Search

Aim: To assess the changes in the angiogenic status of rectal cancer before and after preoperative radiotherapy (RT) using endosonography (ES). Material and Methods: Fifty-four patients with rectal cancer were examined by ES before and 6-7 weeks after preoperative RT and . The tumour size, stage, echostructure and vascularization before and after RT were compared. Tumour vascularization was determined by qualitative power Doppler and by computer-assisted method. Results: Compared to the histological data, ES restaging after RT was accurate in 65% of the cases for the T parameter and in 83% for the N parameter (TNM tumour classification). The histological data compared with the initial ES examination revealed downstaging in relation to the T parameter in 33% and for the N stage in 24% of the cases. The tumour structure following RT became hyperechogenic in 89% of tumours and remained hypoechogenic in 11% of tumours. Power Doppler found a reduction in tumour vascularization after RT in 61% of the tumours. The PDVI before RT was 10.7+/-5.8% and 6.3+/-4.6% after RT (р<0.05). A strong correlation between the qualitative assessment of the vascularization and PDVI was found (r=0.536, p<0.001). The vascularization reduction after RT was found to be a protective factor which decreased the death risk by about 86 % (ОR=0.14, р=0.001). Conclusions: Endorectal Doppler sonographic findings are promising in the evaluation of tumour vascularization in patients with rectal cancer. The qualitative and quantitative digital assessment of the vascularization gives supplementary information about the patients' prognosis. [ABSTRACT FROM AUTHOR]

Effective adverse event (AE) management is critical to maintaining patients on anticancer therapies. The DECISION trial was a multicenter, randomized, double-blind, placebo-controlled, Phase 3 trial which investigated sorafenib for treatment of progressive, advanced, or metastatic radioactive iodine-refractory, differentiated thyroid carcinoma. Four hundred and seventeen adult patients were randomized (1:1) to receive oral sorafenib (400 mg, twice daily) or placebo, until progression, unacceptable toxicity, noncompliance, or withdrawal. Progression-free survival, the primary endpoint of DECISION, was reported previously. To elucidate the patterns and management of AEs in sorafenib-treated patients in the DECISION trial, this report describes detailed, by-treatment-cycle analyses of the incidence, prevalence, and severity of hand-foot skin reaction (HFSR), rash/desquamation, hypertension, diarrhea, fatigue, weight loss, increased serum thyroid stimulating hormone, and hypocalcemia, as well as the interventions used to manage these AEs. By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased. AE prevalence generally increased over cycles 2-6 then stabilized or declined. Among these AEs, only weight loss tended to increase in severity (from grade 1 to 2) over time; severity of HFSR and rash/desquamation declined over time. AEs were mostly grade 1 or 2, and were generally managed with dose interruptions/reductions, and concomitant medications (e.g. antidiarrheals, antihypertensives, dermatologic preparations). Most dose interruptions/reductions occurred in early cycles. In conclusion, AEs with sorafenib in DECISION were typically grade 1 or 2, occurred early during the treatment course, and were manageable over time., (© 2015 The authors.)

The paper reveals the changing pattern of Bulgarian Radiotherapy (RT) care after the successful implementation of 15 projects for 100 million euro under the European Regional Development Fund in Operational Programme for Regional Development 2007-2013. The project enables a total one-step modernization of 14 Bulgarian RT Centres and creation of a new one. At the end of the Programme (mid 2015), 16 new Linacs and 2 modern cobalt machines will be available together with 11 virtual CT simulators, 5 CT simulators, 1 MRI and 1 PET CT for RT planning and all dosimetry facilities needed. Such a modernization has moved Bulgarian RT forward, with 2.7 MV units per one million of population (MV/mln.inh) in comparison with 0.9 MV/mln.inh in 2012. Guild of Bulgarian Radiotherapists includes 70 doctors, 46 physicists and 10 engineers, together with 118 RTTs and 114 nurses and they all have treated 16,447 patients in 2013. Major problems are inadequate reimbursement from the monopolistic Health Insurance Fund (900 euro for 3D conformal RT and 1500 euro for IMRT); fragmentation of RT care with 1-2 MV units per Centre; no payment for patient travel expenses; need for quick and profound education of 26% of doctors and 46% of physicists without RT license, along with continuous education for all others; and resource for 5000-9000 more patients to be treated yearly by RT in order to reach 45-50% from current service of 32%. After 15 years of struggle of RT experts, finally the pattern of Bulgarian RT care at 2014-2015 is approaching the level of modern European RT.

Background and Purpose: In planning to meet evidence based needs for radiotherapy, guidelines for the provision of capital and human resources are central if access, quality and safety are not to be compromised. A component of the ESTRO-HERO (Health Economics in Radiation Oncology) project is to document the current availability and content of guidelines for radiotherapy in Europe., Materials and Methods: An 84 part questionnaire was distributed to the European countries through their national scientific and professional radiotherapy societies with 30 items relating to the availability of guidelines for equipment and staffing and selected operational issues. Twenty-nine countries provided full or partial evaluable responses., Results: The availability of guidelines across Europe is far from uniform. The metrics used for capital and human resources are variable. There seem to have been no major changes in the availability or specifics of guidelines over the ten-year period since the QUARTS study with the exception of the recent expansion of RTT staffing models. Where comparison is possible it appears that staffing for radiation oncologists, medical physicists and particularly RTTs tend to exceed guidelines suggesting developments in clinical radiotherapy are moving faster than guideline updating., Conclusion: The efficient provision of safe, high quality radiotherapy services would benefit from the availability of well-structured guidelines for capital and human resources, based on agreed upon metrics, which could be linked to detailed estimates of need., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Documenting the distribution of radiotherapy departments and the availability of radiotherapy equipment in the European countries is an important part of HERO - the ESTRO Health Economics in Radiation Oncology project. HERO has the overall aim to develop a knowledge base of the provision of radiotherapy in Europe and build a model for health economic evaluation of radiation treatments at the European level. The aim of the current report is to describe the distribution of radiotherapy equipment in European countries., Methods: An 84-item questionnaire was sent out to European countries, principally through their national societies. The current report includes a detailed analysis of radiotherapy departments and equipment (questionnaire items 26-29), analyzed in relation to the annual number of treatment courses and the socio-economic status of the countries. The analysis is based on validated responses from 28 of the 40 European countries defined by the European Cancer Observatory (ECO)., Results: A large variation between countries was found for most parameters studied. There were 2192 linear accelerators, 96 dedicated stereotactic machines, and 77 cobalt machines reported in the 27 countries where this information was available. A total of 12 countries had at least one cobalt machine in use. There was a median of 0.5 simulator per MV unit (range 0.3-1.5) and 1.4 (range 0.4-4.4) simulators per department. Of the 874 simulators, a total of 654 (75%) were capable of 3D imaging (CT-scanner or CBCT-option). The number of MV machines (cobalt, linear accelerators, and dedicated stereotactic machines) per million inhabitants ranged from 1.4 to 9.5 (median 5.3) and the average number of MV machines per department from 0.9 to 8.2 (median 2.6). The average number of treatment courses per year per MV machine varied from 262 to 1061 (median 419). While 69% of MV units were capable of IMRT only 49% were equipped for image guidance (IGRT). There was a clear relation between socio-economic status, as measured by GNI per capita, and availability of radiotherapy equipment in the countries. In many low income countries in Southern and Central-Eastern Europe there was very limited access to radiotherapy and especially to equipment for IMRT or IGRT., Conclusions: The European average number of MV machines per million inhabitants and per department is now better in line with QUARTS recommendations from 2005, but the survey also showed a significant heterogeneity in the access to modern radiotherapy equipment in Europe. High income countries especially in Northern-Western Europe are well-served with radiotherapy resources, other countries are facing important shortages of both equipment in general and especially machines capable of delivering high precision conformal treatments (IMRT, IGRT)., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: CAM2028, a vehicle that forms a bioadhesive lipid barrier when applied to the oral mucosa, was developed as a carrier system for local delivery of benzydamine, an NSAID used for pain relief in oral mucositis. This trial compared the analgesic effect of CAM2028 plus benzydamine (CAM2028-benzydamine) with unmedicated CAM2028 (CAM2028-control) for the treatment of oral mucositis in patients with head-and-neck cancer., Methods: Thirty-eight study participants were enrolled during their 3rd to 4th week of radiation therapy. Participants were required to have symptomatic oral mucositis (WHO Grade 2 or above) at screening and pain scores of at least 6 on an 11-point Likert scale at screening and on each day before treatment with study medication. After undergoing radiation, patients were administered a single dose of CAM2028-control or CAM2028-benzydamine 2 days apart, in a randomized crossover fashion. Pain was assessed over the following 8 h., Results: With both treatments, patients experienced a mean 40 % decrease in pain intensity at 6 h (the primary study endpoint). Both treatments resulted in significant pain relief within 5 min of application that was evident during the entire 8-h assessment period. There was no difference in pain relief between the two interventions at any time point. Both treatments were safe and well tolerated., Conclusions: CAM2028-benzydamine and CAM2028-control were both efficacious in reducing pain in patients with oral mucositis related to radiation therapy for head-and-neck cancer. Analgesic effects of both medications were immediate, clinically significant, and persistent for up to 8 h.

