Combined External Beam Radiotherapy Research Articles

Multimodality adjuvant treatment is associated with a survival benefit for patients with stage IIIC uterine carcinosarcoma

<h3>Objectives:</h3> Investigate outcomes of patients with stage IIIC uterine carcinosarcoma who received adjuvant chemotherapy with or without adjuvant radiation therapy. <h3>Methods:</h3> Patients with no history of another tumor diagnosed between 2004-2015 with lymph node positive (stage IIIC) uterine carcinosarcoma following hysterectomy with at least one month of follow-up were identified in the National Cancer Database. Patients who received adjuvant chemotherapy (administered within 6 months from surgery) with or without adjuvant radiation therapy (vaginal brachytherapy and/or external beam radiation therapy) were selected for further analysis. Median overall survival (OS) was compared with the log-rank test following generation of Kaplan-Meier curves while a multivariate Cox model was constructed to evaluate the impact of multimodality adjuvant treatment after controlling confounders. <h3>Results:</h3> A total of 726 patients who met the inclusion criteria were identified; 47.1% received chemoradiation. Among patients who received chemoradiation, 48.2% had external beam radiation, 30.4% combination of external beam radiation and brachytherapy and 20.4% brachytherapy only. Patients who received chemoradiation were younger (age 64 vs 66 years, p=0.024), and more likely to have private insurance (52% vs 48%, p=0.042). There were no statistically significant differences between the two groups in terms of tumor extent, patient race, presence of comorbidities, type of treatment facility, and extent of lymphadenectomy. Median OS for patients who received chemotherapy only was 38.14 months compared to 49.84 months for those who received chemoradiation, p=0.008. After controlling for the presence of cervical stroma invasion, patient age, race, insurance status, and presence of comorbidities, patients who received chemoradiation had better survival compared to those who received chemotherapy alone (HR: 0.77, 95% CI: 0.62, 0.95). <h3>Conclusions:</h3> Multimodality adjuvant treatment may be associated with a survival benefit for patients with lymph node positive carcinosarcoma.

Optimal adjuvant therapy and outcomes for early-stage uterine serous and clear cell carcinoma

Objectives: Despite recent advances in adjuvant therapy for various gynecologic malignancies, the prognosis of patients presenting with stage IVB uterine serous carcinoma (USC) remains extremely poor, with a reported 5-year survival of Methods: A multicenter retrospective analysis of patients with stage IVB USC was conducted from 2000 - 2018. Inclusion criteria were patients who had undergone comprehensive surgical staging/tumor debulking; followed by adjuvant chemotherapy±external beam radiation therapy (EBRT). Optimal cytoreduction (R1) was defined as residual disease =1cm. Patients receiving neoadjuvant chemotherapy were excluded from analysis. Progression free survival (PFS) and overall survival (OS) analysis was performed using Kaplan-Meier estimates. Multivariate analysis (MVA) was performed using Cox proportional hazards model. Results: Final analysis included 68 patients. 50 (74%) patients were cytoreduced to R1 and 18 (26%) to R2. Additionally, 11 (16%) R1 patients were cytoreduced to no gross residual disease (R0). The mean age was 66 years (range 44-89) and 96% of patients were African American. The majority of patients, 56 (82%), received systemic chemotherapy alone and 12 (18%) received a combination of chemotherapy and EBRT±vaginal brachytherapy (chemoradiation). Adjuvant therapy regimens were well-balanced between R1 and R2 patients (p=0.992). There was no difference in the frequency of treatment delays between regimens (p=0.832). 96% of patients received platinum-based chemotherapy. There was no difference in the age (p=0.227), race (p=0.936), type of radiotherapy (p=0.852) or chemotherapy regimen received (p=0.996) between R1 and R2 cohorts. The median PFS for all patients was 8 months and the median OS was 13 months. Cytoreduction to R1 was associated with a median PFS of 9 months, compared to R2 with a median PFS of 4 months (p Conclusions: In stage IVB USC, the amount of residual disease follow cytoreductive surgery is an important determinant of survival. Optimal cytoreduction should be the goal at the time of primary surgery. The combination of chemoradiation was associated with superior survival compared to chemotherapy alone and should be further investigated in this patient population.

