[en] Radiation therapy (RT) has been used as a definitive treatment for many solid tumors. While tumoricidal properties of RT are instrumental for standard clinical application, irradiated tumors can potentially serve as a source of tumor antigens in vivo, where dying tumor cells would release tumor antigens and danger signals and serve as autologous in situ tumor vaccines. Using murine tumor models of prostate, metastatic lung cancer and melanoma, we have demonstrated evidence of radiation-enhanced tumor-specific immune response that resulted in improved primary tumor control and reduction in systemic metastasis and cure. We will discuss the immunogenic properties of RT and determine how immunotherapeutic approaches can synergize with RT in boosting immune cells cell function. (author)

[en] Exposure to high doses of ionizing radiation in the event of accidental or intentional incident such as nuclear/radiological terrorism can lead to debilitating injuries to multiple organs resulting in death within days depending on the amount of radiation dose and the quality of radiation. Unfortunately, there is not a single FDA-licensed drug approved against acute radiation injury. The RadStem Center for Medical Countermeasures against Radiation (RadStem CMGR) program at Einstein is developing stem cell-based therapies to treat acute radiation syndrome (ARS). We have demonstrated that intravenous transplantation of bone marrow-derived and adipose-derived stromal cells, consisting of a mixture of mesenchymal, endothelial and myeloid progenitors can mitigate mice exposed to whole body irradiation of 12 Gy or whole abdominal irradiation of up to 20 Gy. We identified a variety of growth and differentiation factors that individually is unable to improve survival of animals exposed to lethal irradiation, but when administered sequentially mitigates radiation injury and improves survival. We termed this phenomenon as synthetic survival and describe a new paradigm whereby the 'synthetic survival' of irradiated tissues can be promoted by systemic administration of growth factors to amplify residual stem cell clonogens post-radiation exposure, followed by a differentiation factor that favors tissue stem cell differentiation. Synthetic survival can be applied to mitigate lethal radiation injury in multiple organs following radiation-induced hematopoeitic, gastrointestinal and pulmonary syndromes. (author)

[en] Purpose: To determine whether a dose-response relationship exists between the biologic effective dose (BED) at Point A and the bladder and rectum and the clinical outcomes in our experience with external beam radiotherapy (EBRT) and high-dose-rate brachytherapy in the treatment of cervical carcinoma. Methods and Materials: This was a retrospective study. A total of 49 patients with cervical cancer were treated with a combination of EBRT (median 45 Gy, range 41.4-50.4) and high-dose-rate brachytherapy (median 18 Gy; range 18-19, in two fractions). Twenty-three patients received concomitant cisplatin-based chemotherapy. The cumulative BEDs were calculated at Point A (BED10) and at bladder and rectal reference points (BED3) using the linear-quadratic equation. The BED10 values, after incorporating a time factor (BED10tf) in the formula, were also calculated. Results: In patients treated with RT alone, the local failure rate was 10% (1 of 10) and 19% (3 of 16) in patients receiving a BED10 >89 Gy10 or <89 Gy10 to Point A, respectively (p=0.2). The corresponding local failure rates were 20% (3 of 15) and 0% (0 of 8) in patients treated with concomitant chemotherapy (p=0.3). In patients treated with RT alone, the local failure rate was 7.7% (1 of 13) and 23% (3 of 13) in patients with a BED10tf >64 Gy10 or <64 Gy10 (p=0.1), respectively. The median BED3 values at the rectal and bladder point was 95.5 Gy3 and 103.6 Gy3, respectively. Only 1 case of Grade 2 late rectal toxicity (2%) and no late bladder toxicity occurred. Conclusion: In patients treated with RT alone, a BED10 >89 Gy and a BED10tf >64 Gy indicated a trend toward a better local control rate. This difference was not observed in patients receiving chemotherapy. A BED3 <100 Gy3 was associated with negligible late toxicity. Although the BED10 in our study was about 10-15 Gy10 less than that in the published data, the 4-year local control rate of 80% and 83% and disease-free survival rate of 75% and 70% with and without chemotherapy, respectively, compare well with the rates in other studies in the literature

