Prospective assessment of mask versus frame fixation during Gamma Knife treatment for brain metastases.

PURPOSE: The newest generation of the Leksell Gamma Knife (GK) allows frame based as well as frameless treatment. We here report outcomes of a prospective non-randomized study on mask fixation (MF) versus frame fixation (FF) for GK treatment of brain metastases. METHODS: The decision for FF or MF was made on a case-by-case basis. Factors considered were patients' preference, proximity of critical structures, V12 and treatment time. Either stereotactic radiosurgery or fractionated stereotactic radiotherapy in up to 3 fractions was performed. For MF, a PTV margin of 1 mm was added. Follow-up included quarterly MRI scans. The primary outcome was local control. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and the incidence of radionecrosis. RESULTS: A total of 197 lesions (169 FF and 28 MF) were treated in 76 patients (59 FF and 17 MF). 187 lesions were treated with SRS and 10 with FSRT. Median dose was 22 Gy in both groups and median follow-up was 9.3 months. There was a higher local failure rate (HR: 3.69; 95%CI: 1.13-12.0; p = 0.03) with 11 local failures in the FF and none in the MF cohort. No differences were observed between the groups for OS (median: n.r. vs. 16.9 months; HR:1.00; 95%CI: 0.41-2.46; p = 0.999) and PFS (median: 6.9 vs. 8.4 months; HR: 0.92; 95%CI: 0.47-1.79; p = 0.800). Three cases of radionecrosis occurred with FF but none with MF (p = 0.67). CONCLUSIONS: Gamma Knife treatment with MF does not result in worse outcome or increased rates of radionecrosis in this non-randomized study.

Postoperative stereotactic radiosurgery and hypofractionated radiotherapy for brain metastases using Gamma Knife and CyberKnife: a dual-center analysis.

BACKGROUND: Postoperative stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hFSRT) to tumor cavities is emerging as a new standard of care after resection of brain metastases. Both Gamma Knife (GK) and CyberKnife (CK) are modalities commonly used for stereotactic radiotherapy, but fractional schemes are not consistent. The objective of this study was to evaluate outcomes in patients receiving postoperative stereotactic radiotherapy of resected brain metastases (BM) using different fractionation schedules and modalities in two large centers. METHODS: Patients with newly diagnosed BM who underwent postoperative SRS or hFSRT with either GK or CK at two large cancer centers were retrospectively evaluated. We analyzed local control (LC), regional control (RC) and overall survival (OS). RESULTS: From 04/14 to 05/18 79 patients with 81 resection cavities were treated. Forty-seven patients (59.5%) received GK and 32 patients (40.5%) received CK treatment. Fifty-four cavities (66.7%) were treated with hFSRT and 27 (33.3%) with SRS. The most common hFSRT and SRS scheme was 3x10 Gy and 1x16 Gy, respectively. Median OS was 11.7 months with survival rates of 44.7% at 1 year and 18.5% at 2 years. LC was 83.3% after 1 year. Median time to regional progression was 12.0 months with RC rates of 61.1% at 6 months and 41.0% at 12 months. There was no difference in OS, LC or RC between GK and CK treatments or SRS and hFSRT. CONCLUSIONS: Both SRS and hFSRT provide high local control rates in resected BM regardless of the applied modality.

Combined adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low renal toxicity in gastric cancer.

OBJECTIVES: Adjuvant radiochemotherapy improves survival of patients with advanced gastric cancer. We assessed in two sequential cohorts whether improved radiotherapy technique (IMRT) together with intensified chemotherapy improves outcome vs. conventional three-dimensional conformal radiotherapy (3D-CRT) and standard chemotherapy in these patients while maintaining or reducing renal toxicity. MATERIALS AND METHODS: Sixty consecutive patients treated for gastric cancer either with 3D-CRT (n = 27) and IMRT (n = 33) were evaluated. More than 70% had undergone D2 resection. Although there was a slight imbalance in R0 status between cohorts, N+ status was balanced. Chemotherapy consisted predominantly of 5-fluorouracil/folinic acid (n = 36) in the earlier cohort and mostly of oxaliplatin/capecitabine (XELOX, n = 24) in the later cohort. Primary end points were overall survival (OS), disease-free survival (DFS), and renal toxicity based on creatinine levels. RESULTS: Median follow-up (FU) of all patients in the 3D-CRT group was 18 months and in the IMRT group 22 months (median FU of surviving patients 67 months in the 3D-CRT group and 25 months in the IMRT group). Overall median survival (and DFS) were 18 (13) months in the 3D-CRT group and both not reached in the IMRT group (p = 0.0492 and 0.0216). Actuarial 2-year survival was 37% and 67% in the 3D-CRT and IMRT groups, respectively. No late renal toxicity >Grade 2 (LENT-SOMA scale) was observed in either cohort. CONCLUSION: When comparing sequentially treated patient cohorts with similar characteristics, OS and DFS improved with the use of IMRT and intensified chemotherapy without signs of increased renal toxicity.