Dose escalation in advanced floor of the mouth cancer: a pilot study using a combination of IMRT and stereotactic boost

PurposeWe evaluated the efficiency and toxicity of stereotactic hypofractionated boost in combination with conventionally fractionated radiotherapy in the treatment of advanced floor of the mouth cancer.MethodsThirty-seven patients with advanced stage of the floor of the mouth cancer, histologically confirmed squamous cell carcinoma (p16 negative) ineligible for surgical treatment, were indicated for radiochemotherapy or hyperfractionated accelerated radiotherapy (HART). The radiotherapy protocol combined external beam radiotherapy (EBRT) and a stereotactic hypofractionated boost to the primary tumor. The dose delivered from EBRT was 70–72.5 Gy in 35/50 fractions. The hypofractionated boost followed with 10 Gy in two fractions. For the variables—tumor volume, stage and grade a multivariate analysis was performed to find the relationship between overall survival, local progression and metastasis. Toxicity was evaluated according to CTCAE scale version 4.ResultsAfter a median follow-up of 16 months, 23 patients (62%) achieved complete remission. The median time to local progression and metastasis was 7 months. Local control (LC) at 2 and 5-years was 70% and 62%, respectively. Progression-free survival (PFS) and overall survival (OS) were 57% and 49% at 2 years and 41% and 27% at 5 years, respectively. Statistical analysis revealed that larger tumors had worse overall survival and a greater chance of metastasis. Log-Rank GTV > 44 ccm (HR = 1.96; [95% CI (0.87; 4.38)]; p = 0.11). No boost-related severe acute toxicity was observed. Late osteonecrosis was observed in 3 patients (8%).ConclusionThe combination of EBRT and stereotactic hypofractionated boost is safe and seems to be an effective option for dose escalation in patients with advanced floor of the mouth tumors who are ineligible for surgical treatment and require a non-invasive approach.

Brachytherapy with 198Au grains for cancer of the floor of the mouth: relationships between radiation dose and complications.

This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused by 198Au grain brachytherapy alone or the combination with other modalities in patients with the cancer of the floor of the mouth. Twelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated with 198Au grain brachytherapy alone (n = 5) or the combination of external beam radiotherapy (EBRT) and/or chemotherapy and 198Au grain brachytherapy (n = 7) from January 2005 to December 2016, were included. The relationships between the radiation dose and the complications of the soft tissue or mandible were investigated. Seven of 12 patients had died. Of these 7 patients, one with T1 and 2 with T2 had died of the causes related to the cancer of the floor of the mouth. Two with T1 and 2 with T2 had died of other diseases. Two patients had grade 2 complications of the soft tissue and mandible. These patients were treated by the combination of EBRT and/or chemotherapy and 198Au grain brachytherapy and irradiated with 123 or 139Gy in total dose, respectively. And one of these patients was treated by the chemotherapy in addition to EBRT. Our study showed that the combination of EBRT and 198Au grains brachytherapy for the floor of the mouth cancer patients might be associated with risks of developing complications of soft tissue ulcer and mandibular bone necrosis.

Palliative radiotherapy combined with stent insertion to reduce recurrent dysphagia in oesophageal cancer patients: the ROCS RCT.

