Sources of marine litter along the Bulgarian Black Sea coast: Identification, scoring and contribution.

The sources of marine litter (ML) pollution along the Bulgarian Black Sea coast in 2019 were identified and categorized to: Public litter, Fishing, Shipping, Sanitary and sewage, Fly tipped, Medical and Non-sourced, following Veiga et al., 2016 approach. Largest was the contribution of Public litter - 48.3% and Non-sourced - 38.5% of the total. Most Public litter items were attributed to recreational activities - 82.9% Public litter Recreation and less to Public litter Smoking-related - 17.1%. Regarding to Non-sourced, the following sub-categories seemed to contribute clearly more: Land (run off) - 8.79% and Tourism beach users - 8.58%. Considerably lower was the contribution of Fishing, Offshore and Shipping. None of the items were attributed to Sewage related. The ML pollution on the individual beaches (10 sites) exhibited largest contribution of Public litter with most significant input of Public litter Recreation, varying from 65.9 to 86.7% between beaches.

Marine litter accumulation along the Bulgarian Black Sea coast: Categories and predominance.

Quantitative assessment of marine litter (ML) along the Bulgarian Black Sea coastline was presented. ML surveys were conducted every season in a total of 8 beach monitoring sites during 2015-2016. Eight main categories of material were determined, based on standard OSPAR monitoring protocol. Annual accumulation of 19,805 nos. was recorded. The highest was the quantity of items related to artificial polymer materials category - 16,690 nos. The most dominant in this category were cigarette butts and filters - 4496 nos., followed by plastic caps/lids drinks - 1413 nos. and cups and cup lids - 1194 nos. The highest was the abundance of most of the litter during the summer period, related to the increased number of beach visitors, numerous temporarily working fast - food eateries, some big and small restaurants and cafes in close proximity to the beaches, as well as fishing, wild camping, etc. The contribution of ML types to the coastal pollution, presented by number and weight of items was determined. The highest was the contribution (by number) of cigarette butts and filters - 29.7%, followed by plastic caps/lids of beverages - 9.4%; plastic cups and cup lids - 7.9%, etc. According to the weight drink bottles > 5 L exhibited highest percentage - 30.7%, followed by shopping bags incl. pieces - 15.5% and drink bottles ≤ 0.5 L - 13.2%. The ML accumulation, presented by number and weight gives more detailed information about litter characteristics, the levels of coastal pollution and improves ML management.

Seasonal dynamics of marine litter along the Bulgarian Black Sea coast.

In this study marine litter (ML) surveys were conducted in 8 beaches along the Bulgarian Black Sea coastline within 4 seasons for 2015-2016. The monitoring applied OSPAR guideline, classifying ML in eight categories and 167 types. The results exhibited predominance of artificial polymer materials - 84.3%. ML densities ranged from 0.0587±0.005 to 0.1343±0.008 n/m2, highest on the urban beaches. The seasonal dynamics of most top 10 ML showed highest quantities in summer than the other seasons, as the differences are of high statistical significance (0.001≤P≤0.05). Top 1 ML item for most of the beaches was cigarette butts and filters reaching 1008±10.58 nos. in summer and from 19±3.41 to 89±7.81 nos. during the rest of the seasons (P<0.001). For the pronounced seasonality contributed the recreational activities, increased tourist flow and the wild camping. The investigation will enrich data scarcity for Descriptor 10 "Marine litter".

Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03).

