Exploring predictive molecules of acute adverse events in response to volumetric­modulated arc therapy for prostate cancer using urinary metabolites.

Volumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.

Long-Term Survival of a Patient With Anaplastic Thyroid Carcinoma Treated With Hypofractionated Radiotherapy: A Case Report.

Anaplastic thyroid carcinoma, a rare type of primary thyroid cancer, is one of the most aggressive neoplasms with a poor prognosis. Many cases are in the advanced stage at the time of the initial visit, and curative treatment is impossible. Because of the highly radioresistant nature of anaplastic thyroid carcinoma, this condition cannot be properly controlled with conventional radiotherapy. Herein, we report the case of a patient with anaplastic thyroid carcinoma who underwent hypofractionated radiotherapy, attained a complete response, and is still alive more than 10 years after treatment with no evidence of disease. To overcome the high radioresistance of anaplastic thyroid carcinoma, we administered 50 Gy in 10 fractions three times a week. Furthermore, we administered paclitaxel and carboplatin sequentially before and after radiotherapy. Consequently, the patient completed treatment and reached a complete response. He is still alive more than 10 years after treatment with no evidence of disease or severe adverse events. Hypofractionated radiation therapy may provide good control of locally advanced anaplastic thyroid carcinoma.

Investigation of the efficacy of the change ratio of brain natriuretic peptide for predicting the cardiac effects of chemoradiotherapy on esophageal cancer.

The aim of this study was to investigate the effectiveness of brain natriuretic peptide (BNP) as a predictor of radiological effects on the heart. A total of 41 patients with esophageal cancer who underwent chemoradiotherapy (CRT) were retrospectively investigated. The BNP levels were measured on the first day of CRT (pre-CRT) and the last day of CRT (post-CRT), and the median concentration of BNP and dosimetric parameters of the heart were calculated. The change ratio of BNP was calculated as follows: [(BNP post-CRT) - (BNP pre-CRT)]/(BNP pre-CRT). The comparison of BNP pre-CRT with post-CRT was performed using a Wilcoxon signed-rank test. The relationship between dosimetric parameters and change ratio was analyzed using Spearman's correlation coefficient. The median levels of BNP of pre-CRT and post-CRT were 10 and 22 pg/ml, respectively, and the difference was statistically significant (P<0.0001). Significant correlations (all P<0.05) were observed between the change ratio and mean dose, V5, V10, V20, and V30. Of the cohort, 14 patients developed acute-to-subacute cardiac events, such as pericardial effusion, cardiomegaly, acute exacerbation of chronic heart failure, and a decreased ejection fraction. The change ratios of BNP, V5, V10, V20, and V30 were significantly higher in patients who experienced cardiac events compared with those who did not. The results of this study showed that BNP measurement, particularly the change ratio of BNP pre- and post-CRT, may be a useful cardiac event predictor in addition to dosimetric parameters.

Effects of six-cycle completion and earlier use of radium-223 therapy on prognosis for metastatic castration-resistant prostate cancer: A real-world multicenter retrospective study.

OBJECTIVES: To evaluate the effect of 6-cycle completion and earlier use of radium-233 dichloride (Ra223) on the prognosis of patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We retrospectively evaluated 75 patients with bone metastases-predominant mCRPC who were treated with Ra223 between August 2016 and August 2021. The primary purpose of the study was to assess the effect of Ra223 completion (6 cycles) on patient prognosis, and the secondary purpose was to investigate factors associated with Ra223 incompletion (fewer than 6 cycles) and overall survival. RESULTS: The median age of the patients was 72 years. The median number of Ra223 administrations was 6 (interquartile range, 5-6), and the median Ra223 completion rate was 75%. The median time from mCRPC diagnosis to Ra223 administration was 17 months, and the median number of prior treatments was 2. Multivariable analysis indicated that unfavorable performance status (>0), prostate-specific antigen (PSA) level >10 ng/ml, extension of bone metastasis score 3 to 4, and Ra223 incompletion were significantly associated with poor overall survival. In addition, EOD 3 to 4 and 3 or more prior CRPC treatments were significantly associated with Ra223 incompletion. CONCLUSION: Six-cycle completion and earlier administration of Ra233 are potentially associated with favorable survival. Unfavorable factors (EOD 3-4 and ≥3 prior treatments) were significantly associated with Ra223 incompletion.

Impact of low iodine density tumor area ratio on the local control of non-small cell lung cancer through stereotactic body radiotherapy.

