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Background: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015.Methods: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities.Results: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less).Conclusions: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem. [ABSTRACT FROM AUTHOR]

Purpose: Fixed bulky nodal disease in patients with head and neck cancer of unknown primary (HNCUP) remains difficult to treat. This retrospective study evaluated the therapeutic efficacy of selective intra-arterial chemoradiotherapy with docetaxel and nedaplatin for fixed bulky nodal disease in HNCUP. Methods: Data from seven consecutive patients with fixed bulky nodal disease in HNCUP who had undergone selective intra-arterial chemoradiotherapy were analyzed. Whole pharyngeal mucosa and all bilateral nodal areas were irradiated (total dose 50 Gy), and bulky nodal lesions were provided an additional 20 Gy. Intra-arterial chemotherapy used a combination of nedaplatin (80 mg/m2) and docetaxel (60 mg/m2). Outcome measures were local control, disease-free survival, overall survival, and adverse events. Statistical analyses were performed using the Kaplan–Meier method. Results: Median follow-up period was 24 months (range 9–64). All patients had extracapsular extension (N3b) on imaging and clinical findings. Symptoms due to bulky disease were neck discomfort (100%), tumor bleeding (43%), tracheal obstruction (14%), and carotid sinus syndrome (28%). Median value for maximum diameter of cervical disease was 84 mm (range 70–107), and 3-year local control, disease-free survival, and overall survival rates were 100, 54, and 64%, respectively. Symptoms due to bulky disease disappeared in all patients after intra-arterial chemoradiotherapy. Grade 4 leukopenia occurred in two patients (28%) as an acute adverse event. No other serious acute adverse events were observed. Conclusion: Selective intra-arterial chemoradiotherapy with docetaxel and nedaplatin can potentially achieve both favorable local control and survival in in HNCUP with fixed bulky nodal disease. [ABSTRACT FROM AUTHOR]

Objective: Human papilloma virus-negative oropharyngeal cancer has not achieved satisfactory outcomes compared with those of human papilloma virus-positive oropharyngeal cancer. This study evaluated the therapeutic efficacy of selective intraarterial chemoradiotherapy with the docetaxel and nedaplatin regimen for human papilloma virus-negative oropharyngeal cancer.Methods: Twenty-two consecutive patients with human papilloma virus-negative oropharyngeal cancer who had undergone selective intraarterial chemoradiotherapy were retrospectively analyzed. The primary tumor and whole neck were irradiated (50 Gy). Subsequently, the primary site and metastatic lymph nodes were boosted by 20 Gy. The intraarterial chemotherapy regimen comprised a combination of nedaplatin (80 mg/m2) and docetaxel (60 mg/m2), which was initially administered at the start of radiotherapy and was given every 4 weeks for three sessions. Each intraarterial dose of an anticancer agent was determined according to the percentage of the tumor volume supplied by the target artery to the total tumor volume, which was intraoperatively measured via cone-beam computed tomography. The outcome measures were locoregional control, disease-free survival, and overall survival rates and adverse events. Statistical analyses were performed using the Kaplan-Meier method.Results: The median follow-up period was 59 (range, 15-103) months. The T stage was T1/T2 in 5 patients (23%), T3 in 5 patients (23%), and T4 in 12 patients (54%). Cervical lymph node metastasis was staged as ≥N2c in 7 (32%) patients. Complete response was achieved in all patients at the first imaging examination after intraarterial chemoradiotherapy. The 5-year locoregional control, disease-free survival, and overall survival rates were 96% (95% confidence interval, 0.72-0.99), 91% (95% confidence interval, 0.68-0.98), and 100% (95% confidence interval, not available), respectively. Regarding serious acute adverse events, grade 4 laryngeal edema and leukopenia were observed in 1 (5%) and 11 patients (50%), respectively. No other serious acute adverse events were observed.Conclusion: Selective intraarterial chemoradiotherapy with docetaxel and nedaplatin has the potential to achieve favorable locoregional control, disease-free survival, and overall survival rates in human papilloma virus-negative oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: This prospective study investigated the feasibility, toxicity, and oncologic outcomes of definitive radiotherapy (RT) consisting of whole pelvic radiotherapy with no central shielding (noCS-WPRT) and CT-based intracavitary brachytherapy (ICBT) in Japanese patients with cervical cancer. Methods: Patients with cervical cancer of FIGO stages IB1–IVA were eligible. The treatment protocol consisted of noCS-WPRT of 45 Gy in 25 fractions and CT-based high dose-rate ICBT of 15 or 20 Gy in 3 or 4 fractions prescribed at point A. The prescribed ICBT dose was decreased if the manual dwell time/position optimization failed to meet organs-at-risk constraints. Graphical optimization and additional interstitial needles were not applied. Results: We enrolled 40 patients. FIGO stages were IB1: 11, IB2: 13, IIA2: 1, IIB: 11, IIIB: 3, and IVA: 1. Median (range) pretreatment tumor diameter was 47 (14–81) mm. Point A doses were decreased in 19 of 153 ICBT sessions (12%). The median follow-up duration was 33 months. The 2-year rates of pelvic control, local control (LC), and progression-free survival were 83%, 85%, and 75%, respectively. Pre-ICBT tumor diameter, high-risk clinical target volume (HR-CTV), total HR-CTV D90, and overall treatment time (OTT) significantly affected LC. Late adverse events (grade ≥ 3) were observed in 3 patients (2 in the bladder, 1 in the rectum). Conclusions: Definitive RT consisting of noCS-WPRT and CT-based ICBT was feasible for Japanese patients with cervical cancer. To further improve LC, additional interstitial needles for patients with a large HR-CTV and shorter OTT should be considered. [ABSTRACT FROM AUTHOR]

