Nikolaos Tselis

High-Dose-Rate Interstitial Brachytherapy as Monotherapy for Clinically Localized Prostate Cancer: Treatment Evolution and Mature Results

PURPOSE To report the clinical outcome of high-dose-rate (HDR) interstitial (IRT) brachytherapy (BRT) as sole treatment (monotherapy) for clinically localized prostate cancer. METHODS AND MATERIALS Between January 2002 and December 2009, 718 consecutive patients with clinically localized prostate cancer were treated with transrectal ultrasound (TRUS)-guided HDR monotherapy. Three treatment protocols were applied; 141 patients received 38.0 Gy using one implant in 4 fractions of 9.5 Gy with computed tomography-based treatment planning; 351 patients received 38.0 Gy in 4 fractions of 9.5 Gy, using 2 implants (2 weeks apart) and intraoperative TRUS real-time treatment planning; and 226 patients received 34.5 Gy, using 3 single-fraction implants of 11.5 Gy (3 weeks apart) and intraoperative TRUS real-time treatment planning. Biochemical failure was defined according to the Phoenix consensus, and toxicity was evaluated using Common Toxicity Criteria for Adverse Events version 3. RESULTS The median follow-up time was 52.8 months. The 36-, 60-, and 96-month biochemical control and metastasis-free survival rates for the entire cohort were 97%, 94%, and 90% and 99%, 98%, and 97%, respectively. Toxicity was scored per event, with 5.4% acute grade 3 genitourinary and 0.2% acute grade 3 gastrointestinal toxicity. Late grade 3 genitourinary and gastrointestinal toxicities were 3.5% and 1.6%, respectively. Two patients developed grade 4 incontinence. No other instance of grade 4 or greater acute or late toxicity was reported. CONCLUSION Our results confirm IRT-HDR-BRT is safe and effective as monotherapy for clinically localized prostate cancer.

Radiation therapy for painful heel spurs: results of a prospective randomized study.

Purpose:To evaluate the efficacy of two different dose-fractionation schedules for radiation therapy (RT) in patients with painful heel spurs.Patients and Methods:130 patients were randomized into two groups: the low-dose (LD) group (n = 65 heels) received a total dose of 3.0 Gy given in two weekly fractions of 0.5 Gy; in the high-dose (HD) group (n = 65 heels), two weekly fractions of 1.0 Gy were applied over 3 weeks (total dose 6.0 Gy). In 24 sites of the HD group and 17 sites of the LD group, a second RT course was given. The results were assessed using a five-level function score which was documented before RT, at the end of each RT course, and at 6 weeks and 6 months thereafter.Results:At 6-month follow-up, RT led to a highly significant reduction of symptoms in both groups. In the HD group, 31 sites were classified as excellent (score: 90–100), 13 as good (score: 70–85), twelve as moderate (score: 45–65), and nine as poor (score: 0–40). In the LD group, 35 sites were classified as excellent, eight as good, ten as moderate, and twelve as poor. The comparison of the difference of the sum score and the single criteria before RT and at 6 months after RT using the Wilcoxon-Mann-Whitney U-test revealed no statistically significant difference of response to RT between both groups.Conclusion:RT is an effective treatment option for the management of inflammatory heel spurs. The dose for an RT course should not exceed 3.0 Gy.Ziel:Prospektiv-randomisierte Untersuchung der Effektivität zweier verschiedener Dosisregime für die Strahlentherapie von Patienten mit schmerzhaften Fersenspornen.Patienten und Methodik:130 Patienten wurden in zwei Gruppen randomisiert: Die Gruppe mit niedriger Dosis (LD-Gruppe, n = 65) wurde mit 2 × 0,5 Gy pro Woche bis zu einer Gesamtdosis von 3,0 Gy pro Serie bestrahlt, die Gruppe mit höherer Dosis (HD-Gruppe, n = 65) erhielt zwei wöchentliche Fraktionen à 1,0 Gy bis zu einer Gesamtdosis von 6,0 Gy/Serie. 24 Fälle der HD-Gruppe und 17 der LD-Gruppe erhielten eine zweite Bestrahlungsserie. Die Evaluierung der Ergebnisse erfolgte anhand eines Funktionsscores vor Bestrahlungsbeginn, am Ende jeder Serie sowie 6 Wochen und 6 Monate nach der Therapie.Ergebnisse:6 Monate nach der Bestrahlung fand sich in beiden Gruppen eine hochsignifikante Verbesserung des Scores. In der HD-Gruppe wurden 31 Patienten als exzellent (Score: 90–100), 13 als gut (Score: 70–85), zwölf als zufriedenstellend (Score: 45–65) und neun als schlecht (Score: 0–40) eingestuft. In der LD-Gruppe wurden 35 Patienten als exzellent, acht als gut, 10 als zufriedenstellend und 12 als schlecht bewertet. Der Vergleich des Summenscores und Einzelkriterien mittels des Wilcoxon-Mann-Whitney-U-Tests zeigte keinen statistisch signifikanten Unterschied zwischen beiden Gruppen.Schlussfolgerung:Die Strahlentherapie ist eine effektive Therapieoption für die Behandlung entzündlicher Fersensporne. Die Gesamtdosis von 3,0 Gy pro Serie erwies sich als ausreichend.