Lung cancer with low average iodine density measured via contrast-enhanced computed tomography (CT) using dual-energy CT technology has shown a reduced local control rate after stereotactic body radiotherapy (SBRT). The current study therefore investigated the relationship between low iodine density tumor area and its ratio and local recurrence after SBRT. Dual-energy CT was performed on the day before SBRT initiation, with a low iodine density tumor area being defined as that with an iodine density of <1.81 mg cm-3. The low iodine density tumor area, the ratio between the low iodine density tumor area and the entire tumor, and the local recurrence rate were then determined. No correlation was observed between the low iodine density tumor area and the local recurrence rate. However, tumors with a large low iodine density tumor area ratio showed an increased local recurrence rate, with the prognostic accuracy almost similar to that in previous studies using average iodine densities. Our results therefore suggest that the low iodine density tumor area ratio was a useful prognostic index after SBRT, with an accuracy comparable with that of the average iodine density.

A Phase I/II Study of Biweekly Carboplatin and Nab-paclitaxel With Concurrent Radiotherapy for Patients With Locally Advanced Unresectable Stage III Non-small-cell Lung Cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small-cell lung cell cancer (LA-NSCLC). We conducted a phase I/II study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with radiotherapy (RT). MATERIALS AND METHODS: In the phase I part, patients with inoperable stage IIIA/IIIB NSCLC were treated with carboplatin (area under the time-concentration curve, 4) and nab-PTX (60-100 mg/m2) on days 1, 15, and 29. Thoracic RT was administered from day 1 to a total dose of 60 Gy in 30 fractions. In the phase II part, patients were administered carboplatin and nab-PTX on days 1, 15, and 29 at the recommended dose (RD). The primary endpoint of the phase I part was to determine the maximum tolerated dose and the RD. In the phase II part, the primary endpoint was 2-year overall survival (OS) rate, and secondary endpoints were the objective response rate, progression-free survival, OS, and safety profile. RESULTS: In the phase I part, although maximum tolerated dose was not obtained, the RD was carboplatin (area under the time-concentration curve, 4) and nab-PTX (100 mg/m2). Of the evaluable 28 patients, the rate of 2-year OS was 67.8% (95% confidence interval, 49.3%-82.1%). The objective response rate was 96.4%, and the median follow-up time was 33.2 months. The median progression-free survival was 18.2 months (95% confidence interval, 13.1 months to not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.2%), and pneumonitis (3.6%). CONCLUSIONS: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT was well-tolerated and exerted promising antitumor activity.

Leptomeningeal Metastases in a Patient with Castration-Resistant Prostate Cancer.

A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5 + 4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.

What motivated medical students and residents to become radiation oncologists in Japan?-Questionnaire report by the radiotherapy promotion committee of JASTRO.

This study aimed to clarify the motivations and timing of the decision to become radiation oncologists. MATERIALS AND METHODS: We conducted an online survey for new members of the Japanese Society for Radiation Oncology (JASTRO). RESULTS: The response rate was 43.3%. Data of the 79 respondents who wanted to obtain a board-certification of JASTRO were analysed. We divided the respondents into two groups: Group A, those who entered a single radiation oncology department, and Group B, those who joined a radiology department in which the radiation oncology department and diagnostic radiology department were integrated. The most common period when respondents were most attracted to radiation oncology was "5th year of university" in Group A and "2nd year of junior residency" and "senior residency" in Group B. Furthermore, 79.5% of Group A and 40% of Group B chose periods before graduation from a university with a significant difference. The most common period when respondents made up their minds to become radiation oncologists was "2nd year of junior residency" in both groups. Internal medicine was the most common department to consider if they did not join the radiation oncology or radiology department. CONCLUSION: To increase the radiation oncologists, it is crucial to enhance clinical training in the fifth year of university for Group A and to continue an active approach to maintain interest in radiation oncology until the end of junior residency. In Group B facilities, it is desirable to provide undergraduates more opportunities to come in contact with radiation oncology.

Proton Beam Therapy for Locally Recurrent Parotid Gland Cancer.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5-8 weeks). The median follow-up was 24 months (range 10-49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3-5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

The potential failure risk of the cone-beam computed tomography-based planning target volume margin definition for prostate image-guided radiotherapy based on a prospective single-institutional hybrid analysis.

