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.

Utility of Laparoscopic Uterine Myomectomy as a Treatment for Infertility with No Obvious Cause Except for Uterine Fibroids.

OBJECTIVES: Uterine fibroids are capable of causing infertility, but there are no definite criteria for which laparoscopic uterine myomectomy (LM) is known to be beneficial. To investigate the usefulness of LM, we examined pregnancy rates in patients with infertility with no obvious cause except for the presence of uterine fibroids. MATERIALS AND METHODS: We retrospectively reviewed the clinical records at Suzuki Memorial Hospital between June 2010 and August 2014. We found 60 eligible patients (LM group, 46; non-LM group, 14). The criteria for performing LM were a maximal fibroid diameter of 40 mm or more or the presence of >4 fibroids. RESULTS: The duration of infertility before the first visit was significantly longer in the LM group; although there was no significant difference in the mean patient age and body mass index. Pregnancy was achieved in 45.7% of patients (21/46) in the LM group and 28.6% (4/14) in the non-LM group. There were no pregnancies in patients with >10 fibroids. The postoperative pregnancy rate in the LM group was comparable to previously reported pregnancy rates. CONCLUSIONS: Our criteria for performing LM in patients with no obvious cause for infertility except for uterine fibroids seem appropriate, especially when the fibroids are large and the number of fibroids is between 4 and 9. However, our results suggest that the effectiveness of LM is low in patients with 10 or more uterine fibroids.

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.

Particle Therapy Using Protons or Carbon Ions for Unresectable or Incompletely Resected Bone and Soft Tissue Sarcomas of the Pelvis.

PURPOSE: To retrospectively analyze the treatment outcomes of particle therapy using protons or carbon ions for unresectable or incompletely resected bone and soft tissue sarcomas (BSTSs) of the pelvis. METHODS AND MATERIALS: From May 2005 to December 2014, 91 patients with nonmetastatic histologically proven unresectable or incompletely resected pelvic BSTSs underwent particle therapy with curative intent. The particle therapy used protons (52 patients) or carbon ions (39 patients). All patients received a dose of 70.4 Gy (relative biologic effectiveness) in 32 fractions (55 patients) or 16 fractions (36 patients). RESULTS: The median patient age was 67 years (range 18-87). The median planning target volume (PTV) was 455 cm3 (range 108-1984). The histologic type was chordoma in 53 patients, chondrosarcoma in 14, osteosarcoma in 10, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma in 5, and other in 9 patients. Of the 91 patients, 82 had a primary tumor and 9 a recurrent tumor. The median follow-up period was 32 months (range 3-112). The 3-year rate of overall survival (OS), progression-free survival (PFS), and local control was 83%, 72%, and 92%, respectively. A Cox proportional hazards model revealed that chordoma histologic features and a PTV of ≤500 cm3 were significantly associated with better OS, and a primary tumor and PTV of ≤500 cm3 were significantly associated with better PFS. Ion type and number of fractions were not significantly associated with OS, PFS, or local control. Late grade ≥3 toxicities were observed in 23 patients. Compared with the 32-fraction protocol, the 16-fraction protocol was associated with significantly more frequent late grade ≥3 toxicities (18 of 36 vs 5 of 55; P<.001). CONCLUSIONS: Particle therapy using protons or carbon ions was effective for unresectable or incompletely resected pelvic BSTS, and the 32-fraction protocol was effective and relatively less toxic. Nevertheless, a longer follow-up period is needed to confirm these results.

Unexpected radiation laryngeal necrosis after carbon ion therapy using conventional dose fractionation for laryngeal cancer.

Carbon ion therapy is a type of radiotherapy that can deliver high-dose radiation to a tumor while minimizing the dose delivered to organs at risk. Moreover, carbon ions are classified as high linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. A 73-year-old man with glottic squamous cell carcinoma, T3N0M0, refused laryngectomy and received carbon ion therapy of 70 Gy (relative biological effectiveness) in 35 fractions. Three months after the therapy, the patient had an upper airway inflammation, and then laryngeal edema and pain occurred. Five months after the therapy, the airway stenosis was severe and computed tomography showed lack of the left arytenoid cartilage and exacerbation of laryngeal necrosis. Despite the treatment, 5 and a half months after the therapy, the laryngeal edema and necrosis had become even worse and the surrounding mucosa was edematous and pale. Six months after the therapy, pharyngolaryngoesophagectomy and reconstruction with free jejunal autograft were performed. The surgical specimen pathologically showed massive necrosis and no residual tumor. Three years after the carbon ion therapy, he is alive without recurrence. The first reported laryngeal squamous cell carcinoma case treated with carbon ion therapy resulted in an unexpected radiation laryngeal necrosis. Tissue damage caused by carbon ion therapy may be difficult to repair even for radioresistant cartilage; therefore, hollow organs reinforced by cartilage, such as the larynx, may be vulnerable to carbon ion therapy. Caution should be exercised when treating tumors in or adjacent to such organs with carbon ion therapy.

