Amira Bajrovic

Prognostic Factors for Local Control and Survival After Radiotherapy of Metastatic Spinal Cord Compression

PURPOSE To evaluate potential prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression (MSCC). PATIENTS AND METHODS The following potential prognostic factors were investigated retrospectively in 1,852 patients irradiated for MSCC: age, sex, performance status, primary tumor, interval between tumor diagnosis and MSCC (< or = 15 v > 15 months), number of involved vertebrae (one to two v > or = three), other bone metastases, visceral metastases, pretreatment ambulatory status, time of developing motor deficits before radiotherapy (faster, 1 to 14 v slower, > 14 days), and radiation schedule (short-course v long-course radiotherapy). RESULTS On univariate analysis, improved local control of MSCC was associated significantly with favorable histology (breast cancer, prostate cancer, lymphoma/myeloma), no visceral metastases, and long-course radiotherapy. On multivariate analysis, absence of visceral metastases and radiation schedule maintained significance. On univariate analysis, improved survival was associated significantly with female sex, favorable histology, no visceral or other bone metastases, good performance status, being ambulatory before radiotherapy, longer interval between tumor diagnosis and MSCC, and slower development of motor deficits before radiotherapy. Long-course radiotherapy showed a trend. On multivariate analysis, histology, visceral metastases, other bone metastases, ambulatory status before radiotherapy, interval between tumor diagnosis and MSCC, and time of developing motor deficits maintained significance. CONCLUSION Poorer local control after radiotherapy for MSCC is associated with visceral metastases and short-course radiotherapy. Long-course radiotherapy seems preferable for patients with more favorable prognoses, given that these patients may live long enough to develop MSCC recurrences. Long-term survival after radiotherapy for MSCC may be predicted if several prognostic factors are considered.

Matched Pair Analysis Comparing Surgery Followed By Radiotherapy and Radiotherapy Alone for Metastatic Spinal Cord Compression

PURPOSE The appropriate treatment for MSCC is controversial. A small randomized trial showed that decompressive surgery followed by radiotherapy was superior to radiotherapy alone. That study was limited to highly selected patients. Additional studies comparing surgery plus radiotherapy to radiotherapy could better clarify the role of surgery. METHODS Data from 108 patients receiving surgery plus radiotherapy were matched to 216 patients (1:2) receiving radiotherapy alone. Groups were matched for 11 potential prognostic factors and compared for post-treatment motor function, ambulatory status, regaining ambulatory status, local control, and survival. Subgroup analyses were performed for patients receiving adequate surgery (direct decompressive surgery plus stabilization of involved vertebrae), patients receiving laminectomy, patients with solid tumors, patients with solid tumors receiving adequate surgery, and patients with solid tumors receiving laminectomy. RESULTS Improvement of motor function occurred in 27% of patients after surgery plus radiotherapy and 26% after radiotherapy alone (P = .92). Post-treatment ambulatory rates were 69% after surgery plus radiotherapy and 68% after radiotherapy alone (P = .99). Of the nonambulatory patients, 30% and 26%, respectively, (P = .86) regained ambulatory status after treatment. One-year local control rates were 90% after surgery plus radiotherapy and 91% after radiotherapy alone (P = .48). One-year overall survival rates were 47% and 40%, respectively (P = .50). The subgroup analyses did not show significant differences between both groups. Surgery-related complications occurred in 11% of patients. CONCLUSION In this study, the outcomes of the end points evaluated after radiotherapy alone appeared similar to those of surgery plus radiotherapy. A new randomized trial comparing both treatments is justified.

Long-term radiation sequelae after breast-conserving therapy in women with early-stage breast cancer: an observational study using the LENT-SOMA scoring system

