Abstract The Japanese Society for Radiation Oncology (JASTRO) Guidelines for Radiotherapy Treatment Planning have been revised every four years to incorporate the latest findings since the publication of the first edition in 2004. This is a review which presents the 2024 JASTRO Guidelines for radiotherapy treatment planning for esophageal cancer in English. Regarding the treatment of esophageal cancer, various new findings have emerged over the past 4 years, leading to significant updates in the 2020 edition, particularly in the following six areas: (i) additional details on indications for superficial cancer, (ii) inclusion of clinical trial results (JCOG1109) for neoadjuvant chemotherapy and chemoradiotherapy in locally advanced cases in Japan, (iii) updated references on prophylactic lymph node irradiation, (iv) updates on IMRT, (v) revisions in accordance with the 5th edition of the Esophageal Cancer Treatment Guidelines, and (vi) additions of FOLFOX to concurrent chemotherapy regimens.

Abstract In the last decade, the role of radiotherapy in rectal cancer has changed significantly with the introduction of total neoadjuvant therapy (TNT) and nonoperative management (NOM). For the setting of irradiation field in rectal cancer, the pararectal, lateral lymph nodes, and those along the inferior mesenteric artery (IMA) are most important. In total mesorectal excision (TME), the root of the IMA is dissected. In the atlas of pelvic irradiation for rectal cancer, the setting of the upper margin of the mesorectum varies from atlas to atlas, and no atlas sets the upper margin of the mesorectum to the root of the IMA. In particular, there is no consensus on the definition of anatomical boundaries regarding the lymph nodes along the superior rectal artery (SRA). The upper margin of the irradiation field in clinical trials of preoperative radiotherapy and TNT is generally set at the level of the internal and external iliac artery branches, L5/S1, or S2/S3. However, it is not necessary to include the entire mesorectum to the root of the IMA in patients undergoing preoperative radiotherapy plus TME. Conversely, for patients receiving NOM, the irradiation field may have to include the mesorectum to the IMA root, though the incidence of lymph node metastasis and gastrointestinal adverse events merits consideration. It is increasingly important to determine the extent of clinical target volume around the SRA region and the setting of the upper margin of the irradiation field after formulating the treatment policy together with the surgeons and medical oncologists.

Introduction: In August 2018, the Japanese PMDA approved nivolumab, an immune checkpoint inhibitor, for previously treated, unresectable, advanced, or recurrent pleural mesothelioma (PM) based on the MERIT trial, a phase II study of 34 cases. However, concerns regarding limited evidence persist. Methods: We retrospectively analyzed 83 patients with previously treated, unresectable, advanced, or recurrent malignant PM treated with nivolumab from August 2018 to May 2022. Efficacy was evaluated using overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) per modified RECIST criteria. Safety was assessed by treatment-related adverse events (TRAEs) according to CTCAE v5.0. PD-L1 expression was analyzed with the anti-PD-1 antibody (22C3). Results: The median age was 73 years. Histological subtypes included epithelioid (60), sarcomatoid (15), biphasic (6), and unknown (2). Lines of treatment were 2nd (62), 3rd (13), and 4th or later (8). Partial response was seen in 16 patients, stable disease in 30, progressive disease in 29, and not evaluable in 8, with an ORR of 19.3% and a disease control rate of 55.4%. Median PFS and OS were 5.1 and 12.4 months, respectively. TRAEs occurred in 45 patients (54.2%), with grade ≥3 in 6 (7.2%) and one treatment-related death. PFS correlated with male gender, TRAEs, and good performance status (PS: 0–1), while OS correlated with PS. Conclusion: Nivolumab demonstrated efficacy and safety in clinical practice, supporting its use in patients with good PS, even in later lines.

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.

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.

Abstract Background Primary cardiac angiosarcomas are extremely rare and their prognosis is poor. Surgical resection is the first-line treatment; however, no clear standard of care has been clearly established because of the rarity of these tumors. Case presentation A 61-year-old man who had presented with dyspnea on exertion was referred to our hospital. Contrast-enhanced computed tomography revealed massive pericardial effusion and a 40-mm enhanced mass adherent to the anterior wall of the right atrium and involving the right coronary artery. Having diagnosed the mass as a cardiac tumor, we resected the mass under the guidance of epi-cardiac echocardiography guidance, which showed continuity between the tumor and the right atrium, reconstructed the right atrial free wall with a bovine pericardial patch, and performed coronary artery bypass grafting to the right coronary artery using the great saphenous vein. The right atrial wall was resected with adequate tumor-free margin. On the right ventricular side, we resected the right atrial wall 1 cm from the tumor, 2 cm from the atrioventricular groove. Because hemodynamic deterioration occurred after aortic declamping, intra-aortic balloon pumping and veno-arterial extracorporeal membrane oxygenation were instituted. Postoperatively, circulatory support devices were removed safely, and the patient was discharged on the 25th postoperative day. Histopathological examination of the surgical specimens resulted in a diagnosis of angiosarcoma, with positive surgical margins. Chemotherapy and radiotherapy (69 Gy in 30 fractions) were therefore initiated after discharge. To date, the patient has been alive and well with no recurrence of tumor for 4 years and 10 months since surgery. Discussion This case study suggests the usefulness of multimodality treatment comprising surgical resection and adjuvant therapy, for cardiac angiosarcoma.

PURPOSE: To evaluate whether knowledge-based volumetric modulated arc therapy plans for prostate cancer with a multi-institution model (broad model) are clinically useful and effective as a standardization method. METHODS: A knowledge-based planning (KBP) model was trained with 561 prostate VMAT plans from five institutions with different contouring and planning policies. Five clinical plans at each institution were reoptimized with the broad and single institution model, and the dosimetric parameters and relationship between Dmean and the overlapping volume (rectum or bladder and target) were compared. RESULTS: The differences between the broad and single institution models in the dosimetric parameters for V50, V80, V90, and Dmean were: rectum; 9.5% ± 10.3%, 3.3% ± 1.5%, 1.7% ± 1.6%, and 3.6% ± 3.6%, (p < 0.001), bladder; 8.7% ± 12.8%, 1.5% ± 2.6%, 0.7% ± 2.4%, and 2.7% ± 4.6% (p < 0.02), respectively. The differences between the broad model and clinical plans were: rectum; 2.4% ± 4.6%, 1.7% ± 1.7%, 0.7% ± 2.4%, and 1.5% ± 2.0%, (p = 0.004, 0.015, 0.112, and 0.009) bladder; 2.9% ± 5.8%, 1.6% ± 1.9%, 0.9% ± 1.7%, and 1.1% ± 4.8%, (p < 0.018), respectively. Positive values indicate that the broad model has a lower value. Strong correlations were observed (p < 0.001) in the relationship between Dmean and the rectal and bladder volume overlapping with the target in the broad model (R = 0.815 and 0.891, respectively). The broad model had the smallest R2 of the three plans. CONCLUSIONS: KBP with the broad model is clinically effective and applicable as a standardization method at multiple institutions.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4-109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax < 125 Gy (BED10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax < 125 Gy (BED10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax < 125 Gy (BED10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume.

Abstract The risk factors for severe radiation pneumonitis (RP) in patients with lung cancer who undergo rotating gantry intensity-modulated radiation therapy (IMRT) using volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT) are poorly understood. Fifty-two patients who received rotating gantry IMRT for locally advanced lung cancer were included in this retrospective study. In total, 31 and 21 patients received VMAT and HT, respectively. The median follow-up duration was 14 months (range, 5.2–33.6). Twenty (38%) and eight (15%) patients developed grade ≥ 2 and ≥ 3 RP, respectively. In multivariate analysis, lung V5 ≥ 40% was associated with grade ≥ 2 RP (P = 0.02), and past medical history of pneumonectomy and total lung volume ≤ 3260 cc were independently associated with grade ≥ 3 RP (P = 0.02 and P = 0.03, respectively). Rotating gantry IMRT was feasible and safe in patients with lung cancer undergoing definitive radiotherapy. Reducing lung V5 may decrease the risk of symptomatic RP, and care should be taken to avoid severe RP after radiotherapy in patients with a past medical history of pneumonectomy and small total lung volume.

Although bone is the second-most frequent site of distant metastases of head and neck squamous cell carcinoma (HNSCC), variable prognostic factors in patients with bone metastases from HNSCC have not been fully investigated. The aim of the present study was to assess the prognostic factors affecting overall survival (OS) in these patients. The medical records of 97 patients at two institutions who developed bone metastases from HNSCC between January 2010 and December 2020 were retrospectively reviewed. A multivariate analysis using a Cox proportional hazards model was performed to identify potential clinical predictive factors for longer OS. The median OS was 7 months, and the 1- and 2-year OS rates for all patients were 35.4 and 19.2%, respectively. The independent predictive factors for longer OS were single bone metastasis, good performance status and administration of systemic chemotherapy. The median OS with each predictor was 10, 10 and 10.5 months, respectively. In a selected group of patients with these three factors, the OS was 14.5 months. In conclusion, single bone metastasis, a good performance status and systemic chemotherapy were independent predictors of longer OS in patients with HNSCC, but their contributions were limited.

