Dirk Rades

Prognostic value of the MIB-1 labeling index for central neurocytomas

Although central neurocytomas are generally described as benign CNS lesions, malignant behavior including craniospinal dissemination and tumor-related death may occur. This meta-analysis was performed to investigate the prognostic value of the MIB-1 labeling index. Data were obtained not from the literature alone but also from contact with the authors. The data suggested an MIB-1 index score of >3% to be associated with a worse prognosis for local control (p < 0.0001) and survival (p = 0.0004).

Association of single nucleotide polymorphisms in ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with clinical and cellular radiosensitivity

PURPOSEnTo examine the association of polymorphisms in ATM (codon 158), GSTP1 (codon 105), SOD2 (codon 16), TGFB1 (position -509), XPD (codon 751), and XRCC1 (codon 399) with fibrosis and also individual radiosensitivity.nnnMETHODS AND MATERIALSnRetrospective analysis with 69 breast cancer patients treated with breast-conserving radiotherapy; total dose delivered was restricted to vary between 54 and 55Gy. Fibrosis was evaluated according to LENT/SOMA score. DNA was extracted from blood samples; cellular radiosensitivity was measured using the G0 assay and polymorphisms by PCR-RFLP and MALDI-TOF, respectively.nnnRESULTSnTwenty-five percent of all patients developed fibrosis of grade 2 or 3. This proportion tends to be higher in patients being polymorphic in TGFB1 or XRCC1 when compared to patients with wildtype genotype, whereas for ATM, GSTP1, SOD2 and XPD the polymorphic genotype appears to be associated with a lower risk of fibrosis. However, none of these associations are significant. In contrast, when a risk score is calculated based on all risk alleles, there was significant association with an increased risk of fibrosis (per risk allele odds ratio (ORs)=2.09, 95% confidence interval (CI): 1.32-3.55, p=0.0005). All six polymorphisms were found to have no significant effect on cellular radiosensitivity.nnnCONCLUSIONSnIt is most likely that risk for radiation-induced fibrosis can be assessed by a combination of risk alleles. This finding needs to be replicated in further studies.

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.

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck.

Background and Purpose:The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN).Patients and Methods:Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) or two courses cisplatin (20 mg/m2/d1–5 + 29–33) + 5-fluorouracil (5-FU; 600 mg/m2/d1–5 + 29–33; n = 74).Results:At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different.The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week.Conclusion:Two courses of fractionated cisplatin (20 mg/m2/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity.Hintergrund und Ziel:Das optimale Radiochemotherapieregime bei der Behandlung fortgeschrittener Kopf-Hals-Tumoren ist nicht hinreichend geklärt. Diese nichtrandomisierte Studie vergleicht zwei cisplatinbasierte Regimes in einer Serie von 128 Patienten (Tabelle 1) mit lokal fortgeschrittenem (Stadium IV) nichtresektablem Plattenepithelkarzinom der Kopf-Hals-Region (SCCHN).Patienten und Methodik:Die simultan zur Strahlentherapie applizierte Chemotherapie bestand aus zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) oder zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33) + 5-Fluorouracil (5-FU; 600 mg/m2/ d1–5 + 29–33; n = 74).Ergebnisse:Mindestens eine Grad-3-Toxizitat trat bei 25 von 54 Patienten (46%) unter alleiniger Cisplatingabe und bei 52 von 74 Patienten (70%) unter Cisplatin + 5-FU auf. Das letztgenannte Regime war insbesondere mit hoheren Raten an Mukositis (p = 0,027) und akuter Hauttoxizitat (p = 0,001) assoziiert (Abbildung 1). Sieben von 54 (13%) und 20 von 74 Patienten (27%) erhielten toxizitatsbedingt nur einen Kurs Chemotherapie. Die Spattoxizitat (Xerostomie, Halsfibrose, Hauttoxizitat, Lymphodem) war in beiden Gruppen vergleichbar (Abbildung 2).Die Raten fur die lokoregionale Kontrolle nach 2 Jahren betrugen 67% nach alleiniger Cisplatingabe sowie 52% nach Cisplatin + 5-FU (p = 0,35; Abbildung 3). Die Raten fur das metastasenfreie Uberleben lagen bei 79% und 69% (p = 0,65; Abbildung 4), die Raten für das Gesamtüberleben bei 70% und 51% (p = 0,10; Abbildung 5). In der Multivarianzanalyse waren die Therapieergebnisse signifikant mit dem Allgemeinzustand, der T-Kategorie, der N-Kategorie, dem Hamoglobinwert vor Strahlentherapie und einer Radiotherapiepause > 1 Woche assoziiert (Abbildung 3, Tabelle 2).Schlussfolgerung:Das aus alleiniger fraktionierter Cisplatingabe (20 mg/m2/d) bestehende Regime scheint besser geeignet zu sein als die Kombination Cisplatin + 5-FU. Das erstgenannte Regime führte zu vergleichbaren Therapieergebnissen, war allerdings mit signifikant geringerer Akuttoxizitat assoziiert als die Kombination Cisplatin + 5-FU.

