Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study.

AIMS: Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. METHODS AND RESULTS: Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16 years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54 months (interquartile range 28-111), 25 (28%) patients had 53 appropriate therapies [ICD shock n = 45, anti-tachycardia pacing (ATP) n = 8], incidence rate 4.7 per 100 patient years (95% CI 2.9-7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n = 4, ATP n = 4), incidence rate 1.1/100 patient years (95% CI 0.4-2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n = 15) and infection (n = 10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication. CONCLUSION: In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

A phase III randomized trial of high-dose CEOP + filgrastim versus standard-dose CEOP in patients with non-Hodgkin lymphoma: 10-year follow-up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial.

Increasing dose intensity (DI) of chemotherapy for patients with aggressive non-Hodgkin lymphoma (NHL) may improve outcomes at the cost of increased toxicity. This issue was addressed in a randomized trial aiming to double the DI of myelosuppressive drugs. Between 1994 and 1999, 250 patients with previously untreated aggressive NHL were randomized to treatment with six cycles of 3-weekly standard (s) or intensive (i) chemotherapy: s-CEOP-cyclophosphamide 750, epirubicin 75, vincristine 1.4 mg/m(2) all on day 1, and prednisolone 100 mg days 1-5; i-CEOP-cyclophosphamide 1,500, epirubicin 150, vincristine 1.4 mg/m(2) all on day 1, and prednisolone 100 mg days 1-5. Primary endpoint was 5-year overall survival (OS). Relative to s-CEOP patients, i-CEOP patients achieved a 78% increase in the DI of cyclophosphamide and epirubicin. Despite this, there was no significant difference in any outcome: 5-year OS (56.7% i-CEOP; 55.1% s-CEOP; P = 0.80), 5-year progression free survival (PFS; 41% i-CEOP; 43% s-CEOP; P = 0.73), 5-year time to progression (TTP; 44% i-CEOP; 47% s-CEOP; P = 0.72), or complete remission (CR) + unconfirmed CR (CRu) rates (53% i-CEOP; 59% s-CEOP; P = 0.64). Long-term follow up at 10 years also showed no significant differences in OS, PFS, or TTP. The i-CEOP arm had higher rates of febrile neutropenia (70 vs. 26%), hospitalisations, blood product utilisation, haematological and gastrointestinal toxicities, and lower quality of life scores during treatment, although without significant differences 6-month later. In the treatment of aggressive NHL in the prerituximab era, increasing DI did not result in improved outcomes, while at the same time lead to increased toxicity.

Cost-effectiveness of smoking cessation to prevent age-related macular degeneration.

BACKGROUND: Tobacco smoking is a risk factor for age-related macular degeneration, but studies of ex-smokers suggest quitting can reduce the risk. METHODS: We fitted a function predicting the decline in risk of macular degeneration after quitting to data from 7 studies involving 1,488 patients. We assessed the cost-effectiveness of smoking cessation in terms of its impact on macular degeneration-related outcomes for 1,000 randomly selected U.S. smokers. We used a computer simulation model to predict the incidence of macular degeneration and blindness, the number of quality-adjusted life-years (QALYs), and direct costs (in 2004 U.S. dollars) until age 85 years. Cost-effectiveness ratios were based on the cost of the Massachusetts Tobacco Control Program. Costs and QALYs were discounted at 3% per year. RESULTS: If 1,000 smokers quit, our model predicted 48 fewer cases of macular degeneration, 12 fewer cases of blindness, and a gain of 1,600 QALYs. Macular degeneration-related costs would decrease by $2.5 million if the costs of caregivers for people with vision loss were included, or by $1.1 million if caregiver costs were excluded. At a cost of $1,400 per quitter, smoking cessation was cost-saving when caregiver costs were included, and cost about $200 per QALY gained when caregiver costs were excluded. Sensitivity analyses had a negligible impact. The cost per quitter would have to exceed $77,000 for the cost per QALY for smoking cessation to reach $50,000, a threshold above which interventions are sometimes viewed as not cost-effective. CONCLUSION: Smoking cessation is unequivocally cost-effective in terms of its impact on age-related macular degeneration outcomes alone.

