Phase I/II study of stereotactic body radiotherapy boost in patients with cervical cancer ineligible for intracavitary brachytherapy.

PURPOSE: Stereotactic body radiotherapy (SBRT) boost is a promising treatment for cervical cancer patients who are ineligible for intracavitary brachytherapy (ICBT). The aim of this multicenter, single-arm, phase I/II study was to prospectively evaluate the efficacy and toxicity of SBRT boost. MATERIALS AND METHODS: ICBT-ineligible patients with untreated cervical cancer were enrolled. Patients underwent whole-pelvic radiotherapy (45 Gy in 25 fractions) with SBRT boost to the primary lesion. In the phase I dose-escalation cohort (3 + 3 design), patients were treated with SBRT boost of 21 or 22.5 Gy in three fractions. Although dose-limiting toxicity was not confirmed, a dose of 21 Gy was selected for the phase II cohort because it was difficult to reproduce the pelvic organs position in two patients during the phase I trial. The primary endpoint was 2-year progression-free survival. RESULTS: Twenty-one patients (phase I, n = 3; phase II, n = 18) were enrolled between April 2016 and October 2020; 17 (81%) had clinical stage III-IV (with para-aortic lymph node metastases) disease. The median (range) follow-up was 40 (10-84) months. The initial response was complete response in 20 patients and partial response in one patient. The 2-year locoregional control, progression-free survival, and overall survival rates were 84%, 67%, and 81%, respectively. Grade ≥ 3 toxicity was confirmed in one patient each in the acute (diarrhea) and late (urinary tract obstruction) phases. CONCLUSION: These findings suggested that a SBRT boost is more effective than the conventional EBRT boost and can be an important treatment option for ICBT-ineligible patients with cervical cancer. STUDY REGISTRATION: This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000036845).

Analysis of source dwell position during treatment in brachytherapy using CT scout images.

Purpose: Several cases of inaccurate irradiation in brachytherapy have been reported, occurring similarly to external radiation. Due to a large dose per fraction in brachytherapy, inaccurate irradiation can seriously harm a patient. Although various studies have been conducted, systems that detect inaccurate irradiation in brachytherapy are not as developed as those for external irradiation. This study aimed to construct a system that analyzes the source dwell position during irradiation using computed tomography (CT) scout images. The novelty of the study was that by using CT scout images, high versatility and analysis of absolute coordinates can be achieved. Material and methods: A treatment plan was designed with an iridium-192 (192Ir) source delivering radiation at two dwell positions in a tandem applicator. CT scout images were taken during irradiation, and acquired under different imaging conditions and applicator geometries. First, we confirmed whether a source was visible in CT scout images. Then, employing in-house MATLAB program, source dwell coordinates were analyzed using the images. An analysis was considered adequate when the resulting source dwell coordinates agreed with the treatment plan within ±1 mm, in accordance with AAPM TG56 guidelines for source dwell position accuracy. Results: The source dwelling was visible in CT scout image, which was enlarged or reduced depending on applicator geometries. The applicator was enlarged by 127% when 130 mm away from the center of CT gantry. The analysis results using our in-house program were considered adequate; although, analysis parameters required adjustments depending on imaging conditions. Conclusions: The proposed system can be easily implemented for image-guided brachytherapy and can analyze the absolute coordinates of source dwell position. Therefore, the system could be used for preventing inaccurate irradiation by verifying whether brachytherapy was performed properly.

Incidence and Prognostic Factors of Painful Vertebral Compression Fracture Caused by Spine Stereotactic Body Radiotherapy.

Most studies of vertebral compression fractures (VCF) caused by stereotactic body radiotherapy (SBRT) do not discuss the symptoms of this complication. In this paper, we aimed to determine the rate and prognostic factors of painful VCF caused by SBRT for spinal metastases. Spinal segments with VCF in patients treated with spine SBRT between 2013 and 2021 were retrospectively reviewed. The primary endpoint was the rate of painful VCF (grades 2-3). Patient demographic and clinical characteristics were evaluated as prognosticators. In total, 779 spinal segments in 391 patients were analyzed. The median follow-up after SBRT was 18 (range: 1-107) months. Sixty iatrogenic VCFs (7.7%) were identified. The rate of painful VCF was 2.4% (19/779). Eight (1.0%) VCFs required surgery for internal fixation or spinal canal decompression. The painful VCF rate was significantly higher in patients with no posterolateral tumor involvement than in those with bilateral or unilateral involvement (50% vs. 23%; p = 0.042); it was also higher in patients with spine without fixation than in those with fixation (44% vs. 0%; p < 0.001). Painful VCFs were confirmed in only 2.4% of all the irradiated spinal segments. The absence of posterolateral tumor involvement and no fixation was significantly associated with painful VCF.

