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Rectal/Anal Flashcards

1
Q

What was the pCR rate on the German rectal cancer trial for pre-op chemoRT?

A
  • 8%
  • Far lower than on most trials, which report ~ 15%
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2
Q

What was the pCR in the RAPIDO trial for the standard arm?

A

14%

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3
Q

What is the pCR in the RAPIDO trial for the TNT arm?

A

28%

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4
Q

What is the TF rate in the RAPIDO TNT vs. standard arms?

A

23.7% vs. 30.4%, favoring TNT

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5
Q

Did RAPIDO differ in LR, DM, or OS b/w TNT and standard arms?

A
  • DM better w/ TNT
  • No diff in LR or OS
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6
Q

What were the 2 arms of the RAPIDO trial?

A
  • TNT
    – Short-course RT f/b 6/9 cycles of CAPOX/FOLFOX4 f/b TME)
  • Standard
    – Long-course chemoRT f/b surgery f/b TME f/b adjuvant CHT, if indicated (8/12 cycles of CAPOX/FOLFOX4)
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7
Q

What was the dose-response relationship between cycles of neoadjuvant chemo after LC-CRT (TNT) and pCR in the Aguilar (Lancet Oncol 2015) trial?

A

Cycle # → pCR
- 0 → 18%
- 2 → 25%
- 4 → 30%
- 6 → 38%
- However, adding cycles of chemo increases grade 3 and 4 heme tox

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8
Q

What were the results of the RAPIDO trial?

A

Note NS diff in OS

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9
Q

What did the 5-yr update of the RAPIDO trial show?

A

Increased LRR w/ TNT, indicating the need to refine TNT

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10
Q

How do we manage diarrhea during pelvis RT?

A
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11
Q

What is the main takeaway about sphincter-preserving surgery rates between the two arms of the German rectal cancer trial?

A
  • Sphincter-preserving surgery rates were not different b/w the two arms (~70%)
  • In pts deemed to require APR pre-op by a surgeon, sphincter-preserving surgery was performed in 39% of pre-op and 19% of post-op pts.
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12
Q

What were the two arms of the German rectal cancer trial?

A
  • Pre-op chemoRT
    – 50.4 Gy in 28 fx w/ concurrent 5-FU (1-5 d of wk 1 and 5)
  • Post-op chemoRT
    – 50.4/28 + 5.4/3
  • Everyone received adjuvant CHT
    – Bolus 5-FU x 5C
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13
Q

What were the rates of 10-yr LR in the German Rectal Ca trial?

A
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14
Q

What is one disadvantage of pre-op CRT in light of the German rectal cancer trial?

A

20% of clinical T3 and/or N1 tumors will be pT1-2 N0 at surgery and would not have required multi-modal treatment

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15
Q

What were the rates of acute and late G3-4 tox in the German rectal CA trial?

A

Top Row: Pre-op
Bottom Row: Post-op

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16
Q

What are the anterior-posterior borders for the 3D Rectal Ca RT field?

A
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17
Q

What are the lateral field borders for the 3D Rectal Ca RT field?

A
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18
Q

Which MRI sequence is best for the T staging of rectal ca?

A

Rationale: Mesorectum has a higher water content → bright on T2

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19
Q

How do neoadjuvant vs. adjuvant chemoRT affect LR, DR, and OS in advanced rectal ca?

A

Neo-adjuvant CRT improves LR only

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20
Q

Does adjuvant CRT vs. chemo alone improve outcomes in locally advanced colon cancers post-surgery?

A
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21
Q

What were the results of the PROSPECT Study w/ respect to DFS, OS, and tx toxicities?

A
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22
Q

What were the results of the PROSPECT study w/ respect to PRO (2nd publication)?

A
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23
Q

What were the main takeaways of the PROSPECT study w/ respect to DFS and PRO?

A
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24
Q

What are the RT doses of pre-op and post-op CRT for locally advanced rectal cancer?

