External Beam Radiotherapy Dose Research Articles

The incidence of hypothyroidism in patients of head and neck carcinoma treated with radiotherapy and added risk of hypothyroidism with the addition of chemotherapy

AbstractBackground:Head and neck cancer (HNC) is the most common malignancy in the Indian males. Most of the cases of HNC present in locally advanced stage and requires a multidisciplinary management approach. Radical or adjuvant external beam radiotherapy (EBRT) is one of the important integral components of the management of HNC.Aim:To find the incidence of hypothyroidism (HT) in patients of HNC treated with radiotherapy with or without concurrent chemotherapy.Methods:A prospective, single institutional longitudinal observational study conducted at the department of radiotherapy, Institute of Post Graduate Medical Education and Research, Kolkata.Results:In this study, data of 118 patients were analysed. The median age at presentation was 56 years. The most common primary site of malignancy was oral cavity (39%). The patients were stage I, stage II and stage III as 11, 37·3 and 51·7% respectively. The median dose of EBRT was 66 Gy. HT statistically significantly correlated with primary site of malignancy (p = 0·001), dose of EBRT (p = 0·005). At the end of follow-up of 6 months, 39·8% developed HT.Conclusion:The thyroid gland is an important organ at risk while considering EBRT to neck region. The inclusion of thyroid function test in routine follow-up is mandated.

Low dose rate permanent seed brachytherapy: tracing its evolution and current status

AbstractA recent surge in publications on low dose rate permanent seed brachytherapy prompted us to review the currently available literature in order to provide a summary of the therapy. To this end, we composed a comprehensive review on the available English language publications in PubMed, EMBASE, and Google Scholar. The general principles of seed brachytherapy are discussed, along with radiobiology and technical aspects. Seed brachytherapy has been increasingly used in various sites for primary treatment, and is considered to be particularly useful in cases of reirradiation and otherwise untreatable malignancies. In recent decades, there have been considerable advances in the technology used in seed brachytherapy, including steps to prevent the migration of seeds, reduce personnel exposure to radiation, and use of sophisticated 3‐D planning for better dosimetric results, which have ultimately translated into better clinical outputs. Technical advances in seed brachytherapy have lagged behind those in external beam radiotherapy and high dose rate brachytherapy; however, there is renewed interest due to encouraging clinical results in the primary setting, as well as reirradiation for recurrent disease across several sites.

Abstract 6281: Differential response of irradiated breast carcinoma cells to DNA-PK inhibition: Spheroid response is governed by cell adhesion effects rather than changes in radiosensitivity

Abstract Agents that increase tumor radiosensitivity are of interest in improving outcomes in radiotherapy (XRT). DNA-PKcs inhibitors lead to radiosensitization and also to alterations in cell adhesion proteins. Using a HER2 positive mammary carcinoma cell line, NT2.5, we investigated the impact of Nu7441, a potent and selective DNA-PKcs inhibitor together with external beam irradiation in both 2D monolayer and 3D spheroid cell culture systems. Colony formation assays were performed for cells irradiated as monolayers and also for cells disaggregated from spheroids. Cells grown in monolayer culture and as spheroids were incubated with Nu7441 (5 µM) for 24 h after different doses of external beam irradiation. In monolayer culture cells, α/β increased from 3.0 ± 0.2 Gy (XRT alone) to 6.9 ± 0.2 Gy when XRT was followed by Nu7441 incubation. Corresponding α/β values for cells obtained by disaggregating treated spheroids were 3.6 ± 0.7 Gy (XRT alone) and 3.5 ± 0.2 Gy (XRT+Nu7441). In contrast to the minimal change in α/β, spheroids survival was highly sensitive to Nu7441 incubation. 21 days after 0, 2, 4, 6, 8, or 10 Gy XRT alone 100, 83, 75, 63, 56, and 31%, respectively, of the irradiated spheroids remained intact; when Nu7441 treatment was involved, 56% remained intact at 2 Gy and 13% at 4 Gy, no spheroids survived to 3 weeks at 6 Gy or more. We also found a progressive increase in fragmentation for spheroids exposed only to Nu7441 (0 Gy): 3/24, 9/24 and 17/24 fragmented after 14, 21 and 28 days of incubation, respectively. The discrepancy between the minimal change in α/β from cells derived from spheroids and the spheroid growth response was not related to poor penetration of Nu7441 since the colony formation assay results for different sizes of spheroids (180 to 400 µm) treated with 4 Gy with or without Nu7441were not significantly different. The results suggest that spheroid response to DNA-PKcs inhibitors is driven by their known inhibition of cell-cell adhesion pathways and potentially less so by radiosensitization. Citation Format: Jing Yu, Ryan Lu, Jessie Nedrow, George Sgouros. Differential response of irradiated breast carcinoma cells to DNA-PK inhibition: Spheroid response is governed by cell adhesion effects rather than changes in radiosensitivity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6281.