PURPOSE To evaluate the long-term toxicity after breast-conserving therapy in women with early-stage breast cancer. METHODS AND MATERIALS Late toxicity according to the late effects of normal tissue-subjective, objective, management, and analytic (LENT-SOMA) criteria and cosmetic outcome (graded by physicians) were evaluated in 590 of 2943 women with early-stage breast cancer who were irradiated between 1983 and 1995 using the following fractionation schedules: group A, 1983-1987, 2.5 Gy 4x/wk to 60 Gy; group B, 1988-1993, 2.5 Gy 4x/wk to 55 Gy, group C, 1994-1995, 2.0 Gy 5x/wk to 55 Gy. RESULTS LENT-SOMA Grade 3-4 toxicity was observed as follows: group A (median follow-up 171 months; range 154-222 months), fibrosis 16% (7 of 45), telangiectasia 18% (8 of 45), and atrophy 4% (2 of 45); group B (median follow-up 113 months; range 78-164 months), pain 2% (8 of 345), fibrosis 10% (34 of 345), telangiectasia 10% (33 of 345), arm edema 1% (2 of 345), and atrophy 8% (27 of 345); and group C (median follow-up 75 months, range 51-96 months, n = 200), occurrence of Grade 3-4 late morbidity <or=2%. The cosmetic outcome was very good to acceptable in 78% (35 of 45) of patients in group A, 83% (286 of 345) in group B, and 94% (187 of 200) in group C. CONCLUSION In our population, the long-term side effects after breast-conserving therapy were not rare, but were mainly asymptomatic. The LENT-SOMA breast module is a practical tool to assess radiation-induced long-term toxicity.

PRELIMINARY RESULTS OF SPINAL CORD COMPRESSION RECURRENCE EVALUATION (SCORE-1) STUDY COMPARING SHORT-COURSE VERSUS LONG- COURSE RADIOTHERAPY FOR LOCAL CONTROL OF MALIGNANT EPIDURAL SPINAL CORD COMPRESSION

PURPOSE To compare the results of short-course vs. long-course radiotherapy (RT) for metastatic spinal cord compression. METHODS AND MATERIALS A total of 231 patients who underwent RT between January 2006 and August 2007 were included in this two-arm prospective nonrandomized study. Patients received short-course (n = 114) or long-course (n = 117) RT. The primary endpoint was progression-free survival (PFS). The secondary endpoints were local control (LC), functional outcome, and overall survival (OS). An additional 10 potential prognostic factors were investigated for outcomes. PFS and LC were judged according to motor function, not pain control. RESULTS The PFS rate at 12 months was 72% after long-course and 55% after short-course RT (p = 0.034). These results were confirmed in a multivariate analysis (relative risk, 1.33; 95% confidence interval, 1.01-1.79; p = 0.046). The 12-month LC rate was 77% and 61% after long-course and short-course RT, respectively (p = 0.032). These results were also confirmed in a multivariate analysis (relative risk, 1.49; 95% confidence interval, 1.03-2.24; p = 0.035). The corresponding 12-month OS rates were 32% and 25% (p = 0.37). Improvement in motor function was observed in 30% and 28% of patients undergoing long-course vs. short-course RT, respectively (p = 0.61). In addition to radiation schedule, PFS was associated with the interval to developing motor deficits before RT (relative risk, 1.99; 95% confidence interval, 1.10-3.55; p = 0.024). LC was associated only with the radiation schedule. Post-RT motor function was associated with performance status (p = 0.031), tumor type (p = 0.013), interval to developing motor deficits (p = 0.001), and bisphosphonate administration (p = 0.006). OS was associated with performance status (p < 0.001), number of involved vertebrae (p = 0.007), visceral metastases (p < 0.001), ambulatory status (p < 0.001), and bisphosphonate administration (p < 0.001). CONCLUSION Short-course and long-course RT resulted in similar functional outcome and OS. Long-course RT was significant for improved PFS and improved LC.

Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression

Based on an analysis of 1852 retrospectively evaluated patients with metastatic spinal cord compression (MSCC), a scoring system was developed to predict survival. This study was performed to validate the scoring system in a new data set.

The effect of amifostine or IMRT to preserve the parotid function after radiotherapy of the head and neck region measured by quantitative salivary gland scintigraphy