Preliminary Study on Establishing a Heart Rate Variability-based Method for Objectively Evaluating Bone Metastasis Pain.

BACKGROUND/AIM: The aim of this study was to establish an objective evaluation method for pain due to bone metastasis, based on heart rate variability (HRV). PATIENTS AND METHODS: In this prospective study, patients who underwent radiotherapy for painful bone metastases were enrolled. Pain was assessed using a numerical rating scale (NRS), and anxiety and depression were evaluated using the Hospital Anxiety and Depression Scale (HADS). Autonomic and physical activities were evaluated by measuring HRV using a wearable device. NRS, HADS, and R-R interval (RRI) values were obtained upon starting, completing, and 3-5 weeks after radiotherapy. RESULTS: Between July 2020 and July 2021, 11 patients were enrolled. The median average NRS score was 5 (range=2-10). HADS-assessed median anxiety and depression scores were 8 (range=1-13 and 2-21). For patients with an NRS score ≥4, NRS score was significantly associated with low-frequency/high-frequency (LF/HF) component ratio (p=0.03). Heart rate during physical activity was significantly higher than resting heart rate; however, mean resting LF/HF was significantly higher than LF/HF during physical activity. During rest, excluding patients with a HADS depression score ≥7 in an NRS score 1-3, there was a trend for a positive correlation between the NRS score and the mean LF/HF (p=0.07). CONCLUSION: HRV measurements can objectively evaluate pain due to bone metastasis. However, we must consider that the effects of mental status, such as depression, on LF/HF also affect HRV in patients with cancer with mild pain.

A phase II study of concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C for squamous cell carcinoma of the anal canal (the JROSG 10-2 trial).

This study assessed the efficacy of chemoradiotherapy for squamous cell carcinoma of the anal canal (SCCAC). Patients with T1-4N0-3M0 SCCAC received chemoradiotherapy with 5-fluorouracil (5-FU, 800 mg/m2/day, 96-h infusion) and mitomycin-C (MMC, 10 mg/m2 bolus). Patients treated with 3-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) were administered 36.0 Gy in 20 fractions or 49.5 Gy in 33 fractions for elective nodal irradiation and 59.4 Gy in 33 fractions for primary tumor and metastatic nodal irradiation. The sample size was considered sufficient to estimate 95% confidence intervals (CIs) for the true 2-year disease-free survival (DFS) within a width of +15% when the expected true 2-year DFS was 70%. The primary endpoint was 2-year DFS. The secondary endpoints were 2-year overall survival (OS), locoregional control (LC), colostomy-free survival (CFS) and adverse events. Thirty-one patients were enrolled between January 2014 and July 2019. The median follow-up was 33.3 months (range, 16.2-65.8 months). Among the 31 patients, 13%, 32%, 16% and 39% had stage I, II, IIIA and IIIB disease, respectively. Thirty patients were treated with IMRT. Complete response (CR) was achieved in 27 patients. The 2-year DFS, OS, LC and CFS rates were 77.4% (95% CI, 58.4-88.5%), 93.5% (95% CI, 76.6-98.3%), 83.9% (95% CI, 65.5-92.9%) and 80.6% (95% CI, 61.9-90.8%), respectively. One patient experienced grade 3 late adverse events; however, no grade ≥ 4 late adverse events occurred. Good DFS with a low rate of late adverse events was observed. Chemoradiotherapy with 5-FU and MMC was effective for SCCAC.

Phase I trial of myeloablative conditioning with 3-day total marrow and lymphoid irradiation for leukemia.

