S. Agostinelli

Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma

To evaluate whether androgen deprivation impacts late rectal toxicity in patients with localised prostate carcinoma treated with three-dimensional conformal radiotherapy. One hundred and eighty-two consecutive patients treated with 3DCRT between 1995 and 1999 at our Institution and with at least 12 months follow-up were analysed. three-dimensional conformal radiotherapy consisted in 70–76 Gy delivered with a conformal 3-field arrangement to the prostate±seminal vesicles. As part of treatment, 117 patients (64%) received neo-adjuvant and concomitant androgen deprivation while 88 (48.4%) patients were continued on androgen deprivation at the end of three-dimensional conformal radiotherapy as well. Late rectal toxicity was graded according to the RTOG morbidity scoring scale. Median follow up is 25.8 (range: 12–70.2 months). The 2-year actuarial likelihood of grade 2–4 rectal toxicity was 21.8±3.2%. A multivariate analysis identified the use of adjuvant androgen deprivation (P=0.0196) along with the dose to the posterior wall of the rectum on the central axis (P=0.0055) and the grade of acute rectal toxicity (P=0.0172) as independent predictors of grade 2–4 late rectal toxicity. The 2-year estimates of grade 2–4 late rectal toxicity for patients receiving or not adjuvant hormonal treatment were 30.3±5.2% and 14.1±3.8%, respectively. Rectal tolerance is reduced in presence of adjuvant androgen deprivation.

Does treatment of the pelvic nodes with IMRT increase late rectal toxicity over conformal prostate-only radiotherapy to 76 Gy?

Purpose:To compare late rectal toxicity rates after three-dimensional conformal radiotherapy to the prostate alone (P-3D-CRT) and whole-pelvis intensity-modulated radiotherapy along with a prostate boost (WP-IMRT/PB) to the same nominal total dose to the prostate.Patients and Methods:68 patients treated with conformal radiotherapy to the prostate only to 76 Gy at the National Institute for Cancer Research, Genoa, Italy, represented the first group (P-3D-CRT). The second group consisted of 45 patients treated at the University of Texas Medical Branch (UTMB), Galveston, TX, USA, with IMRT covering the pelvic nodes and seminal vesicles to 54 Gy at 1.8 Gy per fraction and the prostate to 60 Gy in the same 30 fractions. A separate phase boosted the prostate to 76 Gy (WP-IMRT/PB). Major aspects of planning were remarkably similar at both institutions leaving the inclusion or not of pelvic nodes as the main treatment-related difference between the two groups. Late rectal toxicity was prospectively scored according to the RTOG scale. All patients have a 12-month minimum follow-up, and mean follow-up, similar in both groups, is 25.9 months (SD [standard deviation]: 8.4 months).Results:At 2 years, the estimated cumulative incidence of grade 2 late rectal toxicity is 6% ± 4% for WP-IMRT/PB and 21.2% ± 6% for P-3D-CRT (p = 0.06). The difference became significant (HR [hazard ratio] = 0.1, 95% CI [confidence interval]: 0.0–0.6; p = 0.01) at multivariate analysis. None of the patients developed grade 3+ toxicity.Conclusion:Despite the larger treated volume, WP-IMRT/PB allows more rectal sparing than P-3D-CRT.Ziel:Vergleich der rektalen Spättoxizität nach alleiniger dreidimensionaler konformaler Strahlentherapie der Prostata (P-3D-CRT) und nach intensitätsmodulierter Radiotherapie des gesamten Beckens mit Prostataradiochirurgie (WP-IMRT/PB) bei gleicher Gesamtdosis.Patienten und Methodik:Die erste Gruppe bestand aus 68 Patienten, die eine alleinige konformale Strahlentherapie der Prostata bis 76 Gy am National Institute for Cancer Research in Genua, Italien, erhielten (P-3D-CRT). Die zweite Gruppe umfasste 45 Patienten, welche am University of Texas Medical Branch (UTMB), Galveston, TX, USA, mit IMRT der Beckenlymphknoten und der Samenbläschen bis 54 Gy zu 1,8 Gy pro Fraktion und der Prostata bis 60 Gy, ebenfalls in 30 Fraktionen, behandelt wurden. Die Radiochirurgie der Prostata erfolgte separat bis 76 Gy (WP-IMRT/PB). Die Hauptaspekte bei der Planung waren an beiden Einrichtungen bemerkenswert ähnlich, so dass lediglich die Frage des Einschlusses der Beckenlymphknoten als Hauptunterschied bei der Behandlung der beiden Gruppen übrig blieb. Die rektale Spättoxizität wurde anhand der RTOG-Skala bewertet. Alle Patienten erhalten eine mindestens 12-monatige Nachsorge; die durchschnittliche Nachsorgedauer beträgt bei beiden Gruppen 25,9 Monate (SD [Standardabweichung]: 8,4 Monate).Ergebnisse:Nach 2 Jahren liegt die geschätzte kumulative Inzidenz der rektalen Spättoxizität Grad 2 bei 6% ± 4% für WP-IMRT/PB und 21,2% ± 6% für P-3D-CRT (p = 0,06). Der Unterschied wurde bei der Multivarianzanalyse signifikant (HR [Hazard-Ratio] = 0,1, 95%-CI [Konfidenzintervall]: 0,0–0,6; p = 0,01). Kein Patient entwickelte eine rektale Spättoxizität Grad 3+.Schlussfolgerung:Trotz des größeren Behandlungsumfangs ermöglicht die WP-IMRT/PB eine schonendere Behandlung des Rektalbereichs als die P-3D-CRT.

Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

BACKGROUND AND PURPOSE To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT). MATERIALS AND METHODS Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). RESULTS Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease. CONCLUSIONS This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.

Determination of the correction factors for different ionization chambers used for the calibration of the helical tomotherapy static beam.

BACKGROUND AND PURPOSE To determine the machine-specific correction factors for three commercial ionization chambers (Exradin A1SL, PTW Semiflex and PTW PinPoint) to be applied in the dose calibration of a helical tomotherapy (HT) unit. MATERIALS AND METHODS Machine-specific reference (msr) conditions for HT unit involved a 10 × 5 cm(2) (IEC x×y) radiation field at 85 cm SSD with the ionization chamber (IC) positioned at 10 cm depth in Virtual Water. Each msr correction factor was determined using the formalism proposed by the AAPM Task Group 148 (i.e. k(Q[HT)(TG-51])) and was compared to direct calibration of the ICs against radiochromic films, calibrated in absolute dose at our institute, following the formalism proposed by the IAEA-AAPM joint committee (i.e. [Formula: see text] ). RESULTS TPR(20,10) values under HT msr conditions were 0.608, 0.608 and 0.615 corresponding to %dd(10)(x[HT)(Ref]) of 0.606, 0.606 and 0.613 for A1SL, Semiflex and PinPoint ICs, respectively. Based on these findings, k(Q[HT)(TG-51]) determination resulted 0.998±0.001, 0.998±0.001 and 0.991±0.002 for A1SL, Semiflex and PinPoint ICs, respectively. The [Formula: see text] correction factors obtained through direct calibration were 1.000±0.010, 1.004±0.007 and 0.998±0.006 for A1SL, Semiflex and PinPoint ICs, respectively. CONCLUSIONS Direct calibration of ICs versus radiochromic films provided correction factors equivalent to those obtained following the TG-148 formalism. This study showed that ICs calibrated for conventional linear accelerators can be used for the calibration of the static beam delivered by a HT unit taking into account the particular reference conditions.

Radiosurgery with Helical Tomotherapy Outcomes for Patients with One or Multifocal Brain Metastasis

To evaluate the feasibility and report the preliminary results for stereotactic radiosurgery (SRS) treatments of single or multiple brain metastases delivered with helical tomotherapy (HT) by means of the InterFix™ Radiosurgery kit. Between September 2010 and August 2012, thirty patients underwent SRS for treatment of 46 brain metastases with a median prescription dose of 20 Gy (range 15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic resonance imaging (MRI). Dose distribution indexes were computed and compared with published data for SRS performed with dedicated machines. After a median follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was 70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was 72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as headache and epileptic crisis occurred in only two patients. The mean values of conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50 respectively. HT-SRS for single or multiple brain metastases appears a reliable technique with encouraging clinical outcomes and competitive dosimetrical results.

