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Aim: Understanding and supporting quality of life (QoL) and daily functioning in glioma patients is a clinical imperative. In this study, we examined the relationship between cognition, psychological factors, measures of health-related QoL and functioning in glioma survivors. Materials & methods: We examined neuropsychological, self-reported cognition, mood and QoL correlates of work and non-work-related daily functioning in 23 glioma survivors, and carried out linear models of the best predictors. Results & conclusion: A total of 13/23 participants were working at the time of enrollment. The best model for worse work-related functioning (R2 = .83) included worse self-reported cognitive function, depression, loneliness and brain tumor symptoms. The best model for worse non-work-related functioning (R2 = .61) included worse self-reported cognitive functioning, anxiety, sleep disturbance and physical functioning. Neuropsychological variables were not among the most highly correlated with function. Worse cognitive, particularly self-reported and psychosocial outcomes may compromise optimal functioning in glioma survivors.

Supervivència lliure de progressió; Tumors neuroendocrins Supervivencia libre de progresión; Tumores neuroendocrinos Progression-free survival; Neuroendocrine tumors Accessible prognostic tools are needed to individualize treatment of neuroendocrine tumors (NETs). Data suggest neutrophil/lymphocyte ratios (NLRs) have prognostic value in some solid tumors, including NETs. In the randomized double-blind CLARINET study (NCT00353496; EudraCT 2005-004904-35), the somatostatin analog lanreotide autogel/depot increased progression-free survival (PFS) compared with placebo in patients with inoperable or metastatic intestinal and pancreatic NETs (grades 1–2, Ki-67 4; n = 25)]. Furthermore, NLRs were not prognostic in Cox models, irrespective of subgroups used. The therapeutic effect of lanreotide autogel/depot 120 mg was independent of NLRs (P > 0.1). These exploratory post-hoc analyses in patients with advanced intestinal and pancreatic NETs contrast with previous data suggesting NLR has prognostic potential in NETs. This may reflect the inclusion of patients with lower-grade tumors or use of higher NLR cutoff values in the current analysis. The CLARINET study was sponsored by Ipsen, the manufacturer of lanreotide autogel/depot. Medical writing services were provided by Nicky French PhD of Watermeadow Medical (Macclesfield, UK) – an Ashfield Company, part of UDG Healthcare plc – sponsored by Ipsen Ltd, Slough, UK in accordance with Good Publication Practice guidelines.

For glioma survivors, cognitive impairment can be a central determinant of quality of life, but we need better understanding of their unique challenges and supportive care needs. In this qualitative study, we aimed to explore the post-treatment experiences of cognitive and functional challenges and their impact on quality of life from the perspectives of glioma survivors. Glioma survivors in an observational study were invited to participate in an in-depth qualitative interview. Using a semi-structured interview guide, interviews were audio-recorded and transcribed verbatim. Data were analyzed using a reflexive thematic analysis approach to develop key themes to inform clinical practice. Participants (n=9) ranged in age from 29 to 72 years, and were at least 4 years post-diagnosis. Under the overarching survivorship theme, three key themes were developed. The first theme, “Learning what my brain can and can’t handle,” centered on functional challenges related to cognitive impairments, including difficulties at work and managing home and family responsibilities. In response, participants described generating their own strategies to manage cognitive limitations in daily activities. The second theme, “Such an important crossroads”, reflected the significant emotional impact of persisting impairments (e.g., frustration, disappointment, reduced self-esteem, acceptance), increased anxiety around an uncertain future, and a shift in personal values towards an increased sense of gratitude, crystalizing of intentions, and focus on things of greatest importance. The final theme, “A solid foundation of people around me”, referred to the necessity of social support, in both emotional and instrumental terms. Many expressed a desire for and appreciation of coping tools and support for the support people in their lives. Nearly all participants expressed interest in cognitive rehabilitation – whether or not they were experiencing significant cognitive problems. These findings have implications for clinical practice and can inform the development of effective patient-centered supportive care interventions in this population.

