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Cancer of the Rectum US scenario 2011

Cancer of the Rectum US scenario 2011. Ashwin Sama, MD Ashok Kumar, MS Madhavan Pillai , MD. Methodology.

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Cancer of the Rectum US scenario 2011

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  1. Cancer of the RectumUS scenario 2011 Ashwin Sama, MD Ashok Kumar, MS MadhavanPillai, MD

  2. Methodology • Pubmed: "rectal cancer"[All Fields] AND (2011[All Fields] AND ("united states"[MeSH Terms] OR ("united"[All Fields] AND "states"[All Fields]) OR "united states"[All Fields])) AND ("humans"[MeSH Terms] AND English[lang] AND cancer[sb] AND "2011/01/01"[PDAT] : "2012/02/03"[PDAT]) • ASCO GI 2011 symposium abstracts

  3. Epidemiology • Surgery • Surgical outcomes • Neoadjuvant treatment • Metastatic treatment

  4. Is it time to lower the recommended screening age for CRC? • Though colorectal cancer (CRC) incidence in the US has decreased over the last 30 years in the general population, it has increased in patients younger than 50. • Across age groups 20 to 49, CRC incidence was higher in 2006 than in 1987. • The most significant increase was from age 40 to 44, where CRC increased from 10.7 per 100,000 in 1988 to 17.9 per 100,000 in 2006 (67% increase) J Am CollSurg 2011;213: 352–362.

  5. J Am CollSurg 2011;213: 352–362.

  6. Screening for CRC • Colon and rectal cancer increased 56% and 94%,respectively in this age group. • Consideration for colonoscopy screening beginning at age 40 should be given J Am CollSurg2011;213: 352–362.

  7. Relationship between moderate alcohol intake and rectal cancer • 1033 cases and 1011 controlsstudied • The odds ratio for rectal cancer comparing any versussno alcohol intake was 0.73 (95% CI 0.60, 0.90), adjusted for age, sex, race, smoking status, obesity, education, red meat intake, use of NSAIDs and family history of colorectal cancer. Dis Colon Rectum. 2011 Jul;54(7):887-94.

  8. The odds ratio for moderate alcohol (≤14 g/day) was 0.66 (95% CI 0.53, 0.82), whereas the odds ratio for heavy alcohol (>14 g/day) was 0.93 (95% CI 0.70, 1.23). • Moderate beer and wine intakes were also inversely associated with distal colorectal cancer: odds ratios 0.76 (95% CI 0.60, 0.96) and 0.69 (95% CI 0.56, 0.86). Dis Colon Rectum. 2011 Jul;54(7):887-94.

  9. Pre-diagnostic smoking history, alcohol consumption and CRC survival • Smoking and alcohol consumption are associated with an increased risk of developing colorectal cancer. • However, it is unclear whether these exposures are associated with survival after colorectal cancer diagnosis. • This study looked at survival of CRC patients by smoking status. Cancer 2011;117:4948–57.

  10. Disease-specific and all-cause mortality were significantly higher for smokers (HR, 1.30; 95% CI,1.09-1.74) compared with never-smokers (HR, 1.51; 95% CI, 1.24-1.83). • This association was most prominent in those with tumors exhibiting high MSI (HR, 3.83; 95% CI, 1.32-11.11) and did not extend to those with rectal cancer (HR, 1.08; 95% CI, 0.72-1.61) Cancer 2011;117:4948–57

  11. Levels of vitamin D and colon and rectal cancer • Significant inverse association for colorectal cancer (OR = 0.66; 95% CI, 0.54-0.81), comparing top versus bottom quartiles of circulating 25(OH)D levels. • The inverse association was stronger for rectal cancer (OR = 0.50 for top versus bottom quartiles; 95% CI, 0.28-0.88) than colon cancer (OR = 0.77; 95% CI, 0.56-1.07; P value for difference between colon and rectal cancer = 0.20). Cancer Prev Res (Phila). 2011 May;4(5):735-43

  12. Epidemiology • Surgery • Neoadjuvant treatment • Metastatic treatment

  13. Utilization of laparoscopy for colorectal surgery. • The aim of this study was to determine the rate of use of laparoscopic colorectal surgery for cancer at academic medical centers and to evaluate if the site of cancer influences the rate of use laparoscopy. • The overall rate for use of laparoscopy was 14.8 per cent. Am Surg. 2011 Oct;77(10):1300-4.