BACKGROUND: Experimental data demonstrated that concurrent anti-angiogenic treatment with sunitinib may improve the efficacy of radiation therapy (RT). Here we report the results of a phase I trial performed within the German Interdisciplinary Sarcoma Group (GISG-03) of combined sunitinib and RT for neoadjuvant treatment of locally advanced soft tissue sarcoma (STS). METHODS: The primary endpoint of the study was to explore the recommended dose of sunitinib combined with RT for subsequent trials. Treatment response, postoperative complications after tumor resection and toxicity according to CTCAE 4.0 were secondary endpoints. The study used a 3 + 3 design. Patients received either 25 mg (dose level 1) or 37.5 mg (dose level 2) sunitinib two weeks prior to and throughout RT (28 × 1.8 Gy). Surgery was scheduled 5-8 weeks after completion of neoadjuvant treatment. STUDY REGISTRATION: NCT01498835. RESULTS: Six patients were enrolled in dose level 1 and three patients in dose level 2. Median tumor size was 11 cm. Tumors were located in the retroperitoneum (4/9), lower leg (3/9) or trunk (2/9). At dose level 1, 1/6 patients developed dose limiting lymphopenia. At dose level 2, no patient developed dose limiting toxicity. Most frequent toxicities were hematological (8/9) and oral (5/9). Dose adjustments of sunitinib were necessary in 5/9 patients. All patients received full dose RT and underwent tumor resection (8/9 R0 and 1/9 R1). Local toxicity of RT did not exceed Grade 2. 2/9 patients had postoperative complications requiring re-intervention. Treatment response according to RECIST was as follows: partial response 1/9, stable disease 7/9, and progressive disease 1/9. Pathological examination revealed ≥ 95 % tumor necrosis in 3/9 resected specimens. CONCLUSIONS: Combined sunitinib and RT was tolerable as neoadjuvant treatment for locally advanced STS patients regardless of tumor localization. The recommended sunitinib dose for subsequent trials is 37.5 mg.

Combined radiation therapy and sunitinib for preoperative treatment of soft tissue sarcoma.

BACKGROUND: Antiangiogenic substances and radiation therapy (RT) may have synergistic effects and improve irradiation efficacy. We present a cohort study evaluating the toxicity of combined sunitinib and RT as neoadjuvant treatment of extremity and retroperitoneal soft tissue sarcoma (STS). METHODS: Sixteen patients with locally advanced extremity (6/16) or retroperitoneal (10/16) STS were treated with continuous-dosing sunitinib (15/16: 37.5 mg daily; 1/16: 25 mg daily) and standard RT (45-50.4 Gy) preoperatively. Surgery was scheduled 5-9 weeks following neoadjuvant treatment. The primary goal of the study was to determine combined treatment toxicity according to the Common Terminology Criteria for Adverse Events. Secondary goals were the evaluation of postoperative morbidity and treatment response. RESULTS: Eight of 16 patients developed grade 3, and one patient developed grade 4, hematological toxicity. One patient experienced grade 3 hand-foot syndrome. The most frequent treatment toxicities of any grade were hematological (15/16) or dermatological (9/16). Three patients had partial response, 11 had stable disease, and 2 had progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST). Fourteen of 16 patients underwent surgery; tumors were not removed in two patients because of patient refusal or intercurrent metastatic disease. The proportion of tumor necrosis exceeded 90 % in 5 of 14 patients, and 4 patients had postoperative complications requiring reintervention. CONCLUSIONS: Preoperative treatment with concurrent sunitinib and RT was tolerable, and postoperative morbidity did not increase. Combined treatment with RT and sunitinib was also feasible in patients with retroperitoneal STS, and warrants further investigation.

Impact of flattening-filter-free radiation on the clonogenic survival of astrocytic cell lines.

