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Median Dose (median + dose)
Selected AbstractsApplicability and safety of recombinant activated factor VII to control non-haemophilic haemorrhage: investigational experience in 265 childrenHAEMOPHILIA, Issue 4 2008M. HERBERTSON Summary., Experience of recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark) to control haemorrhage in non-haemophilic children is limited. The object of this study was to examine the applicability and safety of rFVIIa amongst a group of non-haemophilic paediatric subjects. Details of all non-haemophilic children ,16 years receiving rFVIIa whose data were recorded in the investigational, internet-based registry, haemostasis.com were analysed. A total of 265 children (mean age 7.7 years) were treated with rFVIIa; the median dose administered was 78.4 ,g kg,1 body weight (range 9.0,393.4) and the median total dose received 100.0 ,g kg,1 body weight (range 10.9,1341.2). Therapeutic areas included surgery (34.5%), coagulopathy (including thrombocytopenia; 29.0%), spontaneous bleeding (17.2%), trauma (8.4%) and intracranial haemorrhage (4.5%). Two patients experienced thromboembolic events following administration of rFVIIa. Thirty-nine patients died on account of haemorrhage or complications relating to their underlying condition; neither the thromboembolic events nor the deaths were related to rFVIIa administration. Bleeding stopped in 118/237 (49.8%), markedly decreased in 54/237 (22.8%), decreased in 51/237 (21.5%), remained unchanged in 13/237 (5.5%) and increased in 1/237 (0.4%) patients. These results suggest that rFVIIa is safe and widely applicable in children to control non-haemophilic haemorrhage. [source] Recurrent salivary gland carcinomas treated by surgery with or without intraoperative radiation therapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2008Allen M. Chen MD Abstract Background. The optimal treatment for patients with locally recurrent carcinomas of the salivary glands is unclear. Methods. Ninety-nine patients underwent salvage surgery for locally recurrent salivary gland carcinomas. Eighty-one (82%) had previously received radiation. Thirty-seven patients (37%) received intraoperative radiation therapy (IORT) to a median dose of 15 Gy (range, 12,18 Gy) at the time of salvage. Results. The 1-, 3-, and 5-year estimates of local control after salvage surgery were 88%, 75%, and 69%, respectively. A Cox proportional hazard model identified positive margins (0.01) and the omission of IORT (p = .001) as independent predictors of local failure. The 5-year overall survival was 34%. Distant metastasis was the most common site of subsequent failure, occurring in 42% of patients. Conclusions. IORT significantly improves disease control for patients with locally recurrent carcinomas of the salivary glands. The high rate of distant metastasis emphasizes the need for effective systemic therapies. © 2007 Wiley Periodicals, Inc. Head Neck, 2008 [source] Isolated neck recurrence after definitive radiotherapy for node-positive head and neck cancer: Salvage in the dissected or undissected neckHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 8 2007Stanley L. Liauw MD Abstract Background. The role of salvage neck dissection for isolated regional recurrences after definitive radiotherapy (RT) is ill-defined. Methods. Five-hundred fifty patients were treated with RT for lymph node,positive head and neck cancer. RT consisted of a median dose of 74.4 Gy. Chemotherapy was administered in 133 patients (24%). Patients were followed for neck failure after planned neck dissection (n = 341) or observation (n = 209). Salvage therapy was offered to those with isolated neck recurrences. Results. There were 54 (10%) failures in the neck at a median 3.7 months after RT (range, 0 to 17 months). Thirteen patients had isolated recurrences after receiving definitive RT with (n = 11) or without (n = 2) neck dissection. Nine patients underwent attempted surgical salvage with or without re-irradiation and 4 were successfully salvaged without major complications. Conclusions. Patients with neck failure after definitive therapy usually have poor outcomes, but salvage attempts may be successful in selected patients with an isolated neck recurrence. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [source] Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2005Noel M. Kramer DO Abstract Background. Patients with local recurrences or new head and neck primary tumors in previously irradiated tissues have few options for salvage treatment. One option for select patients is to undergo reirradiation with concurrent chemotherapy. The purpose of this study is to report the initial clinical results of the Fox Chase phase I and II prospective reirradiation and chemotherapy studies. Methods. Between July 1996 and January 2002, 38 patients with locally recurrent unresectable squamous cell carcinoma of the head and neck were treated with concurrent chemotherapy and reirradiation on two prospective trials. All patients had received prior radiation therapy to the head and neck region (median dose, 64.2 Gy). Patients received cisplatin and paclitaxel along with hyperfractionated external beam radiation therapy to the site of recurrence. Results. The median follow-up was 10 months. The median survival was 12.4 months, with actuarial rates of overall survival of 50% and 35% at 1 and 2 years, respectively. During follow-up, 63% of patients experienced local progression of disease, all in the irradiated field. Actuarial progression-free survival at 1 year was 33%, with a median time to progression of 7.3 months. Acute grade 3 to 4 toxicity included neutropenia, nausea, emesis, and mucositis. Conclusions. Hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates durable locoregional control in select patients, although late toxicity may occasionally be significant. Only sites of disease recurrence need to be covered in the reirradiation fields. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Salvage surgery after radical accelerated radiotherapy with concomitant boost technique for head and neck carcinomasHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2005Daniel Taussky MD Abstract Background. Definitive radiotherapy (RT) for head and neck cancer is increasingly used to preserve organ function, whereas surgery is reserved for treatment failure. However, data are sparse regarding the feasibility of salvage surgery, particularly for unselected patients after accelerated RT. Methods. From 1991 to 2001, 297 patients, most with stage III to IV cancer (Union Internationale Contre le Cancer) were treated with concomitant boost RT (median dose, 69.9 Gy in 41 fractions) with or without chemotherapy (in 33%, usually cisplatin with or without 5-fluorouracil). The 75 patients seen with local and/or regional failure were studied. We analyzed the factors influencing the decision to attempt surgical salvage, the oncologic outcome, and the associated complications. Results. Seventeen (23%) of the 75 patients had a salvage operation. This included all five patients with laryngeal cancers but only 16% to 20% of patients with tumors in other locations. Most patients could not be operated on because of disease extension (40%) and poor general condition/advanced age (30%). Patients with low initial primary T and N classification were more likely to undergo surgery (p = .002 and .014, respectively). Median post-recurrence survival was significantly better for patients who had salvage operations than for those without surgical salvage treatment (44 vs 11 months, p = .0001). Thirteen patients were initially seen with postoperative complications (mostly delayed wound healing and fistula formation). Conclusions. After definitive accelerated RT with the concomitant boost technique, only a minority of patients with local or regional recurrence underwent salvage surgery. Disease stage, tumor location, and patient's general condition at the initial diagnosis seemed to be the main factors influencing the decision to attempt surgical salvage. For patients with initially resectable disease who undergo radical nonsurgical treatment, more effective follow-up is needed to favor early detection of treatment failure, which may lead to a timely and effective salvage surgery. © 2004 Wiley Periodicals, Inc. Head Neck27: 182,186, 2005 [source] Salvage treatment for persistent and recurrent T1,2 nasopharyngeal carcinoma by stereotactic radiosurgeryHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 9 2001Daniel T. T. Chua FRCR Abstract Objective To study the efficacy of stereotactic radiosurgery in salvaging early-stage persistent and recurrent nasopharyngeal carcinoma (NPC) after primary radiotherapy. Methods A prospective single-arm study evaluating the response and outcome of patients with rT1,2 NPC treated by stereotactic radiosurgery. Eleven patients with rT1,2 were treated by radiosurgery between March 1998 and March 2000. Four patients were treated for persistent disease occurring within 4 months after primary radiotherapy, six were treated for first recurrence, and one for third recurrence. Six patients had rT1 disease and five had rT2 disease. Most patients had disease not amenable to brachytherapy, surgery, or external re-irradiation. The median target volume was 5.8 cc (range, 3.3,16.9). Radiosurgery was performed with multiple noncoplanar arcs of photon, with a median dose of 12.5 Gy delivered to the 80% isodose line (range, 12,14 Gy). Median follow-up time after radiosurgery was 18 months (range, 9,30). Results Nine patients had complete regression of tumor as assessed by imaging, nasopharyngoscopy, and biopsy; one patient had partial regression of tumor; whereas one patient had static disease. The overall response rate was 91% (10 of 11) and the complete response rate was 82% (9 of 11). Two patients with complete response subsequently had local relapse