Cancer of the Colon and Rectum Flashcards by Mario Luna

Colorectal
(from PBRRO1)

Which is FALSE regarding the relationship of the colon and the peritoneum?

I. The posterior and superior surfaces of the ascending and descending colon are in direct contact with the retroperitoneum, whereas the anterior surface is draped with peritoneum.

II. The posterior attachments can prevent significant mobility, increasing the difficulty of surgical resection.

III. The transverse colon is completely surrounded with peritoneum and supported on a long mesentery.

IV. As the sigmoid colon evolves distally into the rectum, the peritoneal coverage
recedes.

I only
II only
III only
IV only
I & III only
II & IV only
III & II only
IV & I only
ALL

I only

It’s the posterior and “lateral” surfaces.

Uh-huh. yeah. ganyang klase ng tanongs.

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Colorectal
(from PBRRO1)

Which is FALSE regarding the relationship of the rectum and the peritoneum?

I. The upper one-third of the rectum is draped with peritoneum anteriorly and on both sides.

II. As the middle one-third of the rectum moves deeper into the pelvis, only the lateral surfaces are covered with peritoneum.

III. The lowest one-third of the rectum is devoid of peritoneal covering and in close proximity to adjacent structures, including the bony pelvis

II.

As the middle one-third of the rectum moves deeper into the pelvis, only the anterior surface is covered with peritoneum, which forms the posterior border of the rectouterine pouch or rectovesical space.

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Colorectal Cancer

Give 3 main risk factors for the development of rectal cancer?

increasing age
male sex
excessive alcohol intake

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Colorectal Cancer

Tumors possessing a high frequency of microsatellite instability have more favorable outcomes and lower likelihood of developing metastatic disease.

TRUE or FALSE?

may be more TRUE as studies suggest.

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Colon Cancer

Cancers of the right colon are often _______ and commonly associated with
___________ due to ___________, resulting in delayed diagnosis.

Cancers of the left colon and sigmoid colon are often deeply invasive and annular (“apple core lesions”) and commonly presents with ___________.

Right
exophytic; iron deficiency anemia; occult blood loss

Left
obstruction, rectal bleeding, and alteration in bowel habits.

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Colorectal Cancer

Age to start screening in the general population (average-risk)

Also in patients with single, first-degree relative with CRC diagnosed after 60y.

50y

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Colorectal Cancer

Age to start screening in patients with FAP?

10 to 12 years until 35 to 40 if negative.

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Colorectal Cancer

Age to start screening in patients with HNPCC?

20 to 25 years

or 10 years prior to earliest familial CRC diagnosis.

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Colorectal Cancer

Age to start screening in patients with IBD?

8 to 10 years after initial diagnosis

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Colorectal Cancer

Given the data in favor of screening, health organizations such as the
American Cancer Society (ACS), the United States Preventive Services Task
Force, and the American College of Radiology recommend screening in
average-risk individuals starting at age 50.

What are the tests advocated by the ACS that
detect adenomatous polyps and cancer?

Flexible sigmoidoscopy every 5 years.
Double-contrast barium enema every 5 years.
Computed tomography (CT) colonography every 5 years.
Colonoscopy every 10 years.19
Guaiac-based fecal occult blood, fecal immunohistochemical, and stool DNA
tests may be performed for CRC, but not polyp, detection

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Colorectal Cancer

CT appears to be more useful in identifying enlarged pelvic lymph nodes and metastasis outside the pelvis than the extent or stage of the primary tumor.

Why is CT limited in its utility in the assessment of smaller primary cancers?

CT does not permit the visualization of the layers of the rectal
wall

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Colorectal Cancer

The ability of CT scans for
detecting distant metastasis (DM), including pelvic and para-aortic lymph nodes, is higher than for detecting perirectal nodal involvement. Therefore, any lymphadenopathy near the rectum seen on a CT scan should be considered abnormal.

TRUE or FALSE?

True

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Colorectal Cancer

For rectal malignancies, endoscopic ultrasound (EUS) or pelvic magnetic resonance imaging (MRI) can assess primary disease and evaluate nodal extent.

