Title: Meta-analysis shows clinically relevant and long-lasting deterioration in health-related quality of life after esophageal cancer surgery.
Running head: HRQL after esophageal cancer
M. Jacobs1, R.C. Macefield2, R.G. Elbers3, K. Sitnikova1, I.J. Korfage4, E.M.A. Smets1, I.Henselmans1, M.I. van Berge Henegouwen5, J.C.J.M. de Haes1, J.M. Blazeby2,6, M.A.G. Sprangers1
1Department of Medical Psychology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
2 School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom
3 Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam,
Amsterdam, TheNetherlands
4 Department of Public Health, UniversityMedicalCenterRotterdam, Rotterdam, The Netherlands
5 Department of Surgery, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
6 Division of Surgery Head and Neck, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
Corresponding author at:
Marc Jacobs
Dept. Medical Psychology
AcademicMedicalCenter, University of Amsterdam
Meibergdreef 5, 1100DD Amsterdam
PO Box 22660
Netherlands
Tel: +31-20-5668508, fax: +31-20-5669104
E-mail:
Study characteristics: HRQL assessment
HRQL assessment in 15 studies included in the meta-analysis.Author / HRQL
aima / Sample size
eligible / Sample
size
baselineb / Handling of missing
datac / HRQL
questionnaire(s)
used to evaluate treatment / Timing
of baseline
assessmentc / Time
window
baseline
assessment / Time window
follow-up assessments / Timing of HRQL assessmentd
3
months / 6 months / 9
months / 12 months
Included in meta-analysis
Scarpa / Primary / 126 / 51* / Unclear / QLQ-C30, -OES18 / Time of diagnosis / Unclear / 14-days§ / Yes§ / Yes§ / No / Yes§
Teoh / Secondary / 45 / 34* / Intention to treat / QLQ-C30, -OES24 / Pre-treatment / Unclear / Unclear / Yes / Yes / No / No
Nafteux / Primary / 166 / 135* / Unclear / QLQ-C30, -OES18 / Beforesurgery / 1 day / 14 days§ / Yes§ / Yes§ / Yes§ / Yes§
Parameswaran / Primary / 62 / 55 / EORTC manual / QLQ-C30, -OES18 / Beforesurgery / 3 weeks / 14 days / No / Yes / No / Yes
Wang / Primary / 97 / 97 / Unclear / QLQ-C30, -OES18 / Beforesurgery / Unclear / Unclear / Yes / Yes / No / No
Wang / Primary / 29 / 29 / Unclear / QLQ-C30, -OES18 / Beforesurgery / Unclear / Unclear / Yes / Yes / No / No
Safedienne / Primary / 53 / 40 / Unclear / FACT-E / Pre -treatment / Unclear / Unclear / Yes / No / No / Yes
Van Meerten / Secondary / 54 / 50 / EORTC manual / QLQ-C30, -OES18 / Pre -neoadjuvant / Unclear / Unclear / Yes / Yes / Yes / Yes
Barbour / Primary / 20 / 19 / Unclear / QLQ-C30 / Beforesurgery / 4 weeks / 7 weeks / No / Yes / No / No
Avery / Primary / 81 / 63* / EORTC manual / QLQ-C30, -OES18 / Pre-treatment / 4 weeks / 14 days / Yes / Yes / No / No
Lagergren / Primary / 47 / 45* / EORTC manual / QLQ-C30, -OES18 / Beforesurgery / 6 weeks / 14 - 50 days / Yes / Yes / Yes♯ / Yes
Tan / Unclear / 21 / 21 / Unclear / SF-36, PAIS / Beforesurgery / Unclear / Unclear / Yes / Yes / No / Yes
Reynolds / Primary / 202 / 147 / Unclear / QLQ-C30, -OES24‡ / Beforesurgery / 1-2 weeks / 14 days / Yes / Yes / No / Yes
de Boer / Secondary / 250 / 199 / Group mean / MOS-SF-20, A-RSCL / Afterrandomization / Unclear / Unclear / Yes / Yes / Yes / Yes
Brooks / Primary / 38 / 23 / Unclear / FACT-E, POMS / At diagnosis / Unclear / Unclear / Yes / Yes / Yes / No
QLQ-C30 quality of life questionnaire cancer-30, QLQ-OES18 quality of life questionnaire esophagus-18, SF-36 medical outcomes study short-form general health survey, GERD-HRQL gastroesophageal reflux disease-health-related quality of life, a-RSCL adapted Rotterdam symptom checklist, QLQ-OES24 quality of life questionnaire esophagus-24, MOS-SF-20 medical outcomes study short-form general health survey, FACT-E functional assessment of cancer therapy scale esophageal cancer, PAIS psychosocial adjustment to illness scale, POMS profile of mood states.