Cost-effectiveness of ranibizumab for neovascular age-related macular degeneration.

BACKGROUND: Intravitreal ranibizumab prevents vision loss and improves visual acuity in patients with neovascular age-related macular degeneration, but it is expensive, and efficacy beyond 2 years is uncertain. METHODS: We assessed the cost-effectiveness of ranibizumab compared with no ranibizumab over 10 years, using randomized trial efficacy data for the first 2 years, post-trial efficacy assumptions, and ranibizumab acquisition costs ranging from the wholesale price ($1,950 per dose) to the price of bevazicumab ($50), a similar molecule which may be equally efficacious. We used a computer simulation model to estimate the probability of blindness, the number of quality-adjusted life-years (QALYs), direct costs (in 2004 U.S. dollars), and cost-effectiveness ratios for a 67-year old woman. Costs and QALYs were discounted at 3% per year. RESULTS: The probability of blindness over 10 years was reduced from 56% to 34% if ranibizumab was efficacious for only 2 years, 27% if efficacy was maintained for a further 2 years only (base-case scenario), and 17% if visual acuity at 4 years was then sustained. It was cost-saving under all price assumptions, when caregiver costs were included. When caregiver costs were excluded, the cost per QALY for the base-case ranged from $5,600, assuming the bevazicumab price, to $91,900 assuming the wholesale ranibizumab price. The cost per QALY was < $50,000 when the cost of ranibizumab was less than $1000. CONCLUSION: From a societal perspective, ranibizumab was cost-saving. From a health care funder's perspective, ranibizumab was an efficient treatment when it cost less than $1000 per dose.

Flexible low-intensity combination chemotherapy for elderly patients with acute myeloid leukaemia: a multicentre, phase II study.

OBJECTIVE: To evaluate the efficacy of a flexible low-intensity combination chemotherapy (FLICC) protocol in a multicentre, phase II study of elderly patients with acute myeloid leukaemia (AML). METHOD: Twenty-five patients aged 61-78 years (median 70 years) with de novo (n = 17) or secondary (n = 8) AML (cytogenetic risk: favourable 2, intermediate 18, adverse 2, unknown 3) from eight Australian centres were enrolled. Treatment comprised mitoxantrone 6 mg/m(2) intravenously daily for 3 days, cytarabine 10mg/m(2) subcutaneously every 12 hours for 7-14 days and etoposide 100mg orally for 7-14 days. RESULTS: The treatment was generally well tolerated, and 13 patients (52%) achieved a complete remission (CR). One patient achieved a partial remission but died on day 28 due to pneumonia. Five patients (20%) had no response, whilst six (24%) died on or before day 30 and so were not evaluable. The median overall survival (OS) was 6.5 months, and the median remission duration was 7.7 months. Estimated 1-year survival was 32%, but patients achieving CR had an estimated 1-year survival of 64%, whereas none in the non-CR group survived to 1 year. Two of the CR patients have survived beyond 2 years. OS was significantly shorter in the adverse cytogenetic risk group of patients compared with the favourable- and intermediate-risk groups, with the rates of death relative to the adverse group being 0.02 and 0.08 in the favourable- and intermediate-risk groups, respectively. There was no significant association between CR rate and pre-existing myelodysplasia or the presence of multilineage dysplasia. The median durations of significant neutropenia (<0.5 x 10(9)/L) and thrombocytopenia (<20 x10(9)/L) with the first course of treatment in the 19 evaluable patients were 19 days (range 12-26) and 11 days (range 1-25), respectively. The median duration of stay in the hospital was 27 days (range 14-42). These values were much shorter for the second course of treatment: 6 days, 5 days and 15 days, respectively. CONCLUSION: The findings of this multicentre, phase II study validate the previously reported single-institution experience with the FLICC protocol in elderly patients with AML. The clinical outcome with this protocol is comparable to those reported with more aggressive anti-leukaemia protocols.

