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Article ; Online: Comparing Outcomes of Segmentectomy and Lobectomy for Non-small Cell Lung Cancer: Is Less Truly More?

Roman, Marius A / Nakas, Apostolos

2020 Volume 159, Issue 1, Page(s) 21–22

MeSH term(s)	Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Humans ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Neoplasm Staging ; Pneumonectomy ; Thoracic Surgery, Video-Assisted
Language	English
Publishing date	2020-12-04
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1032552-9
ISSN	1931-3543 ; 0012-3692
ISSN (online)	1931-3543
ISSN	0012-3692
DOI	10.1016/j.chest.2020.07.063
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Zs.MO 349: Show issues

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Article ; Online: Metastatic renal cell carcinoma extending to the left atrium through the inferior pulmonary vein.

Dawson, Alan G / Richards, Cathy J / Hadjinikolaou, Leonidas / Nakas, Apostolos

Interactive cardiovascular and thoracic surgery

2021 Volume 32, Issue 6, Page(s) 991–992

Abstract: Metastatic renal cell carcinoma with involvement through the pulmonary veins to the left atrium is very rare. We report the case of a 70-year-old male with metastatic renal cell carcinoma to the right lower lobe of the lung abutting the inferior ... ...

Abstract	Metastatic renal cell carcinoma with involvement through the pulmonary veins to the left atrium is very rare. We report the case of a 70-year-old male with metastatic renal cell carcinoma to the right lower lobe of the lung abutting the inferior pulmonary vein with extension to the left atrium without pre-operative evidence. Surgical resection was achieved through a posterolateral thoracotomy. Lung masses that abut the pulmonary veins should prompt further investigation with a pre-operative transoesophageal echocardiogram to minimize unexpected intraoperative findings.
MeSH term(s)	Aged ; Carcinoma, Renal Cell/diagnostic imaging ; Carcinoma, Renal Cell/surgery ; Heart Atria/diagnostic imaging ; Heart Atria/surgery ; Humans ; Kidney Neoplasms/diagnostic imaging ; Kidney Neoplasms/surgery ; Lung ; Male ; Pulmonary Veins/diagnostic imaging ; Pulmonary Veins/surgery
Language	English
Publishing date	2021-01-27
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2095298-3
ISSN	1569-9285 ; 1569-9293
ISSN (online)	1569-9285
ISSN	1569-9293
DOI	10.1093/icvts/ivab018
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Article ; Online: Cytoreductive surgery with hyperthermic intrathoracic chemotherapy for malignant pleural mesothelioma: a systematic review.

Dawson, Alan G / Kutywayo, Kudzayi / Mohammed, Seid B / Fennell, Dean A / Nakas, Apostolos

Thorax

2022 Volume 78, Issue 4, Page(s) 409–417

Abstract: Introduction: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. ... ...

