Dosimetric differences among volumetric modulated arc radiotherapy (RapidArc) plans based on different target volumes in radiotherapy of hepatocellular carcinoma

We investigated the dosimetric differences among volumetric-modulated arc radiotherapy (RapidArc, RA) plans designed for various target volumes in hepatocellular carcinoma (HCC). Ten HCC patients underwent 3D-CT scanning at free breathing (FB), 3D-CT at end inspiration hold (EIH) assisted by an Active Breathing Coordinator (ABC), and 4D-CT scanning. Gross tumor volumes (GTVs) were manually contoured on CT images. The individualized internal gross target volume (IGTV₁) was obtained from 10 GTVs from 4D-CT images. Tumor individual margins were measured from GTV_FB to IGTV₁. The IGTV₂ was obtained from GTV_FB by applying individual margins. Four planning target volumes (PTV_1-4) were obtained from IGTV₁, IGTV₂, GTV_FB, and GTV_EIH, respectively. An RA plan was designed for each of the PTVs (RA_1–4). One 358° arc was used for PTVs_1–3, while three 135° arcs were used for PTV₄. It was found that PTV₂ and PTV₃ were larger than PTV₁ and PTV₄. The mean values of PTV₃/PTV₁ and PTV₃/PTV₄ were 2.5 and 1.9, respectively. The individual margins in the X, Y and Z axial directions varied greatly among these patients. There were no significant differences in the conformal index or homogeneity index among the four RA plans. RA₁ and RA₄ significantly reduced the radiation dose of normal liver tissue compared with RA₂ and RA₃ (P < 0.01). There were no significant differences between the radiation doses of the stomach and duodenum. RapidArc combined with 4D-CT or ABC technology is a promising method in radiotherapy of HCC, and accurately targeted the tumor volume while sparing more normal liver tissue.     

Evaluation of dosimetric variance in whole breast forward-planned intensity-modulated radiotherapy based on 4DCT and 3DCT

This study was performed to explore and compare the dosimetric variance caused by respiratory movement in the breast during forward-planned IMRT after breast-conserving surgery. A total of 17 enrolled patients underwent the 3DCT simulation scans followed by 4DCT simulation scans during free breathing. The treatment planning constructed using the 3DCT images was copied and applied to the end expiration (EE) and end inspiration (EI) scans and the dose distributions were calculated separately. CTV volume variance amplitude was very small (11.93 ± 28.64 cm³), and the percentage change of CTV volumes receiving 50 Gy and 55 Gy between different scans were all less than 0.8%. There was no statistically significant difference between EI and EE scans (Z =–0.26, P = 0.795). However, significant differences were found when comparing the D_mean at 3DCT planning with the EI and EE planning (P = 0.010 and 0.019, respectively). The homogeneity index at EI, EE and 3D plannings were 0.139, 0.141 and 0.127, respectively, and significant differences existed between 3D and EI, and between 3D and EE (P = 0.001 and 0.006, respectively). The conformal index (CI) increased significantly in 3D treatment planning (0.74 ± 0.07) compared with the EI and EE phase plannings (P = 0.005 and 0.005, respectively). The V₃₀, V₄₀, V₅₀ and D_mean of the ipsilateral lung for EE phase planning were significantly lower than for EI (P = 0.001–0.042). There were no significant differences in all the DVH parameters for the heart among these plannings (P = 0.128–0.866). The breast deformation during respiration can be disregarded in whole breast IMRT. 3D treatment planning is sufficient for whole breast forward-planned IMRT on the basis of our DVH analysis, but 4D treatment planning, breath-hold, or respiratory gate may ensure precise delivery of radiation dose.     