PURPOSE In this retrospective study, two approaches to preserve the parotid function after radiotherapy (RT) were compared: application of the radioprotective agent amifostine during RT and parotid-sparing intensity-modulated radiotherapy (IMRT). PATIENTS AND METHODS Patients were qualified for this analysis if (1) both parotid glands received a radiation dose of >or=50Gy using conventional radiotherapy techniques (cRT) or if they received a parotid-sparing IMRT as alternative, if (2) salivary gland scintigraphies before and after RT were performed, and if (3) a normal parotid function was present before RT. Quantitative salivary gland scintigraphy was used to assess the parotid gland function. RESULTS Altogether 275 salivary gland scintigraphies of 100 patients were analyzed. The mean relative tracer uptake (DeltaU) of patients treated with cRT, cRT with amifostine and IMRT 1-12 months after RT was 0.59 (95%CI 0.54-0.65), 0.67 (95%CI 0.59-0.76), and 0.93 (95%CI 0.78-1.07), respectively. The mean relative DeltaU 13-47 months after RT was 0.40 (95%CI 0.32-0.49), 0.60 (95%CI 0.48-0.71), and 0.92 (95%CI 0.56-1.28). At 1-12 months after RT, ANOVA testing with post-hoc comparison using the Bonferroni correction showed a significant difference between IMRT and cRT (p<0.001) or IMRT and amifostine (p<0.01). The difference between amifostine and cRT was not significant during the first year. At 13-47 months after RT, the difference between cRT and amifostine was significant (p=0.02). CONCLUSION Our data suggest that both amifostine and IMRT are able to partially preserve the parotid function after radiotherapy. The effect of IMRT appeared to be much greater.

Surgery Followed by Radiotherapy Versus Radiotherapy Alone for Metastatic Spinal Cord Compression From Unfavorable Tumors

PURPOSE Despite a previously published randomized trial, controversy exists regarding the benefit of adding surgery to radiotherapy for metastatic spinal cord compression (MSCC). It is thought that patients with MSCC from relatively radioresistant tumors or tumors associated with poor functional outcome after radiotherapy alone may benefit from surgery. This study focuses on these tumors. METHODS AND MATERIALS Data from 67 patients receiving surgery plus radiotherapy (S+RT) were matched to 134 patients (1:2) receiving radiotherapy alone (RT). Groups were matched for 10 factors and compared for motor function, ambulatory status, local control, and survival. Additional separate matched-pair analyses were performed for patients receiving direct decompressive surgery plus stabilization of involved vertebrae (DDSS) and patients receiving laminectomy (LE). RESULTS Improvement of motor function occurred in 22% of patients after S+RT and 16% after RT (p=0.25). Posttreatment ambulatory rates were 67% and 61%, respectively (p=0.68). Of nonambulatory patients, 29% and 19% (p=0.53) regained ambulatory status. One-year local control rates were 85% and 89% (p=0.87). One-year survival rates were 38% and 24% (p=0.20). The matched-pair analysis of patients receiving LE showed no significant differences between both therapies. In the matched-pair analysis of patients receiving DDSS, improvement of motor function occurred more often after DDSS+RT than RT (28% vs. 19%, p=0.024). Posttreatment ambulatory rates were 86% and 67% (p=0.30); 45% and 18% of patients regained ambulatory status (p=0.29). CONCLUSIONS Patients with MSCC from an unfavorable primary tumor appeared to benefit from DDSS but not LE when added to radiotherapy in terms of improved functional outcome.

Radiotherapy for Oligometastatic Disease in Patients with Spinal Cord Compression (MSCC) from Relatively Radioresistant Tumors