What are the advantages of MRI vs. EUS?

less operator dependent
able to assess proximal and stenotic tumors
able to to visualize lymph nodes outside the perirectum (larger field of view)
able to characterize lymph nodes other than from size-basis.
able to determine lateral extent of disease

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Colorectal Cancer

What is the preferred imaging procedure (test of choice) to evaluate hepatic metastases in patients with CRC?

A. CT scan of the liver with contrast
B. Liver MRI
C. Liver ultrasound
D. PET-CT scan

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Colorectal Cancer

Prognostic factors influencing survival in CRC

depth of invasion into and beyond bowel wall

number of involved RLN

+/- distant metastases

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Colorectal Cancer

2017 AJCC staging.
Identify the T-stage:

Invasion of the lamina propria

Tis

Carcinoma in situ

intraepithelial (intramucosal)

invasion of lamina propria (without extension through the muscularis mucosa)

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Colorectal Cancer

2017 AJCC staging.
Identify the T-stage:

Tumor invades muscularis propria

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Colorectal Cancer

2017 AJCC staging.
Identify the T-stage:

Tumor invades muscularis mucosa

Tumor invades submucosa (through the muscularis mucosa but not into the muscularis propria)

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Colorectal Cancer

2017 AJCC staging.
Identify the T-stage:

Tumor invades through the muscularis propria into the pericolorectal tissues

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Colorectal Cancer

2017 AJCC staging.
Identify the T-stage:

Tumor invades through the visceral peritoneum

T4a

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Colorectal Cancer

2017 AJCC staging.
Identify the N-stage:

7 or more regional lymph nodes

N2b

N2 is 4 or more
therefore 4-6 is N2a

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Colorectal Cancer

2017 AJCC staging.
Identify the N-stage:

2-3 regional lymph nodes

N1b

N1a is 1 regional lymph node

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Colorectal Cancer

2017 AJCC staging.
Identify the N-stage:

No regional nodes, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues

N1c

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Colorectal Cancer

2017 AJCC staging.
Identify the M-stage:

2 or more sites or organs

M1b

m1a is one organ
m1c is peritoneal surface with or without organ metastases

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Colorectal Cancer 2017 AJCC staging. Identify the stage group: T3 N0 M0

IIA

Colorectal Cancer 2017 AJCC staging. Identify the stage group: T2 N0 M0

stage I T1-2 N0 M0 are both stage I

Colorectal Cancer 2017 AJCC staging. Identify the stage group: T4a N0 M0

IIB T4b N0 M0 is IIC

Colorectal Cancer What is Dukes C in staging?

any node+

Colorectal Cancer What is Dukes B in staging?

locally advanced but node negative. T3-T4b N0 M0

Colorectal Cancer What is the main change from AJCC 2010 to 2017?

addition of M1c

Colon Cancer How many lymph nodes should be excised for adequate staging?

Colon Cancer The addition of chemotherapy in resected stage III (node +) colon cancers resulted in improved OS and DFS. What are the standard combinations of chemotherapeutic agents being used?

FOLFOX (folinic acid/FU/oxaliplatin) XELOX (capecitabine/oxaliplatin)

Colon Cancer The addition of irinotecan (FOLFIRI) to folinic acid+FU in the adjuvant setting showed improved DFS. TRUE or FALSE?

False. No OS or DFS benefit

Colon Cancer Based on the MGH experience, T4 tumors significantly benefit from adjuvant RT compared to T3 tumors who received adjuvant RT when compared to non-irradiated population. TRUE or FALSE?

TRUE. Both benefited, however, only T4 tumors significantly benefited.

Colon Cancer Adjuvant RT What is the initial dose to large fields?

45/1.8/25

Colon Cancer Adjuvant RT What is the total dose for T4 tumors?

50 to 60 Gy

Colon Cancer Adjuvant RT Dose limit for the kidney?

at least 2/3 of one functional kidney should receive no more than 18 to 20 Gy

Colon Cancer Adjuvant RT Dose limit for the liver?

2/3 of the total liver should not receive >30 Gy

Colon Cancer Adjuvant RT BONUS: Dose limit for the spinal cord and small bowels?

45 Gy

Colon Cancer Adjuvant RT Margins for RT volumes?

