neoadjuvant chemotherapy without routine use of radiation...

台北榮民總醫院血液腫瘤科

Supervisor: VS 鄧豪偉Presenter: R4 王浩元

Deborah Schrag, Martin R. Weiser, Karyn A. Goodman, Mithat Gon¨en, Ellen

Hollywood, Andrea Cercek, Diane L. Reidy-Lagunes, Marc J. Gollub, Jinru Shia,

Jose G. Guillem, Larissa K.F. Temple, Philip B. Paty, Leonard B. Saltz

《Journal of Clinical Oncology 2014; 32: 513》

Memorial Sloan-Kettering Cancer Center, New York, NY

Neoadjuvant Chemotherapy Without

Routine Use of Radiation Therapy for

Locally Advanced Rectal Cancer:

A Pilot Trial

ESMO for stage I/II/III rectal cancer

Combine-modality therapy for stage II/III

resectable non-metastatic rectal cancer:

Surgery (OP)

Radiation therapy (RT)

Chemotherapy (CT)

CRT TME Adjuvant CT

Pre-OP vs Post-OP

Which regimen

CCRT vs scRT

Combine-modality therapy for stage II/III

resectable non-metastatic rectal cancer:

Surgery (OP)

Radiation therapy (RT)

Chemotherapy (CT)

CRT TME Adjuvant CT

>25% distant mets0 3M

Rare local recurrence Pre-OP vs Post-OP

Which regimen

CCRT vs scRT

II & III

Arm- A Arm- B

Response to neoadjuvant treatment correlates

with long-term outcomes in rectal cancer

MERCURY prospective cohort trial (111 P’t):

MRI-assessed tumor regression grade

significantly associated with OS & DFS

J Clin Oncol 2011;29:3753-3760

Poor tumor

regression

Good tumor

regression

P

5-year OS 27% 72% 0.001

DFS 31% 64% 0.007

A retrospective review of 725 patients with

rectal cancer found similar results

Pathological response to neoadjuvant treatment

correlated with long-term outcomes.

Distant metastases and local recurrences also

correlated with the level of response.

J Clin Oncol 2012;30:1770-1776.

Response to neoadjuvant treatment correlates

with long-term outcomes in rectal cancer

Pathological response Good Intermediate poor

5Y recurrence-free

survival rate90.5% 78.7% 58.5%

Combine-modality therapy for stage II/III

resectable non-metastatic rectal cancer:

Surgery (OP)

Radiation therapy (RT)

Chemotherapy (CT)

CRT TME Adjuvant CT

>25% distant mets0 3M

Rare local recurrence

Combine-modality therapy for stage II/III

resectable non-metastatic rectal cancer:

Surgery (OP)

Radiation therapy (RT)

Chemotherapy (CT)

CRT TME Adjuvant CT

>25% distant mets0M

Rare local recurrence

Neoadjuvant

Combine-modality therapy for stage II/III

resectable non-metastatic rectal cancer:

Surgery (OP)

Radiation therapy (RT)

Chemotherapy (CT)

TME Adjuvant CT

>25% distant mets0M

Rare local recurrence

Neoadjuvant

Methods

Inclusion: Rectal adenocarcinoma

No previous treament

No metastatic disease

Amenable to sphincter-preserving TME

Distal edge of tumor: 5-12cm

Exclusion: T4

Clinical obstruction

≥ 4 pelvic LNs (>2cm) on MRI/ERUS

Tx for another primary cancer within 5 years

Thrombotic episode within 6 months

Work-up:• Rigid proctoscopy

• ERUS & Pelvis MRI (for LN)

• Chest/Abdomen/Pelvis CT (for M1)

• ECOG: 0-2

• ANC > 1500/uL,

• PLT > 100K/uL

• CCr > 30 mL/min

• T-bil < 2X UNL

• ALT/ALP < 3X UNL

cT3N(+), cT3N(-): N(-): NO perirectal LN > 5mm

N(+): ≥ 1 perirectal LN > 5mm

Intolerance

Progression (PD)

No response (SD) Clinical response

3–6 wk

3–6 wk

Primary endpoint: R0 resection rate

(no evidence of tumor within 1mm of tumor margin)

Secondary endpoint: Disease-free survival (DFS)

Proportion of trial participants receiving

preoperative or postoperative radiation

Results

Enrollement: 32 patients (2007/03 - 2009/10)

Median follow-up time: 54 months (26-81m)

Median age: 52y (26-81y)

Women: 53% (17 of 32)

LN(+): 72% (23 of 32)

Results

T3N(+) 63% (20 of 32)

T2N(+) 9% (3 of 32)

T3N(--) 28% (9 of 32)

pCR

pCR

pCR

pCR

pCR

pCR

pCR

pCR

Pre-OP

Pre-OP

Post-OP

Lung

Lung

Lung

Lung

Discussion

Highlights

CRT OP Adjuvant CT

Rare local recurrence

>25% distant mets0 3M

Neoadjuvant OP Adjuvant CT

Rare local recurrence

16% distant metsCRT

94%

6 %

Could low recurrence rate be

attributed to other factors ?

Rectal tumor: 5-12cm from AV

Bevacizumab: negative results in adjuvant setting

LNs: 72% of participants had nodal involvement

Limitationsmall number of participants

single center

ConclusionFor selected clinical stages II to III rectal

cancer, neoadjuvant chemotherapy

(without routine use of radiation) does

NOT compromise outcomes.

Thanks for your attention