Robustness of hypofractionated breast radiotherapy after breast-conserving surgery with free breathing.

Purpose: This study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery. Methods: Twenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated. Results: All plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V 95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V 95% maintained >95% up until (5,5). Conclusion: Considering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty<5 mm.

A phase II study of concurrent involved-field radiotherapy and intrathecal chemotherapy for leptomeningeal metastasis from solid tumors.

BACKGROUND: The role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. MATERIALS AND METHODS: Enrolled patients were given induction IC first and then concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). RESULTS: Fifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3-4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3-7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4-11.4 months), and 0.8 months (95% CI, 0.08-1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5-8.1 months). CONCLUSION: Concurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.

Effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung VMAT SBRT with 6 MV FFF beam.

PURPOSE: The purpose of this study is to investigate the effect of plan complexity on the dosimetry, delivery accuracy, and interplay effect in lung stereotactic body radiation therapy (SBRT) using volumetric modulated arc therapy (VMAT) with 6 MV flattening-filter-free (FFF) beam. METHODS: Twenty patients with early stage non-small cell lung cancer were included. For each patient, high-complexity (HC) and low-complexity (LC) three-partial-arc VMAT plans were optimized by adjusting the normal tissue objectives and the maximum monitoring units (MUs) for a Varian TrueBeam linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) using 6 MV FFF beam. The effect of plan complexity was comprehensively evaluated in three aspects: (1) The dosimetric parameters, including CI, D2cm, R50, and dose-volume parameters of organs at risk were compared. (2) The delivery accuracy was assessed by pretreatment quality assurance for two groups of plans. (3) The motion-induced dose deviation was evaluated based on point dose measurements near the tumor center by using a programmable phantom. The standard deviation (SD) and maximum dose difference of five measurements were used to quantify the interplay effect. RESULTS: The dosimetry of HC and LC plans were similar except the CI (1.003 ± 0.032 and 1.026 ± 0.043, p = 0.030) and Dmax to the spinal cord (10.6 ± 3.2 and 9.9 ± 3.0, p = 0.012). The gamma passing rates were significantly higher in LC plans for all arcs (p < 0.001). The SDs of HC and LC plans ranged from 0.5-16.6% and 0.03-2.9%, respectively, under the conditions of one-field, two-field, and three-field delivery for each plan with 0.5, 1, 2, and 3 cm motion amplitudes. The maximum dose differences of HC and LC plans were 34.5% and 9.1%, respectively. CONCLUSION: For lung VMAT SBRT, LC plans have a higher delivery accuracy and a lower motion-induced dose deviation with similar dosimetry compared with HC plans.

Selection Strategy of Jaw Tracking in VMAT Planning for Lung SBRT.

PURPOSE: This study aimed to investigate the dosimetric effect and delivery reliability of jaw tracking (JT) with increasing planning target volume (PTV) for lung stereotactic body radiation therapy (SBRT) plans. A threshold of PTV was proposed as a selection criterion between JT and fixed-jaw (FJ) techniques. METHODS: A total of 28 patients with early-stage non-small-cell lung cancer were retrospectively included. The PTVs ranged from 4.88 cc to 68.74 cc, prescribed with 48 Gy in four fractions. Three-partial-arc volumetric modulated arc therapy (VMAT) plans with FJ and with JT were created for each patient with the same optimization objectives. These two sets of plans were compared using metrics, including conformity index (CI), V50%, R50%, D2cm, dose-volume parameters of organs at risk, and monitor units (MUs). The ratio of small subfields (<3 cm in either dimension), %SS, was acquired as a surrogate for the small-field uncertainty. Statistical analyses were performed to evaluate the correlation between the differences in these parameters and the PTV. RESULTS: The V50%, R50%, D2cm, and V20Gy, D1,500cc, and D1,000cc of the lung showed a statistically significant improvement in JT plans as opposed to FJ plans, while the number of MU in JT plans was higher by an average of 1.9%. Between FJ and JT plans, the PTV was strongly correlated with the differences in V50%, moderately correlated with those in V20Gy of the lung, and weakly correlated with those in D2cm and D1,500cc of the lung. By using JT, %SS was found to be negatively correlated with the PTV, and the PTV should be at least approximately 12.5 cc for an expected %SS <50%, which was 15 cc for a %SS <20% and 20 cc for a %SS <5%. CONCLUSIONS: Considering the dosimetric differences and small-field uncertainties, JT could be selected using a PTV threshold, such as 12.5, 15, or 20 cc, on the basis of the demand of delivery reliability for lung SBRT.

