[ROQs] GI, Rectal/Anal Flashcards
What was the pCR rate on the German rectal cancer trial for pre-op chemoRT?
- 8%
- Far lower than on most trials, which report ~ 15%
What was the pCR in the RAPIDO trial for the standard arm?
14%
What is the pCR in the RAPIDO trial for the TNT arm?
28%
What is the TF rate in the RAPIDO TNT vs. standard arms?
23.7% vs. 30.4%, favoring TNT
Did RAPIDO differ in LR, DM, or OS b/w TNT and standard arms?
- DM better w/ TNT
- No diff in LR or OS
What were the 2 arms of the RAPIDO trial?
- 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)
What was the dose-response relationship between cycles of neoadjuvant chemo after LC-CRT (TNT) and pCR in the Aguilar (Lancet Oncol 2015) trial?
Cycle # → pCR
- 0 → 18%
- 2 → 25%
- 4 → 30%
- 6 → 38%
- However, adding cycles of chemo increases grade 3 and 4 heme tox
What were the results of the RAPIDO trial?
Note NS diff in OS
What did the 5-yr update of the RAPIDO trial show?
Increased LRR w/ TNT, indicating the need to refine TNT
How do we manage diarrhea during pelvis RT?
What is the main takeaway about sphincter-preserving surgery rates between the two arms of the German rectal cancer trial?
- 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.
What were the two arms of the German rectal cancer trial?
- 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
What were the rates of 10-yr LR in the German Rectal Ca trial?
What is one disadvantage of pre-op CRT in light of the German rectal cancer trial?
20% of clinical T3 and/or N1 tumors will be pT1-2 N0 at surgery and would not have required multi-modal treatment
What were the rates of acute and late G3-4 tox in the German rectal CA trial?
Top Row: Pre-op
Bottom Row: Post-op
What are the anterior-posterior borders for the 3D Rectal Ca RT field?
What are the lateral field borders for the 3D Rectal Ca RT field?
Which MRI sequence is best for the T staging of rectal ca?
Rationale: Mesorectum has a higher water content → bright on T2
How do neoadjuvant vs. adjuvant chemoRT affect LR, DR, and OS in advanced rectal ca?
Neo-adjuvant CRT improves LR only
Does adjuvant CRT vs. chemo alone improve outcomes in locally advanced colon cancers post-surgery?
What were the results of the PROSPECT Study w/ respect to DFS, OS, and tx toxicities?
What were the results of the PROSPECT study w/ respect to PRO (2nd publication)?
What were the main takeaways of the PROSPECT study w/ respect to DFS and PRO?
What are the RT doses of pre-op and post-op CRT for locally advanced rectal cancer?
When is neoadjuvant chemoRT indicated for colon cancers (contrast w/ rectal cancers)?
What are the implications of the PROSPECT trial on TNT for tx of locally advanced rectal cancer?
- Unclear since the trial only pitched CRT w/o chemo against chemo alone
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?
When is EUS used instead of a pelvic MRI for T staging of rectal cancer?
Only when an MRI (pt has a PM, etc) is contraindicated.
What is the standard post-op RT dose for colon cancer being tx 2/2 +margins?
Do you get a PET scan for rectal cancer staging?
CT CAP is obtained, w/ PET only obtained if there are equivocal findings on the CT.
What is the minimum # of LNs removed for colon cancer to be considered adequate surgery?
12
What are the criteria for covering external iliac vessels in RT fields for rectal cancer?
- T4 disease
- Disease w/ anterior organ involvement
What is the anterior border of the mesorectum when contouring the CTV for a rectal cancer case?
Should extend by 1 cm into the bladder, vagina, or the prostate.
What is the difference in different oncologic metrics b/w LC CRT and SC CRT?
What are the colonoscopy guidelines for someone w/ Lynch syndrome (HNPCC)?
Colonoscopy q 1-2 yrs starting at 20-25
What are the colonoscopy guidelines for some with/ IBD (UC or Crohn’s)?
Annual colonoscopy 8-10 yrs after symptom onset
What are the colonoscopy guidelines for someone w/ FAP?
Elective colectomy or proctocolectomy after the onset of polyposis.
Which mutations are a/w Lynch syndrome?
- MLH1
- MSH2
- MSH6
- PMS2
What are the colonoscopy guidelines for someone w/ a family hx of colon cancer?
