To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC).
Eligibility ...criteria included histologically or cytologically proven NSCLC, clinical T1N0M0. Prescribed dose was 48 Gy at the isocenter in 4 fractions. The primary endpoint was the percent (%) 3-year overall survival. The threshold % 3-year survival to be rejected was set at 35% for inoperable patients, whereas the expected % 3-year survival was 80% for operable patients.
Between July 2004 and November 2008, 169 patients from 15 institutions were registered. One hundred inoperable and 64 operable patients (total 164) were eligible. Patients' characteristics were 122 male, 47 female; median age 78 years (range, 50-91 years); adenocarcinomas, 90; squamous cell carcinomas, 61; others, 18. Of the 100 inoperable patients, the % 3-year OS was 59.9% (95% confidence interval 49.6%-68.8%). Grade 3 and 4 toxicities were observed in 10 and 2 patients, respectively. No grade 5 toxicity was observed. Of the 64 operable patients, the % 3-year OS was 76.5% (95% confidence interval 64.0%-85.1%). Grade 3 toxicities were observed in 5 patients. No grade 4 and 5 toxicities were observed.
Stereotactic body radiation therapy for stage I NSCLC is effective, with low incidences of severe toxicity. This treatment can be considered a standard treatment for inoperable stage I NSCLC. This treatment is promising as an alternative to surgery for operable stage I NSCLC.
To review treatment outcomes for stereotactic body radiotherapy (SBRT) in medically operable patients with Stage I non-small-cell lung cancer (NSCLC), using a Japanese multi-institutional database.
...Between 1995 and 2004, a total of 87 patients with Stage I NSCLC (median age, 74 years; T1N0M0, n=65; T2N0M0, n=22) who were medically operable but refused surgery were treated using SBRT alone in 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. Total dose was 45-72.5 Gy at the isocenter, administered in 3-10 fractions. Median calculated biological effective dose was 116 Gy (range, 100-141 Gy). Data were collected and analyzed retrospectively.
During follow-up (median, 55 months), cumulative local control rates for T1 and T2 tumors at 5 years after SBRT were 92% and 73%, respectively. Pulmonary complications above Grade 2 arose in 1 patient (1.1%). Five-year overall survival rates for Stage IA and IB subgroups were 72% and 62%, respectively. One patient who developed local recurrences safely underwent salvage surgery.
Stereotactic body radiotherapy is safe and promising as a radical treatment for operable Stage I NSCLC. The survival rate for SBRT is potentially comparable to that for surgery.
Highlights • We analyzed the impact of consolidation/tumor ratio (CTR) on the outcomes after SBRT for early lung cancer. • Local control rates were high for patients with a CTR < 1. • Disease-free ...survival rates were associated with the CTR. • CTR effectively predicts outcomes after SBRT.
Abstract
Background
There are few reports from Japan about the outcomes of intensity-modulated radiation therapy for localized prostate cancer. This study was aimed at assessing the efficacy and ...toxicity of intensity-modulated radiation therapy in patients with intermediate- or high-risk prostate cancer.
Methods
We conducted a review of the data, retrieved from our institutional database, of patients who had received intensity-modulated radiation therapy for localized prostate cancer at a radiation dose of 78 Gy in 39 fractions. Data of 201 patients with intermediate-risk prostate cancer and 311 patients with high-risk prostate cancer were analyzed.
Results
The median follow-up period after the completion of intensity-modulated radiation therapy was 100 months (range, 24–154). The rates of cause-specific survival, overall survival, metastasis-free survival and biochemical recurrence-free survival in the intermediate-risk patients were 99, 95, 95 and 94% at 5 years and 99, 91, 90 and 86% at 8 years, respectively; the corresponding rates in the high-risk patients were 100, 97, 91 and 84% at 5 years and 96, 92, 84 and 76% at 8 years, respectively. The crude incidence of late grade 2–3 genitourinary toxicity was 28.1%, and that of late grade 3 genitourinary toxicity was 2.0%. The crude incidence of late grade 2 gastrointestinal toxicity was 5.1%, and there were no cases of late grade 3 gastrointestinal toxicity.
Conclusions
Our data demonstrated that intensity-modulated radiation therapy is effective for patients with localized intermediate-risk or high-risk prostate cancer while having minimal toxicity.
This study evaluated the efficacy and toxicity of IMRT in 512 patients with locaized prostate cancer, and we demonstrated that clinical outcomes were satisfactory.
To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas.
From February 2002 through April 2005, 74 patients with clinical Stage I-IVB carcinoma ...of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer.
The median age was 67 years (range, 45-83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005).
The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.
This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, ...from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity.
