Radiotherapy after radical prostatectomy for prostate cancer: clinical outcomes and factors influencing biochemical recurrence.

BACKGROUND: Radiotherapy (RT) after radical prostatectomy (RP) includes adjuvant radiotherapy (ART) and salvage radiotherapy (SRT), which can prevent or cure biochemical recurrence. AIMS: To evaluate long-term outcomes of RT after RP and to examine factors affecting biochemical recurrence-free survival (bRFS). METHODS: Sixty-six received ART and 73 received SRT between 2005 and 2012 were included. The clinical outcomes and late toxicities were evaluated. Univariate and multivariate analyses were performed to examine factors affecting bRFS. RESULTS: Median follow-up from RP was 111 months. Five-year bRFS and 10-year distant metastasis-free survival from RP were 82.8% and 84.5% in ART, and 74.6% and 92.4% in SRT, respectively. The most frequent late toxicity was hematuria, which was higher in ART (p = .01). No recurrence within RT field was occurred. On univariate analysis, pelvic RT was associated with favorable bRFS in ART (p = .048). In SRT, post-RP prostate-specific antigen (PSA) level (< 0.05 ng/mL), PSA nadir after RT (≤ 0.01 ng/mL), and time to PSA nadir (≥ 10 months) were associated with favorable bRFS (p = .03, p < .001, and p = .002, respectively). On multivariate analysis, post-RP PSA level and time to PSA nadir were independent predictive factors for bRFS in SRT (p = .04 and p = .005). CONCLUSIONS: ART and SRT had favorable outcomes with no recurrence within RT field. In SRT, the time to PSA nadir after RT (≥ 10 months) was found to be a new predictor for favorable bRFS and useful in assessing treatment efficacy.

Gene Expression Profile Signature of Aggressive Waldenström Macroglobulinemia with Chromosome 6q Deletion.

BACKGROUND: Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoma. Clinically, chromosome 6q deletion (6q del) including loss of the B lymphocyte-induced maturation protein 1 gene (BLIMP-1) is reported to be associated with poor prognosis. However, it remains unclear how the underlying biological mechanism contributes to the aggressiveness of WM with 6q del. METHODS: Here, we conducted oligonucleotide microarray analysis to clarify the differences in gene expression between WM with and without 6q del. Gene ontology (GO) analysis was performed to identify the main pathways underlying differences in gene expression. Eight bone marrow formalin-fixed paraffin-embedded samples of WM were processed for interphase fluorescence in situ hybridization analysis, and three were shown to have 6q del. RESULTS: GO analysis revealed significant terms including "lymphocyte activation" (corrected p value=6.68E-11), which included 31 probes. Moreover, IL21R and JAK3 expression upregulation and activation of the B-cell receptor signaling (BCR) pathway including CD79a, SYK, BLNK, PLCγ2, and CARD11 were detected in WM with 6q del compared with WM without 6q del. CONCLUSION: The present study suggested that the BCR signaling pathway and IL21R expression are activated in WM with 6q del. Moreover, FOXP1 and CBLB appear to act as positive regulators of the BCR signaling pathway. These findings might be attributed to the aggressiveness of the WM with 6q del expression signature.

Environmentally Driven Migration in a Social Network Game.

Cooperative behaviors are common in humans, and they are the fundamental basis of our society. Theoretical and experimental studies have modeled environments where the behaviors of humans, or agents, have been restricted to analyze their social behavior. However, it is important that such studies can be generalized to a less restrictive environment in order to understand human society. Social network games (SNGs) provide a powerful tool for the quantitative study of human behavior using a less restrictive environment than in previous studies. We focused on multilevel selection, one of the theoretical frameworks used to study the evolution of cooperation. The evolution of cooperation by multilevel selection requires that the continual assortment between cooperators and noncooperators is generated; thus, humans may have acquired mechanisms that ensure assortment (e.g., migration between groups). This study aims to investigate this mechanism in a less restrictive environment. For this purpose, we researched the effect of migration based on data analysis in an SNG where the players could behave more freely than was possible in the environments used in the previous studies. We showed that players maintained assortment between cooperators and defectors in this SNG, where it appears that environmentally driven migration generated the assortment.

Biological responses in rats exposed to mainstream smoke from a heated cigarette compared to a conventional reference cigarette.