BACKGROUND AND PURPOSE: Flattening-filter-free (FFF) beams are increasingly used in radiotherapy as delivery times can be substantially reduced. However, the relative biologic effectiveness (RBE) of FFF may be increased relative to conventional flattened (FLAT) beams due to differences in energy spectra. Therefore, we investigated the effects of FFF and FLAT beams on the clonogenic survival of astrocytoma cells. MATERIAL AND METHODS: Three cell lines (U251, U251-MGMT, and U87) were irradiated with 6-MV and 10-MV X-rays from a linear accelerator in FFF- or FLAT-beam modes at dose rates in the range of 0.5-24 Gy/min. The surviving fraction (SF) as function of dose (2-12 Gy) was determined by the colony formation assay and fitted by the linear-quadratic model. For both beams (FFF or FLAT), the cells were pelleted in conical 15-ml centrifuge tubes and irradiated at 2-cm depth in a 1 × 1-cm(2) area on the central axis of a 30 × 30-cm(2) field. Dosimetry was performed with a 0.3-cm(3) rigid ionization chamber. RBE was determined for FFF versus FLAT irradiation. RESULTS: The RBE of FFF at 7.3-11.3 Gy was 1.027 ± 0.013 and 1.063 ± 0.018 relative to FLAT beams for 6- and 10-MV beams, respectively, and was only significantly higher than 1 for 10 MV. Significantly increased survival rates were seen for lower dose rates (0.5 Gy/min FLAT vs. 5 Gy/min FLAT) at higher doses (11.9 Gy), while no differences were seen at dose rates ≥ 1.4 Gy/min (1.4 Gy/min FFF vs. 14 Gy/min FFF and 2.4 Gy/min FFF vs. 24 Gy/min FFF). CONCLUSIONS: FFF beams showed only a slightly increased RBE relative to FLAT beams in this experimental set-up, which is unlikely to result in clinically relevant differences in outcome.

Volumetric-modulated arc radiotherapy for pancreatic malignancies: dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy.

Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

Clinical outcome of hypofractionated breath-hold image-guided SABR of primary lung tumors and lung metastases.

BACKGROUND: Stereotactic Ablative RadioTherapy (SABR) of lung tumors/metastases has been shown to be an effective treatment modality with low toxicity. Outcome and toxicity were retrospectively evaluated in a unique single-institution cohort treated with intensity-modulated image-guided breath-hold SABR (igSABR) without external immobilization. The dose-response relationship is analyzed based on Biologically Equivalent Dose (BED). PATIENTS AND METHODS: 50 lesions in 43 patients with primary NSCLC (n = 27) or lung-metastases of various primaries (n = 16) were consecutively treated with igSABR with Active-Breathing-Coordinator (ABC®) and repeat-breath-hold cone-beam-CT. After an initial dose-finding/-escalation period, 5 x 12 Gy for peripheral lesions and single doses of 5 Gy to varying dose levels for central lesions were applied. Overall-survival (OS), progression-free-survival (PFS), progression pattern, local control (LC) and toxicity were analyzed. RESULTS: The median BED2 was 83 Gy. 12 lesions were treated with a BED2 of <80 Gy, and 38 lesions with a BED2 of >80 Gy. Median follow-up was 15 months. Actuarial 1- and 2-year OS were 67% and 43%; respectively. Cause of death was non-disease-related in 27%. Actuarial 1- and 2-year PFS was 42% and 28%. Progression site was predominantly distant. Actuarial 1- and 2 year LC was 90% and 85%. LC showed a trend for a correlation to BED2 (p = 0.1167). Pneumonitis requiring conservative treatment occurred in 23%. CONCLUSION: Intensity-modulated breath-hold igSABR results in high LC-rates and low toxicity in this unfavorable patient cohort with inoperable lung tumors or metastases. A BED2 of <80 Gy was associated with reduced local control.

Intensity modulated radiosurgery of brain metastases with flattening filter-free beams.

