Concurrent Therapy Research Articles

Lessons learned from COVID-19 pandemic: outcomes after SARS-CoV-2 infection in hematopoietic cell transplant and cell therapy recipients

We investigated the outcomes after Coronavirus disease 2019 (COVID) in hematopoietic cell transplant (HCT) or chimeric antigen receptor-T cell (CART) therapy recipients in a single-centre study including all (n = 261)HCT/CART recipients (allogeneic-HCT 49%, autologous-HCT 40%, CART 11%). The median age was 60 (22-80) years. COVID severity was mild (74%), moderate (11%), and severe/critical (16%) with a mortality rate of 7% and a median duration of infection of 5.7 weeks. Significant predictors of COVID severe disease or mortality included concurrent infection (HR 14.9, 95% CI 2.2-5.6) and immunosuppressive therapy (OR 4.8, 95% CI 1.2-3.4).HCT/CART recipients have a higher risk of mortality with COVID and warrant vigilant interventions.

Capecitabine/cisplatin combined with concurrent intensity-modulated radiation therapy: a feasible therapeutic strategy for anal squamous cell carcinoma.

To evaluate the efficacy and safety of capecitabine/cisplatin (XP) combined with intensity-modulated radiation therapy (IMRT) in patients with non-metastatic anal squamous cell carcinoma (ASCC). All patients with ASCC who received radical concurrent chemoradiotherapy in the past 8years were screened. Patients who received XP or mitomycin/5-fluorouracil (MF) were selected and analyzed retrospectively. ASCC is an uncommon cancer, there were 36 patients were included in our study. The XP group and MF group included 18 patients each. The clinical complete response (cCR) rates in the XP group and the MF group were 94.4% and 88.9%, respectively (P = 1). The 2-year local control (LC), disease-free survival (DFS), and colostomy-free survival (CFS) rates were higher in the XP group than in the MF group (100% vs 93.3%, P = 0.32). Hematologic toxicities, especially grade ≥ 3 leukopenia (11.1% vs 44.4%, P = 0.06) and neutropenia (5.6% vs 61.1%, P = 0.001), were lower in the XP group than MF group. As a result of fewer side effects, fewer patients in the XP group demanded the dose reduction of chemotherapy (11.1% vs 50%, P = 0.03) and radiation interruption (55.6% vs 77.8%, P = 0.289). Delayed radiotherapy was shorter in the XP group (2.5 vs 6.5days, P = 0.042) than in the MF group. The XP regimen was as effective as the MF regimen in non-metastatic ASCC. Compared with the standard MF regimen, XP combined with IMRT showed higher treatment completion and lower toxicities. It could be considered a feasible alternative for patients with non-metastatic ASCC.

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort.

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0-10), oral function burden (scale 0-6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer.

LMAP-22 STEREOTACTIC RADIOSURGERY FOR PATIENTS WITH BRAIN METASTASES FROM GASTROESOPHAGEAL PRIMARY CANCERS

Abstract BACKGROUND Patients with brain metastases from gastroesophageal primary cancers have poor prognoses, and current management remains unclear. The authors present the largest single-institution experience of utilizing stereotactic radiosurgery (SRS) to treat patients with brain metastases from primary gastroesophageal cancers. METHODS A retrospective review of 71 patients (64 male, 90.14%) treated with Gamma Knife SRS from 2000 to 2022 for gastroesophageal primary cancers was conducted. Overall, 243 brain metastases were treated, and the median number of metastases per patient was 2 (range:1-21). The primary sites were esophagus (59 patients, 83.10%), gastric (7 patients, 9.86%), and gastroesophageal junction (5 patients, 7.04%). The median age at SRS was 66 years (range: 26-85), and the median KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7 cc (range: 0.27-104.76), and the median margin dose was 18 Gy (range: 11-20). RESULTS The median overall survival after SRS was 7 months (range: 1-64). At the last follow-up, 54 (76.06%) patients were deceased, and 8 (14.81%) patients died due to intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. On univariate analysis, &amp;gt; 2 brain metastases at SRS presentation (p=0.02, HR: 10.76, 95% CI: 1.48-78.40) was found to be the only significant predictor of local tumor progression. Ten patients (14.08%) experienced new tumor development at a median time of 4 months (range: 0-14) after SRS. On multivariate analysis, both the absence of concurrent systemic therapy (p=0.01, HR: 6.58, 95% CI: 1.55-27.0) and ≤ 2 tumors at SRS presentation (p&amp;lt;0.01, HR: 1.21, CI: 1.08-1.36) were found to be significant predictors of distant tumor control. The incidence of transient adverse radiation effects was 8.45%. CONCLUSIONS SRS can safely and effectively be used to treat primary gastroesophageal cancer brain metastases while allowing patients to focus on primary disease management.