BACKGROUND/AIM: To evaluate the incidence and grade of radiation pneumonitis after volumetric modulated arc therapy (VMAT) performed for the treatment of non-small cell cancer (NSCLC). PATIENTS AND METHODS: Fifty consecutive non-surgical candidates with NSCLC underwent VMAT. Thirty-five patients had stage-III tumors and 15 had recurrent tumors. The prescribed radiation dose for the gross tumor and the elective nodal area was 69 Gy in 30 fractions and 51 Gy in 30 fractions, respectively. RESULTS: Radiation pneumonitis developed in 38 patients (76%, 38/50), and grade ≥2 radiation pneumonitis developed in 11 patients (22%, 11/50). The percentage of lung volume that received a dose in excess of 5 Gy (V5), V10, V20, V30, and the mean lung dose (MLD) in the bilateral and ipsilateral lung were significantly associated with the development of grade ≥2 radiation pneumonitis. CONCLUSION: The incidence and degree of radiation pneumonitis are acceptable following treatment of NSCLC with VMAT.

We have developed soft rubber (SR) bolus that can be shaped in real-time by heating flexibly and repeatedly. This study investigated whether the SR bolus could be used as an ideal bolus, such as not changing of the beam characteristics and homogeneity through the bolus and high plasticity to adhere a patient in addition to real-time shapeable and reusability, in electron radiotherapy. Percentage depth doses (PDDs) and lateral dose profiles (LDPs) were obtained for 4, 6, and 9 MeV electron beams and were compared between the SR and conventional gel boluses. For the LDP at depth of 90% dose, the penumbra as lateral distance between the 80% and 20% isodose lines (P80-20) and the width of 90% dose level (r90) were compared. To evaluate adhesion, the air gap volume between the boluses and nose of a head phantom was evaluated on CT image. The dose profiles along the center axis for the 6 MeV electron beam with SR, gel, and virtual boluses (thickness = 5 mm) on the head phantom were also calculated for the irradiation of 200 monitor unit with a treatment planning system and the depth of the maximum dose (dmax) and maximum dose (Dmax) were compared. The PDDs,P80-20, andr90between the SR and gel boluses corresponded well (within 2%, 0.4 mm, and 0.7 mm, respectively). The air gap volumes of the SR and gel boluses were 3.14 and 50.35 cm3, respectively. Thedmaxwith SR, gel and virtual boluses were 8.0, 6.0, and 7.0 mm (no bolus: 12.0 mm), and theDmaxvalues were 186.4, 170.6, and 186.8 cGy, respectively. The SR bolus had the equivalent electron beam characteristics and homogeneity to the gel bolus and achieved excellent adhesion to a body surface, which can be used in electron radiotherapy as an ideal bolus.

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.

BACKGROUND/AIM: We investigated the plan complexity of volumetric modulated arc therapy (VMAT) with knowledge-based plan (KBP) for oropharyngeal cancer (OPC) with a single optimization and whether it could be used clinically. MATERIALS AND METHODS: KBP model was configured using 55 consecutive OPC and nasopharyngeal cancer plans. Plan complexity as a characteristic of multileaf collimator (MLC) motion and γ pass rate (2%/2 mm criterion) were compared between clinical manual plan (CMP) and KBP for other 10 plans. RESULTS: Plan complexity metrics that had significant differences (p<0.05) (CMP vs. KBP), were mean lateral displacement of MLC from central axis (15.82 mm vs. 18.90 mm), proportions of MLC aperture sizes of ≤5 mm (0.14 vs. 0.11), ≤10 mm (0.24 vs. 0.19), and ≤20 mm (0.41 vs. 0.34), and monitor units (578.68 vs. 505.04). The γ pass rate was 91.3% vs. 93.3%. CONCLUSION: Single optimized KBP for OPC had simple plan complexity features and comparable delivery accuracy to CMP, and could be clinically applied.

