Intensity modulated proton therapy (IMPT) is a promising radiation therapy (RT) modality for cervical cancer treatment, especially for its potential role in reducing hematologic toxicity. IMPT dose distribution is known to be sensitive to patient anatomical changes during the treatment course. This study quantifies the effect of the anatomical change on IMPT’s target coverage for cervical cancer treatment. In this IRB-approved study, 3-beam IMPT plans were generated on the planning computed tomography (CT) image for 6 enrolled patients. Three or 4 weekly CT images were obtained for each patient using the same imaging protocol in subsequent weeks after the simulation day, for a total of 21 weekly CT images. CTs of the same patient were rigidly registered to the planning CT by matching bony anatomy. The geometric cervical and nodal target volumes were the same in subsequent CTs as in the planning CT, while major organs-at-risk including bowel, bladder, and rectum were re-contoured on each weekly CT. Patient body weights at the time of each weekly CT scan were also recorded. Dose from the IMPT plan was recomputed on these weekly CTs. Dose received by at least 95% of the cervical and nodal internal target volumes (Cervical DITV95% and Nodal DITV95%, respectively) were compared to their planned values. Univariate analysis was performed to discover the correlation between DITV95% to the relative changes of various anatomical factors, as well as the correlation between the anatomical factors. Body weight increase was found to be significantly correlated to the decrease of both Cervical DITV95% (Spearman rank correlation coefficient SCC=-0.653, P=.001) and Nodal DITV95% (SCC=-0.713, P

Background and purpose: This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity.Material and methods: IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated X-ray therapy (IMRT). Functional bone marrow was identified by F-18-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5-40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with +/- 3% range uncertainty errors and/or +/- 3 mm translational setup errors in all three principal dimensions.Results: In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V-5Gy, 47% for V-10Gy, 54% for V-20Gy, and 57% for V-40Gy, all with p < 0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V-5Gy, 37% for V-10Gy, 41% for V-20Gy, and 39% for V-40Gy, all with p < 0.01.Conclusions: The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Intensity-modulated proton therapy (IMPT) is a promising radiation therapy modality for cervical cancer treatment, especially for its potential role in sparing pelvic bone marrow (BM) and reducing hematologic toxicity. The delivered IMPT dose distributions may be sensitive to anatomical changes in the patient during the treatment course. This study investigates the effect of the body weight change on the dose distribution of bone-marrow sparing IMPT for cervical cancer treatment. In this IRB-approved study, 28 weekly computed tomography (CT) images were obtained from 7 enrolled patients. Three-beam bone-marrow sparing (BMS) IMPT plans were generated on CT obtained on the simulation day. Dose from the IMPT plan was re-computed on CTs obtained from the same scanner using the same protocol in subsequent weeks until 30 days after the clinical intensity-modulated photon radiation therapy (IMRT) treatment. CTs of the same patient were rigidly registered by matching bony anatomy; the geometric target volume and bone marrow volume were copied from planning CT to subsequent CT. Patient body weight at the time of each CT scan were recorded. Dose received by at least 95% of the target volume (DTV95%) and the volume of bone marrow receiving at least 5 Gy (VBM5Gy) were compared to their planned values. Univariate analysis was performed to correlate the relative change in DTV95% and VBM5Gy, respectively, to the relative change of body weight. Target coverage is considered adequate if DTV95% is equal to or above 95% of the planned value. An analysis was performed to predict the probability of adequate target coverage under certain weight changes. Among the available data, relative body weight changes ranged between -6.1% to +9.4%. Relative body weight increase was significantly correlated to the decrease of DTV95%, with Pearson correlation coefficient (PCC) of -0.5537 (p = 0.0022, 95% Confidence Interval(CI): -0.7681 to -0.2276). With 2% weight increases, the probability of adequate target coverage drops to only 70.7% (95% CI: 36.1% to 88.9%). Relative body weight decrease was found to be significantly correlated to the increase of VBM5Gy, with PCC of -0.7552 (p < 0.0001, 95%CI: -0.8803 to -0.5320). In all cases, IMPT VBM5Gy was still significantly less than IMRT VBM5Gy (p < 0.0001), with a mean reduction of 30.5% (95%CI: 28.7% to 33.0%). IMPT dose distributions in the pelvis are very sensitive to changes in body weight. Body weight increase significantly reduces target coverage in cervical cancer IMPT. Active monitoring of patient body weight throughout the treatment, and potentially adaptive re-planning, may be necessary to maintain adequate target coverage in IMPT for cervical cancer.