Life-threatening hemoptysis in patients with metastatic kidney cancer.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n=4, 67%), concurrent anticoagulant therapy (n=1, 17%) and concurrent systemic therapy (n=4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n=130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.

What We Have Learned About Combining a Ketogenic Diet and Chemoimmunotherapy: a Case Report and Review of Literature.

A high-fat, moderate-protein, low-carbohydrate ketogenic diet has been reported in the literature as a treatment option for patients with cancer. A 69-year-old veteran was initially diagnosed with stage III colorectal cancer and progressed to having liver, pancreatic, and omental lymph node involvement despite completing adjuvant FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin) after surgery. The patient was treated with FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) and bevacizumab, followed by encorafenib and cetuximab on progression. Subsequently, he received pembrolizumab but continued to progress. The patient was later placed on trifluridine/tipiracil and bevacizumab concurrent with a ketogenic diet. Positron emission tomography and carcinoembryonic antigen levels indicated disease stabilization for 10 months. On progression, the patient was transitioned to ipilumimab and nivolumab and continued to adhere to the ketogenic diet. The patient's disease has continued to remain stable for the past 1 year. His degree of ketosis was determined using the glucose ketone index. The patient continues to have a good quality of life during concurrent ketogenic diet and therapy. This case supports the tolerability of the ketogenic diet along with chemotherapy and immunotherapy and should be considered as an adjunct to standard cancer treatment. In this report, we reviewed the latest literature about cellular mechanism of the ketogenic diet and the efficacy and relationship with chemotherapy and immunotherapy. We are about to open a ketogenic diet protocol at the Veterans Affairs Central California Health Care System in Fresno.

Endovascular brachytherapy with iodine-125 seed strand for extensive portal vein tumor thrombus in patients with hepatocellular carcinoma.

The aim of this study is to investigate the feasibility and effectiveness of endovascular brachytherapy with iodine-125 (I-125) seed strand for the treatment of extensive portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. A total of 40 HCC patients complicated by extensive PVTT who received I-125 seed strand implantation from January 2015 to December 2022 in our center were analyzed retrospectively. Endpoints included technical success rate, concurrent therapies, overall survival time, and complications. Multivariate and subgroup analyses were conducted for overall survival. The successful rate of operation was 100%, and there was no operation-related death. A total of 37 patients received single I-125 seed strand implantation, and three patients received double I-125 seed strand implantation. A total of 23 patients received a concurrent therapy: transarterial chemoembolization (TACE) combined with systematic treatment (n = 6), TACE alone (n = 10), and systematic treatment alone (n = 9). At a median follow-up of 3.5 (interquartile range (IQR), 2~8.5) months, the median overall survival (OS) of all patients was 92 days (95% confidence interval (CI): 77~108). In the subgroup analysis, the median OS was 128 days (95% CI: 101~155 days) in the I-125 seed strand implantation plus systematic treatment group and was longer than that (75 days (95% CI: 36~114) of the I-125 seed strand alone group (p = 0.037). Multivariate analysis revealed that no systematic treatment was an independent risk factor affecting the prognosis in this study. Six patients died of upper gastrointestinal bleeding: four patients in the I-125 seed strand alone group and two patients in the combination of I-125 seed strand with systematic treatment group. The study shows that endovascular brachytherapy with I-125 seed strand implantation is a safe and effective treatment method for extensive PVTT in HCC patients. The combination of I-125 seed strand implantation and systematic treatment can prolong the survival time.

An expanded safety/feasibility study of the EMulate Therapeutics Voyager™ System in patients with recurrent glioblastoma.

