Fabian Fehlauer

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.

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.

Increasing the rate of late toxicity by changing the score? A comparison of RTOG/EORTC and LENT/SOMA scores

PURPOSE The Radiation Therapy Oncology Group (RTOG) and Late Effects Normal Tissue Task Force subjective, objective, management, and analytic (LENT/SOMA) scores were compared in a group of breast cancer patients. The impact of the classification system on grading late effects was evaluated. MATERIALS AND METHODS Telangiectasia, skin pigmentation, and fibrosis were scored according to both LENT/SOMA and RTOG criteria. The results were compared with respect to up- or downgrading and correlated (Spearmans rho). Other side effects were recorded using LENT/SOMA criteria. Interobserver variability was calculated with Cohens kappa. Two hundred fifty-nine subsequent relapse-free patients who underwent breast-conserving therapy between 1981 and 1995 were examined. The median dose of radiotherapy to the breast was 55 Gy. Adjuvant chemotherapy was given to 31 patients and tamoxifen to 52 patients. The median follow-up was 8 years. RTOG skin and s.c. tissue scales and LENT/SOMA breast and pigmentation scales were used. Two doctors examined 45 patients jointly. RESULTS Of all patients, 20% had telangiectasia, 22% pigmentation, 43% fibrosis, 4% breast edema, 77% retraction/atrophy, and 54% pain. In comparison, when LENT/SOMA criteria were used, telangiectasia and pigmentation were upgraded in 34% and 36%, respectively, and telangiectasia was downgraded in 45%. Fibrosis correlated well (Spearmans rho 0.78, p = 0.01). An additional 356 side effects, mainly retraction/atrophy were observed in 226 patients using LENT/SOMA criteria. Interobserver variability was similar for both classification systems and ranged from Cohens kappa 0.3 (retraction) to 0.91 (telangiectasia). CONCLUSIONS LENT/SOMA criteria seem to be the better tool in grading and recording late radiation toxicity compared with the RTOG scale. There was some upgrading with the RTOG score when skin toxicity is evaluated. In contrast, fibrosis scores correlated very well. Adjustments of the LENT/SOMA scoring system should be considered to standardize reporting of late radiation morbidity.

Treatment options for central neurocytoma

Based on the data published since 1982 and on additional data from the authors, this retrospective analysis compares four different therapeutic approaches in the treatment of central neurocytoma: complete resection (n = 108), complete resection plus radiotherapy (n = 30), incomplete resection (n = 74), and incomplete resection plus radiotherapy (n = 98). The data suggest that complete resection leads to significantly better local control and survival than incomplete resection. After incomplete resection, patients benefit from postoperative radiotherapy.

Late effects and cosmetic results of conventional versus hypofractionated irradiation in breast-conserving therapy.

Background and Purpose:Breast irradiation after lumpectomy is an integral component of breast-conserving therapy (BCT). As the prognosis is general good following BCT, late morbidity and cosmesis are important. The present study compares two different radiation schedules with respect to these two endpoints.Patients and Methods:129 breast cancer patients (pT1–2 pN0–1 cM0) were irradiated between 09/1992 and 08/1994 with either a 22-day fractionation schedule (2.5 Gy to 55 Gy, 4×/week, n = 65) or with a conventional fractionation schedule (28 days, 2.0 Gy to 55 Gy, 5×/week, n = 64), both without additional boost. The equivalent dose of 2-Gy fractions (EQD2) was 55 Gy and 62 Gy, respectively. Late toxicity, assessed according to the LENT-SOMA criteria, and cosmetic outcome, graded on a 5-point scale, were evaluated after a median of 86 months (range 72–94 months) in tumor-free breast cancer patients.Results:LENT-SOMA grade 2/3 toxicity (2.5 Gy vs. 2.0 Gy): breast pain (18% vs. 11%; p = 0.3), fibrosis (57% vs. 16%; p < 0.001), telangiectasia (22% vs. 3%; p = 0.002), atrophy (31% vs. 3%; p < 0.001). Medication to breast pain was taken by 8% versus 9% of patients. Cosmesis was very good/good/acceptable in 75% versus 93% (2.5 Gy vs. 2.0 Gy; p = 0.006).Conclusion:Late morbidity was significantly frequent and cosmesis was significantly worse after hypofractionated radiotherapy (2.5 Gy to 55 Gy). However, morbidity was not associated with major implications on daily life.Hintergrund und Ziel:Die adjuvante Bestrahlung der Brust nach Operation ist ein integraler Bestandteil der brusterhaltenden Therapie (BET). Da die Prognose nach BET sehr gut ist, stellen die Spättoxizität und Kosmetik wichtige Untersuchungsparameter dar. Die vorliegende Untersuchung vergleicht zwei unterschiedliche Fraktionierungsschemata in Bezug auf diese Endpunkte.Patienten und Methodik:129 Patientinnen mit Brustkrebs (pT1–2 pN0–1 cM0) wurden zwischen 09/1992 und 08/1994 entweder mit einem 22-Tage-Fraktionierungsschema (2,5 Gy bis 55 Gy, 4×/Woche, n = 65) oder mit einem 28-Tage-Fraktionierungsschema (2,0 Gy bis 55 Gy, 5×/Woche, n = 64), jeweils ohne Boost, behandelt. Die Äquivalentdosis für 2 Gy pro Fraktion betrug 55 Gy und 62 Gy. Die Spätnebenwirkungen (LENT-SOMA) und das kosmetische Ergebnis (5-Punkte-Skala) wurden erfasst (mittlere Nachbeobachtungszeit 86 Monate, 72–94 Monate).Ergebnisse:Folgende LENT-SOMA-Nebenwirkungen Grad 2/3 (2,5 Gy vs. 2,0 Gy) traten auf: Brustschmerzen (18% vs. 11%; p = 0,3), Fibrose (57% vs. 16%; p < 0,001), Teleangiektasien (22% vs. 3%; p = 0,002), Atrophie (31% vs. 3%; p < 0,001). Schmerzmittel wurden von 8% versus 9% der Patientinnen eingenommen. Das kosmetische Ergebnis war sehr gut/gut/moderat in 75% versus 93% (2,5 Gy vs. 2,0 Gy; p = 0,006).Schlussfolgerung:Im eigenen Kollektiv ist die Häufigkeit von Spätnebenwirkungen und beeinträchtigter Kosmetik nach hypofraktionierter Strahlentherapie signifikant erhöht, allerdings ohne wesentliche Einschränkungen für den Alltag.

Additive cytotoxic effect of cisplatin and X-irradiation on human glioma cell cultures derived from biopsy-tissue

Purpose: Investigation of the in vitro cytotoxic effect of X-rays, either alone or combined with cisplatin on early passage cell cultures derived from human glioblastoma multiforme biopsy tissue. Materials and methods: Fresh tumour specimens from four patients were processed to cell cultures. The U373 glioma cell line was used as a reference. Early passage cell cultures were X-irradiated (0–8 Gy) either alone or in combination with cisplatin (0.5–1 μg/ml). Cell survival was determined by either clonogenic assay or the colorimetric MTT assay. Survival curves were generated and mathematically analysed using the linear quadratic model, to obtain the radiosensitivity parameters α, β, and SF2, i.e., the Surviving Fraction after 2 Gy. Results: Two patient-derived glioma cell cultures and the U373 cell line showed rather high SF2 values of 0.61–0.72 in the clonogenic assay, indicating relative high radiation resistance. Cisplatin alone (1 μg/ml) reduced cell survival by 10–30% (n=4). When combined with irradiation, a clear additive cytotoxic effect of cisplatin was demonstrated by the unaltered value of the α-parameter for reproductive cell death. Conclusion: Cisplatin exerted an additive rather than radiosensitising cytotoxic effect in uncharacterised patient derived glioma cell cultures.

[Treatment for central neurocytoma: a meta-analysis based on the data of 358 patients].

