Protective Effect of Polaprezinc and Hyperbaric Oxygen Therapy on Radiation-induced Small Intestinal Damage in Mice.

BACKGROUND/AIM: To investigate the effect of polaprezinc (antioxidant) administration and hyperbaric oxygen therapy on radiation-induced intestinal injury. MATERIALS AND METHODS: Forty-five C57BL/6J mice underwent total body radiation of 2 Gy. Polaprezinc was given in 12 mice, hyperbaric oxygen in 12 mice, and both in 12 mice. The other 9 mice did not undergo any treatment. Mice were sacrificed 2, 4, and 6 h after radiation, and 9 specimens (3 each from the duodenum, jejunum, and ileum) were harvested. Apoptotic intestinal crypt cells were histologically evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: Apoptotic cell number per 1,000 crypt cells was 31.0±6.7 at 2 h, 28.4±5.2 at 4 h, and 32.9±5.1 at 6 h in the mice group treated by radiation alone. Both polaprezinc administration and hyperbaric oxygen therapy significantly suppressed apoptosis. Although the effect of polaprezinc administration on suppressing apoptosis became less over time (4.9±5.7 and 19.4±13.2 at 2 and 6 h, respectively), that of hyperbaric oxygen therapy was stable regardless of time (23.6±4.8 and 25.8±4.1 at 2 and 6 h). Administration of both polaprezinc and hyperbaric oxygen showed a significant synergetic or additive effect on suppressing apoptosis at 6 h (11.4±10.5, p<0.0035 vs. polaprezinc, p<0.0001 vs. hyperbaric oxygen). CONCLUSION: Both polaprezinc administration and hyperbaric oxygen therapy are effective in relieving radiation-induced small intestinal damage, and a synergistic or additive effect is expected when using both.

Proton Therapy for Localized Prostate Cancer: Long-Term Results From a Single-Center Experience.

PURPOSE: Although proton therapy is controversial, it has been used to treat localized prostate cancer over the past 2 decades. The purpose of this study is to examine the long-term efficacy and toxicity of proton therapy for localized prostate cancer. METHODS AND MATERIALS: This was a retrospective observational study of 2021 patients from 2003 to 2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and 6% of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated using the Kaplan-Meier method and were analyzed using multivariable Cox proportional hazards models. RESULTS: The median follow-up period was 84 months (interquartile range, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100% and 100%, 99% and 88%, 93% and 86%, 90% and 79%, 88% and 68%, and 76% and 63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high-risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. The results of multivariable analyses indicate that younger patients more often experienced biochemical relapse. CONCLUSIONS: This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that accounts for the patient's age.

Treatment outcomes of proton or carbon ion therapy for skull base chordoma: a retrospective study.

BACKGROUND: The usefulness of particle therapy for skull base chordoma has not been established. The aim of this retrospective study was to analyse the treatment outcomes of proton therapy (PT) and carbon ion therapy (CIT) in patients with skull base chordoma at a single institution. METHODS: All patients who underwent PT or CIT with curative intent between 2003 and 2014 at Hyogo Ion Beam Medical Center were included in this study. Twenty-four patients were enrolled. Eleven (46%) received PT and 13 (54%) received CIT. Overall survival (OS), progression-free survival (PFS) and local control (LC) were calculated using the Kaplan-Meier method. Late toxicities were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up was 71.5 months (range, 14-175 months). The five-year LC, PFS and OS rates were 85, 81, and 86%, respectively. The LC (P = 0.048), PFS (P = 0.028) and OS (P = 0.012) were significantly improved in patients who had undergone surgery before particle therapy. No significant differences were observed in the LC rate and the incidence of grade 2 or higher late toxicities between patients who received PT and CIT. CONCLUSIONS: Both PT and CIT appear to be effective and safe treatments and show potential to become the standard treatments for skull base chordoma. To increase the local control, surgery before particle therapy is preferable.

Long-term outcomes in patients treated with proton therapy for localized prostate cancer.

