Dosimetric advantages for cardiac substructures in radiotherapy of esophageal cancer in deep-inspiration breath hold.

BACKGROUND: Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. MATERIALS AND METHODS: In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. RESULTS: There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. CONCLUSION: Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy : A retrospective study.

PURPOSE: Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. METHODS: In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. RESULTS: SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2­Gy fractions with α/ß 10 Gy (EQD2α/ß10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/ß3-8 dose to the liver (12.8-12.6) with a 10% likelihood of ncRILD. CONCLUSION: SBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61-73.1 Gy, coupled with a mean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Combination of nivolumab with standard induction chemotherapy in children and adults with EBV-positive nasopharyngeal carcinoma : Protocol of a prospective multicenter phase 2 trial.

BACKGROUND: Treatment of Epstein-Barr virus(EBV)-positive nasopharyngeal carcinoma (NPC) with cisplatin/5-fluorouracil (5-FU) induction chemotherapy, followed by radiochemotherapy and subsequent interferon­ß, has yielded high survival rates in children, adolescents, and young adults. A previous study has shown that reduction of radiation dose from 59.4 to 54.0 Gy appears to be safe in patients with complete response (CR) to induction chemotherapy. As immune checkpoint-inhibitors have shown activity in NPC, we hypothesize that the addition of nivolumab to standard induction chemotherapy would increase the rate of complete tumor responses, thus allowing for a reduced radiation dose in a greater proportion of patients. METHODS: This is a prospective multicenter phase 2 clinical trial including pediatric and adult patients with their first diagnosis of EBV-positive NPC, scheduled to receive nivolumab in addition to standard induction chemotherapy. In cases of non-response to induction therapy (stable or progressive disease), and in patients with initial distant metastasis, treatment with nivolumab will be continued during radiochemotherapy. Primary endpoint is tumor response on magnetic resonance imaging (MRI) and positron emission tomography (PET) after three cycles of induction chemotherapy. Secondary endpoints are event-free (EFS) and overall survival (OS), safety, and correlation of tumor response with programmed cell death ligand 1 (PD-L1) expression. DISCUSSION: As cure rates in localized EBV-positive NPC today are high with standard multimodal treatment, the focus increasingly shifts toward prevention of late effects, the burden of which is exceptionally high, mainly due to intense radiotherapy. Furthermore, survival in patients with metastatic disease and resistant to conventional chemotherapy remains poor. Primary objective of this study is to investigate whether the addition of nivolumab to standard induction chemotherapy in children and adults with EBV-positive NPC is able to increase the rate of complete responses, thus enabling a reduction in radiation dose in more patients, but also offer patients with high risk of treatment failure the chance to benefit from the addition of nivolumab. TRIAL REGISTRATION: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) No. 2021-006477-32.

Stereotactic radiotherapy in the management of oligometastatic and recurrent head and neck cancer: a single-center experience.

INTRODUCTION: Oligometastatic disease (OMD) is a metastatic stage that could benefit maximally from local therapies. Patients in this state have a better prognosis relative to those with disseminated metastases. Stereotactic radiotherapy provides a non-invasive ablative tool for primary malignant tumors and metastases. MATERIALS AND METHODS: We searched our register for patients with oligometastatic or recurrent head and neck cancer (OMD/R-HNC) who received stereotactic radiotherapy to manage their OMD/R. We evaluated the survival outcomes and prognostic factors that affected the survival of those patients. RESULTS: In all, 31 patients with 48 lesions met the inclusion criteria for the analysis. The lesions comprised various metastatic sites, with the majority being pulmonary (37 lesions). Squamous cell cancer was the most common histology (26 patients). The median overall survival (mOS) was 33 months, with a progression-free survival (PFS) of 9.6 months. Eight patients received subsequent stereotactic radiotherapy after disease progression. The local control (LC) rates were 91.3, 87.7, and 83% at 6, 12, and 36 months. Patients with the de novo OMD who received stereotactic radiotherapy as their initial treatment had a median systemic treatment-free survival of 23.9 months. In univariate analysis, a trend for better OS was observed in patients with p16-positive squamous cell tumors; patients who progressed within 150 days after diagnosis had a significantly lower OS. De novo OMD showed significantly better PFS compared to induced OMD. Multivariate analyses identified p16-positive squamous cell cancer, metachronous OMD and a longer time to progression as positive predictors of OS, while de novo OMD was the only positive predictor for PFS. Treatment-related toxicities were generally mild, with two cases of grade 3 dysphagia reported. CONCLUSION: Stereotactic radiotherapy demonstrated favorable outcomes in patients with OMD/R-HNC with limited toxicities. Further studies are warranted to validate these findings and optimize treatment strategies for this patient population.

