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Accurate grading of patients with neuroendocrine neoplasms (NENs) is essential for risk stratification and optimal choice of therapy. Currently, grading is based on histologically assessed degree of tumor proliferation. The aim of the present study was to assess the long-term prognostic value of (18)F-FDG PET imaging for risk stratification of NENs and compare it with tumor grading (World Health Organization 2010 classification). Methods: We conducted a prospective cohort study evaluating the prognostic value of (18)F-FDG PET imaging and compared it with histologic grading. Enrolled were 166 patients of all grades and with histologically confirmed NENs of gastroenteropancreatic origin. The primary endpoint was overall survival (OS). Progression-free survival (PFS) was a secondary endpoint. In addition, OS in relation to peptide receptor radionuclide therapy (PRRT) was analyzed as an exploratory endpoint. The median follow-up time was 9.8 y. Results: Analysis of the whole cohort revealed that a positive (18)F-FDG PET scan was associated with a shorter OS than a negative (18)F-FDG PET scan (hazard ratio: 3.8; 95% CI: 2.4–5.9; P < 0.001). In G1 and G2 patients (n = 140), a positive (18)F-FDG PET scan was the only identifier of high risk for death (hazard ratio: 3.6; 95% CI, 2.2–5.9; P < 0.001). In multivariate analysis, (18)F-FDG PET, G3 tumor, ≥2 liver metastases, and ≥2 prior therapies were independent prognostic factors for OS, and (18)F-FDG PET, G3 tumor, and ≥3 liver metastases were independent prognostic factors for PFS. For patients receiving PRRT, (18)F-FDG–negative cases had a significantly longer survival than (18)F-FDG–positive cases, whereas no difference was identified for tumor grading. (18)F-FDG–positive patients receiving PRRT had a significantly longer median survival than patients not receiving PRRT (4.4 vs. 1.4 y, P = 0.001), whereas no difference was seen for (18)F-FDG–negative patients. Conclusion: (18)F-FDG PET is useful for risk stratification of all NEN grades and is superior to histologic grading. (18)F-FDG PET could differentiate G1 and G2 tumors into low- and high-risk groups. In the selection of therapy and for risk stratification of NEN patients, (18)F-FDG PET status should be considered.

Background High grade gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) with a Ki67 proliferation index > 20%, include well-differentiated tumours grade 3 (NET G3) and poorly differentiated (PD) neuroendocrine carcinomas (NEC). Abnormal p53-expression is a feature of PD tumours, while expression of chromogranin A (CgA) and somatostatin-receptor 2a (SSTR-2a) may be a feature of well-differentiated tumours. The aim of this study was to elucidate the expression and prognostic value of these three markers in 163 GEP-NEN patients with a Ki67-index > 20%. Method Clinical data, histopathology and overall survival were analysed according to Kaplan-Meier’s method and Cox regression. The expression of SSTR-2a, CgA and synaptophysin was analysed in tumour specimens by immunohistochemistry, and semi-quantitatively scored as negative ( 30%). P53 was defined as normal when scored as heterogeneously positive (1–30%), and abnormal when negative (0%) or strongly positive (> 30%). Results In multivariate analysis, better survival was observed among patients with heterogeneously positive p53 compared to strongly positive (p p = 0.002). Survival was significantly worse for negative CgA compared to heterogeneously positive CgA (p = 0.02). Strongly positive SSTR-2a expression was found in 26% of the 163 included patients. Well-differentiated morphology correlated with strong expression of SSTR-2a and CgA, and heterogeneously positive p53-staining, and was more frequent in pancreatic primaries. In pancreatic primaries, strongly positive SSTR-2a was associated with longer survival (univariate analysis, p = 0.02). A significantly lower Ki67 proliferation index was found in patients with a heterogeneously positive p53, a positive SSTR-2a and CgA expression. Conclusion Our results suggest that abnormal p53-expression is an independent negative prognostic marker in GEP-NEN with a Ki67-index > 20%. Patients with heterogeneously positive p53 had the best prognosis. SSTR-2a was a positive prognostic marker in pancreatic NEN. Negative CgA was associated with a significantly worse OS compared to heterogeneously positive CgA-expression in a multivariate sub-analysis. Lower Ki67 index correlated significantly with heterogeneously positive p53, positive SSTR-2a and CgA expression.

