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Medical oncology > Rectal Cancer > Flashcards

Rectal Cancer Flashcards

1
Q

What is the definition of a rectal cancer?

A 
Cancer within 15cm of anal verge by rigid proctoscopy
- 5cm or less = Low
- 5.1-10cm = Mid
- 10.1 to 15cm = High 
At or below the peritoneal reflection
Below the 1st or 2nd sacral vertebrae
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2
Q

What is the main histology for rectal cancer?

A

Adenocarcinomas 95-98%

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3
Q

What is T4?

A

(A) Perforation into visceral peritoneum
Or
(B) invasion to other organs

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4
Q

What is N1

A

1-3 regional LN involved

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5
Q

What is N2

A

4 or more regional LN involved

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6
Q

What is the sub classification in M1 disease?

A

M1a = one distant organ or set of LN

M1b = More than one organ or to the peritoneum

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7
Q

What are the layers of the GI tract

A

(M.S. M.S.)

Muscularis mucosae
Submucosae
Muscularis propria
Subserosal connective tissue

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8
Q

What is the Haggitt classification

A

This represents the histological classification of the extent of invasion of pedunculated malignant colorectal polyps

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9
Q

What is T2 and T3?

A 
T2 = invasion into Muscularis propria 
T3 = invasion into Subserosa/perirectal tissue
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10
Q

What is T1?

A

Invasion into Submucosae

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11
Q

Why is pre-op treatment preferred?

A

More effective

Less toxic

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12
Q

What is Total mesorectal excision (TME)?

A

Total mesorectal excision = TME

Excision of all the mesorectal fat, including all lymph nodes.

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13
Q

If an abdominoperineal excision is planned, what must the dissection encompass?

A

Dissection from above must be stopped at the tip of the coccyx,
Be continued from below (to get a cylindrical specimen)
Without a waist effect towards the tumor carrying a risk of cram+ or an R1/2 resection

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14
Q

Is postop CRT encouraged?

A

Not anymore. However, this can be used in :

  • positive crm
  • perforation in the tumor area
  • defects in the mesorectum
  • in cases with high risk of local recurrence if preop RT was not given.
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15
Q

What are the risks of short-course RT?

A

Increases:

  • risk of poor anal and sphincter sexual function
  • small bowel toxic effect with obstruction
  • secondary malignancies
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16
Q

What are considered high-risk features on transanal excision ?

A

Positive margins
LVI+
Poorly differentiated tumor
Sm3 invasion

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17
Q

What are the options available if a pt has symptomatic rectal cancer but Unresectable synchronous mets?

A

1) Combination systemic chemo
2) Infusional 5FU/RT or Bolus 5-FU/RT or Cape/RT
3) Resection of involved rectal segment
4) Laser recanalization
5) Diverting ostomy
6) Stenting

After above then proceed to chemo for advanced/met disease

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18
Q

What are the ways that recurrence in rectal cancer can occur?

A

1) Serial CEA elevation
2) Isolated pelvic/anastomotic recurrence
3) Documented metachronous mets by CT/MRI/biopsy

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19
Q

What is considered as a negative circumferential resection margin?

A

> 1mm

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20
Q

What is the no. Of LN retrieved dependent on?

A

Age
Gender
Tumor grade
Tumor site

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21
Q

What are considered tumor clusters?

A

These are

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22
Q

What are the criteria to render a rectal cancer amenable for transanal excision?

A

3mm)
Mobile, not fixed
Within 8cm of anal verge
T1 only (i.e. Does not invade beyond Submucosae)
Endoscopic ally removed polyp with cancer/indeterminate pathology
No LVI
No PNI
Well-to moderately differentiated
No evidence of LN on pretreatment imaging

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23
Q

What are the ways in which concurrent ChemoRT can be given for 5FU?

A

1) RT + CI5FU
- 5FU (225) over 24 hours
- 5-7 days a week during RT

2) RT + Cape
- Cape (825) BD, 5 days a week
- RT for 5 weeks

3) RT + 5FU/Leucovorin
- Bolus 5FU (400) + Bolus Leucovorin (20)
- 4 days, Week 1 and Week 5 of RT

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24
Q

What should RT in Rectal Ca encompass ?

A
  • Tumor/Tumor Bed with a 2-5cm margin
  • Presacral nodes
  • Internal iliac LN
  • External Iliac LN if T4 tumors which involved anterior structures.
  • Perineal wound if APR done
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25
Q

How is MMR deficiency detected?