PURPOSE: To provide additional clinical data about the re-irradiation tolerance of the spinal cord. METHODS: This was a retrospective bi-institutional study of patients re-irradiated to the cervical or thoracic spinal cord with minimum follow-up of 6 months. The maximum dose (Dmax) and dose to 0.1cc (D0.1cc) were determined (magnetic resonance imaging [MRI]-defined cord) and expressed as equivalent dose in 2‑Gy fractions (EQD2) with an α/β value of 2 Gy. RESULTS: All 32 patients remained free from radiation myelopathy after a median follow-up of 12 months. Re-irradiation was performed after 6-97 months (median 15). In 22 cases (69%) the re-irradiation spinal cord EQD2 Dmax was higher than that of the first treatment course. Forty-eight of 64 treatment courses employed fraction sizes of 2.5 to 4 Gy to the target volume. The median cumulative spinal cord EQD2 Dmax was 80.7 Gy, minimum 61.12 Gy, maximum 114.79 Gy. The median cumulative spinal cord D0.1cc EQD2 was 76.1 Gy, minimum 61.12 Gy, maximum 95.62 Gy. Besides cumulative dose, other risk factors for myelopathy were present (single-course Dmax EQD2 ≥51 Gy in 9 patients, single-course D0.1cc EQD2 ≥51 Gy in 5 patients). CONCLUSION: Even patients treated to higher cumulative doses than previously recommended, or at a considerable risk of myelopathy according to a published risk score, remained free from this complication, although one must acknowledge the potential for manifestation of damage in patients currently alive, i.e., still at risk. Individualized decisions to re-irradiate after appropriate informed consent are an acceptable strategy, including scenarios where low re-irradiation doses to the spinal cord would compromise target coverage and tumor control probability to an unacceptable degree.

PURPOSE: We investigated the performance of the simplified knowledge-based plans (KBPs) in stereotactic body radiotherapy (SBRT) with volumetric-modulated arc therapy (VMAT) for lung cancer. MATERIALS AND METHODS: For 50 cases who underwent SBRT, only three structures were registered into knowledge-based model: total lung, spinal cord, and planning target volume. We performed single auto-optimization on VMAT plans in two steps: 19 cases used for the model training (closed-loop validation) and 16 new cases outside of training set (open-loop validation) for TrueBeam (TB) and Halcyon (Hal) linacs. The dosimetric parameters were compared between clinical plans (CLPs) and KBPs: CLPclosed, KBPclosed-TB and KBPclosed-Hal in closed-loop validation, CLPopen, KBPopen-TB and KBPopen-Hal in open-loop validation. RESULTS: All organs at risk were comparable between CLPs and KBPs except for contralateral lung: V5 of KBPs was approximately 3%-7% higher than that of CLPs. V20 of total lung for KBPs showed comparable to CLPs; CLPclosed vs. KBPclosed-TB and CLPclosed vs. KBPclosed-Hal: 4.36% ± 2.87% vs. 3.54% ± 1.95% and 4.36 ± 2.87% vs. 3.54% ± 1.94% (P = 0.54 and 0.54); CLPopen vs. KBPopen-TB and CLPopen vs. KBPopen-Hal: 4.18% ± 1.57% vs. 3.55% ± 1.27% and 4.18% ± 1.57% vs. 3.67% ± 1.26% (P = 0.19 and 0.27). CI95 of KBPs with both linacs was superior to that of the CLP in closed-loop validation: CLPclosed vs. KBPclosed-TB vs. KBPclosed-Hal: 1.32% ± 0.12% vs. 1.18% ± 0.09% vs. 1.17% ± 0.06% (P < 0.01); and open-loop validation: CLPopen vs. KBPopen-TB vs. KBPopen-Hal: 1.22% ± 0.09% vs. 1.14% ± 0.04% vs. 1.16% ± 0.05% (P ≤ 0.01). CONCLUSIONS: The simplified KBPs with limited number of structures and without planner intervention were clinically acceptable in the dosimetric parameters for lung VMAT-SBRT planning.

<b><i>Background:</i></b> Cisplatin-pemetrexed combination chemotherapy is the current standard primary treatment for malignant pleural mesothelioma (MPM). It was first approved for untreated and unresectable MPM in the 2003 National Comprehensive Cancer Network (NCCN) guidelines. However, to date, standard treatments for patients with MPM who previously underwent chemotherapy, as recommended by the NCCN Malignant Pleural Mesothelioma guidelines, have been inadequate. To explore treatment options for such patients, we performed this retrospective study of patients who received irinotecan plus gemcitabine as second-line therapy for MPM. <b><i>Methods:</i></b> We investigated 62 patients diagnosed with unresectable MPM between January 2008 and October 2017 who experienced recurrence following cisplatin treatment (or carboplatin) plus pemetrexed or pemetrexed monotherapy as first-line treatment, and who underwent irinotecan plus gemcitabine combination therapy as second-line treatment. Irinotecan (60 mg/m²) and gemcitabine (800 mg/m²) were administered on days 1 and 8 every 3 weeks, including a 1-week washout period. Our endpoints were efficacy, survival period, and toxicity. <b><i>Results:</i></b> patients’ median age was 65 years (range 50–79), and the histological MPM types were epithelioid (<i>n</i> = 48), sarcomatoid (<i>n</i> = 6), biphasic (<i>n</i> = 6), and desmoplastic (<i>n</i> = 2). One patient experienced a partial response, 40 had stable disease, and 21 had progressive disease. The disease control rate was 66.1% and the response rate 2.1%. Additionally, the median progression-free and overall survival time were 5.7 and 11.3 months, respectively. The most common adverse events were neutropenia (32.2%), loss of appetite (16.1%), nausea/diarrhea (11.3%), and thrombocytopenia/phlebitis (9.7%). Grade 3 adverse events included neutropenia (12.9%) and thrombocytopenia/phlebitis (2.1%); however, all adverse events were managed with symptomatic therapy. <b><i>Conclusions:</i></b> Despite the fact that second-line irinotecan plus gemcitabine combination therapy did not produce marked tumor shrinkage, it achieved a relatively high disease control rate of &#x3e;65% with an acceptable toxicity profile. Hence, the combination of irinotecan plus gemcitabine may be considered for MPM treatment, with consideration of combination with immune checkpoint inhibitors as a potential next step.

