Treatment results and prognostic factors in primary thyroid lymphoma patients: a rare cancer network study.

Background: This study analyzed prognostic factors and treatment outcomes of primary thyroid lymphoma. Patients and Methods: Data were retrospectively collected for 87 patients (53 stage I and 34 stage II) with median age 65 years. Fifty-two patients were treated with single modality (31 with chemotherapy alone and 21 with radiotherapy alone) and 35 with combined modality treatment. Median follow-up was 51 months. Results: Sixty patients had aggressive lymphoma and 27 had indolent lymphoma. The 5- and 10-year overall survival (OS) rates were 74% and 71%, respectively, and the disease-free survival (DFS) rates were 68% and 64%. Univariate analysis revealed that age, tumor size, stage, lymph node involvement, B symptoms, and treatment modality were prognostic factors for OS, DFS, and local control (LC). Patients with thyroiditis had significantly better LC rates. In multivariate analysis, OS was influenced by age, B symptoms, lymph node involvement, and tumor size, whereas DFS and LC were influenced by B symptoms and tumor size. Compared with single modality treatment, patients treated with combined modality had better 5-year OS, DFS, and LC. Conclusions: Combined modality leads to an excellent prognosis for patients with aggressive lymphoma but does not improve OS and LC in patients with indolent lymphoma.

Medulloblastomas in adults: prognostic factors and lessons from paediatrics.

Purpose of reviewMedulloblastomas are very rare in adults. Usual treatment consists of craniospinal radiation with or without chemotherapy. Current efforts focus on a better understanding of tumour biology, stratifying patients into risk groups and adapting treatment accordingly. This review discusses clinical and new molecular risk factors that will help to optimize treatment in adult medulloblastoma patients.Recent findingsThe clinical risk stratification should be complemented with new molecular prognostic markers. Gene-expression profiling has permitted identification of four to six molecular medulloblastoma subgroups. The WNT subgroup shows overexpression of genes of the WNT/wingless signalling pathway with frequent mutations of the CNNTB1 gene, loss of chromosome 6 and accumulation of nuclear beta-catenin, and is most often seen in children with medulloblastomas of classical histology. This variant has a good prognosis. Activation of the sonic hedgehog pathway with frequent mutations of the PTCH and SUFU genes, loss of 9q, and positivity for GLI1 and SFRP1 is more frequent in children less than 3 years old and in adults, commonly associated with desmoplastic histology. Other subgroups are not so well defined and have overlapping characteristics, but MYC/MYCN amplification, 17q gain and, large cell/anaplastic histology are factors of poor prognosis.SummaryNew molecular subgroups will help tailor treatment and further develop new targeted therapies. Prospective and ideally randomized trials should be performed in adults, including risk stratification by molecular markers, to identify optimal treatment for each risk group.

Clinical Prognostic Factors Predicting Outcomes Of Patients With Recurrent Gbm And Nomograms

BACKGROUND: Prognostic models and nomograms were recently developed to predict survival of patients with newly diagnosed glioblastoma multiforme (GBM).1 To improve predictions, models should be updated with the most recent patient and disease information. Nomograms predicting patient outcome at the time of disease progression are required. METHODS: Baseline information from 299 patients with recurrent GBM recruited in 8 phase I or II trials of the EORTC Brain Tumor Group was used to evaluate clinical parameters as prognosticators of patient outcome. Univariate (log rank) and multivariate (Cox models) analyses were made to assess the ability of patients' characteristics (age, sex, performance status [WHO PS], and MRC neurological deficit scale), disease history (prior treatments, time since last treatment or initial diagnosis, and administration of steroids or antiepileptics) and disease characteristics (tumor size and number of lesions) to predict progression free survival (PFS) and overall survival (OS). Bootstrap technique was used for models internal validation. Nomograms were computed to provide individual patients predictions. RESULTS: Poor PS and more than 1 lesion had a significant prognostic impact for both PFS and OS. Antiepileptic drug use was significantly associated with worse PFS. Larger tumors (split by the median of the largest tumor diameter >42.5 mm) and steroid use had shorter OS. Age, sex, neurologic deficit, prior therapies, and time since last therapy or initial diagnosis did not show independent prognostic value for PFS or OS. CONCLUSIONS: This analysis confirms that PS but not age is a major prognostic factor for PFS and OS. Multiple or large tumors and the need to administer steroids significantly increase the risk of progression and death. Nomograms at the recurrence could be used to obtain accurate predictions for the design of new targeted therapy trials or retrospective analyses. (1. T. Gorlia et al., Nomograms for predicting survival of patients with newly diagnosed glioblastoma. Lancet Oncol 9 (1): 29-38, 2008.)