Background: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. Methods: Patients aged 20–75 years with stages II–IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). Results: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%–94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59–80%] and 77% [66–85%], respectively. Although no grade 4–5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. Conclusions: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to compare the efficacy of radiotherapy (RT) combined with transcatheter arterial chemoembolization (TACE) with RT alone for the treatment of bone metastases from renal cell carcinoma (RCC).Methods: We included in this retrospective study 25 RCC patients (28 bone metastases), who were treated with RT at our institution. Patients were divided into two groups: patients treated with RT alone (monotherapy group; n = 17) and those treated with RT combined with TACE (combined therapy group; n = 11). The administered median RT dose was 30 Gy in 10 fractions. Anti-cancer agents used in TACE were cisplatin (median dose, 50 mg) and carboplatin (median dose, 240 mg) for patients with reduced renal function. We evaluated the objective response, post-RT-skeletal-related event (PR-SRE)-free rate, and adverse events associated with treatment for each group.Results: The objective response rates for bone metastases in the monotherapy and combined therapy groups were 33% and 82%, respectively (p = 0.009). The 2-year PR-SRE-free rate in the monotherapy and combined therapy groups was 41.8% and 100%, respectively (p = 0.009). The objective response and PR-SRE-free rates were significantly superior in the combined therapy than in the monotherapy group. There were no significant differences in adverse events or survival between the two groups.Conclusion: RT combined with TACE is a promising treatment for bone metastases from RCC, as it results in higher objective response, and PR-SRE-free rates compared with RT alone.Key Points: • Skeletal-related events (SREs) are common in patients with bone metastases from renal cell carcinoma (RCC). • Radiotherapy (RT) provides pain relief in patients with bone metastases from RCC, but rarely achieves objective response. • Combination of RT with transcatheter arterial chemoembolization results in higher objective response and post-RT-SRE-free rates compared with RT alone and is a promising treatment for bone metastases from RCC, as it. [ABSTRACT FROM AUTHOR]

Arterial spin labeling (ASL) magnetic resonance angiography (MRA) (ASL-MRA) is a newly developed method that can visualize small arteries, particularly those running tortuously and inferiorly at slow flow rates. It provides excellent visualization of the external carotid artery system, with superior performance in visualizing the middle meningeal artery (MMA) compared to that of computed tomography angiography (CTA). Here, we report a case of maxillary sinus carcinoma in which ASL-MRA revealed an ipsilateral ophthalmic artery originating from the MMA that was not visualized on CTA. Volume rendering or maximum intensity projection images of CTA may fail to depict small arteries that run close to bony structures, including anomalies of the MMA originating from the external carotid artery system. In such cases, ASL-MRA may serve as a useful tool to easily visualize the arteries., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Diterpenoid Phytoalexin Factor (DPF) is a key transcription factor involved in diterpenoid phytoalexin (DP) biosynthesis under non-stressed conditions in rice (Oryza sativa L.). Using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9, DPF knockout rice lines were generated. Treatments with abiotic stresses (copper chloride, ultraviolet light, and jasmonic acid) and biotic stress (blast fungus infection) to the knockout lines revealed that the DPF positively regulates stress-induced DP biosynthesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