This study aimed to evaluate the possibility of reducing the imaging dose for image-guided radiotherapy by using planar kilovoltage orthogonal imaging and fiducial markers (kV-FM). We tested kilovoltage planar images under clinical imaging conditions for the pelvis (75 kVp, 200 mA, 50 ms) at a decreasing tube current (from 200 to 10 mA). Imaging doses were measured with a semiconductor detector. The visibility of the kV-FM, aspects of image quality (spatial resolution, low contrast resolution), and the resultant image registration reproducibility were evaluated using various shapes (folded, linear, tadpole-like) of fiducial markers containing 0.5% iron [Gold Anchor™ (GA); Naslund Medical AB, Huddinge, Sweden]. The GA phantom was created by placing these variously shaped GAs in an agar phantom. The imaging doses with 200 and 10 mA were approximately 0.74 and 0.04 mGy and they were correlated to the tube current (R2  = 0.999). Regardless of the marker's shape, the GA phantom ensured visibility even when the tube current was reduced to the minimum value (10 mA). The low contrast resolution was gradually decreased at less than 50 mA, but the spatial resolution did not change. Although the auto-registration function could not be used, manual-registration could be achieved with an accuracy of within 1 mm, even when the imaging dose was reduced to 1/20 of the clinical imaging condition for the pelvis. When using the GA as the fiducial marker, the imaging dose could be reduced to 1/20 of that used clinically while maintaining the accuracy of manual-registration using the kV-FM for image-guided radiotherapy of the pelvis.

The present study aimed to evaluate whether knowledge-based plans (KBP) from a single optimization could be used clinically, and to compare dose-volume histogram (DVH) parameters and plan quality between KBP with (KBPCONST) and without (KBPORIG) manual objective constraints and clinical manual optimized (CMO) plans for pharyngeal cancer. KBPs were produced from a system trained on clinical plans from 55 patients with pharyngeal cancer who had undergone intensity-modulated radiation therapy or volumetric-modulated arc therapy (VMAT). For another 15 patients, DVH parameters of KBPCONST and KBPORIG from a single optimization were compared with CMO plans with respect to the planning target volume (D98%, D50%, D2%), brainstem maximum dose (Dmax), spinal cord Dmax, parotid gland median and mean dose (Dmed and Dmean), monitor units and modulation complexity score for VMAT. The Dmax of spinal cord and brainstem and the Dmed and Dmean of ipsilateral parotid glands were unacceptably high for KBPORIG, although the KBPCONST DVH parameters met our goal for most patients. KBPCONST and CMO plans produced comparable DVH parameters. The monitor units of KBPCONST were significantly lower than those of the CMO plans (P < 0.001). Dose distribution of the KBPCONST was better than or comparable to that of the CMO plans for 13 (87%) of the 15 patients. In conclusion, KBPORIG was found to be clinically unacceptable, while KBPCONST from a single optimization was comparable or superior to CMO plans for most patients with head and neck cancer.

