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FRCR2 > Colorectal > Flashcards

Colorectal Flashcards

1
Q

What are the boundaries of the rectum

A

From dentate line (margin with anal canal) to rectosigmoid junction

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2
Q

What is the nodal drainage of the rectum

A

2/3 to para-rectal LNs -> inferior mesenteric nodes
1/3 to internal iliac nodes

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3
Q

What are the MMR proteins

A

MLH1
PMS2
MSH2
MSH6

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4
Q

What rate of MMR deficiency is sporadic

A

2/3
1/3 germline

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5
Q

Loss of which proteins indicates potential Lynch syndrome

A

MSH2 and/or MSH6 loss - paired - suspect Lynch syndrome

MLH1 & PMS2 loss - paired - need to determine B-Raf mutation or B-raf promotor hypermethylation

Approximately 1/3 have B-RAF mutation
B-RAF mutated: Unlikely to be Lynch (more likely MLH1 somatic acquired mutation)
B-RAF wild-type & no promoter hypermethylation - likely Lynch

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6
Q

What is Lynch syndrome
What is the inheritance
What is the lifetime risk of colorectal cancer

A

germline AD loss of MMR function, causing microsatellite instability
80% lifetime risk, typically right-sided tumours

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7
Q

What is Muir-Torre syndrome
What cancers are predisposed
What genes are affected

A

Subtype of Lynch syndrome
Develop colon, GU, and skin lesions - keratoacanthomas and sebaceous tumours
Genes affected = MLH1, MSH2, and MSH6

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8
Q

What tumours are associated with Lynch syndrome
What screening takes place

A

Renal
Upper GI - pancreatic and gastric
Ovarian and endometrial

2yrly colonoscopy from age 25
2yrly OGD from age 50-70
Consider TAH+BSO from age 40

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9
Q

What are the criteria within the Modified Amsterdam Criteria, to suggest Lynch syndrome

A

3+ relatives affected, with a related cancer (colorectal, small bowel, gastric, pancreatic, endometrial, ovarian, renal pelvis TCC (but not bladder))
2 generations affected
1 person diagnosed <50yrs
1 must be a first degree relative
Must exclude FAP

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10
Q

How is FAP inherited
What is the gene and chromosome
What surveillance takes place

A

AD inherited loss of APC on chromosome 5
Colonoscopy from age 15

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11
Q

What are the variants of FAP (3)

A

Gardner’s syndrome - colorectal polyps, skull and mandible osteomas, desmoid tumours & cysts, sebaceous cysts

Turcot’s syndrome - Colorectal polyps with CNS tumours (ependymomas, medulloblastomas)

Attenuated FAP - fewer polyps and lower risk of cancer

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12
Q

What is Gardner’s syndrome & what are its features

A

Variant of FAP
colorectal polyps, skull and mandible osteomas, desmoid tumours & cysts, sebaceous cysts

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13
Q

What is Turcot’s syndrome & what are its features

A

Variant of FAP
Colorectal polyps with CNS tumours (ependymomas, medulloblastomas)

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14
Q

What breast variant can metastasise to the bowel

A

Lobular breast cancer

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15
Q

What does B-raf predispose to

A

R sided tumours, worse prognosis

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16
Q

What are the commonest Ras mutations seen in colorectal cancer
What are the treatment implications

A

Ras G12 mutations
Can only given EGFR inhibitors (cetuximab / panitumumab) in Ras WT tumours

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17
Q

What screening exists for colorectal cancer

What is the outcome

A

Faecal immunohistochemical test (FIT)

Age 60-74 - 2-yearly
If ≥75 – can request to keep testing

Approx. 2% are positive -> undergo colonoscopy of which 1/300 will have cancer
High false positive rate (>90%)
Approx.15% reduction in mortality from screening (Nottingham trial 2006)

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18
Q

What investigations are needed for a newly diagnosed bowel cancer

A

Histology incl B-Raf & Ras status, and MMR
Imaging - CTCAP, MRI pelvis for rectal cancer

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19
Q

What are the Duke’s staging for colorectal cancer

A

A - T1-2 N0
B - T3-4 N0
C - T Any N1-2
D - metastatic disease

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20
Q

When should a colonoscopy be repeated following removal of an adenoma

A

1-2yrs

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21
Q

When should a colonoscopy be repeated following removal of an adenocarcinoma of pT1 only (submucosal invasion, not muscular)

A

1-2yrs

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22
Q

What risk factors would make a pT1 adenocarcinoma seen on colonoscopy, better managed by surgical workup and removal rather than removal at colonoscopy

A

Lymphatic or venous invasion
Grade 3 differentiation
Significant tumour budding

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23
Q

How is a stage 1 (T1-2 N0) colorectal cancer managed

A

Surgery only - no benefit to adjuvant chemotherapy

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24
Q

What are the options for neoadjuvant chemotherapy
and what duration

A

CapOx - capecitabine and oxaliplatin (3wkly regimen)
FolFox - Folinic acid, 5-FU, oxaliplatin (2wkly regimen)

