Preoperative chemotherapy for non-small-cell lung cancer

Preoperative chemotherapy for non-small-cell lung cancer

Correspondence intervention such as developing a positive therapeutic alliance, developing a collaborative care plan through a systematic need assess...

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intervention such as developing a positive therapeutic alliance, developing a collaborative care plan through a systematic need assessment, suicide risk assessment, adherence management, psycho-education, health promotion, rehabilitation, methods to enhance social recovery, and providing care for families were discussed. The final week of the training was devoted to discussions about future supervision arrangements and documentation requirements of the trial. The training was done by the collaborating psychiatrists and the intervention coordinators (who were either psychologists or psychiatric social workers) using didactic lectures, audiovisual materials, and through meetings with caregivers, service providers from rehabilitation facilities, and representatives of community agencies. In general, didactic lectures were kept to a minimum and community health workers were encouraged to participate through interactive guided group discussions and role-play sessions involving a variety of scenarios that they would be likely to experience, as well as dedicated time for reflective learning. The costs incurred in the training involved the stipend provided to the community health workers during the 6 weeks, the time spent by the trainers, the venue and equipment use charges (like projectors, films), and stationery costs. A highly structured system of continued assessment was put in place to ensure that community health workers met expected standards of competence throughout the duration of the training. This included the use of multiple choice questions, rating of their participation in group discussions, and their performance in role-plays done at the end of each module. There were also formal endpoint assessments, which involved each community health workers being individually assessed by three experts on their performance in six clinical scenarios chosen for their importance in ensuring quality assurance and safety standards. 232

The minimum entry criteria for the community health workers in the COPSI trial was completion of 10 years of formal schooling. In situations where existing non-specialist health workers are involved, the 6-week training programme could be shortened to 3 weeks by including the most essential elements of the nature of schizophrenia and the intervention as well as by removing the section on supervision and documentation that were specific to the trial requirements. We declare no competing interests.

Sudipto Chatterjee, *Graham Thornicroft, Vikram Patel, Rangaswamy Thara [email protected] Sangath, Goa, India (SC, VK); Institute of Psychiatry, King’s College London, London SE5 8AF, UK (GT); and Schizophrenia Research Foundation, Chennai, India (RT) 1

Chatterjee S, Naik S, John S, et al. Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial. Lancet 2014; 383: 1385–94.

Preoperative chemotherapy for nonsmall-cell lung cancer The survival improvement following preoperative chemotherapy in patients with non-small-cell lung cancer (NSCLC) considered for surgery reported by the NSCLC Meta-analysis Collaborative Group (May 3, p 1561)1 is encouraging. However, the question still remains as to the optimal sequence of surgery and systemic therapy. The absolute improvement in overall survival of 5% at 5 years is comparable to the gains reported with adjuvant chemotherapy. Delaying definitive treatment (surgery) until after preoperative chemotherapy carries the risk of disease progression during systemic therapy and the possibility that an operable tumour might become inoperable. In studies reporting outcomes after preoperative chemotherapy, disease progression

rates following chemotherapy range from 2% to 14%.2–5 While the authors have provided information on incomplete resection rates, no information has been provided on disease progression rates during preoperative chemotherapy and subsequent operability rates. Quantifying this risk would be useful for patients and clinicians in making decisions regarding the timing of chemotherapy. Although the meta-analysis indicates an overall population survival benefit of preoperative chemotherapy, the question remains whether the subset of patients who progress might have benefitted more from the sequence of definitive surgery followed by adjuvant chemotherapy. At an individual patient level, the lost opportunity for curative resection can be devastating. Given the risk of disease progression with preoperative systemic therapy, the comparable outcomes with adjuvant systemic therapy and the fact that primary surgical resection provides accurate pathological staging rather than clinical staging, our preferred approach is to recommend surgery followed by adjuvant chemotherapy.5 We declare no competing interests.

*Gerard G Hanna, Shankar Siva, Nikki Plumridge, Benjamin Solomon, David L Ball [email protected] Queen’s University of Belfast, Belfast, BT97AE UK (GGH); and Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (SS, NP, BS, DLB) 1



NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet 2014; 383: 1561–71. Gilligan D, Nicolson M, Smith I, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet 2007; 369: 1929–37. Pisters KM, Vallières E, Crowley JJ, et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol 2010; 28: 1843–49. Vol 384 July 19, 2014



van Meerbeeck JP, Kramer GW, Van Schil PE, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007; 99: 442–50. Felip E, Rosell R, Maestre JA, et al, and the Spanish Lung Cancer Group. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alonein early-stage nonsmall-cell lung cancer. J Clin Oncol 2010; 28: 3138–45.

