PS Patients Research Articles

Palliative radiotherapy regimens for patients with thoracic symptoms from non-small cell lung cancer.

Palliative radiotherapy to the chest is often used in patients with lung cancer, but radiotherapy regimens are more often based on tradition than research results. This is an update of a Cochrane review first published in 2001 and previously updated in 2006. The two objectives of this review were:1. To assess the effects of different palliative radiotherapy regimens on improving thoracic symptoms in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent.2. To assess the effects of radiotherapy dose on overall survival in patients with locally advanced or metastatic non-small cell lung cancer who are not suitable for radical RT given with curative intent. The electronic databases MEDLINE (1966 - Jan 2014), EMBASE and the Cochrane Central Register of Controlled Trials, reference lists, handsearching of journals and conference proceedings, and discussion with experts were used to identify potentially eligible trials, published and unpublished.Two authors (FM and RS) independently identified all studies that may be suitable for inclusion in the review.We updated the search up to January 2014. Randomised controlled clinical trials comparing different regimens of palliative thoracic radiotherapy in patients with non-small cell lung cancer. The reviewers assessed search results independently and possible studies were highlighted and the full text obtained. Data were extracted and attempts were made to contact the original authors for missing information.The primary outcome measure was improvement in major thoracic symptoms (degree and duration). Secondary outcome measures were short and long term toxicities, effect on quality of life and overall survival.Patient reported outcomes were reported descriptively. Quantitative data such as survival and toxicity were analysed as dichotomous variables and reported using relative risks (RR).For this update of the review a meta-analysis of the survival data was carried out. Fourteen randomised controlled trials (3576 patients) were included, with no new studies added in this update.There were important differences in the doses of radiotherapy investigated, the patient characteristics including disease stage and performance status and the outcome measures.The doses of RT investigated ranged from 10 Gy in 1 fraction (10Gy/1F) to 60 Gy/30F over six weeks, with a total of 19 different dose/ fractionation regimens.Potential biases were identified in some studies. Methods of randomisation, assessment of symptoms and statistical methods used were unclear in some papers. Withdrawal and drop-outs were accounted for in all but one study.All 13 studies that investigated symptoms reported that major thoracic symptoms improved following RT.There is no strong evidence that any regimen gives greater palliation. Higher dose regimens may give more acute toxicity and some regimens are associated with an increased risk of radiation myelitis. Variation in reporting of toxicities, in particular the absence of clear grading, means results of the meta-analysis should be treated with caution.Meta-analysis of overall survival broken down by performance status, a key variable, is included in this update. Further information was sought from all the original authors if stratified data was not included in the original publication. Three published studies contained sufficient data and seven authors were able to provide further information which represented 1992 patients (56% of all patients). The absence of data for nearly half of the patients has affected the quality of evidence.The meta-analysis showed no significant difference in 1-year overall survival between regimens with fewer radiotherapy fractions compared with regimens with more when patients were stratified by performance status. The results of the meta-analysis of 1-year overall survival for patients with good performance status (WHO performance status 0-1) showed moderately high heterogeneity and a summary result was not thought meaningful. The results of 1-year overall survival for patients with poor performance status was RR 0.96 (95% CI 0.91 to 1.02; moderate quality of evidence). Radiotherapy for patients with incurable non-small cell lung cancer can improve thoracic symptoms. Care should be taken with the dose to the spinal cord to reduce the risk of radiation myelopathy. The higher dose, more fractionated palliative radiotherapy regimens do not provide better or more durable palliation and their use to prolong survival is not supported by strong evidence. More research is needed into reducing the acute toxicity of large fraction regimens and into the role of radical compared to high dose palliative radiotherapy. In the future, large trials comparing different RT regimens may be difficult to set up because of the increasing use of systemic chemotherapy. Trials looking at how best to integrate these two modalities, particularly in good PS patients, need to be carried out.

