First-line Anti-cancer Treatment Research Articles

Outcome of patients with solid malignancies considered for intensive care unit admission: a single-center prospective cohort study.

To identify the predictors and outcomes of ICU triage decisions in patients with solid malignancies (SM) and to investigate the usefulness of the National Early Warning Score (NEWS) and quick Sequential Organ Failure Assessment (qSOFA) score at triage. All patients with SM for whom ICU admission was requested between July 2019 and December 2021 in a French university-affiliated hospital were included prospectively. Of the 6262 patients considered for ICU admission, 410 (6.5%) had SM (age, 66 [58-73] years; metastases, 60.1%; and performance status 0-2, 81%). Of these 410 patients, 176 (42.9%) were admitted to the ICU, including 141 (80.1%) subsequently discharged alive. Breast cancer, hemoptysis, and pneumothorax were associated with ICU admission; whereas older age, performance status 3-4, metastatic disease, and request at night were associated with denial of ICU admission. The NEWS, and the qSOFA score in patients with suspected infection, determined at triage performed poorly for predicting hospital mortality (area under the receiver operating characteristics curve, 0.52 and 0.62, respectively). Performance status 3-4 was independently associated with higher 6-month mortality and first-line anticancer treatment with lower 6-month mortality. Hospital mortality was 33.3% in patients admitted to the ICU after refusal of the first request. Patients with SM were frequently denied ICU admission despite excellent in-ICU survival. Poor performance status was associated with ICU admission denial and higher 6-month mortality, but none of the other reasons for denying ICU admission predicted 6-month mortality. Physiological scores had limited usefulness in this setting.

Regression of ovarian cancer xenografts by depleting or inhibiting RLIP

Ovarian cancer (OC) is the most prevalent and deadly cancer of the female reproductive system. Women will continue to be impacted by OC-related morbidity and mortality. Despite the fact that chemotherapy with cisplatin is the main component as the first-line anticancer treatment for OC, chemoresistance and unfavorable side effects are important obstacles to effective treatment. Targets for effective cancer therapy are required for cancer cells but not for non-malignant cells because they are expressed differently in cancer cells compared to normal cells. Targets for cancer therapy should preferably be components that already exist in biochemical and signalling frameworks and that significantly contribute to the development of cancer or regulate the response to therapy. RLIP is an important mercapturic acid pathway transporter that is crucial for survival and therapy resistance in cancers, therefore, we examined the role of RLIP in regulating essential signalling proteins involved in relaying the inputs from upstream survival pathways and mechanisms contributing to chemo-radiotherapy resistance in OC. The findings of our research offer insight into a novel anticancer effect of RLIP depletion/inhibition on OC and might open up new therapeutic avenues for OC therapy.

Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer

PurposeThe aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines.MethodsWe analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011–2019. „Succesful treatment “ was defined as PFS ≥ 6 months, a „good responder “ was a patient with ˃50% of „successful treatment “ lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used.ResultsThe first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort.ConclusionWe concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.

Clinical Outcomes of Chemotherapeutic Molecules as Single and Multiple Agents in Advanced Non-Small-Cell Lung Carcinoma (NSCLC) Patients.

Background and Objectives: Lung cancer is the second most common cancer in the world. Non-small-cell lung carcinoma (NSCLC) makes up 85% of all lung cancer cases and the majority of patients are diagnosed when the cancer is advanced. Over the years, many anticancer drugs have been designed and introduced into the market to treat patients with advanced NSCLC. This review aims to discuss the comparative therapeutic benefits of conventional chemotherapeutics and other drugs available for treating advanced NSCLC. Materials and Methods: A literature search for first-line treatment of advanced NSCLC was carried out on PubMed and Google Scholar. Objective response rate (ORR) and overall survival were chosen as target endpoints. Results: Monotherapy showed lower treatment endpoints compared to combination therapy. Different combinations of platinum-based doublets demonstrated similar efficacies in treating NSCLC. However, pemetrexed–platinum doublets showed significantly better treatment endpoint in patients with non-squamous NSCLC. Most studies showing the best complete response rate (CRR) utilized epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), while most studies producing the best overall survival included programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in their treatment regimens. Conclusions: The findings of this review indicate that targeted therapy using specific inhibitors is now the most promising first-line anticancer treatment available in the market. However, chemotherapy is still effective in treating advanced NSCLC and is viable as a first-line treatment.

