Volker Rudat

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.

Tangential beam IMRT versus tangential beam 3D-CRT of the chest wall in postmastectomy breast cancer patients: A dosimetric comparison

BackgroundThis study evaluates the dose distribution of reversed planned tangential beam intensity modulated radiotherapy (IMRT) compared to standard wedged tangential beam three-dimensionally planned conformal radiotherapy (3D-CRT) of the chest wall in unselected postmastectomy breast cancer patientsMethodsFor 20 unselected subsequent postmastectomy breast cancer patients tangential beam IMRT and tangential beam 3D-CRT plans were generated for the radiotherapy of the chest wall. The prescribed dose was 50 Gy in 25 fractions. Dose-volume histograms were evaluated for the PTV and organs at risk. Parameters of the dose distribution were compared using the Wilcoxon matched pairs test.ResultsTangential beam IMRT statistically significantly reduced the ipsilateral mean lung dose by an average of 21% (1129 cGy versus 1437 cGy). In all patients treated on the left side, the heart volume encompassed by the 70% isodose line (V70%; 35 Gy) was reduced by an average of 43% (5.7% versus 10.6%), and the mean heart dose by an average of 20% (704 cGy versus 877 cGy). The PTV showed a significantly better conformity index with IMRT; the homogeneity index was not significantly different.ConclusionsTangential beam IMRT significantly reduced the dose-volume of the ipsilateral lung and heart in unselected postmastectomy breast cancer patients.

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.

Radiotherapy With 4 Gy × 5 Versus 3 Gy × 10 for Metastatic Epidural Spinal Cord Compression: Final Results of the SCORE-2 Trial (ARO 2009/01)

PURPOSE To compare short-course radiotherapy (RT) (4 Gy × 5) to longer-course RT (3 Gy × 10) for metastatic epidural spinal cord compression (MESCC). PATIENTS AND METHODS Two-hundred three patients with MESCC and poor to intermediate expected survival were randomly assigned to 4 Gy × 5 in 1 week (n = 101) or 3 Gy × 10 in 2 weeks (n = 102). Patients were stratified according to ambulatory status, time developing motor deficits, and primary tumor type. Seventy-eight and 77 patients, respectively, were evaluable for the primary end point, 1-month overall response regarding motor function defined as improvement or no further progression of motor deficits. Other study end points included ambulatory status, local progression-free survival, and overall survival. End points were evaluated immediately after RT and at 1, 3, and 6 months thereafter. RESULTS At 1 month, overall response rates regarding motor function were 87.2% after 4 Gy × 5 and 89.6% after 3 Gy × 10 (P = .73). Improvement rates were 38.5% and 44.2%, respectively, no further progression rates 48.7% and 45.5%, respectively, and deterioration rates 12.8% and 10.4%, respectively (P = .44). Ambulatory rates at 1 month were 71.8% and 74.0%, respectively (P = .86). At other times after RT, the results were also not significantly different. Six-month local progression-free survival was 75.2% after 4 Gy × 5 and 81.8% after 3 Gy × 10 (P = .51); 6-month overall survival was 42.3% and 37.8% (P = .68). CONCLUSION Short-course RT with 4 Gy × 5 was not significantly inferior to 3 Gy × 10 in patients with MESCC and poor to intermediate expected survival.

Impact of the frequency of online verifications on the patient set-up accuracy and set-up margins

PurposeThe purpose of the study was to evaluate the patient set-up error of different anatomical sites, to estimate the effect of different frequencies of online verifications on the patient set-up accuracy, and to calculate margins to accommodate for the patient set-up error (ICRU set-up margin, SM).Methods and materialsAlignment data of 148 patients treated with inversed planned intensity modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) of the head and neck (n = 31), chest (n = 72), abdomen (n = 15), and pelvis (n = 30) were evaluated. The patient set-up accuracy was assessed using orthogonal megavoltage electronic portal images of 2328 fractions of 173 planning target volumes (PTV). In 25 patients, two PTVs were analyzed where the PTVs were located in different anatomical sites and treated in two different radiotherapy courses. The patient set-up error and the corresponding SM were retrospectively determined assuming no online verification, online verification once a week and online verification every other day.ResultsThe SM could be effectively reduced with increasing frequency of online verifications. However, a significant frequency of relevant set-up errors remained even after online verification every other day. For example, residual set-up errors larger than 5 mm were observed on average in 18% to 27% of all fractions of patients treated in the chest, abdomen and pelvis, and in 10% of fractions of patients treated in the head and neck after online verification every other day.ConclusionIn patients where high set-up accuracy is desired, daily online verification is highly recommended.

Prognostic factors for different outcomes in patients with metastatic spinal cord compression from cancer of unknown primary

BackgroundPatients with cancer of unknown primary account for 10% of patients with metastatic spinal cord compression (MSCC). This retrospective study was performed to identify prognostic factors for functional outcome, local control of MSCC, and survival in 175 of such patients treated with radiotherapy alone.MethodsInvestigated were nine potential prognostic factors including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), number of involved vertebrae, pre-radiotherapy ambulatory status, other bone metastases, visceral metastases, time developing motor deficits before radiotherapy, and the radiation schedule.ResultsOn multivariate analysis, better functional outcome was associated with absence of visceral metastases (estimate: 0.72; 95%-confidence interval [CI]: 0.07-1.36; p = 0.030) and a slower (>7 days) development of motor deficits (estimate: 1.93; 95%-CI: 1.18-2.68; p < 0.001). Improved local control of MSCC was associated with absence of visceral metastases (risk ratio [RR]: 10.26; 95%-CI: 2.11-74.73; p = 0.004). Improved survival was associated with favorable ECOG-PS (RR: 2.12; 95%-CI: 1.40-3.29; p < 0.001), being ambulatory prior to radiotherapy (RR: 1.98; 95%-CI: 1.40-2.81; p < 0.001), absence of visceral metastases (RR: 2.74; 95%-CI: 1.93-3.91; p < 0.001), and slower development of motor deficits (RR: 1.27; 95%-CI: 1.07-1.51; p = 0.007). Absence of other bone metastases showed a trend (RR: 1.38; 95%-CI: 0.98-1.95; p = 0.07).ConclusionsThis study identified additional independent prognostic factors for functional outcome, local control of MSCC, and survival after radiotherapy of MSCC from cancer of unknown primary. These prognostic factors can help select the best treatment regimen for each individual patient.