A
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25
Q

When is neoadjuvant chemoRT indicated for colon cancers (contrast w/ rectal cancers)?

A
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26
Q

What are the implications of the PROSPECT trial on TNT for tx of locally advanced rectal cancer?

A
  • Unclear since the trial only pitched CRT w/o chemo against chemo alone
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27
Q

In the MSKCC experience (2019), what were the outcomes for NAT pts who underwent WW vs. surgical resection w/ respect to rectal preservation, LC, OS, DFS, DSS, and DM?

A
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28
Q

When is EUS used instead of a pelvic MRI for T staging of rectal cancer?

A

Only when an MRI (pt has a PM, etc) is contraindicated.

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29
Q

What is the standard post-op RT dose for colon cancer being tx 2/2 +margins?

A
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30
Q

Do you get a PET scan for rectal cancer staging?

A

CT CAP is obtained, w/ PET only obtained if there are equivocal findings on the CT.

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31
Q

What is the minimum # of LNs removed for colon cancer to be considered adequate surgery?

A

12

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32
Q

What are the criteria for covering external iliac vessels in RT fields for rectal cancer?

A
  • T4 disease
  • Disease w/ anterior organ involvement
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33
Q

What is the anterior border of the mesorectum when contouring the CTV for a rectal cancer case?

A

Should extend by 1 cm into the bladder, vagina, or the prostate.

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34
Q

What is the difference in different oncologic metrics b/w LC CRT and SC CRT?

A
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35
Q

What are the colonoscopy guidelines for someone w/ Lynch syndrome (HNPCC)?

A

Colonoscopy q 1-2 yrs starting at 20-25

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36
Q

What are the colonoscopy guidelines for some with/ IBD (UC or Crohn’s)?

A

Annual colonoscopy 8-10 yrs after symptom onset

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37
Q

What are the colonoscopy guidelines for someone w/ FAP?

A

Elective colectomy or proctocolectomy after the onset of polyposis.

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38
Q

Which mutations are a/w Lynch syndrome?

A
  • MLH1
  • MSH2
  • MSH6
  • PMS2
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39
Q

What are the colonoscopy guidelines for someone w/ a family hx of colon cancer?

A
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40
Q

What are the colonoscopy guidelines for someone w/ Peutz-Jeghers syndrome?

A

Colonoscopy q 2-3 yrs beginning at age 18

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41
Q

What is the N1c LN stage for rectal cancer?

A
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42
Q

What are the different LN stages for rectal cancer?

A
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43
Q

What are the different T stages of colorectal cancer?

A
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44
Q

Why is the Swedish trial the only trial to show an OS benefit to neoadjuvant RT?

A
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45
Q

Which study did not show a benefit to IMRT in rectal cancer?

A

RTOG 0822

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46
Q

What was the pt population and the tx delivered on RTOG 0822 trial for rectal cancer?

A
  • Resectable Rectal Ca
  • Phase II IMRT.
    – Comparison to RTOG 0247.
    – IMRT 45 Gy with 3DCRT boost to 5.4 Gy + concurrent cape/ox → surgery → FOLFOX
  • Primary EP
    – Improvement in ≥ Gr 2 GI tox
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47
Q

What were the result of RTOG 0822 for rectal cancer?

A
  • Gr 2+ GI toxicity
    – 51.5% vs. 57.7% per RTOG 0247 historical control (NS)
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48
Q

What is one possible explanation for the lack of +ve results on RTOG 0822 for rectal cancer?

A

Results could be confounded by oxaliplatin, which has Gl effects such as nausea, vomiting,
and diarrhea.

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49
Q

What is one possible explanation for the lack of an improved GI side effects profile w/ the use of IMRT vs. 3D for rectal cancer?

A

The study used concurrent capecitabine and oxaliplatin (ox has GI side-effects of its own and could be a potential confounder)

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50
Q

How was IMRT delivered in RTOG 0822?

