Three-dimensional dose-distribution measurement of therapeutic carbon-ion beams using a ZnS scintillator sheet.

The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: In this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. RESULTS: Of 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non-squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. CONCLUSION: Addition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non-small-cell lung cancer, particularly squamous cell carcinoma.

A phase II study of palliative radiotherapy combined with zoledronic acid hydrate for metastatic bone tumour from renal cell carcinoma.

PURPOSE: Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. METHODS: Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. RESULTS: Twenty-seven patients were included in the study. The median age was 65 (range, 50-84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0-34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2-89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. CONCLUSION: Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

Influence of chemoradiotherapy on nutritional status in locally advanced rectal cancer: Prospective multicenter study.

OBJECTIVE: The aim of this study was to investigate the influence of chemoradiotherapy (CRT) on nutritional status and the association between changes in nutritional status and clinical outcomes (treatment completion, adverse events, perioperative complications, and relapse-free survival [RFS]) in patients with locally advanced rectal cancer (LARC). METHODS: In this multicenter, phase II study, 41 patients with LARC underwent CRT for 5 wk, followed by a 6- to 8-wk interval before surgery. Body weight, body mass index (BMI), lean body mass, serum albumin, and prealbumin levels were measured before (pre-), during, and after CRT, and before surgery. Changes in these data and scores on the Malnutrition Universal Screening Tool (MUST) were calculated based on pre-CRT status. RESULTS: Twelve patients (29.3%) experienced body weight loss (BWL) ≥5% (defined as malnutrition) after CRT (P < 0.001) and before surgery (P = 0.035). Significant changes were seen in serum albumin levels and BMI during and after CRT (P < 0.001), and in MUST scores after CRT (P = 0.003) and before surgery (P = 0.035). Treatment completion was significantly associated with BWL (P = 0.028), MUST score (P = 0.013), and decreased serum albumin level (P = 0.001) after CRT. Regarding adverse events, MUST score before surgery (P = 0.009) and serum albumin level after CRT (P = 0.002) were significantly associated with diarrhea severity. Serum albumin level during CRT was associated with the onset of neutropenia (P = 0.005). No association was found between BWL and RFS. CONCLUSIONS: These findings suggest that malnutrition and changes in nutritional status are not only commonly observed after CRT, but also associated with treatment completion and adverse events.

Potential Mechanisms for Protective Effect of D-Methionine on Plasmid DNA Damage Induced by Therapeutic Carbon Ions.

D-methionine (D-met), a dextrorotatory isoform of the amino acid L-methionine (L-met), can prevent oral mucositis and salivary hypofunction in mice exposed to radiation. However, the mechanism of its radioprotection is unclear, especially with regard to the stereospecific functions of D-met. Radiation is known to cause injury to normal tissue by triggering DNA damage in cells. Thus, in this study we sought to determine whether the chirality of D-/L-met affects radiation-induced events at the DNA level. We selected plasmid DNA assays to examine this effect in vitro, since these assays are highly sensitive and allow easy detection of DNA damage. Samples of supercoiled pBR322 plasmid DNA mixed with D-met, L-met or dimethylsulfoxide (DMSO) were prepared and irradiated with a Bragg peak beam of carbon ions (∼290 MeV/u) with a 6-cm spread. DNA strand breaks were indicated by the change in the form of the plasmid and were subsequently quantified using agarose gel electrophoresis. We found that D-met yielded approximately equivalent protection from carbon-ion-induced DNA damage as DMSO. Thus, we propose that the protective functions of methionine against plasmid DNA damage could be explained by the same mechanism as that for DMSO, namely, hydroxyl radical scavenging. This stereospecific radioprotective mechanism occurred at a level other than the DNA level. There was no significant difference between the radioprotective effect of D-met and L-met on DNA.

Imaging Cherenkov emission for quality assurance of high-dose-rate brachytherapy.

With advances in high-dose-rate (HDR) brachytherapy, the importance of quality assurance (QA) is increasing to ensure safe delivery of the treatment by measuring dose distribution and positioning the source with much closer intervals for highly active sources. However, conventional QA is time-consuming, involving the use of several different measurement tools. Here, we developed simple QA method for HDR brachytherapy based on the imaging of Cherenkov emission and evaluated its performance. Light emission from pure water irradiated by an 192Ir γ-ray source was captured using a charge-coupled device camera. Monte Carlo calculations showed that the observed light was primarily Cherenkov emissions produced by Compton-scattered electrons from the γ-rays. The uncorrected Cherenkov light distribution, which was 5% on average except near the source (within 7 mm from the centre), agreed with the dose distribution calculated using the treatment planning system. The accuracy was attributed to isotropic radiation and short-range Compton electrons. The source positional interval, as measured from the light images, was comparable to the expected intervals, yielding spatial resolution similar to that permitted by conventional film measurements. The method should be highly suitable for quick and easy QA investigations of HDR brachytherapy as it allows simultaneous measurements of dose distribution, source strength, and source position using a single image.

