Radiation Oncology: A Question-Based Review

51
Colorectal and Small Bowel Cancer Colorectal and Small Bowel Cancer

Boris Hristov and Joseph M. Herman

image Background


What is the incidence of rectal cancer in the U.S.?

34,000 cases/yr of rectal cancer in the U.S.

What is the median age for rectal cancer?

The median age for rectal cancer is the 7th decade of life.

What is the incidence of colon cancer in the U.S.?

The incidence of colon cancer in the U.S. is 180,000 cases/yr and is the #2 cause of cancer deaths in the U.S. after lung cancer.

What is the median age for sporadic colon cancer?

The median age for sporadic colon cancer is 63 yrs.

What is the sup/cranial extent of the rectum, and how long is it?

The rectum begins at S3 and is ~15 cm long.

What are the most common sites of mets in rectal cancer?

Rectal cancer metastasizes mostly to the liver (via the sup rectal vein) → and the lung.

Where in the GI tract does small bowel cancer most frequently arise?

Small bowel cancer arises most frequently in the duodenum (duodenum > jejunum > ileum).

What type of adenomas are more likely to progress to invasive rectal cancer?

Villous adenomas are more likely to progress to invasive rectal cancer (than tubular adenomas).

How are avg-risk individuals defined as far as colorectal cancer is concerned?

Avg-risk colorectal individuals are ≥50 yo asymptomatic pts without a family Hx of colorectal cancer.

What are the colorectal cancer screening options for avg-risk individuals?

Colonoscopy (q10yrs), fecal occult blood test (q1yr) and sigmoidoscopy (q5yrs), or double-contrast barium enema (q5yrs) are the colorectal screening options for avg-risk individuals.

How frequently should individuals with inflammatory bowel disease (IBD) have a screening colonoscopy?

Individuals with IBD should undergo a screening colonoscopy every 1–2 yrs.

How frequently should individuals with a family Hx of colorectal cancer have a screening colonoscopy? When should screening begin for such individuals?

Individuals with a family Hx of colorectal cancer should have a colonoscopy every 1–5 yrs and should begin screening at age 40 yrs or 10 yrs prior to the earliest cancer Dx in the family.

What are the dietary risk factors for developing colorectal cancer?

Risk factors for colorectal cancer include a diet rich in fat and low in fiber and antioxidants.

What are 2 common familial/heritable risk factors for developing colorectal cancer?

The 2 most common familial conditions associated with colorectal cancer are familial adenomatous polyposis (FAP) and HNPCC (aka Lynch syndrome).

What % of colorectal cancer cases are attributable to HNPCC?

5% of colorectal cancer cases are attributable to HNPCC.

What 2 familial syndromes, other than FAP and HNPCC, have been associated with a higher risk for developing colon cancer?

Cowden syndrome and Gardner syndrome predispose pts to developing colon cancer (in addition to other cancers).

Is smoking a risk factor for colorectal cancer?

Yes. Smoking is a risk factor for colorectal cancer. (St¨rmer T et al., J Natl Cancer Inst 2000)

Which supplements and which drug have shown promise as chemopreventative agents in colorectal cancer?

Calcium, vitamin D, and folic acid supplementation have shown some benefit in preventing colorectal cancer, while aspirin administration has been associated with a lower risk of developing colorectal polyps.

Initial mutation of what tumor suppressor gene leads to a greater chance for developing colorectal cancer? With what familial condition is this mutation associated?

Initial mutation in the APC tumor suppressor gene leads to a higher chance for developing colorectal cancer; this mutation is also associated with FAP.

Mutation of what oncogene leads to a greater chance for developing colorectal cancer?

Initial mutation in the K-ras oncogene leads to a higher chance for developing colorectal cancer.

Most familial HNPCC cases have been associated with mutations in what genes? What do these genes regulate?

Most familial cases identified as HNPCC have been associated with mutations in the hMLH1 or hMSH2 genes, which regulate mismatch repair.

Pts with what chronic inflammatory condition are at an ~20-fold increased risk for developing colorectal cancer?