Geometrical differences in gross target volumes between 3DCT and 4DCT imaging in radiotherapy for non-small-cell lung cancer

The aim of this study was to explore the characteristic of 3DCT scanning phases and estimate the comparative amount of respiration motion information included in 3DCT and 4DCT by comparing the volumetric and positional difference between the volumes from 3DCT and 4DCT for the radiotherapy of non-small-cell lung cancer (NSCLC). A total of 28 patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The 4DCT images with respiratory signal data were reconstructed and sorted into 10 phases throughout a respiratory cycle. GTV-3D from 3DCT, GTV-0%, GTV-20%, GTV-50% and GTV-70% from end-inspiration, mid-expiration, end-expiration and mid-inspiration of 4DCT, and the internal GTV (IGTV-10) from the fused phase of 4DCT were delineated based on the 50% phase image, respectively. The differences in the position, size, matching index (MI) and degree of inclusion (DI) for different volumes were evaluated. The variation in the centroid shifts of GTV-0% and GTV-3D, GTV-20% and GTV-3D, GTV-50% and GTV-3D, and GTV-90% and GTV-3D in the 3D direction was not significant (P = 0.990). The size ratios of GTV-0%, GTV-20%, GTV-50%, GTV-70% and IGTV-10 to GTV-3D were 0.94 ± 0.18, 0.95 ± 0.18, 0.98 ± 0.15, 1.00 ± 0.18 and 1.60 ± 0.55, respectively. DIs of GTV-3D in IGTV-10, and IGTV-10 in GTV-3D were 0.88 ± 0.14 and 0.59 ± 0.16 (P < 0.001). The 3DCT scanning phases are irregular. The CTV-to-ITV expansion should be isotropic when defining the ITV on the 3DCT. The internal GTV derived from 4DCT cannot completely include the GTV from 3DCT. An additional margin may be required when defining the ITV-based 4DCT.     

Amplitude-based gated phase-controlled rescanning in carbon-ion scanning beam treatment planning under irregular breathing conditions using lung and liver 4DCTs

Amplitude-based gating aids treatment planning in scanned particle therapy because it gives better control of uncertainty with the gate window. We have installed an X-ray fluoroscopic imaging system in our treatment room for clinical use with an amplitude-based gating strategy. We evaluated the effects of this gating under realistic organ motion conditions using 4DCT data of lung and liver tumors. 4DCT imaging was done for 24 lung and liver patients using the area-detector CT. We calculated the field-specific target volume (FTV) for the gating window, which was defined for a single respiratory cycle. Prescribed doses of 48 Gy relative biological effectiveness (RBE)/fraction/four fields and 45 Gy RBE/two fractions/two fields were delivered to the FTVs for lung and liver treatments, respectively. Dose distributions were calculated for the repeated first respiratory cycle (= planning dose) and the whole respiratory data (= treatment dose). We applied eight phase-controlled rescannings with the amplitude-based gating. For the lung cases, D95 of the treatment dose (= 96.0 ± 1.0%) was almost the same as that of the planning dose (= 96.6 ± 0.9%). D_max/D_min of the treatment dose (= 104.5 ± 2.2%/89.4 ± 2.6%) was slightly increased over that of the planning dose (= 102.1 ± 1.0%/89.8 ± 2.5%) due to hot spots. For the liver cases, D₉₅ of the treatment dose (= 97.6 ± 0.5%) was decreased by ∼ 1% when compared with the planning dose (= 98.5 ± 0.4%). D_max/D_min of the treatment dose was degraded by 3.0%/0.4% compared with the planning dose. Average treatment times were extended by 46.5 s and 65.9 s from those of the planning dose for lung and liver cases, respectively. As with regular respiratory patterns, amplitude-based gated multiple phase-controlled rescanning preserves target coverage to a moving target under irregular respiratory patterns.     

