Interstitial Irradiation Research Articles

Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data

Abstract Background and study aims Pancreatic cancer is a devastating disease with limited locoregional treatment options. Diffusing alpha-emitter radiation therapy (Alpha DaRT), a novel cancer treatment using alpha-particle interstitial radiotherapy, may help address this challenge. The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasound (EUS)-guided Alpha DaRT for advanced pancreatic cancer. Patients and methods Patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were treated with EUS-guided Alpha DaRT insertion. The Alpha DaRT sources were delivered into pancreatic tumors using a standard EUS needle with a novel proprietary applicator. Adverse events (AEs) were assessed based on the Common Terminology Criteria for Adverse Events version 5.0. Tumor response was evaluated by imaging 4 to 6 weeks post treatment. Results The first five patients were treated between March and September 2023. The procedure was technically successful in all cases, with Alpha DaRT sources inserted into the target tumor. Estimated gross tumor volume coverage ranged from 8% to 44%. Fourteen AEs were reported among three patients. Four were serious AEs, none of which was associated with the treatment, but rather, with disease progression or medical assistance in dying. Only two AEs (mild) were deemed possibly related to the study device. At the 35-day visit, two patients had progressive disease and three had stable disease, with one of the latter showing partial response 2 months post procedure. Conclusions Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe, with no device-associated serious AEs. Further investigation of this promising novel modality is underway.

Clinical use of high dose-rate brachytherapy in treatment of patients with localized prostate cancer and infravesical obstruction

Background. High dose-rate brachytherapy is a new method of interstitial radiation therapy for treatment of localized prostate cancer. The difference from low dose therapy is temporary implantation of radiation sources with targeted high dose-rate irradiation of the affected organ.Aim. To evaluate 3-year effectiveness and safety of high dose-rate brachytherapy in patients with infravesical obstruction. Materials and methods. Between January of 2017 and December of 2019 at the Central Clinical Hospital “RZD-medicine”, 49 patients (mean age 67.8 ± 7.5 years) with verified prostate cancer diagnosis underwent high dose-rate brachytherapy in the regimen of 2 sessions of 15 Gy with 192Ir source. The inclusion criteria were disease stage ≤сТ2с, Gleason score ≤7. Patients were divided into 2 groups: 1st – patients with incidental prostate cancer (n = 21) who previously (more than 6 months ago, mean time 9.4 ± 2.4 months) underwent transurethral prostatectomy; 2nd – patients with verified prostate cancer (mean prostate volume 56 cm3) and obstructive symptoms without previous transurethral prostatectomy (n = 28).Results. In both groups, no intraoperative complications were observed. In 6 (28 %) patients of the 1st group and 2 patients of the 2nd group, grade II genitourinary toxicity in the form of moderate dysuria and nocturia was observed. Acute gastrointestinal toxicity was observed in 3 (14 %) patients of the 1st group, in the 2nd group such complications were absent. In the 2nd group during the postoperative period after the 2nd session, 4 patients (14 %) experienced acute urinary retention requiring cystostomy.Conclusion. High dose-rate brachytherapy is a safe and effective radical treatment method for patients with localized prostate cancer with obstructive symptoms who have contraindications for surgical treatment.

Long-Term Biochemical Control of a Prospective Cohort of Prostate Cancer Patients Treated With Interstitial Brachytherapy Versus Radical Prostatectomy

