Image-guided radiation therapy produces lower acute and chronic gastrointestinal and genitourinary toxicity in prostate cancer patients.

PURPOSE: This paper compares individual radiation therapy techniques used for prostate cancer and their benefits in clinical practice. METHODS: We retrospectively analyzed 921 patients with localized prostate tumors treated between 1997 and 2012. We divided the patients into four groups according to the selected treatment technique (conformal radiation therapy [3DCRT], intensity-modulated radiation therapy [IMRT], image-guided radiation therapy [IGRT], and volumetric-modulated arc therapy [VMAT]) and evaluated the incidence of acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicity. RESULTS: The incidence of grade 2 or greater acute GU and GI toxicity was significantly higher among techniques other than IGRT (p˂0.001). We found the same results in the case of grade 3 or greater acute GU toxicity (p˂0.001). Grade 3 or higher acute GI toxicity occurred only in one patient treated by 3DCRT. Cumulative late GI toxicity of grade 2 or higher and grade 3 or higher was recorded over 3 years significantly more frequently among non-IGRT techniques as compared to IGRT (p˂0.001). As regards GU toxicity, we found significantly higher incidence only for grade 2 or higher (p˂0.001), not for grade 3 or higher. No occurrence of grade 4 toxicity was recorded. The greatest incidence of patients without acute and chronic GI/GU toxicity was recorded in connection with VMAT. CONCLUSION: IGRT demonstrated a pronounced reduction in acute and chronic GU and GI toxicity as compared to non-IGRT techniques in the treatment of localized prostate cancer.

Giant locally advanced and metastatic squamous cell skin carcinoma of head and neck region: case report.

INTRODUCTION: At the present time, the skin tumors are among the most common cancers. Optimal therapy is based on the extent of the disease and the age of the patient. The need for radiotherapy occurs for inoperable locally advanced tumors and in the event of failure, salvage surgery is applied. MATERIALS AND METHODS: We provided a case report of an older patient with giant squamous cell skin carcinoma and a review of published articles. RESULTS: We present a rare case of giant squamous cell skin carcinoma with metastatic satellite tumors that was primarily treated with curative radiotherapy. Five months after radiotherapy, a recurrent tumor was detected at the site of origin and the treatment was completed by salvage surgery. Full remission was achieved for four years. CONCLUSION: Despite the seemingly incurable finding it is always necessary to consider radical treatment regardless of the patient´s age. Curative treatment could achieve long term remission in the group of older patients.

Audio-visual navigation reduces treatment time in deep-inspiration breath hold radiotherapy.

AIMS: The purpose of this study was to compare the treatment times for deep-inspiration breath hold with and without audio-visual (A-V) navigation. METHODS: We measured the real treatment time in 60 patients with breast cancer undergoing postoperative radiotherapy. Thirty consecutive patients were treated without deep-inspiration breath hold (DIBH) and another 30 patients using deep-inspiration breath hold (10 patients with DIBH only, 10 patients with DIBH using visual feedback and 10 patients with DIBH using visual feedback following breath training). The treatment time was relativized to number of fields and 100 monitor units (MU). The independent t-test was used to analyse differences between cohorts. RESULTS: The mean treatment time for patients without DIBH was 46.5 seconds per field and 90.9 seconds per 100 MU, for DIBH only 92.3 and 170.2 seconds, for DIBH with audio-visual navigation 68.1 and 133.8 seconds, and for DIBH with A-V feedback including breath training 66.1 and 132.5 seconds. The treatment times for patients treated using DIBH with visual navigation were significantly shorter in comparison with patients without visual feedback. We were not able to prove any significant benefit for breath training in terms of reducing the treatment time. CONCLUSION: Audio-visual navigation enables to significantly reduce the treatment time in comparison with DIBH without A-V feedback.

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer.

Breast cancer with high expression of human epidermal growth factor receptor (HER)-2 represents a biologically and clinically heterogeneous group of neoplastic disorders. Importantly, hormone receptor expression has an effect on biological properties and affects the selection of therapies. On the basis of molecular genetics, four principal subtypes, including luminal A, luminal B, HER2-enriched (HER-2-E), and basal-like can be distinguished. Breast tumors characterized by HER-2 positivity and simultaneous expression of hormone receptors, triple positive breast cancers (TPBC) are of increasing interest owing to the unique biological characteristics associated with complex interactions between HER-2 and hormone receptor signaling pathways. Interactions between hormone receptors and HER-2 explain the decreased efficacy of hormonal therapy in comparison with HER-2-negative patients. The expression of estrogen receptors in HER-2 positive tumors may also be associated with resistance to anti-HER-2 treatment. Multiple available therapeutic options, including hormonal therapy, anti-HER-2 agents and cytotoxic drugs explain favorable prognosis of TPBC. Escalation and de-escalation therapeutic strategies that could result in lower toxicities are being investigated as well as combinations of anti-HER-2 agents with hormonal therapy, immunotherapy, cyclin dependent kinase 4/6 and phosphatidyl inositol-3-kinase inhibitors. Distinction between subtypes of HER-2-positive breast cancer and treatment diversification may result in improved outcomes in TPBC. A response to neoadjuvant therapy may serve in the tailoring of therapy management.

Tumor bed radiotherapy in women following breast conserving surgery for breast cancer-safety margin with/without image guidance.

Image guided radiation therapy (IGRT) enables the achievement of higher precision in radiation delivery, a reduction in safety margins and a reduced risk of toxicity in healthy tissues. The present study investigated the magnitude of safety margins for the radiation boost setup on skin marks or metal clips implanted into the tumor bed during breast cancer surgery. One hundred eighty-four patients after breast conserving surgery with implanted metal clips into tumor bed were analyzed. The present study investigated the difference in safety margin required for the treatment setup on skin marks and metal clips. The skin marks were created using a positioning laser system in the treatment room. Metal clips implanted in the tumor bed were registered using IGRT with kilovoltage X-rays in orthogonal projection. Treatment setup was performed during free breathing. The safety margin corresponding to the planning target volume (PTV) was calculated from the recorded data. Calculated safety margins for the treatment setup on skin marks were 9.4, 11.1 and 11.1 mm in the anteroposterior, craniocaudal, and laterolateral directions, respectively. Corresponding safety margins with the use of IGRT and metal clips registration were 4.7, 5.1 and 5.9 mm, respectively. The safe PTV margin was 12 mm using setup on skin marks without IGRT, whereas a 6-mm margin was sufficient with the use of metal clip-based IGRT with daily online correction. IGRT has been adopted as the standard treatment method within the Oncology Centre of Multiscan and Pardubice Hospital (Pardubice, Czech Republic).

Metastatic carcinoma of breast or a chordoma? A case report and clinical perspectives.

We present a case of chordoma in a patient who had been previously treated for ductal carcinoma of the breast. The initial clinical findings and radiological studies suggested a possibility of metastases. However, the findings also adhered to the classical presentations and findings of the chordoma of the base of skull. It was only after the surgical resection and immunohistochemical confirmation that the diagnosis of chordoma could be established. Here, we discuss chordoma with the analysis of our clinical intrigue.

Interfraction variation in prostate cancer - analysis of 11726 cone-beam CT.

PURPOSE: To investigate the setup margins in prostate cancer treatment without using daily online repositioning methods. METHODS: We analysed the data from patients treated with curative-intend radiotherapy. Each patient underwent a series of pretreatment online localizations during daily setup using conebeam CT. The skin-prostate shifts and bone-prostate shifts were recorded in anteroposterior (AP), craniocaudal (CC), and laterolateral (LL)direction. The safety margins based on van Herk equation (2.5Σ+0.7σ) were calculated and the correlations between margins and various patient characteristics and prostate locations were investigated. RESULTS: A total of 307 patients were included, representing 11,726 localisations resulting in 70,356 shifts. The man skin-prostate setup inaccuracy was 0.8 ± 5.4mm in AP, 1.3 ± 4.8mm for CC, and 0.1 ± 5.6mm in LL direction. The man bone-prostate setup inaccuracy was 0.4 ± 3.3mm in AP, 0.1 ± 2.5mm for CC, and 0.1 ± 1.4mm in LL direction. According to van Herk equation, clinical target volume (CTV)-planning target volume (PTV) margins of 11.4, 10.6, and 11.8 mm (AP, CC, and LL, respectively) would be required for setup using skin markers and margins of 7.0, 4.7, and 2.1mm would be necessary for setup using bone structures. The average rectal area < 11cm(2) and volume of bladder > 300 cm(3) were associated with smaller CTV-PTV margins for setup using bone structures. The largest margins (15.8 mm in LL direction) were needed in patients with body mass index (BMI) > 35 using skin markers. CONCLUSIONS: Our results confirm that the commonly used CTV-PTV margins are inadequate.

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer.

PURPOSE: The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: A total of 553 patients with prostate cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. RESULTS: The 5-year risk of grade 2-4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2-4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. CONCLUSION: Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity.

Radiotherapy equipment and departments in the European countries: final results from the ESTRO-HERO survey.

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).

Searching for an appropriate image-guided radiotherapy method in prostate cancer--implications for safety margin.

AIMS AND BACKGROUND: The aim of the study was to compare the safety margin width using skin marks, pelvic skeleton-based targeting and adaptive protocol combining cone-beam computed tomography and kilovoltage image matching. METHODS: A total of 434 consecutive patients were treated by image-guided radiotherapy from November 2008 to April 2012. An adaptive protocol combining cone-beam computed tomography and kilovoltage image matching with individualized safety margin calculation according to the Van Herk method was used in a total of 201 patients. The remaining 233 patients had their setup corrected using cone-beam computed tomography daily. RESULTS: Analysis of the 3,137 cone-beam computed tomography images (201 patients) revealed that the margins between the clinical target volume and planning target volume with skin marks registration should be 1.24 cm in the anteroposterior, 0.98 cm in the craniocaudal, and 1.03 cm in the laterolateral direction. Considering pelvic skeleton-based setup, values of the clinical target volume and planning target volume margins in the anteroposterior, craniocaudal and laterolateral axis were 0.79 cm, 0.41 cm, and 0.19 cm, respectively. In a group of 8,872 cone-beam computed tomography images (233 patients) using CBCT assessment, the calculated margins between clinical target volume and planning target volume with skin marks were 1.15 cm in anteroposterior, 1.06 in craniocaudal, and 1.19 in laterolateral directions. Considering the pelvic skeleton-based setup, the corresponding values were 0.74 cm, 0.51 cm, and 0.25 cm. With the adaptive technique, the margins of most patients in the anteroposterior, craniocaudal, and laterolateral axes were 6 mm, 6 mm, and 6 mm or 8 mm, 6 mm, and 6 mm, respectively. CONCLUSIONS: The adaptive protocol combining cone-beam computed tomography and kilovoltage image matching or daily cone-beam computed tomography allowed us to substantially reduce the safety margins compared with skin marks targeting.

Prognostic significance of human papillomavirus (HPV) status and expression of selected markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki67/MIB-1) on outcome after (chemo-) radiotherapy in patients with squamous cell carcinoma of uterine cervix.