A

As changes in the length of repetitive DNA elements in tumor tissue caused by the insertion deletion of repeated units

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26
Q

How is Lynch syndrome detectable by?

A

1) IHC analysis for MMR protein expression
- often diminished because of mutation

2) Analysis for micro satellite instability
- This results from MMR deficiency
- detected as changes in the length of repetitive DNA elements in tumor tissue, which is caused by the insertion/deletion of repeated units

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27
Q

When MLH1 expression is absent, what does BRAF gene mutation indicate?

A

BRAF mutation indicates that MLH1 expression is down regulated through somatic methylation of the promote region of the gene, and NOT through a Germline mutation

28
Q

What does an Abdominoperineal resection (APR) include?

A 
En Bloc resection of the recto sigmoid, Rectum, anus
\+
Surrounding mesentery, mesorectum (TME)
\+ 
Perianal soft tissue
\+ 
Creation of a colostomy
29
Q

Any evidence for preop CRT?

A

Large prospective RCT from the German Rectal Ca Study group compared preop vs postop CRT in Stage II/III rectal Ca.

RESULTS: preop Therapy a/w:
- reduction in LR 6% v 13%
>>10y LR 7% vs 10%
- reduction in tx-associated toxicity 30% vs 40%
- ~OS
30
Q

What are the advantages of pre-op RT?

A

Reducing tumor volume may facilitate resection, increase likelihood of sphincter-sparing procedure

Surgery-naiive tissue is better oxygenated. Irradiating preop may result in increased sensitivity to RT

Preop RT can avoid the occurrence of radiation-induced injury to small bowel rapped in the pelvis. By post-surgical adhesions

Anastomosis remains unaffected by effects of RT as irradiated tissues resected

31
Q

What are the disadvantage of using preopRT?

A

Possibility over over-treating early-stage tumors that do not require adjuvant radiation

32
Q

What is the advantage of concurrent CRT?

A

Local RT sensitization
Systemic control of disease (eradication of micromet)

Preop CRT can also increase pCR rate

33
Q

What is the NSABP R-04 trial?

A

Cape = 5FU in periop CRT therapy.

N=1600, stage II/III rectal cancer

2x2 factorial:

10) Infusional 5FU +/- Ox
2) Cape +/- Ox

RESULTS:

  • no differences in local-regional events, DFS, OS, complete pCR, SSS, or surgical down staging
  • However, toxicity increased with inclusion of Ox.
34
Q

Cape = 5FU for CRT. True?

A

Yes

1) NSABP R-04
- O’connell et al
- n=1600; 2x2 factorial design
- 5FU+/-Ox vs Cape +/-Ox
- no difference in Local-regional events/DFS/OS/pCR/SSS/surgical down stating.
- Tox worse with Ox.

2) Hofheinz et al Lancet Onco 2012
N=400
2arms: 2#Cape-->CRT-->3#Cape vs 2#bolus 5FU-->CRT-->2#bolus 5FU
RESULTS:
- 5yOS in Cape non-inferior
- Cape with fewer distant met 20% vs 30%
35
Q

How is short-course radiation therapy administered?

A

25Gy in 5 fractions
Surgery within 1-2 weeks of completion of therapy
Not combined with chemotherapy

36
Q

What is the advantages of short-course RT and in which group of patients do we use this?

A

Gives effective local control and the same OS

T3N0 or T1-2N1-2 rectal Cancer
NOT recommended for T4 disease

37
Q

What evidence do you know for short-course RT?

A

1) Dutch TME trial
Peeters Ann Surg 2007

Aim: To invx efficacy of Short-course RT + Total mesorectal excision in resectable rectal CA

2 arms:

1) RT–>TME
- 5x5Gy
2) TME alone
* No chemo allowed in both arms.

RESULTS:
F/u 6 years
5y Local recurrence risk 6% vs 11% (RT) 
5y OS ~60%
ESP useful for: lesions 5-10cm from anal verge and for pts with uninvolved CRM
38
Q

What does a good response to neoadjuvant in rectal cancer tell us?

