Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis.

OBJECTIVE: This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution. METHODS: Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy. RESULTS: All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes. CONCLUSION: Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.

Estimation of secondary cancer risk after radiotherapy in high-risk prostate cancer patients with pelvic irradiation.

We aimed to estimate the risk of secondary cancer after radiotherapy (RT) in high-risk prostate cancer (HRPC) patients with pelvic irradiation. Computed tomography data of five biopsy-proven HRPC patients were selected for this study. Two different planning target volumes (PTV1 and PTV2 ) were contoured for each patient. The PTV1 included the prostate, seminal vesicles, and pelvic lymphatics, while the PTV2 included only the prostate and seminal vesicles. The prescribed dose was 54 Gy for the PTV1 with a sequential boost (24 Gy for the PTV2 ). Intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT) techniques were used to generate treatment plans with 6 and 10 MV photon energies with the flattening filter (FF) or flattening filter-free (FFF) irradiation mode. The excess absolute risks (EARs) were calculated and compared for the bladder, rectum, pelvic bone, and soft tissue based on the linear-exponential, plateau, full mechanistic, and specific mechanistic sarcoma dose-response model. According to the models, all treatment plans resulted in similar risks of secondary bladder or rectal cancer and pelvic bone or soft tissue sarcoma except for the estimated risk of the bladder according to the full mechanistic model using IMRT(6MV;FF) technique compared with VMAT techniques with FFF options. The overall estimation of EAR indicated that the radiation-induced cancer risk due to RT in HRPC was lower for bladder than the rectum. EAR values ranged from 1.47 to 5.82 for bladder and 6.36 to 7.94 for rectum, depending on the dose-response models used. The absolute risks of the secondary pelvic bone and soft tissue sarcoma were small for the plans examined. We theoretically predicted the radiation-induced secondary cancer risk in HRPC patients with pelvic irradiation. Nevertheless, prospective clinical trials, with larger patient cohorts with a long-term follow-up, are needed to validate these model predictions.

Comparison of Radiation-Induced Secondary Malignancy Risk Between Sequential and Simultaneous Integrated Boost for the Treatment of Nasopharyngeal Carcinoma: Intensity-Modulated Radiotherapy versus Volumetric-Modulated Arc Therapy.

PURPOSE: This study aimed to compare the secondary cancer risk (SCR) between the sequential boost (SEQ) technique and simultaneous integrated boost (SIB) technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with nasopharyngeal carcinoma (NPC) using the concepts of organ equivalent dose (OED) and excess absolute risk (EAR). PATIENTS AND METHODS: IMRT-SEQ, VMAT-SEQ, IMRT-SIB, and VMAT-SIB plans were created with identical objective functions for five patients with early-stage NPC. Three different planning tumor volumes (PTVs; PTV1, PTV2, and PTV3) were delineated for each patient, and the prescribed doses were 50 Gy, 60 Gy, and 70 Gy (2 Gy/fraction), respectively, for the SEQ technique and 52.8 Gy, 59.4 Gy, and 69.3 Gy (33 fractions), respectively, for the SIB technique. RESULTS: All plans were clinically acceptable. There was no difference in most OED-based SCRs between IMRT and VMAT when the same fractionation scheme was used. Compared with the SEQ technique, the SIB technique in IMRT and VMAT was associated with the lowest OEDs for the oral cavity, pharynx, parotids, and submandibular glands, resulting in SCR reduction. SCR for the parotids was much lower than that for the other assessed organs when the SIB technique was used. CONCLUSION: Our findings suggest that OED-based SCRs are lower with the SIB technique than with the SEQ technique in IMRT and VMAT in most organs for which SCR was calculated; furthermore, SCR for the parotids is much lower than that for other organs when the SIB technique is used in patients with NPC.

Secondary cancer risk after whole-breast radiation therapy: field-in-field versus intensity modulated radiation therapy versus volumetric modulated arc therapy.

OBJECTIVE: In this study, we used the concept of organ-equivalent dose (OED) to evaluate the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for breast cancer. METHODS: Using CT data set of 12 patients, we generated three different whole-breast radiation treatment plans using 50 Gy in 2 Gy fractions: three-dimensional conformal radiotherapy with a field-in-field (FinF) technique, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The OEDs were calculated from differential dose-volume histograms on the basis of the "linear-exponential," "plateau," and "full mechanistic" dose-response models. Secondary cancer risks of the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL) were estimated and compared. RESULTS: The lowest EARs for the CB, CL, and IL were achieved with FinF, which reduced the EARs by 77%, 88%, and 56% relative to those with IMRT, and by 77%, 84%, and 58% relative to those with VMAT, respectively. The secondary cancer risk for FinF was significantly lower than those of IMRT and VMAT. OED-based secondary cancer risks for CB and IL were similar when IMRT and VMAT were used, but the risk for CL was statistically lower when VMAT was used. CONCLUSION: The overall estimation of EAR indicated that the radiation-induced cancer risk of breast radiation therapy was lower with FinF than with IMRT and VMAT. Therefore, when secondary cancer risk is a major concern, FinF is considered to be the preferred treatment option in irradiation of whole-breast. ADVANCES IN KNOWLEDGE: Secondary malignancy estimation after breast radiotherapy is becoming an important subject for comparative treatment planning.When secondary cancer risk a major concern, FinF technique is considered the preferred treatment option in whole breast patients.

Effect of dose constraint on the thyroid gland during locoregional intensity-modulated radiotherapy in breast cancer patients.

The aim of the present study was to compare radiation dose received by thyroid gland using different radiotherapy (RT) techniques with or without thyroid dose constraint (DC) for breast cancer patients. Computerized tomography (CT) image sets for 10 patients with breast cancer were selected. All patients were treated originally with opposite tangential field-in field (FinF) for the chest wall and anteroposterior fields for the ipsilateral supraclavicular field. The thyroid gland was not contoured on the CT images at the time of the original scheduled treatment. Four new treatment plans were created for each patient, including intensity-modulated radiotherapy (IMRT) and helical tomotherapy (HT) plans with thyroid DC exclusion and inclusion (IMRTDC(-) , IMRTDC(+) , HTDC(-) , and HTDC(+) , respectively). Thyroid DCs were used to create acceptable dose limits to avoid hypothyroidism as follows: percentage of thyroid volume exceeding 30 Gy less than 50% (V30  < 50%) and mean dose of thyroid (TDmean ) ≤ 21 Gy. Dose-volume histograms (DVHs) for TDmean and percentages of thyroid volume exceeding 10, 20, 30, 40, and 50 Gy (V10 , V20 , V30 , V40 , and V50 , respectively) were also analyzed. The Dmean of the FinF, IMRTDC(-) , HTDC(-) , IMRTDC(+) and HTDC(+) plans were 30.56 ± 5.38 Gy, 25.56 ± 6.66 Gy, 27.48 ± 4.16 Gy, 18.57 ± 2.14 Gy, and 17.34 ± 2.70 Gy, respectively. Median V30 values were 55%, 33%, 36%, 18%, and 17%, for FinF, IMRTDC(-) , HTDC(-) , IMRTDC(+) , and HTDC(+) , respectively. Differences between treatment plans with or without DC with respect to Dmean and V30 values were statistically significant (P < 0.05). When thyroid DC during breast cancer RT was applied to IMRT and HT, the TDmean and V30 values significantly decreased. Therefore, recognition of the thyroid as an organ at risk (OAR) and the use of DCs during IMRT and HT planning to minimize radiation dose and thyroid volume exposure are recommended.

The choice of multi-beam IMRT for whole breast radiotherapy in early-stage right breast cancer.

The aim of this study was to identify a rational strategy for the selection of multi-beam IMRT in patients with right breast cancer through the comparison of dosimetric parameters of the planning target volume (PTV) and organs at risk (OARs) using five different radiotherapy modalities. This was a retrospective study using computed tomography scans from ten patients with early-stage right breast cancer who had been treated previously. Three dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), inverse-planned IMRT (inv-IMRT), helical tomotherapy (HT), and volumetric-modulated arc therapy (VMAT) were planned for each patient. The plans were compared according to dose-volume histogram analysis. The most significant impact of inverse-planned multi-beam modalities for right breast cancer was the reduction of Dmax, Dmean, V53.5 and prescribed dose volume (cc) outside of the PTV (breast) (OB-V50) of the PTV. HT decreased the ipsilateral OAR volumes receiving higher doses. In exchange, HT also increased the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies. The heart, LAD, and contralateral doses for 3DCRT and for-IMRT were significantly lower than those for inv-IMRT, HT, and VMAT. In addition, inv-IMRT demonstrated an increase in exposed volume of heart, LAD, ipsilateral lung, and contralateral lung compared with those parameters for HT or VMAT. Although it is known to reduce cardiac toxicity with breath hold technique in left sided breast cancer, similarly it is possible for 3DCRT and for-IMRT techniques in right sided breast cancer even in free breathing.

Comparison of the effects of melatonin and genistein on radiation-induced nephrotoxicity: Results of an experimental study.

The aim of the present study was to compare the effects of melatonin and genistein on radiation-induced nephrotoxicity (RIN). A total of 70 Swiss Albino mice were divided into 7 groups. Five control groups were defined, which were sham irradiation (C, G1), radiation therapy only (RT, G2), melatonin (M, G3), genistein (G, G4) and polyethylene glycol-400 (G5), respectively. The co-treatment groups were the RT plus melatonin (RT+M, G6) and RT plus genistein (RT+G, G7) groups. Irradiation was applied using a cobalt-60 teletherapy machine (80-cm fixed source-to-surface distance, 2.5-cm depth). Melatonin was administered (100 mg/kg, intraperitoneal injection) 30 min before the single dose of irradiation, whereas genistein was administered (200 mg/kg, subcutaneous injection) 1 day before the single dose of irradiation. All the mice were sacrificed 6 months after irradiation. As an end point, the extent of renal tubular atrophy for each mouse was quantified with image analysis of histological sections of the kidney. Tissue malondialdehyde (MDA) levels were also measured in each animal. In the histopathological examination of the mouse kidneys, there was a statistically significant reduction (P<0.05) in the presence of tubular atrophy between the RT+M and RT+G groups and the RT group. There was a statistically significant increase in MDA levels in the irradiated versus sham groups (RT vs. C; P<0.05); however, MDA levels were significantly decreased by co-treatment with melatonin or genistein vs. RT alone (RT+M and RT+G vs. RT; P<0.05). In conclusion, the present experimental study showed that melatonin and genistein supplementation prior to irradiation-protected mice against RIN, which may have therapeutic implications for radiation-induced injuries.

Long-term results of a concomitant boost radiotherapy technique for elderly patients with muscle-invasive bladder cancer.

OBJECTIVES: To evaluate the long-term clinical efficacy and toxicity of concomitant boost radiotherapy (CBRT) in elderly patients with invasive bladder cancer. METHODS AND MATERIALS: Elderly patients (n=188; mean 75-year-old, range 70-91 years; 88.3% male/11.7% female) with T1-T4a bladder carcinoma were irradiated with CBRT. A total of 24 (12.8%) patients were diagnosed at stage T1, 117 (62.2%) were at stage T2, 28 (14.9%) at were stage T3a, 14 (7.4%) were stage T3b, and 5 (2.7%) were stage T4a. A dose of 45Gy in 1.8Gy fractions was administered to the whole pelvis 5 days/week over 5 weeks. A concomitant boost limited to the bladder tumor area plus margin or whole bladder of 22.5Gy in 1.5Gy fractions was administered from weeks 3×5. Thus, irradiation totalled 67.5Gy over 5 weeks. The interfraction interval was ≥6h/treatment day. We assessed prognostic factors for overall survival (OS), cause-specific survival (CSS) and relapse-free survival (RFS). RESULTS: Median follow-up was 46.2 months (range 4.7-155.7 months). Median overall survival was 27 months (95% CI:21-33 months). In this study, 146 (77.7%) patients had complete response, 39 (20.7%) had residual disease and 4 (1.6%) had progressive disease. The mean 3-, 5- and 10-year OS rates were respectively 41.2% (S.E.±0.036), 29% (S.E.±0.034), and 13.8% (S.E.±0.031). Significant prognostic factors for OS and CSS, by multivariate analysis, were tumor T-stage and urothelial obstruction. CONCLUSION: This CBRT protocol provided excellent results with a high complete response rate and good tolerance. This approach may therefore be particularly appropriate for elderly patients with invasive bladder cancer.

Comparison of dose distributions hippocampus in high grade gliomas irradiation with linac-based imrt and volumetric arc therapy: a dosimetric study.

The aim of this study was to assess the feasibility of sparing contralateral hippocampus during partial brain radiotherapy in high grade gliomas. 20 previously treated patients were replanned to 60 Gy in 30 fractions with sparing intensity-modulated radiotherapy (IMRT) and volumetric modulated arctherapy (VMAT) using the following planning objectives: 100 % of PTV covered by 95% isodose without violating organs at risk (OAR) and hot spot dose constraints. For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as sparing IMRT and VMAT plans which spared contralateral (hemispheric cases) hippocampus. When the three plans were compared, there was equivalent PTV coverage, homogeneity, and conformality. Sparing IMRT significantly reduced maximum, mean, V20, V30 and V40 hippocampus doses compared with standart IMRT and VMAT (p < 0.05). VMAT significantly reduced maximum left lens and mean eye doses compared with standart IMRT and sparing IMRT (p < 0.05). Brainstem, chiasm, left and right optic nerves, right eyes and lens doses were similar. VMAT significantly reduced monitor units compared with standart IMRT and sparing IMRT (p < 0.05). It is possible to spare contralateral hippocampus during PBRT for high grade gliomas using IMRT. This approach may reduce late cognitive sequelae of cranial radiotherapy.

Dosimetric comparison of left-sided whole-breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and volumetric arc therapy.

PURPOSE: This study evaluated the dose distribution and homogeneity of four different types of intensity-modulated radiotherapy (IMRT) in comparison with standard wedged tangential-beam three-dimensional conformal radiotherapy (3DCRT) of the left breast in patients who had undergone lumpectomy. MATERIALS AND METHODS: Five radiotherapy treatment plans, including 3DCRT, forward-planned IMRT (for-IMRT), inverse IMRT (inv-IMRT), helical tomotherapy (HT) and volumetric-modulated arc therapy (VMAT), were created for 15 consecutive patients. RESULTS: All modalities presented similar target coverage. Target max doses were reduced with for-IMRT compared to 3DCRT, and these doses were further reduced with inv-IMRT and HT. HT resulted in the lowest max doses delivered to the heart, left anterior descending artery (LAD), and ipsilateral lung, but had higher mean, max, and low doses delivered to contralateral breast. HT resulted in increased low doses to a large volume of healthy tissue. Compared to other techniques, all inverse-planned modalities significantly improved conformity number; however, VMAT had worse homogeneity. The for-IMRT plan significantly lowered monitor unit (MU) compared to the inverse-planned techniques. CONCLUSION: All modalities evaluated provide adequate coverage of the whole breast. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned inv-IMRT and HT. HT decreases the ipsilateral OAR volumes receiving higher and mean doses with an increase in the volumes receiving low doses, which is known to lead to an increased rate of radiation-induced secondary malignancies.

Long-term outcomes in treatment of invasive bladder cancer with concomitant boost and accelerated hyperfractionated radiation therapy.

PURPOSE: The aim of this study was to evaluate the long-term clinical efficacy and toxicity of concomitant boost and accelerated hyperfractionated radiation therapy (CBAHRT) in patients with invasive bladder cancer. METHODS AND MATERIALS: Between October 1997 and September 2012, 334 patients with diagnoses of invasive bladder cancer were selected. These patients received CBAHRT as a bladder-conserving approach. The treatment consisted of a dose of 45 Gy/1.8 Gy to the whole pelvis with a daily concomitant boost of 1.5 Gy to the tumor. Total dose was 67.5 Gy in 5 weeks. A total of 32 patients (10.3%) had a diagnosis of stage T1, 202 (64.3%) were at stage T2, 46 (14.6%) were at stage T3a, 22 (7%) were at stage T3b, and 12 (3.8%) were at stage T4a. RESULTS: The follow-up period was 33.1 months (range, 4.3-223.3 months). Grade 3 late intestinal toxicity was observed in 9 patients (2.9%), whereas grade 3 late urinary toxicity was observed in 8 patients (2.5%). The median overall survival (OS) was 26.3 months (95% confidence interval [CI]: 21.4-31.2). The 5-, 10, and 15-year OS rates were 32.1% (standard error [SE], ± 0.027), 17.9% (SE, ± 0.025) and 12.5% (SE, ± 0.028), respectively. The median cause-specific survival (CSS) was 42.1 months (95% CI: 28.7-55.5). The 5-, 10-, and 15-year CSS rates were 43.2% (SE, ± 0.03), 30.3% (SE, ± 0.03), and 28% (SE, ± 0.04), respectively. The median relapse-free survival (RFS) was 111.8 months (95% CI: 99.6-124). The 5-, 10-, and 15-year RFS rates were 61.9% (SE, ± 0.03), 57.6% (SE, ± 0.04), and 48.2% (SE, ± 0.07), respectively. CONCLUSIONS: The CBAHRT technique demonstrated acceptable toxicity and local control rates in patients with invasive bladder cancer, and this therapy facilitated bladder conservation. In selected patients, the CBAHRT technique is a practical alternative treatment option with acceptable 5-, 10-, and 15-year results in patients undergoing cystectomy as well as concurrent chemoradiation therapy.