gastric & rectal cancer d. genovesi radiation oncology department chieti
TRANSCRIPT
Gastric & Rectal CancerGastric & Rectal CancerD. Genovesi
Radiation Oncology Department CHIETIwww.radioterapia.unich.it
GASTRIC CANCER
GASTRIC CANCER
GASTRIC CANCERTNM Classifications
AJCC
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 Thorax+abdomen (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 gastrectomy+limphoadenectomy D2.Histology: Macroscopic: vegetant lesion of 4. 5 cm of antropyloric region at 1 cmfrom distal marginMicroscopic: Carcinoma G3 (70%) and Adenocarcinoma G2 (30%) with entire gastric wall invasion. Free duodenal stump. Free proximal marginM+ 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
Key Points
Diagnostic Work-up for Staging
Prognostic Factors
Surgical Treatment
Adjuvant Treatments
Neoadjuvant Treatments
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 > 10 mm
Endoscopic Ultrasonography (EUS)
MRI has not achieved clinical importance
CT-PET: investigational procedure
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 +
Key PointsSurgical 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)
Key PointsNeoadjuvant 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 Gy+S vs S Further Randomised Trials are required
Key PointsAdjuvant 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% (p<0.001) 5yrs DFS: 31% vs 25% (p<0.001) 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
Type II Level of Evidence
Macdonald JS et Al – New Eng J Med -2001Macdonald JS et Al – New Eng J Med -2001
RESULTS
41%41% 48%48%
3 yr OS:3 yr OS:
41%41%
Type III Level of Evidence
OS DFS
Results
Kim IJROBP, 2005
GASTRIC CANCER: EBM for Radiotherapy
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 Thorax+abdomen (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 gastrectomy+limphoadenectomy D2.Histology: Macroscopic: vegetant lesion of 4. 5 cm of antropyloric region at 1 cmfrom distal marginMicroscopic: Carcinoma G3 (70%) and Adenocarcinoma G2 (30%) with entire gastric wall invasion. Free duodenal stump. Free proximal marginM+ 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
FU-FA(5 gg)
FU-FA(5 gg)
FU-FA(5 gg)
FU-FA(5 gg)
FU-FA(3 gg)
FU-FA(3 gg)
FU-FA(4 gg)
FU-FA(4 gg)
RadiotherapyRadiotherapy
Day 1- Day 28-31 Day 56-58 Day 84-98 Day 112-6
FU-FA(5 gg)
FU-FA(5 gg)
Macdonald JS et Al – New Eng J Med -2001INT-0116
GASTRIC CANCER: Management of our Clinical Case
Ajani JA et Al – JCO - 2005 Ajani JA et Al – JCO - 2005
R0 vs R+ R0 vs R+
pCR pCR
Why preoperative treatments ?Why preoperative treatments ?
RECTAL CANCER
De Carli A., La Vecchia C. – 2002Verdecchia A., Micheli A., Gatta G. – 2002
11.000 – 12.000 new cases/year in Italy
RECTAL CANCER
RECTAL CANCER
RECTAL CANCER
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 Thorax+abdomen (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
Key Points
Diagnostic Work-up for Staging
Pathology
Surgical Treatment
Ongoing Research
Radiotherapy and Chemotherapy
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 StagingDifficulty 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-PET:disappointing results on N; role in response evaluation
The Circumferential Resection Margin predictivityMRI
Sensitivity: 60-80%; Specificity: 73-100%
T3 with involved mesorectal fascia
Beets-Tan et al. Lancet 2001 357 (9255) 497 - 504Beets-Tan et al. Lancet 2001 357 (9255) 497 - 504
The Value of CRM
Macroscopic assessment of Mesorectal excision
CRM ( cm ) % incomplete < 0.1 43.9 % 0.1 - 0.2 27.8 % 0.2 - 0.5 27.8 % 0.5 - 1.0 12.9 % > 1.0 11.1 %
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.
Metastatic nodes: less than Ø 5mm in > 50%
Dworak et al. Surg Endos 1989;3:96-9Brown et al. Radiology 2003;227:371-7
USPIO MRI for nodal staging
Key Points
Pathology
Guideline and experience significantly improve the quality:www.rcpath.org/resources/pdf/colorectalcancer.pdf
Careful Macroscopic and Microscopic examination
Tumor Regression Grade (TRG) scales
Tumor-Regression-Grading: TRG
Complete Regression (100%) Good Regression (> 50%) Moderate Regression (25-50%) Minimal Regression (< 25) No Regression (0%)
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
Key PointsRadiotherapy 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
Key PointsRadiotherapy 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
50.4 Gy BolusCI 5-FU Surgery 5-FU x 4wks 1,5
T3
50.4 Gy BolusSurgery CI 5-FU 5-FU x 4
wks 1,5
PHASE
III
CAO/ARO/AIO 94Trial
Sauer et al NEJM 2004
Post-op Pre-op PEvaluable # 394 405 -5-Yr LF % 15 6 0.0065-Yr Survival % 76 74 nsAcute toxicity 40 27 0.001Chronic toxicity 24 14 0.0125-Yr DF % 38 36 ns
SphincterPreservation 15/78 (20%) 45/116 (39%) 0.004
CAO/ARO/AIO 94
PHASE
TrialIII
C. Rödel et al., J Clin Oncol 2005; 23:8688-96
CAO/ARO/AIO 94
The Value of Downstaging !!!Trial
PHASE
III
PatientspT0-2/TOT
LC 5 aa
% pT0-2
OS 5 aa
% pT0-2
DFS 5 aa
% pT0-2
Berger ’97
Hosp Bretonneau19/167 - 92 87
Kaminsky-F ’98
Alexis Vautrin Cent.21/98 94 100 94
Janjan ’99
M.D.Anderson68/117 - 93-100 75-83
Mohiuddin ’00
Kentucky Univer.22/77 100 100 100
Valentini ’02
Catholic Univer76/165 96 90 80-83
Theodoropoulos ’02
Grant Med Center 16/88 100 100 100Aguilar ’03
Univ of Minnesota
21/168 100 95 95
Meaning of Downstaging Meaning of Downstaging
Key PointsRadiotherapy 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
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
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 Thorax+abdomen (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
Rectal Cancer: management of our clinical case
PLAFUR Schedule
50.4 Gy S
Follow-upFollow-up
CDDP 60 mg/mq 1° gg
5-FU 1000 mg/mq 1-5 gg
8 ws
Chemo: N+Chemo: N+
Pre CRTPre CRT Post CRTPost CRT
Ulcer
y p T0
Diffusion MRIDiffusion MRIPreCRTPreCRT
ypT0ypT0
PostCRTPostCRT