Long-term Treatment Outcomes In Patients Research Articles

Switch from Every Two Weeks to Every Four Weeks Administration Schedule of AOP2014, an Innovative Pegylated Interferon Alpha, in Polycythemia Very Patients Allows Maintaining of Efficacy with Improved Toxicity Profile in Phase I/II Study

Background AOP2014 is a next generation long-acting pegylated IFN-alpha-2b, consisting predominantly of only one isoform, as opposed to other commercially available pegylated interferons. Due to this property, reduced dosing frequencies, better tolerability, improved compliance and more favorable long-term treatment outcomes in patients with Polycythemia Vera (PV) are expected. The drug has Orphan designation by EMA and FDA and is currently in the phase III stage of development.Study design This phase I/II single arm dose escalation study with cohort extension included 51 patients with PV who could be either cytoreduction therapy naive or pre-treated. AOP2014 was administered subcutaneously in a dose range of 50-540 mcg every two weeks. Main objectives were to define the maximum tolerated dose as well as observe the long term safety and efficacy in terms of normalization of blood parameters and molecular abnormalities (results were already presented at the ASH 2013 annual meeting by Gisslinger et al). The option to switch to an "once every four weeks" schedule has been implemented by the amended protocol for patients who responded well to the treatment and participated in the study for longer than one year. The dose of the study drug had to remain unchanged after the switch, resulting in a decrease (by approx. the half) of the overall exposure to the drug. Outcomes of this switch are presented here.Results Patients (period A, median exposure duration 34 weeks, mean monthly dose 484 mcg) were dosed every two weeks based on the Phase II dosing rules prior having switch option. 33 patients (period B, median exposure duration 12 weeks, mean monthly dose 413 mcg) were dosed every two weeks beyond the first year and, showing benefit from treatment, have been assessed as eligible for switch. 28 patients (period C, median exposure duration 42 weeks) were then switched to once every four weeks schedule (mean monthly dose 221 mcg). Blood parameters were normalized and remained stable following one year of treatment and could be maintained after the switch (hematocrit, median,% - period A: 43, period B: 43, period C: 42; WBC, median, G/l - period A: 6.1, period B: 5.9, period C: 5.7; platelets, median, G/l - period A: 246, period B: 211, period C: 204). Spleen length stayed stable within the normal range following the switch in the majority of patients either (mean, in cm – period A: 11.4, period B: 8.3, period C: 10.3). Complete response as best individual response could be maintained in 42% from the period A, 55% in the period B and 67% of the period C patients, while for the partial hematological responders the results were 60%, 71% and 67%, respectively. Molecular response improved continuously over time, being maintained at the best individual level in 31% of period A patients, compared to 42% of period B and 75% of period C patients. Decrease of application frequency and total dose exposure led to decrease of the occurrence of all/drug related AEs (measured as mean count of adverse events [AE] per patient week exposure) to 0.17/0.09 (arm A) from 0.3/0.09 (arm B) and 0.08/0.03 (arm C).Conclusions This explorative data from endpoints pre-defined in the prospective study demonstrate the feasibility to further reduce the frequency of AOP2014 administration to once every four weeks in responding patients, previously treated every two weeks. Reduced injection frequency is not associated with a lack of- response, but clearly improves tolerability. Finally, continuous reduction of the JAK2 allelic burden indicates that duration of interferon exposure rather than dose of interferon is an important variable inducing molecular responses. The here presented findings support the idea that interferon alpha effects in PV are pleiotropic, such as induction of immune-surveillance, which is continuously maintained at lower AOP2014 levels. DisclosuresGisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Buxhofer-Ausch:AOP Orphan Pharmaceuticals AG: Research Funding. Thaler:AOP Orphan Pharmaceuticals AG: Research Funding. Schloegl:AOP Orphan Pharmaceuticals AG: Research Funding. Gastl:AOP Orphan Pharmaceuticals AG: Research Funding. Wolf:AOP Orphan Pharmaceuticals AG: Research Funding. Kralovics:AOP Orphan Pharmaceuticals AG: Research Funding. Gisslinger:AOP Orphan Pharmaceuticals AG: Research Funding. Strecker:AOP Orphan Pharmaceuticals AG: Research Funding. Egle:AOP Orphan Pharmaceuticals AG: Research Funding. Melchardt:AOP Orphan Pharmaceuticals AG: Research Funding. Burgstaller:AOP Orphan Pharmaceuticals AG: Research Funding. Willenbacher:AOP Orphan Pharmaceuticals AG: Research Funding. Zoerer:AOP Orphan Pharmaceuticals AG: Employment. Kadlecova:AOP Orphan Pharmaceuticals AG: Consultancy. Zagrijtschuk:AOP Orphan Pharmaceuticals AG: Employment. Klade:AOP Orphan Pharmaceuticals AG: Employment. Greil:AOP Orphan Pharmaceuticals AG: Research Funding.