PURPOSE: Flattening filter free (FFF) irradiation potentially reduces treatment delivery time in radiosurgery thus eliminating intrafraction motion and increasing patient comfort. We compared plan quality and efficiency of VMAT and IMRT plans for FFF- and standard delivery for brain metastases with single fraction doses of 20 Gy and validated the dosimetric accuracy of the FFF delivery. MATERIAL AND METHODS: CT data of 15 patients with brain metastases were included in this study. For every patient, 2 IMRT- and 2 VMAT-plans were created using a high-resolution MLC with two different delivery modes (6MV standard vs. 6MV FFF). Plan quality and efficiency was assessed by analysis of conformity, homogeneity, dose gradients, treatment delivery time and number of monitor units (MU). Dosimetric evaluation was performed for 10 FFF plans with radiochromic film and ion chamber. RESULTS: Plan quality was similar for both approaches. FFF provided a mean treatment time reduction of 51.5% with similar MU for VMAT and IMRT for this low-modulation paradigm. The dosimetric validations showed an absolute dose deviation of +0.93 ± 0.99% and γ-index analysis (3%/3mm and 3%/1mm) resulted in agreement of 99.08 ± 1.58% respectively 93.46 ± 2.41%. CONCLUSION: FFF radiosurgery is an efficient technique for intensity modulated hypofractionated or single fraction treatments with similar plan quality when compared to flattened beams at reduced treatment time.

Flattening-filter-free intensity modulated breath-hold image-guided SABR (Stereotactic ABlative Radiotherapy) can be applied in a 15-min treatment slot.

Hypofractionated image-guided stereotactic ablative radiotherapy (igSABR) is effective in small lung/liver lesions. Computer-assisted breath-hold reduces intrafraction motion but, as every gating/triggering strategy, reduces the duty cycle, resulting in long fraction times if combined with intensity-modulated radiotherapy (IMRT). 10 MV flattening-filter-free IMRT reduces daily fraction duration to <10 min for single doses of 5-20 Gy.

Factors of influence on acute skin toxicity of breast cancer patients treated with standard three-dimensional conformal radiotherapy (3D-CRT) after breast conserving surgery (BCS).

PURPOSE/OBJECTIVES: Standard 3D-CRT after BCS may cause skin toxicity with a wide range of intensity including acute effects like erythema or late effects. In order to reduce these side effects it is mandatory to identify potential factors of influence in breast cancer patients undergoing standard three-dimensional conformal radiation therapy (3D-CRT) of the breast and modern systemic therapy. MATERIALS/METHODS: Between 2006 and 2010 a total of 211 breast cancer patients (median age 52,4 years, range 24-77) after BCS consecutively treated in our institution with 3D-CRT (50 Gy whole breast photon radiotherapy followed by 16 Gy electron boost to the tumorbed) were evaluated with special focus on documented skin toxicity at the end of the 50 Gy-course. Standardized photodocumentation of the treated breast was done in each patient lying on the linac table with arms elevated. Skin toxicity was documented according to the common toxicity criteria (CTC)-score. Potential influencing factors were classified in three groups: patient-specific (smoking, age, breast size, body mass index = BMI, allergies), tumor-specific (tumorsize) and treatment-specific factors (antihormonal therapy with tamoxifen or aromatase inhibitors, chemotherapy). Uni- and multivariate statistical analyses were done using IBM SPSS version 19. RESULTS: After 50 Gy 3D-CRT to the whole breast 28.9% of all 211 patients had no erythema, 62.2% showed erythema grade 1 (G1) and 8.5% erythema grade 2. None of the patients had grade 3/4 (G3/4) erythema.In univariate analyses a significant influence or trend on the development of acute skin toxicities (erythema G0 versus G1 versus G2) was observed for larger breast volumes (p=0,004), smoking during radiation therapy (p=0,064) and absence of allergies (p=0,014) as well as larger tumorsize (p=0,009) and antihormonal therapy (p=0.005).Neither patient age, BMI nor choice of chemotherapy showed any significant effect on higher grade toxicity. In the multivariate analysis, factors associated with higher grade skin toxicity were larger breast target volume (p=0,003), smoking (p=0,034) and absence of allergies (p=0,002). CONCLUSION: Patients treated in this study showed less objectively documented skin toxicity after 50 Gy 3D-CRT compared to similar patient cohorts. Factors associated with higher grade skin toxicity were smoking during 3D-CRT, absence of allergies and larger breast volumes.

Comparison of anisotropic aperture based intensity modulated radiotherapy with 3D-conformal radiotherapy for the treatment of large lung tumors.

