Trial Of Intraoperative Radiotherapy Research Articles

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

TARGIT E(lderly): Prospective phase II trial of intraoperative radiotherapy (IORT) in elderly patients with small breast cancer.

563 Background: TARGIT E is a prospective, multicentric single-arm phase II trial (NCT01299987; Neumaier et al. BMC Cancer 2012) that is based on the experimental arm of the protocol of the international randomized TARGIT A study. The trial was designed to investigate the efficiency of a risk-adapted approach consisting of a single dose of intraoperative radiotherapy (IORT) followed by whole breast radiotherapy (WBRT) only when risk factors are present in elderly patients. Methods: Patients with low-risk breast cancer (≥70 years, cT1, cN0, cM0, invasive carcinoma of no special type) were enrolled between February 2011 and September 2014. During breast conserving surgery, a single dose of 20 Gy of low-energy IORT was given (Intrabeam, Carl Zeiss Meditec, Germany). Additional postoperative WBRT (46 – 50 Gy) was applied in case risk factors (larger size, other histology, free margin < 1 cm, lymphatic vessel invasion (L1), positive nodes, multifocality/multicentricity, extensive intraductal component (EIC)) were present. Systemic therapy was applied according to international standards and guidelines. The primary outcome was the local relapse rate. Discontinuation of the trial was judged to be necessary if the local relapse rates exceed 3/4/6% at 2.5/5/7.5 years. Results: A total of 541 patients were screened. Of those 474 patients were enrolled, whereas 347 (73.1%) received IORT only, 99 (10.8%) IORT plus WBRT, 22 (4.6 %) WBRT only and 7 (1.5%) surgery only with no subsequent adjuvant therapies. After a median follow-up of 3.25 years, four ipsilateral in-breast recurrences were observed (after 11, 33, 42 and 43 months) resulting in an actuarial local relapse-free survival of 99.8% after 2.5 years and 98.5% after 5 years. Conclusions: The results of the prospective TARGIT E trial consolidate earlier reports from the randomized TARGIT A trial, supporting the use of accelerated partial breast radiotherapy (APBI) in selected patients. The observed local relapse rates at 2.5 and 5 years are far below the predefined stopping rules. Clinical trial information: NCT01299987.

Pros and Cons of Intraoperative Radiotherapy: Comparison of Two Clinical Trials in Breast Cancer Management

Context: Intraoperative radiotherapy (IORT) is an accepted standard treatment for early stages of breast cancer in the selected cases. This is proven in two large clinical trials including ELIOT and TARGIT-A ones, which are based on high energy electron beam and low kV X-ray energy, respectively. Published results of two trials aimed at evaluating the local recurrence as the final outcome. In ELIOT study, the local recurrence rate is 4.4% versus 0.4% in patients, who received IORT and External Beam Radiotherapy (EBRT), in comparison to 3.2% and 1.3% in TARGIT-A trial. These differences need to be further evaluated regarding the efficacy and beneficence of IORT. Objectives: The aim of this study is to further analyze the data of these two trials to confirm the strategy of IORT in breast cancer as boost or radical modality. Evidence Acquisition: Two main breast IORT trials were considered in this study. To this end, a computerized search was performed through MEDLINE, PubMed, PubMed Central, ISI web of knowledge, and reference list of related articles. All of the published data from these trials were gathered and their subjects were analyzed and compared. Results: Statistical analysis revealed that in patients with matching clinical, pathological, and biological profiles in both trials, radical IORT using either electron or low kV X-ray is effective and acceptable. It seems that in patients with low risk factors, IORT is more effective than EBRT. Patient selection according to America Society of Radiation Oncology or European Society of Radiation Therapy classification guidelines confirmed that the local recurrence rate of ELIOT in low risk patients, similar to TARGIT, was less than 1.9%. Conclusions: We compared the ELIOT and TARGIT-A trial documents and found all of similarities and differences referred to these two trials recommend, using IORT for selected cases of breast cancer with at least non inferiority in Disease free survival (DFS) and overall survival (OS) as well as superiority in cosmetic, non-breast cancer death, and more.

Intraoperative Radiotherapy: Is it Ready for Prime Time?

A single dose of intraoperative radiotherapy (IORT) delivered during breast conservation surgery may offer an alternative to external beam breast radiotherapy in selected women with early breast cancer. Two phase 3 trials testing single doses of X-rays to the post-resection tumour bed (TARGIT) or electrons to the mobilized tumour bed (electron intraoperative radiotherapy trial (ELIOT)) reported increased local breast recurrence after IORT. At a median 2.4 years follow-up in TARGIT, there was a 3.3 (after immediate IORT) to 5.4 % (after delayed IORT) local tumour relapse compared with 1.3 % after external beam radiotherapy. At a median 5.8 years follow-up in ELIOT, local relapse was 4.4 % after IORT versus 0.4 % after external beam radiotherapy. Significant adverse effects were uncommon following all treatments and generally less after IORT unless followed by external beam radiotherapy. With no survival differences reported so far, balancing increased local risk of relapse, patient convenience and financial costs require longer follow-up, at least in TARGIT, before reliable treatment recommendations can be considered.

TARGIT-A trial: Updated results for local recurrence and survival for the German centers.