A phase I dose-escalation trial of stereotactic body radiotherapy using 4 fractions for patients with localized prostate cancer.

PURPOSE: To report results from our phase I dose-escalation study of stereotactic body radiotherapy (SBRT) using 4 fractions for patients with localized prostate cancer. MATERIALS & METHODS: Fraction sizes of 8 Gy, 8.5 Gy, and 9 Gy were defined as levels 1, 2, and 3. The prescribed dose was delivered to at least 95% of the planning target volume. Image-guided, intensity-modulated radiotherapy was delivered to all patients. Dose-limiting toxicity (DLT) was defined as acute toxicity of Grade 3 or higher. The maximum tolerated dose (MTD) was defined as the level at which ≥30% of patients showed DLT. The recommended dose (RD) was defined to be one dose level below the MTD. If no patients at level 3 showed DLT, level 3 was defined as the recommended dose (RD). RESULTS: Nine patients were enrolled in each level. All patients were low or intermediate risk. Median durations of follow-up for patients at levels 1-3 were 48.9 months, 42.6 months, and 18.4 months, respectively. Protocol treatment was completed for all patients. No patient showed DLT at each dose level. Level 3 was therefore designated as the RD for the phase II study. Although most toxicities were Grade 1, genitourinary toxicity was common compared to gastrointestinal toxicity. Three-year biochemical control rate was 90.3%. CONCLUSION: The dose level of 36 Gy in 4 fractions with a 2-day break was tolerable and highly encouraging for SBRT of localized prostate cancer. The phase II trial to confirm the efficacy and toxicity of this treatment is now on going. TRIAL REGISTRATION: UMIN, UMIN000010236 . Registered 13 March 2013.

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

Strategy to avoid local recurrence in patients with locally advanced rectal cancer.

BACKGROUND: To clarify the short- and long-term outcomes of radical surgery after neoadjuvant chemoradiotherapy (NCRT) with TS-1 and irinotecan, which enhances radiosensitivity, in patients with locally advanced rectal cancer. METHODS: The study group comprised 105 patients with locally advanced rectal cancer who received NCRT followed by radical surgery. NCRT consisted of pelvic radiotherapy (45 Gy in 25 fractions over a period of 5 weeks), S-1 (80 mg/m2) given concurrently for 25 days, and irinotecan (60 mg/m2), given once a week as a continuous intravenous infusion. Radical surgery was performed 8 weeks after treatment. RESULTS: A pathological complete response was confirmed in 23.8%. The 5-year recurrence-free survival rate was 79.3%, and the 5-year overall survival rate was 87.1%. Multivariate analysis showed that the following 4 variables were independent predictors of recurrence-free survival: Sex (male: p = 0.0172), Pre-treatment tumor diameter (< 40 mm: p = 0.0223), Histopathological treatment response (grade 0,1: p = 0.0169), and ypN (ypN1: p = 0.1995; ypN2: p = 0.0007). Only ypN was an independent predictor of overall survival (ypN1: p = 0.0009; ypN2: p = 0.0012). CONCLUSIONS: Our treatment strategy combining TS-1 with irinotecan to increase radiosensitivity had a high response rate.

Risk factors for radiotherapy incidents: a single institutional experience.

We aimed to analyze risk factors for incidents occurring during the practice of external beam radiotherapy (EBRT) at a single Japanese center. Treatment data for EBRT from June 2014 to March 2017 were collected. Data from incident reports submitted during this period were reviewed. Near-miss cases were not included. Risk factors for incidents, including patient characteristics and treatment-related factors, were explored using uni- and multivariate analyses. Factors contributing to each incident were also retrospectively categorized according to the recommendations of the American Association of Physicists in Medicine (AAPM). A total of 2887 patients were treated during the study period, and 26 incidents occurred (0.90% per patient). Previous history of radiotherapy and large fraction size were identified as risk factors for incidents by univariate analysis. Only previous history of radiotherapy was detected as a risk factor in multivariate analysis. Identified categories of contributing factors were human behavior (50.0%), communication (40.6%), and technical (9.4%). The incident rate of EBRT was 0.90% per patient in our institution. Previous history of radiotherapy and large fraction size were detected as risk factors for incidents. Human behavior and communication errors were identified as contributing factors for most incidents.