The increasing prevalence of dermatophyte resistance to terbinafine, a key drug in the treatment of dermatophytosis, represents a significant obstacle to treatment. Trichophyton rubrum is the most commonly isolated fungus in dermatophytosis. In T. rubrum , we identified TERG_07844, a gene encoding a previously uncharacterized putative protein kinase, as an ortholog of budding yeast Saccharomyces cerevisiae polyamine transport kinase 2 (Ptk2), and found that T. rubrum Ptk2 (TrPtk2) is involved in terbinafine tolerance. In both T. rubrum and S. cerevisiae , Ptk2 knockout strains were more sensitive to terbinafine compared with the wild types, suggesting that promotion of terbinafine tolerance is a conserved function of fungal Ptk2. Pma1 is activated through phosphorylation by Ptk2 in S. cerevisiae . Overexpression of T. rubrum Pma1 (TrPma1) in T. rubrum Ptk2 knockout strain (ΔTrPtk2) suppressed terbinafine sensitivity, suggesting that the induction of terbinafine tolerance by TrPtk2 is mediated by TrPma1. Furthermore, omeprazole, an inhibitor of plasma membrane proton pump Pma1, increased the terbinafine sensitivity of clinically isolated terbinafine-resistant strains. These findings suggest that, in dermatophytes, the TrPtk2-TrPma1 pathway plays a key role in promoting intrinsic terbinafine tolerance and may serve as a potential target for combinational antifungal therapy against terbinafine-resistant dermatophytes., Competing Interests: The authors declare no conflict of interest.

Purpose: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC)., Methods: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33)., Results: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively)., Conclusion: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Rationale and Objectives: Pericardial fat (PF)-the thoracic visceral fat surrounding the heart-promotes the development of coronary artery disease by inducing inflammation of the coronary arteries. To evaluate PF, we generated pericardial fat count images (PFCIs) from chest radiographs (CXRs) using a dedicated deep-learning model., Materials and Methods: We reviewed data of 269 consecutive patients who underwent coronary computed tomography (CT). We excluded patients with metal implants, pleural effusion, history of thoracic surgery, or malignancy. Thus, the data of 191 patients were used. We generated PFCIs from the projection of three-dimensional CT images, wherein fat accumulation was represented by a high pixel value. Three different deep-learning models, including CycleGAN were combined in the proposed method to generate PFCIs from CXRs. A single CycleGAN-based model was used to generate PFCIs from CXRs for comparison with the proposed method. To evaluate the image quality of the generated PFCIs, structural similarity index measure (SSIM), mean squared error (MSE), and mean absolute error (MAE) of (i) the PFCI generated using the proposed method and (ii) the PFCI generated using the single model were compared., Results: The mean SSIM, MSE, and MAE were 8.56 × 10 -1 , 1.28 × 10 -2 , and 3.57 × 10 -2 , respectively, for the proposed model, and 7.62 × 10 -1 , 1.98 × 10 -2 , and 5.04 × 10 -2 , respectively, for the single CycleGAN-based model., Conclusion: PFCIs generated from CXRs with the proposed model showed better performance than those generated with the single model. The evaluation of PF without CT may be possible using the proposed method., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Akie Katsuki and Kazuyuki Ohmura are employees of GE HealthCare Japan., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

This study aimed to assess the performance of arterial-spin labeling MRA (ASL-MRA) for visualizing the external carotid artery (ECA) branches in comparison with time-of-flight MRA (TOF-MRA) and CT angiography (CTA). We retrospectively selected 31 consecutive patients, who underwent both MRAs and CTA, prior to the intra-arterial chemoradiotherapy (IACRT) for head and neck cancer. Four patients underwent IACRT bilaterally, so we analyzed 35 ECAs. Pseudo-continuous, three-dimensional ASL using a turbo field echo sequence was acquired. For the TOF-MRA and CTA, clinically used parameters were applied. Two observers evaluated each ECA branch with reference to the angiogram at the IACRT, using five-point scale, in consensus. Friedman test for multiple comparisons was applied. ASL-MRA and CTA better visualized the superior thyroid, lingual, facial, submental, transverse facial, and internal maxillary arteries (IMAs) better than TOF-MRA (p < 0.05). In addition, CTA was superior to ASL-MRA in visualizing only submental artery among these arteries (p = 0.0005). Alternatively, the ASL-MRA was superior for visualizing the middle meningeal artery (MMA) and IMA, compared to the CTA (p = 0.0001 and 0.0007, respectively). ASL-MRA was superior to the TOF-MRA and similar to the CTA in visualizing most of ECA branches. Furthermore, ASL-MRA can better visualize the periphery of MMA and IMA than CTA., (© 2024. The Author(s).)