Hintergrund: Das zentrale Neurozytom wird als seltene benigne Läsion des zentralen Nervensystems beschrieben. Die Frage des adäquaten Therapieregimes ist noch nicht hinreichend geklärt. Diese retrospektive Analyse vergleicht vier Therapien bezüglich lokaler Kontrolle und Gesamtüberleben: alleinige komplette Resektion (KR), komplette Resektion plus Strahlentherapie (KR-RT), alleinige inkomplette Resektion (IR) und inkomplette Resektion plus Strahlentherapie (IR-RT). Material und Methoden: Die seit 1982 in der Literatur veröffentlichten Fälle wurden hinsichtlich folgender Parameter untersucht: Alter, Geschlecht, Ausmaß der Resektion, Vorliegen eines atypischen Neurozytoms, lokale Kontrolle und Gesamtüberleben (Follow-up mindestens 12 Monate). Durch direkten Kontakt mit den Autoren wurden zusätzliche Daten gewonnen. Im Vergleich zu den publizierten Daten ergaben sich hierdurch detailliertere Informationen über die Patienten und ein längeres Follow-up. Die statistische Analyse erfolgte mittels Kaplan-Meier-Analyse und Log-rank-Test. Ergebnisse: Vollständige Daten wurden für 358 Patienten (KR 118, KR-RT 35, IR 91, IR-RT 114) gewonnen. Nach KR, KR-RT oder IR-RT zeigte sich eine signifikant bessere lokale Kontrolle als nach IR. Kein signifikanter Unterschied ergab sich zwischen KR, KRRT und IR-RT. Das mediane rezidivfreie Intervall betrug 36 (KR), 39 (KR-RT), 21 (IR) und 32 (IR-RT) Monate. Der Vergleich der Gruppen untereinander für das Gesamtüberleben ergab ein signifikant besseres Überleben nach KR als nach IR. Die 5-Jahres-Überlebensraten betrugen 99,2% und 86,1%. Schlussfolgerungen: Die komplette Resektion ist bei der Behandlung des zentralen Neurozytoms deutlich effektiver als die inkomplette Resektion. Ob die Patienten nach einer kompletten Resektion von einer Strahlentherapie profitieren, bleibt unklar. Nach inkompletter Resektion führt die Strahlentherapie zu einer signifikanten Verbesserung der lokalen Kontrolle, nicht aber des Gesamtüberlebens.Background: Central neurocytomas are described as uncommon benign CNS lesions. Uncertainty exists about the most appropriate treatment regimen. This retrospective analysis compares four therapies for local control and overall survival: complete resection alone (KR), complete resection plus radiotherapy (KR-RT), incomplete resection alone (IR), and incomplete resection plus radiotherapy (ITR-RT). Material and Methods: The cases published in the literature since 1982 were reviewed for age, gender, extent of resection, atypical neurocytoma, radiotherapy, local control, and overall survival (minimum follow-up 12 months). From direct contact with the authors additional data were obtained providing more detailed information about the patients and a longer follow-up. Statistical analysis was performed with the Kaplan-Meier analysis and the log-rank test. Results: Complete data were obtained from 358 patients (KR 118, KR-RT 35, IR 91, IR-RT 114). Local control was significantly better after KR, KR-RT and IR-RT than after IR (Figure 1). No significant difference was found between KR, KR-RT and IR-RT. Median time to progression was 36 (KR), 39 (KR-RT), 21 (IR) and 32 (IR-RT) months. The comparison of the four groups for overall survival demonstrated that KR provided a significantly better overall survival than IR (Figure 2). Overall survival rates were 99.2% and 86.1%, respectively. Conclusions: Complete resection is much more effective for the treatment of central neurocytoma than incomplete resection. After complete resection the additional benefit of postoperative radiotherapy remains unclear. After incomplete resection postoperative radiotherapy significantly improved local control, but not overall survival.

Die behandlung des zentralen neurozytoms: Eine metaanalyse basierend auf den daten von 358 patienten

