Carbon Ion Beam Radiation Therapy as Part of a Trimodal Therapy for Non-small Cell Superior Sulcus Tumors: The INKA Study

Abstract

Purpose: Superior sulcus tumors are frequently treated with neoadjuvant chemoradiation therapy (nCRT) followed by surgery via a trimodal approach. The INKA study evaluated the replacement of photon irradiation by carbon ion radiation therapy (C12-RT) in this regimen.

Methods and materials: The prospective INKA study included patients with locally advanced non-small cell superior sulcus tumors (<cN3 cM0). Patients received 2 cycles of cisplatin and vinorelbine as per local standard. During the second cycle, 39 Gy(Relative biological effectiveness (RBE)) of hypofractionated C12-RT in 13 fractions were applied. Surgery following fludeoxyglucose F18 positron emission tomography-computed tomography restaging was performed 2 weeks later. The primary endpoint was feasibility and safety measured by the incidence of Common Terminology Criteria for Adverse Events (version 4.0) grade 3/4 toxicity and/or discontinuation because of any reason. Secondary endpoints included the morphologic (Response Evaluation Criteria in Solid Tumors 1.0), metabolic (Positron Emission Tomography Response Criteria in Solid Tumors 1.0), and histopathologic response after nCRT as well as quality of life measurement (QLQ-C30/LC13).

Results: Between 2015 and 2020, 14 patients were included and received nCRT. No grade 3/4 toxicity occurred, with no discontinuation because of toxicity. Before surgery, 8 patients (57%) showed a partial response on computed tomography scan. Thirteen patients showed a metabolic response (metabolic complete remission (mCR), 1; metabolic partial remission (mPR), 12). Three patients (21%) were deemed inoperable after nCRT. In patients with resection, a pathologic Complete remission (CR) was seen in 2 patients (19%) and near-complete remission (<10% vital tumor cells) in 6 patients (55%). Pain score was more than half of that at baseline (mean, 69.2 ± 26.2 vs 30.6 ± 29.1; P = .005) after completion of nCRT and before surgery.

Conclusions: The INKA trial is the first study to evaluate nCRT with C12-RT and showed excellent response, low toxicity, and rapid pain relief.

Figure 1

Scheme of the INKA trial, including the number of patients treated at each treatment step and response assessment. Abbreviations: CT = computed tomography; FDG = fludeoxyglucose F18; NSCLC = non-small cell lung cancer; PET = positron emission tomography.

Figure 2

Toxicity according to Common Terminology Criteria for Adverse Events (version 4.0): grade 0 (none), grade 1 (mild), grade 2 (moderate), and grade 3 (severe).

Figure 3

Case study: (A) computed tomography scan, (B) positron emission tomography scan, and (C) fused computed tomography/positron emission tomography images before (left column) and after (right column) chemoradiation therapy; the surgical specimen later revealed complete remission (Junker grade 3). Abbreviations: SUV = standardized uptake value.