Authors’ reply We thank Gerard Hanna and

colleagues for their interest in our study, 1 and agree it raises questions about the best sequence of treatments for patients with operable non-small-cell lung cancer. We found no difference in the number of complete resections between patients receiving chemotherapy compared with those receiving immediate surgery. Equally, although the numbers of patients are small, we found no increase in the number of incomplete resections for patients receiving chemotherapy, although this finding was not clearly reported. Unfortunately, with the data we have collected, we cannot reliably distinguish between disease progression and disease recurrence. As described in our paper, the data on recurrence were analysed using a landmark date of 6 months. This allows for all patients to have completed their treatment. However, if we look at the crude rates of local recurrence by treatment group within the 6 months following randomisation (when treatment for those receiving preoperative chemotherapy would be ongoing), there is no excess of events in the chemotherapy group (6%) compared with the surgery group (6%). This is despite 25% of all local recurrences (as first events) being recorded during this period. It should be borne in mind that patients included here have been staged using older, less accurate methods than those used today. Patients seemingly progressing on Vol 384 July 19, 2014

preoperative chemotherapy might reflect the presence of metastatic disease at the time of randomisation. In the surgery-only group, these patients would likely have been categorised as having a recurrence when in reality they should also be regarded as having progressed. These findings are based on limited data, but taken together they do not suggest an increase in the number of progressions in the chemotherapy group or operable tumours becoming inoperable during preoperative chemotherapy. Overall there is still an absolute survival improvement of 5% for patients receiving preoperative chemotherapy and this approach might allow chemosensitivity testing of the tumour to avoid ineffective treatment after surgery. There are different potential reasons for giving either preoperative or postoperative chemotherapy in this setting. Patients selected for preoperative chemotherapy are more likely to have a better prognosis than those selected for postoperative chemotherapy, because unfit patients and patients with incomplete resection would be excluded. Our research hopefully reassures those treating patients that preoperative chemotherapy is better than surgery alone with a benefit size comparable to that of postoperative chemotherapy. Further investigations of these treatments might be warranted to explore whether certain patients benefit more or less from either preoperative or postoperative chemotherapy or indeed, a combination of both. We declare no competing interests.

*Sarah Burdett, Larysa HM Rydzewska, Jayne F Tierney, Anne Auperin, Jean-Pierre Pignon, Cécile Le Pechoux, Thierry Le Chevalier, Jan van Meerbeeck [email protected] MRC Clinical Trials Unit at UCL, London WC2B 6NH, UK (SB, LHMR, JFT); Service de Biostatistique et d’Epidemiologie, Institut Gustave-Roussy, Villejuif, France (AA, J-PP, CLP, TLC); and University Hospital Antwerp, Antwerp, Belgium (JvM)


NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small cell lung cancer: a systematic review and metaanalysis of individual participant data. Lancet 2014; 383: 1561–71.

Standardised packaging and tobacco-industryfunded research We recently assessed the (possible) effect of plain packaging on the smoking behaviour of young Australian individuals (aged 14–17 years). 1 Our conclusion was that there is no evidence that plain packaging has lowered smoking prevalence among young Australians. Our study1 has been criticised by Anthony Laverty and colleagues (April 19, p 1384).2 They state that “in view of the short time span since the measure was introduced, the variability in the measure, and the small sample size” failing to find any evidence for a plain packaging effect “is neither an unexpected nor a meaningful conclusion”.2 On the basis of a reasoning that is not explained in sufficient detail, they further claim that a reduction of 1·25 percentage points “would be required to be statistically significant using this analysis”.2 First, any actual reduction will only turn out to be statistically significant with a certain probability, and this probability is known as the power of the test. Therefore, the authors need to attach a power (number) to the specific effect of 1·25 percentage points (unless they have a power of 1 in mind, which is unrealistic). Second, an effect as large as 1·25 percentage points is not needed to be detected with any reasonable power. For example, power against a reduction of 0·5 percentage points is about 0·65; power against a reduction of 1·0 percentage point is about 0·80; and power against a reduction of 1·25 percentage points about 0·85.1 Power of 0·8 is a commonly accepted industry standard,3 so even

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