Abstract	Introduction: Cytoreductive surgery has been used a part of multimodality treatment in patients with malignant pleural mesothelioma (MPM). The residual microscopic disease that remains will lead to disease progression in the majority of patients. Delivery of hyperthermic intrathoracic chemotherapy at the time of surgery has been used to address this microscopic disease, however it's effect and place in the multimodality treatment sphere is unknown. The aim of this systematic review was to assess the effect of surgery and hyperthermic intrathoracic chemotherapy in patients with MPM on overall survival and disease-free interval. Methods: Ovid MEDLINE, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from database inception through to June 2021. Studies reporting overall survival and/or disease-free interval in patients with MPM undergoing cytoreductive surgery with hyperthermic intrathoracic chemotherapy were considered. Study quality was assessed using the Newcastle-Ottawa Scale. A narrative review was performed. Results: Fifteen studies were eligible for inclusion comprising 598 patients. Surgery with hyperthermic intrathoracic chemotherapy was associated with a median overall survival and disease-free interval ranging from 11 to 75 months and 7.2 to 57 months, respectively. These appeared to be superior to patients not receiving hyperthermic intrathoracic chemotherapy (overall survival: 5-36 months and disease-free interval: 12.1-21 months). A higher dose of hyperthermic intrathoracic chemotherapy was associated with an improvement in overall survival compared with a lower dose: 18-31 months versus 6-18 months, respectively. The most common morbidity was atrial fibrillation followed by renal complications. Conclusion: Surgery with hyperthermic intrathoracic chemotherapy offers a safe and effective therapy with an improvement in disease-free interval and overall survival, particularly when hyperthermic intrathoracic chemotherapy is administered at a higher dose. Prospero registration number: CRD42019129002.
MeSH term(s)	Humans ; Mesothelioma, Malignant ; Mesothelioma/surgery ; Cisplatin/therapeutic use ; Cytoreduction Surgical Procedures ; Pleural Neoplasms/drug therapy ; Pleural Neoplasms/surgery ; Combined Modality Therapy
Chemical Substances	Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-04-11
Publishing country	England
Document type	Review ; Journal Article ; Systematic Review
ZDB-ID	204353-1
ISSN	1468-3296 ; 0040-6376
ISSN (online)	1468-3296
ISSN	0040-6376
DOI	10.1136/thoraxjnl-2021-218214
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Article ; Online: Predictors of long-term survival following radical surgery for malignant pleural mesothelioma.

Nakas, Apostolos / Waller, David

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2014 Volume 46, Issue 3, Page(s) 380–5; discussion 385

Abstract: Objectives: The aim of radical surgery for malignant pleural mesothelioma (MPM) is to achieve greater survival than from chemotherapy alone. Although adverse overall prognostic factors have already been determined, our aim was to identify the most ... ...

Abstract	Objectives: The aim of radical surgery for malignant pleural mesothelioma (MPM) is to achieve greater survival than from chemotherapy alone. Although adverse overall prognostic factors have already been determined, our aim was to identify the most important factors affecting long-term survival arbitrarily defined as >24 months. Methods: We retrospectively reviewed the records of 252 patients (35 females; 193 epithelioid and 59 biphasic; 112 extrapleural pneumonectomy (EPP); 140 extended pleurectomy decortication (EPD)) who survived for at least 90 postoperative days. We tested for factors affecting overall cancer-related mortality and specific clinical factors predicting the 24-month survival. Results: The overall median survival was 18.2 (SE 1.3, 95% CI 15.8-20.7 months). There was no difference in survival between EPP and EPD (P = 0.92). One hundred and twenty-eight patients received induction, adjuvant or palliative chemotherapy. Seventy-seven (30.6%) patients survived for >24 months. On univariate analysis, age at operation over 60 years (P = 0.044), pT4 stage (P = 0.041), any lymph node metastases (P = 0.002), biphasic cell type (P = 0.00) and no administration of chemotherapy (P = 0.00) were associated with decreased survival. On multivariate analysis, age <60 (P = 0.018, OR = 0.7), epithelioid disease (P = 0.001, OR = 0.56) and negative nodes (P = 0.009, OR = 0.67) were associated with increased survival and no administration of chemotherapy (P = 0.00, OR = 1.9) with decreased survival. Factors predicting survival over 24 months included: age at operation under 60 (P = 0.014), epithelioid histology (P ≤ 0.00), negative nodes (P = 0.002) and chemotherapy (P = 0.022). Conclusions: These results support a policy of accurate preoperative tissue diagnosis, nodal staging and induction chemotherapy prior to radical surgery for MPM, which can result in long-term survival. Trials investigating the role of surgery should be focused on confirming and refining these selection criteria.
MeSH term(s)	Adolescent ; Adult ; Aged ; Analysis of Variance ; Female ; Humans ; Lung Neoplasms/surgery ; Male ; Mesothelioma/surgery ; Mesothelioma, Malignant ; Middle Aged ; Pleural Neoplasms/surgery ; Pneumonectomy/methods ; Prognosis ; Retrospective Studies ; Survival Analysis ; Survival Rate ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2014-01-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezt664
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Article ; Online: Gene fusions during the early evolution of mesothelioma correlate with impaired DNA repair and Hippo pathways.

Jama, Maymun / Zhang, Min / Poile, Charlotte / Nakas, Apostolos / Sharkey, Annabel / Dzialo, Joanna / Dawson, Alan / Kutywayo, Kudazyi / Fennell, Dean A / Hollox, Edward J

Genes, chromosomes & cancer

2023 Volume 63, Issue 1, Page(s) e23189

Abstract: Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene fusions arising ... ...

Abstract	Malignant pleural mesothelioma (MPM), a rare cancer a long latency period (up to 40 years) between asbestos exposure and disease presentation. The mechanisms coupling asbestos to recurrent somatic alterations are poorly defined. Gene fusions arising through genomic instability may create novel drivers during early MPM evolution. We explored the gene fusions that occurred early in the evolutionary history of the tumor. We conducted multiregional whole exome sequencing (WES) of 106 samples from 20 patients undergoing pleurectomy decortication and identified 24 clonal nonrecurrent gene fusions, three of which were novel (FMO9P-OR2W5, GBA3, and SP9). The number of early gene fusion events detected varied from zero to eight per tumor, and presence of gene fusions was associated with clonal losses involving the Hippo pathway genes and homologous recombination DNA repair genes. Fusions involved known tumor suppressors BAP1, MTAP, and LRP1B, and a clonal oncogenic fusion involving CACNA1D-ERC2, PARD3B-NT5DC2, and STAB2-NT5DC2 fusions were also identified as clonal fusions. Gene fusions events occur early during MPM evolution. Individual fusions are rare as no recurrent truncal fusions event were found. This suggests the importance of early disruption of these pathways in generating genomic rearrangements resulting in potentially oncogenic gene fusions.
MeSH term(s)	Humans ; Mesothelioma, Malignant/genetics ; Hippo Signaling Pathway ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Mesothelioma/genetics ; Asbestos ; DNA Repair/genetics ; Gene Fusion
Chemical Substances	Asbestos (1332-21-4)
Language	English
Publishing date	2023-07-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23189
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Zs.A 2966: Show issues

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Article ; Online: Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells.

Chernova, Tatyana / Grosso, Stefano / Sun, Xiao-Ming / Tenor, Angela Rubio / Cabeza, Joaquin Zacarias / Craxton, Andrew / Self, Emily L / Nakas, Apostolos / Cain, Kelvin / MacFarlane, Marion / Willis, Anne E

International journal of molecular sciences

2022 Volume 23, Issue 20

Abstract: Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. ... ...

Abstract	Malignant mesothelioma is an aggressive tumour of the pleura (MPM) or peritoneum with a clinical presentation at an advanced stage of the disease. Current therapies only marginally improve survival and there is an urgent need to identify new treatments. Carcinoma-associated fibroblasts (CAFs) represent the main component of a vast stroma within MPM and play an important role in the tumour microenvironment. The influence of CAFs on cancer progression, aggressiveness and metastasis is well understood; however, the role of CAF-derived extracellular vesicles (CAF-EVs) in the promotion of tumour development and invasiveness is underexplored. We purified CAF-EVs from MPM-associated cells and healthy dermal human fibroblasts and examined their effect on cell proliferation and motility. The data show that exposure of healthy mesothelial cells to EVs derived from CAFs, but not from normal dermal human fibroblasts (NDHF) resulted in activating pro-oncogenic signalling pathways and increased proliferation and motility. Consistent with its role in suppressing Yes-Associated Protein (YAP) activation (which in MPM is a result of Hippo pathway inactivation), treatment with Simvastatin ameliorated the pro-oncogenic effects instigated by CAF-EVs by mechanisms involving both a reduction in EV number and changes in EV cargo. Collectively, these data determine the significance of CAF-derived EVs in mesothelioma development and progression and suggest new targets in cancer therapy.
MeSH term(s)	Humans ; Mesothelioma, Malignant ; Cancer-Associated Fibroblasts/metabolism ; YAP-Signaling Proteins ; Cell Line, Tumor ; Mesothelioma/pathology ; Extracellular Vesicles/metabolism ; Carcinogenesis/metabolism ; Simvastatin ; Tumor Microenvironment
Chemical Substances	YAP-Signaling Proteins ; Simvastatin (AGG2FN16EV)
Language	English
Publishing date	2022-10-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232012469
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Article ; Online: BAP1 loss induces mitotic defects in mesothelioma cells through BRCA1-dependent and independent mechanisms.