Hintergrund: Das zentrale Neurozytom wird als seltene benigne Läsion des zentralen Nervensystems beschrieben. Die Frage des adäquaten Therapieregimes ist noch nicht hinreichend geklärt. Diese retrospektive Analyse vergleicht vier Therapien bezüglich lokaler Kontrolle und Gesamtüberleben: alleinige komplette Resektion (KR), komplette Resektion plus Strahlentherapie (KR-RT), alleinige inkomplette Resektion (IR) und inkomplette Resektion plus Strahlentherapie (IR-RT). Material und Methoden: Die seit 1982 in der Literatur veröffentlichten Fälle wurden hinsichtlich folgender Parameter untersucht: Alter, Geschlecht, Ausmaß der Resektion, Vorliegen eines atypischen Neurozytoms, lokale Kontrolle und Gesamtüberleben (Follow-up mindestens 12 Monate). Durch direkten Kontakt mit den Autoren wurden zusätzliche Daten gewonnen. Im Vergleich zu den publizierten Daten ergaben sich hierdurch detailliertere Informationen über die Patienten und ein längeres Follow-up. Die statistische Analyse erfolgte mittels Kaplan-Meier-Analyse und Log-rank-Test. Ergebnisse: Vollständige Daten wurden für 358 Patienten (KR 118, KR-RT 35, IR 91, IR-RT 114) gewonnen. Nach KR, KR-RT oder IR-RT zeigte sich eine signifikant bessere lokale Kontrolle als nach IR. Kein signifikanter Unterschied ergab sich zwischen KR, KRRT und IR-RT. Das mediane rezidivfreie Intervall betrug 36 (KR), 39 (KR-RT), 21 (IR) und 32 (IR-RT) Monate. Der Vergleich der Gruppen untereinander für das Gesamtüberleben ergab ein signifikant besseres Überleben nach KR als nach IR. Die 5-Jahres-Überlebensraten betrugen 99,2% und 86,1%. Schlussfolgerungen: Die komplette Resektion ist bei der Behandlung des zentralen Neurozytoms deutlich effektiver als die inkomplette Resektion. Ob die Patienten nach einer kompletten Resektion von einer Strahlentherapie profitieren, bleibt unklar. Nach inkompletter Resektion führt die Strahlentherapie zu einer signifikanten Verbesserung der lokalen Kontrolle, nicht aber des Gesamtüberlebens.Background: Central neurocytomas are described as uncommon benign CNS lesions. Uncertainty exists about the most appropriate treatment regimen. This retrospective analysis compares four therapies for local control and overall survival: complete resection alone (KR), complete resection plus radiotherapy (KR-RT), incomplete resection alone (IR), and incomplete resection plus radiotherapy (ITR-RT). Material and Methods: The cases published in the literature since 1982 were reviewed for age, gender, extent of resection, atypical neurocytoma, radiotherapy, local control, and overall survival (minimum follow-up 12 months). From direct contact with the authors additional data were obtained providing more detailed information about the patients and a longer follow-up. Statistical analysis was performed with the Kaplan-Meier analysis and the log-rank test. Results: Complete data were obtained from 358 patients (KR 118, KR-RT 35, IR 91, IR-RT 114). Local control was significantly better after KR, KR-RT and IR-RT than after IR (Figure 1). No significant difference was found between KR, KR-RT and IR-RT. Median time to progression was 36 (KR), 39 (KR-RT), 21 (IR) and 32 (IR-RT) months. The comparison of the four groups for overall survival demonstrated that KR provided a significantly better overall survival than IR (Figure 2). Overall survival rates were 99.2% and 86.1%, respectively. Conclusions: Complete resection is much more effective for the treatment of central neurocytoma than incomplete resection. After complete resection the additional benefit of postoperative radiotherapy remains unclear. After incomplete resection postoperative radiotherapy significantly improved local control, but not overall survival.

Reducing the overall treatment time for radiotherapy of metastatic spinal cord compression (MSCC): 3-year results of a prospective observational multi-center study.

AbstractBackground: This prospective multi-center study investigates a reduction of the overall treatment time for radiotherapy of MSCC, which is important for these mostly disabled patients. Patients and methods: Two standard fractionation schedules, 30 Gy/10 fractions/2 weeks (n= 71) and 40 Gy/20 fractions/4 weeks (n= 65) were compared for functional outcome and ambulatory status. Motor function was graded using an 8-point-scale before RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis was performed for functional outcome. Included variables were the fractionation schedule and the three relevant prognostic factors. These factors are the type of primary tumor, the time of developing motor deficits before RT and the pre-treatment ambulatory status. Results: The ambulatory rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P= 0.888), and 56% and 60% after RT (P= 0.888). Improvement of motor function occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P= 0.752). The relevant prognostic factors were comparably distributed in both groups. According to the multivariate analysis, a slower development of motor deficits (P < 0.001), a favorable histology (P= 0.040) and being ambulatory (P= 0.045) were associated with better functional outcome, whereas the fractionation schedule had no significant impact (P= 0.311). Conclusions: The data suggest both schedules to be comparably effective for functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall treatment time from 4 to 2 weeks means less discomfort for the paraparetic or paraplegic patient.

Letter to 'Central neurocytoma with craniospinal dissemination' by H. Takao et al.

Takao et al. [1] reported a case of a central neurocytoma and discussed the treatment options such as surgery and radiation therapy for this rare tumor entity. We would like to contribute to the discussion. The authors state that ‘the best treatment policy has yet to be determined’ and that ‘the benefit of radiation therapy after a partial resection is controversial’. We presented a meta-analysis with 358 patients comparing four different therapeutic approaches, complete resection alone (CR), complete resection followed by radiation therapy (CR-RT), incomplete resection alone (IR), and incomplete resection followed by radiation therapy (IR-RT) [2,3].