Results from two retrospective studies using data from a large registry confirmed that the rate of local recurrence (LR) following stereotactic ablative radiotherapy (SABR) for treatment of early-stage non-small-cell lung cancer (NSCLC) is low, but recurrence detected at 87 months suggests that a long follow-up is needed post SABR. Further findings showed that, in some cases, surgical salvage following LR can be done with limited post-surgical complications and may prolong overall survival.
Dr Naomi Verstegen, Department of Radiation Oncology, Vrije University Medical Centre (VUMC), Amsterdam, Netherlands, presented two data analyses during the Proffered Papers – New Treatment Avenues session at the European Lung Cancer Conference, held 15 – 18 April 2015 in Geneva, Switzerland.
Incidence of second primary lung cancer (SPLC) and local recurrences per year in a large cohort of patients treated with SABR for early stage NSCLC.
©Naomi Verstegen
Both studies used data from the Vrije University Medical Centre, which contains data of all patients receiving SABR at the institution.
The aim of the first study was to identify risk factors for disease recurrence and determine the optimal follow-up regime following SABR, which is a guideline-recommended treatment for early-stage NSCLC that has been associated with local control rates of ≥90%. SABR was performed at the recommended minimal biologically effective dose (BED10) of 100Gy according to 2013 ESMO Clinical Practice Guidelines.
Data of patients having received prior treatment for the index tumour, having double tumours, or presenting with disease TNM-stages other than T1-T2N0M0 were excluded from the analysis.
Local recurrences following SABR occurred in 46 of the 855 patients undergoing this treatment for early-stage NSCLC within follow-up of median 52 months. Actuarial local control rates were 92.4% and 90.9% at 3 and 5 years respectively, and the median time to LR was 22 months (range: 7 to 87 months). The diagnosis of local recurrence was made on computed tomography (CT) scans in 44 patients, this was confirmed by pathology in 18 (39%) patients and/or FDG-PET scans in 32 (70%) patients. Recurrence was local in 25 (54%) patients and loco-regional in 31 (67%) patients.
Cox regression analysis was done to evaluate age, gender, TNM-stage, fractionation scheme, PTV-size, histology, and a history of prior malignancy as prognostic of LR. The investigators found no significant association between any of the investigated parameters with local control.
Since 74% of patients with LR were initially considered inoperable, just 21% of patients experiencing LR were given radical salvage therapy; of these 6, 3, 1, 3, and 1 patients underwent surgery, treatment with adjuvant chemotherapy, radiotherapy, high-dose radiotherapy, or chemo-radiation. The median survival was 13 months in all patients following diagnosis of a LR and the 2-year survival rate was just 23%. Patients undergoing radical salvage achieved median survival of 36 months following LR diagnosis.
Salvage surgery for local recurrence performed with limited post surgical complications
Example of patient with local recurrence following SABR for NSCLC. A: CT-scan at the time of diagnosis of the primary tumour. B: CT-scan one year after SABR. C: CT-scan at the time of local recurrence. D: Histological specimen of this patient showing poorly differentiated tumour cells (100x enlarged).
©Naomi Verstegen
Noting the paucity of data on surgical salvage for LR following SABR, the authors evaluated the data of patients recorded in the database that were identified as having received surgical salvage for a LR following SABR for peripheral pulmonary lesions. Median time to LR following SABR was 15.6 months; diagnoses of LR were based on CT- and FDG-PET-scans and four patients had a pathological diagnosis of recurrence prior to surgery. All patients had peripheral tumours and viable tumour cells in the resection specimen. One patient each had extensive adhesions and limited adhesions.
Following surgery, which included lobectomy in 15 cases, sleeve-lobectomy, wedge resection, segment resection and pneumonectomy in one case each, two grade II complications by Clavien-Dindo classification were observed. Also, two patients had a persistent air leakage treated with a thoracic tube (grade IIIa). The 30-day mortality rate was 0% and the median length of hospital stay was 7 days. Mediastinal metastases were detected in three patients by lymph node dissection who were given adjuvant therapy. The median overall survival after surgery was 38 months with a median follow-up of 40.6 months.
Dr Eric Vallières of the Swedish Cancer Institute in Seattle, USA, who discussed the results, said that a very large experience on patterns of disease recurrence after SABR for early stage of proven or suspected NSCLC and outcomes of surgical salvage for local failures following SABR was reported at ELCC 2015 by leading Dutch group. Long term follow-up is recommended after SABR for monitoring the treated area and discovering new primary tumours.
For operable patients, surgery remains the standard of care. For “inoperable” patients, mutidisciplinary evaluation/discussion should be in place and involve the surgeon. Inoperability is not the same for everyone. Clinical stage I cancer does not always translate into pathological stage I cancer. For solid pericentimeter lesion, 10% are found to have nodal involvement after good surgery. The larger the tumour, the higher the risk of nodal involvement. A proportion of these patients with node positive disease “are doomed”, another proportion benefit from the nodal resection plus/minus adjuvant chemotherapy.
Conclusions
Although the results confirmed a similar low rate of local recurrence following SABR for early-stage NSCLC, the authors found no statistical association between recurrence and several parameters, including age, gender, TNM-stage, fractionation scheme, PTV-size, histology, or a history of prior malignancy.
Since local recurrence was observed as late as 87 months post SABR in up to 54% of patients, the authors advise long-term follow-up after SABR to diagnose recurrence and to identify patients with recurrence that may benefit from salvage therapies.
Based upon results, patients who underwent surgical salvage for local recurrences indicate a 30-day mortality rate of 0% and only two post-surgical grade IIIa complications. The authors concluded that surgical salvage may be a viable treatment for patients experiencing LR after SABR for early-stage NSCLC, especially since patients achieved a post-surgical median overall survival of 38 months. As clinical experience is still limited, the study authors encouraged other centres to report their experience with salvage surgery.
References
60O. Analysis of local recurrences following stereotactic ablative radiotherapy (SABR): Data from a large institutional database
61O. Outcome of surgical salvage for local failures following stereotactic ablative radiotherapy (SABR)