develop, with one recurrence outside the treated volume 8 months after radiosurgery, and the other within the treated volume 6 months after radiosurgery. One patient with a partial response had neck node recurrence develop. Temporal lobe necrosis occurred in one patient but probably represents sequelae of primary radiation after reviewing the dosimetry. Ten patients are still alive, whereas one patient with local relapse had distant metastases develop and died. The estimated 1-year local control rate after radiosurgery was 82%. Conclusions Our preliminary results indicate that stereotactic radiosurgery is an effective treatment modality for persistent and recurrent T1,T2 NPC, and early control rate seems to be comparable to other salvage treatments. More clinical experiences and longer follow-up are still needed to validate our results and to address fully the role of radiosurgery in salvaging local failures of NPC. © 2001 John Wiley & Sons, Inc. Head Neck 23: 791,798, 2001. [source] Radical radiotherapy with high-dose-rate brachytherapy for uterine cervix cancer long-term results,JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 6 2007TH Khor Summary The aim of this is to report the results of radical radiotherapy in carcinoma of the cervix treated by high-dose rate (HDR) intracavitary brachytherapy and external beam radiotherapy (XRT) at a single centre in Singapore. This is a retrospective analysis of 106 consecutive cases with histologically proven cervical cancer, treated by HDR brachytherapy and XRT at the Mount Elizabeth Hospital from 1990 to 1993. External beam radiotherapy to the pelvis was delivered with 6 MV photons, to 45,50.4 Gy in 1.8 Gy fractions. High-dose-rate brachytherapy comprised two to three applications of an intrauterine tandem with paired ovoids, to a median dose of 18 Gy to point ,A', carried out during XRT. All 106 patients completed treatment. Their ages ranged from 32 to 80 years (median 57 years). Most patients presented with stage II or III disease (44 and 37%, respectively) and with squamous cell carcinoma (91%). Median follow-up time was 59 months (range 2,169 months). The 5-year relapse-free survival rate across all stages was 71%. The corresponding overall survival rate was 69%. Local control was achieved in 86 patients (81%); six patients had residual disease (6%), and 14 patients had local recurrence (13%). Fourteen patients developed metastatic disease (13%). On univariate analysis, tumour stage, haemoglobin level, number of brachytherapy treatments and overall treatment time were found to be prognostic factors for overall survival. Late complications were mild (Radiation Therapy Oncology Group score 1,2), except for one patient with grade 4 rectal toxicity. The complication rates were 8, 14 and 45%, respectively, for the rectum, bladder and vagina (stenosis). The use of two to three fractions of HDR intracavitary brachytherapy in addition to pelvic XRT achieves good outcomes. [source] Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapyJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2001Frank A. Vicini MD Abstract Background and Objectives We reviewed our institution's experience treating patients with ductal carcinoma-in-situ (DCIS) with breast-conserving therapy (BCT) to help define the interrelationship between excision volume, margin status, and tumor size with local recurrence. Methods From January 1980 to December 1993, 146 patients received BCT for DCIS. All patients underwent excisional biopsy and 95 cases (64%) underwent re-excision. Each patient received whole breast radiation to a median dose of 45 Gy. An additional 139 cases (94%) received a supplemental boost to the tumor bed (median total dose 60.4 Gy). The median follow-up is 7.2 years. Results Seventeen patients developed an ipsilateral breast failure for a 5- and 10-year actuarial rate of 10.2 and 12.4%, respectively. On multivariate analysis, patient age, margin status, the number of slides containing DCIS, the number of DCIS/cancerization of lobules (COL) foci near (< 5,mm) the margin, and a smaller volume of excision (< 60,cm3) were all independently associated with outcome. Although the local recurrence rate generally decreased as margin distance increased, these differences did not achieve statistical significance unless the volume of excision was taken into consideration. Conclusions These findings suggest that the success of BCT is directly related to the degree of surgical removal of DCIS and that margin status alone may be suboptimal in defining excision adequacy. J. Surg. Oncol. 