Molecular effects of photon irradiation and subsequent aftercare treatment with dexpanthenol-containing ointment or liquid in 3D models of human skin and non-keratinized oral mucosa.

This study aimed to investigate the molecular effects of radiation and subsequent aftercare treatment with dexpanthenol-containing ointment and liquid on established full-thickness 3D skin models depicting acute radiodermatitis and mucositis. To mimic radiomucositis and radiodermatitis, non-keratinized mucous membrane and normal human skin models were irradiated with 5 Gray. Afterwards, models were treated topically every second day with dexpanthenol-containing ointment or liquid in comparison with placebo and untreated controls. On day 7 after irradiation, histological examination showed impairments in irradiated models. In contrast, models treated with dexpanthenol-containing ointment or liquid showed a completely restored epidermal part. While gene expression profiling revealed an induction of genes related to a pro-inflammatory milieu, oxidative stress and an impaired epidermal differentiation after irradiation of the models, aftercare treatment with dexpanthenol-containing ointment or liquid revealed anti-oxidative and anti-inflammatory effects and had a positive effect on epidermal differentiation and structures important for physical and antimicrobial barrier function. Our findings confirm the potential of our established models as in vitro tools for the replacement of pharmacological in vivo studies regarding radiation-induced skin injuries and give indications of the positive effects of dexpanthenol-containing externals after radiation treatments as part of supportive tumor treatment.

Quality of life more than 10 years after radiotherapy for localized prostate cancer-impact of time after treatment and prescription dose.

PURPOSE: Analysis of quality of life changes after radiotherapy with focus on the impact of time after treatment and prescription dose. METHODS: Consecutive patients were treated with doses from 70.2/1.8 Gy (n = 206) to 72/1.8-2.0 Gy (n = 176) in a single centre and surveyed using the Expanded Prostate Cancer Index Composite questionnaire. RESULTS: Urinary and bowel bother scores decreased 1 / 3 / 6 points and 7 / 7 / 9 points on average 1 / 5 / 10 years after RT in comparison to baseline scores. The rate of urinary (need of pads in 8% vs. 15% before vs. 10 years after RT; p = 0.01) and bowel (uncontrolled leakage of stool in 5% vs. 12% before vs. 10 years after RT; p < 0.01) incontinence, as well as rectal bleeding (4% vs. 8% before vs. 10 years after RT; p = 0.05) increased. Sexual function scores decreased (erections sufficient for intercourse in 36% vs. 12% before vs. 10 years after RT; p < 0.01). A higher dose had a statistically significant impact on urinary bother and stool incontinence, but also tended to decrease urinary continence. Age and comorbidities did not have an influence on score changes, but on baseline urinary function/bother and baseline sexual function. CONCLUSION: Apart from an increasing rate of erectile dysfunction, urinary and bowel incontinence rates increased with increasing follow-up period. A higher dose was found to be associated with increased urinary problems and larger stool incontinence rates. Age and comorbidities were found to be relevant for baseline scores, but not for score changes.

Prediction of survival outcomes following postoperative radiotherapy after radical prostatectomy for prostate cancer.