A 73-year-old female presenting with haemoptysis and dyspnoea was found to have a locally advanced left thyroid mass and vocal cord palsy. A CT scan of the neck and thorax and endoscopy demonstrated invasion into the tracheal lumen. Histopathology of the intraluminal tracheal mass confirmed a papillary thyroid cancer (PTC). The tumour was deemed unresectable due to local extent and patient comorbidities. TKI therapy with lenvatinib was used for 14 months. On serial scanning, a marked reduction in tumour volume from 31 × 59 × 32 mm to 17 × 28 × 22 mm was noted. This subsequently allowed a successful surgical resection with a total thyroidectomy and central neck dissection with no evidence of residual macroscopic disease. Histopathology confirmed a well-differentiated PTC with features of tumour regression. In this case, TKI therapy in a locally advanced unresectable DTC reduced tumour size and infiltration to a degree that surgical resection of macroscopic disease was possible, without requiring airway resection. This raises the possibility that TKIs may have a neoadjuvant role in selected cases of locally advanced DTC to reduce tumour volume and therefore morbidity of subsequent surgical resection.

Background Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. Methods Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. Results In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47–0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65–1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13–0.70). Conclusions SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. Clinical trial registration ISRCTN71070888; ClinialTrials.gov (NCT03529175).

Background Depression has substantial effects on cancer patients' quality of life. Estimates of its prevalence vary widely. We aimed to systematically review published studies to obtain the best estimate of the prevalence of depression in clinically meaningful subgroups of cancer patients. Design Systematic review that addressed the limitations of previous reviews by (i) including only studies that used diagnostic interviews; (ii) including only studies that met basic quality criteria (random or consecutive sampling, ≥70% response rate, clear definition of depression caseness, sample size ≥100); (iii) grouping studies into clinically meaningful subgroups; (iv) describing the effect on prevalence estimates of different methods of diagnosing depression. Results Of 66 relevant studies, only 15 (23%) met quality criteria. The estimated prevalence of depression in the defined subgroups was as follows: 5% to 16% in outpatients, 4% to 14% in inpatients, 4% to 11% in mixed outpatient and inpatient samples and 7% to 49% in palliative care. Studies which used expert interviewers (psychiatrists or clinical psychologists) reported lower prevalence estimates. Conclusions Of the large number of relevant studies, few met our inclusion criteria, and prevalence estimates are consequently imprecise. We propose that future studies should be designed to meet basic quality criteria and employ expert interviewers.

Supplemental Digital Content is available in the text., Introduction: Neoadjuvant chemotherapy (NA) is routinely offered to patients undergoing resection for locally advanced (≥cT3Nx or cTxN+) esophageal or esophagogastric junctional (EGJ) cancer in the United Kingdom. Patients with comorbidity precluding the use of NA can be considered for resection yet the effect of omitting NA on survival is unclear. Methods: Retrospective review of prospectively collected clinical data from patients undergoing attempted curative therapy for ≥cT3Nx or cTxN+ esophageal or EGJ (Siewert type I-III) cancer between 2001 and 2013. Results: NA was commenced in 289 patients and primarily comprised 2 cycles of cisplatin and 5-fluorouracil (264 patients, 91%). Surgery alone was planned for 82 patients with NA omitted due to comorbidity. Patients undergoing surgery alone were matched for clinical variables and stage with those undergoing NA but were significantly older (mean=8 y, P

Background Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. Methods This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Committee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecitabine (1000 mg/m2 po, twice daily, days 1–14) and oxaliplatin (130 mg/m2 i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. Results Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8 % (95 % CI 12.05–39.5 %). Stable disease was observed in a further 13 patients (31 %) and progressive disease observed in 12 (28.6 %) of patients. The median progression-free survival was 4.6 months (95 % CI 2.8–6.4 months; Fig. 1) and the median overall survival 7.9 months (95 % CI 5.3–10.4 months; Fig. 2).Fig. 1Progression-free survivalFig. 2Overall survival Conclusion Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. However, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated.

Context In surgical and clinical oncology, there is a growing need for patient-centered outcomes that are responsive, meaningful, and fit for purpose. Objectives The aim of this study was to validate physical activity (PA) monitoring as a responsive outcome measure at different stages of disease and treatment, by verifying correlations between PA, performance score, and quality of life (QoL). Methods Daily life PA of 162 cancer patients, monitored by a device that records time sitting/lying, time standing, time walking, number of steps taken, and walking cadence, was compared with 20 healthy volunteers. In a subgroup of patients, functional status and QoL were assessed using the World Health Organization/Eastern Cooperative Oncology Group and the Karnofsky Performance Status scores and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire. Results The PA of patients with resectable gastrointestinal cancer did not differ significantly from controls. In contrast, patients with advanced cancer took 45% fewer steps and spent an extra 2.8 hours/day lying/sitting (P=0.001). Patients undergoing neoadjuvant chemotherapy and surgery (5–6 weeks after operation) experienced a similar reduction in PA. There were significant correlations between PA and the physical and role domains as well as fatigue subscale of the EORTC QLQ-C30 scale. Conclusion Objective PA scores correlate significantly with disease stage, functional status, and QoL of patients with cancer. Therefore, activity monitoring can make meaningful objective estimates of patient function in response to cancer and its treatment and may provide surrogate outcomes of QoL.

Background There is speculation that peripheral neuropathy (PN) with capecitabine and oxaliplatin (CapOx; 130 mg/m2, day 1, every 21 days) may be more common than with FOLFOX4 (5-fluorouracil and oxaliplatin 85 mg/m2, day 1, every 14 days). We aimed to determine PN incidence and associations during CapOx, and 6 and 12 months after CapOx. Patients and methods Retrospective audit of 188 oxaliplatin-naive colorectal cancer patients (87 adjuvant, 101 palliative) who received at least one cycle of CapOx. Neurosensory Common Toxicity Criteria Adverse Events version 3 were applied. Results Overall, 94% experienced acute PN. Worst severities for adjuvant and palliative patients, respectively, were grade 1, 44% and 54%; grade 2, 35% and 32%; grade 3, 16% and 3%; grade 4, 0% and 1% and grade unclear 1% and 1%. Two patients developed PN after CapOx completion despite no symptoms during treatment. Chronic PN at 6 months affected 57% and 18% of adjuvant and palliative patients, respectively. At 12 months, 35% and 16% were affected. Chronic PN at 12 months was associated with cumulative oxaliplatin dose but not age, gender, acute myotonia, pseudolaryngospasm or grade 2 or more PN during treatment. Conclusion Incidence of acute PN during CapOx appears similar to FOLFOX4 but chronic PN in adjuvant patients may be more common with CapOx.

Summary Background Major depressive disorder severely impairs the quality of life of patients with medical disorders such as cancer, but evidence to guide its management is scarce. We aimed to assess the efficacy and cost of a nurse-delivered complex intervention that was designed to treat major depressive disorder in patients who have cancer. Methods We did a randomised trial in a regional cancer centre in Scotland, UK. 200 outpatients who had cancer with a prognosis of greater than 6 months and major depressive disorder (identified by screening) were eligible and agreed to take part. Their mean age was 56·6 (SD 11·9) years, and 141 (71%) were women. We randomly assigned 99 of these participants to usual care, and 101 to usual care plus the intervention, with minimisation for sex, age, diagnosis, and extent of disease. The intervention was delivered by a cancer nurse at the centre over an average of seven sessions. The primary outcome was the difference in mean score on the self-reported Symptom Checklist-20 depression scale (range 0 to 4) at 3 months after randomisation. Analysis was by intention to treat. This trial is registered as ISRCTN84767225. Findings Primary outcome data were missing for four patients. For 196 patients for whom we had data at 3 months, the adjusted difference in mean Symptom Checklist-20 depression score, between those who received the intervention and those who did not, was 0·34 (95% CI 0·13–0·55). This treatment effect was sustained at 6 and 12 months. The intervention also improved anxiety and fatigue but not pain or physical functioning. It cost an additional £5278 (US$10 556) per quality-adjusted life-year gained. Interpretation The intervention—Depression Care for People with Cancer—offers a model for the management of major depressive disorder in patients with cancer and other medical disorders who are attending specialist medical services that is feasible, acceptable, and potentially cost effective. Funding Cancer Research UK.

The object of this article is to assess current staging accuracies for individual modalities and to investigate the influence of the multidisciplinary team (MDT) on clinical staging accuracies and treatment selection for patients with gastro-esophageal cancer. Patients newly diagnosed with gastric or esophageal cancer and who were deemed suitable for surgical resection by the MDT were studied. Patients were staged with a combination of computerized tomography (CT), endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS). Additionally, the MDT determined an overall clinical stage for each patient after discussion at the MDT meeting. Treatments were selected according to this final clinical stage. Final histopathological staging (pTNM) was available for all patients and was used as the gold standard for determining staging accuracy. Suitability of treatment selection was assessed once final pTNM was available. One hundred and eighteen patients were studied. Endoscopic ultrasound was the most accurate individual staging modality for the loco-regional assessment of esophageal tumors (T stage accuracy 78%, N stage accuracy 70%). Laparoscopic ultrasound was the most accurate modality in T staging of gastric cancers (91%). The MDT stage was more accurate than each individual staging modality for T and N staging for both gastric and esophageal cancers (accuracy range: 88-89%) and was better for the assessment of nodal disease than each individual modality (CT P < 0.001, EUS P < 0.01, LUS P < 0.01). Overall staging accuracy as determined at the MDT meeting was increased and resulted in only 2/118 (2%) patients being under-treated. The MDT significantly improves staging accuracy for gastro-esophageal cancer and ensures that correct management decisions are made for the highest number of individual patients.

Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited activity. This study assesses the feasibility and activity of gemcitabine and cisplatin in this group of patients. In total, 42 patients with locally advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated with gemcitabine 1250 mg m(-2) days 1 and 8 and cisplatin 75 mg m(-2) day 1 in a 21-day cycle. Interim safety analysis was carried out after the first 19 patients suggested significant toxicity. The dose of gemcitabine was subsequently reduced to 1000 mg m(-2). Patients were assessed for toxicity and response. The median number of treatment cycles per patient was 4 (range 1-6). Grade 3-4 neutropenia occurred in 37% of cycles; however, there was only one episode of neutropenic fever. Nonhaematological toxicities included fatigue, nausea and vomiting. Among 32 patients eligible for response, there were three complete responses and 16 partial responses (overall response rate of 45%); nine patients had stable disease. Median survival was 11 months. The response rate appears to be greatest in those with squamous carcinoma compared to adenocarcinoma (71 vs 33%, P=0.036). The combination of gemcitabine and cisplatin in this schedule has manageable toxicity and significant activity in patients with locally advanced/metastatic oesophageal cancer and is worthy of further study.

4006 Background: Despite improvements in multidisciplinary management, BTC has a poor outcome. Approximately 20% of cases are suitable for surgical resection with a 5 year survival of < 10%. BILCAP aimed to determine whether capecitabine (Cape) improves overall survival (OS) compared to observation (Obs) following radical surgery. Methods: Patients with completely-resected cholangiocarcinoma (CCA) or gallbladder cancer (including liver and pancreatic resection, as appropriate), with adequate biliary drainage, no ongoing infection, adequate renal, haematological and liver function, and ECOG PS ≤2, were randomized 1:1 to Cape (1250 mg/m2 D1-14 every 21 days, for 8 cycles) or Obs. Randomization was minimized on tumor site, resection status, ECOG PS and surgical center. The primary outcome was OS in the intention to treat (ITT) population. 410 patients were needed to detect a hazard ratio (HR) of 0.69 (2-sided α = 0.05 and 80% power). HR was estimated by Cox survival model with adjustment for the minimization factors. Primary analysis performed with at least 24 months (m) follow-up. Results: 447 participants were randomized to Cape (n = 223) or Obs (n = 224) from 44 UK sites between 2006-2014. Median age was 63y (IQR 55, 69) and 201 (45%), 232 (52%), and 14 (3%) patients were ECOG PS 0, 1 and 2 respectively. Primary site: 84 (19%) intrahepatic, 128 (28%) hilar, 156 (35%) extrahepatic CCA and 79 (18%) muscle-invasive gallbladder cancers. Resection margins: R0 in 279 (62%) and R1 in 168 (38%); 207 (46%) were node-negative. Follow up was at least 36m in > 80% of surviving patients. By ITT analysis (n = 447), median OS was 51m (95%CI 35, 59) for Cape and 36m (95%CI 30, 45) for Obs, HR 0.80 (95%CI 0.63, 1.04; p = 0.097). Sensitivity analyses with adjustment for nodal status, grade of disease and gender indicated HR 0.71 (95%CI 0.55, 0.92 p < 0.01). In the per-protocol analysis (Cape n = 210, Obs n = 220) median OS was 53m (95%CI 40, NR) for Cape and 36m (95%CI 30, 44) for Obs, HR 0.75 (95%CI 0.58, 0.97; p = 0.028). Median RFS (ITT) was 25m (95%CI 19, 37) for Cape and 18m (95%CI 13, 28) for Obs. Grade 3-4 toxicity was less than anticipated. Conclusions: Cape improves OS in BTC when used as adjuvant and should become standard of care. Clinical trial information: ISRCTN72785446.

