External Beam Radiotherapy Dose Research Articles

The Important Factor in Local Control of Bone Metastatic Lesions in Radiotherapy

With the advance of systemic therapy, long-term survivors have increased and long-term local control of bone metastases are required for some of patients. The purpose of this study was to search for factors affecting local control of bone metastatic lesions in external-beam radiotherapy (EBRT). Between January 2010 and December 2019, 361 osteolytic bone metastases (spinal column, 192; pelvis, 87; rib/sternum, 35; extremity, 41; facial, 6) in 257 patients received EBRT. Local control was evaluated by follow-up CT. Doses of EBRT were 8-50 Gy (median 30 Gy). One and three-year overall survival rates were 59% and 33%, respectively. One and three-year control rates at EBRT sites were 78% and 67%, respectively. Local recurrence was observed in 18% (64 lesions) and the time of recurrence were 0.5-105 months (median 3 months). Male, age of > 70, rib/sternum and facial bone metastases, bone metastases from hepatobiliary/pancreatic/colorectal carcinoma, extraosseous invasion, EBRT ≤ 20 Gy, no use of bisphosphonates/receptor activator of NF-κB ligand (RANKL) formulation, and no use of systemic therapy after EBRT were statically significant unfavorable factors for local control (p = 0.0155,0.0005, <0.0001, <0.0001, 0.0361, 0.0010, <0.0001, and 0.0008, respectively). In multivariate analysis, age of > 70, rib/sternum/facial bone metastases, bone metastases from hepatobiliary/pancreatic/colorectal carcinoma, EBRT ≤ 20 Gy, and no use of bisphosphonates/RANKL formulation were significant unfavorable factor for local control (p = 0.0001, <0.0001, 0.0006, 0.0010, and 0.0349, respectively). For patients who can expect long-term survival, the use of bisphosphonates/RANKL formulation and higher dose EBRT seemed to be useful. Although further studies are needed, it seemed to be comparatively difficult to control bone metastases of elderly patients, rib/sternal/facial bone, hepatobiliary/pancreatic/colorectal carcinoma.

Recurrence After Surgery for Stage II Endometrial Cancer Leads to Limited Survival: Practice Patterns and Outcomes of Adjuvant Treatment in an Integrated Healthcare System

Though increased risk of locoregional recurrence in intermediate-risk endometrial cancer warrants adjuvant treatment, the type and extent of therapy for FIGO Stage II disease is not well-standardized. Here, we observe practice patterns and outcomes for such patients in our integrated healthcare system. All incident cases of endometrioid adenocarcinoma diagnosed 2010-2017 were identified by central cancer registry. Patients who underwent definitive surgery and had pathological Stage II disease (cervical stromal invasion without extrauterine involvement) were included. Clinical data were obtained by electronic medical record abstraction. Gastrointestinal (GI) and genitourinary (GU) toxicities were graded by CTCAE 5.0. Of 4317 cases identified, 119 patients were eligible for analysis. Median age at diagnosis was 61 years. Median follow-up was 50.4 months (IQR 33.4-83.7). Nodal dissection was performed in 61% of patients with 14 median nodes (range 1-45) identified. Pathological grade was 1 in 55 (46%), 2 in 48 (40%), and 3 in 16 (13%). Lymphovascular invasion was seen in 39 (33%). No adjuvant treatment was given to 27 patients (23%). Pelvic external beam radiotherapy (EBRT) alone was administered to 10 patients (8%), vaginal brachytherapy (VBT) alone to 10 (8%), and both to 72 (61%). The most common EBRT and VBT doses were 4500cGy (range 4140-5040) and 2100cGy (range 1200-2100), respectively. Adjuvant chemotherapy only was given to 7 patients (6%), and with radiation to 6 patients (5%). Late grade 2 GI or GU radiation toxicity was experienced by 4 patients (4%); 2 developed late small bowel obstruction. Recurrences were noted in 23 patients (19%): locoregional in 9, distant in 14. Of locoregional recurrences, 6 were after no radiation and 3 after EBRT; 4 failed at the cuff, 4 in the para-aortic nodes, and 1 in the pelvic nodes, leading to 3 deaths. Of distant recurrences, 5 were in the lung and 5 in the omentum. Of 16 patients with grade 3 tumors, 5 recurred distantly and all died of disease; of these, 2 received 3 and 6 cycles adjuvant chemotherapy each. Median time to death was 4.9 months (range 3.5-26.8). At time of analysis, 98 patients were alive (82%) and 21 (18%) had died, 14 of cancer-related causes. Median time from diagnosis to death overall was 27.3 months (range 6.5 – 50.5); median time from recurrence to death was 9.6 months (range 1.3 – 37.1). Most Stage II patients received adjuvant radiation and tolerated it well with few late effects. While locoregional recurrences were uncommon among those receiving radiation, any recurrence led to limited survival among the majority, particularly in those with distant recurrences. As nearly one-third of patients with grade 3 disease developed distant disease, further study is merited in this group which may benefit from systemic therapy.