1121 Background: In 2010, we reported data on local control and early toxicity for the TARGIT-A trial of intraoperative radiotherapy after lumpectomy for early breast cancer. The updated results and first analysis of survival of the whole cohort (n = 3,451) were presented at San Antonio Breast Cancer Symposium in December 2012. We analysed the German cohort of patients, which was supposed to be more homogeneous (prepathology IORT only, homogeneous treatment in EBRT arm) and lower risk (older, smaller tumors, larger margin) than the international cohort of patients due to legal restrictions for radiotherapy studies in Germany. Methods: TARGIT-A was a randomised trial in patients >=50 years with invasive ductal carcinoma (<= 2cm) undergoing breast conserving surgery comparing standard fractionated whole breast EBRT (56 Gy) with single dose TARGIT (20 Gy) immediately after tumor excision / at the time of the primary operation. The experimental arm mandated additional EBRT (46 Gy, excluding a boost, n = 126) if adverse features were detected on final pathology (EIC, N+, margin < 1 cm) making this a “risk-adapted policy”. Median follow-up was 2 years and 5 months. Results: 734 patients recruited from 7 centres in Germany. Patient’s ages were <=50y 3%, 51-60y 33%, 61-70y 51%, >70y 12%. Tumour sizes were 0-1cm 35%, 1.1-2cm 55% and >2cm 11%. Grade I 29%, II 59%, III 12% and nodes negative 81%, 1-3 nodes 16%, >3 nodes 3%. At 5-years, the absolute number of events in TARGIT vs. EBRT were as follows: Primary outcome: IBR 4 vs. 1, Exploratory outcome: All recurrences (breast +axilla+contralateral+distant recurrence) 11 vs. 7, Secondary outcome: All deaths 6 vs. 12, Breast Cancer deaths 3 vs. 5, Non-Breast Cancer deaths 3 vs. 7. Conclusions: Patients in the TARGIT-A trial have excellent 5 year outcomes (local control > 97%, overall survival >= 94%) in both arms of the trial. Clinical trial information: protocol 99PRT/47.

OC-0236: The TARGIT-A trial of intra-operative radiotherapy for breast cancer: Updated recurrence and survival

OC-0236: The TARGIT-A trial of intra-operative radiotherapy for breast cancer: Updated recurrence and survival

Intraoperative Radiotherapy Following Lumpectomy for Breast Cancer

Intraoperative radiotherapy (IORT) is a promising approach for delivering accelerated, partial breast irradiation (APBI). Condensing the entire therapeutic dose into a single fraction, delivering the treatment at the time of lumpectomy in the operating room, and with the ability to spare normal surrounding tissue to a greater extent than perhaps any other form of APBI, IORT offers many potential benefits. Whether a single fraction is able to provide effective local control, and whether long term tissue tolerance to a large single dose is acceptable, are the greatest concerns for this approach. Breast IORT trials conducted thus far are encouraging. This review will first describe the clinical trials that provided the groundwork for single-fraction breast IORT, and will then summarize ongoing phase I/II and phase III clinical trials evaluating this potentially safe and effective form of APBI.

P60 A prospective trial of intraoperative radiotherapy for breast cancer

P60 A prospective trial of intraoperative radiotherapy for breast cancer

750 Randomized trial of intraoperative radiotherapy for colorectal cancer

To evaluate the value of intraoperative radiotherapy (IORT) in colorectal cancer, a prospective randomized trial is carried out. For colon cancer, IORT plus surgery vs surgery alone is investigated. For rectal cancer, preoperative irradiation to the primary tumor was added to the treatment scheme in the experimental group. IORT was given in dose of 20 Gy, electron beam energy ranged from 8 to 15 MeV. After randomization and exclusion of unresectable and metastatic cases, the group consists of 42 patients. The mean age of patients was 56 years, 73% were males. Most part of the tumors presented B2 cases. There was no postoperative mortality. Approximately 1/2 of patients did not have postoperative complications. After a median follow-up period of 7 months (range 1–15) no patients in the experimental group had the disease recurrence. In the control group, 2 patients developed loco-regional failure.

Intraoperative radiotherapy for the treatment of soft tissue sarcomas of central anatomical sites

AbstractThe results of intense therapy for soft tissue sarcomas located in central anatomic sites using an intraoperative electron boost (10–20 Gy) during surgery, integrated in a multimodal approach including external beam irradiation with or without chemotherapy, are analyzed. The relevant clinical data include a total of 30 patients treated, 13 recurrent tumors, 11 primary locally advanced stages, 15 high grade lesions, common location in the trunk (10 cases) and retroperitoneum (8 cases), and macroscopic residual disease after surgery in 9 cases. The median follow‐up time for the entire series is 25 months (range 4–98+ months).Severe toxicity related to the combined therapy includes peripheral neuropathy in 3 patients, 1 myelopathy, 1 chronic enteritis, 1 rectovaginal fistula, and 1 lethal sepsis. Overall local control rate is 53% (65% in cases with microscopic residual disease and 35% in confirmed macrotumor residue). Subgroup analysis of local control shows a value of 72% (13/18) in patients with lesions of <10 cm in maximum dimension and 28% with tumors >10 cm (4/12). Actuarial survival rates are 36% for the entire series and 53% and 20% for patients with primary and recurrent disease, respectively. It is concluded that intraoperative radiotherapy (IORT) is feasible to be integrated in multidisciplinary programs as a local intensification treatment technique. Peripheral nerves are dose‐limiting structures for IORT trials. Local tumor control rates in central sarcomas appear to be related to the status of postsurgical margins and tumor size. Long‐term survivors are followed with no evidence of disease both in primary (81+ months) and recurrent disease (98+ months) patients. © 1995 Wiley‐Liss, Inc.

Randomized trial of intraoperative radiotherapy in unresectable carcinoma of the pancreas

Randomized trial of intraoperative radiotherapy in unresectable carcinoma of the pancreas

Randomized trial of intraoperative radiotherapy in resected carcinoma of the pancreas

Randomized trial of intraoperative radiotherapy in resected carcinoma of the pancreas