VMAT–SBRT planning based on an average intensity projection for lung tumors located in close proximity to the diaphragm: a phantom and clinical validity study

The aim of the this study was to validate the use of an average intensity projection (AIP) for volumetric-modulated arc therapy for stereotactic body radiation therapy (VMAT–SBRT) planning for a moving lung tumor located near the diaphragm. VMAT–SBRT plans were created using AIPs reconstructed from 10 phases of 4DCT images that were acquired with a target phantom moving with amplitudes of 5, 10, 20 and 30 mm. To generate a 4D dose distribution, the static dose for each phase was recalculated and the doses were accumulated by using the phantom position known for each phase. For 10 patients with lung tumors, a deformable registration was used to generate 4D dose distributions. Doses to the target volume obtained from the AIP plan and the 4D plan were compared, as were the doses obtained from each plan to the organs at risk (OARs). In both phantom and clinical study, dose discrepancies for all parameters of the dose volume (D_min, D₉₉, D_max, D₁ and D_mean) to the target were <3%. The discrepancies of D_max for spinal cord, esophagus and heart were <1 Gy, and the discrepancy of V20 for lung tissue was <1%. However, for OARs with large respiratory motion, the discrepancy of the D_max was as much as 9.6 Gy for liver and 5.7 Gy for stomach. Thus, AIP is clinically acceptable as a planning CT image for predicting 4D dose, but doses to the OARs with large respiratory motion were underestimated with the AIP approach.     

The clinical application of 4D 18F-FDG PET/CT on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer

A combination of four-dimensional computed tomography with ¹⁸F-fluorodeoxyglucose positron emission tomography (4D CT-FDG PET) was used to delineate gross tumor volume (GTV) in esophageal cancer (EC). Eighteen patients with EC were prospectively enrolled. Using 4D images taken during the respiratory cycle, the average CT image phase was fused with the average FDG PET phase in order to analyze the optimal standardized uptake values (SUV) or threshold. PET-based GTV (GTV_PET) was determined with eight different threshold methods using the auto-contouring function on the PET workstation. The difference in volume ratio (VR) and conformality index (CI) between GTV_PET and CT-based GTV (GTV_CT) was investigated. The image sets via automatic co-registrations of 4D CT-FDG PET were available for 12 patients with 13 GTV_CT values. The decision coefficient (R²) of tumor length difference at the threshold levels of SUV 2.5, SUV 20% and SUV 25% were 0.79, 0.65 and 0.54, respectively. The mean volume of GTV_CT was 29.41 ± 19.14 ml. The mean VR ranged from 0.30 to 1.48. The optimal VR of 0.98, close to 1, was at SUV 20% or SUV 2.5. The mean CI ranged from 0.28 to 0.58. The best CI was at SUV 20% (0.58) or SUV 2.5 (0.57). The auto-contouring function of the SUV threshold has the potential to assist in contouring the GTV. The SUV threshold setting of SUV 20% or SUV 2.5 achieves the optimal correlation of tumor length, VR, and CI using 4D-PET/CT images.     

Inverse planning for combination of intracavitary and interstitial brachytherapy for locally advanced cervical cancer

The main purpose of this study was to compare three different treatment plans for locally advanced cervical cancer: (i) the inverse-planning simulated annealing (IPSA) plan for combination brachytherapy (BT) of interstitial and intracavitary brachytherapy, (ii) manual optimization based on the Manchester system for combination-BT, and (iii) the conventional Manchester system using only tandem and ovoids. This was a retrospective study of 25 consecutive implants. The high-risk clinical target volume (HR-CTV) and organs at risk were defined according to the GEC-ESTRO Working Group definitions. A dose of 6 Gy was prescribed. The uniform cost function for dose constraints was applied to all IPSA-generated plans. The coverage of the HR-CTV by IPSA for combination-BT was equivalent to that of manual optimization, and was better than that of the Manchester system using only tandem and ovoids. The mean V₁₀₀ achieved by IPSA for combination-BT, manual optimization and Manchester was 96 ± 3.7%, 95 ± 5.5% and 80 ± 13.4%, respectively. The mean D₁₀₀ was 483 ± 80, 487 ± 97 and 335 ± 119 cGy, respectively. The mean D₉₀ was 677 ± 61, 681 ± 88 and 513 ± 150 cGy, respectively. IPSA resulted in significant reductions of the doses to the rectum (IPSA D_2cm³: 408 ± 71 cGy vs manual optimization D_2cm³: 485 ± 105 cGy; P = 0.03) and the bladder (IPSA D_2cm³: 452 ± 60 cGy vs manual optimization D_2cm³: 583 ± 113 cGy; P < 0.0001). In conclusion, combination-BT achieved better tumor coverage, and plans using IPSA provided significant sparing of normal tissues without compromising CTV coverage.     

