International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Invasive lobular carcinoma (ILC) represents 10% to 15% of invasive breast cancers with limited representation among trials of accelerated partial breast irradiation (APBI). Contemporary guidelines advise against treating ILC with APBI given a paucity of supportive evidence. Here, we evaluated oncologic outcomes among patients with ILC treated with APBI.

Methods and materials: Patients treated from 2010 to 2022 with APBI after breast conserving surgery for ILC (or mixed ILC with other histologies) were ascertained from a prospectively maintained institutional database. All patients received external beam APBI to 40 Gy in 10 daily fractions. Outcomes of interest included local recurrence (LR) and overall survival (OS).

Results: Of 1248 patients who underwent APBI at our center, the study cohort comprised 132 (11%) who had ILC, either exclusively or mixed with another histology (median age 63). Median tumor size was 1.1 cm (interquartile range: 0.8-1.5), nearly all had estrogen receptor positive disease (99%) and received hormone therapy (91%), and most underwent sentinel node biopsy (89%) with the remainder having no axillary surgery. At 530 person-years and a median follow-up of 39 months, 2 LRs were observed yielding a 48-month cumulative incidence of LR of 3.0% (95% CI: 0.56%-9.5%). Both events arose in patients with mixed lobular histology (none arose in patients with pure ILC). Two unrelated deaths were also observed yielding a 48-month OS of 98% (95% CI: 95%-100%).

Conclusion: Among patients with ILC who received APBI after breast conserving surgery, we observed a 4-year LR rate of 3%. No regional or distant recurrences were observed, and OS was excellent. The safety of APBI for ILC will require confirmation among larger trials with longer follow-up, although the excellent outcomes observed here are consistent with those seen for invasive ductal carcinomas among contemporary trials of APBI.

Purpose: We propose a tumor tracking framework for 2D cine magnetic resonance imaging (MRI) based on a pair of deep learning (DL) models relying on patient-specific (PS) training.

Methods and materials: The chosen DL models are: (1) an image registration transformer and (2) an auto-segmentation convolutional neural network (CNN). We collected over 1,400,000 cine MRI frames from 219 patients treated on a 0.35 T MRI-linac plus 7500 frames from additional 35 patients that were manually labeled and subdivided into fine-tuning, validation, and testing sets. The transformer was first trained on the unlabeled data (without segmentations). We then continued training (with segmentations) either on the fine-tuning set or for PS models based on 8 randomly selected frames from the first 5 seconds of each patient's cine MRI. The PS auto-segmentation CNN was trained from scratch with the same 8 frames for each patient, without pre-training. Furthermore, we implemented B-spline image registration as a conventional model, as well as different baselines. Output segmentations of all models were compared on the testing set using the Dice similarity coefficient, the 50% and 95% Hausdorff distance (HD_50%/HD_95%), and the root-mean-square-error of the target centroid in superior-inferior direction.

Results: The PS transformer and CNN significantly outperformed all other models, achieving a median (interquartile range) dice similarity coefficient of 0.92 (0.03)/0.90 (0.04), HD_50% of 1.0 (0.1)/1.0 (0.4) mm, HD_95% of 3.1 (1.9)/3.8 (2.0) mm, and root-mean-square-error of the target centroid in superior-inferior direction of 0.7 (0.4)/0.9 (1.0) mm on the testing set. Their inference time was about 36/8 ms per frame and PS fine-tuning required 3 min for labeling and 8/4 min for training. The transformer was better than the CNN in 9/12 patients, the CNN better in 1/12 patients, and the 2 PS models achieved the same performance on the remaining 2/12 testing patients.

Conclusions: For targets in the thorax, abdomen, and pelvis, we found 2 PS DL models to provide accurate real-time target localization during MRI-guided radiotherapy.

Patients with gynecologic, gastrointestinal, or genitourinary malignancy are at elevated risk of developing premature ovarian insufficiency from the multimodality therapies used to treat their cancers. Premature ovarian insufficiency can result in long-term decrements to all-cause mortality, bone density, cardiovascular health, sexual health, cognitive health, and body mass. Hormone replacement therapy has been demonstrated to reverse these long-term sequalae with the goal of restoring estrogen concentrations to physiological levels. Here, we discuss a practical approach for initiation of hormone replacement therapy as well as challenges to consider.

