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The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- ). Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centre’s activities will also be devoted to the production of known species for preclinical studies and research into innovative radiopharmaceuticals in collaboration with other scientific units of this Campus as well as with members of the Warsaw Consortium for PET Collaboration. Research into the accelerator production route of 99mTc will also begin shortly.

Background: A recent randomized trial (NCT01535209) demonstrated no difference in neurocognitive function between stereotactic radiotherapy of the tumor bed (SRT-TB) and whole brain radiotherapy (WBRT) in patients with resected single brain metastasis. Patients treated with SRT-TB had lower overall survival compared with the WBRT arm. Here, we compared the health-related quality of life (HRQOL) in patients who received WBRT vs. SRT-TB.Methods: A self-reported questionnaire was used to assess HRQOL (EORTC QLQ-C30 with the QLQ-BN20 module) before RT, 2 months after RT, and every 3 months thereafter. HRQOL results are presented as mean scores and compared between groups.Results: Of 59 randomized patients, 37 (64%) were eligible for HRQOL analysis, 15 received SRT-TB, and 22 had WBRT. There were no differences between groups in global health status and main function scales/symptoms (except for drowsiness and appetite loss, which were worse with WBRT 2 months after RT). Global health status decreased 2 and 5 months after RT, but significantly only for SRT-TB (p = 0.025). Physical function decreased significantly 5 months after SRT-TB (p = 0.008). Future uncertainty worsened after RT, but significantly only for SRT-TB after 2 months (p = 0.036). Patients treated with WBRT had significant worsening of appetite, hair loss, and drowsiness after treatment.Conclusions: Despite higher symptom burden after WBRT attributed to the side effects of RT (such as appetite loss, drowsiness, and hair loss), global health status, physical functioning, and future uncertainty favored WBRT compared with SRT-TB. This may be related to the compromised brain tumor control with omission of WBRT. [ABSTRACT FROM AUTHOR]

The planning, history of construction, description of the equipment and the expected activity program of the University of Warsaw Radiopharmaceuticals Production and Research Centre are presented. [ABSTRACT FROM AUTHOR]

The wastes of cross-linked polyurethane resins from adipic acid and ethylene glycol polyester, methylenediisocyanate and 1,4-butandiol were subjected to linearization with ε-caprolac tam. [ABSTRACT FROM PUBLISHER]

