1. Health-related quality of life in patients with oesophageal- and gastric cancer Lovisa Backemar, MD Surgical Care Sciences Department of Molecular Medicine and Surgery

2. Outline  Patient-reported outcomes (PROs)  PRO research in oesophageal and gastric cancer  Predictors of poor HRQOL after surgery  Neoadjuvant therapy  Impact of surgery  Long-term impact  HRQOL among long-term survivors  HRQOL as prognostic factor  Summery Lovisa Backemar2

3. My whole life is ruined! Mr X, everything is perfectly alright. The cancer is gone! I have no appetite I have no energy I cannot sleep © Pernilla Lagergren 3

4. Why PROs?  Evaluate clinical treatment results  Inform patients before and after treatment  Clinical decision-making  Form models of care and rehabilitation programs  Prognostic factor Lovisa Backemar4

5. Examples of PROs  EORTC QLQ-C30  15 outcomes (global HRQL, functions; physical, role, social, emotional, cognitive and symptoms  EORTC QLQ-OG25  16 outcomes (oesophago-gastric symptoms)  Hospital anxiety and depression scale (HADS)  Anxiety and depression evaluation  Benefit finding scale  Positive aspects of the disease event Lovisa Backemar5

6. Scores 0-100 6

7. Clinical relevant difference in HRQOL  A level of change/difference noticeable for the patient  10% = moderate  20% = large  Statistical significance vs clinical significance Lovisa Backemar7 (Osoba et al. J Clin Oncol 1998)

8. PRO research in oesophageal- and gastric cancer 1.Predictors of poor HRQOL after surgery 2.Neoadjuvant therapy 3.Impact of surgery 4.Long-term impact 5.HRQOL among long-term survivors 6.HRQOL as prognostic factor Lovisa Backemar8

9. 1. Predictors of poor HRQOL Oesophageal cancer  Comorbidities (yes)  Histology (SCC)  Tumour stage (III+IV)  Tumour location (proximal) (Djärv et al. J Clin Oncol 2009) 9 Gastric cancer  Age (older than 65) (Jakstaite et al. BMC Surg 2012) Lovisa Backemar

10. 2. Neoadjuvant therapy  Negative impact during therapy  Recovery before surgery  No major influence postoperatively ( Blazeby JM et al Cancer 2005, Reynolds JV et al. BJS 2006, van Meerten et al. Int J Radiation Oncology Biol Phys 2008, Safiddine N et al J Thorac Cardiovasc Surg 2009, Scarpa et al J Gastrointest Surg 2013)  Increased risk of malnutrition (Martin L et al. Br J Surg 2008) Lack of randomised clinical trials! 10Lovisa Backemar

11. Neoadjuvant therapy vs surgery alone 11 (Blazeby et al Cancer 2005) Global QoLNausea/vomiting 21 patients - Surgery alone 34 patients - CRT + surgery 48 patients - Chemotherapy + surgery Similar trends for social, role and physical function Similar trends for dyspnoea, diarrhoea, taste, cough, and dry mouth High scores = better QoL / worse symptoms Lovisa Backemar

12. Impact of neoadjuvant therapy on HRQOL over time cont. 12 (van Meerten et al. Int J Radiation Oncology Biol Phys 2008) Fatigue Global QoL 54 patients - CRT + surgery Similar trends for nausea, pain, dyspnoea and appetite loss Post-CRT = 1 week Lovisa Backemar

13. 3. Impact of esopgagectomy on HRQOL  Negative impact  Surgical procedure itself  Postoperative complications  Short- and long-term  Dyspnoea, fatigue, eating difficulties, sleeping problems, reflux (Derogar et al J Clin Oncol 2012, Rutegård M et al. Br J Surg 2008) Lovisa Backemar13

14. 3. Impact of oesphagectomy on HRQOL cont. Minimally invasive surgery oesophagectomy Earlier recovery  BUT:  Early tumours and HGD patients were included  Generic instrument was used (SF 36) (Luketich JD et al. Ann Surg 2003)  No differences  BUT:  Retrospective study  One center study (Sundaram A et al Surg Endosc 2012) Lack of randomised clinical trials with HRQL! Lovisa Backemar14

