Advances in Radiation Oncology最新文献

Purpose

There is still no effective treatment for the gastrointestinal side effects of radiation therapy. Multilineage-differentiating stress-enduring (Muse) cells are tissue stem cells that have the ability to spontaneously home in on injured tissues and repair them. Several clinical trials have shown that stem cell therapy using human bone marrow-derived Muse (hBM-Muse) cells is effective in treating various diseases, but it is not known whether they are effective in treating radiation-induced intestinal injury. In this study, we investigated whether hBM-Muse cells are homing to the radiation-damaged intestine and promote its repair.

Methods and Materials

hBM-Muse cells were injected into the tail vein of mice 2 hours after high-dose total body irradiation. Then, homing analysis, crypt assay, bromodeoxyuridine assay, Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay, immunostaining, and survival time measurements were performed. In addition, we analyzed the expression of sphingosine monophosphate (S1P), a Muse cell-inducing factor, in the mouse small intestine after irradiation. Finally, we investigated whether the administration of JTE-013, an S1P receptor 2-specific antagonist, inhibits hBM-Muse cells homing to the injured intestine.

Results

S1P expression increased in mouse intestine after irradiation, with hBM-Muse cells homing in on the injured intestine. Injection of hBM-Muse cells after radiation exposure significantly increased the number of crypts, proliferating cells in the crypts, and small intestinal component cells such as intestinal stem cells inhibited radiation-induced apoptosis and prolonged mouse survival. Treatment with JTE-013 significantly inhibited intestinal homing and therapeutic effects of hBM-Muse cells. These findings indicate that hBM-Muse cells homed in on the injured intestine through the S1P-S1P receptor 2 interaction to exert therapeutic effects on the radiation-induced intestinal injury.

Conclusions

This study indicates that hBM-Muse cells are effective in treating radiation-induced intestinal injury, suggesting that hBM-Muse cell-based stem cell therapy has the potential to overcome gastrointestinal side effects that limit the indications for radiation therapy.

Purpose

The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality.

Methods and Materials

Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested.

Results

CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes.

Conclusions

The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography–guided adaptive radiation therapy.

Purpose

Exosomes have been shown to play a role in most, if not all, steps of cancer progression. We still lack a comprehensive understanding of the bidirectional communication of exosomes between tumor cells and immune cells. This article aims to explore how exosomes can influence cancer growth and how they are affected by radiation therapy.

Methods and Materials

We searched on PubMed and Web of Science on the impact of radiation on tumor derived exosomes and immune cell derived exosomes in tumor immune microenvironment. We screened all the related articles and summarized their main discoveries and important results.

Results

This article reviewed the effects of tumor derived exosomes and immune cell-derived exosomes on TME and tumor progression after radiotherapy, suggesting the dual effects of exosomes which may refer to clinical practice. Moreover, we retrospected the clinical applications based on tumor derived exosomes, including liquid biopsy, radio-resistance and drug delivery, and discussed the challenges and prospects.

Conclusions

Exosomes are important in cancer treatment, especially with radiation therapy. Learning more about them could lead to better treatments. However, there are still challenges to overcome. The review points out the need for more research in this area.

Purpose

Radiation therapy for tumors subject to breathing-related motion during breath-holds (BHs) has the potential to substantially reduce the irradiated volume. Mechanically assisted and noninvasive ventilation (MANIV) could ensure the target repositioning accuracy during each BH while facilitating treatment feasibility through oxygen supplementation and a perfectly replicated mechanical support. However, there is currently no clinical evidence substantiating the use of MANIV-induced BH for moving tumors. The aim of this work was, therefore, to evaluate the technique's performance under real treatment conditions.

Methods and Materials

Patients eligible for lung or liver stereotactic body radiation therapy were prospectively included in a single-arm trial. The primary endpoint corresponded to the treatment feasibility with MANIV. Secondary outcomes comprised intrafraction geometric uncertainties extracted from real-time imaging, tolerance to BH, and treatment time.