Primary osteogenic sarcoma of the breast is a rare neoplasm, diagnosed mainly by pathohistological and immunohistochemical analysis. We hereby present a case of primary osteogenic sarcoma in the right breast of a 62-year-old woman with synchronous appearance of an invasive ductal carcinoma. Clinical findings are manifested with two separate painless formations 2.5 cm/2 cm and 1.5 cm/1 cm in size, located on the border of the upper and lower lateral quadrant of the right breast. No axillary lymphadenopathy was diagnosed. The pathohistological and immunohistochemistry findings of both tumors revealed a synchronous manifestation of two distinct neoplasms - epithelial and non-epithelial. Multimodality treatment consisted of Patey's radical mastectomy; 3 cycles of adjuvant chemotherapy; postoperative 50 Gy radiotherapy to the chest wall followed by additional 3 cycles of chemotherapy and anti-estrogen hormonotherapy. Due to the rarity of osteogenic mammary sarcoma, even more so in a combination with epithelial breast tumors, its clinical features are unclear and optimal treatment remains controversial. Considering the poor prognosis of the combination of both malignomas, we discuss a number of diagnostic and therapeutic issues.

Background: Pelvic organs morbidity after irradiation of cancer patients remains a major problem although new technologies have been developed and implemented. A relatively simple and suitable method for routine clinical practice is needed for preliminary assessment of normal tissue intrinsic radiosensitivity. The micronucleus test (MNT) determines the frequency of the radiation induced micronuclei (MN) in peripheral blood lymphocytes, which could serve as an indicator of intrinsic cell radiosensitivity., Aim: To investigate a possible use of the micronucleus test (MNT) for acute radiation morbidity prediction in gynecological cancer patients., Materials and Methods: Forty gynecological cancer patients received 50 Gy conventional external pelvic irradiation after radical surgery. A four-field "box" technique was applied with 2D planning. The control group included 10 healthy females. Acute normal tissue reactions were graded according to NCI CTCAE v.3.0. From all reaction scores, the highest score named "summarized clinical radiosensitivity" was selected for a statistical analysis. MNT was performed before and after in vitro irradiation with 1.5 Gy. The mean radiation induced frequency of micronuclei per 1000 binucleated cells (MN/1000) and lymphocytes containing micronuclei per 1000 binucleated cells (cells with MN/1000) were evaluated for both patients and controls. AN ARBITRARY CUT OFF VALUE WAS CREATED TO PICK UP A RADIOSENSITIVE INDIVIDUAL: the mean value of spontaneous frequency of cells with MN/1000 ± 2SD, found in the control group., Results: Both mean spontaneous frequency of cells with MN/1000 and MN/1000 were registered to be significantly higher in cancer patients compared to the control group (t = 2.46, p = 0.02 and t = 2.51, p = 0.02). No statistical difference was registered when comparing radiation induced MN frequencies between those groups. Eighty percent (32) of patients developed grade 2 summarized clinical radiosensitivity, with great variations in MNT parameters. Only three patients with grade 2 "summarized clinical radiosensitivity" had values of cells with MN/1000 above the chosen radiosensitivity threshold., Conclusion: The present study was not able to confirm in vitro MNT applicability for radiosensitivity prediction in pelvic irradiation.

Background/aims: The accuracy of endoluminal ultrasonographic restaging of rectal cancer after chemoradiation has not been extensively studied and its definitive clinical utility has yet to be defined. The aim of the present study is to assess the benefit of endoluminal ultrasonography with Doppler evaluation for rectal cancer restaging after preoperative radiotherapy., Methodology: Twenty six patients (10 female, 16 males, mean age--58 years) with histologically proven rectal cancer underwent preoperative radiotherapy. All patients were examined by endoluminal (endorectal or endovaginal) ultrasonography. Endosonography was repeated on 13 patients after small fractions preoperative radiotherapy., Results: The mean transversal diameter of lesions before preoperative radiotherapy established by endoluminal ultrasonography is 33mm +/- 11 mm. After preoperative radiotherapy we detect significant reduction of 33% in the transversal tumor size--mean 23mm +/- 7mm (p < 0.001). After radiation the mean distance from the tumor to the internal anal sphincter increases without statistical significance by 5%: from 59 +/- 18 mm to 62 +/- 16 mm (p = 0.165). Compared to histological data, endosonographic restaging after radiotherapy is accurate in 9/13 (69%) for T parameter and 11/13 (85%) for N. After preoperative radiotherapy tumor sonographic structure is hyperechoic (homogeneous or inhomogeneous)--in 9 patients and only in 4 cases the tumor remains hypoechoic. Power Doppler exam before radiotherapy shows poor vascularization in 5 tumors--(19%). Abundant vascularization is found in 9 cases--(35%). In the remaining 12 patients tumor vascularization is considered as moderate. In 8 out of 13 cases (61.5%) after radiotherapy, vascular signals are less expressed. Lack of vascular alterations on pulse color and power Doppler flow is detected in the remaining 5 patients. No patients have more expressed vascularization on power Doppler examination after radiotherapy., Conclusion: According to our results the accuracy of endosonographic restaging after radiotherapy is lower for assessment of T criterion and is better for N parameter. Doppler findings are promising in the evaluation of tumor vascularity, respectively its predictive and prognostic values.

Purpose: To evaluate the role of some nuclear medicine approaches such as (99m)Tc-MIBI scan and (131)I whole-body scintigraphy (WBS) in the monitoring of patients with differentiated thyroid cancer (DTC)., Patients and Methods: 95 patients (69F/26M) aged 17-74 years (mean 44.2) with DTC (56 cases with papillary, 20 with follicular and 19 with papillary-follicular carcinoma) were assessed. All of them had undergone total or near-total thyroidectomy and received radioiodine treatment for ablation of post-surgical residual thyroid tissue. They were examined after 4 weeks of L-thyroxin withdrawal in the follow-up of DTC. Planar and whole-body images were acquired at 15 and 180 min after i.v. administration of (99m)Tc-MIBI (555-740 MBq) and at 48 h after p.o. administration of(131)I(111-185 MBq) on Toshiba GCA gamma camera. Serum thyroglobulin (Tg) estimations were performed to clarify the presence of residual normal tissue or recurrent malignancy., Results: (131)I scan was positive in 63 patients showing thyroid remnants in 31 cases, lymph node metastases in 24 cases (17 to the neck, 7 to the neck/mediastinum), pulmonary metastases in 6 cases, bone and brain lesions in 2 cases. In 15 patients (131)I scan was negative, Tg was undetectable, so patients were considered tumor-free. In 17 patients (131)I scan was negative while serum Tg was increased. These false negative results were observed predominantly in cases with less differentiated metastatic disease, especially after several courses of high-dose (131)I therapy. (99m)Tc-MIBI scan revealed the presence of lymph node and/or lung metastases (non-functioning metastases) in 14 of them, false negative results were obtained in 2 cases, and one false positive in 1 case. Serum Tg was increased in all patients with local lymph node and distant metastases, visualized by (131)I or by (99m)Tc-MIBI, but also in 18 patients with thyroid remnants only., Conclusion: (99m)Tc-MIBI scan has been reported to be a highly sensitive technique for the detection of DTC metastases that have lost the capability to uptake (131)I; the combined (99m)Tc-MIBI scintigraphy and serum Tg estimation appear to be an alternative method of radioiodine imaging in cases with DTC and elevated Tg.