Purpose: Pencil beam scanning (PBS) proton therapy provides excellent dosimetric benefits in pelvic cancer treatment, yet day-to-day anatomical variations in pelvic region tend to cause range uncertainties. This study evaluates the dosimetric robustness under anatomical changes for three PBS intensity-modulated proton therapy (IMPT), IMPT using worstcase robust optimization (thereafter ‘Robust IMPT’), and single-field uniform dose (SFUD), in cervical cancer treatment. Methods: IMPT, Robust IMPT, and SFUD plans using the same beam directions and the same prescription (Rx) were generated on computed tomography (CT) images acquired on the simulation day. The dose from each plan was then recomputed on CT images acquired in subsequent two to five weeks using the same protocol. The weekly CTs were registered to the planning CT based on bony anatomy. Target coverage was considered adequate on each weekly CT if dose to 99% of the internal target volume (D_ITV99%) reached at least 95% of the Rx dose. Statistical analysis was then performed on the 21 weekly CT images available for the 7 enrolled patients. Results: Statistically, IMPT was unable to maintain target coverage (mean D_ITV99% = 90.5% Rx, p = 0.004), and SFUD was able to maintain target coverage (mean D_ITV99% = 98.0% Rx, p = 0.0064), in the weeks following simulation. Robust IMPT was able to improve the robustness of IMPT significantly (p < 0.0001), though its maintenance of target coverage was not statistically significant by the 95% Rx criteria (mean D_ITV99% = 96.0%, p = 0.1677). Conclusion: During the multi-week treatment course with anatomical variations, SFUD is robust in terms of maintaining target coverage while IMPT is not. The worst-case optimized Robust IMPT, assuming ±3.5% range uncertainties, improves the robustness of IMPT under anatomical changes significantly, even though it was not designed to account for anatomical changes by mechanism.

PURPOSE To determine the plan quality of proton spot scanning (SS) radiosurgery as a function of spot size (in-air sigma) in comparison to x-ray radiosurgery for treating peripheral brain lesions. METHODS Single-field optimized (SFO) proton SS plans with sigma ranging from 1 to 8 mm, cone-based x-ray radiosurgery (Cone), and x-ray volumetric modulated arc therapy (VMAT) plans were generated for 11 patients. Plans were evaluated using secondary cancer risk and brain necrosis normal tissue complication probability (NTCP). RESULTS For all patients, secondary cancer is a negligible risk compared to brain necrosis NTCP. Secondary cancer risk was lower in proton SS plans than in photon plans regardless of spot size (p = 0.001). Brain necrosis NTCP increased monotonically from an average of 2.34/100 (range 0.42/100-4.49/100) to 6.05/100 (range 1.38/100-11.6/100) as sigma increased from 1 to 8 mm, compared to the average of 6.01/100 (range 0.82/100-11.5/100) for Cone and 5.22/100 (range 1.37/100-8.00/100) for VMAT. An in-air sigma less than 4.3 mm was required for proton SS plans to reduce NTCP over photon techniques for the cohort of patients studied with statistical significance (p = 0.0186). Proton SS plans with in-air sigma larger than 7.1 mm had significantly greater brain necrosis NTCP than photon techniques (p = 0.0322). CONCLUSIONS For treating peripheral brain lesions--where proton therapy would be expected to have the greatest depth-dose advantage over photon therapy--the lateral penumbra strongly impacts the SS plan quality relative to photon techniques: proton beamlet sigma at patient surface must be small (<7.1 mm for three-beam single-field optimized SS plans) in order to achieve comparable or smaller brain necrosis NTCP relative to photon radiosurgery techniques. Achieving such small in-air sigma values at low energy (<70 MeV) is a major technological challenge in commercially available proton therapy systems.

Purpose: To determine the effectiveness of pelvic bone marrow sparing by utilizing intensity modulated proton therapy (IMPT) in the treatment of cervical cancer, in comparison to that of intensity modulated photon therapy (IMXT); and to investigate the robustness of the bone marrow sparing by IMPT under range uncertainty and patient setup uncertainty. Methods: 3‐field IMPT was planned for five enrolled patients. DVH objectives for PTV and organs‐at‐risk (OAR) aimed to give 45 Gy to the tumor in 25 fractions, matching those of the IMXT plan delivered clinically. The percentage volumes of bone marrow receiving 10 Gy and 20 Gy were set to be reduced in IMPT compared with IMXT. The dose from the IMPT plan was then recalculated in uncertainty scenarios which were combinations of systematic 3% density errors and uniformly random patient setup errors of (0.6cm, 0.6cm, 0.6cm). The robustness of target coverage and bone marrow sparing through the whole course of 25 fractions was then analyzed. Results: In the static scenario, the IMPT plan achieved the same or better PTV coverage and OAR sparing compared to IMXT, and reduced the percentage volume of bone marrow receiving 15 Gy or larger dose (V15Gy) to 32.3% from 60.0% on average. Robustness analysis showed that proper CTV coverage is preserved over the whole course of treatment with the presumed range and positioning errors. The reduction of bone marrow dose is also statistically significant and robust under those uncertainties, with a minimum reduction of V15Gy to 39.9% from 60.0%. Conclusion: IMPT can significantly reduce the volume of active bone marrow receiving low dose radiation, therefore potentially decreasing hematologic toxicity in concurrent chemoradiation therapy for cervical cancer. Bone marrow sparing by IMPT is robust in the context of range and positioning uncertainties.