Prognostic factors and role of adjuvant therapies in the management of parasagittal meningiomas

L'objectif du présent travail de thèse est d'analyser rétrospectivement la série de méningiomes parasagittaux traités au CHUV, soit par traitements simples ou combinés (chirurgie et / ou radiochirurgie et radiothérapie fractionnée), afin de déterminer les facteurs qui influencent leur pronostic. Méthode: Entre Janvier 1999 et mai 2007, 37 méningiomes parasagittaux ont été traités dans notre centre. Nous avons analysé de manière rétrospective les différents paramètres du traitement de ces méningiomes ainsi que leur emplacement le long du sinus sagittal supérieur, leur volume, leur grade histologique et le degré de résection ainsi que le sexe et l'âge du patient afin de comprendre les facteurs qui influencent leur histoire naturelle. Résultats: Le suivi médian était de 6,7 ans (2,4 -12 ans). Les grades histologiques et le degré de résection tumorale (Simpson) étaient répartis uniformément le long du sinus sagittal supérieur. Le taux actuariel de contrôle global des tumeurs était de 65,9%. L'analyse de régression montre que le grade tumoral et le degré de résection sont deux facteurs extrêmement importants pour déterminer le contrôle tumoral (p <0,002 et ρ <0,008). La localisation le long du sinus sagittal supérieur a montré une baisse du taux de contrôle dans le tiers postérieur (p <0,002). Le sexe, l'âge et le volume de la tumeur n'étaient quand à eux pas des facteurs significatifs. Par ailleurs, et de façon inattendue, dans notre série, la proportion du traitement adjuvant a été beaucoup plus élevée que dans les séries décrites jusqu'à maintenant (39% vs 7%) mais avec un taux de contrôle similaire et diminution de la morbidité et la mortalité. Conclusions: Dans notre série, le grade histologique et le degré de résection tumorale (Simpson) sont des facteurs indépendants de récidive et de contrôle tumoral. Fait intéressant, l'emplacement dans le tiers postérieur du sinus sagittal supérieur semble être un autre facteur indépendant de récidive. Afin d'éviter les morbidités importantes liées à la chirurgie nous préconisons une utilisation précoce de traitements adjuvants pour les tumeurs grade histologique élevé et pour les tumeurs situées dans la partie postérieure du sinus sagittal supérieur

Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

New prognostic factors and calculators for outcome prediction in patients with recurrent glioblastoma: A pooled analysis of EORTC Brain Tumour Group phase I and II clinical trials.

BACKGROUND: Prognostic models have been developed to predict survival of patients with newly diagnosed glioblastoma (GBM). To improve predictions, models should be updated with information at the recurrence. We performed a pooled analysis of European Organization for Research and Treatment of Cancer (EORTC) trials on recurrent glioblastoma to validate existing clinical prognostic factors, identify new markers, and derive new predictions for overall survival (OS) and progression free survival (PFS).¦METHODS: Data from 300 patients with recurrent GBM recruited in eight phase I or II trials conducted by the EORTC Brain Tumour Group were used to evaluate patient's age, sex, World Health Organisation (WHO) performance status (PS), presence of neurological deficits, disease history, use of steroids or anti-epileptics and disease characteristics to predict PFS and OS. Prognostic calculators were developed in patients initially treated by chemoradiation with temozolomide.¦RESULTS: Poor PS and more than one target lesion had a significant negative prognostic impact for both PFS and OS. Patients with large tumours measured by the maximum diameter of the largest lesion (⩾42mm) and treated with steroids at baseline had shorter OS. Tumours with predominant frontal location had better survival. Age and sex did not show independent prognostic values for PFS or OS.¦CONCLUSIONS: This analysis confirms performance status but not age as a major prognostic factor for PFS and OS in recurrent GBM. Patients with multiple and large lesions have an increased risk of death. With these data prognostic calculators with confidence intervals for both medians and fixed time probabilities of survival were derived.

Natalizumab versus Interferon B-1b to prevent CDMS in patients with CIS and poor prognostic factors: research protocol

About 85% of multiple sclerosis (MS) cases start as clinically isolated syndrome (CIS).When patients present with a CIS, clinicians face with many questions, most of themrelated with prognosis and treatment. Thereby, patients with CIS have been focus ofresearch. Several studies have demonstrated a relationship between positive IgM lipidspecific oligoclonal band pattern in CSF and higher lesion load on MRI brain scan, higher number of relapses and greater disability, even at the first stages of the disease. On the other hand, no studies have used this previous evidence to treat with more aggressive disease modifying therapy in initial stages of disease course to prevent the earlier axonal damage. The aim of this study is to assess the most effective approved treatment for MS and current therapy for CIS patients presenting high risk to develop CDMS and with biomarkers of poor prognosis. Among this group of patients any disease activity will eventually lead to disability. Therefore, the earlier the treatment is initiated, the more effective to prevent disability will be. It is considered that “time lost is brain lost” and since once damage is established, there is no therapy to be regained later on. In this phase III clinical trial, 172 patients will be randomized 1:1 to receive Interferon β-1b or natalizumab over 96 weeks. Time to develop clinical definitive multiple sclerosis (CDMS) will be included as primary endpoint. Other secondary endpoints will include clinical data, magnetic resonance imaging (MRI) measurements and quality of life tests

