Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases.

BACKGROUND: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. METHODS: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. RESULTS: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. CONCLUSIONS: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.

Radiochemotherapy with temozolomide for patients with glioblastoma. Prognostic factors and long-term outcome of unselected patients from a single institution.

BACKGROUND: The objective of this retrospective analysis was to assess long-term outcome and prognostic factors of unselected patients treated for glioblastoma (GB) at a single center with surgery, standard radiotherapy (RT), and concomitant temozolomide (TMZ). From 1999-2005, the institutional protocol included surgery and RT with TMZ. From 2005 on, adjuvant TMZ was routinely added. PATIENTS AND METHODS: Between April 1999 and September 2009, 181 patients with GB were treated with RT (60 Gy in 30 fractions) and concomitant TMZ (75 mg/m2/day throughout RT). Biopsy only had been performed in 53 patients (29.3%), 128 patients (70.7%) had undergone resection, which was complete based on postoperative MRI in 51 patients (28.2%). Adjuvant TMZ was applied in 67 of 181 patients (37%). RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 15.0 (95% CI, 13.1-16.8) and 7.2 months (95% CI, 5.9-8.5), respectively. After complete resection, partial/subtotal resection and biopsy, median OS was 23.20, 14.75, and 7.89 months (p<0.001), respectively. In multivariate Cox proportional hazards regression models, extent of resection (p<0.0001), Karnofsky's performance score (p<0.0001) and adjuvant TMZ (p=0.001) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 146 patients (80.7%), while 11 patients (6.1%) discontinued RT. Another 35 patients (19.3%) interrupted concomitant chemotherapy. CONCLUSION: RT with concomitant TMZ is a feasible regimen with acceptable toxicity in routine practice. Our data are compatible with a beneficial effect of adjuvant TMZ on OS and PFS.

Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for anal carcinoma: are there differences between HIV-positive and HIV-negative patients in the era of highly active antiretroviral therapy?

PURPOSE: To report treatment compliance, toxicity and clinical outcome of chemoradiotherapy (CRT) for anal carcinoma in HIV-negative vs. HIV-positive patients treated with highly active antiretroviral therapy. MATERIAL AND METHODS: Between 1997 and 2008, 25 HIV-positive and 45 HIV-negative patients received CRT (50.4 Gy at 1.8 Gy/fraction plus 5.4-10.8 Gy boost; 5-fluorouracil, 1000 mg/m(2), Days 1-4 and 29-32, mitomycin C, 10 mg/m(2), Days 1 and 29). Median follow-up was 51 (range, 3-235) months. RESULTS: HIV-positive patients were significantly younger (mean age, 47 vs. 57 years, p<0.001) and predominantly male (92% vs. 29%, p<0.001). CRT could be completed in all patients with a reduction of chemotherapy and/or RT-interruption in 28% and 8%, respectively, in HIV-positive patients, and in 9% and 11%, respectively, in HIV-negative patients. Acute Grade 3/4-toxicity occurred in 44% vs. 49% (p=0.79). Initial complete response (84% vs. 93%, p=0.41), 5-year rates of local control (65% vs. 78%, p=0.44), cancer-specific (78% vs. 90%, p=0.17) and overall survival (71% vs. 77%, p=0.76) were not significantly different. CONCLUSION: HIV-positive patients with anal cancer can be treated with standard CRT, with the same tolerability and toxicity as HIV-negative patients. Long-term local control and survival rates are not significantly different between these groups.

Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma.