Feasibility of definitive chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma: A retrospective study.

PURPOSE: This study was designed to retrospectively analyze the safety and efficacy of chemoradiation therapy with nedaplatin and 5-fluorouracil in elderly patients with esophageal squamous cell carcinoma. METHODS AND MATERIALS: Eligible patients were aged 76 years or older, had a histopathologic diagnosis of esophageal squamous cell carcinoma, and were treated at the Kitasato University Hospital between January 2010 and March 2016. Chemotherapy consisted of nedaplatin in an intravenous dose of 90 mg/m2 on day 1 and 5-fluorouracil in an intravenous dose of 800 mg/m2 on days 1 to 5, repeated every 4 weeks for 2 cycles. Radiation therapy consisted of 50.4 Gy in 28 fractions for thoracic tumors and 61.2 Gy for cervical tumors. RESULTS: Twenty-five patients were studied. Patient characteristics were as follows: median age 79 years (range, 76-85 years), clinical stage I/II/III/IV (7/8/8/2, respectively), and surgically resectable/unresectable (17/8, respectively). The completion rates of radiation therapy and chemoradiation therapy were 100% and 84%, respectively. Grade ≥3 acute toxicities included neutropenia (76%), leukopenia (72%), thrombocytopenia (32%), anemia (28%), anorexia (32%), oral mucositis (20%), febrile neutropenia (12%), and esophagitis (8%). Grade ≥3 late toxicities included esophageal stenosis (12%) and pleural effusion (4%). The complete response rate was 64%. In the median follow-up period of 18.9 months, the 1-year overall survival rate was 68%. CONCLUSIONS: Definitive chemoradiation therapy with nedaplatin and 5-fluorouracil may be a feasible treatment option for elderly patients with esophageal squamous cell carcinoma.

Automated source tracking with a pinhole imaging system during high-dose-rate brachytherapy treatment.

The transportation accuracy of sealed radioisotope sources influences the therapeutic effect of high-dose-rate (HDR) brachytherapy. We have developed a pinhole imaging system for tracking an Ir-192 radiation source during HDR brachytherapy treatment. Our system consists of a dual-pinhole collimator, a scintillator, and a charge-coupled device (CCD) camera. We acquired stereo-shifted images to infer the source position in three dimensions using a dual pinhole collimator with 1.0 mm diameter pinholes. The CCD camera captured consecutive images of scintillation light that corresponds to the source positions every 2 s. The system automatically tracks scintillation light points using template-matching technique and measured the source positions therefrom. By integrating a series of CCD images, we could infer the source dwell time from the pixel values in the integrated image. We investigated the tracking accuracy of our system in monitoring simulated brachytherapy as it would be performed for cervical cancer by using water as a stand-in for human tissue. Ir-192 pellet was moved through a water tank using tandem and ovoid applicators. The CCD camera captured clear images of the scintillation light produced by the underwater Ir-192 source in conditions equivalent to common clinical situations. The differences between the measured and the reference 3D source positions and dwell times were 1.5 ± 0.7 mm and 0.8 ± 0.4 s, respectively. This system has the potential to track in vivo Ir-192 source in real time and may prove a useful tool for quality assurance during HDR brachytherapy treatments in clinical settings.

A retrospective study of treatment for curative synchronous double primary cancers of the head and neck and the esophagus.

OBJECTIVE: Curative synchronous double primary cancers of the head and neck and the esophagus (CSC-HE) are frequently detected, but a standard treatment remains to be established. We studied the clinical course to explore appropriate treatment strategies. METHODS: We retrospectively studied consecutive 33 patients who had CSC-HE. The disease stage was classified into 4 groups: group A, early head and neck cancer (HNC) and early esophageal cancer (EC); group B, early HNC and advanced EC; group C, advanced HNC and early EC; and group D, advanced HNC and advanced EC. As induction chemotherapy, the patients received 3 courses of TPF therapy (docetaxel 75mg/m2 on day 1, cisplatin 75mg/m2 on day 1, and 5-fluorouracil 750mg/m2 on days 1-5) at 3-week intervals. The clinical courses and treatment outcomes were studied according to the disease stage of CSC-HE. RESULTS: The disease stage of CSC-HE was group A in 1 patient (3%), group B in 9 patients (27.3%), group C in 3 patients (9.1%), and group D in 20 patients (60.6%). The median follow-up was 26months, and the 2-year overall survival rate was 67.4%. In groups A, B, and C, the 2-year overall survival rate was 83.3%. In group D, the 2-year overall survival rate was 62.6%. Ten of 20 patients in group D received induction chemotherapy with TPF, and 6 patients were alive and disease free at the time of this writing. CONCLUSION: The treatment outcomes of patients with CSC-HE were relatively good. TPF induction chemotherapy might be an effective treatment for patients with advanced HNC and advanced EC.

A cold spot compensation technique using a combination of trans-rectal ultrasonography and intraoperative computed tomography for interstitial permanent prostate brachytherapy: a single-arm prospective trial.

PURPOSE: To evaluate the efficacy of a cold spot compensation technique using a combination of trans-rectal ultrasonography (TRUS) and computed tomography (CT) for permanent interstitial prostate brachytherapy. MATERIAL AND METHODS: Sixty-five patients were treated with the cold spot compensation technique using TRUS-CT fusion. The prescribed dose was set at 145 Gy. The dose to 90% of prostate volume (D90) was planned to be within 195 Gy (134%) and 205 Gy (141%). After implantation using the conventional technique, additional seeds were implanted if cold spots were detected on TRUS-CT fusion images. RESULTS: Cold spots were detected in 32 of 65 patients (49%) and were compensated by additional seeds. Median number of additional seeds was 3 (range, 1-5). A CT scan 1 month later revealed that the percentage of patients receiving an undesirably low D90 (160-180 Gy) was significantly reduced in the examination arm compared to historical controls. However, mean operation time was significantly longer in the examination arm (64 min) than in historical controls (49 min, p < 0.001). With median follow-up of 18 months (range, 9-24 months), no grade 3 or worse toxicity was encountered. CONCLUSION: The cold spot compensation technique using TRUS-CT fusion appears effective for patients receiving permanent interstitial prostate brachytherapy.

Predisposing Factors for Chemotherapy-induced Nephrotoxicity in Patients with Advanced Esophageal Cancer Who Received Combination Chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil.

BACKGROUND AND OBJECTIVES: We retrospectively studied the predisposing factors for nephrotoxicity in the patients with advanced esophageal squamous-cell carcinoma who received combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF therapy). METHODS: Between January 2010 and March 2014, 41 patients with Stage IB to III esophageal squamous-cell carcinoma received the DCF therapy (docetaxel 70-75 mg/m2, day 1; cisplatin 70-75 mg/m2, day 1; 5-fluorouracil 750 mg/m2, days 1-5) in our hospital. Renal dysfunction was defined as a creatinine clearance (Ccr) of less than 60 mL/min. Predictors of nephrotoxicity were identified through logistic-regression analysis. RESULTS: Nephrotoxicity developed in 20 patients and did not develop in 21 patients. Nephrotoxicity developed during the first course of DCF therapy in 16 patients, the second course in 3 patients, and the third course in 1 patient. The dose of DCF therapy was decreased in 8 patients with nephrotoxicity and 7 patients without nephrotoxicity. Multivariate analysis showed that a low Ccr level immediately before DCF therapy was an independent risk factor for the development of nephrotoxicity (odds ratio, 0.932; 95% confidence interval, 0.876 to 0.992; P = 0.027). On receiver operating characteristic curve analysis, the optimal cutoff value of Ccr for the development of nephrotoxicity was 75.8 mL/min. The 2-year overall survival rate was 84.2% in patients with nephrotoxicity and 90.0% in patients without nephrotoxicity (P = 0.635). CONCLUSIONS: Low Ccr levels immediately before DCF therapy are a risk factor for the development of nephrotoxicity. Patients should therefore be carefully monitored.

The role of prophylactic cranial irradiation for patients with small-cell lung cancer.

Small-cell lung cancer (SCLC) has a particular propensity to metastasize to the brain, affecting ~10% of SCLC patients at diagnosis, but may occur in more than 50% of 2-year survivors. Most cytotoxic drugs have limited ability to cross the blood-brain barrier, and the effectiveness of chemotherapy for brain metastasis is limited. Therefore, prophylactic cranial irradiation (PCI) has been proposed to treat SCLC. A meta-analysis revealed that PCI significantly decreased the risk of brain metastasis and increased the 3-year survival rate; it has been established as a standard therapy for limited-disease SCLC. However, certain aspects of PCI remain unclarified, including the roles in resected SCLC and extensive-disease SCLC, and its neurotoxicities. In addition, information on PCI has been obtained from old clinical trials without the use of new imaging devices, such as magnetic resonance imaging. Evidence from advanced imaging techniques is needed in this era.

