The feasibility of folate receptor alpha- and HER2-targeted intraoperative fluorescence-guided cytoreductive surgery in women with epithelial ovarian cancer: A systematic review.

BACKGROUND: Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging. OBJECTIVE: To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC. METHODS: PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively. RESULTS: All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%-77% and false positives between 10%-25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study. CONCLUSION: FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit.

Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).

BACKGROUND: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.

Lhermitte sign and myelopathy after irradiation of the cervical spinal cord in radiotherapy treatment of head and neck cancer.

BACKGROUND AND PURPOSE: The goal of this work was to examine toxicity and risk factors after irradiation of the cervical spinal cord. PATIENTS AND METHODS: A total of 437 patients irradiated for a laryngeal and oropharyngeal carcinoma were eligible (median follow-up 27 months). Spinal cord contouring was defined differently over time as anatomically defined spinal cord area (SCA) and the spinal cord on CT (SC) with a margin of 3 or 5 mm (SCP3/SCP5). RESULTS: None developed chronic progressive radiation myelopathy (CPRM) (maximum spinal dose 21.8-69 Gy); 3.9% (17/437) developed a Lhermitte sign (LS) with a median duration of 6 months (range 1-30 months) and was reversible in all patients. Risk factors for developing LS were younger age (52 vs. 61 years, p < 0.001), accelerated RT (12/17 patients, p < 0.005), and dose-volume relationships for SCA with ≥ 45 Gy of 14.15 cm(3) and 7.9 cm(3) for patients with and without LS, respectively. CONCLUSION: LS is more frequently observed in younger patients and in patients treated with accelerated radiotherapy. A dose-volume relationship was seen for V45 in the case of SCA. For higher doses, no clear dose-volume relationships were observed.

Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation.

Increasing evidence suggests a role for the immune system in amyotrophic lateral sclerosis (ALS). To determine the extent of the immune activation in ALS we analyzed the expression and cellular distribution of components of innate and adaptive immunity in spinal cord (SC) and motor cortex (MCx) from patients with rapid and slow sporadic ALS and controls. High levels of mRNA and protein of classical complement pathway, C1q and C4, as well as the downstream complement components C3 and C5b-9 were found in all ALS samples. Furthermore, we found higher numbers of activated microglia, reactive astrocytes, dendritic cells (DCs) and CD8(+) T-cells in ALS than in control tissue. Rapid ALS cases had more dendritic cells than slow ALS cases, whereas slow ALS cases had more activated microglia than rapid cases. Our findings demonstrate a persistent and prominent activation of both innate and adaptive immunity in ALS. We propose a complement-driven immune response which may contribute to the progression of the inflammation and ultimately lead to even more motor neuron injury.

Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis.

OBJECTIVE: To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design. METHODS: Between April 2005 and January 2007, 163 ALS patients received VPA 1,500mg or placebo daily. Primary end point was survival. Secondary outcome measure was decline of functional status measured by the revised ALS Functional Rating Scale. Analysis was by intention to treat and according to a sequential trial design. This trial was registered with ClinicalTrials.gov (number NCT00136110). RESULTS: VPA did not affect survival (cumulative survival probability of 0.72 in the VPA group [standard error (SE), 0.06] vs 0.88 in the placebo group [SE, 0.04] at 12 months, and 0.59 in the VPA group [SE, 0.07] vs 0.68 in the placebo group [SE, 0.08] at 16 months) or the rate of decline of functional status. VPA intake did not cause serious adverse reactions. INTERPRETATION: Our finding that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS has implications for future trials with histone deacetylase inhibitors in ALS and other neurodegenerative diseases. The use of a sequential trial design allowed inclusion of only half the number of patients required for a classic trial design and prevented patients from unnecessarily continuing potentially harmful study medication.

Upper motor neuron and extra-motor neuron involvement in amyotrophic lateral sclerosis: a clinical and brain imaging review.

There is an ongoing discussion whether ALS is primarily a disease of upper motor neurons or lower motor neurons. We undertook a review to assess how new insights have contributed to solve this controversy. For this purpose we selected relevant publications from 1995 onwards focussing on (1) primary targets and disease progression in ALS and variants of ALS, (2) brain imaging markers for upper motor neuron lesion, and (3) evidence for ALS being a multisystem disorder. Clinically, upper motor and lower motor neuron symptoms can occur in any order over time. Brain imaging markers show upper motor neuron involvement in early disease. Overlap syndromes of ALS and dementia, and involvement of autonomic and sensory nerves occur frequently. PET/SPECT scans, functional MRI and voxel based morphometry studies clearly show abnormalities in extra-motor areas of the brain. Pathologically, the 43 kDa TAR DNA-binding protein (TDP-43) provides a clue to these overlapping disorders. In conclusion, evidence accumulates that ALS is a multisystem disorder rather than a pure lower and/or upper motor neuron disorder.