Acute neurocognitive impairment during cranial radiation therapy in patients with intracranial tumors.

BACKGROUND AND PURPOSE: The objective of the current study was to evaluate the acute effects of cranial radiation therapy (CNS-RT) using different radiation doses (0, 1.8, 2, 3, >or=20 Gy) on cognitive function with special emphasis on memory. We assessed patients with and without intracranial tumors to distinguish between direct and indirect radiation effects on brain tissue. MATERIALS AND METHODS: Eighty-two patients were evaluated with neuropsychological testing before and acutely after radiotherapy (RT). Sixty-four patients received RT to the brain (55 with, 9 without intracranial tumor). Eighteen patients treated with RT to the breast served as controls. RESULTS: Patients with intracranial tumor demonstrated attention (19-38th percentile) and verbal memory scores (34-46th percentile) below the population average at baseline. The average Verbal Memory score was significantly different between patients with intracranial tumor and controls both at baseline (38th vs. 58th percentile) and after irradiation (27th vs. 52th percentile). Patients with preexisting peritumoral edema performed worse than patients without edema and controls. Radiation dose-related deficits were seen for working memory performance in patients with intracranial tumor. CONCLUSION: Our data indicate no measurable impairment of cognitive functioning acutely after prophylactic cranial irradiation. Patients with intracranial tumor show a deterioration of almost all memory functions with a dose-dependent impairment in working memory. Patients with preexisting peritumoral brain edema show the strongest deterioration.

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.

Memory function before and after whole brain radiotherapy in patients with and without brain metastases.

PURPOSE: To prospectively compare the effect of prophylactic and therapeutic whole brain radiotherapy (WBRT) on memory function in patients with and without brain metastases. METHODS AND MATERIALS: Adult patients with and without brain metastases (n = 44) were prospectively evaluated with serial cognitive testing, before RT (T0), after starting RT (T1), at the end of RT (T2), and 6-8 weeks (T3) after RT completion. Data were obtained from small-cell lung cancer patients treated with prophylactic cranial irradiation, patients with brain metastases treated with therapeutic cranial irradiation (TCI), and breast cancer patients treated with RT to the breast. RESULTS: Before therapy, prophylactic cranial irradiation patients performed worse than TCI patients or than controls on most test scores. During and after WBRT, verbal memory function was influenced by pretreatment cognitive status (p < 0.001) and to a lesser extent by WBRT. Acute (T1) radiation effects on verbal memory function were only observed in TCI patients (p = 0.031). Subacute (T3) radiation effects on verbal memory function were observed in both TCI and prophylactic cranial irradiation patients (p = 0.006). These effects were more pronounced in patients with above-average performance at baseline. Visual memory and attention were not influenced by WBRT. CONCLUSIONS: The results of our study have shown that WBRT causes cognitive dysfunction immediately after the beginning of RT in patients with brain metastases only. At 6-8 weeks after the end of WBRT, cognitive dysfunction was seen in patients with and without brain metastases. Because cognitive dysfunction after WBRT is restricted to verbal memory, patients should not avoid WBRT because of a fear of neurocognitive side effects.

Retrospective evaluation of combined modality treatment and prognostic factors in patients with esophageal cancer.

The influence of prognostic factors and combined modality treatment on survival was evaluated retrospectively for 156 patients with esophageal cancer receiving radiotherapy in different modalities between 1991 and 2001 at the University of Heidelberg and the Universitätsklinikum Mannheim. Forty-six patients (29.5%) were treated with radiotherapy alone, 74 patients (47.4%) had combined radiochemotherapy and 36 patients (23.1%) were operated on after receiving neoadjuvant radiochemotherapy. The median follow-up time was 10 months. Female patients showed a significantly better overall survival compared with male patients (p=0.031), younger patients (age 60 years) (p=0.02). Patients with hemoglobin concentration>13.4 g/dl before therapy (median hemoglobin concentration) had a significantly better overall survival than patients with lower hemoglobin concentration (p=0.044). Patients who received combined radiochemotherapy (with or without operation) had a survival advantage compared with radiotherapy alone. Overall survival after neoadjuvant treatment followed by operation was significantly better than in the two other groups, median survival times were 20 vs. 9 (RCHT) vs. 8 months (RT) (p=0.003). The data presented show for the first time that hemoglobin concentration in addition to gender and age was a prognostic factor for patients with esophageal cancer. A low hemoglobin value was a negative predictor.