Most patients with oesophageal cancer present with incurable disease. For those with advanced disease, the mean survival is 3-5 months. Treatment emphasis is therefore on effective palliation, with the majority of patients requiring intervention for dysphagia. Insertion of a self-expanding metal stent provides rapid relief but dysphagia may recur within 3 months owing to tumour progression. Evidence reviews have called for trials of interventions combined with stenting to better maintain the ability to swallow. The Radiotherapy after Oesophageal Cancer Stenting (ROCS) study examined the effectiveness of palliative radiotherapy, combined with insertion of a stent, in maintaining the ability to swallow. The trial also examined the impact that the ability to swallow had on quality of life, bleeding events, survival and cost-effectiveness. A pragmatic, multicentre, randomised controlled trial with follow-up every 4 weeks for 12 months. An embedded qualitative study examined trial experiences in a participant subgroup. Participants were recruited in secondary care, with all planned follow-up at home. Patients who were referred for stent insertion as the primary management of dysphagia related to incurable oesophageal cancer. Following stent insertion, the external beam radiotherapy arm received palliative oesophageal radiotherapy at a dose of 20 Gy in five fractions or 30 Gy in 10 fractions. The primary outcome was the difference in the proportion of participants with recurrent dysphagia, or death, at 12 weeks. Recurrent dysphagia was defined as deterioration of ≥ 11 points on the dysphagia scale of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire oesophago-gastric module questionnaire. Secondary outcomes included quality of life, bleeding risk and survival. The study recruited 220 patients: 112 were randomised to the usual-care arm and 108 were randomised to the external beam radiotherapy arm. There was no evidence that radiotherapy reduced recurrence of dysphagia at 12 weeks (48.6% in the usual-care arm compared with 45.3% in the external beam radiotherapy arm; adjusted odds ratio 0.82, 95% confidence interval 0.40 to 1.68; p = 0.587) and it was less cost-effective than stent insertion alone. There was no difference in median survival or key quality-of-life outcomes. There were fewer bleeding events in the external beam radiotherapy arm. Exploration of patient experience prompted changes to trial processes. Participants in both trial arms experienced difficulty in managing the physical and psychosocial aspects of eating restriction and uncertainties of living with advanced oesophageal cancer. Change in timing of the primary outcome to 12 weeks may affect the ability to detect a true intervention effect. However, consistency of results across sensitivity analyses is robust, including secondary analysis of dysphagia deterioration-free survival. Widely accessible palliative external beam radiotherapy in combination with stent insertion does not reduce the risk of dysphagia recurrence at 12 weeks, does not have an impact on survival and is less cost-effective than inserting a stent alone. Reductions in bleeding events should be considered in the context of patient-described trade-offs of fatigue and burdens of attending hospital. Trial design elements including at-home data capture, regular multicentre nurse meetings and qualitative enquiry improved recruitment/data capture, and should be considered for future studies. Further studies are required to identify interventions that improve stent efficacy and to address the multidimensional challenges of eating and nutrition in this patient population. Current Controlled Trials ISRCTN12376468 and Clinicaltrials.gov NCT01915693. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 31. See the NIHR Journals Library website for further project information.

PO26: Individualized Vaginal Boost Brachytherapy: Dosimetric Lessons with the Multichannel Vaginal Cylinder

Purpose: Measurable tumors that involve vaginal tissue, including primary vaginal cancer and recurrent endometrial cancer (after prior hysterectomy), are often treated using a combination of external beam radiotherapy (EBRT) and fractionated high-dose-rate (HDR) brachytherapy (BT). BT boost may be achieved with a variety of applicator types, mainly intracavitary (IC) single channel (SCVC) or multichannel vaginal cylinder (MCVC), or an interstitial (IS) implant. In comparison to SCVC, MCVC features an arrangement of peripheral catheters that allow preferential treatment of localized surface targets to higher doses, without the need for an invasive IS component.

PRSOR01 Presentation Time: 12:00 PM: Combination EBRT and Brachytherapy Boost is Associated with Improved Overall Survival Relative to Definitive Brachytherapy in Unfavorable Intermediate-Risk Prostate Cancer

Purpose: The NCCN currently recommends external beam radiotherapy (EBRT) ± brachytherapy (BT) boost ± androgen deprivation therapy (ADT) for men with unfavorable intermediate-risk prostate cancer (UIR-PCa). The role of brachytherapy ± ADT in the absence of EBRT is not well defined in UIR-PCa. Radiation Therapy Oncology Group (RTOG) 0232, which randomized favorable intermediate-risk patients to definitive BT versus EBRT+BT boost, reported no progression-free survival (PFS) benefit to adding EBRT to BT.

P19.11 Endobronchial Brachytherapy as Curative Therapy for Postoperative Intrabronchial Oligometastasis in Non-Small Cell Lung Cancer

Lung cancer is a major health problem and a leading cause of cancer mortality worldwide. Although intratracheal/bronchial oligometastasis is a very rare type of recurrence after surgery of lung cancer, such patients often suffer with symptoms of respiratory tract obstruction, including cough, bloody sputum and dyspnea. Surgical intervention might be difficult to perform due to reduced postoperative general condition and invasiveness associated with reoperation. In such cases of medically inoperable intratracheal/bronchial oligometastasis, endobronchial brachytherapy (EBB) plays an important role as curative treatment. We present 3 cases with recurrent intrabronchial oligometastasis who were curatively treated with a combination of external beam radiotherapy (ERBT) and EBB from May 2013 to October 2018. Patient characteristics are listed in Table1. In accordance with the present Japanese guideline1) for curative EBB, our radiation schedule is composed of 40 Gy of EBRT and 18 Gy in three fractions of EBB. We use a special source-centralizing applicator for EBB developed by Nomoto Y et al.2) to avoid eccentric distribution of the radiation dose and to protect the mucosal membrane of the bronchus from high-dose irradiation. EBB was performed in cooperation with radiologists under mild sedation without hospitalization. There were no complications in all cases using the applicator. Local control was confirmed by bronchoscopic evaluation in all cases. All patients are alive after 17, 24 and 78 months of follow-up, respectively, without evidence of recurrence. In the case of adenocarcinoma (Case 1), two metastatic lung cancers were discovered in the untreated lobe 3 years after EBB and cured by partial wedge resection. As both cases (Case 2,3) of squamous cell carcinoma were intrabronchial metastasis on the operated side which was accompanied with intrathoracic adhesions, the endobronchial brachytherapy was beneficial to avoid extreme invasive redo-surgery. Although good therapeutic result was also obtained in the case of adenocarcinoma (Case 1), it might be a subject for future debate whether local therapy with radiation or systemic therapy such as molecular targeted drugs should be ideal.