Systemic thromboembolism from a misdiagnosed non‑bacterial thrombotic endocarditis in a patient with lung cancer: A case report

Thromboembolic events are frequent in patients with cancer, commonly involving the venous and pulmonary circulation. The arterial system is rarely implicated in embolism and, when involved, a cardiogenic origin should always be excluded. In the present study, a case of a patient who developed multiple embolic events concomitantly with the diagnosis of locally-advanced non-small cell lung cancer with high expression levels of programmed death-ligand 1 (PD-L1) in >50% of tumor cells is reported. A cardiac defect interpreted as a patent foramen ovale required low molecular weight heparin administration. Despite the anti-coagulant therapy, before first-line anticancer treatment with pembrolizumab immunotherapy could be administered due to high PD-L1 expression levels, a new hospitalization was required due to the onset of novel ischemic manifestation. New transthoracic and transesophageal echocardiography revealed a previously misdiagnosed vegetation of the mitral valve that caused systemic embolization. The lack of any sign of infection led to the diagnosis of a non-bacterial thrombotic endocarditis (NBTE), whose embolic sprouting gave rise to the widespread ischemic events. No active anticancer treatment was feasible due to the rapid progression of the disease. NBTE can evolve quickly, eventually preventing any chance of treatment targeting the primary cause, which in the present study was lung cancer. If NBTE can be correctly diagnosed sooner then there may be the potential for anticancer therapy that does not worsen the hypercoagulability state, thus improving cancer-associated survival.

Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study.

The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE). This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison. A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411-0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042). DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.

Abstract 1057: Targeting MTHFD2 using first-in-class inhibitors kills haematological and solid cancer through thymineless-induced replication stress

Abstract Summary Thymidine synthesis pathways are upregulated pathways in cancer. Since the 1940s, targeting nucleotide and folate metabolism to induce thymineless death has remained first-line anti-cancer treatment. Recent discoveries that showing cancer cells have rewired networks and exploit unique enzymes for proliferation, have renewed interest in metabolic pathways. The cancer-specific expression of MTHFD2 has gained wide-spread attention and here we describe an emerging role for MTHFD2 in the DNA damage response (DDR). The folate metabolism enzyme MTHFD2 is one of the most consistently overexpressed metabolic enzymes in cancer and an emerging anticancer target. We show a novel role for MTHFD2 being essential for DNA replication and genomic stability in cancer cells. We describe first-in-class nanomolar MTHFD2 inhibitors (MTHFD2i), with protein co-crystal structures demonstrating binding in the active site of MTHFD2 and engaging with the target in cells and tumours. We show MTHFD2i reduce replication fork speed and induce replication stress, followed by S phase arrest, apoptosis and killing of a range of haematological and solid cancer cells in vitro and in vivo, with a therapeutic window spanning up to four orders of magnitude compared to non-transformed cells. Mechanistically, MTHFD2i prevent thymidine production leading to mis-incorporation of uracil into DNA and replication stress. As MTHFD2 expression is cancer specific there is a potential of MTHFD2i to synergize with other treatments. Here, we show MTHFD2i synergize with dUTPase inhibitors as well as other DDR inhibitors and demonstrate the mechanism of action. These results demonstrate a new link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically. Keywords MTHFD2, one-carbon metabolism, folate metabolism, DNA replication, replication stress, synthetic lethal, thymineless death, small-molecule inhibitor, DNA damage response Citation Format: Thomas Helleday. Targeting MTHFD2 using first-in-class inhibitors kills haematological and solid cancer through thymineless-induced replication stress [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1057.

Transarterial Chemoembolization in Treatment-Naïve and Recurrent Hepatocellular Carcinoma: A Propensity-Matched Outcome Analysis.

