Abstract Besides the local effects of ionizing radiation at the cellular and molecular levels in tumor tissues, the interactions of radiotherapy with the host’s immune system are nowadays at the ...center of many investigations. In some cases, these interactions can be strong enough to immunize the patient against the tumor, leading to a rejection by the host of both the irradiated tumor and distant metastases. In this latter case, the rejection mechanism is called “abscopal effect”. Over the last two decades, increasing attention has also been paid to the combination of various forms of immunotherapies with radiation, as an attempt to boost cancer cell killing mechanisms. In particular, a significant number of translational and clinical studies are now investigating both the effects of immune checkpoint blockade strategies and adoptive immunotherapies in combination with radiation. A better understanding of the mechanisms driving the interactions between ionizing radiation and the immune system help us envision the advantages that may be offered by the adjunction of immunotherapy to radiotherapy in various clinical models.
Il a fallu beaucoup de temps, malgré les observations des premiers contagionistes au XVIIIe siècle, malgré les intuitions de Villemin et d’autres médecins au XIXe siècle, malgré les découvertes de ...Koch en 1882 et malgré tous les progrès de la bactériologie au tournant du XXe siècle, avant que la tuberculose en vienne à être reconnue pour ce qu’elle est, une maladie infectieuse et contagieuse. Cet ouvrage montre combien les croyances ont balisé l’histoire de cette maladie du XVIIIe jusqu’au XXe siècle, et combien certaines s’enracinent loin dans le temps. Même au XXe siècle, les résistances à la théorie de la contagion ont été variées et tenaces. Dans cette histoire de la tuberculose au Québec, l’auteur relate l’évolution des représentations de cette maladie et des façons dont la médecine et les autorités publiques y ont fait face.
To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer.
...The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality.
At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; > or = 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): -2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively.
These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.
Radiation oncology: a century of achievements Bernier, Jacques; Hall, Eric J; Giaccia, Amato
Nature reviews. Cancer,
200409, 2004-09-00, 2004-9-00, 20040901, Letnik:
4, Številka:
9
Journal Article
Recenzirano
Over the twentieth century the discipline of radiation oncology has developed from an experimental application of X-rays to a highly sophisticated treatment of cancer. Experts from many disciplines - ...chiefly clinicians, physicists and biologists - have contributed to these advances. Whereas the emphasis in the past was on refining techniques to ensure the accurate delivery of radiation, the future of radiation oncology lies in exploiting the genetics or the microenvironment of the tumour to turn cancer from an acute disease to a chronic disease that can be treated effectively with radiation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary Background We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external ...irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. Methods For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1–2 prostatic adenocarcinoma with WHO histological grade 3 or T3–4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0–2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov , number NCT00849082. Findings Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1–12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3–29·7) in the radiotherapy-alone group and 47·7% (39·0–56·0) in the combined treatment group (hazard ratio HR 0·42, 95% CI 0·33–0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9–47·5) in patients receiving radiotherapy alone and 58·1% (49·2–66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45–0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2–37·5) and 10·3% (5·1–15·4), respectively (HR 0·38, 95% CI 0·24–0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. Interpretation In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity. Funding AstraZeneca; Ligue Nationale Contre le Cancer (France), through the EORTC Charitable Trust.
Promising results in a randomized phase II trial with the hypoxic cytotoxin tirapazamine (TPZ) combined with cisplatin (CIS) and radiation led to this phase III trial.
Patients with previously ...untreated stage III or IV (excluding T1-2N1 and M1) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx were randomly assigned to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either CIS (100 mg/m(2)) on day 1 of weeks 1, 4, and 7 or CIS (75 mg/m(2)) plus TPZ (290 mg/m(2)/d) on day 1 of weeks 1, 4, and 7 and TPZ alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS). The primary end point was overall survival (OS). The planned sample size was 850, estimated to result in 334 deaths, which would provide 90% power to detect a difference in 2-year survival rates of 60% v 70% for CIS versus TPZ/CIS, respectively (hazard ratio = 0.69).
Eight hundred sixty-one patients were accrued from 89 sites in 16 countries. In an intent-to-treat analysis, the 2-year OS rates were 65.7% for CIS and 66.2% for TPZ/CIS (TPZ/CIS--CIS: 95% CI, -5.9% to 6.9%). There were no significant differences in failure-free survival, time to locoregional failure, or quality of life as measured by Functional Assessment of Cancer Therapy-Head and Neck.
We found no evidence that the addition of TPZ to chemoradiotherapy, in patients with advanced head and neck cancer not selected for the presence of hypoxia, improves OS.
This trial of therapies for unresectable advanced head and neck cancer showed that induction chemotherapy (given before radiotherapy) with a combination of docetaxel plus the standard regimen of ...cisplatin and fluorouracil (TPF) was superior to the standard induction chemotherapy. Progression-free survival and overall survival were improved, and the toxicity of the triple-agent regimen was less than the toxicity of the standard regimen.
Induction chemotherapy with a combination of docetaxel plus the standard regimen of cisplatin and fluorouracil (TPF) was superior to the standard induction chemotherapy.
Head and neck cancer, mostly of squamous-cell origin, ranks sixth among the most common cancers, accounting for approximately 6% of all cases of cancer. Each year, more than 500,000 new cases are diagnosed worldwide.
1
Approximately 60% of patients present with advanced disease (stages III and IV), for which the prognosis is poor.
2
For many years, radiotherapy has been the treatment of choice for unresectable disease,
3
resulting in 5-year rates of survival of less than 20%.
4
,
5
Concurrent chemoradiotherapy has now largely replaced radiotherapy alone in the treatment of unresectable squamous-cell carcinoma of the head and neck,
3
,
6
but induction chemotherapy . . .
Urinary tract infections (UTIs) are a common bacterial infectious disease in humans, and strains of uropathogenic
Escherichia coli
(UPEC) are the most frequent cause of UTIs. During infection, UPEC ...must cope with a variety of stressful conditions in the urinary tract. Here, we demonstrate that the small RNA (sRNA) RyfA of UPEC strains is required for resistance to oxidative and osmotic stresses. Transcriptomic analysis of the
ryfA
mutant showed changes in expression of genes associated with general stress responses, metabolism, biofilm formation and genes coding for cell surface proteins. Inactivation of
ryfA
in UPEC strain CFT073 decreased urinary tract colonization in mice and the
ryfA
mutant also had reduced production of type 1 and P fimbriae (pili), adhesins which are known to be important for UTI. Furthermore, loss of
ryfA
also reduced UPEC survival in human macrophages. Thus,
ryfA
plays a key regulatory role in UPEC adaptation to stress, which contributes to UTI and survival in macrophages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this ...meta-analysis was to assess whether this type of radiotherapy could improve survival.
Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction.
15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III–IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3·4% at 5 years (hazard ratio 0·92, 95% CI 0·86–0·97; p=0·003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1·7% with total dose reduction at 5 years, p=0·02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6·4% at 5 years; p<0·0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0·78 0·65–0·94 for under 50 year olds, 0·95 0·83–1·09 for 51–60 year olds, 0·92 0·81–1·06 for 61–70 year olds, and 1·08 0·89–1·30 for over 70 year olds; test for trends p=0·007).
Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.
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