[en] Purpose Uterine papillary serous carcinoma (UPSC) is an aggressive variant of endometrial carcinoma. The majority of patients with clinical Stage I UPSC are found to have extrauterine disease at the time of surgery. Most authors report survival rates of 35-50% for Stage I-II and 0-15% for Stage III and IV UPSC. Surgical treatment as the sole therapy for patients with Stage I-IV UPSC is unacceptable because of high recurrence rates. Chemotherapy, radiotherapy, or both have been added after surgery in an attempt to improve survival. However, the survival benefit to patients from such multimodality therapy remains uncertain. This study analyzes the patterns of failure in patients with FIGO Stages I-IV UPSC treated by multimodality therapy. Methods and materials Forty-two women with FIGO Stages I-IV UPSC who were treated by multimodality therapy were analyzed retrospectively between 1988 and 1998. Data were obtained from tumor registry, hospital, and radiotherapy chart reviews, operative notes, pathology, and chemotherapy flow sheets. All the patients underwent staging laparotomy, peritoneal cytology, total abdominal hysterectomy and salpingo oophorectomy, pelvic and para-aortic lymph node sampling, omentectomy, and cytoreductive surgery, when indicated followed by radiotherapy and/or chemotherapy. Therapy consisted of external beam radiation therapy in 11 patients (26%), systemic chemotherapy in 20 (48%), and both radiotherapy and chemotherapy in 11 (26%). The treatments were not assigned in a randomized fashion. The dose of external beam radiation therapy ranged from 45-50.40 Gy (median 45). Of the 31 patients (74%) who received chemotherapy, 18 received single-agent (58%), whereas 13 received multiagent chemotherapy (42%). Results Median follow-up for all patients was 19 months (range 4-72). Median follow-up for the surviving patients was 36 months (range 21-72). Their median age was 65 years. Six patients (14%) had Stage I, 8 patients (19%) had Stage II, 10 (24%) had Stage III, and 18 (43%) had Stage IV disease. Twenty-nine patients (69%) had suffered recurrence at the time of last follow-up. The actuarial failure rate at 2 and 5 years was 58% and 67%, respectively. The majority of the patients (19/29) recurred in the abdomen, vagina, or pelvis (66%). Metastases outside the abdomen were much less common as the first site of failure (17%). Twenty-five patients (60%) had died at the time of reporting; the observed survival rate at 2 years and 5 years was 52% and 43%, respectively. Conclusions Our data suggest that, after multimodality therapy of FIGO Stage I-IV UPSC, most patients developed abdominopelvic (locoregional) failure, and the great majority of the failures occurred in the abdomen, vagina, and pelvis (66%). Abdominopelvic failure as a component of distant failure occurred in an additional 5 patients (17%). Distant failure alone occurred in 17% of the patients. We propose that future studies should combine whole abdominal radiotherapy (WART) with pelvic and vaginal boosts, in addition to chemotherapy for FIGO Stage I-IV UPSC, especially in patients with minimal residual disease, to attempt to improve the dismal prognosis of patients with UPSC

[en] Purpose: To evaluate, in a gynecologic cancer setting, changes in bowel position, dose-volume parameters, and biological indices that arise between full-bladder (FB) and empty-bladder (EB) treatment situations; and to evaluate, using cone beam computed tomography (CT), the validity of FB treatment presumption. Methods and Materials: Seventeen gynecologic cancer patients were retrospectively analyzed. Empty-bladder and FB CTs were obtained. Full-bladder CTs were used for planning and dose optimization. Patients were given FB instructions for treatment. For the study purpose, bowel was contoured on the EB CTs for all patients. Bowel position and volume changes between FB and EB states were determined. Full-bladder plans were applied on EB CTs for determining bowel dose-volume changes in EB state. Biological indices (generalized equivalent uniform dose and normal tissue complication probability) were calculated and compared between FB and EB. Weekly cone beam CT data were available in 6 patients to assess bladder volume at treatment. Results: Average (±SD) planned bladder volume was 299.7 ± 68.5 cm³. Median bowel shift in the craniocaudal direction between FB and EB was 12.5 mm (range, 3-30 mm), and corresponding increase in exposed bowel volume was 151.3 cm³ (range, 74.3-251.4 cm³). Absolute bowel volumes receiving 45 Gy were higher for EB compared with FB (mean 328.0 ± 174.8 vs 176.0 ± 87.5 cm³; P=.0038). Bowel normal tissue complication probability increased 1.5× to 23.5× when FB planned treatments were applied in the EB state. For the study, the mean percentage value of relative bladder volume at treatment was 32%. Conclusions: Full-bladder planning does not necessarily translate into FB treatments, with a patient tendency toward EB. Given the uncertainty in daily control over bladder volume for treatment, we strongly recommend a “planning-at-risk volume bowel” (PRV_Bowel) concept to account for bowel motion between FB and EB that can be tailored for the individual patient