The aim of this retrospective study was to report long-term clinical outcomes in patients treated with proton therapy (PT) for localized prostate cancer. Between 2001 and 2014, 1375 consecutive patients were treated with PT. Patients were classified into prognostic risk groups based on the National Comprehensive Cancer Network criteria. Freedom from biochemical relapse (FFBR), cancer-specific survival (CSS) and incidence of late gastrointestinal (GI)/genitourinary (GU) toxicities were calculated. Multivariate analysis was performed to identify clinical prognostic factors for FFBR and late toxicities. The median follow-up period was 70 months (range, 4-145 months). In total, 99% of patients received 74 Gy (relative biologic effectiveness [RBE]); 56% of patients received neoadjuvant androgen deprivation therapy. For the low-, intermediate-, high-, and very high-risk groups, 5-year FFBR was 99% (95% confidence intervals [CI], 96-100%), 91% (95% CI, 88-93%), 86% (95% CI, 82-89%), and 66% (95% CI, 53-76%), respectively, and 5-year CSS was 100% (95% CI, 100-100%), 100% (95% CI, 100-100%) , 99% (95% CI, 97-100%), and 95% (95% CI, 94-98%), respectively. Patient age, T classification, Gleason score, prostate-specific antigen, and percentage of positive cores were significant prognostic factors for FFBR. Grade 2 or higher GI and GU toxicities were 3.9% and 2.0%. Patient age was a prognostic factor for both late GI and GU toxicities. This study represents the largest cohort of patients treated with PT for localized prostate cancer, with the longest follow-up to date. Our results demonstrate that the biochemical control of PT is favorable particularly for high- and very high-risk patients with lower late genitourinary toxicity and indicates the necessity of considering patient age in the treatment protocols.

Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice.

Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant effects. The purpose of the present study was to assess the radioprotective effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally administered at 100 mg/kg body weight in the drinking water. Firstly, the present study compared the survival of normal intestinal crypt epithelial cells with mice that received PZ prior to or following irradiation. Next, the present study examined the sequential changes of the incidence of apoptosis in the normal intestine of mice that received irradiation. The mice that received PZ prior to irradiation demonstrated a stronger protective effect on the normal intestine compared with those that received PZ after irradiation. The present study therefore administrated PZ 2 h before irradiation in the subsequent experiments. The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum and ileum. Radiation-induced cell death occurred with a peak at position 10 or lower from the base of the crypt axis, and was subsequently reduced by PZ treatment. Pretreatment with PZ protected the normal intestinal tissues from radiation-induced apoptosis.

The threshold of hypothyroidism after radiation therapy for head and neck cancer: a retrospective analysis of 116 cases.

The purpose of the present study was to determine the risk factors for developing thyroid disorders based on a dose-volume histograms (DVHs) analysis. Data from a total of 116 consecutive patients undergoing 3D conformal radiation therapy for head and neck cancers was retrospectively evaluated. Radiation therapy was performed between April 2007 and December 2010. There were 108 males and 8 females included in the study. The median follow-up term was 24 months (range, 1-62 months). The thyroid function was evaluated by measuring thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels. The mean thyroid dose, and the volume of thyroid gland spared from doses ≥10, 20, 30 and 40 Gy (VS10, VS20, VS30 and VS40) were calculated for all patients. The thyroid dose and volume were calculated by the radiotherapy planning system (RTPS). The cumulative incidences of hypothyroidism were 21.1% and 36.4% at one year and two years, respectively, after the end of radiation therapy. In the DVH analyses, the patients who received a mean thyroid dose <30 Gy had a significantly lower incidence of hypothyroidism. The univariate analyses showed that the VS10, VS20, VS30 and VS40 were associated with the risk of hypothyroidism. Hypothyroidism was a relatively common type of late radiation-induced toxicity. A mean thyroid dose of 30 Gy may be a useful threshold for predicting the development of hypothyroidism after radiation therapy for head and neck cancers.

Polaprezinc reduces the severity of radiation-induced mucositis in head and neck cancer patients.

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.

Arterial chemoradiotherapy for carcinomas of the external auditory canal and middle ear.

