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Radical multimodality therapy for malignant pleural mesothelioma

Appendices

Appendix 1. Cochrane Central Register of Controlled Trials Register (CENTRAL)

#1 MeSH descriptor: [Mesothelioma] explode all trees

#2 MeSH descriptor: [Pleural Neoplasms] explode all trees

#3 malignant mesothelioma

#4 malignant pleural mesothelioma

#5 pleural neoplasm*

#6 pleural cancer*

#7 #1 or #2 or #3 or #4 or #5 or #6

#8 combin*

#9 multimod*

#10 radical

#11 #8 or #9 or #10

#12 #7 and #11

Appendix 2. MEDLINE (via PubMed) search strategy

#1,"Search mesothelioma[MeSH Terms]"

#2,"Search pleural neoplasms[MeSH Terms]"

#3,"Search ""mesothelioma, malignant""[Supplementary Concept]"

#4,"Search ""malignant pleural mesothelioma""[Other Term]"

#5,"Search malignant mesothelioma[Title/Abstract]"

#6,"Search malignant pleural mesothelioma[Title/Abstract]"

#7,"Search MPM[Title/Abstract]"

#8,"Search pleural neoplas*[Title/Abstract]"

#9,"Search pleural cancer*[Title/Abstract]"

#10,"Search #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9"

#11,"Search ""antineoplastic agents""[MeSH Terms]"

#12,"Search antineoplastic combined chemotherapy protocols[MeSH Terms]"

#13,"Search chemoradiotherapy[MeSH Terms]"

#14,"Search combined modality therapy[MeSH Terms]"

#15,"Search drug therapy[MeSH Terms]"

#16,"Search hyperthermia, induced[MeSH Terms]"

#17,"Search pleura/surgery[MeSH Terms]",1232,06:20:19

#18,"Search pneumonectomy[MeSH Terms]"

#19,"Search radiotherapy[MeSH Terms]"

#20,"Search thoracic surgical procedures[MeSH Terms]"

#21,"Search thoracotomy[MeSH Terms]"

#22,"Search ""pleurectomy""[Other Term]"

#23,"Search ((""decortication""[Other Term] OR ""decortication/pleurectomy""[Other Term] OR ""decortication pleurectomy""[Other Term]))"

#24,"Search radical[Other Term]"

#25,"Search surgery[Other Term]"

#26,"Search adjuvant[Title/Abstract]"

#27,"Search chemoradiotherap*[Title/Abstract]"

#28,"Search chemotherap*[Title/Abstract]"

#29,"Search combination[Title/Abstract]"

#30,"Search cytoreduc*[Title/Abstract]"

#31,"Search decortication[Title/Abstract]"

#32,"Search hypertherm*[Title/Abstract]"

#33,"Search multimod*[Title/Abstract]"

#34,"Search neoadjuvant*[Title/Abstract]"

#35,"Search photochemotherap*[Title/Abstract]"

#36,"Search pleurectom*[Title/Abstract]"

#37,"Search pleuropneumonectom*[Title/Abstract]"

#38,"Search pneumonectom*[Title/Abstract]"

#39,"Search radical[Title/Abstract]"

#40,"Search radiochemotherap*[Title/Abstract]"

#41,"Search radiotherap*[Title/Abstract]"

#42,"Search resection[Title/Abstract]"

#43,"Search surgery[Title/Abstract]"

#44,"Search surgical[Title/Abstract]"

#45,"Search thoracotom*[Title/Abstract]"

#46,"Search trimodal*[Title/Abstract]"

#47,"Search #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43 OR #44 OR #45 OR #46"

#48,"Search #10 AND #47"

#49,"Search randomized controlled trial[Publication Type]"

#50,"Search controlled clinical trial[Publication Type]"

#51,"Search randomized[Title/Abstract]"

#52,"Search placebo[Title/Abstract]"

#53,"Search drug therapy[MeSH Subheading]"

#54,"Search randomly[Title/Abstract]"

#55, "Search trial[Title/Abstract]"

#56,"Search groups[Title/Abstract]"

#57,"Search #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56"

#58,"Search animals[MeSH Terms]"

#59,"Search humans[MeSH Terms]"

#60,"Search #58 NOT #59"

#61,"Search #57 NOT #60"

#62,"Search #48 AND #61"

