Current management of CMV infection in cancer patients (solid tumors). Epidemiology and therapeutic strategies.

Little evidence is available regarding the incidence of CMV disease in patients with solid cancers. Latest data show that approximately 50 % of these patients with CMV PCR positivity developed clinically relevant CMV-viremia, and would require specific therapy. In the clinical arena, CMV reactivation is an important differential diagnosis in the infectological work up of these patients, but guidelines of management on this subject are not yet available. CMV reactivation should be considered during differential diagnosis for patients with a severe decline in lymphocyte counts when receiving chemoradiotherapy or immunochemotherapy with lymphocyte-depleting or blocking agents. Monitoring of CMV reactivation followed by the implementation of preemptive strategies or the establishment of early antiviral treatment improves the prognosis and reduces the morbidity and mortality of these patients.

Pattern of care in radiotherapy at a University Hospital in Spain: the RENORT project.

PURPOSE: RENORT is a novel data mining application developed to extract relevant clinical data from oncology information systems (OIS; ARIA and Mosaiq) used in radiation oncology (RO). METHODS/PATIENTS: We used RENORT to extract demographic and clinical data from the OIS of all patients treated at the RO Department at the General Hospital of Valencia during the year 2019. RESULTS: A total of 1158 treatments were performed. The female/male ratio was 39.3%/60.7%, with a mean age of 66 years. The mean waiting time between the treatment decision/proposal to the first visit was 10.1 days. Mean duration of the treatment preparation process was 21 days. Most patients (90.4%) completed treatment within the prescribed time ± 7 days. The most common sites/treatment types were: metastatic/palliative treatments (n = 300; 25.9%), breast (209; 18.0%), genitourinary (195; 16.8%), digestive (116; 10.0%), thoracic (104; 9.0%), head and neck (62; 5.4%), and skin cancer (51; 4.4%). The distribution according to treatment intent was as follows: palliative (n = 266; 23.0%), adjuvant curative (335; 28.9%), radical without adjuvant treatment (229; 19.8%), radical with concomitant treatment (188; 16.2%), curative neoadjuvant (70; 6.0%), salvage radiotherapy (61; 5.3%); and reirradiation (9; 0.8%). The most common treatment techniques were IMRT/VMAT with IGRT (n = 468; 40.4%), 3D-CRT with IGRT (421; 36.4%), SBRT (127; 11.0%), 2DRT (57; 4.9%), and SFRT (56; 4.8%). A mean of 15.9 fractions were administered per treatment. Hypofractionated schemes were used in 100% of radical intent breast and prostate cancer treatments. CONCLUSIONS: The RENORT application facilitates data retrieval from oncology information systems to allow for a comprehensive determination of the real role of radiotherapy in the treatment of cancer patients. This application is valuable to identify patterns of care and to assess treatment efficacy.

Patterns of treatment failure in patients with prostate cancer treated with 76-80 Gy radiotherapy to the prostate and seminal vesicles ± hormonotherapy.

PURPOSE: To assess the pattern of treatment failure in patients with prostate cancer (PCa) treated with radiotherapy (76-80 Gy) ± hormone therapy (HT). We also evaluated the influence of treatment failure on survival outcomes. METHODS: Retrospective study of patients with PCa (n = 302) treated with radiotherapy (RT) ± HT at our centre between November 1999 and July 2007. The mean patient age was 70.2 years (range 51-87). Distribution by NCCN risk group was low (n = 80, 26.5%), intermediate (n = 86, 28.5%), high (n = 77, 25.5%), and very high (n = 49, 16.2%). Most patients (n = 273, 90.4%) received IMRT at a dose of 76-80 Gy. HT was administered in 237 patients (78.5%), in most cases (n = 167, 55.3%) for < 7 months RESULTS: Survival rates at 10 years were: overall survival (OS), 64.3%; biochemical disease-free survival, 83.9%; disease-free survival, 92.5%; and metastasis-free survival (MFS), 94.3%. Biochemical failure (BF) was observed in 55 cases (18.2%), 32 of whom subsequently developed clinical recurrence: metastasis (n = 17, 5.6%), local failure (n = 11, 3.6%), and regional failure (n = 4, 1.3%). The cause of death (n = 159) was intercurrent disease in 115 cases (72.3%), second cancer in 27 (17.0%), and PCa in 17 (10.7%). Biochemical failure-free survival ≤ 24 months was significantly associated with worse OS and MFS (p = 0.0001). Late genitourinary and gastrointestinal toxicity grade ≥ 3 (RTOG) was observed in 18 (6.0%) and 7 (2.3%) patients, respectively. CONCLUSIONS: The main type of treatment failure after 76-80 Gy of radiotherapy ± HT is local or metastatic. In all cases, biochemical failure occurred prior to treatment failure. BF within 24 months of treatment completion was significantly associated with worse OS and MFS.

Operant self-administration of pregabalin in a mouse model of neuropathic pain.

BACKGROUND: Pregabalin is a first-line agent for neuropathic pain treatment whose abuse liability remains controversial. Surprisingly, studies exploring the reinforcing properties of pregabalin in operant mouse models are missing. METHODS: We evaluated the acquisition of operant pregabalin self-administration in mice exposed to a partial sciatic nerve ligation (PSNL) or a sham operation. After surgery, mice were trained in operant boxes to intravenously self-administer pregabalin at 1.5 or 3 mg/kg/inf or saline during 10 days. Thermal and mechanical sensitivity were assessed before and after self-medication, and depressive-like behaviour was evaluated after discontinuation of the treatment. RESULTS: Partial sciatic nerve ligation and sham-operated mice exposed to pregabalin at 3 mg/kg/inf showed higher active responding compared to mice exposed to saline. The differences in active responding were more robust in nerve-injured than in sham-operated mice. Self-medication at either dose of pregabalin partially inhibited thermal hypersensitivity, whereas only self-medication at 3 mg/kg/inf reduced mechanical sensitivity. Finally, a depressive-like behaviour was revealed after saline treatment in nerve-injured mice, and this emotional manifestation was abolished after pregabalin treatment at the high dose. CONCLUSIONS: Pregabalin showed reinforcing effects both in PSNL and sham-operated mice and attenuated the nociceptive and emotional manifestations of neuropathic pain in mice self-administering this drug. Therefore, pregabalin self-administration was related to neuropathic pain relief, but also to reinforcing properties related to psychotropic drug effects. This study reveals the improvement in nociceptive and emotional manifestations of neuropathic pain after operant pregabalin self-medication in mice and suggests the reinforcing effects of this drug in an operant paradigm. SIGNIFICANCE: This study shows that mice with a nerve injury self-administer pregabalin at doses effective reducing nociceptive hypersensitivity and depressive-like behaviour associated with the neuropathic pain model. Interestingly, mice without neuropathy also develop operant self-administration behaviour, suggesting potential abuse liability of this first-line drug for neuropathic pain treatment.

Looking for complementary alternatives to CTCAE for skin toxicity in radiotherapy: quantitative determinations.

INTRODUCTION: Radiotherapy (RT) is an essential part of the patient's treatment diagnosed with cancer. Determination of the most common RT secondary effect, the cutaneous toxicity, is usually based on visual rating scales, like Common Terminology Criteria for Adverse Events with an inherent subjectivity. The aim of this work is to perform an objective method to evaluate the radiodermatitis using a non-invasive imaging technique based on laser Doppler flowmetry (LDF). MATERIALS AND METHODS: A prospective study was performed analysing 1,824 measurements. A LDF was used to measure the cutaneous microcirculation in real time. A basal measurement was taken prior to radiotherapy treatment. To be able to observe the microcirculation changes related to the delivered dose, several sets of measurements were taken in the irradiated area along the RT treatment and in the contralateral non-irradiated area. RESULTS: A relative increase in blood flow at all measured points was found in the irradiated area. This relative increase in blood flow increases with the dose administered. In the non-irradiated contralateral area, the relative increase in blood flow is not significant and is independent of the dose administered. After treatment, a decrease in blood flow was detected with a trend towards returning to the baseline measurements. CONCLUSIONS: LDF is an objective technique that assesses early radiodermatitis. This method is useful to develop strategies to prevent onset of radiation dermatitis in patients irradiated, such as the modification and individualization of fractionation parameters of the RT. This allows the reduction of radiation morbidities and maintains patient quality of life.

