Significance of radiation therapy in the myxoid round-cell liposarcoma treatment regimen.

BACKGROUND AND PURPOSE: Because myxoid liposarcomas are more radiosensitive than other soft tissue sarcomas, there have been several reports of 50 Gy preoperative radiation therapy combined with surgery, but the wound complication rate is reportedly high. We have performed preoperative irradiation at a reduced dose of 40 Gy and definitive radiation therapy for unresectable cases. This study aimed to report the tumor reduction rate and oncological results with a reduced dose of preoperative irradiation and the outcome of definitive irradiation for unresectable cases. MATERIALS AND METHODS: Forty-one patients with myxoid liposarcoma treated in our institution between 2002 and 2021 were included. We examined the tumor volume shrinkage rate with preoperative radiation, compared complications and oncological outcomes between preoperative radiation and surgery-only cases, and investigated the prognosis and tumor shrinkage of definitive radiation cases. RESULTS: The total dose irradiated was 40 Gy except in two cases. The mean tumor volume reduction rate was 52.0%. A decreased dose of preoperative radiation did not worsen clinical outcomes with fewer complications. The total dose of definitive radiation was approximately 60 Gy. The mean tumor volume reduction rate was 55.0%. The tumor shrinkage maintenance rate was 100% in a median follow-up period of 50.5 months. CONCLUSION: Preoperative radiation therapy for myxoid liposarcoma near vital organs is a good approach because even with a reduced dose of 40 Gy, significant tumor reduction and excellent results were achieved. Definitive radiation therapy is the recommended treatment for older patients with serious comorbidities or inoperable patients.

Phase 3 multicenter randomized trial of PSMA PET/CT prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer [PSMA dRT]: study protocol.

BACKGROUND: Definitive radiation therapy (dRT) is an effective initial treatment of intermediate-risk (IR) and high-risk (HR) prostate cancer (PCa). PSMA PET/CT is superior to standard of care imaging (CT, MRI, bone scan) for detecting regional and distant metastatic PCa. PSMA PET/CT thus has the potential to guide patient selection and the planning for dRT and improve patient outcomes. METHODS: This is a multicenter randomized phase 3 trial (NCT04457245). We will randomize 312 patients to proceed with standard dRT (control Arm, n = 150), or undergo a PSMA PET/CT scan at the study site (both 18F-DCFPyL and 68Ga-PSMA-11 can be used) prior to dRT planning (intervention arm, n = 162). dRT will be performed at the treating radiation oncologist facility. In the control arm, dRT will be performed as routinely planned. In the intervention arm, the treating radiation oncologist can incorporate PSMA PET/CT findings into the RT planning. Androgen deprivation therapy (ADT) is administered per discretion of the treating radiation oncologist and may be modified as a result of the PSMA PET/CT results. We assume that approximately 8% of subjects randomized to the PSMA PET arm will be found to have M1 disease and thus will be more appropriate candidates for long-term systemic or multimodal therapy, rather than curative intent dRT. PET M1 patients will thus not be included in the primary endpoint analysis. The primary endpoint is the success rate of patients with unfavorable IR and HR PCa after standard dRT versus PSMA PET-based dRT. Secondary Endpoints (whole cohort) include progression free survival (PFS), metastasis-free survival after initiation of RT, overall survival (OS), % of change in initial treatment intent and Safety. DISCUSSION: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa who receive dRT. In this trial the incorporation of PSMA PET/CT may improve the success rate of curative intent radiotherapy in two ways: to optimize patient selection as a biomarker and to personalizes the radiotherapy plan. CLINICAL TRIAL REGISTRATION: UCLA IND#147591 ○ Submission: 02.27.2020 ○ Safe-to-proceed letter issued by FDA: 04.01.2020 UCLA IRB #20-000378 ClinicalTrials.gov Identifier NCT04457245 . Date of Registry: 07.07.2020. Essen EudraCT 2020-003526-23.

Impact of histological grade on oncologic outcomes in clinical stage I patients with endometrial carcinoma patients after definitive primary radiation therapy.

