A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.

Effects of Coconut Materials on In vitro Ruminal Methanogenesis and Fermentation Characteristics.

The objective of this study was to evaluate the in vitro effects of coconut materials on ruminal methanogenesis and fermentation characteristics, in particular their effectiveness for mitigating ruminal methanogenesis. Fistulated Holstein cows were used as the donor of rumen fluid. Coconut materials were added to an in vitro fermentation incubated with rumen fluid-buffer mixture and timothy substrate for 24 h incubation. Total gas production, gas profiles, total volatile fatty acids (tVFAs) and the ruminal methanogens diversity were measured. Although gas profiles in added coconut oil and coconut powder were not significantly different, in vitro ruminal methane production was decreased with the level of reduction between 15% and 19% as compared to control, respectively. Coconut oil and coconut powder also inhibited gas production. The tVFAs concentration was increased by coconut materials, but was not affected significantly as compared to control. Acetate concentration was significantly lower (p<0.05), while propionate was significantly higher (p<0.05) by addition of the coconut materials than that of the control. The acetate:propionate ratio was significantly lowered with addition of coconut oil and coconut powder (p<0.05). The methanogens and ciliate-associated methanogens in all added coconut materials were shown to decrease as compared with control. This study showed that ciliate-associated methanogens diversity was reduced by more than 50% in both coconut oil and coconut powder treatments. In conclusion, these results indicate that coconut powder is a potential agent for decreasing in vitro ruminal methane production and as effective as coconut oil.

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.

PURPOSE: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). PATIENTS AND METHODS: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated. RESULTS: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors. CONCLUSION: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis.

BACKGROUND: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). METHODS: Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. RESULTS: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. CONCLUSIONS: Anti-IL-33 antibody has a therapeutic potential for experimental AR.

Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children.

OBJECTIVE: Previous studies on the relationship of bisphenol-A (BPA) with fractional exhaled nitric oxide (FeNO) had conflicting results, suggesting that other factors may modulate this relationship. Thus, we investigated the modulating effect of vitamin D on the relationship of BPA with FeNO in children. PATIENTS AND METHODS: This study recruited 432 children (10 to 12 years old) from the general pediatric population of Korea between June and July 2017. We conducted measurements of urinary BPA, serum vitamin D, specific serum IgE, FeNO, and data from impulse oscillometry (reactance area [AX], airway resistance at 5 Hz [Rrs5] and 20 Hz [Rrs10], and the difference of Rrs5 and Rrs20 [Rrs5-20]). RESULTS: Serum vitamin D (adjusted ß =- 0.014, p=0.002) and urinary BPA (ß = 0.006, p<0.001) level was significantly associated with FeNO. Urinary BPA level was significantly associated with FeNO in children with low vitamin D levels (≤23 ng/mL; αß = 0.006, p < 0.001), but not in children with high vitamin D levels (>23 ng/mL). The interaction of vitamin D and BPA had a significant effect on FeNO (pint = 0.005). There was no relationship with the airway lung function (Rrs5, AX, and Rrs5-20) to serum vitamin D and urinary BPA level. Vitamin D ameliorated the BPA-mediated increase of FeNO in children. CONCLUSIONS: These results suggest that children with low vitamin D levels may be more susceptible to airway inflammation due to BPA.

Epigenotype-phenotype correlations in Silver-Russell syndrome.

BACKGROUND: Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 are found in 5-10% and up to 60% of patients with SRS, respectively. As many features are non-specific, diagnosis of SRS remains difficult. Studies of patients in whom the molecular diagnosis is confirmed therefore provide valuable clinical information on the condition. METHODS: A detailed, prospective study of 64 patients with mUPD7 (n=20) or ICR1 hypomethylation (n=44) was undertaken. RESULTS AND CONCLUSIONS: The considerable overlap in clinical phenotype makes it difficult to distinguish these two molecular subgroups reliably. ICR1 hypomethylation was more likely to be scored as 'classical' SRS. Asymmetry, fifth finger clinodactyly and congenital anomalies were more commonly seen with ICR1 hypomethylation, whereas learning difficulties and referral for speech therapy were more likely with mUPD7. Myoclonus-dystonia has been reported previously in one mUPD7 patient. The authors report mild movement disorders in three further cases. No correlation was found between clinical severity and level of ICR1 hypomethylation. Use of assisted reproductive technology in association with ICR1 hypomethylation seems increased compared with the general population. ICR1 hypomethylation was also observed in affected siblings, although recurrence risk remains low in the majority of cases. Overall, a wide range of severity was observed, particularly with ICR1 hypomethylation. A low threshold for investigation of patients with features suggestive, but not typical, of SRS is therefore recommended.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

Rational Design of Low Cost and High Energy Lithium Batteries through Tailored Fluorine-free Electrolyte and Nanostructured S/C Composite.