Salvage Low Dose Rate Prostate Brachytherapy: Clinical Outcomes of a Phase II Trial for Local Recurrence after External Beam Radiotherapy (NRG/RTOG -0526)

Prior studies of low dose rate (LDR) prostate brachytherapy (BT) for salvage of local recurrence (LR) of prostate cancer (PCa) after external beam radiotherapy (EBRT) are limited by retrospective reporting. We previously reported adverse events (AEs) of a prospective Phase II trial (NCT00450411) and now report efficacy outcomes with a minimum potential follow up of 5 yrs. Eligible patients had low or intermediate risk PCa prior to EBRT and biopsy-proven LR > 30 mos after EBRT, with PSA < 10 ng/mL and no regional or distant disease. Prescribed minimum target dose was 140 Gy with I-125, or 120 Gy with Pd-103. The primary endpoint, late GI/GU AEs occurring 9-24 mos after BT (CTCAE V3.0 > Grade 3; attributed to BT) was 14%. All eligible patients were followed for a minimum of 5 yrs after salvage BT and analyzed for secondary clinical outcomes. Disease-free (DFS), disease-specific (DSS), and overall (OS)survivals were estimated using the Kaplan-Meier method and 95% confidence intervals computed using Cox proportional hazards models. Local tumor progression (LR), distant failure (DF), and biochemical failure (BF) were estimated using nonparametric estimation of cumulative incidence accounting for competing risk events. Time to LR, DF and BF were modeled by cause-specific Cox proportional hazards regression and adjusted for clinical and treatment factors. From May 2007 – January 2014, 20 centers registered 100 patients with 92 analyzable. Median follow up is 6.9 yrs (range: 0.3-11.2); median age 70 (IQR: 66-74). Initial Gleason score was 7 in 48% and PSA >10 ng/mL in 16%. Median prior EBRT dose was 74 Gy (IQR: 70-76). Androgen deprivation was combined with salvage BT in 16%. Median interval from prior EBRT was 85 mos (IQR: 60-119). 10-yr OS is 70% (95% CI: 58 -83). Nineteen patients died (5 PCa, 10 other, 4 unknown). 4 had LR (one biopsy-confirmed). 10-yr LF rate is 5% (95% CI:1-11). 14 patients had DF (10-yr rate 19% (95% CI:10-29)). The 10-yr freedom from BF rate is 54% (95% CI:43-66). DFS is 61% at 5 yrs (includes death from any cause) but falls to 33% at 10 yrs. None of the baseline characteristics, including % of prostate covered by 100% of the prescription dose and interval from EBRT to BT were significantly associated with OS, DFS, local, distant, or biochemical failure. This is the first prospective multicenter trial to report outcomes of salvage LDR BT for LR after EBRT. We previously reported late grade 3 GU/GI adverse events occurring in14%. We now report 5-yr freedom from biochemical failure at 68%, comparable to other salvage modalities. Although further local LF is rare (5%), there is a continued toll of PCa recurrence such that freedom from biochemical failure at 10 yrs is 54%.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: A Single-Institution Experience

We assessed patient outcomes and toxicity after the use of intraoperative low-energy photon radiotherapy for select early-stage breast cancer (ESBC) patients. This is a retrospective review of patients with unilateral ESBC treated with breast-conservation surgery followed by low-energy photon intraoperative radiotherapy (IORT) at a single institution between 2010 and 2017. Institutional suitability guidelines included: age ≥ 50 years, invasive ductal carcinoma (IDC) with or without DCIS, grade 1 – 2 tumors < 3 cm, ER and or PR positive, Her2 negative, clinically node negative, no lymphovascular space invasion (LVSI), and negative margins (>2 mm). 20 Gy was prescribed to the surface of the spherical applicator fitted to the surgical cavity at surgery. Postoperative patients who did not meet institutional guidelines for IORT alone were recommended adjuvant treatment, including possible additional surgery, external-beam radiotherapy (EBRT), chemotherapy, and/or endocrine therapy. Kaplan-Meier estimates and Cox regression analysis were used to assess ipsilateral breast tumor recurrence (IBTR), overall survival (OS), and relapse-free survival (RFS). 201 patients were included with a median follow up of 5.1 years. Most patients met institutional guidelines for IORT for ESBC. The median age was 67 years; 88% were Her2 negative and ER positive and/or PR positive, 97% had IDC, 87% had grade 1 or 2 disease on biopsy, and 95% had T1 disease. On final pathology, 8% had LVSI, 25% had close (<2 mm) margins, and 3% had positive margins. Most had pathological T1 (93%) N0 (95%) disease. The median IORT applicator size was 4.5 cm with a mean dose at 1 cm depth of 6.3 Gy delivered over an average of 37 minutes. 10% of patients completed additional surgery, 11% additional EBRT, 9% adjuvant chemotherapy, and 74% received adjuvant hormonal therapy. The median total EBRT dose was 42.4 Gy (range 40.05 - 63 Gy) with a median dose of 2.65 Gy/fraction. The 5-year cumulative risk of IBTR was 2%. There was no statistically significant difference in IBTR between patients considered unsuitable by our institutional guidelines (p = 0.93) or by the 2016 ASTRO consensus guidelines (p = 0.26) compared to patients who were considered suitable for IORT alone, by respective guidelines. Of the 98 patients who did not meet institutional criteria based on final surgical pathology, 32% received adjuvant EBRT. Of the 9 patients who experienced IBTR, 5 patients did not undergo indicated EBRT. The 5-year OS rate was 95% with no breast cancer-related deaths. The 5-year RFS rate was 96%. 83% of patients had documented toxicity information and the overall highest reported grade 3 toxicity was 8%; seroma was the most common grade 3 toxicity (4%). IORT for select patients with ESBC has led to acceptable outcomes in regards to ipsilateral breast tumor recurrence and toxicity. We continue to recommend adjuvant EBRT for patients who do not meet IORT suitability criteria upon review of final pathology.

Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied?

PURPOSERadical external-beam radiotherapy (EBRT) followed by intracavitary brachytherapy is standard of care for patients with localized carcinoma of the cervix unsuitable for radical surgery. However, outcome data are scarce in resource-limited settings. We conducted a retrospective analysis of survival in a cohort of patients treated with this strategy in Sri Lanka.PATIENTS AND METHODSAll patients with localized cervical cancer treated with primary EBRT and intracavitary brachytherapy from 2014 to 2015 were included in the study. Primary end point was disease-free survival (DFS), defined as time to local or systemic recurrence or death. Univariable analysis was performed to determine the prognostic significance of the following variables: age, stage, use of concurrent chemotherapy, EBRT dose, brachytherapy dose, and time to completion of treatment (dichotomized at 60 days). Factors significant on univariable analysis were included in a multivariable model.RESULTSA total of 113 patients with available data were included in the analysis. Mean age was 58 years (range, 35-85 years), and most patients (n = 103 of 113) presented with stage ≥ IIB disease. Median time to delivery of brachytherapy from commencement of EBRT was 110 days (range, 34-215 days), with only 12 (11%) of 113 patients completing treatment within 60 days. Median follow-up was 28 months (range, 5-60 months), and 2-year DFS was 63.7% (95% CI, 55.4% to 73.2%). Treatment delay was the only significant factor associated with inferior DFS on univariable analysis (log-rank P = .03), and therefore, multivariable analysis was not performed.CONCLUSIONThere are significant delays in receiving intracavitary brachytherapy after completing EBRT for cervical cancer in Sri Lanka, which is associated with inferior DFS. Increasing brachytherapy resources is an urgent priority to improve outcomes of patients with cervical cancer.

20 TREATMENT OPTIMIZATION AND PROGNOSTIC FACTORS IN ADVANCED ESOPHAGEAL CANCER

Abstract Esophageal cancer is a disease with high mortality due to advanced stage at the time of diagnosis in patients with poor general condition and/or multiple comorbidities which makes them unsuitable for radical treatment. The goal of this clinical trial is finding optimal treatment for this group of patients. Methods Hypothesis of this clinical trial is that sequential use of high dose rate intraluminal brachytherapy, external beam radiotherapy and chemotherapy decreases symptoms of disease, improves quality of life and prolongs overall survival in patients with esophageal cancer that are not candidates for radical treatment. We have included patients with esophageal cancer that are not candidates for radical treatment. Statistical analysis was done only for the patients that have completed planned treatment and not for the intent to treat population. Therefore, statistical analysis was done for 39 patients, 22 in control group and 17 in interventional group. Results In a survival analysis adapted for AJCC stage of the disease, addition of sequential chemotherapy improves overall survival statistically significant (P = 0.004). Sequential use of high dose rate intraluminal brachytherapy and external beam radiotherapy decreases the degree of: dysphagia (P = 0.001), odynophagia (P = 0.002) and regurgitation (P = 0.008) statistically significant. Decrease of a pain degree is statistically significant only with the use of sequential chemotherapy (P = 0.031). Sequential use of chemotherapy does not improve control over dysphagia (P = 0.872), odynophagia (P = 0.872) and regurgitation (P = 0.872) any further. Patients of female gender have greater improvement of regurgitation score (P = 0.068), pain score (P = 0.09) and quality of life (P = 0.019). Conclusion Sequential use of high dose rate intraluminal brachytherapy and external beam radiotherapy provides a safe use of high radiotherapy doses with minimal exposure of organs at risk, according to dose-volume histogram analysis. Sequential use of chemotherapy, after high dose rate intraluminal brachytherapy and external beam radiotherapy, improves overall survival in patients with esophageal cancer that are not candidates for radical treatment, in comparison to patients who do not receive chemotherapy (P = 0.09).

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...