The purpose of this study was to examine the characteristics and treatment plans of patients who experienced fatal radiation pneumonitis after stereotactic body radiation therapy for primary or ...oligometastatic lung cancer. Records of 1789 patients treated with stereotactic body radiation therapy for primary or oligometastatic lung cancer were retrospectively reviewed to identify those who developed fatal radiation pneumonitis. Twenty-three (1.3%; 18 men and 5 women) patients developed fatal radiation pneumonitis after stereotactic body radiation therapy for lung cancer; their median age was 74 years. The mean Krebs von den Lungen-6 level and percent vital capacity were 1320 U/mL and 82%, respectively. Prestereotactic body radiation therapy computed tomography revealed pulmonary interstitial change in 14 (73.7%) of 19 patients in whom computed tomography data could be reviewed. Seven (30.4%) of 23 patients had regularly used steroids. The median time duration between stereotactic body radiation therapy commencement and pneumonia symptom appearance was 75 (range: 14-204) days. Median survival time following pneumonia symptom appearance was 53 (range: 4-802) days. The 6- and 12-month overall survival rates were 34.8% and 13.0%, respectively. The 6-month overall survival rates in patients with and without heart disease were 50.0%, 16.7%, and 46.7% for heart disease existence, respectively. There were 4 patients in whom fatal radiation pneumonitis occurred within 2 months after stereotactic body radiation therapy and who died within 1 month. Three of them had no pulmonary interstitial change before stereotactic body radiation therapy, but had heart disease. In summary, the survival time in this case series was generally short but varied widely. More than half of the patients had pulmonary interstitial change before stereotactic body radiation therapy, although immediately progressive fatal radiation pneumonitis was also observed in patients without pulmonary interstitial change. True risk factors for fatal radiation pneumonitis should be examined in a prospective study with a larger cohort.
The aim of this study was to evaluate the clinical impact of a combination of systemic sequential therapy and locoregional therapy on the long-term survival of patients with Barcelona Clinic Liver ...Cancer (BCLC) stage C hepatocellular carcinoma (HCC).
Sixty-four consecutive patients with intrahepatic target nodules who had initially received systemic therapy (lenvatinib and atezolizumab plus bevacizumab) were reviewed. The clinical impact of the combined use of systemic sequential therapy and locoregional therapy was evaluated by determining overall survival (OS). The combined use of systemic sequential therapy with more than two agents and locoregional treatment was defined as multidisciplinary combination therapy (MCT), while only systemic sequential therapy and repeated locoregional-treatment was defined as a single treatment procedure (STP).
R0 resection, MCT, and STP resulted in significantly better OS compared with no additional treatment (median OS, not reached vs. 18.2 months and 12.6 vs. 8.1 months, respectively;
= 0.002). Multivariate analysis confirmed that the use of R0 resection and MCT were associated with better OS (hazard ratio HR; 0.053,
= 0.006 and 0.189,
< 0.001, respectively) compared with that for STP (HR; 0.279,
= 0.003).
MCT is may effective in patients with BCLC stage C HCC and intrahepatic target nodules who have previously received systemic therapy-based treatment.
Purpose
The present study compared the complications associated with hypofractionated intensity-modulated radiation therapy (Hypo-IMRT) of prostate cancer to conventionally fractionated IMRT ...(Conv-IMRT).
Materials and methods
Hypo-IMRT delivered 70 Gy in 28 fractions, whereas Conv-IMRT delivered 78 Gy in 39 fractions. Toxicity was graded with the Common Terminology Criteria for Adverse Events, version 4.0, weekly during radiotherapy, 1 month after radiotherapy, and annually in both patient groups.
Results
The median follow-ups were 39.1 and 38.7 months for patients in the Hypo- and Conv-IMRT groups, respectively. There was no significant difference in rates of acute and late adverse events. The proportions of grade 2 acute genitourinary complications were 48.4 and 51.2% in the Hypo- and Conv-IMRT groups, respectively. The presence of a baseline International Prostate Symptom Score (IPSS) of ten or more was the only significant prognostic factor for grade 2 acute genitourinary toxicity. The incidence of grade 2 late rectal hemorrhage at 3 years was 3.2 and 3.5% in the Hypo- and Conv-IMRT groups, respectively. Small rectal volume was significantly associated with grade 2 late rectal hemorrhage.
Conclusion
Regarding acute and late adverse events, hypofractionated IMRT for prostate cancer was well tolerated and comparable with conventionally fractionated IMRT.
Clinical trial registration no. UMIN000003218.
To compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) ...as salvage radiation therapy (SRT) after prostatectomy.
A total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first.
The median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively.
Dose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.
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