Dosimetric Feasibility Study of Dose Escalated Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients: It Is Time to Raise the Bar.

BACKGROUND AND OBJECTIVE: To assess the dosimetric feasibility of a stereotactic body radiotherapy (SBRT) dose escalated protocol, with a simultaneous integrated boost (SIB) and a simultaneous integrated protection (SIP) approach, in patients with locally advanced pancreatic cancer (LAPC). MATERIAL AND METHODS: Twenty LAPC lesions, previously treated with SBRT at our Institution, were re-planned. The original prescribed and administered dose was 50/30/25 Gy in five fractions to PTVsib (tumor-vessel interface [TVI])/PTVt (tumor volume)/PTVsip (overlap area between PTVt and planning organs at risk volume [PRVoars]), respectively. At re-planning, the prescribed dose was escalated up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively. All plans were performed using an inspiration breath hold (IBH) technique and generated with volumetric modulated arc therapy (VMAT). Well-established and accepted OAR dose constraints were used (D0.5cc < 33 Gy for luminal OARs and D0.5cc < 38 Gy for corresponding PRVoars). The primary end-point was to achieve a median dose equal to the prescription dose for the PTVsib with D98≥ 95% (95% of prescription dose is the minimum dose), and a coverage for PTVt and PTVsip of D95≥95%, with minor deviations in OAR dose constraints in < 10% of the plans. RESULTS: PTVsib median (± SD) dose/D95/conformity index (CI) were 60.54 (± 0.85) Gy/58.96 (± 0.86) Gy/0.99 (± 0.01), respectively; whilst PTVt median (± SD) dose/D95 were 44.51 (± 2.69) Gy/38.44 (± 0.82) Gy, and PTVsip median (± SD) dose/D95 were 35.18 (± 1.42) Gy/33.01 (± 0.84) Gy, respectively. With regard to OARs, median (± SD) maximum dose (D0.5cc) to duodenum/stomach/bowel was 29.31 (± 5.72) Gy/25.29 (± 6.90) Gy/27.03 (± 5.67) Gy, respectively. A minor acceptable deviation was found for a single plan (bowel and duodenum D0.5cc=34.8 Gy). V38 < 0.5 cc was achieved for all PRV luminal OARs. CONCLUSIONS: In LAPC patients SBRT, with a SIB/SIP dose escalation approach up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively, is dosimetrically feasible with adequate PTVs coverage and respect for OAR dose constraints.

Multi-variable models of large International Prostate Symptom Score worsening at the end of therapy in prostate cancer radiotherapy.

PURPOSE/OBJECTIVE: Prospectively assessing clinical/dosimetry factors affecting the acute worsening of urinary functionality after radiotherapy for prostate cancer. MATERIAL/METHODS: DUE01 population was considered, including patients treated with conventional or moderate hypo-fractionation (2.2-2.7 Gy/fr). Relevant clinical factors were collected, urinary symptoms were self-reported through the International Prostate Symptom Score (IPSS) before and at the end of radiotherapy; while absolute weekly dose-surface histograms (DSHw) were chosen as dosimetry descriptors. An IPSS increase of at least 10 and 15 points (ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15) were chosen as endpoints. Patients with baseline IPSS>20 were excluded. Relevant factors were chosen through a bootstrap-based in silico methodology. RESULTS: Complete information was available for 380 patients: 77/380 (20%) and 28/380 (7%) with ΔIPSS ⩾ 10 and ΔIPSS ⩾ 15, respectively. Neoadjuvant hormone was protective (OR=0.49 and 0.69). DSHw at 8.5 Gy/week and 12 Gy/week were risk factors, with additional risk for patients who use cardiovascular drugs and anti-hypercholesterolemia drugs. In the hypo-fractionated subgroup (n=209) the role of cardiovascular drugs (OR=2.16) for ΔIPSS ⩾ 10 and anti-hypercholesterolemia drugs (OR=2.80) for ΔIPSS⩾15, together with DSHw (10 Gy/week and 12.5 Gy/week, respectively), was confirmed. CONCLUSION: Current study shows a dose-surface/volume effect for acute large worsening of urinary functionality; several clinical variables largely impact the risk and especially all the factors related with vascular diseases.

Relationships between bladder dose-volume/surface histograms and acute urinary toxicity after radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8-2Gy/fr, CONV) or moderate hypo-fractionation (2.35-2.7Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS)⩾15/20 at the end of radiotherapy. MATERIALS AND METHODS: Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS⩾15/20 at the end of radiotherapy. Logistic uni- and backward multi-variable (MVA) analyses were performed. RESULTS: Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/DSHc predicted the risk of IPSS⩾15 at the end of radiotherapy (n=77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving ⩾8.5Gy/week and ⩾12.5Gy/week was developed (AUC=0.78, 95% CI: 0.72-0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose-volume/surface parameters remained when excluding patients with baseline IPSS⩾15 and in HYPO. IPSS⩾20 at the end of radiotherapy (n=27/247) was mainly correlated to baseline IPSS and T stage. CONCLUSIONS: Although the baseline IPSS was the main predictor, constraining v8.5w<56cc and v12.5w<5cc may significantly reduce acute GU toxicity.