This prospective phase I trial aimed to determine the recommended dose of 3-day total marrow and lymphoid irradiation (TMLI) for a myeloablative conditioning regimen by increasing the dose per fraction. The primary end-point of this single-institution dose escalation study was the recommended TMLI dose based on the frequency of dose-limiting toxicity (DLT) ≤100 days posthematopoietic stem cell transplantation (HSCT); a 3 + 3 design was used to evaluate the safety of TMLI. Three dose levels of TMLI (14/16/18 Gy in six fractions over 3 days) were set. The treatment protocol began at 14 Gy. Dose-limiting toxicities were defined as grade 3 or 4 nonhematological toxicities. Nine patients, with a median age of 42 years (range, 35-48), eight with acute lymphoblastic leukemia and one with chronic myeloblastic leukemia, received TMLI followed by unrelated bone marrow transplant. The median follow-up period after HSCT was 575 days (range, 253-1037). Three patients were enrolled for each dose level. No patient showed DLT within 100 days of HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. All patients achieved neutrophil engraftment at a median of 19 days (range, 14-25). One-year overall and disease-free survival rates were 83.3% and 57.1%, respectively. Three patients experienced relapse, and no nonrelapse mortality was documented during the observation period. One patient died due to disease relapse 306 days post-HSCT. The recommended dose of 3-day TMLI was 18 Gy in six fractions. The efficacy evaluation of this regimen is currently being planned in a phase II study.

Outcomes of allogeneic haematopoietic stem cell transplantation with intensity-modulated total body irradiation by helical tomotherapy: a 2-year prospective follow-up study.

BACKGROUND AND OBJECTIVES: Intensity-modulated radiation therapy (IMRT) helps achieve good radiation dose conformity and precise dose evaluation. We conducted a single-centre prospective study to assess the safety and feasibility of total body irradiation with IMRT (IMRT-TBI) using helical tomotherapy in allogeneic haematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Thirty-nine adult patients with haematological malignancy (acute lymphoblastic leukaemia [n = 21], chronic myeloid leukaemia [n = 6], mixed phenotype acute leukaemia [n = 5], acute myeloid leukaemia [n = 4], and malignant lymphoma [n = 3]) who received 12 Gy IMRT-TBI were enrolled with a median follow-up of 934.5 (range, 617-1254) d. At the time of transplantation, 33 patients (85%) achieved complete remission. The conditioning regimen used IMRT-TBI (12 Gy in 6 fractions twice daily, for 3 d) and cyclophosphamide (60 mg/kg/d, for 2 d), seven patients were combined with cytarabine, and five with etoposide. We set dose constraints for the lungs, kidneys and lens as the organs at risk. RESULTS: The mean doses for the lungs and kidneys were 7.50 and 9.11 Gy, respectively. The mean maximum dose for the lens (right/left) was 5.75/5.87 Gy. The 2-year overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 69, 64, 18 and 18%, respectively. Thirty-six patients developed early adverse events (AEs) (including four patients with Grade 3/4 toxicities), most of which were reversible oral mucositis and may partially have been related to IMRT-TBI. However, the incidence of toxicity was comparable to conventional TBI-based conditioning transplantation. None of the patients developed primary graft failure, or Grade III-IV acute graft-versus-host disease (GVHD). In late complications, chronic kidney disease was observed in six patients, a lower incidence compared to conventional TBI-based conditioning transplantation. No radiation pneumonitis or cataracts were observed in any of the patients. CONCLUSIONS: IMRT-TBI is safe and feasible for haematological malignancies with acceptable clinical outcomes.KEY MESSAGESIMRT-TBI-helical tomotherapy aids in accurate dose calculation and conformity.It could be used without any considerable increase in the rate of TBI-related AEs.Allo-HSCT with IMRT-TBI may be an alternative to conventional TBI for clinical use.

Palliative Efficacy of High-Dose Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Painful Non-Spine Bone Metastases: A Propensity Score-Matched Analysis.

