International Journal of Radiation Oncology Biology Physics最新文献

Introduction: Total neoadjuvant therapy (TNT) is a promising strategy to improve tumor response and oncological outcomes in locally advanced rectal cancer (LARC) patients, particularly in those with high-risk tumor characteristics. Although triplet chemotherapy (i.e., FOLFOXIRI) is currently used exclusively for metastatic disease, it may offer benefits in the curative treatment of high-risk LARC by enhancing tumor response and reducing the risk of distant metastases. However, its broader use is limited by concerns regarding toxicity. The XXX trial evaluated an intensified TNT regimen in high-risk LARC.

Methods: This was a national, multicenter, phase II trial to evaluate neoadjuvant FOLFOXIRI followed by chemoradiotherapy in high-risk LARC patients, enrolled between November 2021 until October 2024. The primary outcome was complete response rate. This manuscript focuses on secondary outcomes, including treatment completion rate, dose reductions, and short-term toxicity (≥ grade 3 serious adverse events (SAE) and adverse events (AE)). Associations with toxicity were analyzed using binary logistic regression.

Results: Of 128 enrolled patients, 124 were eligible for evaluation and monitored until three months after completion of TNT. Dose reductions were required in 67 patients (54%), most often for oxaliplatin (n = 59; 47.6%). A total of 116 patients (93.5%) completed at least four cycles of FOLFOXIRI and chemoradiotherapy, and 102 patients (82.3%) completed all six cycles and chemoradiotherapy. No patients were unable to start with chemoradiotherapy due to chemotherapy-related toxicity. SAEs and AEs (≥ grade 3/hematologic ≥ grade 4) occurred in 46 patients (37.1%), of whom 31 (25.0%) had SAEs. Diarrhea and nausea were reported most frequently, representing 26.9% (n = 18) and 17.9% (n = 12) of all reported events, respectively.

Conclusion: Patients treated with neoadjuvant FOLFOXIRI and chemoradiotherapy had manageable toxicity levels and high treatment completion rates, supporting its feasibility in well-selected high-risk LARC patients. Randomized trials are warranted to compare efficacy and toxicity of triplet versus other TNT regimens.

Purpose: We previously developed a model of pre-treatment growth and on-treatment response dynamics, the proliferation saturation index (PSI) model, which derives the proliferating and radiosensitive proportion of a tumor based on clinically observed net growth prior to therapy. We hypothesized that personalization of fractionation using PSI would increase the percentage of patients achieving a rapid reduction in tumor size during radiotherapy (RT) for early-stage human papillomavirus related squamous cancers of the oropharynx.

Patients and methods: In this single center nonrandomized phase 2 single arm trial, 113 patients underwent screening, and 57 patients were consented and enrolled. Pretreatment PSI was calculated, and patients were assigned to 60 - 70 Gy in 30 - 35 fractions given once daily (PSI≤ 0.75) or 60 - 69.6 Gy in in 50 - 58 fractions given twice daily (PSI>0.75). The primary endpoint of the study was the rate of patients with ≥ 32% reduction in tumor volume at 4 weeks of RT, with a planned sample size of 60 patients, with an interim analysis after 49 patients. Secondary end points included locoregional failure (LRF), progression free survival (PFS), and overall survival (OS).

Results: A total of 55 patients evaluable for the primary endpoint were consented and enrolled, and 32 (58%; 95% CI = 44%-71%) met the primary endpoint of ≥ 32% reduction at 4 weeks of RT, meeting criteria for efficacy, leading to early study closure. For the 54 patients evaluable for secondary endpoints, the cumulative incidence of LRF at 2 years was 2% (95% CI: 0-5.8), with a 2-year PFS of 92% (95% CI: 85-100), and a 2 year OS of 96% (95% CI: 91-100).

Conclusions: Personalized RT fractionation based on PSI suggests a promising rate of mid-treatment response with favorable LF, PFS, and OS.

Trial registration: ClinicalTrials.gov Identifier: NCTXXXX.

Background: Although immunotherapy-chemotherapy represents the latest first-line standard for unresectable biliary tract cancer (BTC), the survival outcome remains unsatisfactory. Radiotherapy exerts synergistic effects with immunotherapy and chemotherapy, generating potential survival benefit for BTC patients.

Method: This retrospective analysis evaluated 497 participants with histopathologically confirmed unresectable BTC treated at two tertiary medical centers between January 2020 and August 2024. Participants were stratified into two treatment groups: radiotherapy combined with immuno-chemotherapy (RT+IO+CT) versus immuno-chemotherapy alone (IO+CT). Propensity score matching (PSM) was implemented to control for baseline covariates. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), and treatment-emergent adverse events (TEAEs).