We report a new Li-S cell concept based on an optimized F-free catholyte solution and a high loading nanostructured C/S composite cathode. The Li2 S8 present in the electrolyte ensures both buffering against active material dissolution and Li+ conduction. The high S loading is obtained by confining elemental S (≈80 %) in the pores of a highly ordered mesopores carbon (CMK3). With this concept we demonstrate stabilization of a high energy density and excellent cycling performance over 500 cycles. This Li-S cell has a specific capacity that reaches over 1000 mA h g-1 , with an overall S loading of 3.6 mg cm-2 and low electrolyte volume (i.e., 10 µL cm-2 ), resulting in a practical energy density of 365 Wh kg-1 . The Li-S system proposed thus meets the requirements for large scale energy storage systems and is expected to be environmentally friendly and have lower cost compared with the commercial Li-ion battery thanks to the removal of both Co and F from the overall formulation.

Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma.

From June 1997 to August 2005, 52 consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ASCR). Total body irradiation (TBI) in the first HDCT/ASCR and a shorter interval (< 12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P = 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year event-free survival (EFS) (+/- 95% confidence interval) for all 52 patients was 62.1+/-13.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P = 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.

Evaluation of 3D printed PCL/PLGA/ß-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/ß-tricalcium phosphate (PCL/PLGA/ß-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/ß-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/ß-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/ß-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/ß-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/ß-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

Genome-wide microRNA expression profiling in placentas of fetuses with Down syndrome.

INTRODUCTION: Down syndrome (DS) is the most common aneuploidy, caused by an extra copy of all or part of chromosome 21 (chr21). Differential microRNA (miRNA) expression is involved in many human diseases including DS. However, the genome-wide changes in miRNA expression in DS fetal placentas have yet to be determined, and the function of these changes is also unclear. METHODS: We profiled genome-wide miRNA expression in placenta samples from euploid or DS fetuses by using microarray technology and predicted the functions of differentially expressed miRNAs using bioinformatics tools. RESULTS: Thirty-four miRNAs were significantly differentially expressed in the DS placenta compared with the normal placenta (16 up-regulated and 18 down-regulated). However, expression of chr21-derived miRNAs did not change. Predicted target genes included 7434 genes targeted by up-regulated miRNAs and 6071 genes targeted by down-regulated miRNAs. Seventy-six of these target genes were located on chr21 (10 genes controlled by down-regulated miRNAs and 34 genes by up-regulated miRNAs, and 32 genes by both). Target genes on chr21 were significantly associated with DS and DS-related disorders, such as mental retardation, neurobehavioral manifestations, and congenital abnormalities. DISCUSSION: To our knowledge, this is the first genome-wide study to comprehensively survey placental miRNAs in DS fetuses. Our results provide new insight into miRNA expression in placentas of fetuses with DS. Additionally, our findings indicate that the differentially expressed miRNAs in the DS placenta may potentially affect various pathways related to DS pathogenesis.

Effect of customized small bowel displacement system in pelvic irradiation.

PURPOSE: Authors designed a customized small bowel displacement system (SBDS) to displace the small bowel out of the pelvic radiation fields and to minimize treatment related bowel morbidity. METHODS AND MATERIALS: From August 1995 to May 1996, 55 consecutive patients who received pelvic radiation therapy with the SBDS were included in this study. The SBDS consists of a customized Styrofoam compression device that can displace the small bowel out of the radiation fields and an individualized immobilization abdominal board for easy daily setup of the patient in prone position. After opacifying the small bowel with barium, the patients were laid prone and posterior-anterior (PA) and lateral (LAT) simulation films were taken with and without the SBDS. The volume of the small bowel included in the radiation fields with and without the SBDS were compared. RESULTS: Using the SBDS, the mean small bowel volume was reduced by 59% on PA and 51% on LAT films (p = 0.0001). In six patients (6 of 55, 11%), it was possible that no small bowel was included within the treatment fields. The mean upward displacement of the most caudal small bowel was 4.8 cm using the SBDS. Patients treated with the SBDS manifested a significantly lower incidence of diarrhea requiring medication (8 of 55, 15%) vs. those without the SBDS (24 of 39, 62%) (p < 0.05). CONCLUSION: The SBDS is a novel method that can be used to displace the small bowel away from the treatment portal effectively and to reduce the radiation therapy morbidity. Compliance with setup is excellent.