  14. Laparoscopy was most often used for total colectomy (22.6%), sigmoid colectomy (17.3%), cecectomy (17.1%), and right hemicolectomy (17.0%). • Laparoscopy was most infrequently used for abdominoperineal resection (8.0%), transverse colectomy (10.0%), and left hemicolectomy(13.1%). Am Surg. 2011 Oct;77(10):1300-4.

  15. Length of stay for laparoscopic colon and rectal procedures was 3.2 days shorter than for open surgery. • Although the benefits of laparoscopic colorectal surgery for cancer have been demonstrated, the use of laparoscopy for colorectal resection remains under 20 per cent for colon cancer and under 10 per cent for rectal cancer. Am Surg. 2011 Oct;77(10):1300-4.

  16. Am Surg. 2011 Oct;77(10):1300-4.

  17. Outcomes after Laproscopic assisted proctectomy (LAP) for rectal cancer • Patients who underwent elective LAP or open proctectomy for cancer during 2005 to 2009 were identified from the ACS NSQIP database. • Of 5,420 patients who underwent surgery for rectal cancer, 4,380 underwent open proctectomy and 1,040 (19.2%) had LAP. J Am CollSurg 2011;212:844–854

  18. Outcomes J Am CollSurg 2011;212:844–854.

  19. QOL and pain in patients with recurrent rectal cancer • Curative surgery prolonged survival, but significant pain exists among long-term survivors. • Noncurativesurgery did not offer apparent advantages over nonsurgical palliation. Ann SurgOncol. 2011 April ; 18(4): 989–996.

  20. Lymph node examination after neo-adjuvant chemoradiation • Preoperative chemoradiation for rectal cancer can decrease the number of evaluable LN. • Compared with patients who had <7 lymph nodes examined, patients who had >7 lymph nodes had higher 5-year rates of freedom from relapse(86% vs 72%; log-rank P ¼ .005) and cancer-specific survival (95% vs 86%; log-rank P ¼ .0004), but no significant difference was observed in the overall survival rate (87% vs 81%; log-rank P ¼ .07). Cancer 2011;117:3713–22.

  21. Multivariate Cox proportional models demonstrated that patients who had >7 lymph nodes examined had a significantly lower risk of relapse (hazard ratio [HR], 0.39; P ¼ .003) and death from rectal cancer (HR, 0.45; P ¼ .04) but a similar risk of all-cause mortality (HR,0.75; 95% CI, 0.46-1.20; P ¼ .23) compared with patients who had 7 lymph nodes examined. Cancer 2011;117:3713–22.

  22. Epidemiology • Surgery • Neoadjuvant treatment • Metastatic treatment

  23. Optimal timing of surgery after chemoradiation for rectal cancer • Stage II and III rectal cancer patients were treated concurrently with 5-Fluorouracil (FU) and radiation for 5 to 6 weeks. • Patients in study group 1 underwent total mesorectal excision (TME) 6 weeks later. • Patients in study group 2 with evidence of a clinical response 4 weeks after CRT received 2 cycles of modified FOLFOX-6 (mFOLFOX-6) followed by TME 3 to 5 weeks later. • Tumor response, CRT-related toxicity and surgical complications were recorded. Ann Surg. 2011 Jul;254(1):97-102.

  24. CRT-related toxicity was comparable. • Average time from CRT-to-surgery was 6 (SG1) and 11 weeks (SG2). • Pathologic complete response (pCR) was higher in (SG) 2. 18% (SG1) Vs25% (SG2). • Postoperative complications were similar between SGs. Ann Surg. 2011 Jul;254(1):97-102

  25. Presence of specialty surgeons reduces the likelihood of colostomy after proctectomy for rectal cancer • Based on county of residence information, nonrestorativeproctectomy with colostomy was performed in greater than 60% of all patients with rectal cancer in 26% (n = 125) of counties. • On multivariate analysis, more specialty surgeons (OR = 0.70; CI = 0.51-0.96) were protective against colostomy formation at the county level. Dis Colon Rectum. 2011 Feb;54(2):207-13.