OBJECTIVES: To determine the impact of histological grade on overall survival in patients with clinical stage I endometrioid endometrial adenocarcinoma when radiation therapy is used as primary definitive treatment. METHODS: Patients with stage I endometrioid endometrial adenocarcinomas who underwent definitive radiation therapy with brachytherapy ± external beam radiation therapy were identified from the National Cancer Database. Overall survival was estimated using the Kaplan-Meier method. Univariable and multivariable analyses were performed to determine factors affecting overall survival. Inverse probability of treatment weights were also used in multivariable analysis to estimate casual effects of external beam radiation therapy. RESULTS: A total of 947 patients were identified. Median overall survival for grade 1, grade 2, and grade 3 tumors was 62 months (95% CI 53.8 to 70.2), 48.5 months (95% CI 38.2 to 58.8), and 33.5 months (95% CI: 23.1 to 43.8), respectively. Grade, age, and insurance status were associated with overall survival in univariate analysis with only grade and age remaining significant in multivariate analysis. Brachytherapy with external beam radiation therapy was not associated with survival in comparison with brachytherapy alone. Compared with grade 1 tumors, patients with grade 3 (HR 1.4, 95% CI 1.15 to 1.89), but not grade 2 (HR 1.0, 95% CI 0.82 to 1.26), had an increased risk of death, which persisted in an inverse probability of treatment weights-adjusted model (HR 1.56, 95% CI 1.21 to 1.93). CONCLUSIONS: Patients with grade 3 stage I endometrioid endometrial adenocarcinoma treated with primary definitive radiation therapy have worse survival than those with lower grade tumors. Addition of external beam radiation therapy to brachytherapy did not affect survival.

Treatment Outcomes in Patients with Carcinoma In Situ of the Larynx.

OBJECTIVE: To compare survival endpoints in patients with laryngeal carcinoma in situ (L-CIS) who received definitive radiotherapy (RT) versus other modalities as first-line treatment and after disease recurrence. METHODS: This is a retrospective study of patients with L-CIS treated between June 2001 and December 2021. Survival outcomes (recurrence-free (RFS), invasion-free (IFS), laryngectomy-free (LFS), and overall survival (OS)) were compared between patients who had first-line RT versus non-RT modalities and for patients with recurrent disease who underwent second-line RT. RESULTS: A total of 85 patients with L-CIS were included (73 men [85.9%] and 12 [14.1%] women, median age of 65 [IQR: 55-74] years). Of these, 42 had first-line RT (49.4%) and 43 (50.6%) had non-RT treatment. After median follow-up of 4.8 (IQR: 2.8-9) years, patients in the first-line RT group had improved 2-year (94.2% [95% confidence interval (CI): 86.7-100] versus 41.7% [CI: 29.3-59.5]) and 5-year (90.6% [CI: 80.9-100] versus 27.5% [CI: 16.4-48.2]) RFS relative to non-RT recipients (p < 0.001). OS and IFS were similar between groups. However, patients in the RT group had worse 2-year (94% [CI: 87-100] versus 98% [CI: 93-100]) and 5-year (82% [CI: 68-99] versus 98% [CI: 93-100]; p = 0.013) LFS. All 35 patients with recurrent L-CIS were successfully cured with second-line treatments (12 received RT [34.3%]), and no differences in any survival endpoints were seen in these patients based on first-line and second-line treatments. CONCLUSION: Although first-line RT for L-CIS led to improved recurrence-free survival compared with other modalities, second-line RT may be a particularly valuable option for recurrent CIS. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities.

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3-4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT.

The predictors of lymphopenia and its effects on survival in locally advanced esophageal squamous cell carcinoma.

To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

Risk factors for aortoesophageal fistula in cT4b esophageal squamous cell carcinoma after definitive radiation therapy.

Background: Esophageal fistula (EF) is a serious complication in patients with cT4b esophageal squamous cell carcinoma (ESCC) with adjacent organ involvement. Among EFs, aortoesophageal fistula (AEF), forming a fistula with the aorta, could be fatal. This study aimed to identify the risk factors for AEF in patients with cT4b ESCC with obvious or suspected aortic invasion who underwent definitive radiotherapy (DRT). Methods: Forty-four patients with cT4b ESCC with obvious or suspected invasion to the aorta who underwent DRT were included. Blood tests and computed tomography (CT) findings before and after DRT were compared between the patients with and without AEF to identify the potential risk factors for AEF. Results: Nine patients (20.5%) developed AEF after DRT. Comparing between patients with and without AEF, pre-DRT white blood cell counts and post-DRT C-reactive protein (CRP) levels were significantly higher in patients with AEF. Furthermore, pre-DRT CT findings were similar between the two groups. However, post-DRT CT findings demonstrated significantly larger picus angle and lower esophageal wall thickness on the aortic side in patients with AEF. Multivariate analysis identified elevated post-DRT CRP levels [<3.3 versus ≥3.3 mg/dL; odds ratio (OR): 30.7; 95% confidence interval (CI): 2.92-323.2; P=0.004] and esophageal wall thinning on post-DRT CT scans (>6 versus ≤6 mm; OR: 13.2; 95% CI: 1.24-140.1; P=0.033) as risk factors for AEF. Conclusions: We found that post-DRT esophageal wall thinning on the aortic side, as observed on CT scans, and elevated CRP levels were predictive factors for AEF in patients with cT4b ESCC with obvious or suspected invasion to the aorta.

Definitive radiation therapy and liver local therapy in de novo liver metastatic nasopharyngeal carcinoma: Large cohort study.

BACKGROUND: We aimed to evaluate patients suitable for definitive radiation therapy (DRT) and liver local therapy (LLT) in addition to palliative chemotherapy (PCT) among those with de novo liver metastatic nasopharyngeal carcinoma (lmNPC). METHODS: The overall survival (OS) and progression-free survival (PFS) rates were calculated and compared in 610 patients with lmNPC. RESULTS: Both the PCT+DRT and PCT+DRT+LLT groups had better survival outcomes than the PCT group. Among patients with complete response/partial response (CR/PR) after PCT, no significant differences in survival rates were observed between those treated with PCT+DRT and PCT+DRT+LLT (2-year PFS: 27.0% vs. 32.9%, p = 0.263). Among patients with progressive disease/stable disease (PD/SD) after PCT, significantly better survival rates were observed in patients treated with PCT+DRT+LLT. CONCLUSIONS: DRT might benefit patients with lmNPC regardless of the tumor response after PCT. For patients with CR/PR, LLT might not be needed. For patients with PD/SD, LLT might improve survival outcomes.

A validation study on the lung immune prognostic index for prognostic value in patients with locally advanced non-small cell lung cancer.

BACKGROUND: Baseline lung immune prognostic index (LIPI) was reported as a potential predictive biomarker of immune checkpoint inhibitor treatment and a prognostic biomarker for metastatic non-small cell lung cancer (NSCLC). However, it remains unclear whether LIPI is associated with outcomes in locally advanced NSCLC (LA-NSCLC). MATERIALS/METHODS: Patients with LA-NSCLC receiving radiotherapy between 2000 to 2017 were retrospectively reviewed. Based on pretreatment dNLR and LDH level made up LIPI per previous publications, patients were divided into good group (0 score) and intermediate-poor group (1 or 2 scores). Propensity score matching (PSM) was conducted to balance confounding variables. RESULTS: A total of 1079 patients were eligible for analysis. Patients with intermediate-poor pretreatment LIPI had inferior overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) than those with good LIPI. Multivariate analysis suggested that LIPI was an independent prognostic marker for OS (hazard ratio [HR] = 1.19, 95% CI: 1.02-1.40), PFS (HR = 1.18, 95% CI: 1.02-1.36), and LRRFS (HR = 1.22, 95% CI: 1.05-1.41) in patients with inoperable LA-NSCLC. PSM analysis further verified that intermediate-poor LIPI was an independent prognostic factor for shorter survivals (OS, PFS and LRRFS). CONCLUSIONS: LIPI is a simple and promising prognostic marker for patients with unresectable LA-NSCLC. Further prospected studies are warranted to validated these findings.

Phase II Trial of Epigallocatechin-3-Gallate in Acute Radiation-Induced Esophagitis for Esophagus Cancer.

