Palliative Chemotherapy In Patients Research Articles

Abdominal Visceral-to-Subcutaneous Fat Volume Ratio Predicts Survival and Response to First-Line Palliative Chemotherapy in Patients with Advanced Gastric Cancer.

Prognosis in advanced gastric cancer (aGC) is predicted by clinical factors, such as stage, performance status, metastasis location, and the neutrophil-to-lymphocyte ratio. However, the role of body composition and sarcopenia in aGC survival remains debated. This study aimed to evaluate how abdominal visceral and subcutaneous fat volumes, psoas muscle volume, and the visceral-to-subcutaneous (VF/SF) volume ratio impact overall survival (OS) and progression-free survival (PFS) in aGC patients receiving first-line palliative chemotherapy. We retrospectively examined CT scans of 65 aGC patients, quantifying body composition parameters (BCPs) in 2D and 3D. Normalized 3D BCP volumes were determined, and the VF/SF ratio was computed. Survival outcomes were analyzed using the Cox Proportional Hazard model between the upper and lower halves of the distribution. Additionally, response to first-line chemotherapy was compared using the χ2 test. Patients with a higher VF/SF ratio (N = 33) exhibited significantly poorer OS (p = 0.02) and PFS (p < 0.005) and had a less favorable response to first-line chemotherapy (p = 0.033), with a lower Disease Control Rate (p = 0.016). Notably, absolute BCP measures and sarcopenia did not predict survival. In conclusion, radiologically assessed VF/SF volume ratio emerged as a robust and independent predictor of both survival and treatment response in aGC patients.

Patients with Advanced Pancreatic Cancer Treated with Mistletoe and Hyperthermia in Addition to Palliative Chemotherapy: A Retrospective Single-Center Analysis.

This retrospective analysis investigated the influence of integrative therapies in addition to palliative chemotherapy in patients with advanced pancreatic cancer, treated at a single institution specialized in integrative oncology between January 2015 and December 2019. In total, 206 consecutive patients were included in the study, whereof 142 patients (68.9%) received palliative chemotherapy (gemcitabine/nab-paclitaxel 33.8%; FOLFIRINOX 35.9%; gemcitabine 30.3%) while the remainder were treated with best supportive and integrative care. Integrative therapies were used in 117 of 142 patients (82.4%) in addition to conventional chemotherapy, whereby mistletoe was used in 117 patients (82.4%) and hyperthermia in 74 patients (52.1%). A total of 107/142 patients (86.3%) died during the observation period, whereby survival times differed significantly depending on the additional use of integrative mistletoe or hyperthermia: chemotherapy alone 8.6 months (95% CI 4.7-15.4), chemotherapy and only mistletoe therapy 11.2 months (95% CI 7.1-14.2), or a combination of chemotherapy with mistletoe and hyperthermia 18.9 months (95% CI 15.2-24.5). While the survival times observed for patients with advanced pancreatic cancer receiving chemotherapy alone are consistent with pivotal phase-III studies and German registry data, we found significantly improved survival using additional mistletoe and/or hyperthermia.

Early prediction of response to palliative chemotherapy in patients with stage-IV gastric and esophageal cancer

BackgroundThe goal of therapy for many patients with advanced stage malignancies, including those with metastatic gastric and esophageal cancers, is to extend overall survival while also maintaining quality of life. After weighing the risks and benefits of treatment with palliative chemotherapy (PC) with non-curative intent, many patients decide to pursue treatment. It is known that a subset of patients who are treated with PC experience significant side effects without clinically significant survival benefits from PC.MethodsWe use data from 150 patients with stage-IV gastric and esophageal cancers to train machine learning models that predict whether a patient with stage-IV gastric or esophageal cancers would benefit from PC, in terms of increased survival duration, at very early stages of the treatment.ResultsOur findings show that machine learning can predict with high accuracy whether a patient will benefit from PC at the time of diagnosis. More accurate predictions can be obtained after only two cycles of PC (i.e., about 4 weeks after diagnosis). The results from this study are promising with regard to potential improvements in quality of life for patients near the end of life and a potential overall survival benefit by optimizing systemic therapy earlier in the treatment course of patients.

Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with stage III or IV pancreatic ductal adenocarcinoma

BackgroundPancreatic ductal adenocarcinoma remains one of the major causes of cancer-related mortality globally. Unfortunately, current prognostic biomarkers are limited, and no predictive biomarkers exist. This study examined promoter hypermethylation of secreted frizzled-related protein 1 (phSFRP1) in cfDNA as a prognostic biomarker and predictor of treatment effect in patients with metastatic FOLFIRINOX-treated PDAC and locally advanced PDAC. MethodsWe performed methylation-specific PCR of the SFRP1 genes’ promoter region, based on bisulfite treatment. Survival was assessed as time-to-event data using the pseudo-observation method and analyzed with Kaplan-Meier curves and generalized linear regressions. ResultsThe study included 52 patients with FOLFIRINOX-treated metastatic PDAC. Patients with unmethylated (um) SFRP1 (n = 29) had a longer median overall survival (15.7 months) than those with phSFRP1 (6.8 months). In crude regression, phSFRP1 was associated with an increased risk of death of 36.9% (95% CI 12.0%–61.7%) and 19.8% (95% CI 1.9–37.6) at 12 and 24-months, respectively. In supplementary regression analysis, interaction terms between SFRP1 methylation status and treatment were significant, indicating reduced benefit of chemotherapy. Forty-four patients with locally advanced PDAC were included. phSFRP1 was associated with an increased risk of death at 24-months ConclusionsThis indicates that phSFRP1 is a clinically useful prognostic biomarker in metastatic PDAC and possibly in locally advanced PDAC. Together with existing literature, results could indicate the value of cfDNA-measured phSFRP1 as a predictive biomarker of standard palliative chemotherapy in patients with metastatic PDAC. This could facilitate personalized treatment of patients with metastatic PDAC.

Efficacy of cisplatin combined with vinorelbine as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer.

The aim of this study was to assess the therapeutic efficacy of a cisplatin and vinorelbine combination as second- or higher-line palliative chemotherapy in patients with advanced ovarian cancer. We retrospectively reviewed the medical records of patients with advanced ovarian cancer who were treated with cisplatin (60 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1 and 8) every 3 weeks between January 2004 and March 2021. Treatment responses, progression-free survival (PFS), and overall survival (OS) were assessed; laboratory data were reviewed to determine toxicity. Thirty-two patients with advanced ovarian cancer were treated with a combination of vinorelbine and cisplatin. The objective response rate (ORR) was 18.8% and the disease control rate was 75.1%. The median PFS was 4.13 months (95% confidence interval [CI], 2.4-5.8 months). The median OS was 56.9 months (95% CI, 50.5-63.7 months). The ORR (42.9% vs 9.1%; P = .035) was higher in the platinum-sensitive group than in the platinum-resistant group. The median PFS tended to be longer in the platinum-sensitive group (5.3 vs 3.8 months; P = .339) and the median OS was significantly longer in the platinum-sensitive group than in the platinum-resistant group (69.6 vs 24 months; P < .001). All patients developed hematological toxicities, with 56% experiencing grade 3 to 4 neutropenia. Two (6.2%) patients developed febrile neutropenia, but no treatment-related death occurred. This combination therapy may be effective in patients with heavily treated advanced ovarian cancer, particularly in platinum-sensitive patients.

OD1-4 Pilot study examining the feasibility and safety of exercise intervention during palliative chemotherapy in patients with advanced gastrointestinal cancer

OD1-4 Pilot study examining the feasibility and safety of exercise intervention during palliative chemotherapy in patients with advanced gastrointestinal cancer

Impact of Different Lines of Palliative Chemotherapy in Patients with Metastatic Breast Cancer

Impact of Different Lines of Palliative Chemotherapy in Patients with Metastatic Breast Cancer

The Right Treatment of the Right Patient: Integrating Genetic Profiling Into Clinical Decision Making in Advanced Gastric Cancer in Asia.