Background: The incidence of small intestinal (SI) and pancreatic neuroendocrine tumors (siNETs and pNETs) seems to have increased. The increased frequency of incidental findings might be a possible explanation. The study aimed to examine (1) changes in incidence and the stage at diagnosis (2010–2011 vs. 2019–2020), (2) changes in the initial indication for diagnostic workup and 3) the differences in stage between incidentally discovered vs. symptomatic disease during the entire study period. Methods: We performed a retrospective study, that includes consecutive siNET and pNET patients referred to the Copenhagen ENETS center of excellence in 2010–2011 and 2019–2020. Results: The annual incidence of siNET per 100,000 increased from 1.39 to 1.84, (p = 0.05). There was no change in the stage at diagnosis, and in both periods approximately 30% of patients were incidentally diagnosed (p = 0.62). Dissemination was found in 72/121 (60%) of symptomatic vs. 22/50 (44%) of incidentally discovered SI tumors in the entire cohort, (p = 0.06). The annual incidence of pNET increased from 0.42 to 1.39 per 100,000, (p &lt, 0.001). The proportion of patients with disseminated disease decreased from 8/21 (38%) to 12/75 (16%), (p = 0.02) and the number of incidental findings increased from 4/21 (19%) to 43/75 (57%), (p = 0.002). More symptomatic patients had disseminated disease compared to patients with incidentally discovered tumors (15/49 (31%) vs. 5/47 (11%), (p = 0.01)). Conclusion: The incidence of siNET and pNETs increased over the past decade. For siNETs, the stage of disease and the distribution of symptomatic vs. incidentally discovered tumors were unchanged between the two periods. Patients with pNETs presented with more local and incidentally discovered tumors in the latter period. Patients with incidentally discovered siNETs had disseminated disease in 44% of the overall cases. The vast majority of incidentally found pNETs were localized.

An increase in the Ki-67 index in neuroendocrine neoplasms over time in relation to prognosis has scarcely been investigated. We aimed to assess whether the Ki-67 index changed over time and also whether a change influenced prognosis. Second, we investigated the difference in the Ki-67 index between primary tumour and metastases. From 1 January 1995 to 31 December 2019, 108 consecutive patients with gastroenteropancreatic tumours were included. Patients were followed with regard to an increase in the Ki-67 index and all-cause mortality. Ki-67 determination of the primary tumour at diagnosis and at the time of radiological progression, including developed metastases, was performed. A significant increase in the Ki-67 index was defined as a doubling of the value at disease progression compared to the value at diagnosis. In addition, in 14 patients, the Ki-67 index of the primary tumour and present metastases at the time of diagnosis was investigated. At diagnosis, there were no differences in the Ki-67 index between primary tumours and metastases (P = .41). Sixty-five patients had a doubling of the Ki-67 index. The median Ki-67 index at the time of progression 17% (1%-90%) vs 5% (1%-60%) at the time of diagnosis (P = .006). A doubling of the Ki-67 index was independently associated with all-cause mortality (hazard ratio = 2.7 [1.3-6.3], P = 0.02), after adjustment for relevant co-variables including the Ki-67 index at baseline. Doubling of the Ki-67 index at the time of disease progression was associated with a significantly higher risk of all-cause mortality. We recommend that a Ki-67 index is obtained whenever disease progression is recorded by demonstrated progression because it may have impact on the choice of treatment.

IntroductionDiagnosis and pathological classification of insulinomas are challenging.AimTo characterize localization of tumors, surgery outcomes, and histopathology in patients with insulinoma.MethodsPatients with surgically resected sporadic insulinoma were included.ResultsEighty patients were included. Seven had a malignant tumor. A total of 312 diagnostic examinations were performed: endoscopic ultrasonography (EUS; n = 59; sensitivity, 70%), MRI (n = 33; sensitivity, 58%), CT (n = 55; sensitivity, 47%), transabdominal ultrasonography (US; n = 45; sensitivity, 40%), somatostatin receptor imaging (n = 17; sensitivity, 29%), 18F-fluorodeoxyglucose positron emission tomography/CT (n = 1; negative), percutaneous transhepatic venous sampling (n = 10; sensitivity, 90%), arterial stimulation venous sampling (n = 20; sensitivity, 65%), and intraoperative US (n = 72; sensitivity, 89%). Fourteen tumors could not be visualized. Invasive methods were used in 7 of these 14 patients and localized the tumor in all cases. Median tumor size was 15 mm (range, 7 to 80 mm). Tumors with malignant vs benign behavior showed less staining for insulin (3 of 7 vs 66 of 73; P = 0.015) and for proinsulin (3 of 6 vs 58 of 59; P < 0.001). Staining for glucagon was seen in 2 of 6 malignant tumors and in no benign tumors (P < 0.001). Forty-three insulinomas stained negative for somatostatin receptor subtype 2a.ConclusionLocalization of insulinomas requires many different diagnostic procedures. Most tumors can be localized by conventional imaging, including EUS. For nonvisible tumors, invasive methods may be a useful diagnostic tool. Malignant tumors showed reduced staining for insulin and proinsulin and increased staining for glucagon.

Bronchopulmonary neuroendocrine tumours are divided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC).To thoroughly describe a cohort of 252 patients with TC, AC and LCNEC (SCLC excluded).Collection of data from 252 patients referred to and treated at Rigshospitalet 2008-2016. Data was collected from electronic patient files and our prospective NET database. Statistics were performed in SPSS.162 (64%) had TC, 29 (12%) had AC and 61 (24%) had LCNEC. Median age at diagnosis was 69 years (range: 19-89) with no difference between genders. Thoraco-abdominal CT was performed in all patients at diagnosis. FDG-PET/CT was performed in 207 (82%) at diagnosis and was positive in 95% of the entire cohort, with no difference between tumour types. Synaptophysin was positive in 98%, chromogranin A in 92% and CD56 in 97%. Mean Ki67 index was 5% in TC, 16% in AC and 69% in LCNEC (p 0.001). Metastatic disease was found in 4% of TC, 27% of AC and 58% of LCNEC at time of initial diagnosis (p 0.001). In total 179 patients (71%) underwent surgical resection; TC: 87%, AC: 72% and LCNEC: 28% (p 0.001). Of the resected patients, 11 (6%) had recurrence. Five-year survival rate was 88% for TC, 63% for AC and 20% for LCNEC.In this comprehensive study of a cohort of 252 patients, one of the largest until date, with TC, AC and LCNEC, the gender distribution showed female predominance with 68%. FDG-PET/CT was positive in 95% of the patients independent of tumour type, which confirms that FDG-PET/CT should be a part of the preoperative work-up for TC, AC and LCNEC. Tumour type was the single most potent independent prognostic factor.

