OBJECTIVE: To evaluate the association between prophylactic administration of clarithromycin (CAM) and the development of radiation pneumonitis (RP) in patients treated with intensity modulated radiation therapy (IMRT) for lung cancer.
METHODS: A total of 89 patients who underwent definitive or salvage IMRT for lung cancer were retrospectively evaluated. The median total and daily doses were 60 Gy and 2 Gy, respectively. A total of 39 patients (44%) received CAM for a median of three months after the start of IMRT. The relationship between the development of RP and certain clinical factors was analyzed.
RESULTS: RP of Grade ≥2 was recognized in 10 (11%) patients; Grade 2 in six patients and Grade 3 in four patients. The incidence of Grade ≥2 RP was 3% (1/39) in patients treated with CAM, which was significantly lower than that of 18% (9/50) in patients without CAM. The median lung V20 and V5 in the 10 patients with RP Grade ≥2 were 24% and 46%, respectively, compared with 18% and 37% in the 79 patients with RP Grade 0-1, and the differences were significant. Durvalumab administration after IMRT was also a significant factor for RP Grade ≥2.
CONCLUSIONS: Prophylactic administration of CAM may reduce Grade ≥2 RP in patients treated with IMRT for lung cancer. Therefore, further clinical trials are warranted.

This study investigates the dosimetric effects of different gantry rotation angles used in volumetric modulated arc therapy (VMAT) for early glottic carcinoma. VMAT treatment plans using full-arc, half-arc, and partial-arc gantry rotation angles were generated from 22 computed tomography datasets of early-stage (T1-2N0) glottic laryngeal cancer. Dosimetric parameters associated with the planning target volume (PTV) and organs at risk (OARs), specifically the carotid arteries and thyroid, were compared. To assess the robustness of the VMAT plans, dose variations were analyzed by introducing positional shifts of 1, 3, and 5 mm from the isocenter of each plan along the superior-inferior, left-right, and anterior-posterior axes. Furthermore, we examined the size of the PTV, the air cavity volume within the PTV, and the variability of the beam path length through the gantry angles to investigate their correlations with PTV dose variations in the presence of positioning errors. Compared to full-arc and half-arc plans, the dosimetric parameters of partial-arc plans were found to be higher in PTV (D2%, D5%, D50%, and Dmean) and lower in OARs, while their dose variations of OAR parameters were greater for positioning errors. In addition, a correlation was observed between PTV size and PTV dose variations. Air cavity volume and depth variability were also correlated with some PTV parameters, depending on the arc plan. The results presented in this study suggest that the partial-arc gantry angles can allow higher PTV doses while minimizing OAR doses in VMAT treatment planning for early glottic cancer. However, the small delivery angles may lead to greater dose variations in the OARs when positioning errors occur.

OBJECTIVE: This study aimed to develop a hybrid multi-channel network to detect multileaf collimator (MLC) positional errors using dose difference (DD) maps and gamma maps generated from low-resolution detectors in patient-specific quality assurance (QA) for Intensity Modulated Radiation Therapy (IMRT).
METHODS: A total of 68 plans with 358 beams of IMRT were included in this study. The MLC leaf positions of all control points in the original IMRT plans were modified to simulate four types of errors: shift error, opening error, closing error, and random error. These modified plans were imported into the treatment planning system (TPS) to calculate the predicted dose, while the PTW seven29 phantom was utilized to obtain the measured dose distributions. Based on the measured and predicted dose, DD maps and gamma maps, both with and without errors, were generated, resulting in a dataset with 3222 samples. The network\'s performance was evaluated using various metrics, including accuracy, sensitivity, specificity, precision, F1-score, ROC curves, and normalized confusion matrix. Besides, other baseline methods, such as single-channel hybrid network, ResNet-18, and Swin-Transformer, were also evaluated as a comparison.
RESULTS: The experimental results showed that the multi-channel hybrid network outperformed other methods, demonstrating higher average precision, accuracy, sensitivity, specificity, and F1-scores, with values of 0.87, 0.89, 0.85, 0.97, and 0.85, respectively. The multi-channel hybrid network also achieved higher AUC values in the random errors (0.964) and the error-free (0.946) categories. Although the average accuracy of the multi-channel hybrid network was only marginally better than that of ResNet-18 and Swin Transformer, it significantly outperformed them regarding precision in the error-free category.
CONCLUSIONS: The proposed multi-channel hybrid network exhibits a high level of accuracy in identifying MLC errors using low-resolution detectors. The method offers an effective and reliable solution for promoting quality and safety of IMRT QA.