Design and development of new collimator cones for fractionated stereotactic radiation therapy in Samsung Medical Center.

PURPOSE: In stereotactic radiotherapy using X-Knife system, the commercially supplied collimator cone system had a few mechanical limitations. The authors have developed new collimator cones to overcome these limitations and named them "SMC type" collimator cones. METHODS: We made use of cadmium-free cerrobend alloy within the stainless steel cylinder housing. We made nine cones of relatively larger sizes (3.0 cm to 7.0 cm in diameter) and of shorter length with bigger clearance from the isocenter than the commercial cones. The cone housing and the collimator cones were designed to insert into the wedge mount of the gantry head to enable double-exposure linac-gram taking. RESULTS: The mechanical accuracy of pointing to the isocenter was tested by ball test and cone rotation test, and the dosimetric measurements were performed, all of which were with satisfactory results. A new innovative quality assurance procedure using linac-grams on the patients at the actual treatment setup was attempted after taking 10 sets of AP and lateral linac-grams and the overall mechanical isocenter accuracy was excellent (average error = 0.4 +/- 0.2 mm). CONCLUSIONS: We have developed the SMC type collimator cone system mainly for fractionated stereotactic radiation therapy use with our innovative ideas. The new cones' mechanical accuracy and physical properties were satisfactory for clinical use, and the verification of the isocenter accuracy on the actual treatment setup has become possible.

Fractionated stereotactic radiation therapy for extracranial head and neck tumors.

BACKGROUND: This study is to report the clinical experiences of fractionated stereotactic radiation therapy (FSRT) for extracranial head and neck tumors. METHODS AND MATERIALS: Between the period of July 1995 and November 1998, 48 patients with extracranial head and neck tumors were given FSRT as a boost and sole modality. Individualized treatment planning was performed using XKnife-3 system with relocatable Gill-Thomas-Cosman frame. In 24 patients, FSRT was applied as a boost technique following the 2-dimensional conventional external radiation therapy (ERT); in 24 patients FSRT was the sole radiotherapy modality. The primary diseases in the boost group consisted of nasopharynx cancer (19), lacrimal gland adenoid cystic carcinoma (3), orbital lymphoma (1), and skull-base recurrence of maxillary sinus adenoid cystic carcinoma (1). The primary diseases in the sole modality group consisted of recurrent nasopharynx cancer (12), orbital pseudotumor (4), skull-base recurrence of maxillary sinus, submandibular gland, and hypopharynx cancers (3), orbital rhabdomyosarcoma (2), orbital lymphoma (1), orbital metastasis of neuroblastoma (1), and nasal cavity melanoma (1). The fractionation schedule was to give 5 treatments per one week and the fractional doses were 2.0-3 Gy depending on the treatment aim and the FSRT volume. The FSRT doses varied depending on the nature of the primary diseases. RESULTS: The local tumor response in nasopharynx cancer patients was excellent compared to retrospective data without occurrence of unexpectedly severe complication. FSRT to other regions was well tolerated by the patients and resulted in good to excellent local tumor responses with no unacceptable side effects as expected by the authors. CONCLUSION: Based on the current observations, FSRT is a very effective and safe modality in the treatment of extracranial head and neck tumors.

A glass compensator filter to improve breast image quality in radiation therapy simulation.

PURPOSE: To improve the image quality of simulation films in tangential radiotherapy for breast cancer, we have designed a new compensator filter for the variation of breast contour using high-density-glass material. METHODS AND MATERIALS: The measurements and analyses of the body contour were done using CT scans, taken in the treatment position, of 20 breast cancer patients. The maximum tissue deficit that needed to be compensated for was 8 cm, and the authors fabricated the compensator system using high-density-glass material to maintain transparency. The glass compensator can be attached to the accessory mount of the simulator head and its position can be easily adjusted according to breast shape and position. The image qualities of simulation films taken with and without the glass compensator in tangential breast radiotherapy field were compared and the film densitometry was performed using the humanoid phantom. RESULTS: Using this compensator system, the overall image quality improved, resulting in enhanced contrast and resolution of the breast simulation image. The delineator wires for the beam margins were also well depicted, and the surgical clips within the breast tissue can be easily demonstrated. The film densitometry resulted in much less saturation over the breast tissue when using the glass compensator. CONCLUSION: Using the glass compensator system, the geographical miss may be reduced with the virtue of the improved image quality.