Little is known about the optimal amount and timing of exercise strain in concern of the operation wound and with regard improvement of physical function and quality of life (QOL) after surgery for lung cancer. On this background, we decided to investigate the effect of early vs. late initiated postoperative rehabilitation in patients with operable lung cancer on exercise capacity, functional capacity, muscle strength, and QOL.The study was designed as a two-armed randomized controlled trial with randomization to either early initiated postoperative rehabilitation (14 days after surgery (ERG)) or a control arm with late initiated postoperative rehabilitation (14 weeks after surgery (LRG)). The primary endpoint was a change in maximum oxygen consumption (VO2peak) from baseline to post intervention 26 weeks following lung resection. Fatigue was measured with EORTC QLQ C30 LC13.From April 2013 to June 2016, 582 patients with operable NSCLC were screened for eligibility. With 119 patients randomized in the early rehabilitation group (ERG) and 116 randomized to late rehabilitation group (LRG). There was no significant difference from baseline to 26 weeks between ERG and LRG (p = 0.926). There was a significant difference from baseline to 14 weeks between groups (p = 0.0018). There was a significant difference from 14 weeks to 26 weeks between the two groups (p 0.001). We found no significant differences in QOL but we found a significant difference between ERG and LRG from baseline to 14 weeks in fatigue level in favour of ERG.This is the first randomized controlled trial to investigate the effects of early vs. late initiated postoperative rehabilitation in patients with lung cancer. There is no difference in the commencement (early vs. late) of a postoperative exercise program for patients with lung cancer on exercise capacity. But to reduce fatigue patients should be recommended to initiate early exercise programs.

Gastroenteropancreatic (GEP) mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN), are rare tumors [1,2] comprising a neuroendocrine and a non-neuroendocrine component, both accounting for at ...

Radiation-induced changes may cause a non-malignant high 2-deoxy-2-[18F]fluoro-D-glucose (FDG)-uptake. The 3′-deoxy-3′-[18F]fluorothymidine (FLT)-PET/CT performs better in the differential diagnosis of inflammatory changes and lung lesions with a higher specificity than FDG-PET/CT. We investigated the association between post-radiotherapy FDG-PET-parameters, FLT-PET-parameters, and outcome. Sixty-one patients suspected for having a relapse after definitive radiotherapy for lung cancer were included. All the patients had FDG-PET/CT and FLT-PET/CT. FDG-PET- and FLT-PET-parameters were collected from within the irradiated high-dose volume (HDV) and from recurrent pulmonary lesions. For associations between PET-parameters and relapse status, respectively, the overall survival was analyzed. Thirty patients had a relapse, of these, 16 patients had a relapse within the HDV. FDG-SUVmax and FLT-SUVmax were higher in relapsed HDVs compared with non-relapsed HDVs (median FDG-SUVmax: 12.8 vs. 4.2; p < 0.001; median FLT-SUVmax 3.9 vs. 2.2; p < 0.001). A relapse within HDV had higher FDG-SUVpeak (median FDG-SUVpeak: 7.1 vs. 3.5; p = 0.014) and was larger (median metabolic tumor volume (MTV50%): 2.5 vs. 0.7; 0.014) than the relapsed lesions outside of HDV. The proliferative tumor volume (PTV50%) was prognostic for the overall survival (hazard ratio: 1.07 pr cm3 [1.01–1.13]; p = 0.014) in the univariate analysis, but not in the multivariate analysis. FDG-SUVmax and FLT-SUVmax may be helpful tools for differentiating the relapse from radiation-induced changes, however, they should not be used definitively for relapse detection.

Many studies have suggested a prognostic value of one or several positron emission tomography (PET) parameters in patients with small cell lung cancer (SCLC). However, studies are often small, and there is a considerable interstudy disagreement about which PET parameters have a prognostic value. The objective of this study was to perform a review and meta-analysis to identify the most promising PET parameter for prognostication. PubMed®, Cochrane, and Embase® were searched for papers addressing the prognostic value of any PET parameter at any treatment phase with any endpoint in patients with SCLC. Pooled hazard ratios (HRs) were calculated by a random effects model for the prognostic value of the baseline maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV). The qualitative analysis included 38 studies, of these, 19 studies were included in the meta-analyses. The pooled results showed that high baseline MTV was prognostic for overall survival (OS) (HR: 2.83 (95% confidence interval [CI]: 2.00–4.01) and progression-free survival (PFS) (HR: 3.11 (95% CI: 1.99–4.90)). The prognostic value of SUVmax was less pronounced (OS: HR: 1.50 (95% CI: 1.17–1.91); PFS: HR: 1.24 (95% CI: 0.94–1.63)). Baseline MTV is a strong prognosticator for OS and PFS in patients with SCLC. MTV has a prognostic value superior to those of other PET parameters, but whether MTV is superior to other prognosticators of tumor burden needs further investigation.