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.

Carbon ion therapy for early-stage non-small-cell lung cancer.

Carbon ion therapy is a type of radiotherapies that can deliver high-dose radiation to a tumor while minimizing the dose delivered to the organs at risk; this profile differs from that of photon radiotherapy. Moreover, carbon ions are classified as high-linear energy transfer radiation and are expected to be effective for even photon-resistant tumors. Recently, high-precision radiotherapy modalities such as stereotactic body radiotherapy (SBRT), proton therapy, and carbon ion therapy have been used for patients with early-stage non-small-cell lung cancer, and the results are promising, as, for carbon ion therapy, local control and overall survival rates at 5 years are 80-90% and 40-50%, respectively. Carbon ion therapy may be theoretically superior to SBRT and proton therapy, but the literature that is currently available does not show a statistically significant difference among these treatments. Carbon ion therapy demonstrates a better dose distribution than both SBRT and proton therapy in most cases of early-stage lung cancer. Therefore, carbon ion therapy may be safer for treating patients with adverse conditions such as large tumors, central tumors, and poor pulmonary function. Furthermore, carbon ion therapy may also be suitable for dose escalation and hypofractionation.

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.

Two-stage treatment with hepatectomy and carbon-ion radiotherapy for multiple hepatic epithelioid hemangioendotheliomas.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare neoplasm of vascular origin with variable malignant potential. Because most patients with this condition have multiple bilobar lesions, liver transplantation is the standard treatment, and hepatectomy is much less frequently indicated. We describe a case of a 35-year-old woman with unresectable multiple bilobar HEH successfully treated by combination treatment with hepatectomy and carbon-ion radiotherapy. This case is very meaningful since it demonstrated the effectiveness of carbon-ion radiotherapy for HEH and the possibility of expanding the curative treatment options for multiple bilobar hepatic tumors.

Combined analysis of V20, VS5, pulmonary fibrosis score on baseline computed tomography, and patient age improves prediction of severe radiation pneumonitis after concurrent chemoradiotherapy for locally advanced non-small-cell lung cancer.

INTRODUCTION: We aimed to develop a more accurate model for predicting severe radiation pneumonitis (RP) after concurrent chemoradiotherapy for non-small-cell lung cancer. METHODS: We retrospectively analyzed data from 122 patients with locally advanced non-small-cell lung cancer treated with concurrent chemoradiotherapy. Several dose-volume histogram metrics including absolute lung volume spared from a 5 Gy dose (VS5) were analyzed for an association with RP above NCI-CTC grade 3 (RP ≥ G3). Clinical factors including pulmonary fibrosis score (PFS) and pulmonary emphysema score on baseline chest computed tomography (CT) were also analyzed. RESULTS: Fourteen patients (11.4%) developed RP greater than or equal to G3. On univariate analysis, all dose-volume histogram metrics, sex, and PFS on baseline CT were significantly (p < 0.05) associated with occurrence of RP greater than or equal to G3. Multivariate analysis revealed that V20 greater than or equal to 26%, VS5 less than 1500 cc, age greater than or equal to 68 years, and PFS on baseline CT greater than or equal to 2 were significant risk factors. Thus, we defined a new predictive risk score (PRS) that combines these factors. The cumulative incidence of RP greater than or equal to G3 at 12 months were 0%, 7.8%, 26.6%, and 71.4% when the PRS was 0, 3-5, 6-8, and 9-14, respectively (p < 0.001). This PRS was superior at predicting RP than both V20 and VS5 combined, or V20 alone by receiver operating characteristic analysis (area under the curve, 0.888 versus 0.779 versus 0.678). CONCLUSIONS: V20, VS5, age, and PFS on baseline CT are independent and significant risk factors for occurrence of severe RP. Combining these factors may improve the predictability of severe RP.

Particle radiotherapy using protons or carbon ions for unresectable locally advanced head and neck cancers with skull base invasion.

OBJECTIVE: To study the oncological outcome of the patients with unresectable locally advanced primary head and neck cancers invading the skull base, treated with particle radiotherapy. METHODS: Fifty-seven patients with unresectable primary head and neck cancers invading the skull base received proton or carbon ion radiotherapy as definitive treatment at Hyogo Ion Beam Medical Center between 2003 and 2009. Forty-seven patients were treated with proton radiotherapy and 10 patients were treated with carbon ion radiotherapy. A retrospective review was performed with clinical charts and recorded imagings. RESULTS: With a median follow-up of 32 months, the 3-year actual survival and local progression-free rates of all the patients were 61 and 56%, respectively. The 3-year actual survival rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 83, 44, 75, 0 and 38%, respectively. The 3-year actual local control rates of adenoid cystic carcinoma, squamous cell carcinoma, olfactory neuroblastoma, adenocarcinoma and malignant melanoma were 63, 31, 83, 50 and 0%, respectively. Distant metastasis was observed in 13 of 25 patients in adenoid cystic carcinoma, two of 14 patients in squamous cell carcinoma, one of six patients with olfactory neuroblastoma, two of four patients with adenocarcinoma, three of four patients with malignant melanoma and two of three patients with undifferentiated carcinoma. Mucositis and dermatitis were seen as acute toxicities. The most common late toxicity was visual disorder. Grades 2, 3 and 4 visual disorders were observed in seven, five and two patients, respectively. CONCLUSIONS: Proton and carbon ion radiotherapy resulted in satisfactory local control in patients with locally advanced unresectable primary head and neck cancers invading the skull base.