(1) Background: The superiority of stereotactic body radiotherapy (SBRT) over conventional external beam radiotherapy (cEBRT) in terms of pain palliation for bone metastases remains controversial. (2) Methods: This propensity score-matched study compared the overall pain response (OR) 3 months after radiotherapy among patients with painful (≥2 points on a 0-to-10 scale) non-spine bone metastases. Patients with lesions that were treated with SBRT or cEBRT and whose pain scores were evaluated 3 months after radiotherapy were included in this study. Pain response was evaluated according to the International Consensus Criteria. (3) Results: A total of 234 lesions (SBRT, n = 129; cEBRT, n = 105) were identified in our institutional database. To reduce the confounding effects, 162 patients were selected using a propensity score-matched analysis (n = 81 for each treatment). The OR rate at 3 months after SBRT was significantly higher than that after cEBRT (76.5% vs. 56.8%; p = 0.012). A noteworthy finding of our study is that the same trend was observed even after 6 months (75.9% vs. 50.0%; p = 0.011). The 1-year local failure rates after SBRT and cEBRT were 10.2% and 33.3% (p < 0.001), respectively. (4) Conclusions: Our findings suggest that SBRT is superior to cEBRT for pain palliation in patients with non-spine bone metastases.

Re-irradiation with interstitial brachytherapy in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation.

PURPOSE: This study aimed to evaluate the outcomes and dose-volume parameters of re-irradiation with interstitial brachytherapy (ISBT) in uterine cancer patients with vaginal recurrence after post-operative pelvic irradiation. MATERIAL AND METHODS: We evaluated six uterine cancer patients who received re-irradiation with ISBT between January, 2012 and December, 2016. As an initial treatment, all patients received post-operative whole pelvic irradiation of 45-50.4 Gy in 25-28 fractions. For vaginal recurrence, all patients were treated with ISBT alone at a dose of 38-42 Gy in 6-7 fractions for clinical target volumes (CTVs) for 3-4 days. RESULTS: Post-operative pelvic irradiation was delivered to five and one patients, using a three-dimensional conformal technique and intensity-modulated radiotherapy, respectively. Median duration from surgery to vaginal recurrence was 25.7 months. Median tumor size just before ISBT was 3.3 cm. Median time from completion of pelvic irradiation to ISBT initiation was 24.1 months. Mean doses per fraction of ISBT for CTV D90 (the minimum dose received by 90% of CTV) and minimum dose received by 2cc (D2cc) for the bladder and for rectum were 6.1 Gy, 4.4 Gy, and 3.8 Gy, respectively. Mean total equivalent dose in 2 Gy fractions (EQD2), including external beam radiotherapy and ISBT, for D2cc for the bladder, sigmoid, and rectum were 92.1 Gy, 50.4 Gy, and 81.6 Gy, respectively. Median follow-up duration was 53.3 months. Local recurrence was observed in two patients, and four of the six patients were alive. Grade 2 late rectal complications occurred in two patients, and no late grade ≥ 3 complications were observed in four alive patients. CONCLUSIONS: Re-irradiation with ISBT may be an effective treatment strategy for gynecological cancer patients with vaginal recurrence after post-operative pelvic irradiation.

Safety of biliary stent placement followed by definitive chemoradiotherapy in patients with pancreatic cancer with bile duct obstruction.

BACKGROUND: Although patients with malignant bile duct obstruction due to pancreatic cancer are often initially treated with biliary stent placement, concurrent chemoradiotherapy with stents poses a potential risk of increased toxicity. This retrospective study aimed to evaluate the safety of biliary stent placement followed by definitive concurrent chemoradiotherapy in patients with pancreatic cancer. METHODS: Patients with pancreatic cancer who underwent either a plastic stent or a self-expanding metallic stent placement for malignant bile duct obstruction before definitive concurrent chemoradiotherapy were retrospectively reviewed. Radiotherapy was delivered in 1.8 Gy per fraction to a total dose of 50.4 Gy. Gemcitabine, TS-1 plus Gemcitabine, or TS-1 was the concurrent chemotherapy/regimen. The primary endpoint was the rate of biliary stent-related toxicities, defined as biliary bleeding, duodenal perforation, or bile duct perforation. RESULTS: Thirty patients were included. Plastic stents were placed in 23 patients and self-expanding metallic stent in seven patients at the start of irradiation. The median follow-up time was 20 (range, 2-63) months, and 27 patients (90%) completed concurrent chemoradiotherapy. Biliary stent-related toxicity (grade 3 biliary bleeding) was confirmed in one patient (3%) with a plastic stent 9 months after concurrent chemoradiotherapy. The median duration of locoregional control, progression-free survival, and overall survival were 31.1, 7.3, and 10.5 months, respectively. CONCLUSIONS: Stent placement followed by concurrent chemoradiotherapy was not associated with an apparent increase in toxicity and may be an appropriate treatment for patients with locally advanced pancreatic head cancer with bile duct obstruction.