BACKGROUND: The purpose of this study was to evaluate the impact of markerless on-board kilovoltage (kV) cone-beam computed tomography (CBCT)-based positioning uncertainty on determination of the planning target volume (PTV) margin by comparison with kV on-board imaging (OBI) with gold fiducial markers (FMs), and to validate a methodology for the evaluation of PTV margins for markerless kV-CBCT in prostate image-guided radiotherapy (IGRT). METHODS: A total of 1177 pre- and 1177 post-treatment kV-OBI and 1177 pre- and 206 post-treatment kV-CBCT images were analyzed in 25 patients who received prostate IGRT with daily localization by implanted FMs. Intrafractional motion of the prostate was evaluated between each pre- and post-treatment image with these two different techniques. The differences in prostate deviations and intrafractional motions between matching by FM in kV-OBI (OBI-FM) and matching by soft tissues in kV-CBCT (CBCT-ST) were compared by Bland-Altman limits of agreement. Compensated PTV margins were determined and compensated by references. RESULTS: Mean differences between OBI-FM and CBCT-ST in the anterior to posterior (AP), superior to inferior (SI), and left to right (LR) directions were - 0.43 ± 1.45, - 0.09 ± 1.65, and - 0.12 ± 0.80 mm, respectively, with R2 = 0.85, 0.88, and 0.83, respectively. Intrafractional motions obtained from CBCT-ST were 0.00 ± 1.46, 0.02 ± 1.49, and 0.15 ± 0.64 mm, respectively, which were smaller than the results from OBI-FM, with 0.43 ± 1.90, 0.12 ± 1.98, and 0.26 ± 0.80 mm, respectively, with R2 = 0.42, 0.33, and 0.16, respectively. Bland-Altman analysis showed a significant proportional bias. PTV margins of 1.5 mm, 1.4 mm, and 0.9 mm for CBCT-ST were calculated from the values of CBCT-ST, which were also smaller than the values of 3.15 mm, 3.66 mm, and 1.60 mm from OBI-FM. The practical PTV margin for CBCT-ST was compensated with the values from OBI-FM as 4.1 mm, 4.8 mm, and 2.2 mm. CONCLUSIONS: PTV margins calculated from CBCT-ST might be underestimated compared to the true PTV margins. To determine a reliable CBCT-ST-based PTV margin, at least the systemic error Σ and the random error σ for on-line matching errors need to be investigated by supportive preliminary FM evaluation at least once.

Analysis of the relationship between prescribed dose and dosimetric advantage of real-time intraoperatively built custom-linked seeds in iodine-125 prostate brachytherapy.

BACKGROUND: The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. METHODS: We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. RESULTS: The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. CONCLUSIONS: Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone.

Safe and successful birth following pelvic radiotherapy for rectal mucosa-associated lymphoid tissue lymphoma: a case report.

BACKGROUND: Mucosa-associated lymphoid tissue lymphomas can occur in various parts of the body, and half of mucosa-associated lymphoid tissue lymphomas occur in the gastrointestinal tract. Gastric mucosa-associated lymphoid tissue lymphoma is the most common lymphoma of the gastrointestinal tract and primary rectal mucosa-associated lymphoid tissue lymphoma is very rare. Because of the high radiosensitivity of mucosa-associated lymphoid tissue lymphomas, this condition can be controlled with radiotherapy of approximately 30 Gy alone. However, ovarian dysfunction as an adverse event of radiotherapy for pelvic lesions can become a problem in girls and women. We report a case of a 28-year-old woman with rectal mucosa-associated lymphoid tissue lymphoma who safely gave birth to a baby following 30.6 Gy radiotherapy to her whole rectum. CASE PRESENTATION: A 28-year-old Japanese woman became aware of bloody stools and was diagnosed as having Lugano I rectal mucosa-associated lymphoid tissue lymphoma. She was referred to our institute and initiated on radiotherapy. However, she expressed a desire to bear children. We used horizontally opposed pair fields for radiotherapy to minimize the irradiation to her endometrium and ovary. A total dose of 30.6 Gy was given in 17 fractions of 1.8 Gy by 10-Megavolt X-ray linear accelerator. As a result, one-third of her uterus and half of her ovary were outside the irradiation field. After approximately 1 year of treatment, positive pregnancy was confirmed and finally she safely gave birth to a baby girl without congenital abnormalities. CONCLUSIONS: This report provides hope for girls and women who have undergone irradiation for pelvic mucosa-associated lymphoid tissue lymphomas and who desire to bear children.

Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer.

AIM: The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. METHODS: Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. RESULTS: For all patients, the median follow-up was 25 months (range, 3-77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. CONCLUSION: Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.

The retrospective analysis of the relationship between prescribed dose and risk factor for seed migration in iodine-125 prostate brachytherapy.

PURPOSE: The aim was to determine the dose-specific incidence and predictors of seed loss/migration after permanent seed implantation (PI) for localized prostate cancer. MATERIALS AND METHODS: The records of 79 patients with T1c-T3a prostate cancer who underwent prostate brachytherapy with loose iodine-125 seeds were retrospectively reviewed. Of these patients, 33 with low or intermediate risk underwent PI with the prescribed dose of 160 Gy for the clinical target volume (CTV), and 46 with high risk underwent PI with 110 Gy for the CTV followed by external beam radiotherapy (EBRT) with 45 Gy. Each CTV was defined as a contoured prostate. After PI, the incidence of seed loss/migration was assessed by a series of radiographs. RESULTS: Seed migration occurred in 22 (0.479 %) of 4589 implanted seeds 1 month after implantation. In PI alone, the number of needles (P = 0.081) and the number of seeds (P = 0.071) showed a trend for a difference between those with and without seed loss. In PI + EBRT, there was a significant difference in the discrepancy between the seed numbers calculated by the nomogram and actually implanted (P = 0.032). CONCLUSIONS: It is suggested that the discrepancy in seed numbers might be the predictor for seed migration in PI with 110 Gy.

