Eastern Cooperative Group Performance Status Research Articles

Prognostic factors for survival in patients with advanced gastric cancer treated with chemotherapy.

142 Background: A prognostic model in advanced gastric cancer that integrates the Her2 status,histopathological classifications and other patient’s or treatment-dependent parameters is lacking. The aim is to identify clinicopathological factors for overall survival in a cohort of patients with advanced gastric cancer. Methods: 526 consecutive patients with advanced adenocarcinoma of the distal esophagus, gastroesophageal junction or stomach were analyzed. All patients were treated with poly-chemotherapy ( ≥ 2 drugs) at 19 Spanish and one Chilean centers between 2012 and 2015. Characteristics of patients, tumors, therapies and pathological factors, were analyzed by a Cox proportional hazards model. Results: The median overall survival was 10.3 months [95% confidence interval (CI), 9.5-11.1], and the time to progression was 6.7 months (95% CI, 6.1-7.2). Independent prognostic factors associated with overall survival were: distal non-diffuse histopathological subtype (hazard ratio, (HR) 0.73), Her2 positive 3+ (HR 0.54), Her2 positive 2+ with FISH + (HR 0.68), surgery of metastases (HR 0.34), Eastern Cooperative Group performance status (ECOG PS) 2 (HR 2.5), ECOG PS 3 (HR 7.37), and only distant lymph node metastases (HR 0.63) (Table 1). Conclusions: We have identified clinicopathological prognostic factors that could be important to stratify advanced gastric cancer, with potential implications in research and treatment. [Table: see text]

Ovarian Non-Hodgkin’s Lymphoma from a Regional Cancer Centre in South India

Primary Non-Hodgkin’s Lymphoma of Ovary is a rare cancer. There is limited data in Indian population. Hence we undertook this retrospective observational study at our center in Southern India. This study includes 5 consecutive cases diagnosed as Primary Non-Hodgkin’s Lymphoma of Ovary between January 2009 and December 2015. Primary Non-Hodgkin’s lymphoma (NHL) of the ovary is rare with an incidence in the literature of 0.5% of NHL and 1.5% of ovarian tumours. Diffuse large B-cell type accounts for about 20% of PONHL. We studied five cases of primary ovarian NHL. All cases were diffuse large B-cell lymphoma of ovary. The patients ranged in age from 41years to 59 years with median age of presentation 50 years. Pain abdomen was the most common symptom (3/5-60%). According to Ann Arbor stage- Advanced stage ( IVE) was seen in 3 patients ( 60 %) and the rest 2 patients (40% ) had stage IE. 4 patients had Eastern co-operative oncology group (ECOG) performance status -1 and 1 patient had ECOG PS -2. B symptoms were seen in 3 out of 5 patients (60 %). According to IPI, 3 patients (60%) were in low intermediate risk and 2 patients (40%) had low risk score. 1 case was positive for BCL-6, 1 case was positive for CD10, 3 cases were positive for BCL-2, and 4 cases were positive for CD 20 . Patients were treated by various combinations of surgery, chemotherapy, and radiotherapy. Overall survival ranged from 6 months to 41 months with median OS of 23 months.

Long-Term Survival for Platinum-Sensitive Recurrent Ovarian Cancer Patients Treated with Secondary Cytoreductive Surgery Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS+HIPEC and secondary recurrence or death, respectively. The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73months (range 48-128months), and the median PFI-1 was 19months (range 6-100months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6%). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6%) and cisplatin in 43 cases (61.4%). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6%. The median PFS duration was 27months (range 5-104months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7%, (median PRS 63months). The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS+HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.

How to select elderly colorectal cancer patients for surgery: a pilot study in an Italian academic medical center.

ObjectiveCancer is one of the most common diagnoses in elderly patients. Of all types of abdominal cancer, colorectal cancer (CRC) is undoubtedly the most frequent. Median age at diagnosis is approximately 70 years old worldwide. Due to the multiple comorbidities affecting elderly people, frailty evaluation is very important in order to avoid over- or under-treatment. This pilot study was designed to investigate the variables capable of predicting the long-term risk of mortality and living situation after surgery for CRC.MethodsPatients with 70 years old and older undergoing elective surgery for CRC were prospectively enrolled in the study. The patients were preoperatively screened using 11 internationally-validated-frailty-assessment tests. The endpoints of the study were long-term mortality and living situation. The data were analyzed using univariate Cox proportional-hazard regression analysis to verify the predictive value of score indices in order to identify possible risk factors.ResultsForty-six patients were studied. The median follow-up time after surgery was 4.6 years (range, 2.9-5.7 years) and no patients were lost to follow-up. The overall mortality rate was 39%. Four of the patients who survived (4/28, 14%) lost their functional autonomy. The preoperative impaired Timed Up and Go (TUG), Eastern Cooperative Group Performance Status (ECOG PS), Instrumental Activities of Daily Living (IADLs), Vulnerable Elders Survey (VES-13) scoring systems were significantly associated with increased long term mortality risk.ConclusionSimplified frailty-assessing tools should be routinely used in elderly cancer patients before treatment in order to stratify patient risk. The TUG, ECOG-PS, IADLs and VES-13 scoring systems are potentially able to predict long-term mortality and disability. Additional studies will be needed to confirm the preliminary data in order to improve management strategies for oncogeriatric surgical patients.

