gp educational day lower gi malignancy... · 2019-10-23 · anal cancer trials 1987-1994 major...

The Royal Marsden

GP Educational Day Lower GI malignancy

The Royal Marsden Educational & Conference Centre

16th October 2019

Dr Diana Tait Consultant Clinical Oncologist The Royal Marsden Hospital

In Your practice how many patients are you aware of who have/had a diagnosis of

anal cancer?

1 or 2

2- 5

> 5

In your practice how many patients are you aware of who have/had a diagnosis of

rectal cancer?

1 or 2

2 - 5

5 - 10

> 10

What is the standard treatment for Squamous anal cancer ?

Surgery Surgery Chemotherapy

Chemotherapy Chemoradiation


What % of patients with squamous anal cancer have evidence of HPV infection ?

10 - 20%

20 - 40% 40 - 60% 60 - 80%

80 - 100%

In Rectal cancer what % of patients will achieve complete clinical response after

chemoradiation?

5 - 10%

15 - 25%

25 - 40%

40 - 50%

At what age does bowel screening start?

50

55

60

65

Malignancy Low Rectum/Anal Canal

• Sag MRI


• CURED

• AVOID STOMA

Treatment Low Rectal/Anal Cancer

1980 APR/permanent Stoma

Anal Cancer Trials 1987-1994

Major Practice Change

CHEMORADIATION

Anal Cancer – Pivotal Trials (1)

ACT 1 – UK RT +/- MMC +5FU EORTC – European

RT +/- MMC + 5FU similar reduction

RTOG – USA

RT + 5FU +/- MMC superior results MMC

LRF 36% v 59%

Anal Cancer – Pivotal Trials (2)

RTOG – USA

CRT-MF V CRT cisplatin FU inferior outcomes

ACT 2 - UK

CRT-MF V CRT cisplatin F

+/- maintenance cisp FU No benefit

ACCORD

+/- Neoadjuvant cisplatin FU No benefit

Lessons from ANAL CANCER

• Rare Cancer

• National/International collaboration

•Provide Practice Changing Evidence

• Enormous significance for patients

Radiosensitive

Wilms tumour

Ewings Sarcoma

Lymphoma

Multiple myeloma

Seminoma/

dysgerminoma

SCC

Radioresistant

Osteosarcoma

Fibrosarcoma/

Liposarcoma/

myosarcoma

Malignant melanoma

Gliomas

Adenocarcinomas

Radiocurable Disease - SCC

Head and Neck

Skin cancer

Anal Penis and Cervix Anal

Skin cancer Oesophageal

Rectum Preservation – locally advanced

2000 patients/yr - Pre-op Radiotherapy and Resection

Low Rectal Cancer Treatment Strategy

APR/permanent stoma

LR 30%

Pre-operative RT (25Gy in 5#)

LR 10%

IMAGING 1990s

SURGERY 1982

Evolutionary(Revolutionary)changes Rectal Cancer

Total Mesorectal Excision (TME)

MRI Staging

LR < 5% Selection/prognosis

Evolution of Rectal Cancer Management

1990s SURGERY

1990s + CHEMOTHERAPY

1990 + RADIOTHERAPY

POST OPERATIVE

PRE-OPERATIVE

Evolution of Rectal Cancer Management

SELECTION

EARLY

SURGERY

MRI

ADVANCED

NEOADJUVANT Chemoradiaton

Short course RT

Chemotherapy Short course RT

Where are the nodes?

EUS coverage MRI coverage

MRI coverage

EUS

Neo-adjuvant Strategies in Rectal Cancer

Do nothing

SCPRT

CRT

Systemic Treatment

Pre-Operative Radiotherapy Schedules

SCPRT V CRT

25Gy 5# 1w ≥ 45Gy 25# 5w

Min Acute Toxicity Mod Acute Toxicity

Long Term Morbidity ? Long-term Morbidity

Organ motion - bladder status

Small Bowel

Small Bowel

Rectum

Rectum

Bladder

Bladder

Benefits of bladder distension demonstrated by

Brierely et al. (1994) and Nuyttens et al. (2001).

Week 1 Week 3

Bladder Filling

Pelvic Radiotherapy Supine Treatment Position

IMRT - Dose Distribution

Pre-treatment Post-treatment

Clinical Complete Response MR = black scar on T2 imaging

Smith JJ et al., BMC Cancer, 2015.

MR TRG

RT Responsiveness

TRG 2

TRG 3

TRG 1

TRG 4/5

MRI Tumour Regression Grading

MRI After Treatment of Locally Advanced Rectal Cancer: How to report Tumor Response - The MERCURY Experience (AJR 199: 2012)

Timing after CRT? When is maximum response reached?

6 weeks

mrT3b

12 weeks

mrT2

Baseline

mrT4

Final Pathology: ypT2N0

Dose Response Relationship

Appelt et al, International Journal of Radiation Oncology*Biology*Physics Volume 85, Issue 1 2013 74 - 80

TRG1

(Solid line, filled squares)

TRG1-2

(Dashed line, open squares)

Headaches !!

• New concept Slow Accrual

• Suitability for surgery Poor PS patients

• Point of Entry Selection bias

Headaches !!

Entry point to trial –Non Standard

Introduced bias – selection of maintained responders

Per protocol (PP) At least one MRI

later than 8w post CRT

Late Entry (LE)

Consent ≤ 70d post CRT Consent ≥ 71d post CRT

60 40

Primary Endpoints

• Time to Local disease regrowth (PP set) By 2 years - 29 events - 2 patients censored Kaplan-Meier probability of continued cCR at 2 years 50% (C1 37% - 62%)

• Time to Local Failure (PP set) By 2 years - 4 Local failures - 25 successful resection - 2 Censored – no regrowth Kaplan-Meier probability of local failure at 2 years 8% (C1 3.2% - 29%)

SUMMARY

• Ground breaking study – lot of learning!

• Accrual and 2yr follow-up achieved (12yrs)

• Probability of continued CR at 2yrs 50%

• Probability LF at 2yrs 8%

Functional Outcome

No LARS

Minor LARS

Major LARS

• 3yr colostomy free rate >90% • EORTC CR38 • Better in most domains • LARS

Netherland Cancer Institute Series

Major LARS

Minor LARS

Watch-and-Wait CRT/TME

No LARS