Background The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic. Aim These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group’s current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians. publishedVersion

BACKGROUND: Plasma chromogranin A (CgA) is related to tumor burden and recommended in the follow-up of patients diagnosed with neuroendocrine tumors (NETs). The use of CgA in the workup of a suspected NET is more questionable.OBJECTIVE: To assess the positive predictive value (PPV) of CgA plasma concentrations above the upper reference limit (URL) in patients with suspected NET.METHOD: Patients referred to the NET Centre, Rigshospitalet, Copenhagen from 2015 to 2019 with clinically suspected NET were included if a CgA measurement was performed prior to referral. The utility of CgA was assessed by comparing pre-referral CgA concentrations to the outcome of a thorough workup. In 47 selected cases with continuously unexplained elevated CgA concentrations, a processing-independent analysis (PIA) for CgA was performed.RESULTS: A total of 197 patients were included. NET was ultimately diagnosed in 25 patients. CgA plasma concentrations were above the URL (elevated) in 19/25 patients diagnosed with NET. In total, 167/197 had elevated CgA concentrations at referral. The positive predictive value (PPV) of elevated CgA concentration was 11% (19/167). Proton pump inhibitor (PPI) treatment was identified as the possible cause of CgA elevation in 55/148 patients with falsely elevated CgA. CgA concentration was normal in 28/47 patients when using PIA.CONCLUSION: Our data do not support using measurement of CgA for screening when NET is suspected since the PPV was rather low. PPI treatment is a common cause of increased CgA concentrations and should always be discontinued before CgA measurement. PIA of CgA could be a way of excluding NET when suspicion is based primarily on elevated CgA.

Introduction Patients with lung cancer report a lower degree of Health Related Quality of Life (HRQoL) compared with other cancer patients. HRQoL reflects how patients experience the impact of their disease and its treatment on their quality of daily living. A widely used questionnaire in lung cancer patients is the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire. Here we report the secondary outcomes on FACT-L data from the Postoperative Rehabilitation in Operation for Lung CAncer (PROLUCA) study, which describes the effect of early (14 days) versus late initiated (14 weeks) postoperative rehabilitation. Materials and methods The PROLUCA study was designed as a two-armed randomized controlled trial with an early rehabilitation group (14 days after surgery (ERG)) or a control arm with a late rehabilitation group (14 weeks after surgery (LRG)). The results for seven domain scores obtained using the FACT-L at the following time-points: baseline, 14 weeks, 26 weeks and 52 weeks after surgery are presented here. Results 119 patients were randomized to the ERG and 116 to the LRG. In the ERG, HRQoL measured by both FACT-L and FACT-G (general core instrument) showed a continuous improvement up to 26 weeks after which HRQoL decreased after further 26 weeks without structured intervention. In the LRG a non-significant deterioration was detected over the first 14 weeks after surgery. After participation in the 12 weeks rehabilitation program, an increase in HRQoL was seen, without reaching the same level as the early group. Conclusion Analyses of the seven domain scores obtained using FACT-L and FACT-G reflect the importance of starting exercise early after surgery since the ERG avoid a temporary decrease in HRQoL. It is therefore recommended to start up a structured rehabilitation program 14 days after surgery, containing high intensity interval training and strength exercise twice a week for 12 weeks.

Objective Exercise can improve treatment-related side effects, quality of life, and function in patients with various types of cancer; however, more evidence is needed for patients with advanced inoperable lung cancer. Material and methods We randomized 218 patients with advanced inoperable lung cancer to a 12-week supervised, structured exercise training program (aerobic, strength, and relaxation training) twice weekly versus usual care. Primary outcome was change in maximal oxygen uptake (VO2 peak). Secondary outcomes were muscle strength, functional capacity, forced expiratory volume in 1 s, health-related quality of life, anxiety, and depression. Results There was no significant difference between the intervention and control groups in VO2 peak. There was a significant improvement in muscle strength. There was also a significant difference between the two for social well-being (Functional Assessment of Cancer Therapy—Lung, FACT-L), anxiety, and depression. Conclusion There was a significant reduction in the level of anxiety and depression and a significant increase in all muscle strength outcomes in the intervention group compared to patients randomized to usual care. There was a significant difference between the groups for social well-being. The primary outcome did not show a significant improvement in VO2 peak. Based on our results, future patients with advanced inoperable lung cancer should be considered for supervised exercise during the course of their disease.

Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

9007 Background: Concurrent chemoradiotherapy is the standard treatment of LD SCLC. Some patients are cured, but most relapse and better treatment is needed. 45 Gy in 30 fractions BID is the most recommended TRT-schedule. Studies suggest that a higher TRT-dose might prolong survival, but hitherto, this has not been confirmed in randomized trials. We aimed to investigate whether high-dose BID TRT of 60 Gy in 40 fractions was feasible, tolerated, and improved survival. Methods: Patients > 18 years, performance status (PS) 0-2 and confirmed LD SCLC were to receive 4 courses of platinum/etoposide and were randomized to BID TRT of 60 or 45 Gy. Responders were offered prophylactic cranial irradiation of 25-30 Gy. Primary endpoint was 2-year survival; secondary endpoints were toxicity, progression free survival (PFS), and overall survival (OS). To demonstrate a 25% improvement of 2-year survival from 53% to 66% with a one-sided α = .10 and β = .80, 75 patients were required on each arm. Results: Between 2014-2018, 176 patients were enrolled at 22 Scandinavian hospitals. 160 completed TRT per protocol and were eligible for the present analyses (60 Gy: n = 84, 45 Gy: n = 76). Median age was 65, 58% women, 90% PS 0-1. There were no significant differences in grade 3–4 esophagitis (60 Gy: 19%, 45 Gy: 18%, p = .92) or grade 3–4 pneumonitis (60 Gy: 4%, 45 Gy: 0%, p = .10). There was a trend towards more neutropenic infections on the 45 Gy arm (60 Gy: 21%, 45 Gy: 36%, p = .05). There were no significant differences in other grade 3-4 toxicity. Three patients died during the study treatment period (60 Gy: one neutropenic infection and one aortic dissection; 45 Gy: one thrombocytopenic bleeding). There were no statistically significant differences in response rates (60 Gy: 88% [95% CI 81-95], 45 Gy: 85% [95% CI 76-93], p = .52) or median PFS (60 Gy: 20 months [95% CI 11-29], 45 Gy: 14 months [95% CI 10-19], p = .31). Significantly more patients on the 60 Gy arm were alive after 2 years (60 Gy: 73% [95% CI 63-83], 45 Gy: 46% [95% CI 36-60], p = .001), and they had a significantly longer median overall survival (60 Gy: 42 months [95% CI 32-51], 45 Gy: 23 months [95% CI 17-28], HR .63 [95% CI .41-.96], p = .031). Conclusions: LD SCLC patients who received BID TRT of 60 Gy had a statistically significant and numerically substantial benefit in terms of 2-year survival (primary endpoint) and median overall survival compared with those who received BID TRT of 45 Gy. The higher TRT dose did not cause more toxicity than the standard dose. Clinical trial information: NCT02041845.

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.

Key Clinical Message Survival of stage 4 ganglioneuroblastoma (GNB) patients is poor; no reports exist of patients surviving up to 5 years (1, 2). We report the clinical and therapeutic course of a patient with stage 4 GNB surviving beyond expectations due to a multimodal treatment approach incorporating new technologies in cancer diagnostic and treatment.

Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce. The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended curative resection/RFA of liver metastases, were identified among 840 patients from two Nordic GEP-NEC registries. Tumor morphology (well vs poor differentiation) was reassessed. Overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan Meier analyses for the entire cohort and for subgroups. Results: Median OS after resection/RFA of liver metastases was 35.9 months (95% -CI: 20.6-51.3) with a five-year OS of 43%. The median PFS was 8.4 months (95% -CI: 3.9-13). Four patients (13%) were disease -free after 5 years. Two patients had well -differentiated morphology (NET G3) and 20 patients (63%) had Ki-67 >= 55%. A Ki-67

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with18F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma.

Background: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second-line treatment in small cell lung cancer, which also responds markedly on first-line platin/etoposide. Hence, we investigated the feasibility of topotecan in previously treated patients with neuroendocrine carcinomas. Material and Methods: Retrospective analysis of 22 patients with disseminated and progressive neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m2 d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after every three courses. Hematological toxicity was assessed by CTC-criteria. Results: Twenty-two eligible patients received a median of 2 courses [range1-6]. Median age: 65 years [35-77]. Male/female: 11/11. Median Ki-67 index: 95% [25-100%]. Median number previous chemotherapy regimens: 2 [1-3]. All patients were evaluable for response: Five achieved stable disease (SD) and 17 progressed (PD). The median overall survival for the 22 patients was 3.2 months and the median progression-free survival was 2.1 months. The one-year survival was 18%. There were no treatment related deaths. The treatment was well tolerated: Haematological toxicity comprised leukopenia CTC grade 3 (14%), grade 4 (9%) and thrombocytopenia grade 3 (14%). Conclusion: Topotecan monotherapy shows modest anti-tumor activity in heavily treated patients with progressive disseminated G3 neuroendocrine carcinomas.

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumors arising in various organs and with a large span of aggressiveness and survival rates. The Ki-67 proliferation index is presently used as the key marker of prognosis, and treatment guidelines are largely based on this index. 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) is a proliferation tracer for PET imaging valuable in the monitoring of disease progression and treatment response in various types of cancer. However, until now only data from 10 patients with NEN were available in the literature. The aim of the present study was to investigate 18F-FLT PET as a prognostic marker for NENs in comparison with 18F-FDG PET and Ki-67 index. Methods: One hundred patients were PET-scanned with both 18F-FLT and 18F-FDG within the same week, and the prognostic value of a positive scan was examined in terms of progression-free survival (PFS) and overall survival (OS). The correlation between the Ki-67 index and 18F-FLT uptake was also investigated. Results: Thirty-seven percent of patients had a positive 18F-FLT PET scan, and 49% had 18F-FDG PET–positive foci. Patients with a high 18F-FLT uptake had a significantly shorter OS and PFS than patients with low or no 18F-FLT uptake. No correlation was found between Ki-67 index and 18F-FLT uptake. In a multivariate analysis 18F-FLT, 18F-FDG, and Ki-67 all were significant prognostic markers of PFS. For OS, only 18F-FDG and Ki-67 remained significant. Conclusion:18F-FLT PET has prognostic value in NEN patients but when 18F-FDG PET and Ki-67 index are also available, a multivariate model revealed that 18F-FLT PET only adds information regarding PFS but not OS, whereas 18F-FDG PET remains predictive of both PFS and OS. However, a clinically robust algorithm including 18F-FLT in addition to 18F-FDG and Ki-67 could not be found. Accordingly, the exact role, if any, of 18F-FLT PET in NENs remains to be established.

Background. Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results.Patients and Methods. Analysis of consecutive patients with neuroendocrine carcinomas (Ki-67 proliferation index >20%) and performance status 0–2 treated with temozolomide 200 mg/sqm orally days 1–5 every 28 days after at least one previous platin-containing chemotherapy regimen.Results. Twenty-eight eligible patients received a median of 3 courses. Sixteen patients were evaluable for response: Six achieved stable disease and ten progressed. The median survival for the 28 patients was 3.5 months. Survival in patients with tumors of pancreatic origin (n=7) was 7.0 months versus 2.9 months in non-pancreatic origin (n=21). Patients in PS 0-1 (n=22) had a median survival of 4.5 months versus 1.1 months in patients in PS 2 (n=6). Ki-67 index ≥50% was associated with a significantly shorter median survival than Ki-67 index Conclusion. Temozolomide monotherapy has limited effect in treatment of recurrent neuroendocrine carcinomas. Second line treatment with temozolomide in combination with other compounds should be further investigated in patients in good performance with Ki-67 index

Introduction Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. Methods Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC, adequate organ functions and performance status less than 3 were eligible. Topotecan (2.0 mg/m 2 , intravenously) was administered on days 1 to 3 with cisplatin (50 mg/m 2 , intravenously) on day 3 every 3 weeks for a total of six cycles. Results Forty-three patients received 219 cycles of chemotherapy. Median age was 59 (range 44–74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes of fatal sepsis occurred. Non-hematologic toxicity was mild and manageable. Overall and complete response rates were 72.1% and 9.3%, respectively. The median overall survival and response duration were 10.3 months (95% confidence interval: 8.6–12.0) and 7.0 months (95% confidence interval: 6.3–7.7), respectively. Conclusion Three-day topotecan with cisplatin on day 3 is active and safe in extensive disease SCLC. An ongoing phase III randomized trial compares this combination to standard treatment.

Summary Introduction The longest survival time reported in randomised trials of limited disease (LD) SCLC has been achieved with early twice-daily concurrent chemoradiation. Topotecan is active in recurrent SCLC and in extensive disease as first line treatment. Aim: To incorporate and assess the effect of topotecan with concurrent twice-daily radiochemotherapy in LD SCLC. Patient and Methods Multicentre phase II study of three cycles of regimen A (topotecan i.v., 1.5 mg/m 2 , day 1–5; cisplatin 50 mg/m 2 , day 1) and three cycles of regimen B (etoposide i.v., 120 mg/m 2 , day 1–3; carboplatin, AUC = 5, day 1; vincristine, 1.3 mg/m 2 , day 1) given in the following sequence: A–B–B–A–B–A every 21 days. Twice-daily radiotherapy (1.5 Gy × 30, 10 fr/wk, 45 Gy) was delivered concurrently with the first cycle B. Prophylactic cranial irradiation was offered to patients (pts) in complete remission. Eligible were pts with LD SCLC with no prior treatment for SCLC, adequate organ functions, and WHO performance status (PS) ≤2. Pts older than 64 years with PS = 2 and LDH > two times the upper limit were excluded. Result Fourty-five pts were included in four centres. Five patients did not meet the inclusion criteria. The median age of the eligible pts was 60 years, range 43–75. PS was ≤1 in 90% of pts. Non-haematological toxicity was mild except grade 3 esophagitis, which was observed in 26.5% of pts. One pt developed an esophageal stricture. Grade 3/4 leucopenia and thrombocytopenia were observed in 82.5% and 75.0 of pts, respectively. One patient died due to neutropenic sepsis. The overall response rate was 77.5% with 30.0% achieving a complete response. Median progression-free survival was 11.8 months (95% CI: 1.3–22.2). Median overall survival was 22.9 months (95% CI: 13.4–31.5) and 5-year survival was 21%. Conclusion The combination of topotecan and cisplatin with concurrent twice-daily chemoradiation results in long-term survivors. As expected the incidence of severe esophagitis is high.

BACKGROUND: Appendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features.PATIENTS AND METHODS: Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27) diagnosed 1992-2013.RESULTS: Median age for f/m was 59/58 years, respectively, and similar for localized and disseminated disease. At diagnosis 54 patients had localized appendiceal disease (f/m: 29/25). According to TNM 24% had Stage I, 70% had Stage II and 6% had Stage III. Twenty-nine patients had disseminated disease (f/m: 27/2). Chromogranin A, synaptophysin and p53 were positive in >90%. Serotonin was positive in 70%. Median Ki67 index was 32% (6-75%) and higher in Tang group C (50%) compared to group A (30%; pCONCLUSION: The Tang classification was found to be a significant prognostic factor, while the Ki67 index was not. Localized GCCs occurred equally in males and females, while disseminated GCCs were mostly seen in females. Median age of patients with localized disease and disseminated disease was identical. Cox regression analysis found Stage IV, focally positive synaptophysin and non-radical surgery as strongest negative prognostic factors.

e20020 Background: Approximately two thirds of patients diagnosed with SCLC will have ED at the time of diagnosis. Response rates to chemotherapy are high but median overall survival for patients treated with chemotherapy is only 9 to 10 months. Patients with ED SCLC considered fit for chemotherapy is normally treated with combination chemotherapy including cisplatin or carboplatin, and etoposide or irinotecan. The usual dosing scheme is 3 weeks intervals with the platin administered on day 1 and etoposide given day 1-3 or 1-5. Etoposide is available in as well intravenous as oral formulations. Concerns about the incomplete and variable bioavailability of oral etoposide have been raised. A randomized study of cisplatin with either oral or IV etoposide found no significant difference in treatment outcome but increased rate of severe or life-threatening hematologic toxicity. Methods: The two cancer hospitals serving the Copenhagen area are using carboplatin + etoposide for palliative treatment of SCLC ED. While carboplatin is used identically (AUC5, IV d1), etoposide is given IV by HUH (120mg/m2, IV d1-3) and orally by CUH (200mg/m2 O, d1-3). From the hospital patient database, we identified patients with SCLC, ED treated in 2011-2013. Route of etoposide administration, dose reductions and GCSF use was noted. PFS and OS was calculated from hospital records. Results: 200 SCLC, ED patients received treatment (116 at HUH, 84 at CUH). A non-significant higher proportion of women were treated at HUH while median age was identical. PFS was longer at HUH than CUH (195 vs 140 days), but the OS was identical (235 vs 227 days). Conclusions: The two dosing schemes: O and IV yield similar OS, but longer PFS with the IV schedule. The survival seen is in line with results from randomized trials although the present study includes all patients irrespectible of PS or comorbidity. We have no information on adverse events, quality of life or rates of hospitalization.

Dexrazoxane has been in clinical use for more than 25 years for prevention of cardiotoxicity in anthracycline based anticancer therapy. However, we discovered another property of the compound, i.e. the ability to prevent the devastating tissue necrosis after accidental extravasation of anthracyclines. The preclinical and clinical studies leading to the clinical implementation of Savene™ (dexrazoxane) as the first and only proven antidote in anthracycline extravasation are described in short.

As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients.Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively registered at 12 Nordic hospitals.The median survival was 11 months in 252 patients given palliative chemotherapy and 1 month in 53 patients receiving best supportive care (BSC) only. The response rate to first-line chemotherapy was 31% and 33% had stable disease. Ki-6755% was by receiver operating characteristic analysis the best cut-off value concerning correlation to the response rate. Patients with Ki-6755% had a lower response rate (15% versus 42%, P0.001), but better survival than patients with Ki-67≥55% (14 versus 10 months, P0.001). Platinum schedule did not affect the response rate or survival. The most important negative prognostic factors for survival were poor performance status (PS), primary colorectal tumors and elevated platelets or lactate dehydrogenase (LDH) levels.Advanced GI-NEC patients should be considered for chemotherapy treatment without delay.PS, colorectal primary and elevated platelets and LDH levels were prognostic factors for survival. Patients with Ki-6755% were less responsive to platinum-based chemotherapy, but had a longer survival. Our data indicate that it may not be correct to consider all GI-NEC as one single disease entity.

Poorly differentiated neuroendocrine carcinomas (PDECs) represent highly malignant tumors with an immense tendency to metastasize and with a poor prognosis. The treatment consists of palliative chemotherapy and corresponds to the treatment of extensive stage small cell lung cancer. Material and methods. We present the patient characteristics and treatment results of 31 consecutive, chemona i ve patients with PDECs treated with carboplatin, etoposide, and vincristine. Results. The response rate was 52%, the disease control rate 77%, and the median overall survival 15.3 months. The one-year survival rate was 55%, and the two-year survival rate was 19%. The median progression free survival (PFS) time was 6.6 months. Survival rates did not correlate with the Ki-67 proliferation index. The treatment was well tolerated. Conclusion . Treatment results with carboplatin, etoposide, and vincristine in chemona i ve patients with PDECs are comparable to those in patients with SCLC. The prognosis is however poor.

Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane.

e17609 Background: In Greenland, the incidence of lung cancer (LC) is now as high as in the other Nordic countries; 59.8/100,000 for men and 43.9/100.000 for women. In 2004, oncological treatment o...

7519 Background: Randomized trials in extensive disease (ED) small cell lung cancer (SCLC) comparing the camptothecins to standard etoposide based chemotherapy have reached conflicting results. Her...

The incidence of brain metastases secondary to small cell lung cancer (SCLC) is about 35% and the treatment strategy of brain irradiation with respect to dose and fractionation is controversial. In order to evaluate treatment outcome of brain irradiation in SCLC patients with brain relapse, we retrospectively evaluated all patients treated with brain irradiation in the eastern part of Denmark from 1988 to 1992 (PCI patients excluded). During this 5-year period, 101 evaluable patients were included (44 females, 57 males) (median age 61 years; range, 39-75 years). Forty-four patients, of whom 43 were in extracerebral complete remission (CR), received extended course (EC) brain irradiation (> 45 Gy, treatment schedule > 4 weeks). Fifty-seven patients received short course (SC) brain irradiation (< 30 Gy, treatment schedule < 1 week). Among the SC treated patients, 14 were in CR, 20 had partial remission or stable disease and 23 had progressive extracerebral disease. The median survival (from diagnosis of brain metastases) in the group receiving irradiation with EC (44 patients) was 160 days (range, 74-2021 days), while the 57 patients treated with SC had a median survival of 88 days (range, 20-948 days) (P = 0.00001, Log-Rank analysis). In a subgroup of 14 patients in extracerebral CR, receiving SC irradiation, the median survival was 83 days (range, 15-948 days). When the latter patients were compared to the 43 patients in CR in the group treated with EC, a statistically significant difference was shown (P = 0.034, Log-Rank analysis). Using Cox-hazard regression analysis with backward elimination, liver metastases and poor performance status were adverse prognostic signs, although the only significant parameters of survival were gender (female vs. male, relative risk of dying 1 and 1.52, P = 0.05) and schedule of brain irradiation (extended course vs. short course, relative risk of dying, 0.36 and 1, P < 0.001). Extended course irradiation of brain relapse secondary to SCLC seems in general to be of limited value, although a significant prolonged survival at approximately 7 weeks, was obtained. The prolongation of survival does not seem worthwhile considering the length of treatment time (5-6 weeks) compared to SC treatment (1 week). However, the data do not permit evaluation of the quality of life of the patients. This retrospective evaluation suggests the need for randomized trials with carefully planned quality-of-life assessments.

Background: The poorly differentiated neuroendocrine carcinomas (PDEC) represent a highly malignant tumor with an immense tendency to metastasize and a poor prognosis, with a median survival of approximately 6 months without treatment. Treatment based on platin and etoposide is widely recommended as palliative chemotherapy and corresponds to the treatment of extensive stage small cell lung cancer. The recommendation is based on relatively few, older studies, which did not use the 2000 WHO tumor classification, and no controlled, randomised studies have been published. Method: Successive chemonaïve patients with disseminated PDEC (small cell carcinomas excluded) allocated for treatment from May 2007 to June 2008 were identified. Patients received carboplatin AUC 5 IV day 1 + etoposide 100 mg/m2 PO day 1-3, and vincristine 1.3 mg/m2 (maximum 2.0 mg) IV day 1. Treatment was repeated every 3 weeks until progression or intolerable toxicity up to a maximum of 6 courses. Results: Twenty-two patients diagnosed with PDEC according to the 2000 WHO tumor classification were eligible for analysis, 11 females and 11 males. The median age was 61 years (range 35-80). Performance status: 0/1/2 = 9/11/2. All patients had disseminated disease. Immunohistochemical analyses of synaptophysin were positive in 21/22 (95.4%), and chromogranin A positive in 17/21 (80.9%). In one patient (4.5%) both analyses were negative; in 17/21 (80.9%) both were positive. The Ki-67 proliferation index ranged from 20% to 100%; the index reaching 50% or higher in 17 patients (77.2%). Octreotide scintigraphy was negative in 10 of 12 scanned patients (83,3%). Three patients (13.6%) achieved complete response (CR), 11 (50%) partial response (PR), 4 (18.2%) no change (NC), and 4 (18.2%) progressive disease (PD). The overall response rate (CR+PR) was 63.6%, and the disease control rate (CR+PR+NC) 81.8%. The median progression free survival time was 7.4 months. The median overall survival time was 10.5 months, and the 1-year survival 48%. Conclusion: In conclusion, treatment with carboplatin, etoposide, and vincristin in previously untreated patients with disseminated PDEC results in a noticeable survival benefit compared to untreated historical controls. The prognosis is however still poor. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3671.

Accidental extravasation of anthracycline-based chemotherapy is a complication that has been feared since the introduction of the anthracyclines more than 40 years ago. Tissue infiltration with vesicant drugs may lead to progressive necrosis and destruction of muscles, tendons, nerves, and joints, and may be associated with severe functional and cosmetic changes. During the last four decades, much effort has been made to prevent such accidents from happening. In addition, different surgical approaches and several non-pharmacolgical and pharmacological treatments have been used to counteract the devastating effects of the extravasation. Most treatment modalities have been empirically based, and only a few have undergone thorough evaluation. Recently, dexrazoxane was shown to be an effective and non-toxic acute treatment for anthracycline extravasation. It has since become a widely recommended treatment, and Totect® is currently the only approved drug for this indication.

7207 Background: The role of campthotecins in small cell lung cancer (SCLC) is emerging, and 5-day regimens with topetecan alone or with cisplatin have been shown to be active and tolerable. In ord...