Hypofractionated Proton Beam Therapy for cT1-2N0M0 Non-small Cell Lung Cancer Patients With Interstitial Lung Disease.

BACKGROUND/AIM: To evaluate the outcomes of proton beam therapy (PBT) for early-stage non-small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD). PATIENTS AND METHODS: Between 2002 and 2017, 110 patients receiving hypofractionated PBT for cT1-2N0M0 NSCLC were reviewed. RESULTS: Of the 110 patients, 17 were diagnosed with ILD. The median follow-up period was 37.8 months. No significant difference in the 1-year cumulative rate of grade ≥2 pneumonitis was observed between patients with and those without ILD (17.6% vs. 14.1%, p=0.708). The lung doses were significantly lower in patients with than in those without ILD among patients without grade ≥2 pneumonitis. There were no significant differences in overall survival or local recurrence-free rates according to the presence of ILD. CONCLUSION: PBT appears to be a feasible and effective treatment for cT1-2N0M0 NSCLC in patients with ILD, but the lung dose should be strictly reduced.

Risk factors for venous thromboembolism induced by prolonged bed rest during interstitial brachytherapy for gynecological cancer: a retrospective study.

BACKGROUND: Screening and management of venous thromboembolism (VTE) after surgery is important in preventing sublethal VTE. However, the risk factors for VTE during interstitial brachytherapy (ISBT) remain unknown, and appropriate screening and management strategies are yet to be established. Therefore, this study aimed to evaluate the risk factors for VTE resulting from requisite bed rest during ISBT for gynecologic cancers. METHODS: We retrospectively analyzed 47 patients. For patients without definitive preceding radiotherapy, whole pelvic irradiation (30-50 Gy) followed by ISBT of 12-30 Gy/2-5 fx/1-3 days was administered to CTV D90. For patients with preceding radiotherapy, 36-42 Gy/6-7 fx/3-4 days was delivered by ISBT alone. The supine position was required during ISBT. D-dimer (DD) was measured at initial presentation, 1 week before ISBT, pre-ISBT, on the day of, and the day following needle removal. Patients were divided into three groups according to the risk of VTE and were managed accordingly; Group 1: DD was not detected (negative) before ISBT, Group 2: VTE was not detected on venous ultrasound imaging, although DD was positive before ISBT, and Group 3: VTE was detected (positive) before ISBT. An intermittent pneumatic compression device was used during ISBT; for the patients without VTE before ISBT. Heparin or oral anticoagulants were administered to patients with VTE before ISBT. RESULTS: Overall, the median values of DD pre-ISBT, on the day of, and on the day following needle removal were 1.0 (0.4-5.8), 1.1 (0.5-88.9), and 1.5 (0.7-40.6) µg/mL, respectively. After ISBT, no patients had deep vein thrombosis (DVT) in groups 1 and 2. In group 3, 7 of 14 patients experienced worsening of VTE but remained asymptomatic. In univariate analysis, DVT diagnosed before ISBT, Caprini score ≥ 7, and difference in DD values between pre-ISBT and the day of or the day following needle removal ≥ 1 were associated with the incidence or worsening of VTE. CONCLUSION: DD should be measured before and after ISBT to detect the incidence or worsening of VTE in patients with DVT. The Caprini score may help in the prediction of VTE during or after ISBT.

Impact of pre-brachytherapy magnetic resonance imaging on dose-volume histogram of locally advanced cervical cancer patients treated with radiotherapy including high-dose-rate brachytherapy.