Singh, Anita / Busacca, Sara / Gaba, Aarti / Sheaff, Michael / Poile, Charlotte / Nakas, Apostolos / Dzialo, Joanna / Bzura, Aleksandra / Dawson, Alan G / Fennell, Dean A / Fry, Andrew M

Oncogene

2022 Volume 42, Issue 8, Page(s) 572–585

Abstract: The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability ... ...

Abstract	The tumour suppressor BRCA1-associated protein 1 (BAP1) is the most frequently mutated cancer gene in mesothelioma. Here we report novel functions for BAP1 in mitotic progression highlighting the relationship between BAP1 and control of genome stability in mesothelioma cells with therapeutic implications. Depletion of BAP1 protein induced proteasome-mediated degradation of BRCA1 in mesothelioma cells while loss of BAP1 correlated with BRCA1 loss in mesothelioma patient tumour samples. BAP1 loss also led to mitotic defects that phenocopied the loss of BRCA1 including spindle assembly checkpoint failure, centrosome amplification and chromosome segregation errors. However, loss of BAP1 also led to additional mitotic changes that were not observed upon BRCA1 loss, including an increase in spindle length and enhanced growth of astral microtubules. Intriguingly, these consequences could be explained by loss of expression of the KIF18A and KIF18B kinesin motors that occurred upon depletion of BAP1 but not BRCA1, as spindle and astral microtubule defects were rescued by re-expression of KIF18A and KIF18B, respectively. We therefore propose that BAP1 inactivation causes mitotic defects through BRCA1-dependent and independent mechanisms revealing novel routes by which mesothelioma cells lacking BAP1 may acquire genome instability and exhibit altered responses to microtubule-targeted agents.
MeSH term(s)	Humans ; BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; Chromosome Segregation ; Genes, Tumor Suppressor ; Kinesins/genetics ; Kinesins/metabolism ; Lung Neoplasms/pathology ; Mesothelioma/pathology ; Mesothelioma, Malignant/genetics ; Mesothelioma, Malignant/metabolism ; Microtubules/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism ; Ubiquitin Thiolesterase/genetics ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	BAP1 protein, human ; BRCA1 Protein ; BRCA1 protein, human ; KIF18A protein, human (EC 3.6.1.-) ; KIF18B protein, human (EC 3.6.1.-) ; Kinesins (EC 3.6.4.4) ; Tumor Suppressor Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2022-12-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-022-02577-3
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Zs.A 2218: Show issues

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Article ; Online: The effects of an intentional transition from extrapleural pneumonectomy to extended pleurectomy/decortication.

Sharkey, Annabel J / Tenconi, Sara / Nakas, Apostolos / Waller, David A

European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

2016 Volume 49, Issue 6, Page(s) 1632–1641

Abstract: Objectives: For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected ... ...

