Effect of radiation dose on the prevalence of apical periodontitis : a dosimetric analysis

Objectives : The objective of this study is to analyse the effect of the radiation dose of oral radiotherapy for cancer on the presence of apical periodontitis in patients without dental pre-screening or specific preventive measures. Materials and methods : All selected patients had been diagnosed with cancer in the head and neck region and presented in the dental clinic post radiotherapy with side effects (mainly radiation caries). The panoramic radiographs of these patients were examined for several parameters, including tooth decay and apical periodontitis. The total radiation dose per tooth was determined. Results : A total of 36 patient files were included, which accounted for 628 teeth to be scored. Tooth decay was present in 88.2% of teeth. Radiographic signs of apical periodontitis were found in 9.1% of the teeth. Teeth with apical periodontitis had significantly more caries present. The radiation dose was significantly higher for teeth with apical periodontitis (37.2 vs. 24.9 Gy). Binary logistic regression found the radiation dose to be the only explanatory variable in the presence of apical periodontitis. Conclusions : This study found that in zones with higher radiation dose, inflammation of the jawbone due to bacterial infection of the root canal is more likely to develop. This is probably due to bone changes post radiotherapy. Clinical relevance : An increase of this prevalance of apical periodontitis in irradiated bone found in this study needs to be taken into account in the dental evaluation before the start of radiotherapy

Adjuvant radiotherapy after radical cystectomy for patients with muscle invasive bladder cancer : a phase II trial

Background: Neo-adjuvant chemotherapy followed by radical cystectomy with extended pelvic lymph node dissection is considered to be the treatment of choice for patients with muscle invasive bladder cancer (MIBC). Despite this aggressive treatment the outcome is poor and ultimately, 30% of the patients with >= pT3 tumors develop a pelvic recurrence. We hypothesize that postoperative adjuvant external beam radiotherapy (EBRT) might prevent local and lymph node recurrence and improve disease free-and overall survival as loco-regional recurrence is linked to the development of distant metastasis. Methods: We plan to perform a multicentric prospective phase two study including 76 patients. Eligible patients are patients with MIBC, treated with radical cystectomy and presenting with >= 1 of the following characteristics: - Pathological (p) T3 stage + presence of lymphovascular invasion on pathological examination - pT4 stage - < 10 lymph nodes removed - positive lymph nodes - positive surgical margins Patients will have a F-18-FDG PET-CT to rule out the presence of distant metastasis prior to EBRT. A median dose of 50 Gy in 25 fractions is prescribed to the pelvic lymph node regions with inclusion of the operative bladder bed in case of a positive surgical margin. Patients with suspected lymph nodes on PET-CT can still be included in the trial, but a simultaneous integrated boost to 74Gy to the positive lymph nodes will be delivered. Blood and urine samples will be collected on day-1 and last day of EBRT for evaluation of biomarkers. The primary endpoint is evaluation of acute >= Grade 3 intestinal or grade 4 urinary toxicity, in case of a neo-bladder reconstruction, within 12 weeks after EBRT. Secondary endpoints are: assessment of QOL, late RTOG toxicity, local control, disease free survival and overall survival. Biomarkers in urine and blood will be correlated with secondary survival endpoints. Discussion: This is a prospective phase 2 trial re-assessing the feasibility of adjuvant radiotherapy in high-risk MIBC

Clinical Results after High-Dose Intensity-Modulated Radiotherapy for High-Risk Prostate Cancer

Purpose. Patients with high-risk prostate cancer (PC) can be treated with high-dose intensity-modulated radiotherapy (IMRT) and long-term androgen deprivation (AD). In this paper we report on (i) late toxicity and (ii) biochemical (bRFS) and clinical relapse-free survival (cRFS) of this combined treatment. Methods. 126 patients with high-risk PC (T3-4 or PSA >20 ng/mL or Gleason 8–10) and ≥24 months of followup were treated with high-dose IMRT and AD. Late toxicity was recorded. Biochemical relapse was defined as PSA nadir +2 ng/mL. Clinical relapse was defined as local failure or metastases. Results. The incidence of late grade 3 gastrointestinal and genitourinary toxicity was 2 and 6%, respectively. Five-year bRFS and cRFS were 73% and 86% respectively. AD was a significant predictor of bRFS (P = 0.001) and cRFS (P = 0.01). Conclusion. High-dose IMRT and AD for high-risk PC offers excellent biochemical and clinical control with low toxicity

Early biomarkers related to secondary primary cancer risk in radiotherapy treated prostate cancer patients: IMRT versus IMAT

AbstractPurposeTo investigate whether rotational techniques (Volumetric Modulated Arc Therapy – VMAT) are associated with a higher risk for secondary primary malignancies compared to step-and-shoot Intensity Modulated Radiation Therapy (ss-IMRT). To this end, radiation therapy (RT) induced DNA double-strand-breaks and the resulting chromosomal damage were assessed in peripheral blood T-lymphocytes of prostate cancer (PCa) patients applying γH2AX foci and G0 micronucleus (MN) assays.Methods and materialsThe study comprised 33PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced γH2AX foci and MN. The equivalent total body dose (DETB) was calculated based on treatment planning data.ResultsA linear dose response was obtained for γH2AX foci yields versus DETB while MN showed a linear-quadratic dose response. Patients treated with large volume (LV) VMAT show a significantly higher level of induced γH2AX foci and MN compared to IMRT and small volume (SV) VMAT (p<0.01). Assuming a linear-quadratic relationship, a satisfactory correlation was found between both endpoints (R2 0.86).ConclusionsBiomarker responses were governed by dose and irradiated volume of normal tissues. No significant differences between IMRT and rotational therapy inherent to the technique itself were observed

Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients

Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18-24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation

A trial-based cost-utility analysis of metastasis-directed therapy for oligorecurrent prostate cancer

The optimal management of patients with oligorecurrent prostate cancer (PCa) is unknown. There is growing interest in metastasis-directed therapy (MDT) for this population. The objective was to assess cost-utility from a Belgian healthcare payer's perspective of MDT and delayed androgen deprivation therapy (ADT) in comparison with surveillance and delayed ADT, and with immediate ADT. A Markov decision-analytic trial-based model was developed, projecting the results over a 5-year time horizon with one-month cycles. Clinical data were derived from the STOMP trial and literature. Treatment costs were derived from official government documents. Probabilistic sensitivity analyses showed that MDT is cost-effective compared to surveillance (ICER: Euro8393/quality adjusted life year (QALY)) and immediate ADT (dominant strategy). The ICER is most sensitive to utilities in the different health states and the first month MDT cost. At a willingness-to-pay threshold of Euro40,000 per QALY, the cost of the first month MDT should not exceed Euro8136 to be cost-effective compared to surveillance. The Markov-model suggests that MDT for oligorecurrent PCa is potentially cost-effective in comparison with surveillance and delayed ADT, and in comparison with immediate ADT

The potential of radiotherapy to enhance the efficacy of renal cell carcinoma therapy

Renal cell carcinoma (RCC) is an immunogenic tumor, but uses several immune-suppressive mechanisms to shift the balance from tumor immune response toward tumor growth. Although RCC has traditionally been considered to be radiation resistant, recent evidence suggests that hypofractionated radiotherapy contributes to systemic antitumor immunity. Because the efficacy of antitumor immune responses depends on the complex balance between diverse immune cells and progressing tumor cells, radiotherapy alone is unlikely to induce persistent antitumor immunity. Therefore, the combination of radiotherapy with drugs having synergistic immunomodulatory properties holds great promise with the optimal timing and sequence of modalities depending on the agent used. We highlight the immunomodulatory properties of targeted therapies, such as tyrosine kinase inhibitors, mammalian target of rapamycin (mTOR) inhibitors and vascular endothelial growth factor (VEGF) neutralizing antibodies, and will suggest a combination schedule with radiotherapy based on the available literature. We also address the combination of radiotherapy with innovative treatments in the field of immunotherapy