6wks - 2 cycles capox or 3 cycles folfox

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25
Q

When is there minimal benefit from adjuvant chemotherapy
What drug should be avoided

A

dMMR / MSI-high
Potentiating effect of capecitabine
Use folfox or no adjuvant chemo

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26
Q

How is stage 2 colorectal cancer defined

A

T3-T4b N0

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27
Q

How is stage 3 colorectal cancer defined

A

Node positive disease
T1-4b N1-2

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28
Q

When should NACT be omitted for a stage ≥2 cancer

A

dMMR - no benefit to NACT as per Foxtrot trial
Proceed straight to surgery

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29
Q

How is stage 2 (T3-T4b N0) split regarding adjuvant tx

A

Low, intermediate and high risk
Low risk has no major or minor risk factors
Intermediate has minor, but not major risk factors
High risk has at least one major risk factor

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30
Q

What are the major risk factors when deciding adjuvant tx for stage 2 colorectal cancer (2)

A

pT4a stage including perforation
<12 LNs sampled

31
Q

What are the minor risk factors when deciding adjuvant tx for stage 2 colorectal cancer (4)

A

Presentation with obstruction
LVSI / PNI
High grade / poor differentiation
High CEA pre-operatively (>5)

32
Q

What adjuvant tx does a low risk stage 2 colorectal cancer receive

A

Assuming pMMR & No major or minor risk factors
No adjuvant tx indicated

33
Q

What adjuvant tx does an intermediate risk colorectal cancer receive

A

Assuming pMMR, no major risk factors, but minor risk factor present
6mths single agent capecitabine or 5FU

34
Q

What adjuvant treatment does a high risk stage 2 colorectal cancer receive

A

Assuming pMMR, and major risk factor present
3mths CapOx or 6mths Folfox

35
Q

When might FolFox be a better adjuvant ChT regimen than CapOx?

A

Impaired renal function and ileostomy, as capox causes higher rates of diarrhoea

36
Q

What is the benefit of adjuvant oxaliplatin, in addition to 5FU

A

4-5% benefit in OS - mosaic trial

37
Q

What biomarkers should be sent for metastatic colon cancer

A

K-ras, N-Ras, EGF-R, B-raf, MMR, HER2

Imaging - CTCAP, MRI liver, PET CT

DPYD status

38
Q

What is the follow up after surgery and adjuvant chemotherapy for colorectal cancer

A

Years 1-3:
3-6 month history, physical examination and CEA level
CT every 6-12mths
Colonoscopy every 3-5yrs, starting 1yr after surgery

Year 4-5:
6-12 month history, physical examination and CEA level
CT every 12mths
Colonoscopy every 3-5yrs

39
Q

Where is the mesorectal fascia considered as the circumferential resection margin

A

Only for the non-peritonealised part of the rectum

40
Q

What is the treatment for a stage I (T1-2 N0) rectal cancer

A

surgery - trans-anal, endoscopic submucosal or TME
Radical RT can be considered for those unwilling to have a stoma (necessary in APER), or unfit for surgery

41
Q

What is the overall management of T3-4 or node positive rectal cancer

A

Pre-op RT/CRT followed by surgery

42
Q

What are the indications for defunctioning ahead of treatment for rectal cancer?

A

Significant faecal urgency or incontinence which may compromise their ability to complete treatment
Symptoms or signs of obstruction on imaging or scope
Rectovaginal or rectovesical fistula from tumour

43
Q

What are the indications for Neo-adjuvant treatment for rectal cancer

A

Involvement of the CRM
T3-4
Node positive disease

44
Q

What are the benefits of neoadjuvant treatment in rectal cancer

A

Downstage disease, increasing rates of R0 resection
Reduce risk of local recurrence

45
Q

When is long course Neo-adjuvant CRT indicated for treatment of rectal cancer

A

Threatened CRM (<1mm) or breached
Low tumours encroaching onto the intersphincteric plane or levator muscles

46
Q

What is the long course neoadjuvant CRT regimen

A

45Gy/25# +/- 5.4Gy/3# boost to the tumour (50.4Gy/28# overall)
Or SIB to tumour (50Gy/25#) with 45Gy/25# to elective volume

With concurrent capecitabine 825mg/m2 bd on treatment days OR bolus 5FU on weeks 1 & 5

47
Q

What is the follow up post long course NA CRT for rectal cancer

A

MRI pelvis and CTCAP 6-8wks following treatment, then proceed to surgery

48
Q

What are the indications for short course neoadjuvant CRT for rectal cancer

And what is the regimen

A

CRM not threatened, but not felt pt would tolerate long course CRT

> T3b
Node positive
EMVI +

25Gy/5# over 5 days, and surgery within 10 days

49
Q

What are the surgical options for a >T1 rectal cancer

A

TME
Anterior resection - middle / high rectal cancers
APER - very low rectal tumours

50
Q

When is adjuvant chemoradiotherapy given in rectal cancer

What is the regimen

A

Only if pre-op LC-CRT or SC-CRT were not given (Primary surgery)

pT4 (not if pT4a above peritoneal reflection)
Tumour perforation (T4a)
Positive margins or residual disease
EMVI
Node positive disease

Regimen:
45Gy/25#/5wks +/- concomitant chemotherapy
If there is residual macroscopic disease, consider boost to tumour site up to 50Gy

51
Q

What adjuvant regimen is given for a high risk stage 2 (T3-4 N0) rectal cancer

A

6mths of CapOx or Folfox (not 3mths CapOx like colon)
only if no NACT or SCPRT given (not long course)

52
Q

How is oligometastatic disease defined

A

Up to 5 metastatic lesions, in up to 2 sites, with a controlled or resected primary, with all mets treatable

53
Q

How is liver resectability defined?