RT-22 * MRI AND FET PET FOR RADIOTHERAPY PLANNING IN RECURRENT HIGH-GRADE GLIOMA (HGG) IN A PROSPECTIVE PHASE I TRIAL

BACKGROUND AND PURPOSE: Re-irradiation of HGG at recurrence may be a viable treatment option for some patients. Positron emission tomography (PET) using the amino acid tracer, 18F-fluoro-ethyltyrosine (FET) may have higher specificity and sensitivity than MRI in this setting. Both FET PET and MRI were used for target delineation in a prospective trial. The purpose of this study was to evaluate the impact of FET PET on the radiotherapy target. MATERIAL AND METHODS: A phase I trial examined the safety of hypofractionated stereotactic re-irradiation at different dose levels. Patients in PS 0-2 with localized recurrence of HGG and no other treatment options were eligible. With MRI, tumor was manually contoured using T1 contrast enhanced sequences. For PET, a threshold of 1.6x mean in background was used in a semi-automatic segmentation procedure. The planning target volume for treatment was the combination of both tumor volumes (MRI and PET) plus a 2 mm margin. Matlab software was used for spatial analyses. (Trial identifier: NCT02025231). RESULTS: Twenty-eight patients were included (GBM: n = 22; grade 3 glioma: n = 6). All patients had received radiotherapy and temozolomide, and 61 % had previously received bevacizumab. Median tumor volume defined by MRI and PET was 34 cm3 (range: 0-230 cm3) and 24 cm3 (range:0-214 cm3), respectively. Using PET increased the total gross tumor volume by a median of 10 cm3 (range:0-77 cm3), compared to MRI alone. The median longest distance from the MRI-target to encompass the PET-target was 10 mm (range: 0.6 to 43 mm). CONCLUSION: Tumor volumes defined by MRI and PET were spatially separated by up to 43 mm indicating that large portions of PET positive tumor would be missed if the target was solely based on MRI (T1 + contrast). FET PET may be useful for tumor delineation in re-irradiation of HGG.

Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.

ObjectiveThe immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases.MethodsPeripheral blood CD14+ and CD14− cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Paired synovial (n = 3, RA, PsA) and skin biopsies (n = 5, Ps) were also collected. Gene expression was analyzed by microarrays.Results26 out of 31 subjects responded to IFX. The transcriptional response of CD14+ cells to IFX was unique for the three diseases, with little overlap (<25%) in significantly changed gene lists (with PsA having the largest number of changed genes). In Ps, altered gene expression was more pronounced in lesional skin (relative to paired, healthy skin) compared to blood (relative to healthy controls). Marked suppression of up-regulated genes in affected skin was noted 2 weeks after therapy but the expression patterns differed from uninvolved skin. Divergent patterns of expression were noted between the blood cells and skin or synovial tissues in individual patients. Functions that promote cell differentiation, proliferation and apoptosis in all three diseases were enriched. RA was enriched in functions in CD14− cells, PsA in CD14+ cells and Ps in both CD14+ and CD14− cells, however, the specific functions showed little overlap in the 3 disorders.ConclusionDivergent patterns of altered gene expression are observed in RA, PsA and Ps patients in blood cells and target organs in IFX responders. Differential gene expression profiles in the blood do not correlate with those in target organs.

P2-24-4 - Proper Palliative Care Allows Re-Administration of Chemotherapy in Poor Ps Patients That Results in Better Prognosis

Cancer is the leading cause of death in Japan and accounts for approximately 350000 deaths per annum. Accompanied with cancer progression, aggravation of performance status (PS) cause difficulty for patients in receiving active treatments such as chemotherapy and radiotherapy. Primary purpose of palliative care therapy is considered to be removal of all kinds of pain such as spiritual, physical, and social as much as possible throughout the rest of the patient' s life. Under this situation, palliative care is expected to not only ameliorate pain but also to improve the quality of life, activities of daily living, and PS, and occasionally capable to accept the effects of anticancer therapies such as radiotherapy and chemotherapy that lead to improved prognosis. Here, we report the outcomes of three patients with highly advanced cancer, who received palliative care at our department and whose predictive prognosis indices indicated a life expectancy of less than 3-4 weeks. PS was improved after implementation of proper palliative care with medications or local treatment; this encouraged us to administer chemotherapy. As a result, the chemotherapies were safely adapted, resulting in prognostic extension. All the patients were discharged from our hospital and continued to receive chemotherapy as out-patients. Thus, our findings indicate that proper palliative treatment allows patients with highly advanced cancer with poor PS to again receive active treatments such as chemotherapy or radiotherapy by improving PS that results in improved prognosis.

