Prospective study investigating hypofractionated proton beam therapy in patients with inoperable early stage non-small cell lung cancer
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SUBMITTER: Yang K
PROVIDER: S-EPMC10912465 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:This study presents the first data of a Japanese nationwide multi-institutional cohort and compares them with the findings of systematic literature reviews on radiation therapies and inoperable stage III non-small cell lung cancer (NSCLC) conducted by the Lung Cancer Working Group in the Particle Beam Therapy (PBT) Committee and Subcommittee at Japanese Society for Radiation Oncology. The Lung Cancer Working Group extracted eight reports and compared their data with those of the PBT registry from May 2016 to June 2018. All the analyzed 75 patients aged ≤80 years underwent proton therapy (PT) with concurrent chemotherapy for inoperable stage III NSCLC. The median follow-up period of the surviving patients was 39.5 (range, 1.6-55.6) months. The 2- and 3-year overall survival (OS) and progression-free survival rates were 73.6%/64.7% and 28.9%/25.1%, respectively. During the follow-up period, six patients (8.0%) had adverse events of Grade ≥ 3, excluding abnormal laboratory values. These included esophagitis in four patients, dermatitis in one and pneumonitis in one. Adverse events of Grade ≥ 4 were not observed. The results of these PBT registry data in patients with inoperable stage III NSCLC suggest that the OS rate was at least equivalent to that of radiation therapy using X-rays and that the incidence of severe radiation pneumonitis was low. PT may be an effective treatment to reduce toxicities of healthy tissues, including the lungs and heart, in patients with inoperable stage III NSCLC.
| S-EPMC10278876 | biostudies-literature
Project description:PurposeDue to the excellent outcomes with image-guided stereotactic body radiotherapy for patients with early-stage non-small cell lung cancer (NSCLC) and the low treatment-related toxicities using proton therapy (PT), we investigated treatment outcomes and toxicities when delivering hypofractionated PT.Materials and methodsBetween 2009 and 2018, 22 patients with T1 to T2 N0M0 NSCLC (45% T1, 55% T2) received image-guided hypofractionated PT. The median age at diagnosis was 72 years (range, 58-90). Patients underwent 4-dimensional computed tomography simulation following fiducial marker placement, and daily image guidance was performed. Nine patients (41%) were treated with 48 GyRBE in 4 fractions for peripheral lesions, and 13 patients (59%) were treated with 60 GyRBE in 10 fractions for central lesions. Patients were assessed for CTCAEv4 toxicities with computed tomography imaging for tumor assessment. The primary endpoint was grade 3 to 5 toxicity at 1 year.ResultsThe median follow-up for all patients was 3.5 years (range, 0.2-8.8 years). The overall survival rates at 3 and 5 years were 81% and 49%, respectively. Cause-specific survival rates at 3 and 5 years were 100% and 75%, respectively. The 3-year local, regional, and distant control rates were 86%, 85%, and 95%, respectively. Four patients experienced in-field recurrences between 18 and 45 months after treatment. One patient (5%) developed a late grade 3 bronchial stricture requiring hospitalization and stent.ConclusionImage-guided hypofractionated PT for early-stage NSCLC provides promising local control and long-term survival with a low likelihood of toxicity. Regional nodal and distant relapses remain a problem.
| S-EPMC7707327 | biostudies-literature
Project description:ObjectiveTo evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC).ResultsOverall, treatment was well tolerated with no grade toxicity ≥3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The three-year local progression-free survival (LPFS), relapse-free survival (RFS) and OS rates were 89.9%, 26.8%, and 74.4%, respectively. Multivariate analysis revealed that the tumour response was an independent prognostic factor for LPFS, RFS, and OS.ConclusionMost CR was achieved within 1 year after PBT and further salvage treatments in PBT field might be postponed up to approximately 18-24 months. Hypofractionated PBT could be good alternative for HCC patients who are unsuitable for surgical or invasive treatments with curative intent.Materials and methodsSeventy-one inoperable or recurrent HCC patients underwent hypofractionated PBT using 66 GyE in 10 fractions. The tumour responses were defined as the maximal tumour response observed during the follow-up period using the modified Response Evaluation Criteria in Solid Tumors criteria.