Transarterial chemoembolization (TACE) improves the survival of patients with hepatocellular carcinoma (HCC); however, TACE treatment outcomes of patients with treatment-naïve HCC (TN-HCC) and those with recurrent HCC after curative resection (R-HCC) have not yet been compared. We recruited 448 patients with TN-HCC, and 275 patients with R-HCC treated with TACE as first-line anti-cancer treatment. At first TACE, patients with TN-HCC showed a significantly lower proportion of male gender (74.9% vs. 84.3%), higher proportion of liver cirrhosis (61.9% vs. 49.3%), higher aspartate aminotransferase (median 48 vs. 31IU/L), alanine aminotransferase (median 38 vs. 26IU/L), alpha-fetoprotein (AFP) (median 96.6 vs. 7.7ng/mL), and total bilirubin (mean 1.0 vs. 0.8mg/dL) levels, longer prothrombin time (median 1.05 vs. 1.01 international normalized ratio), higher tumor number (mean 2.1 vs. 1.7), larger tumor size (median 3.1 vs. 1.6cm), and lower proportion of Barcelona Clinic Liver Cancer stage 0-A (55.6% vs. 71.9%) than patients with R-HCC (all P < 0.05). Multivariate analysis showed that TACE for TN-HCC (vs. R-HCC) was an independent predictor of mortality (hazard ratio, 1.328; P = 0.024) with AFP level and tumor number (all P < 0.05). However, treatment outcomes between TN-HCC and R-HCC became statistically similar after propensity score-matched (PSM) analysis using liver cirrhosis, tumor size, and multiple tumors (P < 0.05). Based on the similar TACE treatment outcomes observed with the PSM analysis, the current TACE treatment guideline for patients with TN-HCC might similarly be applied for patients with R-HCC.

Update on distress management for cancer patients

Many cancer patients experience psychological suffering during their journey from diagnosis, through treatment, to survivorship or the end of life. Their psychological distress can become severe enough to interfere with their ability to cope with cancer. Conditions such as anxiety, depression, insomnia, and delirium often occur among cancer patients. Although distress is prevalent in cancer patients, it is often under-recognized and under-treated in the oncology setting. Psychological distress may have a negative effect on patients' quality of life. The prevention, early detection, and proper management of distress are important for improving patients' quality of life during and after cancer treatment. It is therefore necessary to develop a system for assessing and managing distress. The US National Comprehensive Cancer Network developed guidelines for distress management in 1999. Korean recommendations for distress management were released in 2009. The Korean government recently designated integrated supportive care centers for survivors at the National Cancer Center and regional cancer centers. The supportive care service is provided for cancer survivors who have completed first-line anti-cancer treatment. Psycho-oncology is one of the most important components of supportive care in cancer. Distress management yields many benefits for cancer patients, but the reality is that significantly distressed patients are often not properly referred for psychosocial care. All distressed patients should be properly referred for psychosocial care, and the psychosocial care of cancer patients should be integrated into routine cancer care practice.

P3.01-113 A Multicenter Survey of One Year Survival Among Chinese Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer (CTONG1506)

Previous results of CTONG1506 study showed that gene aberration test rate was increasing in Chinese NSCLC patients and first-line treatment was standardized accordingly. This survey further described one year survival of patients with different gene aberration status and under different first-line treatments. CTONG1506 was a two-year series cross-sectional study. Patients with advanced nonsquamous NSCLC who were admitted from August 2015 to March 2016 and who received first-line anti-cancer treatment at one of 12 tertiary hospitals across China were included. Data extracted from medical charts were entered into medical record abstraction forms, which were collated for analysis. Survival information was collected one year after patients were admitted to hospital. One year survival rate and its 95% confidence interval were analysed by Kaplan-Meier method. A total of 707 patients were analysed, with mean age of 57 years and 56.7% were male. Among the 487 patients who had survival data, 192 were EGFR- mutation positive (86 mutated in exon 19 [one year survival rate 0.90, 95% CI: 0.81-0.94] and 88 mutated in exon 21 [one year survival rate 0.84, 95% CI: 0.75-0.90]), 27 patients were ALK positive and 164 patients were EGFR and ALK wild type. Most EGFR mutation positive patients (128/192) received tyrosine kinase inhibitors (TKIs) as first-line treatment and most EGFR wild type patients (155/175) received first-line chemotherapy (Chemo). Pemetrexed was the most common non-platinum chemotherapy-backbone agent (120/155) in platinum doublet regimens. One year survival rates are shown in the table. This national-wide real world study of tertiary hospitals in China revealed that a majority of (>75%) advanced nonsquamous NSCLC patients survived more than one year and was comparable to well-controlled clinical trial results, indicating survival benefits by gene aberration status guided standard of care. This result may be further validated by our on-going two-year survey.