Safety and activity of RRx-001 in patients with advanced cancer: a first-in-human, open-label, dose-escalation phase 1 study

Epigenetic alterations have been strongly associated with tumour formation and resistance to chemotherapeutic drugs, and epigenetic modifications are an attractive target in cancer research. RRx-001 is activated by hypoxia and induces the generation of reactive oxygen and nitrogen species that can epigenetically modulate DNA methylation, histone deacetylation, and lysine demethylation. The aim of this phase 1 study was to assess the safety, tolerability, and pharmacokinetics of RRx-001. In this open-label, dose-escalation, phase 1 study, we recruited adult patients (aged >18 years) with histologically or cytologically confirmed diagnosis of advanced, malignant, incurable solid tumours from University of California at San Diego, CA, USA, and Sarah Cannon Research Institute, Nashville, TN, USA. Key eligibility criteria included evaluable disease, Eastern Cooperative Group performance status of 2 or less, an estimated life expectancy of at least 12 weeks, adequate laboratory parameters, discontinuation of all previous antineoplastic therapies at least 6 weeks before intervention, and no residual side-effects from previous therapies. Patients were assigned to receive intravenous infusions of RRx-001 at increasing doses (10 mg/m(2), 16·7 mg/m(2), 24·6 mg/m(2), 33 mg/m(2), 55 mg/m(2), and 83 mg/m(2)) either once or twice-weekly for at least 4 weeks, with at least three patients per dose cohort and allowing a 2-week observation period before dose escalation. Samples for safety and pharmacokinetics analysis, including standard chemistry and haematological panels, were taken on each treatment day. The primary objective was to assess safety, tolerability, and dose-limiting toxic effects of RRx-001, to determine single-dose pharmacokinetics, and to identify a recommended dose for phase 2 trials. All analyses were done per protocol. Accrual is complete and follow-up is still on-going. This trial is registered with ClinicalTrials.gov, number NCT01359982. Between Oct 10, 2011, and March 18, 2013, we enrolled 25 patients and treated six patients in the 10 mg/m(2) cohort, three patients in the 16·7 mg/m(2) cohort, three patients in the 24·6 mg/m(2) cohort, four patients in the 33 mg/m(2) cohort, three patients in the 55 mg/m(2), and six patients in the 83 mg/m(2) cohort. Pain at the injection site, mostly grade 1 and grade 2, was the most common adverse event related to treatment, experienced by 21 (84%) patients. Other common drug-related adverse events included arm swelling or oedema (eight [32%] patients), and vein hardening (seven [28%] patients). No dose-limiting toxicities were observed. Time constraints related to management of infusion pain from RRx-001 resulted in a maximally feasible dose of 83 mg/m(2). Of the 21 evaluable patients, one (5%) patient had a partial response, 14 (67%) patients had stable disease, and six (29%) patients had progressive disease; all responses were across a variety of tumour types. Four patients who had received RRx-001 were subsequently rechallenged with a treatment that they had become refractory to; all four responded to the rechallenge. RRx-001 is a well-tolerated novel compound without clinically significant toxic effects at the tested doses. Preliminary evidence of activity is promising and, on the basis of all findings, a dose of 16·7 mg/m(2) was recommended as the targeted dose for phase 2 trials. EpicentRx (formerly RadioRx).

