European Journal of Cancer (2014) 50, 675– 677

A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m

ScienceDirect

journa l homepag e : www.e j cancer . com

Letter to the Editor

Surgery for early-stage lung cancer: Post-operative30-day versus 90-day mortality and patient-centred care

0959-8049/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.ejca.2013.09.029

⇑ Corresponding author at: Department of Radiation Oncology, VUUniversity Medical Center, De Boelelaan 1118, 1081 HV Amsterdam,The Netherlands. Tel.: +31 (0) 20 4440414; fax: +31 (0) 20 4440410.

E-mail address: s.senthi@vumc.nl (S. Senthi).

Sashendra Senthi a,b,⇑, Suresh Senan a

a Department of Radiation Oncology, VU University Medical Center, Amsterdam, The Netherlandsb William Buckland Radiation Oncology, Alfred Health, Melbourne, Australia

Dear Editor,

We read with interest the results of the randomisedtrial performed by Westeel et al. showing that fourcycles of preoperative chemotherapy did not increasesurvival compared to two preoperative and two post-operative cycles in Stage I and II non-small cell lungcancer (NSCLC) [1]. The 3-year disease-free survivalof 56% in both study arms highlights the guarded prog-nosis for NSCLC, even for young (75-years of less), rel-atively fit (World Health Organisation (WHO)performance score 0–2), clinically well-staged patientsreceiving chemotherapy. We would appreciate it if theauthors could clarify the mortality data observed intheir trial.

Although 30-day mortality is an important bench-mark for clinicians and hospital administrators, its def-initions vary and may omit deaths occurring followingprolonged admission, discharge into high dependencyunits or following readmission, thus underestimatingsurgical risk [2,3]. It was therefore surprising thatWeestel et al. reported identical 30-day and 90-daymortality rates, which ranged between 4.2% and 4.9%in either study arm. This observation is out of keepingwith published literature. Table 1 summarises recentdata, highlighting the ratio of deaths occurring within90 days of surgery, to those within 30 days, ranges

between 1.3 and 3.0 times. The ongoing mortality riskfollowing surgery persist when analyses exclude elderlypatients [4], surgery is limited to sublobar resections[3,5] or performed with video-assisted thoracoscopy[6]. Importantly, a significant proportion of deaths thatoccur between 31 and 90 days, are not attributable todisease recurrence and occur for ‘unknown reasons’ [2].

A primary barrier to shared decision making is thefact that delivery of care can be based largely on a singleclinician’s willingness to provide it [7]. The definition ofoperability for a resectable lung tumour is a primeexample of this, where the ‘threshold’ mortality riskaccepted by a surgeon may not be in keeping with thatof other surgeons or acceptable to different patients[8]. Additionally, as patients may lack the understandingor confidence to seek out appropriate information them-selves [7], mortality outcomes should be placed in con-text, relative to alternative curative options. Inparticular, stereotactic ablative radiotherapy (SABR)for early stage NSCLC has been shown to achievelong-term local control rates in excess of 90% [9] andthree recent propensity-matched analyses comparingsurgery and SABR found no major survival differences[10]. Table 1 also highlights this, showing 30-daymortality to be uncommon following SABR, a findingthat continues to hold true 90 days following treatment.Similarly, a systematic review found the 30-day mortal-ity following SABR for Stage I NSCLC in patients withsevere chronic obstructive pulmonary disease to be0% [11], putting into context one of the factors which

Table 1Recent studies reporting 30-day and 90-day mortality following surgery or SABR.

