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Nutritional Consequences of Radiotherapy Simon Lal Consultant Gastroenterologist Intestinal Failure Unit Salford Royal Foundation Trust BAPEN, November 2010 Nutritional Consequences. SHORT-TERM LONG-TERM UNITED KINDGOM Pelvic XRT:

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Nutritional Consequences

  • f Radiotherapy

Simon Lal

Consultant Gastroenterologist Intestinal Failure Unit Salford Royal Foundation Trust

BAPEN, November 2010

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Nutritional Consequences….

SHORT-TERM LONG-TERM

UNITED KINDGOM Pelvic XRT: ~17000 patients/yr1 H&N XRT: ~3500 patients/yr2

  • 1. West CM Curr Opin Supp Paliative Care 2009. 3: 36-40
  • 2. Cancer research UK 2007.
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SLIDE 3

Nutritional Consequences….

SHORT-TERM LONG-TERM

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‘Short-term’ Consequences – H&N XRT

MUCOSITIS

57% malnourished before XRT1

  • 1. Lees J Eur J Cancer Care 1999; 8(3): 133-5
  • 2. Nugent B et al. Cochrane Review 2010.

Upto 80% lose weight during XRT 2

  • Mucositis
  • Dysgeusia
  • Xerostomia
  • Dysphagia
  • Odynophagia
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SLIDE 5

‘Short-term’ Consequences - Pelvic XRT

ACUTE RADIATION ENTERITIS

11-33% malnourished before XRT1 Upto 83% lose weight during XRT1

  • 1. McGough C et al. Br J Cancer 2004; 90:2278-87
  • 2. Resbeut M et al. Radiother Oncol 1997; 44: 59-63

Acute Radiation Enteritis >70%2

  • Diarrhoea
  • Bloating
  • Abdo pain
  • Nausea
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SLIDE 6

‘Short-term’ Consequences

MALNUTRITION RADIOTHERAPY

1.Beaver M H&N Surgery 1998;124:1141-4

  • 2. Paccagnella A Support Care Cancer 2010;18:837-45
  • 3. Lee JH Archives of Otolaryngology.124:871-5
  • ve

XRT Toxicity1 Hospitalisation1,2,3 Interrupted XRT1,2,4 Incomplete XRT5,6 Surgical complications

  • 4. Beer K Nutrition & Cancer 2005; 52: 29-34
  • 5. Margolis M Ann Thorac Surg 2003;76:1694-7
  • 6. Odelli C. Clin Oncol 2005; 17: 639-45
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‘Short-term’ Consequences

MALNUTRITION RADIOTHERAPY

1.Beaver M H&N Surgery 1998;124:1141-4

  • 2. Paccagnella A Support Care Cancer 2010;18:837-45
  • 3. Lee JH Archives of Otolaryngology.124:871-5
  • ve

XRT Toxicity1 Hospitalisation1,2,3 Interrupted XRT1,2,4 Incomplete XRT5,6 Surgical complications

  • 4. Beer K Nutrition & Cancer 2005; 52: 29-34
  • 5. Margolis M Ann Thorac Surg 2003;76:1694-7
  • 6. Odelli C. Clin Oncol 2005; 17: 639-45

Sarcopenia?

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SLIDE 8

Sarcopenia & Cancer Outcome

  • Loss muscle

mass/function.

  • Can be masked in
  • verweight/obese.1
  • Increased chemotherapy

toxicity & faster tumour progression.2

  • Impact on radiotherapy
  • utcome?

Identical BMI=24.3 kg/m2

Patient A Patient B

1.Prado C et al. Curr Opin Supp Pall Care 2009. 3: 269-75

  • 2. Prado C et al. Clin Cancer Res 2009. 15(8): 2920-6
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Nutritional Status & Cancer Treatment

Diagnosis XRT Surgery

Nutritional Status

Wt, BMI  Sarcopenia?

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Nutritional Status & Cancer Treatment

Diagnosis XRT Surgery

Nutritional Status

Wt, BMI  Sarcopenia?

