ΜΑΘΗΜΑΤΑ ΟΓΚΟΛΟΓΙΑΣ: Γαςσπο-οιςουαγικόρ καπκίνορ ΓΝΑ Ιπποκπάσειο 19/2/13. Κίκα Πλοιαπφοπούλοτ

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1 ΜΑΘΗΜΑΤΑ ΟΓΚΟΛΟΓΙΑΣ: Γαςσπο-οιςουαγικόρ καπκίνορ ΓΝΑ Ιπποκπάσειο 19/2/13 Κίκα Πλοιαπφοπούλοτ

2 Άνδπαρ, 72 εσών Καπνιςσήρ: 80 πακέσα/έση Α.Α: ΣΝ αγγειοπλαςσική (2000) Οπιςθοςσεπνικό άλγορ δτςυαγία Eνδοςκόπηςη: ενδοατλική μάζα μεςόσησαρ οιςουάγοτ Βιοχία: μέςηρ διαυοποποίηςηρ πλακώδερ Ca οιςουάγοτ

3 ΕUS EUS/FNA CT θώπακορ CT άνψ-κάσψ κοιλίαρ CT εγκευάλοτ Scanning οςσών PET/CT

4 Impact of EUS-guided fine-needle aspiration on lymph node staging in patients with esophageal carcinoma Gastrointestinal Endoscopy 2001; 53(7):

5 Methods: 74 patients with esophageal carcinoma underwent preoperative EUS. EUS-guided FNA was performed on nonperitumoral lymph nodes greater than 5 mm in width. Final diagnosis was based on surgical results or EUS-guided FNA malignant cytology. Final diagnosis was obtained in the remaining 64 patients (33 from the EUS only group and 31 from the EUS-FNA group). Results: The results of EUS versus EUS-FNA for lymph node staging were sensitivity 63% versus 93% (p = 0.01), specificity 81% versus 100% (not significant), and accuracy 70% versus 93% (p = 0.02), respectively. Conclusions: EUS-FNA is more sensitive and accurate than EUS alone for preoperative staging of locoregional and celiac lymph nodes associated with esophageal carcinoma. EUS-FNA of nonperitumoral lymph nodes in patients with esophageal carcinoma is safe and should be routinely performed when treatment decisions will be affected by nodal stage.

6 Impact of lymph node staging on therapy of esophageal carcinoma Gastroenterology 2003 ;125(6):

7 METHODS: 125 patients patients with esophageal carcinoma were prospectively evaluated with CT, EUS, and EUS FNA. The impact of tumor stage on final therapy was assessed RESULTS: EUS-FNA was more sensitive (83% vs. 29%; P < 0.001) than CT and more accurate than CT (87% vs. 51%; P < 0.001) or EUS (87% vs. 74%; P = 0.012) for nodal staging Tumor location, patient age, comorbidities, and tumor stage determined by CT, EUS, and EUS FNA were associated with treatment decisions (P < 0.05). EUS FNA resulting in a higher/worse stage than CT (41 patients) was associated with a greater rate of treatments that were not direct surgeries compared with cases in which the stage was the same or better. CONCLUSIONS: EUS FNA is more accurate for nodal staging and impacts on therapy of patients with esophageal carcinoma. EUS FNA should be included in the preoperative staging algorithm of these patients.

8 Routine positron emission tomography does not alter nodal staging in patients undergoing EUS-guided FNA for esophageal cancer Gastrointestinal Endoscopy 2009; 69(7):

9 RESULTS: Of 242 patients who underwent esophageal EUS for a malignant indication, 148 also underwent PET within 30 days. EUS detected locoregional-node disease by EUS criteria or cytology in 92 patients, and PET was positive in a minority of these patients (n = 41 [45%]). For celiac-node staging, PET was positive in 2 of 17 patients (12%) with celiac-node involvement detected by EUS. EUS was also significantly more sensitive than PET in the detection of nodal disease confirmed by cytology or histology (86% vs 44%). PET did not alter nodal staging in any patient with complete EUS- FNA. CONCLUSIONS: The addition of PET to a complete EUS examination did not alter regional-node or celiac-node staging. PET performance in overall staging is strongly associated with EUS assessment of lymph nodes.

11 JCO 2004;22(18):

12 ΕUS EUS/FNA CT θώπακορ CT άνψ-κάσψ κοιλίαρ CT εγκευάλοτ Scanning οςσών PET/CT

13 EUS: εξεπγαςία 4 εκ. με διήθηςη σοτ μτικού φισώνα και παποτςία 2 πεπιοιςουαγικών λεμυαδένψν, διαμέσποτ 1.7 και 2 εκ CT θώπακορ: πάφτνςη σοιφώμασορ μεςόσησαρ οιςουάγοτ CT άνψ-κάσψ κοιλίαρ με iv ςκιαγπαυικό: φψπίρ δετσεποπαθείρ ενσοπίςειρ