Maintenance Therapy With Cetuximab Every Second Week in the First-Line Treatment of Metastatic Colorectal Cancer: The NORDIC-7.5 Study by the Nordic Colorectal Cancer Biomodulation Group

BackgroundIn the NORDIC-7.5 trial, how cetuximab might safely and conveniently be added to an intermittent treatment strategy in patients with prospectively selected Kirsten rat sarcoma viral oncogene homolog wild type (KRASwt) metastatic colorectal cancer (mCRC) was investigated. Patients were treated in a multicenter phase II trial with cetuximab in combination with the Nordic bolus FLOX (oxaliplatin, 5-fluorouracil, and folinic acid) for 4 months followed by maintenance cetuximab. Patients and MethodsPatients had KRASwt, nonresectable mCRC, no previous chemotherapy, and Eastern Cooperative Group performance status of 0 to 2. Patients received 8 courses of Nordic FLOX (oxaliplatin 85 mg/m2 over 1 hour on day 1, and 5-fluorouracil 500 mg/m2 as a bolus injection, followed 30 minutes later with bolus folinic acid 60 mg/m2 on days 1 and 2). Cetuximab was administered every 2 weeks at a dose of 500 mg/m2 for 16 weeks followed by cetuximab as maintenance therapy until disease progression. ResultsBetween July 2008 and September 2010, 152 KRASwt patients were included. The response rate was 62% (95% confidence interval [CI], 54%-69%), median progression-free survival was 8.0 months (95% CI, 7.5-8.9) and median overall survival was 23.2 (95% CI, 18.1-27.4) months. Twenty-one patients (14%) had later R0-resection of metastasis. FLOX with cetuximab was reintroduced in 47 of 85 patients (55%). The most common Grade 3/4 nonhematologic adverse events were diarrhea in 14 patients (9%), skin rash in 13 patients (9%), infection without neutropenia in 11 patients (7%), and fatigue in 11 patients (7%). ConclusionIn a prospectively selected KRASwt population, biweekly cetuximab was safely integrated in an intermittent chemotherapy strategy and might have added to a longer chemotherapy-free interval. However, the combination of biweekly cetuximab with chemotherapy needs to be validated in trials using FOLFOX (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).

Quality of Life of Patients Undergoing Cancer Treatment in B.P. Koirala Memorial Cancer Hospital, Bharatpur, Chitwan, Nepal

This research entitled “Quality of Life of Patients Undergoing Cancer Treatment in B.P. Koirala Memorial Cancer Hospital, Bharatpur, Chitwan” was conducted to assess the quality of life of cancer patients. It was carried out among patients attending B. P. Koirala Memorial Cancer Hospital, Bharatpur, Chitwan. Background: In patients with different type of cancers and the quality of life (QoL) improvement is the main goal, since survival can be prolonged marginally. A diagnosis is very stressful for people, affecting all aspects of their being and quality of life. Up to date, knowledge on QoL impairments throughout the entire treatment process, often including several treatment modalities is scarce. One objective of this study was to assess the quality of life of cancer patient undergoing cancer treatment. Methods: A quantitative, cross-sectional, descriptive, design was adapted. A total of 245 cancer patients above 20 years old, were enrolled in the studies during August-September, 2013. Inclusion criteria were patients who had already received at least one type of cancer treatment and had attended the hospital for receiving the same or next type of treatment again. Exclusion criteria were any other chronic co-morbidity condition that could be influenced their QoL. The most commonly listed medical co-morbidities were: diabetes mellitus, hypertension, coronary artery disease. Cancer patients who have Eastern Co-operative Oncology Group (ECOG) performance status of 4 (i.e. fully bed-ridden) were excluded from the study. The data was collected by interview, using modified, structured scale of European Organization for Research and Treatment of Cancer Quality of life Questionnaire (EORTC QLQ- C30), prepared by the EORTC group. Information about the patient’s disease condition and treatment were obtained from the patient’s medical records. The collected data was analyzed by using SPSS version 16. Descriptive and inferential statistics were used to describe the respondent’s quality of life (QoL) scores and to identify the factors affecting it respectively. Results: The study findings revealed the quality of life of cancer patients to be influenced by many factors such as: site of cancer, stage of cancer, time elapsed since diagnosis and Eastern Co-operative Oncology Group (ECOG) performance status. The average QoL scores (out of 100) for different scales were 85.54 (global health/QoL), 77.03 (functional), and 16.14 (symptom). Loss of appetite was the most frequent complaint (mean = 20.27) and was present in almost all the patients. As the overall QoL of the patients was significantly correlated with different QoL scales as-, cognitive, emotional, physical, social, role functioning, pain, fatigue, dyspnoea, loss of appetite and nausea/vomiting and financial problem. Conclusion: Hence, in average, the quality of life of cancer patients was found to be relatively better, although there were higher ratings for some (as: cognitive, physical, role and emotional functioning) and lower for others (like social functioning). Additional research should be done in this area for improving the quality of life of specific type of cancer patients in Nepal, though the findings of this study are expected to provide the baseline knowledge regarding it.

Head and neck cancer in geriatric patients: Analysis of the pattern of care given at a tertiary cancer care center.

The percentage of elderly people with head and neck cancers (HNC) is on the rise. This makes HNC in this group of patients an important issue for healthcare providers. The present study was planned to analyze the patterns of care given to the geriatric patients and to identify the factors influencing the decision making process. Data of all the elderly patients (≥65 years) registered in the year 2012, with histologically proven HNC (all sites, stages, histopathological types, except lymphoma, sarcoma and cervical metastasis of unknown origin) receiving treatment (definitive/palliative) were collected. A total of 270 patients were included in this study. The median age was 72 years (range: 65-101), with predominant male population (70%, n = 190). Oral cavity squamous cell carcinoma (SCC) was the most common cancer (57%, n = 154). Eastern Co-Operative Oncology Group performance status (PS) of 0-2 was seen in 91% of the patients. Co-morbidities were present in 139 (51.5%) patients. 50% (n = 134) of the patients received palliative intent treatment, 45% (n = 123) definitive treatment, whereas in 5% (n = 13) the intent was not mentioned. Age, a clinical stage and PS significantly influenced the decision making on the intent of treatment. 208 (77%) patients completed their treatment irrespective of the intent. Age was the only factor influencing treatment completion irrespective of the intent. Geriatric HNC patients frequently present with advanced disease, having multiple co-morbidities. Hence, a multidisciplinary team management of these patients is essential, also taking into account of the social and financial support available to these patients.

Pomalidomide and Dexamethasone Is an Effective Regimen for Advanced-Stage Relapsed/Refractory Multiple Myeloma: Experience of a Single Center

Introduction Almost all patients with MM eventually relapse, and the remission duration in relapsed MM decreases with each regimen. Pomalidomide is an IMiD with antiproliferative, anti-inflammatory and anti-angiogenic effects that was recently approved for the use of relapsed MM failing lenalidomide and bortezomib. Based on these findings, we aimed to evaluate the efficacy of pomalidomide and dexamethasone (PD) for heavily-pretreated relapsed or refractory MM (RRMM) at our Institution. Methods We retrospectively reviewed the records of all patients with RRMM treated with PD at Tom Baker Cancer Center between 01/10 and 06/14. Eligible patients were age 18 years or older; had RRMM after two or more prior therapies (including lenalidomide, bortezomib or thalidomide); and had an Eastern Cooperative Group performance status of 0 to 2. Patients received oral pomalidomide 2-4 mg/d on days 1-21, and dexamethasone 20 mg or 40 mg on a weekly basis. Definitions of response and progression were used according to the EBMT modified criteria. The primary endpoint of the study was to assess the efficacy and feasibility of PD in this group of patients. All analyses were performed using the SPSS 20.0 software and all p-values were 2-sided and statistically significant if <0.05 Results Between 01/10 and 06/14, 31 patients were identified for the study. Clinical and laboratory characteristics are listed in Table 1.The median age for this cohort of patients was 64 years (46-81). Seventy-one percent of patients had IgG isotype, 19.4% had IgA, and 9.7% had light chain only disease. The median number of therapies prior to PD was 4 (2-11). All patients received lenalidomide and bortezomib prior to PD; 11 patients had bortezomib, 8 had lenalidomide and 7 had both prior to PD. Six patients out of 11 receiving bortezomib prior to PD responded (54%) versus 12.5% (1/8), 14% (1/7), and 20% (1/5) for those receiving lenalidomide, lenalidomide/bortezomib and other regimens respectively prior to PD. (p=0.07) Two patients received pomalidomide at a dose of 3 mg, 1 at 2 mg and 28 at 4 mg. After a median of 5 cycles, the ORR was 29% (9/31) with 1 patient achieving nCR and 8 patients (25.8%) PR. (Table 2 ) The median time to first response was 8 weeks with majority of cases achieving at least PR after 2 cycles of therapy. Stable disease was seen in 22.6% and progression in 29% of cases. FISH cytogenetics at relapse were available in 24 patients with 6 cases exhibiting high risk disease (25%). At a median follow-up of 20 months, 16 patients (51.6%) are alive and 21 (67.7%) had already progressed. Median OS was 19.1 months and median PFS 5.6 months. Median PFS was 6.5 months in the group with SR cytogenetics compared to 3.1 months for the HR group. (p0.2) Median OS was similar between SR and HR (19.4 vs 23 months) (p=0.14) With regards to toxicity, 9 patients experienced grade 3/4 hematological toxicity. Eight patients required blood transfusion and one patient discontinued therapy due to grade 4 thrombocytopenia. In conclusion, Pomalidomide is an efficacious drug for the treatment of RRMM. The current report confirms the ORR seen in previous studies and the benefit in HR disease. Further combinations with pomalidomide in the setting of HR disease and for those patients who immediately progressed on IMiD therapies should be considered.Table 1Clinical and Laboratory characteristics for RRMM patients treated with Pomalidomide and DexamethasoneCharacteristicNMedianRange%Age (years)316446-81Gender-Male -Female14 1745.2% 54.8%ISS StageI II III5 14 1216.1% 45.2% 38.7%Heavy chainIgG IgA Free light chain only Light chainKappa Lambda22 6 3 25 671% 19.4% 9.7% <![if !supportEmptyParas]> <![endif]>80.6% 19.4%Hemoglobin (g/L)3111375-142Creatinine (µmol/L)318650-290Calcium (µmol/L)312.32.06-2.64LDH (IU/L)3118984-489B2-microglobulin (mg/L)314.21.36-16.3Albumin (g/L)313321-42BMPC (%)31308-98FISH CytogeneticsStandard risk High risk24 18 675% 25%Prior TherapiesASCT Thalidomide Lenalidomide Bortezomib Carfilzomib21 13 31 31 667.7% 41.9% 100% 100% 19.4%Table 2Response rates for RRMM patients treated with Pomalidomide and DexamethasoneCharacteristicMedian (Range)N%Number of cycles5 (1-31)Overall Response rate9/3129%Near Complete Response Complete Response1 03.2% 0%Very Good Partial Response00%Partial Response825.8%Stable Disease722.6%Minimal Response619.4%Progression929%Alive1651.6% DisclosuresJimenez Zepeda:Janssen Ortho: Honoraria. Bahlis:Celgene: Honoraria, Research Funding.

Mitomycin C and capecitabine in pretreated patients with metastatic gastric cancer: a multicenter phase II study

We conducted a multicenter phase II study to assess the toxicity and efficacy of a combination of mitomycin C (MMC) and capecitabine in pretreated patients with metastatic or locally advanced gastric cancer. Thirty-nine patients (77 % male) between 33 and 78 years (median 66) with pretreated locally advanced or metastatic esophagogastric adenocarcinoma and eastern cooperative oncology group performance status of ≤2, measurable lesions, and adequate organ functions were recruited into the study. Eight patients (21 %) had received more than one prior chemotherapy regimen. Treatment consisted of three-weekly MMC 10 mg/m(2) day 1 and capecitabine 2,000 mg/m(2) (day 1-14; repeated day 22). A median of three cycles of therapy was administered. Grade 3 toxicity occurred in 20 patients (54 %). Main grade 3 adverse events were thrombocytopenia (11 %, n = 4), fatigue (8 %, n = 3), and neuropathy (8 %, n = 3). Two events of grade 4 toxicity were reported (5 %) (dyspnea and elevation of alkaline phosphatase due to bone metastases). Partial remission was noticed in 10.3 % (n = 4), stable disease in 33.3 % (n = 13) adding to a tumor control rate of 43.6 %. The median progression-free and overall survival were 2.8 and 5.6 months, respectively. The combination of MMC and capecitabine exhibited a favorable tolerability profile in pretreated patients with gastric cancer. The disease control rate compares adequately with that of other phase II and phase III trials for second-line therapy in gastric cancer. This regimen may be considered as an alternative second-line treatment, especially for patients not suitable for or pretreated with taxanes and/or irinotecan.

Ten-day decitabine as initial therapy for newly diagnosed patients with acute myeloid leukemia unfit for intensive chemotherapy

We retrospectively reviewed outcomes in 45 previously untreated patients with acute myeloid leukemia (AML) considered unfit for chemotherapy who were treated with 10-day courses of decitabine 20 mg/m2 daily outside of a clinical trial, with no cut-offs for organ function or performance status (PS). Nineteen had Eastern Cooperative Group performance status (ECOG PS) ≥ 2, and 39 had ≥ 2 comorbidities. Fourteen patients (31%) achieved complete remission (CR) and five (11%) CR with incomplete count recovery, for an overall response rate of 42%, after a median of 2 (range, 1–4) courses. The only pretreatment characteristic that differed significantly between responders and non-responders was percent marrow blasts (median 42% vs. 65%; p = 0.01). Median overall survival was 9.0 months; it was 19.4 and 2.3 months for responders and non-responders, respectively (p < 0.001). Thus 10-day decitabine therapy has efficacy in patients with AML considered unfit for chemotherapy, and may serve as a backbone for the addition of other novel agents.

Percutaneous Vertebroplasty in Vertebral Metastases from Breast Cancer: Interest in Terms of Pain Relief and Quality of Life

Percutaneous vertebroplasty (PV) is a therapeutic option in patients with vertebral metastases (VM). However its efficacy in pain relief, improvement in quality of life and safety in patients with VM from breast cancer has not been reported. We present a longitudinal retrospective study of 31 consecutively treated female patients with VM from breast cancer where 88 vertebrae were treated in 44 sessions of PV, in which osteolytic, osteoblastic and mixed lesions were recorded. The visual analogue pain scale (VAS) was used to evaluate pain pre-PV, at one, three, six and 12 months post-PV. The Eastern Cooperative Group (ECOG) performance status scale was used at the same time intervals to measure quality of life: 90.3% pain relief was identified with a VAS reduction from 5.7 ± 2.0 pre-PV to 2.9 ± 2.2 post-PV at one-month follow-up (p<0.001) and 0.6 ± 1.0 at 12-month follow-up (p<0.001). In our series 48.4% of patients were classified as having an ECOG grade 0 and 1 pre-PV, which increased to 80.8% at the 12-month follow-up. While 22.6% of the patients were classified at ECOG grades 3 and 4 pre-PV, this improved to 0% at 12 months follow-up. The morbidity rate for this procedure was 12.9% immediately and only 3.2% at 30 days post-PV with all complications being resolved medically or with CT-guided infiltration. PV is a safe procedure with a high efficacy in pain relief, and improvement of quality of life in patients with diverse types of VM from breast cancer.

Serum ferritin is elevated in advanced non-small cell lung cancer patients and is associated with efficacy of platinum-based chemotherapy.

The aim of this study was to determine the expression levels of serum ferritin (SF) and investigate the correlation between SF expression levels and clinical characteristics as well as the efficacy to platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC) patients. Electrochemiluminescence method was used to determine the expression levels of SF in the peripheral blood of 46 advanced NSCLC patients and 63 healthy subjects. The expression levels of SF in healthy subjects were significantly lower than those in patients with advanced NSCLC patients (t = -3.279,P = 0.001). There was a statistically significant difference between SF expression levels and distant metastasis, regional lymph node metastasis, respectively (P < 0.05). However, there was no correlation between SF expression levels and sex, age, eastern cooperative oncology group performance status, smoking history, pathological type, tumor location and tumor-node-metastasis stage (All P > 0.05). The overall response rate to platinum-based chemotherapy was 57.1% (12/21) in normal SF expression levels group, which was significantly higher than that was 28% (7/25) in high SF expression levels group (χ² = 3.998,P = 0.046). SF may be a valuable blood marker for predicting the tumor progression and the efficacy of platinum-based therapies for advanced NSCLC patients.

Outcomes Of Chronic Lymphocytic Leukemia Patients With Richter Syndrome

▪ IntroductionApproximately 2-8% chronic lymphocytic leukemia (CLL) patients develop diffuse large B-cell lymphoma (DLBCL, so-called Richter syndrome [RS]) over long-term follow-up. The outcomes of patients with RS are variable and poorly understood. MethodsCLL patients seen at Mayo Clinic from January 1995 to April 2013 who developed biopsy-proven DLBCL during follow-up were included in this analysis. Clinical characteristics, therapy and overall survival (OS) of all patients with RS were analyzed. ResultsOne hundred and twenty patients with biopsy-proven RS were identified in the Mayo Clinic database. The median age at diagnosis of RS was 67 years (range, 29-88 years), 87 (73%) were male, and 83 (69%) had received prior CLL therapy. The median duration between diagnosis of CLL and development of RS was 3.8 years (range, 0-34.5 years). Stereotyped B-cell receptors were found in 9/30 (30%) RS patients compared to 219/1294 (17%) non-RS patients (OR=2.1, p=0.07). IGHV4-39 gene usage was present in 2/26 (8%) RS patients compared to 57/1354 (4%) non-RS patients (p=0.3). Of the 30 RS biopsy samples in which Epstein Barr virus (EBV) in-situ hybridization studies were performed, EBV was detected in 7 (23%) patients.After a median follow-up of 5.2 years, 86 (72%) patients have died. Causes of death were as follows: progressive DLBCL (n=46, 53%), progressive CLL (n=2, 2%), infection (n=8, 9%), unknown (n=20, 23%) and other (n=10, 12%). The median OS of the entire cohort was 0.9 years (95% CI, 0.5-1.3 years). Tsimberidou and colleagues proposed a prognosis score (RS score) based on the following variables at the time of RS diagnosis: Eastern Co-operative Group performance status of 2-4, lactate dehydrogenase >1.5 x normal, platelets<100 x 109/L, tumour size >5 cm and >1 prior therapy for CLL. Each parameter was assigned one point, and patients were then assigned to one of four risk groups based on their calculated RS score: 0 or 1, low risk; 2, low-intermediate risk; 3, high-intermediate risk; 4 or 5, high risk. The OS according to the RS score for our group of patients is shown in Figure 1. Median survival in the low, intermediate-1, intermediate-2 and high-risk groups were 2.4 years, 0.7 years, 0.3 years and 0.2 years, respectively (p<0.001). [Display omitted] Fifteen (12%) patients received cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) as initial therapy for RS, and 68 (57%) received rituximab in addition to CHOP (R-CHOP). There was no difference in survival among patients who received CHOP compared to R-CHOP (median, 1.8 years. vs. 1.2 years, p=0.5). Twenty-four patients (20%) received non-CHOP-based chemotherapy, and treatment was unknown in 4 (3%) patients. Nine patients (7%) died before definitive therapy could be instituted.Thirteen (11%) patients were able to proceed to stem cell transplantation (SCT): 10 (8%) autologous SCT, 2 (2%) allogeneic SCT and 1 (1%) autologous SCT followed by an allogeneic SCT. Although RS patients who underwent SCT were younger compared to those who did not undergo SCT (median, 59 years. vs. 69 years, p=0.001), no differences in prior CLL therapy or receipt of R-CHOP therapy for DLBCL was noted between the two groups. The median survival of patients who proceeded to SCT was superior compared to those who did not (5.2 years vs. 0.7 years; p=0.005). ConclusionStereotyped B-cell receptors but not VH4-39 had a suggested evidence of an increased risk of RS in our cohort. Although 90% RS patients received intensive chemotherapy, only 11% patients were able to proceed to SCT. Median survival of RS patients remains dismal at 1 year, and newer therapies are needed to improve outcomes. Disclosures:Shanafelt:Genentech: Research Funding; Glaxo-Smith-Kline: Research Funding; Cephalon: Research Funding; Hospira: Research Funding; Celgene: Research Funding; Polyphenon E International: Research Funding.

Serum cytokine levels in patients with advanced non-small cell lung cancer: correlation with clinical outcome of erlotinib treatment

Background Serum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC. Methods A total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL-2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≤26.5 pg/ml) and high (&gt;26.5 pg/ml)), IL-2R (low (≤115 pmol/L) and high (&gt;15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (&gt;49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (&gt;48.5 pg/ ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS). Results Between January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P=0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P &lt;0.05). These cytokines remained significant upon multivariate analysis (P &lt;0.05). Conclusion IL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.

Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different

The Eastern Cooperative Group Performance Status (ECOG PS) is a widely used standard functional classification in oncology practice, the verbal descriptors of which refer to physical activity (PA). Little is known about the cut-off points of this scale and measured PA levels. This research investigated the relationship between PS assigned, objectively measured PA, and patient age. One hundred ambulatory patients with treatment-naive cancer wore an accelerometer (RT3) for a mean (SD) of 5.6 (1.1) days before initial oncology evaluation and ECOG PS assignment. Seventy five participants (75%) were <65 years and 25 were ≥65 years. Eighty nine (89%) were assigned an ECOG PS of 0 or 1 and 11% a PS of 2 or 3. A weak but significant inverse association was found between objectively measured PA and PS (rho = -0.26, p = 0.01). Seventy one participants (80%) with a PS of 0 or 1 spent more than 50% of waking hours resting. Participants assigned a PS of 2-3 spent significantly more time resting than those assigned a PS of 0 (p = 0.01). Age ≥65 years was significantly related to PS assigned (p = 0.04), although the older cohort were no less sedentary than younger patients. PA levels were low, but PS scoring reflected relative PA levels and differentiated between patients of PS 0 and 2-3. Chronological age was not predictive of activity levels, but older patients were assigned lower PS scores. Incorporation of objective PA measures may merit further investigation especially in the geriatric oncology setting.

Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network

BackgroundCentral nervous system (CNS) involvement in mantle cell lymphoma (MCL) is uncommon, and the manifestations and natural history are not well described. Patients and methodsWe present the data on 57 patients with MCL who developed CNS involvement, from a database of 1396 consecutively treated patients at 14 institutions. ResultsThe crude incidence of CNS involvement was 4.1%, with 0.9% having CNS involvement at diagnosis. Blastoid histology, B-symptoms, elevated lactate dehydrogenase, Eastern Cooperative Group performance status ≥2 and a high Mantle Cell Lymphoma International Prognostic Index score were enriched in the cohort with CNS involvement, and the presence of ≥1 of these features defined a high-risk subset (an actuarial risk of CNS involvement 15% at 5 years) in a single-institution subset. The median time to CNS relapse was 15.2 months, and the median survival from time of CNS diagnosis was 3.7 months. The white blood cell count at diagnosis <10.9 × 109/l, treatment of CNS involvement with high-dose anti-metabolites, consolidation with stem cell transplant and achievement of complete response were all associated with improved survival. ConclusionsIn MCL, CNS involvement is uncommon, although some features may predict risk. Once manifest outlook is poor; however, some patients who receive intensive therapy survive longer than 12 months.

Five-year outcome of concurrent radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer: single-institution experience

BACKGROUND AND OBJECTIVESWe aimed to evaluate long-term treatment outcomes and toxicity profile of combined radiotherapy and chemotherapy in Saudi women with locally advanced cervical cancer.DESIGN AND SETTINGSRetrospective study in a tertiary care cancer center in Riyadh, Saudi Arabia.METHODS AND MATERIALSThe medical records of patients with histopathologically proven, locally advanced cervical cancer were analyzed. These patients received three-dimensional conformal radiotherapy with concurrent chemotherapy followed by high dose rate brachytherapy in our center between July 2007 and April 2012. The data regarding the safety profile, response rates, occurrence of locoregional or distant failure, disease-free survival, and overall survival rates were recorded.RESULTSThe median follow-up period was 60 months (range, 8–66) for 74 patients. The median age of study population was 52.3 years (32–78), and the stage IIB was the predominant stage (49 patients [66.2%]). A total of 45 patients (60.9%) had radiologic-positive pelvic ± para-aortic lymphadenopathy. The 5-year locoregional and distant control rates were 84.3% and 78.5%, respectively. The 5-year disease-free and overall survival rates were 75.7% and 64.5%, respectively. Stage, nodal status, and hemoglobin levels were found to be important prognostic factors for locoregional and distant control. Acute grade 3 hematological and nonhematological toxicities were seen in 4 (5.4%) and 4 (5.4%) patients. Late toxicities were mild, and only 1 (1.4%) patient presented with subacute intestinal obstruction.CONCLUSIONConcurrent chemoradiation in Saudi women with locally advanced cervical cancer showed better locoregional and distant control and survival rates with minimal toxicity.

Development and validation of a prognostic model in patients with metastatic renal cell carcinoma treated with sunitinib: a European collaboration.

Background:Accurate prediction of outcome for metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy is essential. Most of the available models have been developed in patients treated with cytokines, while most of them are fairly complex, including at least five factors. We developed and externally validated a simple model for overall survival (OS) in mRCC. We also studied the recently validated International Database Consortium (IDC) model in our data sets.Methods:The development cohort included 170 mRCC patients treated with sunitinib. The final prognostic model was selected by uni- and multivariate Cox regression analyses. Risk groups were defined by the number of risk factors and by the 25th and 75th percentiles of the model's prognostic index distribution. The model was validated using an independent data set of 266 mRCC patients (validation cohort) treated with the same agent.Results:Eastern Co-operative Oncology Group (ECOG) performance status (PS), time from diagnosis of RCC and number of metastatic sites were included in the final model. Median OS of patients with 1, 2 and 3 risk factors were: 24.7, 12.8 and 5.9 months, respectively, whereas median OS was not reached for patients with 0 risk factors. Concordance (C) index for internal validation was 0.712, whereas C-index for external validation was 0.634, due to differences in survival especially in poor-risk populations between the two cohorts. Predictive performance of the model was improved after recalibration. Application of the mRCC International Database Consortium (IDC) model resulted in a C-index of 0.574 in the development and 0.576 in the validation cohorts (lower than those recently reported for this model). Predictive ability was also improved after recalibration in this analysis. Risk stratification according to IDC model showed more similar outcomes across the development and validation cohorts compared with our model.Conclusion:Our model provides a simple prognostic tool in mRCC patients treated with a targeted agent. It had similar performance with the IDC model, which, however, produced more consistent survival results across the development and validation cohorts. The predictive ability of both models was lower than that suggested by internal validation (our model) or recent published data (IDC model), due to differences between observed and predicted survival among intermediate and poor-risk patients. Our results highlight the importance of external validation and the need for further refinement of existing prognostic models.

Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial

Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285 FINDINGS: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We recorded a higher incidence of grade 3-4 gastrointestinal disorders (182 [30%] vs 48 [8·0%]), haemorrhagic events (32 [5·2%] vs ten [1·7%]), hypertension (81 [13%] vs 20 [3·3%]), fatigue (97 [16%] vs 46 [7·7%]), infections (123 [20%] vs 60 [10%]) and treatment-related fatal adverse events (21 [3·4%] vs nine [1·5%]) in the aflibercept group than in the placebo group. Aflibercept in combination with docetaxel and prednisone given as first-line chemotherapy for men with metastatic castrate-resistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need first-line chemotherapy. Sanofi and Regeneron Pharmaceuticals Inc.