Background: To evaluate predictive factors for survival outcomes after post-prostatectomy radiotherapy.Material and methods: In the years 2003-2008, 324 patients have received postoperative radiotherapy a median time of 14 months after radical prostatectomy. All patients have been treated up to 66.0-66.6 Gy in 1.8-2.0 Gy fractions. Predictive factors were analyzed at two stages, using a multivariable Cox regression analysis: (1) based on factors known before radiotherapy and (2) based on prostate-specific antigen response after radiotherapy.Results: Median follow-up after radiotherapy was 121 months. Prostate-specific antigen before radiotherapy, pN1 and Gleason score remained predictive factors for disease-free (hazard ratio, HR of 6.0, 2.3 and 2.5) and overall survival (HR of 2.8, 2.0 and 1.6) in multivariable analysis. Prostate-specific antigen levels increased despite radiotherapy in 27% of patients in the first six months. Failed response following salvage radiotherapy and prostate-specific antigen doubling time at the time of biochemical recurrence were predictive factors for disease-free (HR of 2.8 and 7.3; p < .01) and overall survival (HR of 2.2 and 2.6; p < .01).Conclusion: To reach the best survival outcomes following prostatectomy, salvage radiotherapy should be initiated early with low prostate-specific antigen levels, especially in patients with higher Gleason scores. Patients not responding to radiotherapy and/or patients with a short prostate-specific antigen doubling time after radiotherapy are candidates for early additional treatments.

Dosimetric and volumetric effects in clinical target volume and organs at risk during postprostatectomy radiotherapy.

PURPOSE: To assess the reproducibility of the dose-volume distribution of the initial simulation CT, generated using volumetric modulated arc therapy (VMAT) planning, during the radiotherapy of the prostatic bed based on weekly cone beam CTs (CBCT). METHODS: Twenty-three patients, after radical prostatectomy were treated with adjuvant or salvage radiotherapy between July and December 2016 and considered for this evaluation. Weekly CBCT scans (n = 138) were imported into the treatment planning system, and the clinical tumor volume (CTV), the rectum and the bladder were contoured. The initially calculated dose distribution and the dose-volume histograms generated from weekly CBCTs were compared. The prostatic fossa dose coverage was assessed by the proportion of the CTV fully encompassed by the 95% and 98% isodose lines. Rectal and bladder volumes receiving 50, 60 and 65 Gy during the treatment were compared to the initial plan, with statistical significance determined using the one-sample t­test. RESULTS: Marked variations in the total organ volume of the rectum and the bladder were observed. The correlation between rectum volume and V50 was not significant (p = 0.487), while the bladder volume and V50 demonstrated a significant correlation. There was no correlation between urinary bladder volume and CTV. The change in rectal volume correlated significantly with CTV. The dose coverage (D98% and D95%) to the prostatic bed could be achieved for all patients due to the ventral shift in the volume differences of the rectum. CONCLUSION: Weekly CBCTs can be considered as adequate verification tools to assess the interfractional variability of the CTV and organs at risk. The proven volume changes in the urinary bladder and the rectum do not compromise the final delivered dose in the CTV.

Intensity-modulated radiotherapy of prostate cancer with simultaneous integrated boost after molecular imaging with 18F-choline-PET/CT : Clinical results and quality of life.

PURPOSE: To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB. METHODS: A total of 134 patients underwent intensity-modulated radiotherapy from 2007-2010. All patients received a total dose of 76 Gy with 2 Gy fractions to the prostate; 67 patients received an additional SIB of 80 Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire. RESULTS: Baseline characteristics were similar in both groups (prostate-specific antigen 11 ng/ml vs. 8 ng/ml, p = 0.20, Gleason score <6 in 36% vs. 46%, p = 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5-6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p = 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p = 0.17). CONCLUSIONS: The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group.

Hydrogel injection reduces rectal toxicity after radiotherapy for localized prostate cancer.

PURPOSE: Injection of a hydrogel spacer before prostate cancer radiotherapy (RT) is known to reduce the dose to the rectal wall. Clinical results from the patient's perspective are needed to better assess a possible benefit. METHODS: A group of 167 consecutive patients who received prostate RT during the years 2010 to 2013 with 2­Gy fractions up to 76 Gy (without hydrogel, n = 66) or 76-80 Gy (with hydrogel, n = 101) were included. The numbers of interventions resulting from bowel problems during the first 2 years after RT were compared. Patients were surveyed prospectively before RT, at the last day of RT, and at a median of 2 and 17 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). RESULTS: Baseline patient characteristics were well balanced. Treatment for bowel symptoms (0 vs. 11 %; p < 0.01) and endoscopic examinations (3 vs. 19 %; p < 0.01) were performed less frequently with a spacer. Mean bowel function scores did not change for patients with a spacer in contrast to patients without a spacer (mean decrease of 5 points) >1 year after RT in comparison to baseline, with 0 vs. 12 % reporting a new moderate/big problem with passing stools (p < 0.01). Statistically significant differences were found for the items "loose stools", "bloody stools", "painful bowel movements" and "frequency of bowel movements". CONCLUSION: Spacer injection is associated with a significant benefit for patients after prostate cancer RT.

Usefulness of a thermoplastic breast bra for breast cancer radiotherapy : A prospective analysis.

BACKGROUND: Despite modern techniques, in some patients receiving whole breast radiotherapy (WBI) parts of the heart and the lung might receive doses which are nowadays considered relevant for the development of late morbidity. Our aim was to analyze the usefulness of a thermoplastic breast brassiere to reduce lung and heart doses. PATIENTS AND METHODS: A total of 29 patients with left-sided and 16 patients with right-sided breast cancer treated with breast conserving surgery and WBI between 2012 and 2013 were included in a prospective study analyzing the effectiveness of a thermoplastic breast bra. WBI was performed using 3D tangential fields up to 50.4 Gy. Treatment planning was performed with and without bra. Several dosimetrical parameters were analyzed comparatively focusing on the heart and ipsilateral lung. For heart dose comparisons, subvolumes like the left anterior descending artery (LAD) and a defined apical region, so-called "apical myocardial territory" (AMT), were defined. RESULTS: By using the bra, the mean lung dose was reduced by 30.6 % (left-sided cancer) and 29.5 % (right-sided; p < 0.001). The V20Gy for the left lung was reduced by 39.5 % (4.9 vs. 8.1 % of volume; p < 0.001). The mean and maximum heart doses were significantly lower (1.6 vs. 2.1 Gy and 30.7 vs. 39.3 Gy; p = 0.01 and p < 0.001), which also applies to the mean and maximum dose for the AMT (2.5 vs. 4.4 Gy and 31.0 vs. 47.2 Gy; p < 0.01 and p < 0.001). The mean and maximum dose for LAD was lower without reaching significance. No acute skin toxicities > grade 2 were observed. CONCLUSION: By using a thermoplastic breast bra, radiation doses to the heart and especially parts of the heart apex and ipsilateral lung can be significantly lowered without additional skin toxicity.

Prediction of radiation-induced toxicity by in vitro radiosensitivity of lymphocytes in prostate cancer patients.

AIM: To identify predictive assays for radiation-induced toxicity in prostate cancer patients. PATIENTS & METHODS: Patients have been surveyed prospectively before and up to 16 months after radiotherapy using a validated questionnaire. Subgroups of 25 patients with minor and larger score changes, respectively, were selected for γ-H2AX, G2 and Annexin V assays. RESULTS: A significantly higher spontaneous chromatid aberration yield (HR: 1.46 [95% CI: 1.02-2.09]; p = 0.04), higher levels of early apoptotic (HR: 1.12 [95% CI: 1.01-1.24]; p = 0.04) and late apoptotic and necrotic (HR: 1.10 [95% CI: 0.99-1.23]; p = 0.08) lymphocytes 24 h post-irradiation were found in patients with a bowel bother score decrease greater than 20 points more than 1 year after treatment. CONCLUSION: Chromatid aberration and apoptosis/necrosis assays appear to be suitable for the prediction of radiation-induced toxicity.

Application of a hydrogel spacer for postoperative salvage radiotherapy of prostate cancer.