What are the colonoscopy guidelines for someone w/ Peutz-Jeghers syndrome?
Colonoscopy q 2-3 yrs beginning at age 18
What is the N1c LN stage for rectal cancer?
What are the different LN stages for rectal cancer?
What are the different T stages of colorectal cancer?
Why is the Swedish trial the only trial to show an OS benefit to neoadjuvant RT?
Which study did not show a benefit to IMRT in rectal cancer?
RTOG 0822
What was the pt population and the tx delivered on RTOG 0822 trial for rectal cancer?
- 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
What were the result of RTOG 0822 for rectal cancer?
- Gr 2+ GI toxicity
– 51.5% vs. 57.7% per RTOG 0247 historical control (NS)
What is one possible explanation for the lack of +ve results on RTOG 0822 for rectal cancer?
Results could be confounded by oxaliplatin, which has Gl effects such as nausea, vomiting,
and diarrhea.
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?
The study used concurrent capecitabine and oxaliplatin (ox has GI side-effects of its own and could be a potential confounder)
How was IMRT delivered in RTOG 0822?
45 Gy IMRT f/b 5.4 Gy 3D boost
How is the boost field contoured for pre-op rectal cancer tx?
- 2-3 cm GTV Expansion
- Entire sacral hollow
What are some of the benefits of delaying surgery after SC CRT for rectal cancer?
- Improved pCR (44% vs. 13%, Polish 2012)
- Reduced post-op complications (41% vs. 53%, Stockholm III 2017)
What was the pt population, randomization, and primary endpoint of Stockholm III trial for rectal cancer?
- 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:
What are the main results of Stockholm III trial for rectal ca?
- Time to LR and pCR were best with short course plus delay
- There is some dispute regarding how to interpret the toxicity results.
What were the results of the GITSG 7175 trial comparing the addition of different adj tx to surgery?
OS w/ surg + chemoRT + adj RT was the only statistically sig. OS result. This benefit was eliminated in updated publications.
Is RT for GI cancers consistently a/w a risk of secondary cancers?
No, but this is likely 2/2 tx of subclinical PCa at the same time as the orig rectal cancer.
What does FOLFOX consist of?
- Folinic Acid
- 5-FU
- Oxaliplatin
What is the dose-limiting tx of 5-FU?
- Heme (more common w/ bolus)
- Mucositis
- Hand-foot syndrome (more common w/ CVI)
How is continuous PVI 5-FU dosed during CRT for rectal ACA?
225 mg/m2 over 24 hours for 5 or 7 days a week during radiation
Which enzyme deficiency predisposes pts to higher toxicity w/ 5-FU?
Dihydropyrimidine dehydrogenase (DPD)
How many cases of CRC are diagnosed in the UR in a year?
- ~ 150,000
– ~ 50,00 are rectal
– ~ 105,00 are colon
What were the two arms of the Nigro protocol?
30/15
What are the superior and inferior borders of the inguinal LNs CTV?
- Superior: When the external iliac artery becomes the femoral artery at the level of the bony pelvis.
- Inferior: Level of the lesser trochanter
What is the chemo regimen for definitive tx of anal DqCC?
What are the 5-yr results of RTOG 9811 for Anal SqCC?
According to the Anal SqCC RTOG 9811 subset analysis, how do OS, DFS, and colostomy rates depend on T and N staging?
What was the pt population and randomization for RTOG 9811 for rectal cancer?
What is the salvage therapy for Anal SqCC?
APR
What is the follow-up schedule for Anal SqCC pt’s after a great response to definitive CRT?
What are the three most common appendiceal tumors?
What were the treatment arms of RTOF 8704 for Anal SqCC?
What is the benefit of TME vs. non-TME surgical approaches for rectal cancer?
- 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
What were the results of RTOG 8704 for Anal SqCC?
What was the pt population, randomization, and primary endpoint of the ACT II trial for anal SqCC?
- 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
Per the post hoc analysis of ACT II, what is the optimal time to assess tx response to CRT for anal SqCC?
26 wks from the start of CRT (6.5 mos)
What subset of tumors of the anal canal and peri-anal skin can be tx w/ WLE ± CRT (if inadequate margins) alone?
What is an adequate resection margin for T1N0 SqCC of the peri-anal skin?
> 1 cm
What tumors of the anal canal can be tx w/ local excision only?