A multicenter survey of first-line treatment patterns and gene aberration test status of patients with unresectable Stage IIIB/IV nonsquamous non-small cell lung cancer in China (CTONG 1506)

BackgroundIn recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China.MethodsPatients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record ion Forms (MERAFs), which were collated for analysis.ResultsOverall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs.ConclusionsFindings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results.

431P First-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) in China in the era of precision medicine

Background Over 40% of advanced nonsquamous NSCLC patients in China have an epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion and would benefit from treatment with EGFR or ALK tyrosine kinase inhibitors (TKIs), which are associated with significantly higher response rates and longer progression-free survival. We analysed first-line treatment according to gene aberration test status in advanced nonsquamous NSCLC patients in China (CTONG- 1506). Methods Our survey of 12 tertiary hospitals in China included advanced nonsquamous NSCLC patients admitted for first-line anti-cancer treatment from August 2015 to March 2016. Data extracted from medical charts for analysis were patient demographics, tumor histologic type, gene aberration test status and results (if performed), and first-line anti-cancer treatment regimen. Results The gene aberration test rate for patients (N = 932; median age, 59 years; male, 56%) with advanced nonsquamous NSCLC was 71% and varied with hospital location (Beijing, Shanghai, Guangzhou vs other locations) and type (general vs specialist), and patient residence (urban vs rural). Although 67% of patients with EGFR mutations (mainly in exons 19 or 21; n = 280) received first-line EGFR TKIs, 31% received first- line chemotherapy (chemo.; Table). Most patients with ALK fusions received first-line chemotherapy (56%) or ALK TKIs (35%); 3 patients had co-existing EGFR mutations and received first-line EGFR TKIs (Table). Nearly all patients with negative or unknown gene aberration status (96%) received first-line chemotherapy (Table), of which pemetrexed (66%, 367/554) was the predominant nonplatinum chemotherapy- backbone agent.Tabled 1Table: 431PGene aberrationn (%)PositiveNegative/UnknownEGFRALKROSIN = 309N = 48N = 1N = 574TKIs207 (67)20 (42)115 (3)EGFR2053015ALK11710VEGFR1000Chemo.a95 (31)27 (56)0554 (96)TKIs 1 Chemo.7 (2)1 (2)05 (1)EGFR7002nonEGFR0103 Open table in a new tab aIncluding bevacizumab-triplet Conclusions Results from our survey of tertiary hospitals in China suggest that first- line treatment of advanced nonsquamous NSCLC patients is mostly aligned with the presence or absence of gene aberrations. Clinical trial indentification Chinese Thoracic Oncology Group (CTONG) study number 1506 Legal entity responsible for the study Lilly Suzhou Pharmaceutical Co. Ltd., China Funding: Lilly Suzhou Pharmaceutical Co. Ltd., China Disclosure Q. Shi, L.L. Yang, P.H. Zhang: Employee of Lilly Suzhou Pharmaceutical Co., China. Y-L. Wu: Honoraria: F. Hoffmann-La Roche, Eli Lilly, AstraZeneca, Pfizer. All other authors have declared no conflicts of interest.

Overall survival of patients with HER2-negative metastatic breast cancer treated with a first-line paclitaxel with or without bevacizumab in real-life setting: Results of a multicenter national observational study.

1013Background: In 2014, UNICANCER (composed of 18 French Comprehensive Cancer Centers) launched the Epidemiological Strategy and Medical Economics (ESME) program to centralize real-world data in oncology. Metastatic breast cancer (mBC) was first selected to address the value of bevacizumab (B) added to paclitaxel (P) as first-line chemotherapy (CT) for HER2-negative tumours, while randomized trials have led to mixed results on outcome. Methods: The ESME-mBC database was built from information systems, treatment databases and patients’ electronic files including quality control processes. All patients who started a first-line anti-cancer treatment for mBC between 01-Jan-2008 and 31-Dec-2013 were selected. The primary objective of the present study was to assess overall survival (OS) in patients with HER2-mBC treated with a first-line P-based CT ± B. Cox regression with adjustment for the main prognostic covariates was used to estimate the hazard ratio (HR) for OS and progression-free survival (PFS). To ad...

First-line treatment of metastatic NSCLC (mNSCLC) patients without actionable mutations in U.S. community oncology clinical practice.

