Single-center long-term follow-up after intraoperative radiotherapy as a boost during breast-conserving surgery using low-kilovoltage x-rays.

BACKGROUND: Intraoperative radiotherapy (IORT) during breast-conserving surgery as a boost followed by whole-breast radiotherapy is increasingly used. METHODS: Between February 2002 and December 2008, a total of 197 patients were treated with IORT as a boost (20 Gy, 50 kV x-rays; Intrabeam System, Carl Zeiss Surgical, Oberkochen, Germany) during breast-conserving surgery, followed by whole-breast radiotherapy (46-50 Gy). Systemic therapy was provided according to the St. Gallen consensus. Patients were recalled every 6-12 months for follow-up. Findings were scored according to the LENT-SOMA scale. RESULTS: Median age was 61.8 (range 30-84) years, and median follow-up was 37 (range 5-91) months. There were T1, T2, and Tx tumors in 129, 67, and 1 patients, respectively, and N0, N1, N2, and N3 disease in 144, 36, 15, and 2 patients, respectively. Until December 2009, 5 local invasive relapses, 1 local ductal carcinoma-in-situ, 1 axillary relapse, 6 secondary cancers, and 11 distant metastases were seen, resulting in a 5-year disease-free survival of 81.0% and an overall survival of 91.3%. Local relapse-free survival (invasive cancers) at 3 and 5 years was 97.0%. After a follow-up of 5 years (n =58), only 8 patients (13.8%) had chronic skin toxicities, and 2 patients (3.4%) had a marked increase in density (fibrosis III), while 62.0% had no/barely palpable fibrosis 0-I. Other toxicities observed included severe pain (n = 4, 6.9%), retraction (n =17, 29.3%), edema of the breast (n =1, 1.7%), and lymphedema in general (n =2, 3.4%). CONCLUSIONS: After IORT as a tumor bed boost with low-kilovoltage x-rays followed by whole-breast radiotherapy, low local recurrence and chronic toxicity rates were seen after 5-year follow-up.

Quality of Life and Decision Regret After Postoperative Radiation Therapy to the Prostatic Bed Region With or Without Elective Pelvic Nodal Radiation Therapy.

PURPOSE: To evaluate patient-reported health-related quality of life (HRQOL) and decision regret (DR surgery or DR radiation therapy) after radiation therapy to the prostatic bed (PBRT) with or without whole pelvic radiation therapy (WPRT). METHODS AND MATERIALS: Patients received 79.29 Gy (n = 78; R1/detectable tumors) or 71.43 Gy (n = 56; R0/undetectable tumors) equivalent dose in 2-Gy fractions (EQD-2). Out of 134 patients, 51 had received additional WPRT with 44 Gy. Decision regret was reported using a 5-item instrument (best/worst scores: 0-100); European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-PR25 questionnaires were used for HRQOL evaluation. RESULTS: At a median follow-up of 53 months, 134 valid questionnaires were returned. Most patients had locally advanced, node-positive (T3-4/N0 = 54.5%; N1 = 17.2%) or high-risk tumors (27.6%). Mean DR surgery was 17.61 and not associated with positive margins, salvage strategy, or radiation therapy regimen. Mean DR radiation therapy was 18.64 and better in patients who had PBRT compared with WPRT (P = .034; 24.39 vs. 15.24). Patient-reported bowel and urinary symptoms were worse after WPRT compared with PBRT (both P < .05); general HRQOL was numerically but not significantly better after PBRT without WPRT (P = .055). Subset analyses identified increased bowel and urinary symptom scores after WPRT irrespective of higher or lower dose cohorts (all P < .05). CONCLUSIONS: WPRT was associated with increased symptom burden and decision regret compared with PBRT. It is uncertain if the results can be extrapolated to lower-dose (<70 Gy) regimens. Further research is required to evaluate if specific decision support tools or treatment modifications according to the individual risk situation may be beneficial in this setting.

Postoperative elective pelvic nodal irradiation compared to prostate bed irradiation in locally advanced prostate cancer - a retrospective analysis of dose-escalated patients.

BACKGROUND: It is uncertain if whole-pelvic irradiation (WPRT) in addition to dose-escalated prostate bed irradiation (PBRT) improves biochemical progression-free survival (bPFS) after prostatectomy for locally advanced tumors. This study was initiated to analyze if WPRT is associated with bPFS in a patient cohort with dose-escalated (> 70 Gy) PBRT. METHODS: Patients with locally advanced, node-negative prostate carcinoma who had PBRT with or without WPRT after prostatectomy between 2009 and 2017 were retrospectively analyzed. A simultaneous integrated boost with equivalent-doses-in-2-Gy-fractions (EQD-2) of 79.29 Gy or 71.43 Gy to the prostate bed was applied in patients with margin-positive (or detectable) and margin-negative/undetectable tumors, respectively. WPRT (44 Gy) was offered to patients at an increased risk of lymph node metastases. RESULTS: Forty-three patients with PBRT/WPRT and 77 with PBRT-only were identified. Baseline imbalances included shorter surgery-radiotherapy intervals (S-RT-Intervals) and fewer resected lymph nodes in the WPRT group. WPRT was significantly associated with better bPFS in univariate (p = 0.032) and multivariate models (HR = 0.484, p = 0.015). Subgroup analysis indicated a benefit of WPRT (p = 0.029) in patients treated with rising PSA values who mostly had negative margins (74.1%); WPRT was not associated with a longer bPFS in the postoperative setting with almost exclusively positive margins (96.8%). CONCLUSION: We observed a longer bPFS after WPRT compared to PBRT in patients with locally advanced prostate carcinoma who underwent dose-escalated radiotherapy. In subset analyses, the association was only observed in patients with rising PSA values but not in patients with non-salvage postoperative radiotherapy for positive margins.

Long-term outcome after combined radiochemotherapy for anal cancer - retrospective analysis of efficacy, prognostic factors, and toxicity.

BACKGROUND: This retrospective study evaluated the efficacy, prognostic factors, and toxicity of combined radiochemotherapy for anal cancer. PATIENTS AND METHODS: Data of 90 patients treated with radiochemotherapy between 1990 and 2006 were analyzed. Mean follow-up was 30 months (range: 2-129 months). Endpoints were disease-specific survival, local control, freedom from metastasis, and colostomy-free survival. Tumor stage, nodal status, age, sex, tumor site, tumor resection, and radiation dose were analyzed for prognostic value. Acute toxicity was scored according to the RTOG/EORTC scale, late toxicity according to the LENT/ SOMA scale. RESULTS: Disease-specific survival was 86%, local control 79%, freedom from metastasis 92%, and colostomy-free survival 83%. Higher T category was associated with inferior prognosis for colostomy-free survival (p = 0.000), male sex for local control (p = 0.004) and diseasespecific survival (p = 0.002), and tumor site at the anal margin for local control (p = 0.03). 4 of 7 patients with recurrent anal margin tumors had human papillomavirus (HPV)-related disease. 49% of patients suffered from > or = grade 3 acute toxicity. 3 patients had late toxicity of grade 3 concerning sphincter control. CONCLUSION: Combined radiochemotherapy for anal cancer is a highly effective therapy with pronounced acute and minor late toxicity. In the case of higher T stage, male sex, and cancer at the anal margin, treatment intensification should be considered.

Hippocampal volume reduction and HPA-system activity in major depression.

Structural imaging studies investigating hippocampal volumes in patients suffering from major depression have yielded mixed results. Here, 24 unipolar depressed in-patients and 14 healthy controls carefully matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI). Saliva cortisol was measured at 0800 and 1600 h in patients during a one-week wash-out and the following 4 weeks. Hippocampal volumes were significantly reduced in the patient group even after adjusting for intracranial brain volume (ICV) and age. Across groups, age was significantly negatively correlated with uncorrected hippocampal volumes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to hippocampal volumes. However, there was a negative association between duration of the index episode before hospitalization and hippocampal volumes. Additionally, hippocampal volumes were significantly negatively correlated with duration of illness. Finally, we observed a trend for higher hippocampal volumes in those patients who showed a subsequent decrease in cortisol levels under pharmacotherapy.

MR spectroscopy in Alzheimer's disease: gender differences in probabilistic learning capacity.

Degenerative alterations of cortical and subcortical regions in Alzheimer disease (AD) can be estimated by the extent of brain metabolite changes as measured by magnetic resonance spectroscopic imaging (MRSI). A neuropsychological assessment may correlate with metabolite levels and could evaluate underlying degenerative processes. Probabilistic-related classification learning, which represents one form of procedural learning, is associated with the neostriatum. The present study was aimed at examining the correlation of spectroscopic imaging in subcortical regions with the evaluation of specific neuropsychological findings. Twenty-two patients with Alzheimer's disease were compared to 15 healthy elderly control subjects. Proton MRSI of the basal ganglia (BG) and thalamus region was performed for detection of N-acetylaspartate (NAA), trimethylamine (TMA) and creatine ((P)Cr). In addition, a probabilistic-related classification learning task (Weather Prediction Task (WT)) was applied. We observed that in patients a high TMA signal in the basal ganglia region was correlated with a poorer performance in the probabilistic learning task (Spearman rank order correlation (SROC)=-0.6, P<0.009). Although Alzheimer's patients, as a group, did not differ from controls with regard to probabilistic learning capacity (PLC), male AD patients, as compared to male controls, displayed an impairment in the task performance by 28% (P<0.03) and showed a 16% elevation in TMA signaling (P<0.04). The altered metabolite signals and ratios in combination with the cognitive performance might suggest gender-related neuronal degeneration and dysfunction within subcortical regions in AD.

Reduced rectal toxicity with ultrasound-based image guided radiotherapy using BAT (B-mode acquisition and targeting system) for prostate cancer.

PURPOSE: To evaluate the effect of image guided radiotherapy with stereotactic ultrasound BAT (B-mode acquisition and targeting system) on rectal toxicity in conformal radiotherapy of prostate cancer. PATIENTS AND METHODS: 42 sequential patients with prostate cancer undergoing radiotherapy before and after the introduction of BAT were included. Planning computed tomography (CT) was performed with empty rectum and moderately filled bladder. The planning target volume (PTV) included the prostate and seminal vesicles with a safety margin of 1.5 cm in anterior and lateral direction. In posterior direction the anterior 1/3 of the rectum circumference were included. Total dose was 66 Gy and a boost of 4 Gy excluding the seminal vesicles. 22 patients (BAT group) were treated with daily stereotactic ultrasound positioning, for the other 20 patients (NoBAT group) an EPID (electronic portal imaging device) was performed once a week. Acute and late genito-urinary (GU) and rectal toxicity and PSA values were evaluated after 1.5, 3, 6, 9 and 12 months. The total median follow up of toxicity was 3 years in the BAT group and 4 years in the NoBAT group. RESULTS: In the NoBAT group significant more rectal toxicity occurred, while in GU toxicity no difference was seen. Two patients in the NoBAT group showed late rectal toxicity grade 3, no toxicity>grade 2 occurred in the BAT group. There was no significant difference in PSA reduction between the groups. CONCLUSION: Without BAT significant more acute and a trend to more late rectal toxicity was found. With regard to dose escalation this aspect is currently evaluated with a larger number of patients using intensity-modulated radiotherapy (IMRT).