Objectives: With decreasing PICU mortality, survivor morbidity has increased. This study aims to evaluate feasibility of virtual PICU-led follow-up of patients at risk for pediatric postintensive care syndrome., Design: Prospective cohort study., Setting: Single-center, quaternary children's hospital., Patients: Children less than or equal to 4 years without known preexisting neurodevelopmental deficits requiring greater than or equal to 12 hours mechanical ventilation., Interventions: None., Measurements and Main Results: Age-appropriate Ages and Stages Questionnaires, Third Edition (ASQ-3) were administered via a web-based system at 3, 6, and 12 months following PICU discharge. Primary-care physicians were notified of results; at-risk patients were referred to early developmental intervention. Forty-eight patients enrolled with median age 11.5 months (interquartile range [IQR], 2-19.5 mo) and median mechanical ventilation duration 92.5 hours (IQR, 40.5-147 hr). Fifty-eight percent completed greater than or equal to 1 ASQ-3. Lower caregiver educational achievement, lower income, and single-caregiver status were associated with lower ASQ-3 completion rates. Of those completing any ASQ-3, 50% flagged as at-risk for developmental delay and referred to early developmental intervention. There was no association between patient characteristics and abnormal ASQ-3., Conclusions: Virtual caregiver-completed surveillance is a promising method to screen children for neurodevelopmental abnormalities following PICU hospitalization and facilitate early referral for developmental intervention, but special attention must be dedicated to families with limited resources for follow-up., Competing Interests: Dr. Boyle received support for article research from the Indiana University School of Medicine Department of Physics. Dr. Abu-Sultaneh received funding from the Indiana University School of Medicine Department of Physics. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background and Purpose: A detailed contouring atlas of the heart valves is lacking. Existing heart contouring atlases have not been evaluated on average intensity projection four-dimensional non-contrast computed tomography (AVE-4D-CT) scans, routinely used for organ-at-risk delineation in lung cancer radiotherapy. We aimed to develop the heart valve contouring atlas and to assess inter-observer variation in delineation of the heart, its substructures, and coronary arteries on AVE-4D-CT scans, along with its impact on radiotherapy doses., Materials and Methods: A heart valve contouring atlas was developed. Five radiation oncologists and four cardiologists delineated the valves according to this atlas, and the remaining heart substructures according to the existing atlases, on AVE-4D-CT scans of ten patients who underwent radio(chemo)therapy for NSCLC. The observer contours were then compared to the collectively defined "reference" contours. Spatial variation was assessed using the Sørensen-Dice similarity coefficient (DSC), directed average Hausdorff distance (DAH), directed Hausdorff distance (HD), and the mean distance to agreement (MDA). The effect of spatial variation on radiotherapy doses was assessed using the patients' treatment plans., Results: Inter-observer contour overlap (mean DSC) was 0.68, 0.49, 0.45 and 0.45, and inter-observer contour separation (mean DAH) was 2.1, 3.4, 2.6 and 2.9 mm for the pulmonic (PV), aortic (AV), mitral (MV) and tricuspid valve (TV), respectively. Mean HD was higher for TV and MV (13.3 and 11.7 mm) than for AV and PV (7.8 and 7 mm). The highest mean MDA of 3.1 mm was found for AV, and the lowest (1.9 mm) for PV. Inter-observer agreement was the lowest for the coronary arteries, but statistically significant dose variation was found mainly in the left ventricular septal and anterior segments., Conclusion: Our atlas enables reproducible delineation of the heart valves. Delineation of the heart and its substructures on AVE-4D-CT scans is feasible, with inter-observer variability similar to that reported on conventional non-contrast CT scans., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Although autism spectrum disorder (ASD) can be reliably detected in the second year of life, the average age of diagnosis is 4 to 5 years. Limitations in access to timely ASD diagnostic evaluations delay enrollment in interventions known to improve developmental outcomes. As such, developing and testing streamlined methods for ASD diagnosis is a public health and research priority. In this report, we describe the Early Autism Evaluation (EAE) Hub system, a statewide initiative for ASD screening and diagnosis in the primary care setting. Development of the EAE Hub system involved geographically targeted provision of developmental screening technical assistance to primary care, community outreach, and training primary care clinicians in ASD evaluation. At the EAE Hubs, a standard clinical pathway was implemented for evaluation of children, ages 18 to 48 months, at risk for ASD. From 2012 to 2018, 2076 children were evaluated (mean age: 30 months; median evaluation wait time: 62 days), and 33% of children received a diagnosis of ASD. Our findings suggest that developing a tiered system of developmental screening and early ASD evaluation is feasible in a geographic region facing health care access problems. Through targeted delivery of education, outreach, and intensive practice-based training, large numbers of young children at risk for ASD can be identified, referred, and evaluated in the local primary care setting. The EAE Hub model has potential for dissemination to other states facing similar neurodevelopmental health care system burdens. Implementation lessons learned and key system successes, challenges, and future directions are reviewed., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Objective: Group visits (GVs) are a promising intervention, but more work is needed to establish intervention effects. The objective was to evaluate the effectiveness of GVs and compare them with individual visits (INDs) for chronic care of attention deficit-hyperactivity disorder (ADHD)., Methods: Caregivers and children (6-12 yrs) with ADHD participated in a comparative effectiveness trial from April 2014 to June 2015. Families were offered ADHD follow-up every 3 months as GVs versus INDs. Outcomes included ADHD core symptoms, child functioning at home, quality of life, perceived social support, and ADHD-related parenting challenges. Change scores from baseline to the study end were examined for parent and child outcomes within and between treatment conditions., Results: Ninety-one children from 84 families participated. Eighteen families withdrew or were lost to follow-up. GV families attended more visits over 12 months, had significant improvement in mean parental emotional health (p = 0.04), and had a greater decrease in challenges related to misbehavior compared with IND families (p < 0.03). GV families experienced significant improvements in child functioning at home (p = 0.01) and reported more time for themselves, other siblings, and routine household activities (p < 0.01). Children receiving care as INDs reported a significant drop in mean emotional health. There were no significant changes in other outcomes., Conclusion: Families participating in GVs experienced multiple improvements related to family functioning and attended more follow-up visits. Findings confirm the effectiveness of the GV intervention in delivering critical parenting support as part of ADHD management.

