Poly(ADP-ribose) polymerase inhibition in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment options. Recently, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib has been approved for maintenance therapy after successful platinum-based chemotherapy in patients with germline mutations in BRCA1 and BRCA2. Approval was based on the POLO study that has shown a significant improvement in progression-free survival for patients with metastatic PDAC after at least 4 months of platinum-based chemotherapy. Hopefully, this first biomarker-directed targeted therapy for a relevant subgroup of pancreatic cancer patients is only the beginning of an era of personalized therapy for pancreatic cancer. The potential role for PARPi in improving survival in patients with pancreatic cancer containing somatic tumor mutations has yet to be established. Multiple studies investigating whether PARPi therapy might benefit a larger group of pancreatic cancer patients with homologous recombination repair deficiency and whether combinations with chemotherapy, immunotherapy, or small molecules can improve efficacy are currently underway. We here review the molecular basis for PARPi therapy in PDAC patients and recent developments in clinical studies.

Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease.

BACKGROUND: Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance. METHODS: Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER). RESULTS: We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion. CONCLUSION: Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study.

Prognostic significance of microsatellite-instability in gastric and gastroesophageal junction cancer patients undergoing neoadjuvant chemotherapy.

Perioperative systemic treatment is standard of care for Caucasian patients with locally advanced, resectable gastric adenocarcinoma. The prognostic relevance of the microsatellite instability (MSI) status in patients undergoing neoadjuvant chemotherapy followed by resection is unclear. We analyzed the association of the MSI status with histological regression and clinical outcome in patients undergoing neoadjuvant systemic treatment. Tumor tissue from patients undergoing neoadjuvant chemotherapy followed by resection for gastric or gastroesophageal-junction adenocarcinoma was analyzed for MSI status using a mononucleotide marker panel encompassing the markers BAT25, BAT26, and CAT25. Histological regression, relapse-free survival and overall survival were calculated and correlated with MSI status. We identified the MSI-H phenotype in 9 (8.9%) out of 101 analyzed tumors. Though a poor histological response was observed in eight out of nine MSI-H patients, overall survival was significantly better for patients with MSI-H compared to MSS tumors (median overall survival not reached vs. 38.6 months, log-rank test p = 0.014). Among MSI-H patients, an unexpected long-term survival after relapse was observed. Our data indicate that the MSI-H phenotype is a favorable prognostic marker in gastric cancer patients undergoing neoadjuvant treatment. The benefit of perioperative cytotoxic treatment in patients with MSI-H gastric cancer, however, remains questionable. Future trials should stratify patients according to their MSI status, and novel treatment modalities focusing on MSI-H tumors should be considered.

Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial.

BACKGROUND: To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival. RESULTS: Forty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045). CONCLUSIONS: We demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Delineation of Focal Nodular Hyperplasia: Superiority of High-Flip-Angle Imaging.

OBJECTIVE: The aim of this study was to investigate whether hepatobiliary-phase (HBP) flip-angle (FA) increase to 25° improves conspicuity of focal nodular hyperplasia (FNH) and enables HBP delay reduction. METHODS: This was a retrospective study of 23 patients with 46 FNHs. In each patient, HBP was performed with reduced-delay high FA (early/high), standard-delay high FA (late/high), and standard-delay standard FA (standard). Relative enhancement of liver and FNH periphery, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were compared between each HBP. RESULTS: Early/high, late/high, and standard HBPs were performed after 13.00 ± 2.12, 19.12 ± 3.10, and 19.68 ± 3.22 minutes, respectively. Liver and FNH periphery relative enhancement, FNH periphery-to-liver contrast ratio, and FNH periphery-to-central scar contrast ratio were higher for early/high and late/high than for standard HBP (P < 0.001 to P = 0.0048). CONCLUSIONS: Increasing FA to 25° improves delineation of FNHs in HBP. Combining FA increase with delay reduction is superior to standard HBP and is sufficient for FNH characterization.

Perioperative Chemotherapy in Elderly Patients with Locally Advanced Adenocarcinoma of the Stomach and the Esophagogastric Junction: A Retrospective Cohort Analysis of Toxicity and Efficacy at the National Center for Tumor Diseases, Heidelberg.

OBJECTIVE: Esophagogastric cancer occurs more frequently in older patients, but these are underrepresented in clinical studies establishing the current treatment standards for perioperative chemotherapy in locally advanced disease. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens. METHODS: Using a prospectively generated database, we analyzed 63 patients aged ≥70 years undergoing perioperative chemotherapy for locally advanced esophagogastric cancer. The information included Eastern Cooperative Oncology Group (ECOG) performance status, comorbidity index, body mass index, regimen of chemotherapy, toxicity, dosage adjustments, date of surgery, application of adjuvant treatment, date of progression, and date of death. Survival times were calculated. RESULTS: The median age was 73 years. 96.8% of the patients received an oxaliplatin-containing regimen. In 17.5% of the patients, the dosage was reduced, and treatment was previously permanently stopped in 7.9%; 80% of the patients underwent curatively intended surgery, but only 27.5% of those undergoing resection started adjuvant treatment. Major histological regression was observed in 21.6% of the patients. The median survival was 19.1 months. Significantly improved survival times were observed for patients undergoing surgery (p = 0.008) and for patients with a triplet therapy (p = 0.004). Survival was worse for patients aged ≥75 years. CONCLUSION: perioperative treatment is feasible and effective in elderly patients with esophagogastric cancer.

High prevalence of incidental and symptomatic venous thromboembolic events in patients with advanced pancreatic cancer under palliative chemotherapy: A retrospective cohort study.

OBJECTIVES: Pancreatic cancer patients are at high risk for venous thromboembolic events (VTEs), and chemotherapy is a known additional risk factor. In this context, there is a controversial discussion whether prophylactic anticoagulation should be offered to all outpatients receiving chemotherapy. METHODS: In this retrospective study, we analyzed incidental and symptomatic VTEs in 150 pancreatic cancer patients receiving either gemcitabine-based chemotherapy or chemotherapy according to the FOLFIRINOX protocol. RESULTS: VTEs were identified in 25% of patients, but were not associated with an adverse survival. There was no significant difference in VTE incidence between patients treated with gemcitabine-based chemotherapy or the more intensive FOLFIRINOX protocol. A commonly used risk score to predict VTEs in cancer patients did not predict the occurrence of VTEs in our patients. The occurrence of VTEs was not associated with one of the recently described pancreatic cancer subtypes. CONCLUSION: One quarter of pancreatic cancer patients treated with palliative chemotherapy develops symptomatic or incidental VTEs that cannot be predicted by type of chemotherapy, subtype of pancreatic cancer or a commonly used risk score. Further studies are necessary to identify patients at risk, and to better define which patients at risk should be treated with prophylactic anticoagulation.

Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient.

BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. METHODS: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients. RESULTS: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients. CONCLUSION: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient's performance status and comorbidities.

Chemotherapy for advanced pancreatic adenocarcinoma in elderly patients (≥70 years of age): a retrospective cohort study at the National Center for Tumor Diseases Heidelberg.