Result: Following 1:1 PSM, the analytical cohort comprised 210 patients: 105 undergoing RT+IO+CT and 105 receiving IO+CT alone. At a median follow-up of 23.0 months, the RT+IO+CT cohort demonstrated significantly superior OS (15.0 vs 9.0 months; HR=0.58, P=0.0014) and PFS (10.0 vs 5.0 months; HR=0.56, P<0.001) versus the IO+CT group. Multivariate analysis identified non-intrahepatic metastasis, tumor size<5cm, baseline CA19-9 level<74 U/mL, first treatmentline and RT+IO+CT treatment as independent predictors of prolonged OS. No significant difference between groups was observed in grade ≥3 TEAEs incidence (58.1% vs 55.2%; P=0.676). In the intrahepatic cholangiocarcinoma (ICC) subgroup (n=155), radiotherapy integration significantly improved both OS (HR=0.56, P=0.0025) and PFS (HR=0.54, P<0.001). Sequential radiotherapy demonstrated superior OS compared to IO + CT, whereas concurrent radiotherapy did not show a similar benefit.

Conclusion: The integration of radiotherapy with immunotherapy-chemotherapy significantly enhances survival outcomes in unresectable BTC without increasing severe toxicities, particularly demonstrating pronounced benefit in ICC. However, its efficacy and generalizability require confirmation through randomized controlled trials.

Purpose: Ion-beam radiotherapy offers steep dose gradients and high biological effectiveness required for the treatment of complex cancer cases. While the vast majority of ion-beam therapy centers today use protons and carbon ions, there is renewed interest in helium ions for their unique physical and radiobiological properties. All ion-beam treatments suffer from beam-range uncertainties mainly caused by potential changes of the patient morphology. In-vivo treatment monitoring with secondary ions could potentially provide feedback about the treatment quality that would allow a dose reduction in the healthy tissue or an escalation of the tumor dose.

Methods and materials: This work presents the first in-vivo monitoring of a helium-ion therapy patient treated for a solitary fibrous tumor. The method is based on the tracking of secondary ions that leave the patient as a natural by-product of ion-beam radiotherapy.

Results: The comparison of two measured secondary-ion distributions confirmed a high treatment reproducibility for the reported patient. However, significant differences between the two fractions were detected at the border of the skull base and the sinus sphenoidalis that could originate from potential inter-fractional cavity filling.

Conclusions: The world's first in-vivo monitoring of innovative helium-ion therapy was performed successfully. In the future, the observed signals will need to be validated with patients that receive regular control CTs. Moreover, Monte Carlo simulations and phantom measurements will help to establish a robust link between changes in the secondary-ion distribution and clinically relevant dose changes.

Purpose: While fractionated stereotactic radiotherapy (FSRT) remains understudied for the management of breast cancer brain metastases(BCBM), this study aimed to investigate its therapeutic efficacy and safety in the context of contemporary systemic therapies. We enrolled patients with 1-10 brain lesions.

Methods and materials: This was a prospective, single-arm, phase II trial involving 173 breast cancer patients with 436 brain metastases, all treated with FSRT at a dose of 3-5 fractions of 8 Gy each. The primary endpoint was the local control rate, and secondary endpoints included the intracranial distant control rate, overall survival (OS) and central nervous system progression-free survival (CNS-PFS).

Results: With a median follow-up of 15 months, the 1-year local control rate was 88.6% and the 1-year intracranial distant control rate was 52.1% (95% CI: 44.7-60.8%). The median OS was 29 months (95% CI: 21-35 months), and the median CNS-PFS for patients with evaluable lesions was 12 months (95% CI: 9-16 months). Of the treated lesions, 27 out of 436 (6.2%) experienced radiation necrosis, no grade 3 or 4 FSRT-related adverse events were observed. Local control rates exceeded 86% at 1 year across all subtypes whereas the DMFS lower ranging from 39.7%-57.9%.

Conclusions: In this single-institution trial, FSRT at a dose of three to five 8 Gy fractions for breast cancer brain metastases yielded high local control with low rates of radiation necrosis in the background of modern systemic treatment.