OBJECTIVES/HYPOTHESIS: The purpose of this study was to estimate the efficacy of superselective arterial chemoradiotherapy for locally advanced carcinomas of the external auditory canal and middle ear. STUDY DESIGN: A retrospective study of clinical data for consecutive patients with locally advanced carcinomas of the external auditory canal and middle ear. METHODS: Thirteen patients with locally advanced carcinomas of the external auditory canal and middle ear (T3: one patient, T4: 12 patients) were reviewed. The median follow-up duration in the living patients was 33 months. The total dose of radiation therapy was 60 Gy using conventional fractionation. Four, five, or six courses of a superselective arterial infusion (cisplatin 50 mg) were given weekly. RESULTS: The overall survival and progression-free survival rates at 2 years, calculated by the Kaplan-Meier method, were 58.7% and 53.8%, respectively. No late-phase adverse effects due to chemoradiation and no adverse effects due to catheterization were observed. CONCLUSIONS: These results suggest that superselective arterial chemoradiation can be a treatment option for locally advanced carcinomas of the external auditory canal and middle ear.

Particle therapy for clinically diagnosed stage I lung cancer: comparison with pathologically proven non-small cell lung cancer.

BACKGROUND: The purpose of the present study was to present the treatment outcomes of particle therapy for indeterminate pulmonary nodules (IPNs) diagnosed as stage I non-small cell lung cancer, including a comparative analysis involving pathologically proven lung cancer (PPLC). MATERIAL AND METHODS: A total of 54 patients (57 lesions) who underwent particle therapy for IPNs were enrolled in this study. Median patient age was 76 (range 52-87) years. T-classification was: T1a, 30; T1b, 16; and T2a, 11. Particle therapy using protons or carbon ions was delivered at total doses of 52.8-80 Gy equivalent in 4-26 fractions. The PPLC cohort included 111 patients. RESULTS: The median follow-up time was 41 (range 7-90) months. For all IPN patients, the three-year overall survival, progression-free survival, local control and distant progression-free survival rates were 90%, 72%, 94% and 79%, respectively. Grade 2 toxicities were radiation pneumonitis (19%), dermatitis (9%), rib fracture (2%), chest wall pain (2%) and neuropathy (2%). No ≥grade 3 toxicities were observed. In univariate analysis, the IPN group showed significantly better survival relative to the PPLC group. However, after adjustment for baseline imbalances between these two groups in multivariate analysis, pathological confirmation did not correlate with survival. CONCLUSIONS: Particle therapy for IPNs provided favorable outcomes with minimal toxicities, which may be comparable to those for PPLC patients. Further studies are needed to clarify the optimal management of IPN patients.

Treatment outcomes of particle radiotherapy using protons or carbon ions as a single-modality therapy for adenoid cystic carcinoma of the head and neck.

BACKGROUND AND PURPOSE: The aim of this study was to retrospectively analyse the outcomes of cases of adenoid cystic carcinomas (ACCs) of the head and neck that were treated at a single institution with particle therapy consisting of either protons or carbon ions. METHODS AND MATERIALS: Between February 2002 and March 2012, 80 patients were treated with proton therapy (PT) or carbon ion therapy (CIT) alone. PT and CIT were employed in 40 (50%) patients each, and more than half of the patients received 65.0 GyE in 26 fractions (n=47, 59%). RESULTS: The median duration of follow-up was 38 months (range, 6-115 months). For all patients, the 5-year for overall survival (OS) rate, progression-free survival (PFS) rate, and local control (LC) rate were 63%, 39%, and 75%, respectively. No significant differences between PT and CIT were observed. The 5-year LC rates for T4 and inoperable cases were 66% and 68%, respectively. Twenty-one patients (26%) experienced grade 3 or greater late toxicities, including three patients who developed grade 5 bleeding from nasopharyngeal ulcers. CONCLUSIONS: Particle radiotherapy for ACC achieves favourable LC, and its efficacy in inoperable or T4 cases is promising. There were no significant differences between PT and CIT in terms of OS, PFS and LC.

Particle beam radiation therapy using carbon ions and protons for oligometastatic lung tumors.