Aim: The EMulate Therapeutics Voyager™ is a simple, wearable, home-use device that uses an alternating electromagneticfieldto alter biologic signaling within cells. Objective: To assess the safety/feasibility of the Voyager in the treatment of recurrent glioblastoma (rGBM). Methods: In this study, patients with rGBM were treated with Voyager as monotherapy or in combination with standard chemotherapy at the Investigator's discretion. Safety was assessed by incidence of adverse events associated with the Voyager. Patients were followed until death. Results: A total of 75 patients were enrolled and treated for at least one day with the Voyager (safety population). Device-related adverse events were uncommon and generally did not result in interruption or withdrawal from treatment. There were no serious adverse events associated with Voyager. A total of60 patients were treated for at least one month (clinical utility population). The median progression-free survival (PFS) was 17weeks (4.3months) in the Voyager only group (n=24) and 21weeks (5.3months) in the Voyager+ concurrent therapy group (n=36). The median overall survival (OS) was 7months in the Voyager only group and 9months in the Voyager+ concurrent therapy group. In patients treated with Voyager+ concurrent therapy, the median OS for patients enrolled with their 1st or 2nd recurrence (n=26) was 10months, while in patients enrolled with their 3rd or 4th recurrence (n=10) OS was 7months. Conclusion: The data support the safety and feasibilityof the Voyager for the treatment of rGBM. Further prospective study of the device is warranted. Trial Registration Number: NCT02296580 (ClinicalTrials.gov).

Evaluation of Interfraction Setup Uncertainty of Patients With Glioblastoma Wearing TTFields (Tumor Treating Fields) During Radiation Therapy

Tumor treating fields (TTFields) with concurrent radiation therapy (RT) might improve the outcome of patients with newly diagnosed glioblastoma. Several trials, including that conducted in our center, have allowed patients to wear TTFields during RT. We aimed to evaluate the setup uncertainty introduced by TTFields and calculate the planning target volume (PTV) margin for clinical reference. We collected and analyzed 201 cone beam computed tomography images of 22 patients in our center. Patients with or without TTFields were divided into the control and TTFields groups. We evaluated the setup errors in 6 degrees of freedom and 3 degrees of freedom and the magnitudes in the 3-dimensional vectors. An estimated PTV margin for patients requiring nonimaging-guided RT was recommended. A significant difference was observed in the longitudinal axis between the TTFields and control groups (P < .05). These results were consistent with that of the intragroup comparison of the TTFields group. The position error of the longitudinal axis (from head to feet) was -0.51 ± 2.05 mm in the TTFields group. Wearing TTFields during RT increased the uncertainty, especially in the longitudinal axis, with a system error of 1.40 mm and a random error of 1.28 mm. Daily image guided RT for TTFields patients seems necessary. However, the recommended expansion margin of the PTV is 5 mm for patients requiring nonimage-guided RT to enhance the safety and efficacy of treatment.

Concurrent intensity-modulated radiation therapy and chemotherapy plus nimotuzumab for locally advanced cervical squamous cell cancer: A long-term follow-up result

The study aimed to evaluate the safety and efficacy of concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy plus nimotuzumab for the treatment of locally advanced cervical squamous cell cancer (LACSCC). From December 2013 to March 2017, 34 patients with stages IB2&amp;ndash;IVA (FIGO 2009) cervical squamous cell cancer were enrolled and received concurrent chemoradiotherapy plus nimotuzumab. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30&amp;ndash;36 Gy to Point A was delivered with high-dose-rate brachytherapy. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously weekly. The main and secondary outcome measures were toxicity evaluated using common terminology criteria for adverse events 4.03. and the outcome evaluated using response evaluation criteria in solid tumors 1.1, respectively. The median follow-up duration was 66 months (13 &amp;ndash; 98 months). All patients received 6 times of IMRT, brachytherapy, and nimotuzumab. Among them, 24 received six cycles of chemotherapy, while 11 received 4&amp;ndash;5 cycles. No life-threatening toxicity was found. The incidence of acute Grade 3 bone marrow depression was 52.9% (18/34), and Grade 3 gastrointestinal tract reaction was 8.8% (3/34). The incidence of late toxicities was 58.8% (20/34), including vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, vaginal stenosis, and paresthesia. About 90% of those were Grades 1&amp;ndash;2. Complete response was achieved in 33 cases (97.1%). The 3-year disease-free survival, local progression-free survival (LPFS), and overall survival rates were 79.4%, 91.2%, and 82.4%, respectively. The corresponding 5-year values were 79.4%, 91.2%, and 79.3%. In conclusion, concurrent IMRT and chemotherapy plus nimotuzumab may represent a well-tolerated and effective treatment regimen in patients with LACSCC.