CT-Guided Interstitial HDR Brachytherapy for Recurrent Glioblastoma Multiforme

Background and Purpose:Recurrences of glioblastoma multiforme (GBM) within previously irradiated volumes pose a serious therapeutic challenge. This retrospective study evaluates the long-term tumor control of recurrent GBM treated with interstitial high-dose-rate brachytherapy (HDR-BRT).Patients and Methods:Between 1995 and 2003, 84 patients were treated for recurrent cerebral GBM located within previously irradiated volumes. All patients had received adjuvant external radiotherapy following primary surgery, with a focal dose up to 60 Gy. The median recurrent tumor volume was 51 cm3 (3–207cm3), and the HDR-BRT consisted of an afterloading 192Ir implant which delivered a median dose of 40 Gy (30–50 Gy). Catheter implantation was implemented using interactive computed tomography (CT) guidance under local anesthesia and sedoanalgesia.Results:After a median follow-up of 61 months, 5/84 patients (6%) were alive. The median post-BRT survival was 37 weeks, and the median overall survival 78 weeks. Moderate to severe complications occurred in 5/84 cases (6%).Conclusion:For patients with recurrences of GBM within previously irradiated volumes, CT-guided interstitial HDR-BRT is a feasible treatment option that can play an important role in providing palliation.Hintergrund und Ziel:Glioblastoma-multiforme-(GBM-)Rezidive innerhalb vorbestrahlter Volumina stellen eine therapeutische Herausforderung dar. Ziel dieser Studie ist die Vorstellung der CT-gestützten interstitiellen High-Dose-Rate-Brachytherapie (HDRBRT) bei der Behandlung zerebraler GBM-Rezidive.Patienten und Methodik:Von 1995 bis 2003 wurden insgesamt 84 Patienten mit rezidiviertem GBM mittels interstitieller HDR-BRT behandelt. Alle Patienten waren voroperiert und hatten im Rahmen der Primärtherapie eine adjuvante perkutane Teilhirnbestrahlung bis 60 Gy erhalten. In der Rezidivsituation erhielten alle eine fraktionierte interstitielle 192Ir-HDR-BRT bis zu einer medianen Gesamtdosis von 40 Gy (30–50 Gy). Die Implantation der BRT-Katheter wurde bei einem medianen Tumorvolumen von 51 cm3 (3–207 cm3) unter CT-Kontrolle in Sedoanalgesie und Lokalanästhesie durchgeführt.Ergebnisse:Bei einer medianen Nachbeobachtung von 61 Monaten betrug das mediane Überleben 37 Wochen vom Zeitpunkt der Brachytherapie sowie 78 Wochen ab Diagnosestellung. Moderate bis schwerwiegende Komplikationen ereigneten sich in 5/84 Fällen (6%).Schlussfolgerung:Die CT-gestützte interstitielle HDR-BRT ist ein wertvolles Instrument für die palliative Behandlung von Patienten mit rezidiviertem GBM.

Reirradiation for Recurrent Neck Metastases of Head-and-Neck Tumors Using CT-Guided Interstitial 192Ir HDR Brachytherapy

