A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been increasingly used as a new radiation modality for unresectable non-small cell lung cancer (NSCLC). The risk factors for radiation pneumonitis (RP) during consolidation durvalumab following concurrent chemoradiotherapy (CCRT) using IMRT have not been thoroughly investigated. METHODS: This retrospective study analyzed medical record data from consecutive patients diagnosed with NSCLC who underwent CCRT and consolidation durvalumab at our institution between April 2018 and September 2022. Since we adopted IMRT for the treatment of NSCLC in April 2020, these patients were categorized into two groups: those treated with IMRT after April 2020 and those treated with three-dimensional conformal radiotherapy (3D-CRT) before April 2020. RESULTS: A total of 31 patients underwent IMRT (the IMRT group), while 25 patients underwent 3D-CRT (the 3D-CRT group). In both groups, the total dose was 60 Gy in 30 fractions. The cumulative incidence of ≥ grade 2 RP at 12 months was significantly lower in the IMRT group than in the 3D-CRT group (27.0% vs. 64.0%, hazard ratio [HR]: 0.338, 95% confidence interval [CI]: 0.144-0.793, p = 0.013). In the multivariable analysis, V20 (≥ 25.6%, HR: 2.706, 95% CI: 1.168-6.269, p = 0.020) and radiotherapy technique (IMRT, HR: 0.414, 95% CI: 0.172-0.994, p = 0.048) were identified as significant risk factors for ≥ grade 2 RP. CONCLUSIONS: IMRT is associated with a lower rate of ≥ grade 2 RP in patients with NSCLC who received CCRT followed by durvalumab.

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer.

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial.

OBJECTIVE: This is the preliminary results of a multi-center prospective clinical trial evaluating the feasibility of the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer. METHODS: Patients with FIGO stage IB2, IIA2, IIB, IIIA, IIIB and IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by MRI were eligible. Protocol therapy consisted of 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of hybrid of intracavitary and interstitial and pelvic radiotherapy with central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase I part was that the rate of grade ≥ 3 acute non-hematologic adverse events related to hybrid of intracavitary and interstitial would be <10%. RESULTS: Between October 2015 and October 2019, 74 patients underwent primary registration, with 52 patients eventually proceeding to the secondary registration. The median pretreatment tumor width was 5.7 cm, and FIGO Stages were IB2 10, IIA2 2, IIB 20 and IIIB 20, respectively. The median high-risk clinical target volume D90 was 72.0 Gy (54.8-86.6 Gy, EQD2), rectum D2cc was 53.7 Gy (29.3-80.3 Gy) and bladder D2cc was 69.8 Gy (38.9-84.8 Gy). The rate of grade ≥ 3 non-hematologic adverse events related to hybrid of intracavitary and interstitial was 1.9% (1/52), and 17.3% (9/52) of patients experienced non-hematologic adverse events related to hybrid of intracavitary and interstitial of any grade. In multivariate analysis, high-risk clinical target volume ≥ 35 ml was associated with an increased risk of any grade of acute non-hematologic adverse events related to hybrid of intracavitary and interstitial (P = 0.036). CONCLUSION: The feasibility and reproducibility of hybrid of intracavitary and interstitial were demonstrated from a multi-center prospective clinical trial.

Local control of stereotactic body radiotherapy with dynamic tumor tracking for lung tumors: a propensity score-matched analysis.

BACKGROUND: Dynamic tumor tracking (DTT) is a method of respiratory motion management in radiotherapy. It reduces the radiation field but risks delivering an insufficient radiation dose to the tumor. We investigated the local control of DTT-stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Patients treated with SBRT for early-stage, non-small-cell lung cancer and lung metastases (2013-18) were retrospectively reviewed. Patients with tumor motion >1 cm were treated with DTT-SBRT (DTT group); those with tumor motion ≤1 cm were treated with static-SBRT (static group). A static planning target volume for the static-SBRT plan was also created for patients in the DTT group, and planning target volume reduction relative to the planning target volume for the DTT-SBRT plan was assessed. Patients were matched in a 1:1 ratio using a propensity score predictive of the SBRT technique. RESULTS: Of the 245 lesions in 218 patients (median follow-up, 25.4 months), 69 were treated with DTT-SBRT and 176 with static-SBRT. The median planning target volume reduction in the DTT group was 30.3%. After propensity score matching, 124 lesions were included (62 per group). Two-year local control rates for the DTT and static groups were 94.2 and 95.9%, respectively, for all lesions (P = 0.19) and 96.3 and 94.5%, respectively, for matched lesions (P = 0.79). In univariate analysis, DTT-SBRT was not associated with local control for all lesions (hazard ratio, 2.06; P = 0.20) or matched lesions (hazard ratio, 1.22; P = 0.79). No grade 4/5 toxicities were observed. CONCLUSIONS: DTT-SBRT for lung tumors reduced the planning target volume, but not local control rates. DTT was useful for respiratory motion management.

Accelerated Hypofractionated Radiotherapy Versus Stereotactic Body Radiotherapy for the Treatment of Stage I Nonsmall Cell Lung Cancer-A Single Institution Experience With Long-Term Follow-Up.

PURPOSE: Although stereotactic body radiation therapy is one of the standard treatments for stage I nonsmall cell lung cancer, in the case of central tumors it carries the risk of severe adverse events for serial organs. Accelerated hypofractionated radiotherapy is considered a reasonable alternative to treat central tumors. We have been treating central tumors with accelerated hypofractionated radiotherapy using a 75 Gy/25 fr/5 weeks regimen, and we compared the results with those of stereotactic body radiation therapy using 48 Gy/4 fr/1 week. METHODS: Patients with central tumors and/or unfit for 1-hour fixation were candidates for accelerated hypofractionated radiotherapy. Based on the proximity to the biologically effective dose at 10 Gy, above accelerated hypofractionated radiotherapy regimen was adopted. RESULTS: From October 2003 to December 2010, 159 patients, who received either accelerated hypofractionated radiotherapy (103 cases) or stereotactic body radiation therapy (56 cases), were included in the analysis. In the accelerated hypofractionated radiotherapy group, 40 (39%) cases were central tumors, whereas all cases were peripheral tumors in the stereotactic body radiation therapy group. Overall 5-year local control and survival rates were 81.9% (95% confidence interval 73.6%-90.1%) and 46.5% (95% confidence interval 36.7%-56.2%), respectively for the accelerated hypofractionated radiotherapy group, and 75.4% (95% confidence interval 63.0%-87.8%) and 44.6% (95% confidence interval 31.6%-57.7%), respectively for the stereotactic body radiation therapy group (n.s.). Among central tumors, ultracentral tumors (21 cases) and the remaining central tumors (19 cases) were similar in both local control and survival. On multivariate analysis, hazard ratios for accelerated hypofractionated radiotherapy versus stereotactic body radiation therapy were <1 for both local control and survival. Pulmonary toxicity was similar in both groups. No serial organ toxicity was observed for central tumors. CONCLUSIONS: Accelerated hypofractionated radiotherapy with a 75 Gy/25 fr/5 weeks regimen is promising in that it can obtain similar local control and survival results to stereotactic body radiation therapy, and it can control both central and peripheral tumors without any serial organ toxicities. Based on these results, prospective multicenter trials are worth conducting, especially for ultracentral tumors.

A comparison of clinical outcomes between three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) reduces the dose delivered to organs at risk. However, there have been few direct comparisons of IMRT with conventional three-dimensional conformal radiotherapy (3DCRT). The aim of this study was to evaluate the clinical benefit of IMRT in terms of toxicity and biochemical control. METHODS: The medical records of 203 consecutive patients with localized to non-metastatic (stage T1a-T3bN0M0) prostate cancer between 2007 and 2011 were retrospectively reviewed. The prescribed dose was 76 Gy delivered in 38 fractions in both the 3DCRT and IMRT treatment groups. The frequency of grade 2 or greater late gastrointestinal (GI) and genitourinary toxicity and biochemical control were estimated by the log-rank test and Cox proportional hazards model with and without adjustment by the propensity score for treatment choice. RESULTS: A total of 159 patients were included in the study (3DCRT: 70 patients, IMRT: 89 patients). The median follow-up period was 4.7 years. The estimated 5-year cumulative risk of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group (3.6 vs 13.2%, respectively, p = 0.022). After adjustment by propensity score, IMRT remained associated with a lower risk of late GI toxicity (hazard ratio 0.22; 95% confidence interval 0.058-0.85; p = 0.028). The 5-year biochemical failure-free rate was 93.2% in the 3DCRT group and 95.4% in the IMRT group (non-significant difference). CONCLUSIONS: The incidence of late GI toxicity was significantly lower in the IMRT group than in the 3DCRT group, while the biochemical control rates were no different between the two groups. These clinical data suggest the benefit of IMRT in the reduction of late GI toxicity.