Background:Radiotherapy alone is the most common treatment for metastatic spinal cord compression (MSCC). Patients with relatively radioresistant tumors and oligometastatic disease may benefit from more intensive therapies (surgery, high-precision radiotherapy). If such therapies are not available, one can speculate whether patients benefit from dose escalation beyond the standard regimen 30 Gy in ten fractions.Patients and Methods:Of 206 patients with MSCC from relatively radioresistant tumors (renal cell carcinoma, colorectal cancer, malignant melanoma), 51 had oligometastatic disease (no visceral or other bone metastases, involvement of only one to three vertebrae). In this subset, 21 patients receiving 30 Gy in ten fractions were retrospectively compared to 30 patients receiving higher doses. Seven further potential prognostic factors were investigated: age, gender, tumor type, performance status, interval from tumor diagnosis to radiotherapy of MSCC, pretreatment ambulatory status, and time developing motor deficits before radiotherapy.Results:Motor function improved in 52% of patients after 30 Gy and 40% after higher doses (p = 0.44). On multivariate analysis, functional outcome was associated with interval from tumor diagnosis to radiotherapy (p = 0.020). 1-year local control rates were 84% after 30 Gy and 82% after higher doses (p = 0.75). No factor was associated with local control. 1-year survival rates were 76% after 30 Gy and 63% after higher doses (p = 0.52). On multivariate analysis, survival was associated with performance status (p = 0.022) and interval from tumor diagnosis to radiotherapy (p = 0.039), and almost with pretreatment ambulatory status (p = 0.069).Conclusion:Dose escalation beyond 30 Gy in ten fractions did not improve motor function, local control, and survival in MSCC patients with oligometastatic disease from relatively radioresistant tumors.ZusammenfassungHintergrund:Die alleinige Strahlentherapie ist die häufigste Behandlung der metastatisch bedingten Rückenmarkkompression (MSCC). Patienten mit relativ strahlenresistenten Tumoren und oligometastatischer Erkrankung könnten von intensiveren Therapien (Operation, Hochpräzisionsstrahlentherapie) profitieren. Sind diese nicht verfügbar, stellt sich die Frage, ob eine Dosiseskalation über das Standardregime 30 Gy in zehn Fraktionen hinaus zu einer Verbesserung der Prognose führt.Patienten und Methodik:Von 206 Patienten mit MSCC und relativ strahlenresistenten Tumoren (Nierenzellkarzinom, kolorektale Karzinome, malignes Melanom) hatten 51 eine oligometastatische Erkrankung (keine Organ- oder weiteren Knochenmetastasen, nur ein bis drei Wirbelkörper betroffen). 21 Patienten, die 30 Gy in zehn Fraktionen erhielten, wurden mit 30 Patienten, die höhere Dosen erhielten, verglichen (Tabelle 1). Sieben weitere mögliche Prognosefaktoren wurden untersucht: Alter, Geschlecht, Tumorart, Allgemeinzustand, Intervall von Erstdiagnose der Tumorerkrankung bis Strahlentherapie, Gehfähigkeit und Entwicklungszeit motorischer Defizite.Ergebnisse:52% der Patienten nach 30 Gy sowie 40% nach höheren Dosen zeigten eine Verbesserung der motorischen Funktion (p = 0,44; Abbildung 1, Tabelle 2). In der Multivarianzanalyse war die posttherapeutische motorische Funktion mit dem Intervall von Erstdiagnose bis Strahlentherapie assoziiert (p = 0,020). Die lokale Kontrolle nach 1 Jahr betrug 84% nach 30 Gy und 82% nach höheren Dosen (p = 0,75; Abbildung 2, Tabelle 3). Kein Faktor war signifikant mit der lokalen Kontrolle assoziiert. Das Überleben nach 1 Jahr betrug 76% nach 30 Gy und 63% nach höheren Dosen (p = 0,52; Abbildung 3, Tabelle 4). In der Multivarianzanalyse war das Überleben mit dem Allgemeinzustand (p = 0,022) und dem Intervall von Erstdiagnose bis Strahlentherapie (p = 0,039) assoziiert.Schlussfolgerung:Eine Dosiseskalation über 30 Gy in zehn Fraktionen hinaus führte nicht zu einer Verbesserung von motorischer Funktion, lokaler Kontrolle und Überleben bei MSCC-Patienten mit oligometastatischer Erkrankung und relativ strahlenresistenten Tumoren.

Is there a dose-effect relationship for the treatment of symptomatic vertebral hemangioma?

PURPOSE Symptomatic vertebral hemangiomas are rare vascular lesions. Radiotherapy is the most common treatment. Because of a lack of information in the literature, uncertainty exists about the total radiation dose to be applied. METHODS AND MATERIALS Individual data from our own and published patients with symptomatic vertebral hemangioma treated with radiotherapy alone were obtained. The data were pooled, and the impact of the total dose on complete pain relief was evaluated using the chi-square test. Because different single-fraction doses were used, the equivalent dose in 2-Gy fractions (EQD(2)) was used for the analysis. RESULTS Complete data could be obtained from 117 patients. Patients were categorized according to total dose (EQD(2)) into two groups of similar size (Group A: 20-34 Gy, n = 62; and Group B: 36-44 Gy, n = 55). Radiation-induced complete pain relief was achieved in 39% (24/62) of the patients in Group A and in 82% (45/55) of the patients in Group B. The difference was statistically significant (p = 0.003). CONCLUSIONS The data suggest a dose-effect relationship in the radiotherapy of symptomatic vertebral hemangiomas. We recommend a total radiation dose 36-40 Gy with a dose per fraction of 2.0 Gy.