Prognostic factors for functional outcome and survival after reirradiation for in‐field recurrences of metastatic spinal cord compression

The purpose of the current study was to retrospectively investigate clinical outcome and potential prognostic factors after reirradiation (Re‐RT) for in‐field recurrence of metastatic spinal cord compression (MSCC).

Treatment recommendations for the various subgroups of neurocytomas.

SummaryNeurocytomas gained importance since 1995, which is reflected by the increasing number of reports on this entity. This study was performed to determine the best available treatment for typical and atypical neurocytomas (MIB-1 labeling index >‰3%, atypical histology) in various age groups (‰≤‰18xa0years, >‰18xa0years).The data of all neurocytoma patients reported since 1982, when this entity were reviewed for age, gender, extent of resection, MIB-1 labeling index, histology, radiotherapy, and outcome of therapy. Patients were treated with complete resection alone (CTR), CTR plus radiotherapy (CTRxa0+xa0RT), incomplete resection alone (ITR), or ITR plus radiotherapy (ITRxa0+xa0RT). If the reported data were incomplete, the authors were contacted for additional data. Follow up had to be at least 12xa0months.Data were complete in 438 patients (73 children, 365 adults). Three hundred and fifty-one patients had typical, 87 atypical lesions. Typical lesions were associated with better local control and survival than atypical lesions (Pu200a<u200a0.001). CTR was superior to ITR (Pu200a<u200a0.001). After CTR, outcome was not significantly improved by RT. After ITR, RT improved survival in typical lesions (Pxa0=xa00.03) and atypical lesions (Pxa0=xa00.05), not in children (Pxa0=xa00.16). Local control was improved in all groups (Pu200a<u200a0.001, children Pxa0=xa00.01). Doses >‰54xa0Gy appeared beneficial after ITR of atypical lesions. In children, ≤50xa0Gy and >50xa0Gy were comparable.CTR does not require post-operative RT. Following ITR, RT improves outcome. Of 50–54xa0Gy appear sufficient for typical lesions, 50xa0Gy for children. Atypical lesions require 56–60xa0Gy.

Well-differentiated neurocytoma: What is the best available treatment?

Most neurocytomas are well differentiated, being associated with better long-term survival than the more aggressive atypical lesions. Atypical neurocytomas are characterized by an MIB-1 labeling index >3% or atypical histologic features. This analysis focuses on well differentiated neurocytomas in order to define the optimal treatment. A case with a follow-up of 132 months is presented. The patient developed two recurrences two and four years after first surgery, each showing an increasing proliferation activity. Furthermore, all published well-differentiated neurocytoma cases were reviewed for surgery, radiotherapy, and prognosis. Additional relevant data were obtained from the authors. Complete resection (CTR), complete resection plus radiotherapy (CTR + RT), incomplete resection (ITR), and incomplete resection plus radiotherapy (ITR + RT) were compared for outcome by using the Kaplan-Meier method and the log-rank test. Data were complete in 301 patients (CTR, 108; CTR + RT, 27; ITR, 81; ITR + RT, 85). Local control and survival were better after CTR than after ITR (P < 0.0001 and P = 0.0085, respectively). Radiotherapy improved local control after ITR (P < 0.0001) and after CTR (P = 0.0474), but not survival (P = 0.17 and P = 1.0, respectively). In the ITR + RT group, doses < or =54 Gy (n = 33) and >54 Gy (n = 32) were not significantly different for local control (P = 0.88) and survival (P = 0.95). The data demonstrated CTR to be superior to ITR for local control and survival. After CTR and ITR, radiotherapy improved local control, but not survival. A radiation dose of 54 Gy appeared sufficient. Application of postoperative radiotherapy should be decided individually, taking into account the risk of local failure, the need for another craniotomy, and potential radiation toxicity.