AimsTo report long-term oncological outcomes of men treated prospectively as part of the American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT) at our institution. Materials and methodsIn 2003–2004, patients eligible for SPRIT attended a multidisciplinary educational session, following which they could choose radical prostatectomy, low dose rate brachytherapy (LDR-BT) or randomisation to SPIRIT. Biochemical failure was determined by the accepted definitions of a prostate-specific antigen (PSA) level ≥0.2 ng/ml after radical prostatectomy and the Phoenix definition of PSA ≥2 ng/ml above the nadir after LDR-BT. A sensitivity analysis, using a PSA >0.5 ng/ml to define biochemical failure after LDR-BT and a threshold PSA ≥0.2 ng/ml, was carried out to test the robustness of the results. To account for the competing risk of death, Gray's test was used to test the equality of the cumulative incidence function of biochemical failure between treatment groups. The Kaplan–Meier method was used to estimate overall survival and prostate cancer-specific survival. A P-value ≤0.05 was considered statistically significant. ResultsOf 156 patients, 100 received LDR-BT (15 after randomisation) and 56 underwent radical prostatectomy (15 after randomisation). The median follow-up was 12.6 and 14.7 years for LDR-BT and radical prostatectomy, respectively. The median age was 60 years; the median pre-treatment PSA was 5.5 (interquartile range 4.3–7.1). No significant differences in patient characteristics were found between groups. Two patients received adjuvant radiotherapy after radical prostatectomy. The cumulative incidence function of biochemical failure was 0%, 1.1% and 2.4% at 5, 10 and 15 years, respectively, in the LDR-BT arm versus 8.5%, 15.8% and 15.8% in the radical prostatectomy arm (P < 0.001). These results were consistent when varying the definition of biochemical failure defined as PSA ≥0.5 ng/ml (P = 0.01). At 15 years, overall survival was higher in patients treated with radical prostatectomy compared with those treated with LDR-BT; however, no statistical difference was found in prostate cancer-specific survival. ConclusionIn low-risk prostate cancer patients, LDR-BT offers excellent long-term oncological outcomes comparable with radical prostatectomy, in addition to the previously reported advantage for LDR-BT in urinary and sexual quality of life domains and patient satisfaction.

High-Dose Brachytherapy in Chemoradiation Schemes of Patients &#x0D; with Oral Mucosa Cancer

The aim of the study was to improve clinical outcomes of oral mucosa cancer in case of surgical treatment failure.Materials and methods. A clinical case of combined radiation treatment of a patient with oral floor mucosa cancer St III T3N1M0 was presented. Pathogistological diagnosis # xxxxxx was: highly differentiated squamous cell carcinoma. A treatment plan was developed. Chemoradiotherapy at the first stage included 3 courses of intra-arterial chemotherapy (Selective (superselective) embolization (chemoembolization) of tumor vessels in the basin of the left and right facial and left lingual arteries, cisplatin 150 mg, combined with a daily infusion of 5-fluorouracil 4000 mg), with an interval 21 day. Chemoradiotherapy at the second stage included volume modulated arc therapy (VMAT) on the area of ​​the primary tumor (oral floor mucosa) and the regional metastasis pathways (total boost dose 60 Gy to the area of ​​regional lymph flow, otal boost dose 50 Gy to the oral cavity). Chemoradiotherapy at stage 3 included interstitial radiation therapy. A single boost dose (SBD) for the primary focus was 3 Gy/per fraction, 2 times a day, with an interval of 6 hours until total boost dose reached 21 Gy, 7 fractions.Results. After treatment, a complete regression of the tumor was noted. No pathological accumulation of radiopharmaceuticals, features of the tumor process was detected on PET/CT 48 months after treatment.Conclusions. Chemoradiotherapy combined with brachytherapy can be considered as an equal alternative to surgical treatment of patients with oral mucosa cancer.

A Multicenter Prospective Trial of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Cutaneous Cancers: Early Results from a Pilot Feasibility Study in the United States

<h3>Purpose/Objective(s)</h3> Recurrent or unresectable cutaneous cancers may have limited treatment options. Diffusing alpha-emitter Radiation Therapy (DaRT, AlphaTau Medical, Tel Aviv, Israel) is a novel method of treating solid tumors using alpha-particle interstitial radiotherapy. A prior study conducted outside the United States demonstrated the feasibility, safety and efficacy of DaRT in patients with squamous cell carcinoma of the skin or mucosa of the head and neck. In this prospective multicenter trial conducted in the United States, we tested the hypothesis that DaRT for recurrent and unresectable cutaneous cancers was feasible, and also characterized preliminary safety and efficacy. <h3>Materials/Methods</h3> Patients with malignant skin or soft tissue tumors were recruited if they had limited treatment options, including recurrent disease, unresectable tumors, or those with metastases which could not be rendered disease-free with surgery. After baseline patient and tumor assessment, pre-treatment planning was performed. Patients underwent temporary DaRT placement to deliver a physical dose of 10 Gy to the tumor. Patients were followed for adverse events and tumor response 6, 12 and 24 weeks after removal. The primary objectives were to determine the feasibility of the procedure (based on successful implantation of DaRT device in the tumor) as well as the safety (based on adverse events (AEs) graded by CTCAE V5.0). Secondary objectives included response (based on RECIST V1.1 criteria), among others. <h3>Results</h3> Ten patients were recruited to the study and all successfully underwent the DaRT procedure, confirming feasibility. Median patient age was 72 years (range 57-92 years), with 6 men and 4 women participating. Six patients had recurrent disease, 4 were deemed unresectable and none had metastases. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. The baseline mean tumor volume was 3.4 cm³ (range 0.65-12.65 cm³). Mean prescription dose coverage of the gross tumor volume was 91%, with all tumors having ≥85% coverage. No device-related grade 3 AEs were noted. Common AEs were grade 1-2 erythema, edema, and pruritis. At 12 weeks following treatment, there was a 100% complete response (CR) rate. Nine out of the ten CRs were confirmed by CT imaging. <h3>Conclusion</h3> This trial demonstrated the feasibility, and preliminary safety and efficacy of DaRT in the treatment of recurrent or unresectable cutaneous cancers. The favorable safety profile and high response rate are promising. A pivotal US trial for marketing approval is expected to be underway by the time of this presentation.