[Nutritional] Interventions

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SLIDE 11

Radiotherapy: Nutritional Management What are the roles of…

Oral nutrition support/Dietary Counselling? Enteral tube feeding? Parenteral Nutrition? Nutritional ‘Therapies’?

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SLIDE 12

Radiotherapy: Nutritional Management What are the roles of…

Oral nutrition support/Dietary Counselling? Enteral tube feeding? Parenteral Nutrition? Nutritional ‘Therapies’?

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Standardised mean difference (95% CI) No supplement favourable Oral supplement favourable

Role of Oral Nutrition Support

Study Oral No suppl Study length Douglass 1978

15 15 6-35d

Moloney 1983

42 42 21-35d

Arnold 1989

23 27 70d

ONS increased energy intake by 381kcal/d

Elia M et al. Int J Oncol (2006) 28: 5-23

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SLIDE 14

.

Ravasco P et al. JCO 2005;23:1431-1438

Dietary Counselling: sustained increase in nutritional intake in patients undergoing XRT

Protein Intake (grams)

Counselling Supplements Control

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ESPEN Guidelines on EN 2006: Non-surgical Oncology

Recommendation Grade

During radio- therapy

Use intensive dietary counselling & ONS to increase intake & prevent therapy-associated wt loss & interruption of radiation therapy in patients undergoing radiotherapy of GI

  • r H+N areas.

A

RECOMMENDATION GRADE A=At least 1 randomised controlled trial C=Expert opinions and/or clinical experience

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SLIDE 16

Radiotherapy: Nutritional Management What are the roles of…

Oral nutrition support/Dietary Counselling? Enteral tube feeding? Parenteral Nutrition? Nutritional ‘Therapies’?

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ONS vs. Tube Feeding?

  • Both can reduce wt loss &

Maintain QOL Reduce hosp admissions Reduce interruptions to treatment

  • No RCTs  Choice depends
  • n tolerability.

MUCOSITIS OESOPH CA

Arends J et al. Clin Nutr 2006; 25: 245-59

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NG vs. Gastrostomy?

1.Lees J. Eur J Cancer Care 1997;6:45-9 2.Baredes ENT Journal 2004;83:417-9 3, Mekhail T Cancer 2001;91:1785-90

  • NG vs. Gastrostomy?

mobility, cosmesis, QOL1 irritation, blockage1,2

COCHRANE: 1 RCT (n=33)  insufficient evidence4,5

  • vs. gastrostomy risk inc.

persistent dysphagia?3

7.Wiggenraad R Clin Otolaryngology 2007;32:384-90 8.Beer K Nutr&Cancer 2005;52:29-34.

  • 9. Margolis M Ann Thorac Surg 2003; 76: 1694-7

4.Corry J J Med Imag Rad Onc 2008;52:503-10 5.Nugent B Cochrane Review 2010 6.Lee JH Archives Otolaryngology 1998;124:871-5

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NG vs. Gastrostomy?

1.Lees J. Eur J Cancer Care 1997;6:45-9 2.Baredes ENT Journal 2004;83:417-9 3, Mekhail T Cancer 2001;91:1785-90

  • NG vs. Gastrostomy?

mobility, cosmesis, QOL1 irritation, blockage1,2

COCHRANE: 1 RCT (n=33)  insufficient evidence4,5

  • Prophylactic Gastrostomy vs. ‘as required’?

Wt loss, hospitalisation, Rx interruption6,7,8 Achieve target chemo-radiation dose9

NO RANDOMISED STUDIES

  • vs. gastrostomy risk inc.

persistent dysphagia?3

7.Wiggenraad R Clin Otolaryngology 2007;32:384-90 8.Beer K Nutr&Cancer 2005;52:29-34.

  • 9. Margolis M Ann Thorac Surg 2003; 76: 1694-7

4.Corry J J Med Imag Rad Onc 2008;52:503-10 5.Nugent B Cochrane Review 2010 6.Lee JH Archives Otolaryngology 1998;124:871-5

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Pull through vs. Push Gastrostomy?