PURPOSE: This study investigated the suitability of brachytherapy technique selection based on pre-brachytherapy magnetic resonance imaging (MRI) findings in cervical cancer by evaluating dose-volume histogram parameters. MATERIAL AND METHODS: We retrospectively evaluated data from 61 patients with cervical cancer who underwent pre-brachytherapy MRI within 7 days before their first high-dose-rate brachytherapy treatment, selected according to pre-brachytherapy MRI findings. Combined intracavitary brachytherapy with interstitial techniques (IC/ISBT) or interstitial brachytherapy (ISBT) were favored treatments for poor-responding tumors after concurrent chemoradiotherapy, asymmetrical tumors, bulky parametrial extensions, bulky primary disease, and extensive paravaginal or distal vaginal involvement. Intracavitary brachytherapy (ICBT) was the preferred treatment for small tumors without extensive involvement of the vagina and parametrium. RESULTS: The median tumor size was 58 mm on pre-treatment MRI and 38 mm on pre-brachytherapy MRI. On pre-brachytherapy MRI, 13 patients had a tumor with severe vaginal invasion, 15 patients presented with an asymmetrical bulky tumor, and 4 patients had bulky residual tumors. IC/ISBT or ISBT were administered to 26 patients (43%). Median equivalent dose in 2 Gy fractions of clinical target volume D90 was 70.8 Gy for all patients. Median clinical target volume D90 in each brachytherapy session exceeded the prescribed dose in both patients treated with ICBT and IC/ISBT or ISBT. Median equivalent dose in 2 Gy fractions of D2cc to the bladder, sigmoid colon, and rectum was 69.5, 52.0, and 58.4 Gy, respectively. All cases remained within the doses recommended for organs at risk. CONCLUSIONS: Pre-brachytherapy MRI may be helpful in selecting suitable candidates for each type of brachytherapy and deliver the recommended doses to the tumor and organs at risk, particularly in cases with large tumors, poor response to concurrent chemoradiotherapy, asymmetrical tumors, severe vaginal invasion, extensive parametrial invasion, and/or corpus invasion.

Selection Criteria and Clinical Outcomes of Patients With Asymmetrical Cervical Cancer Treated With Various High-dose-rate Brachytherapy Techniques.

BACKGROUND/AIM: We aimed to evaluate the efficacy of high-dose-rate brachytherapy techniques selected according to pre-brachytherapy magnetic resonance imaging (MRI) findings in asymmetrical cervical cancer (ACC). PATIENTS AND METHODS: We analyzed 33 ACC patients. Asymmetric tumors were defined as those in which the difference between the distance from the cervical canal to the farthest end of the tumor [long distance (LD)] and the distance from the cervical canal to the contralateral tumor edge [short distance (SD)] is equal to or greater than 2 cm on the basis of MRI prior to treatment. On pre-treatment and pre-brachytherapy MRI, the median LDs were 40 mm and 21 mm, respectively. Patients with LD≥2 cm and LD - SD≥1 cm on pre-brachytherapy MRI received non-conventional intracavitary brachytherapy (ICBT). RESULTS: Sixteen patients (48%) received non-conventional ICBT. There was no significant difference in 3-year local control between the two treatment groups (100% vs. 81.2%, p=0.07); two patients had grade 2 radiation proctitis. CONCLUSION: Brachytherapy techniques selected according to pre-brachytherapy MRI findings were effective for ACC treatment.

Concurrent chemoradiotherapy using proton beams for unresectable locally advanced pancreatic cancer.

BACKGROUND AND PURPOSE: We investigated clinical outcomes of proton beam concurrent chemoradiotherapy (CCRT) for unresectable, locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: Records from 42 unresectable LAPC patients (21 male and 21 female, 39-83 years old) with IIB/III clinical staging of 1/41 treated by proton beam CCRT were retrospectively reviewed. Twelve patients received a conventional 50 Gray equivalents (GyE) in 25 fractions protocol and 30 others received a higher dose protocol of 54.0-67.5 GyE in 25-33 fractions. Gemcitabine or S-1 (Tegafur, Gimeracil and Oteracil) was used concurrently. Toxicity, overall survival (OS) and local control (LC) were examined. RESULTS: Acute adverse events of grades 1, 2, 3 and 4 were found in 4, 15, 17 and 2 patients, respectively. All grade 3 and 4 events were hematologic. Late adverse events of grades 1 and 2 were found in 3 and 2 patients, respectively. No late adverse effects of grade 3 or higher were observed. The 1-year/2-year OS rates from the start of CCRT were 77.8/50.8% with median survival time (MST) of 25.6 months. The 1-year/2-year LC rate from CCRT start was 83.3/78.9% with a median time to local recurrence of more than 36 months. Total irradiation dose was the only significant factor in univariate analyses of OS and LC (p = 0.015 and 0.023, respectively). CONCLUSION: Proton beam CCRT lengthened survival periods compared to previous photon CCRT data and higher dose irradiation prolonged LC and OS for unresectable LAPC patients. Proton beam therapy is therefore safe and effective in these cases.