BACKGROUND: A study was undertaken to analyze the efficacy and feasibility of particle beam radiation therapy (PBRT) using carbon ions and protons for the treatment of patients with oligometastatic lung tumors. METHODS: A total of 47 patients with 59 lesions who underwent PBRT for oligometastatic lung tumors between 2003 and 2011 were included in this study. Patient median age was 66 (range, 39-84) years. The primary tumor site was the colorectum in 11 patients (23.4%), lung in 10 patients (21.3%) and a variety of other sites in 26 patients (55.3%). Thirty-one patients (66%) received chemotherapy prior to PBRT. Thirty-three lesions were treated with 320-MeV carbon ions and 26 were treated with 150- or 210-Mev protons in 1-4 portals. A median total dose of 60 (range, 52.8-70.2) GyE was delivered at the isocenter in 8 (range, 4-26) fractions. RESULTS: The median follow-up time was 17 months. The local control, overall survival and progression-free survival rates at 2 years were 79%, 54 and 27% respectively. PBRT-related toxicities were observed; six patients (13%) had grade 2 toxicity (including grade 2 radiation pneumonitis in 2) and six patients (13%) had grade 3 toxicity. Univariate analysis indicated that patients treated with a biologically equivalent dose of 10 (BED10) <110 GyE10, had a significantly higher local recurrence rate. Local control rates were relatively lower in the subsets of patients with the colorectum as the primary tumor site. No local progression was observed in metastases from colorectal cancer irradiated with a BED10 ≥ 110 GyE10. There was no difference in treatment results between proton and carbon ion therapy. CONCLUSIONS: PRBT is well tolerated and effective in the treatment of oligometastatic lung tumors. To further improve local control, high-dose PBRT with a BED10 ≥ 110 GyE10 may be promising. Further investigation of PBRT for lung oligometastases is warranted.

Body mass index can affect gastrointestinal and genitourinary toxicity in patients with prostate cancer treated with external beam radiation therapy.

The aim of the present study was to determine the impact of obesity on radiation-induced gastrointestinal (GI) and genitourinary (GU) toxicity. The cases of 54 patients with prostate cancer, treated with three-dimensional conformal radiation therapy (RT), were reviewed. For each patient, the body mass index (BMI), distance between the prostate and rectum (D) on a computerised tomography scan and the dosimetric parameters of the rectum and bladder in the planning data of RT, were analyzed. GI and GU toxicity was assessed during and following RT. The results of the patients with a BMI of <25 (lower BMI) were compared with those of the patients with a BMI of ≥25 (higher BMI). The higher BMI group exhibited significantly lower doses of V60 and V65 in the rectum than the lower BMI group. No significant differences were found in D and bladder doses between the two groups. The incidence of acute GI and GU toxicity and late GI and GU toxicity were 41.7, 19.4, 35.3 and 5.7% in the lower BMI group, respectively, and 27.8, 27.8, 5.9 and 35.3% in the higher BMI group, respectively. In addition, a significant difference was found in the incidence of late GU toxicity between the two groups. Among patients who underwent RT for prostate cancer, those with higher BMIs had a tendency to show lower incidences of GI toxicity and higher incidences of GU toxicity than patients with lower BMIs. To conclude, an increased effort must be made to reduce rectal doses in patients with lower BMIs. Conversely, increased care for GU toxicity must be provided for overweight patients.

A retrospective comparison of proton therapy and carbon ion therapy for stage I non-small cell lung cancer.

BACKGROUND AND PURPOSE: This retrospective study aimed to compare the clinical outcomes and late toxicities of proton therapy (PT) with those of carbon ion therapy (CIT) for stage I non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 111 patients who underwent particle therapy for stage I NSCLC between April 2003 and December 2009 were enrolled in this study. PT (n=70) and CIT (n=41) were delivered to total doses of 52.8-80 GyE in 4-26 fractions and 52.8-70.2 GyE in 4-26 fractions, respectively. The median follow-up time was 41 months. RESULTS: Differences in outcome between the PT and CIT groups regarding 3-year overall survival (72% and 76%, respectively), progression-free survival (44% and 53%, respectively), and local control (81% and 78%, respectively) were not statistically significant. In multivariate analysis, the type of treatment beam did not correlate with overall survival. The severity of late toxicities was comparable between the two groups. CONCLUSIONS: Clinical results in the PT group were comparable to those in the CIT group. However, this study was a retrospective analysis of a highly heterogeneous population. Consequently, more homogeneous prospective data, large multicentric databases and, ideally, randomized trials are warranted.

Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials.

Three-dimensional radiochromic film dosimetry for volumetric modulated arc therapy using a spiral water phantom.