307 Background: Benchmarking high quality care requires defining optimally effective practice patterns. As first step, contemporary real-world practice must be detailed. The purpose of this study is to describe patient flow from diagnosis of mNSCLC to initiation of anti-cancer drug therapy in patients without known EGFR/ALK genomic tumor aberrations; the characteristics and first-line (1L) anti-cancer treatment of these patients, including induction and maintenance therapy. Methods: Retrospective database cohort study using data from an oncology EHR system, representing 17% of incident cancer cases from US community setting. Study population includes patients diagnosed with stage IV mNSCLC treated between 11/ 1/12 and 1/31/15 with follow-up to 7/31/15. Treatment patterns include regimen, number of doses, and time to regimen discontinuation. Data are analyzed descriptively, for overall cohort and by histology, with time to treatment discontinuation analyses using the Kaplan Meier method. Results: Of 4441 patients with mNSCLC, 88% had EGFR/ALK negative or unknown status. Of 79% who initiated 1L therapy, 69.5% (n = 2014) of patients (78.4% non-squamous, 21.7% squamous) were included. 55.1% were men; 89.8% were age 65+. 83.4% received induction therapy only; 16.6% received induction and maintenance therapy. 85% received a platinum combination as induction therapy; the majority either received a carboplatin doublet (53.5%) or carboplatin doublet in combination with targeted therapy (23.3%). 14.4% received a non-platinum based regimen. During induction therapy only, mean duration for the most common regimen category (platinum based combination) was 96.9 (IQR 43-129) for squamous and 79.45 (IQR 36-108) days for non-squamous patients. Of non-squamous patients who received induction followed by maintenance, mean duration of therapy was 103.9 (IQR 66-134) and 140.7 (IQR 45-208) days for induction and maintenance, respectively. Conclusions: Results describe treatment patterns in the US community 1L setting, prior to introduction of anti-PD1/PD-L1 inhibitors and new angiogenesis inhibitors. These form a starting point for benchmarking high quality care in mNSCLC.

Health-related quality of life after first-line anti-cancer treatments for advanced non-small cell lung cancer in clinical practice.

This study attempted to compare changes in the Quality-of-Life (QoL) scores after three different first-line anti-cancer treatments for advanced non-small cell lung cancer (NSCLC) in a real-world clinical setting. From May 2011 to December 2013, we prospectively measured the QoL scores of patients with locally advanced or metastatic NSCLC using the World Health Organization Quality-of-Life-Brief (WHOQOL-BREF) questionnaire. Each QoL measurement was matched by age and sex with one healthy referent from the National Health Interview Survey. Dynamic changes in patients' QoL scores and major determinants were repeatedly assessed by construction of a mixed-effects model to adjust for possible confounders. A total of 336 patients with 577 QoL measurements related to first-line anti-cancer treatments were enrolled. Performance status was the most important predictor of QoL scores in all domains after controlling for potential confounders. With age- and sex-matched healthy subjects as the reference, patients treated with gemcitabine+platinum showed significantly lower scores in multiple physical and psychological domain items in the WHOQOL-BREF. However, pemetrexed+platinum and gefitinib/erlotinib affected patients' QoL scores in 'energy/fatigue' and 'daily activities' with smaller magnitudes, and the scores appeared to improve after 3-4months of treatment. Patients receiving gemcitabine+platinum as first-line anti-cancer treatment for advanced NSCLC experienced relatively poor QoL scores throughout treatment course. Studies to develop a real-time computerized system automatically updating the mixed-effects model for QoL to facilitate participatory clinical decision making by physicians, patients, and their families merit further research.

Biweekly gemcitabine plus S-1 for locally advanced and metastatic pancreatic cancer: a preliminary feasibility study

Chemotherapy for unresectable pancreatic cancer should not only prolong survival but maintain quality of life, considering its limited life expectancy. To achieve these goals, biweekly gemcitabine plus S-1 was assessed in the clinical practice setting. Fifty-two patients with either locally advanced or metastatic pancreatic cancer who received biweekly gemcitabine plus S-1 as a first-line anti-cancer treatment were included in this study. Treatment delivery, toxicity, response, and survival were reviewed to assess the feasibility and efficacy. The completion rate of treatment delivery was 95.1%, with relative dose intensity of 97.1% for gemcitabine and 97.3% for S-1. Overall, grade 3 or worse adverse events were rare, with hematologic toxicities occurring in 5.8%. The objective response rate was 30.8%, and more than a 50% reduction of CA19-9 was observed in 77.1%. Surgical conversion was completed with a margin-negative resection in four patients whose tumor had shrunk for at least 6 months. The median progression-free and overall survivals were 10.4 and 18.2 months, respectively. Reduction of CA19-9 was associated with longer survival. Biweekly gemcitabine plus S-1 may be a good alternative to current standard chemotherapies for unresectable pancreatic cancer with less toxicity and less treatment burden without losing efficacy.