Biomimetic radiosensitizers unlock radiogenetics for local interstitial radiotherapy to activate systematic immune responses and resist tumor metastasis

BackgroundSimilar to other local therapeutic methods, local interstitial radiotherapy (IRT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis.ResultsMn-based IRT radiosensitizers consisting of 131I, MnO2 and bovine serum albumin (BSA) (131I-MnO2-BSA) were engineered. Such Mn-based IRT radiosensitizers successfully unlocked radiogenetics to magnify systematic immune responses of local IRT via remodeling hypoxic and immunosuppressive microenvironments and resist tumor metastasis. The MnO2 in 131I-MnO2-BSA caused decomposition of H2O2 enriched in tumors to generate O2 for alleviating hypoxic microenvironment and removing tumor resistances to IRT. Concurrently, hypoxia mitigation by such radiosensitizers-unlocked radiogenetics can effectively remodel immunosuppressive microenvironment associated with regulatory T (Treg) cells and tumor-associated macrophages (TAMs) infiltration inhibition to induce immunogenic cell death (ICD), which, along with hypoxia mitigation, activates systematic immune responses. More intriguingly, 131I-MnO2-BSA-enabled radiogenetics can upregulate PD-L1 expression, which allows anti-PD-L1-combined therapy to exert a robust antitumor effect on primary tumors and elicit memory effects to suppress metastatic tumors in both tumor models (4T1 and CT26).ConclusionsIRT radiosensitizer-unlocked radiogenetics and the corresponding design principle provide a general pathway to address the insufficient systematic immune responses of local IRT.Graphical

Clinical advantage and outcomes of computed tomography-based transvaginal hybrid brachytherapy performed only by sedation without general or saddle block anesthesia.

Three-dimensional image-guided brachytherapy is the standard of care in cervical cancer radiotherapy. In addition, the usefulness of the so-called "hybrid brachytherapy (HBT)" has been reported, which involves the addition of needle applicators to conventional intracavitary brachytherapy for interstitial irradiation. To evaluate the clinical outcomes of CT-based HBT consisting of transvaginal insertion of needle applicators (CT-based transvaginal HBT) and only intravenous sedation without general or saddle block anesthesia. This is a retrospective chart review of patients who received definitive radiotherapy, including CT-based transvaginal HBT, between February 2012 and July 2019. The inclusion criteria were as follows: (i) histologically diagnosed disease, (ii) untreated cervical cancer, (iii) International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IVA disease in the 2008 FIGO staging system, and (iv) patients who underwent CT-based transvaginal HBT at least once in a series of intracavitary brachytherapy. Overall, 54 patients fulfilled the eligibility criteria in the present study. The median follow-up period was 32 (IQR, 19-44) months. No patient complained of symptoms such as persistent bleeding or abdominal pain after the treatment. The 3-year local control (LC), disease-free survival, and overall survival rates for all 54 patients were 86.6%, 60.3%, and 90.7% (95% CI [81.3%-100.0%]), respectively. The 3-year LC rate was 87.7% in patients with FIGO III-IVA and 90.4% in tumor size >6.0cm. The incidence rate of late adverse events, grade ≥3, in the rectum and bladder was 0% and 1.8%, respectively. In the dose-volume histogram analyses, transvaginal HBT increased the dose of HR-CTVD90 by ~7.5% without significantly increasing the dose of organs at risk. Considering the favorable clinical outcomes, CT-based transvaginal HBT may be a good option for treating cervical cancer.

Safety of immune checkpoint inhibitors in non-small-cell lung cancer patients with idiopathic interstitial pneumonia: a matched case\u2013control study

PurposeThe immune checkpoint inhibitor nivolumab is commonly used for non-small-cell lung cancer treatment. Immune checkpoint inhibitors cause immune-related adverse events, including interstitial pneumonia. However, there are no studies on the risk factors for interstitial pneumonia exacerbation after immune checkpoint inhibitor administration in patients with a history of different types of interstitial pneumonia. Therefore, we aimed to investigate the risk factors for interstitial pneumonia exacerbation in patients with non-small-cell lung cancer and a history of interstitial pneumonia. We also aimed to explore differences in the risk of interstitial pneumonia exacerbation due to various types of interstitial pneumonia—idiopathic interstitial pneumonia, immune-related pneumonitis, and radiation pneumonitis.MethodsEleven patients with a history of interstitial pneumonia exacerbation following the administration of immune checkpoint inhibitor were included in the study. We performed 1:2 matching based on age and sex. Twenty-two patients whose interstitial pneumonia did not worsen after immune checkpoint inhibitor administration belonged to the control group. We calculated odds ratios for each factor in the patients and control subjects.ResultsThe odds ratio of idiopathic interstitial pneumonia in the case group was 0.15 (95% confidence interval: 0.03–0.89) (p = 0.03). There were no significant differences in other factors, such as smoking history, pulmonary emphysema, and chronic obstructive pulmonary disease.ConclusionThe administration of immune checkpoint inhibitors in non-small-cell lung cancer patients with a history of idiopathic interstitial pneumonia might be a viable treatment option and have clinical benefits.

An endovaginal MRI array with a forward-looking coil for advanced gynecological cancer brachytherapy procedures: Design and initial results.

To develop an endovaginal MRI array that provides signal enhancement forward into the posterior parametrium and sideways into the vaginal wall, accelerating multiple-contrast detection of residual tumors that survive external beam radiation. The array's enclosure should form an obturator for cervical cancer brachytherapy, allowing integration with MRI-guided catheter placement, CT, and interstitial radiation dose delivery. The endovaginal array consisted of forward-looking and sideways-looking components. The forward-looking element imaged the cervix and posterior endometrium, and the sideways-looking elements imaged the vaginal wall. Electromagnetic simulation was performed to optimize the geometry of a forward-looking coil placed on a conductive-metallic substrate, extending the forward penetration above the coil's tip. Thereafter, an endovaginal array with one forward-looking coil and four sideways-looking elements was constructed and tested at 1.5 Tesla in saline and gel phantoms, and three sexually mature swine. Each coil's tuning, matching, and decoupling were optimized theoretically, implemented with electronic circuits, and validated with network-analyzer measurements. The array enclosure emulates a conventional brachytherapy obturator, allowing use of the internal imaging array together with tandem coils and interstitial catheters, as well as use of the enclosure alone during CT and radiation delivery. To evaluate the receive magnetic field ( ) spatial profile, the endovaginal array's specific absorption-rate (SAR) distribution was simulated inside a gel ASTM phantom to determine extreme heating locations in advance of a heating test. Heating tests were then performed during high SAR imaging in a gel phantom at the predetermined locations, testing compliance with MRI safety standards. To assess array imaging performance, signal-to-noise-ratios (SNR) were calculated in a saline phantom and in vivo. Swine images were acquired with the endovaginal array combined with the scanner's body and spine arrays. Simulated profiles for the forward-looking lobe pattern, obtained while varying several geometric parameters, disclosed that a forward-looking coil placed on a metal-backed substrate could double the effective forward penetration from approximately 25 to ∼40mm. An endovaginal array, enclosed in an obturator enclosure was then constructed, with all coils tuned, matched, and decoupled. The ASTM gel-phantom SAR test showed that peak local SAR was 1.2 W/kg in the forward-looking coil and 0.3 W/kg in the sideways-looking elements, well within ASTM/FDA/IEC guidelines. A 15-min 4 W/kg average SAR imaging experiment resulted inless than2o C temperature increase, also within ASTM/FDA/IEC heating limits. In a saline phantom, the forward-looking coil and sideways-looking array's SNR was four to eight times, over a 20-30mm field-of-view (FOV), and five to eight times, over a 15-25mm FOV, relative to the spine array's SNR, respectively. In three sexually mature swine, the forward-looking coil provided a 5+0.2 SNR enhancement factor within the cervix and posterior endometrium, and the sideways-looking array provided a 4+0.2 SNR gain factor in the vaginal wall, relative to the Siemens spine array, demonstrating that the array could significantly reduce imaging time. Higher SNR gynecological imaging is supported by forward-looking and sideways-looking coils. A forward-looking endovaginal coil for cervix and parametrium imaging was built with optimized metal backing. Array placement within an obturator enhanced integration with the brachytherapy procedure and accelerated imaging for detecting postexternal-beam residual tumors.