Natalizumab versus Interferon B-1b to prevent CDMS in patients with CIS and poor prognostic factors: research protocol

About 85% of multiple sclerosis (MS) cases start as clinically isolated syndrome (CIS).When patients present with a CIS, clinicians face with many questions, most of themrelated with prognosis and treatment. Thereby, patients with CIS have been focus ofresearch. Several studies have demonstrated a relationship between positive IgM lipidspecific oligoclonal band pattern in CSF and higher lesion load on MRI brain scan, higher number of relapses and greater disability, even at the first stages of the disease. On the other hand, no studies have used this previous evidence to treat with more aggressive disease modifying therapy in initial stages of disease course to prevent the earlier axonal damage. The aim of this study is to assess the most effective approved treatment for MS and current therapy for CIS patients presenting high risk to develop CDMS and with biomarkers of poor prognosis. Among this group of patients any disease activity will eventually lead to disability. Therefore, the earlier the treatment is initiated, the more effective to prevent disability will be. It is considered that “time lost is brain lost” and since once damage is established, there is no therapy to be regained later on. In this phase III clinical trial, 172 patients will be randomized 1:1 to receive Interferon β-1b or natalizumab over 96 weeks. Time to develop clinical definitive multiple sclerosis (CDMS) will be included as primary endpoint. Other secondary endpoints will include clinical data, magnetic resonance imaging (MRI) measurements and quality of life tests

Primary breast lymphoma: patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study.

BACKGROUND: To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). METHODS: Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12-55 Gy). RESULTS: Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. CONCLUSION: The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently.

Reversible cerebral vasoconstriction syndrome identification of prognostic factors.

OBJECT: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a clinical and radiological entity characterized by thunderclap headaches, a reversible segmental or multifocal vasoconstriction of cerebral arteries with or without focal neurological deficits or seizures. The purpose of this study is to determine risk factors of poor outcome in patients presented a RCVS. METHODS: A retrospective multi-center review of invasive and non-invasive neurovascular imaging between January 2006 and January 2011 has identified 10 patients with criterion of reversible segmental vasoconstriction syndrome. Demographics data, vascular risks and evolution of each of these patients were analyzed. RESULTS: Seven of the ten patients were females with a mean age of 46 years. In four patients, we did not found any causative factors. Two cases presented RCVS in post-partum period between their first and their third week after delivery. The other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was found as the causative factor in two patient, Sumatriptan identified in one patient while cyclosporine was the causative agent in also one patient. The mean duration of clinical follow-up was 10.2 months (range: 0-28 months). Two patients had neurological sequelae: one patient kept a dysphasia and the other had a homonymous lateral hemianopia. We could not find any significant difference of the evolution between secondary RCVS and idiopathic RCVS. The only two factors, which could be correlated to the clinical outcome were the neurological status at admission and the presence of intraparenchymal abnormalities (ischemic stroke, hematoma) in brain imaging. CONCLUSIONS: Fulminant vasoconstriction resulting in progressive symptoms or death has been reported in exceptional frequency. Physicians had to remember that such evolution could happen and predict them by identifying all factors of poor prognosis (neurological status at admission, the presence of intraparenchymal abnormalities).

Subjective perceptions as prognostic factors of time to fitness for work during a 4-year period after inpatient rehabilitation for orthopaedic trauma.

INTRODUCTION: Time to fitness for work (TFW) was measured as the number of days that were paid as compensation for work disability during the 4 years after discharge from the rehabilitation clinic in a population of patients hospitalised for rehabilitation after orthopaedic trauma. The aim of this study was to test whether some psychological variables can be used as potential early prognostic factors of TFW. MATERIAL AND METHODS: A Cox proportional hazards model was used to estimate the associations between predictive variables and TFW. Predictors were global health, pain at hospitalisation and pain decrease during the stay (all continuous and standardised by subtracting the mean and dividing by two standard deviations), perceived severity of the trauma and expectation of a positive evolution (both binary variables). RESULTS: Full data were available for 807 inpatients (660 men, 147 women). TFW was positively associated with better perceived health (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.13-1.19), pain decrease (HR 1.46, 95% CI 1.30-1.64) and expectation of a positive evolution (HR 1.50, 95% CI 1.32-1.70) and negatively associated with pain at hospitalisation (HR 0.67, 95% CI 0.59-0.76) and high perceived severity (HR 0.72, 95% CI 0.61-0.85). DISCUSSION: The present results provide some evidence that work disability during a four-year period after rehabilitation may be predicted by prerehabilitation perceptions of general health, pain, injury severity, as well as positive expectation of evolution.

Prognostic factors for progression-free and overall survival in advanced biliary tract cancer.

BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.