A

45 Gy IMRT f/b 5.4 Gy 3D boost

51
Q

How is the boost field contoured for pre-op rectal cancer tx?

A
  • 2-3 cm GTV Expansion
  • Entire sacral hollow
52
Q

What are some of the benefits of delaying surgery after SC CRT for rectal cancer?

A
  • Improved pCR (44% vs. 13%, Polish 2012)
  • Reduced post-op complications (41% vs. 53%, Stockholm III 2017)
53
Q

What was the pt population, randomization, and primary endpoint of Stockholm III trial for rectal cancer?

A
  • Resectable rectal adenocarcinoma
    Randomization:
    – 25 Gy/5 fx then surgery in 1 week
    – 25 Gy/5 fx then surgery in 4-8 weeks
    – 50 Gy/25 fx with surgery in 4-8 wks
    – No chemo in any arm
  • Primary endpoint:
54
Q

What are the main results of Stockholm III trial for rectal ca?

A
  • Time to LR and pCR were best with short course plus delay
  • There is some dispute regarding how to interpret the toxicity results.
55
Q

What were the results of the GITSG 7175 trial comparing the addition of different adj tx to surgery?

A

OS w/ surg + chemoRT + adj RT was the only statistically sig. OS result. This benefit was eliminated in updated publications.

56
Q

Is RT for GI cancers consistently a/w a risk of secondary cancers?

A

No, but this is likely 2/2 tx of subclinical PCa at the same time as the orig rectal cancer.

57
Q

What does FOLFOX consist of?

A
  • Folinic Acid
  • 5-FU
  • Oxaliplatin
58
Q

What is the dose-limiting tx of 5-FU?

A
  • Heme (more common w/ bolus)
  • Mucositis
  • Hand-foot syndrome (more common w/ CVI)
59
Q

How is continuous PVI 5-FU dosed during CRT for rectal ACA?

A

225 mg/m2 over 24 hours for 5 or 7 days a week during radiation

60
Q

Which enzyme deficiency predisposes pts to higher toxicity w/ 5-FU?

A

Dihydropyrimidine dehydrogenase (DPD)

61
Q

How many cases of CRC are diagnosed in the UR in a year?

A
  • ~ 150,000
    – ~ 50,00 are rectal
    – ~ 105,00 are colon
62
Q

What were the two arms of the Nigro protocol?

A

30/15

63
Q

What are the superior and inferior borders of the inguinal LNs CTV?

A
  • Superior: When the external iliac artery becomes the femoral artery at the level of the bony pelvis.
  • Inferior: Level of the lesser trochanter
64
Q

What is the chemo regimen for definitive tx of anal DqCC?

A
65
Q

What are the 5-yr results of RTOG 9811 for Anal SqCC?

A
66
Q

According to the Anal SqCC RTOG 9811 subset analysis, how do OS, DFS, and colostomy rates depend on T and N staging?

A
67
Q

What was the pt population and randomization for RTOG 9811 for rectal cancer?

A
68
Q

What is the salvage therapy for Anal SqCC?

A

APR

69
Q

What is the follow-up schedule for Anal SqCC pt’s after a great response to definitive CRT?

A
70
Q

What are the three most common appendiceal tumors?

A
71
Q

What were the treatment arms of RTOF 8704 for Anal SqCC?

A
72
Q

What is the benefit of TME vs. non-TME surgical approaches for rectal cancer?

A
  • Improved LC
  • Improved OS in (retrospective studies)
  • Improved autonomic function due to a careful dissection and sparing of autonomic pelvic nerves
  • Concern about higher anastamotic leak rates
73
Q

What were the results of RTOG 8704 for Anal SqCC?

A
74
Q

What was the pt population, randomization, and primary endpoint of the ACT II trial for anal SqCC?

A
  • Anal SqCC, all stages
  • Tx:
    – 🏆 50.4 Gy RT w/ 5FU/MMC (1C)
    – 50.4 Gy RT w/ 5FU/Cis (60 mg/m2 x2)
  • Maintenance
    – 5FU/cis
    – 🏆 none
75
Q

Per the post hoc analysis of ACT II, what is the optimal time to assess tx response to CRT for anal SqCC?