Systematic quantitative evaluation of Plan-IQ for intensity-modulated radiation therapy after modified radical mastectomy.

Radiotherapy (RT) is one of the main treatment strategies of breast cancer. It is challenging to design RT plans that can completely cover the target area while protecting organs at risk (OAR). The Plan-IQ feasibility tool can estimate the best sparing dose of OAR before optimizing the Plan. A systematic quantitative evaluation of the quality change of intensity-modulated radiation therapy (IMRT) using the Plan-IQ feasibility tool was performed for modified radical mastectomy in this study. We selected 50 patients with breast cancer treated with IMRT. All patients received the same dose in the planning target volume (PTV). The plans are categorized into two groups, with each patient having one plan in each group: the clinically accepted normal plan group (NP group) and the repeat plan group (RP group). An automated planning strategy was generated using a Plan-IQ feasibility dose volume histogram (FDVH) in RP group. These plans were assessed according to the dosimetry parameters. A detailed scoring strategy was based on the RTOG9804 report and 2018 National Comprehensive Cancer Network guidelines, combined with clinical experience. PTV coverage in both groups was achieved at 100% of the prescribed dose. Except for the thyroid coverage, the dose limit of organs at risk (OAR) in RP group was significantly better than that in NP group. In the scoring analysis, the total scores of RP group decreased compared to that of NP group (P < 0.05), and the individual scores of PTV and OAR significantly changed. PTV scores in RP group decreased (P < 0.01); however, OAR scores improved (P < 0.01). The Plan-IQ FDVH was useful for evaluating a class solution for IMRT planning. Plan-IQ can automatically help physicians design the best OAR protection plan, which sacrifices part of PTV, but still meets clinical requirements.

Optimization of collimator angles in dual-arc volumetric modulated arc therapy planning for whole-brain radiotherapy with hippocampus and inner ear sparing.

To optimize the collimator angles in dual-arc volumetric modulated arc therapy (VMAT) plans for whole-brain radiotherapy with hippocampus and inner ear sparing (HIS-WBRT). Two sets of dual-arc VMAT plans were generated for 13 small-cell lung cancer patients: (1) The collimator angles of arcs 1 and 2 (θ1/θ2) were 350°/10°, 350°/30°, 350°/45°, 350°/60°, and 350°/80°, i.e., the intersection angle of θ1 and θ2 (Δθ) increased. (2) θ1/θ2 were 280°/10°, 300°/30°, 315°/45°, 330°/60°, and 350°/80°, i.e., Δθ = 90°. The conformity index (CI), homogeneity index (HI), monitor units (MUs), and dosimetric parameters of organs-at-risk were analyzed. Quality assurance for Δθ = 90° plans was performed. With Δθ increasing towards 90°, a significant improvement was observed for most parameters. In 350°/80° plans compared with 350°/10° ones, CI and HI were improved by 1.1% and 25.2%, respectively; MUs were reduced by 16.2%; minimum, maximum, and mean doses (D100%, Dmax, and Dmean, respectively) to the hippocampus were reduced by 5.5%, 6.3%, and 5.4%, respectively; Dmean to the inner ear and eye were reduced by 0.7% and 5.1%, respectively. With Δθ kept at 90°, the plan quality was not significantly affected by θ1/θ2 combinations. The gamma-index passing rates in 280°/10° and 350°/80° plans were relatively lower compared with the other Δθ = 90° plans. Δθ showed a significant effect on dual-arc VMAT plans for HIS-WBRT. With Δθ approaching 90°, the plan quality exhibited a nearly continuous improvement, whereas with Δθ = 90°, the effect of θ1/θ2 combination was insignificant.