The Quit Benefits Model: a Markov model for assessing the health benefits and health care cost savings of quitting smoking.

BACKGROUND: In response to the lack of comprehensive information about the health and economic benefits of quitting smoking for Australians, we developed the Quit Benefits Model (QBM). METHODS: The QBM is a Markov model, programmed in TreeAge, that assesses the consequences of quitting in terms of cases avoided of the four most common smoking-associated diseases, deaths avoided, and quality-adjusted life-years (QALYs) and health care costs saved (in Australian dollars, A$). Quitting outcomes can be assessed for males and females in 14 five year age-groups from 15-19 to 80-84 years. Exponential models, based on data from large case-control and cohort studies, were developed to estimate the decline over time after quitting in the risk of acute myocardial infarction (AMI), stroke, lung cancer, chronic obstructive pulmonary disease (COPD), and death. Australian data for the year 2001 were sourced for disease incidence and mortality and health care costs. Utility of life estimates were sourced from an international registry and a meta analysis. In this paper, outcomes are reported for simulated subjects followed up for ten years after quitting smoking. Life-years, QALYs and costs were estimated with 0%, 3% and 5% per annum discount rates. Summary results are presented for a group of 1,000 simulated quitters chosen at random from the Australian population of smokers aged between 15 and 74. RESULTS: For every 1,000 males chosen at random from the reference population who quit smoking, there is a an average saving in the first ten years following quitting of A$408,000 in health care costs associated with AMI, COPD, lung cancer and stroke, and a corresponding saving of A$328,000 for every 1,000 female quitters. The average saving per 1,000 random quitters is A$373,000. Overall 40 of these quitters will be spared a diagnosis of AMI, COPD, lung cancer and stroke in the first ten years following quitting, with an estimated saving of 47 life-years and 75 QALYs. Sensitivity analyses indicated that QBM predictions were robust to variations of +/- 10% in parameter estimates. CONCLUSION: The QBM can answer many of the questions posed by Australian policy-makers and health program funders about the benefits of quitting, and is a useful tool to evaluate tobacco control programs. It can easily be re-programmed with updated information or a set of epidemiologic data from another country.

The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement.

BACKGROUND: The prognostic significance of marrow involvement in diffuse large cell lymphoma (DLCL) is controversial. Factors that that have been reported to influence prognosis include the pattern and extent of marrow infiltration and histological discordance between the primary site and the bone marrow. METHODS: Bone marrow biopsies from 172 patients with newly diagnosed DLCL entered in two consecutive trials of the Australasian Leukaemia and Lymphoma Group were analyzed. Progression-free (PFS) and overall survival (OS) were calculated according to the absence or presence of bone marrow involvement (BMI), the extent of lymphomatous infiltration and the presence of histological discordance between the primary site and the bone marrow. RESULTS: Of 172 patients with DLCL accrued between 1982 and 1990, who were treated with CHOP or CHOP-like regimens, 47 (27%) demonstrated marrow involvement on examination of multiple levels. Seventy two percent (34/47) of patients had discordant marrow involvement (<50% large cells) and 28 had minimal (<10%) involvement; these latter patients with minimal marrow involvement (<10%) had similar PFS & OS to the 113 patients without involvement. Within the group of 47 patients with marrow involvement, an increasing percentage of BM involvement was significantly associated with an increasing percentage of concordant histology and a decreasing PFS & OS. CONCLUSIONS: Minimal BMI, seen in the majority of patients with DLCL with marrow infiltration, appears not to influence the PFS & OS. However, an increasing degree of marrow involvement is associated with an increasing component of large cells and a poorer prognosis in DLCL patients, independent of other risk factors.

Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery.