2001;76:245,254. © 2001 Wiley-Liss, Inc. [source] Recovery after paediatric daycase herniotomy performed under spinal anaesthesiaPEDIATRIC ANESTHESIA, Issue 4 2000Hannu Kokki MD Summary In this prospective survey, recovery in hospital and at home was evaluated in 195 children aged 6 months to 10 years who had undergone herniotomy under spinal anaesthesia as a daycase procedure. Spinal anaesthesia was successful in most of the children, with only two patients being given general anaesthesia. Eighty-three percent of the children had pain at home and 19% had moderate or severe pain. Eighty-five percent of the children needed pain medication at home; the median dose of analgesics was 4 (1,9, 10th and 90th percentiles). Vomiting was noted in two of 195 children in hospital and in 10 of 192 children at home. Eleven children developed a mild position-dependent headache. Most of the children (183/191) recovered their normal daily activities during the first three postoperative days. We conclude that spinal anaesthesia is a safe and effective technique for paediatric herniotomy. Moreover, pain is common following herniotomy and children should be given analgesics for the first two or three postoperative days. [source] Impact of alemtuzumab as conditioning regimen component on transplantation outcomes in case of CMV-seropositive recipients and donorsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2008Yee Soo Chae We studied the incidence of cytomegalovirus (CMV) infection, clinical outcomes, and complications in 39 recipients of alemtuzumab-containing conditioning-stem cell transplantation, who were classified into two groups based on the median dose (35 mg) of alemtuzumab. All the recipients and donors were CMV-seropositive before transplantation. The median survival duration was 321 days (range, 46,1098 days) and the 2-year survival rate was 47.8%. The probability of nonrelapse mortality at 100 days and 2 years was 14.6% and 31.2%, respectively. The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) at Day 100 was 21.8%. The overall incidence of chronic GVHD (cGVHD) was 28.6%, including a 17.9% incidence of extensive cGVHD. The cumulative incidence of CMV antigenemia was 68.0%. There were no statistical differences in the engraftment, acute and cGVHD, relapse, CMV antigenemia, and overall survival (OS) between the two groups. Yet, the nonrelapse mortality (NRM) was significantly lower for the low-dose group (5.9% vs. 51.7%, P = 0.010). The present study showed that alemtuzumab was effective for GVHD prevention, yet caused a relatively high incidence of CMV antigenemia, regardless of the dose. Thus, a low dose of alemtuzumab (, 35 mg) would seem to be preferable in an allogeneic SCT setting when both the recipient and the donor are CMV seropositive. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Management of Stage IV Glottic Carcinoma: Therapeutic OutcomesTHE LARYNGOSCOPE, Issue 8 2004Gershon J. Spector MD Abstract Objectives/Hypothesis: The best therapeutic approach for the treatment of stage IV glottic carcinoma is controversial. Study Design: A retrospective study. Methods: A retrospective study of Tumor Research Project data was performed using patients with stage IV glottic squamous cell carcinoma treated with curative intent by five different treatment modalities from 1955 to 1998 at Washington University School of Medicine and Barnes-Jewish Hospital (St. Louis, MO). Results: Ninety-six patients with stage IV glottic carcinoma were treated by five modalities: total laryngectomy (TL) (n = 13), total laryngectomy with neck dissection (TL/ND) (n = 18), radiation therapy alone (RT) (n = 7) (median dose, 69.5 Gy), total laryngectomy combined with radiation therapy (TL/RT) (n = 10), and total laryngectomy and neck dissection combined with radiation therapy (TL/ND/RT) (n = 48). The overall 5-year observed survival (OS) rate was 39%, and the 5-year disease-specific survival (DSS) rate was 45%. The 5-year DSS rates for the individual treatment modalities included the following: TL, 58.3%; TL/ND, 42.9%; RT, 50.0%; TL/RT, 30.0%; and TL/ND/RT, 43.9%. There was no significant difference in DSS for any individual treatment modality (P = .759). The overall locoregional control rate was 69% (66 of 96). The overall recurrence rate was 39% with recurrence at the primary site and in the neck at 19% and 17%, respectively. Recurrence was not related to treatment modality. The 5-year DSS after treatment of locally recurrent cancer (salvage rate) was 30% (3 of 10) and for recurrent neck disease (28 of 67) was 42%. The incidence of delayed regional metastases was 28%; of distant metastasis, 12%; and of second primary cancers, 9%. There was no statistically significant difference in survival between node-negative (N0) necks initially treated (5-y DSS, 31%) versus N0 necks observed and later treated if necessary (5-y DSS, 44%) (P = .685). Conclusion: The five treatment modalities had statistically similar survival, recurrence, and complication rates. The overall 5-year DSS for patients with stage IV glottic carcinoma was 45%, and the OS was 39%. The cumulative disease-specific survival (CDSS) was 0.4770 with a mean survival of 10.1 years and a median survival of 3.9 years. Patients younger than age 55 years had better survival (DSS) than patients 56 years of age or older (P = .0002). Patients with early T stage had better survival than patients with more advanced T stage (P = .04). Tumor recurrence at the primary site (P = .0001) and in the neck (P = .014) and distant metastasis (P = .0001) had a deleterious effect on survival. Tumor recurrence was not related to treatment modality. Patients with clear margins of resection had a statistically significant improved survival (DSS and CDSS) compared with patients with close or involved margins (P = .0001). Post-treatment quality of life was not significantly related to treatment modality. Patients whose N0 neck was treated with observation and appropriate treatment for subsequent neck disease had statistically similar survival compared with patients whose N0 neck was treated prophylactically at the time of treatment of the primary. A minimum of 7 years of follow-up is recommended for early identification of recurrent disease, second primary tumors, and distant metastasis. None of the standard treatment modalities currently employed has a statistical advantage regarding survival, recurrence, complications, or quality of life. [source] Role of definitive radiotherapy in treating patients with inoperable Merkel cell carcinoma: The Westmead Hospital experience and a review of the literatureAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2009Clare SL Koh ABSTRACT Merkel cell carcinoma (MCC) is an uncommon aggressive primary cutaneous neuroendocrine carcinoma with a propensity to spread to regional lymph nodes and distant sites. The head and neck is the commonest site for presentation (50,60%) and recent evidence suggests patients treated with excision (to achieve a negative microscopic margin) and adjuvant wide-field radiotherapy (RTx) have an improved survival compared with surgery alone. Surgery is often not possible in elderly patients with multiple co-morbidities and in patients with advanced lesions. Definitive RTx therefore remains an option in these inoperable patients, with data to report its benefit. We report the results of eight patients with inoperable MCC treated with RTx alone between 1993 and 2007 at Westmead Hospital, Sydney, Australia, and also review the relevant literature on definitive RTx in the treatment of MCC. The median age at diagnosis was 82.5 years in five women and three men. All patients were Caucasian and none were immunosuppressed. Seven of eight patients were clinically node-positive. The mean duration of follow up was 12 months. A median dose of 50 Gy was prescribed. Seven of eight patients with inoperable MCC achieved in-field control, with most eventually relapsing distantly. Treatment-related toxicity was acceptable. In keeping with our results, other studies also report high rates of in-field locoregional control following RTx alone. These findings highlight the radioresponsiveness of advanced MCC and support a recommendation of moderate-dose RTx alone in select cases. Lower-dose palliative dose fractionation schedules (e.g. 25 Gy in five fractions) may be considered in patients of very poor performance status. [source] Trilostane treatment in dogs with pituitary-dependent hyperadreno-corticismAUSTRALIAN VETERINARY JOURNAL, Issue 10 2003JA BRADDOCK Objective To evaluate the efficacy of trilostane in treating dogs with pituitary-dependent hyperadrenocorticism. Design Prospective clinical trial using client-owned dogs with pituitary-dependent hyperadrenocorticism treated at University Veterinary Centre, Sydney from September 1999 to July 2001. Procedure Thirty dogs with pituitary-dependent hyperadrenocorticism treated with trilostane, a competitive inhibitor ,-HSD, were monitored at days 10, 30 and 90 then 3-monthly by clinical examination, tetracosactrin stimulation testing, urinary corticoid:creatinine ratio measurement and by client questionnaire. Results Twenty-nine of 30 dogs were successfully treated with trilostane (median dose 16.7 mg/kg; range 5.3 to 50 mg/kg, administered once daily); one responded favourably but died of unrelated disease before full control was achieved. Conclusion Trilostane administration controlled pituitary-dependent hyperadrenocorticism in these dogs. It was safe, effective and free of side-effects at the doses used. Most dogs were initially quite sensitive to the drug for 10 to 30 days, then required higher doses until a prolonged phase of stable dose requirements occurred. Urinary corticoid:creatinine ratio was useful in assessing duration of drug effect. Some dogs treated for more than 2 years required reduction or temporary cessation of drug because of iatrogenic hypoadrenocorticism. [source] An unrandomized prospective comparison of urinary continence, bowel symptoms and the need for further procedures in patients with and with no adjuvant radiation after radical prostatectomyBJU INTERNATIONAL, Issue 4 2003T. Hofmann OBJECTIVE To prospectively assess, using a questionnaire-based study, the relative differences and changes in urinary continence and bowel symptoms, and the need for further surgery, within the first year after radical retropubic prostatectomy (RRP) in patients with and with no adjuvant radiotherapy (aRT). PATIENTS AND METHODS The study included 96 men with clinically organ-confined adenocarcinoma of the prostate who underwent RRP between March 1998 and June 1999. A subset of 36 patients was recommended aRT of the prostatic fossa (median dose 54 Gy) because of positive surgical margins and/or seminal vesicle involvement. Using a mailed questionnaire all patients were prospectively assessed at 4-month intervals for the first year after RRP. RESULTS Valid data were analysed from 83 patients (overall response rate 86%), of whom 30 (36%) had received aRT. At 4 months a significantly lower proportion used no pads and significantly more used 1 pad/day in the aRT than in the RRP group (both P < 0.05). Eight and 12 months after RRP there was no statistically significant difference between the groups in urinary incontinence. However, 53% of men in the aRT group had stool urgency and 13% reported fecal incontinence at 4 months, compared with 1.9% and none (both P < 0.01) of the RRP group. At 1 year after RRP bowel symptoms and fecal continence improved in the aRT group and there was no significant difference for these symptoms between the groups. Starting aRT early (, 12 weeks after RP) or late (> 12 weeks) had no significant effect on urinary continence, bowel symptoms and fecal incontinence. Apart from dilatation of urethral strictures in one patient in each group, no further procedures were reported during the follow-up. CONCLUSION A moderate dose of aRT after RRP had a temporary effect on subjective urinary continence at 4 months but not at 8 and 12 months. More patients receiving aRT reported significant bowel symptoms at 4 and 8 months than those with RRP only, but at 1 year most of these symptoms had resolved and there were no significant differences between the groups. [source] An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczemaBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2007S.C. Weatherhead Summary Background, Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. Objectives, We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. Methods, All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2·5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. Results, On average, disease activity improved by 52% from baseline (95% confidence interval 45,60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as ,marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. Conclusions, We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted. [source] Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS)ACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010S. Dupont Dupont S, Striano S, Trinka E, Springub J, Giallonardo AT, Smith P, Ellis S, Yeates A, Baker G. Flexible dosing of adjunctive zonisamide in the treatment of adult partial-onset seizures: a non-comparative, open-label study (ZEUS). Acta Neurol Scand: 2010: 121: 141,148. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives,,, To assess the efficacy and tolerability of zonisamide in a study allowing flexible dosing in a more diverse and less refractory population than assessed in randomized controlled trials. Methods,,, This 19-week, non-comparative study of adjunctive zonisamide included 281 adults who had at least four partial-onset seizures within 8 weeks on one or two antiepileptic drugs. Alterations to zonisamide doses were allowed after titration, except during two fixed-dose periods (weeks 10,13 and 16,19). Results,,, At the end of the second fixed-dose period (median dose 300 mg/day), the median reduction in monthly seizure frequency was 33.3,41.1%; ,50% responder rate was 40.9,44.2%; and seizure freedom rate was 15.0,15.9%, depending on the analysis used. The most common adverse events were fatigue (16.7%) and somnolence (15.3%). Conclusions,,, Zonisamide demonstrated efficacy in a setting more reflective of clinical practice and was generally well tolerated. [source] Conversion from valproic acid onto topiramate in adolescents and adults with epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 5 2009A. Schreiner Objective,,, To explore efficacy and tolerability outcomes of topiramate (TPM) in patients with epilepsy transitioning from valproic acid (VPA) because of insufficient efficacy and/or tolerability onto TPM. Methods,,, Multicenter, open label, single arm, non-interventional study examining patients (,12 years) with epilepsy, transitioning onto TPM from baseline mono-or combination therapy with VPA. TPM was added onto the existing antiepileptic drug (AED) treatment and started at a dose of 25 mg once daily. The dose was titrated up with 25 mg/day increments, once every 1,2 weeks, until a final dose between 50,200 mg/day was reached. Based on clinical judgment, the treating physician decided whether or not and when the existing AED treatment especially with VPA could be