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Oncology Morning Report

Oncology Morning Report. Dr. Sohail Chaudhry Dr. Padma Poddutoori. Epidemiology of CRC. 148,810 cases diagnosed and 49,960 deaths each yr in U.S CRC accounts 9% of cancer deaths. Incidence: Rare before 40, increases significantly between 40-50, increases in succeeding decades thereafter.

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Oncology Morning Report

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  1. Oncology Morning Report Dr. Sohail Chaudhry Dr. Padma Poddutoori

  2. Epidemiology of CRC • 148,810 cases diagnosed and 49,960 deaths each yr in U.S • CRC accounts 9% of cancer deaths. • Incidence: • Rare before 40, increases significantly between 40-50, increases in succeeding decades thereafter. • 5% lifetime risk in pts at average risk • 90% occur after age 50

  3. Risk Factors for CRC • Family history- FAP and HNPCC <5% of cases. • FAP: average 16 at symptom onset, colon ca in 90% by 45 yrs of age. • HNPCC[Lynch Syndrome]: AD syndrome accounts 1-5% of colonic adeno carcinoma • Mutations in mismatch repair genes- hmlh1, hmsh2, hmsh6 or pms2 • Mean age at diagnosis- 48 some in20’s, 70% proximal to splenic flexure, 10% synchronous or metachronous lesions • Family h/o single 1st degree relative-1.7 fold, increased if 2 1st degree relatives or if index case<55 yrs • Personal h/o large[>1cm] adenomatous polyps with villous or tubulovillous histology, multiple.

  4. Risk Factors for CRC IBD-ulcerative colitis- 0.5%/yr 10-20 yrs of disease, then 1%/yr thereafter, pancolitis-8-10 yrs, 15-20 yrs left sided colitis. • DM-IGF-1, chronic insulin use. • Cholecystectomy • Alcohol >45gm/day, cigarette smoking • Obesity- 1.5 fold • Diets rich in sucrose, fat and red meat. • Prior pelvic radiation, CAD, ureterocolic anastomosis. • Factors which decrease the risk-fruits and vegetables, folate, vitamin B6, calcium intake>1250mg, Mg, physical activity, aspirin, NSAIDS, HRT, statins.

  5. Screening • Most effective way to prevent CRC is screening for and removal of adenomatous polyps. • FOBT, flexible sigmoidoscopy, colonoscopy, and barium enema used for diagnosis of adenomatous polyps. • Genetic counseling and testing should be considered for patients with a family history of familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer.

  6. Comparison of Screening Tests for CRC Test Tolerance Sensitivity/Specificity Cost Availability Ideal test High High Low High Fecal occult blood test High Low Low High Flexible sigmoidoscopy Low Moderate Moderate Moderate Fecal occult blood test plus flexible sigmoidoscopy Low Moderate Moderate Moderate Colonoscopy Moderately high High High ?High Double-contrast barium enema examination Moderately high Moderate Moderate Moderate Double-contrast barium enema examination plus flexible sigmoidoscopy Not generally recommended CT colonography (virtual colonoscopy) Not yet recommended

  7. Surveillance after CRC resection • Pts with resected stage 2 or 3 colon or rectal cancer- physician visit every 3-6 months for 1st 3 yrs and every 6 m 4th and 5th yrs and then yearly thereafter. • CEA levels every 3 m stage 2 or 3 yrs • All pts with CRC undergo a colonoscopy either before or within few months after resection to exclude synchronous polyps and cancer. • Colonoscopy repeated one yr after primary resection, if normal 3 yrs later, if normal 5 yrs interval • Post low antr resection of rectal cancer with no RT- flexible proctosigmoidoscopy every 6 m for 5 yrs • Resected stage 2 or 3 –annual CT chest and abdomen or pelvis for 3 yrs • FOBT, LFT, CBC, CXR, PET scan not recommended after surgery for f-up.

  8. Glossary of Treatments for Colorectal Cancer Meyerhardt J and Mayer R. N Engl J Med 2005;352:476-487

  9. Fluoropyrimidines • Fluorouracil, a fluorinated pyrimidine, acts primarily by inhibiting thymidylate synthase. FU is administered with leucovorin, a reduced folate, which stabilizes binding of FU to thymidylate synthase. • In advanced CRC, treatment with FU and leucovorin reduces tumor size by 50% or more in 20% and prolongs median survival from 6 m to about 11 months. • Side effects: • loading schedule- 5 days every 4-5 wks-neutropenia and stomatitis • Wkly bolus doses-diarrhea • Continuous IV infusion-palmar-plantar dysesthesia[hand-foot syndrome] • Oral[cepacitabine {xeloda}]- hand foot syndrome

  10. Adjuvant therapy with FU • In stage 3- adjuvant chemotherapy increased tumor free duration after five yrs from 42% to 58% and 5 yr survival from 51-64%, equally beneficial in elderly and in younger pts. • Survival advantage in stage 2: 5%, pts with adherence of tumor to adjacent organ or bowel perforation or obstruction may benefit from adjuvant chemotherapy • Regional therapy with fluoropyrimidines: • Infusion of FU or its analogue floxuridine into hepatic artery doubles response rates achieved with systemic administration of FU. • Toxicity: chemical hepatitis, cholangitis, catheter related complications, high overall costs limit its use.