UNLABELLED: Predicting outcome after aggressive therapy for advanced rectal cancer remains difficult. (18)F-FDG PET has emerged as a valid method for predicting patient outcomes after therapy in an increasing number of cancers. We evaluated the prognostic information obtained from the degree of change in tumor (18)F-FDG PET uptake induced by chemoradiation before radical curative surgery in patients with T3/T4 rectal cancer. METHODS: The study included 34 consecutive patients with T3/T4 Nx M0 rectal cancer on structural imaging, who underwent staging and postchemoradiation (18)F-FDG PET before planned curative surgery. Change in (18)F-FDG uptake was graded visually as complete (CMR), partial (PMR), or no (NoMR) metabolic response. Pre- and postchemoradiation (18)F-FDG PET-derived standardized uptake values (SUVs) were then obtained for PMR patients to determine whether SUV further stratified this subgroup. Operative findings were available in 30 patients (3 excluded because of (18)F-FDG PET-defined M1 disease, 1 refused surgery). Clinical status at study closeout (alive free from disease, FFD; alive with disease, AWD; or died of disease, DOD) was available for all patients. RESULTS: A pathologic complete response was found in only 6 of 30 patients (5 CMR, 1 false-positive PMR). However, after an estimated median 3.1 y of follow-up, all 17 CMR patients were FFD, 6 of 10 PMR patients were FFD, 2 of 10 had DOD, and 2 of 10 were AWD. All 3 NoMR patients DOD. PET response was highly significantly associated with overall survival duration (P < 0.0001) and time to progression (P < 0.0001). Pathologic complete response was the only other statistically significant prognostic factor (P < 0.03). The percentage of maximum SUV change after chemoradiation was not predictive of survival in PMR patients. CONCLUSION: Using a simple qualitative assessment, postchemoradiation (18)F-FDG PET scintigraphy provides good medium-term prognostic information in patients with advanced rectal cancer undergoing radical surgery with curative intent.

Unexpected long-term survival after low-dose palliative radiotherapy for non-small cell lung cancer.

BACKGROUND: Many experienced oncologists have encountered patients with proven non-small cell lung cancer (NCLC) who received modest doses of palliative radiotherapy (RT) and who unexpectedly survived for > 5 years; some were apparently cured. We used a very large prospective database to estimate the frequency of this phenomenon and to look for correlative prognostic factors. METHODS: Patients with histologically or cytologically proven NSCLC, treated with palliative RT to a dose of < or = 36 Gy, were identified from a prospective database containing details of 3035 new patients registered from 1984-1990. RESULTS: An estimated 1.1% (95% confidence interval, 0.7-1.6%) of 2337 palliative RT patients survived for 5 or more years after commencement of RT, including 18 patients who survived progression-free for 5 years. Estimated median survival was 4.6 months. Five-year survivors had significantly better Eastern Cooperative Oncology Group performance status at presentation than non-5-year survivors (P = 0.024) and were less likely to have distant metastases (P = 0.020). RT dose did not appear to be a significant prognostic factor. Patients who survived 5 years without progression had an estimated 78% probability of remaining free from progression in the next 5 years. CONCLUSIONS: Approximately 1% of patients with proven NSCLC survived for > 5 years after palliative RT, and many of these patients appeared to have been cured by a treatment usually considered to be without curative potential. Because of the potential for long-term survival, doses to late-reacting normal tissues should be kept within tolerance when prescribing palliative RT in NSCLC.

Metabolic (FDG-PET) response after radical radiotherapy/chemoradiotherapy for non-small cell lung cancer correlates with patterns of failure.

BACKGROUND: We previously reported that F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) response correlated strongly with survival after radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer (NSCLC). PET-response, survival and patterns of failure data are presented with long-term follow-up. METHODS: Pre- and post-treatment FDG-PET scans were performed for 88 patients after concurrent platinum-based radical chemo/RT (n = 73) or radical RT alone (n = 15). PET responses were prospectively assessed as either complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), or progressive metabolic disease (PMD). RESULTS: RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32 (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow-up PET was 23 months; median follow-up duration 35 months. One and 2 year survival after follow-up PET was 68% and 45%, respectively. Median survival for CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One-year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2 years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR patients had higher rates of local failure (HR 2.15, p = 0.009) and distant metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or both (n = 10). CONCLUSIONS: Attainment of CMR after radical RT/chemoRT for NSCLC bestows superior freedom from local and distant relapse; late local relapse is common.

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine.

The value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 x 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 x 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily x 5, idarubicin x 2, etoposide x 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.

Usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with a residual structural abnormality after definitive treatment for squamous cell carcinoma of the head and neck.

BACKGROUND: Residual structural abnormalities after definitive treatment of head and neck squamous cell carcinoma (HNSCC) are common and pose difficult management problems. The usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) to supplement conventional evaluation with clinical and standard radiologic examination (CE) in such patients was assessed. METHODS: Fifty-three eligible patients were identified with residual structural abnormalities on CE. True disease extent could be validated in 46 patients. Patients had a median potential follow-up of 55 months (range, 41-75 months) from the date of PET scan to the analysis closeout date. RESULTS: PET had better diagnostic accuracy than CE (p = .0002) and induced management change in 21 patients (40%; 95% confidence interval [CI], 26%-54%), including avoidance of unnecessary planned surgery in 14 patients with negative PET. Appropriate management change was confirmed in 19 (95%) of 20 evaluable cases. Disease presence and extent assessment by PET were significant predictors of survival (p < .0001), whereas the extent of disease determined by CE was not. CONCLUSION: PET added significantly to the value of CE in restaging disease in patients with structural abnormalities after definitive treatment of HNSCC. Management decisions based on PET were appropriate in most patients.

Early FDG-PET imaging after radical radiotherapy for non-small-cell lung cancer: inflammatory changes in normal tissues correlate with tumor response and do not confound therapeutic response evaluation.

PURPOSE: To investigate the relationship between positron emission tomography (PET) detected inflammatory changes in irradiated normal tissues and metabolic response at tumor sites in patients receiving radical radiotherapy for non-small-cell lung cancer. The prognostic significance of these changes was also studied. METHODS: In 73 consecutive patients, (18)F-fluorodeoxyglucose (FDG) PET was performed at a median of 70 days after completion of radical radiotherapy. Radiation-induced inflammatory change was scored for normal tissues within the radiation treatment volume using a 0-3 grading scale. Metabolic tumor response was assessed using a pattern-recognition algorithm comparing pre- and posttreatment scans. Prognostic significance of inflammatory changes was tested using the Cox proportional hazards regression model. RESULTS: Increased FDG uptake in normal tissues (radiotoxicity) was associated with a greater likelihood of complete or partial tumor response on both PET (p = 0.0044) and computed tomography (p = 0.029). Prognostic stratification provided by PET response was both significant and of a similar magnitude in patients with low- and high-grade radiotoxicity. CONCLUSION: Postradiotherapy inflammatory changes detected by FDG-PET are positively correlated with tumor response, suggesting that tumor radioresponsiveness and normal tissue radiosensitivity may be linked. Prognostic stratification provided by PET is not compromised by inflammatory changes if a meticulous visual response assessment technique is used.

Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer.

