Impact of Respiratory Motion on the Skin Dose for Breast Cancer in Tomotherapy: A Study in the In-house Moving Phantom.

Purpose: The dose expansion methods as the skin flash and virtual bolus were used to solve intrafraction movement for breast planning due to breathing motion. We investigated the skin dose in each planning method by using optically stimulated luminescence on an in-house moving phantom for breast cancer treatment in tomotherapy. The impact of respiratory motion on skin dose between static and dynamic phantom's conditions was evaluated. Methods: A phantom was developed with movement controlled by the respirator for generating the respiratory waveforms to simulate respiratory motion. Five optically stimulated luminescence dosimeters were placed on the phantom surface to investigate the skin dose for the TomoDirect and TomoHelical under static and dynamic conditions. Eight treatment plans were generated with and without skin flash or virtual bolus by varying the thickness. The difference in skin dose between the two phantom conditions for each plan was explored. Results: All plans demonstrated a skin dose of more than 87% of the prescription dose under static conditions. However, the skin dose was reduced to 84.1% (TomoDirect) and 78.9% (TomoHelical) for dynamic conditions. The treatment plans without skin flash or virtual bolus showed significant skin dose differences under static and dynamic conditions by 4.83% (TomoDirect) and 9.43% (TomoHelical), whereas the skin flash with two leaves (TomoDirect 2L) or virtual bolus of at least 1.0 cm thickness (VB1.0) application compensated the skin dose in case of intrafraction movements by presenting a skin dose difference of less than 2% between the static and dynamic conditions. Conclusion: The skin dose was reduced under dynamic conditions due to breathing motion. The skin flash method with TomoDirect 2L or virtual bolus application with 1.0 cm thickness was useful for maintaining skin dose following the prescription by compensating for intrafraction movement due to respiratory motion for breast cancer in tomotherapy.

Plan quality analysis of stereotactic ablative body radiotherapy treatment planning in liver tumor.

PURPOSE: Stereotactic ablative body radiotherapy (SABR) in the liver, RTOG-1112 guides the treatment modalities including the dose constraints for this technique but not the plan parameters. This study is not only analyzing the plan quality by utilizing the plan parameters and indexes but also compares treatment modalities from the protocol implementation. METHOD AND MATERIAL: Twenty-five patients treated in the period from February 2020 to September 2022 were recruited in this analysis. Two planners randomly selected the patients and modalities. The modalities employed were Volumetric-Modulated Arc Therapy (VMAT) and Helical Tomotherapy (HT). Various parameters and indexes were used to access not only the plan quality but also to compare each modality. The parameters and indexes studied were the homogeneity index (HI), conformity index (CI), gradient distance (GD), and the dose received by the organs at risk. RESULT: The data reveals that the mean volume of PTV is 60.8 ± 53.9 cc where these targets exhibit no significant difference between each modality. The HI shows a consistent value for both modalities. Between each modality, the CI value shows less deviation, but the HT shows slightly higher performance than VMAT. The value of GD is 1.5 ± 0.3 cm where the HT provides a shorter distance compared to VMAT as well. CONCLUSION: The parameters and indexes should be utilized for the plan evaluation although in the guidelines this was not required. Various modalities were employed for treatment. Both can achieve the treatment criteria with slightly low performance of VMAT.

Survival outcome of cervical cancer patients treated by image-guided brachytherapy: a 'real world' single center experience in Thailand from 2008 to 2018.

The objective of our study was to evaluate the survival outcome of cervical cancer patients treated using image-guided brachytherapy (IGBT). From 2008 to 2018, 341 patients with cervical cancer were treated by radical radiotherapy. IGBT (by computed tomography [CT] or transabdominal ultrasound [TAUS]) was used to treat all of these patients. The characteristic data and patient status after treatment were recorded. All data were evaluated for survival outcome analysis. From a total of 341 patients, 295 patients were analyzed and 46 patients were excluded due to data missing in the survival outcomes. At the median follow-up time of 48 months (IQR 30-80 months), The 4-year local control, progression-free survival and overall survival rates were 89.5%, 74.9% and 69.1%, respectively. For overall survival, the size (> 5 cm), pathology (non-SCCA), stage (stage III-IV by FIGO 2009), lymph node (LN) (presented) and overall treatment time (OTT) (> 56 days) showed statistical significance in univariate analysis while non-SCCA pathology, advanced stage, presented LN and longer OTT showed statistical significance in multivariate analysis. In conclusion, our analysis reports a 4-year overall survival rate of 69.1%. Non-SCCA pathology, advanced stage disease, LN presence and longer OTT showed worse prognostic factors in multivariate analysis.