Results

Treatment was successfully delivered in 92.9% (13/14) of patients: 1 patient with a liver tumor was excluded because of a mechanically induced gastric insufflation displacing the liver cranially by more than 1 cm. In the left-right/anteroposterior/craniocaudal directions, the recalculated safety margins based on intrafraction positional data were 4.6 mm/5.1 mm/5.6 mm and 4.7 mm/7.3 mm/5.9 mm for lung and liver lesions, respectively. Compared with the free-breathing internal target volume and midposition approaches, the average reduction in the planning target volume with MANIV reached −47.2% ± 15.3%, P < .001, and −29.4% ± 19.2%, P = .007, for intrathoracic tumors and −23.3% ± 12.4%, P < .001, and −9.3% ± 15.3%, P = .073, for upper abdominal tumors, respectively. For 1 liver lesion, large caudal drifts of occasionally more than 1 cm were measured. The total slot time was 53.1 ± 10.6 minutes with a BH comfort level of 80.1% ± 10.6%.

Conclusions

MANIV enables high treatment feasibility within a nonselected population. Accurate intrafraction tumor repositioning is achieved for lung tumors. Because of occasional intra-BH caudal drifts, pretreatment assessment of BH stability for liver lesions is, however, recommended.

Purpose

Optical surface monitoring systems (OSMSs) have gained substantial attention in modern radiation therapy, specifically in the context of surface guided radiation therapy, which offers real-time patient surface monitoring, ensuring accurate and effective radiation therapy treatments. The aim of this article is to evaluate the OSMS camera sensitivity toward different skin tones, categorized according to the Fitzpatrick scale, a universal classification of human skin tones, using a phantom.

Methods and Materials

This study used Catalyst and Sentinel OSMSs (C-RAD). The Alderson RANDO female pelvis phantom, located at the isocenter in computed tomography simulation and treatment rooms, served as an experimental subject. Eighteen skin tone–matching cotton cloths, selected on the basis of Von Luschan chromatic and Fitzpatrick scales, were wrapped around the phantom for sensitivity evaluation. Camera sensitivity was optimized by adjusting threshold/gain (100%-600%) and integration time during individual scans in both rooms. Temporal response analysis spanned 2 months, with 16 measurements for each OSMS taken in varying light conditions.

Results

The OSMSs successfully detected the surface of cloth-covered phantoms with varying mean (SD) integration times: 550 (34) to 950 (43) μs for the Sentinel system and 2300 (71) to 12,000 (400) μs for the Catalyst system. The sensitivity parameters differed for each skin tone, with lighter skin requiring shorter integration times and gain/threshold values. Darker skin tones necessitated higher parameters for optimal surface images. The reliability of the systems declined with excessive parameters, leading to noise and compromised accuracy in patient positioning.

Conclusions

Optimized sensitivity parameters tailored to individual skin tones are crucial for effective real-time patient surface monitoring in radiation therapy, as variations in skin color can affect the accuracy of measurements. The precision of skin color measurements in OSMSs relies on carefully adjusting camera sensitivity parameters. However, careful consideration is essential, as larger values are required for darker skin tones, compromising reliability. This suggests the need for exploring alternative image guidance methods for patients with darker skin tones.

Purpose

Methods and Materials

Results

Conclusions

Purpose

Owing to substantial interfraction motion in cervical cancer, plan-of-the-day (PotD) adaptive radiation therapy may be of benefit to patients. Implementation is limited by uncertainty over how to generate the planning target volumes (PTVs). We compared published methods on our own patients.

Methods and Materials

Forty patients each had 3 planning scans with variable bladder filling and daily cone beam computed tomographies (cone beam CTs) during radiation therapy; 5 to 11 cone beam CTs were selected to represent interfraction motion. Clinical target volumes (CTVs) and organs at risk were contoured following EMBRACE-II guidelines. A literature search identified 30 adaptive and nonadaptive solutions to PTV generation, which we applied to our patients. PTV sizes and mean coverage of the daily CTV were determined. For 11 patients, the clinically implemented, subjectively edited plan library was also investigated.