| S-EPMC5790519 | biostudies-literature
Project description:ImportanceStereotactic body radiotherapy (SBRT) is widely used for stage I medically inoperable non-small cell lung cancer (NSCLC), yet varied results from randomized clinical trials (RCTs) and concerns in treating centrally located tumors persist.ObjectiveTo examine whether SBRT would improve local control (LC) compared with hypofractionated conventional radiotherapy (CRT).Design setting and participantsThis phase 3 RCT was conducted in 16 Canadian centers. Patients with medically inoperable stage I (≤5 cm) NSCLC were randomized 2:1 to SBRT of 48 Gy in 4 fractions (peripheral NSCLC) or 60 Gy in 8 fractions (central NSCLC) vs CRT of 60 Gy in 15 fractions. Data were collected from May 2014 to January 2020, and data were analyzed from July 2022 to July 2023.InterventionsSBRT or CRT.Main outcomes and measuresThe primary objective was to determine the effectiveness of SBRT compared with CRT based on LC at 3 years. Secondary outcomes included event-free survival, overall survival, and toxic effects. All radiation plans were subject to real-time/final review. Local failures were centrally adjudicated. The study was designed to detect a 3-year LC improvement of SBRT from 75% to 87.5%. The target sample size was 324 patients.ResultsOf 233 included patients, 119 (51.1%) were male, and the mean (SD) age was 75.4 (7.7) years; the median (IQR) follow-up was 36.1 (26.4-52.8) months. A total of 154 patients received SBRT and 79 received CRT. The 3-year LC was 87.6% (95% CI, 81.9%-93.4%) for SBRT and 81.2% (95% CI, 71.9%-90.5%) for CRT (hazard ratio [HR], 0.61; 95% CI, 0.31-1.20; P = .15). The HR was 1.02 (95% CI, 0.72-1.45; P = .87) for event-free survival and 1.18 (95% CI, 0.80-1.76; P = .40) for overall survival. Minimal acute toxic effects were observed. Among those randomized to SBRT, late grade 3 or 4 toxic effects occurred in 5 of 45 (11%) with central NSCLC and 2 of 109 (1.8%) with peripheral NSCLC; among those randomized to CRT, in 1 of 19 (5%) with central NSCLC and 1 of 60 (2%) with peripheral NSCLC. One patient who received SBRT for an ultracentral lesion (target overlapping proximal bronchus) experienced a possible treatment-related grade 5 event (hemoptysis).Conclusions and relevanceThis RCT compared lung SBRT with hypofractionated CRT that included central/ultracentral tumors. No difference was detected in LC between groups. Severe toxic effects were limited, including patients with central tumors. The trial provides important prospective data evaluating SBRT; however, further research is necessary to determine if SBRT is more effective than CRT for peripheral and central NSCLC.Trial registrationClinicalTrials.gov Identifier: NCT03924869.
| S-EPMC11413752 | biostudies-literature
Project description:Proton beam therapy (PBT) and photon radiotherapy for stage I non-small cell lung cancer (NSCLC) were compared in terms of clinical outcomes and dosimetry. Data were obtained from patients who underwent PBT or photon radiotherapy at two institutions-the only two facilities where PBT is available in the Republic of Korea. Multivariate Cox proportional hazards models and propensity score-matched analyses were used to compare local progression-free survival (PFS) and overall survival (OS). Survival and radiation exposure to the lungs were compared in the matched population. Of 289 patients included in the analyses, 112 and 177 underwent PBT and photon radiotherapy, respectively. With a median follow-up duration of 27 months, the 2-year local PFS and OS rates were 94.0% and 83.0%, respectively. In the multivariate analysis, a biologically effective dose (BED10, using α/β = 10 Gy) of ≥125 cobalt gray equivalents was significantly associated with improved local PFS and OS. In the matched analyses, the local PFS and OS did not differ between groups. However, PBT showed significantly lower lung and heart radiation exposure in the mean dose, V5, and V10 than photon radiotherapy. PBT significantly reduced radiation exposure to the heart and lungs without worsening disease control in stage I NSCLC patients.