Interpretation of electrodiagnostic findings in sporadic progressive muscular atrophy.

OBJECTIVE: We present the electrophysiologic data at baseline of 37 patients who were included in our prospective study on sporadic adult-onset progressive muscular atrophy (PMA). The aim was to correlate electrophysiological signs of lower motor neuron (LMN) loss with clinical signs of LMN loss, and to determine the prognostic value of the distribution of electrophysiological abnormalities in patients who presented clinically with only lower motor neuron signs. METHODS: Thirty-seven patients, who met our inclusion criteria for a prospective study on sporadic adult-onset PMA, underwent extensive standardized electrophysiological examination at baseline, consisting of concentric needle EMG in three regions (cervical, thoracic and lumbosacral) and standardized nerve conduction studies. RESULTS: Denervation on needle EMG was found in 88 % of clinically affected and in 40 % of clinically unaffected limb regions. All patients with a segmental or distal phenotype at baseline who developed generalized weakness had denervation in the thoracic region. Motor nerve conduction abnormalities were found in a substantial number of nerves and included reduced CMAP amplitude, increased distal motor latency, decreased motor conduction velocity, and F-wave abnormalities. Signs of demyelination and sensory nerve conduction abnormalities were rare. CONCLUSIONS: Our electrophysiological data in patients recently diagnosed with sporadic progressive muscular atrophy are consistent with widespread LMN loss. Progression in patients with a segmental or distal onset of PMA may be likely if denervation is found in clinically unaffected regions, including the thoracic region.

Disease course and prognostic factors of progressive muscular atrophy.

OBJECTIVE: To investigate the natural history and prognostic factors in patients with nonhereditary, adult-onset progressive muscular atrophy. DESIGN: Inception cohort conducted for 18 months. Settings Three university hospitals in the Netherlands (referral centers for neuromuscular diseases). Patients Thirty-seven consecutive patients newly diagnosed (onset of weakness <4 years) with progressive muscular atrophy enrolled between 1998 and 2001. MAIN OUTCOME MEASURES: Disease progression was measured at 0, 3, 6, 9, 12, 15, and 18 months by the Medical Research Council sum score, number of affected limb regions, and the Amyotrophic Lateral Sclerosis Functional Rating Scale score. Multivariate linear regression analysis was used to identify predictors of poor outcome. Clinical features and classification of phenotype during follow-up were evaluated. Survival analysis was planned after data collection, performed 5 years after the end of the study. RESULTS: Significant decline of muscle strength (mean, 6.01 Medical Research Council sum score points [95% confidence interval [CI], 3.84-8.18]; P value <.001) and significant increase in the number of affected regions (mean, 0.53 affected region [95% CI, 0.42-0.65]; P value <.001) and functional impairment (mean, 1.85 Amyotrophic Lateral Sclerosis Functional Rating Scale score points [95% CI, 1.38-2.33]; P value <.001) were found. Vital capacity (VC) at baseline and decrease of VC during the first 6 months were significantly associated with outcome. Median survival duration after initial weakness was 56 months. CONCLUSIONS: This study shows that patients with progressive muscular atrophy have a relentlessly progressive disease course. Patients with a low VC at baseline and a sharp decline of VC during the first 6 months have an especially poor prognosis.

Euthanasia and physician-assisted suicide among patients with amyotrophic lateral sclerosis in the Netherlands.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease that causes progressive paralysis leading to respiratory failure. Patients with ALS may consider physician-assisted suicide. However, it is not known how many patients, if given the option, would actually decide to end their lives by physician-assisted suicide or euthanasia nor at what stage of the disease they would choose to do so. METHODS: We identified physicians of 279 patients in the Netherlands with a diagnosis of ALS who died between 1994 and 1999. Physicians were asked to fill out a validated questionnaire about the end-of-life decisions that were made. Of 241 eligible physicians, 203 returned the questionnaire (84 percent). RESULTS: Of the 203 patients, 35 (17 percent) chose euthanasia and died that way. An additional six patients (3 percent) died as a result of physician-assisted suicide. Patients to whom religion was important were less likely to have died as a result of euthanasia or physician-assisted suicide. The choice of euthanasia or physician-assisted suicide was not associated with any particular characteristics of the disease or of the patient's care, nor was it associated with income or educational level. Disability before death was significantly more severe in patients who died as a result of euthanasia than among those who died in other ways. Physician-assisted suicide appeared to occur somewhat earlier in the course of the disease than did euthanasia. An additional 48 patients (24 percent) received palliative treatment, which probably shortened their lives. CONCLUSIONS: In the Netherlands, we found that one in five patients with ALS died as a result of euthanasia or physician-assisted suicide.