Gastric cancer is a major global health burden, especially when patients are diagnosed with recurrent or metastatic gastric cancer. Despite recent advances in treatment options with palliative chemotherapy, the median overall survival of patients with gastric cancer remains within 1 or 2 years after the diagnosis of metastatic disease. Gastric cancer is significantly more prevalent in eastern Asia (e.g., Japan and Korea). Next-generation sequencing (NGS) is rapidly being adopted as part of clinical practice in Korea and Japan, especially in patients with gastric cancer. Approximately 10% to 15% of the patients with gastric cancer who undergo NGS of their tumor specimen are allocated to target-matched clinical trials in Japan and Korea. In Japan and Korea, a cell-free DNA NGS panel is also actively being investigated as an alternative NGS test for patients with gastric cancer, which may reflect the tumor heterogeneity of gastric cancer. In Japan and Korea, multiple biomarkers, such as HER2, mismatch repair, Epstein-Barr virus, PD-L1 (combined positive score), EGFR, FGFR2, and CLDN18.2, are routinely assessed through immunohistochemistry or in situ hybridization before initiation of the first-line treatment in all patients with gastric cancer. Most tertiary cancer centers in Korea routinely perform HER2, mismatch repair, Epstein-Barr virus, and PD-L1 NGS before palliative chemotherapy in patients with gastric cancer. Biomarker evaluation for all patients with metastatic gastric cancer enables clinicians to identify available biomarker-based clinical trials early during the course of treatment, which expands treatment opportunities while patients are medically fit for clinical trials, if available. Comprehensive genomic profiling using a tissue or circulating tumor DNA NGS panel is considered necessary during second-line or subsequent treatment. It is hoped that a comprehensive molecular profiling strategy will facilitate greater use of precision medicine through molecularly targeted therapies for patients with gastric cancer in the near future.

136 - Assessing outcomes in patients that received consolidation radiotherapy following palliative chemotherapy in patients diagnosed with extensive stage small cell lung cancer

136 - Assessing outcomes in patients that received consolidation radiotherapy following palliative chemotherapy in patients diagnosed with extensive stage small cell lung cancer

Real-world outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma.

387 Background: Optimal management of patients with recurrent pancreatic ductal adenocarcinoma (PDAC) is unknown. In the clinical trials that established a survival benefit with combination chemotherapy compared to single agent gemcitabine, patients with recurrent PDAC were either excluded (PRODIGE-4) or severely underrepresented (MPACT). In this study, we evaluated clinical outcomes of recurrent PDAC patients who receive systemic therapy and compared outcomes to patients with de novo advanced PDAC. Methods: Patients diagnosed with advanced PDAC between 2014 and October of 2019 were included using the nationwide Flatiron Health EHR-derived de-identified database. Patients without a clinic visit or initiation of treatment within 90 days of diagnosis were excluded. Patients were characterized as either de novo or recurrent PDAC based on stage at diagnosis and history of surgery. Patients with recurrent PDAC were further stratified based on time to recurrent disease. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates, and compared between groups in the context of univariable and multivariable Cox proportional hazards models. The covariates adjusted for were gender, age, race, ECOG, smoking status, primary site, CA199, albumin, lymphocytes, neutrophils and monocytes. Results: We included 5170 patients with advanced PDAC, of which 1101 (21.3%) met criteria for recurrent disease. Patients with recurrent PDAC were more likely to have tumors in the head of the pancreas (71% vs 40%, p &lt; 0.001) and had lower median CA19-9 (92.8 vs 617, p &lt; 0.001), compared to the de novo PDAC patients. Median OS for the recurrent group was 10.8 m (95% CI = 9.9-11.7) vs. 7.3 m (95% CI = 7.0-7.7) in the de novo group (p &lt; 0.001, both univariate and multivariable adjusted analyses). The most common first line palliative chemotherapy in patients with recurrent disease was Nab-paclitaxel plus gemcitabine (41%) or FOLFIRINOX (21%). Patients who recurred within six months of surgery (28%) had an OS of 10.0 m (95% CI = 8.7 -11) vs. 11.6 m (95% CI 10-12, p = 0.256) in those who recurred greater than six months from surgery. Conclusions: Our data suggest that patients with recurrent disease have significantly better survival outcomes compared to patients with de novo metastatic disease. We did not observe a significant difference in survival of patients who recurred within 6 months of resection compared to those who recurred greater than six months after surgery. These data support the inclusion of patients with recurrent PDAC in clinical trials, including those who develop recurrent disease within 6 months of surgery, with appropriate stratification for these variables.

