PSMA PET-based stereotactic body radiotherapy for locally recurrent prostate cancer after definitive first-line therapy.

BACKGROUND: Advances in prostate-specific membrane antigen (PSMA) PET-computed tomography (CT) and magnetic resonance imaging (MRI) allow the detection and localization of exclusively local prostate-cancer-recurrences after definitive first-line therapy. PSMA-based early detection of circumscribed local recurrences followed by hypofractionated high-precision stereotactic body radiotherapy (SBRT) might yield long-term disease control at moderate rates of adverse effects. METHODS: Retrospective analysis of 35 patients treated for locally recurrent prostate cancer between November 2012 and December 2021 with PSMA PET- and MRI-based robotic SBRT. RESULTS: Thirty-five patients treated with local prostate cancer recurrence post surgery, post surgery, and adjuvant/salvage radiotherapy (RT) and after definitive RT. All but one patients had fractionated SBRT in 3-5 fractions. Median progression-free survival (PFS) was 52.2 months for all patients and 52.2 months in the radical prostatectomy (RPE) group, 31.2 months in the RPE + RT group and not reached in the RT group. The most common event was increased urinary frequency grade 1-2. 54.3% of all patients had no acute and 79.4% no late toxicity during follow-up. DISCUSSION: Our PFS of 52.2 months (RPE), 31.2 months (RPE + RT) and not reached (RT) compares favorably with published data. This method constitutes a valid alternative to morbidity-prone invasive approaches or palliative systemic therapy.

Depression and anxiety in patients with uveal melanoma undergoing curative proton treatment-A prospective study.

OBJECTIVE: We prospectively addressed whether patient characteristics, oncological outcomes, or metastatic risk impacted depression and anxiety in patients undergoing curative proton treatment for uveal melanoma (UM). METHODS: We assessed patient-reported outcomes regarding anxiety (GAD-7) before and 2 years after proton therapy and depression (PHQ-9) before, 1, and 2 years after proton therapy. We performed descriptive statistics and used linear mixed effect modeling to analyze how the oncological outcome and baseline characteristics impacted anxiety and depression scores. RESULTS: Of 130 (65 female) patients included, six developed metastatic disease and three died during the 2-year follow-up. The mean anxiety declined from 5.86 (SE = 0.56) at baseline to 3.74 (SE = 0.46) at 2 years (ß = 2.11; SE = 0.6; p < .001). Depressive symptoms decreased moderately from 4.36 (SE = 0.37) at baseline to 3.67 (SE = 0.38) 2 years later. Patients with unfavorable metastatic risk or disease progression had elevated anxiety and depression scores. Although female patients reported overall higher anxiety scores, both sexes recovered substantially and to a similar extent during the 2-year follow-up (ß = 2.35; SE 0.87; p = .007 vs. ß = 1.88; SE = 0.60; p = .002). A trend for prolonged depressive symptoms was observed in patients living alone compared to patients living with family members 1 year after the treatment (M = 5.04 [SE = 0.85] vs. M = 3.73 [SE = 0.31], ß = 1.32; SE = 0.92; p = .152). Patients with high baseline anxiety levels showed initially more severe depressive symptoms, which improved significantly during follow-up (ß = 1.65; SE = 0.68; p = .017). CONCLUSION: Most patients undergoing proton therapy for UM experienced mild, transient depressive symptoms and anxiety. Patients with high pre-treatment anxiety, unfavorable prognoses, and patients living alone may be more vulnerable to prolonged depressive symptoms. To these patients a more tailored support could be offered at an early stage of the disease.

Postoperative Radiotherapy of Prostate Cancer: Adjuvant versus Early Salvage.

Results of three randomized clinical trials (RCTs) comparing adjuvant radiotherapy (ART) and early salvage radiotherapy (eSRT) of prostate carcinoma and a subsequent meta-analysis of the individual patient data from these RCTs were recently published. The results suggest that early eSRT is as effective and potentially less toxic than ART. Therefore, eSRT should be considered the standard of care. However, due to limitations in the RCTs, ART remains a valid treatment option in patients with the combination of high-risk features such as Gleason Score (GS) 8-10, positive surgical margins (R1) and pathological T-stage 3 or 4 (pT3/4). This article provides a critical appraisal of the RCTs and the rationale for recommendations adopted in the current national guidelines regarding patients with high-risk features after radical prostatectomy (RP): ART should be offered in case of pT3/pT4 and R1 and Gleason Score 8-10; ART can be offered in case of pT3/pT4 and R0 and Gleason Score 8-10 as well as in case of multifocal R1 (including pT2) and Gleason Score 8-10. In any case, the alternative treatment option of eSRT in case of rising PSA should be discussed with the patient.

