J. Dunst

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.

Ewing's tumors with primary lung metastases: survival analysis of 114 (European Intergroup) Cooperative Ewing's Sarcoma Studies patients.

PURPOSE To analyze event-free survival (EFS) and prognostic factors in patients who present with Ewings tumors (ET) of bone and synchronous pulmonary and/or pleural metastases (ppm). PATIENTS AND METHODS Of 1,270 patients (pts) registered at the continental office of the German/European Intergroup Cooperative Ewings Sarcoma Studies (CESS81, CESS86, EICESS92), 114 were diagnosed ET with ppm. Patients underwent neoadjuvant therapy and local treatment of the primary tumor. Whole-lung irradiation 15 to 18 Gy was applied to 75 ppm-pts. EFS and 95% confidence intervals (CIs) were estimated according to the Kaplan-Meier method, and prognostic factors were analyzed by log-rank tests and Cox and logistic regression procedures. RESULTS On November 1, 1997, at a median time under study of 5.9 years, the 5-year EFS was 0.36 (95% CI, 0.26 to 0.46) and the 10-year EFS was 0.30 (95% CI, 0.19 to 0.41). Thirty-seven of 59 (63%) first relapses involved lung and/or pleura, and the lungs were the only site of relapse in 26 of 59 (44%) ppm-pts. Risk factors identified in univariate and multivariate tests were poor response of the primary tumor toward chemotherapy, metastatic lesions in both lungs, and treatment without additional lung irradiation. CONCLUSION Chemotherapy response of the primary tumor is a prognostic factor in patients with ET with ppm. Strategies of treatment intensification warrant further evaluation.

ANEMIA IN CERVICAL CANCERS: IMPACT ON SURVIVAL, PATTERNS OF RELAPSE, AND ASSOCIATION WITH HYPOXIA AND ANGIOGENESIS

PURPOSE The prognostic impact of anemia in cervical cancers is well established. We have investigated the impact of anemia on prognosis and patterns of relapse in cervical cancers. Furthermore, we analyzed the relationship between anemia, tumor hypoxia, and angiogenesis. METHODS AND MATERIALS Eighty-seven patients (mean age 58 years) with squamous cell cancer of the cervix (Stage IIB: n = 19; Stage IIIB: n = 59; Stage IVA: n = 9) were prospectively enrolled in the study from 1995 through 1999. Patients underwent definitive radiotherapy with a combination of external beam radiotherapy (45-50.4 Gy) and high-dose-rate brachytherapy (5 x 7 Gy). Tumor oxygenation was measured with the Eppendorf pO(2)-histograph before radiotherapy and after 19.8 Gy. Angiogenesis was determined by measuring the microvessel density in pretreatment biopsies in 46 patients. The impact of tumor oxygenation (at 0 Gy and 19.8 Gy), hemoglobin (hb) level (at 0 Gy and 19.8 Gy), angiogenesis and clinical parameters on survival and relapse was investigated. RESULTS The 3-year overall survival rate (after a median follow-up of 42 months) was 57% for the whole group of patients, 72% for Stage IIB, 60% for Stage IIIB, and 22% for Stage IVA. The presence of pretreatment anemia had a significant impact on the relapse rate. However, the midtherapy hb level (at 19.8 Gy) had the strongest impact on local failure rate and survival: 3-year local failure rate was 6% in 20 patients with a hb > 13 g/dL at 19.8 Gy, 15% in 47 patients with an hb between 11 and 13 g/dL, and 67% in 20 patients with an hb < 11 g/dL, p = 0.0001. This was associated with a significant impact on the 3-year overall survival, 79% vs. 64% vs. 32%. Twenty-three tumors were poorly oxygenated at both measurements (oxygen pressure [median pO(2)] < 15 mm Hg before therapy and at 19.8 Gy). This group had a significantly lower 3-year overall survival as compared with patients with high pO(2) before and/or at 19.8 Gy (38% vs. 68%, p = 0.02), and these poorly oxygenated tumors had also a significantly increased microvessel density. In a multivariate model, the midtherapy hb level maintained an overwhelming impact on local failure rate and survival. CONCLUSION Hemoglobin level during radiotherapy was the strongest prognostic factor for local control and survival. We could further identify a poor prognostic subgroup with persisting hypoxia during radiotherapy, low hb levels, and increased angiogenesis. According to these findings, an association between anemia, poor tumor oxygenation, and angiogenesis is likely.

