Search

Immune checkpoint inhibitors are emerging as a therapeutic approach for patients with advanced or metastatic gastrointestinal malignancies following the recent Food and Drug Administration and Asian approvals for colorectal, gastric, and hepatocellular carcinoma. As discussed in earlier articles, phase I-II trials demonstrate quite positive clinical activity, particularly in patients with immunogenic cancer subtypes. This outreach paper discusses some of the next innovative immunotherapy strategies under development. Here, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells are increasingly coming into focus as new targets. Besides the well described use of checkpoint inhibitors, blockade of ‘Wnt' or Csf1R signaling pathways as well as combinatorial treatment strategies offer promising examples for overcoming immune silencing within the resistant tumor microenvironment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Somatic evolution of the cancer genome resulting in genetically different subclones is thought to be involved in the development of treatment resistance but might also offer new therapeutic opportunities in metastatic breast cancer. No data are available if clonal evolution differs in patients treated with chemotherapy (chemo) or CDK4/6 inhibitors given with endocrine treatment (CE treatment). Methods: We performed a prospective analysis of circulating tumor DNA (ctDNA) by targeted next-generation sequencing in 46 patients before the beginning of a systemic first-line (n = 37) or second-line (n = 9) treatment. Ct DNA was analyzed again upon disease progression. Results: New mutations in ctDNA of patients with progressive disease were detected in 1/11 patients who started chemo, in 4/9 patients treated with chemo followed by CE maintenance treatment, and in 9/26 patients receiving CE therapy. The number of acquired new mutations did not differ significantly between the three therapy cohorts (all p values >0.05). However, in patients classified as secondary resistant (n = 37), occurrence of new mutations significantly differed between patients who started chemo (0/9) compared to patients treated with chemo followed by CE (4/11; p = 0.041) and patients receiving CE therapy (8/19; p = 0.024), respectively. Conclusion: Clonal evolution might differ significantly between metastatic breast cancer patients with hormone receptor positive and HER-2 negative disease treated with chemo or CDK4/6 inhibitors. These results should be confirmed in larger patient cohorts. [ABSTRACT FROM AUTHOR]

Introduction: A young woman presented at a local hospital with severe dyspnea directly after childbirth. She was di-agnosed with choriocarcinoma and massive pulmonary metastases. Shortly after administration of polychemotherapy she developed severe acute respiratory distress syndrome (ARDS). Case Presentation: The patient was transferred to the intensive care unit (ICU) and extracorporeal membrane oxygenation (ECMO) center of the university hospital. Venovenous ECMO support was implemented for 28 days while enabling continuous chemotherapy. After 49 days in the ICU, she was transferred to the oncology ward in a stable respiratory state. Discussion/Conclusion: Although the survival rates of ARDS in the general ICU population have improved lately due to improved management of ARDS and ECMO support, the data on adult cancer patients receiving ECMO support are very limited. Only few small retrospective studies on ECMO support in adult cancer patients have been conducted. Unfortunately the survival rates of patients after allogenic hematopoietic stem cell transplantation and ECMO support were discouraging. Nevertheless, cancer patients with at least stable disease who are eligible for full-code ICU management may be potential candidates for ECMO in case of severe ARDS. Our case report not only shows that patients suffering from choriocarcinoma with pulmonary metastases may develop severe ARDS in the context of polychemotherapy, but also demonstrates that ECMO support enables chemotherapy continuation and complete remission of the underlying choriocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Gemcitabine-cisplatin (GP) has been regarded as standard first-line chemotherapy for advanced biliary tract cancer (BTC). Fluoropyrimidine-cisplatin (FP) has also shown a survival benefit. However, the clinical choice between them is controversial. Methods: We performed a meta-analysis to assess the efficacy and safety of the two chemotherapy regimens. Results: A total of 5 studies (2 randomized controlled trials, RCTs, and 3 retrospective studies) involving 727 patients were included. There were no statistically significant differences between the two groups in overall response rate, ORR (risk ratio, RR = 1.13, 95% confidence interval, CI, 0.80–1.58, p = 0.489), disease control rate, DCR (RR = 1.02, 95% CI 0.91–1.13, p = 0.751), progression-free survival/time to progression (hazard rate, HR = 0.95, 95% CI 0.86–1.05, p = 0.315) and overall survival (HR = 1.06, 95% CI 0.98–1.14, p = 0.125). As compared with GP, FP showed lower incidences of all grade 3/4 adverse events with statistical significance (p < 0.001). In a subgroup analysis of RCTs, no statistical differences were found between FP and GP in ORR (RR = 1.06; 95% CI 0.58–1.95; p = 0.842) and DCR (RR = 1.22; 95% CI 1.00–1.50; p = 0.056), but FP showed significantly lower incidences of all grade 3/4 adverse events compared with GP (p < 0.01). Some limitations of the meta-analysis are retrospective studies included, some end points within the trials missing rendering a pooled analysis of the two RCTs impossible and heterogeneous fluoropyrimidine combinations. All studies were performed in Asia which are not completely transferable to European patients. Conclusion: With some limitations, the meta-analysis suggested that FP seems to be as effective as GP with a more favorable safety profile in first-line chemotherapy for Asian patients with advanced BTC. [ABSTRACT FROM AUTHOR]

