Colorectal Cancer
Question 1:
What is CORRECT about the following epidemiology statements concerning colorectal cancer
(A) It is the most common cancer in men, and second most common cancer related death
(B) It is the second most common cancer, and the second most common cause of cancer related death
(C) It is the fourth most common cancer, and the first most common cause of death
(D) It is not related to ageing
(E) Low dose aspirin or NSAIDS when used continuously have no role in chemoprevention according to the Danish trial
B: Answer C is correct for lung cancer. In fact, low dose aspirin or NSAIDS when used continuously do have a role in cancer chemoprevention, especially in the subgroup of patients with HNPCC
Question 2:
What statement is FALSE regarding the molecular biology of colorectal cancer
(A) KRAS and NRAS mutational analysis is vital for predicting the response to EGFR1 inhibitors
(B) CpG island hypermethylation is NOT a mechanism in the BRAF/ serrated adenoma à carcinoma sequence
(C) Bevacizumab works by its anti-angiogenic role in blocking signalling through VEGF-R
(D) Microsatellite instability can be detected by molecular analysis
(E) The DNA mismatch repair gene mutations may be detected by their absence in tissue through immunohistochemistry
B: This is a current mechanism known, through epigenetic silencing (RPA lecture notes and RPA course)
Question 3:
A 22 year old male with ulcerative colitis and pancolitis with concomitant p-ANCA associated primary sclerosing cholangitis is referred to the colorectal cancer screening program. What regime should be suggested based on the current screening guidelines?
(A) Colonoscopy should be offered in the year of diagnosis because he has PSC, and then should be offered annually
(B) Colonoscopy should be offered at 8 years from diagnosis because he has pancolitis, and then 2 yearly
(C) Biopsy should be done at every 5cm in the colon with special staining techniques
(D) Inflammatory bowel disease is NOT a risk factor for colon cancer and the patient should undergo regular screening, which at its latest would be FOBT at the age of 50 every 2 years or sigmoidoscopy/ colonoscopy every 5 years
(E) Colonoscopy should be offered in the year of diagnosis because he has PSC, and then should be offered second yearly
A: If patient has pancolitis without PSC then screening should begin at 8 years after diagnosis, if the patient has left sided disease only then screening can commence from 12 – 15y post diagnosis, with repeat colonoscopy every 2 years thereafter. Biopsies should be taken every 10 cm NOT 5cm’s.
Question 4:
A 52 year old male is concerned about his risk of colorectal cancer and engages in the colorectal cancer screening program. He has a FOBT that comes back positive. He then undergoes colonoscopy where a non dysplastic adenomatous polyp is discovered in the sigmoid colon, about 2cm in size. As his treating doctor, what is the best recommended follow-up program for this man.
(A) He has a small non-dysplastic polyp, and therefore he can be re-assured that he has a very low risk of colorectal cancer and re-screening should be offered 5 – 10 years later
(B) Screening was not recommended in this individual, and should only be recommended in individuals who have a family history of colorectal cancer, and screening should begin 10 years before the diagnosis of colorectal cancer in the first degree family member.
(C) His polyp is adenomatous; therefore he should undergo a repeat colonoscopy in 3 – 6 months time
(D) Because he has a sigmoidal polyp, he now only requires sigmoidoscopy for future screening
(E) He has a large but non-dysplastic polyp, therefore he should have repeat colonoscopy 3 years from now.
E: The correct guidelines for a large non-dysplastic polyp (>1cm) is repeat colonoscopy screening in 3 years time. If the polyp was <1cm, then A would be the correct answer (knowing that the adenoma – carcinoma sequence takes 5 – 10 years), family history is important, and should start at age 50 or 10 years before the diagnosis in the first degree relative. If the patient has HNPCC then, if a germline mutation is detected the pt would start screening at age 25 or 5 yr before ealiest diagnosis at a frequency of every 2 yrs. If the pt had FAP then screening would begin at age 12 – 25, unless it was attenuated FAP
Question 5
A 64-year old male with diabetes and NYHA class 2 heart failure that is stable is diagnosed with a colorectal cancer and is offered a hemicolectomy. There was no lymph node involvement and the stage was considered to be 2A. He comes to the oncology practice for his first appointment post operatively, 3 months down the track from his operation. With regards to his screening, what is the CORRECT answer
(A) He should have an intensified screening program consisting of monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(B) He should have annual colonoscopies and CT C/A/P for the following 5 years
(C) He should have an intensified screening program consisting of 3 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(D) He should have an intensified screening program consisting of 3 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for a further 10 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(E) He should have an intensified screening program consisting of 6 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then annually for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT fir first 3 yrs, then annually thereafter
C – RPA lecture notes and course notes
Question 6
A 63-year-old patient with Eastern Co-operative Oncology Group class 2 symptoms has been diagnosed with metastatic colorectal cancer that involves the lungs and liver. Mutational analysis shows that he is wild-type for KRAS but has mutation in NRAS. He is subsequently commenced on Bevacizumab + FOLFIRI chemotherapy.