PCR analysis of the effect of photodynamic therapy on breast tumors

Photodynamic therapy (PDT) is a promising therapeutic modality for treating cancer, including breast tumors. The oxidative damage caused by PDT culminates in cell death, induction of immune response, and the resulting destruction of the tumor. This study aimed to evaluate the gene expression profiling of genes BCL-2, BAX, and HER-2 and their proteins after PDT, associating it with the necrosis caused by this therapy under different fluences. Twenty-eight female rats received a single dose of 7,12-dimethylbenz (a) anthracene (DMBA - 80mg/kg), by gavage, for breast tumor induction. After the tumors grew, the animals were divided into four groups: G1 - control group – untreated breast tumor – and G2, G3, and G4 groups treated with PDT using Photogem@ as photosensitizer and interstitial irradiation, with fluences of 50J/cm, 100J/cm, and 150J/cm, respectively. Samples of tumors were harvested for histological examination by RT-qPCR. The RT-qPCR showed that the gene expression profiling of BCL-2, BAX, and HER-2 was not altered after PDT. Hemorrhagic necrosis and qualitatively greater vascular and cellular damage were observed and correlated positively with the fluence. PDT does not seem to induce the modulation of genes related to apoptosis. The results indicate that the type of cell death stimulated by PDT in breast tumor is necrosis.

Брахитерапия локализованного рака предстательной железы отечественными источниками I-125: собственный опыт Национального медицинского исследовательского центра радиологии

Introduction. One of the effective and minimally invasive methods prostate cancer treatment is interstitial radiation therapy, the essence of which is the implantation of radioactive microsources into the tumor tissue. Brachytherapy of prostate cancer is performed in more than 20 clinics in the Russian Federation using mainly foreign microsources, but their high cost does not allow increasing the number of operations and opening new brachytherapy departments in the Russian Federation. Based on the model of foreign microsources such as seed No. 6711 (Nicomed Amersham), a technology for the manufacture of microsources with iodine-125 (IPPE SEED) has been developed at the State Research Center of the Russian Federation - IPPE, as well as a pilot production facility with a capacity of up to 50 thousand items per year. Materials and methods. In order to assess the safety of microsources for medical personnel during brachytherapy, local dosimetric control was carried out. As part of a clinical study in 2015, 36 patients with stage T1 – T2 prostate cancer underwent low-power brachytherapy using domestic microsources. Results. The obtained values of absorbed doses do not differ within the limits of measurement errors from the values of doses determined during the operation with foreign microsources under similar conditions. It follows from the data obtained that even the maximum values of the measured local absorbed doses do not pose a radiation hazard when using IPPE SEED microsources for brachytherapy. Among the treated patients, adverse reactions were in the expected manifestations of grade 1 dysuria according to the RTOG / EORTC classification. No gastrointestinal toxicity has been reported. Patient monitoring was continued in order to obtain long-term results of treatment. PSA disease-free survival at 5-year follow-up was 94.4%. Discussion. Clinical trials of Russian medical devices have demonstrated their safety for patients and medical personnel, which was proved by conducting dosimetry control during the procedure itself, as well as during examination of patients after brachytherapy. The effectiveness of Russian microsources I-125 during low-power brachytherapy is demonstrated by a decrease in PSA level from baseline by 87% at a follow-up period of 6 months. The disease-free survival rate for 5 years was 94.4%. The absence of significant radiation reactions both in the early and in the late postoperative period is important. The low cost of microsources produced by JSC «SSC RF – IPPE» relative to foreign analogs makes it possible to increase the number of operations performed annually, and also gives prospects for opening new divisions performing interstitial radiation therapy operations. Conclusions. Russian microsources «IPPE SEED» have successfully passed clinical trials, during which their effectiveness and safety were proved. The study also demonstrated high rates of relapse-free survival and a low level of adverse reactions in treated patients.