4 to 5 cm proximally and distally 3 to 4 cm laterally

Rectal Cancer The rectum extends __ to __ cm from the anal verge.

12 to 15 cm.

Rectal Cancer Which is/are TRUE regarding the anorectal ring? I. Marks the beginning of the true surgical rectum II. Represents the internal anal sphincteric muscle and is necessary for anal continence III. Represents the practical inferior limit for functional sphincter preservation surgery IV. defines the lymphatic watershed for rectal cancer spread

all

Rectal Cancer The prognosis of patients worsens with more distal location of cancer. TRUE or FALSE?

True.

Rectal Cancer What is the landmark for the superior border of the proximal rectum?

S3 | -level of peritoneal reflection

Rectal Cancer What is an endoscopic landmark that can differentiate tumors into proximal and distal? This is about 6 cm from the anorectal ring.

middle valve of Houston

Rectal Cancer What are the main factors predictive of recurrence?

depth of invasion number of nodes

Rectal Cancer What are the prognostic factor for survival?

T-stage

Rectal Cancer What is the margin considered adequate in the surgical management of rectal cancers?

2 cm. *** Historically, the distal and proximal resection margins were considered important determinants in outcome, and a 5-cm distal margin of normal rectum was considered necessary for adequate surgical resection.114–116 However, several retrospective studies have shown that distal intramural spread of tumor is rare beyond 1.5 cm, and, therefore, a 2-cm distal margin is generally considered acceptable, except in lesions that are poorly differentiated or widely metastatic.

Rectal Cancer What must be the distance of T1 tumor from the anal verge in order to be amenable for a transanal approach to resection?

<8 cm

Rectal Cancer Identify the study/group being described: examined the efficacy of local excision in patients with distal cancers. Patients that are T1 or 2, low grade, ≥3mm margins, no LVI and no large nodes are observed. The rest underwent adjuvant RT to 59.4 to 65 Gy and 5-FU. None of the T1 tumors receiving postoperative treatment relapsed, compared to one DM and one LR in the T1 observation arm. Five patients in the T2 group relapsed (2 local, 1 distant, 2 both), and 4 patients in the T3 group had recurrence (1 distant, 3 both). Therefore, 20% of T2 and 23% of T3 tumors experienced LR after local excision plus chemoradiation (CRT).

RTOG 89-02

Rectal Cancer Identify the study/group being described: provides some support for postoperative CRT after local excision for appropriately selected early stage rectal cancers. T1 disease were treated with local excision alone T2 disease received adjuvant therapy with 54 Gy and 5-FU At 10 years, LR, DFS, and OS were 8%, 75%, and 84%, respectively, in T1 tumors. For T2 tumors LR, DFS, and OS were 18%, 64%, and 66%, respectively. This study supports the possibility of conservative sphincter-sparing surgery for well-selected T1 lesions, but for T2 tumors, the high rate of LR despite CRT warrants caution.

CALGB 8984

Rectal Cancer Identify the study/group being described: Although the observed 3-year DFS was not as high as anticipated, the investigators suggested that neoadjuvant chemoradiotherapy followed by local excision might be considered as an organ-preserving alternative in carefully selected patients with clinically staged T2N0 tumors who refuse or are not candidates for transabdominal resection.

ACOSOG study

Rectal Cancer When using APR as the surgical approach, how much distal margin of normal rectum with normal function should be preserved for optimal bowel function?

2 cm

Rectal Cancer What is the "gold" standard surgical procedure for distal cancers that requires a complete proctectomy (along with the tumor) that leads to a permanent colostomy?

APR

Rectal Cancer Emerging as the new standard procedure for all radical rectal cancer resections which involves en bloc removal of the tumor within the envelope of the endopelvic fascia as necessary to obtain adequate lateral clearance of disease and reduced likelihood of LR. Multiple series using this approach have reported low rates of LR (ranging from 5% to 10%) and an improvement in OS approaching 80% to 85% for stage II and 65% to 70% for stage III disease.

TME

Rectal Cancer What two trials/group demonstrated a survival benefit with the addition of postoperative CRT?

GITSG | NCCTG

Rectal Cancer Which trials/group that demonstrated a survival benefit with the addition of postoperative CRT used 40 to 50.4 Gy of RT?