BACKGROUND: Pancreatic cancer is mainly a disease of the elderly population, but clinical trials do not reflect this age distribution. Data on treatment strategies and outcome of older patients are limited. The aim of our study was to analyze safety and outcome in elderly patients with advanced pancreatic cancer treated with palliative chemotherapy at the outpatient clinic of the National Center for Tumor Diseases (NCT) at Heidelberg University Hospital. MATERIALS AND METHODS: We retrospectively analyzed 53 patients ≥70 years using a prospectively maintained database. Requirements were (1) histologically proven diagnosis of ductal pancreatic adenocarcinoma, (2) age ≥70 at time of diagnosis of advanced disease, and (3) measurable advanced disease. RESULTS: The median age was 73 years. 81% of the patients received a gemcitabine-based first-line therapy. Median overall survival was 6.7 months. Survival differed significantly between patient groups with low (≤1) and high (≥2) Eastern Cooperative Oncology Group performance status (7.8 vs. 3.9 months, p = 0.002). 30.2% of the patients developed side effects resulting in dosage reductions. 39.6% of the patients received second-line treatment. Residual survival after disease progression was significantly longer for second-line treatment compared to best supportive care (151 vs. 39 days, p = 0.019). CONCLUSIONS: Overall, our older patients did not have an inferior outcome compared to the reported trial populations that included younger patients. Thus, palliative chemotherapy should be considered independently from chronological age, but the performance status should be carefully noticed. Second-line therapy should be considered for patients in good performance status after first progression.

Durvalumab Plus Gemcitabine and Cisplatin in Patients with Advanced Biliary Tract Cancer: An Exploratory Analysis of Real-World Data.

BACKGROUND: The combination of gemcitabine and cisplatin (gem/cis) with the anti-PD-L1-antibody durvalumab was recently approved as first line therapy for biliary tract cancer (BTC) based on the results of the TOPAZ-1 trial. OBJECTIVE: We aim to analyse the feasibility and efficacy of the triple combination therapy in patients with BTC in a real-world setting and in correspondence with the genetic alterations of the cancer. METHODS: In this single-centre retrospective analysis, all patients with BTC and treated with durvalumab plus gem/cis from April 2022 to September 2023 were included. Survival and treatment response were investigated, within the context of the inclusion and exclusion criteria of TOPAZ-1 and in correspondence with genetic alterations of the cancer. RESULTS: In total, 35 patients, of which 51% met the inclusion criteria of the TOPAZ-1 trial, were analysed. Patients treated within TOPAZ-1 criteria did not have a significantly different median overall survival and progression free survival than the rest of the patients (10.3 versus 9.7 months and 5.3 versus 5 months, respectively). The disease control rate of patients within the TOPAZ-1 criteria was 61.1%, in comparison to 58.8% in the rest of patients. A total of 51 grade 3 and 4 adverse events were observed without significant differences in the subgroups. No specific correlating patterns of genetic alterations with survival and response were observed. CONCLUSIONS: The treatment of advanced patients with BTC with durvalumab and gem/cis, even beyond the inclusion criteria of the TOPAZ-1 trial, shows promising safety.

Providing the basis for a patient-centred and effective screening for cancer-related fatigue (MERLIN study): design of a longitudinal observational study.

INTRODUCTION: Cancer-related fatigue (CRF) is a frequent and burdensome sequela of cancer and cancer therapies. It can persist from months to years and has a substantial impact on patients' quality of life and functioning. CRF is often still not adequately diagnosed and insufficiently treated. According to guideline recommendations, patients should be routinely screened for CRF from cancer diagnosis onwards. We will investigate how an effective screening should be designed regarding timing, frequency, screening type and cut-off points. METHODS AND ANALYSIS: MERLIN is a longitudinal observational study that will include 300 patients with cancer at the beginning of cancer therapy. The main study centre is the National Center for Tumour Diseases Heidelberg, Germany. Patients answer five items to shortly screen for CRF at high frequency during their therapy and at lower frequency during the post-treatment phase for 18 months. Further, CRF is assessed at wider intervals based on the Cella criteria, the Brief Fatigue Inventory impact scale, the quality of life fatigue questionnaire (QLQ-FA12) and the fatigue and cognitive items of the quality of life core questionnaire (QLQ-C30), both of the European Organisation for Research and Treatment of Cancer. Important psychological, socio-demographical or medical factors, which may exacerbate CRF are assessed. All assessments are performed online. Receiver operating curves, areas under the curve, sensitivity, specificity, positive and negative predictive values and likelihood ratios will be calculated to determine optimal short screening modalities. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of the Medical Faculty of the Heidelberg University, Germany (approval number: S-336/2022). Written informed consent is obtained from all participants. The study is conducted in full conformance with the principles of the Declaration of Helsinki. Results will be published in peer-reviewed scientific journals, presented at conferences and communicated to clinical stakeholders to foster the implementation of an effective CRF management. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov; registration number: NCT05448573.

A phase II study for metabolic in vivo response monitoring with sequential 18FDG-PET-CT during treatment with the EGFR-monoclonal-antibody cetuximab in metastatic colorectal cancer: the Heidelberg REMOTUX trial.

BACKGROUND: The epidermal growth factor receptor monoclonal antibody cetuximab has proven activity in metastatic colorectal cancer. To date, the mechanisms of action are not completely understood. Especially the impact on tumor glucose metabolism, or tumor vascularization remains largely unclear. The understanding of mechanisms such as early changes in tumor metabolism is of clinical importance since there may be a substantial influence on choice and sequence of drug combinations. Early signals of response to cetuximab may prove useful to identify patients having a relevant clinical treatment benefit. The objective of this trial is to evaluate the predictive relevance of the relative change in (18)F-Fluorodeoxyglucose tumor uptake for early clinical response during short-term single agent treatment with cetuximab. Early clinical response will be routinely measured according to the response evaluation criteria in solid tumors. Accompanying research includes cytokine immune monitoring and analysis of tumor proteins and tumor genes. METHODS/DESIGN: The REMOTUX trial is an investigator-initiated, prospective, open-label, single-arm, single-center early exploratory predictive study. The first (18)F-FDG PET-CT is conducted at baseline followed by the run-in phase with cetuximab at days 1 and 8. At day 14, the second (18)F-FDG PET-CT is performed. Subsequently, patients are treated according to the Folfiri-cetuximab regimen as an active and approved first-line regimen for metastatic colorectal carcinoma. At day 56, clinical response is evaluated with a CT-scan compared to the baseline analysis. Tracer uptake is assessed using standardized uptake values (SUVs). The main hypothesis to be tested in the primary analysis is whether or not the relative change in the SUV from baseline to day 14 has any predictive relevance for early clinical response determined at day 56. Patients are followed until death from any cause or until 24 months after the last patient has ended trial treatment. DISCUSSION: The aim of this trial is to evaluate metabolic changes in metastatic colorectal cancer during short-term single agent treatment with cetuximab and to analyse their potential of predicting early clinical response. This could be helpful to answer the question if early identification of patients not responding to cetuximab is possible. TRIAL REGISTRATION: ClinicalTrials.gov NCT200811021020; EudraCT 200901327923.

Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer - The PICCASSO phase I trial.

BACKGROUND: PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC. METHODS: Twenty patients received pembrolizumab and maraviroc (core period, eight cycles), followed by pembrolizumab monotherapy. Primary endpoint was the feasibility rate (patients without treatment-related grade ≥3 immune-related adverse events, treatment-related grade ≥4 adverse events, or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Optional biopsies of liver metastases were performed for analyses of the micromilieu. RESULTS: The feasibility rate was 94.7% [90% CI 77.4-99.7%], with one grade 4 hyperglycemia and no additional ≥ grade 3 treatment-related toxicities. ORR according to RECIST was 5.3%. Median PFS according to RECIST was 2.10 months [95%CI 1.68-2.30], median OS 9.83 months [95% CI, 5.59-20.02]. Disease control rate of poststudy salvage treatment was >70%. Translational analyses showed an increase of antitumoral chemokines during treatment; eotaxin, a chemokine involved in chemotaxis, was identified as a biomarker linked to OS. CONCLUSIONS: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MMRp CRC patients was limited with prolonged disease stabilizations observed in single patients. Efficacy of poststudy salvage treatment and OS was higher than expected in this heavily pretreated population. THIS TRIAL IS REGISTERED AT CLINICALTRIALS.GOV: NCT03274804.

Sequential Geriatric Assessment in Older Patients with Colorectal Cancer during Chemotherapy: Subgroup Analysis of a Prospective, Multicenter Study EpiReal 75.

INTRODUCTION: Colorectal cancer (CRC) is a disease of older patients, but evidence-based guidelines for chemotherapy in older patients are scarce. Geriatric assessment (GA) evaluates a patient's functional status (FS) and helps in decision-making when choosing chemotherapy for older patients. However, the change of FS during chemotherapy is rarely studied as GA is mostly performed once instead of sequentially. METHODS: We performed a subgroup analysis of a prospective, multicenter study EpiReal 75. Patients aged ≥75 years with gastrointestinal malignancy prior to initiation of chemotherapy or receiving palliative chemotherapy were screened. We defined geriatric core assessments including the Eastern Cooperative Oncology Group score, Barthel's activities of daily living (ADL) scale, Lawton's instrumental activities of daily living (IADL) scale, and G-8 questionnaire, which were performed at baseline and repeated every 3 months. Quality of life (QoL) assessed by QLQ-C30 questionnaire was also re-evaluated every 3 months. We defined any deterioration in any of the geriatric parameters as unstable in the corresponding function. RESULTS: 28 patients with CRC were enrolled between April 2014 and December 2018. 20 patients were evaluable for statistical analysis with a mean age of 78.5 years (range, 75-88). Most patients received chemotherapy in palliative setting. During 3 months of chemotherapy, 25% of patients became more dependent as measured by ADL or IADL. During a median follow-up of 15 months, patients with unstable ADL or IADL had a significantly shorter overall survival (OS) than those with stable ADL or IADL (plogrank = 0.0055 and 0.0253, respectively), without a significant difference in progression-free survival (PFS). Also, unstable IADL correlated with a deterioration in aspects of QoL such as role functioning and emotional functioning (p = 0.0189 and 0.0239, respectively). 20% of patients experienced treatment-related grade 3 adverse events (AEs), no grade 4-5 AEs occurred. CONCLUSION: Sequential GA revealed changes in FS in older patients with CRC receiving chemotherapy. A deterioration of FS during chemotherapy did not influence PFS but had a negative impact on OS and QoL. It is therefore important to maintain FS in older patients with cancer, and regular performance of geriatric core assessments should be encouraged in the clinical practice.

Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent and clinically inapparent under cancer immunotherapy.

Patients with cancer frequently receive immune-checkpoint inhibitors (ICIs), which may modulate immune responses to COVID-19 vaccines. Recently, cytokine release syndrome (CRS) was observed in a patient with cancer who received BTN162b2 vaccination under ICI treatment. Here, we analyzed adverse events and serum cytokines in patients with 23 different tumors undergoing (n = 64) or not undergoing (n = 26) COVID-19 vaccination under ICI therapy in a prospectively planned German single-center cohort study (n = 220). We did not observe clinically relevant CRS (≥grade 2) after vaccination (95% CI 0-5.6%; Common Terminology of Adverse Events v.5.0) in this small cohort. Within 4 weeks after vaccination, serious adverse events occurred in eight patients (12.5% 95% CI 5.6-23%): six patients were hospitalized due to events common under cancer therapy including immune related adverse events and two patients died due to conditions present before vaccination. Despite absence of CRS symptoms, a set of pairwise-correlated CRS-associated cytokines, including CXCL8 and interleukin-6 was >1.5-fold upregulated in 40% (95% CI 23.9-57.9%) of patients after vaccination. Hence, elevated cytokine levels are common and not sufficient to establish CRS diagnosis.

Metastatic Acinar Cell Carcinoma of the Pancreas: A Retrospective Cohort Study on Systemic Chemotherapy and Review of the Literature.

OBJECTIVES: Acinar cell carcinoma of the pancreas (pACC) forms a rare subgroup of pancreatic tumors. We report on our institutional experience with systemic first- and further-line therapy in patients with metastatic pACC and embed our findings in a review of the literature. METHODS: Patients with stage IV pACC who started systemic treatment between 2008 and 2019 at our institution were identified via our institutional database. Clinical data were extracted from the patients' electronic data records. Survival times were calculated by the Kaplan-Meier method. RESULTS: Six patients received a fluoropyrimidine- and oxaliplatin-containing first-line treatment, and 4 patients were started on gemcitabine-based protocols. Median progression-free survival was 4.8 months [95% confidence interval (CI), 3.3 to not available (n.a.)], and median overall survival was 15.3 months (95% CI, 10.1 to n.a.). Residual survival for second-line treatment was 2.1 months (95% CI, 1.3 to n.a.), although 1 patient experienced almost complete remission under targeted therapy. CONCLUSIONS: The most encouraging and deep responses result from poly-chemotherapy with leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), which seems to be the appropriate choice in fit patients. Gemcitabine monotherapy seems without substantial activity in pACC. Whenever possible, patients with pACC should be screened for targetable mutations.

Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study.

Background: Checkpoint inhibitors are a standard of care in the treatment of advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC). Patients with these tumors often suffer from concomitant chronic kidney disease (CKD). Limited data are available on the efficacy and toxicity of checkpoint inhibitors in patients with CKD. Methods: We retrospectively analyzed 126 patients who received checkpoint inhibitors for RCC (n = 85) or UC (n = 41) and analyzed the frequency of treatment- and immune-related adverse events (AEs). We performed a multivariate analysis to determine progression-free survival (PFS) and overall survival (OS). Results: A total of 38.9% of patients had CKD. Frequencies of general AEs (49.0% in CKD vs. 48.1%, p > 0.99999) and immune-related AEs (28.6 vs. 24.7%, p ≥ 0.9999) did not significantly differ between the groups. There was no difference in PFS for patients with RCC or UC and CKD or without CKD (RCC: 6.81 vs. 7.54 months, HR 1.000 (95%CI 0.548-01.822), p = 0.999; UC:2.33 vs. 3.67 months, HR 01.492 (95%CI 0.686-3.247), p = 0.431). CKD appeared to be a potential effect modifier for OS in both RCC and UC (RCC: NR vs. 23.9 months, HR 0.502 (95%CI 0.219-1.152), p = 0.104; UC:18.84 vs. 15.42 months, HR 0.656 (95%CI 0.296-1.454), p = 0.299). Conclusions: Checkpoint inhibitor treatment in our cohort of patients with CKD was as safe and efficient as in the cohort of patients without CKD.

Cancer-related microangiopathic hemolytic anemia in patients with advanced gastric cancer: A retrospective single-center analysis.

