Harun Badakhshi

Testicular Dose in Prostate Cancer Radiotherapy Impact on Impairment of Fertility and Hormonal Function

Purpose:To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature.Patients and Methods:The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated.Results:The mean total dose (± standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (± 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (± 145 cGy). The results of this study are appraised with the available data in the literature.Conclusion:The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.Ziel:Bestimmung der Strahlendosis an ungeschützten Hoden während einer Serie mit 20-MV-Photonen und konventioneller externer Strahlentherapie bei Patienten mit lokalisiertem Prostatakarzinom. Kritische Evaluation des potentiellen Einflusses auf Fertilität und hormonale Störungen dieser Patienten anhand der Literatur.Patienten und Methodik:Die absolute Hodendosis von 20 zufällig ausgewählten Patienten, die sich einer Strahlentherapie bei Prostatakarzinom unterzogen, wurde mittels Thermolumineszenzdosimetrie gemessen. Alle Patienten wurden in Rückenlage, mit einem Immobilisationskissen unter den Knien stabilisiert, behandelt. Flexible Katheter, die jeweils drei kalibrierte Thermolumineszenzdosimeter (TLD) enthielten, wurden täglich abwechselnd auf oder unter dem Hoden fixiert, der dem Perineum am nächsten lag. Die tägliche Einzeldosis für das Planungszielvolumen betrug 1,8 Gy. Zehn aufeinander folgende Hodenmessungen wurden für jeden Patienten durchgeführt. Die individuellen TLD wurden ausgewertet und die absorbierte Gesamtdosis berechnet.Ergebnisse:Die mittlere Gesamtdosis (± Standardabweichung), welche während der Serie von 10 aufeinander folgenden Behandlungstagen gemessen wurde, betrug 49 cGy (± 36 cGy). Die Hochrechnung auf eine Serie von 40 Fraktionen externer Radiatio betrug 196 cGy (± 145 cGy). Die Ergebnisse werden unter Einschluss der verfügbaren Literatur bewertet.Schlussfolgerung:Die während einer Bestrahlungsserie bei Prostatakarzinompatienten von den Hoden absorbierte Strahlendosis kann als Ursache eines erhöhten Risikos für eine bleibende Infertilität und hormonale Störung angesehen werden.

Testicular Dose in Prostate Cancer Radiotherapy

Purpose:To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature.Patients and Methods:The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated.Results:The mean total dose (± standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (± 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (± 145 cGy). The results of this study are appraised with the available data in the literature.Conclusion:The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.Ziel:Bestimmung der Strahlendosis an ungeschützten Hoden während einer Serie mit 20-MV-Photonen und konventioneller externer Strahlentherapie bei Patienten mit lokalisiertem Prostatakarzinom. Kritische Evaluation des potentiellen Einflusses auf Fertilität und hormonale Störungen dieser Patienten anhand der Literatur.Patienten und Methodik:Die absolute Hodendosis von 20 zufällig ausgewählten Patienten, die sich einer Strahlentherapie bei Prostatakarzinom unterzogen, wurde mittels Thermolumineszenzdosimetrie gemessen. Alle Patienten wurden in Rückenlage, mit einem Immobilisationskissen unter den Knien stabilisiert, behandelt. Flexible Katheter, die jeweils drei kalibrierte Thermolumineszenzdosimeter (TLD) enthielten, wurden täglich abwechselnd auf oder unter dem Hoden fixiert, der dem Perineum am nächsten lag. Die tägliche Einzeldosis für das Planungszielvolumen betrug 1,8 Gy. Zehn aufeinander folgende Hodenmessungen wurden für jeden Patienten durchgeführt. Die individuellen TLD wurden ausgewertet und die absorbierte Gesamtdosis berechnet.Ergebnisse:Die mittlere Gesamtdosis (± Standardabweichung), welche während der Serie von 10 aufeinander folgenden Behandlungstagen gemessen wurde, betrug 49 cGy (± 36 cGy). Die Hochrechnung auf eine Serie von 40 Fraktionen externer Radiatio betrug 196 cGy (± 145 cGy). Die Ergebnisse werden unter Einschluss der verfügbaren Literatur bewertet.Schlussfolgerung:Die während einer Bestrahlungsserie bei Prostatakarzinompatienten von den Hoden absorbierte Strahlendosis kann als Ursache eines erhöhten Risikos für eine bleibende Infertilität und hormonale Störung angesehen werden.