Tumour Seeding

  • Incidence [estimates]:

0.06% to 3% gastrostomy insertions1,2

  • BSG recommend direct

introducer or RIG approach.3

  • 77% UK H&N Units: pull-

through technique.1

1.Barber A, Lowe D, Lal S, Rogers S. J Craniomaxfacial Surg.2010.38:60-3

  • 2. Pickhardt P et al. Am J Radiol. 2002;179:735-9

2.O’Toole P. Complications of GI Endoscopy. BSG Guidelines. 2006.

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ESPEN Guidelines on EN 2006: Non-surgical Oncology

Recommendation Grade

During radio- therapy

If an obstructing H+N or oesophageal tumour interferes with swallowing, EN should be delivered by tube.

C

Tube feeding is suggested if severe local mucositis is expected.

C

PEG may be preferred because of oral

  • r oesophageal mucositis.

C

RECOMMENDATION GRADE C=Expert opinions and/or clinical experience

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Radiotherapy: Nutritional Management What are the roles of…

Oral nutrition support/Dietary Counselling? Enteral tube feeding? Parenteral Nutrition? Nutritional ‘Therapies’?

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ESPEN Guidelines on PN 2009: Non-surgical Oncology

Recommendation Grade

During radio- therapy

The routine use of PN during radio- or radio-chemotherapy is not recommended.

A

PN is recommended if patients are malnourished or facing a period longer than one week of starvation and EN is not feasible.

C

RECOMMENDATION GRADE A=At least 1 randomised controlled trial C=Expert opinions and/or clinical experience

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SLIDE 24

Radiotherapy: Nutritional Management What are the roles of…

Oral nutrition support/Dietary Counselling? Enteral tube feeding? Parenteral Nutrition? Nutritional ‘Therapies’?

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Nutritional ‘Therapies’?

REDUCED RADIATION INJURY? Elemental Diet Probiotics Fish Oil Glutamine

McGough C Br J Cancer 2004; 90: 2278-87 Crowther M Proc Nutr Soc 2009; 68: 269-73 Fuccio L J Clin Gastro 2009; 43: 506-513 Spyropoulos B Dig Dis Sci 2010. Epub

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Fuccio L J Clin Gastro 2009; 43: 506-513

Efficacy of probiotics in the prevention of radiation-induced diarrhoea

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Nutritional ‘Therapies’?

REDUCED RADIATION INJURY? Elemental Diet Probiotics Fish Oil Glutamine

McGough C Br J Cancer 2004; 90: 2278-87 Crowther M Proc Nutr Soc 2009; 68: 269-73 Fuccio L J Clin Gastro 2009; 43: 506-513 Spyropoulos B Dig Dis Sci 2010. Epub

Mixed results…more studies required

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Reduced Treatment Toxicities

Nutrition Support

XRT

SHORT TERM

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Anti Inflammatory

Appetite Stimulants Anabolic Agents Physical Activity Counselling

Reduced Treatment Toxicities

Nutrition Support Cachexia Anorexia

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Nutritional Intervention

MALNUTRITION RADIOTHERAPY

XRT Toxicity Hospitalisation Interrupted XRT Incomplete XRT Surgical complications

X X

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Nutritional Consequences….

UNITED KINDGOM Pelvic XRT: ~17000 patients/yr1 H&N XRT: ~3500 patients/yr2

  • 1. West CM Curr Opin Supp Paliative Care 2009. 3: 36-40
  • 2. Cancer research UK 2007.

SHORT-TERM LONG-TERM

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Nutritional Consequences….

SHORT-TERM LONG-TERM Chronic Radiation Enteritis

UNITED KINDGOM Pelvic XRT: ~17000 patients/yr1

  • 1. West CM Curr Opin Supp Paliative Care 2009. 3: 36-40
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Radiation Enteritis

Acute RE: Resolves within 3 months of XRT. Chronic RE: Onset >3 months – 6 yrs….or later.

Theis V, Sripadam R, Ramani V, Lal S. Clin Onc 2010: 22(1): 70-83

Chronic RE:- Histopathological changes

Obliterative endarteritis Submucosal fibrosis Lymphatic dilatation Ischaemic necrosis

malabsorption, bleeding, stricture, fistulae…

20% of patients receiving pelvic XRT or more?