The effect of health insurance on racial disparities in patients with isolated colorectal liver metastases

Presenter: Anastasios Mitsakos MD | East Carolina University Background: Resection of colorectal liver metastases (CRLM) is associated with improved overall survival compared to palliative chemotherapy in patients with stage IV colorectal cancer. Prior literature has demonstrated that Black patients are less likely to undergo surgical treatment for metastatic disease compared to patients of other races. However, little is known about the impact of health insurance on racial disparities. The primary aim of this study was to evaluate the potential effect of health insurance status on racial disparities in receipt of surgical therapy in patients with CRLM. Methods: A retrospective cohort study of patients diagnosed with stage IV colorectal cancer with CRLM in the absence of extrahepatic metastatic disease was performed using the National Cancer Database (NCDB) (2006-2016). The primary outcome of interest was receipt of surgical therapy for hepatic metastatic disease. Multivariable logistic regression (MVR) was performed to evaluate the association of race and health insurance status with the odds of surgical resection. A two-way interaction term was incorporated in the MVR to evaluate the potential heterogeneity of race effect across insurance status. Results: A total of 6,002 patients were included: 70.5% White, 16.7% Black, 6.6% Hispanic, and 6.2% Other race. Rates of resection were lower among Black compared to White patients (17.7% vs. 22.0%), as were rates of systemic chemotherapy (72.0% vs. 75.1%) and multimodality therapy (40.1% vs. 44.9%). By MVR, Black patients had lower odds of undergoing resection for CRLM compared to White patients (OR 0.81, 95% CI 0.67-0.99). No difference was observed among patients of Hispanic or Other races compared to White patients. Uninsured patients were also less likely to undergo resection compared to patients with private health insurance (OR 0.53, 95% CI 0.36-0.76). No statistically significant difference in the odds of resection was observed among other health insurance categories. On MVR of race stratified by health insurance status, only Black patients with Medicare insurance had decreased odds of undergoing surgical therapy for CRLM compared to their White counterparts (OR 0.55, 95% CI 0.38-0.78). No difference in odds of resection was observed among patients of any other race or health insurance category. [Table] Conclusion: Black patients with CRLM have lower odds of receipt of resection for CRLM compared to White patients, particularly among the Medicare-insured population. Further investigation is warranted to better understand racial disparities in the Medicare population and develop implementation strategies to address them.

Possibilities of palliative chemotherapy in patients with locally advanced and metastatic pancreatic cancer

Currently, pancreatic cancer remains one of the most unfavorable tumor pathologies, characterized by pronounced difficulties in diagnostics and treatment, a significant impact on the ability to work and quality of life of patients, and low indicators of patient life expectancy. Features of the development of malignant neoplasms of this localization contribute to limiting the possibility of performing radical surgery, and therefore a special role in the treatment of patients with pancreatic cancer is assigned to chemotherapy. Specific systemic drug therapy for this pathology is the most important and, in the majority of cases, mandatory element of treatment. It can be carried out in a neoadjuvant, adjuvant and independent mode, include mono- or multi- component schemes, and be combined with other types of systemic or local antitumor effects. The choice of chemotherapy regimen depends primarily on the General somatic status of the patient and is determined by the potential toxicity of a particular combination of cytostatics. This review of the literature demonstrates the effectiveness of various chemotherapy regimens in patients with stage III–IV pancreatic cancer in the first and second lines, describes the frequency of adverse reactions to treatment and their nature, and mentions ways to reduce the toxicity of multicomponent drug therapy regimens. This review is based on the analysis of scientific sources of the Internet resource "National Center for Biotechnological Information".

