Total Reference Air Kerma is Associated with Late Bowel Morbidity in Locally Advanced Cervical Cancer Patients Treated with Image-Guided Adaptive Brachytherapy

No dose volume parameter has been identified to predict late bowel toxicities in locally advanced cervical cancer (LACC) patients treated with image-guided adaptive brachytherapy. We examined the incidence of bowel toxicities according to the total reference air kerma (TRAK) in 260 LACC patients. In both univariate and multivariate analysis, late morbidity positively correlated with a TRAK ≥2 cGy (centigray) at 1 meter, emphasizing the importance of this parameter in term of late bowel morbidity. Objective: There is no validated dose volume parameter to predict late bowel toxicities in cervical cancer patients treated with image-guided adaptive brachytherapy (IGABT). We examined the incidence of bowel toxicities according to the TRAK, which is proportional to the integral dose to the patients. Material/Methods: Clinical data of 260 LACC patients treated with curative intent from 2004 to 2016 were examined. Patients received chemoradiation plus a pulse-dose rate IGABT boost. The relationship between TRAK and morbidity was assessed by Kaplan-Meier method, log-rank tests, and Cox proportional-hazards model on event-free periods. Results: Median follow-up was 5.2 years (SE (Standard Error): 0.21). Probability of survival without late bowel toxicity Grade ≥ 2 rate for patients without recurrence (n = 227) at 5 years was 66.4% (SE 3.7). In univariate analysis, bowel and/or sigmoid dose/volume parameters were not significant. Late morbidity positively correlated with active smoking, CTVHR volume >25 cm3, and a TRAK ≥2 cGy at 1 meter. In multivariate analysis, the following factors were significant: Active smoking (p < 0.001; HR: 2.6; 95%CI: 1.4⁻5.0), and the TRAK (p = 0.02; HR: 2.4; 95%CI: 1.2⁻5.0). Conclusion: TRAK was associated with late bowel toxicities probability, suggesting that the integral dose should be considered, even in the era of IGABT

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer

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Analysis of Radiation Dose/Volume Effect Relationship for Anorectal Morbidity in Children Treated for Pelvic Malignancies

International audiencePurpose: To examine dose-volume effect relationships for anorectal morbidity in children treated with image-guided brachytherapy for pelvic tumors.Methods and materials: Medical records of all consecutive children with pelvic tumors treated in our center and receiving image-guided pulsed-dose-rate brachytherapy with or without external beam radiation therapy (EBRT) between 2005 and 2019 were reviewed. The effect of the minimal doses to the most exposed 0.5 cm3, 1 cm3, and 2 cm3 of the anorectum (respectively: D0.5cm3, D1cm3, and D2cm3), total reference air kerma (TRAK), and volume of 100% isodose was examined for anorectal toxicities.Results: Seventy-eight consecutive children were included. Median age was 2.9 years (range, 0.8-14.9 years). Most of the tumors were bladder or prostate (67%) or vaginal (22%) rhabdomyosarcoma. Six patients received EBRT in addition to brachytherapy. Median follow-up was 21.3 months. At last follow-up, 30 children (38%) had experienced Common Terminology Criteria for Adverse Events version 5 grade ≥1 acute or late anorectal events: 24% had grade 1 events, 7.7% had grade 2 events, and 6.4% had grade 3 events. No toxicity greater than grade 3 was observed (eg, fistula or stricture). In univariate analysis, the D0.5cm3 and D1cm3 were significant for probability of grade 1 to 3 (P = .009 and P = .017, respectively) and grade 2 to 3 anorectal morbidity (P = .007 and P = .049, respectively). There was no significant correlation for D2cm3 (P = .057 for grade 1-3; P = .407 for grade 2-3). A 10% probability (95% confidence interval, 4%-20%) for anorectal toxicity of grade 2 or greater was reached for a D0.5cm3 = 52 Gy. The age, EBRT use, TRAK, and treated volume values were not significant.Conclusions: To our knowledge, this study is the first to show a significant dose-volume effect relationships for anorectal morbidity in children undergoing treatment with brachytherapy. Integrating these data into brachytherapy treatment planning could help to optimize the therapeutic index in these young patients

Pulsed Dose Rate Brachytherapy of Lip Carcinoma: Clinical Outcome and Quality of Life Analysis

Purpose: Lip carcinoma represents one of the most common types of head and neck cancer. Brachytherapy is a highly effective therapeutic option for all stages of lip cancers. We report our experience of pulsed dose rate brachytherapy (PDR) as treatment of lip carcinoma. Methods and Materials: this retrospective single center study included all consecutive patients treated for a lip PDR brachytherapy in our institution from 2010 to 2019. The toxicities and outcomes of the patients were reported, and a retrospective quality of life assessment was conducted by phone interviews (FACT H&N). Results: From October 2010 to December 2019, 38 patients were treated in our institution for a lip carcinoma by PDR brachytherapy. The median age was 73, and the majority of patients presented T1-T2 tumors (79%). The median total dose was 70.14 Gy (range: 60–85 Gy). With a mean follow-up of 35.4 months, two patients (5.6%) presented local failure, and seven patients (19%) had lymph node progression. The Kaplan–Meier estimated probability of local failure was 7.2% (95% CI: 0.84–1) at two and four years. All patients encountered radiomucitis grade II or higher. The rate of late toxicities was low: three patients (8.3%) had grade II fibrosis, and one patient had grade II chronic pain. All patients would highly recommend the treatment. The median FACT H&N total score was 127 out of 148, and the median FACT H&N Trial Outcome Index was 84. Conclusions: This study confirms that an excellent local control rate is achieved with PDR brachytherapy as treatment of lip carcinoma, with very limited late side effects and satisfactory functional outcomes. A multimodal approach should help to improve regional control

Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities

Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We here describe a novel application of cytotoxic saporin-conjugated tetramers to kill antigen-specific T-cells without significant off-target effects. The relative efficacy of distinct antiviral CD8+ T-cell specificity can be directly assessed via antigen-specific CD8+ T-cell depletion. The utility of these reagents is demonstrated here in identifying the CD8+ T-cell specificity most effective in preventing HIV progression in HIV-infected HLA-B*27-positive immune controllers

Dissertatio historica de initiis monarchiae Babyloniorum, quam, cum cons. ampliss. Colleg. Philos. in Reg. Acad. Upsal. sub praesidio ... Jacobi Arrhenii ... publico examini modeste subjicit Petrus Hagberg Gestr. In audit. Gustav. maj. ad d. 25. Maji. Anni MDCCV.

International audienceBackground : The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedlybecause of changing environmental factors, which are yet largely unknown. The purpose of the study was tounravel environmental markers associated with T1D. Methods : Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends ofthe patients. Parents were asked to fill a 845-item questionnaire investigating the child’s environment before diagnosis.The analysis took into account the matching between cases and controls. A second analysis used propensity scoremethods. Results : We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnutcocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a petby old age. Conclusions : The found statistical association of new environmental markers with T1D calls for replication in othercohorts and investigation of new environmental areas

Additional file 1: of Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case–control study

The questionnaire used in the current study. (PDF 620 kb