SY37-1 * LESSONS LEARNED FROM A COMPARISON OF EVIDENCE-BASED RESEARCH IN PREGNANT OPIOID-DEPENDENT WOMEN

Objectives. Lessons learned in research and treatment of opioid dependence demonstrate the need to include pregnant women in clinical trials. Methods. Two double-blind, double-dummy, randomized controlled trials comparing buprenorphine and methadone in opioid-dependent pregnant women were conducted. In both studies, participants received voucher-based incentives for attendance and completion of study assessments. In the MOTHER trial, participants additionally received escalating voucher incentives for drug-free urine samples. Neonatal abstinence syndrome was treated with oral morphine solution based on standardized modified Finnegan scores. Results. After a mean treatment period of 13.79 weeks in the Pilot study (PS, n = 18) and 20.78 weeks in the MOTHER-trial (MT, n = 41), respectively (p < 0.001), PS patients delivered at mean doses of 14.00mg buprenorphine/52.50mg methadone and MT participants at 13.44mg buprenorphine/63.68mg methadone. Nonsignificant differences regarding dropout rates were found (22% in PS versus 10% in MT), but dropout was significantly earlier in the MT (p = 0.013). Significantly higher rates of concomitant consumption of opioids and benzodiazepines occurred in the PS compared with the MT (p < 0.001), however, with no significant differences in neonatal data between both settings. Conclusions. Early treatment enrolment combined with contingency management contributes to reduced illicit drug use throughout pregnancy, surprisingly without influencing neonatal outcome parameters.

Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus

BackgroundCommon DNA variants in IL12B, IL23R and IL23A have been associated with an increased susceptibility to psoriasis (Ps) and psoriatic arthritis (PsA). Metabolic comorbidities and cardiovascular risk factors have also been associated to both Ps and PsA. ObjectiveTo analyze the effect of single nucleotide polymorphisms (SNPs) previously linked to Ps (IL12B rs6887695 and rs3212227, IL23R rs2201841 and rs11209026, and IL23Ars2066808) in the main phenotype and metabolic/cardiovascular characteristics among Ps patients from a Northern Spanish population. MethodsThe aforementioned genetic variants were determined in a total of 405 chronic plaque Ps patients and 426 controls. Subsequent statistical analysis included stratification for psoriatic clinical characteristics (age of onset, disease severity, familial psoriasis, HLA-Cw6, nail psoriasis) plus diabetes mellitus type 2, arterial hypertension, dyslipidemia and ischemic cardiac events as comorbidities. ResultsAn association between IL23R rs11209026-GG genotype with a more severe disease (p=0.02, OR=2.11, 95% CI=1.13–3.95). Carriers of the IL23A rs2066808-A allele were significantly more frequent among PsA patients (p=0.016, OR= 3.04, 95% CI=1.19–7.78). We found significant associations between three SNP genotypes and type 2 diabetes: IL12B rs6887695-CC (p=0.03, OR=2.90, 95% CI=1.09–7.69), IL12B rs3212227-CC (p=0.035, OR=5.90, 95% CI= 1.35–25.73) and IL23R rs2201841-GG (p= 0.027, OR=2.69, 95% CI=1.09–6.66). ConclusionIn our population, genetic variation at IL12B, IL23R and IL23A has an influence not only on the risk for Ps but also on disease severity and type 2 diabetes mellitus.

THU0092 Telomere Length in Patients with Spondyloarthritis: A Cross-Sectional Study Comparing with Psoriasis, Osteoarthritis and Healthy Controls

BackgroundThe length of telomeric DNA shortens during cell replication and leading to a critical role in protecting DNA damage. In recent years, telomere attrition has been implicated in several systemic...