Pts with ulcerative colitis are at an ~20-fold increased risk for developing colorectal cancer.

image Workup/Staging


What is the most common presenting Sx in rectal cancer?

Hematochezia is the most common presenting Sx in rectal cancer.

What must the physical exam include for pts with suspected rectal cancer?

The physical must include DRE (pelvic exam for women) for presumed rectal cancer pts.

How is the Dx of rectal cancer typically established?

Endoscopic Bx is a typical way of establishing the Dx. A full colonoscopy should be performed to r/o more proximal lesions.

What studies are performed in the workup of rectal cancer pts, and what is the purpose of each modality?

For staging purposes, EUS must be performed in rectal cancer pts. To r/o metastatic Dz, CT C/A/P is performed.

What labs are collected as part of the staging workup for colorectal cancers?

Labs for the workup of colorectal cancer: CBC, Chem 7, LFTs, CEA

Is a PET scan routinely indicated for pts with rectal cancer?

No. A PET scan is not routinely indicated in pts with localized rectal cancer.

What is the AJCC 7th edition (2009) T staging for colorectal cancer?

The T staging for rectal cancer is based on the DOI:

1.     Tis: CIS or invasion into lamina propria

2.     T1: invades submucosa

3.     T2: invades muscularis propria

4.     T3: invades through muscularis and into pericolorectal tissues

5.     T4a: penetrates surface of visceral peritoneum

6.     T4b: invades or adheres to adjacent organs

What is the AJCC 7th edition (2009) N staging for colorectal cancer?

In the 2002 edition of AJCC, N1 designated involvement of 1–3 regional LNs, whereas N2 designated involvement of ≥ 4 LNs.

In the AJCC 7th edition, N1 and N2 are further broken down:

1.     N1a: mets to 1 regional LN

2.     N1b: mets to 2–3 regional LNs

3.     N1c: tumor deposits in subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional LN mets

4.     N2a: mets to 4–6 LNs

5.     N2b: mets to ≥7 LNs

What is the AJCC 7th edition (2009) breakdown of M staging for colorectal cancer?

1.     M1a: DMs to a single organ or site (e.g., liver, lung, ovary, nonregional LNs)

2.     M1b: mets >1 organ/site or deposits in peritoneum

What are the AJCC 7th edition (2009) TNM stage groupings for colorectal cancer?

1.     Stage I: T1-2N0

2.     Stage IIA: T3N0

3.     Stage IIB: T4aN0

4.     Stage IIC: T4bN0

5.     Stage IIIA: T1-2N1 or N1c; T1N2a

6.     Stage IIIB: T3-4aN1 or N1c; T2-3N2a; T1-2N2b

7.     Stage IIIC: T4aN2a; T3-4aN2b; T4bN1-2

8.     Stage IVA: TXNXM1a

9.     Stage IVB: TXNXM1b

How does the old Dukes staging for colorectal cancers correspond to the current AJCC staging system?

1.     Dukes A: stage I

2.     Dukes B: stage II

3.     Dukes C: any nodal involvement (or stage III)

What is the AJCC 7th edition (2009) T staging for small intestine cancers?

1.     Tis: CIS

2.     T1a: lamina propria

3.     T1b: submucosa

4.     T2: muscularis propria

5.     T3: through muscularis propria into subserosa or into mesentery/retroperitoneum ≤2 cm.

6.     T4*: perforates visceral peritoneum or invades adjacent organs (including other loops of small bowel, mesentery or retroperitoneum >2 cm, and abdominal wall (extension from serosa)

What are the AJCC 7th edition (2009) N and M staging for small intestine cancers?

1.     N0: no regional LNs

2.     N1: mets to 1–3 LNs

3.     N2: ≥4 LNs

4.     M0: no DM

5.     M1: DMs

What are the AJCC 7th edition (2009) stage groupings for small intestine cancers?

1.     Stage 0: Tis

2.     Stage I: T1-2N0

3.     Stage IIA: T3N0

4.     Stage IIB: T4N0

5.     Stage IIIA: TxN1

6.     Stage IIIB: TXN2

7.     Stage IV: TXNXM1

What special laboratory test is routinely performed for colorectal cancer pts? Why?