Influence of Organ at Risk Definition on Rectal Dose-Volume Histograms in Patients with Prostate Cancer Undergoing External-Beam Radiotherapy

Purpose:To evaluate rectal dose-volume relations during three-dimensional conformal radiotherapy of patients with prostate cancer by means of different rectal volume contours.Patients and Methods:55 patients with prostate cancer underwent three-dimensional conformal external-beam radiotherapy. Rectal dose-volume histograms were calculated for four separately contoured rectal volumes in all patients resulting in four groups. In group 1 the outer rectal wall was contoured two CT slices above and below the planning target volume. The rectal contour of group 2 was drawn from the anal verge up to the sigmoid. Furthermore, the posterior half of the rectum was contoured for both volumes mentioned above (groups 1a and 2a). Statistical analysis was then performed using nonparametric Wilcoxon tests.Results:The mean target dose was 72.9 Gy (standard deviation [SD] ± 2.1 Gy). The minimum target dose was 70.2 Gy. Mean rectum dose (± SD) over all patients was 50.7 Gy (± 4.6 Gy), 45.2 Gy (± 5.4 Gy), 43.2 Gy (± 4.2 Gy), and 38.7 Gy (± 5.5 Gy) for group 1, 2, 1a, and 2a, respectively. The corresponding volumes receiving ≥ 70 Gy for groups 1 and 2 were 14.0% (± 5.3%) and 11.9% (± 4.5%). These differences were statistically significant. Comparison of minimum and mean rectal dose also revealed a statistically significant difference toward higher doses in groups 1 and 1a (p < 0.001). Maximum rectal doses for groups 1 and 2 as well as for groups 1a and 2a revealed no statistically significant difference (p = 1.0).Conclusion:Data from the literature on normal-tissue complication probability (rectal bleeding) refer to different rectal contours. When applying dose restrictions to the rectum, contouring becomes a significant factor that determines the risk of rectal toxicity. The results of this study show that different ways of rectal contouring significantly influence doses to the rectum. The influence of organ at risk contouring should be considered thoroughly in conformal radiotherapy of prostate cancer patients, especially in dose escalation studies. It is recommended to calculate the doses for absolute rectal volumes and correlate these data with toxicity in order to be able to achieve comparable results among different institutions.Ziel:Aufzeigen unterschiedlicher rektaler Dosis-Volumen-Verhältnisse in der dreidimensionalen konformalen Strahlentherapie von Patienten mit Prostatakarzinom mittels verschiedener Konturierungen des rektalen Volumens.Patienten und Methodik:55 Patienten mit Prostatakarzinom erhielten eine dreidimensionale konformale Strahlentherapie. Für alle Patienten wurden rektale Dosis-Volumen-Histogramme für unterschiedliche Rektumkonturierungen angefertigt. Die unterschiedlichen Konturierungen dieser vier Gruppen waren wie folgt: In Gruppe 1 wurde die Rektumaußenkontur für den Bereich des Planungszielvolumens (PTV) plus zwei CT-Schichten ober- und unterhalb des PTV festgelegt. Die Rektumkontur der Gruppe 2 wurde vom Analring bis zum rektosigmoidalen Übergang markiert. Als weitere Risikoorgankontur wurde die dorsale Hälfte des Rektums für beide o.g. Volumina definiert, so dass sich daraus die Gruppen 1a und 2a ergaben. Die Ergebnisse der Dosis-Volumen- Berechnungen wurden mittels Wilcoxon-Tests für nichtparametrische Stichproben analysiert.Ergebnisse:Die mittlere Zielvolumendosis betrug 72,9 Gy (Standardabweichung [SD] ± 2,1 Gy). Die minimale Zielvolumendosis lag bei 70,2 Gy. Die mittlere Rektumdosis (± SD) über alle Patienten betrug 50,7 Gy (± 4,6 Gy), 45,2 Gy (± 5,4 Gy), 43,2 Gy (± 4,2 Gy) und 38,7 Gy (± 5,5 Gy) für die Gruppen 1, 2, 1a und 2a. Die berechneten Risikoorganvolumina, welche eine Dosis von ≥ 70 Gy erhielten, betrugen für die Gruppen 1 und 2 14,0% (± 5,3%) und 11,9% (± 4,5%). Diese Unterschiede waren statistisch signifikant. Auch der Vergleich der minimalen und mittleren Zielvolumendosis ergab einen statistisch signifikanten Unterschied zu höheren Dosen für die Gruppen 1 and 1a (p < 0,001). Die maximalen Rektumdosen im Vergleich der Gruppen 1 und 2 sowie der Gruppen 1a und 2a ergaben keinen signifikanten Unterschied (p = 1,0).Schlussfolgerung:Daten der Literatur bezüglich der Komplikationswahrscheinlichkeit für rektale Blutungen beziehen sich auf unterschiedliche Rektumvolumina. Bei der Festlegung von Dosisrestriktionen für das Risikoorgan Rektum kommt der Art der Rektumvolumendefinition für das Risiko rektaler Toxizität eine entscheidende Bedeutung zu. Die Ergebnisse dieser Studie zeigen, dass die Unterschiede der Rektumvolumendefinition einen signifikanten Einfluss auf die Dosisbelastung des Rektums haben. Der Einfluss der Risikoorgankonturierung muss bei der konformalen Strahlentherapie des Prostatakarzinoms sorgfältig berücksichtigt werden, insbesondere bei der Dosiseskalation. Es wird empfohlen, die Dosisbelastung für absolute Rektumvolumina zu berechnen und diese mit der Toxizität zu korrelieren, um die Ergebnisse verschiedener Institutionen vergleichbar zu machen.

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.

Oligometastases: the new paradigm and options for radiotherapy. A critical review

Traditional oncology distinguishes between two separate and incommensurable states in the evolution of solid malignancies: the localized disease, which is curable; and the disseminated status, which is per se palliative. Recently, a huge body of evidence suggests a fundamental change in the understanding of cancer, indicating an intermediate state in the trajectory of solid malignancies: the oligometastatic state. The following review will critically analyse existing hypotheses and facts from the basic sciences and try to contextualize it in regard to the clinical evidence available to date. Consecutively, it will try to draw possible clinical consequences for application of radiotherapy in this specific clinical scenario.ZusammenfassungDie traditionelle Onkologie trennt hinsichtlich therapeutischer Optionen zwei grundlegend unterschiedliche klinische Situationen: die lokalisierte Erkrankung mit kurativen Therapiechancen und die disseminierte Situation mit nur noch palliativen Lösungen. Die aktuelle Datenlage suggeriert die Notwendigkeit der Adaptation unseres klinischen Verständnisses onkologischer Erkrankungen im Sinne des Vorliegens einer intermediären, nämlich oligometastasierten Situation. Diese Arbeit setzt sich kritisch mit den Hypothesen und dem Wissen der Grundlagenforschung auseinander und kontextualisiert die vorliegende klinische Evidenz. Ziel ist die Auslotung der Radiotherapieoptionen für oligometastasierte Patienten.

Oligometastases: the new paradigm and options for radiotherapy

Traditional oncology distinguishes between two separate and incommensurable states in the evolution of solid malignancies: the localized disease, which is curable; and the disseminated status, which is per se palliative. Recently, a huge body of evidence suggests a fundamental change in the understanding of cancer, indicating an intermediate state in the trajectory of solid malignancies: the oligometastatic state. The following review will critically analyse existing hypotheses and facts from the basic sciences and try to contextualize it in regard to the clinical evidence available to date. Consecutively, it will try to draw possible clinical consequences for application of radiotherapy in this specific clinical scenario.ZusammenfassungDie traditionelle Onkologie trennt hinsichtlich therapeutischer Optionen zwei grundlegend unterschiedliche klinische Situationen: die lokalisierte Erkrankung mit kurativen Therapiechancen und die disseminierte Situation mit nur noch palliativen Lösungen. Die aktuelle Datenlage suggeriert die Notwendigkeit der Adaptation unseres klinischen Verständnisses onkologischer Erkrankungen im Sinne des Vorliegens einer intermediären, nämlich oligometastasierten Situation. Diese Arbeit setzt sich kritisch mit den Hypothesen und dem Wissen der Grundlagenforschung auseinander und kontextualisiert die vorliegende klinische Evidenz. Ziel ist die Auslotung der Radiotherapieoptionen für oligometastasierte Patienten.

Preoperative irradiation for the prevention of heterotopic ossification induces local inflammation in humans

Radiation of the hip is an established method to prevent heterotopic ossification (HO) following total hip arthroplasty (THA) but the precise mechanism is unclear. As inflammatory processes are suggested to be involved in the pathogenesis of HO, we hypothesized that the preoperative irradiation impacts local immune components. Therefore, we quantified immune cell populations and cytokines in hematomas resulting from the transection of the femur in two groups of patients receiving THA: patients irradiated preoperatively (THA-X-hematoma: THA-X-H group) in the hip region (7 Gy) in order to prevent HO and patients who were not irradiated (THA-H group) but were postoperatively treated with non-steroidal anti-inflammatory drugs (NSAIDs). Radiation resulted in significantly increased frequencies of T cells, cytotoxic T cells, NKT cells and CD25+CD127- Treg cells, whereas the number of naive CD45RA-expressing cytotoxic T cells was reduced. These results indicate differential immune cell activation, corroborated by our findings of significantly higher concentrations of pro-inflammatory cytokines (e.g., IL-6, IFNγ) and chemokines (e.g., MCP-1, RANTES) in the THA-X-H group as compared to THA-H group. In contrast, the concentration of the angiogenic VEGF was significantly suppressed in the THA-X-H group. We conclude that preoperative irradiation results in significant changes in immune cell composition and cytokine secretion in THA-hematomas, establishing a specific - rather proinflammatory - milieu. This increase of inflammatory activity together with the observed suppression in VEGF secretion may contribute to the prevention of HO.

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

IntroductionMagnetic resonance imaging (MRI) and computed tomography (CT) with 68Ga-DOTATOC positron emission tomography (68Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.MethodsFifty patients with 56 meningiomas of the SB underwent MRI, CT, and 68Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) or PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.ResultsWithin the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm3, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm3).Conclusions68Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.

Results for local control and functional outcome after linac-based image-guided stereotactic radiosurgery in 190 patients with vestibular schwannoma

Background We assessed local control (LC) and functional outcome after linac-based stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). Methods Between 1998 and 2008, 190 patients with VS were treated with SRS. All patients had tumors <2 cm diameter. Patients received 13.5 Gy prescribed to the 80th isodose at the tumor margin. The primary endpoint was LC. Secondary endpoints were symptomatic control and morbidity. Results Median follow-up was 40 months. LC was achieved in 88% of patients. There were no acute reactions exceeding Grade I. Trigeminal nerve dysfunction was present in 21.6% (n = 41) prior to SRS. After treatment, 85% (n = 155) had no change, 4.4,% (n = 8) had a relief of symptoms, 10.4% (n = 19) had new symptoms. Facial nerve dysfunction was present in some patients prior to treatment, e.g. paresis (12.6%; n = 24) and dysgeusia (0.5%; n = 1). After treatment 1.1% (n = 2) reported improvement and 6.1% (n = 11) experienced new symptoms. Hearing problems before SRS were present in 69.5% of patients (n = 132). After treatment, 62.6% (n = 144) had no change, 10.4% (n = 19) experienced improvement and 26.9% (n = 49) became hearing impaired. Conclusion This series of SRS for small VS provided similar LC rates to microsurgery; thus, it is effective as a non-invasive, image-guided procedure. The functional outcomes observed indicate the safety and effectiveness of linac-based SRS. Patients may now be informed of the clinical equivalence of SRS to microsurgery.

Dosimetric comparison of different treatment modalities for stereotactic radiosurgery of meningioma

The original version of this article unfortunately contained mistakes. The name of Constantin Tulaesca is misspelled, it should be Constantin Tuleasca. The correct affiliation of C. Tuleasca and M. Levivier should be: Lausanne University Hospital, Neurosurgery Service and Gamma Knife Center; University of Lausanne, Faculty of Biology and Medicine On the third page, Subtitle “Patient population”, lines 18 and 19: “Gamma Knife planning and optimalisation was performed by Thierry Gevaert” should be: “Gamma Knife planning and optimalisation was performed by Marc Levivier”.