Objective: Children with attention-deficit hyperactivity disorder (ADHD) have ongoing needs that impair home and school functioning. Group visit models are a promising way to deliver timely parenting support but family and provider acceptance has not previously been examined. The objective was to describe the acceptability of ADHD group visits in busy pediatric clinics based on caregivers, child participants and facilitators., Methods: Data were analyzed from school-age children and caregivers who participated in one of two 12-month long randomized controlled studies of the ADHD group visit model from 2012 to 2013 or 2014 to 2015. Feedback was obtained using semi-structured questions at each study end, by telephone or at the last group visit. Sessions were audio-recorded, transcribed and themes were extracted by participant type., Results: A total of 34 caregivers, 41 children and 9 facilitators offered feedback. Caregivers enjoyed the "support group" aspect and learning new things from others. Caregivers reported improved understanding of ADHD and positive changes in the relationship with their child. Children were able to recall specific skills learned including how skills helped at home or school. Facilitators acknowledged systems-level challenges to offering group visits but felt the group format helped increase understanding of families' needs, improved overall care, and provided innovative ways to engage with families., Conclusion: The majority of comments from families and facilitators highlighted a variety of benefits of the use of a group visit model for ADHD chronic care. Despite systems-level barriers to implementation, families and facilitators felt the benefits outweighed the challenges.

Purpose: To evaluate if neurological/cognitive function outcomes in patients with resected single brain metastasis (BM) after stereotactic radiotherapy of the tumor bed (SRT-TB) are not inferior compared to those achieved with whole-brain radiotherapy (WBRT)., Methods: Patients with total/subtotal resection of single BM were randomly assigned either to SRT-TB (n=29) or WBRT (n=30). SRT-TB arm consisted of 15Gy/1 fraction, or 5×5Gy. WBRT consisted of 30Gy/10 fractions. Neurological/cognitive failure was defined as a decrease of neurological score by one point or more, or a worsening of the MiniMental test by at least 3 points, or neurological death. Cumulative incidence of neurological/cognitive failure (CINCF), neurological death (CIND), and overall survival (OS) were compared., Results: Median follow-up was 29months (range: 8-45) for 15 patients still alive. The difference in the probability of CINCF at 6months (primary endpoint) was -8% in favor of WBRT (95% confidence interval: +17% -35%; non-inferiority margin: -20%). In the intention-to-treat analysis, two-year CIND rates were 66% vs. 31%, for SRT-TB and WBRT arm, respectively, p=.015. The corresponding figures for OS were 10% vs. 37%, p=.046., Conclusions: Non-inferiority of SRT-TB was not demonstrated in our underpowered study. More data from randomized studies are needed for confirmation of the value of this method., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: Children with attention-deficit hyperactivity disorder (ADHD) may experience continued impairment at home and school even after medication initiation. Group visits offer a way for pediatricians to provide more time to address ongoing needs. A pilot study was undertaken to examine whether a group visit model improved ADHD management in the pediatric medical home., Methods: Parents and children aged 6 to 18 years with ADHD were recruited and randomized to group visits or a usual care control. Data included attendance at ADHD follow-up visits, parent-rated ADHD symptoms, adaptive functioning, and quality of life. Longitudinal linear mixed models (continuous variables) and generalized linear mixed models (binary outcomes) were used to compare groups. In our statistical models, child and family were random effects; study assignment was a fixed effect., Results: Twenty families representing 29 children participated (intervention: 9 parents/13 children and control: 11 parents/16 children). Aside from race, baseline characteristics of participants were similar. None of the intervention families missed the expected 5 ADHD follow-up visits over 1 year; control families missed 1 or more visits over the same period. Intervention families reported an improved level of adaptive functioning at 12 months compared with control (mean severity score: 3.7 vs 4.4, p = .003). All families reported greater limitations and poorer quality of life compared with national norms., Conclusion: Group visits in the pediatric medical home can improve adherence, and preliminary results show a variety of improvements for the family.