Predictive factors of depression and its therapy

Predictive factors of for the occurrence of depressive episodes include psychosocial and biological risk factors. These factors reflect the heterogeneity and complexity of the disease. They can identify groups that would benefit from preventive measures and provide indications for suitable preventive strategies. In recent decades considerable scientific effort, for example in the field of psychiatric genetics, has been undertaken to identify predictive factors for individual antidepressant therapy response and as an aid for individual treatment decisions. However, no clinically usable conclusions could yet be drawn from the respective findings. In practice clinical factors, such as symptom cluster of the depressive disorder and specific properties of the antidepressant, individual factors and contextual factors, such as the type of treatment facility, decision support and economic aspects, are factors influencing the choice of a specific antidepressant. Early clinical improvement under antidepressant medication in the first 2 weeks of treatment is one of the best predictors for the long-term treatment outcome in patients with major depressive disorder.

Remote Results of Intraarterial Chemotherapy with Local Hyperthermia in the Treatment of Patients with Nasal and Paranasal Sinuses Cancer

ABSTRACT Aim: To study remote results and the role of intraarterial chemotherapy with local hyperthermia in the treatment of nasal and paranasal sinus cancer patients. Methods: 209 patients were treated over the period 2000 - 2008. T3 stage was diagnosed in 106 patients (51.4%) and T4 stage in 103 (48.6%) patients. Squamous cell carcinoma was found in 71.3% patients. Patients were divided into 4 groups: 1) intraarterial chemotherapy with local hyperthermia and radiotherapy (58 patients; 2) intraarterial chemotherapy and radiotherapy (48 patients;, 3) systemic chemotherapy and radiotherapy (58 patients); 4) radiotherapy followed by surgery (45 patients). We used the following regimen: cisplatin 100 mg, fluorouracil 3000 mg and doxorubicin 60 mg. In 1st group 58 patients received local UHF–hyperthermia with the frequency of 40 MHz increasing the temperature up to 41-43°C in the tumour. Patients of the 1st and 2nd groups, received intraarterial chemotherapy with ligation and catheterization of external carotid artery. All patients received telegammatherapy, dose 40-60 Gy. For appreciating of the remote results SPSS-16 statistical methods were used. Results: Continuous regional intraarterial chemical induction in the background of local hyperthermia significantly increased the results of treatment. Surgical treatment was made to 128 (61.2%) patients at second grade of complex therapy. In the 1st group of patients 3-year survival rate was 83.4%, and 5-year survival rate was 73.0%. In the 2nd group those rates were 80.4% and 66.7%, respectively. In the 3rd group those rates were 68.2% and 60.6%, respectively. In the 4th group those rates were 68.1% and 54.1%, respectively. In the study of long-term treatment outcomes of patients receiving integrated and combined treatment it was found that the recurrence rate in the 1st and 2nd groups compared with the 3rd and 4th groups of patients differed significantly. So in the 1st group these figures were 32.4% in the 2nd group 38.1%, and in the third group recurrence was seen in 45.4% of patients. In the 4th group this figure increased further and was observed in 51.3% of patients. Conclusions: Thus, neoadjuvant continuous intraarterial chemotherapy with local UHF-hyperthermia and radiotherapy in the 1st group of patients allowed us to increase significantly the remote results compared with those in the 3rd group who received systemic chemotherapy. Disclosure: All authors have declared no conflicts of interest.