We validated 3D radiochromic film dosimetry for volumetric modulated arc therapy (VMAT) using a newly developed spiral water phantom. The phantom consists of a main body and an insert box, each of which has an acrylic wall thickness of 3 mm and is filled with water. The insert box includes a spiral film box used for dose-distribution measurement, and a film holder for positioning a radiochromic film. The film holder has two parallel walls whose facing inner surfaces are equipped with spiral grooves in a mirrored configuration. The film is inserted into the spiral grooves by its side edges and runs along them to be positioned on a spiral plane. Dose calculation was performed by applying clinical VMAT plans to the spiral water phantom using a commercial Monte Carlo-based treatment-planning system, Monaco, whereas dose was measured by delivering the VMAT beams to the phantom. The calculated dose distributions were resampled on the spiral plane, and the dose distributions recorded on the film were scanned. Comparisons between the calculated and measured dose distributions yielded an average gamma-index pass rate of 87.0% (range, 91.2-84.6%) in nine prostate VMAT plans under 3 mm/3% criteria with a dose-calculation grid size of 2 mm. The pass rates were increased beyond 90% (average, 91.1%; range, 90.1-92.0%) when the dose-calculation grid size was decreased to 1 mm. We have confirmed that 3D radiochromic film dosimetry using the spiral water phantom is a simple and cost-effective approach to VMAT dose verification.

Long-term outcome of proton therapy and carbon-ion therapy for large (T2a-T2bN0M0) non-small-cell lung cancer.

INTRODUCTION: : Although many reports have shown the safety and efficacy of stereotactic body radiotherapy (SBRT) for T1N0M0 non-small-cell lung cancer (NSCLC), it is rather difficult to treat T2N0M0 NSCLC, especially T2b (>5 cm) tumor, with SBRT. Our hypothesis was that particle therapy might be superior to SBRT in T2 patients. We evaluated the clinical outcome of particle therapy for T2a/bN0M0 NSCLC staged according to the 7th edition of the International Union Against Cancer (UICC) tumor, node, metastasis classification. METHODS: : From April 2003 to December 2009, 70 histologically confirmed patients were treated with proton (n = 43) or carbon-ion (n = 27) therapy according to institutional protocols. Forty-seven patients had a T2a tumor and 23 had a T2b tumor. The total dose and fraction (fr) number were 60 (Gray equivalent) GyE/10 fr in 20 patients, 52.8 GyE/4 fr in 16, 66 GyE/10 fr in 16, 80 GyE/20 fr in 14, and other in four patients, respectively. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, Version 4.0. RESULTS: : The median follow-up period for living patients was 51 months (range, 24-103). For all 70 patients, the 4-year overall survival, local control, and progression-free survival rates were 58% (T2a, 53%; T2b, 67%), 75% (T2a, 70%; T2b, 84%), and 46% (T2a, 43%; T2b, 52%), respectively, with no significant differences between the two groups. The 4-year regional recurrence rate was 17%. Grade 3 pulmonary toxicity was observed in only two patients. CONCLUSION: : Particle therapy is well tolerated and effective for T2a/bN0M0 NSCLC. To further improve treatment outcome, adjuvant chemotherapy seems a reasonable option, whenever possible.

A case of acute exacerbation of idiopathic pulmonary fibrosis after proton beam therapy for non-small cell lung cancer.

There have been no reports describing acute exacerbations of idiopathic pulmonary fibrosis after particle radiotherapy for non-small cell lung cancer. The present study describes the case of a 76-year-old Japanese man with squamous cell carcinoma of the lung that relapsed in the left upper lobe 1 year after right upper lobectomy. He had been treated with oral prednisolone 20 mg/day every 2 days for idiopathic pulmonary fibrosis, and the relapsed lung cancer was treated by proton beam therapy, which was expected to cause the least adverse effects on the idiopathic pulmonary fibrosis. Fifteen days after the initiation of proton beam therapy, the idiopathic pulmonary fibrosis exacerbated, centered on the left upper lobe, for which intensive steroid therapy was given. About 3 months later, the acute exacerbation of idiopathic pulmonary fibrosis had improved, and the relapsed lung cancer became undetectable. Clinicians should be aware that an acute exacerbation of idiopathic pulmonary fibrosis may occur even in proton beam therapy, although proton beam therapy appears to be an effective treatment option for patients with idiopathic pulmonary fibrosis.