A

50-60% are down staged with neoadjuvant.
20% showing pCR

It predicts for:

  • OS
  • DFS
  • distant mets
  • response to neoadjuvant treatment response

MERCURY prospective cohort trial:

  • 100 patients assessed by MRI and pathologic staging
  • poor tumor regression grade had 5y OS 30% vs 70% in those with good regression grade.
  • DFS 30% vs 60%

CAO/ARO/AIO094 showed that pCR patients had:

  • 10y incidence of distant met 10% vs 40%
  • 10y DFS 90% vs 60%

EORTC 22921
- patients down staged to ypT0-2 were more likely to benefit from chemo cf to ypT3-4

39
Q

How is OS affected by the delay in adjuvant therapy?

A

2011 systematic review and meta-Analysis, n=15000

Each 4-week delay results in a 14% decrease in OS

40
Q

What do you know about recurrence scores in CLR CA?

A

Oncotype Dx colon cancer assay
quantifies the expression of 7 recurrence-risk genes and 5 reference genes as a prognostic classifier of low, intermediate, or high likelihood of recurrence.

Clinical validation done in QUASAR and NSABPC-07 trials
Recurrence scores are prognostic for recurrence, DFS and OS in stage II/III

Low risk = 3y recurrence 12%
Intermediate risk = 3y recurrence 18%
High risk = 3y recurrence 22%

41
Q

What are the options for T3-4 lesions/nodal involvement/locally Unresectable disease/medically inoperable patients?

A

T3-4/N0
Tany/N1-2
Locally Unresectable disease
Medically inoperable:

1) Chemo+Long-course RT–>resect if possible –> chemo
2) Short-course RT (not for T4) –> Resect if possible–>Chemo
3) Chemo–> CRT –> Resect if possible

42
Q

Radiation dose to small bowel should be limited to how much?

A

45Gy

43
Q

What is intraop RT (IORT) and when do we consider it?

A

IORT involves direct exposure of tumors to RT during surgery, while removing normal structures from the field of treatment.

Considered as an additional boost to facilitate resection.

Considered when:
T4 tumors
Recurrent cancers
Very close/positive margins

44
Q

What is an alternative to IORT?

A

10to 20Gy and/or brachytherapy to a limited volume

45
Q

How often do CLR CA patients p/w synchronous liver mets?

A

20-30%

46
Q

What are some of the liver-directed therapies that you know of?

A 
Hepatic arterial Infusion 
TACE (TransArterial ChemoEmbolization)
Liver-directed radiation 
- Radioembolization with microspheres
- Conformal (Stereotactic) EBRT 
Tumor Ablation 
- RFA
- Microwave ablation
- Cryoablation
- Percutaneous ethanol injection
- electro-coagulation
47
Q

What is Hepatic Arterial Infusion?

A

Placement of a hepatic arterial port or implantable pump during surgical intervention for liver resection
With subsequent infusion of chemotherapy directed to the liver mets through the hepatic artery.

48
Q

What is TACE?

A

TransArterial ChemoEmbolization involves hepatic artery catheterization to cause vessel occlusion with locally delivered chemotherapy

49
Q

How common is peritoneal Carcinomatosis in CLR CA?

A

20% of met CLR CA

2% having the peritoneum as the only site of disease

50
Q

What is the evidence for HIPEC?

What are the criticisms of this trial?

A

Verwaal JCO 2003

Aim: Confirm that aggressive CRS+HIPEC > palliative chemo +/- surgery

N=100
2 arms:
- systemic chemo (5FU based) +/- palliative surgery
- aggressive CRS+HIPEC–> same systemic chemo

RESULTS
2y f/u
Median survival 22m vs 13m

Criticisms:
- No Oxaliplatin/Irinotecan/molecular targets used
- peritoneal carcinomatosis origin from appendiceal, which is known to have better prognosis.
» retrospective study: peritoneal carcinomatosis from Colon median OS 30m vs 77m (appendiceal)

51
Q

What is the survival for stage I rectal CA?

A

80-90%

52
Q

What is the 5y survival for stage II Rectal CA?

A
53
Q

What is the LR rate after surgery alone in the following situations:

1) T1-2N0
2) T3N0
3) T3-4N1-2

A

1) T1-2N0 =

54
Q

What were the 3 trial that formed the basis on adjuvant therapy for rectal cancer in 1990s?

A

1) NSABP -R01
2) GITSG 7175
3) NCCTG-Mayo 794751

Came about because postop RT alone does not confer a survival advantage.

55
Q

Tell me about NSABP-R01

A

N=550
Dukes B and C rectal CA s/p curative resection.