Purpose: To compare accelerated hypofractionated (A-HYPO) radiotherapy (RT) with conventionally fractionated (CF) thoracic RT in patients with limited-disease small-cell lung cancer (LD-SCLC)., Methods: Out of 217 consecutive LD-SCLC patients, treated between 1997 and 2012, 82 received CF-RT (44-60 Gy, 2 Gy/ fraction) sequentially to 4-6 cycles of platinum-based chemotherapy (CHT), and 100 received A-HYPO-RT (42 Gy, 2.8 Gy/ fraction). Forty-two patients (42%) received "early" (before the 3rd cycle of CHT) A-HYPO-RT, and 58 (58%) patients received "late" A-HYPO-RT. Overall survival (OS), locoregional failure risk (LRFR) and toxicities were retrospectively evaluated and compared between CF-RT and A-HYPO-RT groups (also separately for "early" and "late" A-HYPO-RT)., Results: Median survival times (MST) for CF-RT and A-HYPO-RT were 18 and 24 months, respectively; 3-year OS were 19.1 and 39.4%, respectively (p=0.004). Three-year LRFR in CF-RT was 47.3% and 34.0% in the A-HYPO- RT group (p=0.12). Statistically significant difference in OS (p=0.007) and LRFR (p=0.03) was observed, favoring "early" A-HYPO-RT (MST=27 months, 3-year OS=40.0%, 3-year LRFR=28.4%) over CF-RT. Use of CF-RT (relative risk/RR=1.65, p=0.02) and poor CHT compliance (RR=1.69, p=0.03) were independent prognostic factors for poor OS; "early" start of RT was a favorable although non-significant prognostic factor for LRFR (RR=0.42, p=0.05). No difference in toxicities was observed between the groups., Conclusions: A-HYPO-RT results in better outcomes than CF-RT. "Early" A-HYPO-RT provides additional benefit in locoregional control and survival, without increased toxicity. These results indicate the need for a randomized study on the efficacy of A-HYPO-RT.

Introduction: Stereotactic body radiotherapy (SBRT) is rapidly gaining favor as a new treatment modality for malignant liver tumors. Most of the studies have recruited patients with disseminated disease originating from the liver. This study focuses on disease limited to the liver., Aim: To perform a retrospective analysis of all patients with liver tumors treated by robotic stereotactic body radiation therapy in a single center., Material and Methods: The study included 13 patients with 22 lesions. The inclusion criteria were: patients with 1-4 inoperable liver lesions and absence of any extrahepatic disease. All but 3 patients received 3 fractions delivered by the Cyberknife system of a total of 45 grey (Gy). The other 3 patients received 30 Gy., Results: The median follow-up time was 10.8 months (range: 7-16). The median dose was 41.5 Gy (range: 30-45). One lesion regressed (8%). In 5 patients, the disease was locally stabilized (38%), and in 7 other patients progression occurred (54%). Twelve patients (92%) are still alive, and 1 patient (8%) died. In 1 patient a new cancer (leukemia) was diagnosed., Conclusions: The SBRT is well tolerated and effective for local control of most liver malignant tumors. It appears that SBRT is best suited for those patients in whom systemic recurrence can be controlled by chemotherapy. Further studies are mandatory to elucidate these effects on tumors of varying histology and to elaborate upon criteria used to select patients who can benefit most from this treatment.

Aim: To evaluate the results of hypofractionated conformal radiotherapy (RT) in limited disease small cell lung cancer (LD-SCLC) patients, with particular interest in the value of "early" RT, i.e. given before the 3rd chemotherapy (CHT) cycle., Material and Methods: Outcome of hypofractionated RT (42 Gy, 2.8 Gy/fraction, given over 19-21 days, using "concomitant boost" technique - elective volume [39 Gy, 2.6 Gy/fraction] and tumour volumes treated during the same fraction) combined with CHT in 100 consecutive LD-SCLC patients, was retrospectively assessed. The outcomes were compared with a previously published series of 117 LD-SCLC patients treated in the same institution with hyperfractionated or conventionally fractionated RT., Results: Forty-two patients (42%) received "early" RT. Grade 3 NCI CTC acute oesophageal toxicity appeared in 5% of patients. There were three treatment-related deaths. Three-year overall survival (OS) rate was 39.4%, median - 24 months in the examined group vs. 26.0%, and 18 months in historical control, P = 0.02. Three-year OS for 78 patients with completed CHT was 42.2%, median - 28 months vs. 30%, and 14 months for 22 patients who received ≤ 3 CHT cycles, (P = 0.03). The actuarial 3-year locoregional failure risk (LRFR) was 34.0% in the examined group vs. 51.0% in the historical control, P = 0.04. Multivariate analysis showed a marginally significant correlation between the "early" use of RT and LRFR: RR = 0.43 (95% CI: 0.17-1.04), P = 0.06, with no significant impact on OS., Conclusions: Shorter duration of RT using hypofractionation results in encouraging outcomes and acceptable toxicity. Completion of all planned CHT cycles is the most important factor for OS.