Trimodality therapy and definitive chemoradiotherapy for esophageal cancer: a single-center experience and review of the literature.

In the UK, the standard of care for esophageal cancer has generally combined surgery with neoadjuvant chemotherapy, with definitive chemoradiotherapy (dCRT) being reserved for certain subgroups. Chemoradiotherapy followed by surgery (trimodality therapy) has not been widely adopted. The outcomes of patients undergoing dCRT or trimodality therapy at our cancer center between 2004 and 2012 were restrospectively analyzed. Trimodality therapy was offered to selected patients of good performance status (World Health Organisation performance status 0/1), with squamous cell carcinoma or bulky adenocarcinoma. dCRT was offered to patients of good PS but with comorbidities, upper third tumors or at patient's request. Patients received four cycles of chemotherapy with a platinum agent (mostly cisplatin) and a fluoropyrimidine (mostly 5-fluorouracil) over a total of 11 weeks. Cycles 3 and 4 were given concurrently with radiotherapy: 50 Gy in 25 fractions for dCRT and 45 Gy in 25 fractions in the trimodality group. Surgery occurred 8-10 weeks following the completion of chemoradiotherapy. The cut-off length for maximum gross tumor volume length was 10 cm. One hundred two patients were included (47 received dCRT, and 55 received trimodality treatment). The majority of tumors were stage III (80.4%), and two-thirds were located in the distal esophagus (64.7%). Median follow-up was 44 months. The 2-year overall survival (OS) was 57.3% (median OS 39.7 months) for the dCRT group and 77.8% (median not reached) for the trimodality group. The 5-year OS rates were 38% and 58%, respectively. Postoperative mortality rate was low at 1.8%, and the pathological complete response rate was 23.6%. In conclusion, trimodality treatment for patients with esophageal and junctional gastroesophageal tumors offers high rates of 2-year survival, and the potential for long-term cure. dCRT is an established alternative for patients that are not fit or suitable for surgery.

A Prospective, Randomized Comparison of Posterior Stabilized Versus Cruciate-Substituting Total Knee Arthroplasty: A Preliminary Report With Minimum 2-Year Results

We compared 56 patients who received a PS post/cam tibial insert and 55 patients who received a more congruent anterior-lipped tibial insert. We hypothesized that clinical outcomes would be equivalent and that tourniquet time and intraoperative blood loss would differ. The mean follow-up is 45months (30–57months). Clinical and radiographic outcomes were equivalent for both groups, except that male PS patients received significantly more transfusions than male CS patients (P<.039) and tourniquet time was significantly longer for all patients in the PS group (P<.015). At the minimum 2-year follow-up in this ongoing study, the results demonstrate equivalent functional and radiographic outcomes of the 2 devices, and significant differences in the perioperative findings of transfusion rates and tourniquet times.

Risk factors of persistent synovitis development in early undifferentiated arthritis patients

BackgroundPersistent synovitis (PS) may lead to erosive joint damage and result in functional disability.ObjectivesThe aim of the study was to identify the risk factors for development of PS in early undifferentiated arthritis patients (EUA) attending Al Sharqia Governorate Hospitals, Egypt.Patients and methodsA total of 80 EUA patients comprised the patients group. Assessment was performed twice (baseline and after 1 year) using clinical, laboratory, functional, and radiological [high resolution ultrasonography (HRUS) and power Doppler (PD)] assessments.ResultsAmong 80 patients assessed, 20 (25%) showed evidence of self-limiting arthritis and 60 (75%) had PS (PS):16 (27%) developed rheumatoid arthritis, 14 (23%) progressed to spondyloarthropathy, and 30 (50%) remained undifferentiated (UA). Baseline tender and swollen Joint Counts (TJC and SJC) and anti-CCP2 titer were significantly evident in PS patients. Baseline HRUS total score of synovitis and PD total score were significantly higher in PS patients. Family history of any specific rheumatic disease, SJC, anti-CCP2 titer, HRUS total synovitis score, and PD total score were the significant risk factors of PS development. The most significant risk factor of PS (logistic regression analysis) was the baseline PD total score.ConclusionBaseline PD total score is the most significant risk factor for development of PS in EUA patients.RecommendationPD examination of all patients presenting with EUA should be performed.