Radiation necrosis after a combination of external beam radiotherapy and iodine-125 brachytherapy in gliomas

PurposeFrequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown.MethodsPatients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models.ResultsEighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence.ConclusionThe combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

RESPONSE TO EXTERNAL RADIATION AND INTERSTITIAL BRACHYTHERAPY IN BULKY VULVAR CANCER

Vulvar cancer is a gynaecologic malignancy with an incidence of 3-5% of all gynaecologic malignancies. In Indonesia, number of new cases of vulvar cancer reaches 1153 cases with a mortality rate of 420. Multimodal therapy is the main therapy of vulvar cancer at advanced stage which consists of of surgery, radiotherapy, and chemotherapy. The role of brachytherapy as adjunctive therapy combined with EBRT is widely studied, especially its role in the management of patients with comorbidities or contraindications to surgery. The purpose of writing this case report is to assess the response of radiotherapy in the form of external beam radiotherapy (EBRT) and brachytherapy use the MUPIT applicator in patients with vulvar cancer. From the relevant studies, we obtain a good 5-year overall survival rate, disease free survival rate, and local control with tolerable complications. It can be concluded that the combination of EBRT and brachytherapy can be one of the therapeutic modality of choice in vulvar cancer.

Combining radiotherapy and focused ultrasound for pain palliation of cancer induced bone pain; a stage I/IIa study according to the IDEAL framework

BackgroundCancer induced bone pain (CIBP) strongly interferes with patient’s quality of life. Currently, the standard of care includes external beam radiotherapy (EBRT), resulting in pain relief in approximately 60% of patients. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) is a promising treatment modality for CIBP. MethodsA single arm, R-IDEAL stage I/IIa study was conducted. Patients presenting at the department of radiation oncology with symptomatic bone metastases in the appendicular skeleton, as well as in the sacrum and sternum were eligible for inclusion. All participants underwent EBRT, followed by MR-HIFU within 4 days. Safety and feasibility were assessed, and pain scores were monitored for 4 weeks after completing the combined treatment. ResultsSix patients were enrolled. Median age was 67 years, median lesion diameter was 56,5 mm. In all patients it was logistically possible to plan and perform the MR-HIFU treatment within 4 days after EBRT. All patients tolerated the combined procedure well. Pain response was reported by 5 out of 6 patients at 7 days after completion of the combined treatment, and stabilized on 60% at 4 weeks follow up. No treatment related serious adverse events occurred. ConclusionThis is the first study to combine EBRT with MR-HIFU. Our results show that combined EBRT and MR-HIFU in first-line treatment of CIBP is safe and feasible, and is well tolerated by patients. Superiority over standard EBRT, in terms of (time to) pain relief and quality of life need to be evaluated in comparative (randomized) study.

Ovarian Function Preservation in Patients With Cervical Cancer Undergoing Hysterectomy and Ovarian Transposition Before Pelvic Radiotherapy.