Helical tomotherapy and intensity modulated proton therapy in the treatment of early stage prostate cancer: a treatment planning comparison.

PURPOSE: To compare helical tomotherapy (HT) and intensity modulated proton therapy (IMPT) on early stage prostate cancer treatments delivered with simultaneous integrated boost (SIB) in moderate hypofractionation. MATERIAL/METHODS: Eight patients treated with HT were replanned with two-field IMPT (2fIMPT) and five-field IMPT (5fIMPT), using a small pencil beam size (3 mm sigma). The prescribed dose was 74.3 Gy in 28 fractions on PTV1 (prostate) and PTV2 (proximal seminal vesicles), 65.5 Gy on PTV3 (distal seminal vesicles) and on the overlap between rectum and PTVs. RESULTS: IMPT and HT achieved similar target coverage and dose homogeneity, with 5fIMPT providing the best results. The conformity indexes of IMPT were significantly lower for PTV1+2 and PTV3. Above 65 Gy, HT and IMPT were equivalent in the rectum, while IMPT spared the bladder and the penile bulb from 0 to 70 Gy. From 0 up to 60 Gy, IMPT dosimetric values were (much) lower for all OARs except the femur heads, where HT was better than 2fIMPT in the 25-35 Gy dose range. OARs mean doses were typically reduced by 30-50% by IMPT. NTCPs for the rectum were within 1% between the two techniques, except when the endpoint was stool frequency, where IMPT showed a small (though statistically significant) benefit. CONCLUSIONS: HT and IMPT produce similar dose distributions in the target volume. The current knowledge on dose-effect relations does not allow to quantify the clinical impact of the large sparing of IMPT at medium-to-low doses.

Helical tomotherapy vs. intensity-modulated proton therapy for whole pelvis irradiation in high-risk prostate cancer patients: dosimetric, normal tissue complication probability, and generalized equivalent uniform dose analysis.

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for high-risk prostate cancer (HRPCa) patients. METHODS AND MATERIALS: The plans of 8 patients with HRPCa treated with HT were compared with IMPT plans with two quasilateral fields set up (-100°; 100°) and optimized with the Hyperion treatment planning system. Both techniques were optimized to simultaneously deliver 74.2 Gy/Gy relative biologic effectiveness (RBE) in 28 fractions on planning target volumes (PTVs)3-4 (P + proximal seminal vesicles), 65.5 Gy/Gy(RBE) on PTV2 (distal seminal vesicles and rectum/prostate overlapping), and 51.8 Gy/Gy(RBE) to PTV1 (pelvic lymph nodes). Normal tissue calculation probability (NTCP) calculations were performed for the rectum, and generalized equivalent uniform dose (gEUD) was estimated for the bowel cavity, penile bulb and bladder. RESULTS: A slightly better PTV coverage and homogeneity of target dose distribution with IMPT was found: the percentage of PTV volume receiving ≥ 95% of the prescribed dose (V(95%)) was on average > 97% in HT and > 99% in IMPT. The conformity indexes were significantly lower for protons than for photons, and there was a statistically significant reduction of the IMPT dosimetric parameters, up to 50 Gy/Gy(RBE) for the rectum and bowel and 60 Gy/Gy(RBE) for the bladder. The NTCP values for the rectum were higher in HT for all the sets of parameters, but the gain was small and in only a few cases statistically significant. CONCLUSIONS: Comparable PTV coverage was observed. Based on NTCP calculation, IMPT is expected to allow a small reduction in rectal toxicity, and a significant dosimetric gain with IMPT, both in medium-dose and in low-dose range in all OARs, was observed.

Intensity-modulated proton therapy versus helical tomotherapy in nasopharynx cancer: planning comparison and NTCP evaluation.

PURPOSE: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. METHODS AND MATERIALS: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a "beam scanning" technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. RESULTS: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving > or =20 Gy and > or =30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving > or =50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving > or =30, > or =20, and > or =10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. CONCLUSION: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at risk at medium-to-low doses.

Agreement criteria between expected and measured field fluences in IMRT of head and neck cancer: the importance and use of the gamma histograms statistical analysis.

BACKGROUND AND PURPOSE: The aim of this study was to analyse our pre-treatment QA data in order to establish uniquely defined agreement criteria between planned and delivered dose distribution for clinical QA practice in IMRT of head and neck (HN) patients. MATERIALS AND METHODS: Pre-treatment QA dosimetry using films in combination with ionisation chambers is routinely evaluated for each patient. This evaluation is performed by comparing planned and measured dose distributions in terms of absolute point dose measurements, planar dose verification and gamma function analysis using 4%/3mm values as acceptance criteria. In the current investigation, gamma histograms, calculated on dose levels higher than 10% of the prescription dose (1.8Gy/fraction), were further analysed by considering mean values, gamma values corresponding to Delta=mean+1.5 SD (named as gamma(Delta)) and the % of points with gamma<1, gamma<1.5 and gamma>2. When considering the patient population, the average values of all these parameters and their confidence limits (mean value+1.5 SD) were calculated. The results here presented refer to 57 HN patients treated in the period September 04-April 06. RESULTS: Better results were found for treatments performed with our newly installed linac (e.g. average gamma(Delta): 0.8 vs. 1.1 for the preexisting one, p<0.001), due to a more accurate dosimetric configuration. Also, confidence limits for the percentage of points with gamma<1, gamma<1.5 and gamma>2 were found to be quite different for the two linacs (95.3%, 98.9% and 0.4% for the newly installed unit, 87.6%, 95.2% and 2.0% for the preexisting one). CONCLUSIONS: Statistical analyses of gamma evaluation of QA pre-treatment dosimetry are useful to properly define confidence limits of the agreement between expected and measured fluences based on our institutional experience. Our results confirm that the dosimetry configuration of the beam may significantly affect the agreement between planned and measured IMRT beam fluences.

Simultaneous integrated boost (SIB) for nasopharynx cancer with helical tomotherapy. A planning study.

PURPOSE: To explore the potential of helical tomotherapy (HT) in the treatment of nasopharynx cancer. PATIENTS AND METHODS: Six T1-4 N1-3 patients were considered. A simultaneous integrated boost (SIB) technique was planned with inversely optimized conventional intensity-modulated radiotherapy (IMRT; dynamic multileaf collimator using the Eclipse-Helios Varian system) and HT. The prescribed (median) doses were 54 Gy, 61.5 Gy, and 64.5 Gy delivered in 30 fractions to PTV1 (planning target volume), PTV2, and PTV3, respectively. The same constraints for PTV coverage and for parotids, spinal cord, mandible, optic structures, and brain stem were followed in both modalities. The planner also tried to reduce the dose to other structures (mucosae outside PTV1, larynx, esophagus, inner ear, thyroid, brain, lungs, submental connective tissue, bony structures) as much as possible. RESULTS: The fraction of PTV receiving >95% of the prescribed dose (V95%) increased from 97.6% and 94.3% (IMRT) to 99.6% and 97% (HT) for PTV1 and PTV3, respectively (p<0.05); median dose to parotids decreased from 30.1 Gy for IMRT to 25.0 Gy for HT (p<0.05). Significant gains (p<0.05) were found for most organs at risk (OARs): mucosae (V30 decreased from 44 cm(3) [IMRT] to 18 cm(3) [HT]); larynx (V30: 25 cm(3) vs. 11 cm(3)); thyroid (mean dose: 48.7 Gy vs. 41.5 Gy); esophagus (V45: 4 cm(3) vs. 1 cm(3)); brain stem (D1%: 45.1 Gy vs. 37.7 Gy). CONCLUSION: HT improves the homogeneity of dose distribution within PTV and PTV coverage together with a significantly greater sparing of OARs compared to linac five-field IMRT.

Significant improvement in normal tissue sparing and target coverage for head and neck cancer by means of helical tomotherapy.

PURPOSE: In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed. MATERIALS AND METHODS: In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord Dmax similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (n=3), hypopharinx (n=1) and larynx (n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5 cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5 cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54 Gy in 30 fractions on PTV1 and 16.2 Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15 Gy were concomitantly delivered while delivering 16.2 Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose-volume histograms (DVH) and dose statistics on PTVs and OARs. RESULTS: When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96-97% for Tomotherapy plans. Dmax within PTV1 decreased from 60.3 Gy (IMRT) to 57.4 Gy (TOMO-a) and 58.7 Gy (TOMO-b). Spinal cord Dmax decreased from 31.6 Gy (IMRT) to 26.5 Gy (TOMO-a) and 24.6 Gy (TOMO-b). No attempts to further reduce spinal cord Dmax were done. Mean dose to the parotids decreased from 26.1 Gy (IMRT) to 25.1 Gy (TOMO-a) and 20.8 Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9 Gy (IMRT) to 34.0 Gy (TOMO-a) and 30.7 Gy (TOMO-b). When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3. CONCLUSIONS: Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.