The heated cigarette (HC) generates mainstream smoke by vaporizing the components of the tobacco rod using a carbon heat source at the cigarette tip. Mainstream smoke of HC contains markedly less chemical constituents compared to combusted cigarettes. Mainstream smoke from HC was generated under Health Canada Intense regimen and its biological effects were compared to those of Reference (3R4F) cigarettes, using nose-only 5-week and 13-week inhalation studies. In the 13-week study, SD rats were necropsied following exposure to mainstream smoke from each cigarette at 200, 600 or 1000 µg wet total particulate matter/L for 1 h/day, 7 days/week or following a 13-week recovery period. Histopathological changes in the respiratory tract were significantly lesser in HC groups; e.g. respiratory epithelial hyperplasia in the nasal cavity and accumulation of pigmented macrophages in alveoli. After a 13-week recovery, the lesions were completely or partially regressed, except for accumulation of pigmented macrophages in alveoli, in both HC and 3R4F groups. In the 5-week study, SD rats were necropsied following exposure to mainstream smoke of either cigarette at 600 or 1000 µg/L for 1 h, two times/day (with 30 min interval), 7 days/week or following a 4-week recovery period. Bronchoalveolar lavage fluid (BALF) analysis of neutrophil percentages and enzyme levels like γ-GT, ALP and LDH indicated that pulmonary inflammation was significantly less in HC groups compared to 3R4F groups. In conclusion, HC demonstrated significantly lower biological effects compared to 3R4F, based on the BALF parameters and histopathology.

Comparison of dermal tumor promotion activity of cigarette smoke condensate from prototype (heated) cigarette and reference (combusted) cigarette in SENCAR mice.

Test cigarette (prototype "heated" cigarette) was evaluated on its dermal tumor promotion activity in SENCAR mice relative to conventional 3R4F cigarette. Mainstream cigarette smoke was generated under the modified Health Canada Intensive Regimen, and smoke condensate (CSCs) were collected using cold traps and extracted with acetone. Female mice received a topical application of 7,12-dimehtylbenz(a)anthracene (DMBA) as the tumor initiator on the back skin during Week 1. Subsequently, CSC was repeatedly applied as the tumor promoter at 5 doses, up to 30 mg tar/application, three times per week for 30 weeks. Test groups showed a clearly longer latency at lower doses (⩽15 mg), but the difference was less clear at higher doses (⩾22.5 mg), while mortalities were not affected throughout the study. Test groups also had consistently lower incidence and multiplicity of neoplasms, as well as lower incidences of non-neoplastic changes (e.g., inflammations and squamous epithelial hyperplasia on the site of application). The group without DMBA initiation did not induce any neoplasm but the respective Reference group showed an increase in tumorigenicity. In conclusion, the study demonstrated significant reduction in dermal irritancy and tumorigenicity of Test CSC compared to Reference CSC.

[CyberKnife radiotherapy for head and neck cancer].

Locoregional failure after radiation therapy is a significant problem in the management of head and neck cancer. Reirradiation is rarely used in conventional radiation therapy because of concerns about treatment-related toxicity and lack of efficacy. However, stereotactic radiotherapy, which was made possible by the advancement in therapeutic devices enables reirradiation. The CyberKnife system is one of the best devices for stereotactic radiotherapy. We discuss salvage treatment, including reirradiation using the CyberKnife system, in patients with locally recurrent head and neck cancer patients.

A multicenter phase II study of local radiation therapy for stage IEA mucosa-associated lymphoid tissue lymphomas: a preliminary report from the Japan Radiation Oncology Group (JAROG).

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. METHODS AND MATERIALS: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. RESULTS: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. CONCLUSIONS: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

Initial experience with the quality assurance program of radiation therapy on behalf of Japan Radiation Oncology Group (JAROG).

BACKGROUND: We evaluated the efficacy of our quality assurance (QA) program of radiation therapy (RT) in a prospective phase II study. This is the first description of the experience of the Japan Radiation Oncology Group (JAROG) with this program. METHODS: Clinical records, all diagnostic radiological films or color photos that depicted the extent of disease of 37 patients with stage IEA extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) were collected for review. Radiation therapy charts, simulation films or digitally reconstructed radiographs, portal films and isodose distributions at the central axis plan were also reviewed. All documents were digitally processed, mounted on Microsoft PowerPoint, and for security returned from researchers by mail in CD-ROM format. The QA committee members reviewed all documents centrally, utilizing the slide show functionality. RESULTS: All patients were prescribed their specified dose to the dose specification point in accordance with the protocol. Three patients were regarded as deviations, because of a smaller margin than that specified in the protocol (n = 2) or a prolonged overall treatment time (n = 1). No violations were observed in this study. CONCLUSIONS: This is the first report with regard to the QA program in MALT lymphoma. We demonstrated that our QA program was simple and inexpensive. We also confirmed that the radiation oncologists in Japan adhered closely to the protocol guidelines.