aPrimary aim: HRQL was the only outcome mentioned and / or HRQL was the first outcome mentioned in the main text. Secondary aim: HRQL was not the first outcome mentioned in the main text and / or the study referenced a previous study, based on the same data set, reporting on different outcomes
bNumber of patients assessed for HRQL at the first assessment point as reported in the study report
cAs explicitly stated in the study report
dYes if a study explicitly stated in the study report that HRQL was assessed at either 3, 6, 9,or 12 months. Studies that used timeframes to cover several months, for example 1-3 months were assessed as unclear
* Based on the additional HRQL outcome data provided
‡We imputed the standard deviation
§We transformed the timing of assessment
♯The study from Lagergren et al. evaluated the same patient group as Avery et al., and reported outcome data for 9 months follow-up
Study characteristics: treatments
Treatments evaluated in15 studies included in the meta-analysisAuthora / Surgical procedure(s)b / Percentage
neo-adjuvant treatment / Neo-adjuvant treatment(s) / Adjuvanttherapy / Lymphadenectomy / Anostomosis / Replacement
tube / Post-operative
complications
Open surgery
Teoh / Right two phase (75%)
Three phase (16%)
Other (9%) / RT (9%)
CT (5%) / Two-field / Cervical (-)
Inthrathoracic (-) / Gastro (-)
Colon(-) / 39%
Nafteux / Right two right (18%)
Transthoracic left (82%) / Two-field / Cervical (-)
Inthrathoracic (-) / Gastro / ?
Wang / Three-phase (100%) / Two-field / Cervical / Gastro / 44,8 %
Reynolds / Left-sided approach (13%)
Transhiatal (3%)
Right two phase (51%)
Threephase (34%) / Unclear / Unclear / Unclear / 51,7 %
Tan / Two-phase (100%)
- transthoracic left (57%)
- transthoracic right (43%) / Two-field / Cervical (-)
Inthrathoracic (-) / Gastro / Unclear
de Boer / Transhiatal (100%) / Extended en bloc / Cervical / Gastro / Unclear
de Boer / Twophase (100%) / Extended en bloc / Cervical / Gastro / Unclear
Brooks / Unclear / Unclear / Unclear / Unclear / Unclear
Open surgerycombined
Scarpa / Right two phase (-)
Three phase (-) / Total (77%)
CT (43%)
CRT (57%) / Two cycles of Cis + 5-FU
Daily fractions 1,8 Gy to 45-50 Gy & 2 cycles Cis + 5-FU / Unclear (70%) / En-bloc (?%) / Cervical (25%)
Inthrathoracic (75%) / Gastro (93%) Colon (4%)
Jejuno (3%) / 37 %
Safieddine / Left-sided approach (-)
Right two phase (-)
Threephase (-) / CRT (87%) / Cis 30 mg/m2 + Irino 65m/mg2
+ 40 Gy + boost (to 50 Gy) / Two-field / Cervical (-)
Inthrathoracic (-) / Unclear / Unclear
Van Meerten / Transhiatal (88%)
Twophase (12%) / CRT (100%) / Pacl 50 mg/m2 + carb +
23 fractions to 41,4 Gy / Two-field / Cervical / Unclear / 73%
Avery / Two-phase (100%) / Total (100%)
CT (59%)
CRT (41%) / Cis 80 mg/m2 + 5-FU (1g per m2 per day) or four cycles of Epi 50mg/m2 +
Cis 60mg/m2 + 5-FU 200 mg/m2 per infusion
Four cycles of CIS 60 mg/m2 + 12 weeks 5-FU + 45 Gy total in 25 fractions for 5 weeks / Two-field / Unclear / Unclear / 47%
Lagergren / Transhiatal (6%)
Right two phase (89%)
Three phase (4%) / Total (62%)
CT (-)
CRT (-) / Unclear / Two-field / Unclear / Unclear / Unclear
Reynolds / Transhiatal (1%)
Two phase (77%)
Three phase (21%) / CRT (-) / Unclear / Unclear / Unclear / Unclear / 52%
Brooks / (-) / Unclear / Unclear
MinimallyInvasiveSurgery
Nafteux / MinimallyInvasive (100%) / Two-field / Cervical / Gastro / Unclear
Wang / Three-phase (100%) / Two-field / Cervical (retro) / Gastro / 35%
Wang / Three-phase (100%) / Two-field / Cervical (pre) / Gastro / 33%
Minimallyinvasivesurgerycombined
Parameswaran / Minimallyinvasive (100%) / Total (77%)
CTx (100%) / Cis + 5-FU / Two-field / Cervical / Gastro / 50%
Gastrectomy
Barbour / Gastrectomy / CTx (10%) / (-) / One-field / (-) / (-) / 55%
CT: chemotherapy, CRT: chemoradiotherapy, RT: ratiotherapy, Cis: cisplatin, 5-FU: 5-fluorouracil, Gy: Gray, Pacl: paclitaxel, Carb: carboplatin, Irino: irinotecan, VATS: Video-Assisted Thoracoscopic Surgery, Epi: epirubicin, (-): unclear
aStudies that evaluated more than one patient group were entered more than once (e.g. the study from de Boer evaluated two patients groups and thus was entered twice).
bLeft-sided approach included ‘‘left thoracotomy,’’ ‘‘thoracoabdominal’’, ‘‘thoracolaparotomy’’, and "transabdominal". Right two phase included ‘‘Ivor-Lewis’’, ‘‘transthoracic’’, and ‘‘two-phase
esophagectomy’.’ Three phase included ‘‘threephaseesophagectomy’’ and ‘‘McKeownesophagectomy". Minimally invasive approach included "minimally invasive surgery", "Minimally
invasiveesophagectomy", and " VATS". Any techniques not within these categories were classified as ‘‘other’’.