Enhanced activated T cell subsets in prostate cancer patients receiving iodine-125 low-dose-rate prostate brachytherapy.

Radiotherapy (RT) is one of the most important treatments for prostate cancer. Although RT can kill cancer cells through direct and indirect effects of radiation, it occasionally induces an abscopal effect whereby localized radiation treatment is associated with elimination of metastatic cancer at a distance from the irradiated area. Thus, RT may induce an effective antitumor immune response, although the mechanism involved has remained unclear. The present was designed to evaluate this effect of RT in 36 patients with prostate cancer who provided informed consent prior to enrollment in this clinical trial. Peripheral blood samples were collected periodically after low-dose-rate (LDR) prostate brachytherapy, and lymphocyte subsets were analyzed by flow cytometry. The proportion of activated T cells (CD3+HLA-DR+, CD4+HLA-DR+ and CD8+HLA-DR+) in peripheral blood revealed a gradual and bimodal increase after LDR brachytherapy, whereas memory CD8+ T cells bimodally decreased after treatment. The ratios of activated T cells and regulatory T cells gradually increased after the treatment. Thus, LDR brachytherapy was demonstrated to induce effective immune responses in patients. This increase of activated T cells may contribute to maintenance of remission and reduction of relapse rates.

Phase II Study of Concurrent Chemoradiotheapy Using Nedaplatin for Locally Advanced Uterine Cervical Carcinoma (KGROG0501): Final Results.

AIM: This phase II study using nedaplatin evaluated the effectiveness and safely of concurrent chemoradiotherapy for locally advanced uterine cervical carcinoma. PATIENTS AND METHODS: Patients met the following eligibility criteria,: International Federation of Gynecology and Obstetrics (FIGO) stage Ib, IIa, IIb with bulky tumor (≥40 mm) or pelvic lymph node swelling (≥10 mm), in FIGO stage IIIa, IIIb or IVa. Treatment adopted external radiation therapy combined with intracavitary brachyhtherapy using weekly nedaplain at 30 mg/m2 totaling five cycles. The primary endpoint was 3-year overall survival. RESULTS: From June 2005 to May 2010, 45 eligible patients with uterine cervical carcinoma were registered. Histopathology was squamous cell carcinoma in 36 and adenocarcinoma in nine. The median follow-up period was 39 months. The 3-year overall survival rate was 73.0% (95% confidence interval=56.2-84.2%). No severe acute or late toxicities occurred. CONCLUSION: This phase II study showed external radiation therapy combined with intracavitary brachyhtherapy using weekly nedaplain to be effective and safe.

Comparison of prostate contours between conventional stepping transverse imaging and Twister-based sagittal imaging in permanent interstitial prostate brachytherapy.

PURPOSE: To compare prostate contours on conventional stepping transverse image acquisitions with those on twister-based sagittal image acquisitions. MATERIAL AND METHODS: Twenty prostate cancer patients who were planned to have permanent interstitial prostate brachytherapy were prospectively accrued. A transrectal ultrasonography probe was inserted, with the patient in lithotomy position. Transverse images were obtained with stepping movement of the transverse transducer. In the same patient, sagittal images were also obtained through rotation of the sagittal transducer using the "Twister" mode. The differences of prostate size among the two types of image acquisitions were compared. The relationships among the difference of the two types of image acquisitions, dose-volume histogram (DVH) parameters on the post-implant computed tomography (CT) analysis, as well as other factors were analyzed. RESULTS: The sagittal image acquisitions showed a larger prostate size compared to the transverse image acquisitions especially in the anterior-posterior (AP) direction (p < 0.05). Interestingly, relative size of prostate apex in AP direction in sagittal image acquisitions compared to that in transverse image acquisitions was correlated to DVH parameters such as D90 (R = 0.518, p = 0.019), and V100 (R = 0.598, p = 0.005). CONCLUSIONS: There were small but significant differences in the prostate contours between the transverse and the sagittal planning image acquisitions. Furthermore, our study suggested that the differences between the two types of image acquisitions might correlated to dosimetric results on CT analysis.

Impact of five-tiered Gleason grade groups on prognostic prediction in clinical stage T3 prostate cancer undergoing high-dose-rate brachytherapy.

BACKGROUND: We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). METHODS: From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. RESULTS: The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). CONCLUSIONS: Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.