Dosimetric benefits of placing dose constraints on the brachial plexus in patients with nasopharyngeal carcinoma receiving intensity-modulated radiation therapy: a comparative study

This study aimed to evaluate whether placing dose constraints on the brachial plexus (BP) could provide dosimetric benefits in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). Planning CT images for 30 patients with NPC treated with definitive IMRT were retrospectively reviewed. Target volumes, the BP and other critical structures were delineated; two separate IMRT plans were designed for each patient: one set no restrictions for the BP; the other considered the BP as a critical structure for which a maximum dose limit of ≤66 Gy was set. No significant differences between the two plans were observed in the conformity index, homogeneity index, maximum dose to the planning target volumes (PTVs), minimum dose to the PTVs, percentages of the volume of the PTVnx and PTVnd receiving more than 110% of the prescribed dose, or percentages of the volume of the PTVs receiving 95% and > 93% of the prescribed dose. Dose constraints significantly reduced the maximum dose, mean dose, V45, V50, V54, V60, V66 and V70 to the BP. Dose constraints significantly reduced the maximum dose to the BP, V45, V60 and V66 in both N0–1 and N2–3 disease; however, the magnitude of the dosimetric gain for each parameter between N0–1 and N2–3 disease was not significantly different, except for the V60 and V66. In conclusion, placing dose constraints on the BP can significantly decrease the irradiated volume and dose, without compromising adequate dose delivery to the target volume.     

Preoperative chemoradiotherapy for locally advanced low rectal cancer using intensity-modulated radiotherapy to spare the intestines: a single-institutional pilot trial

The irradiated volume of intestines is associated with gastrointestinal toxicity in preoperative chemoradiotherapy for rectal cancer. The current trial prospectively explored how much of the irradiated volume of intestines was reduced by intensity-modulated radiotherapy (IMRT) compared with 3-dimensional conformal radiotherapy (3DCRT) and whether IMRT might alleviate the acute gastrointestinal toxicity in this population. The treatment protocol encompassed preoperative chemoradiotherapy using IMRT plus surgery for patients with clinical T3–4, N0–2 low rectal cancer. IMRT delivered 45 Gy per 25 fractions for gross tumors, mesorectal and lateral lymph nodal regions, and tried to reduce the volume of intestines receiving 15 Gy (V_{15 Gy}) < 120 cc and V_{45 Gy} ≤ 0 cc, respectively, while keeping target coverage. S-1 and irinotecan were concurrently administered. Acute gastrointestinal toxicity, rates of clinical downstaging, sphincter preservation, local regional control (LRC) and overall survival (OS) were evaluated. Twelve enrolled patients completed the chemoradiotherapy protocol. The volumes of intestines receiving medium to high doses were reduced by the current IMRT protocol compared to 3DCRT; however, the predefined constraint of V_{15 Gy} was met only in three patients. The rate of ≥ grade 2 gastrointestinal toxicity excluding anorectal symptoms was 17%. The rates of clinical downstaging, sphincter preservation, three-year LRC and OS were 75%, 92%, 92% and 92%, respectively. In conclusion, preoperative chemoradiotherapy using IMRT for this population might alleviate acute gastrointestinal toxicity, achieving high LRC and sphincter preservation; although further advancement is required to reduce the irradiated volume of intestines, especially those receiving low doses.     