Thoracoscopic lobectomy as salvage surgery for local recurrence of non-small cell lung cancer after carbon ion radiotherapy in an initially operable patient.

Carbon ion radiotherapy (CIRT) for patients with early-stage non-small cell lung cancer (NSCLC) has recently provided favorable local control with very few toxic reactions. Because CIRT for NSCLC has been mostly performed for elderly or inoperable patients, salvage surgery for NSCLC after CIRT has rarely been reported. We describe a case of complete thoracoscopic right upper lobectomy with mediastinal lymphadenectomy performed as salvage surgery for local recurrence of stage IA NSCLC after CIRT in an initially operable patient who had refused surgery 27 months previously. Pleural adhesions caused by CIRT were localized to the pulmonary apex and the central pulmonary structures were intact at the time of the salvage surgery, which allowed us to successfully perform thoracoscopic lobectomy without any complications. Thus, salvage surgery for NSCLC after CIRT may be feasible in an initially operable patient, as CIRT appears to be unlikely to cause any difficulties in the salvage surgery.

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.

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.

[Analysis of the safety and efficacy of percutaneous isolated hepatic perfusion after particle therapy for advanced hepatocellular carcinoma].

Here, we report the efficacy of dual treatment with hepatic resection and percutaneous isolated hepatic perfusion (PIHP) for advanced hepatocellular carcinoma( HCC). Recently, we introduced treatment with combined particle therapy and PIHP for unresectable HCC in cases of insufficient liver function. The purpose of this study was to evaluate the safety and efficacy of PIHP for local control in the liver after particle therapy. From 2006 to 2013, 6 patients underwent particle therapy for the main lesion and subsequent PIHP for remnant liver lesions. Their mean age was 64 years, and the mean size of the main lesion was 6.2 cm (range, 2.0-10.8 cm). All patients had liver cirrhosis. After particle therapy, PIHP was performed by hepatic arterial infusion of 100 mg/m2 of doxorubicin and 30 mg/m2 of mitomycin C. With regard to side effects, neutropenia occurred in all patients but no serious hepatobiliary injury was observed. The response rate for PIHP was 50% (partial response: 3 and stable disease: 3). The mean overall survival time was 26.9 months after particle therapy. In conclusion, even after particle therapy, PIHP is a safe treatment and is associated with a good local control rate for remnant HCCs. Further accumulation of data is needed to evaluate the efficacy of this treatment strategy in terms of prognosis.

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.

Patterns of failure after multimodal treatments for high-grade glioma: effectiveness of MIB-1 labeling index.

BACKGROUND: The purpose of the present study was to analyze the recurrence pattern of high-grade glioma treated with a multimodal treatment approach and to evaluate whether the MIB-1 labeling index (LI) could be a useful marker for predicting the pattern of failure in glioblastoma (GB). METHODS AND MATERIALS: We evaluated histologically confirmed 131 patients with either anaplastic astrocytoma (AA) or GB. A median dose was 60 Gy. Concomitant and adjuvant chemotherapy were administered to 111 patients. MIB-1 LI was assessed by immunohistochemistry. Recurrence patterns were categorized according to the areas of recurrence as follows: central failure (recurrence in the 95% of 60 Gy); in-field (recurrence in the high-dose volume of 50 Gy; marginal (recurrence outside the high-dose volume) and distant (recurrence outside the RT field). RESULTS: The median follow-up durations were 13 months for all patients and 19 months for those remaining alive. Among AA patients, the 2-year progression-free and overall survival rates were 23.1% and 39.2%, respectively, while in GB patients, the rates were 13.3% and 27.6%, respectively. The median survival time was 20 months for AA patients and 15 months for GB patients. Among AA patients, recurrences were central in 68.7% of patients; in-field, 18.8%; and distant, 12.5%, while among GB patients, 69.0% of recurrences were central, 15.5% were in-field, 12.1% were marginal, and 3.4% were distant. The MIB-1 LI medians were 18.2% in AA and 29.8% in GB. Interestingly, in patients with GB, the MIB-1 LI had a strong effect on the pattern of failure (P = 0.014), while the extent of surgical removal (P = 0.47) and regimens of chemotherapy (P = 0.57) did not. CONCLUSIONS: MIB-1 LI predominantly affected the pattern of failure in GB patients treated with a multimodal approach, and it might be a useful tool for the management of the disease.

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.