BACKGROUND: In contrast to primary radiotherapy, no reports are available for a hydrogel spacer application in postoperative salvage radiotherapy for prostate cancer. CASE REPORT: A 77-year-old patient presented 20 years after radical prostatectomy with a digitally palpable local recurrence at the urethrovesical anastomosis (PSA 5.5 ng/ml). The hydrogel spacer (10 ml, SpaceOAR™) was injected between the local recurrence and rectal wall under transrectal ultrasound guidance. Treatment planning was performed with an intensity-modulated technique up to a total dose of 76 Gy in 2-Gy fractions. The same planning was performed based on computed tomography before spacer injection for comparison. RESULTS: The local recurrence, initially directly on the rectal wall, could be displaced more than 1 cm from the rectal wall after hydrogel injection. With a mean total dose of 76 Gy to the planning target volume, rectal wall volumes included in the 70 Gy, 60 Gy, 50 Gy isodoses were 0 cm(3), 0 cm(3), and 0.4 cm(3) with a spacer and 2.9 cm(3), 4.5 cm(3), and 6.2 cm(3) without a spacer, respectively. The patient reported rectal urgency during radiotherapy, completely resolving after the end of treatment. The PSA level was 5.4 ng/ml a week before the end of radiotherapy and dropped to 0.9 ng/ml 5 months after radiotherapy. CONCLUSION: A hydrogel spacer was successfully applied for dose-escalated radiotherapy in a patient with macroscopic local prostate cancer recurrence at the urethrovesical anastomosis to decrease the dose at the rectal wall. This option can be considered in specifically selected patients.

Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity.

BACKGROUND: The primary objective of the study was to identify early hematologic changes predictive for radiotherapy (RT)-associated genitourinary and gastrointestinal toxicity. METHODS: In a group of 91 prostate cancer patients presenting for primary (n = 51) or postoperative (n = 40) curative RT, blood samples (blood count, acute phase proteins, and cytokines) were analyzed before (T1), three times during (T2-T4), and 6-8 weeks after (T5) radiotherapy. Before RT (baseline), on the last day (acute toxicity), a median of 2 months and 16 months (late toxicity) after RT, patients responded to a validated questionnaire (Expanded Prostate Cancer Index Composite). Acute score changes > 20 points and late changes > 10 points were considered clinically relevant. RESULTS: Radiotherapy resulted in significant changes of hematologic parameters, with the largest effect on lymphocytes (mean decrease of 31-45 %) and significant dependence on target volume. C-reactive protein (CRP) elevation > 5 mg/l and hemoglobin level decrease ≥ 5 G/1 at T2 were found to be independently predictive for acute urinary toxicity (p < 0.01, respectively). CRP elevation was predominantly detected in primary prostate RT (p = 0.02). Early lymphocyte level elevation ≥ 0.3G/l at T2 was protective against late urinary and bowel toxicity (p = 0.02, respectively). Other significant predictive factors for late bowel toxicity were decreasing hemoglobin levels (cut-off ≥ 5 G/l) at T2 (p = 0.04); changes of TNF-α (tumor necrosis factor; p = 0.03) and ferritin levels (p = 0.02) at T5. All patients with late bowel toxicity had interleukin (IL)-6 levels < 1.5 ng/l at T2 (63 % without; p = 0.01). CONCLUSION: Early hematologic changes during prostate cancer radiotherapy are predictive for late urinary and bowel toxicity.

Hematologic changes during prostate cancer radiation therapy are dependent on the treatment volume.

AIM: To assess hematologic changes of modern prostate radiation therapy (RT) comparing different target volumes. PATIENTS & METHODS: Blood samples were evaluated before (T1), during (T2-T4) and 6-8 weeks after (T5) RT in a group of 113 patients. Whole-pelvic RT up to 46 Gy was applied in 27 cases. The total dose to the prostatic fossa (n = 46)/prostate (n = 67) was 66/76 Gy. RESULTS: Erythrocyte, leukocyte and platelet levels decreased significantly relative to baseline levels at T2-T5. Neoadjuvant hormonal therapy had an impact on hemoglobin levels before and during RT. The cumulative incidence of grade 2 leukopenia was 15 versus 2% (p = 0.02) and grade 2 anemia 8 versus 0% (p = 0.03) with versus without whole-pelvic RT, respectively. Lymphocyte decrease was larger at times T2-T5 (36 vs 3% grade 3 toxicity; p < 0.01). CONCLUSION: Prostate RT has a small but significant and longer effect on the blood count. Lower lymphocyte levels need to be considered when larger volumes are treated.