| S-EPMC9329768 | biostudies-literature
Project description:PurposeData comparing moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) are lacking. We aim to compare late toxicity profiles of patients with early-stage prostate cancer treated with moderately hypofractionated PBT and IMRT.Methods and materialsThis multi-institutional analysis included patients with low- or intermediate-risk biopsy-proven prostate adenocarcinoma from 7 tertiary referral centers treated from 1998 to 2018. All patients were treated with moderately hypofractionated radiation, defined as 250 to 300 cGy per daily fraction given for 4 to 6 weeks, and stratified by use of IMRT or PBT. Primary outcomes were late genitourinary (GU) and gastrointestinal (GI) toxicity. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, National Comprehensive Cancer Network risk group, age, pretreatment International Prostate Symptom Score (GU only), and anticoagulant use (GI only).ResultsA total of 1850 patients were included: 1282 IMRT (median follow-up 80.0 months) and 568 PBT (median follow-up 43.9 months). Overall toxicity rates were low, with the majority of patients experiencing no late GU (56.6%, n = 1048) or late GI (74.4%, n = 1377) toxicity. No difference was seen in the rates of late toxicity between the groups, with late grade 3+ GU toxicity of 2.0% versus 3.9% (odds ratio [OR] 0.47; 95% confidence interval 0.17-1.28) and late grade 2+ GI toxicity of 14.6% versus 4.7% (OR 2.69; confidence interval 0.80-9.05) for the PBT and IMRT cohorts, respectively. On multivariable analysis, no factors were significantly predictive of GU toxicity, and only anticoagulant use was significantly predictive of GI toxicity (OR 1.90; P = .008).ConclusionsIn this large, multi-institutional analysis of 1850 patients with early-stage prostate cancer, treatment with moderately hypofractionated IMRT and PBT resulted in low rates of toxicity. No difference was seen in late GI and GU toxicity between the modalities during long-term follow-up. Both treatments are safe and well tolerated.
| S-EPMC9610030 | biostudies-literature
Project description:PurposeMolecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC.Materials and methodsThis retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling. A second cohort of ES-NSCLC treated with RT (Stanford, n = 39) was included to power clinical analyses. Prognostic gene alterations were identified and correlated with clinical variables. The primary clinical end point was the correlation of prognostic genes with the cumulative incidence of relapse, disease-free survival, and overall survival (OS) in a pooled RT cohort from the two institutions (N = 62).ResultsAlthough the surgery cohort exhibited lower rates of relapse, the RT cohort was highly enriched for somatic STK11 mutations (43% v 6.7%). Receiving supplemental oxygen (odds ratio [OR] = 5.5), 20+ pack-years of tobacco smoking (OR = 6.1), and Black race (OR = 4.3) were associated with increased frequency of STK11 mutations. In the pooled RT cohort (N = 62), STK11 mutation was strongly associated with inferior oncologic outcomes: 2-year incidence of relapse was 62% versus 20% and 2-year OS was 52% versus 85%, remaining independently prognostic on multivariable analyses (relapse: subdistribution hazard ratio = 4.0, P = .0041; disease-free survival: hazard ratio, 6.8, P = .0002; OS: hazard ratio, 6.0, P = .022). STK11 mutations were predominantly associated with distant failure, rather than local.ConclusionIn this cohort of ES-NSCLC, STK11 inactivation was associated with poor oncologic outcomes after RT and demonstrated a novel association with clinical hypoxia, which may underlie its correlation with medical inoperability. Further validation in larger cohorts and investigation of effective adjuvant systemic therapies may be warranted.