Comparative analysis of long-term results of external beam and combined radiotherapy in high-risk prostate cancer patients

Prostate cancer (PCa) of high risk is one of the crucial problems in urological oncology. Radiation therapy (RT), along with radical prostatectomy, is an important component of the complex treatment of patients with high‑risk PCa. To improve the long‑term oncological results of RT dose escalation is advocated. Currently, dose escalation can be reached via external beam irradiation and interstitial RT techniques. The study included 109 patients with high‑risk PCa who underwent either external beam RT up to 76 Gy, or combined RT (external beam + interstitial RT) using 125I sources with long‑term androgen deprivation therapy. Comparative analysis of long‑term results of patients with high‑risk PCa treatment showed an improvement in 5‑year disease‑free survival rates after combined RT compared with external beam RT. Acute rectal toxicity was decreased in combined RT group compared to patients after external beam RT: 13.2 % and 46.4 %, respectively (p &lt; 0.01).

Modern Techniques for Cervical Cancer Radiotherapy

Cervical cancer is a socially significant illness often impacting women of reproductive and working age. The patients’ young age and social activity warrant the development of effective and safe therapies.The past decades have witnessed the novel radiation techniques to contain cervical cancer: 3DCRT-3D, IMRT, and VMAT, adaptive radiotherapy, CT/MRI-guided intracavitary radiation, combined interstitial and intracavitary radiation, abandoning intracavitary intervention for external beam delivery with sequential or concurrent cervical dose escalation, under brachytherapy unfeasible.Modern equipment and treatment planning systems allow a high dose delivery to the tumour and intracavitary treatment with visual control of the target and organs at risk. Combining of intracavitary and interstitial radiotherapy enables a better dose coverage of the target at a minimal radiation impact on organs at risk.Phasing-out of intracavitary for external radiotherapy may enable a cancericide dose delivery to the tumour under intractable intracavitary treatment.The major goal of technic novelties is the establishment of personalised radiotherapy for improving treatment outcomes and reducing the incidence and/or severity of radiation side effects. The article overviews the radiotherapy techniques for cervical cancer treatment and routes of their development.

Interstitial Photodynamic Therapy Using 5-ALA for Malignant Glioma Recurrences.