Mayo-NCCTG The Mayo–NCCTG study compared postoperative radiation therapy against postoperative CRT. Two hundred four patients with T3/T4 or node-positive tumors received one cycle of 5-FU and semustine before randomization. The radiation dose was 45 to 50.4 Gy to tumor bed and adjacent lymph node regions. Bolus 5-FU (500 mg/m2) was administered concurrently with radiotherapy. The 5-year locoregional failure was higher in the radiation-only arm, 25% versus 13%, and the 5-year OS was 40% versus 55% (in favor of CRT). Postoperative CRT reduced recurrence by 47%, LR by 46%, and DM by 37%. Cancer deaths were reduced by 36%, and overall deaths were reduced by 29%.

Rectal Cancer What study compared bolus vs. continuous infusion 5-FU and found 27% improvement in RFS in favor of CI. They also showed an improvement in 4-year OS also in favor of CI. The time to relapse and DM rate were also lower. No difference in LR

NCCTG 86-47-51

Rectal Cancer What study on adjuvant treatment showed that semustine was of no additional benefit beyond 5-FU chemotherapy?

NCCTG 86-47-51

Rectal Cancer What study on adjuvant treatment showed that levimasole was of no additional benefit beyond 5-FU chemotherapy?

Intergroup 0114

Rectal Cancer What are the treatment arms of the SWEDISH rectal cancer trial that included Dukes A to C from 1987 to 1990?

surgery alone vs RT 25/5/5 (1 week) followed by surgery after 1 week

Rectal Cancer What are the results of the SWEDISH rectal cancer trial that included Dukes A to C from 1987 to 1990?

5-yr decreased LR, improved OS that persisted after long-term follow-up. 5-year LR (11% vs. 27%) 13-year LR (9% vs. 26%) ``` 5y OS (58% vs. 48%) 13y OS (38% vs. 30%) ``` all stages benefited.

Rectal Cancer What are the caveats of the SWEDISH rectal cancer trial that included Dukes A to C from 1987 to 1990?

surgery alone arm did not use TME high RT dose/fx --> high late toxicity short interval from RT to surgery

Rectal Cancer What study improved on the time interval factor from preop RT to surgery? This study randomized patients to surgery within 2 weeks of RT vs at 6-8 weeks post RT.

French trial, Lyon 90-01

Rectal Cancer RT dose used in the Lyon 90-01

39 Gy in 3 Gy/fx

Rectal Cancer What is the significant finding of Lyon 90-01?

``` pathologic downstaging (10% vs. 20%) in favor of the longer interval (6-8 weeks vs. 2 weeks) ``` LC and OS are similar pCR was lower in the shorter time but not statistically significant.

Rectal Cancer What are the treatment arms of the Dutch trial (CKVO 95-04) that evaluated preoperative RT vs. surgery?

TME alone vs. 25 Gy/5 fx followed by TME.

Rectal Cancer What are the results of the Dutch trial (CKVO 95-04)?

``` similar OS (82%) at 2 years. 2year LR was 2.4% in the RT arm vs. 8.2% in the surgery alone arm ``` This LR benefit persisted after 10 year follow up (5% vs. 11%).

Rectal Cancer Long-term follow-up of the Dutch trial (CKVO 95-04) showed poorer QOL in the preop arm. TRUE or FALSE?

True. higher incidence of sexual dysfunction and slower recovery of bowel function, more fecal incontinence, and generally poorer quality of life

Rectal Cancer What are the two early trials on neoadjuvant CRT?

French Study 9203 | EORTC 22921

Rectal Cancer | What are the treatment arms of French study 9203? resectable T3-4 accessible by DRE

RT alone (45 Gy) vs. RT + bolus5FU + LV +adjuvant

Rectal Cancer What are the treatment arms of EORTC 22921?

2x2 design RT alone (45 Gy) vs. RT (45 Gy) + 5-FU + LV patients further randomized to 5-FU/LV or no adjuvant therapy

Rectal Cancer What are the results of neoadjuvant CRT trials (EORTC 22921 and French 9203)?

no difference in OS compared to RT alone. increased pCR decreased LR

Rectal Cancer What study/group demonstrated that there were no differences were observed in local efficacy between 5 × 5 Gy with consolidation chemotherapy and long-course chemoradiation. The investigators concluded that an improved OS and lower acute toxicity favored the 5 × 5-Gy schedule with consolidation chemotherapy.