CEA is routinely ordered for pts with colorectal cancer b/c it may help monitor response to therapy and Dz progression.

Describe the CEA trends for colorectal cancer pts after surgery and in the setting of a relapse.

Post resection for colorectal cancer, CEA levels should return to reference range in 4–6 wks. CEA increases 4–6 mos before a recurrence are clinically apparent (a rapid rise suggests hepatic or bony mets, while a slow rise suggests LR).

What is the most powerful predictor of LN involvement in rectal cancer?

The most powerful predictor of LN involvement in rectal cancer is DOI.

What % of T1 rectal cancer pts have micrometastatic Dz in the LNs that is undetectable by current imaging techniques?

Up to 15% of T1 rectal cancer pts have micrometastatic Dz in the LNs that is undetectable by imaging.

image Treatment/Prognosis


What is the Tx paradigm for nonmetastatic rectal cancer?

Nonmetastatic rectal cancer Tx paradigm: In general, T1-2N0 rectal cancer pts can get upfront surgery +/− adj CRT, whereas T3-T4 or N+ pts should rcv neoadj CRT → surgery and adj 5-FU/leukovorin or FOLFOX.

What are the surgical options for rectal cancer pts?

The surgical options for rectal cancer include local excision (transanal excision), abdominoperineal resection (APR) for low-lying lesions, or low anterior resection (LAR) for mid/upper-lying lesions.

What are the criteria for local excision (transanal excision) alone in rectal cancer? On what 2 studies is this based?

The criteria for local excision alone in rectal cancer include T1 lesion, ≤3-cm tumor that is superficial (<3 mm submucosal depth), lesion involving less than or equal to one third of rectal circumference, N0 by EUS or MRI, low-grade tumor/no LVI, reliable pt.

CALGB 89-84 (Steel GD et al., Ann Surg Onc 1999): phase I–II intergroup trial that treated all T1 or T2 Dz with local excision. Eligibility were tumor ≤4 cm, <10 cm from anal verge, <40% bowel circumference, and at least 2 mm deep margin. T1 Dz had surgery alone, and T2 Dz all rcv adj CRT. 6-yr OS was 85%–87%, and the LF rate was 4% (T1) and 14% (T2).

RTOG 82-02 (Russell AH et al., IJROBP 2000): same eligibility criteria as CALGB 89-84, phase II, all transanal excision. T1 lesions ≤3 cm, >3-mm margins, well to moderately differentiated tumors, no LVSI; normal CEA levels were observed after surgery. Pts with T1 with poor risk features and all T2-T3 N0 pts rcv adj CRT (5-FU). 5-yr OS was 78%, with an LF rate of 4% (T1), 16% (T2), and 23% (T3).

What are the indications for adj CRT after surgical resection of rectal cancer?

Adj CRT alone should be administered to pts with a poor-risk T1 lesion after local excision that is poorly differentiated, with bad histologies, margins <3 mm, >3-cm size, and +LVSI; all T2 cancer after local excision; and for all T3-T4 or N+ cancers after LAR or APR.

Low-risk T1 tumors after local excision and T2N0 tumors after LAR to clean margins do not need adj therapy.

What surgical approach for rectal cancer is preferred for sphincter preservation?

LAR spares the sphincter and is therefore a preferred surgical option (if feasible) for rectal cancer pts; in contrast, APR requires a colostomy.

What is the pattern of failure for rectal cancer historically after surgery alone?

For rectal cancer, the pattern of failure after surgery is primarily locoregional.

What is the approximate LR rate for T3-T4 or N1 rectal cancer after surgery alone?

The historic LR rate for T3-T4 or N1 rectal cancer is ~25%. This is improved with better surgery (i.e., total mesorectal excision [TME], LR 11% [Dutch TME study]).

What is the significance of a positive circumferential margin at the time of surgery for rectal cancer?

A positive circumferential margin predicts for inferior LC, DM, and OS rates after surgery for rectal cancer based on meta-analysis. (Nagtegaal ID et al., JCO 2008)

What kind of surgical technique is currently standard in the surgical management of rectal cancer? Why is this important?

TME is a standard surgical technique in the operative management of rectal cancer, as it helps reduce the rate of positive radial margins and improves LC.

What are the indications for adj CRT after definitive resection for rectal cancer?

After a definitive resection for rectal cancer, CRT is indicated if the pathology is nodeor ≥T2.

What are some options for rectal cancer pts with solitary or oligometastatic Dz to the liver that is resectable?

Surgical resection of the metastatic site is the only modality with proven survival benefit. How these cases should be managed needs to be determined on a case-by-case basis in a multidisciplinary setting. Some options for metastatic (resectable) rectal cancer include:

1.     Induction chemo → restaging → resection of the mets → CRT to primary → LAR if possible +/− additional chemo

2.     If the pt is symptomatic, consider preop CRT or short-course RT (5 Gy × 5) as done in Europe → surgery of both primary and metastatic site → adj chemo (FOLFOX/Avastin)

What % of rectal cancer pts are technically resectable at presentation?

80% of rectal cancer pts are technically resectable at presentation.

What is the chemo of choice for rectal cancer with RT? How is it given?

5-FU (225 mg/m2) is given concurrently with RT via continuous infusion (CI), as the NCCTG 86-47-51/Intergroup trial (O–Connell MJ et al., NEJM 1994) showed improved 4-yr OS when compared to bolus administration in the adj CRT setting (70% vs. 60%).

What is the data addressing adj RT alone in rectal cancer, and what does it show?

There are many RCTs (e.g., MRC 3, NSABP R-01) that investigated adj RT alone, showing improvement in LC only but no improvement in OS, DFS, or MFS); this was confirmed by a CCCG meta-analysis (CCCG, Lancet 2001).

What major studies established a role for adj CRT in rectal cancer?

GITSG 7175 (GITSG collaborators, NEJM 1985; Thomas PR et al., Radiother Oncol 1988) randomized pts after surgery to observation, chemo alone, RT alone, or CRT and found that adj CRT in rectal cancer significantly improved OS (45% vs. 27% at 10 yrs) and LF rates (10% vs. 25%) when compared to surgery alone.

Intergroup/NCCTG 79-47-51 (Krook JE et al., NEJM 1991) randomized stage II–III rectal cancer pts to RT alone or CRT (5-FU × 2 > 5-FU + RT > 5-FU × 2) after surgery (50% APR). 5-yr LR, DM, and OS were better for CRT (LR: 14% vs. 25%; DM: 29% vs. 46%; OS: 55% vs. 45%). There was worse acute grade 3–4 diarrhea (20% vs. 5%) but no late complications for the CRT arm.

What are some major criticisms of the rectal cancer trial GITSG 7175?

GITSG 7175 is criticized b/c it was underpowered, 5-FU was given by bolus with semustine (which causes leukemias), randomization was unequal, and there was no intention-to-treat analysis.

Which studies demonstrated that semustine is not a necessary component of CRT in rectal cancer?

GITSG 7180 and NCCTG 86-47-51 demonstrated that semustine is not a necessary component of CRT in rectal cancer.

Which study compared preop RT to postop RT (without chemo) in rectal cancer?

The Swedish Uppsala trial (Frykholm GJ et al., Dis Colon Rectum 1993) compared adj to neoadj RT in rectal cancer and found no OS benefit but improved LR rates (13% vs. 22%) and lower SBO rates (5% vs. 11%) with preop RT.

Which study compared surgery alone to preop RT in rectal cancer? What did it find, and what were its limitations?

The Swedish Rectal Cancer trial (NEJM 1997) compared neoadj RT (25 Gy in 5 fx) to surgery alone in rectal cancer and found a significant improvement in OS (38% vs. 30%) and LR (9% vs. 26%) at 13 yrs with neoadj RT. The trial is often criticized b/c TME was not used and there was a high recurrence rate for the surgery alone arm (26%).