SU-E-T-514: Implementation and Commissioning of a Micro Multileaf Collimator in Pinnacle Treatment Planning System.

PURPOSE: To model and validate, in a Pinnacle treatment planning system, a Brainlab micromultileaf collimator mounted on a Primus Siemens accelerator. The objective is to take advantage of the collapsed cone convolution algorithm and the ability of this system modelling rounded leaf- end MLC's. METHOD: The micro multileaf collimator was modelled using fixed accelerator jaws with a value of 9.2×9.2 cm2 . Profiles and depth dose curves for a wide range of square fields at SSD of 100 cm and depths of 1.5,5,10 and 20 cm were measured using a Scanditronix stereotactic SFD diode. Output factors were measured using a stereotactic unshielded diode for field sizes from 0.6×0.6 cm2 to 3×3 cm2 . For wider fields a Scanditronix ic15 ionization chamber was used. EDR2 films were used to measure adjacent fields in the transverse and longitudinal direction. The film measurements were compared to Pinnacle calculations to model and validate the leaf tip radius, leaf offset calibration values and tongue and groove width. RESULTS: Pinnacle calculations and measurements agree within 2% or 2mm except for the tails of largest fields where differences are <3.5%. Comparison of film measurements and Pinnacle calculations give the optimal value for leaf tip radius of 15 cm and for tongue and groove width of 0.04 cm. CONCLUSIONS: Pinnacle models a Brainlab micromultileaf collimator mounted on a Siemens Primus accelerator with acceptable results for clinical treatments.

SU-E-T-02: Radiobiological Comparison of Two Treatment Schemas in IMRT Prostate Radiotherapy.

PURPOSE: Different fractionation schemas are used for the treatment of prostate with IMRT. Due to the low α/ß of prostate hypofractionated schemas are achieving more importance. The purpose of this study is to compare two IMRT techniques from a radiobiological point of view in the treatment of high risk prostate cancer, the sequential IMRT technique (SIMRT) and a simultaneous integrated boost IMRT treatment (SIBIMRT). METHODS: 20 patients were selected and planned using both treatment strategies to give an EQD2 of 82 Gy to prostate, 70 Gy to vesicles and 46 Gy to lymph nodes, using the linear quadratic model LQ supposing an α/ß prostate=1.5 Gy. Dose volume histograms of prostate, rectum and bladder were calculated. Tumour Control Probabilities (TCP) and Normal Tissue Complication Probabilities (NTCP) were also calculated. As the prostate α/ß is not known exactly the TCP has been calculated for different a/bprostate values ranging from 1.5 to 10 Gy. NTCPs of bladder and rectum were calculated also for α/ß oar values ranging between 1 to 15 Gy. RESULTS: Both treatment strategies were found to be equivalent in terms of prostate ptv TCP and EQD2 for low α/ß prostate=1.5 Gy. In the case of high α/ß prostate values, 3 Gy and 10 Gy, EQD2 and TCP for prostate ptv are lower for the SIBIMRT technique. For rectum and bladder, if a/boar ranges between 2 and 15 Gy EQD2 values are higher for the SIMRT treatment schema. NTCP for bladder and rectum is higher for the SIMRT technique when α/ß OAR >= 2 -3 Gy. CONCLUSIONS: In this study a comparison between two treatments strategies have been done. Our results show that a hypofractionated technique for high risk prostate cancer reduces, or equals, EQD2 and NTCP for bladder and rectum while maintaining the TCP of prostate for the typical α/ß values in use.