Normal liver tissue change after proton beam therapy.

PURPOSE: Normal liver tissue changes after proton beam therapy (PBT) were investigated in patients at 1 and 2 years after the therapy. MATERIALS AND METHODS: Changes in normal liver tissue volume were examined. The dose distribution of the normal liver tissue was also simulated on the follow-up CTs. RESULTS: The normal liver tissue volume was 1149 ± 215 cm3 before treatment, 1089 ± 188 cm3 at 1 year, and 1080 ± 236 cm3 at 2 years after treatment. The normal liver tissue volume was increased in 10 and decreased in 20 patients at 2 years and was smaller than that before the treatment in total (P = 0.03). The simulated volume that received more than 30 Gray equivalent [V30 (cm3)] at 1 year was 258 ± 187 cm3 and that at 2 years (244 ± 171 cm3) was smaller than that before treatment (297 ± 140 cm3) (P = 0.03). CONCLUSIONS: The changes in the shape and volume of normal liver tissue are not constant, which cause a large dose distribution discrepancy in the normal liver for 2 years. Therefore, careful consideration of the dose distribution of normal liver tissue is required when planning re-irradiation.

A Clinical Evaluation of American Brachytherapy Society Consensus Guideline for Bulky Vaginal Mass in Gynecological Cancer.

OBJECTIVES: American Brachytherapy Society (ABS)-recommended interstitial brachytherapy (IBT) should be considered for bulky vaginal tumor thicker than 5 mm. The aim of this study was to evaluate the ABS consensus guideline for patients with severe vaginal invasion based on our long-term follow-up results. METHODS/MATERIALS: The study included 7 patients with vaginal cancer and 14 patients with cervical cancer invading to the lower vagina. Based on prebrachytherapy magnetic resonance imaging findings, patients received intracavitary brachytherapy (ICT) for vaginal tumors 5 mm or less or IBT for vaginal tumors less than 5 mm. Nine patients received ICT and the remaining 12 patients received IBT. For dosimetric comparison, an experimental recalculation as the virtual IBT for patients actually treated by ICT, and vice versa, was performed. RESULTS: The 5-year local control rate for all tumors was 89.4%. No differences in local control between ICT- and IBT-treated groups were observed (P = 0.21). One patient experienced a grade 3 rectal complication. There were no significant differences in the CTV D90 and rectum D2cc between the 2 groups (P = 0.13 and 0.39, respectively). In the dosimetric study of ICT-treated patients, neither the actual ICT plans nor the experimental IBT plans exceeded the limited dose for organs at risk, which were recommended in the guideline published from the ABS. In the IBT-treated patients, D2cc for bladder and rectum of the experimental ICT plans was significantly higher than for the actual IBT plans (P < 0.001 and <0.001, respectively), and 11 experimental ICT plans (92%) exceeded the limited dose for bladder and/or rectum D2cc. CONCLUSIONS: Tumor control and toxicity after selected brachytherapy according to vaginal tumor thickness were satisfactory; IBT instead of ICT is recommended for patients with vaginal tumor thickness greater than 5 mm to maintain bladder and/or rectum D2cc.

Impact of visual feedback on dose-volume histograms for organs at risk in postoperative radiotherapy with deep inspiration breath-holding for patients treated with breast-conserving therapy: a planning study.