Transurethral resection of the prostate after radiotherapy for prostate cancer: impact on quality of life.

OBJECTIVES: To evaluate the impact of transurethral resection of the prostate on quality of life after radiotherapy for prostate cancer. METHODS: A group of 49 consecutive patients with and 487 without prior transurethral resection of the prostate responded to the Expanded Prostate Cancer Index Composite questionnaire before, on the last day, and a median time of 2 months and 16 months after external beam radiotherapy (70-78 Gy). A matched-pair analysis was used to avoid the influence of treatment-associated confounding factors, including dose, treatment volume and hormonal therapy. RESULTS: Significantly smaller acute urinary score changes relative to baseline levels resulted with versus without prior transurethral resection of the prostate (mean function/bother score decrease of 3/6 vs 18/21 points at the end of radiotherapy; P < 0.01), affecting urinary incontinence (pads to control urinary leakage in 4% vs 24%; P = 0.03) and irritative/obstructive symptoms (big/moderate problem with weak urinary stream in 11% vs 37%; P = 0.02). As opposed to acute changes, transurethral resection of the prostate was a significant predisposing factor for a long-term urinary function score decrease >10 points (20% vs 6% of patients with vs without prior resection; P = 0.04). Urinary incontinence risk was higher for patients with a longer time from resection to radiotherapy. CONCLUSIONS: Transurethral resection of the prostate significantly affects acute (considerably fewer symptoms) and long-term (relevant toxicity in some cases) urinary quality of life after radiotherapy for prostate cancer.

Monitoring of radiochemotherapy in patients with glioblastoma using O-(2-¹8Fluoroethyl)-L-tyrosine positron emission tomography: is dynamic imaging helpful?

Monitoring of radiochemotherapy (RCX) in patients with glioblastoma is difficult because unspecific alterations in magnetic resonance imaging with contrast enhancement can mimic tumor progression. Changes in tumor to brain ratios (TBRs) in positron emission tomography (PET) using O-(2-¹8fluoroethyl)-l-tyrosine (¹8F-FET) after RCX with temozolomide of patients with glioblastoma have been shown to be valuable parameters to predict survival. The kinetic behavior of ¹8F-FET in the tumors is another promising parameter to analyze tumor metabolism. In this study, we investigated the predictive value of dynamic ¹8F-FET PET during RCX of glioblastoma. Time-activity curves (TACs) of ¹8F-FET uptake of 25 patients with glioblastoma were evaluated after surgery (FET-1), early (7-10 days) after completion of RCX (FET-2), and 6 to 8 weeks later (FET-3). Changes in the time to peak (TTP) and the slope of the TAC (10-50 minutes postinjection) were analyzed and related to survival. Changes in kinetic parameters of ¹8F-FET uptake after RCX showed no relationship with survival time. In contrast, the high predictive value of changes of TBR to predict survival was confirmed. We conclude that dynamic ¹8F-FET PET does not provide additional prognostic information during RCX. Static ¹8F-FET PET imaging (20-40 minutes postinjection) appears to be sufficient for this purpose and reduces costs.

Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma.

BACKGROUND: Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels. METHODS: We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4). The primary end point was freedom from treatment failure; secondary end points included efficacy and toxicity of treatment. RESULTS: The two chemotherapy regimens did not differ significantly with respect to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5 years, the rates of freedom from treatment failure were 93.0% (95% confidence interval [CI], 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI, 88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy doses of radiation therapy were compared, there were also no significant differences in freedom from treatment failure (P=1.00) or overall survival (P=0.61). Adverse events and acute toxic effects of treatment were most common in the patients who received four cycles of ABVD and 30 Gy of radiation therapy (group 1). CONCLUSIONS: In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed. (Funded by the Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number, NCT00265018.)