Author Type Time n Stage I Stage II Sublobarresections

30-day(%)

90-day(%)

Ratio90/ 30-day

Surgery

Fernando (2011) [3] Multi-centre RCT 2005–2010 222 100% – 100% (all <3 cm) 1.4 2.7 1.9Powell (2013) [13] National registry 2004–2010 10,991 48% 17% 22% 3.0 5.9 2.0Haasbeek (2012) [14] National registry 2001–2009 1698 100% – 6% 5.4 9.3 1.7Rueth (2012) [4] State registry 2000–2005 4171 100% – 0% 4.2 6.3 1.5Cheung (2009) [15] State registry 1998–2002 13,469 59% ‘local’ 35%

‘regional’14% 2.3 6.3 2.7

Damhuis (2013) [16] Regional registry 1997–2008 2668 Not reported 0% 4.5 7.5 1.7Rivera2011 [17] Voluntary registry 2004–2008 1969 74% 26% 8% 3.6 4.7 1.3Greillier (2007) [18] Single-centre prospective 2002–2004 110 55% 27% 0% 3.2 9.5 3.0Bryant (2010) [2] Single-centre retrospective 2002–2008 1845 Not reported 39% 4.1 6.4 1ca.6He (2011) [6] Single-centre retrospective 2000–2007 1058 41% 28% 5% 2.7 4.1 1.5Schuchert 2012 [5] Single-centre retrospective 2002–2010 785 81% 8% 100% 1.1 3.0 2.7St Julien (2012) [19] Single-centre retrospective 2005–2010 78 100% 89% 3.8 6.4 1.7

Stereotactic ablative radiotherapy

Crabtree (2013) [20] Multi-centre prospective 2004–2006 59 100% – – 0.0 0.0 –Verstegen (2013) [21] Single-centre retrospective 2003–2012 64 100% – – 0.0 0.0 –

676 S. Senthi, S. Senan / European Journal of Cancer 50 (2014) 675–677

potentially operable patients should consider whenchoosing their primary treatment. Clarification of themortality details from a contemporary European studysuch as IFCT 0002 would provide high quality data,despite the fact outcomes reported in clinical trials typ-ically exceed those in routine clinical practice [12].

Role of funding source

No direct funding supported this research.

Conflict of interest statement

The VU University Medical Center has researchcollaborations with Varian Medical Systems, BrainlabAG and Velocity Medical Solutions. S.U.S. has receivedhonoraria and travel support from Varian MedicalSystems. S.A.S. declares no personal conflicts of interest.

Acknowledgement

None.

References

[1] Westeel V, Quoix E, Puyraveau M, Lavole A, Braun D, LaporteS, et al. A randomised trial comparing preoperative to perioper-ative chemotherapy in early-stage non-small-cell lung cancer(IFCT 0002 trial). Eur J Cancer 2013;49(12):2654–64.

[2] Bryant AS, Rudemiller K, Cerfolio RJ. The 30- versus 90-dayoperative mortality after pulmonary resection. Ann Thorac Surg2010;89(6):1717–22 [discussion 1722–3].

[3] Fernando HC, Landreneau RJ, Mandrekar SJ, Hillman SL,Nichols FC, Meyers B, et al. The impact of adjuvant brachyther-apy with sublobar resection on pulmonary function and dyspneain high-risk patients with operable disease: preliminary resultsfrom the American College of Surgeons Oncology Group Z4032trial. J Thorac Cardiovasc Surg 2011;142(3):554–62.

[4] Rueth NM, Parsons HM, Habermann EB, Groth SS, Virnig BA,Tuttle TM, et al. Surgical treatment of lung cancer: predictingpostoperative morbidity in the elderly population. J ThoracCardiovasc Surg 2012;143(6):1314–23.

[5] Schuchert MJ, Abbas G, Awais O, Pennathur A, Nason KS,Wilson DO, et al. Anatomic segmentectomy for the solitarypulmonary nodule and early-stage lung cancer. Ann Thorac Surg2012;93(6):1780–5 [discussion 1786–7].

[6] He J, Shao W, Cao C, Yan T, Wang D, Xiong XG, et al. Long-term outcome and cost-effectiveness of complete versus assistedvideo-assisted thoracic surgery for non-small cell lung cancer. JSurg Oncol 2011;104(2):162–8.

[7] Salzburg Global S. Salzburg statement on shared decisionmaking. BMJ 2011;342:d1745.

