BackgroundAccelerated hypofractionated radiotherapy can shorten total treatment time and overcome the accelerated repopulation of tumour cells during radiotherapy. This therapeutic approach has demonstrated good efficacy in the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the optimal fractionation scheme remains uncertain. The purpose of this phase I trial was to explore the maximum tolerated dose (MTD) of accelerated hypofractionated three-dimensional conformal radiotherapy (3-DCRT) (at 3 Gy/fraction) administered in combination with concurrent vinorelbine (NVB) and carboplatin (CBP) chemotherapy for unresectable stage III NSCLC.MethodsPreviously untreated cases of unresectable stage III NSCLC received accelerated hypofractionated 3-DCRT, delivered at 3 Gy per fraction, once daily, with five fractions per week. The starting dose was 66 Gy and an increment of 3 Gy was utilized. Higher doses continued to be tested in patient groups until the emergence of dose-limiting toxicity (DLT). The MTD was regarded as the dose that was one step below the dose at which DLT occurred. Patients received at least one cycle of a concurrent two-drug chemotherapy regimen of NVB and CBP.ResultsA total of 13 patients were enrolled and progressed through three dose escalation groups: 66 Gy, 69 Gy, and 72 Gy. No treatment-related deaths occurred. The major adverse events included radiation oesophagitis, radiation pneumonitis, and neutropenia. Nausea, fatigue, and anorexia were commonly observed, although the magnitude of these events was typically relatively minor. Among the entire group, four instances of DLT were observed, including two cases of grade 3 radiation oesophagitis, one case of grade 3 radiation pneumonitis, and one case of grade 4 neutropenia. All of these cases of DLT occurred in the 72 Gy group. Therefore, 72 Gy was designated as the DLT dose level, and the lower dose of 69 Gy was regarded as the MTD.ConclusionsFor unresectable stage III NSCLC 69 Gy (at 3 Gy/fraction) was the MTD of accelerated hypofractionated 3-DCRT administered in combination with concurrent NVB and CBP chemotherapy. The toxicity of this chemoradiotherapy regimen could be tolerated. A phase II trial is recommended to further evaluate the efficacy and safety of this regimen.

The Radiation Therapy Oncology Group reported a maximum tolerated dose of 74 Gy for patients with non-small cell lung cancer (NSCLC); however, it was unclear whether this dose could be safely administered to Asian patients due to differences in their physique compared to Western patients. We therefore conducted a modified Phase I trial to determine whether 70 Gy could be safely delivered to Chinese patients with NSCLC undergoing 3D-conformal radiation therapy (3D-CRT) with concurrent chemotherapy. Previously untreated NSCLC patients received 3D-CRT (2 Gy/day, 5 fractions per week). Three dose levels were examined: 62, 66 and 70 Gy. Two cycles of concurrent chemotherapy (vinorelbine and carboplatin) were started on the first day of radiation therapy. Dose-limiting toxicity (DLT) was defined as severe or life-threatening side effects that altered the continued implementation of chemoradiotherapy. Among the 19 patients recruited in this study, most of the haematologic and non-haematologic toxicities were mild to moderate and clinically manageable. Only one patient, in the 70 Gy cohort, experienced a DLT of Grade 3 radiation-induced pneumonia. The overall response rate was 77.8% (14/18). The median progression-free survival (PFS) was 12 months, and the 1-year PFS was 37.6%. Our results support both the feasibility of incorporating 3D-CRT with concurrent vinorelbine and carboplatin and a dose escalation to 70 Gy for Chinese patients with NSCLC, based on the acceptable toxicity and encouraging overall response and survival rates. A further evaluation of this regimen in a prospective Phase II trial is ongoing.

BackgroundPatients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer.MethodsPatients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT).ResultsFrom March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups.ConclusionCompared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial.

Lung cancer is one of the most common malignant tumors. It has the highest incidence and mortality rate of all cancers worldwide. Late diagnosis of non-small cell lung cancer (NSCLC) is very common in clinical practice, and most patients miss the chance for radical surgery. Thus, radiotherapy plays an indispensable role in the treatment of NSCLC. Radiotherapy technology has evolved from the classic two-dimensional approach to three-dimensional conformal and intensity-modulated radiotherapy. However, how to ensure delivery of an accurate dose to the tumor while minimizing the irradiation of normal tissues remains a huge challenge for radiation oncologists, especially due to the positioning error between fractions and the autonomous movement of organs. In recent years, image-guided radiotherapy (IGRT) has greatly increased the accuracy of tumor irradiation while reducing the irradiation dose delivered to healthy tissues and organs. This paper presents a brief review of the definition of IGRT and the various technologies and applications of IGRT. IGRT can help ensure accurate dosing of the target area and reduce radiation damage to the surrounding normal tissue. IGRT may increase the local control rate of tumors and reduce the incidence of radio-therapeutic complications.