PURPOSE: This study aimed to investigate the influence of cleaned-up knowledge-based treatment planning (KBP) models on the plan quality for volumetric-modulated arc therapy (VMAT) of prostate cancer. MATERIALS AND METHODS: Thirty prostate cancer VMAT plans were enrolled and evaluated according to four KBP modeling methods as follows: (1) model not cleaned - trained by fifty other clinical plans (KBPORIG); (2) cases cleaned by removing plans that did not meet all clinical goals of the dosimetric parameters, derived from dose-volume histogram (DVH) (KBPC-DVH); (3) cases cleaned outside the range of ±1 standard deviation through the principal component analysis regression plots (KBPC-REG); and (4) cases cleaned using both methods (2) and (3) (KBPC-ALL). Rectal and bladder structures in the training models numbered 34 and 48 for KBPC-DVH, 37 and 33 for KBPC-REG, and 26 and 33 for KBPC-ALL, respectively. The dosimetric parameters for each model with one-time auto-optimization were compared. RESULTS: All KBP models improved target dose coverage and conformity and provided comparable sparing of organs at risks (rectal and bladder walls). There were no significant differences in plan quality among the KBP models. Nevertheless, only the KBPC-ALL model generated no cases of >1% V78 Gy (prescribed dose) to the rectal wall, whereas the KBPORIG, KBPC-DVH, and KBPC-REG models included two, four, and three cases, respectively, which were difficult to overcome with KBP because the planning target volume (PTV) and rectum regions overlapped. CONCLUSIONS: The cleaned-up KBP model based on DVH and regression plots improved plan quality in the PTV-rectum overlap region.

BACKGROUND/AIM: We aimed to elucidate the pathological findings following acute and late re-irradiation in a preclinical model. MATERIALS AND METHODS: Mice were divided into five treatment groups: sham-irradiation (Sham-IR), 10-12 Gy (Single IR Acute), 15 Gy (Single IR Late), 15 Gy followed by 10-12 Gy re-irradiation 7 days later (Re-IR Acute), or 15 Gy followed by 10-12 Gy re-irradiation 12 weeks later (Re-IR Late). Mice were sacrificed after either single irradiation or re-irradiation for pathological assessment. RESULTS: The Re-IR Late group had significantly lower numbers of crypts with apoptotic cells than those observed in mice in the Single IR Acute group. There were no significant differences between the Single IR Acute and re-IR Acute groups in cell proliferation or in a crypt survival assay. CONCLUSION: Re-irradiation with a long interval after the first irradiation may cause similar acute biological effects in normal intestine as observed following irradiation without re-irradiation.

OBJECTIVE: To report clinical features of bone metastases (BM) from head and neck squamous cell carcinoma (HNSCC). METHODS: Among 772 patients with HNSCC diagnosed at our hospital over 9 years, 30 patients (3.9%) had clinical evidence of BM (24 men and 6 women; mean age: 63 years). We assessed the time interval from the primary diagnosis to BM development, symptoms attributable to BM, presence of distant metastases to other organs, number of BM, sites of BM, morphologic changes on computed tomography (CT) images, treatment for BM, and overall survival (OS). RESULTS: BM at the initial stage were found in 9 patients with HNSCC (30%), and in 21 patients (70%) with HNSCC during the course of the disease. In the later patients, the median time interval from the primary diagnosis was 11.5 months. Nineteen patients (63%) did not have BM-related symptoms, 6 (20%) had pain, 3 (10%) had neurologic symptoms resulting from vertebral or skull metastases, and 2 (7%) had hypercalcemia. Seventeen patients (57%) showed bone-exclusive metastases, and 13 (43%) had distant metastases in other organs. Eleven patients (37%) had monostotic metastases (solitary BM), and 19 patients (63%) had polyostotic metastases (multiple BM). When combined, 9 patients (30%) showed bone-exclusive and monostotic metastases. The most commonly affected site was the thoracolumbar spine, accounting for 34% of total BM, followed by the pelvis (24%), shoulder and thorax (21%), and the extremities (17%). Notably, metastases to bones above the clavicle (craniofacial bones and cervical spine) accounted for only 3% of all bone lesions. CT images showed variable morphologic patterns with osteolytic type in 17 patients (57%), intertrabecular in 7 (23%), osteoblastic in 4 (13%), and mixed in 2 (7%). Systematic chemotherapy for BM was performed in 19 patients and radiotherapy in 18. The median survival time for patients with bone-exclusive and monostotic metastases was significantly longer than that for patients with multi-organ metastases or polyostotic metastases at 18.2 months vs. 5.7 months (p=0.02). Neither chemotherapy nor radiotherapy extended OS. CONCLUSION: Thirty percent of BM cases from HNSCC showed bone-exclusive and monostotic metastases. These patients tended to show a more favorable prognosis than patients with multi-organ metastases or polyostotic metastases.