What is FALSE regarding this man’s case?
(A) Bevacizumab should be used because the patient has mutational NRAS, making him not suitable for EGFR1 monoclonal antibody blockers
(B) He is NOT a candidate for curative resection therapy because he has multiple metastatic sites
(C) Bevacizumab when added to his regime may extend survival by about 3.7 months
(D) Bevacizumab side effects include hypotension and a pre-disposition to excessive bleeding
(E) Venous thromboembolism and increased gastrointestinal fistulas are side-effects of his treatment
D: Side effects of Bevacizumab include hypertension, venous thromboembolism and gastrointestinal fistulas. When added to conventional therapy, it does increase overall survival by 3.7 months. Resection should only be considered if there are only liver OR lung metastasis – RPA lecture notes + ESMO CPG 2014
Question 7
A 49 year old male is diagnosed with Stage 2B colorectal cancer. With regards to offering adjuvant therapy, what is CORRECT?
(A) Capecitabine or 5-FU can be considered and decreases death rate by 3 – 5% in carefully selected patients with stage 2 CRC with high risk features
(B) FOLFOX or XELOX should be offered to this patient as she has a very high risk of progressing to metastatic disease
(C) Capecitabine carries a lower risk of hand-foot syndrome compared to 5-FU
(D) Capecitabine carries a higher risk of constipation than 5-FU
(E) There is insufficient evidence to offer adjuvant chemotherapy to patients with stage 2B colorectal cancer
A: In accordance to ESMO CPGs 2013.
Question 8
With regards to Bevacizumab related therapy, what is most CORRECT
(A) Bevacizumab acts by blocking the VEGF receptor directly
(B) Bevacizumab can be used alone
(C) Bevacizumab does not cause a significant increase in proteinuria
(D) Bevacizumab cannot be added on to a second line treatment option as it is not validated in this setting
(E) Bevacizumab is targeted more at VEGF-B than VEGF-A
A: ESMO clinical practice guidelines 2014. Bevacizumab is not validated for use by itself in chemotherapy regimes. It can be added to second line therapy and in this setting it does improve progression free survival.
What is CORRECT about the following epidemiology statements concerning colorectal cancer
(A) It is the most common cancer in men, and second most common cancer related death
(B) It is the second most common cancer, and the second most common cause of cancer related death
(C) It is the fourth most common cancer, and the first most common cause of death
(D) It is not related to ageing
(E) Low dose aspirin or NSAIDS when used continuously have no role in chemoprevention according to the Danish trial
B: Answer C is correct for lung cancer. In fact, low dose aspirin or NSAIDS when used continuously do have a role in cancer chemoprevention, especially in the subgroup of patients with HNPCC
Question 2:
What statement is FALSE regarding the molecular biology of colorectal cancer
(A) KRAS and NRAS mutational analysis is vital for predicting the response to EGFR1 inhibitors
(B) CpG island hypermethylation is NOT a mechanism in the BRAF/ serrated adenoma à carcinoma sequence
(C) Bevacizumab works by its anti-angiogenic role in blocking signalling through VEGF-R
(D) Microsatellite instability can be detected by molecular analysis
(E) The DNA mismatch repair gene mutations may be detected by their absence in tissue through immunohistochemistry
B: This is a current mechanism known, through epigenetic silencing (RPA lecture notes and RPA course)
Question 3:
A 22 year old male with ulcerative colitis and pancolitis with concomitant p-ANCA associated primary sclerosing cholangitis is referred to the colorectal cancer screening program. What regime should be suggested based on the current screening guidelines?
(A) Colonoscopy should be offered in the year of diagnosis because he has PSC, and then should be offered annually
(B) Colonoscopy should be offered at 8 years from diagnosis because he has pancolitis, and then 2 yearly
(C) Biopsy should be done at every 5cm in the colon with special staining techniques
(D) Inflammatory bowel disease is NOT a risk factor for colon cancer and the patient should undergo regular screening, which at its latest would be FOBT at the age of 50 every 2 years or sigmoidoscopy/ colonoscopy every 5 years
(E) Colonoscopy should be offered in the year of diagnosis because he has PSC, and then should be offered second yearly
A: If patient has pancolitis without PSC then screening should begin at 8 years after diagnosis, if the patient has left sided disease only then screening can commence from 12 – 15y post diagnosis, with repeat colonoscopy every 2 years thereafter. Biopsies should be taken every 10 cm NOT 5cm’s.
Question 4:
A 52 year old male is concerned about his risk of colorectal cancer and engages in the colorectal cancer screening program. He has a FOBT that comes back positive. He then undergoes colonoscopy where a non dysplastic adenomatous polyp is discovered in the sigmoid colon, about 2cm in size. As his treating doctor, what is the best recommended follow-up program for this man.
(A) He has a small non-dysplastic polyp, and therefore he can be re-assured that he has a very low risk of colorectal cancer and re-screening should be offered 5 – 10 years later
(B) Screening was not recommended in this individual, and should only be recommended in individuals who have a family history of colorectal cancer, and screening should begin 10 years before the diagnosis of colorectal cancer in the first degree family member.
(C) His polyp is adenomatous; therefore he should undergo a repeat colonoscopy in 3 – 6 months time
(D) Because he has a sigmoidal polyp, he now only requires sigmoidoscopy for future screening
(E) He has a large but non-dysplastic polyp, therefore he should have repeat colonoscopy 3 years from now.
E: The correct guidelines for a large non-dysplastic polyp (>1cm) is repeat colonoscopy screening in 3 years time. If the polyp was <1cm, then A would be the correct answer (knowing that the adenoma – carcinoma sequence takes 5 – 10 years), family history is important, and should start at age 50 or 10 years before the diagnosis in the first degree relative. If the patient has HNPCC then, if a germline mutation is detected the pt would start screening at age 25 or 5 yr before ealiest diagnosis at a frequency of every 2 yrs. If the pt had FAP then screening would begin at age 12 – 25, unless it was attenuated FAP
Question 5
A 64-year old male with diabetes and NYHA class 2 heart failure that is stable is diagnosed with a colorectal cancer and is offered a hemicolectomy. There was no lymph node involvement and the stage was considered to be 2A. He comes to the oncology practice for his first appointment post operatively, 3 months down the track from his operation. With regards to his screening, what is the CORRECT answer
(A) He should have an intensified screening program consisting of monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(B) He should have annual colonoscopies and CT C/A/P for the following 5 years
(C) He should have an intensified screening program consisting of 3 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(D) He should have an intensified screening program consisting of 3 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then 6 monthly for a further 10 years. In addition, he should have 6- monthly CT C/A/P CT for first 2 yrs, then annually thereafter
(E) He should have an intensified screening program consisting of 6 monthly CEA’s, physical examination, DRE +/- sigmoidoscopy for 2 years, then annually for the remaining 3 years. In addition, he should have 6- monthly CT C/A/P CT fir first 3 yrs, then annually thereafter
C – RPA lecture notes and course notes
Question 6
A 63-year-old patient with Eastern Co-operative Oncology Group class 2 symptoms has been diagnosed with metastatic colorectal cancer that involves the lungs and liver. Mutational analysis shows that he is wild-type for KRAS but has mutation in NRAS. He is subsequently commenced on Bevacizumab + FOLFIRI chemotherapy.
What is FALSE regarding this man’s case?
(A) Bevacizumab should be used because the patient has mutational NRAS, making him not suitable for EGFR1 monoclonal antibody blockers
(B) He is NOT a candidate for curative resection therapy because he has multiple metastatic sites
(C) Bevacizumab when added to his regime may extend survival by about 3.7 months
(D) Bevacizumab side effects include hypotension and a pre-disposition to excessive bleeding
(E) Venous thromboembolism and increased gastrointestinal fistulas are side-effects of his treatment
D: Side effects of Bevacizumab include hypertension, venous thromboembolism and gastrointestinal fistulas. When added to conventional therapy, it does increase overall survival by 3.7 months. Resection should only be considered if there are only liver OR lung metastasis – RPA lecture notes + ESMO CPG 2014
Question 7
A 49 year old male is diagnosed with Stage 2B colorectal cancer. With regards to offering adjuvant therapy, what is CORRECT?
(A) Capecitabine or 5-FU can be considered and decreases death rate by 3 – 5% in carefully selected patients with stage 2 CRC with high risk features
(B) FOLFOX or XELOX should be offered to this patient as she has a very high risk of progressing to metastatic disease
(C) Capecitabine carries a lower risk of hand-foot syndrome compared to 5-FU
(D) Capecitabine carries a higher risk of constipation than 5-FU
(E) There is insufficient evidence to offer adjuvant chemotherapy to patients with stage 2B colorectal cancer
A: In accordance to ESMO CPGs 2013.
Question 8
With regards to Bevacizumab related therapy, what is most CORRECT
(A) Bevacizumab acts by blocking the VEGF receptor directly
(B) Bevacizumab can be used alone
(C) Bevacizumab does not cause a significant increase in proteinuria
(D) Bevacizumab cannot be added on to a second line treatment option as it is not validated in this setting
(E) Bevacizumab is targeted more at VEGF-B than VEGF-A
A: ESMO clinical practice guidelines 2014. Bevacizumab is not validated for use by itself in chemotherapy regimes. It can be added to second line therapy and in this setting it does improve progression free survival.