[en] The purpose of this study was to evaluate normal tissue dose constraints while maintaining planning target volume (PTV) prescription without reducing PTV margins. Sixteen patients with oral cavity carcinoma (group I), 27 patients with oropharyngeal carcinoma (group II), and 28 patients with laryngeal carcinoma (group III) were reviewed. Parotid constraints were a mean dose to either parotid < 26 Gy (PP1), 50% of either parotid < 30 Gy (PP2), or 20 cc of total parotid < 20 Gy (PP3). Treatment was intensity modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB). All patients met constraints for cord and brain stem. The mandibular constraints were met in 66%, 29%, and 57% of patients with oral, oropharyngeal, and laryngeal cancers, respectively. Mean dose of 26 Gy (PP1) was achieved in 44%, 41%, and 38% of oral, oropharyngeal, and laryngeal patients. PP2 (parotid constraint of 30 Gy to less than 50% of one parotid) was the easiest to achieve (group I, II, and III: 82%, 76%, and 78%, respectively). PP3 (20 cc of total parotid < 20 Gy) was difficult, and was achieved in 25%, 17%, and 35% of oral, oropharyngeal, and laryngeal patients, respectively. Mean parotid dose of 26 Gy was met 40% of the time. However, a combination of constraints allowed for sparing of the parotid based on different criteria and was met in high numbers. This was accomplished without reducing PTV-parotid overlap. What dose constraint best correlates with subjective and objective functional outcomes remains a focus for future study.

[en] Background and Purpose: IMRT clinical trials lack dose prescription and specification standards similar to ICRU standards for two- and three-dimensional external beam planning. In this study, we analyzed dose distributions for patients whose treatment plans incorporated IMRT, and compared the dose determined at the ICRU reference point to the PTV doses determined from dose-volume histograms. Additionally, we evaluated if ICRU reference type single-point dose prescriptions are suitable for IMRT dose prescriptions. Materials and methods: For this study, IMRT plans of 117 patients treated at our institution were randomly selected and analyzed. The treatment plans were clinically applied to the following disease sites: abdominal (11), anal (10), brain (11), gynecological (15), head and neck (25), lung (15), male pelvis (10) and prostate (20). The ICRU reference point was located in each treatment plan following ICRU Report 50 guidelines. The reference point was placed in the central part of the PTV and at or near the isocenter. In each case, the dose was calculated and recorded to this point. For each patient - volume and dose (PTV, PTV mean, median and modal) information was extracted from the planned dose-volume histogram. Results: The ICRU reference dose vs PTV mean dose relationship in IMRT exhibited a weak positive association (Pearson correlation coefficient 0.63). In approximately 65% of the cases studied, dose at the ICRU reference point was greater than the corresponding PTV mean dose. The dose difference between ICRU reference and PTV mean doses was ≤2% in approximately 79% of the cases studied (average 1.21% (±1.55), range -4% to +4%). Paired t-test analyses showed that the ICRU reference doses and PTV median doses were statistically similar (p = 0.42). The magnitude of PTV did not influence the difference between ICRU reference and PTV mean doses. Conclusions: The general relationship between ICRU reference and PTV mean doses in IMRT is similar to that in 3D CRT distributions. Point doses in IMRT are influenced by the degree of intensity modulation as well as calculation grid size utilized. Although the ICRU reference point type prescriptions conceptually may be extended for IMRT dose prescriptions and used as a representative of tumor dose, new universally acceptable dose prescription and specification standards for IMRT based on RTOG IMRT prescription model incorporating dose-volume specification would likely lead to greater consistency among treatment centers

