Nanomedicine allows achievement of tumor-selective drug delivery because of the enhanced permeability and retention (EPR) effect of solid tumors. We report here the first clinical application of a new agent-HPMA copolymer-conjugated pirarubicin (P-THP)-with a molecular size of about 8 nm, or 38.5 kDa. A patient had advanced prostate cancer with multiple metastases in the lung, pelvis, femur, and perhaps the sacrum. In April 2013, this 60-year-old patient started treatment with leuprorelin and estradiol, which continued until July 2014, but the patient became refractory to this treatment. So the patient underwent proton beam radiotherapy targeted to the primary prostate cancer, and P-THP was administered for numerous metastatic tumor nodules concomitantly with radiotherapy. This combination therapy had remarkable results, with complete remission of multiple metastases in the lung and bone. The prostate-specific antigen (PSA) value was decreased from about 1000 ng/mL on April 30, 2013, to about 100 ng/mL on June 24, 2013, with hormone therapy, but rose again to 964.2 ng/mL and then to 1472 ng/mL in July 2013, during leuprorelin administration. P-THP treatment administered concomitantly with proton beam irradiation was started in August 2013. The PSA value was decreased to 102 ng/mL on August 26, 2013, and then to 0.971 ng/mL on October 8, 2013, and 0.277 ng/mL on January 15, 2015. The P-THP doses ranged from 30 to 75 mg of free THP equivalent/patient every 2-3 weeks without signs of serious toxicity, such as cardiovascular side effects or a reduction in quality of life. No evidence of relapse was found more than 20 months after P-THP administration. This case demonstrates the value of hydrazone-bonded polymeric drugs in multimodal therapy.

This is the first multi‐institutional retrospective survey of the long‐term outcomes of proton therapy (PT) for prostate cancer in Japan. This retrospective analysis comprised prostate cancer patients treated with PT at seven centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. Biochemical relapse was based on the Phoenix definition (nadir + 2.0 ng/mL). Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. There were 215, 520, and 556 patients in the low‐risk, intermediate‐risk, and high‐risk groups, respectively. The median follow‐up period of surviving patients was 69 months (range: 7–107). Among all patients, 98.8% were treated using a conventional fractionation schedule and 1.2% with a hypofractionation schedule; 58.5% and 21.5% received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5‐year biochemical relapse‐free survival (bRFS) and overall survival rates in the low‐risk, intermediate‐risk, and high‐risk groups were 97.0%, 91.1%, and 83.1%, and 98.4%, 96.8%, and 95.2%, respectively. In the multivariate analysis, the NCCN classification was a significant prognostic factor for bRFS, but not overall survival. The incidence rates of grade 2 or more severe late gastrointestinal and genitourinary toxicities were 4.1% and 4.0%, retrospectively. This retrospective analysis of a multi‐institutional survey suggested that PT is effective and well‐tolerated for prostate cancer. Based on this result, a multi‐institutional prospective clinical trial (UMIN000025453) on PT for prostate cancer has just been initiated in order to define its role in Japan.

Purpose To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). Materials and methods From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. Results Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). Conclusion Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

It is well known that radiotherapy causes malfunctions of cardiac implantable electronic devices such as pacemaker (PM) and implantable cardioverter-defibrillator because of incidental neutron production. Here, we report our experience with two cases of PM reset among seven patients with PM who underwent proton beam therapy (PBT) from January 2011 to April 2015 at our centre. Our experience shows PM reset can occur also with abdominal PBT. In both cases, PM reset was not detected by electrocardiogram (ECG) monitoring but was rather discovered by post-treatment programmer analysis. Our cases suggest that PM malfunction may not always be detected by ECG monitoring and emphasize the importance of daily programmer analysis.