Background: It is known that chemotherapeutic agents cause myocardial cell damage leading to left ventricular dysfunction and heart failure. Fragmented QRS is an indication of fibrosis developing as a result of myocardial cell damage. The aim of this study is to assess whether there is a relationship between the chemotherapeutic treatment and the development of the fragmented QRS complex in electrocardiography (ECG). Patients and Methods: Among 130 patients who were diagnosed with non-Hodgkin lymphoma and received an R-CHOP treatment regimen, the potential emergence of fragmented QRS on ECG as well as the changes in the left ventricular ejection fraction (LVEF) (on transthoracic echocardiography) in response to various chemotherapeutic regimens were sought. Results: New development of a fragmented QRS pattern was observed in 53 of the 130 patients (40.8%). These patients were found to have lower LVEF values along with higher numbers of chemotherapy courses and cumulative doses. In the logistic regression analysis, age (OR = 1.042; 95% CI 1.009–1.076; p = 0.012) and number of courses (OR = 1.848; 95% CI 1.409–2.423; p < 0.001) were found to be the most important predictors of fragmented QRS development. In subjects with a fragmented QRS pattern, there was a significant difference between the initial and repeat LVEF values (p < 0.001). Importantly the emergence of a fragmentation pattern occurred much earlier compared to the drop in LVEF values (10.62 ± 4.04 vs. 15.24 ± 7.49 months). Conclusion: Development of a fragmented QRS pattern in response to cancer therapy emerges as a new parameter potentially predictive of chemotherapy-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC, pancreatic cancer) carries one of the poorest overall prognoses of all human malignancies known to date. Despite the introduction of novel therapeutic regimens, the outcome has not markedly improved over the past decades, the incidence rates are almost identical to the mortality rates, and PDAC is projected to soon become the second most common cause of cancer-related mortality in Western countries. Despite this clear medical need to develop novel therapeutic strategies against this dire malady, this need has so far not been addressed with sufficient institutional attention and support in terms of research funding and strategical programs. Given the still growing life expectancy and projected demographic changes with a growing proportion of senior citizens in many European societies, this discrepancy is likely to become even more pressing in the future. This article provides a brief overview of ongoing preclinical efforts to identify novel targets and, based on this, to develop novel strategies to treat advanced pancreatic cancer and improve survival and the quality of life of patients suffering from this malignancy. [ABSTRACT FROM AUTHOR]

Background: The treatment of metachronous Krukenberg tumor (mKT) from gastric cancer remains unexplored. We performed a literature review to evaluate whether or not surgical treatment improves survival. Methods: A systematic review according to PRISMA guidelines was performed. Studies reporting on patients who underwent surgical treatment for mKT from gastric cancer were selected. Metachronous disease was divided as follows: confined to the ovaries, confined to the pelvis, or beyond the pelvis. Outcomes evaluated included overall survival (OS), progression-free survival (PFS), resection rate (R0), and factors predicting survival. Results: 13 retrospective reports fulfilled the selection criteria (512 patients). Most of the patients presented at a premenopausal age. The median presentation interval from gastrectomy ranged from 16 to 21.4 months. Median OS ranged between 9 and 36 months. 1-year OS ranged between 52.5 and 59%, and 3-years OS between 9.8 and 36.5%. Resection margin, peritoneal seeding, and chemotherapy regimen and cycles influenced survival. Conclusion: Surgical treatment and adjuvant chemotherapy in patients with mKT from gastric cancer seems to be associated with improved survival and is justified especially in young patients. Disease location and R0 resection should be considered when selecting patients. [ABSTRACT FROM AUTHOR]

