Leptomeningeal Carcinomatosis: A Clinical Dilemma in Neuroendocrine Neoplasms

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases

Dosing 225Ac-DOTATOC in patients with somatostatin-receptor-positive solid tumors: 5-year follow-up of hematological and renal toxicity

Purpose!#!The aim of this retrospective analysis is to estimate the most appropriate single cycle and cumulative doses of !##!Methods!#!225!##!Results!#!Dose-dependent acute hematological toxicity was seen at single doses above 40 MBq or repeated doses greater than approximately 20 MBq !##!Conclusion!#!Treatment activities of approx. 20 MBq per cycle (4 monthly repetition) and cumulative doses up to 60-80 MBq generally avoided both acute and chronic grade 3/4 hematotoxicity in patients with advanced stage malignancies. Chronic renal toxicity was observed at these doses, but pre-existing renal risk factors were important co-factors. These data represent a starting point for additional research to more precisely define safety thresholds o

Financial toxicity in patients with colorectal cancer and neuroendocrine tumors.

Apostolidis L, Mehlis K, Witte J, et al. Financial toxicity in patients with colorectal cancer and neuroendocrine tumors. Journal of Clinical Oncology. 2018;36(15_suppl):6533-6533

Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)

Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed

Patient expectations are better for immunotherapy than traditional chemotherapy for cancer

Purpose!#!The main aim of the study was to explore the expectations and knowledge of advanced-stage cancer patients about immunotherapy.!##!Methods!#!This mixed methods study included 53 cancer patients on immune checkpoint inhibitors (ICIs), 55 cancer patients undergoing chemotherapy (CT), and 53 non-cancer patients. Participants' expectations about ICIs and CT were compared. Additional qualitative data were derived from semi-structured interviews.!##!Results!#!Among patients who did not receive ICIs, 63 (58%) had never heard of ICIs and 94 (87%) had large gaps in their knowledge of ICIs. Among ICI patients, 33 (62%) simply described ICIs without errors. ICI perception was positive, regardless of whether respondents received or had heard of ICIs, which became particularly evident when compared to CT. ICIs were rated as more promising, and all adverse effects were expected to be significantly lower than those of CT. Knowledge about ICIs was also limited in the interviewed ICI patients. Some patients reported adverse effects of ICIs that were mostly mild and well-tolerated or easily treated.!##!Conclusions!#!The lack of understanding of ICIs should be improved by activities to increase the knowledge of ICI patients and the general population. In contrast to CT, ICIs invoked fewer negative associations with efficacy and toxicity. Therefore, attention should be paid to risk awareness when educating patients. (Clinical trial registration number: DRKS00011868) Trial Registration: German clinical trials register, www.germanctr.de , number DRKS00011868

The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients.

Mehlis K, Witte J, Surmann B, et al. The patient-level effect of the cost of Cancer care - financial burden in German Cancer patients. BMC cancer. 2020;20(1): 529.BACKGROUND: Financial toxicity of cancer has so far been discussed primarily in the US health care system and is associated with higher morbidity and mortality. In European health care systems, the socio-economic impact of cancer is poorly understood. This study investigates the financial burden and patient-reported outcomes of neuroendocrine (NET) or colorectal (CRC) cancer patients at a German Comprehensive Cancer Center.; METHODS: This prospective cross-sectional study surveyed 247 advanced stage patients (n=122 NET/n=125 CRC) at the National Center for Tumor Diseases, in Germany about cancer-related out-of-pocket costs, income loss, distress, and quality of life. Multiple linear regression analysis was performed to demonstrate the effects of economic deterioration on patients' quality of life and distress.; RESULTS: 81% (n=199) of the patients reported out-of-pocket costs, and 37% (n=92) income loss as a consequence of their disease. While monthly out-of-pocket costs did not exceed 200 in 77% of affected patients, 24% of those with income losses reported losing more than 1.200 per month. High financial loss relative to income was significantly associated with patients' reporting a worse quality of life (p<.05) and more distress (p<.05).; CONCLUSIONS: Financial toxicity in third-party payer health care systems like Germany is caused rather by income loss than by co-payments. Distress and reduced quality of life due to financial problems seem to amplify the burden that already results from a cancer diagnosis and treatment. If confirmed at a broader scale, there is a need for targeted support measures at the individual and system level

Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment

Purpose!#!Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose.!##!Methods!#!For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1-t4) with the following median and ranges in months: 3.1 (0.4-4.9), 6.2 (5.3-7.8), 10.4 (8.2-11.9), and 18.4 (12.8-49.8).!##!Results!#!DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p &amp;lt; 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p &amp;lt; 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08).!##!Conclusion!#!CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker