Appearance Of New Lesions Research Articles

Pazopanib in advanced germ cell tumors after chemotherapy failure: results of the open-label, single-arm, phase 2 Pazotest trial

Therapeutic options for patients with chemoresistant germ cell tumors (GCTs) are limited. Pazopanib is a selective tyrosine kinase inhibitor with distinct antiangiogenic activity. We aimed to evaluate pazopanib activity in patients with refractory GCT. In the open-label, single-arm, phase 2 Pazotest study (NCT01743482), patient eligibility included failure of ≥2 platinum-based regimens, and allowed prior high-dose chemotherapy administration. Patients were given pazopanib 800 mg/day until disease progression (PD) or onset of unacceptable toxicity. Measurements of serum tumor markers (STM), computed tomography and FDG-PET were carried out at baseline, after 4 weeks of pazopanib treatment, and every 8 weeks thereafter. PD was defined as increasing levels of STM, increasing size of non-teratomatous masses, or appearance of new lesions. The study primary endpoint was progression-free survival (PFS, H0: 3-month PFS ≤ 10%, H1: ≥25%, α = 5%, β = 20%). Forty-three patients were enrolled from May 2013 to July 2016. The number of prior chemotherapy regimens was: 2 (11.6%), 3 (51.2%), >3 (37.2%). Grade 3 adverse events were observed in six patients (13.9%). Overall, 70.3% of patients had reduced levels of STM after 4 weeks. There were 2 partial responses (4.7%), 19 cases of stable disease, and 16 cases of PD (6 not evaluable by RECIST). The median follow-up duration was 29.6 months. The 3-month PFS probability was 12.8% [95% confidence interval (CI): 5.7%-28.9%]. The 24-month OS probability was 14.2% (95% CI: 6.0%-33.7%). In patients with a >50% decline in STM, the 24-month OS probability was 24.1% (95% CI: 8.3%-69.6%). The small sample size was the major limitation. Despite pazopanib showed potent but short-lived activity in refractory GCT, long-term survival was obtained in a proportion of treated patients. According to the kinetics of pazopanib activity, this drug may be investigated in less pre-treated patients as an optimal bridging therapy preceding and/or combined with salvage chemotherapy.

Translating prostate cancer working group (PCWG) criteria into a quantitative progression biomarker in metastatic castration resistant prostate cancer (mCRPC).

5068 Background: mCRPC is a bone dominant lethal disease. A validated endpoint in mCRPC trials is bone scan progression, which is semi-quantitative and rely on the appearance of new lesions as proposed by the PCWG. The validated automated bone scan index (BSI) quantifies the bone tumor burden as the fraction of total skeletal weight. To build on the current definition of disease progression, we sought to compare the association of time to progression with overall survival (OS) using PCWG criteria and BSI increase. Methods: mCRPC patients (pts) enrolled on trials of agents targeting androgen-receptor (AR) were assessed. Pts were required to have a raw bone scan image for BSI analysis concurrent with disease assessments. The EXINI automated computing platform generated the BSI values. Thresholds for the absolute and relative increase in BSI from 1st follow-up (≤12 weeks) were explored for the time to BSI progression. The association with survival time was computed for each threshold defined time to BSI progression. Kendall’s Tau, derived from the Clayton copula, was used to associate time to BSI progression with survival time, where both endpoints may be censored. Results: A total of 257 pts were assessed, of whom 169 had raw bone scans images needed for the BSI analysis. 90 pts (53%) met progression by PCWG criteria, the association between the time to PCWG progression and OS was 0.52. The association between time to BSI progression and OS was comparable to the PCWG progression when the absolute increase in BSI was 0.6 or more (table below). Conclusions: Progression in bone can be expressed as a single quantitative metric that describes the increase in total disease burden while retaining the same association that PCWG has with OS. These data represent the first steps to a quantitative expression of bone disease progression as a clinical trials endpoint. [Table: see text]

Radical treatment of oligometastatic non-small cell lung cancer: Ready for prime time?

Oligometastatic non-small cell lung cancer (NSCLC), defined as a disease with low metastatic burden and limited organ involvement, is conceived as an intermediate condition between a truly localised disease and a widely metastatic tumour.Traditionally, local ablative therapies (LATs), such as surgery and radiotherapy, have been limited to symptoms' palliation in advanced NSCLC.Several retrospective studies suggest that using local ablative therapy for oligometastatic disease could offer good local control of the disease and improvement in terms of progression-free survival.The first randomised study of local consolidative therapy versus maintenance therapy or observation in oligometastatic NSCLC has been recently published. The results of this phase II trial showed an impressive improvement in median progression-free survival with local therapy and a delay in the appearance of new lesions, suggesting a systemically extended benefit of consolidation therapies.Nevertheless, further confirmation of this evidence with additional future trials is needed to definitively consider the combination of local treatment techniques with novel systemic agents recently approved for NSCLC therapy, such as immune checkpoint inhibitors.

Assessing Response of High-Grade Gliomas to Immune Checkpoint Inhibitors.

Immunotherapeutic agents, especially checkpoint inhibitors, have emerged as the mainstay of therapy for several solid and hematological malignancies. These therapies are under investigation for the treatment of high-grade gliomas and brain metastases. This article reviews the unique challenges encountered when evaluating changes on magnetic resonance imaging (MRI) of glioblastomas seen in response to immunotherapy and checkpoint inhibitors and how to effectively incorporate MRI findings into the response assessment of high-grade gliomas to these emerging therapies. An increase in tumor size or the appearance of new lesions on MRI may represent either an immune-mediated inflammatory response or true tumor progression, which may precede the subsequent stabilization or response of high-grade gliomas to immunotherapy. These MRI findings should not result in the mandatory cessation of immunotherapy in patients with high-grade glioma. Although immunotherapy Response Assessment for Neuro-Oncology criteria have been developed to assist with response assessment of high-grade gliomas to immunotherapy and to provide guidance with treatment decisions, these criteria have not been validated in prospective clinical trials. In patients with brain tumors who are receiving immunotherapy, MRI findings suggestive of disease progression should be evaluated with caution to prevent premature discontinuation of potentially beneficial therapies. Close, clinical monitoring with appropriate short-term, follow-up imaging is often necessary, and histopathological analysis may be required in some cases to confirm disease progression before a decision on continuation of these novel therapies can accurately be made.

Pazopanib (PZP) in germ cell tumors (GCT) after chemotherapy (CT) failure: Final results of the open label, single-group, phase II Pazotest trial.

414 Background: Therapeutic options for patients (pts) with chemoresistant GCT are limited and prognosis is poor. PZP is a potent and selective tyrosine kinase inhibitor (TKI) with distinct antiangiogenic activity. Methods: In Pazotest trial (NCT01743482), pts were given PZP 800 mg/day until disease progression (PD) or unacceptable toxicity. Eligibility included failure of ≥ 2 platinum-based CT, including high-dose (HD)-CT. Baseline serum tumor markers (STM), computed tomography and FDG-PET were repeated after 4 wks and q8 weeks thereafter. The primary endpoint was PFS (H0: 3-m PFS ≤ 10%, H1: ≥ 25%, α = 5%/β = 20%). PD was defined as rising STM, increasing size of nonteratomatous masses (RECIST v1.1), or the appearance of new lesions. Translational analyses included circulating IL8 levels and next generation sequencing of pre-PZP tissue from extreme responders. Results: 43 pts were enrolled from 05/2013 to 07/2016. 35 pts (81.4%) had nonseminoma, 6 (14%) primary mediastinal GCT. The number of failed CT regimen was: 2 (11.6%), 3 (51.2%), > 3 (37.2%). 53.5% had failed HDCT. 39 pts had elevated STM: 56.4% AFP, 43.6% HCG. Grade 3-4 adverse events were seen in 4 pts (increased AST/ALT). 26/39 pts (66.7%) had STM reduction (38.5% > 50% from baseline) after 4 wks. RECIST results: 1 partial response, 20 stable disease, 16 PD (6 not evaluable). 12 (27.9%) had a decreased FDG uptake. Median follow-up was 29.6 months. 3-m PFS was 12.8% (95%CI: 5.7-28.9), median PFS was 2.5 m (IQR: 1.0-3.0). 24-m OS was 14.2% (95%CI: 6.0-33.7). In pts with > 50% STM decline, 24-m OS was 24.1% (95%CI: 8.3-69.6). Univariably, STM was associated with OS (HCG vs AFP: HR: 2.73, 95%CI: 1.24-6.02, p = 0.042). Baseline and +4wks IL8 levels did not predict for PFS/OS. In 2 responding pts, new mutations were found ( FLT3, G846V and RAD50 E448Q classified as damaging; TSC2, R197M and TNF A16V classified as benign). Conclusions: PZP was well tolerated and showed predictable activity, with early but short-living STM decline. Long term survival was obtained in a significant proportion of pts. Based on the present results, PZP may be investigated in earlier disease stages as an optimal bridging therapy preceding salvage curative treatment. Clinical trial information: NCT01743482.

Tratamiento de la esclerosis múltiple remitente recurrente con fingolimod en la práctica clínica habitual

Fingolimod is a selective immunosuppressant that targets the S1P receptor, and is indicated in the treatment of aggressive relapsing-remitting multiple sclerosis (RRMS) and following treatment failure with first-order drugs. To investigate the safety and effectiveness of fingolimod under the conditions of routine clinical practice. We conducted an observational study with prospective follow-up of patients with RRMS who received fingolimod from January 2011 until February 2014. Data assessed were the annualised relapse rate (ARR), disability measured by the Expanded Disability Status Scale (EDSS), magnetic resonance activity and the appearance of side effects. Our sample consisted of 122 patients, 79.5% of them females and with a mean age of 26.8 years. They were classified, according to the last treatment received, as being: naive (aggressive RRMS; n = 17), previous treatment failure (n = 67) and withdrawal of natalizumab due to risk of progressive multifocal leukoencephalopathy (n = 38). After a mean follow-up of 29.9 ± 15.9 months, the ARR and the appearance of new lesions with gadolinium enhancement were reduced in both the naive and the previous treatment failure groups. There were no differences between the various subgroups as regards the progression of EDSS or the time elapsed until the first attack or treatment failure. The risk of treatment failure is higher with a baseline EDSS > 3 (hazard ratio: 4.24; p = 0.001) and presence of IgM oligoclonal bands (hazard ratio: 2.45; p < 0.022). Fingolimod is an effective and well-tolerated drug under conditions of routine clinical practice. Having a baseline EDSS > 3 and IgM oligoclonal bands is predictive of a poor response to fingolimod.

Cancer Imaging in Immunotherapy.

Immune therapeutics are revolutionizing cancer treatments. In tandem, new and confounding imaging characteristics have appeared that are distinct from those typically seen with conventional cytotoxic therapies. In fact, only 10% of patients on immunotherapy may show tumor shrinkage, typical of positive responses on conventional therapy. Conversely, those on immune therapies may initially demonstrate a delayed response, transient enlargement followed by tumor shrinkage, stable size, or the appearance of new lesions. New imaging response criteria such as the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and immune-related Response Criteria (irRC) are being implemented in many trials. However, FDA approval of emerging therapies including immunotherapies still relies on the current RECIST criteria. In this review, we review the traditional and new imaging response criteria for evaluation of solid tumors and briefly touch on some of the more commonly associated immunotherapy-induced adverse events.

Unusual cause of angina in postpercutaneous transluminal coronary angioplasty patient

Among the many causes of Post Percutaneous transluminal coronary angioplasty angina (Post PTCA angina), stent restenosis is the most important cause. Other causes include incomplete revascularization, microvascular angina, and appearance of new lesions. Coronary arterio-venous (A-V) fistula is a rare cause of angina following PTCA. We hereby report a case of post-PTCA angina caused by coronary A-V fistula.

Gamma Knife radiosurgery for brain metastases from pulmonary large cell neuroendocrine carcinoma: a Japanese multi-institutional cooperative study (JLGK1401).

OBJECTIVE In 1999, the World Health Organization categorized large cell neuroendocrine carcinoma (LCNEC) of the lung as a variant of large cell carcinoma, and LCNEC now accounts for 3% of all lung cancers. Although LCNEC is categorized among the non-small cell lung cancers, its biological behavior has recently been suggested to be very similar to that of a small cell pulmonary malignancy. The clinical outcome for patients with LCNEC is generally poor, and the optimal treatment for this malignancy has not yet been established. Little information is available regarding management of LCNEC patients with brain metastases (METs). This study aimed to evaluate the efficacy of Gamma Knife radiosurgery (GKRS) for patients with brain METs from LCNEC. METHODS The Japanese Leksell Gamma Knife Society planned this retrospective study in which 21 Gamma Knife centers in Japan participated. Data from 101 patients were reviewed for this study. Most of the patients with LCNEC were men (80%), and the mean age was 67 years (range 39-84 years). Primary lung tumors were reported as well controlled in one-third of the patients. More than half of the patients had extracranial METs. Brain metastasis and lung cancer had been detected simultaneously in 25% of the patients. Before GKRS, brain METs had manifested with neurological symptoms in 37 patients. Additionally, prior to GKRS, resection was performed in 17 patients and radiation therapy in 10. A small cell lung carcinoma-based chemotherapy regimen was chosen for 48 patients. The median lesion number was 3 (range 1-33). The median cumulative tumor volume was 3.5 cm3, and the median radiation dose was 20.0 Gy. For statistical analysis, the standard Kaplan-Meier method was used to determine post-GKRS survival. Competing risk analysis was applied to estimate GKRS cumulative incidences of maintenance of neurological function and death, local recurrence, appearance of new lesions, and complications. RESULTS The overall median survival time (MST) was 9.6 months. MSTs for patients classified according to the modified recursive partitioning analysis (RPA) system were 25.7, 11.0, and 5.9 months for Class 1+2a (20 patients), Class 2b (28), and Class 3 (46), respectively. At 12 months after GKRS, neurological death-free and deterioration-free survival rates were 93% and 87%, respectively. Follow-up imaging studies were available in 78 patients. The tumor control rate was 86% at 12 months after GKRS. CONCLUSIONS The present study suggests that GKRS is an effective treatment for LCNEC patients with brain METs, particularly in terms of maintaining neurological status.

Successful Treatment of Pyoderma Gangrenosum after Augmentation Mastopexy Using Vacuum Therapy.

Pyoderma gangrenosum (PG) is a rare, severe, destructive neutrophilic dermatosis characterized by a progressive, necrotizing process after skin injury. Its cause is still unknown, and diagnosis represents a challenge when ulcers are seen after surgery. Bacterial infection is not found in the wounds. Patients exhibit "pathergy" with the appearance of new lesions after local trauma such as surgical procedures, debridements, and wound care, suggesting altered inflammatory response. The objective of this study was to review the literature and report a case of PG that was satisfactorily treated with vacuum therapy (vacuum-assisted closure [VAC]). A 19-year-old healthy patient presented with skin ulceration 4 days after augmentation mastopexy, progressing to extensive necrosis. On the eighth day, she underwent debridement and implant removal. Two days later, the necrotic process was again evident and progressed, resulting in a significant increase in wound size, with each wound reaching 20 × 25 cm. Intense and diffuse neutrophilic exudate and areas of necrosis were present. Systemic corticosteroids and VAC under general anesthesia were initiated 5 days after the second surgery. From the fourth VAC session, some adherence between the mammary gland and pectoral muscles was visible, so deep sutures avoiding the dermis were placed to direct wound closure. PG is a life-threatening complication with devastating outcomes. Early diagnosis is critical. Although some reported cases needed up to 2 years for wound closure, in this case, VAC therapy allowed the patient to be discharged after only 42 days and permitted wound closure without the need for skin grafts.

Coronary Angioplasty and Stenting in Patients Older Than 80 Years: Immediate and Long-Term Results

to assess immediate and long-term results of coronary angioplasty and stenting in patients older than 80 years - a high risk group in view of the severity of concomitant pathology and extent of coronary atherosclerosis. We conducted retrospective analysis of data from 167 patients older than 80 years (mean age 81.43+/-2.14 years) subjected to percutaneous coronary intervention from 2006 to 2013 (3.2% from total number of patients). Multivessel involvement was present in 128 patients (76.6%) including 20 (12.4%) with stenosis in left main coronary artery. In 215 out of 270 stenotic lesions complicated stenoses type B2, C were detected . Number of chronic occlusions was 31 (10.3%) out of 301 treated lesions. There were 46 patients (27.5%) with diabetes, 16 (9.6%) with chronic anemia, 35 (21%) with chronic renal failure. Concomitant multifocal lesions in other arterial beds were found in 67 patients (40.1%). Radial, femoral, and combined femoral-radial accesses was used in 157 (94%), 5 (3%), and 5 (3%) patients, respectively. Results were studied with the help of automated system of digital computer angiography and intracoronary ultrasound. Long-term results were assessed with the help of questioning, control angiography, and echocardiography. Immediate angiographic and clinical success was achieved in 97 and 94% of cases, respectively. Revascularization was complete in 62.2% of cases. Hospital mortality was 0.7%. Major adverse cardiac events (MACE) were registered in 4.6 and 22.4% of patients during periods of 30 days and >24 months, respectively. Stent thrombosis was diagnosed in 3 cases (1.79%) in 6-18 months after intervention. Repeat revascularization in remote period was performed in 20 patients (12.8%), in 8 of them because of appearance of new lesion. Survival after 40 months was 91%, survival without MACE after 60 months was 74.8%. Complications related to access artery was 4.2% (1.9% in 157 transradial Interventions). According of logistic regression analysis, the following predictors of MACE in remote period were determined: initial depressed left ventricular function, diabetes mellitus, and lesion length >35 mm. Coronary angioplasty and stenting is an effective method of treatment of coronary atherosclerosis in patients older than 80 years with acceptable rate of MACE. Radial access lowers rate of access related vascular complications.

Natural history of nonenhancing lesions incidentally detected during the diagnosis of hepatocellular carcinoma

Incidental detection of nonenhancing tumors during imaging studies for patients with classical hepatocellular carcinoma is not unusual. These tumors are considered to have a high potential of malignant transformation. The aim of this study was to clarify the natural history of such tumors. In 93 patients who underwent liver resection for hepatocellular carcinoma, 138 nonenhancing or enhancing nodules without washout were detected during dynamic computed tomography and observed without further treatments. We subsequently compared the cumulative occurrence of new hepatocellular carcinomas to that of the malignant transformation of these lesions. We additionally compared the appearance of new hepatocellular carcinomas between the patients with (n = 93) and without (n = 782) nonenhancing lesions or enhancing lesions without washout. After a median follow-up period of 0.7years (range, 0.2-6.8), the median intervals from resection to the appearance of new classical hepatocellular carcinoma and malignant transformation of nonenhancing lesions or enhancing lesions without washout were 1.6years (95% confidence interval, 1.2-1.9) and 2.3years (1.9-6.8years; P = .002), respectively. On the other hand, the median intervals from resection to the appearance of new lesions in patients with and without nonenhancing lesions or enhancing lesions without washout were 1.6years (95% confidence interval, 1.2-1.9) and 2.1years (1.9-2.1years; P = .031), respectively. During the natural history of nonenhancing lesions and enhancing lesions without washout that coexist with hepatocellular carcinoma, new lesions often develop prior to the malignant transformation of these lesions. This should be considered a risk factor for the appearance of new hepatocellular carcinoma.

New systemic treatments to improve survival in melanoma patients whose brain metastases are controlled by an on demand Gamma-knife radiosurgical strategy.

9573Background: On demand Gamma - knife (OD -GK), ie repeated sessions as many times as required by the appearance of new lesion(s) upon imaging follow-up, is one of the best strategies to control ...

Characterization of patients treated with a programmed cell death protein 1 inhibitor (anti-PD-1) past RECIST progression from a metastatic non-small cell lung cancer (mNSCLC) trial.

3000 Background: Anti-PD-1 monoclonal antibodies are immunotherapy agents that block T cell inhibitory signal pathways. Anecdotal cases have been reported of clinically important decrease in tumor size following initial evidence of RECIST-defined disease progression. We describe the findings in patients with treatment past RECIST-defined progression (TPP) observed in a trial of mNSCLC patients receiving an anti-PD-1. Methods: Data from a trial evaluating an anti-PD-1 for the treatment of patients with mNSCLC who progressed after platinum- doublet chemotherapy, demonstrating a clinical benefit for an anti-PD-1, was evaluated. Per protocol, patients were allowed to receive TPP if they were not experiencing rapid disease progression, had stable performance status, and written informed consent was obtained. We identified anti-PD-1-treated patients with TPP in this study and evaluated the changes in tumor burden following RECIST-defined progression in these patients. Results: In total, 71 patients received TPP with an anti-PD-1 and their best overall responses by RECIST v1.1 were progressive disease in 35 (49%), stable disease in 23 (32%), and partial response (PR) in 13 (18%); the PR rate was similar in patients with and without TPP. Among patients with TPP, RECIST-defined progression was based on an increase in the sum of longest diameter (SLD) of target lesions (TLs) in 37 (52%) patients, the appearance of new lesions (NLs) in 33 (46%), and/or unequivocal progression of non-target lesions (NTLs) in 28 (39%) patients. Among the TPP patients, 4 patients (5.6%) experienced additional tumor shrinkage. One patient with RECIST-defined progression based on ≥ 20% increase in SLD of TLs and three patients based on NLs or unequivocal progression of NTLs demonstrated a subsequent ≥ 30% decrease in SLD as compared to nadir. Conclusions: Our evaluation suggests that anti-PD-1-treated patients with mNSCLC generally do not benefit from TPP. The risks of continued treatment should be considered in light of the low likelihood of tumor shrinkage with TPP with an anti-PD-1 agent.

Stabilization of the disease as an important factor in the evaluation of the effectiveness of treatment and prognosis of survival for cancer patients

Currently, the effectiveness of treatment is assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The stabilization of the disease is the one of the results of the treatment. This term means a slight growth or regression of the tumor without the appearance of new lesions, when it is impossible to assign these changes neither to the progression of the disease nor to partial regression, but in any case stabilization of disease is evaluated as ineffective treatment. But the stabilization of the disease often leads to the improvement of the quality of life, slowdown in the growth of the tumor and metastasis and thereby to the win in terms of life expectancy. The purpose of the study. A study of the concept of ‘stabilization of the disease ’ as a criterion that determines the control of tumor growth. Methods. There was performed an analysis of various scientific works on the study of the efficiency of the treatment of solid tumors: ovarian cancer, small-cell lung cancer (SCLC), non small-cell lung cancer (NSCLC), colon cancer, prostate cancer, breast cancer. Conclusion. Stabilization of the disease is an important criterion for the evaluation of the antitumor treatment in patients and has the important prognostic value.

Continuous epidermal growth factor receptor-tyrosine kinase inhibitor administration in primary lung adenocarcinoma patients harboring favorable mutations with controlled target lung tumors dose not hinder survival benefit despite small new lesions

BackgroundIn this study, we investigated the efficacy of continuous epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) administration in lung adenocarcinoma patients harboring favorable mutations regarding the progressive disease (PD) status with appearance of indolent new lesions. MethodsFrom June 2010 to October 2012, 102 patients with lung adenocarcinoma, harboring favorable EGFR mutations and treated with EGFR-TKI were analyzed. Definite new lesions were detected during EGFR-TKI therapy, even though the primary target tumors were controlled. ResultsOf the 102 patients, 57 continued and 45 discontinued EGFR-TKI therapy. The median overall survival was 529 days for the discontinuation group and 791 days for the continuation group (p = 0.0197). Median survival time after the discontinuation of EGFR-TKI was 181 days and 115 days in the discontinuation and continuation groups, respectively (p = 0.1776), whereas median survival time after the appearance of indolent new lesions was 204 days and 262 days, respectively (p = 0.0237). ConclusionContinuous EGFR-TKI administration in favorable EGFR-mutative lung adenocarcinoma patients with controlled primary tumors did not hinder the survival benefit, despite the appearance of new lesions.

Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests

Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.

Joint model for left-censored longitudinal data, recurrent events and terminal event: Predictive abilities of tumor burden for cancer evolution with application to the FFCD 2000-05 trial.

In oncology, the international WHO and RECIST criteria have allowed the standardization of tumor response evaluation in order to identify the time of disease progression. These semi-quantitative measurements are often used as endpoints in phase II and phase III trials to study the efficacy of new therapies. However, through categorization of the continuous tumor size, information can be lost and they can be challenged by recently developed methods of modeling biomarkers in a longitudinal way. Thus, it is of interest to compare the predictive ability of cancer progressions based on categorical criteria and quantitative measures of tumor size (left-censored due to detection limit problems) and/or appearance of new lesions on overall survival. We propose a joint model for a simultaneous analysis of three types of data: a longitudinal marker, recurrent events, and a terminal event. The model allows to determine in a randomized clinical trial on which particular component treatment acts mostly. A simulation study is performed and shows that the proposed trivariate model is appropriate for practical use. We propose statistical tools that evaluate predictive accuracy for joint models to compare our model to models based on categorical criteria and their components. We apply the model to a randomized phase III clinical trial of metastatic colorectal cancer, conducted by the Fédération Francophone de Cancérologie Digestive (FFCD 2000-05 trial), which assigned 410 patients to two therapeutic strategies with multiple successive chemotherapy regimens.

SIRFLOX: Differences in site of first progression between mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 ± bev + selective internal radiation therapy (SIRT) in first-line patients (pts) with metastatic colorectal cancer (mCRC).

637 Background: SIRFLOX, an international multi-centre open-label RCT in first-line pts with non-resectable, liver-only or liver-dominant mCRC, showed that compared to FOLFOX (± bev) chemotherapy alone [arm A] FOLFOX (± bev) plus SIRT using Y-90 resin microspheres [arm B] did not improve overall PFS (median 10.2 v 10.7 months arm A v B, HR: 0.93; 95% CI 0.77–1.12; p = 0.429). However, liver PFS by competing risk analysis was improved with the addition of SIRT (median 12.6 v 20.5 months in arm A v B, HR: 0.69; 95% CI 0.55–0.90; p = 0.002). The current analysis examines patterns of disease progression and potential impact on the primary study endpoint. Methods: Site and pattern (intra/extra-hepatic) of first progression, and whether progression was due to growth of existing lesions or the appearance of new lesions, was judged by an independent reader blinded to study arm. Results: From Oct 2006 to Apr 2013, 530 pts were randomised (arm A, n = 263; arm B, n = 267); 212 (40%) had extra-hepatic metastases at study entry; 292 (55%) were stratified to receive bev. As of 31 Jan 2015, the total number of patients with disease progression in arm A v B were 178 and 166, respectively. The site of first progression was more frequently in the liver (± other sites) in arm A v B (92.1% v 72.3%; p &lt; 0.001). Conversely, site of first progression was less frequent in the lung (± other sites) in arm A v B (19.1% v 42.8%; p &lt; 0.001). A higher proportion of first progression occurred in the liver alone in arm A v B (77.0% v 52.4%; p &lt; 0.001). Conversely, a lower proportion of first progression occurred only in non-liver sites, primarily lung, in arm A v B (7.9% v 47.7%; p &lt; 0.001). Of patients with first progression in the liver, a higher proportion occurred in existing liver lesions (± extrahepatic sites) in arm A v B (72.5% v48.2%; p &lt; 0.001). Conclusions: The addition of SIRT to FOLFOX chemotherapy alone (± bev) reduced the frequency at which first disease progression occurred in the liver. Where first progression did occur in the liver, the addition of SIRT led to this more frequently being due to the appearance of lesions not evident on baseline imaging. Clinical trial information: NCT00724503.

Tumor response in the CLARINET study of lanreotide depot vs. placebo in patients with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

434 Background: In the CLARINET study, significant improvement in progression-free survival (primary endpoint) was reported in patients (pts) treated with lanreotide depot (LAN), a long-acting somatostatin analog, for moderately- or well-differentiated, nonfunctioning, locally advanced or metastatic GEP-NETs. A favorable safety profile was also observed. This retrospective analysis presents tumor response from CLARINET. Methods: Pts were randomized to LAN 120 mg (n=101) or PBO (n=103) once every 28 days for 96 weeks. Tumor response was evaluated centrally using RECIST version 1.0. Pts’ tumors were measured by sum of the longest diameter (SLD) of target lesions (TLs). Change was calculated for each pt’s SLD from baseline to last available post-baseline assessment. Tumor response was classified as complete response (CR): disappearance of all TLs and non-target lesions (NTLs) and no new lesions; partial response (PR): ≥30% decrease in SDL and no progressive disease (PD); stable disease (SD): not meeting criteria for CR/PR or PD; PD: ≥20% increase in SLD from baseline or nadir, unequivocal progression of NTLs or appearance of new lesions. The remaining pts were not evaluable (NE) for response. Results: 101 pts treated with LAN and 103 pts treated with PBO were assessed for tumor response. Among pts receiving LAN, 64% (65/101) demonstrated SD compared to 43% (44/103) of pts receiving PBO (Table). An additional 2 pts in the LAN group achieved a PR. Similar trends were observed in pts with pancreas and midgut origin tumors. Conclusions: A clinical benefit (defined as CR+PR+SD) of 66% (67/101) was observed with single agent LAN vs 43% (44/103) with PBO in the CLARINET population, further supporting the clinical efficacy of LAN. Clinical trial information: NCT00353496. [Table: see text]