Is the health-related quality of life and functional status of patients with psoriatic arthritis worse than that of patients with psoriasis alone?

The aim of this study was to compare the health-related quality of life and functional status of patients with psoriasis (Ps), psoriatic arthritis (PsA) and control subjects. Eighty patients with PsA, 40 patients with Ps and 40 healthy subjects were included. Physical functions were evaluated with the Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) while life satisfaction was evaluated with the Psoriatic Arthritis Quality of Life (PsAQoL) questionnaire. The Disease Activity Score 28 (DAS28), Disease Activity Index for the Assessment of Reactive Arthritis (DAREA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Maastrich Ankylosing Spondylitis Enthesitis Score (MASES) and visual analog scale-pain were calculated. The HAQ-S data revealed that physical functional status in the PsA group was worse than the Ps and control groups (mean scores: 0.5±0.5, 0.2±0.5 and 0.1±0.3, respectively). The PsAQoL data revealed a worse quality of life in the PsA and Ps groups than in the control group but the same quality of life in the PsA and Ps groups (mean scores: 6.9±5.4, 7±5.9 and 3.3±4.2, respectively). Both the HAQ-S and PsAQoL data were found to be moderately to weakly correlated with disease activity measures (DAS28, DAREA, BASDAI, ASDAS-CRP), pain and enthesitis. Patients with Ps and PsA had worse quality of life and patients with PsA had worse functional status than healthy individuals. Although Ps patients with arthritis had a worse functional status than the ones without arthritis, quality of life according to PSAQoL was found to be similar between them.

Comparison between propofol and dexmedetomidine on depth of anesthesia: A prospective randomized trial.

Background and Aims:Intravenous agents such as propofol are commonly used to maintain adequate depth of anesthesia. Dexmedetomidine which has an anesthetic sparing effect is being considered for maintaining intraoperative depth of anesthesia. We hypothesized to compare the effect of dexmedetomidine on depth of anesthesia with propofol and evaluated whether dexmedetomidine can be used as sole anesthetic agent in maintaining depth of anesthesia.Materials and Methods:Sixty patients of ASA PS I, 18-65 years of age, scheduled for laparotomy under general anesthesia were randomly divided into two groups of 30 each. Group A received propofol 1 mg/kg bolus followed by infusion (50 mcg/kg/min) and Group B received dexmedetomidine 1 mcg/kg bolus followed by infusion (0.5 mcg/kg/h). Both the groups were administered standard general anesthesia with routine monitoring along with Bispectral index (BIS) and values were recorded at intervals of 10 min. In all patients Ramsay sedation score was recorded after extubation and they were assessed for recall of intraoperative events using Modified Brice questionnaire.Results:Heart rate and mean arterial pressure were less in Group B than Group A. Intraoperative BIS values were significantly lower in Group B (P < 0.0001). Although sedation score was more in Group B it did not prolong recovery. No recall was found in any patient.Conclusion:Dexmedetomidine was comparable with propofol in maintaining anesthesia and it can produce better control of hemodynamics and BIS value. Thus dexmedetomidine can be used as the sole maintenance anesthetic agent.

Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different

The Eastern Cooperative Group Performance Status (ECOG PS) is a widely used standard functional classification in oncology practice, the verbal descriptors of which refer to physical activity (PA). Little is known about the cut-off points of this scale and measured PA levels. This research investigated the relationship between PS assigned, objectively measured PA, and patient age. One hundred ambulatory patients with treatment-naive cancer wore an accelerometer (RT3) for a mean (SD) of 5.6 (1.1) days before initial oncology evaluation and ECOG PS assignment. Seventy five participants (75%) were <65 years and 25 were ≥65 years. Eighty nine (89%) were assigned an ECOG PS of 0 or 1 and 11% a PS of 2 or 3. A weak but significant inverse association was found between objectively measured PA and PS (rho = -0.26, p = 0.01). Seventy one participants (80%) with a PS of 0 or 1 spent more than 50% of waking hours resting. Participants assigned a PS of 2-3 spent significantly more time resting than those assigned a PS of 0 (p = 0.01). Age ≥65 years was significantly related to PS assigned (p = 0.04), although the older cohort were no less sedentary than younger patients. PA levels were low, but PS scoring reflected relative PA levels and differentiated between patients of PS 0 and 2-3. Chronological age was not predictive of activity levels, but older patients were assigned lower PS scores. Incorporation of objective PA measures may merit further investigation especially in the geriatric oncology setting.

Value of color Doppler ultrasound in the examination of prethrombotic state

To explore the clinical value of color Doppler ultrasound in patients with prethrombotic state (PTS). From October 2011 to November 2012, a total of 201 patients were diagnosed with PTS. There were 95 males and 106 females with an average age of 52 years (range: 15-78). They were divided into intervention and observation groups on the basis of drug intervention. And the relevant literatures were reviewed and the images of color Doppler ultrasound before and after treatment compared. Before treatment, blood flow peak rates of common femoral, popliteal and calf intermuscular veins were (0.16 ± 0.03), (0.14 ± 0.03) and (0.13 ± 0.02) m/s; after treatment, (0.19 ± 0.03), (0.17 ± 0.03) and (0.15 ± 0.01) m/s respectively. The peak flow increased and sluggish flow decreased or disappeared in 152 PS patients. It indicated a relief or an obvious resolution of hypercoagulable state. And the symptom of lower extremity soreness was greatly relieved. Among 49 patients without drug intervention, severe full-lumen storm floating occurred in 12 cases. And 8 of them suffered deep vein thrombosis within 2 weeks. The incidence of thrombus was 66.7%. Color Doppler ultrasound may detect and assess PTS effectively so as to guide effective interventions.

SAT0295 Comparison of subclinical carotid atherosclerosis in patients with psoriatic arthritis, psoriasis alone and controls

BackgroundPatients with psoriatic arthritis (PsA) and cutaneous psoriasis alone (PsC) are known to have an increased risk of Cardiovascular (CV) disease. The increase of Carotid Intima-Media Thickness (cIMT) in patients...

SAT0287 High prevalence of articular involvement in patients with severe psoriasis with poor performance of screening questionnaires

BackgroundDelay in diagnosis of psoriatic arthritis (PsA) remains a significant contributor to poor patient outcome. Clinical predictors of the development of arthritis among patients with psoriasis (Ps) have been proposed...

AB0587 Is health-related quality of life of patients with psoriatic arthritis worse than that of patients with psoriasis alone?

BackgroundPsoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthropathy associated with psoriasis (Ps). PsA can be as destructive as other arthropathies such as rheumatoid arthritis. Both Ps and PsA negatively...

Randomized phase II study comparing dose-escalated weekly paclitaxel versus standard dose weekly paclitaxel for patients with previously treated advanced gastric cancer.