15. 3. Impact of surgery on HRQOL cont. Laparoscopy-assisted gastrectomy Better HRQOL 3 month after surgery compared to open Lovisa Backemar15 (Kim et al. Ann Surg 2008)

16. 4. Long-term impact of oesophageactomy on HRQOL  Much worse HRQOL than the general population at 6 months and 3 years postoperatively  No improvements between 6 months and 3 years post- operatively (Djärv T et al. BJS 2008) Lovisa Backemar16

17. 4. Long-term impact of oesophageactomy on HRQOL cont. Baselin e score Higher score = better function * p 0.007 Preoperative score * * p 0.0008 * Preoperative score (Lagergren P et al. Cancer 2007) Lovisa Backemar17

18. 4. Long-term impact of oesophageactomy on HRQOL cont. Higher score = more symptoms * * p 0.0001 * 75 % of the patients (Lagergren P et al. Cancer 2007) Lovisa Backemar18

19. Lovisa Backemar19 4. Long-term impact of gastrectomy on HRQOL  Only few small studies  Problems sleeping, eating, distress.  But physical and social functioning, energy and vitality the same (TyrvainenT et al. J Surg Onc 2008)  Worse to 6 months -> stable  Patients who die within 2 years experience limited postoperative recovery (Avery et al Eur J Cancer surg 2009)

20. 5. HRQOL among long-term survivors  Patients who improve or are stable report HRQOL comparable to the background population for most measures at 5 years  Patients who deteriorate over time report clinically and statistically significant much worse for all functions (range -23 to -45) and symptoms (range 25 to 59) Lovisa Backemar (Derogar M et al. J Clin Oncol 2012) 20

21. 5. HRQOL among long-term survivors cont. Lovisa Backemar *Adjusted for age, sex and comorbidity. Based on 117 patients and 4910 background people HRQOL 5 years after surgery compared to the background population Physical functionDifficulty eating

22. 6. HRQOL as a prognostic factor HRQOL before surgery  Improved survival  Good physical function  Good role function  Good global quality of life  Increased mortality  Fatigue  Appetite loss  Dyspnoea  Pain Blazeby JM et al, Gut 2001 Chau I et al JCO 2004 Blazeby JM et al, BJS 2005 McKernan M et al BJC 2008 Quinten C et al Lancet Oncol 2009 Djärv T et al J Clin Oncol 2010 van Heijl M et al Ann Surg Oncol 2010 Lovisa Backemar22

23. 6. HRQOL as a prognostic factor cont. Changes over time to 6 months after surgery  Relation to longer survival time  Improvement in physical function  Improvement in emotional function  Relation to higher risk of mortality  Worsening in fatigue  Worsening in pain Lovisa Backemar (Djärv T et al, J Clin Oncol 2010, Blazeby JM et al. Gut 2001) 23

24. 6. HRQOL as a prognostic factor cont. Difference in survival - Physical function Difference in survival - Pain Number of years Stable or improvedDeteriorated (Djärv T et al J Clin Oncol 2010) Changes over time to 6 months after surgery cont. Lovisa Backemar24

25. 6. HRQOL as a prognostic factor cont. Postoperative HRQOL  Physical function, role function, global quality of life  50-60% increased risk  Fatigue, pain, dyspnoea, appetite loss, dysphagia, odynophagia  30-70% increased risk Lovisa Backemar (Djärv T et al EJC 2011) 25

26. Summary  Patients with oesophageal and gastric cancer have a reduced HRQOL in a short and long-term postoperative perspective  Comorbidity, histological type, tumour stage and tumour location predict HRQOL  Complications strongly predict poor HRQOL  Most patients recover their HRQOL within 5 years after surgery  A sub-group of long-term survivors strongly deteriorate in HRQOL  HRQOL measurements may predict survival Lovisa Backemar26

27. Thank you