BACKGROUND: We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. METHODS: We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. RESULTS: For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I-II and III-IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II-III, and IV). CONCLUSIONS: The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

We sought to validate new couch modeling optimization for tomotherapy planning and delivery. We constructed simplified virtual structures just above a default setting couch through a planning support system (MIM Maestro, version 8.2, MIM Software Inc, Cleveland, OH, USA). Based on ionization chamber measurements, we performed interactive optimization and determined the most appropriate physical density of these virtual structures in a treatment planning system (TPS). To validate this couch optimization, Gamma analysis and these statistical analyses between a three-dimensional diode array QA system (ArcCHECK, Sun Nuclear, Melbourne, FL, USA) results and calculations from ionization chamber measurements were performed at 3%/2 mm criteria with a threshold of 10% in clinical QA plans. Using a virtual model consisting of a center slab density of 4.2 g/cm3 and both side slabs density of 1.9 g/cm3 , we demonstrated close agreement between measured dose and the TPS calculated dose. Agreement was within 1% for all gantry angles at the isocenter and within 2% in off-axis plans. In validation of the couch modeling in a clinical QA plan, the average gamma passing rate improved approximately 0.6%-5.1%. It was statistically significant (P < 0.05) for all treatment sites. We successfully generated an accurate couch model for a TomoTherapy TPS by interactively optimizing the physical density of the couch using a planning support system. This modeling proved to be an efficient way of correcting the dosimetric effects of the treatment couch in tomotherapy planning and delivery.

This study aimed to identify factors that predict prognosis after radiotherapy for brain metastases (BMs) from small-cell lung cancer (SCLC). This study retrospectively evaluated 48 consecutive patients who underwent whole-brain radiotherapy (WBRT) for BMs from SCLC between February 2008 and December 2017. WBRT was delivered at a median dose of 30 Gy (range: 30-40 Gy) in 10 fractions (range: 10-16 fractions). Clinical factors were tested for associations with overall survival after WBRT. The median survival and 1-year overall survival rate after WBRT treatment were 232 days and 34.4%, respectively. Univariate analyses revealed that longer survival was associated with Eastern Cooperative Oncology Group performance status of 0-1, asymptomatic BMs, lactate dehydrogenase (LDH) in the normal range, Radiation Therapy Oncology Group-recursive partitioning analysis class 2, and a graded prognostic assessment score of ≥1.5 (P < 0.01, P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). In the multivariate analyses, longer survival was independently associated with asymptomatic BMs [hazard ratio for death (HR), 0.32; 95% confidence interval (CI), 0.12-0.79; P < 0.05] and LDH in the normal range (HR, 0.42; 95% CI, 0.21-0.83; P < 0.05). The presence of symptoms due to BMs and LDH values independently predicted prognosis after WBRT for BMs from SCLC. Elevated LDH may provide valuable information for identifying patients with BMs who could have poor survival outcomes.

PURPOSE: To evaluate therapeutic response to chemoradiotherapy and prediction of recurrence and death in patients with head and neck squamous cell carcinoma (HNSCC) using Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). MATERIALS AND METHODS: Forty-two patients (mean 63.4, range 20-79 years) with nasopharyngeal (n = 10), oropharyngeal (n = 13), hypopharyngeal (n = 11), or laryngeal (n = 8) cancer underwent fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) before and approximately 3 months (mean 95.0, range 70-119 days) after undergoing concurrent chemoradiotherapy. The effect of PERCIST regarding progression-free survival (PFS) and overall survival (OS) was examined using log-rank and Cox methods. RESULTS: Complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease shown by PERCIST were seen in 30 (71.4%), 9 (21.4%), 3 (7.1%), and 0 patients, respectively. Fourteen (33.3%) developed recurrent disease (median follow-up 27.2, range 8.7-123.1 months) and 9 (21.4%) died (median follow-up 43.6, range 9.6-132.6 months). Furthermore, 4 (13.3%) of 30 patients with CMR developed recurrence, while 7 (77.8%) of 9 with PMR and all 3 (100%) with SMD developed recurrence. Two (6.7%) of 30 patients with CMR, 4 (44.4%) of 9 with PMR, and all 3 (100%) with SMD died. Patients who achieved CMR showed significantly longer PFS and OS as compared to those who did not (PMR and SMD) (both, p < 0.0001). CONCLUSION: PERCIST is useful for evaluating therapeutic response to chemoradiotherapy and predicting recurrence and death in HNSCC patients.

AIM: To evaluate the clinical results of two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. PATIENTS AND METHODS: Eighty patients were treated with two-step IMRT between 2002 and 2014. Whole-neck radiotherapy (44.0-50.0 Gy/22-25 fractions) was delivered by IMRT, followed by boost IMRT to the high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Forty-seven patients received concurrent chemotherapy. Immunohistochemistry for human papillomavirus type 16 (HPV/p16) was performed for 64 patients. RESULTS: The 5-year overall survival and locoregional control rates for stage I, II, III, and IVA-B disease were 80.0%, 75.0%, 78.0%, and 64.0% and 100.0%, 75.0%, 92.0%, and 82.0%, respectively. Overall survival was significantly higher in HPV/p16-positive patients than in HPV/p16-negative patients (p=0.01). Xerostomia of grade 2 or more was noted in 10 patients. CONCLUSION: Favourable overall survival and locoregional control rates with excellent salivary preservation were obtained using the two-step IMRT method for oropharyngeal cancer.