Results

Eleven studies assessed 15 PotD strategies against nonadaptive comparators on a median of 14 patients (range, 9-23). Some PotD approaches applied margin recipes to the CTV on each planning scan, some modeled the CTV against bladder volume, and others applied incremental isotropic margins to the CTV with a single planning scan. Generally, coverage improved as PTV size increased. The fixed isotropic margin required to provide 100% coverage of all patients was 44 mm, with a mean PTV size of 3316 cm³. The PotD strategy with the best coverage was a 2-plan library formed by modeling the CTV against bladder volume with extrapolation; it provided 98% mean coverage with 1419-cm³ mean PTV size. A 3-plan library consisting of the CTV on each planning scan with 10-mm margin provided 96% mean coverage with 1346-cm³ mean PTV size. The clinically implemented solution that employed subjective extrapolation had mean 100% coverage and 1282-cm³ PTV size on the 11-patient subset. Coverage provided by the best nonadaptive strategies was not statistically superior to the best PotD strategy (P = .13), but PTVs were larger (P = .02).

Conclusions

We identified a modeled 2-plan method and a simple 3-plan method, both of which provided excellent coverage with small PTVs compared with nonadaptive strategies.

Purpose

Hypofractionated radiation therapy (RT) was recommended for several cancer sites to reduce outpatient visits during the COVID-19 pandemic. This study aimed to identify the impact of the pandemic on hypofractionated RT for breast cancer in Japan.

Methods and Materials

The monthly number of courses for hypofractionated and conventional RTs was counted using sample data sets from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, a nationwide database accumulating insurance claims data comprehensively. Changes in the number of hypofractionated and conventional RTs were estimated using an interrupted time-series analysis.

Results

The number of hypofractionated RT courses gradually increased before the pandemic in contrast to that of conventional RT courses, which gradually decreased. However, conventional RT remained outnumbered by hypofractionated RT throughout the observation period. After the outbreak of the pandemic, the use of hypofractionated RT significantly increased in April 2020 (1312 courses; 95% CI, 801-1823) but decreased in October 2020 (−601; 95% CI, −1111 to −92). Subgroup analysis by age and the number of beds in medical institutions revealed similar trends.

Conclusions

Although conventional RT for breast cancer has been gradually replaced by hypofractionated RT, it remains predominant. The use of hypofractionated RT increased briefly early in the COVID-19 pandemic; however, this increase was not sustained, unlike in other countries. Considering the benefits of hypofractionated RT for breast cancer, its use should be encouraged in Japan.

Purpose

To evaluate the safety and efficacy of pencil beam scanning (PBS) proton radiation therapy (RT) in trimodality therapy for esophageal cancer.

Methods and Materials

This prospective pilot study was planned to accrue 30 patients with locally advanced esophageal or gastroesophageal junction carcinoma medically suitable for chemoradiation therapy (CRT) followed by esophagectomy. PBS proton RT consisted of 25 fractions, 50 Gy to tumor + 1 cm and 45 Gy to a 3.5 cm mucosal expansion and regional lymph nodes. Chemotherapy included weekly carboplatin (area under the curve, 2 mg/mL/min) and paclitaxel (50 mg/m²). At 4 to 8 weeks after CRT, patients underwent restaging and potential esophagectomy. The primary endpoint was acute grade 3+ adverse events (AEs) attributed to CRT. Overall survival and progression-free survival were assessed using the Kaplan-Meier methodology; local-regional recurrence and distant metastases rates were assessed using the cumulative incidence methodology. The Functional Assessment of Cancer Therapy–Esophagus assessed quality of life.

Results

Thirty eligible patients were enrolled from June 2015 to April 2017. Median age was 68 years. Histology was adenocarcinoma in 87%, and location was distal esophagus/gastroesophageal junction in 90%. Stage was T3 to T4 in 87% and N1 to N3 in 80%. All patients completed the planned RT dose. Acute grade 3+ AEs occurred in 30%, most commonly leukopenia and neutropenia. Acute grade 3+ nonhematologic AEs occurred in 3%. Esophagectomy was performed in 90% of patients (R0 in 93%). Pathologic complete response rate was 40%. Major postoperative complications (Clavien-Dindo score, ≥3) occurred in 34%. Postoperative mortality at 30 days was 3.7%. Median follow-up was 5.2 years. Five-year outcome estimates were overall survival at 46%, progression-free survival at 39%, local-regional recurrence at 17%, and distant metastases at 40%. Functional Assessment of Cancer Therapy–Esophagus scores (medians) at baseline, at the end of CRT, before esophagectomy, at 12 months, and at 24 months were 145, 136 (p = .0002 vs baseline), 144, 146 and 157, respectively.

Conclusions

PBS proton RT is feasible and safe as a component of trimodality therapy for esophageal cancer.