Polish rectal cancer group trial

Rectal Cancer This trial evaluated both fracionation and timing after RT to surgery in patients with resectable cancer. 5x5 +surgery 1w vs. 5x5 +surgery4-8 vs. 50/25 +surgery 4-8w

Stockholm III

Rectal Cancer What are the results of the Stockholm III trial?

no difference in 3y LR increase in RT related toxicity in short course significant decrease in postop complications in short course

Rectal Cancer What enzyme is required by capecitabine for it to be converted to the active form of 5-FU within the cells?

thymidine phosphorylase (TP)

Rectal Cancer What are the results of the German trial which compared capecitabine and FU, in terms of OS, DFS, LR, and DM?

Noninferior 5y OS 3y DFS better Similar LR lesser DM all in favor of capecitabine

Rectal Cancer | What are the adverse reactions to capecitabine and FU? Which are more common in which? based on the German trial

Diarrhea was the most common adverse event in both groups (any grade, 53% patients in the capecitabine group vs. 44% in the fluorouracil group; grade 3 to 4, 9% vs. 2%). Patients in the capecitabine group had more hand–foot skin reaction, fatigue, and proctitis than did those in the fluorouracil group, whereas leukopenia was more frequent with fluorouracil arm

Rectal Cancer What trial showed the definitive evidence in favor or pre-operative vs. postoperative RT in rectal cancer?

German CAO/ARO/AIO-94

Rectal Cancer What are the arms of German CAO/ARO/AIO-94?

T3-4, N+ randomized to: CRT (FU and 50/28) followed by TME vs. TME followed by postoperative CRT (FU and 50.4/28 +5.4 boost)

Rectal Cancer What are the results of German CAO/ARO/AIO-94?

decreased pelvic recurrence rates (6% vs. 13%; .02) downstaging and lesser nodal positivity but similar OS and DFS

Rectal Cancer What is the result of the MRC CR07 regarding the use of selective post-operative CRT in patients with ≤1-mm circumferential margin?

inferior to upfront preop RT 5x5 or CRT (50/28)+FU).

Colorectal Cancer (from in-service bank) 28. Based on the American College of Radiology (ACR) guidelines for pretreatment staging of colorectal cancer, which among the following has the highest rating for locoregional staging? A. MRI pelvis (3T, with endorectal coil) with and without IV contrast B. US pelvis transrectal C. CT abdomen and pelvis with IV contrast

Colorectal Cancer (from in-service bank) ``` 29. For Questions 29-30: A 65 year old female presented with a 1-year history of alternating constipation and diarrhea and episodes of bright red blood per rectum. She sought consult with her GI who did a colostomy showing a bulky, fungating tumor at 12 cm FAV, with extension 15mm beyond the muscularis propria. Tumor was 1.5 away from the mesorectal fascia. There were no enlarged (>7mm) lymphadenopathies seen. What is the clinical T stage of and MRF status of the patient? A. T3c MRF+ B. T3c MRF- C. T3d MRF+ D. T3f MRF- ```

Colorectal Cancer (from in-service bank) 30. Further work-up of the above patient showed no evidence of metastatic disease. Your opinion is needed in this patient’s cancer MDT. What would be your recommended treatment and rationale. A. Preoperative therapy (chemoradiation) is your preferred treatment for this patient as the German Rectal Cancer Trial by Sauer et al. showed OS benefit (7% benefit at 5 years, 3% benefit after 10 years) with this approach versus upfront surgery and postoperative chemoradiation. B. Upfront surgery followed by postoperative chemoradiation is your preferred treatment since her the tumor is high in the rectum and because there is a risk of overestimating the clinical stage. C. Preoperative chemoradiation is your recommendation since a 20% (39% vs 19%) improvement in sphincter preservation was seen with this approach versus upfront surgery and postoperative chemoradiation in the German Rectal Cancer Trial by Sauer et al. D. Preoperative chemoradiation is your recommendation as the French FFCD 9203 (Gérard et al.) and the EORTC 22921 (Bosset et al.) trials showed improvement in LC/LRR and pCR rates without an OS benefit with this approach versus preoperative radiotherapy.

