Multiple primary lung cancers are not an uncommon clinical presentation.

ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of lung cancer state that synchronously detected lesions should be treated as multiple primary tumours.

A curative approach for both lesions has been associated with improved survival in the surgical literature.

However, many patients with multiple primary lung cancers are elderly and have multiple co-morbidities, which can render them unfit for surgery to both lesions.

Findings presented at the European Multidisciplinary Conference in Thoracic Oncology (EMCTO), by Dr Gwendolyn Griffioen of the VU University Medical Center, Amsterdam, Netherlands support the use of stereotactic ablative radiotherapy as an alternative treatment in patients with multiple primary lung cancers who were not fit to undergo surgery.

The Dutch researchers evaluated the clinical outcomes of 62 patients who have been diagnosed with multiple primary lung cancers at their institution from 2003 to 2012 and treated by stereotactic ablative radiotherapy.

Patients’ disease was staged by FDG-PET scan and a pathological diagnosis was available for both lesions in 3%, and for one lesion in 48% of patients. All patient data were reviewed by a multi-disciplinary tumour board. In all, 56 patients were treated by stereotactic ablative radiotherapy as a single modality for both lesions and 6 patients underwent to such treatment in combination with surgery for the second lesion.

Stereotactic ablative radiotherapy was delivered to a total dose of 54-60 Gy in 3-8 fractions, depending on tumour size and location.

Clinical outcome, including survival, pattern of relapse and toxicity were evaluated. A sub-analysis was performed for ipsilateral and bilateral lung lesions.

The analysis showed a median overall survival of 31 months, with an actuarial survival of 40% at three years post stereotactic ablative radiotherapy. At this time, overall lesion local control was 78%; local control associated significantly (p=0.005) with tumour size, with the number of fractions delivered (p=0.013), and with lesion location (p=0.004). At the same follow-up, regional failures were observed in 17% and distant failures were seen in 45% of patients. A sub-analysis performed for ipsilateral and bilateral lung lesions showed lesion control at three years for bilateral lesions of 92% compared to 58% for ipsilateral lesions (p=0.009).

No grade ≥3 early toxicity was observed and grade 3 late toxicity was reported in 3 (5%) patients that included one case of pneumonitis, one case of rib fracture and chest wall pain has been reported in one patient. No grades 4-5 late toxicity occurred.

These findings suggest that stereotactic ablative radiotherapy either alone or combined with surgery is an effective curative treatment for multiple primary lung cancers in poor surgical candidates. It has limited toxicity and can lead to long-term survival.

The authors stated that further study should be done regarding the disappointing local control rates observed for ipsilateral double lesions following stereotactic ablative radiotherapy. Patients with multiple ipsilateral lesions also had a higher rate of nodal recurrence suggesting that invasive nodal staging may be required for such cases.

The study discussant, Dr Cecile Le Pechoux, said that up to 10% of patients have multiple primary lung cancer with surgery being the standard treatment. Generally, patients with synchronous multiple primary lung cancers show poor survival compared to metachronous lesions. In ipsilateral multiple primary lung cancer, second primary lung cancer is technically difficult to operate because of lung adhesion (ipsilateral re-thoracotomy).

In contralateral multiple primary lung cancers, there is a risk of deterioration of respiratory function with an impact on quality of life. Regarding surgical results in multiple primary lung cancer, Dr Le Pechoux said that the risk of metachronous lung cancer after resection of early stage lung cancer is around 2% to 3% per year ; for metachronous lung cancer 5-year survival rate is between 18% and 51% ; for synchronous lung cancer 5-year survival is between 0% and 20%. There is a higher rate of postoperative complications, and in Japanese studies, better results were seen for adenocarcinoma.

Dr Le Pechoux commented that SABR for two synchronous lesions is safe and effective; incidence of grade 3 or higher toxicity is 5%. Local control after SABR for synchronous lesions (85%) is poorer than after SABR for single lung tumours (93%). Incidence of regional relapses overall (17%) is higher for synchronous lesions than for single lesions (12%), therefore she speculated on possible role for endoscopic nodal staging. Furthermore, she said that the results from the current study are very interesting, but more studies are needed with longer follow-up.

Source: ESMO