The aim of the retrospective study was to evaluate prognostic significance of human papillomavirus (HPV) status and expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2/neu), vascular endothelial growth factor (VEGF), CD34 antigen, tumor suppressors p63 and p53, and Ki67/MIB-1 in squamous cell carcinoma of the uterine cervix (SCCC) treated with radiotherapy or chemoradiotherapy. Seventy-two consecutive patients with SCCC, diagnosed and treated with (chemo-) radiotherapy with a curative intent at the University Hospital Hradec Kralove between August 1998 and August 2008, were enrolled in the study. The median follow-up period was 57 months (range 5-152). The tested biological factors were evaluated by polymerase chain reaction (HPV status) and by immunohistochemistry (remaining above mentioned markers) from archival paraffin embedded original diagnostic tumor samples. A statistical significant correlation was observed between low expression of p63 and poor overall survival (p = 0.001), although the complete response probability was influenced with borderline statistical significance (p = 0.05). However, the results could be affected by the statistical error due to the small number of p63 negative patients. HPV positivity and EGFR staining intensity was associated with higher complete response probability (p = 0.038 and p = 0.044, resp.). All other results were not significant. Neither HPV positivity nor EGFR staining intensity were reflected in the overall survival evaluation. In conclusion, the presented study did not confirm any apparently significant association of the suggested markers with prognosis of SCCC in patients treated with (chemo-) radiotherapy.

Statistical analysis of dose-volume profiles and its implication for radiation therapy planning in prostate carcinoma.

PURPOSE: The study aimed to analyze the dose-volume profiles of 3-dimensional radiation therapy (3D-CRT) and intensity modulated RT (IMRT) in the treatment of prostate carcinoma and to specify the profiles responsible for the development of gastrointestinal (GI) toxicity. METHODS AND MATERIALS: In the period 1997 to 2007, 483 patients with prostate carcinoma in stage T1-3 N0 (pN0) M0 were treated with definitive RT. Two groups of patients were defined for the analysis: the 3D-CRT group (n=305 patients) and the IMRT group (n=178 patients). In the entire cohort of 483 patients, the median follow-up time reached 4.4 years (range, 2.0-11.7 years). The cumulative absolute and relative volumes of irradiated rectum exposed to a given dose (area under the dose-volume curve, AUC) were estimated. The receiver operating characteristic analysis was then used to search for the optimal dose and volume cutoff points with the potential to distinguish patients with enhanced or escalated toxicity. RESULTS: Despite the application of high doses (78-82 Gy) in the IMRT group, GI toxicity was lower in that group than in the group treated by 3D-CRT with prescribed doses of 70 to 74 Gy. Both RT methods showed specific rectal dose-volume distribution curves. The total AUC values for IMRT were significantly lower than those for 3D-CRT. Furthermore, IMRT significantly decreased the rectal volume receiving low to intermediate radiation doses in comparison with 3D-CRT; specific cutoff limits predictable for the level of GI toxicity are presented and defined in our work. CONCLUSIONS: Total area under the dose-volume profiles and specific cutoff points in low and intermediate dose levels have significant predictive potential toward the RT GI toxicity. In treatment planning, it seems that it is valuable to take into consideration the entire dose-volume primary distribution.

MRI-based preplanning using CT and MRI data fusion in patients with cervical cancer treated with 3D-based brachytherapy: feasibility and accuracy study.

PURPOSE: Magnetic resonance imaging (MRI)-assisted radiation treatment planning enables enhanced target contouring. The purpose of this study is to analyze the feasibility and accuracy of computed tomography (CT) and MRI data fusion for MRI-based treatment planning in an institution where an MRI scanner is not available in the radiotherapy department. METHODS AND MATERIALS: The registration inaccuracy of applicators and soft tissue was assessed in 42 applications with CT/MRI data fusion. The absolute positional difference of the center of the applicators was measured in four different planes from the top of the tandem to the cervix. Any inaccuracy of registration of soft tissue in relation to the position of applicators was determined and dose-volume parameters for MRI preplans and for CT/MRI fusion plans with or without target and organs at risk (OAR) adaptation were evaluated. RESULTS: We performed 6,132 measurements in 42 CT/MRI image fusions. Median absolute difference of the center of tandem on CT and MRI was 1.1 mm. Median distance between the center of the right ovoid on CT and MRI was 1.7 and 1.9 mm in the laterolateral and anteroposterior direction, respectively. Corresponding values for the left ovoid were 1.6 and 1.8 mm. Rotation of applicators was 3.1°. Median absolute difference in position of applicators in relation to soft tissue was 1.93, 1.50, 1.05, and 0.84 mm in the respective transverse planes, and 1.17, 1.28, 1.27, and 1.17 mm in selected angular directions. The dosimetric parameters for organs at risk on CT/MRI fusion plans without OAR adaptation were significantly impaired whereas the target coverage was not influenced. Planning without target adaptation led to overdosing of the target volume, especially high-risk clinical target volume--D90 88.2 vs. 83.1 (p < 0.05). CONCLUSIONS: MRI-based preplanning with consecutive CT/MRI data fusion can be safe and feasible, with an acceptable inaccuracy of soft tissue registration.