Treatment selection for tonsillar squamous cell carcinoma

BackgroundThe optimal treatment for tonsillar squamous cell carcinoma (SCC) remains controversial. The purpose of this study was to evaluate long-term treatment outcomes of patients with tonsillar SCC, in order to aid in appropriate treatment selection. MethodsWe conducted a retrospective chart review of 105 patients with curatively treated tonsillar SCC between January 1996 and December 2005. Forty-three patients (41.0%) underwent primary surgery with or without adjuvant therapy (primary surgery group), and 62 patients (59.0%) were treated with radiotherapy/chemoradiotherapy (RT/CRT, organ preservation group). Twenty patients (19%) received tumor tonsillectomy before definitive RT/CRT and were grouped into the organ preservation group. ResultsNo significant differences were observed between the primary surgery and organ preservation groups in terms of local control (p = 0.212), regional control (p = 0.684), distant metastasis (p = 0.627), 5-year disease-specific survival (DSS, p = 0.774), and overall survival rates (OS, p = 0.667). The rates of major complication (p = 0.216), long-term dependency on feeding tubes (p = 0.876), and tracheostomy (p = 0.401) were also similar. Advanced T classification (T3–4) was the only factor associated with significantly worse DSS (p = 0.007) and OS (p = 0.012). However, there was also no difference in final treatment outcomes in T3–4 patients regardless of whether they were treated with primary surgery or RT/CRT. In the organ preservation group, tumor tonsillectomy before RT/CRT did not improve local control (p = 0.520) or other treatment outcomes, including 5-year DSS (p = 0.707) and OS (p = 0.745). ConclusionBoth primary surgery and RT/CRT organ preservation are effective treatments for tonsillar SCC. Single modality treatment, either surgery or RT/CRT, can typically be provided for stage I–II diseases. Although RT/CRT organ preservation is used more frequently for stage III–IV tonsillar SCC in recent years, primary surgery combined with adjuvant therapy still achieves equivalent outcomes. Multidisciplinary pretreatment counseling and the facilities and personnel available are therefore important for decision-making. In addition, if RT/CRT organ preservation is selected as the primary treatment, tumor tonsillectomy is not indicated.

Long-term treatment outcomes in patients with interstitial cystitis/painful bladder syndrome: 10-year experience in NCKUH

ObjectiveA retrospective review of long-term treatment outcomes for patients diagnosed with interstitial cystitis/painful bladder syndrome (IC/PBS) over a 10-year period. Materials and MethodsPatients who were diagnosed with IC/PBS based on cystoscopic hydrodistention from 2001 to 2010 and thereafter received regular follow-up treatments were enrolled in this study. Clinical information was collected via a retrospective chart review. The following aspects were evaluated: treatment modalities and outcomes; symptom manifestation before and after treatments; and patients' perception on treatment effectiveness. The O'Leary–Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), and the Global Response Assessment Questionnaire were used as evaluation tools. ResultsA total of 54 patients with adequate clinical information were included for analysis in this study. The mean age was 38.11 ± 12.71 years and the female-to-male ratio was 3.15:1. The average follow-up duration was 30.61 ± 25.54 months. All patients had bladder or pelvic pain. Pretreatment urinary frequency and nocturia were 13.43 ± 5.09 times per day and 3.74 ± 2.18 times per night, respectively. Functional bladder capacity recorded from urinary diary was 228.1 ± 116.5 mL. Under anesthesia, bladder capacity at the start of a 10-minute therapeutic hydrodistention was 422.0 ± 197.5 mL, which increased to 542.9 ± 220.1 mL at the end of hydrodistention. No major complications were reported during and after the procedure. Additional treatments including oral medications and bladder instillation therapies were instituted in 98.1% of patients. Compared with pretreatment condition, the O'Leary–Sant ICSI and ICPI were decreased by 24% and 15.5%, respectively, after treatments. The subjective improvement rate, which was evaluated by the Global Response Assessment Questionnaire, was 81.6%. ConclusionLong-term continual treatments for IC/PBS are appreciated by most patients even though combinations of modalities are required and the improvements in symptoms and problems are only moderate.

Laparoscopic Nissen fundoplication in the treatment of Barrett's esophagus - 10 years of experience.

IntroductionBarrett's esophagus (BE) is a state in which the distal portion of esophageal mucosa becomes lined with cylindrical epithelium as a result of adaptive remodeling. It is widely accepted that the metaplastic lesions result from chronic irritation with gastric and/or duodenal contents in the course of reflux disease. For many years, research centered on the risk factors of BE and resulting adenocarcinoma. Anti-reflux operations are the only procedures which offer the possibility of treating the cause by restoring the anatomic barrier responsible for guarding against irritating effects of gastroduodenal content on the distal esophagus. Total (i.e. 360°) laparoscopic Nissen fundoplication (LNF) is considered the most effective amongst these procedures. Still, controversies related to the indications for anti-reflux surgery are frequently encountered.AimRetrospective analysis of long-term treatment outcomes in patients with BE subjected to laparoscopic Nissen fundoplication.Material and methodsThe group included 42 BE patients, amongst them 30 men and 12 women. Initially, all the patients were treated conservatively for at least 1 year. The subgroup with dysplasia was subjected to preoperative argon plasma coagulation (APC). From 1 year after surgery (laparoscopic Nissen fundoplication), control biopsy specimens were obtained from the gastroesophageal junction of all the patients.ResultsNone of the patients showed the development of esophageal adenocarcinoma during the follow-up period. Furthermore, no cases of dysplasia progression or de novo development of dysplasia were observed in the analyzed group. In the initial 12-24 months after surgery, complete regression of metaplasia was documented in 7 (31.8%) patients from group A, and a reduction in the area of Barrett's metaplasia was observed in another 7 patients (31.8%). Throughout the period of this study, persistent planoepithelial re-epithelialization was observed in 14 (70%) group B patients, i.e. in individuals with baseline dysplasia subjected to preoperative argon plasma ablation. In the remaining patients of this group, the developed changes of BE character were less advanced than at baseline.ConclusionsOur opinion is that laparoscopic Nissen fundoplication, as a result of high effectiveness, represents the method of choice in the treatment of BE in the case of patients who were qualified for surgery.

Association between Pretreatment Levels of Serum Vascular Endothelial Growth Factor (VEGF) and Survival Outcomes in Locally Advanced Cervical Cancer Patients

Objective: To evaluate the association between pretreatment levels of serum vascular endothelial growth factor (VEGF) and long-term treatment outcomes in patients with locally advanced cervical cancer (LACC). Methods: Thirty-nine patients diagnosed with LACC (stage IIB-IVA) and obtaining blood for serum VEGF were identified. All patients received complete treatment as radical radiotherapy with or without concurrent chemotherapy. Surveillance for all patients was every 3 months during the first 2 years, and every 6 months later. Results: Mean age of 39 patients was 52.3 ± 10.8 years old. Twenty-three patients (59.0%) had stage IIB, and 16 patients (41.0%) had stage IIIB. Histological cell type was mostly squamous cell carcinoma (89.7%). The median and 75th percentile level of serum VEGF were 610.2 pg/ml (0.0 - 4067.2 pg/ml) and 825.6 pg/ml, respectively. At median follow-up of 37.0 months (range, 26.8 - 46.3 months), the 3-year OS rate was 78.6%. Clinical stage (p = 0.04) and 75th percentile of VEGF level (p = 0.04) were impacted on OS in univariable analysis. The 3-year OS of patients in stage IIB with serum VEGF of ≤825.6 pg/ml and of > 825.6 pg/ml was slightly different, 94.4% and 80.0% respectively (p = 0.34), whereas there were many differences in stage IIIB, 71.4% and 25.0% in patients with serum VEGF of ≤825.6 pg/ml and of >825.6 pg/ml respectively (p = 0.05). Conclusion: High pretreatment serum VEGF level has an influence on OS for LACC. It is potentially used as a predictive factor, especially in patients stage IIIB, in order to provide efficient treatment and improve survival outcomes in the future.

Treatment Outcomes of World Health Organization Grade 2 (Atypical) Meningiomas After Surgery With or Without Postoperative Upfront Radiation Therapy