! data extracted from retrieved patient database
*data extracted from previous report on clinical outcomes
Study characteristics: patients
Patients' demographic and clinical characteristics of the 15 studies included in the meta-analysisAuthor / Age / Sex / Tumour site / Histology / Tumour stage
Mean ± SD
(range) / (M / F ratio) / Adeno / SCC / HGD / Staging method / pCR / Stage
0 / I / Stage
IIA +IIB / Stage
III / Stage
IV
Open surgery
Teoh / 62 ± 9,4!
(47-75) / 88% / 12%! / O (100%) / 100% / unclear / unclear / unclear / unclear / unclear
Nafteux / 64,1 ± (-)
(29-82) / 82%/18% / O (92%)
OGJ (7%)
Cardia (1%) / 69%! / 25%! / 1%! / pTNM / 79%! / 14%! / 3%!
Wang / 58,2 ± 11.5
(-) / 66% / 34% / O / 7% / 93% / pTNM / 17% / 66% / 17%
Reynolds / 64m ± (-)
(29-79) / unclear / O / 62% / 38% / pTNM / 11% / 31% / 56% / 2%
Tan / 60.3m ± 8.7
(51-69) / 81% / 19% / Unclear / 100% / pTNM / unclear / unclear / unclear / unclear
de Boer / 62 ± (-)
(23-78) / 88% / 12% / O/OGJ (84%)
Cardia (16%) / 100% / pTNM / 13%* / 30%* / 50%* / 7%*
de Boer / 62 ± (-)
(35-78) / 86% / 14% / O/OGJ (84%)
Cardia (16%) / 100% / pTNM / 16%* / 15%* / 54%* / 15%*
Brooks / 68,2 ± 10.1
(43-82) / 89% / 11% / O / 67% / 17% / 11% / cTNM / 22% / 44% / 33%
Open surgerycombined
Scarpa / 60,5 ± (-)
(53-67) / 81% / 19% / O / 60% / 40% / unclear / unclear / unclear / unclear / unclear
Safieddine / 60 ± (-)
(33-79) / 77% / 23% / O (71%)
OGJ (29%) / 74% / 26% / c-TNM / 40% / 39% / 21%
van Meerten / 59m ± (-)
(40-75) / 91% / 9% / Thoracic (9%)
Lower (91%) / 76% / 22% / unclear / unclear / unclear / unclear / unclear
Avery / 62.4 ± 8.5
(-) / 70% / 30% / O / 79% / 21% / cTNM / 17% / 83%
Lagergren / 63 ± (-)
(44-79) / 66% / 34% / O (51%)
OGJ (49%) / 74% / 19% / 6% / pTNM / 13% / 25% / 49% / 13%
Reynolds / 58m ± (-)
(44-74) / unclear / O / 72% / 28% / pTNM / 21% / 16% / 36% / 25% / 1%
Brooks / 57,1 ± 8.7
(42-71) / 95% / 5% / O / 95% / 5% / cTNM / 10% / 90%
Minimallyinvasivesurgery
Nafteux / 63.1 ± (-)
(41-82) / 80% / 20% / O(92%)
OGJ (8%) / 78%! / 19%! / 2%! / pTNM / 94%! / 6%!
Wang / 60.3 ± 7.8
(-) / 67% / 33% / O / 4% / 96% / pTNM / 23% / 64% / 13%
Wang / 61.8 ± 8.7
(-) / 61% / 39% / O / 2% / 98% / pTNM / 25% / 67% / 8%
Minimallyinvasivesurgerycombined
Parameswaran / 67m ± (-)
(49-80) / 90% / 10% / O / 89% / 8% / 3% / unclear / 16% / 34% / 44% / 6%
Gastrectomy
Barbour / 69 ± 10
(-) / 80% / 20% / OGJ / 100% / pTNM / 5% / 40% / 45% / 10%
SD-standard deviation, Adeno-adenocarcinoma, SCC-Squamous cell carcinoma, HGD-high grade dysplasia, O-oesphagus, OGJ-oesophageal-gastric junction, pTNM-pathological staging, cTNM-clinical staging
mmedian
(-) unclear
! data extracted from patient database received from the first author
*data extracted from a previous report on clinical outcomes
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