Purpose:To report the therapeutic results obtained with CT-guided interstitial high-dose-rate brachytherapy (HDR-BRT) as exclusive treatment for recurrent neck metastases of head-and-neck tumors.Patients and Methods:Between 1995 and 1999, 49 patients with prior radiation therapy (RT) with or without surgery for primary head-and-neck tumors were treated for recurrent neck metastases located within previously irradiated volumes. All patients had fixed lymphadenopathy with a mean tumor volume of 96 cm3 (range, 15–452 cm3). There were 38 males and eleven females with a mean age of 60 years (range, 28–79 years). All patients had previously received RT as primary or adjuvant treatment with a mean dose of 54 Gy (range, 45–80 Gy). 36 patients (73%) underwent surgery, and 26 (53%) received adjuvant or palliative chemotherapy. The accelerated hyperfractionated interstitial HDR-BRT (2 × 3.0 Gy/day) delivered 30 Gy in 37/49 (75%) and 36 Gy in 12/49 implants (25%).Results:At a minimum 6-week follow-up, the response rate was 83% (41/49) with complete remission in 20% (10/49) and partial remission in 63% (31/49) of the implanted tumor sites. 8/49 patients (17%) did not respond to the treatment. After 19 months of median follow-up, the local control rate was 69% and a total of 15/49 patients (30%) experienced local disease progression. Of these, nine (18%) had locoregional progression and six (12%) progression within the treated volume. The median post-BRT survival was 14 months. The overall survival rate was 52% at 1 year, 31% at 2 years, and 6% at 3 years.Conclusion:In patients with recurrent cervical lymphadenopathy of head-and-neck tumors, exclusive interstitial HDR-BRT can provide palliation and tumor control.Ziel:Vorstellung der CT-gestützten interstitiellen High-Dose-Rate-Brachytherapie (HDR-BRT) als ausschließliches Therapieverfahren in der Behandlung zervikaler Lymphknotenrezidive von Kopf-Hals-Tumoren.Patienten und Methodik:Zwischen 1995 und 1999 wurden insgesamt 49 Patienten mit zervikalen Lymphknotenrezidiven behandelt. Alle 49 Patienten (38 männlich, elf weiblich, Durchschnittsalter 60 Jahre [28–79 Jahre]) waren mit einer durchschnittlichen Zielvolumendosis von 54 Gy (45–80 Gy) vorbestrahlt, und 36 (73%) waren voroperiert. Eine adjuvante oder palliative Chemotherapie war bei 26 Patienten (53%) durchgeführt worden. Alle Patienten erhielten eine akzeleriert-hyperfraktionierte BRT (2 × 3 Gy/Tag) bis zu einer Gesamtdosis von 30 Gy in 37/49 (75%) und 36 Gy in 12/49 Implantaten (25%). Das durchschnittliche Tumorvolumen betrug 96 cm3 (15–452 cm3).Ergebnisse:Die Ansprechrate nach 6 Wochen betrug 83%. Bei 10/49 Patienten (20%) wurde eine komplette Remission, bei 31/49 (63%) eine partielle Remission erzielt. 8/49 (17%) zeigten kein Ansprechen bzw. eine lokale Progredienz. Nach einer medianen Nachbeobachtungszeit von 19 Monaten betrug die lokale Kontrollrate 69%, bei 15/49 Patienten (30%) lag ein Tumorprogress vor. Dabei zeigten 9/15 (60%) eine lokoregionäre Progression. Lediglich bei 6/15 (40%) handelte es sich um echte In-loco-Rezidive, die innerhalb des BRT-Volumens gelegen waren. Das mediane Überleben betrug 14 Monate, die Gesamtüberlebensrate nach 1 Jahr 52%, nach 2 Jahren 31% und nach 3 Jahren 6%.Schlussfolgerung:Die CT-gestützte interstitielle HDR-BRT ist ein wertvolles Instrument für die palliative Behandlung von Patienten mit Halslymphknotenrezidiven bei Kopf-Hals-Tumoren.

Prognostic value of combined triple-reverse transcription-PCR analysis for prostate-specific antigen, human kallikrein 2, and prostate-specific membrane antigen mRNA in Peripheral blood and lymph nodes of prostate cancer patients

Purpose: We present the largest study of both peripheral blood and lymph node samples examining the utility of reverse transcription-polymerase chain reaction (RT-PCR) for established molecular markers as a diagnostic tool in the molecular staging of prostate cancer patients undergoing radical prostatectomy. Experimental Design: Peripheral blood from 358 patients was obtained before radical prostatectomy. Corresponding obturatory lymph node samples were collected from 153 of these patients. Nested RT-PCR for prostate-specific antigen (PSA), human kallikrein 2 (hK2), and prostate-specific membrane antigen (PSMA) were performed on cDNA from peripheral blood. The lymph node cDNA was analyzed for PSA und hK2 expression. Results: RT-PCR in peripheral blood was positive in 124 (34.6%) of 358 samples for PSA, 215 (60.1%) of 358 for PSMA, and 97 (27.1%) of 358 for hK2. Comparison of positive RT-PCR rates of pT2 and pT3 tumors in corresponding peripheral blood for PSA, PSMA, and hK2 were 31.9 and 40.0%, 58.8 and 62.5%, and 26.9 and 27.5%, respectively. Histopathologically, cancer-free lymph node samples were positive in RT-PCR for PSA and hK2 in 70 (49.6%) of 141 and 89 (63.2%) of 141 of cases. All histologically positive lymph node samples (n = 12, pN+) were positive for PSA RT-PCR. PSA RT-PCR alone, as well as combined PSA/PSMA RT-PCR evaluation, in peripheral blood showed a significant association with grading. PSA RT-PCR lymph node-negative samples were significantly less likely positive in their corresponding peripheral blood RT-PCR sample. Conclusions Although the preoperative PSA RT-PCR in peripheral blood correlated with the grading of prostate cancer, no combination of RT-PCR results using “triple” markers (PSA, hK2, PSMA) in peripheral blood and/or lymph nodes yielded additional preoperative staging information.