Fear of prognosis? How anxiety, coping, and expected burden impact the decision to have cytogenetic assessment in uveal melanoma patients.

BACKGROUND: Cytogenetic testing (CGT) in uveal melanoma patients reveals prognostic information about the individual risk of developing distant metastasis with dismal prognosis. There is currently no medical intervention strategy with proven effect on the prognosis, rendering the result of the cytogenetic testing purely informative. We explored patients' socio-demographic backgrounds, psychological preconditions, coping strategies, external influences, and concerns about "knowing their fate" to study their possible interactions with decision-making for CGT. METHODS: Uveal melanoma patients were asked to complete questionnaires on their interest in undergoing CGT for prognostication and the factors influencing their decision. Data were collected on socio-demographics, baseline anxiety (GAD-7), depression (PHQ-9), coping strategies (Brief COPE), and assumed future concerns regarding the CGT result. Data were analyzed by using multiple ordinal logistic regression and exploring estimated marginal effects. RESULTS: Questionnaires were returned by 121 of 131 (92.4%) patients. Fifty-two patients (43%) had no interest in CGT, 34 (28.1%) were undecided, and 35 (28.9%) were interested. We observed no significant differences regarding age, sex, partnership, education, occupation, baseline anxiety, or depression. Decision-making favoring CGT was influenced by the treating physicians, internet resources, and level of baseline anxiety. Patients were likely to reject CGT when they worried that "knowing the result will have an unintended influence" on their life. CONCLUSION: Decision-making about CGT for prognostication in uveal melanoma is burdensome to many patients and in general not guided by medical advice regarding further treatment and screening procedures. The psychological impact of the decision is therefore unique and requires careful support by psycho-oncologists considering the patient's fears and expectations.

Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies.

BACKGROUND: Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen. METHODS: Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2-228 months). RESULTS: Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3). CONCLUSION: TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.' quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.

Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma.

BACKGROUND: Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation. The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment. METHODS: During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens. RESULTS: We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0-T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients. CONCLUSION: The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care.

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991.

PURPOSE: Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer. PATIENTS AND METHODS: A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%. RESULTS: The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet. CONCLUSION: Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.

Staging lymphadenectomy in patients with localized high risk prostate cancer: comparison of the laparoendoscopic single site (LESS) technique with conventional multiport laparoscopy.

BACKGROUND: In patients with localized high-risk prostate cancer awaiting radiation therapy, pelvic lymphadenectomy (PL) is a reliable minimally invasive staging procedure. We compared outcomes after laparoendoscopic single site PL (LESSPL) with those after conventional multiport laparoscopic PL (MLPL). METHODS: A retrospective case-control study was carried out at the authors' center. For LESSPL the reusable X-Cone single port was combined with straight and prebent laparoscopic instruments and an additional 3 mm needlescopic grasper. MLPL was performed via four trocars of different sizes using standard laparoscopic instruments. RESULTS: Patients who underwent either LESSPL (n = 20) or MLPL (n = 97) between January 2008 and July 2013, were included in the study. Demographic data were comparable between groups. Patients in the LESSPL group tended to be older and had a significantly higher ASA-score. The mean operating time was 172.4 ± 34.1 min for LESSPL and 116.6 ± 40.1 min for MLPL (P < .001). During LESSPL, no conversion to MLPL was necessary. An average of 12 lymph nodes per patient was retrieved, with no significant difference between study groups. Postoperative pain scores were similar between groups. The hospital stay was 2.3 ± 0.7 days after LESSPL and 3.1 ± 1.2 days after MLPL (P = .01). Two days postoperatively, significantly more patients after LESSPL than after MLPL recovered their normal physical activity (P < .001). Six months postoperatively, no complications were registered in the LESSPL group and cosmetic results were excellent. CONCLUSIONS: In the present study, shorter hospitalization and quicker postoperative recovery were major benefits of LESSPL over MLPL. In patients with localized prostate cancer, staging LESS pelvic lymphadenectomy may be a safe alternative to conventional multiport laparoscopy.

