גידולי רקטום כירורגים.pptx

Hernia surgery complications

1. גידולי רקטום שלב 2-3 טומור בורד אונקו כירורגי 10.22

2. הצגת מטופלת א.ב בת 57 מחלות רקע: יל"ד , שוללת עישון, מוצא טריפולי, לאם סרטן שד, לאחות סרטן בכיס השתן עקב דם סמוי חיובי עשתה קולונסקופיה - נראה גידול בגובה 2 ס"מ, מיצר את החלל, מכוייב באורך כ 4 ס"מ. שוללת ירידה במשקל, ללא קולונסקופיות קודמות, ללא דם גלוי ביציאות פתולוגיה: אדנוקרצינומה גרייד 1-2 MMRP CEA 0.9 CT חזה בטן אגן ללא גרורות MRI: T3N0 clear CRM

3. Mesorectal fascia involvement   = circumferential resection margin T his finding is highly predictive of residual tumor which places the patient at high risk of local recurrence and inferior survival .

4. איך להתקדם? האם לפני הניתוח לתת רק קרינה או קרינה וכימותרפיה ( TNT )? קרינה קצרה או ארוכה עם קסלודה ? אם נותנים TNT , קודם קרינה או קודם כימותרפיה? מה הסיכוי שנוכל להמנע מניתוח?

5. Rectal cancer –simplified NCCN guidelines Workup: H+P (medical history, family history of cancer) Colonscopy , Biopsy MMR/MSI Consider proctoscopy Chest CT+abdominal CT/MRI Pelvic MRI (or TRUS) CBC, chemistry, CEA Genetic counseling Colonoscopy for family Rectal cancer T1-2, N0 T3, N any with clear CRM or T1-2, N1-2 T3, N any with involved\threatened CRM or T4, N any Surgery TNT or neoadjuvant CRT TNT

6. Radiotherapy for rectal cancer Long course RT: 50.4 Gy in 25 or 28 fractions Capecitabine ( xeloda ) twice daily on radiotherapy days Short course RT: 5Gy in 5 fractions (5X5) No chemo Chemotherapy for rectal cancer FOLFOX: Every 2 weeks 5FU bolus+46h infusor , leucovorin , oxaliplatin XELOX/CAPOX: Every 3 weeks Capecitabine ( xeloda ) twice daily for 14 days, oxaliplatin on first day

7. Rectal cancer –simplified NCCN guidelines FOLFOX/CAPEOX 3-4 m TNT=Total neoadjuvant treatment Long course chemo+RT o r short course RT Long course chemo+RT o r short course RT FOLFOX/CAPEOX 3-4 m Restaging-> Surgery Neoadjuvant CRT Long course chemo+RT o r short course RT Surgery FOLFOX/CAPEOX 3-4 m 25% cCR by DRE, MRI, proctoscopy- watch and wait

8. Radiotherapy is better than surgery alone   T he Dutch trial ( Kapiteijn , NEJM 2001) 1861 patients The Swedish study ( Birgisson JCO 2005) 1168 patients TME: 5 y local recurrence 10.9% Y5 OS 64% RT 5X5 -> TME 5 y local recurrence 5.6% Y5 OS 64% TME: 5 y local recurrence 27% Y5 OS 48% RT 5X5 -> TME 5 y local recurrence 11% Y5 OS 58%

9. Preoperative is better than postoperative therapy German Rectal Cancer Study Group trial   (Sauer, NEJM, 2004)  823 patients, T3/4 or node-positive. long CRT-> surgery->adjuvant 5FU 10 year local recurrence 7% DFS 68%, OS 60% Surgery-> long CRT- >adjuvant 5FU 10 year local recurrence 10% DFS 68%, OS 60 %

10. Long course radiotherapy has more pCR The Polish trial (Br J Surg. 2006) 316 patients with T3/4 long CRT-> immediate surgery pCR 16% DFS 58% Short RT -> immediate surgery pCR 1% DFS 56%

11. Total neoadjuvant therapy + Long-course CRT  P hase III PRODIGE 23 461 patients, T3-4 3m FOLFIRINOX->long CRT->surgery->3m FOLFOX/ xeloda pCR 28% 3yDFS 76% Higher compliance long CRT->surgery- >6m FOLFOX pCR 12% 3yDFS 69% During the whole treatment period, serious adverse events occurred in 11% of patients in the neoadjuvant chemotherapy group and 23% in the standard-of-care group (p = .0049).

12. Total neoadjuvant therapy + Short-course RT  RAPIDO trial , 920 patients with T4a/b, extramural vascular invasion, cN2 disease, involved mesorectal fascia<1mm, or enlarged lateral lymph nodes>1cm long CRT->surgery->3m FOLFOX/XELOX pCR 14% 3y disease related treatment failure 30% 3y distant mets 27 % 57% completed 75% of chemo *fewer than 50% received postop chemo Short RT->4m FOLFOX/XELOX-> surgery pCR 28% 3y disease related treatment failure 24% 3y distant mets 20 % 84% completed 75% of chemo Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy , TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised , open-label, phase 3 trial . Bahadoer RR, et al. Lancet Oncol . 2021;22(1):29.