Can the use of TME obviate the need for neoadj RT for rectal cancer?

No. TME does not offset the benefit of neoadj RT based on the Dutch TME study (Peeters KC et al., Ann Surg 2007). The study compared TME alone to neoadj RT and TME and found no OS benefit, but there was an improved LR rate (6% vs. 11%) with the addition of neoadj RT.

What was the RT dose/fractionation scheme in the Dutch and Swedish rectal cancer studies? How long after the completion of RT do pts go to surgery?

Both the Dutch and Swedish rectal cancer studies used neoadj RT in 25 Gy in 5 fx (5 Gy × 5). Pts typically underwent surgical resection within 1 wk of RT completion.

What were the arms in the MRC CR07/NCIC C016 rectal cancer study, and what were its main findings?

The MRC CR07/NCIC C016 rectal cancer study (Sebag-Montefiore D et al., Lancet 2009) randomized pts to preop RT (25 Gy in 5 fx) vs. selective postop CRT (45 Gy in 25 fx) and found better outcomes with preop RT in terms of LR (4% vs. 11%, SS) and DFS (77% vs. 71%, SS). OS was similar at 4-yr follow-up. A short neoadj RT course is an acceptable option.

Which major European rectal cancer study compared neoadj CRT to adj CRT, and what were its findings?

The German Rectal Cancer trial (Sauer R et al., NEJM 2004) compared preop to postop CRT in T3-T4 or node+ rectal cancer (RT was to 50.4 Gy for the neoadj arm and 55.8 Gy for the postop arm with 5-FU chemo (CI 5-FU days 1–5 at 1,000 mg/day, wks 1 and 5). All pts rcv 4 additional cycles of bolus 5-FU (500 mg/m2/day, days 1–5, q4wks) at 4 wks after completion of initial therapy. The study found a similar 5-yr OS and DFS between the 2 arms but better LR rates (6% vs. 13%), fewer acute (27% vs. 40%) and late toxicities (14% vs. 24%), and better sphincter-preservation rates (39% vs. 19%) in the preop CRT arm. Most of the acute and late toxicities were especially due to acute/chronic diarrhea and anastomatic stricture.

What is the pathologic CR rate for preop CRT for rectal cancer?

According to the German Rectal Cancer trial, the pCR rate is 8%.

What % of pts receiving neoadj CRT will be overtreated b/c of having stage I Dz instead of the presumed more advanced Dz?

~18% of pts will be overtreated with neoadj CRT b/c of an apparent stage I Dz. This is based on the results of the postop arm of the German Rectal Cancer trial, where 18% of the pts did not rcv postop CRT b/c of T1-T2 N0 Dz found at resection. All of these pts were thought to have T3-T4 or node+ Dz based on EUS.

What was a major criticism of the German Rectal Cancer trial (Sauer R et al., NEJM 2004)?

A major criticism of the German Rectal Cancer trial (Sauer R et al., NEJM 2004) was that only 54% of adj pts rcv a full RT dose (vs. 92% in the neoadj arm).

Did pts in the German Rectal Cancer trial have TME as part of their surgery?

Yes. All pts in the German Rectal Cancer trial (Sauer R et al., NEJM 2004) had TME at the time of surgery.

What was the sphincter-preservation rate in the neoadj CRT arm in the German Rectal Cancer trial (Sauer R et al., NEJM 2004)?

The sphincter-preservation rate in the neoadj CRT arm in the German Rectal Cancer trial (Sauer R et al., NEJM 2004) was 39% at 5 yrs (compared to 19% in the postop CRT arm).

How long after neoadj CRT should surgery be performed for rectal cancer? Why is this done?

Surgery should be performed ~6–8 wks after neoadj CRT for rectal cancer to allow for adequate downstaging.

How long after surgery should adj CRT be initiated for rectal cancer?

Adj CRT for rectal cancer should begin 4–6 wks after surgery.

What did all pts in the German Rectal Cancer trial (Sauer R et al., NEJM 2004) rcv after either surgery (neoadj CRT arm) or CRT (adj arm)?

