Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience.
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ABSTRACT: Background
Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest.Method
Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16-30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan-Meyer analysis were applied.Results
The mean follow-up time was 10.8 months (range, 0-39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3-100%), 71.4% (95%-CI 50.2-92.6%) and 58.0% (95%-CI 34.1-81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required.Conclusion
In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis.
SUBMITTER: Diehl CD
PROVIDER: S-EPMC9817795 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience.
Diehl Christian D CD Pigorsch Steffi U SU Gempt Jens J Krieg Sandro M SM Reitz Silvia S Waltenberger Maria M Barz Melanie M Meyer Hanno S HS Wagner Arthur A Wilkens Jan J Wiestler Benedikt B Zimmer Claus C Meyer Bernhard B Combs Stephanie E SE
Cancers 20221220 1
<h4>Background</h4>Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest.<h4>Method</h4>Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16-30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-sp ...[more]
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Project description:Purpose/objectiveWe present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines.Materials/methodsWe identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient's ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time.Results237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 - 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%.ConclusionThere is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.
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Project description:Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials.
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Project description:Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose directly to the breast tumor bed. The synergistic effects of simultaneous surgery and radiation are poorly understood. We here explored the cellular and molecular changes induced by IORT in the tumor bed compared to no-IORT exposed breast tissues. Squamous metaplasia (SM) was identified in both cohorts; however, squamous metaplasia with atypia (SMwA) was only seen in IORT specimens (63.6%, p=0.004). SMwA mimicked DCIS on histology, requiring confirmatory stains (i.e., estrogen receptor and p63) for diagnosis. Neither SM nor SMwA were found in the initial BCS specimen. We identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). Notably, when only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling (p<0.001). Finally, we inferred a higher abundance of gamma delta T-cells, dendritic cells, and monocytes in the IORT samples compared to non-IORT samples. In conclusion, IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with intrinsic apoptotic signaling and immune response pathways. The higher abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity in traditionally considered immune-desert tumors such as HR-positive/HER2-negative breast cancer.
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Project description:AimsCutaneous metastases of internal malignancies occur in 1-10% of cancer patients. The diagnosis can sometimes be challenging, especially in cases with an unknown primary cancer.Materials and methodsA retrospective case review was performed including all cases of skin metastases from primary internal malignancies diagnosed at the Department of Pathology at the Maastricht University Medical Centre+ from 2007 to 2021. The clinicopathological data were collected and immunohistochemical and molecular diagnostic tests were performed to confirm the primary origin of the metastases.ResultsWe identified 152 cases (71 female; 31 male patients) of cutaneous metastases of internal malignancies. 28 patients (20 women and 8 men) were diagnosed with multiple cutaneous metastases. Among the female patients, the most common primary tumour was breast cancer (50% of the cases), followed by lung (13.6%), gynaecological (7.3%), and gastrointestinal origin (7.3%). Among the male patients, the most common primary sites were gastrointestinal and lung origin (altogether, 50% of the cases). In 19 patients, the cutaneous metastasis was the first presentation of a clinically silent internal malignancy (18.6%), of which most (78.9%) represented metastatic lung carcinomas. Finally, metastasizing patterns were different across tumour types and gender.ConclusionBreast, lung, gastrointestinal, and gynaecologic cancers are the most common primary tumours demonstrating skin metastases. Infrequently, cutaneous metastases can be the first clinically visual manifestation of an underlying not yet diagnosed internal malignancy; therefore, occasional broad immunohistochemical profiling, molecular clonal analysis, and a continuous high level of awareness are necessary for a precise diagnosis of cutaneous metastases of internal malignancies.
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Project description:BackgroundThe spine is the most frequent location of bone metastases. Local treatment aims at palliation of pain and, given the increased likelihood of long-term cancer survival, at local control. Kyphoplasty and intraoperative radiotherapy (Kypho-IORT) provided instantaneous pain relief in 70% of patients at the first day after the intervention and resulted in local control rates of > 93% at 1 year in a recently conducted phase I/II trial. To assess its clinical value, we designed a phase III trial which tests Kypho-IORT against the most widespread standard-of-care, external beam radiotherapy (EBRT), in patients with painful vertebral metastases.MethodsThis phase III study includes patients ≥50 years of age with up to 4 vertebral metastases and a pain score of at least 3/10 points on the visual/numeric analogy scale (VAS). Patients randomized into the experimental arm (A) will undergo Kypho-IORT (Kyphoplasty plus IORT with 8 Gy prescribed to 13 mm depth). Patients randomized into the control arm (B) will receive EBRT with either 30 Gy in 10 fractions or 8 Gy as a single dose. The primary end point is pain reduction defined as at least - 3 points on the VAS compared to baseline at day 1. Assuming that 40% of patients in the Kypho-IORT arm and 5% of patients in the control arm will achieve this reduction and 20% will drop out, a total of 54 patients will have to be included to reach a power of 0.817 with a two-sided alpha of 0.05. Secondary endpoints are evaluation of the percentage of patients with a pain reduction of at least 3 points at 2 and 6 weeks, local tumor control, frequency of re-intervention, secondary fractures/sintering, complication rates, skin toxicity/wound healing, progression-free survival (PFS), overall survival (OS) and quality of life.DiscussionThis trial will generate level 1 evidence on the clinical value of a one-stop procedure which may provide instantaneous pain relief, long-term control and shortened intervals to further adjuvant (systemic) therapies in patients with spinal metastases.Trial registrationRegistered with ClinicalTrials.gov, number: NCT02773966 (Registration date: 05/16/2016).