PURPOSE/OBJECTIVE(S): IMRT allows dose escalation for large lung tumors, but respiratory motion may compromise delivery. A treatment plan that modulates fluence predominantly in the transversal direction and leaves the fluence identical in the direction of the breathing motion may reduce this problem. MATERIALS/METHODS: Planning-CT-datasets of 20 patients with Stage I-IV non small cell lung cancer (NSCLC) formed the basis of this study. A total of two IMRT plans and one 3D plan were created for each patient. Prescription dose was 60 Gy to the CTV and 70 Gy to the GTV. For the 3D plans an energy of 18 MV photons was used. IMRT plans were calculated for 6 MV photons with 13 coplanar and with 17 noncoplanar beams. Robustness of the used method of anisotropic modulation toward breathing motion was tested in a 13-field IMRT plan. RESULTS: As a consequence of identical prescription doses, mean target doses were similar for 3D and IMRT. Differences between 3D and 13- and 17-field IMRT were significant for CTV Dmin (43 Gy vs. 49.1 Gy vs. 48.6 Gy; p<0.001) and CTV D(95) (53.2 Gy vs. 55.0 Gy vs. 55.4 Gy; p=0.001). The D(mean) of the contralateral lung was significantly lower in the 17-field plans (17-field IMRT vs. 13- vs. 3D: 12.5 Gy vs. 14.8 Gy vs. 15.8 Gy: p<0.05). The spinal cord dose limit of 50 Gy was always respected in IMRT plans and only in 17 of 20 3D-plans. Heart D(max) was only marginally reduced with IMRT (3D vs. 13- vs. 17-field IMRT: 38.2 Gy vs. 36.8 Gy vs. 37.8 Gy). Simulated breathing motion caused only minor changes in the IMRT dose distribution (~0.5-1 Gy). CONCLUSIONS: Anisotropic modulation of IMRT improves dose delivery over 3D-RT and renders IMRT plans robust toward breathing induced organ motion, effectively preventing interplay effects.

Are three doses of stereotactic ablative radiotherapy (SABR) more effective than 30 doses of conventional radiotherapy?

In early stage non-small cell lung cancer (NSCLC) definitive radiation therapy is an appropriate alternative to surgery. Recent studies show, that in such patients hypofractionation schedules (for example 3 times 18 Gy or 5 times 12 Gy), can be safely applied, without causing severe toxicities and achieving high local control rates of up to 90% and more. In the last couple of years a lot of knowledge about the cancer biology, technical aspects, clinical outcomes and toxicities has been accumulated from different clinical trials. The purpose of this review is to summarize recent outcomes and developments in stereotactic radiation therapy for patients with early stage NSCLC.

Bone marrow-sparing intensity-modulated radiotherapy (IMRT) for neo-adjuvant therapy of inoperable cervical cancer in a patient with severe thrombocytopenia.

BACKGROUND: Therapy possibilities are limited in patients with cervix carcinoma and thrombocytopenia. CASE REPORT: We describe a 50-year-old woman with inoperable cervical carcinoma and chronic lymphatic B cell leukemia (B-CLL). Due to thrombocytopenia, a combined radiochemotherapy could not be performed. Intensitymodulated radiotherapy (IMRT) aiming at maximal bone sparing was planned. After a total dose of 45 Gy, a laparoscopic omentum plastic was performed to enable radiotherapy (RT) to full dose. 3 days later, an external beam boost was restarted to a cumulative dose of 50.4 Gy. Regular blood analysis showed low but stable blood counts. 4 weeks after RT, magnetic resonance imaging (MRI) showed a 30% regression of the tumor volume and, after transfusion of fresh-frozen plasma, a hysterectomy could be performed. 6 months after therapy, no recurrence or late toxicities had occurred. CONCLUSION: The clinical implementation of IMRT may potentially improve the therapeutic outcome of patients with cervix cancer, allowing dose escalation without increasing normal-tissue toxicity.