A

26 wks from the start of CRT (6.5 mos)

76
Q

What subset of tumors of the anal canal and peri-anal skin can be tx w/ WLE ± CRT (if inadequate margins) alone?

A
77
Q

What is an adequate resection margin for T1N0 SqCC of the peri-anal skin?

A

> 1 cm

78
Q

What tumors of the anal canal can be tx w/ local excision only?

A
  • < 3 mm invasion past basement membrane
  • < 7 mm horizontal spread
79
Q

Where do anal tumors inferior to the dentate line drain?

A

Inguinal LNs

80
Q

Where do anal tumors superior to the dentate line drain?

A
  • Along hemorrhoidal vessels
    – Perirectal LNs
    – Internal Iliac LNs
81
Q

What is the T staging for anal cancers?

A
82
Q

What is the N staging for anal cancer?

A
83
Q

How do we assess clinical response to CRT for anal SqCC?

A
84
Q

How long should a patient be followed while assessing for a CR for anal SqCC tx w/ CRT?

A

≥ 6 mos

85
Q

What is the IMRT dosing for high-risk (T3/T4 or N+) anal SqCC?

A
86
Q

What is the IMRT dosing for low-risk (T1/T2) anal SqCC?

A
87
Q

When should a dose of 59.4 Gy to the primary be considered for anal SqCC?

A
88
Q

What is the best simulation position for anal cancer pts?

A
  • Supine frog leg position to reduce inguinal folds and reduce skin tox!
  • Bowel sparing is achieved via conformal IMRT.
  • Prone positioning w/ a belly board is more suitable for rectal ca where 3D techniques are utilized.
89
Q

What are some simulation considerations for anal ca?

A
  • Anal marker to delineate the anal verge.
  • Full bladder to displace the bowel superiorly.
  • Scan borders should be well above and below the field borders
    – ~L2/3 → below lesser trochanters.
  • Oral and rectal contrast.
  • If vaginal invasion, a vaginal marker should be placed at the cervix.
  • The inguinal node regions can be wired if treating clinically.
90
Q

What are some of the risk factors for anal SqCC?

A
91
Q

What were the results of the ACT II study for anal SqCC?

A
  • Tested replacing MMC w/ cisplatin AND the role for maintenance CHT.
  • CT ~ 90% at 26 wks w/ either regimen
92
Q

What were the results of RTOG 9811 study for anal SqCC?

A
  • Tested replacing MMC/5-FU w/ induction and concurrent cisplatin/5-FU
  • The use of induction cisplatin/5-FU but not 5-FU/MMC is a major criticism of the trial
93
Q

Why have there been so many studies to replace MMC w/ other drugs for CRT for anal SqCC?

A

Recall that although the original “Wayne State Nigro regimen” for anal cancer used infusional 5-FU/MMC, the role of MMC as an “ideal” choice of chemotherapy in this setting was called into question by the fact that MMC has no inherent radio-sensitizing properties, only modest activity against squamous cell cancers, and carries with it the risk of significant renal, pulmonary, and hematologic side effects.

94
Q

What is the benefit of using IMRT over 3D for anal SqCC?

A

IMRT offers substantial benefits over conventional radiation for patients undergoing concurrent chemoradiation for anal cancer, as demonstrated by this VA database study that showed:
- Higher rates of patients receiving 2 cycles of chemotherapy
- Decreased radiation treatment breaks
- Decreased rates of ostomy placement with IMRT

95
Q

What is the main benefit of adding radiosensitizing chemotherapy to CRT for anal SqCC?

A

Sensitizing chemotherapy improves LRC and colostomy free survival in patients anal cancer. With effective salvage management (APR) local recurrences are unlikely to cause a statistically significant survival detriment.

96
Q

What is the salvage therapy for locally recurrent anal SqCC s/p definitive CRT?