Colon Cancer Notes
- Epidemiology
- 2nd most common cancer + 2nd most common cause of cancer death
- Age biggest RF, western diet, lifestyle, lack of physical activity, obesity
- Genetics
- Adenoma --> carcinoma sequence with KRAS mutation usually a key step. MSI also implicated.
- CpG methylator phenotype --> serrated polyp, BRAF mutation common
- Genetic syndromes
- 25% have a family history
- 1% FAP: A/D, 100’s of polyps, includes duodenum, stomach, bones, skin à prophylactic colectomy late/ early teens
- 2-3% HNPCC (Lynch syndrome): A/D, high penetrance, right sided tumours, mucinous, high inflammatory infiltrate, other cancers include endometrial + stomach, MSI due to genetic abnormalities in mis-match repair enzymes, germline mutations occur in HNPCC, loss of expression MMR 15% sporadic CRCs b/c of methylation. FHx = 3:2:1 rule, 3 cases, 2 1st deg, 1 <50yoa
- 25% have a family history
- Cancer Chemoprevention evidence:
- Danish population study --> long term continuous low dose aspirin, effect also present when NSAId used alone. Also gives less mets and less advanced cancer at Dx
- Lynch syndrome there is definite benefit + FAP
- Screening
- FOBT has the best evidence in terms of all cancer screening. Other one is breast Ca and cervical cancers
- Program: Category 1 [low] vs category [2]. Category 1--> FOBT every 2nd yr from age 50, flexible sigmoidoscopy/ colonoscopy every 5 yrs. No evidence directly for colonoscopy but still done. Category 2 --> Start at age 50 or 10 yr before first Dx of cancer in first deg rel, which ever came first. Always refer Cat 2 to cancer genetics program
- FAP: Screening at age 12-25 except attenuated FAP
- HNPCC: annually [if germline mutation] or 2-yrly at age 25 or 5 years before earliest cancer Dx
- If IBD then:
- Colonoscopy every 2yrs, annually if PSC and straight away at time of diagnosis of PSC, otherwise 8yrs after pancolitis, 12-15y if left sided disease, biopsy every 10cm
- If polyp, then f/u depends on type
- Malignant --> 3/12, incomplete --> 3-6/12, large polyp >1cm +/- high risk dysplasia +/- multiple (>2) --> 3y, single small adenoma --> 5-10y
- Rx early stage. Note capecitabine = prodrug of 5-FU
- Staging: CT C/A/P for Mets, pre-op CEA helps with determining recurrence, if Rectal Ca then MRI/ rectal US
- Rectal Ca --> radiotherapy offered
- Stage 1 --> [Localised to bowel, based on thickness of invasion] wide local resection + anastomosis, no adjuvant therapy
- Stage 2 --> [No LN involvement, greater thickness than stage 1] WLR + anastomosis. If high risk features consider CTx [5FU OR capecitabine], decreases risk of death by 3 – 5%
- If tumour is MSI+, then will not benefit from CTx --> potential for immunotherapy [research ongoing in this field]
- Stage 3 --> Offer adjuvant in addition to WLR + anastamosis. Regimes include 5-FU [SE = palmar plantar syndrome, diarrhea, mucositis, folic acid depletion] + oxaliplatin [SE = neuropathy] AKA FOLFOX4, capecitabine [SE = palmar plantar syndrome] + oxaliplatin AKA XELOX [PO]
- Staging: CT C/A/P for Mets, pre-op CEA helps with determining recurrence, if Rectal Ca then MRI/ rectal US
- Rx Metastatic disease
- First principles: EGFR1 --> colon + NSCLC, EGFR2 --> Breast, VEGF = bevacizumab
- Curative if --> low burden liver/ lung mets
- KRAS and NRAS W/T --> cetuximab or panitumimab [SE = acneform rash --> predicts drug working on EGFR1] + FOLFIRI [IRI = iranotacen] or FOLFOX
- KRAS and NRAS mutant --> bevacizumab [S/E = HTN/ thromboembolism] + FOLFIRI or FOLFOX
- Surveillance post Rx
- In first 2 years --> 3 monthly CEA + Physical including DRE +/- sigmoidoscopy in rooms, then 6 monthly for 5 yrs
- In addition to above: CT C/A/P 6/12ly first 2 yrs, then annually until 5 yr mark
- In addition to above: Colonoscopy at anniversary of Surgery then 3 – 5 yrs after Dx and every 3-5y after that