Abstract 477: Comparing type 1 interferon activation in tumor cells following external beam radiotherapy versus targeted radionuclide therapy

Abstract Background: Radiation (RT) activates a type 1 interferon (IFN-1) response and, in preclinical studies, this is critical to the effect of RT in priming a response to immune checkpoint blockade. Recent studies report the impact of external beam radiotherapy (EBRT) dose and fractionation on IFN-1 response, however little is known about the time course of this effect. Clinical interest in utilizing systemically administered targeted radionuclide therapy agents (TRT) is growing. It is unclear how IFN-1 activation induced by continuous delivery of RT during exponential decay of a TRT source will compare to that induced following instantaneous EBRT. Here we report the time course of IFN-1 response following RT in vitro and in vivo. Methods: For in vitro studies, we utilized murine models of melanoma (B16, B16 STING knockout, B78), and head and neck cancer (MOC2). EBRT was prescribed to 12 Gy, 20 Gy, or 3 fractions of 8 Gy. For in vivo studies, syngeneic C57BL/6 mice were engrafted with either B78 or MOC2 cells on the flank and RT was delivered when mean tumor size was ~ 150 mm3. EBRT was prescribed to 2 Gy or 12 Gy. For TRT, we used 90Y conjugated to NM600, an alkylphosphocholine analog that exhibits selective uptake and retention in tumor cells of nearly any type, including B78 and MOC2. Tumor-specific dosimetry for 90Y-NM600 was determined using sequential 86Y-NM600PET/CT imaging (3h, 24h, 72h) and a Monte Carlo based dose calculation platform. TRT was prescribed to a dose of 2 Gy or 12 Gy. Following delivery of RT in vitro or in vivo, cells or tumors were harvested at 24h, 7d, and 14 d post RT and RNA was isolated. Gene expression of Ifn-β and IFN response elements (Oas2, Oas3, and Mx1) was quantified by qPCR and normalized to untreated controls. Results: In agreement with prior studies, we observed significant IFN-1 activation 24 hours following 8 Gy x 3 in our B16, B78, and MOC2 tumor cell lines. At 12 Gy and 20 Gy, we continued to detect significant IFN-1 activation. Peak activation was 7d following EBRT for all doses, raising the potential for a lead-time bias when comparing fractionated to single dose treatments. For all doses, select IFN response genes remained upregulated at 14d. In vivo delivery of EBRT and TRT to B78 and MOC2 tumors resulted in a comparable time course of IFN-1 activation peaking 7d after RT and persisting to 14d. Using a STING knockout variant of B16 melanoma, we confirmed that activation of IFN-1 response by RT was STING dependent at all time points evaluated. Conclusions: We report the time course for activation of a STING-dependent IFN-1 response following RT in multiple murine tumor models. We observe maximal activation 7d following both EBRT and TRT. We show the potential of TRT to generate EBRT comparable IFN-1 activation. Further studies evaluating the time course and magnitude of IFN-1 response following TRT may be critical in metastatic settings to integrating this modality with immunotherapy. Citation Format: Justin C. Jagodinsky, Ian S. Arthur, Juliana S. Castillo, Ishan Chakravarty, Luke M. Zangl, Ryan J. Brown, Ravi B. Patel, Wonjon J. Jin, Peter M. Carlson, Reinier Hernandez, Joseph J. Grudzinski, Ian R. Marsh, Jamey P. Weichert, Bryan P. Bednarz, Zachary S. Morris. Comparing type 1 interferon activation in tumor cells following external beam radiotherapy versus targeted radionuclide therapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 477.