Background: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC)., Methods: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy., Results: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients., Conclusion: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Postoperative chemoradiotherapy is recommended for patients with head and neck squamous cell carcinoma with positive margins or extracapsular extension at high risk of recurrence. However, high-dose radiotherapy in the head and neck region often causes severe acute and late radiation-related adversities. In our institution, the radiation dose has been relatively lower than that used in Western countries to reduce radiation-related toxicities. Therefore, in this study, we examined the treatment outcomes of low-dose postoperative chemoradiotherapy., Methods: The outcomes of 90 consecutive head and neck squamous cell carcinoma patients who received postoperative radiotherapy between June 2009 and December 2016 were retrospectively analyzed. All patients received postoperative three-dimensional conformal radiotherapy with or without concurrent systemic chemotherapy. The median patient age was 65 years. Concurrent chemoradiotherapy was administered at a total dose of 50.4 Gy in 28 fractions (daily fraction, 1.8 Gy). High-risk patients received 10.8 Gy of boost irradiation in six fractions. For radiotherapy alone, the irradiation dose was up to 54 Gy in 30 fractions and 64.8 Gy in 36 fractions for high-risk patients to increase the treatment intensity., Results: The median follow-up period was 40.5 months. The 3-year locoregional control and overall survival rates were 67.5% and 82.7%, respectively. A significantly higher proportion of patients with oral cavity carcinoma experienced locoregional failure (p = 0.004). The acute adverse events were mild, and the only late adverse event was grade 3 dysphagia (n = 3)., Conclusion: This study suggests that de-escalation of the postoperative radiation dose can potentially reduce the severe adverse events of irradiation in patients while ensuring its effectiveness. In patients with oral cavity carcinoma, it might be necessary to increase the radiation dose., (© 2021. The Author(s).)

Purpose: To evaluate the efficacy of chemoembolization for inoperable metastatic epidural spinal cord compression (MESCC) refractory to re-radiotherapy., Methods: Nineteen consecutive patients with recurrent MESCC after re-radiotherapy who had undergone chemoembolization were retrospectively analyzed. Outcome measures were pain relief rate, neurological improvement rate, objective response rate, and adverse events. MESCC degree classification was assessed using Bilsky grades. Pain assessment was performed using Numerical Rating Scale, and neurological function was evaluated using the Frankel classification., Results: The median follow-up period was 7 (range 2-44) months. All participants had MESCC grade 2 or higher and had severe pain. Fifteen patients (79%) had neurological deficits, and ten had Frankel classification C and five had D. Symptoms were relieved in almost all patients the day following chemoembolization. Pain relief was achieved in 18 of 19 (95%) patients; the median decrease in Numerical Rating Scale score was 8 (range 0-10; p < 0.001). Neurological improvement was achieved in 11 of 15 patients (73%); the median increase in Frankel classification was 1 (range 0-2; p = 0.006). Ten of 19 (53%) patients showed a reduction in MESCC; the median decrease in Bilsky grade was 1 (range 0-2; p = 0.005). There was no correlation between the change in Bilsky grade and pain relief (p = 0.421). However, the decrease in Bilsky grade significantly improved neurological symptoms (p = 0.01). No serious adverse events occurred., Conclusion: Chemoembolization may be a useful palliative treatment modality for MESCC refractory to re-radiotherapy., Level of Evidence: Level 3b, Follow up Study., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated., Methods: Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60 Gy and concurrent platinum-based doublet chemotherapy., Results: The median follow-up period for surviving patients was 36 months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival., Conclusions: Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

Purpose: To compare the efficacy and safety of transarterial chemoembolization for the palliation of radiotherapy (RT)-failure bone metastases (BMs) with those of re-radiotherapy (Re-RT) in achieving pain relief., Materials and Methods: Fifty consecutive patients with RT-failure BMs who had undergone Re-RT (23 patients) and transarterial chemoembolization (27 patients) were retrospectively analyzed. The primary endpoint was clinical response, and the secondary endpoints were objective response and adverse events. Pain assessment was performed using the numerical rating scale, and tumor response was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Pain relief was defined as lack of pain with no analgesic usage (complete pain response) or a decrease in pain score by ≥3 points with analgesic usage (partial pain response)., Results: The pain relief rates in the Re-RT and transarterial chemoembolization groups were 57% and 92%, respectively (P = .006). The median pain relief duration was 2 and 3 months in the Re-RT and transarterial chemoembolization groups, respectively (P = .002). The 6-month pain-free survival rates were 30% and 51% in the Re-RT and transarterial chemoembolization groups, respectively (P = .08). The median tumor reduction rates were -4% and 9% in the Re-RT and transarterial chemoembolization groups, respectively (P < .001). The objective response rates were 0% and 11% in the Re-RT and transarterial chemoembolization groups, respectively (P = .29). No serious adverse events or complications were observed., Conclusions: Transarterial chemoembolization achieved a superior response rate and longer duration of palliation in symptomatic RT-failure BMs., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