Objective: This study assessed the prevalence of failed developmental screens in 30- to 60-month-old children who presented with a behavioral complaint of disruptive behavior to a referral clinic., Methods: A retrospective chart review was performed in a specialty behavioral pediatric clinic. Outcome measures were obtained from children referred to the clinic with parental concern of disruptive behavior., Results: Out of 151 patients, 66% (99/151) had been screened for developmental delays with a formal screening instrument. Of these, 71% (70/99) failed developmental screening in one or more domains., Conclusions: Preschoolers referred to a behavioral clinic for parental concerns of disruptive behaviors were more than 4 times more likely to be at risk for developmental delays than the general population, with a majority of suspected delays in communication and problem-solving domains. This finding suggests that developmental screening should be a part of the initial workup for children with disruptive behaviors.

Aim: To present a retrospective analysis of results of definitive radiotherapy for rectal cancer., Material and Methods: Forty-one consecutive patients with rectal cancer (32% primary, 61% pelvic recurrence and 7% after R2 resection) who could not be treated with surgery underwent external beam radiotherapy. A median tumour dose of 64 Gy was given with 1.8-2.5 Gy per fraction using 2D or 3D technique. In 46% of patients, concurrent 5-Fu-based chemotherapy was given. The median follow-up was 54 months., Results: Clinical complete response was achieved in 39% of patients. Five-year cumulative incidence of local failure, overall survival and cancer specific survival were 76%, 26% and 30%, respectively. Of 11 patients with local control, in five cases the tumour was larger than 5 cm and in the other five the tumour was fixed. Two patients, regarded as locally controlled had non-progressive tumour without local symptoms at the last follow-up of 54 and 118 months post-radiotherapy. Late toxicity occurred in 22% of patients, all with acceptable severity. There was no bowel obstruction requiring surgery despite that in 18 patients the small bowel dose was >60 Gy to a mean volume of 51 cm(3)., Conclusion: Definitive radio(chemo)therapy provides a chance for local control even in patients with large fixed or recurrent rectal cancer.

In this article, we have presented evidenced-based recommendations for primary care providers in their approach to the treatment of acne in adolescents. Table 2 summarizes the treatment recommendations proposed in this article.

Background and Aim: Long-term survival of lung cancer patients with brain metastases (BM) is very rare. Our aim is to report the characteristics of patients who survived for at least three years after a BM diagnosis., Materials and Methods: Nineteen lung cancer patients who had survived ≥3 years after a BM diagnosis were identified in our database. Seven (37%) had undergone whole-brain radiotherapy (WBRT) only, five (26%) BM surgery + WBRT, three (16%) BM surgery + WBRT + BM radiosurgery, and four (21%) no WBRT (one, surgery; one, radiosurgery; two, BM surgery + radiosurgery). Their characteristics were compared with historical data for 322 lung cancer patients with BM (control group, CG), who had received WBRT between 1986 and 1997., Results: Median survival from BM in long survivors group was 73 months (in CG - 4 months). Characteristics comparison: median age 55 vs. 58 (CG), p = 0.16; female sex 68% vs. 28% (CG), p = 0.003; RTOG/RPA class 1 - 75% vs. 13% (CG), p = 0.00001; adenocarcinoma histology 84% vs. 24% (CG), p < 0.00001; control of primary tumor 95% vs. 27% (CG), p < 0.00001; extracranial metastases 0 vs. 26% (CG), p = 0.01; single BM 63% vs. 9% (CG), p = 0.00001; surgery of BM 53% vs. 14% (CG), p = 0.00001., Conclusions: Beside prognostic factors already recognized as favorable in patients with BM, the adenocarcinoma histology and female sex were prevalent in long-term survivors of BM from lung cancer.

Introduction: In early stage non-small cell lung cancer (NSCLC) the stereotactic body radiation therapy (SBRT) gives promising results, similar to the results of surgical series. However, not all such patients are the candidates for this treatment method. The retrospective analysis of the results of three-dimensional conformal radiotherapy (3D-CRT) in stage I and II of NSCLC was undertaken, with a special focus on the patients who were candidates for SBRT treatment, but received 3D-CRT due to no access to the SBRT., Material and Methods: One hundred thirty-two consecutive stage I-II NSCLC patients who received radical 3D-CRT between 1998 and 2009 were included. Different radiotherapy schedules were used; thus the biologically equivalent doses (BED) were calculated for all. Sixty-eight patients met criteria of qualification for SBRT (peripheral T1-3N0 tumors with diameter £ 5 cm). Overall survival and local progression free survival (LPFS) were estimated for the whole group and compared for patients being and not being candidates for SBRT. Uni- and multivariate analyses were performed for prognostic factors., Results: Median BED value was 74 Gy (58-82 Gy). Patients who met SBRT criteria had significantly smaller gross tumor volume (GTV) comparing to the remainder (p 〈 0.00001). Three-year overall and local progression free survival rates were 37% and 50%, respectively. In comparison of SBRT candidates and others, only significant difference in three-year LPFS was obtained, 58% and 35%, respectively, p = 0.04. However, in the multivariate analysis, GTV, performance status, and stage were the only three prognostic factors for LPFS., Conclusions: After 3D-CRT, superior local control for early stage NSCLC patients who met criteria of inclusion for SBRT in comparison with the remainder was demonstrated. However, this outcome was inferior to the local control after SBRT reported in the literature.