Cytokinesis-blocked micronucleus assay (MNT) was applied in the peripheral blood lymphocytes of patients undergoing radioiodine-131 ((131)I) therapy for differentiated thyroid carcinoma (DTC) after thyroidectomy to assess the genotoxic risk of this therapy. The amount of administered (131)I activity varied from 3,330 to 4,030 MBq. Blood samples were taken immediately before (131)I administration and one month later, along with routine blood tests. Twenty-six patients underwent radioiodine ablation (RIA) or radioiodine therapy (RIT) after radical thyroidectomy. The aim of this therapy was to ablate residual thyroid tissue, to treat lymph node metastases and/or distant lung metastases. The amount of orally administered activity of (131)I ranged between 3,330 and 4,030 MBq according to the kind of therapy (RIA or RIT). In five patients the cytogenetic analysis was performed immediately before and one month after the second therapy which was given to them 6 months to 1 year after the first. Three patients were male and 23 female. The age of the patients ranged between 23 and 76 years (mean age: 48.6 years). Results show that after radioiodine therapy there is a significant increase in the frequency of micronuclei. Comparing the average frequency of micronuclei in the patients studied before and after (131)I, a more than doubling increase was found. Mean values +/- SD of the patients before and after (131)I therapy were 10.72 per thousand +/- 5.84 per thousandand 25.28 per thousand +/- 12.6 per thousand respectively. These findings indicate a genotoxic activity of (131)I therapy estimated after a period of one month.

Background and Purpose: Single agent mitomycin c (MMC) has been shown to improve the outcome of radiotherapy in single institution trials. In order to confirm these findings in a broader worldwide setting, the International Atomic Energy Agency (IAEA) initiated a multicentre trial randomising between radiotherapy alone versus radiotherapy plus MMC., Material and Methods: Patients with advanced head and neck cancer were treated with primary curative radiotherapy (66 Gy in 33 fractions with five fractions per week) +/-a single injection (15 mg/m(2)) of MMC at the end of the first week of radiotherapy. Stratification parameters were tumour localization, T-stage, N-stage, and institution. A total of 558 patients were recruited in the trial from February 1996 to December 1999. Insufficient accrual and reporting led to the exclusion of three centres. The final study population consisted of 478 patients from seven centres. Patients had stage III (n=223) or stage IV (n=255) squamous cell carcinoma of the oral cavity (n=230), oropharynx (n=140), hypopharynx (n=65) or larynx (n=43). Prognostic factors like age, gender, site, size, differentiation and stage were well balanced between the two arms., Results: The haematological side effects of MMC were very modest (<5% grade 3-4) and did not require any specific interventions. Furthermore, MMC did not enhance the incidence or severity of acute and late radiation side effects. Confluent mucositis and dry skin desquamation was common, occurring in 56% and 62% of patients, respectively. The overall 3-year primary locoregional tumour control, disease-specific and overall survival rates were 19, 36 and 30%, respectively. Gender, haemoglobin drop, tumour site, tumour and nodal stage were significant parameters for loco-regional tumour control. There was no significant effect of MMC on locoregional control or survival, except for the 161 N0 patients, where MMC resulted in a better loco-regional control (3-year estimate 16% vs. 29%, P=0.01)., Conclusions: The study did not show any major influence of MMC on loco-regional tumour control, survival or morbidity after primary radiotherapy in stage III-IV head and neck cancer except in N0 patients where loco-regional control was significantly improved.

Purpose: To assess the efficacy of breast conserving surgery (BCS), followed by postoperative radiation treatment (RT), chemotherapy and/or hormonotherapy in patients with early invasive lobular breast cancer (ILC)., Patients and Methods: 48 patients with TNM stages I and II ILC of the breast were treated conservatively by BCS (quadrantectomy) and axillary dissection to levels I and II, followed by RT and adjuvant chemotherapy or hormonal treatment. In patients with pN0 the remaining breast with scar and chest were treated by RT, with a total radiation dose (TRD) of 50 Gy. In cases with pN1 the axilla was included to the described field with TRD 50 Gy. In patients with high risk factors (pT2, tumor necrosis, infiltration of the subcutaneous fat and of lymph and/or blood vessels) the tumor bed was boosted up to a TRD of 60 Gy. The 5 and 10- year cancer-specific and recurrence-free survival were calculated according to the Kaplan-Meyer life-table method., Results: With a median observation period of 6.5 years (range 1.5-11.5 years) 2 (4.1%) patients developed local recurrence and 2 (4.1%) distant metastases. Ten-year cancer- specific and recurrence-free survival are 97% and 90%, respectively., Conclusion: The obtained good treatment results proved that the conservative treatment strategy in cases with ILC of the breast is a correct therapeutic choice.