BACKGROUND: Microangiopathic hemolytic anemia (MAHA) with thrombocytopenia and organ failure caused by tumor-associated thrombotic microangiopathy (TMA) is a life-threatening oncological emergency. Rapid diagnosis and precise distinction from other forms of TMA is crucial for appropriate therapy, which aims at treating the underlying malignancy. However, the prognosis of patients with cancer-related (CR)-MAHA is limited. To date, less than 50 patients with gastric cancer and CR-MAHA have been reported, mainly as single case reports, and detailed information on treatment strategies and outcome are scarce. We analyzed the characteristics and outcomes data of CR-MAHA patients with gastric cancer treated at our center between 2012 and 2019. AIM: To gain knowledge about CR-MAHA and the course of disease. METHODS: We retrospectively analyzed patients using an institutional prospectively maintained database. Patients who had CR-MAHA but other cancer types or cancer of unknown primary were excluded. The basic requirements for inclusion were: Histologically proven gastric adenocarcinoma; and clinical diagnosis of hemolytic anemia with schistocytes with or without thrombocytopenia. The observation period for each patient started with the first day of documented symptoms. The follow-up period for this analysis ended on February 1, 2020. RESULTS: We identified eight patients with a median age of 54 years. Histologically, all patients had (partial) diffuse subtypes of gastric adenocarcinoma with partial or complete signet cell morphology. All patients had metastatic disease and one patient had a microsatellite instability-high (MSI-H) tumor. In three patients, clinical signs of MAHA preceded the diagnosis of cancer, and in two patients, CR-MAHA indicated recurrent disease. All patients had severe hemolytic anemia and thrombocytopenia. Six patients experienced severe bone pain, and five patients had dyspnea. Systemic, 5-fluorouracil-based combination chemotherapy was initiated in six patients, which resulted in rapid initial response with significant improvement of clinical symptoms and blood values. Progression-free survival (PFS) of the whole cohort was 1.9 wk and median overall survival (OS) was 1.9 wk. For patients with chemotherapy, PFS was 9.0 wk and OS was 10.3 wk. The patient with the MSI-H tumor has been undergoing immunotherapy for more than 3 years. CONCLUSION: The benefit of chemotherapy in CR-MAHA patients is limited. Immunotherapy for patients with MSI-H tumors may lead to long-term tumor control even in CR-MAHA patients.

Improving radiologic communication in oncology: a single-centre experience with structured reporting for cancer patients.

OBJECTIVES: Our aim was to develop a structured reporting concept (structured oncology report, SOR) for general follow-up assessment of cancer patients in clinical routine. Furthermore, we analysed the report quality of SOR compared to conventional reports (CR) as assessed by referring oncologists. METHODS: SOR was designed to provide standardised layout, tabulated tumour burden documentation and standardised conclusion using uniform terminology. A software application for reporting was programmed to ensure consistency of layout and vocabulary and to facilitate utilisation of SOR. Report quality was analysed for 25 SOR and 25 CR retrospectively by 6 medical oncologists using a 7-point scale (score 1 representing the best score) for 6 questionnaire items addressing different elements of report quality and overall satisfaction. A score of ≤ 3 was defined as a positive rating. RESULTS: In the first year after full implementation, 7471 imaging examinations were reported using SOR. The proportion of SOR in relation to all oncology reports increased from 49 to 95% within a few months. Report quality scores were better for SOR for each questionnaire item (p < 0.001 each). Averaged over all questionnaire item scores were 1.98 ± 1.22 for SOR and 3.05 ± 1.93 for CR (p < 0.001). The overall satisfaction score was 2.15 ± 1.32 for SOR and 3.39 ± 2.08 for CR (p < 0.001). The proportion of positive ratings was higher for SOR (89% versus 67%; p < 0.001). CONCLUSIONS: Department-wide structured reporting for follow-up imaging performed for assessment of anticancer treatment efficacy is feasible using a dedicated software application. Satisfaction of referring oncologist with report quality is superior for structured reports.

Symptomatic hyponatraemia caused by cylophosphamide.

BACKGROUND: Acute hyponatraemia after administration of alkylating agents such as cyclophosphamide or ifosfamide has been documented as an infrequent but life-threatening complication. CASE REPORT: A 69-year-old female patient with metastatic adenocarcinoma of the salivary glands presented with severe symptomatic hyponatraemia (nadir 112 mmol/l) after chemotherapy with cyclophosphamide, cisplatin, and doxorubicin. Serum sodium was carefully corrected at the intensive care unit. The patient recovered completely from her neurological symptoms within a couple of days. A literature review showed only few cases with cyclophosphamide-induced acute hyponatraemia, and to our knowledge this is the first case where hyponatraemia was seen with a dose of only 500 mg/m(2) of cyclophosphamide. CONCLUSION: Oncologists should be aware of cyclophosphamide-induced acute hyponatraemia as a rare but life-threatening side-effect, especially since its clinical features may mimic those of chemotherapy-induced nausea.