Dosimetric analysis of Tomotherapy-based intracranial stereotactic radiosurgery of brain metastasis

PURPOSE This paper analyzes Tomotherapy-based intracranial stereotactic radiosurgery (HTSRS) of brain metastasis targeting two end-points: 1) evaluation of dose homogeneity, conformity and gradient scores for single and multiple lesions and 2) assay of dosimetric criticality of completion of HTSRS procedures. METHODS 42 treatment plans of 33 patients (53 brain lesions) treated with HTSRS were analyzed. Dose to healthy brain, homogeneity, conformity and gradient indexes were evaluated for each lesion. Influence of Field Length and multiple lesions cross-talk effect were assessed. Treatment interruption and completion was investigated using radiochromic films in order to examine the delivered dose and its robustness to patient intrafraction movement. RESULTS The average dose homogeneity index was 1.04 ± 0.02 (SD). Average dose conformity and gradient score indexes were 1.4 ± 0.2 and 50 ± 14 respectively. We found a strong correlation of the dose to healthy brain and conformity and gradient indexes with target(s) volume for which analytical functions were obtained. Field Length and cross-talk effect were significantly correlated with poor gradient scores, but were found not to affect dose conformity. CONCLUSIONS Homogeneity and conformity of HTSRS plans achieved excellent scores, while dose falloff and dose to healthy brain were slightly larger when compared with non-coplanar SRS techniques. Care should be given if treating large (>3 cc) or multiple near in-plane lesions in order to reduce dose to healthy brain. Analysis of interrupted treatments suggests splitting HTSRS treatments in two consecutive fractions in order to prevent target miss and overdosage due to patient intrafraction movement.

Excellent survival regardless of disease stage in patients with advanced nasopharyngeal cancer.

Background We present our experience in assessing the feasibility and efficacy outcomes of intensified intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) delivered to patients with nasopharyngeal carcinoma (NPC). Methods Between March 2009 and December 2014, 35 patients affected by advanced NPC with a median age of 53 years (range 11-77) were treated with definitive radiotherapy. Radiotherapy was delivered by helical tomotherapy with the SIB technique. The prescribed doses were 66 Gy to macroscopic disease, 60 Gy to high-risk subclinical disease, and 54 Gy to low-risk disease in 30 fractions. The daily SIB dose was 2.2 Gy to macroscopic disease. Results At the end of treatment 33 (94%) patients had obtained complete clearance of disease and 2 patients had died (1 of persistent disease after 3 months and 1 of cancer-unrelated causes after 4 months). At a median follow-up of 40 months (range 5-69), locoregional control rates at 2 and 4 years were 92.9% and 88.2%, respectively, and the overall survival after 4 years was 93.9%. The most significant acute toxicities were grade 2 and 3 mucositis (43%). No grade 3 and 4 late toxicities were observed; grade 2 xerostomia after 6 months from the end of treatment was reported in 11 patients; xerostomia toxicity decreased to grade 1 in 6/11 patients within 12 months. Conclusions These results show that intensified IMRT with SIB is an excellent strategy offering high local control rates for NPC patients with mild acute and late toxicity.

PO-0993: Intra-operative radiotherapy for prostate cancer: preliminary midterm results of a mono institutional study

was then possible to develop software for calculating the dose distribution at any angle made of the applicator with the surface. Results: The software calculates the dose distribution by varying the angle and the depth to which you want to know. The variation of homogeneity is very important. For an angle of 25°, the inhomogeneity in the surface plane is between 100 and 40 %. Conclusions: A software has been developed, based on the computation code PENELOPE to know the dose distribution at any depth as a function of angle applicator with the surface.