A
  • APR
  • Because this is an effective salvage therapy, anal cancer trials only demonstrate a difference in colostomy-free survival, but OS
97
Q

When contouring inguinal LNs, what are the borders?

A
  • Medial: 10- to 20-mm around the femoral vessels.
  • Lateral: Medial edge of the sartorius or iliopsoas muscle.
  • Cranial: Where external iliac artery becomes the femoral artery at the level of the bony pelvis.
  • Caudal: Many definitions:
    – The position where the great saphenous vein enters the femoral vein with a margin (2 cm caudad).
    – Where the muscles of sartorius and adductor longus muscles cross.
    – Compromise: lower edge of the ischial tuberosities, which lies between 1 and 2 as described defined above.
98
Q

What is the annual # of cases of anal cancers in the US?

A

~ 9,500

99
Q

How is the management of anal adenocarcinoma different than SqCC?

A
  • SqCC → treat w/ def CRT
  • Adenocarcinoma (rare w/ worse prognosis) → treat like recta ca (aggressive)
100
Q

What are the primary, secondary, and tertiary prevention methods for anal SqCC?

A
  • Primary: Interventions before there is any evidence of disease (anal cancer or precancerous lesions)
    – HAART in HIV+ PTS
    – HPV Vax
  • Secondary: Screening programs for individuals at increased risk of high-grade
    AIN and anal cancer and the treatment of precancerous lesions
  • Tertiary: Dx and early and effective treatment of invasive cancer, to reduce morbidity and mortality
101
Q

What is the follow-up regimen to assess tx response for anal SqCC?

A
  • DRE at 8-12 wks, then q4 wks until CR
  • Once a CR is achieved
    – DRE and inguinal node palpation q3-6 mos for next 5 yrs
    – Anoscopy q6-12 mos for 3 yrs
    – CT CAP annually for 3 yrs in patients who were T3-T4 or inguinal node positive.
    – Bx only after evidence of progression or significant clinical concern for residual disease.
102
Q

What are the practice defining trials for Anal SqCC?

A
  • Nigro Regimen
  • ACT I
    – CRT vs. RT
  • EORTC 22861
    – CRT vs. RT
  • RTOG 8704
    – CRT w/ 5-FU ± MMC
  • RTOG 9811
    – SOC CRT vs. induction + concurrent cisplatin
  • ACT II (2x2)
    – SOC CRT vs. concurrent -FU/Cisplatin
    – ± adj CHT (5-FU/Cisplatin)
  • RTOG 0529
    – Benefit of IMRT
103
Q

What was the purpose of the ACT I Trial?

A

Concurrent chemo

104
Q

What is the patient population of the ACT I Trial?

A
  • 585
  • Anal canal or anal margin SCC, incl. metastatic
  • Excl. T1N0, prior tx
105
Q

What are the arms of the ACT I Trial?

A

→🏆 RT concurrent 5FU/MMC
vs.
→RT alone

  • RT 45 Gy/20-25 fx. 6 weeks after RT, boost given if >50% response with 15 Gy photons or 25 Gy brachy.
  • RT given AP/PA to anus and inguinal LN
106
Q

What are the main results of the ACT I Trial?

A
  • Risk of anal CA-related death improved though no OS advantage.
  • CFS also improved.

– yr LC 66% CMT vs. 41%.
– 12-yr LRC 66% vs. 42%
– 12-yr CFS 30% vs. 20%
– 12-yr OS 33% vs. 27% (NS)
– In the first five years of CRT, 9.1% increase in non-anal cancer deaths, disappearing in 10 years

107
Q

What is the primary RadOnc interpretation of the ACT I Trial?

A
  • Adding concurrent 5FU/MMC to RT improves outcomes and should be the standard of care
108
Q

What percentage of anal cancers are SqCCs?

A
  • ~ 80%
  • Less common histologies include adenocarcinomas, etc
109
Q

What are the typical 5 yr colostomy-free survival rates for Anal SqCC?

