Mature Results of an Individualized Radiation Dose Prescription Study Based on Normal Tissue Constraints in Stages I to III Non–Small-Cell Lung Cancer

Abstract

A B S T R A C T PurposeWe previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach. Patients and MethodsIn total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide Ն 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0. ResultsThe median prescribed TTD was 64.8 Gy (standard deviation, Ϯ 11.4 Gy) delivered in 25 Ϯ 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P Ͻ .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable. ConclusionIndividualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.

Joint Mean-Variance Overall Survival Time fitted Models from Stage III Non-Small Cell Lung Cancer

“…But in the present report, equivalent dose is positively associated with the mean OST, which supports the clinician views [5,6]. It is reported in the earlier studies that the higher radiation doses lead to improved local control and higher survival rates [5,6].…”

“…Equivalent dose is negatively associated with the OST in [16], indicating that the OST increases as the equivalent dose decreases, which also contradicts the clinician views [5,6]. But in the present report, equivalent dose is positively associated with the mean OST, which supports the clinician views [5,6].…”

“…Heterogeneity is more clear from the description of tumors, and patients based on genomics, imaging modalities, and proteomics examinations. Consequently, the different treatment options such as individualized chemotherapy, new radiation therapy schemes and techniques, proton therapy, targeted agents, surgery, or a combination of these options are being used as the medical treatment process for lung cancer patients [5][6]. In practice, a decision support system (DSS) could offer assistance for making treatment decision which is currently lacking.…”

4D PET-CT guided radiation therapy

“…2). The dose to the PET volume is individually increased until a set of pre-defined dose-limiting normal tissue constraints is reached for lungs, heart, oesophagus, plexus brachialis and mediastinal structures (18).…”

Learning from Failure; Hypoxia Is an Evil Foe

“…However, dose-limiting toxicity in adjacent tissues mandates that this can be achieved only by reducing radiation treatment volumes (9). To address this challenge, a consortium of 15 academic PET facilities sought to mitigate the poor outcomes in NSCLC treated with radiotherapy by escalating radiation to subregions identified to be hypoxic on 18 F-misonidazole ( 18 F-FMISO) PET/CT.…”