Long term results of a phase II trial of hypofractionated adjuvant radiotherapy for early-stage breast cancer with volumetric modulated arc therapy and simultaneous integrated boost.

PURPOSE: to report toxicity and cosmetic outcome with a median follow-up of 6 years of a phase II trial of hypofractionated radiotherapy with volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) for early-stage breast cancer after conservative surgery. MATERIALS AND METHODS: From August 2010 to September 2014, patients requiring adjuvant radiotherapy for early-stage breast cancer were treated according to a phase I-II protocol with SIB to 40.5 and 48 Gy to the breast and the boost region, respectively, with VMAT technique. The primary endpoint evaluated the treatment feasibility regarding adherence to required dose constraints for target, heart and lungs. Acute and late toxicity, local and distant control were secondary endpoints. RESULTS: 450 patients were included in the trial and analysed after a median follow-up of 6 years. Acute toxicity was already presented in a previous paper. Regarding late toxicity, 93% of patients had no skin alteration at five years, while 5.3% and 1.3% did record G1 and G2 residual toxicity, respectively. Cosmetic outcome was scored good or excellent in almost all cases (97.2%), fair only in 2.3% of patients. Residual tenderness in the irradiated breast was reported by 10% of patients. Cosmesis and breast pain improved during follow-up. Two cases of G2 pneumonitis and two cases of ischemic cardiopathy were registered during follow-up. Five cases presented local recurrence in the homolateral breast, four patients had a new primary cancer in the contralateral breast, while distant metastasis developed in 7 patients. CONCLUSION: After more than six years, hypofractionated VMAT with SIB for adjuvant radiotherapy in early-stage breast cancer patients remains a safe and effective approach. Mature data on skin toxicity and cosmetic outcome are encouraging. However, longer follow-up is required to evaluate local control, cardiac toxicity and secondary carcinogenesis.

RapidPlan knowledge based planning: iterative learning process and model ability to steer planning strategies.

PURPOSE: To determine if the performance of a knowledge based RapidPlan (RP) planning model could be improved with an iterative learning process, i.e. if plans generated by an RP model could be used as new input to re-train the model and achieve better performance. METHODS: Clinical VMAT plans from 83 patients presenting with head and neck cancer were selected to train an RP model, CL-1. With this model, new plans on the same patients were generated, and subsequently used as input to train a novel model, CL-2. Both models were validated on a cohort of 20 patients and dosimetric results compared. Another set of 83 plans was realised on the same patients with different planning criteria, by using a simple template with no attempt to manually improve the plan quality. Those plans were employed to train another model, TP-1. The differences between the plans generated by CL-1 and TP-1 for the validation cohort of patients were compared with respect to the differences between the original plans used to build the two models. RESULTS: The CL-2 model presented an improvement relative to CL-1, with higher R2 values and better regression plots. The mean doses to parallel organs decreased with CL-2, while D1% to serial organs increased (but not significantly). The different models CL-1 and TP-1 were able to yield plans according to each original strategy. CONCLUSION: A refined RP model allowed the generation of plans with improved quality, mostly for parallel organs at risk and, possibly, also the intrinsic model quality.

Small field characterization of a Nanochamber prototype under flattening filter free photon beams.

INTRODUCTION: Nanochambers present some advantages in terms of energy independence and absolute dose measurement for small field dosimetry in the SBRT scenario. Characterization of a micro-chamber prototype was carried out both under flattened and flattening-filter-free (FFF) beams with particular focus on stem effect. METHODS: The study included characterization of leakage and stem effects, dose rate and dose per pulse dependence, measurement of profiles, and percentage depth doses (PDDs). Ion collection efficiency and polarity effects were measured and evaluated against field size and dose per pulse. The 6_MV, 6_MV_FFF and 10_MV FFF beams of a Varian EDGE were used. Output factors were measured for field sizes ranging from 0.8×0.8cm2 to 20×20cm2 and were compared with other detectors. RESULTS: The 2mm diameter of this chamber guarantees a high spatial resolution with low penumbra values. In orthogonal configuration a strong stem (and cable) effect was observed for small fields. Dose rate and dose per pulse dependence were <0.3% and 0.6% respectively for the whole range of considered values. The Nanochamber exhibits a field size (FS) dependence of the polarity correction >2%. The OF values were compared with other small field detectors showing a good agreement for field sizes >2×2cm2. The large field over-response was corrected applying kpol(FS). CONCLUSIONS: Nanochamber is an interesting option for small field measurements. The spherical shape of the active volume is an advantage in terms of reduced angular dependence. An interesting feature of the Nanochamber is its beam quality independence and, as a future development, the possibility to use it for small field absolute dosimetry.

RapidPlan head and neck model: the objectives and possible clinical benefit.