Dose escalation of radiotherapy for Metastatic Spinal Cord Compression (MSCC) in patients with relatively favorable survival prognosis

Background and PurposeLocal control of metastatic spinal cord compression (MSCC) is particularly important for long-term survivors. Radiotherapy alone is the most common treatment for MSCC. The most frequently used schedule world wide is 30 Gy/10 fractions. This study investigated whether patients with favorable survival prognoses benefit from a dose escalation beyond 30 Gy.Patients and MethodsData from 191 patients treated with 30 Gy/10 fractions were matched to 191 patients (1:1) receiving higher doses (37.5 Gy/15 fractions or 40 Gy/20 fractions). All patients had favorable survival prognoses based on a validated scoring system and were matched for age, gender, tumor type, performance status, number of involved vertebrae, visceral or other bone metastases, interval from tumor diagnosis to radiotherapy, ambulatory status, and time developing motor deficits. Both groups were compared for local control, progression-free survival, overall survival, and functional outcome.ResultsLocal control rates at 2 years were 71 % after 30 Gy and 92 % after higher doses (p = 0.012). Two-year progression-free survival rates were 68 % and 90 %, respectively (p = 0.013). Two-year overall survival rates were 53 % and 68 %, respectively (p = 0.032). Results maintained significance in the multivariate analyses (Cox proportional hazards model; stratified model) with respect to local control (p = 0.011; p = 0.012), progression-free survival (p = 0.010; p = 0.018), and overall survival (p = 0.014; p = 0.015). Functional outcome was similar in both groups. Motor function improved in 40 % of patients after 30 Gy and 41 % after higher doses (p = 0.98).ConclusionEscalation of the radiation dose beyond 30 Gy resulted in significantly better local control, progression-free survival, and overall survival in patients with favorable survival prognoses.ZusammenfassungHintergrundDie lokale Kontrolle der metastatisch bedingten Rückenmarkkompression (MSCC) ist von besonderer Bedeutung für Patienten mit vergleichsweise guter Überlebensprognose. Die alleinige Strahlentherapie ist die häufigste Behandlungsform der MSCC; das am meisten verwendete Fraktionierungsschema ist 30 Gy/10 Fraktionen. Diese Studie untersuchte, ob Patienten mit vergleichsweise guter Überlebensprognose von einer Dosiseskalation über 30 Gy hinaus profitieren.Patienten und Methoden191 Patienten, die 30 Gy/10 Fraktionen erhielten, wurden mit 191 Patienten, die höhere Dosen (37,5 Gy/15 Fraktionen oder 40 Gy/20 Fraktionen) erhielten, verglichen (Matched-Pair-Analyse). Alle Patienten hatten nach einem validierten Score eine vergleichsweise gute Überlebensprognose. Die Paarbildung erfolgte unter Berücksichtigung folgender Faktoren: Alter, Geschlecht, Art des Primärtumors, Allgemeinzustand, Anzahl betroffener Wirbelkörper, viszerale Metastasen, weitere Knochenmetastasen, Intervall von der Erstdiagnose der Tumorerkrankung bis zur Bestrahlung, Gehfähigkeit, Entwicklungszeit motorischer Defizite. Beide Grupen wurden hinsichtlich lokaler Kontrolle, progressionsfreiem Überleben, Gesamtüberleben und motorischer Funktion verglichen.ErgebnisseDie Raten für die lokale Kontrolle nach 2 Jahren betrugen 71 % nach 30 Gy und 92 % nach höheren Dosen (p = 0,012). Die Raten für das progressionsfreie Überleben waren 68 % und 90 % (p = 0,013), die Raten für das Gesamtüberleben 53 % und 68 % (p = 0,032). Die Ergebnisse blieben in den Multivarianzanalysen (Cox proportional hazards model; stratified model) signifikant für die lokale Kontrolle (p = 0,011; p = 0,012), das progressionsfreie Überleben (p = 0,010; p = 0,018) und das Gesamtüberleben (p = 0,014; p = 0,015). Eine Verbesserung der motorischen Funktion war bei 40 % der Patienten nach 30 Gy und bei 41 % nach höheren Dosen zu verzeichnen (p = 0,98).SchlussfolgerungEine Dosiseskalation über 30 Gy hinaus führt zu einer signifikanten Verbesserung von lokaler Kontrolle, progressionsfreiem Überleben und Gesamtüberleben.