withdrawn. Documented were type and frequency of seizures, TPM dose, quality of life (QOLIE-10 questionnaire), subjective perception of improvement, and adverse events (AE). Results,,, One hundered and forty-seven patients (59% women, mean age 41 years) switched from baseline VPA treatment onto TPM because of insufficient efficacy (61%) and/or poor tolerability (81%). Average duration of follow-up was 20.3 weeks with an overall discontinuation rate of 16.3% of patients, mainly because of AE (in 8.2% of 147 patients). At study endpoint, the intended shift to TPM monotherapy was achieved in 70% of patients at a median dose of 150 mg/day. A seizure reduction of ,50% was achieved in 75% of patients in the last scheduled period (week 8,20), and 51% of patients entering that period remained seizure-free. Quality of life improved significantly as compared with baseline for all domains of QOLIE-10 (P < 0.001). Most frequent AEs were weight decrease (4.8%), paraesthesia and fatigue (4.1% each), speech disorder and headaches (2.7% each). Conclusions,,, In patients with epilepsy not satisfactorily treated with VPA, conversion to TPM was associated with improved seizure control as well as improvement in several aspects of quality of life. [source] Osteosarcoma of the jaw/craniofacial regionCANCER, Issue 14 2009Outcomes after multimodality treatment Abstract BACKGROUND: The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT). METHODS: Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7-77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50-66 Gy). RESULTS: The median follow-up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease,specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT-associated complications were 40% and 47% at 5 years and 10 years, respectively. CONCLUSIONS: The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins. Cancer 2009. © 2009 American Cancer Society. [source] Unexpectedly frequent hepatitis B reactivation by chemoradiation in postgastrectomy patients,CANCER, Issue 9 2004Jason Chia-Hsien Cheng M.D., M.S. Abstract BACKGROUND Postgastrectomy patients undergoing chemoradiation risk chemoradiation-induced liver disease (CRILD). The objectives of this study were to investigate dosimetric implications and assess biologic susceptibility to CRILD in these patients. METHODS Sixty-two patients with Stage IB,IV gastric/gastroesophageal adenocarcinoma without metastases underwent radical total/subtotal gastrectomy; regional lymph node dissection; and postoperative, adjuvant, concomitant chemoradiotherapy (CCRT). Among these, 8 patients developed CRILD (defined as Grade 3,4 liver toxicity), and 11 patients were chronic hepatitis B virus (HBV) carriers (HBV+). Chemotherapy consisted of 1 cycle of etoposide, leucovorin, and 5-fluorouracil (ELF); followed by 5 weekly high doses of 5-fluorouracil (2000,2600 mg/m2) and leucovorin concurrent with radiotherapy (median dose, 45 grays [Gy] to the tumor bed/regional lymphatics); followed by 3 cycles of ELF separated by a 21-day interval. Patients were followed for , 4 months after CCRT. Patient-related and dosimetric factors were correlated with CRILD. RESULTS HBV+ status was the only independent factor associated with CRILD. HBV+ patients had a higher CRILD incidence (6 of 11 patients vs. 2 of 51 patients; P < 0.001). HBV-negative patients with CRILD were recipients of a higher mean liver dose (MLD) (23.8 Gy vs. 15.2 Gy; P = 0.009) and a higher volume fraction of liver that received > 30 Gy (36.5% vs. 19.7%; P = 0.009) compared with noncarriers without CRILD, but no MLD difference was found between HBV+ patients with or without CRILD. Moreover, in four of six carriers with CRILD, HBV infection was reactivated during CRILD. Two of the toxicities were fatal. CONCLUSIONS HBV carriers had a higher incidence of CRILD after postgastrectomy CCRT, probably related to HBV reactivation. Dosimetric parameters modulated the risk of CRILD in noncarriers, but not in carriers. These factors deserve attention in CRILD/HBV+ patients, and the underlying pathogenesis warrants investigation. Cancer 2004. © 2004 American Cancer Society. [source] Adjuvant irradiation for cervical lymph node metastases from melanomaCANCER, Issue 7 2003Matthew T. Ballo M.D. Abstract BACKGROUND The risk of regional disease recurrence after surgery alone for lymph node metastases from melanoma is well documented. The role of adjuvant irradiation remains controversial. METHODS The medical records of 160 patients with cervical lymph node metastases from melanoma were reviewed retrospectively. Of these, 148 (93%) presented with clinically palpable lymph node metastases. All patients underwent surgery and radiation to a median dose of 30 grays (Gy) at 6 Gy per fraction delivered twice weekly. Surgical resection was either a selective neck dissection in 90 patients or local excision of the lymph node metastasis in 35 patients. Only 35 patients underwent a radical, modified radical, or functional neck