  11. Irinotecan[camptosar] • A semisynthetic derivative of natural alkaloid camptothecin exerts it cytotoxic effect through topoisomerase- it stabilizes the DNA breaks and leads to cell death • Toxic effects: N/V/diarrhea, bone marrow suppression and allopecia. • 3 drug combination of IFL- twice as likely as FL to result in 50% or greater shrinkage of tumor dimensions with 2 m increase in median survival

  12. Oxaliplatin • A 3rd gen platinum derivative that forms bulky DNA adducts and induces cellular apoptosis • Oxaliplatin and FU were highly synergistic due to down regulation of thymidylate synthase by OX which potentiates the efficacy of FU. • Toxicity:renal dysfunction, alopecia, ototoxicity uncommon but neuropathy more frequent. • Clinical benefit when combined with blous FU and leukovorin followed by 46 hr infusion of FU-FOLFOX. • Can be used as a 1st line combination therapy for metastatic disease • Greater likelihood of remaining disease free of recurrence after 4 yrs[76% vs 69%] stage 3-76 vs 69%, stage 2- 85 vs 81% and not significant.

  13. Targeted therapies • Cetuximab[erbitux] is a monoclonal antibody against the extra cellular binding domain of the EGF receptor and is also approved for metastatic CRC. • Has synergistic effect with irinotecan and also occurs in pts already resistant to irinotecan. Combination- 19%-23% radiographically objective tumor shrinkage, 10%-11 with erbitux alone. • Side effects; mild rash, drying and fissuring of skin, severity of rash correlated with increased objective response

  14. Targeted therapies • Bevacizumab [avastin]:a humanized antibody directed against VEGF • Addition of avastin to IFL: 4.7 m prolongation in median overall survival[20.3 from 15.6 m] • Statistically significant prolongation in survival with addition of avastin to FOLFOX compared to FOLFOX alone. • Approved for combination therapy with FU as initial therapy in advanced CRC • Side effects:reversible HTN, proteinuria

  15. Trends in the Median Survival of Patients with Advanced Colorectal Cancer Meyerhardt J and Mayer R. N Engl J Med 2005;352:476-487

  16. A 61 yr old woman is evaluated after 2-m h/o BRB on defecation and a change in stool caliber. Medical history is otherwise noncontributory, family history is unremarkable. On exam, a tumor is palpated just above the anal sphincter. Lab studies Hb of 11.1 g/dL. LFTs normal. CT abd reveals a distal rectal mass. Adenocarcinoma of the confirmed by biopsy. Which of the following treatment approaches is most likely to preserve the anal sphincter in this patient? • A Preoperative radiation therapy plus chemotherapy • B Preoperative chemotherapy • C Abdominoperitoneal resection • D Preoperative radiation therapy

  17. A 50-yr-old woman is evaluated for a routine F-up visit. Has h/o stage II colon cancer 2 yrs ago for which she underwent a surgical resection and received no adjuvant therapy. Exam -normal. Lab studies CEA increased from recent baseline of <5 ng/mL to 41 ng/mL. CT abd six hepatic lesions 2 to 7 cm. Multiple pulmonary nodules <1 cm on CT lung. Biopsy- liver lesions adenocarcinoma consistent with the initial primary tumor. Which of the following is the most appropriate next step in management? A Abdominal and chest PET B Hepatic resection C Systemic chemotherapy D Colonoscopy E Pulmonary nodule biopsy

  18. 78-yr-old woman evaluated for worsening symptoms of metastatic CRC. At diagnosis 5 m ago, had 11-cm liver lesion, extensive large pulmonary nodules, and a 5-cm sigmoid mass. She underwent resection of the primary tumor to relieve obstructive symptoms but developed multiple PE postoperatively. Her initial treatment regimen consisted of 5-FU and oxaliplatin but resulted in disease progression after 8 wks of therapy. Currently, she cannot care for herself because of cancer-related symptoms and is mostly bedbound. Which of the following is the most appropriate next step in management? A Irinotecan chemotherapy B Palliative care C Cryotherapy D Radiotherapy

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