A

≥30% of liver should remain
≥2 contiguous liver segments should remain disease free
No involvement of the hepatic vein
Limited extra-hepatic disease

54
Q

For resectable metastatic liver disease, what is the recommended treatment?

If unfavourable prognostic criteria - what is the recommended treatment

A

No neoadjuvant treatment
Resect primary and liver mets
Adjuvant Folfox

Unfavourable prognostic criteria, but resectable:
3mths neoadjuvant folfox/folfoxiri, resection, followed by adjuvant CapOx/Folfox for 6mths
No additional benefit for cetuximab (pts did worse)

55
Q

What is the treatment recommendation for a resectable primary tumour but unresectable mets

A

Attempt to convert unresectable mets into resectable, with Folfox/Folfiri/folfoxiri +/- cetux/panitumumab (L-sided tumour; EGFR WT) or +/- bevacizumab (R-sided tumour)

Once resectable, resect primary and mets.
If no converted to resectable, continue palliative ChT

56
Q

What is the first line treatment for advanced metastatic colorectal cancer, that is L-sided
And dependent on what mutations

A

Folfox / CapOx / Folfiri / Folfirinox +/- Cetuximab (with folfiri) / Panitumumab (with folfox)
If Ras WT & B-Raf WT & left sided tumour -> add Cetuximab/panitumumab
3-4 month PFS & OS benefit

If Ras/Raf-mut, can consider doublet/triplet ChT with bevacizumab

FOLFOXIRI
Superior OS and response cf to FOLFIRI, but toxic and need to be fit!

57
Q

What is the first line treatment for advanced metastatic colorectal cancer, that is R-sided

A

Folfox / CapOx / Folfiri / Folfirinox +/- Bevacizumab
If right sided tumour

FOLFOXIRI
Superior OS and response cf to FOLFIRI, but toxic and need to be fit!

58
Q

What is the first line treatment for advanced metastatic colorectal cancer, if the pt is not fit enough for combination chemotherapy

A

5FU or capecitabine alone - if not fit enough for combination chemotherapy

59
Q

What is the first line treatment for advanced metastatic colorectal cancer, that is dMMR/MSI-H

A

1st line - consider pembrolizumab (for 2yrs or until progression)
2nd line - chemo +/- targeted agent (ipi/nivo 2nd line if chemotherapy used 1st line)

60
Q

What is licensed second line for the treatment of B-Raf V600E positive colorectal cancer

A

Encorafenib-cetuximab
Based on Beacon trial

61
Q

What is the second line treatment of dMMR colorectal cancer after first line chemotherapy

A

Ipi-nivo (only if pembro not used first line)

62
Q

What drug combination cannot be used with cetuximab/panitumumab

A

CapOx

63
Q

What is the prognosis of metastatic colorectal cancer treated with folfox/folfiri

A

Combination chemo (FOLFOX/FOLFIRI): 22-24 months

64
Q

How is the involvement of the MRF classified in rectal cancer

A

<1mm - involved
1-2mm - threatened
>1-2mm - clear

65
Q

When should pre-op chemoRT not be offered for rectal cancer

A

Early rectal cancer - T1-2 N0
Offer to T1-2, N1-2 or any T3-4W

66
Q

When is TNT indicated for rectal cancer

A

Stage II & III rectal cancer (T3-4 or node positive)
Fit pts
Large tumour, node positive
CRM involved
MMR proficient

67
Q

What drug is contraindicated with capecitabine

A

warfarin

68
Q

How is de novo metastatic rectal cancer managed

A

If resectable or potentially resectable, SCRT and 3/12 neoadjuvant chemotherapy, followed by imaging assessment and potentially surgery

If CRM not threatened in primary, can omit neoadjuvant chemotherapy

69
Q

When is SCPRT followed by delayed imaging and surgery (10wks) used

A

In pts with poor performance status but still with an indication for pre-op RT

70
Q

what adjuvant treatment is recommended for pts >70?

A

single agent cape/5FU (6mths) or surveillance

71
Q

is levator involvement by a rectal cancer an indication for neoadjuvant chemotherapy

A

yes - indication for long course pre-op chemoRT

72
Q

what must be tested for in colorectal cancer before deciding adjuvant treatment

how is this relevant in stage 2 disease

A

MSI status

dMMR in stage II disease:
Minimal benefit from adjuvant chemotherapy
Adjuvant capecitabine increases risk of potentiating mutation
Therefore give combination = FOLFOX or No adjuvant chemo

73
Q
A

FRCR2 (38 decks)

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