[8] Lim E, Baldwin D, Beckles M, Duffy J, Entwisle J, Faivre-Finn C,et al. Guidelines on the radical management of patients with lungcancer. Thorax 2010;65(Suppl. 3):iii1–27.

[9] Palma DA, Senan S. Improving outcomes for high-risk patientswith early-stage non-small-cell lung cancer: insights from popu-lation-based data and the role of stereotactic ablative radiother-apy. Clin Lung Cancer 2013;14(1):1–5.

[10] Senan S. Surgery versus stereotactic radiotherapy for patientswith early-stage non-small cell lung cancer: more data fromobservational studies and growing clinical equipoise. Cancer 2013[Epub ahead of print].

[11] Palma D, Lagerwaard F, Rodrigues G, Haasbeek C, Senan S.Curative treatment of Stage I non-small-cell lung cancer in patientswith severe COPD: stereotactic radiotherapy outcomes and system-atic review. Int J Radiat Oncol Biol Phys 2012;82(3):1149–56.

[12] Chow CJ, Habermann EB, Abraham A, Zhu Y, Vickers SM,Rothenberger DA, et al. Does enrollment in cancer trials improvesurvival? J Am Coll Surg 2013;216(4):774–80 [discussion 780–1].

[13] Powell HA, Tata LJ, Baldwin DR, Stanley RA, Khakwani A,Hubbard RB. Early mortality after surgical resection for lungcancer: an analysis of the English National Lung cancer audit.Thorax 2013;68(9):826–34.

[14] Haasbeek CJ, Palma D, Visser O, Lagerwaard FJ, Slotman B,Senan S. Early-stage lung cancer in elderly patients: a population-based study of changes in treatment patterns and survival in theNetherlands. Ann Oncol 2012;23(10):2743–7.

[15] Cheung MC, Hamilton K, Sherman R, Byrne MM, Nguyen DM,Franceschi D, et al. Impact of teaching facility status and high-volume centers on outcomes for lung cancer resection: an

S. Senthi, S. Senan / European Journal of Cancer 50 (2014) 675–677 677

examination of 13,469 surgical patients. Ann Surg Oncol2009;16(1):3–13.

[16] Damhuis RA, Wijnhoven BP, Plaisier PW, Kirkels WJ, Kranse R,van Lanschot JJ. Comparison of 30-day, 90-day and in-hospitalpostoperative mortality for eight different cancer types. Br J Surg2012;99(8):1149–54.

[17] Rivera C, Falcoz PE, Bernard A, Thomas PA, Dahan M. Surgicalmanagement and outcomes of elderly patients with early stagenon-small cell lung cancer: a nested case-control study. Chest2011;140(4):874–80.

[18] Greillier L, Thomas P, Loundou A, Doddoli C, Badier M,Auquier P, et al. Pulmonary function tests as a predictor ofquantitative and qualitative outcomes after thoracic surgery forlung cancer. Clin Lung Cancer 2007;8(9):554–61.

[19] St Julien JB, Pinkerman R, Aldrich MC, Chen H, Deppen SA,Callaway-Lane C, et al. Poor survival for veterans with patho-

logic stage I non-small-cell lung cancer. Am J Surg2012;204(5):637–42.

[20] Crabtree T, Puri V, Timmerman R, Fernando H, Bradley J,Decker PA, et al. Treatment of stage I lung cancer in high-riskand inoperable patients: comparison of prospective clinicaltrials using stereotactic body radiotherapy (RTOG 0236),sublobar resection (ACOSOG Z4032), and radiofrequencyablation (ACOSOG Z4033). J Thorac Cardiovasc Surg2013;145(3):692–9.

[21] Verstegen NE, Oosterhuis JW, Palma DA, Rodrigues G,Lagerwaard FJ, van der Elst A, et al. Stage I–II non-small-cell lung cancer treated using either stereotactic ablativeradiotherapy (SABR) or lobectomy by video-assisted thoraco-scopic surgery (VATS): outcomes of a propensity score-matched analysis. Ann Oncol 2013;24(6):1543–8.