Meridian acupuncture plus massage for children with spastic cerebral palsy.

OBJECTIVE: To evaluate the effect of combination therapy of meridian acupuncture and massage on motor development in children with spastic cerebral palsy (SCP). METHODS: A total of 113 children with SCP in our hospital were allocated into research group (63 cases, treated with meridian acupuncture plus massage) and control group (50 cases, treated with routine rehabilitation measures). Clinical efficacy and alterations of inflammatory factors were observed. Peabody Developmental Motor Scale (PDMS) and gross motor function measure (GMFM-88; sitting, standing, walking) were employed for the assessment of motor ability. Changes in muscle tension were monitored with the Ashworth scale (AS), and modified Barthel index (MBI) and Gesell's Developmental Schedule (GDS) were used to evaluate children's daily activities, language, fine motor skills, and adaptability. Finally, the development of children in the two groups was monitored. RESULTS: The research group had higher total effective rate than the control group (P=0.018). After treatment, the levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in the research group were lower than those in the control group (P<0.05); the PDMS and AS scores were reduced in both groups, and the reduction was greater in research group (P<0.05); GFMF-88, Barthel and GDS scores increased in both groups, especially in the research group; children in research group were better developed than those in control group (P<0.05). CONCLUSION: Meridian acupuncture plus massage contributes to a significant improvement of motor development in children with SCP.

Technical Note: Induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model.

PURPOSE: The induced radioactivity in stereotactic body radiation therapy with a flattening-filter-free 10 MV beam model (10 FFF SBRT) was investigated for the risk to therapists. METHODS: This study was performed on a Varian TrueBeam linac. The induced radioisotopes were identified by γ spectroscopy. The dose rate from the induced activity was measured for 12 treatment cycles in 4 h continuously. The impacts of the characteristic factors of 10 FFF SBRT on the dose rate were investigated, including monitor units (MU), beam rate, field size, and flattening filter. The dose rate was compared between the SBRT plans and conventional fractionation plans. A mathematical model was used to analyze the results and estimate the annual dose to therapists. RESULTS: (a) The induced radioisotopes included 24 Na, 28 Al, 38 Cl, 56 Mn, 66 Cu, 187 W, and 196 Au. (b) In 4 h, the total dose contribution ratios were more than 70% for 28 Al, about 20% for 56 Mn, and 10% for all other long-lived radioisotopes, combining doses at the isocenter and end of the treatment couch. (c) The dose rate showed a nonlinear growth with increasing MU and beam rate. The variation of the dose rate was complicated with the jaw field and not sensitive to the MLC field. The removal of the flattening filter reduced the dose rate by about 40%. The dose level of SBRT was two to three times that of conventional fractionation. (d) The estimated annual dose to therapists was up to 0.20 mSv/y. CONCLUSIONS: The induced radioactivity in 10 FFF SBRT was higher compared with that in 10 MV conventional fractionation. More MU and higher beam rate were the primary factors that caused the increase. The therapists should wait longer after beam-off to reduce the occupational dose. In addition, aluminum and manganese should be less used in the treatment room.

Intrathecal pemetrexed combined with involved-field radiotherapy as a first-line intra-CSF therapy for leptomeningeal metastases from solid tumors: a phase I/II study.