[en] The increase in research and application of various phototherapy methods, especially photodynamic therapy (PDT) has created the need to study in depth the mechanisms of interaction of light with biological tissue using a photosensitizing drug in order to increase the therapeutic effectiveness. In this issue, two systems for controlled irradiation of in-vitro cell culture and temperature monitoring of the culture are presented. The first system was designed to irradiate 24 wells in a 96-well microplate. The second one was constructed for the irradiation and control of a 24-well microplate using larger volumes of cultured cells. Both systems can independently irradiate and control the temperature of each well. The systems include a module for contactless measurement of the temperature in each well. Light sources are located in an interchangeable module, so that it can be replaced to irradiate with different wavelengths. These prototypes count with various operation modes, controlled by a computer, which permits establishing specific settings in accordance with the desired experiment. The systems allow the automated experiment execution with precise control of dosimetry, irradiation and temperature, which reduces the sample-handling while, saves time. (Author)

[en] Highlights: • Iron doped phosphate glasses prepared using microwave heating and conventional heating under air and reducing atmosphere. • Presence of iron predominantly in the ferrous oxidation state in all the glasses. • Significant concentrations of iron in the ferrous oxidation state on both octahedral and tetrahedral sites in all the glasses. • Ratio of Fe²⁺ with total iron is found higher in microwave prepared glasses in comparison to conventional prepared glasses. - Abstract: Iron doped phosphate glasses containing P₂O₅–MgO–ZnO–B₂O₃–Al₂O₃ were melted using conventional resistance heating and microwave heating in air and under reducing atmosphere. All the glasses were characterised by UV–Vis–NIR spectroscopy, Mössbauer spectroscopy, thermogravimetric analysis and wet colorimetry analysis. Mössbauer spectroscopy revealed presence of iron predominantly in the ferrous oxidation state on two different sites in all the glasses. The intensity of the ferrous absorption peaks in UV–Vis–NIR spectrum was found to be more in glasses prepared using microwave radiation compared to the glasses prepared in a resistance heating furnace. Thermogravimetric analysis showed increasing weight gain on heating under oxygen atmosphere for glass corroborating higher ratio of FeO/(FeO + Fe₂O₃) in glass melted by direct microwave heating. Wet chemical analysis also substantiated the finding of higher ratio Fe⁺²/ΣFe in microwave melted glasses. It was found that iron redox ratio was highest in the glasses prepared in a microwave furnace under reducing atmosphere

[en] Purpose: To examine associations between radiation therapy (RT) noncompliance and clinical outcomes. Methods and Materials: We reviewed all patients who completed courses of external beam RT with curative intent in our department from the years 2007 to 2012 for cancers of the head and neck, breast, lung, cervix, uterus, or rectum. Patients who missed 2 or more scheduled RT appointments (excluding planned treatment breaks) were deemed noncompliant. Univariate, multivariable, and propensity-matched analyses were performed to examine associations between RT noncompliance and clinical outcomes. Results: Of 1227 patients, 266 (21.7%) were noncompliant. With median follow-up of 50.9 months, 108 recurrences (8.8%) and 228 deaths (18.6%) occurred. In univariate analyses, RT noncompliance was associated with increased recurrence risk (5-year cumulative incidence 16% vs 7%, P<.001), inferior recurrence-free survival (5-year actuarial rate 63% vs 79%, P<.001), and inferior overall survival (5-year actuarial rate 72% vs 83%, P<.001). In multivariable analyses that were adjusted for disease site and stage, comorbidity score, gender, ethnicity, race, and socioeconomic status (SES), RT noncompliance was associated with inferior recurrence, recurrence-free survival, and overall survival rates. Propensity score–matched models yielded results nearly identical to those seen in univariate analyses. Low SES was associated with RT noncompliance and was associated with inferior clinical outcomes in univariate analyses, but SES was not associated with inferior outcomes in multivariable models. Conclusion: For cancer patients being treated with curative intent, RT noncompliance is associated with inferior clinical outcomes. The magnitudes of these effects demonstrate that RT noncompliance can serve as a behavioral biomarker to identify high-risk patients who require additional interventions. Treatment compliance may mediate the associations that have been observed linking SES and clinical outcomes.