To examine the factors associated with ovarian failure (OF) and assess the effectiveness of ovarian transposition (OT) before pelvic irradiation for preserving ovarian function in patients with cervical cancer (CC) undergoing hysterectomy. During 2003 to 2017, patients who underwent hysterectomy with preservation of one or both ovaries were retrospectively enrolled. Patients were divided into 4 groups, depending on whether radiotherapy (RT) and OT were performed: group 1, RT(+) and OT(+); group 2, RT(+) and OT(−); group 3, RT(−) and OT(+); group 4, RT(−) and OT(−). OF was defined as serum follicle-stimulating hormone levels of ≥30 mIU/mL. Sixty-six patients (59 [89.4%] invasive CC and 7 [10.6%] cervical intraepithelial neoplasia) were included. The 2-year OF-free survival rate was 61.4% (95% confidence interval [CI] 37.8-86.0), 0%, 91.7% (95% CI 76.0-100), and 75.8% (95% CI 58.2-93.4) for groups 1, 2, 3, and 4, respectively. In groups 1 and 2 receiving RT, OT, and combination of external beam radiotherapy and vaginal brachytherapy were associated with OF on multivariate analysis (MVA) (P-value = .002 and .046, respectively). In groups 3 and 4 without RT, older age (40 years old) and OT did not affect OF; however, the number of remaining ovaries was independently associated with OF in MVA (P = .035). OT could effectively preserve ovarian function in patients treated with adjuvant RT, while OT procedure itself did not affect ovarian failure. OT should be considered in the management of premenopausal cervical cancer patients.

Multiparameter MRI and Clinical Factors for Predicting Early Response to Chemoradiotherapy in Cervical Cancer.

HomeRadiology: Imaging CancerVol. 3, No. 1 PreviousNext Research HighlightsFree AccessMultiparameter MRI and Clinical Factors for Predicting Early Response to Chemoradiotherapy in Cervical CancerSanaz Javadi, Vikas KundraSanaz Javadi, Vikas KundraSanaz JavadiVikas KundraPublished Online:Jan 29 2021https://doi.org/10.1148/rycan.2021209038MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked InEmail Take-Away Points■ Major Focus: To assess a combination of multiparametric MRI with clinical prognostic factors for predicting treatment outcomes in patients with cervical cancer.■ Key Result: Pretreatment individual multiple MRI parameters (diffusion coefficient, volume transfer constant, and extravascular extracellular space) and stage were found to be independent prognostic factors for prediction. Combining multiple MRI parameters, multiparametric MRI biomarkers, and their combination with clinical stage can parse categories favorable, intermediate, and unfavorable for recurrence after chemoradiotherapy.■ Impact: Further assessment of this combination is warranted for improving prediction of treatment responses in patients with cervical cancer.Cervical cancer is the fourth most common cause of cancer-related mortality in women globally. Chemoradiotherapy is the treatment of choice for locally advanced cervical cancer. Early prediction of treatment response could provide a window of opportunity to modify therapy if needed. Clinical prognostic factors alone have limitations in prediction of early response. A few studies have shown functional imaging methods, including PET and diffusion-weighted MRI, can predict recurrence and response to treatment in patients with cervical cancer (1–3). Zheng et al studied this topic further by combining pre- and posttreatment MRI parameters (intravoxel incoherent motion [IVIM], dynamic contrast-enhanced [DCE] MRI, and apparent diffusion coefficient [ADC]) with clinical prognostic factors (squamous cell carcinoma antigen, tumor stage, histologic type, and lymphadenopathy) to predict response to chemoradiotherapy in patients with cervical cancer.The study included 85 patients with pathologically proven cervical cancer that was greater than 1 cm who had no prior history of chemotherapy or radiation therapy and underwent pre- and posttreatment MRI. The latter was used to assess recurrence using Response Evaluation Criteria in Solid Tumors. Treatment included a combination of external beam radiotherapy, high-dose-rate intracavitary brachytherapy, and concurrent cisplatin chemotherapy. One month after completion of chemoradiotherapy, 40% of patients had residual disease. Patients with residual disease had higher stage but no other differences in clinical prognostic factors.Higher pretreatment ADC, IVIM diffusion-related coefficient (D), and DCE volume of extravascular extracellular space per unit volume of tissue (Ve), as well as lower IVIM perfusion-related parameter (f) and DCE volume transfer constant from blood plasma to the extravascular extracellular space (Ktrans) values were seen in tumors with residual disease on univariate analysis. The authors suggest that higher pretreatment ADC and D values may identify tumor necrosis, whereas high Ve, lower f value, and lower Ktrans may reflect poorer blood supply with decreased drug delivery and hypoxia causing resistance to radiation therapy.Multivariate analysis showed sensitivity and specificity of MRI parameters for predicting posttreatment residual tumor as 82% and 65% for D, 67% and 90% for Ktrans, and 82% and 71% for Ve, respectively. Combining these MRI parameters, the sensitivity and specificity for predicting residual disease were 91% and 90%, respectively. MRI parameters and International Federation of Gynecology and Obstetrics (FIGO) stage together produced 85% sensitivity and 96% specificity. MRI parameters with and without FIGO stage segregated patients into favorable, intermediate, and unfavorable categories for residual tumor recurrence. The study suggests that the combination of multiparametric MRI and clinical stage can predict response to treatment in cervical cancer.Highlighted ArticleZheng X, Guo W, Dong J, Qian L. Prediction of early response to concurrent chemoradiotherapy in cervical cancer: Value of multi-parameter MRI combined with clinical prognostic factors. Magn Reson Imaging 2020;72:159–166. doi: https://doi.org/10.1016/j.mri.2020.06.014

Temporal analysis of type 1 interferon activation in tumor cells following external beam radiotherapy or targeted radionuclide therapy.

Rationale: Clinical interest in combining targeted radionuclide therapies (TRT) with immunotherapies is growing. External beam radiation therapy (EBRT) activates a type 1 interferon (IFN1) response mediated via stimulator of interferon genes (STING), and this is critical to its therapeutic interaction with immune checkpoint blockade. However, little is known about the time course of IFN1 activation after EBRT or whether this may be induced by decay of a TRT source.Methods: We examined the IFN1 response and expression of immune susceptibility markers in B78 and B16 melanomas and MOC2 head and neck cancer murine models using qPCR and western blot. For TRT, we used 90Y chelated to NM600, an alkylphosphocholine analog that exhibits selective uptake and retention in tumor cells including B78 and MOC2.Results: We observed significant IFN1 activation in all cell lines, with peak activation in B78, B16, and MOC2 cell lines occurring 7, 7, and 1 days, respectively, following RT for all doses. This effect was STING-dependent. Select IFN response genes remained upregulated at 14 days following RT. IFN1 activation following STING agonist treatment in vitro was identical to RT suggesting time course differences between cell lines were mediated by STING pathway kinetics and not DNA damage susceptibility. In vivo delivery of EBRT and TRT to B78 and MOC2 tumors resulted in a comparable time course and magnitude of IFN1 activation. In the MOC2 model, the combination of 90Y-NM600 and dual checkpoint blockade therapy reduced tumor growth and prolonged survival compared to single agent therapy and cumulative dose equivalent combination EBRT and dual checkpoint blockade therapy.Conclusions: We report the time course of the STING-dependent IFN1 response following radiation in multiple murine tumor models. We show the potential of TRT to stimulate IFN1 activation that is comparable to that observed with EBRT and this may be critical to the therapeutic integration of TRT with immunotherapies.

The Role of Postoperative Radiotherapy for Carcinosarcoma of the Uterus.

Simple SummaryThe role of radiotherapy on carcinosarcoma, a rare malignant tumor, of the uterus is unclear. We reviewed data published from 2010 on the effects of radiotherapy on tumor control and survival in this patient group. Available data were mainly from cancer registries and suggested that radiotherapy, given either as vaginal brachytherapy (contact radiotherapy of the vagina) or external-beam radiotherapy or a combination of both, reduces the risk of recurrence and improves survival in patients with all stages of carcinosarcoma of the uterus without metastases in other organs.The role of postoperative radiotherapy delivered as external-beam radiotherapy (EBRT), vaginal brachytherapy (VBT) or a combination of both, in the management of carcinosarcoma of the uterus is not clearly defined, as only limited randomized trial data are available, indicating a reduction in locoregional recurrences after EBRT. We performed a structured review of data published from 2010. Although no relevant new data from prospective trials or meta-analyses were identified, 14 analyses of cancer registry data from the United States or Europe, focusing predominantly on the endpoint for overall survival, were identified, four of them using propensity-score matching to compare subgroups treated with vs. without radiotherapy. Although stage-by-stage data are rare, the registry analyses support the idea of a beneficial effect, especially of VBT, on overall survival in International Federation of Gynecology and Obstetrics (FIGO) stage IA patients (to a lesser extent in stage IB). For stages II to III, the data sets indicate the largest effects on overall survival for the combination of EBRT and VBT. In all stages, survival effects of radiotherapy apparently persist when given in addition to chemotherapy. Whereas some studies see the strongest survival effects in patients with positive lymph nodes, propensity-score matched data indicate an overall survival effect of radiotherapy (EBRT + VBT or VBT alone) in FIGO stages I to III regardless of lymph node surgery.