Background/purpose: The benefit of whole brain radiotherapy (WBRT) for RTOG RPA (Radiation Therapy Oncology Group Recursive Partitioning Analysis) class 3 patients with brain metastases is not well established. The aim of this study was to determine whether WBRT has any benefit in terms of symptoms palliation in such patients. Evaluation of patients' preferences for WBRT, changes in performance and neurological status were secondary aims., Methods: Ninety-one RTOG RPA class 3 patients were included. All patients received WBRT (20 Gy in 5 fractions) and were asked to complete a questionnaire about their symptoms before and one month after WBRT. The patient's symptom checklist comprised 17 items scored from 0 to 3; a higher score meant a greater symptom intensity. The mean scores at baseline and after treatment were compared. Karnofsky performance status (KPS) and neurological status before and one month after WBRT were also recorded. Patients were asked to express their preference as to the WBRT undergone., Results: Forty-three (47%) patients completed both symptom checklists. The mean scores on the symptom checklist were 18.21 and 21.09 at baseline and one month after WBRT, respectively (p = 0.02). The KPS was estimated after WBRT in 42 patients: 57% of patients improved, 26% worsened, and 17% did not change from the baseline KPS score (p = 0.06). Neurological status did not change from baseline to one month after WBRT (p = 0.44). Only 7% of respondents would not have consented to the WBRT undergone., Conclusion: Our results challenge the palliative value of the WBRT in RPA class 3 patients.

Purpose: To determine the efficacy of accelerated hypofractionated three-dimensional conformal radiotherapy (3D-CRT) with dose-per-fraction escalation for treatment of stage III non-small cell lung cancer (NSCLC)., Patients and Methods: Between 2001 and 2007, 173 patients with stage III NSCLC were treated using accelerated 3D-CRT and the simultaneous boost technique. Initially, the total dose of 56.7 Gy (including 39.9 Gy to the elective area) was delivered over 4 weeks in fractions of 2.7 Gy (1.9 Gy to the elective area). The dose-per-fraction escalation study commenced after the outcomes of 70 patients had been evaluated. The dose per fraction was increased from 2.7 through 2.8 Gy (level 1 escalation) to 2.9 Gy (level 2 escalation); the total dose increased, respectively, from 56.7 Gy through 58.8 Gy to 60.9 Gy. The dose to the elective area and the overall treatment time remained unchanged. Fit patients received two to three courses of chemotherapy before radiotherapy., Results: The 2- and 3-year overall survival rates were 32 and 19%, respectively (median survival = 17 months). Of the patients, 7% had grade III acute esophageal toxicity and 6% had grade III or greater late pulmonary toxicity. Two of the nine patients who received the level 2 escalation (60.9 Gy) died of pulmonary toxicity. The study was terminated at a dose of 58.8 Gy and this schema was adopted as the institutional policy for treatment of stage III NSCLC., Conclusions: Although dose escalation with accelerated hypofractionated 3D-CRT was limited, the results and toxicity profiles obtained using this technique are promising.

Sialyl Lewis x and related fucosylated glycans are differentially expressed in human cells and form ligands for selectin adhesion receptors. alpha(1,3)Fucosyltransferases (FUTs) that complete their biosynthesis also show tissue specificity. We have established physical maps of the FUT3-6 loci to study regulation of this gene family. FUT4 has previously been localized to chromosome 11q21; FUT3, FUT6, and now FUT5 are localized to chromosome 19p13.3. Conventional and pulsed-field gel electrophoresis mapping of total genomic DNA and large genomic clones were used to generate a fine map of both loci, defining the order, orientation, and distances between FUTs. A P1 clone with all three 19p FUT genes in tandem orientation was isolated and used to study regions flanking FUT3, -5, and -6. Our studies provide preliminary information to study regulation of human FUT genes.