Simple SummaryMalignant glioma has a poor prognosis, especially in recurrent situations. Interstitial photodynamic therapy (iPDT) uses light delivered by implanted light-diffusing fibers to activate a photosensitizing agent to induce tumor cell death. This study examined iPDT for the treatment of malignant glioma recurrences. Forty-four patients treated at one institution were retrospectively analyzed and patient-, tumor- and treatment-related factors were retrieved from hospital charts. Most of the patients (37) had glioblastomas, the most aggressive type of glioma. Brain swelling or small bleedings caused worsening of symptoms in 18 patients, but only in one case severe symptoms persisted for more than six weeks. After iPDT, tumors recurred after a median of 7.1 months and patients lived for a median of 13.0 months. Two years after iPDT treatment, 25% of the patients were still alive. These promising results should be evaluated further in a prospective study.Interstitial photodynamic therapy (iPDT) using 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) as a cytotoxic photosensitizer could be a feasible treatment option for malignant gliomas. In a monocentric cohort of consecutive patients treated between 2006 and 2018, a risk profile analysis of salvage iPDT for local malignant glioma recurrences and associated outcome measures are presented here. It was considered indicated in patients with circumscribed biopsy-proven malignant glioma recurrences after standard therapy, if not deemed eligible for safe complete resection. A 3D treatment-planning software was used to determine the number and suitable positions of the cylindrical diffusing fibers placed stereotactically to ensure optimal interstitial irradiation of the target volume. Outcome measurements included the risk profile of the procedure, estimated time-to-treatment-failure (TTF), post-recurrence survival (PRS) and prognostic factors. Forty-seven patients were treated, of which 44 (median age, 49.4 years, range, 33.4–87.0 years, 27 males) could be retrospectively evaluated. Recurrent gliomas included 37 glioblastomas (WHO grade IV) and 7 anaplastic astrocytomas (WHO grade III). Thirty (68.2%) tumors were O-6-methylguanine-DNA methyltransferase (MGMT)-methylated, 29 (65.9%)—isocitrate dehydrogenase (IDH)-wildtype. Twenty-six (59.1%) patients were treated for their first, 9 (20.5%)—for their second, 9 (20.5%)—for the third or further recurrence. The median iPDT target volume was 3.34 cm3 (range, 0.50–22.8 cm3). Severe neurologic deterioration lasted for more than six weeks in one patient only. The median TTF was 7.1 (95% confidence interval (CI), 4.4–9.8) months and the median PRS was 13.0 (95% CI, 9.2–16.8) months. The 2- and 5-year PRS rates were 25.0% and 4.5%, respectively. The treatment response was heterogeneous and not significantly associated with patient characteristics, treatment-related factors or molecular markers. The promising outcome and acceptable risk profile deserve further prospective evaluation particularly to identify mechanisms and prognostic factors of favorable treatment response.

Chemoradiotherapy for limited-stage small-cell lung cancer and interstitial lung abnormalities

BackgroundPatients with lung cancer and interstitial lung disease treated with radiotherapy are at risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILAs) and radiation pneumonitis in patients with limited-stage small-cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is uncertain for patients with SCLC and ILAs treated with chemoradiotherapy. We investigated the impact of ILAs on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILAs treated with chemoradiotherapy.MethodsWe retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016.ResultsIn the univariate analysis, the patients with ILAs showed a higher incidence rate of radiation pneumonitis compared with those without ILAs (64% vs. 10%, P < 0.001). Multivariate analysis confirmed that ILAs were significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILAs showed poorer overall survival than those without ILAs (median, 18.9 vs. 67.9 months, P = 0.0338). Multivariate analysis showed that ILAs were a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILAs treated with chemoradiotherapy were 36% and 26%, respectively, and 8% and 0%, respectively, for those treated with chemotherapy alone.ConclusionsILAs were found to be a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. Patients with LS-SCLC and ILAs who were treated with chemoradiotherapy had both the possibility of long-term survival and risk of radiation pneumonitis.

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial

Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Long-term outcome of stereotactic brachytherapy with temporary Iodine-125 seeds in patients with WHO grade II gliomas

BackgroundThis long-term retrospective analysis aimed to investigate the outcome and toxicity profile of stereotactic brachytherapy (SBT) in selected low-grade gliomas WHO grade II (LGGII) in a large patient series.MethodsThis analysis comprised 106 consecutive patients who received SBT with temporary Iodine-125 seeds for histologically verified LGGII at the University of Munich between March 1997 and July 2011. Investigation included clinical characteristics, technical aspects of SBT, the application of other treatments, outcome analyses including malignization rates, and prognostic factors with special focus on molecular biomarkers.ResultsFor the entire study population, the 5- and 10-years overall survival (OS) rates were 79% and 62%, respectively, with a median follow-up of 115.9 months. No prognostic factors could be identified. Interstitial radiotherapy was applied in 51 cases as first-line treatment with a median number of two seeds (range 1–5), and a median total implanted activity of 21.8 mCi (range 4.2–43.4). The reference dose average was 54.0 Gy. Five- and ten-years OS and progression-free survival rates after SBT were 72% and 43%, and 40% and 23%, respectively, with a median follow-up of 86.7 months. The procedure-related mortality rate was zero, although an overall complication rate of 16% was registered. Patients with complications had a significantly larger tumor volume (p = 0.029).ConclusionSBT is a minimally invasive treatment modality with a favorable outcome and toxicity profile. It is both an alternative primary treatment method as well as an adjunct to open tumor resection in selected low-grade gliomas.