Purpose: Definitive radiation therapy (RT) of 30 Gy or higher is commonly recommended to treat Helicobacter pylori-independent gastric mucosa-associated lymphoid tissue (MALT) lymphoma with an excellent disease control rate. However, the efficacy of reduced-dose RT has not yet been evaluated in a prospective cohort study. This multi-institutional study aimed to determine the role of reduced-dose RT in the treatment of stage IE gastric MALT lymphoma.

Methods and materials: Between March 2017 and June 2022, 62 patients with histologically confirmed stage IE gastric MALT lymphoma without evidence of H pylori infection were enrolled. The patients were treated with reduced-dose RT at a total dose of 24 to 25.5 Gy to the entire stomach. The response to therapy was evaluated by endoscopy with a biopsy of suspicious lesions if necessary. The primary endpoints were 6-month complete remission (CR) and local failure-free survival.

Results: Among 62 patients, 32 (51.6%) were previously treated for H pylori eradication. Radiation therapy was delivered using 3D-conformal (n = 20, 32.3%) or intensity modulated radiation therapy (n = 42, 67.7%). The median follow-up duration was 34.5 months (range, 9.6-68.8 months). The 6-month CR rate was 96.7%. The 5-year local failure-free survival and progression-free survival rates were 92.0% and 90.4%, respectively. None of the patients experienced grade 3 or worse acute toxicities, and grade 2 acute toxicities were reported in 17 patients (27.4%).

Conclusions: Reduced-dose RT exhibited excellent response rates in stage IE gastric MALT lymphoma, comparable to historical controls of standard-dose (≥30 Gy) radiation therapy, with a minimal toxicity profile. Current prospective evidence strongly supports the use of definitive radiation therapy (24-25.5 Gy) for the treatment of H pylori-independent stage IE gastric MALT lymphoma.

Purpose: To investigate the efficacy of metastasis-directed therapy (MDT) when added to camrelizumab (Cam) in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC).

Methods and materials: We conducted a randomized, controlled, multicenter, phase 2 trial in 3 centers from China (NCT04830267). Patients with R/M-NPC, without prior exposure to immunotherapy, who presented with ≥2 lesions, and at least 1 measurable lesion were randomized 1:1 to either Cam alone or Cam plus MDT (Cam+MDT). Patients randomized to the MDT group must have 1 lesion that is amendable to stereotactic body radiation therapy (SBRT) prescribed to 27 Gy in 3 fractions every other day. The primary endpoint was objective response rate (ORR) of unirradiated lesions using Response Evaluation Criteria in Solid Tumors v1.1.

Results: Between April 2021 and August 2023, 39 patients were randomly assigned to receive either Cam (n = 20) or Cam+MDT (n = 19). In total, 17 out of 39 (43.6%) patients had oligometastatic disease (≤3 lesions), 18 out of 39 (46.2%) had liver involvement, and 3 out of 39 (7.7%) had locoregional recurrent disease. ORR of unirradiated lesions did not differ between the treatment groups (26.3% [Cam+MDT] vs 30.0% [Cam], P = 1.0). The disease control rate of unirradiated lesions was 73.7% in the Cam+MDT group compared with 60.0% in the Cam group (P = .571). After a median follow-up of 25.8 months, median progression-free survival was 9.3 (95% CI, 6.2-not reached [NR]) months in the Cam+MDT group and 8.8 (95% CI, 3.3-NR) months in the Cam group (P = .750). Exploratory analyses suggested a longer overall survival (OS) with Cam+MDT for patients with >3 lesions (HR, 0.23; 95% CI, 0.07-0.77; P = .009). G3 and above adverse events were comparable between the treatment groups (15.8% [Cam+MDT] vs 20.0% [Cam]). The overall rate of capillary proliferation was 17.9% (7/39) for the trial.

Conclusions: Our study did not meet its primary endpoint of superior ORR of unirradiated lesions with the addition of MDT to Cam in patients with R/M-NPC.

Background: Mentorship in the field of radiation oncology (RO) promotes career development and satisfaction. Many individuals, however, do not have access to mentorship or are unsatisfied with their mentorship experience, potentially due to insufficient gender-concordant mentorship opportunities. To address this, the Society for Women in Radiation Oncology (SWRO) created the SWRO Mentorship Program for women, gender minorities, and those with intersecting marginalized identities at all stages of training for physicians and medical physicists. We present the five-year experience of the largest multi-institutional mentorship program, to our knowledge, in RO.

