Exclusive radiotherapy for non-small cell lung cancer. A retrospective multicentric study

PurposeTo evaluate the daily practice of management of early inoperable lung cancer (stage I).Materials and methodsThe analysis was based on a questionnaire which was sent to participated centers. Between 1982 and 1994, 123 patients with an early stage I inoperable lung cancer were treated with definitive irradiation in the different institutions. The survival distributions were estimated by the Kaplan-Meier method. The following covarties were analyzed: age, gender, Karnofsky status, symptoms, diagnostic work-up, T stage, tumour size, tumour location, histology, respiratory and cardiac contra-indication. The univariate analysis was performed using log-rank test. Cox regression models were used to find the independent prognostic factors.Results: The 2 and 5-year survival rates were 34% and 8% respectively. The 5-year local failure rate was 42% for T1 and 82% for T2. In a multivariate analysis, the most important prognostic factors for survival were the performance status and the stage. After adjustment for these two covariates, the total dose delivered had no impact for the range of doses used in this series.ConclusionsOur poor data outlined the needs for better radiation technique and for a better staging system

A possible role for Phlebotomus (Anaphlebotomus) rodhaini (Parrot, 1930) in transmission of Leishmania donovani

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis (VL, kala azar), caused by <it>Leishmania donovani </it>is a major health problem in Sudan and other East African countries. In this region the only proven vectors of <it>L. donovani </it>are <it>Phlebotomus orientalis </it>in eastern Sudan, Ethiopia and Upper Nile areas of Southern Sudan and <it>Phlebotomus martini </it>in Ethiopia, Kenya and Southern Sudan. In this report, we present the first evidence that <it>Phlebotomus rodhaini </it>may also play a role in maintaining transmission of <it>L. donovani </it>between animal reservoir hosts in eastern Sudan. The study was conducted in a zoonotic focus of visceral leishmaniasis in Dinder National Park, eastern Sudan, where previous work showed high infection rates of <it>L. donovani </it>in <it>P. orientalis</it>. Sand flies, captured by CDC traps were dissected and examined for infection with <it>Leishmania </it>parasites. Parasite isolates were subjected to <it>L. donovani </it>specific PCR. Field experiments were also carried out to compare efficiency of rodent baited and un-baited CDC traps in collection of <it>P. rodhaini </it>and determine its man-biting rate.</p> <p>Results</p> <p>Three female <it>P. rodhain</it>i were found infected with <it>Leishmania </it>parasites in an astonishingly small number of flies captured in three separate field trips. Two of these isolates were typed by molecular methods as <it>L. donovani</it>, while the third isolate was inoculated into a hamster that was subsequently lost. Although <it>P. rodhaini is </it>generally considered a rare species, results obtained in this study indicate that it can readily be captured by rodent-baited traps. Results of human landing collection showed that it rarely bites humans in the area.</p> <p>Conclusion</p> <p>It is concluded that <it>P. rodhaini </it>is a possible vector of <it>L. donovani </it>between animal reservoir hosts but is not responsible for infecting humans. It is suggested that the role of <it>P</it>. <it>rodhaini </it>in transmission of <it>L. donovani </it>in other zoonotic foci of visceral leishmaniasis in Africa should be re-examined.</p

Molecular analysis of an odorant-binding protein gene in two sympatric species of Lutzomyia longipalpis s.l.

Lutzomyia longipalpis s.l. is the main vector of American visceral leishmaniasis (AVL) and occurs as a species complex. DNA samples from two Brazilian sympatric species that differ in pheromone and courtship song production were used to analyse molecular polymorphisms in an odorant-binding protein ( obp29 ) gene. OBPs are proteins related to olfaction and are involved in activities fundamental to survival, such as foraging, mating and choice of oviposition site. In this study, the marker obp29 was found to be highly polymorphic in Lu. longipalpis s.l. , with no fixed differences observed between the two species. A pairwise fixation index test indicated a moderate level of genetic differentiation between the samples analysed

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials.

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT

Molecular and Behavioral Differentiation among Brazilian Populations of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae)

Lutzomyia longipalpis is the main vector of visceral leishmaniasis in the Americas. There is strong evidence that L. longipalpis is a species complex, but there is still no consensus regarding the number of species occurring in Brazil. We combined molecular and behavioral analyses of a number of L. longipalpis populations in order to help clarify this question. This approach has allowed us to identify two main groups of populations in Brazil. One group probably represents a single species distributed mainly throughout the coastal regions of North and Northeast Brazil and whose males produce the same type of copulation song and pheromone. The second group is more heterogeneous, probably represented by a number of incipient species with different levels of genetic divergence among the siblings that produce different combinations of copulation songs and pheromones. The high level of complexity observed raises important questions concerning the epidemiological consequences of this incipient speciation process

Local Failure Events in Prostate Cancer Treated with Radiotherapy: A Pooled Analysis of 18 Randomized Trials from the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium (LEVIATHAN).

CONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. EVIDENCE SYNTHESIS: The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06-1.30), PCSS (HR 2.02, 95% CI 1.75-2.33), and DMFS (HR 1.94, 95% CI 1.75-2.15, p < 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36-1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21-0.50, p < 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. CONCLUSIONS: Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a "second wave" of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. PATIENT SUMMARY: Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it