The role of postoperative radiation therapy for World Health Organization (WHO) grade II meningiomas has been controversial. We evaluated long-term treatment outcomes in patients with WHO grade II (atypical) meningiomas who had received surgery with or without postoperative radiation therapy. Between 1994 and 2008, 77 patients who underwent resection of WHO grade II meningiomas were reviewed retrospectively. Grade of meningiomas was defined using 2007 WHO criteria by a single neuropathologist. The median age at diagnosis was 52 years (range, 15-77 years). They were 27 male and 50 female. The degree of tumor resection was as follows: Simpson grade 1 in 28 (36.4%), grade 2 in 28 (36.4%), grade 3 in 7 (9.1%), and grade 4 in 14 (18.2%) patients, respectively. Nineteen patients received postoperative upfront radiation therapy according to the surgeons' preferences with the median dose of 5940 cGy (range, 3800-6200 cGy). The median follow-up was 86.7 months (range, 2.1-181.9 months). The 5- and 10-year overall survival rates were 84.4% and 72.8%, respectively. The 5- and 10-year local relapse free survival (LRFS) rates were 62.7% and 47.7%, respectively. The degree of tumor resection was an important factor in predicting tumor recurrence. The 5-year LRFS was 88.9% in patients received Simpson grade 1 resection and 48.0% in Simpson grade 2-4 resection (p < 0.005). Although the incidence of tumor recurrence was not significant according to postoperative upfront radiation therapy in all patients (5-year LRFS: 76.6% vs. 57.9%, p = 0.075), significant difference in local recurrence was observed in patients who received Simpson grade 2-4 resection with or without postoperative upfront radiation therapy (5-year LRFS: 80.2% vs. 37.0%, p = 0.006). The degree of surgical resection was a significant parameter affecting LRFS in patients with WHO grade II meningiomas. Postoperative upfront radiation therapy also demonstrated a significant benefit of reducing tumor recurrence when patients had undergone Simpson grade 2-4 resection. Well-designed prospective study is needed to make a definitive conclusion in regarding to the role of postoperative upfront radiation therapy in patients with WHO grade II meningiomas.

Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy

PurposeTo evaluate the long-term treatment outcome in patients with recurrent nasopharyngeal carcinoma (NPC) treated with salvage intensity modulated radiotherapy (IMRT). Materials and methodsOne hundred and fifty one previously irradiation NPC patients with recurrent disease and re-irradiated by IMRT between 2001 and 2006 had been reviewed. The disease was re-stage I in 7, re-stage II in 21, re-stage III in 50 and re-stage IV in 73. Thirty-seven patients received concurrent chemotherapy, 39 had induction chemotherapy and 75 had radiotherapy alone. ResultsAll patients completed the planned IMRT. The median volume of the recurrent gross target volume of nasopharynx (rGTVnx) was 42.2cm3 (range 1.5–146.3cm3). The median mean re-irradiation dose to the rGTVnx was 70.4Gy (range 62.1–77.6Gy). The median follow-up time after re-irradiation was 40.0months (range 1.9–116.9month). The 5-year local control rate (LCR) and overall survival rate (OS) for re-stage I, II, III, IV were 80.0%, 85.0%, 80.0%, 78.7% and 71.4%, 62.9%, 35.5%, 30.2%, respectively. Multivariate analysis indicated that rT classification (hazard ratio (HR), 2.02; 95%confidence interval (CI), 1.03–3.97; P=0.04) and the volume of rGTVnx (HR, 2.05; 95%CI, 1.31–3.22; P<0.01) were independent predictors for OS. Patients (39.0%) with re-stage III or IV disease experienced Grade 3 or 4 late toxicities. ConclusionRe-irradiation by IMRT for recurrent NPC resulted in encouraging local control. The clinical outcome for patients with early re-stage diseases was satisfactory. Further investigations, focus on optimising radiation dose and establishing effective treatment strategies, are warranted for advanced recurrent disease in order to improve overall survival and minimise late toxicity.

Outcomes of revision external dacryocystorhinostomy and nasal intubation by bicanalicular silicone tubing under endonasal endoscopic guidance.

To evaluate the long-term treatment outcomes in patients who underwent revision of external dacryocystorhinostomy (DCR) and nasal intubation by bicanalicular silicone tubing (BSTI) under endonasal endoscopic guidance. Data from 28 patients with recurrent dacryocystitis were retrospectively reviewed. Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance was performed in 28 eyes of 28 patients. The patients were evaluated with respect to the reason of recurrence, time to recurrence, time to revision, duration of follow-up and surgical success. Endoscopic endonasal examination detected an osteotomy-side obstruction by the excessive granulation tissue in 24 patients (86%), nasal septal deviation in three patients (10%) and nasal polyp in one patient (4%). Recurrence occurred after a mean duration of 5.3±3.7 months following the first operation. The mean time between the first DCR operation and the revision DCR was 11.5 ± 9.3 months. After a mean follow-up of 14.9±7.8 months, the rate of anatomic success alone was 85% (24/28); the rate of subjective success was 78% (22/28). Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance can be recommended in patients with recurrent dacryocystitis as a surgical approach that achieves satisfactory objective and subjective success rates.

Engaging and empowering patients to manage their type 2 diabetes, Part I: a knowledge, attitude, and practice gap?

For over 20 years, the World Health Assembly has recognized diabetes (type 1 and type 2) as a serious threat to national health and economic development and called for action regarding its prevention and control. However, the prevalence of type 2 diabetes continues to rise despite a significant percentage of cases being preventable. Furthermore, data suggest that in many patients diagnosed with type 2 diabetes, glycated hemoglobin (HbA(1c)) levels remain above the agreed international and national target levels, despite the availability of numerous antihyperglycemic agents, the best intentions of both patient and physician, and the support of the wider healthcare team. Part I of this two-part review considers evidence that seems to suggest there is a knowledge, attitude, and practice (KAP) gap in type 2 diabetes, and that although theoretical knowledge of how type 2 diabetes should be managed exists, the attitude of patients and healthcare professionals may influence the practicalities of implementing life-enhancing changes for patients living day-to-day with the condition. Here, we consider why there may be a KAP gap, how type 2 diabetes is currently being assessed and managed, and whether these current management approaches remain valid in the light of recent studies evaluating the impact of lowering current target HbA(1c) levels. This article also explores how encouraging patients to self-manage their disease, as well as engaging all stakeholders in the necessary behavioral changes, can positively influence the long-term treatment outcomes of patients with type 2 diabetes.

Long-term treatment of patients suffering from Restless Legs syndrome does not improve satisfaction with life and sleep compared to healthy controls

Research questions: Amongst the variety of disorders affecting sleep, the Restless Legs Syndrome (RLS) demands particular attention, because of its high clinical overlap with depressive symptoms. However, little is known about the long-term treatment outcome of patients suffering from RLS. Methods: Of 63 patients with diagnosed RLS, 38 (60%) were followed-up after 34 months. An age- and gender-matched control group (HC: healthy controls) was also recruited. Participants completed a series of questionnaires related to sleep, satisfaction with life, and psychological functioning, and a daily sleep-log for seven consecutive days and nights. Results: Groups did not differ with respect to age, gender, duration of disorder, and medication. Compared to controls, patients with RLS showed highly increased depressive symptoms, social withdrawal, and low perceived social support. Moreover, those patients with both diagnosed RLS and depressive symptoms showed higher scores of external locus of control and rumination, compared to HC and to patients with RLS. With respect to sleep, again compared to HC, patients with RLS reported prolonged sleep onset latency, an increased sleep fragmentation, and affected mood and sleep quality. Conclusions: Results: suggest the need to improve the long-term therapy of patients with RLS.

Treatment outcome of radiotherapy alone versus radiochemotherapy in early stage nasal natural killer/T-cell lymphoma

This study aims to investigate the prognostic factors and long-term treatment outcome in patients with early stage nasal natural killer (NK)/T-cell lymphoma. Sixty-four patients were recruited in this study, whose clinical and laboratory data were collected from hospital records. Early stage (stage IE: 51, stage IIE: 13) nasal NK/T-cell lymphoma (NNTCL) was established according to Ann Arbor staging classification. Among these patients, 23 received radiotherapy (RT) alone, the remaining 41 cases were treated with radiochemotherapy (RCT) comprised of 1-6 cycles of anthracycline-based chemotherapeutic regimens. Results show that the median overall survival (OS) time was 41 months. The 5-year OS and progression-free survival rates were 59.2 and 52.3%, respectively. The 5-year OS rate for patients who received RT alone was 57.9%, whereas that for patients who received RCT was 61.5% (P = 0.47). There is no significant difference between two treatment modalities. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (PS) score > or = 2, local tumor invasion out of nasal cavity, and lower complete remission (CR) rates in the initial treatment were significant unfavorable independent prognostic factors. Taken together, our study suggests that RCT did not improve the survival rate of patients with early stage NNTCL. PS score before treatment, local tumor invasion out of nasal cavity, and CR rate of the primary treatment may be independent prognostic factors among the subtype lymphoma entity.

Management of Deep Wound Infection After Posterior Lumbar Interbody Fusion With Cages

To evaluate long-term treatment outcome of patients with infected posterior lumbar interbody fusion (PLIF) managed with surgical debridement and or prolonged antiobiotic treatment without removal of the interbody cages. Between 1996 and 1999, 8 out of 111 patients who underwent PLIF were diagnosed with deep wound infection (7.2%). All infected patients were clinically followed for at least 2 years after completion of the antibiotic treatment. Longer follow-up of at least 6 years duration was performed by a telephone interview. Six patients were managed with surgical debridement, wound irrigation, and primary closure of the wound. None of the patients required removal of the instrumentation. In 2 patients, the PLIF cages were repositioned in the face of infection. All 8 patients received 4 to 6 weeks of intravenous antibiotic therapy followed by another 6 to 9 weeks of oral antibiotic administration. At 2-year follow-up, no clinical or laboratory signs of recurrent infection were evident. Four of the 8 patients reported improved clinical status compared with their prefusion status. At 6-year follow-up, 3 patients had minimal disability according to the Oswestry Disability Index and 2 patients had moderate disability with residual leg pain. In cases of postoperative deep wound infection after PLIF with cages, removal of the interbody implants is not necessary. Treatment is composed of prolonged antibiotic therapy guided by antimicrobial susceptibility of the isolated bacteria and supplemented with extensive surgical debridement if needed.

The Impact of Disability Compensation on Long-term Treatment Outcomes of Patients With Sciatica Due to a Lumbar Disc Herniation

Prospective, observational study. To compare long-term disability and health-related quality of life outcomes of individuals receiving or not receiving workers' compensation at baseline evaluation. Disability compensation has long been associated with poor clinical outcomes. However, most studies have assessed outcomes over short time periods using unvalidated measures without controlling for potential confounders. Patients with sciatica due to a herniated lumbar disc were treated by physicians in community based orthopedic, neurosurgical, and occupational medicine practices throughout Maine. Outcomes assessed included disability compensation and work status, and health-related quality of life, controlling for initial treatment received and factors predicting initial workers' compensation status. Among 440 eligible patients, 172 (86%) receiving workers' compensation and 222 (92%) not receiving workers' compensation at baseline evaluation completed at least one follow-up between 5 and 10 years (80% completed 10-year). Baseline demographics, past back history, imaging findings, symptoms, functional status, and expectations significantly differed according to the patient's baseline workers' compensation status. After 5-10 years, most patients, regardless of baseline workers' compensation status (yes or no), were not receiving disability compensation (83% vs. 96%, respectively) and were employed (78% for both groups). However, workers' compensation patients were significantly more likely to be receiving disability compensation and had worse symptoms, functional status, and satisfaction outcomes. Outcome differences diminished in magnitude after controlling for baseline differences among patients receiving workers' compensation or not but continued to favor those not initially receiving workers' compensation. Initial treatment received, either surgical or nonsurgical, did not influence these findings. Long-term employment and disability outcomes were favorable for most patients with a disc herniation, regardless of initial workers' compensation status. However, individuals initially receiving workers' compensation had worse disability and quality of life outcomes compared to individuals not receiving workers' compensation. Despite these differences, long-term work outcomes were similarly favorable.

Rehospitalization rates of patients with bipolar disorder discharged on a mood stabilizer versus a mood stabilizer plus an atypical or typical antipsychotic

One-year rehospitalization rates of patients with bipolar disorder discharged on a mood stabilizer alone, a mood stabilizer plus a typical antipsychotic, or a mood stabilizer plus an atypical antipsychotic were examined. Time to rehospitalization was measured by using the product-limit (Kaplan-Meier) formula. Twenty-three percent of patients on a mood stabilizer alone, 27% of patients on a mood stabilizer plus a typical antipsychotic, and 25% of patients on a mood stabilizer plus an atypical antipsychotic were rehospitalized within 1 year of discharge. There were no significant differences in rehospitalization rate or time to rehospitalization between groups. One-year rehospitalization rates for patients on a mood stabilizer plus olanzapine or risperidone were 25%. The number of previous psychiatric hospitalizations contributed to the risk of readmission. Risk factors and medication costs should be considered when designing the optimal treatment plan for an individual patient. Long-term prospective studies are needed to better delineate the effectiveness of different pharmacotherapeutic regimens on the long-term treatment outcomes in patients with bipolar disorder.

Does Hyperinsulinemia in Type-II Diabetes Mellitus Influence Disease Presentation and Long-Term Treatment Outcomes of Localized Prostate Cancer?

Purpose/Objective: Preclinical data suggest that insulin is a growth factor which may stimulate the proliferation of prostate cancer cells. In type II diabetes mellitus (DM-II), insulin resistance may lead to a state of hyperinsulinemia. In this study, we examined the influence of DM-II on disease presentation and long-term treatment outcomes of patients with localized prostate cancer undergoing definitive radiation therapy (RT).

