Madam — We congratulate Lewis et al. [ [1] Lewis T.S. Kennedy J.A. Price G.J. Mee T. Woolf D.K. Bayman N.A. et al. Palliative lung radiotherapy: higher dose leads to improved survival?. Clin Oncol. 2020; 32: 674-684 Abstract Full Text Full Text PDF Scopus (5) Google Scholar ] on reporting their outcomes of palliative radiotherapy for lung cancer. The finding of increased survival with higher doses, across all performance status groups, is of particular interest, because it runs counter to the traditions developed from the Medical Research Council trials [ [2] Macbeth F.R. Bolger J.J. Hopwood P. Bleehen N.M. Cartmell J. Girling D.J. et al. Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Clin Oncol. 1996; 8: 167-175 Abstract Full Text PDF PubMed Scopus (192) Google Scholar , [3] Bleehen N.M. Girling D.J. Fayers P.M. Aber V.R. Stephens R.J. Inoperable non-small-cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Br J Cancer. 1991; 63: 265-270 Crossref PubMed Scopus (259) Google Scholar ], but is consistent with other reports [ [4] Ball D. Matthews J. Worotniuk V. Crennan E. Longer survival with higher doses of thoracic radiotherapy in patients with limited non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 1993; 25: 599-604 Abstract Full Text PDF PubMed Scopus (41) Google Scholar ].

Technical developments in the delivery of radiotherapy such as image-guided radiotherapy (IGRT) and intensity modulated radiotherapy (IMRT) have permitted the introduction of advanced radiation techniques such stereotactic ablative radiotherapy (SABR). These new techniques have the advantage of more accurate localisation of the tumour and reduced irradiation of normal tissues. In our centre, we have implemented a range of new techniques to deliver IGRT (such as PET/CT and 4-dimensional CT planning, and cone beam CT during treatment delivery). We postulate that using the advanced techniques increases the access to curative intent radiotherapy treatment of lung cancer. We seek to assess the access rates to curative intent thoracic radiotherapy. Using our institutional lung radiotherapy database we analysed the data recording intent of treatment with reference to the stage and performance status (PS) of all patients with stage 1-3 non-small cell lung cancer (NSCLC) in 2007 and compared this to the same population receiving radiotherapy during 2017 and up to April 2018. In 2007, 217 patients with stages 1-3 NSCLC received any radiotherapy compared to 218 patients for the 2017/2018 cohort. Within the 2017/2018 cohort 96% of patients (n=94) received radical radiotherapy compared to 28% of patients in 2007 (n=26). Of the 94 patients receiving radical treatment in 2017/2018, 61% received SABR. This increase was largely due to in the introduction of SABR. In those patients with stage 3 disease, overall fewer patients received any radiotherapy in 2017/2018 compared to 2007, however the number of patients receiving curative intent radiotherapy increased from 20 (13% of all stage 3 patients) to 44 (37%). Of note in those patients receiving curative intent radiotherapy there was an increase in access for patients with poorer PS, with only 7% of patients with a PS ≥2 in 2007 receiving curative intent radiotherapy compared with 42% of patients in 2017/2018. In our series, we report an increase in the proportion of patients with NSCLC receiving curative intent radiotherapy. Furthermore, more patients with a poorer performance status received curative intent radiotherapy. We suggest that the introduction of advanced radiotherapy techniques has permitted the curative intent treatment of patients who were previously treated with a palliative approach to management.

Madam — We observed a clinical link between radical radiotherapy and Pneumocystis jirovecii pneumonia (PJP) in patients with lung cancer. The incidence of PJP in this population has been reported as 2.6 cases per 100 000 person-years [ [1] Maillet M. Maubon D. Brion J.P. Francois P. Molina L. Stahl J.P. et al. Pneumocystis jirovecii (Pj) quantitative PCR to differentiate Pj pneumonia from Pj colonization in immunocompromised patients. Eur J Clin Microbiol Infect Dis. 2014; 33: 331-336 Crossref PubMed Scopus (55) Google Scholar ]. This infection in HIV-negative patients is known to carry a mortality of 50% [ [2] Worth L.J. Dooley M.J. Seymour J.F. Mileshkin L. Slavin M.A. Thursky K.A. An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital. Br J Cancer. 2005; 92: 867-872 Crossref PubMed Scopus (70) Google Scholar ]. We determined the risk of death from PJP in a cohort of patients treated with curative-intent radiotherapy.

Quality assurance by colleague-led peer review (CPR) is recommended in the radiotherapy treatment planning of curative intent treatments such as for lung cancer. Previous studies have demonstrated a proportion of radiotherapy plans are amended following CPR resulting in enhanced quality and uniformity of treatment approached. CPR is an extra step in the radiotherapy planning process, and it may affect the timeliness of commencing radiotherapy. CPR was initiated in our centre in 2011. This study considers the temporal impact of adding an additional step to the planning process. Using our institutional lung radiotherapy database we recorded the timescales between decision to treat (DTT) and commencement of radical lung radiotherapy, pre-peer review and post-peer review initiation at a single institution. The data for all patients was analysed for the years 2007 to 2017. Prior to peer review for the calendar year of 2007, 71% of the 63 patients receiving curative intent radiotherapy for lung cancer commenced treatment within 28 days of the DTT (median 26 days, range 0-61). In 2016, 80% of the 133 patients receiving curative intent radiotherapy had treatment initiated within 28 days (median 25 days, range 6-41). There was a notable reduction in the variability in planning time making booking of appointments with a reduction in extreme wait times to start treatment (figure 1). Figure 1 Box and whisker plot of the time from the decision to treat until the commencement of radiotherapy for the representative years available for analysis. In our institutional series, CPR does not prolong planning time with the median number of days taken to commence treatment remaining comparable, but may standardise radiotherapy start times due to enhanced team working via the CPR meetings. We recommend that peer review is performed as standard practice as it improves treatment quality without a detrimental prolongation of planning time.

Whilst local and distant control rates for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) have been described for the immediate years following curative-intent radiotherapy, the natural history in patients with long-term disease-free survival (DFS) has not been established. Late relapse has been described in limited, small series (e.g. following surgery or SABR) but there is a paucity of data on relapse and survival after radical radiotherapy for all-comers. With improved radiotherapy planning and delivery, systemic therapy personalisation and surveillance strategies, survival rates at five years are improving. We describe the outcomes in patients with at least five years DFS from the commencement of radiotherapy. Patients with DFS >5 years post-radiotherapy between 1st December 2000 and 1st March 2013 were identified from a prospective database of patients treated with curative-intent radiotherapy at a tertiary centre. Electronic records were interrogated for information pertaining to disease status and cause of death. 680 patients received curative-intent radiotherapy; 503 NSCLC, 176 SCLC. At 5 years, 108 (16%) patients were alive; 66 males, 42 females. Mean age of survivors at treatment 67 years, median ECOG PS 1. SCLC for accounted 32 cases (18% total SCLC); NSCLC for accounted 76 cases (15% total NSCLC). SCLC (n=32 limited-stage) were managed with sequential chemoradiotherapy (n=20), concurrent chemoradiation (n=12). NSCLC (n=37 stage I; n=9 stage II; n=27 stage III; n=3 stage IV) were managed with radiotherapy alone (n=47), sequential chemoradiotherapy (n=19), concurrent chemoradiotherapy (n=7), SABR (n=5). With 80 months total median follow-up 16 (15%) patients surviving 5 years relapsed, 14 NSCLC (2.7% total treated radically), 2 SCLC (1.9% total treated radically). Of 23 patients reaching the 5-year time-point and thereafter developing a further malignancy, 4 were cases of second lung primary. Approximately 1 in 6 patients (all-comers) survived for 5 years after radical radiotherapy. Approximately 1 in 6 patients with 5 year DFS will later go on to relapse, suggesting that such patients should receive active follow-up.

Background to the audit: When quality assured trapped errors are not infrequently found in complex processes (Brunskill IJRBOP 2017).[1] Radiotherapy planning for lung cancer has become more complex over the past decade. We have demonstrated (Rooney Clin Onc 2015)[2] that consultant led peer review meetings capture and rectify errors in –27% of plans and 17% of volumes. We have found an association between these meetings and improved access to radical lung radiotherapy and improved survival. Peer review meetings have formally been documented in a database since 2013. One new consultant joined the team in 2015 and two new consultants in 2016.

Stereotactic ablative radiotherapy (SABR) is a radiotherapy technique using ultra-hypofractionated treatment to deliver a high biological dose to early stage lung cancers. It is believed that SABR is more effective than conventional fractionated external beam radiotherapy (EBRT), however definitive evidence of superior survival outcomes from controlled trial comparisons is lacking. Across the UK access to SABR is not been uniform, with only certain centers delivering the technique. Before the introduction of a routine lung SABR service in 2013, patients from Northern Ireland were referred to English Centers to have SABR. We compare the outcomes of those patients who had SABR to those who had conventional fractionated radiotherapy for early stage lung cancer. Using our institutional electronic database, which includes all patients who had radiotherapy in the treatment of lung cancer, we identified those patients who had received SABR or who were eligible to receive it based on UK consortium guidelines (tumor size <= 4cm, tumor > 2cm from main airways, performance status 0-3). The time period of 2009 to 2015 inclusive was chosen as SABR treatment was funded from this time point onwards. Patient baseline demographics, lung function, tumor size, the reason for the treatment received, details of the treatment received (e.g. dose, use of respiratory compensation, IGRT and Type B planning algorithm) and survival outcomes were recorded for each patient. Between 2009 and 2015, eighty patients received SABR and an additional 63 were eligible to have SABR but received conventional EBRT (62 patients received 55Gy in 20 fractions and 1 patient received 66Gy in 33 fractions). The main reason for eligible patients not receiving SABR was that the patient did not want to travel or was not fit to travel to another country to have treatment with SABR (43% of all non-SABR patients). The 2-year overall survival for those receiving SABR was 68% versus 43% for those receiving conventional radiotherapy (HR 2.3 (95% CI 1.4 – 3.8), p=0.0007). Both disease free survival and metastasis free survival rates were superior in the SABR group. On univariate analysis of the various patient and treatment factors, only tumor size remained significant between the groups. In this cohort of patients there is evidence of improved local control, disease free survival and overall survival for SABR compared to conventional fractionated radiotherapy. SABR should be available in all radiotherapy centers for the treatment of early stage lung cancer.

Background to the audit: Effective surgical salvage for recurrent and second primary NSCLC is possible, with reported five-year survival rates between 8% and 40% and 25% to 53%, respectively.1,2

Our center introduced a consultant (attending physician) who led peer review of all curative intent lung cancer (NSCLC and SCLC) radiation therapy plans in 2011. In this process, all components of the treatment pathway, including decision to treat, target volume delineation, radiation therapy plan coverage, and proposed image guidance are discussed, and the meeting recommendations are recorded on a database. We have previously demonstrated a significant impact on radiation therapy plan target volume delineation. Given this impact, we seek to assess the clinical impact of introducing a consultant led radiation therapy plan peer review process. Using our institutional lung cancer radiation therapy database we identified all patients with NSCLC and SCLC who had curative intent radiation therapy between 2001 and 2015. Using our regional cancer clinical database and cancer registry figures we identified the total number of patients diagnosed with lung cancer. Using these sources, we recorded the proportion of all patients with a lung cancer diagnosis who received curative intent radiation therapy and for the patients who received curative intent radiation therapy, the 90-day mortality and the 2-year overall survival. Survival was estimated using the Kaplan Meier method. In total, 1096 patients were treated with curative intent radiation therapy between 2001 and 2015 in our region. During this time period, there was an increase in the proportion of patients with lung cancer receiving radiation therapy from 5% (95% C.I. 4.6% to 5.4%) before 2011 to 10% (95% C.I. 9.2% to 10.8%) after 2011. This increase was seen across the region. The 90-day mortality rate remained relatively stable 3% versus 4% (NS). Although other factors need to be taken in to account the 2-year overall survival increased from 39% to 46% (HR 0.86 – 95% C.I. =0.70 to 0.97). There has been a doubling of the use of radical radiation therapy, without an increase in short term mortality or a fall in survival which has coincided with the establishment of a regional lung cancer radiation therapy peer review meeting. We propose that peer review is a significant factor in increasing access to and outcomes from curative intent lung cancer radiation therapy.