Acute radiation-induced esophagitis (ARIE) is among the most serious form of toxicities associated with definitive radiotherapy or chemoradiotherapy used for treatment of patients with esophageal cancer. Our preliminary phase I and II trials of lung cancer patients who received radiotherapy indicated epigallocatechin-3-gallate (EGCG) as a promising therapeutic option against ARIE. Therefore, we conducted a prospective phase II study to validate the efficacy and safety of EGCG in the treatment of ARIE. The patients who received chemoradiotherapy or definitive radiotherapy for treatment of esophageal cancer in the Shandong Cancer Hospital and Institute in China were enrolled for the present study. EGCG (440 µM) was administered with first onset of ARIE and then at weeks after final radiotherapy. The patients were monitored every week for dysphagia, Radiation Therapy Oncology Group (RTOG) score, and esophagitis-related pain. Moreover, tumor response and the effect on survival following the treatment were also evaluated. Comparison of the RTOG score in the first, second, third, fourth, fifth, and even sixth week after EGCG prescription and the first and second week after radiotherapy with baseline indicates a significant reduction. The tumor response rate was 86.3%. The overall survival rate in 1, 2, and 3 years was found to be 74.5%, 58%, and 40.5%. Oral administration of EGCG solution seems to be feasible for treating ARIE in patients with esophageal cancer who receive radiation therapy. EGCG might be an ARIE-reliever without compromising the efficacy of radiation therapy. A randomized study with a control group is needed for further evaluation.

The Results of Definitive Radiation Therapy and The Analysis of Prognostic Factors for Non-Small Cell Lung Cancer / 대한방사선종양학회지

PURPOSE: This retrospective study was tried to evaluate the clinical characteristics of patients, patterns of failure, survival rates, prognostic factors affecting survival, and treatment related toxicities when non-small cell lung cancer patients was treated by definitive radiotherapy alone or combined with chemotherapy. MATERIAL AND METHODS: We evaluated the treatment results of 70 patients who were treated by definitive radiation therapy for non-small cell lung cancer at the Department of Radiation Oncology, Ewha Womans University Hospital, between March 1982 and April 1996. The number of patients of each stage was 2 in stage I, 6 in stage II, 30 in stage III-A, 29 in stage III- B, 3 in stage IV. Radiation therapy was administered by 6 MV linear accelerator and daily dose was 1.8-2.0 Gy and total radiation dose was ranged from 50.4 Gy to 72.0 Gy with median dose 59.4 Gy. Thirty four patients was treated with combined therapy with neoadjuvant or concurrent chemotherapy and radiotherapy, and most of them were administered with the multi-drug combined chemotherapy including etoposide and cisplatin. The survival rate was calculated with the Kaplan-Meier methods. RESULTS: The overall 1-year, 2-year, and 3-year survival rates were 63%, 29%, and 26%, respectively. The median survival time of all patients was 17 months. The disease-free survival rate for 1-year and 2-year were 23% and 16%, respectively. The overall 1-year survival rates according to the stage was 100% for stage I, 80% for stage II, 61% for stage III, and 50% for stage IV. The overall 1-year, 2-year, and 3-year survival rates for stage III patients only were 61%, 23%, and 20%, respectively. The median survival time of stage III patients only was 15 months. The complete response rates by radiation therapy was 16% and partial response rate was 50%. Thirty patients (43%) among 70 patients assessed local control at initial 3 months follow-up duration. Twenty four (80%) of these 30 patients was possible to evaluate the pattern of failure after achievement of local control. And then, treatment failure occured in 14 patients (58%); local relapse in 6 patients (43%), distant metastasis in 6 patients (43%) and local relapse with distant metastasis in 2 patients (14%). Therefore, 16 patients (23%) were controlled of disease of primary site with or without distant metastases. Twenty three patients (46%) among 50 patients who were possible to follow-up had distant metastasis. The overall 1-year survival rate according to the treatment modalities was 59% in radiotherapy alone and 66% in chemoirradiation group. The overall 1-year survival rates for stage III patients only was 51% in radiotherapy alone and 68% in chemoirradiation group which was significant different. The significant prognostic factors affecting survival rate were the stage and the achievement of local control for all patients at univariate- analysis. Use of neoadjuvant or concurrent chemotherapy, use of chemotherapy and the achievement of local control for stage III patients only were also prognostic factors. The stage, pretreatment performance status, use of neoadjuvant or concurrent chemotherapy, total radiation dose and the achievement of local control were significant at multivariate analysis. The treatment-related toxicities were esophagitis, radiation pneumonitis, hematologic toxicity and dermatitis, which were spontaneously improved, but 2 patients were died with radiation pneumonitis. CONCLUSION: The conventional radiation therapy was not sufficient therapy for achievement of long-term survival in locally advanced non-small cell lung cancer. Therefore, aggressive treatment including the addition of appropriate chemotherapeutic drug to decrease distant metastasis and preoperative radiotherapy combined with surgery, hyperfractionation radiotherapy or 3-D conformal radiation therapy for increase local control are needed.