Stereotactic Inverse Dose Planning After Yttrium-90 Selective Internal Radiation Therapy in Hepatocellular Cancer

PurposeSelective internal radiation therapy (SIRT) is administered to treat tumors of the liver and is generally well tolerated. Although widely adopted for its therapeutic benefits, SIRT is rarely combined with external beam radiation therapy (EBRT) owing to the complexity of the dosimetry resulting from the combination of treatments with distinct radiobiological effects. The purpose of this study was to establish a dosimetric framework for combining SIRT and EBRT using clinical experience derived from representative patients with hepatocellular carcinoma (HCC) who received both therapies. Methods and MaterialsTreatments from 10 patients with HCC given EBRT either before or after SIRT were analyzed. The dosimetry framework used here considered differences in the radiobiological effects and fractionation schemes of SIRT versus EBRT, making use of the concepts of biological effective dose (BED) and equivalent dose (EQD). Absorbed dose from SIRT was calculated, converted to BED, and summed with BED from EBRT dose plans. Two of these patients were used in a virtual planning exercise to investigate the feasibility of combining stereotactic body radiation therapy and SIRT. ResultsThe combination of EBRT and SIRT in 10 patients with HCC showed no major toxicity. No Child-Pugh scores went above 8 and albumin-bilirubin scores from only 1 patient worsened to grade 3 (> -1.39) from treatment through 3-months follow-up. A framework with radiobiological modeling was developed to manage the combined treatments in terms of their sum BED. The exploratory SIRT plus SABR inverse dose plans for 2 patients, incorporating radiobiologically informed 90Y SIRT dosimetry, achieved dose distributions comparable to SBRT alone. ConclusionsTreatment with both EBRT and SIRT can be given safely to patients with HCC. The BED and EQD concepts should be used in combined dosimetry to account for the differing radiobiological effects of EBRT and SIRT. Inverse dose planning of EBRT after SIRT could provide improved dose distributions and flexibility to the clinical workflow. Further research into combination therapy is needed through prospective trials.

Risk and Prognosis of Secondary Rectal Cancer After Radiation Therapy for Pelvic Cancer.

BackgroundThe relationship between pelvic radiation therapy (RT) and second primary rectal cancer (SPRC) is unclear. The aim of this study was to assess the risk and prognosis of SPRC after pelvic RT.Materials and MethodsData for patients who had primary pelvic cancer (PPC) between 1973 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SPRC. Five-year overall survival (OS) and rectal cancer-specific survival (RCSS) were calculated using Kaplan–Meier curves.ResultsA total of 573,306 PPC patients were included, 141,225 of whom had been treated with RT. Primary cancers were located in the prostate (50.83%), bladder (24.18%), corpus uterus (16.26%), cervix (5.83%), and ovary (2.91%). A total of 1,491 patients developed SPRC. Overall, the patients who received RT were at increased risk of developing SPRC (SIR = 1.39, 95% confidence interval [CI]: 1.27–1.52). The risk of SPRC decreased in patients who did not undergo RT (SIR = 0.85, 95% CI: 0.80–0.91). The SIR for SPRC in patients who underwent external beam radiation therapy (EBRT) was 1.22 (95% CI: 1.09–1.36). The SIR for SPRC in patients who underwent a combination of EBRT and brachytherapy (EBRT–BRT) was 1.85 (95% CI: 1.60–2.14). For patients who received RT, the SIR for SPRC increased with time after a 5-year latency period from PPC diagnosis. The survival of RT-treated SPRC patients was significantly worse than that of patients with primary rectal cancer only (PRCO).ConclusionsPatients receiving pelvic RT were at an increased risk of developing SPRC. Different pelvic RT treatment modalities had different effects on the risk of SPRC. We suggest that long-term surveillance of SPRC risk is required for patients who have undergone pelvic RT, especially young patients.

Report of a Large Cohort of Intermediate-Risk Prostate Cancer Patients Treated with Cs-131 Brachytherapy