4076 Background: Retrospective analyses of neutropenia during chemotherapy of weekly paclitaxel (wPTX) suggested better overall survival (OS) among patients with neutropenia. We conducted a randomized phase II trial comparing dose-escalated wPTX with dose adjustments determined by degree of neutropenia versus standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC). Methods: Ninety-patients with AGC that progressed during one or more previous chemotherapy regimens were randomized to a standard dose of wPTX (80 mg/m2, standard dose arm) or an escalated dose of wPTX (80 mg/m2 on day 1, 100 mg/m2 on day 8, and 120 mg/m2 on day 15 unless severe toxicity nor neutropenia&lt;1.5 x 109/L is observed, escalated dose arm) to assess superiority with a one-sided alpha of 0.3 and a power of 0.8. Results: The primary endpoint of median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs. 9.6 months; hazard ratio [HR], 0.75; 95% CI, 0.45-1.22; one-sided P=0.12). Median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs. 2.5 months, HR, 0.55; 95% CI, 0.34-0.90; P=0.017). Objective response rate was 30.3% with dose-escalation and 17.1% with standard dose (P=0.2). The disease control rate (DCR) was significantly higher with dose-escalation (78.8% vs. 48.6%, P=0.009). Subset-analysis according to stratification factors including ECOG PS, presence of measurable lesions and lines of previous chemotherapy indicated that OS benefit of the dose escalation is more prominent in PS 0-1 patients (N=81, median 13.6 vs. 9.8 months, HR 0.68, 95% CI 0.41-1.11) than PS2 patients with significant interaction (p=0.01) Conclusions: Dose escalated wPTX was associated with sufficiently longer OS in patients with pretreated AGC. In addition, significant longer PFS and higher DCR associated with dose-escalation and subset analysis according PS warrant further investigations in phase III trials, especially in patients with favorable PS patients. Clinical trial information: UMIN000004055.

Sorafenib in Advanced Hepatocellular Carcinoma: A Nationwide Retrospective Study of Efficacy and Tolerability

Background. Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we explore the role of alpha-fetoprotein (αFP) as a potential biomarker for treatment efficacy and correlation to survival. Methods. Seventy-six patients with advanced HCC, not eligible for locoregional therapy, treated with sorafenib between 2007 and 2009 were included. Followup was until 2011. Results. Patients in PS 0-1 had a median overall survival (mOS) of 6.2 months, compared to 1.8 months in patients with poorer PS (P = 0.005). Child-Pugh A patients had a mOS of 6.6 months versus 3.6 months among patients in Child-Pugh B or C (P = 0.0001). Serum αFP ≥ 200 at baseline was prognostic for a shorter survival. All patients with radiologically verified tumor response and baseline αFP ≥ 200 experienced a significant decline in αFP within the first four weeks of treatment. Conclusion. The survival of patients with advanced HCC treated with sorafenib is dependent on performance status and liver function. Treatment of patients with compromised liver function and poor performance status cannot be recommended. The correlation between αFP and objective tumor response warrants further investigation.

Robustness of IMPT treatment plans with respect to inter-fractional set-up uncertainties: Impact of various beam arrangements for cranial targets

In the current study IMPT plan robustness was evaluated with respect to inter-fractional patient positioning for various beam arrangements and two tumor indications in the cranial region. Material and methods. For 14 patients suffering from tumors in the cranial region [skull base (SB; n = 7) and paranasal sinus (PS; n = 7)] the CTV and OARs were delineated. A safety margin of 3 mm was applied to the CTV. A prescribed dose of 2 GyE was planned via three beam arrangements (α, β, γ). Beam arrangement α consisted of lateral opposed fields for both tumor groups while beam arrangement β was optimized according to respective tumor and OAR locations, using two beams only. Beam arrangement γ applied four beams in the SB group and three beams in the PS group. Dose distributions were recalculated subjected to virtual patient translations along the major anatomical axes. The following dosimetric indices were evaluated and compared to original plans: target coverage (TC), target dose homogeneity (HI), CTV median and average dose (Dmedian, Dmean). For OARs near maximum dose and average dose (D2%, Dmean) were evaluated. Results. Dose distributions were distorted after introducing shifts. In the SB group, TC and HI were significantly different for caudal, cranial and anterior shifts for all beam arrangements. For PS patients, all but right shifts differed significantly from the original plans for all beam arrangements, although clinical relevance was not reached for arrangement γ (ΔTC < 1.5%). In general, beam arrangement γ exhibited the least spread of data regarding target indices and was consequently considered the most robust. Dosimetric parameters regarding the brainstem were mostly influenced by shifts along the anterio-posterior axis. Conclusion. For cranial IMPT, set-up uncertainties may lead to pronounced deterioration of dose distributions. According to our investigations, multi-beam arrangements were dosimetrically more robust and hence preferable over two beam arrangements.