BACKGROUND: To evaluate a knowledge based planning model for RapidPlan (RP) generated for advanced head and neck cancer (HNC) patient treatments, as well its ability to possibly improve the clinical plan quality. The stability of the model was assessed also for a different beam geometry, different dose fractionation and different management of bilateral structures (parotids). METHODS: Dosimetric and geometric data from plans of 83 patients presenting HNC were selected for the model training. All the plans used volumetric modulated arc therapy (VMAT, RapidArc) to treat two targets at dose levels of 69.96 and 54.45 Gy in 33 fractions with simultaneous integrated boost. Two models were generated, the first separating the ipsi- and contra-lateral parotids, while the second associating the two parotids to a single structure for training. The optimization objectives were adjusted to the final model to better translate the institutional planning and dosimetric strategies and trade-offs. The models were validated on 20 HNC patients, comparing the RP generated plans and the clinical plans. RP generated plans were also compared between the clinical beam arrangement and a simpler geometry, as well as for a different fractionation scheme. RESULTS: RP improved significantly the clinical plan quality, with a reduction of 2 Gy, 5 Gy, and 10 Gy of the mean parotid, oral cavity and laryngeal doses, respectively. A simpler beam geometry was deteriorating the plan quality, but in a small amount, keeping a significant improvement relative to the clinical plan. The two models, with one or two parotid structures, showed very similar results. NTCP evaluations indicated the possibility of improving (NTCP decreasing of about 7%) the toxicity profile when using the RP solution. CONCLUSIONS: The HNC RP model showed improved plan quality and planning stability for beam geometry and fractionation. An adequate choice of the objectives in the model is necessary for the trade-offs strategies.

Total monitor units influence on plan quality parameters in volumetric modulated arc therapy for breast case.

PURPOSE: To investigate the correlation between total monitor units (MU), dosimetric findings, and pre-treatment quality assurance for volumetric modulated arc therapy (VMAT) by RapidArc (RA). METHODS AND MATERIALS: Ten patients with breast cancer were considered. Dose prescriptions were: 48 Gy and 40.5 Gy in 15 fractions to, respectively, PTV(Boost) and PTVWholeBreast. A reference plan was optimized and four more plans using the "MU Objective", a tool for total MU controlling, were prepared imposing ± 20 and ± 50% total MU for inducing different complexities. Plan objectives were: D95% > 95% for both PTVs, and D2% < 107% for PTV(Boost); mean dose < 9.5 Gy and V20 Gy < 10% for ipsilateral lung; V18 Gy < 5% for heart; mean dose <3 Gy for controlateral breast; furthermore V5 Gy, V10 Gy, V20 Gy, and V30 Gy to body were minimized. Plans were evaluated in terms of technical parameters, dosimetric plan objectives findings and pre-treatment quality assurance (QA). RESULTS: Concerning PTVs, there were no significant differences for target coverage (D95%); mean doses for ipsilateral lung and controlateral breast, and V18 Gy for heart decreased with MUs increasing, reaching a plateau with reference plan. Body volume receiving low dose (V5-10 Gy) was minimized for reference plans. All plans had GAI (3 mm, 3%) > 95%. CONCLUSIONS: The data suggest that the best plan is the reference one, where the "MU Objective" tool was not used during optimisation. Nevertheless, it is advisable to use the "MU Objective" tool for re-planning when low GAI is found to increase its value. In this case, attention should be paid to OARs dose limits, since their values may be increased.

Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy (RapidArc) for prostate cancer. Report of feasibility and acute toxicity.

PURPOSE: In the present study, the acute toxicity profiles for prostate patients treated with simultaneous integrated boost (SIB) with volumetric modulated arcs in a hypofractionated regime are reported. PATIENTS AND METHODS: A total of 70 patients treated with RapidArc between May 2010 and September 2011 were retrospectively evaluated. Patients were stratified into low (36%), intermediate (49%), and high-risk (16%) groups. Target volumes (expanded to define the planning volumes (PTV)) were clinical target volume (CTV) 1: prostate; CTV2: CTV1 + seminal vesicles; CTV3: CTV2 + pelvic nodes. Low-risk patients received 71.4 Gy to PTV1; intermediate-risk 74.2 Gy to PTV1 and 61.6 or 65.5 Gy to PTV2; high-risk 74.2 Gy to PTV1, 61.6 or 65.5 Gy to PTV2, and 51.8 Gy to PTV3. All treatments were in 28 fractions. The median follow-up was 11 months (range 3.5-23 months). The acute rectal, gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to EORTC/RTOG scales. RESULTS: Acute toxicities were recorded for the GU [G0 = 31/70 (44%), G1 = 22/70 (31%); G2 = 16/70 (23%); G3 = 1/70 (1%)], the rectum [G0 = 46/70 (66%); G1 = 12/70 (17%); G2 = 12/70 (17%); no G3], and the GI [G0 = 54/69 (77%); G1 = 11/69 (16%); G2 = 4/69 (6%); no G3]. Median time to rectal, GU, and GI toxicities were 27, 30, and 33 days, respectively. Only the GI toxicity correlated with stage and pelvic irradiation. Univariate analysis presented significant correlations between GI toxicity and intestinal irradiation (V(50 Gy) and V(60 Gy)). In the multivariate analysis, the only significant dosimetric variable was V(50 Gy) for the intestinal cavity. CONCLUSION: Moderate hypofractionation with SIB and RapidArc was shown to be safe, with acceptable acute toxicity. Longer follow-up is needed to assess late toxicity and clinical outcome.