Colorectal Cancer (from in-service bank) 31. For Questions 31-32: A 70 year old male patient (ECOG 1) with rectal adenocarcinoma (4cm FAV) cT4aN+M0 (MRI-staged) was planned to undergo preoperative therapy by his cancer MDT. What preoperative regimen will you choose? A. Radiotherapy (50.4 Gy) with concurrent continuous infusion FU is preferred as the NCCTCG 86-47-51 (O’Connell et al.) showed improved survival and increased time to relapse (albeit with higher leucopenia) with the use of this concurrent regimen versus bolus FU. B. Radiotherapy (50.4 Gy) with concurrent FOLFOX chemotherapy as the German CAO/ARO/AIO-04 study (Rodel et al.) showed higher pCR rates (albeit with increased grade 3-4 diarrhea) with this concurrent regimen preoperatively versus FU alone. C. Radiotherapy (50.4 Gy) with concurrent daily capecitabine is an option, as the German trial by Hofheinz et al. showed non-inferior 5-year OS and superior 3-year DFS (albeit more hand-foot skin reactions and proctitis) with this concurrent regimen vs. FU).

Colorectal Cancer (from in-service bank) 32. The patient above underwent neoadjuvant therapy without issues. There was complete resolution of the previous complaint of hematochezia. Four weeks after completion of preoperative treatment, the patient underwent reassessment with colonoscopy, whole abdominal and chest CT scan, and contrast-enhanced pelvic MRI. There was no evidence of residual tumor on endoscopy (only a pale white scar). CT scan showed no evidence of any regional or distant metastatic disease. Only a slight residual wall thickening at the prior site of the tumor was seen on MRI. Which among the following statements is true? A. If watch and wait is being considered, diffusion-weighted imaging (DWI) can help differentiate residual tumor with postradiation changes and improve the sensitivity of determining complete response to neoadjuvant therapy. B. A PET scan will not help to improve the sensitivity in determining complete response to neoadjuvant treatment. C. Random biopsies of the prior tumor site can help determine if the patient has a pathologic complete response (pCR). D. Since he can be considered a clinical complete responder based on the definition of Habr Gama et al. from Brazil, watch-and-wait is currently the best treatment approach for him due to his age and the distal location of his tumor. He may be spared the morbidity of surgery and a permanent colostomy with little compromise to his oncologic outcomes.

Colorectal Cancer (from in-service bank) 34. Despite multiple retrospective series suggesting benefit with adjuvant radiotherapy for colon cancers with high risk features, radiotherapy is currently used rarely for this disease due to the results of the INT 0130 trial (Martenson et al). However, it is important to note that this study had several criticisms which preclude the development of any definitive conclusions regarding the role of adjuvant radiotherapy for colon cancers. These criticisms include the following, EXCEPT A. Only 47% of the patients in the experimental arm received the complete course of adjuvant chemotherapy and might have affected the survival outcomes in this group. B. Only 19% underwent intraoperative clip placement and preoperative imaging was done in only 48% of the patients. C. Eighteen percent of the patients had their target volumes defined by clinical means only. D. The study was limited by poor accrual, accruing only a total of 222 patients of the initially planned 700 patients, with only 187 eligible and assessable.

Colorectal Cancer (from in-service bank) 35. Which of the following statements Is FALSE about the rectum? A. True surgical rectum begins at the anorectal ring just proximal to the dentate line. B. Transverse folds of the rectum are a useful landmark that can be often be identified endoscopically to differentiate proximal from distal tumors. C. Tumors arising above the anorectal ring tends to have lymph node metastasis to the external iliac nodes.

Colorectal Cancer (from in-service bank) 36. Which among these clinical scenarios would be the most ideal to offer short course neoadjuvant radiation therapy to a patient diagnosed with rectal cancer? A. Oligometastatic disease (ex. Solitary liver metastasis) B. Tumor that extends to the pelvic wall C. 40 year old patient with good performance status and no comorbidities