13. Organ Preservation in Rectal Adenocarcinoma (OPRA) P hase II trial, 324 patients, stage II,III 4m FOLFOX/ XELOX-> long CRT-> surgery or WW pCR 17% 3y disease DFS 76% Local recurrence-free survival 94% Distant metastasis–free survival 84% 28% TME+40% tumor regrowth after WW Preserved rectum at 3 years 41% long CRT-> 4m XELOX/FOLFOX- > surgery or WW pCR 25% 3y distant DFS 76% Local recurrence-free survival 94% Distant metastasis–free survival 82% 24% TME+27 % tumor regrowth after WW P reserved rectum at 3 years 53% Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy . , Garcia-Aguilar J , J Clin Oncol . 2022;40(23):2546 Surveillance protocol for watch-and-wait: DRE, flexible sigmoidoscopy, and CEA every 4 months for the first 2 years, then every 6 months for years 3-5; MRI every 6 months for the first 2 years, then every 12 months for years 3-5; CT chest/abdomen/pelvis once a year for 5 years; and colonoscopy once at year one and again at year 5

14. Surveillance- stage II-III H&P every 3-6m for 2y, then every 6 m for a total of 5 years CEA every 3-6m for 2y, then every 6 m for a total of 5 years CT chest, abdomen, pelvis every 6-12m for 5 years Colonscopy 1 year after surgery or before, then every 1-3 years

15. Rectal cancer –simplified NCCN guidelines Workup: H+P (medical history, family history of cancer) Colonscopy , Biopsy MMR/MSI 5-10% Consider proctoscopy Chest CT+abdominal CT/MRI Pelvic MRI (or TRUS) CBC, chemistry, CEA Genetic counseling Colonoscopy for family Rectal cancer T1-2, N0 T3, N any with clear CRM or T1-2, N1-2 T3, N any with involved\threatened CRM or T4, N any Surgery TNT or neoadjuvant CRT TNT

16. Single-arm phase II study Dostarlimab (antiPD1 antibody) for Locally Advanced dMMR Rectal Cancer: Study Design Cercek. NEJM. 2022;[Epub]. Cercek. ASCO 2022. Abstr LBA5. Patients with stage II/III dMMR rectal cancer (target N = 30) Dostarlimab 500 mg IV Q3W x 9 cycles (n = 16) Radiologic and endoscopic evaluation If residual disease If cCR ChemoRT Surgery Nonoperative follow-up every 4 mo If residual disease If cCR Primary objectives: Overall response to dostarlimab ± chemoRT (reported in this analysis) Sustained cCR 12 mo after completion of dostarlimab (if no surgery) or pCR (if surgery) after completion of dostarlimab ± chemoRT Secondary objectives: safety, tolerability

17. Dostarlimab for Locally Advanced dMMR Rectal Cancer: Baseline Characteristics Cercek. ASCO 2022. Abstr LBA5. Characteristic Patients (N = 18) Sex, n (%) Male Female 6 (33) 12 (67) Median age, yrs (range) 54 (26-78) Race/ethnicity, n (%) White non-Hispanic Hispanic Black Asian Far East/Indian subcontinent 11 (61) 1 (6) 3 (17) 3 (17) Characteristic Patients (N = 18) Tumor staging, n (%) T1/2 T3/4 4 (22) 14 (78) Nodal staging, n (%) Node positive Node negative 17 (94) 1 (6) Germline mutation status (n = 17), n (%) MSH2, MLH1, MSH6 , or PMS2 Negative 10 ( 59 ) 7 (41) BRAF V600E wt , n (%) 18 (100) Mean TMB, mut/Mb (range) 67 (36-106)

18. Dostarlimab for Locally Advanced dMMR Rectal Cancer: Response in Patients Completing Dostarlimab Tx Cercek. NEJM. 2022;[Epub]. Cercek. ASCO 2022. Abstr LBA5. ID Age T Stage N Status F/U, Mo Digital Rectal Exam Response Endoscopic Best Response Rectal MRI Best Response Overall Response 1 38 T4 + 23.8 CR CR CR cCR 2 30 T3 + 20.5 CR CR CR cCR 3 61 T1/2 + 20.6 CR CR CR cCR 4 28 T4 + 20.5 CR CR CR cCR 5 53 T1/2 + 9.1 CR CR CR cCR 6 77 T1/2 + 11.0 CR CR CR cCR 7 77 T1/2 + 8.7 CR CR CR cCR 8 55 T3 + 5.0 CR CR CR cCR 9 68 T3 + 4.9 CR CR CR cCR 10 78 T3 + 1.7 CR CR CR cCR 11 55 T3 + 4.7 CR CR CR cCR 12 27 T3 + 4.4 CR CR CR cCR 13 26 T3 + 0.8 CR CR CR cCR 14 43 T3 + 0.7 CR CR CR cCR

19. Dostarlimab for Locally Advanced dMMR Rectal Cancer: Adverse Events in >10% of Patients *No grade 3/4 AEs were observed. Cercek. NEJM. 2022;[Epub]. Adverse Event, n (%) All Grade Grade 3/4* Rash/dermatitis 5 (31) 0 (0) Fatigue 4 (25) 0 (0) Pruritus 4 (25) 0 (0) Nausea 3 (19) 0 (0) Diarrhea 2 (13) 0 (0) Dry eye 2 (13) 0 (0) Fever 2 (13) 0 (0)

20. הצגת מטופלת א.ב בת 57 מחלות רקע: יל"ד , שוללת עישון, מוצא טריפולי, לאם סרטן שד, לאחות סרטן בכיס השתן עקב דם סמוי חיובי עשתה קולונסקופיה - נראה גידול בגובה 2 ס"מ, מיצר את החלל, מכוייב באורך כ 4 ס"מ. שוללת ירידה במשקל, ללא קולונסקופיות קודמות, ללא דם גלוי ביציאות פתולוגיה: אדנוקרצינומה גרייד 1-2 MMRP CEA 0.9 CT חזה בטן אגן ללא גרורות MRI: T3N0 clear CRM התחילה טיפול טרום ניתוחי בקרינה ממושכת ואח"כ 4 חודשי XELOX