14 Οιςουαγεκσομή Oιςουαγεκσομή μεσεγφειπησική ΧΜΘ Οιςουαγεκσομή μεσεγφειπησική ΧΜΘ-ΑΚΘ Πποεγφειπησική ΧΜΘ-ΑΚΘ Πποεγφειπησική ΧΜΘ ΧΜΘ-ΑΚΘ

$4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week pcr rate was 32.6% Mortality was 3.7% in the surgery alone arm versus 3.8% in the CRT arm R0 resection rate was 92.$

15 Multi-center, randomized, phase III trial 363 patients Paclitaxel (50 mg/m2) and Carboplatin (2AUC) on days 1, 8, 15, 22, 29 External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week pcr rate was 32.6% Mortality was 3.7% in the surgery alone arm versus 3.8% in the CRT arm R0 resection rate was 92.3% in the CRT arm versus 64.9% in the surgery alone arm. The overall survival was significantly better (p = 0.011) in the group of pts treated with CRT (median survival 49 months in the CRT arm vs 26 months in the surgery alone arm) ASCO Meeting proceedings 2010;28(15) suppl

195 patients were randomized 98 were assigned to surgery alone (S group) and 97 to neoadjuvant chemoradiotherapy group (CRT group; 45 Gy/25 F/5 weeks with 2 courses of concomitant chemotherapy 5-FU

16 195 patients were randomized 98 were assigned to surgery alone (S group) and 97 to neoadjuvant chemoradiotherapy group (CRT group; 45 Gy/25 F/5 weeks with 2 courses of concomitant chemotherapy 5-FU 800 mg/m 2 /day D1-D4 and cisplatin 75 mg/m 2 D1 or D2) Postoperative morbidity and 30 day-mortality rates were 49.5% (S group) vs. 43.9% (CRT group) (p = 0.17) and 1.1% (S group) vs. 7.3% (CRT group) (p = 0.054), respectively Median survivals were 43.8 (S group) vs months (CRT group) ( p = 0.66). ASCO Meeting proceedings 2010;28(15) suppl

20 9 RCTs - 1,116 patients A complete pathological response to chemoradiation occurred in 21% of patients. Neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling. Am J Surg 2003; 185(6):538-43

21 Gut 2004;53:

22 4188 pts - 24 studies 1854 pts 12 studies on neoadj chemo-radiotherapy vs surgery 1981 pts 9 studies on neoadj chemo vs surgery 192 pts 2 studies on neoadj chemo-rt vs chemo Lancet Oncol 2011;12(7):681-92

5y OS for combined therapy was 26% vs 0% following RT Treatment failure was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%])

26 5y OS for combined therapy was 26% vs 0% following RT Treatment failure was less common in the groups receiving combined therapy (34/130 [26%]) than in the group treated with RT only (23/62 [37%]) There were no significant differences in severe late toxic effects between the groups However, chemotherapy could be administered in only 68% of patients (10% had life-threatening toxic effects with combined therapy vs 2% in the RT only group) Conclusion Combined therapy increases the survival of patients who have squamous cell or adenocarcinoma of the esophagus, T1-3 N0-1 M0, compared with RT alone JAMA 1999; 5(17):1623-7

27 JCO 2002;20:

$59 patients were staged II to IV and treated with definitive concomitant chemoradiotherapy RT: 50 64 Gy in 25 35 fractions Patients received two cycles of a 1-day regimen containing docetaxel (60$

28 59 patients were staged II to IV and treated with definitive concomitant chemoradiotherapy RT: Gy in fractions Patients received two cycles of a 1-day regimen containing docetaxel (60 mg/m 2 ) and cisplatin (80 mg/m 2 ) Q 3 w ORR was 98.3%, with 42 complete responses and 26 partial responses Median overall survival time was 22.6 months Rates of locoregional progression-free survival, progression-free survival, and overall survival in 3 years was 59.6%, 29.2%, and 36.7% Hematologic toxicity Grade 3 and Grade 4 were observed in 39.0% and 20.3% of patients respectively Dis Esoph 2003;23(3):353-9

38 cisplatin/irinotecan and 19 carboplatin/paclitaxel) patients There were no significant differences in hematologic or nonhematologic toxicities between the groups.

29 38 cisplatin/irinotecan and 19 carboplatin/paclitaxel) patients There were no significant differences in hematologic or nonhematologic toxicities between the groups. The 3-year overall survival estimates was 19.7% for the cisplatin/irinotecan group versus 56.1% for the carboplatin/paclitaxel group (P = 0.022) Estimated 3-year cancer-specific survivals were 24.6% for the cisplatin/irinotecan group versus 59.3% for the carboplatin/paclitaxel group (P = 0.033). Am JCO 2010;33(4):346-52;

The median overall survival was 17 months The median disease-free survival was 9 months The median time to local progression was 14 months Conclusions: Radiotherapy with concurrent weekly paclitaxel

30 The median overall survival was 17 months The median disease-free survival was 9 months The median time to local progression was 14 months Conclusions: Radiotherapy with concurrent weekly paclitaxel and carboplatin as definitive treatment for irresectable esophageal carcinoma is a tolerable regimen, which can be given on an outpatient basis and leads to durable locoregional control and palliation in about half of the patients ASCO Meeting proceedings 2010;28(15)suppl