4089 Background: In the CLARINET core study, lanreotide Autogel (LAN) 120 mg deep sc monthly significantly improved PFS vs PBO in metastatic grade-1/2 enteropancreatic NETs. An interim analysis of patients with stable disease (SD) in the core study continuing LAN in the open-label extension (OLE, of which safety was primary objective) showed continued antitumor effects. Here, we report final LAN PFS analyses for subgroups according to tumor origin and prior therapy. Methods: In the core study, patients with metastatic well/moderately differentiated non-functioning (N-F) enteropancreatic NETs, Ki-67

The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic β2-agonist and an appetite stimulant in patients with cancer cachexia. Thirteen patients (M/F 5:8) with advanced malignancy and involuntary weight loss received oral formoterol (80 μg/day) and megestrol acetate (480 mg/day) for up to 8 weeks. Quadriceps size (MRI), quadriceps and hand-grip strength, lower limb extensor power, physical activity and quality of life were measured at baseline and at 8 weeks. Response criteria were specified pre-trial, with a major response defined as an increase in muscle size ≥4 % or function ≥10 %. Six patients withdrew before 8 weeks, reflecting the frail, comorbid population. In contrast, six out of seven (86 %) patients completing the course achieved a major response for muscle size and/or function. In the six responders, mean quadriceps volume increased significantly (left 0.99 vs. 1.05 L, p = 0.012; right 1.02 vs. 1.06 L, p = 0.004). There was a trend towards an increase in quadriceps and handgrip strength (p > 0.05). The lack of appetite symptom score declined markedly (76.2 vs. 23.8; p = 0.005), indicating improvement. Adverse reactions were few, the commonest being tremor (eight reports), peripheral oedema (three), tachycardia (two) and dyspepsia (two). In this frail cohort with advanced cancer cachexia, an 8-week course of megestrol and formoterol in combination was safe and well tolerated. Muscle mass and/or function were improved to a clinically significant extent in most patients completing the course. This combination regimen warrants further investigation in larger, randomized trials.

Background Oesophageal cancer is a major clinical problem with a generally poor prognosis. As a result there has been interest in combining surgery with neoadjuvant chemotherapy to try and improve outcomes, although the current evidence for benefit is inconsistent. We aimed to compare, in a non-randomised study, the post-operative complication rate and short and long-term survival of patients who underwent surgical resection for carcinoma of the oesophagus and types I and II carcinoma of the oesophago-gastric junction with or without neo-adjuvant chemotherapy. Methods Details of all resections for oesophageal/junctional (types I and II) adenocarcinoma or squamous cell carcinoma between April 2000 and July 2006 were collected prospectively. Data from patients with T3 and/or N1 disease who underwent either neoadjuvant chemotherapy (NAC) or not (non-NAC) were compared. Data were analysed using Kaplan-Meier plots, Mann-Whitney U-test, Cox Regression modelling, and Chi-squared test with Yates' correction where sample sizes

e15180 Background: CLARINET showed LAN 120 mg significantly increased PFS vs PBO (hazard ratio [HR] for progressive disease [PD]/death 0.47 [95% CI: 0.30, 0.73]) in metastatic intestinal and pancre...

e15181 Background: CLARINET was a large 96-week phase 3 study showing that LAN 120 mg significantly improved progression-free survival vs PBO in patients with intestinal and pancreatic NETs. Here, ...

4104 Background: In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo in patients with metastatic grade 1 or 2 (Ki-67

e15177 Background: The somatostatin analog LAN 120 mg significantly prolonged progression-free survival (PFS) vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67

e15182 Background: CLARINET showed antitumor effects with LAN 120 mg in metastatic intestinal/pancreatic NETs. Here, we characterize treatment effects within subgroups defined post hoc by baseline ...

233 Background: The prognosis for patients with metastatic pNETs is generally poor and current treatment options can be complicated by safety considerations. In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 25%, 95% had stable disease, 77% had received no previous treatment, and 38% had had previous surgery on the tumor. Median PFS in the pNET subgroup was not reached at study end with LAN vs. 12.1 months [95% CI: 9.4, 18.3] with PBO (HR for PD/death: 0.58 [0.32, 1.04]). (Median PFS for LAN at first planned analysis in the open-label extension study was 29.7 months [12.0, 32.4].) The incidence of adverse events (AEs) in the core study was 88% with both LAN and PBO, and the most common AE was diarrhea (LAN, 43%; PBO, 37%). Treatment-related AEs occurred in 55% of the LAN group and 24% of the PBO group. Serious AEs (SAEs) occurred in 29% vs. 43%, respectively; only three of these patients had treatment-related SAEs (two with LAN, one with PBO). Two patients in each group had AEs leading to withdrawal. Conclusions: The evidence in the pNET subgroup suggesting antitumor effects with LAN together with the favorable long-term safety profile support a positive benefit:risk profile for LAN as a first-line treatment for pNETs. Clinical trial information: NCT00353496.

Psychological distress is a common problem among cancer patients. Despite the large number of instruments that have been developed to assess distress, their utility remains disappointing. This study aimed to use Rasch models to develop an item-bank which would provide the basis for better means of assessing psychological distress in cancer patients.An item bank was developed from eight psychological distress questionnaires using Rasch analysis to link common items. Items from the questionnaires were added iteratively with common items as anchor points and misfitting items (infit mean square >1.3) removed, and unidimensionality assessed.A total of 4914 patients completed the questionnaires providing an initial pool of 83 items. Twenty items were removed resulting in a final pool of 63 items. Good fit was demonstrated and no additional factor structure was evident from the residuals. However, there was little overlap between item locations and person measures, since items mainly targeted higher levels of distress. The Rasch analysis allowed items to be pooled and generated a unidimensional instrument for measuring psychological distress in cancer patients. Additional items are required to more accurately assess patients across the whole continuum of psychological distress.

8104 Background Psychological distress (PsyD) is common in cancer patients (CP). Self-report screening instruments are disappointing in detecting CP needing specialist intervention for PsyD, and CP...

High-intermediate grade non-Hodgkin's lymphoma (NHL) is an aggressive form of the disease, which can respond well to combination chemotherapy, with long-term survival seen in 40-50% of patients. When NHL relapses following standard treatment, high-dose chemotherapy with peripheral blood stem cell or bone marrow support may still cure a significant proportion of patients. Despite a significant rise in the incidence of NHL over recent years, there remains only limited published economic study concerning the overall lifetime cost of treatment, the cost effectiveness of specific treatments or the overall societal cost burden of the disease. The majority of studies identified for the purposes of this review considered the cost of alternative forms of chemotherapy and bone marrow support strategies for patients with advanced disease. Data from these studies suggest that there is a definite trend towards reduced costs for high-dose therapy, possibly reflecting increasing technical experience and improved bone marrow recovery through the use of stem cell transplantation and growth factors. The limited number of cost-effectiveness evaluations suggest that high-dose therapy, following a chemosensitive relapse, is likely to be considered favourable against commonly quoted cost-effectiveness thresholds. Cost effectiveness is becoming an increasingly important factor to consider in the formal assessment of new interventions conducted by groups such as the UK National Institute for Clinical Excellence. In light of the increasing incidence of NHL and the extended use of high-dose treatments in other subgroups of patients, there is a need for increased research into the economics of new interventions for NHL.

BACKGROUND: The aim of the study was to record the incidence of treatment for infertility prior to development of gestational trophoblastic disease (GTD). METHODS AND RESULTS: A retrospective analysis was undertaken of 231 consecutive women receiving chemotherapy for persistent GTD at Weston Park Hospital, Sheffield, from 1991 to 2001. Three patients in this group had received treatment for infertility prior to their molar pregnancy. In a control group of 226 patients not requiring treatment for persistent GTD, four had had treatment for infertility just before their molar pregnancy, and in a further control group of 208 'normal' pregnancies, eight patients had had treatment for infertility prior to conception. CONCLUSION: We conclude that we can demonstrate no relationship between infertility treatment and subsequent development of GTD.

The purpose of this study was to compare in vitro and in vivo responses of primary human tumor cells to IFN-gamma.IFN-gamma may have therapeutic activity in patients with ovarian cancer. We showed previously that this cytokine had direct antiproliferative activity against human ovarian cancer cell lines and xenografts in nude mice. To further understand the role of IFN-gamma in ovarian cancer, we compared its action on 8 ovarian cancer cell lines with the response of 14 primary cultures of ovarian tumor cells isolated from patients with ascitic disease. A pilot clinical study was then conducted to see whether IFN-gamma would also induce apoptosis in human tumor cells in vivo. Six patients with ascites and advanced disease were given IFN-gamma by i.p. injection, and sequential samples of ascites were analyzed.IFN-gamma had antiproliferative activity in 8 of 8 ovarian cancer cell lines and 11 of 14 primary cultures. This activity was dose related, and cleaved poly(ADP-ribose) polymerase in protein isolates provided evidence of apoptosis. In the clinical study, there was a 3 log(10) pharmacokinetic advantage in peritoneal compared with plasma levels of IFN-gamma. In two of six patients, there was a 90% reduction in tumor cells in ascites after IFN-gamma treatment, and this was related to clinical benefit as assessed by intervals between paracentesis. In all six patients, there were increased amounts of cleaved poly(ADP-ribose) polymerase in protein extracts of ascitic cells sampled during IFN-gamma treatment.IFN-gamma induces apoptosis in vitro and in vivo in human epithelial ovarian cancer.

Aim: QoL in patients with gastroenteropancreatic-NETs can be affected by the symptom burden, but also treatment efficacy and safety. To better evaluate this, the EORTC developed a NET-specific QoL questionnaire (QLQ-GI.NET21), to be used in combination with its more generic questionnaire, EORTC QLQ-C30. Here, we examine the impact of LAN vs. placebo on QoL from the CLARINET study. Methods: CLARINET was a 96-week randomized double-blind phase III study, in which patients with well/moderately differentiated, non-functioning EP-NETs were treated with LAN 120 mg (n = 101) or placebo (n = 103) deep SC injections every 4 weeks (NCT00353496). The primary endpoint was progression-free survival (PFS). Safety was a key secondary endpoint. QoL (also a secondary endpoint) was assessed at each study visit using the EORTC QLQ-C30 and the EORTC QLQ-GI.NET21. Results: LAN significantly prolonged PFS vs. placebo (stratified log rank, p = 0.0002; hazard ratio 0.47 [95% CI: 0.30, 0.73]). Treatment-related adverse events (AEs) occurred in 50% of patients in the LAN group vs. 28% in the placebo group. Gastrointestinal disorders were the most common AEs (37% vs. 19%). The QLQ-C30 global health status scores and the QLQ-GI.NET21 endocrine and gastrointestinal subscale scores were similar in the two treatment groups at baseline and throughout treatment, though inter-individual variation was high (Table). Results for the other subscale scores of the QLQ-C30 and QLQ-GI.NET21 questionnaires were also similar between LAN and placebo. Conclusions: Overall, patients on LAN 120 mg had a significantly improved PFS and a good safety/tolerability profile that did not compromise patients' QoL vs. placebo. Further analyses are ongoing to evaluate QoL based on patient characteristics and treatment response. Table: Effect of LAN treatment on patients' QoL. Values are mean (SD); LVA, last post-baseline value available Data shown are for the transformed scores, which can range from 0 to 100. A higher transformed score for global health status represents a better QoL. A higher transformed score for Endocrine and GI symptoms represents a higher level of symptomatology/problems Baseline Week 48 Week 96 LVA QLQ-C30 Global health status/QoL LAN 70.2 (19.9) [n = 98] 70.9 (17.3) [n = 71] 66.4 (22.1) [n = 57] 64.5 (23.2) [n = 98] Placebo 73.6 (19.6) [n = 99] 72.0 (14.9) [n = 59] 70.1 (22.2) [n = 34] 67.0 (22.4) [n = 102] QLQ-GI.NET21 Endocrine symptoms LAN 10.9 (15.0) [n = 98] 11.0 (15.5) [n = 71] 11.1 (15.1) [n = 56] 11.7 (14.9) [n = 97] Placebo 12.0 (16.9) [n = 98] 13.2 (18.0 [n = 48] 11.8 (11.3) [n = 34] 13.9 (19.0) [n = 102] QLQ-GI.NET21 Gastrointestinal symptoms LAN 17.1 (16.4) [n = 98] 19.9 (17.6) [n = 71] 15.3 (13.8) [n = 56] 18.2 (16.5) [n = 97] Placebo 18.3 (18.0) [n = 98] 16.0 (14.3) [n = 58] 17.4 (17.3) [n = 34] 19.8 (18.5) [n = 102] Disclosure: P. Ruszniewski: Ipsen: Consultant/advisory role; honoraria; research funding; partner is Ipsen employee. Novartis: honoraria and research funding; M. Caplin: IPSEN: honoraria for consultant/advisory role. NOVARTIS: Consulting fee, Advisory Committees or Review Panels; LEXICON: Consulting fee, Advisory Committees or Review Panel; M. Pavel: Ipsen: Consulting & Speaker role fee. Pfizer, Inc.: Consulting & Speaker role fee. Novartis Pharmaceuticals: Consulting & Speaker role fee, research funding. Lexicon Pharmaceuticals, Inc.: Consulting & Speaker role fee; J. Cwikla: Ipsen: Research Funding; A. Phan: Ipsen: Research Funding; M. Raderer: Speaker fee from: Ipsen, Novartis Pharmaceuticals, Roche Pharmaceuticals, Pfizer, Inc., Bayer, Inc., Celgene; G. Cadiot: Ipsen: Consultant and Speaker fee. Novartis Pharmaceuticals: Consultant and Speaker fee. Keocyt: Consultant and Speaker fee; G. Rindi: Ipsen: Consultant and Speaker fee. Novartis Pharmaceuticals: Consultant and Speaker fee. Pfizer, Inc.: Consultant and Speaker fee. Advanced Accelerator Applications: Consultant fee; A. Langley: Ipsen: Consultant fee; J. Blumberg: Ipsen: employee; E. Gomez-Panzani: Ipsen: employee. All other authors have declared no conflicts of interest.

4107^ Background: The CLARINET core study showed that the long-acting somatostatin analog (SSA) LAN 120 mg significantly prolonged PFS vs placebo (PBO) in patients (pts) with metastatic enteropancr...

4081 Background: Most 1st-line combination chemotherapy regimens in pts with advanced GC include 5-FU. Taxanes are also active agents in GC, either alone or in combination. However, there is no recognized 2nd-line regimen for use in pts with advanced GC. DJ-927 is a semi-synthetic novel taxane with in vitro activity against GC cells lines. It is administered orally, with hematologic dose-limiting toxicity (DLT) in Phase I studies. The primary objective of this study was to determine the objective response rate of DJ-927 as 2nd-line therapy in pts with advanced GC. Methods: Eligible pts had confirmed advanced GC with no more than 1 prior systemic 5-FU-containing regimen for advanced disease, with adequate hematologic, renal and liver function, and with measurable disease. The starting dose in the 1st cohort of 6 pts was 27 mg/m2 orally, every 3 weeks. If < 2 DLTs occurred at this dose, the next cohort of 6 pts would start at a dose of 35 mg/m2, every 3 weeks, and all subsequent pts would be treated at the optimal dose level. Measurable disease was assessed after every 2 courses. Pharmacokinetic sampling was performed during course 1 only. Sample size based on a 3-outcome 1-stage design was calculated to be 27 pts evaluable for response, with ≥ 4 responses of 27 pts indicating that DJ-927 has activity in advanced GC. Results: 36 pts (male=25; female = 11), KPS ≥ 60%, with GC (n = 23) or OG junction cancer (n = 13), received 104 courses (median = 2; range 1–9) of DJ-927. 2 DLTs (febrile neutropenia; Grade 4 neutropenia > 5 days) occurred at 35 mg/m2, and the optimal starting dose was confirmed as 27 mg/m2. 6 of 36 pts were not evaluable for response (< 1 complete treatment course) due to early disease progression (3), toxicity (2), and drug not given (1). Response data is available for 26 of 30 evaluable pts with confirmed PR (n = 5), SD (15), and PD (6). Toxicity, ≥ grade 3, in evaluable pts (n = 33) included neutropenia (17), anemia (5), thrombocytopenia (4), diarrhoea (7), fatigue (5), lethargy (4), neutropenic sepsis (5). Conclusions: DJ-927 has modest activity in pts with GC who have failed a 5-FU non-taxane based regimen. Toxicities include neutropenia ± sepsis, diarrhoea and lethargy. Further studies of DJ-927 in combination with other active agents are warranted in pts with GC. [Table: see text]

4034 Background: Current cisplatin based regimens for the treatment of AEC are disappointing with response rates between 25 and 45% and median survival of around 9 months. Gemcitabine (Gem) is active against a range of tumour types. Preclinical models suggest synergistic cytotoxic activity for Gem and Cisplatin (Cis), and in phase II trials this combination is active in NSCLC, head & neck cancer and bladder cancer. Methods: This non-randomised open label phase II study evaluated the efficacy and safety of Gem 1250 mg/m2 on days 1, 8, and Cis 75 mg/m2 on day 1 every 21 days in AEC. Patients with; histologically proven, bidimensionally measurable, locally advanced or metastatic oesophageal carcinoma (squamous or adenocarcinoma), aged >18yrs, with a performance status 0–2 and life expectancy >3 months, and able to give informed consent were eligible. Interim review after 19 patients were enrolled suggested that this was unacceptably toxic, subsequent patients were treated with Gem 1000mg/m2 and Cis 75mg/m2. ...