Impact of pretreatment whole-tumor perfusion computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography measurements on local control of non-small cell lung cancer treated with stereotactic body radiotherapy.

This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan-Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18-45.31) (100 µg/cm3) and 3.2 (range, 0.7-17.6), respectively. No correlation was observed between AID and SUVmax Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4-100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results.

The clinical results of proton beam therapy in patients with idiopathic pulmonary fibrosis: a single center experience.

BACKGROUND: The purpose of this study is to retrospectively evaluate the incidence of lung toxicities after proton beam therapy (PBT) in patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients diagnosed with primary lung cancer or lung metastasis who were treated with PBT between January 2009 and May 2015 were recruited from our database retrospectively. Cases of pneumonitis (excluding infection-related pneumonitis) were evaluated using the Common Terminology Criteria for Adverse Events version 4.0, and the Fletcher-Hugh-Jones classification of respiratory status was used to evaluate pretreatment and posttreatment respiratory function. RESULTS: Sixteen IPF patients received PBT for lung tumors, 15 received PBT for primary lung cancer, and one patient received PBT for metastasis from lung cancer. The cohort was composed of 14 men and 2 women, with a median age of 76 years (range: 63-89 years). The median follow-up time was 12 months (range: 4-39 months). The median dose of PBT was 80.0 Gy relative biological dose effectiveness (RBE) (range: 66.0-86.4 Gy [RBE]). The cumulative incidence of pneumonitis was 19.8 % (95 % confidence interval [CI]: 0-40.0 %), including one case of grade 5 pneumonitis. Reduced respiratory function was observed after PBT in seven patients, including one patient with pleural dissemination; five of these patients required home oxygen therapy. CONCLUSIONS: This study suggests that PBT can be performed more safely in IPF patients than surgery or X-ray irradiation. Although PBT has become a treatment choice for lung tumors of patients with IPF, the adverse events warrant serious attention.

Retrograde intra-arterial chemotherapy and daily concurrent proton beam therapy for recurrent oral cavity squamous cell carcinoma: Analysis of therapeutic results in 46 cases.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC). METHODS: Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6-74.8 GyE in 13-34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30-50 mg/body/week; docetaxel, 5-25 mg/body/week). RESULTS: One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively. CONCLUSION: These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38:1145-1151, 2016.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

BACKGROUND: The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. MATERIALS AND METHODS: Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. RESULTS: The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. CONCLUSION: High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer.

Clinical outcome of stereotactic body radiotherapy for primary and oligometastatic lung tumors: a single institutional study with almost uniform dose with different five treatment schedules.

BACKGROUND: To evaluate clinical outcomes of stereotactic body radiotherapy (SBRT) for localized primary and oligometastatic lung tumors by assessing efficacy and safety of 5 regimens of varying fraction size and number. METHODS: One-hundred patients with primary lung cancer (n = 69) or oligometastatic lung tumors (n = 31), who underwent SBRT between May 2003 and August 2010, were included. The median age was 75 years (range, 45-88). Of them, 98 were judged to have medically inoperable disease, predominantly due to chronic illness or advanced age. SBRT was performed using 3 coplanar and 3 non-coplanar fixed beams with a standard linear accelerator. Fraction sizes were escalated by 1 Gy, and number of fractions given was decreased by 1 for every 20 included patients. Total target doses were between 50 and 56 Gy, administered as 5-9 fractions. The prescribed dose was defined at the isocenter, and median overall treatment duration was 10 days (range, 5-22). RESULTS: The median follow-up was 51.1 months for survivors. The 3-year local recurrence rates for primary lung cancer and oligometastasis was 6 % and 3 %, respectively. The 3-year local recurrence rates for tumor sizes ≤3 cm and >3 cm were 3 % and 14 %, respectively (p = 0.124). Additionally, other factors (fraction size, total target dose, and BED10) were not significant predictors of local control. Radiation pneumonia (≥ grade 2) was observed in 2 patients. Radiation-induced rib fractures were observed in 22 patients. Other late adverse events of greater than grade 2 were not observed. CONCLUSION: Within this dataset, we did not observe a dose response in BED10 values between 86.4 and 102.6 Gy. SBRT with doses between 50 and 56 Gy, administered over 5-9 fractions achieved acceptable tumor control without severe complications.

Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy.

The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.