Surgical Resection Followed by Whole Brain Radiotherapy Versus Whole Brain Radiotherapy Alone for Single Brain Metastasis

PURPOSEnTo compare the outcome of surgical resection followed by whole brain radiotherapy (WBRT) with WBRT alone in patients treated for single brain metastasis.nnnMETHODS AND MATERIALSnThe data from 195 patients with single brain metastases were retrospectively evaluated. Of the 195 patients, 99 underwent resection of the metastasis followed by WBRT and 96 underwent WBRT alone. Seven additional potential prognostic factors were investigated: age, gender, Eastern Cooperative Oncology Group performance score, tumor type, interval between initial tumor diagnosis and WBRT, extracranial metastases, and recursive partitioning analysis class. Both treatment groups were well balanced for these factors.nnnRESULTSnOn multivariate analysis, improved survival was associated with resection (relative risk [RR], 1.20; 95% confidence interval [CI], 1.11-1.31; p < 0.001), lower recursive partitioning analysis class (RR, 1.58; 95% CI, 1.22-2.06; p < 0.001), age < or = 61 years (RR, 1.79; 95% CI, 1.23-2.61; p = 0.002), Eastern Cooperative Oncology Group performance score of 0-1 (RR, 2.47; 95% CI, 1.70-3.59; p < 0.001), and the absence of extracranial metastases (RR, 1.99; 95% CI, 1.41-2.79; p < 0.001). Improved local control was associated with resection (RR, 1.25; 95% CI, 1.11-1.41; p < 0.001) and age < or = 61 years (RR, 1.77; 95% CI, 1.09-2.88; p = 0.020). Improved brain control distant from the original site was associated with lower recursive partitioning analysis class (RR, 1.65; 95% CI, 1.03-2.69; p < 0.035), age < or = 61 years (RR, 1.81; 95% CI, 1.12-2.96; p = 0.016), and the absence of extracranial metastases (RR, 2.42; 95% CI, 1.52-3.88; p < 0.001). Improved control within the entire brain was associated with surgery (RR, 1.24; 95% CI, 1.12-1.38; p < 0.001) and age < or = 61 years (RR, 1.83; 95% CI, 1.21-2.77; p = 0.004).nnnCONCLUSIONnIn patients with a single brain metastasis, the addition of resection to WBRT improved survival, local control at the original metastatic site, and control within the entire brain, but did not prevent the development of new brain metastases distant to the original site.

Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis

BackgroundThis study investigated potential prognostic factors in patients treated with whole-brain irradiation (WBI) alone for brain metastases from relatively radioresistant tumors such as malignant melanoma, renal cell carcinoma, and colorectal cancer. Additionally, a potential benefit from escalating the radiation dose was investigated.MethodsData from 220 patients were retrospectively analyzed for overall survival and local control. Nine potential prognostic factors were evaluated: tumor type, WBI schedule, age, gender, Karnofsky performance score, number of brain metastases, extracerebral metastases, interval from diagnosis of cancer to WBI, and recursive partitioning analysis (RPA) class.ResultsSurvival rates at 6 and 12 months were 32% and 19%, respectively. In the multivariate analysis, WBI doses >30 Gy (p = 0.038), KPS ≥70 (p < 0.001), only 1-3 brain metastases (p = 0.007), no extracerebral metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved survival. Local control rates at 6 and 12 months were 37% and 15%, respectively. In the multivariate analyses, KPS ≥70 (p < 0.001), only 1-3 brain metastases (p < 0.001), and RPA class 1 (p < 0.001) were associated with improved local control. In RPA class 3 patients, survival rates at 6 months were 10% (35 of 39 patients) after 10 × 3 Gy and 9% (2 of 23 patients) after greater doses, respectively (p = 0.98).ConclusionsImproved outcomes were associated with WBI doses >30 Gy, better performance status, fewer brain metastases, lack of extracerebral metastases, and lower RPA class. Patients receiving WBI alone appear to benefit from WBI doses >30 Gy. However, such a benefit is limited to RPA class 1 or 2 patients.