Association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury after intensity-modulated radiotherapy in lung cancer: a retrospective analysis

The aim of this study was to investigate the association between absolute volumes of lung spared from low-dose irradiation and radiation-induced lung injury (RILI) after intensity-modulated radiotherapy (IMRT) for lung cancer. The normal lung relative volumes receiving greater than 5, 10, 20 and 30 Gy (V5–30) mean lung dose (MLD), and absolute volumes spared from greater than 5, 10, 20 and 30 Gy (AVS5–30) for the bilateral and ipsilateral lungs of 83 patients were recorded. Any association of clinical factors and dose–volume parameters with Grade ≥2 RILI was analyzed. The median follow-up was 12.3 months; 18 (21.7%) cases of Grade 2 RILI, seven (8.4%) of Grade 3 and two (2.4%) of Grade 4 were observed. Univariate analysis revealed the located lobe of the primary tumor. V5, V10, V20, MLD of the ipsilateral lung, V5, V10, V20, V30 and MLD of the bilateral lung, and AVS5 and AVS10 of the ipsilateral lung were associated with Grade ≥2 RILI (P < 0.05). Multivariate analysis indicated AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI (P = 0.010, OR = 0.272, 95% CI: 0.102–0.729). Receiver operating characteristic curves indicated Grade ≥2 RILI could be predicted using AVS5 of the ipsilateral lung (area under curve, 0.668; cutoff value, 564.9 cm³; sensitivity, 60.7%; specificity, 70.4%). The incidence of Grade ≥2 RILI was significantly lower with AVS5 of the ipsilateral lung ≥564.9 cm³ than with AVS5 < 564.9 cm³ (P = 0.008). Low-dose irradiation relative volumes and MLD of the bilateral or ipsilateral lung were associated with Grade ≥2 RILI, and AVS5 of the ipsilateral lung was prognostic for Grade ≥2 RILI for lung cancer after IMRT.     

Radiobiological model-based bio-anatomical quality assurance in intensity-modulated radiation therapy for prostate cancer

A bio-anatomical quality assurance (QA) method employing tumor control probability (TCP) and normal tissue complication probability (NTCP) is described that can integrate radiobiological effects into intensity-modulated radiation therapy (IMRT). We evaluated the variations in the radiobiological effects caused by random errors (r-errors) and systematic errors (s-errors) by evaluating TCP and NTCP in two groups: patients with an intact prostate (G_intact) and those who have undergone prostatectomy (G_tectomy). The r-errors were generated using an isocenter shift of ±1 mm to simulate a misaligned patient set-up. The s-errors were generated using individual leaves that were displaced inwardly and outwardly by 1 mm on multileaf collimator field files. Subvolume-based TCP and NTCP were visualized on computed tomography (CT) images to determine the radiobiological effects on the principal structures. The bio-anatomical QA using the TCP and NTCP maps differentiated the critical radiobiological effects on specific volumes, particularly at the anterior rectal walls and planning target volumes. The s-errors showed a TCP variation of –40–25% in G_tectomy and –30–10% in G_intact, while the r-errors were less than 1.5% in both groups. The r-errors for the rectum and bladder showed higher NTCP variations at ±20% and ±10%, respectively, and the s-errors were greater than ±65% for both. This bio-anatomical method, as a patient-specific IMRT QA, can provide distinct indications of clinically significant radiobiological effects beyond the minimization of probable physical dose errors in phantoms.     

Dose rate in the highest irradiation area of the rectum correlates with late rectal complications in patients treated with high-dose-rate computed tomography-based image-guided brachytherapy for cervical cancer

The purpose of this study was to evaluate the effect of dose rate to the rectum on late rectal complications in patients treated with computed tomography (CT)-based image-guided brachytherapy (IGBT) for cervical cancer. The subjects were 142 patients with cervical cancer who underwent Ir-192 high-dose-rate (HDR)-IGBT between March 2012 and January 2018. The dose rate to the rectum was calculated using in-house software. The minimum, mean and maximum effective dose rate (EDR) was calculated for voxels of the rectal volume covered by cumulative doses >D_0.1cc, >D_2cc, and > D_5cc. The average EDR of three to four brachytherapy sessions was calculated (EDR for patients; EDR_p). The total dose of the rectum was calculated as the biologically equivalent dose in 2-Gy fractions (EQD₂). The associations between EDR_p for D_0.1cc, D_2cc, and D_5cc and the respective rectal EQD₂ values with late rectal complications were then analyzed. The median follow-up period was 40 months. Patients with rectal complications of ≥Grade 1 received a significantly higher mean EDR_p for D_0.1cc–5cc and had a greater EQD₂ for D_0.1cc–5cc. Multivariate analysis was performed using the mean EDR_p for D_2cc, EQD₂ for D_2cc, heavy smoking and BMI. Of these four variables, mean EDR_p for D_2cc (HR = 3.38, p = 0.004) and EQD₂ for D_2cc (HR = 2.59, p = 0.045) emerged as independent predictors for late rectal complications. In conclusion, mean EDR_p and EQD₂ were associated with late rectal complications in patients treated with HDR CT-based IGBT for cervical cancer.     