In vivo thermoluminescence dosimetry dose verification of transperineal 192Ir high-dose-rate brachytherapy using CT-based planning for the treatment of prostate cancer

PURPOSE To evaluate the potential of in vivo thermoluminescence dosimetry to estimate the accuracy of dose delivery in conformal high-dose-rate brachytherapy of prostate cancer. METHODS AND MATERIALS A total of 50 LiF, TLD-100 cylindrical rods were calibrated in the dose range of interest and used as a batch for all fractions. Fourteen dosimeters for every treatment fraction were loaded in a plastic 4F catheter that was fixed in either one of the 6F needles implanted for treatment purposes or in an extra needle implanted after consulting with the patient. The 6F needles were placed either close to the urethra or in the vicinity of the median posterior wall of the prostate. Initial results are presented for 18 treatment fractions in 5 patients and compared to corresponding data calculated using the commercial treatment planning system used for the planning of the treatments based on CT images acquired postimplantation. RESULTS The maximum observed mean difference between planned and delivered dose within a single treatment fraction was 8.57% +/- 2.61% (root mean square [RMS] errors from 4.03% to 9.73%). Corresponding values obtained after averaging results over all fractions of a patient were 6.88% +/- 4.93% (RMS errors from 4.82% to 7.32%). Experimental results of each fraction corresponding to the same patient point were found to agree within experimental uncertainties. CONCLUSIONS Experimental results indicate that the proposed method is feasible for dose verification purposes and suggest that dose delivery in transperineal high-dose-rate brachytherapy after CT-based planning can be of acceptable accuracy.

The Importance of Tumor Volume in the Prognosis of Patients with Glioblastoma

Background and Purpose:The importance of tumor volume as a prognostic factor in high-grade gliomas is highly controversial and there are numerous methods estimating this parameter. In this study, a computer-based application was used in order to assess tumor volume from hard copies and a survival analysis was conducted in order to evaluate the prognostic significance of preoperative volumetric data in patients harboring glioblastomas.Patients and Methods:50 patients suffering from glioblastoma were analyzed retrospectively. Tumor volume was determined by the various geometric models as well as by an own specialized software (Volumio). Age, performance status, type of excision, and tumor location were also included in the multivariate analysis.Results:The spheroid and rectangular models overestimated tumor volume, while the ellipsoid model offered the best approximation. Volume failed to attain any statistical significance in prognosis, while age and performance status confirmed their importance in progression-free and overall survival of patients.Conclusion:Geometric models provide a rough approximation of tumor volume and should not be used, as accurate determination of size is of paramount importance in order to draw safe conclusions in oncology. Although the significance of volumetry was not disclosed, further studies are definitely required.Hintergrund und Ziel:Die Bedeutung des Tumorvolumens als prognostischer Faktor fur maligne Gliome ist nach wie vor umstritten. In dieser Studie wurden eine computerbasierte Methode zur Beurteilung des Tumorvolumens anhand von magnetresonanztomographischen Bildern bei Patienten mit Glioblastoma multiforme (GBM) durchgefuhrt und mittels einer Uberlebensanalyse die prognostische Bedeutung praoperativer volumetrischer Daten untersucht.Patienten und Methodik:50 Patienten mit GBM, welche zwei unterschiedliche Chemotherapieregime erhalten hatten, wurden retrospektiv analysiert und die Tumorvolumina durch verschiedene geometrische Modelle sowie eine spezielle Software (Volumio) gemessen. Alter, Performance-Status, Tumorlokalisation sowie Art der Exzision wurden in der multivariaten Uberlebensanalyse berucksichtigt.Ergebnisse:Die angewandten spharoiden und rektangularen geometrischen Modelle uberschatzten das Tumorvolumen, wohingegen die ellipsoiden Modelle die beste Annaherung im Vergleich zu Volumio ermoglichten. Das Tumorvolumen erwies sich nicht als statistisch signifikanter Prognosefaktor. In der multivariaten Analyse bestatigte sich die Bedeutung des Alters und des Performance-Status fur das progressionsfreie Uberleben und das Gesamtuberleben der Patienten.Schlussfolgerung:Geometrische Modelle bieten eine ungenaue Messung des Tumorvolumens und sollten in der klinischen Praxis nicht zur Anwendung kommen, zumal die prazise Erfassung der Tumorgrose von entscheidender onkologischer Bedeutung ist. Obwohl die vorgelegten Daten den Einfluss des Tumorvolumens als statistisch nicht signifikant zeigten, sind weitere Studien bezuglich der Bedeutung dieses Parameters notwendig.

