International Journal of Radiation Oncology Biology Physics最新文献

Purpose: To develop and externally validate a model predicting pathological complete response (pCR) in patients with rectal cancer treated with neoadjuvant radiochemotherapy. The approach combines the classical logit dose-effect curve with individual early response assessed by magnetic resonance imaging during radiochemotherapy.

Methods and materials: The dose-response model incorporating the early regression index (ERI) was derived from 2 published data sets. A population-averaged dose-response curve was obtained by fitting data from a recent meta-analysis. Then, an ERI-based model for pCR prediction was fit to 95 patients treated at San Raffaele Hospital; ERI was incorporated as a dynamic dose-modifying factor in the Hill model, based on Equivalent Uniform Dose to 2 Gy and including the time factor. The model was validated on an external cohort of 132 patients treated at Policlinico Gemelli with standard and dose-escalated schedules. Calibration plots, area under the curve, and average precision were used to assess performance. Recalibration refined predictions for the external cohort.

Results: The final Hill model showed best-fit values of TD50 = 52.2 Gy, dynamic dose-modifying factor = (0.89 + 0.02 × ERI), and steepness k = 5.91 + 0.11 × ERI. The validation cohort had a pCR rate of 35.6%. Agreement between prediction and observed rates was high (offset, 0; slope, 0.84). Discriminative ability was robust (area under the curve, 0.77; average precision, 0.65 vs 0.356 for baseline). ERI-stratified dose-pCR relationships confirmed predictive value across 4 ERI categories: highly responsive (ERI, 1-6.9; pCR, 65%), moderately responsive (ERI, 6.9-13.1; pCR, 55%), poorly responsive (ERI, 13.1-36; pCR, 14% and 35%), and nonresponsive (ERI, >36; pCR, 0%). Predictions aligned with results using median ERI values per group.

Conclusions: The ERI-dose model was validated on an external cohort with distinct radiation therapy regimens. Dose escalation of 8.5 Equivalent Uniform Dose to 2 Gy in moderate-to-good responders corresponds to an increase of approximately 20% in pCR, whereas no benefit was reported in nonresponders. These findings highlight the model's potential for personalizing radiation therapy protocols by optimizing dose escalation based on ERI.

Purpose: The clinical benefit of incorporating oxaliplatin into conventional neoadjuvant chemoradiotherapy (nCRT) for patients with high-risk locally advanced rectal cancer (LARC) remains controversial.

Methods and materials: This multicenter, open-label, randomized controlled trial enrolled 505 patients with high-risk LARC, defined by the presence of at least 1 of the following adverse features: clinical T4 stage, clinical N2 stage, high tumor grade, extramural vascular invasion, involvement of the mesorectal fascia, or perianal musculature involvement. Enrollment took place between August 2017 and April 2022. Patients were randomly assigned to receive long-course radiation therapy combined with a 3-cycle chemotherapy regimen of capecitabine and oxaliplatin (CapeOX group; n = 248) or capecitabine alone (Cape group; n = 257). The primary endpoint was 3-year disease-free survival (3y-DFS).

Results: Following nCRT, radical surgery was performed in 91.5% of the CapeOX group and 92.2% in the Cape group (P = .778). Pathologic complete response rates were comparable between the CapeOX and Cape groups (25.5% vs 25.3%; P = .954). A significantly greater proportion of patients in the CapeOX group achieved marked tumor regression (College of American Pathologists (CAP 0-1)) compared with the Cape group (58.6% vs 46.8%; P = .011). The incidence of grade 3 to 4 treatment-related toxicities was similar between the groups (CapeOX: 14.1% vs Cape: 9.3%; P = .095). After a median follow-up of 37 months, 3y-DFS and 3-year overall survival rates were comparable between the groups (both P > .050). Overall, patients who achieved CAP 0 to 1 had significantly better 3y-DFS than those with CAP 2 to 3 (89.0% vs 80.9%; P = .018).