Final results of the randomized phase III CHARTWEL-trial (ARO 97-1) comparing hyperfractionated-accelerated versus conventionally fractionated radiotherapy in non-small cell lung cancer (NSCLC)

BACKGROUND Continuous hyperfractionated accelerated radiotherapy (CHART) counteracts repopulation and may significantly improve outcome of patients with non-small-cell lung cancer (NSCLC). Nevertheless high local failure rates call for radiation dose escalation. We report here the final results of the multicentric CHARTWEL trial (CHART weekend less, ARO 97-1). PATIENTS AND METHODS Four hundred and six patients with NSCLC were stratified according to stage, histology, neoadjuvant chemotherapy and centre and were randomized to receive 3D-planned radiotherapy to 60Gy/40 fractions/2.5weeks (CHARTWEL) or 66Gy/33 fractions/6.5weeks (conventional fractionation, CF). RESULTS Overall survival (OS, primary endpoint) at 2, 3 and 5yr was not significantly different after CHARTWEL (31%, 22% and 11%) versus CF (32%, 18% and 7%; HR 0.92, 95% CI 0.75-1.13, p=0.43). Also local tumour control rates and distant metastases did not significantly differ. Acute dysphagia and radiological pneumonitis were more pronounced after CHARTWEL, without differences in clinical signs of pneumopathy. Exploratory analysis revealed a significant trend for improved LC after CHARTWEL versus CF with increasing UICC, T or N stage (p=0.006-0.025) and after neoadjuvant chemotherapy (HR 0.48, 0.26-0.89, p=0.019). CONCLUSIONS Overall, outcome after CHARTWEL or CF was not different. The lower total dose in the CHARTWEL arm was compensated by the shorter overall treatment time, confirming a time factor for NSCLC. The higher efficacy of CHARTWEL versus CF in advanced stages and after chemotherapy provides a basis for further trials on treatment intensification for locally advanced NSCLC.

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.

A new scoring system to predicting the survival of patients treated with whole-brain radiotherapy for brain metastases.

Purpose:To create a scoring system to estimate survival of patients who received whole-brain radiotherapy (WBRT) for brain metastases.Material and Methods:Based on a multivariate analysis of 1,085 retrospectively analyzed patients, a scoring system was developed. This score was based on the four significant prognostic factors found in the multivariate analysis including: age, performance status, extracranial metastases at the time of WBRT, and interval between tumor diagnosis and WBRT. The score for each prognostic factor was determined by dividing the 6-month survival rate (in %) by 10. The total score represented the sum of the partial scores for each prognostic factor. Total scores ranged from 9 to 18 points, and patients were divided into four groups. For each group, survival was compared for short-course (5 × 4 Gy) versus longer-course WBRT (10 × 3 Gy/20 × 2 Gy).Results:Actuarial 6-month survival rates were 6% for patients with scores of 9–10 points, 15% for those with scores of 11–13 points, 43% for those with scores of 14–16 points, and 76% for those with scores of 17–18 points (p < 0.001). Longer-course WBRT was not associated with better survival than short-course WBRT in any of the four groups.Conclusion:: Patients with brain metastases receiving WBRT can be grouped with this score to estimate survival. Short-course and longer-course WBRT resulted in similar survival in all groups studied. However, in the more favorable patients with scores of 17–18, longer-course WBRT with lower doses per fraction should be considered, as these schedules have been associated with less neurocognitive toxicity.Ziel:Entwicklung eines Scores zur Abschatzung der Uberlebensprognose von Patienten mit Hirnmetastasen, die eine Ganzhirnbestrahlung (WBRT) erhielten.Material und Methodik:Basierend auf einer Multivarianzanalyse von 1 085 retrospektiv analysierten Patienten wurde ein Score entwickelt. Dieser Score berucksichtigte die vier Prognosefaktoren, die in der Multivarianzanalyse signifikant waren: Alter, Allgemeinzustand, extrakranielle Metastasen zur Zeit der WBRT und Intervall von der Erstdiagnose der Tumorerkrankung bis zur WBRT. Den Score fur jeden einzelnen Prognosefaktor erhielt man, indem man die Uberlebensrate nach 6 Monaten (in %) durch 10 dividierte und auf ganze Zahlen rundete (Tabelle 1). Der Gesamtscore entsprach der Summe der vier Teilscores und betrug zwischen 9 und 18 Punkten (Abbildung 1). Nach dem Score wurden vier Gruppen gebildet. In jeder Gruppe wurden Kurzzeit-WBRT (5 × 4 Gy) und Langzeit-WBRT (10 × 3 Gy/20 × 2 Gy) fur das Uberleben verglichen.Ergebnisse:Die aktuarischen Uberlebensraten nach 6 Monaten betrugen 6% bei Patienten mit einem Score von 9–10 Punkten, 15% bei einem Score von 11–13 Punkten, 43% bei einem Score von 14–16 Punkten und 76% bei einem Score von 17–18 Punkten (p < 0,001; Abbildung 2). Die Langzeit-WBRT fuhrte in keiner Gruppe zu einem besseren Uberleben als die Kurzzeit-WBRT (Abbildung 3).Schlussfolgerung:Bei Patienten mit Hirnmetastasen, die eine WBRT erhalten, kann mit Hilfe dieses Scores die Uberlebensprognose abgeschatzt werden. Langzeit- und Kurzzeit-WBRT fuhrten zu vergleichbaren Uberlebensraten. Bei Patienten mit einem Score von 17–18 Punkten sollte die Langzeit-WBRT mit geringeren Dosen pro Fraktion erortert werden, da diese Schemata nach der Literatur seltener mit neurokognitiven Defiziten einhergehen.