Persisting ring chromosomes detected by mFISH in lymphocytes of a cancer patient-a case report.

We report the case of an 84 years old prostate cancer patient with severe side effects after radiotherapy in 2006. He was cytogenetically analysed in 2009 and in 2012 in a comparative study for individual radiosensitivity of prostate cancer patients. No other patient had clonal aberrations, but this patient showed ring chromosomes in the range of 21-25% of lymphocytes. He received 5 cycles of 5-fluorouracil/folic acid for chemotherapy of sigmoid colon carcinoma in 2003, three years before radiotherapy of prostate cancer. Blood samples were irradiated ex vivo with Cs-137 γ-rays (0.7Gy/min) in the G0-phase of the cell cycle. 100 FISH painted metaphases were analysed for the control and the irradiated samples each. Multicolour in situ hybridisation techniques like mFISH and mBand as well as MYC locus, telomere and centromere painting probes were used to characterise ring metaphases. Metaphase search and autocapture was performed with a Zeiss Axioplan 2 imaging microscope followed by scoring and image analysis using Metafer 4/ISIS software (MetaSystems). In 2009 chromosome 8 rings were found in about 25% of lymphocytes. Rings were stable over time and increased to about 30% until 2012. The ring chromosome 8 always lacked telomere signals and a small amount of rings displayed up to four centromere signals. In aberrant metaphases 8pter and 8qter were either translocated or deleted. Further analyses revealed that the breakpoint at the p arm is localised at 8p21.2-22. The breakpoint at the q arm turned out to be distal from the MYC locus at 8q23-24. We hypothesise that the ring chromosome 8 has been developed during the 5 FU/folic acid treatments in 2003. The long term persistence might be due to clonal expansion of a damaged but viable hematopoietic stem cell giving rise to cycling progenitor cells that permit cell survival and proliferation.

Clinical validation of a semi-automated segmentation algorithm for target volume definition on planning CT and CBCT in stereotactic body radiotherapy (SBRT) for peripheral lung lesions.

INTRODUCTION: Stereotactic body radiotherapy (SBRT) is an ablative method for lung malignancies. Here, the definition of the gross target volume (GTV) is subject to interobserver variation. In this study, we aimed to evaluate the interobserver variability during SBRT and its dosimetric impact, as well as to introduce a semi-automated delineation tool for both planning computer tomography (P-CT) and cone beam CT (CBCT) to help to standardise GTV delineation and adaptive volume-change registration. METHODS: The interobserver variation of GTV manual contours from five physicians was analysed in 15 patients after lung SBRT on free breathing (FB) P-CT (n = 15) and CBCT (n = 90) before and after each fraction. The dosimetric impact from interobserver variations of GTV based on the original treatment plan was analysed. Next, the accuracy of an in-house easy-to-use semi-automated-segmentation algorithm for pulmonary lesions was compared with gold standard contours in FB P-CT and CBCT, as well as 4D P-CT of additional 10 patients. RESULTS: The interobserver variability in manual contours resulted in violations of dose coverage of the planning target volume (PTV), which, in turn, resulted in compromised tumour control probability in contours from four physicians. The validation of the semi-automated delineation algorithm using thorax phantom led to a highly reliable accuracy in defining GTVs. Comparing the unsupervised auto-contours with the gold standard delineation revealed high equal high concordance for FB P-CT, 4D P-CT and CBCT, with a DSC of 0.83, 0.76 and 0.8, respectively. The supervised use of the semi-automated delineation tool improved its accuracy, with DSCs of 0.86, 0.86 and 0.8 for FB P-CT, 4D P-CT and CBCT, respectively. The use of the algorithm was associated with a significantly shorter working time. The semi-automated delineation tool can accurately register volume changes in CBCTs. CONCLUSION: The segmentation algorithm provides a reliable, standardised and time-saving alternative for manual delineation in lung SBRT in P-CT and CBCT.