 43.9
• 0.1 - 0.2 27.8
• 0.2 - 0.5 27.8
• 0.5 - 1.0 12.9
• gt 1.0 11.1

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Criterion for detection of node metastases

• No choice but to use the size of lymph nodes as
  the most reliable criterion
• In most cases, 5mm or larger, or 10mm or larger
  is regarded as criterion for lymph node
  metastases.

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Metastatic nodes less than Ø 5mm in gt 50
Dworak et al. Surg Endos 1989396-9 Brown et al.
Radiology 2003227371-7
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USPIO MRI for nodal staging
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Key Points
Pathology

• Guideline and experience significantly improve
• the qualitywww.rcpath.org/resources/pdf/colore
  ctalcancer.pdf

• Careful Macroscopic and Microscopic examination

• Tumor Regression Grade (TRG) scales

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Tumor-Regression-Grading TRG
Complete Regression
(100) Good Regression (gt 50)
Moderate Regression (25-50) Minimal
Regression (lt 25) No Regression
(0)
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Key Points
Surgical Treatment

• The standard surgery Total Mesorectal Excision
• (TME)

• Preop Radio-chemoterapy S increase sphincter
• preservation (with good sphincter function)
  for
• downsizing

• Pathological studies of CRM in anorectal
  junction
• and anal canal sphincter show higher rates of
  CRM
• involvement

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Key Points
Radiotherapy and Chemotherapy

• Early T local excision (adverse prognostic
  factors evaluation)
• endoluminal radiotherapy
  

• c T3-4/N0 or plus 15 Random Trials 3
  Meta-analysis
• increase LC conflicting results in SVV for
  preop Radiotherapy

• Short-Course preop (5Gyx5) vs RT-CT not seem
  effective
• for pts with predictive positive CRM e low
  tumor location

• 2 Random Trials (EORTC 22921 FFCD 9203) on
  role of
• chemo with preop-Radiotherapy in RT-CT preop
  group
• increase of LC, increase rate of p T0, G3
  tox, no
• benefit of 5 yrs OS

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Key Points
Radiotherapy and Chemotherapy

• Polish Trial in c T3-4 5 Gy x 5 vs preop
  RT-CT
• no difference in sphincter preservation, LC,
  OS but
• LATE TOXICITY

• NCI Consensus Conference 1990 post-op CT-RT
  5FU-based
• Standard treatment in post-op p T3/ p N1-2
  rectal tumors

• Preop RT-CT vs Post-op RT-CT 5FU-based 4
• Random Trials.
• The most important closed Trial is German
  Study
• CAO/ARO/AIO 94

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CAO/ARO/AIO 94
P H A S E
III
Trial
50.4 Gy Bolus CI 5-FU Surgery 5-FU x
4 wks 1,5 T3 50.4 Gy Bolus Surgery CI
5-FU 5-FU x 4 wks 1,5
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CAO/ARO/AIO 94
P H A S E
III
Trial
Post-op Pre-op P Evaluable
394 405 - 5-Yr LF 15 6 0.006 5-Yr
Survival 76 74 ns Acute toxicity 40 27 0
.001 Chronic toxicity 24 14 0.012 5-Yr DF
38 36 ns Sphincter Preservation 15/78
(20) 45/116 (39) 0.004
Sauer et al NEJM 2004
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CAO/ARO/AIO 94
P H A S E
III
Trial
The Value of Downstaging !!!
C. Rödel et al., J Clin Oncol 2005 238688-96
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Meaning of Downstaging
Patients pT0-2/TOT LC 5 aa pT0-2 OS 5 aa pT0-2 DFS 5 aa pT0-2
Berger 97 Hosp Bretonneau 19/167 - 92 87
Kaminsky-F 98 Alexis Vautrin Cent. 21/98 94 100 94
Janjan 99 M.D.Anderson 68/117 - 93-100 75-83
Mohiuddin 00 Kentucky Univer. 22/77 100 100 100
Valentini 02 Catholic Univer 76/165 96 90 80-83
Theodoropoulos 02 Grant Med Center 16/88 100 100 100
Aguilar 03 Univ of Minnesota 21/168 100 95 95
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Key Points
Radiotherapy and Chemotherapy

• No data with level 1 evidence for adjuvant
  post-op chemo
• after preoperative RT-CT it seems an effect
  of adjuvant
• chemo in responder pts

• Unresectable rectal cancer pre-op RT-CT
  5FU-based to
• enhance R0 resectability (50-54 Gy Radiation
  dose)
• IORT single institutions studies support a
  favourable
• effect

• Local Recurrence pre-op RT-CT /- IORT
  (conflicting
• results)
• Re-irradiation is under clinical evaluation

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Key Points
Ongoing Research

• Topic for surgical research enhance organ
  preservation

• Intensification of pre-op RT-CT and post-op
  chemo
• - New Drugs (Oxaliplatin Capecitabine)
• - Altered fractionation RT dose

• EGFR and VEGF promising targets of antitumor
  treatment

• Individualised therapies based on
  clinical-pathological
• features and molecular and genetic markers

• New Imaging for response evaluation

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Rectal Cancer Clinical Case Presentation
PS 100 (Karnofsky) 62
yrs old male no other diseases.
Endoscopy (13/01/2006) ulcerated and vegetant
lesion of 6 cm very near to internal
anal sphincter HISTOLOGY
Adenocarcinoma G2. Contrast CT
Thoraxabdomen (20/01/06) negative lungs and
liver. Neoplastic lesion which makes
the lumen substenotic, presence of some
lesions in perirectal adipous tissue.Two nodes
of 1 cm in perirectal adipous
tissue. CLINICAL STAGE c T3 c
N1 M0 IIIB STAGE
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Rectal Cancer management of our clinical
case
PLAFUR Schedule
Follow-up
8 ws
S
50.4 Gy
CDDP 60 mg/mq 1 gg
Chemo N
5-FU 1000 mg/mq 1-5 gg
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Post CRT
Pre CRT
y p T0
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Diffusion MRI
PreCRT
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