Radiation-induced plexopathy and fibrosis: Is magnetic resonance imaging the adequate diagnostic tool?

Purpose:To investigate magnetic resonance imaging (MRI) features of radiation-induced plexopathy (RIP) and radiation-induced fibrosis frequently associated with RIP.Patients and Methods:Seven patients with late radiation sequelae in the supraclavicular region were examined with MRI after a median interval of 7 years (range, 5–18 years) following radiotherapy and 4–7 years after the onset of RIP. Four patients had RIP plus severe soft-tissue fibrosis, two RIP without soft-tissue fibrosis (n = 2/6), and one patient fibrosis without RIP. Patients underwent surgery of breast cancer (n = 6) or chest wall relapse (n = 1) and radiotherapy to the supraclavicular fossa with cobalt with an anterior portal in fractions of 1.7–2.6 Gy to 43–51.6 Gy in 3 cm depth. All patients were relapse-free at the time of MRI. Fibrosis and RIP were scored clinically (RTOG classification). Fibrosis of the supraclavicular and/or axillary region was marked in three and mild in two patients. RIP was mild, marked and severe in two patients each. MRI was performed with a 1.5-T unit including coronal STIR, coronal and transversal T2-weighted, transversal T1-weighted and fat-saturated post-contrast (gadolinium-DTPA) spin echo sequences.Results:The brachial plexus appeared normal in all patients, but subtle changes of adjoining tissue (slight, linear signal intensity in T2-weighted images or contrast enhancement surrounding the plexus) were detected in patients with RIP (n = 4/6) and the patient without RIP (n = 1). However, alterations of the soft tissue (marked signal intensity in T2-weighted sequences) correlated well with the clinical degree of fibrosis and were restricted to areas of marked to severe fibrosis (n = 3/3).Conclusion:Reliable MRI signs of RIP could not be identified. The severity of fibrosis closely corresponded to MRI features. The role of MRI in the diagnostic work-up of RIP is, therefore, the exclusion of tumor relapse.Ziel:Die Darstellung der radiogenen Schädigung des Plexus brachialis (RP) und der häufig mit der RP assoziierten Weichteilfibrose mit der Magnetresonanztomographie (MRT) wurde untersucht.Patienten und Methodik:Sieben Patientinnen mit ausgeprägten Strahlenreaktionen in der Supraklavikularregion wurden median 7 Jahre nach Therapie untersucht. Vier Patientinnen hatten eine RP und Fibrose, zwei Patientinnen eine RP ohne Fibrose und eine Patientin eine Fibrose ohne RP. Im Rahmen der Primärtherapie (n = 6) bzw. nach Exzision eines Brustwandrezidivs (n = 1) wurde die Supraklavikularregion mit 60Co in Einzeldosen von 1,7–2,6 Gy bis zu einer Gesamtdosis von 43–51,6 Gy in 3 cm Tiefe bestrahlt. Die Patientinnen waren seit mindestens 4 Jahren rezidivfrei. Fibrose und RP wurden klinisch nach RTOG klassifiziert. Die MRT-Untersuchung wurde an einem 1,5-T-Gerät mit koronaren und transversalen T2-gewichteten Sequenzen, koronaren STIR, transversalen T1-gewichteten Sequenzen und fettgesättigten Spinechosequenzen nach Kontrastmittelgabe (Gadolinium-DTPA) durchgeführt.Ergebnisse:Der Plexus brachialis selbst stellte sich unauffällig dar, aber die perineuralen Strukturen zeigten eine geringe lineare Hyperintensität in der T2-gewichteten Sequenz oder nach Kontrastmittelgabe (n = 4/6). Dagegen korrelierte die klinisch mäßiggradige und ausgeprägte Fibrose gut mit einer Hyperintensität des Fett- und Bindegewebes in den T2-gewichteten Sequenzen (n = 3/3).Schlussfolgerung:Zuverlässige Kriterien einer RP wurden nicht gefunden. Dagegen korrelierte der MRT-Befund mit dem klinischen Schweregrad der Fibrose. Das Ziel der MRT-Untersuchung ist der Ausschluss eines Tumorrezidivs als Ursache der Plexopathie.