Stereotactic radiosurgery alone versus resection plus whole-brain radiotherapy for 1 or 2 brain metastases in recursive partitioning analysis class 1 and 2 patients

The objective of this study was to compare stereotactic radiosurgery (SRS) alone with resection plus whole‐brain radiotherapy (WBRT) for the treatment of patients in recursive partitioning analysis (RPA) class 1 and 2 who had 1 or 2 brain metastases.

The first score predicting overall survival in patients with metastatic spinal cord compression

The current study was performed to create a scoring system to estimate the survival of patients with metastatic spinal cord compression (MSCC).

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.

Outcome After Radiotherapy Alone for Metastatic Spinal Cord Compression in Patients With Oligometastases

PURPOSE To investigate outcome and prognosis of metastatic spinal cord compression (MSCC) patients with oligometastatic disease treated with radiotherapy alone. PATIENTS AND METHODS Oligometastatic disease was defined as involvement of three or fewer vertebrae and lack of other bone or visceral metastases. Five hundred twenty-one patients with oligometastatic disease and MSCC were evaluated for functional outcome, ambulatory status, local control of MSCC, and survival. Furthermore, seven potential prognostic factors were investigated. RESULTS Motor function improved in 40% (n = 207), remained stable in 54% (n = 279), and deteriorated in 7% (n = 35) of patients. Fifty-eight (54%) of 107 nonambulatory patients became ambulatory, and 388 (94%) of 414 ambulatory patients remained ambulatory. Improved functional outcome was significantly associated with tumor type and slower development of motor deficits (> 14 days). Local control at 1, 2, and 3 years was 92%, 88%, and 78%, respectively. Improved local control was significantly associated with long-course radiotherapy. Survival at 1, 2, and 3 years was 71%, 58%, and 50%, respectively. Better survival was significantly associated with tumor type, ambulatory status, slower development of motor deficits, and long-course radiotherapy. Patients who developed motor deficits slowly (onset > 14 days before initiating treatment) were further analyzed. In this subgroup, the best results were observed for myeloma/lymphoma and breast cancer patients. No patient had progression of motor deficits. One hundred percent (myeloma/lymphoma) and 99% (breast cancer) of patients were ambulatory after radiotherapy. One-year local control was 100% and 98%, 1-year survival was 94% and 89%. CONCLUSION Given the limitations of a retrospective review, improved outcome of patients with oligometastatic MSCC was associated with myeloma/lymphoma and breast cancer, slower development of motor deficits, and a more prolonged course of radiation.