A prospective, single-arm, phase II clinical trial of intraoperative radiotherapy using a low-energy X-ray source for local advanced Laryngocarcinoma (ILAL): a study protocol

BackgroundLaryngocarcinoma (LC), in most cases a squamous cell carcinoma, accounts for 1 ~ 5% of the incidence of all tumors. At present, laryngocarcinoma is mainly managed with the integration of surgery and radio- and chemo-therapies. The current development trend of treatment is to improve the local control rate of tumor and the quality of life of patients. Intraoperative radiation therapy (IORT) is a radiotherapy that delivers single high dose irradiation at a close range to the tumor bed during the surgical operation process. It has particular radiobiological advantages in protecting normal surrounding tissues by directly applying the irradiation dose to the high-risk tumor bed area.Two forms of IORT, i.e., high dose rate (HDR) brachytherapy and external beam radiotherapy (EBRT, including electron and photono IORT), had been studied before the treatment of head and neck tumors (including laryngocarcinoma). However, no relevant assessment had been carried out on 50KV low-energy X-ray. We are convinced by certain arguments that the application of low-energy X-ray for intraoperative local radiotherapy of laryngocarcinoma can not only achieve the therapeutic effect of IORT but also reduce the incidence of high-energy irradiation related toxic and side effects. The purpose of this study is to observe the safety and short-term efficacy of IORT when used in conjunction with standard of care for the treatment of local advanced laryngocarcinoma (LAL).Methods/designIn consideration of the applications of precise targeted IORT in oncosurgery and in line with the application range and reference clinical medical guidances approved by SFDA (ZEISS radiosurgical operation system has been used for the treatment of solid tumors since 31 December, 2013 with an approval from SFDA), we have preliminarily planned the tumors suitable for IORT, determined the members of MDT in our hospital, improved the MDT diagnosis and treatment processes for the tumors, established the standards, indications and contraindications for the application of IORT, determined the indicators to be observed after the treatment of tumors with surgical operations plus IORT, and carried out follow-up visits and statistical analysis.This is a single-arm, prospective Phase II clinical trial of the treatment of LAL patients with IORT + EBRT. The study subjects are followed up for statistics and information of their acute/chronic toxic reactions and local control rate, DFS, and OS etc. The safety and short-term efficacy of the application of IORT as SIB for the treatment of LAL. The sample size of the study is 125 subjects.DiscussionThe safety and efficacy of IORT for the treatment of head and neck cancers have been proven in studies by multiple institutions (1–3). The purpose of this study is to investigate the maximum safe dose and short-term efficacy of IORT for providing a theoretical basis for clinical trials.Trial registrationTrial registration: Clinicaltrials.gov, NCT04278638. Registered 18 February 2020 - prospectively registered, https://clinicaltrials.gov/ct2/show/NCT04278638

HIP INJURY -- WRESTLING

HISTORY: A 21-year-old college wrestler presented with progressive, persistent pain in his right hip after undergoing arthroscopy at an outside institution. Despite multiple attempts at non-operative management, including activity modification, rest, physical therapy, and use of nonsteroidal anti-inflammatory drugs, pain and stiffness limited his sport-specific function. PHYSICAL EXAMINATION: Markedly limited active range of motion, particularly with hip flexion beyond 90 degrees; pain with range of motion DIFFERENTIAL DIAGNOSIS: 1. Chondral injury to femoral head 2. Injury (recurrence of tear) to acetabular labrum 3. Persistent cam type impingement of right hip 4. Chondromalacia of right acetabulum TEST AND RESULTS: Plain radiographs of pelvis and both hips MRI of right hip MR-arthrogram of right hip Results of all imaging studies were consistent with early progression of osteoarthritis, with changes considered advanced for a patient of his age. FINAL/WORKING DIAGNOSIS: Chondral injury and heterotopic ossification (HO) secondary to chronic cam type femoroacetabular impingement TREATMENT AND OUTCOMES: 1. Right hip revision arthroscopy with labral resection and labral reconstruction with allograft tissue 2. Right hip revision arthroscopic cheilectomy/femoroplasty 3. Right hip arthroscopic excision of HO fragment measuring 3 cm x 2 cm in anterior lateral joint capsule 4. Right hip arthroscopic chondroplasty of acetabulum with microfracture/bone marrow stimulation procedure 5. Immediate post-operative physical therapy (day of surgery) 6. Single dose of external beam radiation on post-operative day 1 to minimize risk of recurrence of HO 7. 20 pounds flat foot weightbearing restriction for six weeks 8. Naproxen 375 mg bid x 6 weeks to minimize risk or recurrence of HO 9. Continuous passive motion in immediate post-operative period