Prompt radiation oncology record access by patient centered digital image chart system.

The authors have developed and evaluated a radiation oncology digital image chart system (RODICS). With this system we could achieve paperless and filmless practice, and thus improved operational efficiency within the department. In this paper, we describe characteristics and clinical usage of RODICS.

Successive double high-dose chemotherapy with peripheral blood stem cell rescue collected during a single leukapheresis round in patients with high-risk pediatric solid tumors: a pilot study in a single center.

In total, 18 of 26 double high-dose chemotherapies (HDCT) in pediatric solid tumors were rescued with peripheral blood stem cells collected during a single leukapheresis round (single-harvest group, SHG). In the remaining eight HDCT, additional leukapheresis were necessary after the first HDCT (HDCT1) to rescue the second HDCT (HDCT2) (double-harvest group, DHG). Stem cell collection after HDCT1 was inefficient and delayed in patients who had received prior chemotherapy before HDCT1. The interval between HDCT1 and HDCT2 was shorter in SHG than in DHG (median 62.5 days vs 178.5 days, P-value=0.002). Hematologic recovery in HDCT2 was delayed compared to HDCT1. However, there was no difference in hematologic recovery between SHG and DHG. A high rate of treatment-related mortality (TRM) was recorded during HDCT2, but there was no evidence that the shorter interval caused a higher rate of TRM (P-value=0.454). The probability of disease-free survival at 2 years after HDCT2 in the SHG and DHG were 66.7 and 25.0%, respectively (P-value=0.031). Therefore, to administer the second HDCT earlier in double HDCT, and thus to improve the survival of patients with high-risk solid tumors, the single-harvest approach is recommended rather than the double-harvest approach.

Secondary angiosarcoma following irradiation--case report and review of the literature.

Angiosarcoma is a rare malignant tumor that accounts for 1% to 2% of all soft tissue sarcomas. This paper reports a case of radiation-associated angiosarcoma with a literature review of 66 cases. Twenty-nine years after transabdominal hysterectomy and adjuvant radiation therapy for uterine cervix cancer, cutaneous angiosarcoma developed in the abdominal wall of a 63-year-old woman. She underwent wide excision of the abdominal wall mass, radiation therapy, and chemotherapy, and has been alive and well without any evidence of metastasis for 23 months since the initial diagnosis of angiosarcoma. After an intensive literature review, we found 66 cases of radiation-associated angiosarcoma. The most common primary disease was breast cancer (44%), with gynecologic cancer (21%) next. Eighty-five percent of radiation-associated angiosarcomas developed in the cutaneous area. The median age at diagnosis was 65 years, and the median latency period from irradiation to diagnosis was 96 months. The median survival period of 48 patients whose survival lengths could be reviewed was 12 months.

Analysis of correlation between rectal complications and rectal dose following high dose rate intracavitary radiotherapy in patients with uterine cervix cancer: in vivo dosimetric analysis.

PURPOSE: To investigate the correlation between late rectal complications and rectal dose in uterine cervix cancer patients treated with high dose rate intracavitary radiotherapy (HDR ICR) and to analyze dose factors reducing complications. METHODS: A retrospective analysis was done of 74 patients treated with external beam RT and HDR ICR between 1995 and 1997. Radiotherapy (RT) consisted of a median 50.4 Gy external beam plus six fractions of HDR ICR given two times per week, concurrent with the last three weeks of external beam therapy, to a total dose of median 24 Gy to point A or the reference point. Rectal doses were calculated at rectal reference points using barium contrast criteria. In vivo measurement of rectal dose was performed with thermoluminescent dosimeters (TLD) immediately prior to the first fraction of HDR ICR. RESULTS: Eight patients developed rectal complications (11%). There was a significant difference between measured rectal doses for patients with rectal complications and those without (p < 0.05), and the doses were higher in complicated patients. A significant increase in the probability of development of complications was found for patients receiving measured rectal doses of ICR fractional dose 320 cGy or more, ICR total dose 2000 cGy or more, and ICR% to point A 80% or more. CONCLUSIONS: This study showed that in vivo dosimetry using TLD during HDR ICR could have a useful role as a predictor of late rectal complications. Dose limitation to the rectum could possibly be achieved by thorough vaginal packing or use of an applicator with proper shielding while maintaining a high dose to the tumor.