BACKGROUND: The addition of temozolomide (TMZ) to radiotherapy (RT) improves survival of patients with glioblastoma (GB) when compared to postoperative RT alone in patients up to 65 years of age. In older patients, RT alone has remained the standard of care because there is concern that radiochemotherapy causes excess toxicity and is less efficacious in this population, but no randomized trials have been reported. We retrospectively assessed feasibility, toxicity and outcome in elderly patients treated at a single institution with RT and concomitant TMZ. PATIENT AND METHODS: Between 04/1999 and 9/2009, 51 patients ≥65 years (median age 70 years, range 65-84) with GB were treated by RT (total dose 60 Gy in 30 fractions) and concomitant TMZ (75 mg/m(2)/day throughout RT). Biopsy only had been performed in 23 patients (45.1%), 15 patients (29.4%) had undergone partial resection, and 13 patients (25.5%) macroscopically complete resection. Adjuvant TMZ was applied in 10 of 51 patients. RESULTS: Median overall survival (OS) and progression-free survival (PFS) were 11.5 (95% CI, 6.7-16.3) and 5.5 months (95% CI, 3.7-7.3 months), respectively, in the total cohort. After complete resection, partial resection and biopsy, median OS was 27.4, 15.5 and 7.9 months (p=0.002), respectively. In multivariate Cox proportional hazards regression models extent of resection (p<0.0001) and Karnofsky's performance score (p=0.002) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 30 patients (59%). Five patients (10%) discontinued RT because of disease progression (n=4) or toxicity (pneumonia, n=1). Another 16 patients interrupted concomitant chemotherapy (cytopenia: 9; pneumonia: 2; transaminase elevation: 2; rash: 3). CONCLUSION: RT with concomitant TMZ is a feasible regimen with acceptable toxicity in elderly patients. The promising outcome in patients with good performance status and patients with gross total resections are notable.

Long-term renal toxicity in children following fractionated total-body irradiation (TBI) before allogeneic stem cell transplantation (SCT).

PURPOSE: To retrospectively assess the incidence and time course of renal dysfunction in children (< or = 16 years) following total- body irradiation (TBI) before allogeneic stem cell transplantation (SCT). PATIENTS AND METHODS: Between 1986 and 2003, 92 children (median age, 11 years; range, 3-16 years) underwent TBI before allogeneic SCT. 43 of them had a minimum follow-up of 12 months (median, 51 months; range, 12-186 months) and were included into this analysis. Conditioning regimen included chemotherapy and fractionated TBI with 12 Gy (n = 26) or 11.1 Gy (n = 17). In one patient, renal dose was limited to 10 Gy by customized renal shielding due to known nephropathy prior to SCT. Renal dysfunction was defined as an increase of serum creatinine > 1.25 times the upper limit of age-dependent normal. RESULTS: Twelve children (28%) experienced an episode of renal dysfunction after a median of 2 months (range, 1-10 months) following SCT. In all but one patient renal dysfunction was transient and resolved after a median of 8 months (range, 3-16 months). One single patient developed persistent renal dysfunction with onset at 10 months after SCT. None of these patients required dialysis. The actuarial 3-year freedom from persistent renal toxicity for children surviving > 12 months after SCT was 97.3%. CONCLUSION: The incidence of persistent renal dysfunction after fractionated TBI with total doses < or = 12 Gy was very low in this analysis.

Complete remission of a lymphoma-associated chylothorax by radiotherapy of the celiac trunk and thoracic duct.

BACKGROUND: A chylothorax is a rare complication of mostly advanced malignant lymphomas. A case of a refractory chylothorax unresponsive to chemotherapy and successfully treated with radiotherapy is reported. CASE REPORT: A 45-year-old woman with recurrent stage IV low-grade follicular non-Hodgkin's lymphoma and a progressive chylothorax is described. The CT scans showed bulky lymphadenopathy at the thoracic trunk but no detectable enlargement of mediastinal lymph nodes. After ineffective pretreatment including chemotherapy and chest drainage, fractionated radiotherapy to the celiac trunk (20.4 Gy) and the thoracic duct (15 Gy) was performed. RESULT: Already after 7.5 Gy a rapid decline of chylothorax was noted and the chest drain could be removed. A complete remission of the chylothorax could be achieved after 20.4 Gy. During a follow-up of 16 months no recurrence of chylothorax occurred. CT scans showed nearly complete remission of the lymphadenopathy of the celiac trunk 12 months after radiotherapy. CONCLUSION: Radiotherapy with limited total doses is an effective treatment option for lymphoma-associated chylothorax and should always be taken into consideration, especially in cases unresponsive to chemotherapy.