3 arms:

1) observation
2) postop adjuvant chemo with MOF
- Semustine, Vincristine, 5FU
3) post-op RT

RESULTS:

1) Chemo>observation
- improvement in DFS and OS
2) Men>Female get the benefit from postop chemo
3) Younger>older
4) Postop RT reduced Loco-regional recurrence it failed to affect DFS and OS

56
Q

How did we prove CRT >RT?

A

NCCTG-Mayo 794751
NEJM 1991
Trial study evolved from GITSG group.

N=200
2 arms:
1) Post op RT
2) Post op CRT (Semustine+5FU)

RESULTS:
CRT had lower LR (50% reduction) and lower chance of death (30% reduction)

57
Q

What are the trials looking at CRT?

A

GITSG
NCCTG-Mayo 794751
Norwegian Adjuvant Rectal Cancer Project
NSABP-R02

58
Q

Tell me about the Norwegian Adjuvant Rectal Cancer Project Group

A

n=136

2 arms:

1) observation
2) postop 5FU+RT

RESULTS:
LR 10% vs 30% (Obs)
Better DFS 60%vs 50%
Better OS 60% vs 50%
No difference in distant mets
59
Q

Tell me about the NSABP-R02

A

N=700
2 arms:
1) Postop CRT (RT + either MOF or 5FU/LV)
2) Postop chemo (either MOF or 5FU/LV)

RESULTS:
5FU/LV had a longer DFS compared to MOF
Addition of RT to adjuvant chemo improved local control 8% vs 13% but not survival 60%

60
Q

What are the trials that talked about optimizing postop CRT?

A

(G.I.I.N.K)

1) GITSG 7180
2) INT 0114
3) INT 0144
4) NCCTG 864751
5) Korean study

61
Q

What is the GITSG 7180 about?

A

N=200
2arms:
1) Postop 5FU/RT -> 5FU/Semustine
2) Postop5FU/RT->5FU

RESULTS
N difference in OS, Semustine is not an essential component

62
Q

Tell me about NCCTG 864751 in rectal cancer

A

N=660
Stage II/III rectal cancer

All received 2# post-op chemo before and after CRT
2 arms:
1) Bolus 5FU
2) prolonged venous infusion

RESULTS:
Infusional 5FU/RT was a/w longer OS, RFS, and few distant mets wen compared to Bolus 5FU, no difference in LRC
No need for Semustine

63
Q

What is INT 0114 about?

A

JCO 2002
N=1700
Locally advanced rectal cancer

4 arms:

1) Postop 5FU + RT
2) Postop 5FU/LV + RT
3) Postop 5FU/LEV + RT
4) Postop 5FU/LV/LEV + RT

No difference in LR, RFS and OS
3-drug with more toxicity

64
Q

Tell me about INT 0144

A

JCO 2006
N=2000

3 arms:

1) 2# Bolus 5FU before and after PIV 5FU/RT
2) CI 5FU before after and during RT
3) 2# Bolus 5FU/LV/LEV before and after Bolus 5FU/RT

No difference in LR, RFS and OS
But toxicity lower past in PVI only arm

65
Q

What about the Korean study?

A

JCO 2002

N=300 resected stage II/III rectal CA
Randomized to t2 arms:
1) Early CRT (RT started with 1st cycle of chemo)
2) Late CRT (RT started with 3rd Cycle of chemo)

RESULTS:
10y f/u no difference in DFS/OS
But in subgroup requiring APR, early CRT had better DFS cf late CRT

66
Q

What is the evidence for using Capecitabine in rectal CA

A

German Phase III Cap/RT study in Lancet 2012

N=400
Stage II/III rectal CA s/p TME surgery
2x2 factorial design

Asking 2 questions:

1) Cape vs Bolus 5FU
2) Preop vs postop CRT

In the neoadjuvant arm:
- Cap/RT –> Surgery –> CapeQ21d x5#
- 5FU/RT –> Surgery –> 5FUQ28d X4#
In the adjuvant arm:
- Surgery –> Cape 2# –> Cap/RT –> Cape 3#
- Surgery –> 5FU 2# –> 5FU/RT –> 5FU 2#

RESULTS:
1) Capecitabine non-inferior to 5FU for OS
- 5y OS 76% vs 67%
- Similar DFS and LR
>3yDFS 75%vs 67%
>LR 6% vs 7%
- Fewer patients developed distant mets in Cape group 20% vs 30%
- Cape a/w more HFS, fatigue and proctitis but less leukopenia
2) In the neoadjuvant arm, ape a/w higher rate of down-staging

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