Methods: Publicly available information and the SWRO mentorship sign-up form were used. Descriptive statistics and binomial tests compared to reference points were conducted.

Results: Between January 2018 and June 2023, 296 individuals from 19 countries participated in the mentorship program, generating 225 mentee-mentor pairs. The majority were female (89.2%), based in the United States (US; 84.8%), and on the physician-track (96.6%). The remainder of the analysis focused on US-based, physician-track participants (n = 244), the majority of whom were female (96.7%) and trainees (58.2%). Among those who have completed RO residency, most accepted a first job in academia (82.1%) and remained in academia at the time of the analysis (76.3%). A significantly higher proportion of SWRO mentorship participants compared to the reference point took a first job in academia (82.1% vs 58.3%; p<0.0001). The most common disease sites of focus for the physician-track trainees who finished residency are breast (50.4%), central nervous system (32.7%), and gynecologic malignancies (30.1%), with 54% listing more than one. The most common expressed goals of mentorship are research (35.8%), leadership (24.5%), and building connections within a specific geography or institution (19.2%).

Conclusions: The SWRO experience demonstrates the feasibility of a large-scale, multi-institutional mentorship program in RO.

Purpose: Fibrosis is a common late complication of radiation therapy. Molecular dysregulations leading to fibrosis have been characterized for the coding part of the genome, notably those involving the TGFB1 gene network. However, because a large part of the human genome encodes RNA transcripts that are not translated into proteins, exploring the involvement of the noncoding part of the genome in fibrosis susceptibility and development was the aim of this work.

Methods and materials: Breast cancer patients having or not having developed severe breast fibrosis after radiation therapy were retrospectively selected from the COPERNIC collection. Exome sequencing and RNA-seq transcriptomic profiling were performed on 19 primary dermal fibroblast strains isolated from the patients' nonirradiated skin. Functional experiments were based on fibrogenic induction by transforming growth factor-Beta1 (TGFB1) and gene knockdown in healthy donor fibroblasts.

Results: Coding and noncoding transcriptomes discriminated fibrosis from nonfibrosis conditions, and a signature of breast fibrosis susceptibility comprising 15 long noncoding RNAs (lncRNAs) was identified. A hazard ratio validation showed that the lncRNA vimentin antisense long noncoding RNA 1 (VIM-AS1) was the best biomarker associated with fibrosis risk. This lncRNA has not been previously associated with any fibrotic disorder, but we found it upregulated in data sets from cardiac fibrosis and scleroderma, suggesting a general role in tissue fibrosis. Functional experiments demonstrated a profibrotic action of VIM-AS1 because its knockdown reduced myofibroblast activation, collagen matrix production, and dermal organoid contraction. RNA-seq data analysis after VIM-AS1 silencing also pointed out the regulation of replication, cell cycle, and DNA repair. Mechanistically, because VIM-AS1 was found coregulated with the vimentin gene, these data support a profibrotic function of the TGFB1/VIM-AS1/vimentin axis, targeting the dynamics of fibroblast-myofibroblast transition.

Conclusions: Noncoding RNA analysis can provide specific biomarkers relevant to the prediction of normal tissue responses after radiation therapy, which opens perspectives of next-generation approaches for treatment, in the frame of the recent developments of RNA-based technologies.

Purpose: The purpose of this study was to assess the prognostic significance of the modified diagnostic biopsy-adapted immunoscore (mIS_b) in determining the outcomes for patients with locally advanced rectal cancer (LARC) in a neoadjuvant setting.

Methods and materials: We included 181 patients with LARC from a single subcenter of a prospective study comparing total neoadjuvant therapy (TNT) based on short-course radiation therapy with long-term chemoradiation therapy (CRT). Tumor biopsies at baseline were stained for CD8+ and CD3+ T-cell densities. The mIS_b was developed using mean percentile of CD8+ T-cell density and CD8/CD3 ratio. Patients were classified into low (0%-25%), intermediate (>25%-70%), and high (>70%-100%) in both groups. The relativity among different lymphocytes and their correlation with survival were illustrated. Survival analyses and Cox regression models were used to compare the prognostic values of mIS_b and diagnostic biopsy immunoscore for survival outcomes and to assess the role of mIS_b in TNT and CRT subgroups, respectively.