31 ECRR: 45% VS 29% TTP: 15.2m vs 9.2m OS: 22.7m vs 15.1m

32 Οιςουαγεκσομή Oιςουαγεκσομή μεσεγφειπησική ΧΜΘ Οιςουαγεκσομή μεσεγφειπησική ΧΜΘ-ΑΚΘ Πποεγφειπησική ΧΜΘ-ΑΚΘ Πποεγφειπησική ΧΜΘ ΧΜΘ-ΑΚΘ

33 Ο αςθενήρ έλαβε 2 κύκλοτρ CDDP 75mg/m2 (d1) και Capecitabine 1000mg/m2 x2 (d1-14)

34 ΕUS EUS/FNA CT θώπακορ CT άνψ-κάσψ κοιλίαρ CT εγκευάλοτ Scanning οςσών PET/CT

35 Endoscopic Ultrasound Restaging After Neoadjuvant Chemotherapy in Esophageal Cancer 21 Am J Gastroenterol 2006;101(6):1216-

36 RESULTS: A total of 49 patients (43 men and 6 women) were evaluated with EUS pre- and post-neoadjuvant chemotherapy. Forty-seven patients had tumor localized at the GE junction and two had mid-esophageal lesions. Tumor and nodal staging accuracy post-chemotherapy were 60% T-stage accuracy post-chemotherapy was superior in patients without a response to chemotherapy (95.7% vs 26.1%, p<0.0001) More than 50% in reduction of tumor thickness postchemotherapy was associated with tumor downstage and better survival. N0 disease on final pathology was the best predictor of improved survival. CONCLUSION: Accuracy of EUS postchemotherapy is lower than initial staging accuracy; therefore the ability to predict downstaging based on EUS is marginal. Pathology N1 disease postchemotherapy is the best predictor of survival. EUS staging post-neoadjuvant chemotherapy should focus on improving nodal staging accuracy with FNA.

37 Post-treatment endoscopic biopsy is a poorpredictor of pathologic response in patients undergoing chemoradiation therapy for esophageal cancer. Ann Surg 2009 ;249(5):764-7

38 RESULTS: 156 patients were identified. Over 80% of patients received cisplatin-based chemotherapy and 5040 cgy of radiation. 118 patients had no tumor identified on endoscopic biopsy. A negative biopsy at endoscopy was a poor predictor of pcr - negative predictive value: 31% - with 69% having local disease at esophagectomy. A positive biopsy was predictive of residual disease positive predictive value: 95%. Negative endoscopic biopsy better predicted a pcr for squamous cell carcinomas versus adenocarcinomas. Nodal status of surgical specimens was not correlated with posttreatment endoscopic findings. Survival was equivalent after surgery in patients with a negative endoscopic biopsy versus patients with positive pathology. CONCLUSION: A negative endoscopic biopsy is not a useful predictor of a pcr after CRT, final nodal status, or overall survival.

39 The accuracy for nodal disease was 78%, 78%, and 93% for CT scan, EUS-FNA and FDG-PET/CT, respectively ( P =.04) FDG-PET/CT accurately predicted complete response in 89% compared with 67% for EUS-FNA ( P =.045) and 71% for CT ( P =.05) Conclusions FDG-PET/CT is more accurate than EUS-FNA and CT scan for predicting nodal status and complete responders after neo-adjuvant therapy in patients with esophageal cancer. J Thor Cardiovasc Surg 2005;129(6):

40 ΕUS EUS/FNA CT θώπακορ CT άνψ-κάσψ κοιλίαρ CT εγκευάλοτ Scanning οςσών PET/CT

41 CT θώπακορ: πάφτνςη σοιφώμασορ οιςουάγοτ CT άνψ-κάσψ κοιλίαρ: φψπίρ παθολογικά ετπήμασα

42 Oιςουαγεκσομή δύο πεδίψν οιςουαγογαςσπική αναςσόμψςη Ιςσολογική διάγνψςη: μέςηρ διαυοποποίηςηρ πλακώδερ καπκίνψμα οιςουάγοτ με διήθηςη σοτ μτικού φισώνα, όλοι οι εξαιπεθένσερ λεμυαδένερ είναι ελεύθεποι διήθηςηρ (Ν0/18) Τ2Ν0Μ0

44 METHODS: 4627 patients from the Worldwide Esophageal Cancer Collaboration database CONCLUSIONS: Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and >or=7 regional lymph nodes positive for cancer) and well-differentiated pn0m0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pt1, 20 for pt2, and >or=30 for pt3/t4 is recommended. Ann Surg 2010;251(1):46-50

45 Cancer 2005;103:

46 κάθε 3-6 μήνερ για 1-2 φπόνια κάθε 6-12 μήνερ για 3-5 φπόνια εσηςίψρ ςση ςτνέφεια O αςθενήρ είναι ελεύθεπορ νόςοτ εδώ και 3 φπόνια

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