A
  • 65-72%
  • Note that both death and colostomy contribute to this number
110
Q

Which pts may experience sig. increased tox w. 5-FU?

A
  • Dihydropyrimidine dehydrogenase (DPD) deactivates > 80% of 5FU.
  • Pts w/ DPD deficiency (~5%) are at risk for profound and severe chemotherapy toxicities 2/2 excessive buildup of 5FU in the bloodstream.
    – Neutropenia
    – Diarrhea
    – Mucositis
111
Q

What is the drug that people w/ DPD deficiency should avoid?

A

5-FU/Capecitabine

112
Q

What is the antidote for 5-FU toxicity?

A
  • Uridine triacetate (Vistogard®) is an oral antidote for 5-FU overdose.
  • It is a pyrimidine analog which competitively inhibits cell damage and death caused by 5FU
113
Q

For a 3-field (Post, Lats x 2) rectal cancer tx plan w/ undercoverage of the pre-sacral space, how can you increase dose to the this space?

A
  • Use a lower energy beam for the PA field!
114
Q

How should capecitabine be timed w/ RT for neoadjuvant CRT for rectal cancer?

A
  • Capecitabine reaches peak concentrations 1-2 hours after ingestion and concentrations rapidly decrease thereafter
  • It is dosed twice daily at 825 mg/m2 (1650 mg/m2 per day) when given concurrently
  • Capecitabine 1 hr before RT had higher rates of complete regression of primary tumors (23.5% vs. 9.6%, p=0.01), good response (44.7% vs.
    25.2%, p=0.006), and lower T stages at resection (p=0.021)
115
Q

How is capecitabine dosed for rectal cancer?

A

Dosed twice daily at 825 mg/m2 (1650 mg/m2 per day) when given concurrently w/ RT

116
Q

What is the rationale behind celiac plexus RT for pain control for pt’s w/ abdominal malignancies?

A
  • Celiac plexus is the main conduit for pain signals
  • SBRT: 25 Gy / 1 fx
    – 54% have at least a partial pain response.
    – Opioid usage decreases by 0.6 mg/d at 3 weeks (NS) and 16.9 mg/d at 6 weeks (p=0.005). – Well tolerated.
117
Q

What are the surveillance recommendations for rectal ca?

A
  • CEA q3-6 mos for 1 yr and q6 mos afterwards
  • CT CAP q6-12 mos for the first 5 yrs
  • Colonoscopy a year after surgery.
118
Q

What % of pts undergoing CRT for rectal cancer experience ≥ Gr 3 or more tox?

A

1/3

119
Q

What are some of the most common late toxicities of CRT for rectal cancer?

A
  • Fecal incontinence; 44%
  • Diarrhea; 27%
  • Ulceration; 23%
120
Q

What portions of the colon are retroperitoneal

A
  • Ascending Colon
  • Descending Colon
121
Q

What was the pt population and randomization for the INT0130 trial for colon cancer?

A
  • Resected colon cancer patients who are T4 at any location or T3N1/N2 in ascending or descending colon
  • Randomization:
    – adj. 5FU and levamisole ± RT
122
Q

What were the results of the INT0130 trial for colon cancer?

A
  • Underpowered, terminated early
  • No change in OS or DFS w/ adj CHT vs. CRT
    – 5-yr OS 62% vs. 58% (NS)
    – 5-yr DFS 51% in both (NS)
    – Grade ≥3 toxicity 42% vs. 54% (p=0.04)”
123
Q

What are the main criticism of the INT0130 trial for colon cancer?

A
  • Trial terminated due to poor accrual (222 out of planned 700 patients) → insufficient power.
  • Outdated CHT
  • LC not assessed.
  • RT was delivered to PA lymph nodes.
  • T3N1 may be too low risk to benefit from RT
  • No pre-op imaging or clips required to locate tumor.
  • Margins often not assessed on pathology.

GI (3 decks)

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