Indication for neoadjuvant chemoradiation based on current NCCN guidelines:
       Stages II & III rectal cancer:

• T3 (invades perirectal tissues) or T4 (invades adjacent organs), with any N disease,
• N1 or N2 disease (at least one regional node/deposit), with any T disease,
• Locally unresectable or medically inoperable tumors
• Some low rectal tumors to allow for sphincter sparing resection

Current neoadjuvant chemotherapy options: 5-FU (infusional fluorouracil or oral capecitabine), oxaliplatin, +/- leucovorin, +/- irinotecan.

Neoadjuvant radiation:

• Long course: ~50 Gy in 2528 fractions daily over 5-6 weeks + radiosensitizing chemotherapy (5-FU or capecitabine)
• Short course: 25 Gy in 5 fractions over 1 week (without chemotherapy)

While highest radiation dose is aimed at the rectum, other organs also receive high doses of radiation, such as the bladder, sacrum, pre-sacral fat, and prostate. Lower radiation fields may be used to encompass inguinal lymphadenopathy in the setting of low rectal tumors.

“Total neoadjuvant therapy” (TNT): All chemotherapy and radiation therapy given prior to surgery, with various permeations available. May be used for any of the following indications: any T4, any N2, tumors with threatened resection margin, and some low rectal tumors to allow for sphincter sparing resections.

*Key sequence to assess residual tumor

Prescribing oblique planes for angled T2-weighted images:

• Provides optimal anatomic information
• Reduces volume averaging

Tumor may be difficult to identify after treatment	Look at the pre-treatment MRI to identify tumor location	Draw oblique lines in the form of a “fishbone” based on the long and short axis of tumor

MRI Features of Treatment Response

Treatment response features on T2:

• Decrease or resolution of T2-intermediate signal of viable tumor
• Development of T2-hypointense fibrosis within the rectal wall or adjacent mesorectal fat (desmoplastic reaction)
• Acellular mucin production: new or increased T2-hyperintense signal, similar to water

1. Fibrosis

	Initial Staging MRI – T2WI	After Neoadjuvant Treatment MRI – T2WI	Comment
Small / focal			Well-defined thin T2-hypointense signal (arrow) Fibrosis confined to the rectal wall Complete response
Semicircular/full-thickness			Thick T2-hypointense signal (*) Fibrosis involves the full thickness of rectal wall (*) +/- Desmoplastic reaction (Arrow: T2-hypointense lines in mesorectal fat) Usually complete response
Spiculated	Irregular spiculated tumor (*)		Spiculated T2-hypointense signal (arrow) Desmoplastic reaction (arrowhead) More frequent residual tumor

2. Mucinous degeneration in non-mucinous adenocarcinoma

Initial MRI – T2WI	During Neoadjuvant Treatment – T2WI	After Neoadjuvant Treatment – T2WI
Nodular T2-intermediate tumor signal (arrow)	Replaced by T2-hyperintense signal of mucin (arrow)	May be replaced by T2-hypointense scar (arrow)

3. Increased mucin in mucinous/signet ring cell cancers

Subtype	Initial MRI	After Neoadjuvant Treatment
Mucinous adenocarcinoma	T2-hyperintense signal reflects acellular /nonviable tumor T2-intermediate signal reflects cellular/viable tumor (Not shown)	Increased T2-hyperintense signal Decreased/Resolved T2-intermediate signal (Not shown)
Signet-ring cell adenocarcinoma

Treatment response features on DWI & ADC:

• Resolved or decreased extent of restricted diffusion in tumor bed
• Increased ADC signal and decreased DWI signal in tumor bed
• Signal on DWI is similar to ADC (high-DWI & high-ADC OR low-ADC & low-DWI)

Non-mucinous Adenocarcinoma

Sequence	Initial MRI	After Neoadjuvant Treatment	Comment
T2	T2-intermediate tumor (*)		Increased signal in tumor bed (*) due to acellular mucin production
DWI	DWI hyperintense tumor (*)		Decreased signal in tumor bed (*) due to loss of cellularity
ADC	ADC hypointense tumor (*)		Increased signal in tumor bed (*) due to loss of cellularity

MRI Features of Residual Tumor

Residual tumor features on T2 and T1FSC+:

• Persistent nodular-shaped T2-intermediate signal in tumor bed (in non-mucinous tumors)
• Persistent T2-intermediate signal in submucosa (signet-ring cell subtype)
• Early enhancement tumor bed ≥ than initial MRI
• Unchanged or minimally decreased cellular mucin (in mucinous tumors)

1. Residual disease in a non-mucinous adenocarcinoma

Initial MRI	After Neoadjuvant Treatment	Comment
T2-intermediate tumor (arrow)		Persistent nodular-shaped T2-intermediate signal in tumor bed (arrow)
Hyperenhancing tumor (*)		Early enhancement tumor bed (arrow) > than initial MRI

2. Residual disease in a mucinous asdenocarcinoma

Initial MRI	After Neoadjuvant Treatment	Comment
T2-hyperintense tumor (arrows) Internal intermediate signal (*)		Decreased T2-hyperintense mucinous tumor (arrows) Persistent T2-intermediate signal (*) of cellular mucin

3. Residual disease in a signet ring cell adenocarcinoma

Initial MRI	After Neoadjuvant Treatment	Comment
T2-intermediate tumor in submucosa (*)		Improved but persistent T2-intermediate signal of cellular mucin in mucinous tumor

Reassessment of Circumferential Resection Margin (CRM)