The intermediate-risk (IR) group of prostate cancer patients is extremely heterogenous. Patients are sub-classified into favorable-IR (FIR) and unfavorable-IR (UIR) groups due to variable prognoses, leading to significant treatment variations. We sought to evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for IR patients and elucidate which factors are important for driving more aggressive treatment. We reviewed a prospectively collected database of men treated with Cs-131 PB between 2006-2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen (PSA) >10 but < 20 ng/mL, or T2b-c on clinical exam. We defined UIR patients as having either Grade Group (GG) 3 or >1 IR factors. Our general treatment schema was to treat FIR with PB alone (115 Gy) and UIR with combined external beam radiation therapy (EBRT) to 45 Gy + PB boost (85 Gy), though this was somewhat variable. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical failure (BF). BF was defined as a serum PSA at least 2 ng/mL greater than posttreatment nadir PSA. Cox regression analysis was performed to identify predictors for BF. These factors included: GG, UIR subgroup, treatment (PB alone vs combined modality), ADT use, age (≤67 vs >67), clinical T-stage, PSA (<10 vs ≥10-20), and >1 IR factors. A total of 327 patients with a median follow-up of 70.6 months (IQR 45.9-102.7 months) were identified. Median age was 67 (IQR 62-72). ADT was used in 12.5% of patients. Most patients (57.5%) were classified as FIR. Of the 139 patients in the UIR subgroup, 69.1% met UIR criteria by virtue of GG 3 only and 30.9% by having >1 IR factor. Twenty-eight patients (20.1%) had a GG 3 and >1 IR factor. FIR patients had a 5-year BF rate (BFR) of 2.5% (SE 0.012). The 5-year BFRs for FIR patients treated with PB alone (81.4%) and combined modality (18.6%) were 1.7% (SE 0.012) and 5.0% (SE 0.035), respectively (p = 0.18). UIR patients had a 5-year BFR of 10.9% (SE 0.030) and were most commonly treated with EBRT+PB (61.9%). Five-year BFRs were 14.0% (SE 0.078) and 10.1% (SE 0.032) for UIR patients treated with PB alone and combined modality, respectively (p = 0.91). UIR patients by virtue of GG 3 only (n = 68) had a 5-year BFR of 13.0% (SE 0.047). The 5-year BFR for UIR due to >1 IR factors (n = 71) was 8.9% (SE 0.038). Six patients had 3 IR factors with a 5-year BFR of 50% (SE 0.25). On multivariate analysis, UIR subgroup was the only significant predictor for BF (p = 0.02; HR 2.49, 95% CI 1.15-5.41). The FIR subgroup is a distinct entity from the UIR subgroup with excellent outcomes when treated with Cs-131 PB alone. UIR patients have excellent outcomes with combined EBRT + PB. The majority of UIR patients do not require ADT, though the group that would benefit still needs to be defined.

An Analysis of Learning Curve Effect on the Speed and Quality of High Dose Rate Prostate Brachytherapy Procedures

To evaluate the impact of learning curve effect on the provision of High Dose Rate (HDR) prostate brachytherapy boost at a recently initiated program within a smaller Canadian Academic Cancer Center. From 2015 to 2019, 266 patients with intermediate or unfavorable risk prostate cancer were treated with single fraction HDR prostate brachytherapy boost (15 Gy), followed by combination external beam radiation therapy (37.5 – 46 Gy) at a single Canadian cancer institution. Detailed time records were recorded for all phases of the procedures including: total procedure time, catheter insertion / placement, contouring, second oncologist check, catheter reconstruction, planning / dose optimization, QA / second checks, and treatment delivery. Dosimetric values from the delivered plans were also analyzed, including metrics for: Prostate (D90, V100, V150, V200), urethra (D10, max), and rectum (V75, V80, V100, max). The experience of each team member (previous number of procedures performed since program inception) was also recorded. Radiation Oncologist (RO) experience was not a significant predictor of total procedure time (p = 0.163) nor total catheter placement time (p = 0.583). Planner experience was significantly correlated with reduced catheter reconstruction time, and consequently, total procedure time (β = -0.376 minutes / case experience, P<0.001). There were statistically significant differences in mean prostate D90 (105.36 vs 106.05%, p = 0.04), V100 (94.69% vs. 95.31%, p = 0.014), and urethra D10 (113.61 vs. 112.74%, p = 0.008) when comparing dosimetry from an oncologist’s first 20 cases compared to those afterwards. RO experience was correlated with improvement in prostate D90 (β = 0.000156, p = 0.008), V100 (β = 0.000144, p = 0.001), and V200 (β = -0.000152, p = 0.008), and urethra D10 (β = -0.000159, p = 0.011). HDR Prostate brachytherapy can provide radiotherapy with excellent dosimetric characteristics regardless of previous institutional experience. In our study, institutional oncologist experience provided a modest, but measurable improvement in dosimetric quality. Institutional experience reduced total procedure time; this improvement was mainly attributable to the planner. These findings support the use of HDR prostate brachytherapy as a robust technique even for newer adopters, and may further inform cancer centers initiating new HDR Brachytherapy programs or training new staff.

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.