Proton beam therapy for locally advanced lung cancer: A review

Table 1 Proton beam therapy trials for stage 3 lung cancer patients

Non-small cell lung cancer:
1 ClinicalTrials.gov identifier NCT00881712 (LU02: University of Florida): A phase II trial of 3-D proton radiotherapy with concomitant chemotherapy for patients with initially unresectable stage III non-small cell lung cancer:
(1) Arm 1: Concurrent chemotherapy and PBT (74 GyE/37 fractions) for unresectable stage 3 patients with nodes > 15 mm in diameter.
(2) Arm 2: Concurrent chemotherapy and PBT (60 GyE/30 fractions) for unresectable stage 3 patients with nodes < 15 mm in diameter.
(3) Arm 3: Resectable stage 3 diseases: preoperative PBT (50 GyE/25 fractions) and surgery.
2 ClinicalTrials.gov identifier NCT01993810: (RTOG1308) phase III randomized trial comparing overall survival after photon vs proton chemoradiotherapy for inoperable stage II-III B NSCLC:
(1) Arm I: XRT (70 Gy/35 fractions) and either paclitaxel and carboplatin or etoposide and cisplatin.
(2) Arm II: PBT (70 GyE/35 fractions) and either paclitaxel and carboplatin or etoposide and cisplatin.
3 ClinicalTrials.gov identifier NCT01770418 (Proton Collaborative Group): A Phase I/II study of hypofractionated proton therapy for stage II-III non-small cell lung cancer:
(1) Proton radiotherapy
Dose Level 1: 60 Gy (RBE) at 2.5 Gy (RBE) per fraction × 24 fractions
Dose Level 2: 60 Gy (RBE) at 3 Gy (RBE) per fraction × 20 fractions
Dose Level 3: 60.01 Gy (RBE) at 3.53 Gy (RBE) per fraction × 17 fractions
Dose Level 4: 60 Gy (RBE) at 4 Gy (RBE) per fraction × 15 fractions
(2) Paclitaxel and carboplatin or cisplatin and etoposide
4 ClinicalTrials.gov identifier NCT01565772 (MGH): A phase I trial of hypofractionated PBT with cisplatin and etoposide followed by surgery in stage III non-small cell lung cancer:
Radiation (PBR): 45-55 Gy total, 1.8-2.2 Gy × 25 fractions with cisplatin and etoposide followed by resection
5 Clinical trials.gov identifier NCT01165658 (MD Anderson) phase I study of Hypofractionated Proton Radiation Therapy in Thoracic Malignancies: The radiation prescription dose ranges from 45 Gy in 3 Gy fractions to 60 GyE in 4 Gy fractions. This is for patients ineligible for chemotherapy.
6 Clinical trials.gov identifier NCT00614484 (Loma Linda University): phase I/II study of combined chemotherapy and high dose, accelerated proton radiation for the treatment of locally advanced non-small cell lung carcinoma. Carboplatin and taxol and 5 wk of daily proton therapy.
7 Clinical trials.gov identifier NCT01629498 (MD Anderson): phase I/II trial of Image-guided, intensity-modulated photon or scanning beam proton therapy. Both with SIB dose escalation to the GTV with concurrent chemotherapy for stage II/III NSCLC
(1) Experimental. IMPT + SIB + chemotherapy phase I starting IMPT dose: 60 Gy (RBE) in 30 fractions; phase I starting SIB dose: (72-84) Gy (RBE). All patients receive standard concurrent chemotherapy.
(2) Experimental. IMRT + SIB + chemotherapy: phase I Starting IMRT dose: 60 Gy (RBE) in 30 fractions; phase I starting SIB Dose: (72-84) Gy (RBE). All patients receive standard concurrent chemotherapy
8 Clinical trials.gov identifier NCT00915005 (MD Anderson): A bayesian randomized trial of image-guided adaptive conformal photon vs proton therapy, with concurrent chemotherapy, for locally advanced NSCLC (treatment related pneumonitis and locoregional recurrence)
(1) Experimental group 1 (photon therapy): 74 Gy/37 fractions + carboplatin and paclitaxel
(2) Experimental group 2 (proton therapy): 74 Gy/37 fractions + carboplatin and paclitaxel
(3) Experimental group 3 (proton therapy): 66 Gy/33 fractions + carboplatin and paclitaxel
9 ClinicalTrials.gov identifier NCT01076231 (University of Pennsylvania) feasibility and phase I/II trial of preoperative PBR with concurrent chemotherapy for resectable stage IIIA or superior sulcus NSCLC: pbr over 5.5-7.5 wk plus concurrent chemotherapy comprising cisplatin and etoposide. Then, patients may undergo surgical resection or additional chemoradiotherapy
10 ClinicalTrials.gov identifier NCT01108666 (University of Pennsylvania): phase I dose escalation trial of PBR with concurrent chemotherapy and nelfinavir for inoperable stage III NSCLC. Determine MTD of nelfinavir and MTD of PBR when given with chemotherapy for stage III NSCLC.
11 ClinicalTrials.gov identifier NCT01808677 (MD Anderson): registry study of thoracic reirradiation for NSCLC utilizing PBT or intensity modulated radiation therapy. Primary objective to assess the prevalence of high-grade toxicity in patients being treated with thoracic re-irradiation with PBT or IMRT for NSCLC, with or without chemotherapy.
12 ClinicalTrials.gov identifier NCT01386697 (University of Pennsylvania): A prospective radiation oncology planning study for lung, gastrointestinal and lymphomatous malignancies using proton radiotherapy as compared to 3D conformal and intensity-modulated X-ray therapy for dosimetric evaluation of tumor coverage and dose to organs-at-risk. The overall objective is to estimate the actual or potential benefit of DIBH treatment in the context of proton radiotherapy as compared to 3DCRT and IMXT.

PBT: Proton beam therapy; RBE: Relative biological effectiveness; IMRT: Intensity modulated radiation therapy; NSCLC: Non-small cell lung cancer; SIB: Simultaneous integrated boost; GTV: Gross tumor volume; DIBH: Deep inspiration breath holding; IMXT: Intensity-modulated X-ray therapy; 3DCRT: Three dimensional conformal radiation therapy.