Functional and biochemical changes in the thyroid gland following exposure to therapeutic doses of external beam radiotherapy in the head-and-neck cancer patients.

Majority of the head-and-neck cancers are locoregionally advanced at the time of diagnosis. Hence, radiotherapy (RT) portals will invariably cover the whole neck and thus, the thyroid gland which may lead to its dysfunction. The purpose of this study is to identify the functional and biochemical changes in the thyroid gland following RT to the neck using single-photon emission computed tomography-computed tomography (SPECT-CT) and thyroid function tests (TFTs). In this prospective study, 45 patients of the head-and-neck cancer, receiving RT with or without chemotherapy were investigated. Baseline TFTs and thyroid scans (on SPECT-CT) were done, and the same were repeated at the completion of RT, at 3 and 6 months. All patients received a minimum of 30 Gy to the whole neck. Baseline TFTs and thyroid scans were normal. None of them developed hypothyroidism clinical or subclinical (C/S) at the completion of RT. Six patients developed hypothyroidism (four subclinical, two clinical) at 3 months of the completion of treatment. At 6 months of follow-up 14 patients (31.1%) developed hypothyroidism (ten subclinical, four clinical) with P≤ 0.01. All patients having clinical or subclinical hypothyroidism had decreased uptake on thyroid scan. Patients having decreased uptake on thyroid scan only, with normal TFTs and no symptoms of hypothyroidism were zero at the completion of RT, 1 at 3 months follow-up, and seven at 6 months follow-up. Hypothyroidism (C/S) is an under-recognized but significant complication of therapeutic doses of RT to the neck. In our study, we recognized hypothyroidism as early as 3 months following the completion of RT. Hence, tests to evaluate functional and biochemical changes in the thyroid gland should be instituted as early as 3 months following RT.

Outcomes of freehand interstitial brachytherapy in advanced gynecologic malignancies

PurposeThe purpose of the study is to present the first results of freehand interstitial brachytherapy (ISBT) used to treat patients with carcinoma of the cervix and the vagina. Methods and MaterialsPatients diagnosed with carcinoma of the cervix or carcinoma of the vagina who were not suitable for intracavitary brachytherapy were treated with freehand ISBT. The implant was performed transperineally using C arm or transrectal ultrasound guidance. Patients received an external beam radiotherapy dose of 50 Gy in 25 fractions. The dose delivered by high-dose-rate ISBT was 18 Gy in three fractions, 6 Gy per fraction, 6 h apart. The brachytherapy dose volume parameters were analyzed after CT-based planning using GEC ESTRO image-guided brachytherapy-based guidelines. ResultsFrom June 2018 till November 2018, 14 patients were treated with freehand ISBT. The mean dose received by 90% of the high-risk clinical target volume (D90) was 82 Gy EQD210 for patients with carcinoma of the cervix and 80 Gy EQD210 for patients with carcinoma of the vagina. The mean dose received by 2 cc volume of the bladder and rectum was 80 Gy EQD23 and 70 Gy EQD23 for patients with carcinoma of the cervix and 75 Gy EQD23 and 72 Gy EQD23 for patients with carcinoma of the vagina, respectively. The mean dose received by 2 cc of the sigmoid was 65 Gy EQD23 for cervical carcinoma and 58 Gy EQD23 for vaginal carcinoma, respectively. At a median followup of 14 months, 2 patients developed local recurrence. Two patients developed Grade 2 gastro intestinal toxicity, and 1 patient developed Grade 2 genitourinary toxicity. None of the patients developed Grade 3 or 4 toxicities. ConclusionA freehand interstitial implant is feasible in resource limited settings and provides acceptable local control with minimal acute toxicity.