Abstract P4-13-08: Five day accelerated partial breast irradiation (APBI) using stereotactic body radiation therapy (SBRT) in stage 0-II breast cancer: A report of 86 patients with up to 2 year follow-up

Abstract Background: Randomized trials in selected early stage breast cancer patients with up to 10 year follow-up have proven that Accelerated Partial Breast Irradiation (APBI) given via High Dose Rate (HDR) implant bid in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given qd in 5-6 weeks in regard to breast tumor local recurrence (LR) [1-2]. However, complications with APBI implant in a Medicare database review have been significant, with 3.95% of women requiring Mastectomy, 16.2% developing infections, and another 16.3% experiencing non-infection complications including rib fractures, fat necrosis, and breast pain [3]. Recently APBI using non-invasive Intensity Modulated Radiation Therapy (IMRT) or Stereotactic Body Radiation Therapy (SBRT) given qd in 5 fractions has been shown in another randomized trial with 5 year follow-up to be equivalent to qd XRT in 6 weeks, with respect to LR [4]. IMRT/SBRT was superior in regard to acute effects, late effects, and cosmesis. Objectives: In the randomized clinical trial of APBI IMRT/SBRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for SBRT. We sought to confirm the APBI SBRT/IMRT results with a simpler fiducial system. Materials and Methods: Between 2017 and 2019, 86 patients have undergone SBRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes ≤ 3 cm, negative surgical margins, and negative sentinel node dissections. SBRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows: V-30 Gy &amp;lt; 105%, Ipsilateral Breast V-15 Gy &amp;lt; 50%, Ipsilateral Lung V-10 Gy &amp;lt; 20%, Contralateral Lung V-5 Gy &amp;lt; 10%, Heart V-3 Gy &amp;lt; 20%, Contralateral Breast Dmax &amp;lt; 2 Gy and Skin Dmax &amp;lt; 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-24 months with a median of 12 months. LR has been 0% (0/86). There were no skin reactions. One patient developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 100% (86/86) of cases. Conclusions:Non-invasive APBI with SBRT given qd over 5 days targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given bid with HDR implant. At last follow-up, there have been no LR, skin reactions, or complications. Cosmesis has been excellent in 100% of patients. Refernces:1. Polgar C, Fodor J, Major T, et al. Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial. Radiother Oncol 2013; 108[2]: 197-202. 2. Strnad V, Ott O, Hildebrandt G, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet 2016; 387[10015]: 229-38. 3. Smith G, Xu Y, Bucholz T, et al. Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer. JAMA 2012; 307[17]: 1827-37. 4. Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial. Eur J Cancer, 2015; 51 [4]: 451-63. Citation Format: Rufus Mark, Valerie Gorman, Steven McCullough. Five day accelerated partial breast irradiation (APBI) using stereotactic body radiation therapy (SBRT) in stage 0-II breast cancer: A report of 86 patients with up to 2 year follow-up [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-08.

Jean Talairach: a cerebral cartographer.

Although French psychiatrist-turned-neurosurgeon Jean Talairach (1911-2007) is perhaps best known for the stereotaxic atlas he produced with Pierre Tournoux and Gábor Szikla, he has left his mark on most aspects of modern stereotactic and functional neurosurgery. In the field of psychosurgery, he expressed critique of the practice of prefrontal lobotomy and subsequently was the first to describe the more selective approach using stereotactic bilateral anterior capsulotomy. Turning his attention to stereotaxy, Talairach spearheaded the team at Hôpital Sainte-Anne in the construction of novel stereotaxic apparatus. Cadaveric investigation using these tools and methods resulted in the first human stereotaxic atlas where the use of the anterior and posterior commissures as intracranial reference points was established. This work revolutionized the approach to cerebral localization as well as leading to the development of numerous novel stereotactic interventions by the Sainte-Anne team, including tumor biopsy, interstitial irradiation, thermal ablation, and endonasal procedures. Together with epileptologist Jean Bancaud, Talairach invented the field of stereo-electroencephalography and developed a robust scientific methodology for the assessment and treatment of epilepsy. In this article the authors review Talairach's career trajectory in its historical context and in view of its impact on modern stereotactic and functional neurosurgery.

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии

Феномен «биохимического скачка простат-специфического антигена» (bounce) после внутритканевой лучевой терапии рака предстательной железы источником высокой мощности дозы в режиме монотерапии