OBJECTIVE: To develop a Total Body Irradiation (TBI) technique using IMRT at extended SSD that can be performed in any size Linac room.
METHODS: Patients studied were placed on a platform close to the floor, directly under the gantry with cranial-caudal axis parallel to the gantry rotation plane and at SSD ∼200 cm. Two abutting fields with the same external isocenter at gantry angles of ±21˚, collimator angle of 90˚, and field size of 25 × 40 cm2 are employed for both supine and prone positions. An iterative optimization algorithm was developed to generate a uniform dose at the patient mid-plane with adequate shielding to critical organs such as lungs and kidneys. The technique was validated in both phantom and patient CT images for treatment planning, and dose measurement and QA were performed in phantom.
RESULTS: A uniform dose distribution in the mid-plane within ±5% of the prescription dose was reached after a few iterations. This was confirmed with ion-chamber measurements in phantom. The mean dose to lungs and kidneys can be adjusted according to clinical requirements and can be as low as ∼25% of the prescription dose. For a typical prescription dose of 200 cGy/fraction, the total MU was ∼2400/1200 for the superior/inferior field. The overall treatment time for both supine/prone positions was ∼54 min to meet the maximum absorbed dose rate criteria of 15 cGy/min. IMRT QA with portal dosimetry shows excellent agreement.
CONCLUSIONS: We have developed a promising TBI technique using abutting IMRT fields at extended SSD. The patient is in a comfortable recumbent position with good reproducibility and less motion during treatment. An additional benefit of this technique is that full 3D dose distribution is available from the TPS with a DVH summary for organs of interest. The technique allows precise sparing of lungs and kidneys and can be executed in any linac room.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Prostate cancer is the second most common cancer in men. Two common radiotherapy techniques, intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc radiotherapy (VMAT), are used for treatment. This study aimed to compare the two techniques for sparing the bladder and bowel. Computed tomography data from prostate cancer patients were analyzed to define the clinical target volume (CTV) and planning target volume (PTV). Treatment plans were generated with Monte Carlo algorithms, and dosimetric analysis was performed using the Monaco Treatment Planning System (TPS). We compared IMRT and VMAT for prostate cancer PTV coverage (% Ref. Volume), with VMAT showing slightly better coverage (98.885±1.704) compared to IMRT (98.594±0.923). VMAT also demonstrated improved PTV conformity. Additionally, VMAT was superior in sparing the bladder (% V4500<40%), while IMRT performed better in bowel preservation (mean Ref. volume CC<195).

UNASSIGNED: The purpose of this study is to evaluate the potential of the flattening filter free (FFF) mode of a linear accelerator for patients with hippocampal avoidance whole-brain radiotherapy (HA-WBRT) by comparison with flattened beams (FF) technique in the application of volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) using dosimetric and radiobiological indexes based on the volume of hippocampus and target.
UNASSIGNED: 2 VMAT- and 2 IMRT- plans were optimized in Eclipse planning system with 2 different delivery modes (6 MV standard vs. 6 MV FFF) for each of 25 patients. Dose distributions of the target and organs at risk (OARs), normal tissue complication probability (NTCP) of the hippocampus, monitor units, treatment time and quality assurance results were evaluated to compare the normal and FFF beam characteristics by Wilcoxon matched-pair signed-rank test with a significance level of 0.05.
UNASSIGNED: VMAT-FFF provided the significantly best homogeneity and conformity of the target, delivered the lowest dose to hippocampus and the other OARs, and led to the lowest NTCP of the hippocampus among all modalities, which has the potential to alleviate neurocognitive decline after WBRT. IMRT-FFF reduced the dose to the lens with similar dose distributions of the target compared with IMRT-FF, whereas the lower dose to the hippocampus was achieved using the conventional beams. The monitor units were obviously increased by 19.2% for VMAT and 33.8% for IMRT, when FFF beams w ere used. The removal of flattening filter for IMRT resulted in a 26% reduction in treatment time, but VMAT had the similar treatment time for the two modes owing to the limitation of gantry rotation speed. Gamma analysis showed an excellent agreement for all plans at 3%/2 mm, and no statistical differences were found between FF and FFF.
UNASSIGNED: In conclusion, this study suggests that FFF mode is feasible and advantageous in HA-WBRT and VMAT-FFF is the optimal solution in terms of dose distribution of the target, OARs sparing, NTCP of the hippocampus and delivery efficiency compared to the other three techniques. Additionally, the advantages of the FFF technique for VMAT are more prominent in cases with small hippocampal volumes.

BACKGROUND: Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN.
METHODS: This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score.
CONCLUSIONS: If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT.
BACKGROUND: This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 ( https://jrct.niph.go.jp/latest-detail/jRCTs031210100 ). Date of Registration: May 2021.

UNASSIGNED: The impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR.
UNASSIGNED: We retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data.
UNASSIGNED: IBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P<0.05). IBBR group also had lower radiotherapy dosimetric parameters in the ipsilateral lung and the heart of left breast cancer patients. The differences in the rates of radiation pneumonia (RP) and radiation dermatitis (RD) between the two groups were not statistically significant (P > 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05).
UNASSIGNED: Patients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy.

OBJECTIVE: The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC).
METHODS: This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival.
RESULTS: Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24).
CONCLUSIONS: The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.