Although radiation therapy quality assurance (RTQA) is important in any clinical trial with a radiation therapy (RT) component, it is paramount in lymphoma trials for several reasons. As lymphoma RT has evolved to use smaller and more complex treatment fields such as involved-site radiation therapy (ISRT) and positron emission tomography (PET)-directed residual-site radiation therapy (pRSRT), accurate target delineation has become more challenging, especially when lymphoma patients comprise only a small proportion of most radiation oncologists' clinical practice. Furthermore, lymphoma is often a highly curable malignancy in young patients, augmenting the detrimental impact of suboptimal RT. The Children's Oncology Group trial AHOD2131 of frontline therapy for Hodgkin lymphoma incorporates real-time central review of PET scans, target volumes, and RT plans. Early experience shows that this rigorous approach identifies protocol deviations and enables timely corrections before treatment begins. Common errors include omitting initially involved disease sites, potentially due to inaccurate fusion of the PET and computed tomography with the simulation computed tomography, and over-generous contouring of target volumes. The AHOD2131 central review methodology may serve as a blueprint for RTQA in future lymphoma trials, improving treatment accuracy and patient outcomes.

Purpose: Brain radiation therapy (RT) combined with immunotherapy is standard for patients with non-small cell lung cancer (NSCLC) with brain metastases. However, RT-induced hematologic toxicities (HTs) can cause treatment interruption and lymphopenia, potentially impairing immunotherapy efficacy. Because the skull bone marrow has recently been identified as a key hematopoietic site, this study evaluated the impact of skull RT dose on HTs in patients with NSCLC undergoing cranial RT and immunotherapy.

Methods and materials: This retrospective study consecutively included 191 patients with NSCLC with brain metastases treated between June 2018 and April 2023. Stereotactic RT or whole-brain RT was selected based on lesion characteristics. All doses were converted to equivalent 2-Gy fractions (EQD2). HTs were graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. Skull dosimetric parameters (Dmean_EQD2, V5_EQD2 - V50_EQD2) were analyzed for associations with grade ≥ 3 HTs (HT3+) using logistic regression. Normal tissue complication probability models and optimal cutoff thresholds were derived using logistic and receiver operating characteristic analyses. Based on these cutoffs, post-RT absolute lymphocyte count (ALC) and immunotherapy response rates were assessed in stratified groups.

Results: HT3+ occurred in 18.8% (36/191) of patients, with neutropenia (18.9%), leukopenia (15.2%), and lymphopenia (15.7%) being most frequent. Multivariate analysis, adjusting for age and other covariates, revealed significant associations between HT3+ and Dmean_EQD2 as well as V5_EQD2 -V20_EQD2 (all P < .05). The normal tissue complication probability models predicted a 50% probability of HT3+ at the following thresholds: Dmean_EQD2 = 41.3 Gy, V5_EQD2 = 94.6%, V10_EQD2 = 86.0%, and V20_EQD2 = 77.0%. Receiver operating characteristic analysis identified optimal HT3+ cutoffs of Dmean_EQD2≥ 32.2 Gy, V5_EQD2≥ 82.0%, V10_EQD2≥ 64.7%, and V20_EQD2≥ 53.4%. Patients above these thresholds had over twice the HT3+ risk, significantly lower post-RT ALC, and reduced immunotherapy response rates (all P < .05), with higher post-RT ALC predicted better response.

Conclusions: Higher skull radiation doses significantly increase severe HTs in patients with NSCLC receiving cranial RT and immunotherapy. Incorporating skull dose constraints may mitigate HTs, preserve lymphocytes, and enhance immunotherapy efficacy, warranting validation in prospective studies.

Purpose: Sequential transarterial chemoembolization (TACE), stereotactic body radiation therapy (SBRT), and immunotherapy (START-FIT) has shown its promising potential as a downstaging therapy of unresectable hepatocellular carcinoma (HCC). This study aims to analyze the dynamic changes in liver volume and hepatic function following START-FIT.

Methods and materials: Thirty-three prospectively recruited patients with unresectable HCC received a single dose of TACE followed by SBRT at day 28, and immunotherapy every 2 weeks thereafter. Dynamic contrast magnetic resonance imaging and hepatic function were evaluated at baseline and 3-monthly intervals until disease progression, death, or end of the study. Future liver remnant (FLR), liver parenchymal, and tumor volumetric changes were assessed over time dynamically.

Results: Right lobe atrophy (P < .001), tumor shrinkage (P < .001), and left lobe hypertrophy (P < .001) were observed from 3 months, which continued throughout the study period. The maximal median %FLR hypertrophy is 27.8% and the fastest rate of percentage FLR hypertrophy occurred within first 3 months and plateaued at around 12 months, whereas the maximal tumor volume shrinkage was observed at 6 months and there was more than a triple decrease in median tumor volume as compared to baseline (78 mL; interquartile range [IQR], 43-309 mL vs 302 mL; IQR, 147-703 mL; P < .001). There was a trend suggesting a decrease in right portal vein size, and large planning target volumes were associated with FLR >30%. Child-Pugh score progression +2 was noted in 12%, 14%, 6%, and 4.3% at 3 months, 6 months, 12 months, and 24 months, respectively. There was no significant change in Child-Pugh score and albumin-bilirubin score at different time points.