Hypofractionated accelerated CT-guided interstitial 192Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer

BACKGROUND Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC. PATIENTS AND METHODS From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0-36.0 Gy) in twice-daily fractions of 2.0-5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0-36.0 Gy) in once-daily fractions of 6.0-10.0 Gy in three patients. RESULTS The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III-IV complications occurred in 13% of patients. CONCLUSIONS In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control.

The importance of tumor volume in the prognosis of patients with glioblastoma: comparison of computerized volumetry and geometric models.

Background and Purpose:The importance of tumor volume as a prognostic factor in high-grade gliomas is highly controversial and there are numerous methods estimating this parameter. In this study, a computer-based application was used in order to assess tumor volume from hard copies and a survival analysis was conducted in order to evaluate the prognostic significance of preoperative volumetric data in patients harboring glioblastomas.Patients and Methods:50 patients suffering from glioblastoma were analyzed retrospectively. Tumor volume was determined by the various geometric models as well as by an own specialized software (Volumio). Age, performance status, type of excision, and tumor location were also included in the multivariate analysis.Results:The spheroid and rectangular models overestimated tumor volume, while the ellipsoid model offered the best approximation. Volume failed to attain any statistical significance in prognosis, while age and performance status confirmed their importance in progression-free and overall survival of patients.Conclusion:Geometric models provide a rough approximation of tumor volume and should not be used, as accurate determination of size is of paramount importance in order to draw safe conclusions in oncology. Although the significance of volumetry was not disclosed, further studies are definitely required.Hintergrund und Ziel:Die Bedeutung des Tumorvolumens als prognostischer Faktor fur maligne Gliome ist nach wie vor umstritten. In dieser Studie wurden eine computerbasierte Methode zur Beurteilung des Tumorvolumens anhand von magnetresonanztomographischen Bildern bei Patienten mit Glioblastoma multiforme (GBM) durchgefuhrt und mittels einer Uberlebensanalyse die prognostische Bedeutung praoperativer volumetrischer Daten untersucht.Patienten und Methodik:50 Patienten mit GBM, welche zwei unterschiedliche Chemotherapieregime erhalten hatten, wurden retrospektiv analysiert und die Tumorvolumina durch verschiedene geometrische Modelle sowie eine spezielle Software (Volumio) gemessen. Alter, Performance-Status, Tumorlokalisation sowie Art der Exzision wurden in der multivariaten Uberlebensanalyse berucksichtigt.Ergebnisse:Die angewandten spharoiden und rektangularen geometrischen Modelle uberschatzten das Tumorvolumen, wohingegen die ellipsoiden Modelle die beste Annaherung im Vergleich zu Volumio ermoglichten. Das Tumorvolumen erwies sich nicht als statistisch signifikanter Prognosefaktor. In der multivariaten Analyse bestatigte sich die Bedeutung des Alters und des Performance-Status fur das progressionsfreie Uberleben und das Gesamtuberleben der Patienten.Schlussfolgerung:Geometrische Modelle bieten eine ungenaue Messung des Tumorvolumens und sollten in der klinischen Praxis nicht zur Anwendung kommen, zumal die prazise Erfassung der Tumorgrose von entscheidender onkologischer Bedeutung ist. Obwohl die vorgelegten Daten den Einfluss des Tumorvolumens als statistisch nicht signifikant zeigten, sind weitere Studien bezuglich der Bedeutung dieses Parameters notwendig.

4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery.

PURPOSE Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. METHODS The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 = PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. RESULTS The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205-1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. CONCLUSIONS Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol.