Philippe Nickers

A Dosimetric Selectivity Intercomparison of HDR Brachytherapy, IMRT and Helical Tomotherapy in Prostate Cancer Radiotherapy

Background and Purpose:Dose escalation in order to improve the biochemical control in prostate cancer requires the application of irradiation techniques with high conformality. The dosimetric selectivity of three radiation modalities is compared: high-dose-rate brachytherapy (HDR-BT), intensity-modulated radiation radiotherapy (IMRT), and helical tomotherapy (HT).Patients and Methods:Ten patients with prostate adenocarcinoma treated by a 10-Gy HDR-BT boost after external-beam radiotherapy were investigated. For each patient, HDR-BT, IMRT and HT theoretical treatment plans were realized using common contour sets. A 10-Gy dose was prescribed to the planning target volume (PTV). The PTVs and critical organs’ dose-volume histograms obtained were compared using Student’s t-test.Results:HDR-BT delivers spontaneously higher mean doses to the PTV with smaller cold spots compared to IMRT and HT. 33% of the rectal volume received a mean HDR-BT dose of 3.86 ± 0.3 Gy in comparison with a mean IMRT dose of 6.57 ± 0.68 Gy and a mean HT dose of 5.58 ± 0.71 Gy (p < 0.0001). HDR-BT also enables to better spare the bladder. The hot spots inside the urethra are greater with HDR-BT. The volume of healthy tissue receiving 10% of the prescribed dose is reduced at least by a factor of 8 with HDR-BT (p < 0.0001).Conclusion:HDR-BT offers better conformality in comparison with HT and IMRT and reduces the volume of healthy tissue receiving a low dose.Hintergrund und Ziel:Eine Dosiseskalation zur Steigerung der biochemischen Kontrollraten beim Prostatakarzinom erfordert die Anwendung von Bestrahlungstechniken, die eine hohe Dosiskonformität ermöglichen. Verglichen wird die dosimetrische Selektivität von drei Bestrahlungsmodalitäten: High-Dose-Rate-Brachytherapie (HDR-BT), intensitätsmodulierte Radiotherapie (IMRT) und helikale Tomotherapie (HT).Patienten und Methodik:Zehn Patienten mit einem Adenokarzinom der Prostata, die im Anschluss an eine perkutane Radiotherapie einen Boost von 10 Gy in Form einer HDR-BT erhielten, wurden untersucht. Für jeden dieser Patienten wurden Bestrahlungspläne für eine HDR-BT, eine IMRT und eine HT unter Anwendung gemeinsamer Konturierungsverfahren erstellt. Für das Planungszielvolumen (PTV) wurden 10 Gy verordnet. Die ermittelten jeweiligen PTV und Dosis-Volumen-Histogramme für die kritischen Organe wurden mittels Student-t-Test miteinander verglichen.Ergebnisse:Die HDR-BT führt zu höheren mittleren Dosen im PTV mit kleineren Cold Spots als die IMRT oder HT. 33% des bestrahlten Volumens des Rektums erhielten bei der HDR-BT eine mittlere Dosis von 3,86 ± 0,3 Gy im Vergleich zu 6,57 ± 0,68 Gy bei der IMRT und 5,58 ± 0,71 Gy bei der HT (p < 0,0001). Die HDR-BT ermöglicht eine bessere Schonung der Harnblase. Die Dosisspitzen (Hot Spots) an der Urethra sind jedoch bei der HDR-BT höher. Das Volumen des gesunden Gewebes, das 10% der vorgeschriebenen Dosis erhält, wird bei Anwendung der HDR-BT etwa um den Faktor 8 verringert (p < 0,0001).Schlussfolgerung:Die HDR-BT führt zu einer günstigeren Dosiskonformität im Vergleich zur HT und zur IMRT und reduziert so das mit einer niedrigen Dosis belastete Volumen gesunden Gewebes.

Which α/β ratio and half-time of repair are useful for predicting outcomes in prostate cancer?

PURPOSE To calculate the α/β of prostate adenocarcinoma. MATERIALS AND METHODS From January 1997 to December 2005, 328 patients were treated consecutively with external beam radiotherapy and brachytherapy boost. The patients with at least one of the following adverse prognostic factors were included: PSA>10 ng/ml, Gleason score ≥7, T≥2B. A total EQD2 of 80 Gy was delivered uniformly within the same timeframe. Prior to August 2002, the patients were treated to low-dose-rate brachytherapy using (192)Ir (n=201), and those treated thereafter received a high-dose-rate brachytherapy boost (n=127). The equivalency of dose was established using the incomplete repair model, with generally accepted α/β ratio of 3 Gy, and half-time for repair of sublethal damage (HTR) of 1.5h. RESULTS In a Cox proportional hazards model, the two groups displayed no difference (HR: 0.99, 95% CI: 0.87-1.1, p=0.98) in biochemical control. Analyzing using the linear quadratic model, the data fit well an α/β ratio of 3.41 Gy (95% CI: 2.56-4.26) and the recently published HTR of 1.9 h (95% CI: 1.4-2.4), but also an α/β of 5.87 Gy (95% CI: 4.67-7.07) and the more widely established HTR of 1.5 h. CONCLUSIONS Unlike the previously published data, calculation of the α/β ratio from consecutive patients and using a uniform treatment duration points to higher values than 2.5 Gy.

DOSIMETRIC COMPARISON OF HIGH-DOSE-RATE BRACHYTHERAPY AND INTENSITY-MODULATED RADIATION THERAPY AS A BOOST TO THE PROSTATE

PURPOSE We compared the dose conformity of two radiation modalities: high-dose-rate brachytherapy (HDR BT) and intensity-modulated radiation therapy (IMRT) to deliver a boost to the prostate after external beam radiotherapy (EBRT). METHODS AND MATERIALS Ten successive patients with prostate adenocarcinoma treated with a single 10-Gy HDR BT boost after EBRT were investigated. Four theoretical IMRT plans were computed: (a) 32.85 Gy IMRT and (b) 26 Gy IMRT with CTV-PTV expansions, doses corresponding to the equivalent dose in 2-Gy fractions (EQD2) of one 10-Gy fraction calculated with a prostate alpha/beta ratio of respectively 1.5 and 3 Gy; and (c) 32.85 Gy IMRT and (d) 26 Gy IMRT without CTV-PTV expansions. The dose-volume histogram values converted in EQD2 with an alpha/beta ratio of 3 Gy for the organs at risk were compared. RESULTS The HDR BT plan delivered higher mean doses to the PTV compared with IMRT plans. In all, 33% of the rectal volume received a mean dose of 5.32 +/- 0.65 Gy and 20% of bladder volume received 4.61 +/- 1.24 Gy with HDR BT. In comparison, doses delivered with IMRT were respectively 13.4 +/- 1.49 Gy and 10.81 +/- 4 Gy, even if only 26 Gy was prescribed to the PTV with no CTV-PTV expansion (p < 0.0001). The hot spots inside the urethra were greater with HDR BT but acceptable. CONCLUSIONS Use of HDR BT produced a more conformal plan for the boost to the prostate than IMRT even without CTV-PTV expansions.

Can intensity-modulated Radiation therapy of the paraaortic region overcome the problems of critical organ tolerance?

Background and Purpose:The recent RTOG guidelines for future clinical developments in gynecologic malignancies included the investigation of dose escalation in the paraaortic (PO) region which is, however, very difficult to target due to the presence of critical organs such as kidneys, liver, spinal cord, and digestive structures. The aim of this study was to investigate intensity-modulated radiotherapy’s (IMRT) possibilites of either increasing, in a safe way, the dose to 50–60 Gy in case of macroscopic disease or decreasing the dose to organs at risk (OR) when treatment is given in an adjuvant setting.Material and Methods:The dosimetric charts of 14 patients irradiated to the PO region at the Department of Radiation Oncology, University Hospital of Liège, Belgium, in 2000 were analyzed in order to compare six-field conformal external-beam radiotherapy (CEBR) and five-beam IMRT approaches. Both CEBR and IMRT investigations were planned to theoretically deliver 60 Gy to the PO region in the safest way possible. Dose-volume histograms (DVHs) were calculated for clinical target volume (CTV), planning target volume (PTV), and OR. Student’s t-test was used to compare the paired DVH data issued from CEBR and IMRT planning.Results:The IMRT approach allowed to cover the PTV at a higher level as compared to CEBR. Using IMRT, the maximal dose to the spinal cord was reduced from 42.5 Gy to 26.2 Gy in comparison with CEBR (p < 0.00001). Doses to the kidneys were significantly reduced, with < 20% receiving ≥ 20 Gy in the IMRT approach (p < 0.00001). Irradiation of digestive structures was not different, with < 25% receiving 35 Gy. Doses to the liver remained low regardless of the method used.Conclusion:At 60 Gy, IMRT is largely sparing the spinal cord and kidneys as compared to CEBR and represents an interesting approach not only for dose escalation up to 50–60 Gy (probably facilitating the radiochemotherapy approaches) but also in an adjuvant setting at lower doses. The dosimetric data of this study are in the same range as those published recently with a dynamic arc conformal approach.Hintergrund und Ziel:Die Erstellung der aktuellen RTOG-Leitlinien für klinische Entwicklungen in der gynäkologischen Onkologie erforderten auch Untersuchungen zur Strahlendosiseskalation in der paraaortalen (PO-) Region, die wegen der Nähe gefährdeter Organe wie Niere, Leber, Rückenmark und Gastrointestinaltrakt ein sehr problematisches Zielgebiet ist. Zweck dieser Studie war zu untersuchen, welche Möglichkeiten die intensitätsmodulierte Radiotherapie (IMRT) bietet, entweder auf sichere Weise die Strahlendosis auf 50–60 Gy im Fall ausgedehnter Malignome zu steigern oder die Strahlendosis gefährdeter „Risikoorgane“ in der adjuvanten Situation zu vermindern.Material und Methoden:Die Dosimetriekarten von 14 Patientinnen, bei denen im Jahr 2000 in der Abteilung für Radioonkologie am Universitätsklinikum Liège, Belgien, eine Radiotherapie der PO-Region durchgeführt worden war, wurden analysiert, um die konformale Sechs-Felder-Radiotherapie (KRT) mit Fünf-Felder-IMRT-Konzepten zu vergleichen. Für sowohl KRT als auch IMRT wurden Untersuchungen geplant, in denen in der PO-Region theoretisch 60 Gy auf sicherste Weise appliziert werden sollten. Dosis-Volumen-Histogramme (DVH) wurden berechnet für das klinische Zielvolumen (CTV), das Planungszielvolumen (PTV) und für die gefährdeten Organe. Mit dem Student-t-Test wurden gepaarte DVH-Daten der KRT- und IMRT-Planungen verglichen.Ergebnisse:Das IMRT-Konzept erlaubte, im PTV eine im Vergleich zur KRT höhere Strahlendosis anzuwenden. Mittels IMRT wurde die maximale Rückenmarkdosis von 42,5 Gy zu 26,2 Gy im Vergleich zur KRT vermindert (p < 0,00001). Die Nierendosis wurde signifikant vermindert, indem im IMRT-Konzept < 20% des Organs ≥ 20 Gy erhielten (p < 0,00001). Die Strahlendosis im Gastrointestinaltrakt ergab mit 35 Gy in < 25% keine Unterschiede. Die Leberdosis blieb—unabhängig von der angewendeten Methode—niedrig.Schlussfolgerung:Bei einer Dosis von 60 Gy schont die IMRT Rückenmark und Nieren im Vergleich zur KRT weitgehend und bietet ein interessantes Konzept nicht nur für die Dosiseskalation bis zu 50–60 Gy (was Radiochemotherapie-Planungen entgegenkommen dürfte), sondern auch für die niedriger dosierte adjuvante Strahlentherapie. Die Dosimetriewerte dieser Studie liegen in der gleichen Größenordnung wie die vor kurzem veröffentlichten Ergebnisse eines Konzeptes mit dynamischer Rotationsbestrahlung.

Volume-based pulsed-dose-rate brachytherapy boosting concurrent chemoradiation as a definitive treatment modality in cervical cancer

PURPOSE To report the treatment outcomes and treatment-induced adverse events (AEs) of concomitant chemoradiotherapy boosted with pulsed-dose-rate brachytherapy using volume-based two-dimensional planning in patients with cervical cancer. PATIENTS AND METHODS After obtaining the institutional review board approval, patients with FIGO Stages IB to IIIB cervical cancer, treated from January 2006 to December 2008 consecutively, were included. Volume-based planning was used and entailed defining an envelope around the tumor on a two-dimensional image and prescribing the dose to this envelope and reporting the dose of the isodose of 60 Gy. Patients and tumor characteristics, dosimetric parameters, AEs and treatment outcomes, local control rate, distant metastases rate, progression-free survival, and overall survival are reported. RESULTS The study included 95 patients; the median age is 50 years. The median tumor size is 50cc (range, 25-78cc). Median brachytherapy dose delivered to the envelope is 20 Gy (range, 15-35 Gy), and median volume encompassed by 60 Gy isodose curve is 137cc (range, 26-365cc). The 3-year overall survival, progression-free survival, local control rate, and distant metastases rate were 83.8%, 72.4%, 84.8%, and 15.4%, respectively. Gastrointestinal and genitourinary Grade 3 and 4 acute AEs were reported in 11.6% and 3.3% and chronic Grade 3 and 4 AEs were reported in 3.2% and 4.2% of all patients, respectively. CONCLUSIONS Chemoradiotherapy followed by pulsed-dose-rate brachytherapy boost is effective and tolerable treatment modality for locally confined cervical cancer.

Hypofractionated stereotactic boost in intermediate risk prostate carcinoma: Preliminary results of a multicenter phase II trial (CKNO-PRO)

Purpose Dose escalation may improve curability in intermediate-risk prostate carcinoma. A multicenter national program was developed to assess toxicity and tumor response with hypofractionated stereotactic boost after conventional radiotherapy in intermediate-risk prostate cancer. Methods and material Between August 2010 and April 2013, 76 patients with intermediated-risk prostate carcinoma were included in the study. A first course delivered 46 Gy by IMRT (68.4% of patients) or 3D conformal radiotherapy (31.6% of patients). The second course delivered a boost of 18 Gy (3x6Gy) within 10 days. Gastrointestinal (GI) and genitourinary (GU) toxicities were evaluated as defined by NCI-CTCAE (v4.0). Secondary outcome measures were local control, overall and metastasis-free survival, PSA kinetics, and patient functional status (urinary and sexual) according to the IIEF5 and IPSS questionnaires. Results The overall treatment time was 45 days (median, range 40–55). Median follow-up was 26.4 months (range, 13.6–29.9 months). Seventy-seven per cent (n = 58) of patients presented a Gleason score of 7. At 24 months, biological-free survival was 98.7% (95% CI, 92.8–99.9%) and median PSA 0.46 ng/mL (range, 0.06–6.20 ng/mL). Grade ≥2 acute GI and GU toxicities were 13.2% and 23.7%, respectively. Grade ≥2 late GI and GU toxicities were observed in 6.6% and 2.6% of patients, respectively. No grade 4 toxicity was observed. Conclusions Hypofractionated stereotactic boost is effective and safely delivered for intermediate-risk prostate carcinoma after conventional radiation. Mild-term relapse-free survival and tolerance results are promising, and further follow-up is warranted to confirm the results at long term. Trial registration ClinicalTrials.gov NCT01596816.

Feasibility Study of Pelvic Helical IMRT for Elderly Patients with Endometrial Cancer

Purpose Standard treatment for early-stage endometrial cancer involves surgery (when possible) followed by brachytherapy or external-beam radiotherapy (EBRT) for high-risk tumors. EBRT is not without toxicity, meaning that it could be difficult to complete for elderly patients, who typically have decreased reserve and resistance to stressors. Patients and methods Patients aged 70 and over treated between April 2009 and May 2013 for endometrial cancer and received IMRT (Intensity-Modulated Radiation Therapy) were included in this observational study. IMRT could be performed as adjuvant treatment or as an exclusive treatment for patients not amenable to surgery. The primary endpoints of this study were to assess the feasibility and toxicity of pelvic IMRT in this population. Secondary endpoints were to assess disease-specific survival, overall survival, and local control. Predictors of toxicity were also explored. Results Forty seven consecutive patients were included in the analysis. Median age at diagnosis was 75 years (range, 70–89 years). Eleven patients were aged 80 years and older. Toxicities were found in thirty four patients (72%) during treatment. Among these, toxicity did not exceed grade 2 for 32 patients (68%). Two patients had a grade 3 toxicity (4%). Overall survival rates were 87% and 83% at 1 and 2 years, respectively. Six patients (12.8%) had a local relapse and nine others (19.1%) had distant relapse. Conclusions Pelvic helical IMRT for patients aged 70 and older is feasible with full standard radiation doses, showing that age greater than 70 should not be considered as a reason not to perform optimal treatment.

A retrospective cohort study to assess adjuvant concurrent chemoradiation (CCRT) compared to adjuvant radiation therapy (RT) in the treatment of grade 2 and 3 extremity soft tissue sarcomas

PURPOSE To evaluate the efficacy and tolerance of adjuvant concurrent chemoradiation (CCRT) as treatment of grade 2 and 3 (G2-3) localized extremity soft tissue sarcomas (STS) by comparing CCRT with standard adjuvant radiation therapy (RT). PATIENTS AND METHODS This monocentric retrospective study included non-pediatric patients (>16years) treated by adjuvant RT with or without chemotherapy (CT) after conservative resection of non-recurrent G2-3 extremity STS. RESULTS A total of 80 patients were treated between 1990 and 2012: 51 by RT and 29 by CCRT. Of the 29 CCRT patients, 25 received doxorubicin monotherapy (75mg/m2/3weeks). The CCRT group contained a greater proportion of grade 3 extremity STS (p<0.001). Median follow up was 68months (9-284). Multivariate analysis revealed greater local control in the CCRT group (1 local recurrence vs 8 in the RT group; HR=0.082, 95% CI 0.011-0.321) and incomplete resection as the major risk factor of local recurrence (HR=25.2, 95% CI 4.767-133.226). The two groups exhibited no differences in distant failure-free survival (HR=1.469, 95% CI 0.668-3.228), disease-free survival (HR=1.096, 95% CI 0.519-2.315) or overall survival (HR=1.378, 95% CI 0.498-3.814). Grade 3 was an adverse prognostic factor for overall survival (HR=3.11, 95% CI 1.04-9.32). Our analyses also revealed that CCRT tended to increase the risk of both grade ≥3 acute dermatitis (14 events vs 6 in the RT group; OR=6.99, 95% CI 2.28-21.47) and grade ≥2 late toxicity (6 events vs 3 in the RT group; p=0.0572). CONCLUSION CCRT could improve local control as part of a limb-preservation strategy. However, with a limited number of patients, CCRT showed no improvement in either distant control or survival and increased toxicity.

NHL-ChirEx: An interprofessional cross-border education initiative in the Greater Region with a focus on radiation morbidity and patient safety

NHL-ChirEx is an interprofessional cross-border education project that addresses the potential excess of radiation induced morbidity throughout the radiation planning and treatment process. NHL-ChirEx is supported by ESTRO and the University of the Greater Region and has been recently approved and funded under INTERREG VA Programme.

Radiothérapie versus radiochimiothérapie comme adjuvant à la chirurgie dans les cancers de l’endomètre à haut risque

Endometrial cancer is a common malignancy. Management of these tumors depends on several risk factors such as FIGO staging, myometrial invasion, histology or pelvic lymph node involvement. According to those factors, low risk, intermediate and high risk groups were defined. A high risk endometrial cancer has a poorer prognostic and more risks of recurrence. Treatment of such disease should be more aggressive. However modalities of these treatments have not yet been clearly defined.