Long-term results of high-dose rate brachytherapy in cervix cancer using a small number of fractions

Objectives. To evaluate the long-term treatment outcome of patients with carcinoma of the cervix treated with high dose rate brachytherapy (HDRB) using a small number of fractions. Methods. Between 1984 and 1997, 282 patients with cervix cancer (stages IB to IVA) were treated with external beam radiotherapy to the whole pelvis (median dose of 45 Gy) and HDRB (median dose of 24 Gy at point A in 3 insertions given weekly). Endpoints assessed were survival, patterns of failure and complications. Multivariate analysis was performed to identify variables predictive for overall survival and local control. Variables investigated were stage, age, overall duration of treatment, HDRB scheduling and total dose to point A. Results. At a median follow-up of 86.3 months for patients at risk, the 5-, 10- and 15-year overall survival rates are 57%, 52% and 47%, respectively. On multivariate analysis, only stage and age correlated with improved survival. Treatment duration beyond 47 days was associated with poorer overall survival, although it did not reach statistical significance ( P = 0.10). Brachytherapy scheduling and BED to point A had no impact on overall survival. Stage and age significantly correlated with pelvic disease control. Duration of therapy, scheduling of the brachytherapy and BED at point A were not individual predictors for overall local control. Overall, gastrointestinal and genitourinary actuarial complication rates were 15% and 8%, respectively. Conclusions. In our experience, HDRB using 3 insertions is well tolerated and the results are comparable to HDRB using larger number of fractions and to low dose rate brachytherapy.

Sustained drug delivery optimizes long-term treatment of patients with schizophrenia.

Chronic disorders such as schizophrenia require long-term treatment programs in order to maintain patients at the lowest level of symptomatology, reduce the likelihood of psychotic relapse, and support achievement of remission and recovery. Evidence suggests that treatment with long-acting injectable antipsychotics reduces the impact of partial compliance and provides predictable release of medication, assuring continuous therapeutic coverage. Until recently, only conventional antipsychotic agents were available in long-acting formulations, thereby foregoing the advantages of the atypical class. Atypical agents which are given orally have been shown to provide long-term efficacy and tolerability benefits compared with conventional agents, but are limited by the need for daily administration. The most recent pharmacological strategy to achieve optimal maintenance treatment has been to combine the benefits of an atypical antipsychotic with delivery in a water-based long-acting formulation. The first antipsychotic to achieve this combination - long-acting risperidone - may thus represent an important advance in the optimization of long-term treatment outcomes in patients with schizophrenia.

Long-term survival after cisplatin-based induction chemotherapy and radiotherapy for nasopharyngeal carcinoma: A pooled data analysis of two phase III trials

5524 Background: To evaluate the long-term treatment outcome in patients with advanced stage nasopharyngeal carcinoma (NPC) treated by cisplatin-based induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). Methods: The updated records of two previously reported phase III studies (the Asian-Oceania Clinical Oncology Association trial and the Guangzhou trial). testing the benefit of adding induction chemotherapy to radiotherapy in NPC were reviewed and the data were pooled together for analysis. A total of 784 patients were included for analysis, with equal number of patients in both the CRT and RT arms. The induction chemotherapy consisting of 2–3 cycles of cisplatin 100 mg/m2 day 1, bleomycin 10 mg/m2 day 1 & 5, and fluorouracil 800 mg/m2 day 1–5, or cisplatin 60 mg/m2 day 1 and epirubicin 110 mg/m2 day 1. Radiotherapy was given to the nasopharynx and neck using megavoltage radiation, with a median dose of 70 Gy. Treatment compliance was 92.6% in the CRT arm and 98% in the RT arm. The median follow-up time for surviving patients was 67 months. Analysis was done by intention to treat. Results: The addition of induction chemotherapy to radiotherapy was associated with a decrease in relapse by 14.3% and cancer deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% in the CRT arm and 42.7% in the RT arm (p=0.014), and the 5-year disease-specific survival rate was 63.5% in the CRT arm and 58.1% in the RT arm (p=0.029). The median disease-specific survival was not yet reached in the CRT arm and it was 82 months in the RT arm. The incidence of loco-regional failure and distant metastases were reduced by 18.3% and 13.3% at 5 years respectively with induction chemotherapy. There was no significant difference in the failure patterns between the 2 arms. Conclusions: The addition of cisplatin-based induction chemotherapy to radiotherapy was associated with a modest but significant improvement in survival in advanced stage NPC. No significant financial relationships to disclose.