Purpose: Fractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones., Materials and Methods: For 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures., Results: Posttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05-0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis., Conclusion: Pretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

Purpose: The aim of this study was to investigate whether additional manual objectives are necessary for the RapidPlan (RP) with a single optimization. We conducted multi-institutional comparisons of plan quality for head and neck cancer (HNC) using the models created at each institute., Methods: The ability of RP to produce acceptable plans for dose requirements was evaluated in two types of oropharynx cancers at five institutes in Japan. Volumetric modulated arc therapy plans created without (RP plan) and with additional manual objectives (M-RP plan) were compared in terms of planning target volume (PTV), brainstem, spinal cord and parotid glands in dosimetric parameters., Results: There were no major dosimetric PTV differences between RP and M-RP plans. For the brainstem and spinal cord in the RP plans, only 40% and 30% of the plans achieved the dose requirements, while the M-RP plans with upper objective added to volume 0% at all institutes achieved them for 90% of the plans. For the L-parotid gland, there was no difference in the RP and M-RP plans (both were 40%) in achieving the acceptable criteria. For the R-parotid gland, 60% and 80% of the RP and M-RP plans achieved the constraint criteria, and in terms of the achievement rate, the RP plans were relatively high., Conclusions: M-RP plans did not require reoptimization; only an upper objective was needed for the brainstem and spinal cord, while the parotid gland dose was reduced in both RP plans with the auto generated line objectives alone., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Background/aim: To determine whether concurrent chemotherapy with radiotherapy should be performed in elderly patients with esophageal cancer., Patients and Methods: A total of 185 patients aged 80 years or older who were treated with definitive radiotherapy alone or combined with chemoradiotherapy for esophageal cancer at seven institutions were enrolled. In order to compare survival rates of patients treated with chemoradiotherapy with those of patients treated with radiotherapy alone, propensity score matching was performed to homogenize the two populations., Results: For the whole patient cohort, the 3-year overall survival (OS) rate was 52.6% and the median survival was 42.5 months. After propensity score matching, the 3-year OS rate for the chemoradiotherapy group was not significantly better than that for the group treated with radiotherapy alone (53.7% vs. 59.9%, p=0.876)., Conclusion: Concurrent chemotherapy with radiotherapy for esophageal cancer in patients aged 80 years or older did not have significant OS benefit over radiotherapy alone., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: This study aimed to identify prognostic factors for response to whole-brain radiotherapy (WBRT) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC)., Patients and Methods: This study retrospectively evaluated 100 patients who underwent WBRT for BMs from NSCLC between December 2012 and October 2017. Clinical factors were tested for associations with overall survival after WBRT., Results: The median follow-up time was 134 days (range=14-1,395 days), the median survival time was 143 days, and the 1-year survival rate was 30.4%. Univariate and multivariate analyses revealed that better survival was independently associated with expression of programmed death-ligand 1 (PD-L1), no previous treatment for BMs, no extracranial disease, and a neutrophil-to-lymphocyte ratio (NLR) of <5.0., Conclusion: A low NLR and positive PD-L1 expression independently predict better prognosis in patients with BMs from NSCLC after WBRT. These findings suggest that the potential immune response may influence survival among patients with BMs., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: 18 F-misonidazole positron emission tomography (FMISO PET)/computed tomography (CT) obtained before and during radiotherapy (RT) was analyzed as to whether it could predict clinical outcome., Patients and Methods: Twenty-two patients were included. FMISO PET/ CT was performed twice before RT and at a dose of approximately 20 Gy/10 fractions. FMISO maximum standardized uptake values (SUV max ), the tumor-to-muscle ratios (T/M), and hypoxic volume (HV) in gross target volumes were measured., Results: Of the 22 tumors, 18 had hypoxic areas (SUV max ≥1.60) before RT. SUV max , T/M, and HV on the first PET/CT were significantly correlated with initial tumor response, although the values during RT were not related to the response. The overall survival and loco-regional control rates of patients below cut-off values were significantly better than those above the cut-off values., Conclusion: Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)