Image-guided intensity-modulated radiotherapy for patients with locally advanced gastric cancer: a clinical feasibility study.

BACKGROUND: The aim of this study was to determine the medical and technical feasibility of intensity-modulated radiotherapy (IMRT) in high-risk nonmetastatic gastric cancer stage II and III after primary gastrectomy and D2 lymphadenectomy. METHODS AND MATERIALS: A prospective nonrandomized phase II trial was performed on 25 consecutive patients with gastric cancer with high risk (T3-4, N1-3, G2-3, R0-1). The dose delivered was 45 Gy (1.80 Gy per fraction) in IMRT technique. Concurrent 5-fluorouracil-based chemotherapy at 225 mg/m(2) was administered as a continuous intravenous infusion. Primary endpoints were acute gastrointestinal toxicity (CTC 4.0) and technical feasibility of IMRT in regard to dose planning and radiation delivery. RESULTS: Early acute events were defined as clinical and chemical adverse effects of IMRT and concurrent chemotherapy during treatment. By definition, 90 days after the end of IMRT has been evaluated as acute-phase toxicity. No patient had grade 4 or higher acute adverse events. Clinical grade 3 toxicity occurred in two patients (8%) with diarrhea and in one case (4%) with nausea. Hematological changes with grade 3 occurred in three cases (12%) with hemoglobin decrease, in five cases (25%) as leukopenia, and in one case (4%) with thrombocytopenia. The mean dose for liver was 16 Gy and the percentage volume exceeding 30 Gy (V30) was 21%. Mean dose for right and left kidney was 9 and 13 Gy, respectively, and V20 was 9% and 13%, respectively. Heart received a median dose of 15 Gy and V40 was 17%. The mean dose to the bowel was 11 Gy and V40 was 6%. Spinal cord had at maximum 33 Gy in median. Specifics of dose distribution, including the coverage, for the target region were as follows: minimum was 33 Gy, maximum 48.6 Gy, and mean dose 44.6 Gy. The prescribed dose (45 Gy) covered 99% and 95% of planning target volume (OTV) in 66% and 92% of cases, respectively. Median PTV was 15.77 ml (range, 805-3,604 ml). CONCLUSIONS: The data support the practical feasibility of IMRT in adjuvant treatment in high-risk gastric cancer in the postoperative setting as a proof of principle. Acute toxicity has been tolerable.

The impact of patient compliance with adjuvant radiotherapy: a comprehensive cohort study.

Postoperative radiotherapy (RT) is the standard of care for early stage breast cancer. It reduces the risk for local recurrence and prolongs survival. We assessed whether, the omission of RT because of patient's preference may influence the prognosis and, thus, the quality of cancer care. Detailed information from a prospectively collected database of a breast cancer center was analyzed. Multiple regression analysis and univariate and multivariate analysis for risk factors for recurrence were performed. The entire cohort of primary breast cancer patients in a given time period was analyzed. Data from 1903 patients undergoing treatment at breast cancer center between 2003 and 2008 were used. All patient underwent breast conserving surgery and RT was performed for all patients of the cohort. Local tumor control and disease-free survival were calculated. After a median follow-up of 2.18 years (maximum 6.39 years), 5.5% of patients did not follow guideline-based recommendations for RT. There was a significant correlation between noncompliance and patient's age, adjuvant hormonal therapy (97.0%), and adjuvant chemotherapy (96.8%). Seventy local recurrences occurred that corresponds to a local recurrence rate of 3.9%. The difference in regard to local recurrence-free 5-year survival between the compliant patients and the noncompliant patients is absolute 17.9 (93.3% and 75.4%). Noncompliant patients had suffered a 5.02-fold increased risk of local recurrence than compliant patients. The omission of RT after breast-conserving surgery results in a higher local failure rate and significantly worsens clinical outcome. Age may play an important role because of the comorbidities of aged patients or the assumed low RT tolerance in this group. On a clinical level, this data suggests that improvement is needed to correct this situation, and the question remains as to how best to improve RT compliance.

Appropriate patient instructions can reduce prostate motion.

BACKGROUND: Interfraction prostate motion must be compensated by increased safety margins. If filling status of rectum and bladder is constant, motion should be reduced. We attempted to reduce interfraction motion errors by proper patient instruction. METHOD: In 38 patients pairs of radio-opaque fiducial markers were implanted prior to definitive radiotherapy. Patients were positioned either according to skin marks or infrared body marker. We measured prostate displacement, i.e. pelvic bones versus intraprostatic marker position, via ExacTrac (two orthogonal radiographies) in 1252 fractions. Systematic and random setup and displacement errors were determined and safety margins estimated. RESULTS: In our study interfraction prostate displacement is < 1 mm in RL direction, and < 2 mm in AP and SI direction. Systematic errors are slightly below random errors (< 1.5 mm). Positioning according skin marks results in higher inaccuracies of ±1.5 - 2 mm in RL and ±2 - 2.5 mm in AP/SI direction. CONCLUSIONS: In case of appropriate patient instructions (constant organ filling) the positioning via bone fusion requires CTV-PTV margins of 2 mm in RL, 4 mm in AP, and 5 mm in SI direction. Studies without any description of patient instruction found much higher margins of > 1 cm in AP and SI direction.

Interfraction rotation of the prostate as evaluated by kilovoltage X-ray fiducial marker imaging in intensity-modulated radiotherapy of localized prostate cancer.

To quantify the daily rotation of the prostate during a radiotherapy course using stereoscopic kilovoltage (kV) x-ray imaging and intraprostatic fiducials for localization and positioning correction. From 2005 to 2009, radio-opaque fiducial markers were inserted into 38 patients via perineum into the prostate. The ExacTrac/Novalis Body X-ray 6-day image acquisition system (ET/NB; BrainLab AG, Feldkirchen, Germany) was used to determine and correct the target position. During the first period in 10 patients we recorded all rotation errors but used only Y (table) for correction. For the next 28 patients we used for correction all rotational coordinates, i.e., in addition Z (superior-inferior [SI] or roll) and X (left-right [LR] or tilt/pitch) according to the fiducial marker position by use of the Robotic Tilt Module and Varian Exact Couch. Rotation correction was applied above a threshold of 1° displacement. The systematic and random errors were specified. Overall, 993 software-assisted rotational corrections were performed. The interfraction rotation errors of the prostate as assessed from the radiodense surrogate markers around the three axes Y, Z, and X were on average 0.09, -0.52, and -0.01° with standard deviations of 2.01, 2.30, and 3.95°, respectively. The systematic uncertainty per patient for prostate rotation was estimated with 2.30, 1.56, and 4.13° and the mean random components with 1.81, 2.02, and 3.09°. The largest rotational errors occurred around the X-axis (pitch), but without preferring a certain orientation. Although the error around Z (roll) can be compensated on average by a transformation with 4 coordinates, a significant error around X remains and advocates the full correction with 6 coordinates. Rotational errors as assessed via daily stereoscopic online imaging are significant and dominate around X. Rotation possibly degrades the dosimetric coverage of the target volume and may require suitable strategies for correction.

Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study.

PURPOSE: This open-label, randomized phase III study was designed to investigate the effects of erythropoietin alfa (EPO) in addition to adjuvant chemotherapy and pelvic radiotherapy (CRT) in patients with stage IB to II cervical cancer who had undergone radical hysterectomy. PATIENTS AND METHODS: Two hundred fifty-seven patients were randomly assigned to four cycles of carboplatin/ifosfamide chemotherapy followed by external-beam pelvic radiotherapy (CRT group) or four cycles of carboplatin/ifosfamide chemotherapy and EPO followed by pelvic radiotherapy and EPO (CRT + EPO group). The primary end point was recurrence-free survival (RFS). Secondary end points included overall survival (OS), change in hemoglobin levels, and safety, including thromboembolic events. RESULTS: The estimated 5-year RFS rates were 78% for patients receiving CRT + EPO and 70% for patients receiving CRT. There was no statistically significant difference in RFS, although a trend favoring patients treated with CRT + EPO was observed (hazard ratio [HR], 0.66; 95% CI, 0.39 to 1.12; log-rank P = .06). Exploratory analyses suggest a benefit with CRT + EPO for patients with stage IB to IIA disease (HR, 0.39; 95% CI, 0.18 to 0.85; P = .014) or patients with complete resection (HR, 0.55; 95% CI, 0.31 to 0.98; P = .039). OS was similar in both groups (HR, 0.88; 95% CI, 0.51 to 1.50; log-rank P = .63). Patients treated with EPO maintained higher hemoglobin levels throughout CRT. No significant differences in safety profiles were observed between the two groups. Incidence of thrombovascular events was low (2%) and comparable between both groups. CONCLUSION: This study confirms that EPO can be added safely to CRT in patients with cervical cancer, but it failed to demonstrate a significant benefit in RFS and OS.

Residual translational and rotational errors after kV X-ray image-guided correction of prostate location using implanted fiducials.

PURPOSE: To evaluate the residual errors and required safety margins after stereoscopic kilovoltage (kV) X-ray target localization of the prostate in image-guided radiotherapy (IGRT) using internal fiducials. PATIENTS AND METHODS: Radiopaque fiducial markers (FMs) have been inserted into the prostate in a cohort of 33 patients. The ExacTrac/Novalis Body™ X-ray 6d image acquisition system (BrainLAB AG, Feldkirchen, Germany) was used. Corrections were performed in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) direction. Rotational errors around LR (x-axis), AP (y) and SI (z) have been recorded for the first series of nine patients, and since 2007 for the subsequent 24 patients in addition corrected in each fraction by using the Robotic Tilt Module™ and Varian Exact Couch™. After positioning, a second set of X-ray images was acquired for verification purposes. Residual errors were registered and again corrected. RESULTS: Standard deviations (SD) of residual translational random errors in LR, AP, and SI coordinates were 1.3, 1.7, and 2.2 mm. Residual random rotation errors were found for lateral (around x, tilt), vertical (around y, table), and longitudinal (around z, roll) and of 3.2°, 1.8°, and 1.5°. Planning target volume (PTV)-clinical target volume (CTV) margins were calculated in LR, AP, and SI direction to 2.3, 3.0, and 3.7 mm. After a second repositioning, the margins could be reduced to 1.8, 2.1, and 1.8 mm. CONCLUSION: On the basis of the residual setup error measurements, the margin required after one to two online X-ray corrections for the patients enrolled in this study would be at minimum 2 mm. The contribution of intrafractional motion to residual random errors has to be evaluated.

Brain metastases from epithelial ovarian cancer: overview and optimal management.

Central nervous system involvement is a rare finding in the management of epithelial ovarian cancer with an incidence between 1-2%. A sharp rise in the incidence has been widely and repeatedly proclaimed for nearly two decades now, but has to be treated with scepticism after a careful review of the current literature. Brain metastases from ovarian cancer are known to be related to a very poor prognosis. Since brain imaging is not part of the routine follow-up care for ovarian cancer patients, and since CA-125--one of the standard tools--cannot be relied upon to detect central nervous system relapse, brain lesions are mostly traced by unspecific neurological symptoms only. Several prognostic factors are still being discussed today. But only a high performance status and the absence of an extra cranial disease at the time of CNS relapse have been accepted throughout the current literature as having a highly significant positive impact on survival. In the past, therapeutic efforts have focused on symptom palliation with corticosteroids and whole-brain radiation therapy (WBRT). During the last years several other therapy options have evolved from encouraging efforts made by several study groups, including chemotherapy, neurosurgery and radiosurgery. It has been shown that a multi-modal approach, combining these strategies, promises the best prolongation of survival and in some cases even resulted in long-term remissions. The present article gives an overview of brain metastases in epithelial ovarian cancer and discusses the current treatment options.

Potentials of on-line repositioning based on implanted fiducial markers and electronic portal imaging in prostate cancer radiotherapy.

BACKGROUND: To evaluate the benefit of an on-line correction protocol based on implanted markers and weekly portal imaging in external beam radiotherapy of prostate cancer. To compare the use of bony anatomy versus implanted markers for calculation of setup-error plus/minus prostate movement. To estimate the error reduction (and the corresponding margin reduction) by reducing the total error to 3 mm once a week, three times per week or every treatment day. METHODS: 23 patients had three to five, 2.5 mm Ø spherical gold markers transrectally inserted into the prostate before radiotherapy. Verification and correction of treatment position by analysis of orthogonal portal images was performed on a weekly basis. We registered with respect to the bony contours (setup error) and to the marker position (prostate motion) and determined the total error. The systematic and random errors are specified. Positioning correction was applied with a threshold of 5 mm displacement. RESULTS: The systematic error (1 standard deviation [SD]) in left-right (LR), superior-inferior (SI) and anterior-posterior (AP) direction contributes for the setup 1.6 mm, 2.1 mm and 2.4 mm and for prostate motion 1.1 mm, 1.9 mm and 2.3 mm. The random error (1 SD) in LR, SI and AP direction amounts for the setup 2.3 mm, 2.7 mm and 2.7 mm and for motion 1.4 mm, 2.3 mm and 2.7 mm. The resulting total error suggests margins of 7.0 mm (LR), 9.5 mm (SI) and 9.5 mm (AP) between clinical target volume (CTV) and planning target volume (PTV). After correction once a week the margins were lowered to 6.7, 8.2 and 8.7 mm and furthermore down to 4.9, 5.1 and 4.8 mm after correcting every treatment day. CONCLUSION: Prostate movement relative to adjacent bony anatomy is significant and contributes substantially to the target position variability. Performing on-line setup correction using implanted radioopaque markers and megavoltage radiography results in reduced treatment margins depending on the online imaging protocol (once a week or more frequently).

Brain metastases in relapsed epithelial ovarian cancer after chemotherapy with pegylated liposomal doxorubicin.

BACKGROUND: Brain metastases in epithelial ovarian cancer (EOC) occur rarely and are associated with a poor prognosis. No significant risk factors have been identified and no evidence-based treatment guidelines are currently available. CASE REPORT: A 56-year-old EOC patient presented with seizure at the Emergency Department eleven days after completion of fourth-line chemotherapy with pegylated liposomal doxorubicin (PLD). A computed tomography (CT) scan revealed multiple metastases. The patient received radiotherapy with a total dose of 30.8 Gy and 8 cycles of paclitaxel resulting in stable disease. Based on the current literature, treatment options are discussed. CONCLUSION: Therapeutic options for brain metastases include radiation, systemic or intrathecal chemotherapy, surgery or a combination regime. Since the effectiveness of systemic chemotherapy remains controversial, current research focuses on developing new anticancer drugs that penetrate the blood-brain barrier in order to prevent and/or treat brain metastases.

Combined radiotherapy and hormonal therapy in the treatment of prostate cancer.

The use of hormonal therapy as an adjunct to radiotherapy has been discussed controversially for years. Results of large RTOG and EORTC trials indicate that the combination of these treatment modalities may improve survival in subsets of patients. Many questions with respect to onset, duration, type of hormonal therapy and appropriate patient selection are still under investigation. Following a short overview of the corresponding literature, evidence-based recommendations for daily clinical practice are provided.

Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group.

The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing post-operative radiotherapy for prostate cancer requires a standardisation of the target volume definition and delineation as well as standardisation of the clinical quality assurance procedures. Recommendations for this are presented on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group and in addition to the already published guidelines for radiotherapy as the primary treatment.

Radiation therapy in prostate cancer.

Adenocarcinoma of the prostate is one of the most frequently diagnosed cancers of men in the Western hemisphere and is second only to lung cancer for male cancer mortality. Most patients are diagnosed in the early/clinically localized stage, which can be treated curatively with radiation therapy alone. Innovative methods such as brachytherapy, three-dimensional conformal radiotherapy (3D-CRT), and IMRT (intensity modulated radiotherapy) are able to deliver very high tumoricidal doses to the diseased prostate, with minimal side effects to the surrounding tissue. Radiation therapy combined with hormonal treatment can be curative in locally advanced disease. Radiation therapy is also very effective in alleviating symptoms of metastatic prostate cancer (bone metastases, spinal cord compression, and bladder outlet obstruction).