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Radiation Enteritis: Risk Factors

Patient Factors Treatment Factors

Low BMI SI volume in XRT field Co-morbid illness XRT dose & fractionation Smoking XRT technique Previous GI surgery Concomitant Chemotherapy

Theis V, Sripadam R, Ramani V, Lal S. Clin Onc 2010: 22(1): 70-83

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  • 87/107 (81%) patients described

new onset GI symptoms >1yr after pelvic XRT.  Only 59/87 (68%) sought medical attention.1

  • 43/95 (45%) females restricted

diet > 6 months following XRT for cervical or endometrial cancer.2

  • 1. Gami B et al. APT 2003. 18: 987-94
  • 2. Abayomi J et al. J Hum Nutr Dietet 2009. 22: 310-6

Chronic Radiation Enteritis

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Chronic GI Symptoms following XRT

Diagnosis % Patients

Bile Salt Malabsn 1-75 SI Bact O’growth 4.5-45 CHO Malabsn 1-63 Stricture 3-15 Fistula 0.6-4.8 New/Recurrent neoplasia 4-12 ‘New’ IBD 1.9-4 Pancreatic insufficiency 1.5

Theis V, Sripadam R, Ramani V, Lal S. Clin Onc 2010: 22(1): 70-83

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SLIDE 37

Chronic GI Symptoms following XRT

Diagnosis % Patients

Bile Salt Malabsn 1-75 SI Bact O’growth 4.5-45 CHO Malabsn 1-63 Stricture 3-15 Fistula 0.6-4.8 New/Recurrent neoplasia 4-12 ‘New’ IBD 1.9-4 Pancreatic insufficiency 1.5

Theis V, Sripadam R, Ramani V, Lal S. Clin Onc 2010: 22(1): 70-83

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Surgery in Chronic Radiation Enteritis

  • ~1/3 patients undergo

surgery (obstrn/fistulae).

  • ~ 60 % undergo > 1

laparotomy.

  • Post-op complications

(anastamotic leak) in upto 30%.  Risk of Intestinal Failure

Theis V, Sripadam R, Ramani V, Lal S. Clin Onc 2010: 22(1): 70-83

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Disease spectrum of Acute ‘Type 2’ Intestinal Failure patients admitted to SRFT IFU (2002-2005)

Surgical complications 8% 2% 2% 8% 14% 13% 21% 32% Crohn's disease GI Ischaemia Motility Cancer Radiation Coeliac disease Other

N=134

Lal S et al. Alimen Pharm Ther 2006; 24: 19-31

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Surgery & Radiation Enteritis

SI obstruction (n=30)

Retrospective, 2 groups with ‘similar signs & symptoms.’

17/30: immediate surgery  10/17 HPN at 2 yrs. 13/30: immediate HPN  6/13 surgery after mean 1yr.  0/13 HPN at 2 yrs.

Gavazzi C et al. Am J Gastro 2006; 101: 374-9

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BANS report 2008 (BAPEN publications)

British Artificial Nutrition Survey: Chronic ‘Type 3’ Intestinal Failure (HPN)

Cancer IBD Ischaemia

  • Misc. (e.g. surg comp)

Pseudo-obstrn

Radiation enteritis

Systemic sclerosis Benign Strictures

5 10 15 20 25 30 % Point Prevalence

Neuro conditions

N=870

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Radiation Enteritis: HPN Survival

HPN: 5-year Survival 1 Radiation Enteritis: 52% Crohn’s Disease: 87%

Role of

  • SI Transplantation 2
  • Intestinal Lengthening? 3

20 40 60 80 100 20 40 60 80 100 20 40 60 80 100

‘Best’ Transplant

% Survival

Years

5

5 10 15

HPN

  • 1. Lloyd DA et al. APT 2006 24:1231-1240
  • 2. Lauro A et al. Transpl Proc. 2007 39: 1987-91
  • 3. Yannan G et al. J GI Surg. Online publication Aug 2010
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LONGTERM CONSEQUENCES

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Nutritional Consequences of Radiotherapy SHORT-TERM LONG-TERM

XRT

Diagnosis Surgery

Nutritional Interventions Reduce Treatment Toxicities

Nutritional Status

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THANK-YOU