Early stage non-small cell lung cancer treated with pencil beam scanning particle therapy: retrospective analysis of early results on safety and efficacy

Abstract

BackgroundTo evaluate the safety and efficacy of particle therapy (PT) using pencil beam scanning (PBS) technique for early stage non-small cell lung cancer (NSCLC).MethodsFrom 08/2014 to 03/2018, 31 consecutive patients with sum of the longest diameters of primary tumor and hilar lymph node < 5 cm, N0–1, M0 NSCLC treated with PT were retrospectively analyzed. Gating/active breathing control techniques were used to control tumor motion in 20 and 7 patients. PBS-based proton radiotherapy (PRT) or carbon ion radiotherapy (CIRT) plans were designed via Syngo® planning system. PRT, PRT + CIRT boost, and CIRT were used in 6, 6 and 19 patients, respectively. Prescriptions were categorized to 3 levels: 5–7.5 GyE * 8–10 Fx, 4–5 GyE * 15–16 Fx and 2.25–3.5 GyE * 20–31 Fx.ResultsThirty-one patients (20 males and 11 females) with a median age of 71 (50–80) years were enrolled with a median follow-up time of 12.1 (2.9–45.2) months. Fourteen were adenocarcinomas, 7 squamous cell carcinomas, 4 non-specified NSCLC and 6 had no histological diagnosis (4/6 had previous resected lung cancer). The median tumor size was 3.1 (1.1–4.7) cm. No grade 4–5 toxicities were observed. One patient experienced grade 3 (per the Common Terminology Criteria for Adverse Events version 4.03) radiation-induced lung injury (RILI) at 6.7 months from radiation started. Grade 2 acute toxicities included hematological toxicities (5 cases), RILI (2), plural pain (1) and dermatitis (1). Grade 2 late toxicities included RILI (3) and asymptomatic rib fracture (1). Three patients had progressed disease at 4.0~10.6 months after the initiation of PT. One experienced local failure with simultaneous distant failure and died of brain metastasis at 10.8 months; one developed regional and distant failure and died of lung infection at 8.7 months; the other experienced isolated distant failure only and his disease was well controlled after salvage systemic therapy. The estimated rates of progression-free survival, local control, cause-specific survival and overall survival at 1, 2 years were 85.5% and 85.5%, 95.2% and 95.2%, 95.0% and 95.0%, 90.7% and 90.7%, respectively.ConclusionsPBS-based PT appears safe and effective for early stage NSCLC. Further follow-up and investigation is warranted.Trial registrationISRCTN, ISRCTN78973763. Registered 14 August 2018- Retrospectively registered, http://www.isrctn.com/ISRCTN78973763.

Innovations in the treatment of non-small cell lung cancer

“…Patients in both arms received concurrent chemotherapy consisting of weekly paclitaxel/ carboplatin with or without cetuximab. Unexpectedly, overall survival was worse in the high dose arm (median OS 29 months versus 20 months) 31 . The results of another doseescalation study, the PET-boost trial (NCT01024829), are upcoming and may provide further clarification in the dose-escalation matter.…”

“…Regional recurrence free survival was comparable (87% for SABR versus 95% for surgery at 3 years; p=0.18) in the final propensity-matched comparison of 56 patients matched on age, tumour size, comorbidity score, forced expiratory volume in the first second of expiration and tumour location. Overall survival (OS) seemed to be better for the surgical patients: the authors report a 3-year OS of 52% for SABR versus 68% for surgery (p=0.05) 31 . Another study reported on the outcomes of SABR or wedge resection for stage I NSCLC in patients ineligible for anatomic lobectomy 32 .…”

“…The 2-year rate of isolated (loco)regional failure following radical treatment NSCLC is approximately 5-10% for early stage NSCLC and 30-40% for locally advanced disease 31,36,37 The preferred treatment depends on the patient performance status, the extent and location of the disease recurrence and the previous treatment. Possibilities include definite surgery (+/-adjuvant systemic therapy), SABR, definite conventional re-irradiation (+/-concurrent chemotherapy) or palliative re-irradiation or systemic therapy.…”

“…The addition of FDG-PET to a diagnostic chest CT enhanced the detection rate of RR after SABR 28 . Most commonly, nodal recurrence was defined as an enlarged, FDG-avid lymph node on an FDG-PET/CT scan [23][24][25][26][28][29][30][31][32][33][34][35] . One study required a biopsy to confirm recurrence 36 .…”

“…Three additional studies compared the outcome of SABR for early stage NSCLC with a cohort of surgically treated patients (wedge resection, pneumonectomy or (sub)lobar resection) 26,31,32 . Crabtree and colleagues 31 compared outcomes of SABR and surgery in an unmatched cohort and in two separate propensity-matched analyses.…”