The association of vagina equivalent dose in 2Gy fraction (EQD2) to late vagina toxicity in patients of cervical cancer treated with WPRT plus IGABT.

AIM: To evaluate the associations of vaginal dose parameters and incidence of vaginal stenosis in patients with cervical cancer treated with image-guided brachytherapy (IGBT). MATERIALS AND METHODS: Fifty-four patients with cervical cancer treated with IGBT were included. The vagina contouring was done on previously treated CT images and the vaginal dose points were marked. The cumulative dose in EQD2 from EBRT and IGBT was calculated for both aspects and the vaginal toxicity was evaluated. RESULTS: At median follow-up time of 18.5 months, grade 2 or higher vaginal stenosis was observed in 24% of patients. On univariate analysis, parameters that were associated with ≥ grade 2 vaginal stenosis were age, mean dose of lateral 5 mm vagina, dose at PIBS-2 cm, mid vaginal D0 .03cc, mid vagina D1cc, lower vagina D0.03cc, lower vagina D0.1cc, lower vagina D1cc and lower vagina D2cc. On multivariate analysis, the significant parameters were age > 68.5 years old (P = 0.038), mean dose of lateral 5-mm (P = 0.034), and dose at PIBS-2 cm (P = 0.042). CONCLUSIONS: Age > 68.5 years old, mean dose of lateral 5 mm vagina and dose at PIBS-2 cm were associated with grade 2 or higher vaginal stenosis.

Gallotannin from Bouea macrophylla Seed Extract Suppresses Cancer Stem-like Cells and Radiosensitizes Head and Neck Cancer.

Cancer stem cells (CSCs) play a critical role in radiation resistance and recurrence. Thus, drugs targeting CSCs can be combined with radiotherapy to improve its antitumor efficacy. Here, we investigated whether a gallotannin extract from Bouea macrophylla seed (MPSE) and its main bioactive compound, pentagalloyl glucose (PGG), could suppress the stemness trait and further confer the radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines. In this study, we evaluate the effect of MPSE or PGG to suppress CSC-like phenotypes and radiosensitization of HNSCC cell lines using a series of in vitro experiments, tumorsphere formation assay, colony formation assay, apoptosis assay, and Western blotting analysis. We demonstrate that MPSE or PGG is able to suppress tumorsphere formation and decrease protein expression of cancer stem cell markers. MPSE or PGG also enhanced the radiosensitivity in HNSCC cells. Pretreatment of cells with MPSE or PGG increased IR-induced DNA damage (γ-H2Ax) and enhanced radiation-induced cell death. Notably, we observed that pretreatment with MPSE or PGG attenuated the IR-induced stemness-like properties characterized by tumorsphere formation and the CD44 CSC marker. Our findings describe a novel strategy for increasing therapeutic efficacy for head and neck cancer patients using the natural products MPSE and PGG.

Comparison of clinical outcomes achieved with image-guided adaptive brachytherapy for cervix cancer using CT or transabdominal ultrasound.

PURPOSE: This study aimed to evaluate retrospectively the treatment results when using various image-guided adaptive brachytherapy treatments for cervical cancer treated by radical radiotherapy. METHODS AND MATERIALS: From 2014 to 2017, 188 patients with cervical carcinoma were treated by whole pelvic radiotherapy plus four fractions of image-guided brachytherapy. Eight patients were excluded because of missing data. Consequently, 180 patients were analyzed. Of 180 patients, 92 were treated by CT-based brachytherapy (CT-BT), and transabdominal ultrasound-based brachytherapy (TAUS-BT) was used to treat another group. The treatment results and toxicity outcomes were evaluated by comparing the image-guidance techniques. RESULTS: The mean follow-up time was 32 months (interquartile range 29.5-42 months). The mean age was 57 years (interquartile range from 50 to 65 years). In the CT-BT group, the mean cumulative doses to high-risk clinical target volume, bladder, rectum, and sigmoid were 87.2 Gy, 84.0 Gy, 68.8 Gy, and 69.8 Gy, respectively. In the TAUS-BT group, the mean cumulative doses to the cervix reference, bladder, and rectum points were 84.0 Gy, 65.5 Gy, and 74.0 Gy, respectively. There were no differences in the 2-year local control rate (p = 0.88) and disease-free survival rate (p = 0.34) in both groups. No difference in gastrointestinal and genitourinary toxicity was observed in both groups, but there was higher vaginal toxicity in the TAUS-BT group compared with the CT-BT group (p = 0.03). CONCLUSIONS: No difference in treatment results was observed between CT-based and TAUS-based approaches. However, TAUS-BT had higher vaginal toxicity in our retrospective analysis.

Dosimetric comparison of TomoDirect, helical tomotherapy, and volumetric modulated arc therapy for postmastectomy treatment.

PURPOSE: To compare dose to the targets and organs at risk (OARs) in different situations for postmastectomy patients who require radiation to the chest wall with or without regional nodal irradiation when using three treatment techniques. METHODS AND MATERIALS: Thirty postmastectomy radiotherapy (PMRT) patients previously treated by helical tomotherapy (HT) at our institution were identified for the study. The treatment targets were classified in three situations which consisted of, the chest wall (CW) only, the chest wall plus supraclavicular lymph nodes (CW + SPC), and the chest wall plus supraclavicular and whole axillary lymph nodes irradiation (CW + SPC+AXLN). The volumetric modulated arc therapy (VMAT) plans and Tomodirect (TD) plans were created for each patient and compared with HT treatment plans which had been treated. The target coverage, dose homogeneity index (HI), conformity index (CI), and dose to OARs were analyzed. The quality scores were used to evaluate the appropriate technique for each situation from multiparameter results. RESULTS: The HT and VMAT plans showed the advantage of target coverage and OARs sparing for the chest wall with regional nodal irradiation with the higher plan quality scores when compared with TD plans. However, TD plans demonstrated superiority to contralateral breast sparing for the chest wall without regional nodal situation reaching the highest of planned quality scores. HT plans showed better HI, CI, and target coverage (P < 0.01) than TD and VMAT plans for all patient situations. Volumetric modulated arc therapy plans generated better contralateral breast and heart sparing at a lower dose than HT. CONCLUSION: The arc-based techniques, HT and VMAT plans, provided an advantage for complex targets in terms of target coverage and OARs sparing. However, the static beam TD plan was superior for contralateral organ sparing meanwhile achieving good target coverage for the chest wall without regional node situations.

Clinical outcomes and dosimetric study of hypofractionated Helical TomoTherapy in breast cancer patients.

We present a single center's experience of treatment outcomes and dosimetric parameters for breast cancer patients treated with hypofractionated Helical TomoTherapy (HT). This is a retrospective study of one hundred and thirty-six patients with invasive breast cancer treated between March 2012 and October 2016. Dosimetric parameters and 3-year loco-regional failure free survival (LRFFS) were analyzed. Dose to ipsilateral lung, heart and contralateral breast as well as acute and late toxicities were recorded. The median follow-up time is 45 months (range: 5-83). Two patients had loco-regional failure. The 3-year LRFFS was 99%. Acute grade 1 and 2 skin toxicities occurred in 95% and 1%, respectively. Coverage of the target volumes was achieved with the mean ± standard deviation (SD) of homogeneity and conformity index being 0.1 ± 0.04, and 0.8 ± 0.07, respectively. Dose to ipsilateral lung, contralateral breast, and heart was also within the limited constraints regardless of the complexity of target volumes. Only two percent of patients experienced late grade 2 skin toxicity. No late grade 2 subcutaneous tissue toxicity was found. Nine percent of patients developed late grade 1 lung toxicity. Hypofractionated radiotherapy using Helical TomoTherapy in breast irradiation provides excellent 3-year LRFFS and minimal acute and late toxicities. A careful, longer follow-up of healthy tissue effects to lung, heart, and contralateral breast is warranted.

Emulsion of Olive Oil and Calcium Hydroxide for the Prevention of Radiation Dermatitis in Hypofractionation Post-Mastectomy Radiotherapy: A Randomized Controlled Trial.

BACKGROUND: Most of the patients who have been treated by post-mastectomy radiotherapy (PMRT) experience skin toxicity. There have been few studies on acute radiation dermatitis in breast cancer patients who received hypofractionation PMRT. METHODS: 62 patients were randomized to receive a general skin care regimen with or without the addition of an emulsion of olive oil and calcium hydroxide twice a day, from the initiation of PMRT to 2 weeks after radiotherapy. Adverse skin reactions and the Skindex-16 score were assessed. RESULTS: At the 8th, 13th, and 16th fraction of PMRT, grade 1 dermatitis was found in 42, 90, and 90% of the control group and in 16, 30, and 71% of the intervention group. At the end of the study, the mean Skindex-16 score of the intervention group was significantly better than that of the control group (p = 0.019). CONCLUSIONS: Addition of an emulsion of olive oil and calcium hydroxide for patients undergoing hypofractionation PMRT yielded superior preventive results over a general skin care regimen alone, in terms of delaying skin toxicity, reducing the severity of acute radiation dermatitis, and a better quality of life in the intervention group. However, a larger number of patients will be required to confirm this result.

Intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer.

OBJECTIVES: To report the intermediate-term results of trans-abdominal ultrasound (TAUS)-guided brachytherapy in cervical cancer. MATERIALS AND METHODS: Ninety-two patients with cervical cancer (stage IB-IVA, according to FIGO staging), were treated by curative radiotherapy from February 2012 to June 2015. All patients were treated with whole pelvic radiotherapy to 50 Gy in 25 fractions and central shielding after 44 Gy, in combination with TAUS-guided brachytherapy, in order to escalate the total dose (EQD2) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS, while maintaining low doses to ICRU bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS: At median follow-up time of 41.2 months (range 8 to 61 months) the pelvic control, disease-free survival, and overall survival rates were 84.8%, 75%, and 88%, respectively. The mean applied doses to cervix, bladder, and rectal points were 83.5, 72.3, and 76.5 Gy, respectively. Eight patients developed grade 2 Gastrointestinal toxicity. CONCLUSION: The 3-year results demonstrated that TAUS-guided brachytherapy is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

Two-year results of transabdominal ultrasound-guided brachytherapy for cervical cancer.

PURPOSE: To report the preliminary results of transabdominal ultrasound (TAUS)-guided brachytherapy (BT) in cervical cancer. METHODS AND MATERIALS: Twenty-nine patients with cervical cancer Stage IB-IVA according to The International Federation of Gynecology and Obstetrics staging were treated by radical radiotherapy from February 2012 to December 2012. Treatment was composed of WPRT to 50 Gy in 25 fractions and central shielding after 44 Gy in combination with TAUS-guided BT to optimize the total dose (equivalent dose of 2 Gy [EQD2]) to the minimal dose at cervical points (in EQD2 concepts) defined by TAUS ≥80 Gy while maintaining low doses to the ICRU report no. 38 bladder and rectal points. The treatment results and toxicity profiles were reported. RESULTS: At median followup time of 19 months (range, 17-27), the local control and disease-free survival rates were 93.1% and 86.2%, respectively. One episode of Grade 3 vaginal toxicity was observed in this followup period. The mean applied doses to cervix, bladder, and rectal points were 82.6, 72.5, and 75 Gy, respectively. TAUS-guided planning reduced bladder (defined as >80 Gy in EQD2) and rectal overdose (defined as >75 Gy in EQD2) in 44.9% and 34.5% of patients, respectively. CONCLUSION: The 2-year results demonstrate that TAUS-guided BT is feasible and associated with excellent tumor control/toxicity rates in cervical cancer.

Image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective study from Chiang Mai University Hospital, Thailand.

PURPOSE: A report of preliminary results and toxicity profiles using image-guided brachytherapy (IGBT) combined with whole pelvic intensity-modulated radiation therapy (WP-IMRT) for locally advanced cervical cancer. MATERIAL AND METHODS: Fifteen patients with locally advanced cervical cancer were enrolled into the study. WP-IMRT was used to treat the Clinical Target Volume (CTV) with a dose of 45 Gy in 25 fractions. Concurrent cisplatin (40 mg/m(2)) was prescribed during radiotherapy (RT) on weekly basis. IGBT using computed tomography was performed at the dose of 7 Gy × 4 fractions to the High-Risk Clinical Target Volume (HR-CTV). RESULTS: The mean cumulative doses - in terms of equivalent dose of 2 Gy (EQD2) - of IGBT plus WP-IMRT to HR-CTV, bladder, rectum, and sigmoid colon were 88.3, 85.0, 68.2 and 73.6 Gy, respectively. In comparison with standard (point A prescription) dose-volume histograms, volume-based image-guided brachytherapy improved the cumulative doses for bladder of 67%, rectum of 47% and sigmoid of 46%. At the median follow-up time of 14 months, the local control, metastasis-free survival and overall survival rates were 93%, 100% and 93%, respectively. No grade 3-4 acute and late toxicities were observed. CONCLUSION: The combination of image-guided brachytherapy and intensity-modulated radiotherapy improved the dose distribution to tumor volumes and avoided overdose in OARs which could be converted in excellent local control and toxicity profiles.

Intermediate-term results of image-guided brachytherapy and high-technology external beam radiotherapy in cervical cancer: Chiang Mai University experience.

OBJECTIVE: To evaluate the outcomes of image-guided brachytherapy combined with 3D conformal or intensity modulated external beam radiotherapy (3D CRT/IMRT) in cervical cancer at Chiang Mai University. METHODS: From 2008 to 2011, forty-seven patients with locally advanced cervical cancer were enrolled in this study. All patients received high-technology (3D CRT/IMRT) whole pelvic radiotherapy with a total dose of 45-46 Gy plus image-guided High-Dose-Rate intracavitary brachytherapy 6.5-7 Gy × 4 fractions to a High-Risk Clinical Target Volume (HR-CTV) according to GEC-ESTRO recommendations. The dose parameters of the HR-CTV for bladder, rectum and sigmoid colon were recorded, as well as toxicity profiles. In addition, the endpoints for local control, disease-free, metastasis-free survival and overall survival were calculated. RESULTS: At the median follow-up time of 26 months, the local control, disease-free survival, and overall survival rates were 97.9%, 85.1%, and 93.6%, respectively. The mean dose of HR-CTV, bladder, rectum and sigmoid were 93.1, 88.2, 69.6, and 72 Gy, respectively. In terms of late toxicity, the incidence of grade 3-4 bladder and rectum morbidity was 2.1% and 2.1%, respectively. CONCLUSIONS: A combination of image-guided brachytherapy and IMRT/3D CRT showed very promising results of local control, disease-free survival, metastasis-free survival and overall survival rates. It also caused a low incidence of grade 3-4 toxicity in treated study patients.

The effect of central shielding in the dose reporting for cervical cancer in EQD2 era.

PURPOSE: To evaluate the cumulative dose at point A for three and four centimeters central shielding. MATERIAL AND METHODS: The plans of external beam radiotherapy plus conventional intracavitary brachytherapy were performed. Three or four centimeters central shieldings (after 44 Gy) were applied to the standard whole pelvis irradiation. Additional intracavitary brachytherapy 4 × 7 Gy at point A was prescribed, and the cumulative dose in EQD2 (α/ß = 10) of 3 cm and 4 cm central shielding were evaluated. RESULTS: The cumulative dose at point A in EQD2 (α/ß = 10) of 3 cm central shielding were 95.7 Gy for AR and 95.5 Gy for AL, while the cumulative dose at point As in EQD2 (α/ß = 10) of 4 cm central shielding were 90.8 Gy for AR and 91.2 Gy for AL. CONCLUSIONS: The 3 cm central shielding caused higher cumulative dose (in terms of EQD2 [α/ß = 10]) than 4 cm central shielding.