Biomarkers of Haemostasis and Occurrence of Venous Thromboembolism Are Associated with Disease Progression and Poor Prognosis in Patients with Pancreatic Cancer

Background: Patients with pancreatic cancer have a high risk for venous thromboembolism (VTE). Activation of haemostasis has been suggested to contribute to the progression of cancer and its metastatic spread. However, clinical data to support the contribution of activation of haemostasis to disease progression are scarce. Our aim was to evaluate the association biomarkers indicating activation of haemostasis and/or hypercoagulability and of VTE occurrence with survival and therapy response in patients with pancreatic cancer. Methods: Within a prospective, observational cohort study (Vienna Cancer and Thrombosis Study, CATS), we evaluated the subgroup of patients with pancreatic cancer (n=145). Levels of a comprehensive panel of haemostatic biomarkers (D-dimer, prothrombin fragment 1+2, fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1), soluble (s)P-selectin, peak thrombin generation, endogenous thrombin potential) were measured at baseline. Differences in levels of haemostatic biomarkers between disease stages were tested for statistical significance by Kruskal-Wallis-test. The association of biomarker levels with overall survival (OS) and therapy response (progression-free survival (PFS) and radiological disease control rate; sub-cohort of patient initiating palliative chemotherapy, n=95) was analysed by multivariable Cox regression, adjusting for disease stage, grade, sex, age, ECOG, VTE (as time-dependent covariable) and vascular infiltration or compression by the primary tumour. Cumulative incidence of VTE was estimated in competing risk analysis, considering death as competing outcome event. The impact of VTE on OS and PFS was evaluated by multi-state modelling, adjusting for stage, grade, sex, age, ECOG and vascular involvement. Results: We observed higher baseline levels of biomarkers according to increasing stage of disease for D-dimer (stage I/II: median 1.25 µg/ml [interquartile range (IQR): 0.65-2.10]; stage III: 1.41 µg/ml [IQR: 0.65-2.24]; stage IV: 1.68 µg/ml [IQR: 0.98-3.82], p=0.035), and sP-selectin (stage I/II: median 34.2 ng/ml [IQR: 26.8-43.1]; stage III: 37.6 ng/ml [IQR: 31.4-49.1]; stage IV: 38.8 ng/ml [IQR:32.9-51.5], p=0.033). Higher levels of D-dimer, PAI-1 and sP-selectin were associated with shorter OS in multivariable analysis (hazard ratio (HR) for death per doubling: 1.33 [95% confidence interval (CI): 1.08-1.66], 1.25 [95% CI: 1.08-1.45, and 1.42 [95% CI: 1.00-2.01] (Figure 1). In the subgroup of patients initiating palliative chemotherapy, pre-therapeutic levels of D-dimer predicted for shorter PFS (HR for disease progression per double: 1.29 [95% CI: 1.03-1.61]) and a decreased probability for radiological therapy response (odds ratio to achieve radiological disease control per double: 0.61 [95% CI: 0.38-0.99]). Cumulative incidence estimates of VTE in competing risk analysis at 3, 6, 12, and 24 months were 9.0% [95% CI: 5.0-14.3], 13.1% [95% CI: 8.2-19.1], 16.6% [95% CI: 11.1-23.1], and 19.5% [95% CI: 13.4-26.2], respectively. The occurrence of VTE was associated with an immediate increase in risk of death (transition hazard ratio, (THR): 2.37 [95% CI: 1.47-3.84]) and early disease progression (THR: 2.34 [95% CI: 1.50-3.66]), which prevailed upon multivariable adjustment. In landmark analyses, median OS and PFS after VTE were 5.5 months [95% CI: 2.2-6.5] and 3.0 months [95% CI: 1.5-3.9] compared to 13.4 months [95% CI: 9.7-16.6] and 7.5 months [95% CI: 5.9-9.8] in those without VTE (Mantel-Byar: both p&amp;lt;0.001). Figure 2 displays landmark analyses of OS and PFS according to occurrence of VTE within the first 3 months of observation. Conclusion: Occurrence of VTE, activation of haemostasis and hypercoagulability, as indicated by elevated levels of D-dimer, PAI-1 and sP-selectin are associated with poor prognosis and D-dimer predicts for unfavourable response to palliative chemotherapy in patients with pancreatic cancer. Disclosures No relevant conflicts of interest to declare.

Impact on prognosis of early weight loss during palliative chemotherapy in patients diagnosed with advanced pancreatic cancer

AimWeight loss at diagnosis is common in pancreatic cancer (PC) and can adversely affect overall survival (OS). Little is known about the impact of weight loss occurring during palliative treatment. This study aimed to investigate if early weight loss during chemotherapy for inoperable PC affects OS. MethodThis retrospective study included patients newly-diagnosed with inoperable PC. Consecutive patients initiating first-line palliative chemotherapy between Jan’15 – Jan’19 with data on percentage weight loss at week 4 of treatment (%WLWeek4) were eligible. %WLWeek4 was dichotomised using 5% cut-off. OS was measured from chemotherapy initiation. Survival analysis was performed using Cox regression. ResultsEligible patients (n = 255); 59.2% with head/neck PC; 52.6% metastatic; received triplet (32.2%), doublet (42.7%) or single-agent (25.1%) palliative chemotherapy. Median %WLWeek4 was −2.05% (95% confidence interval (CI) −2.58 to −1.56); %WLWeek4 was ≥5% in 23.1% patients.Patients on triplet chemotherapy were more likely to develop %WLWeek4 of ≥5% [35.4% (triplet) vs. 19.3% (doublet) vs 14.1% (monotherapy); multivariable Odds Ratio (triplet vs monotherapy) =3.25; 95% CI 1.40-7.56; p-value 0.006].Median OS was 9.7 months (95% CI 8.54–10.41). Multivariable Cox regression demonstrated shorter OS if %WLWeek4 ≥5% (median OS 7.4 months (95% CI 6.27–10.01) vs. 9.9 months (95% CI 9.20–12.05); HR 2.37 (95% CI 1.64–3.42), P < 0.001); this was independent from other factors (stage, age, number of chemotherapy drugs, ECOG-PS), including response to therapy (supporting that %WLWeek4 impacted on OS regardless of response to therapy). ConclusionIn advanced PC treated with palliative chemotherapy, a %WLWeek4 ≥5% was more prevalent in patients undergoing triplet chemotherapy, and was associated with shorter OS, regardless of response/progression to therapy. Early identification and intervention of weight loss seems to be key to improve patient outcomes.

Gastric cancer: Environmental risk factors, treatment, and prevention

Gastric cancer is a heterogeneous, multifactorial, aggressive disease that has been and remains one of the most common causes of cancer-related deaths and a significant public health issue worldwide. Currently, gastric cancer shows decreasing trends in its incidence and mortality in some geographic areas; however, the disease still shows a poor prognosis and remains difficult to cure. The prognosis for gastric cancer patients depends on the stage at which the gastric cancer is detected, and complete excision of the cancer is the only proven curative option. Gastric cancer prevention remains a priority. Patients at higher risk should be screened for early detection and chemoprophylaxis. Surgical resection enhanced by standardized lymphadenectomy remains the gold standard in the treatment of gastric cancer. Systemic therapy improves long-term disease-free survival compared to surgical treatment alone. Palliative chemotherapy in patients with inoperable gastric cancer prolongs survival and improves the quality of life. Demographic, ecological, environmental, cultural, and genetic variables all contribute to the heterogeneity of gastric cancer; however, environmental risk factors play an important role throughout all the stages of the disease progression, management, and surveillance. In this review, we address the role of important environmental risk factors in the onset of gastric cancer and highlight the current treatment modalities and prevention measures.