| S-EPMC10530422 | biostudies-literature
Project description:Forty-seven patients with intrahepatic cholangiocarcinoma (IHCC) who received proton beam therapy (PBT) were analyzed to evaluate the clinical efficacy and safety of hypofractionated PBT in patients with inoperable or recurrent IHCC. The median prescribed dose of PBT was 63.3 GyE (range: 45-80 GyE) in 10 fractions, and the median duration of follow-up in all the patients was 18.3 months (range: 2.4-89.9 months). Disease progression occurred in 35 of the 47 (74.5%) patients; local, intrahepatic, and extrahepatic progression occurred in 5 (10.6%), 20 (42.6%), and 29 (61.7%) patients, respectively. The 2-year freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS) rates, and median time of OS were 86.9% (95% confidence interval [CI], 74.4-99.4%), 16.8% (95% CI, 4.3-29.3%), 42.7% (95% CI, 28.0-57.4%), and 21.9 months (95% CI, 16.2-28.3 months), respectively; grade ≥ 3 adverse events were observed in four (8.5%) patients. In selected patients with localized disease (no viable tumors outside of the PBT sites), the median time of OS was 33.8 months (95% CI, 5.4-62.3). These findings suggest that hypofractionated PBT is safe and could offer a high rate of FFLP and promising OS in patients with inoperable or recurrent IHCC.
| S-EPMC9688899 | biostudies-literature
Project description:IntroductionThe combination of a PD-L1 inhibitor plus carboplatin/cisplatin and etoposide (EC/EP) has become a new standard first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). Combining concurrent palliative hypofractionated radiotherapy of the thorax (HFRT) and immunochemotherapy may have a synergistic effect. In this study, we explored an optimal model of combination radiotherapy with immunochemotherapy as first-line treatment of ES-SCLC.Patients and methodsIn this multicenter single-arm phase 2 trial, patients with ES-SCLC received atezolizumab with EC/EP for two cycles (induction phase), then, those who did not progress received concurrent palliative HFRT and two cycles of atezolizumab with EC/EP (combination phase). Afterward they received atezolizumab every 3 weeks for a maximum of 2 years after study enrolment (maintenance phase). Prophylactic cranial irradiation (PCI) was recommended. The primary endpoints were safety and tolerance; the second endpoints were progression-free survival (PFS).ResultsForty patients were enrolled, and all had completed palliative HFRT and four cycles of immunochemotherapy. There were seven grade 3 adverse events (3 decreased neutrophil count, 1 anemia, 2 pneumonitis, 1 esoenteritis), two grade 4 adverse events (2 decreased white cell count) and no grade 5 toxicities. The pneumonitis rate was 12.5% (three grade 2 and two grade 3 events). At the median follow-up of 14.2 months (range, 6.8-28.7), the median PFS was 8.6 months (95%CI, 6.1-11.1).ConclusionThe addition of concurrent hypofractionated thoracic radiotherapy to first-line immunochemotherapy for ES-SCLC was well tolerated and showed promising clinical efficacy. Additional randomized trials are needed to validate benefits.Clinical trial registrationhttps://clinicaltrials.gov/ (NCT04636762).
| S-EPMC10282832 | biostudies-literature
Project description:Background: Proton beam has an excellent depth dose distribution due to its unique physical properties, and thus proton beam therapy (PBT) has been tried and showed promising outcomes in hepatocellular carcinoma (HCC). The purpose of this phase II study is to evaluate the efficacy of hypofractionated PBT in HCC. Methods: The eligibility criteria for this study were as follows: patients with HCC lesion(s) who were failed after, were difficult to treat with, or refused to other local treatments; tumor size and number of ?7 and ?2 cm, respectively, and HCC lesion(s) of ?2 cm from gastrointestinal organs; Child-Pugh score of ?7; Eastern Cooperative Oncology Group performance status ?1; and age ?18 years. The prescribed dose of PBT was 70 Gy equivalent in 10 fractions. The primary endpoint was 3-year local progression-free survival (LPFS) rate. Results: Forty-five patients were prospectively enrolled, and there were 35 men and 10 women with a median age of 63 years (range, 46-78 years). Thirty-seven patients had recurrent and/or residual disease, and eight patients had treatment-naive disease. All patients received the planned treatments without treatment interruption, and grade ?3 acute toxicity did not occur. The median follow-up duration was 35.1 months (range, 11.2-56.3 months) and local progression occurred in two patients (8.7%). The 3-year rates of LPFS and overall survival (OS) were 95.2% (95% confidence interval [CI], 89.1%-100%) and 86.4% (95% CI, 72.9-99.9%), respectively. Conclusion: Hypofractionated PBT showed promising LPFS and OS, and further studies are warranted to compare PBT with other local modalities.
| S-EPMC7198869 | biostudies-literature