Results: In this study, 151 (83.4%) patients received surgery, and 30 (16.6%) followed a watch and wait strategy. A strong correlation was found between CD8+ and CD3+ T-cell densities (R = 0.86; P < .001), whereas a weak correlation was witnessed between CD8+ and CD8/CD3 ratio (R = 0.45). The 3-year disease-free survival for the entire cohort was 69.9%, with 57.2%, 68.6%, and 85.5% for the low, intermediate, and high mIS_b groups, respectively (P = .01), whereas diagnostic biopsy immunoscore failed to distinguish survival outcomes. Multivariate analysis revealed mIS_b to be an independent prognostic factor for disease-free survival in surgically treated patients (P = .01). Specifically, patients with high mIS_b score showed longer progression-free survival than other subgroups in the TNT cohort (P = .049), but no significant difference was found in the CRT population.

Conclusions: In this study, mIS_b demonstrated significant prognostic value in patients with LARC receiving preoperative therapies, especially in the TNT subgroup. These findings may help tailor the intensity of neoadjuvant therapy for patients.

Purpose: This study aimed to evaluate whether photoacoustic (PA), sound touch elastography (STE), and viscoelasticity (VE) can distinguish between normal and abnormal postradiation therapy breast skin and compare these methods with Radiation Therapy Oncology Group (RTOG) criteria at a 20 Gy threshold.

Methods and materials: Patients who met inclusion and exclusion criteria underwent PA, STE, and VE on the same day. Collected data included radiation dose, molecular type, RTOG, Fitzpatrick skin type, pathology, neoadjuvant chemotherapy status, TNM (tumor, node, metastasis) classification, surgical procedures, primary breast cancer location, body mass index, and age. A sample of 41 patients was determined using a 2-sample t test. Statistical tools such as t-tests, variance analysis, rank sum tests, and χ² tests, along with random forest analysis and receiver operating characteristic curves, were used to evaluate the radiation dose effects.

Results: Data from 66 patients showed significant differences in parameters such as dermis and subcutaneous tissue oxygen saturation, dermal thickness, and skin elasticity (P values < .05). However, minimum values of oxygen saturation and some photoacoustic measures were not significantly different. Notably, at a 20 Gy radiation threshold, significant variations in oxygen saturation, abnormal dermal thickness, and skin STE and VE were observed, proving more accurate than RTOG grading.

Conclusions: Our findings demonstrate that PA and elastography imaging are effective in differentiating between normal and abnormal breast tissue and assessing radiation-induced changes, thereby highlighting the potential of these imaging techniques.

Purpose: The understanding of how varying radiation beam parameter settings affect the induction and magnitude of the FLASH effect remains limited. We sought to systematically evaluate how the magnitude of radiation-induced gastrointestinal toxicity depends on the interplay between mean dose rate (MDR) and dose per pulse (DPP).

Methods and materials: C57BL/6J mice received total abdominal irradiation (TAI, 11-14 Gy single fraction) through either conventional (CONV) irradiation (low-DPP and low MDR, CONV) or through various combinations of DPP and MDR up to ultra-high-dose-rate beam conditions. DPPs ranging from 1 to 6 Gy were evaluated, while the total dose and MDR (>100 Gy/s) were kept constant; the effects of MDR were evaluated for the range of 0.3 to 1440 Gy/s, while the total dose and DPP were kept constant. Radiation-induced gastrointestinal toxicity was quantified in nontumor-bearing mice through the regenerating crypt assay and survival assessment. Tumor response was evaluated through tumor growth delay.

Results: Within each tested total dose using a constant MDR (>100 Gy/s), increasing DPP led to an increase in sparing (an increase in the number of regenerating crypts), with a more prominent effect seen at 12- and 14-Gy TAI. Interestingly, at DPPs of >4 Gy, a similar level of crypt sparing was demonstrated irrespective of the MDR used (from 0.3 to 1440 Gy/s). At a fixed high-DPP of 4.7 Gy, survival was equivalently improved relative to CONV irrespective of MDR. However, at a lower DPP of 0.93 Gy, an MDR of 104 Gy/s produced a greater survival effect compared with 0.3 Gy/s. We also confirmed that high-DPP, regardless of MDR, produced the same magnitude of tumor growth delay relative to CONV using a clinically relevant melanoma mouse model.

Conclusions: This study demonstrates the strong influence that the beam parameter settings have on the magnitude of the FLASH effect. Both high-DPP and ultra-high-dose-rate appeared independently sufficient to produce FLASH sparing of gastrointestinal toxicity while isoeffective tumor response was maintained across all conditions.