- < 3 mm invasion past basement membrane
- < 7 mm horizontal spread
Where do anal tumors inferior to the dentate line drain?
Inguinal LNs
Where do anal tumors superior to the dentate line drain?
- Along hemorrhoidal vessels
– Perirectal LNs
– Internal Iliac LNs
What is the T staging for anal cancers?
What is the N staging for anal cancer?
How do we assess clinical response to CRT for anal SqCC?
How long should a patient be followed while assessing for a CR for anal SqCC tx w/ CRT?
≥ 6 mos
What is the IMRT dosing for high-risk (T3/T4 or N+) anal SqCC?
What is the IMRT dosing for low-risk (T1/T2) anal SqCC?
When should a dose of 59.4 Gy to the primary be considered for anal SqCC?
What is the best simulation position for anal cancer pts?
- 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.
What are some simulation considerations for anal ca?
- 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.
What are some of the risk factors for anal SqCC?
What were the results of the ACT II study for anal SqCC?
- Tested replacing MMC w/ cisplatin AND the role for maintenance CHT.
- CT ~ 90% at 26 wks w/ either regimen
What were the results of RTOG 9811 study for anal SqCC?
- 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
Why have there been so many studies to replace MMC w/ other drugs for CRT for anal SqCC?
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.
What is the benefit of using IMRT over 3D for anal SqCC?
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
What is the main benefit of adding radiosensitizing chemotherapy to CRT for anal SqCC?
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.
What is the salvage therapy for locally recurrent anal SqCC s/p definitive CRT?
- APR
- Because this is an effective salvage therapy, anal cancer trials only demonstrate a difference in colostomy-free survival, but OS
When contouring inguinal LNs, what are the borders?
- 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.
What is the annual # of cases of anal cancers in the US?
~ 9,500
How is the management of anal adenocarcinoma different than SqCC?
- SqCC → treat w/ def CRT
- Adenocarcinoma (rare w/ worse prognosis) → treat like recta ca (aggressive)
What are the primary, secondary, and tertiary prevention methods for anal SqCC?
-
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
What is the follow-up regimen to assess tx response for anal SqCC?
- 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.
What are the practice defining trials for Anal SqCC?
- 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
What was the purpose of the ACT I Trial?
Concurrent chemo
What is the patient population of the ACT I Trial?
- 585
- Anal canal or anal margin SCC, incl. metastatic
- Excl. T1N0, prior tx
What are the arms of the ACT I Trial?
→🏆 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
What are the main results of the ACT I Trial?
- 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
What is the primary RadOnc interpretation of the ACT I Trial?
- Adding concurrent 5FU/MMC to RT improves outcomes and should be the standard of care
What percentage of anal cancers are SqCCs?
- ~ 80%
- Less common histologies include adenocarcinomas, etc
What are the typical 5 yr colostomy-free survival rates for Anal SqCC?
- 65-72%
- Note that both death and colostomy contribute to this number
Which pts may experience sig. increased tox w. 5-FU?
- 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
What is the drug that people w/ DPD deficiency should avoid?
5-FU/Capecitabine
What is the antidote for 5-FU toxicity?
- 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
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?
- Use a lower energy beam for the PA field!
How should capecitabine be timed w/ RT for neoadjuvant CRT for rectal cancer?
- 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)
How is capecitabine dosed for rectal cancer?
Dosed twice daily at 825 mg/m2 (1650 mg/m2 per day) when given concurrently w/ RT
What is the rationale behind celiac plexus RT for pain control for pt’s w/ abdominal malignancies?
- 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.
What are the surveillance recommendations for rectal ca?
- 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.
What % of pts undergoing CRT for rectal cancer experience ≥ Gr 3 or more tox?
1/3
What are some of the most common late toxicities of CRT for rectal cancer?
- Fecal incontinence; 44%
- Diarrhea; 27%
- Ulceration; 23%
What portions of the colon are retroperitoneal
- Ascending Colon
- Descending Colon
What was the pt population and randomization for the INT0130 trial for colon cancer?
- Resected colon cancer patients who are T4 at any location or T3N1/N2 in ascending or descending colon
- Randomization:
– adj. 5FU and levamisole ± RT
What were the results of the INT0130 trial for colon cancer?
- 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)”
What are the main criticism of the INT0130 trial for colon cancer?
- 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.