BACKGROUND: We evaluated the effectiveness of visual feedback (VF) on radiotherapy with deep inspiration breath-holding (DIBH), and reviewed the dose for organs at risk (OARs). METHODS: Respiratory motions during DIBH for 15 s were monitored during planning computed tomography (CT)-scanning and simulation for 40 patients after breast-conserving surgery from June 2007 to February 2008. For 22 of 40 patients, a goggle-type liquid crystal display monitor was used for VF. The opposing tangential field was planned. The prescribed dose was 50.0 Gy in 25 fractions. RESULTS: The mean differences of the chest wall respiratory movement in DIBH between planning CT-scanning and simulation were 4.7 ± 2.6 mm for the patients without VF and 1.0 ± 0.9 mm for those with VF (p < 0.01). The mean chest wall excursion as a whole in DIBH using VF (2.0 ± 1.0 mm) was smaller than in those without VF (4.1 ± 2.4 mm) (p < 0.01). According to reproducibility and stability parameters, 4 mm was added as a posterior margin to the clinical target volume for RT with VF, and 10 mm for those without VF. The mean heart doses were 1.3 ± 0.5 Gy with VF and 2.4 ± 1.1 Gy without VF (p < 0.01). Mean dose and max dose of right breast were significantly reduced in procedures with VF use vs. in those without VF (p < 0.01 and < 0.01, respectively). CONCLUSIONS: VF increases the accuracy of postoperative radiotherapy with DIBH, and also helps reduce the dose for OARs.

Simulation study of dosimetric effect in proton beam therapy using concomitant boost technique for unresectable pancreatic cancers.

PURPOSE: The purpose of this study is to investigate the dose distribution of proton beam therapy (PBT) using a concomitant boost technique for unresectable pancreatic cancers. MATERIALS AND METHODS: This simulation study involved 36 patients with unresectable pancreatic cancer. The irradiation dose was set as 67.5 gray equivalent (GyE) with 25 fractions using concomitant boost technique. The irradiation dose was set as 50 GyE to cover the whole target and another posterior beam of 17.5 GyE was added to ensure that 10% isodose line was not delivered to the gastrointestinal (GI) tract. Dose distribution of the gross tumor volume and GI tract was examined. RESULTS: V55GyE, 60GyE, 65GyE were 80.8, 66.5, and 42.4%, respectively, and mean dose was 64.1 GyE in all patients. The distance from the GI tract showed significant difference in dose distribution (P = 0.002 in V55GyE, 0.0009 in V60GyE, 0.003 in V65GyE, and 0.02 in mean dose, respectively). Location, tumor diameter, or lymph nodes metastasis did not show any difference. CONCLUSIONS: We found that irradiated dose is closely related to the distance from the GI tract. Clinically, this protocol is expected to have outstanding effects on local control of tumors compared to conventional PBT.

Acute and late complications after hypofractionated intensity modulated radiotherapy in prostate cancer.

PURPOSE: The present study compared the complications associated with hypofractionated intensity-modulated radiation therapy (Hypo-IMRT) of prostate cancer to conventionally fractionated IMRT (Conv-IMRT). MATERIALS AND METHODS: Hypo-IMRT delivered 70 Gy in 28 fractions, whereas Conv-IMRT delivered 78 Gy in 39 fractions. Toxicity was graded with the Common Terminology Criteria for Adverse Events, version 4.0, weekly during radiotherapy, 1 month after radiotherapy, and annually in both patient groups. RESULTS: The median follow-ups were 39.1 and 38.7 months for patients in the Hypo- and Conv-IMRT groups, respectively. There was no significant difference in rates of acute and late adverse events. The proportions of grade 2 acute genitourinary complications were 48.4 and 51.2% in the Hypo- and Conv-IMRT groups, respectively. The presence of a baseline International Prostate Symptom Score (IPSS) of ten or more was the only significant prognostic factor for grade 2 acute genitourinary toxicity. The incidence of grade 2 late rectal hemorrhage at 3 years was 3.2 and 3.5% in the Hypo- and Conv-IMRT groups, respectively. Small rectal volume was significantly associated with grade 2 late rectal hemorrhage. CONCLUSION: Regarding acute and late adverse events, hypofractionated IMRT for prostate cancer was well tolerated and comparable with conventionally fractionated IMRT. Clinical trial registration no. UMIN000003218.