790P Palliative chemotherapy in patients with advanced nonseminomatous germ cell tumors (aNSGCT)

790P Palliative chemotherapy in patients with advanced nonseminomatous germ cell tumors (aNSGCT)

P-121 Clinical outcomes of chemotherapy according to biologic agents in elderly patients aged ≥ 80 years with relapsed or metastatic colorectal cancer

5-fluorouracil (5-FU)-based chemotherapy with oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) is usually used in colorectal cancer (CRC). The addition of biologic agents to cytotoxic chemotherapy is currently standard therapy. However, the safety and efficacy of palliative chemotherapy in patients with relapsed or metastatic CRC over 80-years old have not been established yet. The purpose of this study was to assess the clinical features and feasibility of chemotherapy according to the use of biologic agents (bevacizumab or cetuximab) in extremely elderly patients with CRC.

Exploring the role of systemic therapy in adult adrenocortical carcinoma: A single-center experience

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with poor outcomes. Objectives: To analyze the clinicopathologic features, treatment patterns and outcomes of patients with ACC who received systemic therapy at our center. Patients and Methods: This was a retrospective study conducted in a tertiary cancer center in India. Patients aged 15 years and older who were diagnosed with ACC between January 2011 and December 2018 and received systemic therapy were included in this study. For tumor staging, the European Network for the Study of Adrenal Tumors (ENSAT) system was used. The outcomes were reported as progression-free survival (PFS) and overall survival (OS). All statistical calculations were performed using the SPSS statistical software for Windows version 20.0. Results: Out of the 106 patients with ACC, 54 who received systemic therapy were included in this study. The median age of the cohort was 43 years (range, 15–72); 32 (59.3%) were men. Five (9.2%) patients had ENSAT Stage II, 31 (57.4%) had Stage III, and 18 (33.3%) had Stage IV (metastatic) disease at baseline. The chemotherapy drugs used in the palliative setting included etoposide (E), doxorubicin (D), and cisplatin (P), with or without mitotane. The median OS was 140 months (95% confidence interval [CI], 38.2–241.8) for ENSAT Stage II patients; 43 months for Stage III patients (95% CI, 27.2–58.7); and 22 months (95% CI, 9.4–34.6) for Stage IV patients, P = 0.012. The median PFS for patients treated with etoposide and platin (EP) and etoposide, doxorubicin, and platin (EDP) regimens was similar at 7 months (95% CI, 0–14.9) and 6 months (95% CI: 0–14.6) (P = 0.633), respectively. The corresponding median OS was 20.9 months (95% CI, 11.7–30.2) and 13.0 months (95% CI, 2.1–23.8) (P = 0.454), respectively. The patients who received palliative intent mitotane had a median PFS of 13 months (95% CI, 0–26.3) and those who did not had a median PFS of 6 months (95% CI, 1.2–10.7) (P = 0.492). The corresponding median OS was 22.6 months (95% CI, 17.8–27.5) and 15.5 months (95% CI, 5.8–25.2) (P = 0.351), respectively. Grade 3 or higher toxicities were observed in 25% of the patients receiving EP chemotherapy and 76.9% receiving EDP chemotherapy (P = 0.013). Conclusions: The use of mitotane is limited in the real-world setting in view of the financial constraints. The results with palliative chemotherapy in patients with ACC continue to remain poor. Patients with ACC treated with EDP and EP protocols had similar survival, but the three-drug protocol was associated with higher toxicities.

Single-Center Experience with Ifosfamide Monotherapy as Second-Line Treatment of Recurrent/Metastatic Osteosarcoma.