A phase I/II study of gemcitabine-concurrent proton radiotherapy for locally advanced pancreatic cancer without distant metastasis.

PURPOSE: We conducted the study to assess the feasibility and efficacy of gemcitabine-concurrent proton radiotherapy (GPT) for locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Of all 50 patients who participated in the study, 5 patients with gastrointestinal (GI)-adjacent LAPC were enrolled in P-1 (50 Gy equivalent [GyE] in 25 fractions) and 5 patients with non-GI-adjacent LAPC in P-2 (70.2 GyE in 26 fractions), and 40 patients with LAPC regardless of GI-adjacency in P-3 (67.5 GyE in 25 fractions using the field-within-a-field technique). In every protocol, gemcitabine (800 mg/m(2)/week for 3 weeks) was administered concurrently. Every patient received adjuvant chemotherapy including gemcitabine after GPT within the tolerable limit. RESULTS: The median follow-up period was 12.5 months. The scheduled GPT was feasible for all except 6 patients (12%) due to acute hematologic or GI toxicities. Grade 3 or greater late gastric ulcer and hemorrhage were seen in 5 patients (10%) in P-2 and P-3. The one-year freedom from local-progression, progression-free, and overall survival rates were 81.7%, 64.3%, and 76.8%, respectively. CONCLUSION: GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging.

Low-Dose Aspirin Therapy Does not Increase the Severity of Acute Radiation Proctitis.

BACKGROUND: Although anticoagulation therapy is commonly used in the prostate cancer population, there are only a few studies about the correlation between radiation proctitis and anticoagulation therapy. The purpose of the present study was to determine whether low-dose aspirin increases the severity of acute radiation proctitis in an experimental animal model. METHODS: Wistar rats were used in the present study. The rats were administered either aspirin at doses of 5, 10, and 20 mg/kg, or saline, daily before and after irradiation. The rats were irradiated to the rectum as a single fraction of 25 Gy. The rectal mucosal changes of each rat were evaluated macroscopically and pathologically on the tenth day following irradiation. The findings of proctitis were graded from 0 to 4, and then were compared with regard to the status. RESULTS: No apparent correlations were observed between the administration of aspirin and the severity of radiation proctitis in the macroscopic findings and in the morphological mucosal damage in the pathological examination. The proportion of rats with a severe degree of mucosal inflammation was 90.0%, 100.0%, 16.7% and 100.0% at 5 mg/kg, 10 mg/kg, and 20 mg/kg of aspirin, or saline, respectively. The rats receiving aspirin at the dose of 20 mg/kg showed significantly milder inflammation than the other groups (P < 0.05). CONCLUSIONS: In the present study, low-dose aspirin did not increase the severity of acute radiation proctitis. In addition, aspirin might decrease the severity of radiation-induced mucosal inflammation in the rectum.

The effectiveness of particle radiotherapy for hepatocellular carcinoma associated with inferior vena cava tumor thrombus.

BACKGROUND: The prognosis of patients who have hepatocellular carcinoma (HCC) associated with inferior vena cava tumor thrombus (IVCTT) is very poor, and effective treatment modalities are extremely limited. The objective of this study was to determine the therapeutic efficacy of particle radiotherapy for HCC with IVCTT. METHODS: Between June 2001 and January 2009, 16 evaluable patients who had HCC with IVCTT were treated with particle radiotherapy. They were divided into 2 groups: 6 were treated with curative intent; 10 with palliative intent. The local tumor control rates, overall survival rates, and toxicities were evaluated. RESULTS: All tumors treated with particle radiotherapy remained controlled without local recurrence at the last follow-up. The overall survival rates for the 16 patients at 1 and 3 years were 61.1 and 36.7%, respectively. We observed a significant difference in the survival rates according to treatment policy. The median survival time was 25.4 months for patients treated with curative intent and 7.7 months for those treated with palliative intent. The one-year survival rates were 100.0 and 33.3%, respectively. No Grade 3 or higher treatment-related toxicities were observed. CONCLUSIONS: Particle radiotherapy is thought to be potentially effective and safe for HCC with IVCTT. Considering the current lack of effective and less-invasive local therapy for HCC with IVCTT, particle radiotherapy may therefore be an attractive new therapeutic approach for this type of HCC.