Prospective non-interventional multicentre observational trial of first-line anti-cancer treatment in patients with metastatic renal cell cancer in Belgium

Objectives:Renal cell carcinoma (RCC) accounts for 2·4% of all new cancers in Belgium. Over the past decade, the armamentarium for systemic therapy of metastatic RCC (mRCC) has undergone important changes with implementation of targeted therapies directed against pathways involved in the pathogenesis of RCC. We describe first-line treatment choice of a group of patients in 9 Belgian oncology centres between October 2009 and November 2012.Methods:A clinical report form was established to assess patient characteristics, Karnofsky performance score, Memorial Sloan-Kettering Cancer Center risk criteria (MSKCC) and first-line therapy of mRCC patients. Choice of therapy and starting dose was analyzed before and after reimbursement of pazopanib in Belgium.Results:Ninety-six patients were eligible for the study. Non-smokers accounted for 53% of the patients. Seventy-three per cent of the patients had 0 or 1 MSKCC criteria in the group of patients that started treatment more than 1 year after initial diagnosis. In the group of patients that started therapy less than 1 year after diagnosis, 85% had 2 or more MSKCC criteria. This difference was statistically significant (P<0·0001). Overall distribution of the first-line therapies consisted of 43% sunitinib, 33% pazopanib, 14% temsirolimus, 7% everolimus and 3% sorafenib. Seventeen (18%) out of 96 patients started at a reduced dose level.Conclusion:This report shows that the guidelines for the start of first-line treatment in mRCC in 9 centres in Belgium were applied most of the time: a tyrosine kinase inhibitor was the first treatment choice for most patients while temsirolimus was an option for poor prognosis patients. In the majority of patients standard dose levels were initiated, although in some patients adaptation of dosage/treatment schedule was recorded.

A Unique Case of Hepatocellular Carcinoma Treated with Radiofrequency Ablation with More than 12 Years Overall Survival: A Case Report

The case of a 72-year-old male patient with HCC is presented in whom percutaneous RFA was used as the sole first-line anticancer treatment, since he denied having partial hepatectomy. The patient underwent RFA two more times, at 1.5 years for treating a local tumor progression at the initial ablation site and at 11 years after the first session for treating a new remote intrahepatic recurrence. He revealed a long-term survival of more than 12 years so far and still remains in excellent clinical status.

Combination therapy of radiofrequency ablation and transarterial chemoembolization in recurrent hepatocellular carcinoma after hepatectomy compared with single treatment

To assess the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare its outcome with a single modality. We retrospectively studied 103 patients with recurrent HCCs after hepatectomy who were excluded from repeat hepatectomy. Of them, 81 patients were male and 22 were female (mean age 55.8 +/- 10.7 years; range, 30-80 years). According to treatment modality, these patients were divided into three groups: RFA was used as the sole first-line anticancer treatment in 37 patients (RFA group); TACE was used as the sole first-line anticancer treatment in 35 patients (TACE group). RFA followed by TACE was performed in 31 patients (combination group). There was no significant difference in clinical material between the three groups. Indices including treatment success rate, intrahepatic recurrence rate and survival were obtained for analysis and comparison. The treatment success rate of the combination group was significantly higher than that of the TACE group (93.5 vs. 68.6%, P = 0.011). The intrahepatic recurrence rate of the combination group was significantly lower than that of the TACE group (20.7 vs 57.1%, P = 0.002) and the RFA group (20.7 vs 43.2%, P = 0.036). The overall 1-, 3- and 5-year survival rates were 73.9, 51.1 and 28.0% respectively in the RFA group; 65.8, 38.9 and 19.5% respectively in the TACE group; and 88.5, 64.6 and 44.3% respectively in the combination group. There was a significant difference in survival between the combination group and the TACE group (P = 0.028). RFA combined with TACE was more effective in treating recurrent HCC after hepatectomy compared to single RFA or TACE treatment. This combination therapy can thus be a valuable choice of treatment for recurrent HCC.