PURPOSE: To prospectively study the capacity of positron emission tomography (PET) and computed tomography (CT) to determine response soon after radical radiotherapy or chemoradiotherapy and, thereby, predict survival. PET is known to provide a more accurate estimate of true extent of disease than CT when used to stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-three patients with NSCLC underwent [(18)F]fluorodeoxyglucose PET and CT scans before and after radical radiotherapy (n = 10) or chemoradiotherapy (n = 63). Follow-up PET scans were performed at a median of 70 days after radiotherapy. The median PET-CT interval was 1 day. Each patient had determinations of response to therapy made with PET and CT, categorized as complete response, partial response, no response, progressive disease, or nonassessable. Responses were correlated with subsequent survival. RESULTS: Median survival after follow-up PET was 24 months. There was poor agreement between PET and CT responses (weighted kappa = 0.35), which were identical in only 40% of patients. There were significantly more complete responders on PET (n = 34) than CT (n = 10), whereas fewer patients were judged to be nonresponders (12 patients on PET v 20 on CT) or nonassessable (zero patients on PET v six on CT) by PET. Both CT and PET responses were individually significantly associated with survival duration; but on multifactor analysis that included the known prognostic factors of CT response, performance status, weight loss, and stage, only PET response was significantly associated with survival duration (P <.0001). CONCLUSION: In NSCLC, a single, early, posttreatment PET scan is a better predictor of survival than CT response, stage, or pretreatment performance status.

Comparison of the biological activity of grade GUR 1120 and GUR 415HP UHMWPE wear debris.

This study evaluated the in vitro response of murine macrophages to clinically relevant polyethylene particles from two grades of UHMWPE at varying volume doses. Clinically relevant UHMWPE wear debris was generated in vitro using a tri-pin-on-disc tribometer. The debris was observed using a scanning electron microscope and analysed by image analysis. There was no significant difference in the wear rates of the two grades of UHMWPE. Analysis of the wear debris showed that GUR 415HP produced a higher percentage of mass of debris in the submeter size range compared to GUR 1120. The wear debris was co-cultured with C3H murine peritoneal macrophages at particle volume (microm(3)): cell number ratios of 100 :1, 50 :1, 10 :1 and 1 :1 for both grades of UHMWPE and additionally at 0.5 :1 and 0.1 :1 for grade GUR 415HP. The secretion of TNF-alpha was determined by ELISA. Significantly elevated levels of TNF-alpha were secreted at 100 :1 ratio when macrophages were challenged with wear debris from GUR 1120 and at 10 :1 and 1 :1 for debris from GUR 415HP. The results suggested that the greater percentage mass of debris in the submicrometer size range from GUR 415HP lead to a substantial increase in biological activity for this grade of UHMWPE on a volume for volume basis when compared with GUR 1120.

Early mortality after radical radiotherapy for non-small-cell lung cancer: comparison of PET-staged and conventionally staged cohorts treated at a large tertiary referral center.

PURPOSE: At our center, approximately 30% of radical radiotherapy (RRT) candidates become ineligible for RRT for non-small-cell lung cancer (NSCLC) after positron emission tomography (PET). We hypothesized that early cancer death rates would be lower in patients receiving RRT after PET staging compared with conventionally staged patients. METHODS AND MATERIALS: Two prospective cohorts were compared. Cohort 1 consisted of all participants in an Australian randomized trial from our center given 60 Gy conventionally fractionated RRT with or without concurrent carboplatin from 1989 to 1995. Eligible patients had Stage I--III, Eastern Cooperative Oncology Group status 0 or 1, <10% weight loss, and had not undergone PET. Cohort 2 included all RRT candidates between November 1996 and April 1999 who received RRT after PET staging and fulfilled the above criteria for stage, Eastern Cooperative Oncology Group status, and weight loss. RESULTS: Eighty and 77 eligible patients comprised the PET and non-PET groups, respectively. The PET-selected patients had significantly less weight loss; 73% and 49% of the PET and non-PET patients, respectively, received chemotherapy. The median survival was 31 months for PET patients and 16 months for non-PET patients. Mortality from NSCLC and other causes in the first year was 17% and 8% for PET patients and 32% and 4% for non-PET patients, respectively. The hazard ratio for NSCLC mortality for PET vs. non-PET patients was 0.49 (p = 0.0016) on unifactorial analysis and was 0.55 (p = 0.0075) after adjusting for chemotherapy, which significantly improved survival. CONCLUSION: Patients selected for RRT after PET have lower early cancer mortality than those selected using conventional imaging.