BackgroundThe effectiveness of second‐line palliative chemotherapy in patients with recurrent/metastatic osteosarcoma is not well defined. Several small studies (6–19 patients) have reported on ifosfamide as second‐line treatment. In this study we report our single‐center experience with second‐line ifosfamide monotherapy in patients treated for recurrent/metastatic osteosarcoma.MethodsA chart review was conducted of all patients with osteosarcoma treated with ifosfamide from 1978 until 2017. Until 1997 a 5 g/m2 regimen was used, and from 1997 onwards a 9 g/m2 regimen was used. Overall survival (OS) from start of ifosfamide was the primary endpoint. Progression‐free survival (PFS) from start of treatment was also studied. To assess difference in survival between groups the log rank test was applied. To investigate the effect of ifosfamide dose and World Health Organization performance status (PS) a Cox proportional hazard regression model was estimated.ResultsSixty‐two patients were selected with recurrent/metastatic osteosarcoma treated with second‐line ifosfamide monotherapy (dose of 5 g/m2, n = 26; 9 g/m2, n = 36). OS was significantly better in univariate analysis for 9 g/m2 compared with 5 g/m2 (10.9 months [95% confidence interval (CI), 9.3–12.6] vs. 6.7 months [95% CI, 5.9–7.6], respectively) and for PS (median OS PS 0, 13.0 months [95% CI, 2.3–23.8]; PS 1, 8.2 months [95% CI, 5.4–11.1]; PS ≥2, 6.2 months [95% CI, 2.2–10.3]; and unknown PS, 5.4 months [95% CI, 2.2–8.5]). In multivariate analysis only PS showed a significant difference. No difference in PFS was found between 5 and 9 g/m2 ifosfamide treatment or PS.ConclusionThis study suggests that ifosfamide is an effective second‐line treatment for patients with recurrent/metastatic osteosarcoma.Implications for PracticeIfosfamide monotherapy is commonly used as second‐line treatment in osteosarcoma, although large series to support this are lacking. This retrospective study reports overall and progression‐free survival for regimens with 5 g/m2 and with 9 g/m2. This study was unable to show a significant difference in survival between 5 and 9 g/m2 but showed an important impact of World Health Organization performance status on overall survival. This study sets a standard and reference for comparison with the multiple phase II studies under development.

Palliative chemotherapy for patients with synchronous metastases of small-bowel adenocarcinoma: A reflection of daily practice.

As small-bowel adenocarcinoma (SBA) is scarce, no standard systemic regimen in metastatic disease has been defined. To obtain insights into the use and effects of palliative chemotherapy in patients with metastatic SBA in a population-based setting. Data from the Netherlands Cancer Registry of patients with metastatic SBA between 2007 and 2016 were used (n = 522). For patients treated with palliative chemotherapy, differences in treatment regimens and survival were evaluated. Palliative chemotherapy was received by 38% of patients (n = 199). First-line combination chemotherapy was administered to 80% of patients, mainly CAPOX/FOLFOX. Single-agent chemotherapy mostly consisted of capecitabine. Second-line treatment, mostly irinotecan-based (58%), was prescribed to 27% of patients. Age 70 years or older was an adverse predictive factor for receiving first-line combination chemotherapy (odds ratio (OR) 0.2, 95% confidence interval (CI) 0.08-0.62) and second-line therapy (OR 0.3, 95% CI 0.10-0.72). Median overall survival with palliative chemotherapy was 9.3 months, compared with 3.0 months without. In subanalyses, patients who received only first-line treatment had a median overall survival of 5.6 and 7.0 months after single-agent and combination chemotherapy, respectively. A minority of patients were treated with palliative chemotherapy. First-line treatment consisted predominantly of oxaliplatin-based combination chemotherapy, whereas second-line treatment was mainly irinotecan-based. Population-based median overall survival for selected patients treated with chemotherapy amounted to nine months.