For patients aged 60 years or older, the treatment of relapsed aggressive B-cell lymphomas remains challenging. The purpose of this retrospective analysis was to evaluate the results of the R-ICE (rituximab, ifosfamide, carboplatin, etoposide) protocol alone as compared to R-ICE followed by high-dose chemotherapy with autologous transplantation. The 3-year progression-free survival (PFS) and overall survival (OS) rates in 17 patients receiving R-ICE without transplantation were 32% (95% confidence interval (CI): 8.48-55.52) and 35% (95% CI: 11.48-58.52), respectively. Median PFS and OS times were 9 months (95% CI: 2-22) and 12 months (95% CI: 5-19), respectively. In 17 age-matched transplanted patients the respective survival rates were 18% (95% CI: 0.36-35.64) and 24% (95% CI: 4.4-43.6). Median PFS and OS times were 11 months (95% CI: 6-16) and 16 months (95% CI: 13-19), respectively. Thus, R-ICE alone is a reasonable treatment option for elderly patients with relapsed or refractory aggressive B-cell lymphomas. [ABSTRACT FROM AUTHOR]

Background: Despite initial response to chemotherapy, the prognosis of small cell lung cancer (SCLC) patients is limited. Following first-line therapy, the strongest predictor of durable progression-free survival (PFS) is remission quality. Febrile neutropenia (FN) is a frequent complication after chemotherapy, and its prevention could improve treatment density and degree of remission. Patients and Methods: We retrospectively analyzed 39 SCLC patients treated at a German tertiary care lung cancer center between 2013 and 2016. We extracted data sets from electronic records and analyzed anthropometric data, pretherapeutic blood values, and prognostic scores. Discriminant analysis was performed to predict FN. Results: PFS after first-line chemotherapy was significantly shorter in patients with FN (p = 0.003). Pretherapeutic albumin (p = 0.019), C-reactive protein (CRP; p < 0.001), lactate dehydrogenase (p = 0.041), neutrophil-to-lymphocyte ratio (p = 0.009), prognostic nutritional index (p = 0.018), and Glasgow prognostic score (p < 0.001) were significantly associated with FN. CRP in combination with absolute neutrophil count is a strong predictor of FN (positive predictive value 79.8%). Conclusion: SCLC patients with FN after chemotherapy showed significantly reduced PFS. Prevention of FN may improve treatment results. We identified pretherapeutic markers which can predict FN risk. This simple and cost-effective method could serve to identify the need for preventive measures against FN (e.g., prophylactic antibiotic treatment or granulocyte colony stimulating factor administration). [ABSTRACT FROM AUTHOR]

Germ cell tumors (GCT) are a unique tumor entity with excellent cure rates if guideline-endorsed treatment is thoroughly applied. Even patients with widespread metastatic disease can often be cured with cisplatin-based combination chemotherapy as part of a multimodal treatment approach. However, about 30% of patients with metastatic disease at initial presentation, corresponding to about 5-10% of all GCT patients, relapse or progress despite first-line treatment and therefore require salvage chemotherapy. Salvage systemic treatment either consists of conventional-dose cisplatin-based combination chemotherapy or sequential high-dose treatment with carboplatin and etoposide plus subsequent autologous stem cell support. This review is based on a comprehensive literature search of MEDLINE and conference proceedings of ESMO, ASCO, and EAU meetings until 2018 and provides an overview of current treatment options for germ cell cancer patients relapsing after or progressing during first-line cisplatin-based combination chemotherapy. [ABSTRACT FROM AUTHOR]

Long-acting granulocyte colony-stimulating factor (G-CSF) preparations are increasingly used in the management of chemotherapy-associated neutropenia. Due to the fact that they only need to be administered once following chemotherapy, they are more convenient for patients and easier to use in the clinical routine for physicians than short-term G-CSF preparations. Although the efficacy of these growth factors is generally accepted, there remains some concern regarding their safety. In this article we address safety concerns for long-acting growth factors by providing basic information and available data around important clinical issues that may be helpful for the decision to use or not to use these factors in individual clinical situations. After a critical review of the literature, regarding theoretical considerations based on the physiology of hematopoiesis, data from clinical studies show that long-acting G-CSF preparations can be applied safely in approved indications and are broadly beneficial for patients at risk undergoing chemotherapy. [ABSTRACT FROM AUTHOR]