Conclusions: The addition of oxaliplatin to conventional nCRT may enhance pathologic tumor regression in patients with high-risk LARC without a significant increase in severe adverse events. However, this intensified 3-cycle chemotherapy regimen did not translate into a long-term survival benefit.

Background: Grade 2 meningiomas often recur after surgery and radiation therapy. However, large, in-depth failure analyses are lacking, limiting the potential to refine radiation therapy. We report a pattern of failure analysis, encompassing treatment and outcome data from over two decades.

Materials and methods: Patients who underwent proton- or photon-based fractionated adjuvant or salvage radiation therapy for a grade 2 meningioma between 2000 and 2023 were included. Subsequently, an in-depth analysis of the failure pattern was conducted.

Results: A total of 105 patients were included, with 36 patients having 46 progressive or recurrent grade 2 meningiomas during the available follow-up. Most patients received 59.4 Gy (interquartile range [IQR]: 57.6 - 59.4) in 33 fractions (62.9%) and underwent proton radiation therapy (61.0%), with a median voxel-based equivalent uniform dose (EUD) of 60.1 Gy (IQR: 57.3 - 61.3). Most recurrent and progressive tumors were either located in the treatment volume (35/46, 76.1%) or within 2 cm of it (9/46, 19.6%). The median distance to out-of-field failures was 11.9 mm. The EUD (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.59 - 0.98), target volume (HR: 1.6, 95% CI: 1.2 - 2.1), RTOG 0539 risk classification (high vs. intermediate, HR: 7.9, 95% CI: 1.5 - 42.7), male sex (HR: 2.0, 95% CI: 0.9 - 4.4), treatment indication (salvage vs. adjuvant, HR: 2.4, 95% CI: 1.1 - 5.5), and age at radiation therapy (HR: 1.5, 95% CI: 1.0 - 2.1) were associated with progression.

Conclusion: This in-depth pattern of failure analysis for grade 2 meningiomas after radiation therapy demonstrated that treatment failures predominantly occur in close spatial relation to the irradiated target volume. Large treatment volumes, macroscopic disease, and a low EUD considerably impact disease control, underscoring the need for further local treatment and targeting refinements.

Purpose: Because dose escalation radiation therapy can improve local control (LC), stereotactic body radiation therapy has achieved better results than conventional radiation therapy in liver malignancies. This study aimed to investigate the role of dose escalation proton beam therapy (PT) in patients with intrahepatic cholangiocarcinoma (iCCA) and perihilar cholangiocarcinoma (pCCA).

Methods and materials: We analyzed data from a multi-institutional prospective registry that included all Japanese proton beam facilities between May 2016 and May 2021. Endpoints were LC, progression-free survival, overall survival (OS), and toxicity.

Results: We included 236 patients with unresectable cholangiocarcinoma (133 iCCA and 103 pCCA) treated with PT with a median prescribed dose of 72.6 Gy (RBE) (range, 50-76 Gy Relative Biological Effectiveness (RBE)) in 25 fractions (range, 10-38 fractions). With a median follow-up of 20.0 months for surviving patients, the median OS was 19 months, and the 2-year OS was 44.8%. For iCCA and pCCA, the median OSs were 17 and 20 months, respectively. Two-year progression-free survival and LC rates were 20.6% and 66.5%, respectively. Multivariable analyses revealed that liver function and the distance between the tumor and the gastrointestinal tract were significantly associated with OS, whereas the overall treatment time was associated with LC. Furthermore, liver function and tumor diameter were associated with progression-free survival. The median OS for patients with gastrointestinal distance ≥2 cm and a higher prescribed dose (≥74 Gy in equivalent 2-Gy fractions) was 37 months (2-year OS 61.8%), compared with 18.0 months (33.1%) for other patients (P< .001). Twenty-one patients experienced adverse reactions of grade 3 or higher (8.9%).

Conclusions: PT showed good efficacy with acceptable toxicity for unresectable iCCA and pCCA without distant metastasis. Especially in patients with gastrointestinal distance ≥2 cm, high-dose PT was associated with improved OS.

Purpose: Coxarthrosis and greater trochanteric pain syndrome (GTPS) are common etiologies of hip pain. In this retrospective study, we analyzed the treatment response within the 3 to 12 months of low-dose external beam radiation therapy (LD-EBRT) for coxarthrosis and GTPS along with potential predictive factors.

Methods and materials: We evaluated data from patients who were treated with radiation therapy for GTPS or coxarthrosis at our radiation centers between 2014 and 2024. In addition, all planning computed tomography scans were analyzed according to the Kellgren-Lawrence score. Subsequent univariate and multivariate analyses of the data were performed.

Results: The clinical response rate (overall response rate [ORR]) was approximately 64% in GTPS and 58% in coxarthrosis. Approximately 20% of the patients received a second series of LD-EBRT, and approximately 5% a third. In multivariate regression analyses of coxarthrosis, factors negatively correlated with ORR were an initial increase in pain, age ≥ 70 years, and body mass index (BMI) ≥ 25 kg/m². The outcome was independent of symptom duration, LD-EBRT season, and planning target volume. In GTPS, symptom duration >12 months, initial pain increase, and prior hip prosthesis were negatively correlated with ORR. No dependence on the LD-EBRT season or on the definition of the planning target volume was observed.

Conclusions: LD-EBRT may be an effective treatment option for GTPS and coxarthrosis. Early application of this therapy option appears to alleviate symptoms, regardless of season or planning target volume.

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly used for oligometastatic prostate cancer, although most published series include mixed histologies and only a few patients achieve long-term disease-free survival. This retrospective study presents one of the largest prostate-only cohorts, aiming to identify who benefits most from SBRT.

Methods and materials: From 2011 to 2023, 234 patients with ≤3 hormone-sensitive metachronous prostate cancer oligometastases were treated with SBRT at the Royal Marsden Hospital, London, and Sutton, UK. Concurrent androgen deprivation therapy (ADT) was allowed by clinician discretion. Treatment and outcome data were collected to assess the association between covariates and radiological progression-free survival (rPFS), ADT-free survival, and prostate cancer-specific survival (PCSS).

Results: In total, 308 lesions were treated in 234 patients. After a median follow-up of 56.5 months, median rPFS was 22 months and ADT-free survival was 42 months. The 5-year rPFS, ADT-free survival, and PCSS were 22.9%, 42.3%, and 96.4%, respectively. Concurrent ADT was used in 140 patients (59.8%). Prostate-specific antigen doubling time ≤ 3 months was a significant predictor for shorter rPFS [hazard ratio (95% CI) 1.52 (1.07-2.16), P = .001], and concurrent ADT use improved rPFS [0.52 (0.37-0.73), P < .001]. Nodal disease at primary presentation [2.08 (1.10-3.92), P = .023] and greater than 1 oligometastases [1.88 (1.25-2.82), P = .002] were inversely associated with ADT-free survival. Concurrent ADT use [0.40 (0.27-0.58), P < .001] improved ADT-free survival. Concurrent ADT use with SBRT did not improve eugonadal rPFS and eugonadal ADT-free survival. Patients diagnosed with oligometastases using baseline prostate-specific membrane antigen positron emission tomography/computed tomography had longer median ADT-free survival than those diagnosed with "other" imaging methods (52 vs 32 months, P = .041). For PCSS, more than 1 oligometastasis [6.08 (1.20-30.78), P = .029] and nodal disease at primary presentation [6.48 (1.16-36.15), P = .033] were associated with worse survival [5.95 (1.02-34.9), P = .048].

Conclusions: We present one of the largest SBRT case series specific to hormone-sensitive metachronous oligometastatic prostate cancer. After 5 years, 22.9% remained radiologically recurrence free and 42.3% remained ADT-free.

Purpose: Immunotherapy for relapsed/refractory (R/R) osteosarcoma has shown limited success because of its immunosuppressive microenvironment. Recent evidence suggests stereotactic body radiation therapy (SBRT) as not only a local therapy but also a modality with an immunomodulatory role. However, combining SBRT with immune checkpoint inhibitors (ICIs) is yet to be explored in osteosarcoma.

Methods and materials: We retrospectively reviewed patients with R/R osteosarcoma (n = 62) receiving ICIs with concurrent SBRT radiation therapy (ICI+SBRT, n = 18), conventional radiation therapy (CRT) (ICI+CRT, n = 23), or without radiation therapy (ICI-only, n = 21) as a late-line therapy in our institution from January 2020 to March 2024. The therapeutic efficacy, toxicity, and potential abscopal effect were explored by measuring the radiological response of radiated and nonradiated lesions. Peripheral blood flow cytometry and immune intratumoral lymphocyte infiltration were investigated for the correlative biomarker of therapeutic efficacy.

Results: Although the local control did not differ significantly between 2 radiation therapy modalities, patients receiving ICI+SBRT demonstrated significantly better systemic tumor response compared with ICI-only or ICI+CRT, with a median progression-free survival of 5.68 months and a median overall survival (OS) of 12.0 months. Interestingly, nonradiated lesions showed a significantly better response in the ICI+SBRT group than that of the CRT, suggesting a potential abscopal effect. In 8 patients receiving second or more course of SBRT because of disease oligoprogression, we observed a continued clinical benefit of ICIs beyond tumor progression. Common grade 3-4 toxicity of ICI+SBRT included pneumonitis (n = 4, 22.2%), bronchopleural fistula (n = 1, 5.6%), and lymphopenia (n = 1, 5.6%). Flow cytometry analysis suggested that higher baseline CD3 lymphocytes and lower neutrophil-to-lymphocyte ratio were associated with better abscopal effect in patients with ICI+SBRT. Furthermore, higher intratumoral immune infiltration of CD8 lymphocyte and PD-L1 expression were seen in post-SBRT tumor specimens than the pre-SBRT counterpart.

Conclusions: SBRT emerges as an attractive combination strategy to augment the efficacy of ICI-based immunotherapy in R/R osteosarcoma.

Purpose: Malnutrition is common among patients with nasopharyngeal carcinoma (NPC) undergoing radiation therapy and is associated with diminished quality of life (QoL). However, the impact of individualized nutritional interventions (NIs) on QoL improvement in this population remains unclear. This study aimed to evaluate the effectiveness of NIs patients with NPC, guided by dynamic nutritional risk screening, in improving QoL and reducing malnutrition during radiation therapy.

Methods and materials: Patients with histologically confirmed NPC scheduled for intensity modulated radiation therapy (total dose 69.96 Gy in 33 fractions) underwent 1:1 randomization into the NIs or standard of care (SoC) groups. Patients in the NIs group received personalized nutritional support based on weekly assessments using the Patient-Generated Subjective Global Assessment (PG-SGA), whereas those in the SoC group received routine dietary care. NIs commenced during the preradiation therapy clinical assessment and were maintained until radiation therapy completion. The primary endpoint was global health status score at the end of radiation therapy. Secondary outcomes included the Nutritional Risk Screening 2002, PG-SGA scores, and changes in weight and body mass index (BMI).

Results: Of the 268 patients randomized, 249 were included in the final analysis (124 in the NIs and 125 in the SoC). Both cohorts demonstrated male predominance (NIs: 75.8%; SoC: 73.6%) with identical median ages of 52 years. At the end of radiation therapy, the NIs group demonstrated a significantly higher mean global health status score than the SoC group (mean difference [MD]: 21.0 points; 95% CI: 17.4-24.7; P < .001). The NIs group showed significantly less weight loss (MD: 1.5 kg; 95% CI: 0.6-2.3; P = .001) and lower BMI decline (MD: 0.6 kg/m²). Clinically relevant weight loss (≥5%) occurred in 50% and 68% patients in the NIs and SoC groups, respectively. The difference in PG-SGA scores was 3.1 (P < .001). Generalized estimating equation longitudinal analysis confirmed a significantly more gradual decline in weight, BMI, and PG-SGA scores with NIs than SoC.

Conclusions: Individualized NIs significantly improve QoL and nutritional status in patients with NPC undergoing radiation therapy, underscoring the importance of ongoing assessment-guided individualized nutritional support.

Purpose: This study evaluated the feasibility of a direct-to-unit stereotactic magnetic resonance imaging-guided adaptive radiation therapy (SMART) workflow for spine metastases.

Methods and materials: Ten patients with spinal metastases were prospectively enrolled. Preplans were created using diagnostic imaging, with patients proceeding directly to magnetic resonance imaging-guided adaptive treatment using online adaptation and bulk density override for dose calculation. Feasibility was defined as successful completion of the first fraction on the initial on-table attempt in ≥70% of patients. Toxicity, dosimetric outcomes, and clinical response were assessed.

Results: Delivery of first fraction on first attempt was successful 90% of the time. Of 36 total fractions, 10 required online adaptation. The median treatment time per fraction was 87 minutes. Acute toxicity was limited to grade 1 to 2 fatigue. At a median follow-up of 14 months, local control was 90% at 3 months and 67% at 6 months.

Conclusions: Direct-to-unit SMART is a feasible and safe approach for spine stereotactic body radiation therapy, allowing treatment without conventional simulation.

Purpose: Although moderately hypofractionated external beamradiation therapy (H-EBRT) has been practiced for locally advanced cervical carcinoma, prospective evidence remains limited. We evaluated the role of H-EBRT in the definitive management of locally advanced cervical carcinoma in terms of toxicities and clinical outcomes.

Methods and materials: In this prospective phase 2 trial (December 2018-December 2021), 50 patients with histologically confirmed squamous cell carcinoma of the cervix were enrolled. Patients received H-EBRT of 40 Gy in 16 fractions over 3.1 weeks with a sequential boost of 10 Gy in 4 fractions to pelvic lymph nodes, and concurrent weekly cisplatin 40 mg/m². This was followed by brachytherapy of 28 Gy in 4 fractions delivered over 2 to 4 applications. Acute and late toxicities were recorded per National Cancer Institute Common Terminology Criteria for Adverse Events (v4.0). Locoregional recurrence-free survival, disease-free survival, and overall survival were estimated by the Kaplan-Meier method.

Results: Median patient age was 50 years. According to FIGO (International Federation of Gynecology and Obstetrics) 2018 staging, stages IB3, II, IIIA, IIIB, and IIIC1 were present in 5 (10%), 24 (48%), 2 (4%), 10 (20%), and 9 (18%) patients, respectively. The median number of concurrent chemotherapy cycles was 4. Median overall treatment time was 7.1 weeks (range, 5.4-11.6 weeks). Acute ≥grade 2 and ≥grade 3 gastrointestinal (GI), genitourinary, anemia, leucopenia, and thrombocytopenia occurred in 20 (40%) and 10 (20%), 5 (10%) and 3 (6%), 10 (20%) and 3 (6%), 15 (30%) and 4 (8%), and 6 (12%) and 3 (6%) patients, respectively. The median follow-up was 60.8 months (range, 14.7-79.8 months). Late grade 2 and grade 3 GI toxicities were seen in 4 (8%) and 5 (10%) patients, respectively. Late grade 2 and grade 3 genitourinary toxicities occurred in 2(4%) and 1 (2%) patients, respectively. The 5-year locoregional recurrence-free survival, disease-free survival, and overall survival were 85%, 80%, and 77.8%, respectively.

Conclusions: H-EBRT followed by brachytherapy yields acceptable long-term clinical outcomes and late toxicities, albeit with slightly higher acute GI toxicity.