Magnetic resonance imaging in postprostatectomy radiotherapy planning.

PURPOSE: To investigate whether the use of magnetic resonance imaging (MRI) in prostate bed treatment planning could influence definition of the clinical target volume (CTV) and organs at risk. METHODS AND MATERIALS: A total of 21 consecutive patients referred for prostate bed radiotherapy were included in the present retrospective study. The CTV was delineated according to the European Organization for Research and Treatment of Cancer recommendations on computed tomography (CT) and T(1)-weighted (T(1)w) and T(2)-weighted (T(2)w) MRI. The CTV magnitude, agreement, and spatial differences were evaluated on the planning CT scan after registration with the MRI scans. RESULTS: The CTV was significantly reduced on the T(1)w and T(2)w MRI scans (13% and 9%, respectively) compared with the CT scans. The urinary bladder was drawn smaller on the CT scans and the rectum was smaller on the MRI scans. On T(1)w MRI, the rectum and urinary bladder were delineated larger than on T(2)w MRI. Minimal agreement was observed between the CT and T(2)w images. The main spatial differences were measured in the superior and superolateral directions in which the CTV on the MRI scans was 1.8-2.9 mm smaller. In the posterior and inferior border, no difference was seen between the CT and T(1)w MRI scans. On the T(2)w MRI scans, the CTV was larger in these directions (by 1.3 and 1.7 mm, respectively). CONCLUSIONS: The use of MRI in postprostatectomy radiotherapy planning resulted in a reduction of the CTV. The main differences were found in the superior part of the prostate bed. We believe T(2)w MRI enables more precise definition of prostate bed CTV than conventional planning CT.

Accumulation of DNA damage and cell death after fractionated irradiation.

The purpose of this work was to determine how fractionated radiation used in the treatment of tumors affects the ability of cancer as well as normal cells to repair induced DNA double-strand breaks (DSBs) and how cells that have lost this ability die. Lymphocytic leukemia cells (MOLT4) were used as an experimental model, and the results were compared to those for normal cell types. The results show that cancer and normal cells were mostly unable to repair all DSBs before the next radiation dose induced new DNA damage. Accumulation of DSBs was observed in normal human fibroblasts and healthy lymphocytes irradiated in vitro after the second radiation dose. The lymphocytic leukemia cells irradiated with 4 × 1 Gy and a single dose of 4 Gy had very similar survival; however, there was a big difference between human fibroblasts irradiated with 4 × 1.5 Gy and a single dose of 6 Gy. These results suggest that exponentially growing lymphocytic leukemia cells, similar to rapidly proliferating tumors, are not very sensitive to fraction size, in contrast to the more slowly growing fibroblasts and most late-responding (radiation therapy dose-limiting) normal tissues, which have a low proliferation index.

Radical prostatectomy in high-grade prostate cancer, salvage and adjuvant radiotherapy.

INTRODUCTION: Prostate cancer with a Gleason score (GS) of 8-10 is linked to a higher risk of recurrence and progression. The aim of this paper is to evaluate treatment results of our high-risk patient cohort. PATIENTS AND METHODS: The cohort of 42 patients with radical prostatectomy (RP) specimen histology GS 8-10 was assessed. The patients were followed up after RP and radiotherapy (RT) was delivered in case of a biochemical relapse. Adjuvant radiotherapy (aRT) was delivered only in case of a positive surgical margin (PSM). The following parameters were evaluated: biochemical progression-free survival (BPFS), overall survival (OS) and cancer-specific survival (CSS). The second objective was to evaluate adverse effects of RP and RT. RESULTS: The median follow-up time was 88 months (18-168). RP led to BPFS in 16 patients (38%). Five patients with PSM underwent aRT and 20 underwent salvage radiotherapy (sRT). One patient died of myocardial infarction and 1 patient died of metastatic disease. Skeletal metastases were recorded in 2 patients. The BPFS in RP combinations with sRT or aRT was reached in 29 patients (69%). The OS and CSS in our cohort reached 95 and 98%, respectively. CONCLUSION: Management with aRT only in PSM was very effective, according to our retrospective study.

Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer: impact of previous surgery for benign prostatic hyperplasia.

OBJECTIVES: To retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n = 228) and IMRT (n = 112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. RESULTS: There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade >or=2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P = 0.01). CONCLUSIONS: Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity.

Dose escalation in prostate radiotherapy up to 82 Gy using simultaneous integrated boost: direct comparison of acute and late toxicity with 3D-CRT 74 Gy and IMRT 78 Gy.

PURPOSE: To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radiotherapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82). PATIENTS AND METHODS: 94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale. RESULTS: Acute gastrointestinal toxicity >or= grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity >or= grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32) CONCLUSION: SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.

Bisphosphonates for bone metastatic disease from breast cancer: clinical practice in the Czech Republic.

BACKGROUND: The use of bisphosphonates (BPs) represents a standard therapy of bone metastatic disease from breast cancer and has been incorporated in many systemic international guidelines. We have tried to evaluate the use of BPs in current clinical practice across the Czech Republic. PARTICIPANTS AND METHODS: A covering letter, questionnaires and pre-paid envelopes were mailed to the head oncologists of 64 workplaces of Czech Oncology Society. Total 310 questionnaires were sent out. The questionnaire consisted of 23 questions. RESULTS: The questionnaires were completed and returned by 91 oncologists from 32 workplaces. Most of the responding oncologists worked at university hospitals (42%), the most frequent length of work experience was 5 to 10 years (30%) and the most frequent rate of breast cancer patients was from 10 to 25% (45%). Ninety-five percent of the oncologists regularly initiated BP therapy, and oral clodronate was the first choice BP (77%). Once initiated, the treatment was discontinued in less than 5% patients (24%). Seventy-one (79%) oncologists stated that the most important reason leading to therapy termination was impairment of performance status. CONCLUSIONS: The consensual agreement pointed out that it could be a fundamental step towards establishing the national treatment guidelines for the BP use in metastatic breast cancer patients.

The technique of intensity-modulated radiotherapy in the treatment of cholangiocarcinoma.

AIMS AND BACKGROUND: Conventional radiotherapy in inoperable cholangiocarcinoma is limited by radiotolerance of the surrounding tissues. The aim of our dosimetric study was an evaluation of intensity-modulated radiotherapy in the treatment of inoperable bile duct carcinoma. METHODS: Four patients with inoperable cholangiocarcinoma treated by self-expandable stent placed to the biliary tree and radiotherapy were studied. The rotational technique, conformal 3D BOX technique and intensity-modulated radiotherapy plan were compared. Dose volume histograms and the normal tissue complication probability concept were used for comparison. The stent was used for target motion verification. RESULTS: The intensity-modulated radiotherapy plans showed favorable dose distribution in planning target volume and remarkable sparing of organs at risk. CONCLUSIONS: The intensity-modulated radiotherapy technique in bile duct carcinomas deserves further research and clinical evaluation.