Single-Fraction Versus 5-Fraction Radiation Therapy for Metastatic Epidural Spinal Cord Compression in Patients With Limited Survival Prognoses: Results of a Matched-Pair Analysis

PURPOSE This study compared single-fraction to multi-fraction short-course radiation therapy (RT) for symptomatic metastatic epidural spinal cord compression (MESCC) in patients with limited survival prognosis. METHODS AND MATERIALS A total of 121 patients who received 8 Gy × 1 fraction were matched (1:1) to 121 patients treated with 4 Gy × 5 fractions for 10 factors including age, sex, performance status, primary tumor type, number of involved vertebrae, other bone metastases, visceral metastases, interval between tumor diagnosis and MESCC, pre-RT ambulatory status, and time developing motor deficits prior to RT. Endpoints included in-field repeated RT (reRT) for MESCC, overall survival (OS), and impact of RT on motor function. Univariate analyses were performed with the Kaplan-Meier method and log-rank test for in-field reRT for MESCC and OS and with the ordered-logit model for effect of RT on motor function. RESULTS Doses of 8 Gy × 1 fraction and 4 Gy × 5 fractions were not significantly different with respect to the need for in-field reRT for MESCC (P=.11) at 6 months (18% vs 9%, respectively) and 12 months (30% vs 22%, respectively). The RT regimen also had no significant impact on OS (P=.65) and post-RT motor function (P=.21). OS rates at 6 and 12 months were 24% and 9%, respectively, after 8 Gy × 1 fraction versus 25% and 13%, respectively, after 4 Gy × 5 fractions. Improvement of motor function was observed in 17% of patients after 8 Gy × 1 fraction and 23% after 4 Gy × 5 fractions, respectively. CONCLUSIONS There were no significant differences with respect to need for in-field reRT for MESCC, OS, and motor function by dose fractionation regimen. Thus, 8 Gy × 1 fraction may be a reasonable option for patients with survival prognosis of a few months.

Intensity modulated radiotherapy of upper abdominal malignancies: dosimetric comparison with 3D conformal radiotherapy and acute toxicity

BackgroundThe goal of this study was to assess a possible dosimetric advantage of intensity modulated radiotherapy (IMRT) of upper abdominal malignancies compared to three-dimensional conformal radiotherapy (3DCRT), and to assess the impact of IMRT on acute toxicity.MethodsThirty-one unselected consecutive patients with upper abdominal malignancies were treated with definitive (n =16) or postoperative (n =15) IMRT. Twenty-one patients (67.7%) received concomitant chemotherapy. 3DCRT plans were generated for comparison, and analysis of variance (ANOVA) for repeated measurements was used to test for significant difference of dosimetric parameters. Acute toxicity was assessed weekly using the Common Terminology Criteria for Adverse Events (CTCAE) grading scale.ResultsIMRT plans showed a small but statistically significant improvement of the conformity index compared to 3DCRT plans (difference (95% confidence interval), -0.06 (−0.109 to-0.005); p = 0.03). The homogeneity index was not significantly improved (p = 0.10). A significantly reduced high dose volume on cost of a significantly increased low dose volume was observed for the kidneys. The acute toxicity appeared to be less than commonly reported for corresponding patients treated with 3DCRT. No patient developed grade 3 or 4 non-hematological acute toxicity, and the most common grade 2 toxicity was vomiting (9.7%).ConclusionsIMRT offers the potential of a clinically relevant dosimetric advantage compared to 3DCRT in terms of a reduced acute toxicity. Further optimization of the radiotherapy technique and more clinical trials are required before IMRT is routinely used for upper abdominal malignancies.

Excellent outcomes after radiotherapy alone for malignant spinal cord compression from myeloma

Abstract Background Uncertainty exists whether patients with spinal cord compression (SCC) from a highly radiosensitive tumor require decompressive spinal surgery in addition to radiotherapy (RT). This study addressed the question by evaluating patients receiving RT alone for SCC from myeloma. Patients and methods Data of 238 patients were retrospectively analyzed for response to RT and local control of SCC. In addition, the effect of RT on motor function (improvement, no further progression, deterioration) was evaluated. Overall response was defined as improvement or no further progression of motor dysfunction. Prior to RT, patients were presented to a neurosurgeon for evaluation whether upfront decompressive surgery was indicated (e.g. vertebral fracture or unstable spine). Results In the entire cohort, the overall response rate was 97% (53% improvement plus 44% no further progression). Following RT, 88% of the patients were able to walk. Of the 69 non-ambulatory patients 44 patients (64%) regained the ability to walk. Local control rates at 1, 2 and 3 years were 93%, 82% and 82%, respectively. A trend towards better local control was observed for patients who were ambulatory before starting RT (p = 0.08) and those with a more favorable performance status (p = 0.07). Conclusions RT alone provided excellent response rates, functional outcomes and local control in patients with SCC from myeloma. These results should be confirmed in a prospective randomized trial.