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Project description:Background: The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We aimed to assess outcomes and toxicities of treating localized MPM with neoadjuvant radiation therapy (RT) followed by extrapleural pneumonectomy (EPP). Methods: Patients were enrolled on an institutional protocol of surgery for mesothelioma after radiation therapy (SMART) between June 2016 and May 2017. Eligible patients were adults with MPM localized to the ipsilateral pleura. Patients underwent staging with PET/CT, pleuroscopy, bronchoscopy/EBUS, mediastinoscopy, and laparoscopy. Five fractions of RT were delivered using intensity modulated radiation therapy (IMRT), with 30 Gy delivered to gross disease and 25 Gy to the entire pleura. EPP was performed 4-10 days following completion of RT. Results: Five patients were treated on protocol. Median age was 62 years (range 36-66). Histology was epithelioid on initial biopsy in all patients, but one was found to have biphasic histology after surgery. Three patients had surgeon-assessed gross total resection, and two had gross residual disease. While all patients were clinically node negative by pretreatment staging, three had positive nodal disease at surgery. Patients were hospitalized for a median 24 days (range 5-69) following surgery. Two patients developed empyema, one of whom developed respiratory failure and subsequently renal failure requiring dialysis, while the other required multiple surgical debridements. Two patients developed atrial fibrillation with rapid ventricular response after surgery, one of whom developed acute respiratory distress requiring intubation and tracheostomy. At last follow-up, one patient died at 1.4 years after local and distant progression, two were alive with local and distant progression, and the remaining two were alive without evidence of disease at 0.1 and 2.7 years. Median time to progression was 9 months. Three patients received salvage chemotherapy. Conclusions: SMART provided promising oncologic outcomes at the cost of significant treatment related morbidity. Due to the significant treatment associated morbidity and favorable treatment alternatives, we have not broadly adopted SMART at our institution.
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Project description:Background/Objectives: Brain metastases (BrMs) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While the treatment of BrMs requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, the advances in molecular sequencing have improved outcomes in patients with targetable mutations. With a push towards the molecular characterization of cancers, we evaluated the outcomes by treatment modality at our institution with respect to prioritizing RT and targeted therapies. Methods: We identified the patients with NSCLC BrMs treated with surgical resection. The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). The secondary endpoint included index lesion recurrence. The tumor molecular profiles were reviewed. The outcomes were evaluated by treatment modality: surgery followed by adjuvant RT and/or adjuvant systemic therapy. Results: In total, 155/272 (57%) patients who received adjuvant therapy with adequate follow-up were included in this analysis. The patients treated with combination therapy vs. monotherapy had a median FFP time of 10.72 months vs. 5.38 months, respectively (p = 0.072). The patients of Hispanic/Latino vs. non-Hispanic/Latino descent had a statistically significant worse OS of 12.75 months vs. 53.15 months, respectively (p = 0.015). The patients who received multimodality therapy had a trend towards a reduction in index lesion recurrences (χ2 test, p = 0.063) with a statistically significant improvement in the patients receiving immunotherapy (χ2 test, p = 0.0018). Conclusions: We found that systemic therapy combined with RT may have an increasing role in delaying the time to progression; however, there was no statistically significant relationship between OS and treatment modality.
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Project description:Background/objectiveIntra-operative radiation therapy (IORT) is a newer partial breast irradiation technique that has been well studied in 2 large randomized trials, the TARGIT-A and ELIOT trials. We initiated our IORT program in 2018 in the context of a registry trial, and aim to report our early results thus far.MethodsWe instituted an IORT practice using Intrabeam® low energy 50kVp x-rays for selected breast cancer cases in 2018. Patients were enrolled on our institutional registry protocol which allowed for IORT in ER + patients with grade 1-2 DCIS ≤ 2.5 cm or invasive disease ≤ 3.5 cm in patients of at least 45 years of age.ResultsBetween January 2018 and December 2021, 181 patients with clinical stage 0-IIA ER + breast cancer were evaluated. One hundred sixty-seven patients ultimately received IORT to 172 sites. The majority of patients received IORT at the time of initial diagnosis and surgery (160/167; 95.8%). Re-excision post IORT occurred in 16/167 patients (9.6%) due to positive margins. Adjuvant RT to the whole breast +/- LN was ultimately given to 23/167 (13.8%) patients mainly due to positive sentinel LN found on final pathology (12/23; 52%); other reasons were close margins for DCIS (3/23; 13%), tumor size (3/23; 4.3%), and multifactorial (5/23; 17.4%). Five patients (3%) had post-operative complications of wound dehiscence. There were 3 local recurrences (1.6%) at a median follow-up of 27.9 months (range: 0.7- 54.8 months).ConclusionsIORT has been proven to be a safe and patient-centered form of local adjuvant RT for our population, in whom compliance with a longer course of external beam radiation can be an issue. Long term efficacy remains to be evaluated through continued follow up. In the era of COVID-19 and beyond, IORT has been an increasingly attractive option, as it greatly minimizes toxicities and patient visits to the clinic.Trial registrationAll patients were prospectively enrolled on an institutional review board-approved registry trial (IRB number: 2018-9409).
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