PURPOSE: A phase I/II study of intrathecal pemetrexed (IP) combined with involved-field radiotherapy (IFRT) was performed to determine feasibility, safety, and antitumor activity for leptomeningeal metastases (LM) from solid tumors. METHODS: Participants first received induction IP administration, followed by concomitant radiotherapy within 3 days. The concomitant regimen consisted of IP (pemetrexed 10 mg, dexamethasone 5 mg, once per week, 4 times in 4 weeks) and IFRT (40 Gy in 20 fractions). Six participants were recruited to assess feasibility in phase I, and then 28 patients were recruited further. All patients were assessed to investigate safety, efficacy, and outcomes. RESULTS: Between April 2018 and December 2018, 34 patients (male: 15; female: 19; median age: 56 years) were enrolled, including non-small-cell lung cancer (21), small-cell lung cancer (5), breast cancer (4), and others (4). Thirty-two patients received concurrent therapy and 25 (74%) patients completed the treatment. Major adverse events (AEs) consisted of myelosuppression, the elevation of hepatic aminotransferases, and radiculitis. Total AEs rate was 53% (18/34), including 6 (18%) patients with grade 3 and 1 (3%) with grade 4 AEs. The response rate was 68% (23/34). The median overall survival was 5.5 (0.3-16.6) months. Median neurological progression-free survival (NPFS) was 3.5 (0.3-15.2) months. Six-month NPFS rate was 47%. One-year survival rate was 21.6%. CONCLUSION: IP at a 10 mg dose on a schedule of 1-2 times per week presented good efficacy and safety in CSF. The concomitant regimen is an efficacious therapeutic option for LM patients with solid tumors. TRIAL REGISTRATION: This study (IPLM) was registered at https://register.clinicaltrials.gov [ClinicalTrials.gov identifier: NCT03507244].

Application of auto-planning in radiotherapy for breast cancer after breast-conserving surgery.

To evaluate the quality of planning target volume (PTV) and organs at risk (OAR) generated by the manual Pinnacle planning (manP) and Auto-Planning (AP) modules and discuss the feasibility of AP in the application of radiotherapy for patients with breast cancer. Thirty patients who underwent breast-conserving therapy were randomly selected. The Philips Pinnacle 9.10 treatment planning system was used to design the manP and AP modules for PTV and OAR distribution on the same computed tomography. A physician compared the plans in terms of dosimetric parameters and monitor units (MUs) using blind qualitative scoring. Statistical differences were evaluated using paired two-sided Wilcoxon's signed-rank test. On comparing the plans of AP and manP modules, the conformal index (P < 0.01) and D50 (P = 0.04) of PTV in the AP group was lower than those in the manP group, while D1 was higher (P = 0.03). In terms of dosimetry of OAR, ipsilateral lung V20 Gy (P < 0.01), V10 Gy (P < 0.01), V5 Gy (P < 0.05), and Dmean (P < 0.01) of the AP group were better than those of the manP group. Heart V40 Gy and Dmean of all patients with breast cancer in the AP group were lower than those in the manP group (P < 0.01). Moreover, 12 patients with left breast cancer had the same results (P < 0.01). The MU value of the intensity-modulated radiation therapy module designed using two different methods was higher in the AP group than in the manP group (P = 0.32), although there was no statistical significance. The AP module almost had an equal quality of PTV and dose distribution as the manP module, and its OAR was less irradiated.

[Effects of acupoint thread implantation and Chinese herb on PTH and TGF-beta1 in the rate of chronic renal failure].

OBJECTIVE: To probe into the mechanisms of thread implantation at Zusanli(ST 36) and Chinese herbs in treatment of chronic renal failure(CRF). METHODS: CRF rat model was made by Platt subtotal nephrectomy. They were divided into 5 groups, sham operation group, model group, Chinese herbs group, thread implantation group and thread implantation plus Chinese herbs group. After treatment of 8 weeks, serum parathyroid hormone (PHT), transforming growth factor beta1 (TGF-beta1) expression in residual renal cells, malondialdehyde(MDA) content in the residual renal tissue, serum urea nitrogen(BUN) and creatinine(Scr), protein in urine and pathological changes were investigated. RESULTS: The above indexes after treatment by thread implantation at acupoint, Chinese herbs, and acupoint thread implantation plus Chinese herbs showed begin reversion, especially, the most obviously improvement in the acupoint thread implantation plus Chinese herbs treatment group. CONCLUSION: The mechanism of acupoint thread implantation and Chinese herbs in improvement of CRF is related with decrease of PTH, inhibition of TGF-beta1 expression, decrease of MDA content and resisting lesion of renal fibrosis.