Ciliary neurotrophic factor null alleles are not a risk factor for Charcot-Marie-Tooth disease, hereditary neuropathy with pressure palsies and amyotrophic lateral sclerosis.

Growth factors, such as ciliary neurotrophic factor (CNTF), have been implicated in neuronal survival and proliferation. About 2% of the human population is homozygous for a polymorphism that induces truncated and biologically inactive CNTF but does not obviously change the phenotype. In a population of patients with hereditary neuropathy, a higher rate of the CNTF null mutation would indicate greater susceptibility for clinically significant disease, and a recent report attributes early onset and rapid deterioration in a case of familial ALS (FALS) to this mutation. We have, therefore, genotyped the CNTF polymorphism in a large group of patients with CMT 1a, HNPP, sporadic ALS, in one pedigree with FALS, and controls. All groups exhibited a similar distribution of the polymorphism. We conclude that absence of CNTF does not increase susceptibility for these disorders and confirm that it does not affect onset and course of familial and sporadic ALS.

Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This mutation segregated with disease in two kindreds and was present in another two unrelated cases (P = 0.0102), and all mutation carriers shared a common founder haplotype. Annexin A11-positive protein aggregates were abundant in spinal cord motor neurons and hippocampal neuronal axons in an ALS patient carrying the p.D40G mutation. Transfected human embryonic kidney cells expressing ANXA11 with the p.D40G mutation and other N-terminal mutations showed altered binding to calcyclin, and the p.R235Q mutant protein formed insoluble aggregates. We conclude that mutations in ANXA11 are associated with ALS and implicate defective intracellular protein trafficking in disease pathogenesis.

Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.

Sandhoff disease is a lysosomal storage disorder characterized by accumulation of GM2 ganglioside due to mutations in the beta-chain of beta-hexosaminidase. Hexosaminidase activity is negligible in infantile Sandhoff disease whereas residual activity is present in juvenile and adult forms. Here we report the molecular basis of the first described adult form of Sandhoff disease. Southern analysis of chromosomal DNA indicated the absence of chromosomal deletions in the gene encoding the beta-chain. Northern analysis of RNA from cultured fibroblasts demonstrated that at least one of the beta-chain alleles was transcribed into normal-length mRNA. Sequence analysis of the entire cDNA prepared from poly-adenylated RNA showed that only one point mutation was present, consisting of a G-->A transition at nucleotide position 1514. This mutation changes the electric charge at amino acid position 505 by substitution of glutamine for arginine in a highly conserved part of the beta-chain, present even in the slime mold Dictyostelium discoideum. The nucleotide transition generated a new restriction site for DdeI, which was present in only one of the alleles of the patient. Reverse transcription of mRNA followed by restriction with DdeI resulted in complete digestion at the mutation site, demonstrating that the second allele was of an mRNA-negative type. Transfection of COS cells with a cDNA construct containing the mutation but otherwise the normal sequence resulted in the expression of a labile form of beta-hexosaminidase. These results show that the patient's is a genetic compound, and that the lability of beta-hexosaminidase found in this form of Sandhoff disease is based on a single nucleotide transition.

Prospective study on quality of life before and after radical radiotherapy in non-small-cell lung cancer.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with non-small-cell lung cancer (NSCLC) receiving radical radiotherapy (60 Gy). Additionally, the association between the level of symptom relief and objective tumor response, as well as with radiation-induced pulmonary changes, was investigated. PATIENTS AND METHODS: One hundred sixty-four patients were entered onto this prospective study. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 were used to investigate changes in QOL: Assessments were performed before radiotherapy and 2 weeks, 6 weeks, 3 months, 6 months, and 12 months after the completion of radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (83%); good for chest pain (68%), arm/shoulder pain (63%), and appetite loss (60%); and poor for dyspnea (37%), cough (31%), and fatigue (28%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for physical and role functioning to 55% for social and cognitive functioning. The response rate for global QoL was 36%. A significant association was found between tumor response and palliation of chest pain, arm/shoulder pain, and physical functioning. During radiotherapy, a significant increase for most general symptoms and a deterioration in functioning and QoL were noted. CONCLUSION: This study is the first to describe palliation and changes in QoL in radically irradiated patients with NSCLC. Radical radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with NSCLC who have relatively good prognostic features. Although tumor reduction is associated with palliation of respiratory symptoms, it cannot serve as a surrogate for palliation.

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways.

Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS patients and 6405 controls. Several known ALS genes were found to be associated, and TBK1 (the gene encoding TANK-binding kinase 1) was identified as an ALS gene. TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS. These observations reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention.

Phosphatidylethanolamine mediates insertion of the catalytic domain of leader peptidase in membranes.

Leader peptidase is an integral membrane protein of E. coli and it catalyses the removal of most signal peptides from translocated precursor proteins. In this study it is shown that when the transmembrane anchors are removed in vivo, the remaining catalytic domain can bind to inner and outer membranes of E. coli. Furthermore, the purified catalytic domain binds to inner membrane vesicles and vesicles composed of purified inner membrane lipids with comparable efficiency. It is shown that the interaction is caused by penetration of a part of the catalytic domain between the lipids. Penetration is mediated by phosphatidylethanolamine, the most abundant lipid in E. coli, and does not seem to depend on electrostatic interactions. A hydrophobic segment around the catalytically important residue serine 90 is required for the interaction with membranes.

Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis.

BACKGROUND: Free radicals may play a role in the pathogenesis of amyotrophic lateral sclerosis. OBJECTIVE: To investigate the efficacy of the free radical scavenging agent acetylcysteine in patients with amyotrophic lateral sclerosis. DESIGN: Randomized, double-blind, placebo-controlled clinical trial to assess the effect of treatment with acetylcysteine on survival and disease progression. SETTING: A university hospital referral setting. PATIENTS: One hundred ten consecutive patients who fulfilled the diagnostic criteria for amyotrophic lateral sclerosis, followed up at monthly intervals for 12 months. INTERVENTION: Acetylcysteine or placebo in a dose of 50 mg/kg per day subcutaneously for 12 months. MAIN OUTCOME MEASURE: Survival. RESULTS: After 12 months, 35 patients (65%) treated with acetylcysteine and 30 (54%) given placebo were still alive (hazard ratio, 0.74 in the acetylcysteine group relative to the placebo group; 95% confidence interval, 0.41 to 1.33; log-rank test, P = .31). Rates of disease progression, as expressed by decline in muscle strength, pulmonary function, disability, and bulbar function were similar in both groups. In the subgroup of 81 patients with limb onset of the disease, 28 patients (74%) in the acetylcysteine group and 22 (51%) in the placebo group survived 12 months (hazard ratio, 0.50; 95% confidence interval, 0.24 to 1.04; P = .06). In the bulbar subgroup of 29 patients, seven patients (44%) receiving acetylcysteine and eight (62%) receiving placebo were alive at the end of the study (hazard ratio, 1.66; 95% confidence interval, 0.56 to 4.99; P = .36). CONCLUSION: In this trial, treatment with the free radical scavenger acetylcysteine did not result in a major increase in 12-month survival or a reduction in disease progression in patients with amyotrophic lateral sclerosis.

Increased metallothionein in the liver and kidney of patients with amyotrophic lateral sclerosis.

To evaluate the putative role of metals and trace elements in the pathogenesis of classic amyotrophic lateral sclerosis, we studied the metallothionein levels in liver and kidney samples obtained at autopsy from 24 patients with amyotrophic lateral sclerosis and 18 controls. To assay metallothioneins and copper, cadmium, and zinc bound to metallothioneins, we used high-performance liquid chromatography directly coupled to flame atomic absorption spectrometry. Total cadmium, zinc, and copper concentrations were determined separately with the use of graphite furnace atomic absorption spectrometry with Zeeman background correction. The median liver metallothionein level was 60.3 mg/kg (range, 9 to 318 mg/kg) in the patients with amyotrophic lateral sclerosis and 12.6 mg/kg (range, 0 to 104.5 mg/kg) in the controls. In the kidney, median metallothionein levels were 126.9 mg/kg (range, 44 to 387 mg/kg) in the patients with amyotrophic lateral sclerosis and 64 mg/kg (range, 13.1 to 187 mg/kg) in the controls. Total zinc, cadmium, and copper concentrations, as measured by atomic absorption spectrometry, were not significantly different in patients vs controls. Our finding of elevated metallothionein levels in organs from patients with amyotrophic lateral sclerosis may indicate an increased exposure to metals.

Mimic syndromes in sporadic cases of progressive spinal muscular atrophy.

Described are patients initially diagnosed with progressive spinal muscular atrophy (PSMA), in whom further evaluation established another diagnosis. The authors prospectively investigated incident and prevalent cases of PSMA. Seventeen of 89 patients, after initial registration, were later excluded because reassessment revealed a diagnosis other than PSMA. In 11 of the 17 patients with a revised diagnosis, a potential treatment was available: multifocal motor neuropathy (7), chronic inflammatory demyelinating polyneuropathy (2), inflammatory myopathy (1), and MG (1). Other misdiagnoses included myopathy, syringomyelia, ALS, idiopathic chronic axonal polyneuropathy, and idiopathic brachial plexus neuropathy. One patient with a possible herniated lumbar disk recovered spontaneously.

Homozygous deletion of the survival motor neuron 2 gene is a prognostic factor in sporadic ALS.

BACKGROUND: Spinal muscular atrophy (SMA) results from mutations of the survival motor neuron (SMN) gene on chromosome 5. The SMN gene exists in two highly homologous copies, telomeric (SMN1) and centromeric (SMN2). SMA is caused by mutations in SMN1 but not SMN2. The clinical phenotype of SMA appears to be related to the expression of SMN2. Patients suffering from the milder forms of SMA carry more copies of the SMN2 gene compared with patients with more severe SMA. It is suggested that the SMN2 gene is translated into an at least partially functional protein that protects against loss of motor neurons. OBJECTIVE: To investigate whether genetic mechanisms implicated in motor neuron death in SMA have a role in ALS. METHODS: The presence of deletions of exons 7 and 8 of SMN1 and SMN2 was determined in 110 patients with sporadic ALS and compared with 100 unaffected controls. RESULTS: The presence of a homozygous SMN2 deletion was overrepresented in patients with ALS compared with controls (16% versus 4%; OR, 4.4; 95% CI, 1.4 to 13.5). Patients with a homozygous SMN2 deletion had a shorter median time of survival (p < 0.009). Furthermore, multivariate regression analysis showed that the presence of an SMN2 deletion was independently associated with survival time (p < 0.02). No homozygous deletions in SMN1 were found. Carrier status of SMA appeared to be equally present in patients and controls (1 in 20). CONCLUSION: These results indicate that, similar to SMA, the SMN2 gene can act as a prognostic factor and may therefore be a phenotypic modifier in sporadic ALS. Increasing the expression of the SMN2 gene may provide a strategy for treatment of motor neuron disease.

Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective study.

PURPOSE: The purpose of this study was to investigate changes in respiratory symptoms and quality of life (QoL) in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC) receiving thoracic radiotherapy. Additionally, the correlation between the level of symptom relief and objective tumor response was investigated. METHODS AND MATERIALS: Sixty-five patients were entered in this prospective study. The EORTC QLQ-C30 and EORTC QLQ-LC13 were used to investigate changes in QoL. Assessments were performed before radiotherapy and 2 weeks, 6 weeks, and 3 months after radiotherapy. RESULTS: The QoL response rates were excellent for hemoptysis (79%); good for arm/shoulder pain (56%), chest wall pain (53%), and cough (49%); moderate for dyspnea (39%); and minimal for the general symptoms fatigue (22%) and appetite loss (11%). The QoL response rates for the five functioning scales of the QLQ-C30 varied from 35% for role functioning to 57% for emotional functioning. Global QoL improved in 37% of the cases. In general, there was a tendency for better palliation of symptoms and improvement of QoL among patients with an objective tumor response than among those without objective tumor response, which was statistically significant for dyspnea (p = 0.02) and social functioning (p = 0.04). CONCLUSIONS: This study confirms that conventional thoracic radiotherapy offers palliation of respiratory symptoms and improved QoL in a substantial proportion of patients with locally advanced and metastatic NSCLC. Tumor reduction is only one of the mechanisms by which palliation of symptoms and improvement of QoL is achieved.