  26. Molecular responses to neoadjuvantchemoradiation in rectal cancer • Tumor DNA from pre-CRT tumor biopsies was screened for K-rasand p53 mutations. • DNA from paired surgical specimens was then screened for the same mutations using highly sensitive polymerase chain reaction–based techniques. J Am CollSurg 2011;212:1008–1017

  27. Sensitive molecular techniques detect K-rasand p53 mutations in post-CRT surgical specimens in some patients with a pCR. • This suggests histopathological techniques might not be completely accurate, and some patients diagnosed with a pCR to CRT might have occult cancers cells in their surgical specimens. J Am CollSurg 2011;212:1008–1017

  28. TS genotype directed neoadjuvantchemoradiation for rectal cancer • Polymorphisms in the thymidylate synthase gene (TYMS) had previously defined two risk groups associated with disparate tumor DS rates(60% v 22%). • Prospective single-institution phase II study using TYMS genotyping to direct neoadjuvant CRT for patients with rectal cancer. J ClinOncol 29:875-883.

  29. Patients with TYMS *2/*2, *2/*3, or *2/*4 (good risk) were treated with standard chemoradiotherapyusing infusional FU at 225 mg/m2/d. • Patients with TYMS *3/*3 or *3/*4 (poor risk) were treated with FU/RT plus weekly intravenous irinotecan at 50 mg/m2. • The primary end point was pathologic DS. J ClinOncol 29:875-883.

  30. The prespecifiedstatistical goals were achieved, with DS and ypT0 rates reaching 64.4% and 20% for good-risk and 64.5% and 42% for poor-risk patients, respectively. • Further evaluation of this genotype-based strategy using a randomized study design for locally advanced rectal cancer is warranted J ClinOncol 29:875-883.

  31. Does neoadjuvant therapy alter KRAS and/or MSI results in rectal cancer? • The genotoxic effects of neoadjuvantchemoradiation therapy on molecular diagnostic testing results are unknown • Rectal adenocarcinomas both before and after neoadjuvant treatment were evaluated for alterations in KRAS and MSI testing • MSI and KRAS results were unchanged comparing rectal cancer tissue before and after chemoradiotherapy in all 17 patients Am J SurgPathol. 2011 Sep;35(9):1327-30.

  32. EGFR polymorphisms and path CR to Cetuximab based chemoradiation • Cetuximab-containing neoadjuvantchemoradiation has not been shown to improve tumor response in locally advanced rectal cancer • 130 patients with locally advanced rectal cancer who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation • Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP. Clin Cancer Res 2011;17:5161-5169.

  33. Clin Cancer Res 2011;17:5161-5169.

  34. Fisher’s exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) • This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvantchemoradiation of patients with locally advanced rectal cancer. Clin Cancer Res 2011;17:5161-5169.

  35. Epidemiology • Surgery • Neoadjuvant treatment • Metastatic treatment

  36. Regorafenib in mCRC who have progressed after standard therapies. • Regorafenib (BAY 73-4506) is an oral multikinase inhibitor of a broad range of angiogenic, oncogenic, and stromal kinases. • The phase III CORRECT trial was conducted to evaluate efficacy and safety of regorafenib in pts with mCRC who had progressed after all approved standard therapies. J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)

  37. Statistically significant benefit in OS and PFS was observed for regorafenib over PL in pts with mCRC who have failed all approved standard therapies • The most frequent grade 3+ AEs in the regorafenib arm were hand-foot skin reaction (17%), fatigue (15%), diarrhea (8%), hyperbilirubinemia (8%), and hypertension (7%). J Clin Oncol 30, 2012 (suppl 4; abstr LBA385)

  38. FOLFIRI with or without panitumumab in second-line mCRC • pmab+FOLFIRI significantly improved PFS vs FOLFIRI as second-line therapy in patients with wild-type (WT) KRAS mCRC. • PFS and ORR were improved, and there was a trend toward improved OS in pts with WTKRASmCRC. J ClinOncol 30, 2012 (suppl 4; abstr 387)

  39. The large proportion of pts receiving post-progression anti-EGFR therapy may have affected the ability to observe a difference in OS between the tx arms. • In pts with MT KRAS there was no difference in efficacy. J ClinOncol 30, 2012 (suppl 4; abstr 387)

  40. Cetuximab plus brivanib in metastatic chemo refractory K-RAS WT CRC • Brivanib, a tyrosine kinase inhibitor targeting vascular endothelial and fibroblast growth factor receptors (VEGFR/FGFR), added to Cetuximab has shown encouraging activity in an early phase clinical trial. • Despite positive effects on PFS and objective response, the combination of did not significantly improve OS in pts with MET, chemotherapy refractory, K-RAS WT CRC. J ClinOncol 30, 2012 (suppl 4; abstr 386)

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