Surgical resection is a well-established treatment option for sarcoma. However, anatomical barriers often hamper radical surgical procedures. The treatment of unresectable sarcoma, including local or distant failures following initial treatment, is challenging. The aim of the present study was to analyze the outcome of radiotherapy (RT) for refractory sarcoma, including unresectable, metastatic and recurrent disease, following radical treatment. We retrospectively reviewed a total of 67 tumors in 28 patients who were treated with RT between 2007 and 2014. Clinical target volume (CTV) was generally not defined in a preventive manner; therefore, in the majority of the cases, CTV equaled the gross tumor volume. The total delivered dose, number of fractions and biological equivalent dose were 52 (range, 40-69), 10 (range, 4-24) and 92.2 (range, 56-119.6) Gy, respectively. Only 1 patient developed local failure, with a median follow-up of 11 months (range, 1-59 months). Therefore, the 12-month progression-free survival rate for 67 sites was 96.8%. The overall survival rates at 12 and 36 months were 75.8 and 30.2%, respectively. A total of 2 patients developed grade >2 toxicities, including grade 3 mucositis and grade 4 pericardial effusion. Our results demonstrated that radical RT using modern techniques is highly feasible, achieves excellent local control, and may be an effective treatment option for refractory sarcoma.

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant properties. The aim of the present study was to assess the feasibility and efficacy of administering PZ for radiation-induced mucositis in head and neck cancer patients. Patients with newly diagnosed head and neck cancer were enrolled in this prospective study. PZ was prepared as an oral rinse. The PZ oral rinse was used four times per day during the course of radiotherapy. Sequential changes in radiation mucositis were assessed during and after radiotherapy according to the Common Terminology Criteria for Adverse Events, version 3.0. Furthermore, a retrospective comparison analysis was performed to assess the efficacy of PZ for radiation-induced mucositis. A total of 32 patients were enrolled in the prospective study of the PZ oral rinse. Radiotherapy was performed up to a total dose of 60-66 Gy using a conventional schedule combined with chemotherapy. Of the 32 patients, 30 (93.8%) reported no complaints due to the PZ oral rinse. In addition, PZ was not associated with severe adverse effects. Among the patients who received PZ, grade 3 mucositis was observed in 29.0% based on the mucosal findings and in 39.3% based on the symptoms. In the patients who did not receive PZ, the incidence of grade 3 mucositis was 40.0% based on the mucosal findings and 60.7% based on the symptoms. Moreover, PZ promoted the recovery from mucositis caused by chemoradiotherapy and was not associated with reduced tumor response to radiotherapy. Therefore, the PZ oral rinse was well tolerated and proved to be efficient for the treatment of radiotherapy-induced oral mucositis.

Cone-beam CTを用いた自動位置照合における治療計画用CT画像のスライス厚について検討した。被写体として、内部に球体の空気層を包含するPenta-Guideファントム、被写体辺縁での部分容積効果が大きいと思われるアクリル製球体ファントム、骨盤部の人体ファントムを使用した。スライス厚が厚い場合でも照合誤差の平均値はすべて1mm以内で、スライス厚の違いによる照合誤差は有意差を認めなかった。3種類のファントムすべてにおいてスライス厚と照合誤差の間に相関関係を認めなかった。寝台移動量別に比較しても、スライス厚と照合誤差に一定の相関関係はみられなかった。骨盤部ファントムにおいて、誤差方向による有意差を認めた。臨床例では、10mmスライス厚画像を用いた場合に、2mmスライス厚との照合結果に1mm以上の差を生じる症例があったが、ほかのスライス厚では平均0.2〜0.4mmの差であった。

現在までの成果は、放射線直腸障害動物実験モデルの確立と亜鉛製剤の作成・評価がなされた。実験動物よる放射線直腸障害モデルは、麻酔下ラットに陽性造影剤注腸し倒立位にて腸管の下垂と直腸照射範囲の設定を確認でき、外科的処置を行うことなく、直腸に選択的に照射可能とした。照射後変化は内視鏡にて経時的に評価可能である。亜鉛化合物の設計、製剤化は、亜鉛化合物として亜鉛-Lカルノシン錯化合物、透視にて拡散・付着性の検討、白色ワセリン・ラノリン基剤とした軟膏とし、注射器にて肛門より無麻酔下にて確実に投与可能となった。