Abstract	Objectives: For many years, extrapleural pneumonectomy (EPP) was the operation of choice for the radical management of pleural mesothelioma in the UK. However, doubts surrounding the efficacy of EPP, and the change in demographics of the affected population, have prompted a transition in our practice towards extended pleurectomy/decortication (EPD). The aim of this study was to determine the effects an intentional transition from EPP to EPD has had on patient outcome. Methods: Data from 362 patients undergoing radical surgery (229 EPD, 133 EPP) during 1999-2014 were included. Demographics and outcome were compared between the two groups; EPP versus EPD. Results: The median age of patients undergoing EPD was significantly higher than those undergoing EPP [57 years (range 14-70 years) vs 65 years (range 42-81 years), P < 0.001]. There was a significantly higher proportion of patients with performance status ≥1 in the EPD group (46.3 vs 35.4%, P = 0.047). There was no difference in the median length of hospital stay between the two groups [14 days (range 1-133 days) vs 13 days (range 0-93 days), P = 0.409]. There was also no difference between the groups in terms of in-hospital mortality (EPP 5.3% and EPD 6.6%, P = 0.389), 30-day mortality [EPP 8 (6.0%) and EPD 8 (3.5%), P = 0.294] or 90-day mortality [EPP 18 (13.5%) and EPD 21 (9.2%), P = 0.220]. There was a significantly higher early reoperation rate in the EPP group (15.0 vs 6.2%, P = 0.008) but a significantly higher late reoperation rate in the EPD group (0.8 vs 5.3%, P = 0.037). There was no significant difference in overall survival or disease-free interval between the two groups (P = 0.899 and P = 0.399, respectively). However, overall survival was significantly greater in patients over the age of 65 undergoing EPD (12.5 vs 4.7 months, P = 0.001). Conclusion: The transition from EPP to EPD in our standard practice has enabled us to operate on more elderly, frail patients with no significant increase in use of hospital resources, and without detriment to overall survival.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chemotherapy, Adjuvant ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Mesothelioma/surgery ; Mesothelioma/therapy ; Middle Aged ; Pleural Neoplasms/surgery ; Pleural Neoplasms/therapy ; Pneumonectomy/methods ; Pneumonectomy/trends ; Professional Practice/trends ; Radiotherapy, Adjuvant ; Reoperation/statistics & numerical data ; Retrospective Studies ; Treatment Outcome ; Young Adult
Language	English
Publishing date	2016-06
Publishing country	Germany
Document type	Journal Article
ZDB-ID	639293-3
ISSN	1873-734X ; 1010-7940 ; 1567-4258
ISSN (online)	1873-734X
ISSN	1010-7940 ; 1567-4258
DOI	10.1093/ejcts/ezv403
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Article ; Online: Extended pleurectomy decortication for malignant pleural mesothelioma in the elderly: the need for an inclusive yet selective approach.

Sharkey, Annabel Jane / Bilancia, Rocco / Tenconi, Sara / Nakas, Apostolos / Waller, David A

Interactive cardiovascular and thoracic surgery

2017 Volume 25, Issue 5, Page(s) 696–702

Abstract: Objectives: The median age at diagnosis of patients with pleural mesothelioma in the UK is 73 years. Recent series have shown the feasibility of extended pleurectomy decortication in the elderly, but with continuing debate about the efficacy of this ... ...

Abstract	Objectives: The median age at diagnosis of patients with pleural mesothelioma in the UK is 73 years. Recent series have shown the feasibility of extended pleurectomy decortication in the elderly, but with continuing debate about the efficacy of this treatment, we reviewed our experience to identify more detailed selection criteria. Methods: We reviewed prospectively collected data on all patients from 1999 to 2016 undergoing extended pleurectomy decortication. We compared clinical and pathological outcomes and survival data from patients 70 years and older (≥70 years) with those younger than 70 years (<70 years). Results: Eighty-two of the 300 (27.3%) patients were ≥70 years of age at the time of surgery. More patients in the elderly group required intensive care postoperatively (6.2 vs 16.7%, P = 0.01) and developed atrial fibrillation (14.4 vs 24.4%, P = 0.05). There was no intergroup difference in length of hospital stay or in in-hospital, 30-day or 90-day mortality. Elderly patients were less likely to receive neoadjuvant (<70 years 21.2%, ≥70 years 11.0%; P = 0.045) or adjuvant chemotherapy (<70 years 45.4%, ≥70 years 29.3%; P = 0.04). Median overall survival was similar: <70 years 14.0 months, ≥70 years 10.3 months; P = 0.29. However, in node-positive patients, survival was poorer in the elderly (13.0 vs 9.1 months, P = 0.05), particularly in those with non-epithelioid tumours (3.8 vs 6.7 months, P = 0.04). On multivariable analysis, age was not a significant prognostic factor, although lack of adjuvant therapy (P = 0.001) and admission to the intensive care unit (P < 0.001) remained poor prognostic factors. Conclusions: Although age in isolation should not be an exclusion criterion for extended pleurectomy decortication for mesothelioma, in the elderly, a more rigorous preoperative evaluation of nodal disease and an additional assessment of fitness for adjuvant chemotherapy are recommended.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/mortality ; Lung Neoplasms/surgery ; Male ; Mesothelioma/diagnosis ; Mesothelioma/mortality ; Mesothelioma/surgery ; Mesothelioma, Malignant ; Middle Aged ; Patient Selection ; Pleura/diagnostic imaging ; Pleura/surgery ; Pleural Neoplasms/diagnosis ; Pleural Neoplasms/mortality ; Pleural Neoplasms/surgery ; Positron-Emission Tomography ; Retrospective Studies ; Survival Rate/trends ; Thoracic Surgical Procedures/methods ; Tomography, X-Ray Computed ; Treatment Outcome ; United Kingdom/epidemiology
Language	English
Publishing date	2017-10-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2095298-3
ISSN	1569-9285 ; 1569-9293
ISSN (online)	1569-9285
ISSN	1569-9293
DOI	10.1093/icvts/ivx221
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Article ; Online: Inclusion of multiple high-risk histopathological criteria improves the prediction of adjuvant chemotherapy efficacy in lung adenocarcinoma.

Sereno, Marco / He, Zhangyi / Smith, Claire R / Baena, Juvenal / Das, Madhumita / Hastings, Robert K / Rake, Grace / Fennell, Dean A / Nakas, Apostolos / Moore, David A / Le Quesne, John

Histopathology

2021 Volume 78, Issue 6, Page(s) 838–848

Abstract: Aims: The decision to consider adjuvant chemotherapy (AC) for non-small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ... ...

Abstract	Aims: The decision to consider adjuvant chemotherapy (AC) for non-small cell lung cancer is currently governed by clinical stage. This study aims to assess other routinely collected pathological variables related to metastasis and survival for their ability to predict the efficacy of AC in lung adenocarcinoma. Methods and results: A retrospective single-centre series of 620 resected lung non-mucinous adenocarcinoma cases from 2005 to 2015 was used. Digital images of all slides were subjected to central review, and data on tumour histopathology, AC treatment and patient survival were compiled. A statistical case matching approach was used to counter selection bias. Several high-risk pathological criteria predict both pathological nodal involvement and early death: positive vascular invasion status (VI+) (HR = 2.10, P < 0.001), positive visceral pleural invasion status (VPI+) (HR = 2.16, P < 0.001), and solid/micropapillary-predominant WHO tumour type (SPA/MPPA) (HR = 3.29, P < 0.001). Crucially, these criteria also identify patient groups benefiting from AC (VI + HR = 0.69, P = 0.167, VPI + HR = 0.44, P = 0.004, SPA/MPPA HR = 0.36, P = 0.006). Cases showing VI+/VPI+/SPA/MPPA histology in the absence of AC stage criteria were common (170 of 620 total), and 8 had actually received AC. This group showed much better outcomes than equivalent untreated cases in matched analysis (3-year OS 100.0% versus 31.3%). Inclusion of patients with VI+/VPI+/SPA/MPPA histology would increase AC-eligible patients from 51.0% to 84.0% of non-mucinous tumours in our cohort. Conclusions: Our data provide preliminary evidence that the consideration of AC in patients with additional high-risk pathological indicators may significantly improve outcomes in operable lung adenocarcinoma, and that AC may be currently underused.
MeSH term(s)	Adenocarcinoma of Lung/drug therapy ; Adenocarcinoma of Lung/mortality ; Adenocarcinoma of Lung/pathology ; Adenocarcinoma of Lung/surgery ; Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Chemotherapy, Adjuvant ; Female ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/mortality ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Male ; Middle Aged ; Neoplasm Invasiveness/pathology ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14301
Database	MEDical Literature Analysis and Retrieval System OnLINE

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