A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer

The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose–volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm³ (30.5%) and 5.4 cm³ (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6–5.9 Gy, P < 0.001 and 2.1–9.9 Gy, P < 0.001, respectively). The D_mean of the contralateral parotid decreased in 70% of the patients (range, 0.2–4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC.     

Usefulness of double dose contrast-enhanced magnetic resonance imaging for clear delineation of gross tumor volume in stereotactic radiotherapy treatment planning of metastatic brain tumors: a dose comparison study

The purpose of this study was to compare the size and clearness of gross tumor volumes (GTVs) of metastatic brain tumors on T1-weighted magnetic resonance images between a single dose contrast administration protocol and a double dose contrast administration protocol to determine the optimum dose of contrast-enhancement for clear delineation of GTV in stereotactic radiotherapy (SRT). A total of 28 small metastatic brain tumors were evaluated in 13 patients by intra-individual comparison of GTV measurements using single dose and double dose contrast-enhanced thin-slice (1-mm) magnetic resonance imaging (MRI). All patients had confirmed histological types of primary tumors and had undergone hypo-fractionated SRT for metastatic brain tumors. The mean tumor diameter with single dose and double dose contrast-enhancement was 12.0 ± 1.1 mm and 13.2 ± 1.1 mm respectively (P < 0.001). The mean incremental ratio (MIR) obtained by comparing mean tumor diameters was 11.2 ± 0.02 %. The mean volume of GTV-1 (single dose contrast-enhancement) and GTV-2 (double dose contrast-enhancement) was 1.38 ± 0.41 ml and 1.59 ± 0.45 ml respectively (P < 0.01). The MIR by comparing mean tumor volumes was 32.3 ± 0.4 %. The MIR of GTV-1 with < 1ml volume and GTV-1 with > 1ml volume was 41.8 ± 0.05 % and 12.4 ± 0.03 % respectively (P < 0.001). We conclude that double dose contrast-enhanced thin-slice MRI is a more useful technique than single dose contrast-enhanced thin-slice MRI, especially for clear delineation of GTVs of small metastatic brain tumors in treatment planning of highly precise SRT.     

Hormonal Relationships to Bone Mass in Elderly Spanish Men as Influenced by Dietary Calcium and Vitamin D

We aim to evaluate whether calcium and vitamin D intake is associated with 25-hydroxyvitamin D (25-OH-Vitamin D₃) and parathyroid hormone (PTH) serum concentrations or is associated with either the phalangeal dual energy X-ray absorptiometry (pDXA) or the quantitative bone ultrasound (QUS) in independent elderly men. Serum PTH and 25-OH-Vitamin D₃ were measured in 195 healthy elderly men (mean age: 73.31 ± 5.10 year). Food intake was quantified using a dietetic scale. Participants with 25-OH-Vitamin D₃ levels ≥ 30 ng/mL (75 nmol/L) and a calcium intake of 800–1200 mg/day exhibited the lowest PTH levels (41.49 ± 16.72 ng/mL). The highest PTH levels (75.60 ± 14.16 ng/mL) were observed in the <30 ng/mL group 25-OH-Vitamin D₃ with a calcium intake >1200 mg/day. No significant differences in the serum PTH levels based on the serum 25-OH-Vitamin D3 levels were observed among participants with a calcium intake of 800–1200 mg/day. Serum PTH was inversely correlated with serum 25-OH-Vitamin D₃ in the entire patient sample (r = −0.288, p = 0.019). No differences in any of the three densitometry techniques were observed between any of the age groups in the 800–1200 mg/day and >1200 mg/day calcium intake groups. PTH levels correlate negatively with serum 25-OH-Vitamin D₃ levels, and neither calcium nor vitamin D intake exert a strong influence on either of the two parameters.     

Vitamin D Serum Levels in Subjects Tested for SARS-CoV-2: What Are the Differences among Acute,Healed, and Negative COVID-19 Patients? A Multicenter Real-Practice Study

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D₃ serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March–September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D₃ (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D₃ levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D₃ levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D₃ levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)₂D₃. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)₂D₃ (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)₂D₃ might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.     

Effect of different treatment plans on irradiated small-bowel volume in gynecologic patients undergoing whole-pelvic irradiation

To evaluate the effect of different treatment plans for whole-pelvic irradiation on small-bowel volumes (SBVs) in patients with gynecologic malignancies, 40 patients were enrolled in this study. Computed tomography (CT) simulations were performed, and the small bowel of each patient was outlined manually. Treatment plans with equal-weighted (EW) and non-equal-weighted (NEW) (70% in bilateral directions) techniques of four-field and intensity-modulated radiation therapy (IMRT) were performed. The V10–V100 represented the volume (cm³) at different levels of the prescribed doses (10–100%). The V10–V100 was compared among the different treatment planning techniques, and patients who were suitable for IMRT or NEW were identified. IMRT and NEW significantly reduced the V50–V100 and V40–V60 levels compared with EW, respectively. NEW caused a significant reduction in the V30–V60 levels in patients with a BMI ≥26 kg/m². Patients with IMRT demonstrated lower V70–V100 levels compared with those with NEW. In patients with a BMI ≥26 kg/m² or an age ≥55 years, lower V20–V50 levels were noted using NEW compared with IMRT. Treatment planning with larger weighting in the bilateral directions in four-field radiotherapy reduces the low-dose SBV in patients with gynecologic malignancies, especially in those with a high BMI or the elderly. IMRT effectively reduces high-dose SBV, especially in patients with a low BMI.     

Dose–volume histogram comparison between static 5-field IMRT with 18-MV X-rays and helical tomotherapy with 6-MV X-rays

We treated prostate cancer patients with static 5-field intensity-modulated radiation therapy (IMRT) using linac 18-MV X-rays or tomotherapy with 6-MV X-rays. As X-ray energies differ, we hypothesized that 18-MV photon IMRT may be better for large patients and tomotherapy may be more suitable for small patients. Thus, we compared dose–volume parameters for the planning target volume (PTV) and organs at risk (OARs) in 59 patients with T1–3 N0M0 prostate cancer who had been treated using 5-field IMRT. For these same patients, tomotherapy plans were also prepared for comparison. In addition, plans of 18 patients who were actually treated with tomotherapy were analyzed. The evaluated parameters were homogeneity indicies and a conformity index for the PTVs, and D2 (dose received by 2% of the PTV in Gy), D98, Dmean and V_{10–70 Gy} (%) for OARs. To evaluate differences by body size, patients with a known body mass index were grouped by that index ( <21; 21–25; and >25 kg/m²). For the PTV, all parameters were higher in the tomotherapy plans compared with the 5-field IMRT plans. For the rectum, V_{10 Gy} and V_{60 Gy} were higher, whereas V_{20 Gy} and V_{30 Gy} were lower in the tomotherapy plans. For the bladder, all parameters were higher in the tomotherapy plans. However, both plans were considered clinically acceptable. Similar trends were observed in 18 patients treated with tomotherapy. Obvious trends were not observed for body size. Tomotherapy provides equivalent dose distributions for PTVs and OARs compared with 18-MV 5-field IMRT. Tomotherapy could be used as a substitute for high-energy photon IMRT for prostate cancer regardless of body size.