Conclusions: START-FIT can induce FLR hypertrophy while shrinking the primary tumor. Adding TACE and immunotherapy to SBRT did not hamper the process of FLR hypertrophy and liver function recovery. It has the potential to become a novel bridge-to-resection technique in patients with unresectable HCC.

Purpose: To report the prevalence, validity, and relative prognostic value of specific UICC (Union for International Cancer Control)/AJCC (American Joint Committee on Cancer) T4-defining radiologic features in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC).

Methods and materials: We retrospectively reviewed pretreatment computed tomography/magnetic resonance imaging scans of all T4 HPV+ OPSCC patients treated with definitive (chemo)radiation therapy in 2010 to 2021. Nine T4-defining features were assessed: involvement of genioglossus, hyoglossus, palatoglossus, styloglossus, pterygoid muscles (medial and lateral), bone (mandible, hard palate, pterygoid plates, skull base), larynx, nasopharynx, and carotid artery. The prognostic validity of each T4-defining feature was evaluated by comparing the risk of disease progression with that of T3 disease using univariable analysis. Multivariable analysis, stratified by treatment and adjusted for gross tumor volume of the primary lesion (GTVp), estimated the adjusted hazard ratio (aHR) for risk of disease progression associated with each of the 9 features within T4 disease.

Results: A total of 522 cases were included (T4 [239], T3 [283]). The frequencies of individual T4-defining features were as follows: hyoglossus (71%), palatoglossus (71%), styloglossus (68%), genioglossus (38%), carotid encasement (23%), pterygoid muscle (14%), larynx (12%), nasopharynx (8%), and bone (4%). All 9 T4-defining features were associated with higher risk of cancer progression versus T3 (all P < .01). Among T4 cases, invasion of nasopharynx (aHR, 2.42; 95% CI, 1.20-4.90; P = .014) and genioglossus (aHR, 1.99; 95% CI, 1.26-3.14; P = .003) conferred greater risk of disease progression versus other T4-defining features.

Conclusions: All radiologic UICC/AJCC T4-defining features have worse outcomes compared to T3 disease, supporting their retention within the T4 category. Among T4 cases, worse outcomes were observed in cases with deep tongue muscle invasion (genioglossus) and nasopharyngeal extension.

Purpose: Palliative 3D-conformal radiotherapy (3DCRT) is the standard treatment for metastatic epidural spinal cord compression (MESCC) in non-surgical candidates, but pain, motor and neurologic outcomes are variable. We conducted a pilot study to determine feasibility of stereotactic body radiotherapy (SBRT) boost following 3D-CRT and characterize impact on outcomes.

Methods: Eligible patients included those with a solid malignancy, evidence of at least Bilsky 1b MESCC, and Rades motor scale function of at least 3. Patients were initially treated with 3DCRT (either 20 Gy/5 or 8 Gy/1) followed by SBRT boost within 6 weeks to a dose of 18-24 Gy/2 . The primary outcome was feasibility of planning and delivery of 3D CRT and SBRT boost, with a success rate defined as 80% of accrued patients (95% confidence interval 75-97%).

Results: Sixteen patients were initially accrued from 2018-2022. Thirteen patients were treated successfully with SBRT boost following 3DCRT, meeting the primary outcome (0.81, 0.57-0.93). Motor function was maintained in 76.9% and improved by 2 points from baseline in 15.4% of patients at 1-month post-SBRT . Ambulatory function improved at 1, 3, and 6 months post SBRT in 15.4%, 18.2% and 12.5% of patients respectively. Pain improved in 7.7%, 18.2% and 37.5% of patients at 1, 3 and 6 months. Only 1 Grade 3 toxicity (chest wall pain) occurred, which resolved at 3 months. Median global QoL using EORTC QLQ c-30 improved from baseline of 69.2, to 76.3, 76.6 and 82.5 at 1, 3 and 6 months respectively. EORTC BM 22 scores improved in functional and pain domains at 1, 3 and 6 months.

Discussion: SBRT boost following 3DCRT for MESCC was feasible, with no added neurological toxicity, and resulted in moderate improvements from baseline or prolonged maintenance of motor, ambulatory function, and pain control, with suggestion of improved QoL over time.