dissection. RESULTS At a median follow-up of 78 months, the actuarial local, regional, and locoregional control rates at 10 years were 94%, 94%, and 91%, respectively. Univariate analysis of patient, tumor, and treatment characteristics failed to reveal any association with the subsequent rate of local or regional control. The actuarial disease-specific (DSS), disease-free, and distant metastasis-free survival (DMFS) rates at 10 years were 48%, 42%, and 43%, respectively. Univariate and multivariate analyses revealed that patients with four or more involved lymph nodes had a significantly worse DSS and DMFS. Nine patients developed a treatment-related complication requiring medical management, resulting in a 5-year actuarial complication-free survival rate of 90%. CONCLUSIONS Adjuvant radiotherapy resulted in a 10-year regional control rate of 94%. Complications for all patients were rare and manageable when they did occur. The authors recommend adjuvant irradiation for patients with extracapsular extension, lymph nodes measuring 3 cm in size or larger, the involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a selective therapeutic neck dissection. Cancer 2003;97:1789,96. © 2003 American Cancer Society. DOI 10.1002/cncr.11243 [source] Use of inhaled nitric oxide in the new born period: results from the European inhaled nitric oxide registryACTA PAEDIATRICA, Issue 6 2010Chris Dewhurst Abstract Aims:, The aim of this study was to present data relating to the use of inhaled nitric oxide (iNO) in newborn infants included in the European Inhaled Nitric Oxide Registry. Methods:, Demographic, clinical and therapeutic data from seven European centres are reported. Univariate analyses were performed to identify factors associated with acute response to iNO and survival without extra corporeal membrane oxygenation (ECMO). Results:, A total of 112 newborn infants received iNO, with 40% being less than 34 weeks gestational age. The commonest indication for iNO was secondary pulmonary hypertension. Acute response to iNO was more common in infants with a higher oxygenation index (median OI 32.7 vs 22.6, p = 0.040), although acute response did not predict survival without ECMO. Infants who survived without ECMO had a lower OI prior to therapy (median OI 24 vs 43, p = 0.009), were commenced on a higher starting dose (median dose 20 ppm vs 10 ppm p = 0.013) and received a lower maintenance dose (median dose 10 vs 17 ppm, p = 0.027) than those who died or received ECMO. Conclusion:, Collating and reporting data about iNO therapy in neonates across a number of European centres using a web-based system is feasible. These data may be used to monitor the clinical use of iNO, identify adverse effects, generate research hypotheses and promote high standards in the clinical use of iNO. [source] Threshold levels of purified natural Bos d 2 for inducing bronchial airway response in asthmatic patientsCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2002T. Zeiler Summary Background Provocation tests are invaluable in establishing threshold levels and a causal relationship between atopic asthma and a certain allergen source, especially in relation to work-associated exposure. Purified major allergens open possibilities for a more accurate assessment of sensitization. Objective To determine the threshold dose of purified major bovine dander allergen Bos d 2 in bronchial provocation in comparison with the standard allergen and a set of other parameters of allergy. Method Nine consecutive patients referred to hospital for confirming the bovine origin of their occupational asthma were subjected to bronchial provocation tests with purified natural Bos d 2 and a standard bovine dander allergen. Additional tests included bronchial histamine challenge, measurements of total IgE, specific IgE antibody determinations and skin prick tests (SPT) with both allergens. Results In the provocation tests with Bos d 2, a 15% decrease in the forced expiratory volume in 1 s (FEV1) and/or peak expiratory flow (PEF) values in eight out of nine patients confirmed the predominant role of Bos d 2 in the sensitization. The threshold dose of Bos d 2 varied from 0.1 µg to > 100 µg (median ± median absolute deviation = 4.5 ± 3.9 µg). A positive SPT was induced by a median dose of 13.9 ± 9.8 µg of Bos d 2. Bronchial response to histamine and IgE antibodies against Bos d 2 showed the highest correlations to the provocations results. Conclusions The efficacy of Bos d 2 in bronchial provocation in patients with occupational cattle-associated asthma was confirmed and the range of the threshold level was determined. There were individual variations, but the response in provocation remains the reference method for identification of the cause of occupational atopic asthma. SPT and the measurement of specific IgE antibodies, preferably with purified or recombinant major allergens, increase the accuracy of the diagnosis. [source] | |||||||||||||||||||||||||