All pts in the German Rectal Cancer trial (Sauer R et al., NEJM 2004) rcv 4–5 cycles of bolus 5-FU (500 mg/m2/day, days 1–5, q4wks) 4 wks after either surgery (neoadj CRT arm) or CRT (adj arm).

Which 2 major randomized studies compared neoadj RT to neoadj CRT in rectal cancer, and what did they find? How was CRT delivered in both studies? What was a major limitation of these trials?

The French FFCD 9203 (Gerard JP et al., JCO 2006) and EORTC 22921 (Bosset JF et al., NEJM 2006) compared neoadj RT to neoadj CRT in rectal cancer. The French study found no OS difference but did find improved LR with neoadj CRT at 5 yrs (8% vs. 16%, SS). The EORTC study also found no OS difference and improved LR with neoadj CRT at 5 yrs (9% vs. 17%). Grade 3–4 acute toxicity was higher in the CRT vs. RT arms. Both trials used neoadj CRT with 45 Gy (1.8) and 5-FU (350 mg/m2/day, wks 1 and 5 of RT). A small % of pts actually rcv adj CT (EORTC: 43%).

How should rectal cancer pts be simulated in preparation for RT?

Rectal cancer pts should undergo CT simulation in the prone position, on a belly board, and with a full bladder (with optional placement of anal/vaginal markers and/or rectal contrast).

What structures should be encompassed within the RT field for rectal cancer?

For rectal cancer, the tumor bed (+2–5-cm margin) and presacral/internal iliac nodes should be included in the RT fields.

What additional nodal chain needs to be covered in the RT fields with T4 rectal cancer?

The external iliac nodes need to be encompassed for T4 rectal lesions (invasion of bladder, vagina, uterus, but may not be necessary for bony sacrum invasion).

What RT fields are generally employed for rectal cancer?

Whole pelvis fields (3 fields) with a PA field and 2 opposed lat fields are typically employed for rectal cancer.

What are the RT doses for rectal cancer?

RT doses for rectal cancer:

1.     Neoadj/postop: initial whole pelvis (3 field) to 45 Gy in 1.8 Gy/fx; CD to tumor bed +2–3 cm (opposed lats only, or 3D-CRT) to 50.4 Gy (preop) (or 55.8 Gy (postop) if the small bowel is out of the way)

2.     Definitive/unresectable: initial to 45 Gy, CD1 to 50.4 Gy; consider CD2 with conformal RT to 54–59.4 Gy (if dose to the small bowel is limited)

Describe the anatomic boundaries of the RT fields for rectal cancer.

Anatomic boundaries for the RT fields in rectal cancer:

1.     Posterior-Anterior: sup at L5-S1, inf at bottom of ischial tuberosity or 3 cm below tumor volume, lat at 1.5 cm from pelvic inlet

2.     Laterals: 1 cm post behind entire bony sacrum, ant behind pubic symphisis for T3 (in front if T4), sup-inf same as PA; blocks applied to spare small bowel

Which border is not altered for the CD fields in the Tx of rectal cancer?

The post border on the lat fields usually stays the same (behind the bony sacrum) for the CD portion of the RT for rectal cancer given the high rate of LR in this region.

When is IORT indicated for rectal cancer, and what is the dose?

IORT should be considered in rectal cancer for close/margins or as an additional boost, especially with T4 tumors or with recurrent tumors. The typical dose is 10–15 Gy to the 90% IDL.

What study showed a benefit with IORT in colorectal cancer?

A retrospective study from Mayo by Gunderson et al. evaluated IORT in addition to EBRT and found improved OS and LR rates with addition of IORT (10–20 Gy) when compared to historical controls. (IJROBP 1997)

When can RT be considered in colon cancer? When is it given in relation to surgery and to what dose?

RT can be considered for fixed T4 colon cancer lesions or with a close/+ margin. RT is typically given after resection/debulking to a dose of 45–50.4 Gy.

What major study investigated the role of adj RT in colon cancer? What did it find? What was the limitation of this study?

The Intergroup 0130 study (Martenson JA Jr et al., JCO 2004) compared adj chemo to adj CRT in colon cancer and found no difference in OS or LC with addition of RT. This study was underpowered to show a difference between groups.

Which randomized study investigated the role of elective para-aortic (P-A) RT in rectal cancer? What did it conclude?

The EORTC trial by Bosset et al. evaluated the role of elective P-A RT in rectal cancer (25 Gy to LNs and liver) and found no benefit in terms of OS, DFS, or LC. (Radiother Oncol 2001)

Which ongoing RCT is comparing neoadj oxaliplatin/Xeloda to 5-FU/oxaliplatin and Xeloda to CI 5-FU with RT in rectal cancer?

NSABP R04 is enrolling pts with localized rectal cancer to neoadj RT with CI 5-FU vs. Xeloda with a 2nd randomization to include or not include oxaliplatin concurrent with 5-FU and RT. All pts are encouraged to rcv adj chemo.

What is the Tx paradigm for small bowel cancer, and what is the role of adj chemo and/or RT?

Small bowel cancer Tx paradigm: resection → 5-FU–based chemo. CRT is considered in cases of close/+ margins, but retrospective studies have found no convincing benefit (e.g., Kelsey CR et al., IJROBP 2007).

Why did NSABP R-03 (Roh MS et al., JCO 2009) close prematurely, and what were its findings?

NSABP R-03 closed prematurely b/c of poor accrual. It randomized T3-T4 or node+ rectal cancer pts to neoadj CRT vs. postop CRT (5-FU based). There was improved 5-yr DFS (65% vs. 53%, SS) with neoadj CRT but no difference in LR or OS. The pCR rate was 15%.

image Toxicity


How does the toxicity of CI 5-FU differ from that of bolus administration?

Bolus administration of 5-FU confers greater hematologic toxicity, whereas CI confers greater GI toxicity. (Smalley SR et al., JCO 2006)

What was a major late complication of neoadj RT in the Swedish Rectal Cancer trial?

SBO was more likely in the neoadj RT arm in the Swedish Rectal Cancer trial (RR 2.5) (Birgisson H et al., Br J Surg 2008), maybe a limitation of a hypofractionated regimen (5 Gy × 5).

What 3 toxicities were worse with neoadj RT in the Swedish Rectal Cancer trial?

Median bowel movement frequency (20 movements/wk vs. 10 movements/wk, SS), fecal incontinence (62% vs. 27%, SS), and impaired social life (30% vs. 10%, SS) were worse in the neoadj RT arm when compared to surgery alone in the Swedish Rectal Cancer trial.

What should the small bowel RT dose be limited to in rectal cancer?

The small bowel dose should be limited to 45 Gy in the Tx of rectal cancer.

What does the post-Tx surveillance include for colorectal cancer?

Post-Tx rectal cancer surveillance: H&P q3–6 mos for 2 yrs (then q6mos for 5 yrs) and CEA on same schedule for ≥T2 lesions. CT C/A/P is performed q1yr for 3 yrs and colonoscopy at 1 yr (then in 3 yrs, then every 5 yrs if normal vs. annually if abnl/suspicious).

Which retrospective study found comparable Tx results/toxicity with RT in rectal cancer pts with IBD?

Mt. Sinai study by Green et al. found comparable Tx results/toxicity with RT in rectal cancer pts with IBD. (IJROBP 1999)

How long after conventional RT can side effects develop, and what are some common side effects of RT?

Signs and Sx can occur as early as 6–18 mos following RT. Frequent Sx include diarrhea (bloody), colicky abdominal pain, and n/v. Less common are SBO, fistulas, bowel perforation, and severe bleeding. Bowel malabsorption may occur with weight loss. Damage to the ileum can impair resorption of vitamin B12 and bile acid with steatorrhea as a consequence. (Guckenberger et al., Int J Colorectal Dis 2006)

What are some dose limiting structures?

Small bowel: ≤45 Gy, small volume can go to 50.4 Gy

Femoral heads: ≤45 Gy

* Note: For the duodenum, invasion into pancreas or bile duct constitutes T4.