External beam radiation dose escalation for high grade glioma.

External beam radiation dose escalation for high grade glioma.

A single-center analysis of adjuvant sequential versus ‘sandwich’ chemoradiotherapy for patients with stage III endometrial cancer.

e18101 Background: To determine if the sequencing of chemotherapy with external beam radiotherapy (EBRT) in the adjuvant setting for FIGO stage III endometrial cancer impacts 2-year progression free survival (PFS). Methods: As part of our Gynecologic Oncology Multidisciplinary Group's initiative to establish an institutional guideline for the adjuvant treatment of Stage III endometrial cancer, we reviewed 144 cases identified by our cancer registry and departmental database. Treatment regimens were divided into three categories: sequential therapy with six cycles of carboplatin/taxane followed by EBRT, concurrent cisplatin for two cycles with EBRT followed by four cycles of carboplatin/taxane, or ‘sandwich’ therapy with three cycles of carboplatin/taxane followed by EBRT followed by three cycles of carboplatin/taxane. The published results of the phase III GOG-258 study called into question the efficacy of concurrent chemoradiation. Therefore, we only compared sequential versus ‘sandwich’ therapy using a Chi-Square analysis. We conducted a retrospective chart review to assess if patients were able to complete the prescribed six cycles and EBRT, and then measured their PFS at two years. We hypothesized that there would be no difference in PFS between the two groups. Results: There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Ninety-four patients (65%) had stage IIIC disease. The majority of patients received six cycles of paclitaxel with carboplatin. Median EBRT dose was 45 Gy. There was no statistically significant difference in the estimated 2-year PFS between the sequential and ‘sandwich’ groups, which were 82% and 82.5%, respectively (p = 0.84). Conclusions: Adjuvant chemoradiation for FIGO stage III endometrial cancer given sequentially or in a ‘sandwich’ fashion appears to offer equally excellent early clinical patient outcomes.

Impact of leucocyte modifications in patients with locally advanced cervical treated by chemoradiotherapy.

e18014 Background: Concomitant cisplatin-based chemoradiotherapy (CCRT), followed by image guided-adaptive brachytherapy (IGABT) is the recommended treatment for patients suffering from locally advanced cervical cancer (LACC). Methods: Between January 2010 and May 2017, 103 patients with LACC (FIGO 2009-stages IB2-IVA) received CCRT followed by IGABT. The objectives of this study were to evaluate the impact of white blood cells (WBC) and polymorphonuclear neutrophils (PMN) counts variations on outcomes. This variable was calculated by substraction between WBC or PMN levels at the first cycle (CB) and the last cycle (CL) of chemotherapy (CT)(DCB-CL). The data were reviewed retrospectively, with Cox regression for univariate and multivariate analysis. Results: The median age at diagnosis was 50 years. The median tumor size at diagnosis was 47mm. The majority of the patients had FIGO stage II (60.2%) or stage I (21.4%) disease with squamous histology (88.3%). Patients received a median dose of external-beam radiotherapy (EBRT) of 45 Gy (range 40-50.4 Gy) by 1.8-2 Gy fractions, with a median cumulative dose of all the radiotherapy of 85 Gy. The median duration of EBRT+IGABT was 51 days (range 31-94). All patients received at least one cycle of cisplatin, but the majority received 5 (40.4%) or 6 (39.4%) cycles. The median follow-up time for all patients was 30.1 months. The overall survival (OS) and recurrence-free survival (RFS) at 3 years was 81,4% and 76,8% respectively. Univariate analysis associated higher DCB-CL WBC and DCB-CL PMN with better OS and RFS. Multivariate analysis confirmed that DCB-CL WBC (HR, 0.856; 95% CI, 0.737-0.986; p = 0.018) and DCB-CL PMN (HR, 0.863; 95% CI, 0.750-0.994; p = 0.041) were associated with better OS and RFS respectively. A linear regression analysis was performed to cross the DCB-CL WBC/PMN and the number of CT cycles. This analysis reveals that an increasing number of CT cycles is linked to an increased DCB-CL WBC/PMN. Conclusions: Our study reveals the impact of DCB-CL WBC and PMN on outcomes. These two tests could become biomarkers during CCRT to discuss adjuvant treatments, but also to adapt our follow-up.

Preliminary survey of 3D image-guided brachytherapy for cervical cancer at representative hospitals in Asian countries

3D image-guided brachytherapy (3D-IGBT) has become a standard therapy for cervical cancer. However, the use of 3D-IGBT is limited in East and Southeast Asia. This study aimed to clarify the current usage patterns of 3D-IGBT for cervical cancer in East and Southeast Asia. A questionnaire-based survey was performed in 11 countries within the framework of the Forum for Nuclear Cooperation in Asia. The questionnaire collected the treatment information of patients with cervical cancer who underwent 3D-IGBT. The cumulative external beam radiotherapy and 3D-IGBT doses were summarized and normalized to a biological equivalent dose of 2 Gy per fraction (EQD2) using a linear-quadratic model. Of the 11 institutions representing the participating countries, six (55%) responded to the questionnaire. Overall, data of 36 patients were collected from the six institutions. Twenty-one patients underwent whole-pelvic irradiation and 15 underwent whole-pelvic irradiation with central shielding. Patients received a median of four treatment sessions of 3D-IGBT (range, 2–6). All 3D-IGBT sessions were computed tomography (CT)-based and not magnetic resonance image-based. The median doses to the high-risk clinical target volume D90, bladder D2cc, rectum D2cc and sigmoid colon D2cc were 80.9 Gy EQD2 (range, 58.9–105.9), 77.7 Gy EQD2 (range, 56.9–99.1), 68.0 Gy EQD2 (range, 48.6–90.7) and 62.0 Gy EQD2 (range, 39.6–83.7), respectively. This study elucidated the current patterns of 3D-IGBT for the treatment of cervical cancer in East and Southeast Asia. The results indicate the feasibility of observational studies of CT-based 3D-IGBT for cervical cancer in these countries.

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer

PurposeHigh dose-rate (HDR) brachytherapy is commonly administered as a boost to external beam radiation therapy (EBRT). Our purpose was to compare toxicity with increasingly hypofractionated EBRT in combination with a single 15 Gy HDR boost for men with intermediate-risk prostate cancer. Methods and MaterialsForty-two men were enrolled on this phase IB clinical trial to one of three EBRT dose cohorts: 10 fractions, seven fractions, or five fractions. Patients were followed prospectively for safety, efficacy, and health-related quality of life (Expanded Prostate Index Composite). Efficacy was assessed biochemically using the Phoenix definition. ResultsWith a median follow up of 36 months, the biochemical disease-free survival was 95.5%. One man developed metastatic disease at 5 years. There was no significant minimally important difference in EPIC PRO for either urinary, bowel, or sexual domains. There was one acute Grade 3 GI and GU toxicity, but no late Grade 3 GU or GI toxicities. ConclusionFifteen gray HDR brachytherapy followed by a five fraction SBRT approach results in high disease control rates and low toxicity similar to previously reported HDR protocols with significant improvement in patient convenience and resource savings. While mature results with longer follow up are awaited, this treatment approach may be considered a safe and effective option for men with intermediate-risk disease.

Effects of HIV status on non-metastatic cervical cancer progression among patients in Lusaka, Zambia

IntroductionSub-Saharan Africa has the highest global incidence of cervical cancer. Cervical cancer is the most common cause of cancer morbidity and mortality among women in Zambia. HIV increases the risk...

Modeling Complex Deformations of the Sigmoid Colon Between External Beam Radiation Therapy and Brachytherapy Images of Cervical Cancer

In this study, we investigated registration methods for estimating the large interfractional sigmoid deformations that occur between external beam radiation therapy (EBRT) and brachytherapy (BT) for cervical cancer. Sixty-three patients were retrospectively analyzed. The sigmoid colon was delineated on 2 computed tomography images acquired during EBRT (without applicator) and BT (with applicator) for each patient. Five registration approaches were compared to propagate the contour of the sigmoid from BT to EBRT anatomies: rigid registration, commercial hybrid (ANAtomically CONstrained Deformation Algorithm), controlling ROI surface projection of RayStation, and the classical and constrained symmetrical thin-plate spline robust point matching (sTPS-RPM) methods. Deformation of the sigmoid due to insertion of the BT applicator was reported. Registration performance was compared by using the Dice similarity coefficient (DSC), distance to agreement, and Hausdorff distance. The 2 sTPS-RPM methods were compared by using surface triangle quality criteria between deformed surfaces. Using the deformable approaches, the BT dose of the sigmoid was deformed toward the EBRT anatomy. The displacement and discrepancy between the deformable methods to propagate the planned D1cm3 and D2cm3 of the sigmoid from BT to EBRT anatomies were reported for 55 patients. Large and complex deformations of the sigmoid were observed for each patient. Rigid registration resulted in poor sigmoid alignment with a mean DSC of 0.26. Using the contour to drive the deformation, ANAtomically CONstrained Deformation Algorithm was able to slightly improve the alignment of the sigmoid with a mean DSC of 0.57. Using only the sigmoid surface as controlling ROI, the mean DSC was improved to 0.79. The classical and constrained sTPS-RPM methods provided mean DSCs of 0.95 and 0.96, respectively, with an average inverse consistency error <1 mm. The constrained sTPS-RPM provided more realistic deformations and better surface topology of the deformed sigmoids. The planned mean (range) D1cm3 and D2cm3 of the sigmoid were 13.4 Gy (1-24.1) and 12.2 Gy (1-21.5) on the BT anatomy, respectively. Using the constrained sTPS-RPM to deform the sigmoid from BT to EBRT anatomies, these hotspots had a mean (range) displacement of 27.1 mm (6.8-81). Large deformations of the sigmoid were observed between the EBRT and BT anatomies, suggesting that the D1cm3 and D2cm3 of the sigmoid would unlikely to be at the same position throughout treatment. The proposed constrained sTPS-RPM seems to be the preferred approach to manage the large deformation due to BT applicator insertion. Such an approach could be used to map the EBRT dose to the BT anatomy for personalized BT planning optimization.

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer

ABSTRACTCombining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose–volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70–80 , 60–70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = −0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).

Postoperative endometrial carcinoma treated with external beam irradiation plus vaginal-cuff brachytherapy. Is there a dose relationship with G2 vaginal complications?

To analyse the possible relationship between the EQD2(α/β=3Gy) at 2cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC). From 2014 to 2016, 62 postoperative EC patients were treated with EBRT+VBT. The median EBRT dose was 45Gy (44Gy-50.4Gy). VBT involved a single 7Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/β=3Gy) at 2cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT+VBT dose. Statistics: Boxplot, Student's t and Chi-square tests and ROC curves. Mean follow-up: 39.2 months (15-68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/β=3Gy) at 2cm3 in G0-G1 patients was 70.4Gy(SD2.36), being 72.5Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15). Doses >68Gy EQD2(α/β=3Gy) at 2cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT+VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.

Treatment intensity and control rates in combining external-beam radiotherapy and radioactive iodine therapy for metastatic or recurrent differentiated thyroid cancer.

To evaluate the treatment outcomes of external-beam radiotherapy (EBRT) with or without radioactive iodine therapy (RAIT) for metastatic or recurrent lesions of differentiated thyroid cancer (DTC). Between August 1997 and March 2018, 73 lesions (distant metastases, 50; regional lymph-node metastases, 17; postoperative tumor-bed recurrences, 6) in 36 patients that had received EBRT with or without RAIT were reviewed. Doses of EBRT were 8-70Gy (median 40Gy). Seventeen patients received RAIT after EBRT. Median follow-up time of imaging studies was 14months (range 1-110months). Two-year overall survival rates and control rates of EBRT sites were 71% and 62%, respectively. Two-year control rates for EBRT of < 30Gy (n = 7), 30Gy (n = 13), 31-49Gy (n = 25), 50Gy (n = 20), and > 50Gy (n = 8) were 0%, 56%, 53%, 79%, and 100%, respectively. There were statistically significant differences in control rates between < 30Gy and 30Gy (p = 0.003), and between 50Gy and > 50Gy (p = 0.037). Control rates of > 50Gy were significantly better compared to ≤ 50Gy (p = 0.021). Two-year control rates with (n = 28) and without (n = 45) post-EBRT RAIT were 89% and 45%, respectively (p = 0.009). In multivariate analysis, EBRT of > 50Gy and post-EBRT RAIT were significant independent factors for favorable control of EBRT sites (hazard ratio [HR], 5.72; 95% confidence interval [CI], 1.21-27.1; p = 0.028 and HR, 2.98; 95% CI, 1.28-6.98; p = 0.012, respectively). EBRT of > 50Gy and post-EBRT RAIT appeared to be useful for long-term control of EBRT sites for metastatic or recurrent lesions of DTC.

Prognostic Factors for Eye Globe Salvage by External Beam Radiation Therapy for Resistant Intraocular Retinoblastoma.

PURPOSE:To analyse the prognostic factors for eye salvage for eyes with intra-ocular retinoblastoma (RB) that is resistant to systemic chemotherapy and focal therapy by external beam radiation therapy (EBRT).METHODS:A retrospective analysis of 28 eyes with intra-ocular RB that was resistant for systemic chemotherapy and focal consolidation therapy and received EBRT. Outcome measures included tumor stage at diagnosis, stage migration, type of tumor seeds, treatment modalities, eye globe salvage, metastasis, and survival.RESULTS:Most of the patients (83%) had bilateral RB, and 42% were females. All eyes were treated initially by combination of systemic chemotherapy and focal consolidation therapy. The dose of EBRT was 45 Gy. The mean follow-up was 6.5 years, and the overall eye globe salvage rate post EBRT was 46%: 67% (2/3) for group B, 71% (5/7) for group C, and 33% (6/18) for group D. Patient's gender, tumor site, laterality, and tumor stage at diagnosis were not significant prognostic factors (p> 0.05) for final outcome. The significant poor prognostic factors were tumor stage migration during systemic chemotherapy (p= 0.03) and presence of vitreous seeds at time of EBRT (p=0.001). Post EBRT complication rate was 68% (19/28) including; retinal detachment (3), vitreous hemorrhage (4), neovascular glaucoma (1), cataract (16), radiation retinopathy (2), and second malignancy (2).CONCLUSION:EBRT is an alternative for enucleation when RB is resistant to combined chemoreduction/focal consolidation therapy in absence in vitreous seeds. The known risks for EBRT are not justified for patients with unilateral RB and for those who have functional vision in the other eye.

Biological dose summation of external beam radiotherapy for the whole breast and image-guided high-dose-rate interstitial brachytherapy boost in early-stage breast cancer.

PurposeTo develop an alternative method for summing biologically effective doses of external beam radiotherapy (EBRT) with interstitial high-dose-rate (HDR) brachytherapy (BT) boost in breast cancer. The total doses using EBRT boost were compared with BT boost using our method.Material and methodsTwenty-four EBRT plus interstitial HDR-BT plans were selected, and additional plans using EBRT boost were created. The prescribed dose was 2.67/40.05 Gy to whole breast and 4.75/14.25 Gy BT or 2.67/10.7 Gy EBRT to planning target volume (PTV) boost. EBRT and BT computed tomography (CT) were registered twice, including fitting the target volumes and using the lung, and the most exposed volume of critical organs in BT were identified on EBRT CT images. The minimal dose of these from EBRT was summed with their BT dose, and these EQD2 doses were compared using BT vs. EBRT boost. This method was compared with uniform dose conception (UDC).ResultsD90 of PTV boost was significantly higher with BT than with EBRT boost: 67.1 Gy vs. 56.7 Gy, p = 0.0001. There was no significant difference in the dose of non-target and contralateral breast using BT and EBRT boost. D1 to skin, lung, and D0.1 to heart were 58.6 Gy vs. 66.7 Gy (p = 0.0025), 32.6 Gy vs. 50.6 Gy (p = 0.0002), and 52.2 Gy vs. 58.1 Gy (p = 0.0009), respectively, while D0.1 to ribs was 44.3 Gy vs. 37.7 Gy (p = 0.0062). UDC overestimated D1 (lung) by 54% (p = 0.0001) and D1 (ribs) by 28% (p = 0.0003).ConclusionsBased on our biological dose summation method, the total dose of PTV in the breast is higher using BT boost than with EBRT. BT boost yields lower skin, lung, and heart doses, but higher dose to ribs. UDC overestimates lung and ribs doses.