Reassessment of mesorectal fascia (MRF) involvement

• Resolved MRF involvement: Development of clear fat plane (≥ 2mm) ± desmoplastic reaction between tumor and MRF
• Persistent MRF involvement: Persistent T2-intermediate or T2-hyperintense signal infiltration of MRF
• Indeterminate MRF involvement: Diffuse fibrotic (T2-hypointense) infiltration of MRF

Initial MRI	After Neoadjuvant Treatment	Comment
T2-intermediate tumor involves MRF (arrows)		New fat plane (arrow) with desmoplastic reaction (arrowhead) between tumor bed and MRF Resolved MRF Involvement
T2-intermediate tumor involves MRF (arrow)		Persistent T2-intermediate signal of tumor along MRF (arrow) Persistent MRF Involvement
T2-intermediate tumor involves MRF (arrow)		Thick T2-hypointense signal of fibrosis along MRF (arrow) Indeterminate MRF Involvement

Reassessment of sphincter complex in low rectal cancers

• Allow sphincter-sparing surgery: Tumor involves up to the intersphincteric fat but does not involve external sphincter; > 2 cm from anal verge
• Does not allow sphincter-sparing surgery: Tumor invades external sphincter; < 1-2 cm from anal verge

Reassessment of extramural vascular invasion

Initial MRI	After Neoadjuvant Treatment	Comment
T2-intermediate signal along vessels (arrow)		Resolved T2-intermediate signal along mesorectal vessels Replacement by linear T2-hypointense fibrosis (arrow) Resolved extramural vascular invasion (EMVI)
T2-intermediate signal along vessels (arrow)		Improved but persistent nodular T2-intermediate signal along mesorectal vessels (arrow) Persistent extramural vascular invasion (EMVI)

Locoregional nodes (N1/2): Mesorectal, superior rectal, obturator (posterior to external iliac vessels), and internal iliac stations (and inguinal nodes, sometimes considered locoregional if a low rectal cancer involving anal canal).

• “Lateral lymph nodes”: Refers to obturator and internal iliac stations, which are not removed with standard surgical resection; it is important to report these separately as at some institutions, a lateral lymph node dissection will also be performed.

Non–locoregional nodes (M1): external iliac (anterior or lateral to external iliac vessels), common iliac, and paraaortic, and inguinal stations (if mid or high rectal cancer)

MRI Features of Nodal Treatment Response

• Disappearance or decreased size to < 5mm short axis
• Replacement by T2-hypointense fibrosis
• New/Increased T2-hyperintense signal of acellular mucin

Initial MRI	After Neoadjuvant Treatment	Comment
Enlarged and heterogeneous mesorectal (white arrow) and internal iliac nodes (black arrow)		Complete disappearance of mesorectal and internal iliac nodes   Replacement by T2-hypointense fibrosis (arrow)
Enlarged & T2 hyperintense superior rectal nodes (arrows) with internal T2-intermediate signal (*)		New/Increased T2-hyperintense signal of acellular mucin (arrow) Decreased size (arrowhead)

MRI Features of Residual Tumor in Nodes

• Size ≥ 5 mm in short axis (**only feature considered by SAR/ESGAR panels)
• Persistent T2-intermediate signal, irregular contour, heterogeneous signal

Initial MRI	After Neoadjuvant Treatment
Enlarged lymph nodes with T2-intermediate signal and irregular contour in the obturator (white arrow) and internal iliac (black arrow) stations. O=Obturator muscle	Most nodes have decreased size but there is a persistent node with ≥ 5 mm in short axis and irregular contour (white arrow). O=Obturator muscle

Pseudotumor

• Pseudotumor is a mucosal edema after radiation involving the rectal wall not previously involved by tumor, appearing as T2-hyperintense signal

Initial MRI – T2WI	After Neoadjuvant Treatment – T2WI
T2-intermediate tumor invading the mesorectal fat at 12 o’clock (arrow) with heterogeneous tumor deposits (arrowheads)	T2-hypointense fibrosis in rectal wall at 12 o’clock (arrow). New adjacent T2-hyperintense masslike thickening posteriorly (*) (Pseudotumor)

Persistent restricted diffusion versus T2-shine-through OR T2-dark-through

• T2-shine-through and T2-dark-through are seen in tumor response
  • T2-shine-through (hyperintense signal on DWI and ADC) happens due to decreased cellularity at the tumor bed
  • T2-dark-through (hypointense signal on DWI and ADC) happens due to increased cellularity of dense fibrosis replacing the tumor bed
• Tip: Equal (low-low or high-high) signal in DWI and ADC means response rather than viable tumor

T2-shine-through in a patient with a complete response

Sequence	Initial MRI	After Neoadjuvant Treatment
T2WI	Circumferential T2-intermediate tumor (*)	Persistent T2-intermediate signal in tumor bed (*) raises question of residual tumor
DWI	DWI hyperintense tumor (*)	Persistent DWI hyperintense signal (*) in tumor bed also raises question of residual tumor
ADC	ADC hypointense tumor (*)	New ADC hyperintense signal in tumor bed due to T2-shine-through and treatment response

T2-dark-through in a patient with complete response

Sequence	Initial MRI	After Neoadjuvant Treatment
T2WI	T2-intermediate tumor (*)	New T2-hypointense signal in tumor bed (*) due to fibrosis
ADC	ADC hypointense tumor (*)	Persistent ADC hypointense signal in tumor bed (*) raises question of residual tumor
DWI	DWI hyperintense tumor (*)	New DWI hypointense signal in tumor bed (*) due to T2-dark-through

Other (not shown): Avascular necrosis of femoral heads, Cystitis

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