Appendix 3. Embase (via Ovid) search strategy

#1 'mesothelioma'/exp

#2 'pleura tumor'/exp

#3 'mesothelioma':ab,ti

#4 'malignant mesothelioma':ab,ti

#5 'malignant pleural mesothelioma':ab,ti

#6 'mpm':ab,ti

#7 'pleural neoplas*':ab,ti

#8 'pleural cancer*':ab,ti

#9 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8

#10 'antineoplastic agent'/exp

#11 'chemoradiotherapy'/exp

#12 'multimodality cancer therapy'/exp

#13 'drug therapy'/exp

#14 'hyperthermic therapy'/exp

#15 'pleura'/exp AND 'surgery'/exp

#16 'lung resection'/exp

#17 'radiotherapy'/exp

#18 'thorax surgery'/exp

#19 'thoracotomy'/exp

#20 'adjuvant':ab,ti

#21 'chemoradiotherap*':ab,ti

#22 'chemotherap*':ab,ti

#23 'combination':ab,ti

#24 'cytoreduc*':ab,ti

#25 'decortication':ab,ti

#26 'hypertherm*':ab,ti

#27 'multimod*':ab,ti

#28 'neoadjuvant*':ab,ti

#29 'photochemotherap*':ab,ti

#30 'pleurectom*':ab,ti

#31 'pleuropneumonectom*':ab,ti

#32 'pneumonectom*':ab,ti

#33 'radical':ab,ti

#34 'radiochemotherap*':ab,ti

#35 'radiotherap*':ab,ti

#36 'resection':ab,ti

#37 'surgery':ab,ti

#38 'surgical':ab,ti

#39 'thoracotom*':ab,ti

#40 'trimodal*':ab,ti

#41 #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40

#42 #9 AND #41

#43 'crossover procedure'/exp OR 'double‐blind procedure'/exp OR 'randomized controlled trial'/exp OR 'single‐blind procedure'/exp OR random* ORfactorial* OR crossover* OR cross NEXT/1 over* OR placebo* OR doubl* NEAR/1 blind* OR singl* NEAR/1 blind* OR assign* OR allocat* ORvolunteer*

#44 #42 AND #43

Study flow diagram.
Figuras y tablas -
Figure 1

Study flow diagram.

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Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study (the judgement for performance and detection bias is for endpoints other than overall survival).
Figuras y tablas -
Figure 2

Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study (the judgement for performance and detection bias is for endpoints other than overall survival).

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Risk of bias graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies (the judgement for performance and detection bias is for endpoints other than overall survival).
Figuras y tablas -
Figure 3

Risk of bias graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies (the judgement for performance and detection bias is for endpoints other than overall survival).

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Combined EPP plus neoadjuvant platinum‐based chemotherapy plus post operative high‐dose hemithoracic radiotherapy compared with combined EPP plus neoadjuvant platinum‐based chemotherapy for malignant pleural mesothelioma

Patient or population: people with malignant pleural mesothelioma

Settings: specialist hospital

Intervention: combined EPP plus neoadjuvant platinum‐based chemotherapy plus postoperative high‐dose hemithoracic radiotherapy

Comparison: combined EPP plus neoadjuvant platinum‐based chemotherapy

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

combined EPP plus chemotherapy

combined EPP plus chemotherapy plus hemithoracic radiotherapy

Median overall survival

20.8 months (95% CI 14.4 to 27.8)

19.3 months (95% CI 11.5 to 21.8)

‐

54 (1)

⊕⊕⊕⊝

Moderate1

Health‐related health‐related quality of life

No changes in the scores for the overall evaluation of life in both groups up to week 14 after randomisation

‐

54 (1)

⊕⊕⊝⊝

Low2

Adverse events

The following adverse events were observed in the radiotherapy arm: anaemia (74%), nausea or vomiting (44%), oesophagitis (29%), fatigue (24%), weight loss (19%), dyspnoea (4%), diarrhoea (4%), and increased alkaline phosphatase concentration (4%).

There was no comment on the adverse events in the no radiotherapy arm.

‐

54 (1)

⊕⊕⊝⊝

Low2

Postoperative complications

Postoperative complications included mediastinal shift (11%), major infections (8%), bleeding (6%), bronchial stump fistula(3%), pulmonary embolism, chylothorax, and technical failures (2% each). It was not classified in the trial based on treatment arms

‐

54 (1)

⊕⊕⊝⊝

Low2

Treatment‐related death

None reported.

One patient died of a complicated pneumonia during radiotherapy, which was probably related to treatment.

‐

54 (1)

⊕⊕⊝⊝

Low2

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; EPP: extrapleural pneumonectomy.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Due to imprecision, the quality of the evidence was assessed as moderate.

2Due to imprecision as well as high risk of bias, the quality of the evidence was assessed as low.

Figuras y tablas -
Ir a la tabla de la revisión

Combined platinum‐based chemotherapy plus EPP plus postoperative hemithoracic radiotherapy compared with chemotherapy for malignant pleural mesothelioma

Patient or population: people with malignant pleural mesothelioma

Settings: specialist hospital

Intervention: combined chemotherapy plus EPP plus postoperative hemithoracic radiotherapy

Comparison: chemotherapy

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Chemotherapy

Combined chemotherapy plus EPP plus postoperative hemithoracic radiotherapy

Median overall survival

19.5 months (95% CI 13.4 to time‐not‐yet reached)

14.4 months (95% CI 5.3 to 18.7)

‐

50 (1)

⊕⊕⊕⊝

Moderate

1

Health‐related health‐related quality of life

There were no statistically significant differences between treatment groups

‐

50 (1)

⊕⊕⊝⊝

Low2

Adverse events

2 serious adverse events

10 serious adverse events

‐

50 (1)

⊕⊕⊝⊝

Low2

Progression‐free survival

9.0 months (95% CI 7.2 to 14.7)

7.6 months (95% CI 5.0 to 13.4)

‐

50 (1)

⊕⊕⊝⊝

Low2

Treatment‐related death

One perioperative death occurred in the no EPP group (because one of the patients underwent EPP surgery outside the trial).

Three perioperative deaths occurred in patients randomly assigned to EPP.

‐

50 (1)

⊕⊕⊝⊝

Low2

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; EPP: extrapleural pneumonectomy

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Due to imprecision, the quality of the evidence was assessed as moderate.

2Due to imprecision as well as high risk of bias, the quality of the evidence was assessed as low.

Figuras y tablas -
Ir a la tabla de la revisión