Dynamic regulation of drug biodistribution by turning tumors into decoys for biomimetic nanoplatform to enhance the chemotherapeutic efficacy of breast cancer with bone metastasis.

Breast cancer with bone metastasis accounts for serious cancer-associated pain which significantly reduces the quality of life of affected patients and promotes cancer progression. However, effective treatment using nanomedicine remains a formidable challenge owing to poor drug delivery efficiency to multiple cancer lesions and inappropriate management of cancer-associated pain. In this study, using engineered macrophage membrane (EMM) and drugs loaded nanoparticle, we constructed a biomimetic nanoplatform (EMM@DJHAD) for the concurrent therapy of bone metastatic breast cancer and associated pain. Tumor tropism inherited from EMM provided the targeting ability for both primary and metastatic lesions. Subsequently, the synergistic combination of decitabine and JTC801 boosted the lytic and inflammatory responses accompanied by a tumoricidal effect, which transformed the tumor into an ideal decoy for EMM, resulting in prolonged troop migration toward tumors. EMM@DJHAD exerted significant effects on tumor suppression and a pronounced analgesic effect by inhibiting µ-opioid receptors in bone metastasis mouse models. Moreover, the nanoplatform significantly reduced the severe toxicity induced by chemotherapy agents. Overall, this biomimetic nanoplatform with good biocompatibility may be used for the effective treatment of breast cancer with bone metastasis.

Traditional and disease-related cardiovascular risk factors in ANCA-associated vasculitis: A prospective, two-centre cohort study.

ANCA-associated vasculitis (AAV) has been associated with increased risk of cardiovascular (CV) events. The aim was to assess traditional and disease-related CV risk determinants in a two-centre prospective cohort of AAV patients. Patients were recruited from centres in the Netherlands and Canada. A comprehensive CV risk assessment was performed at inclusion. Subjects were followed up yearly for 3-5years until the first CV event, death or end of follow-up. Cox proportional hazards analyses were performed to relate baseline characteristics to the first CV event. A total of 144 patients were included (mean age 62years, female sex 44%, median Framingham risk score 14.3%). Insulin resistance was present in 73% of patients tested at inclusion, independent of concurrent prednisone therapy. After a median follow-up of 2.90years, 16 patients (11%) experienced a CV event (14 non-fatal and 2 fatal). The incidence of CV events was 5.45 per 100 patient-years. Age, Framingham risk score, HbA1c level, Diabetes Mellitus (DM), and previous CV event were significantly associated with CV events. Other factors, such as sex, impaired renal function, dyslipidemia, hypertension, smoking history and microalbuminuria, or disease-specific variables, like ANCA serotype or disease activity, were not significantly related to CV events in univariable or age-adjusted cox regression analysis. Determinants of an increased CV risk were identified. Disease-related factors and treatments can further modify individual risk factors, such as for steroids causing chronic insulin resistance and DM. Treatment of risk factors is essential to optimize long-term outcomes in AAV patients.

Outcomes after definitive radiation therapy for localized prostate cancer in a national health care delivery system.

Accurate information regarding real-world outcomes after contemporary radiation therapy for localized prostate cancer is important for shared decision-making. Clinically relevant end points at 10years among men treated within a national health care delivery system were examined. National administrative, cancer registry, and electronic health record data were used for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy within the Veterans Health Administration from 2005 to 2015. National Death Index data were used through 2019 for overall and prostate cancer-specific survival and identified date of incident metastatic prostate cancer using a validated natural language processing algorithm. Metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods were estimated. Among 41,735 men treated with definitive radiation therapy, the median age at diagnosis was 65years and median follow-up was 8.7years. Most had intermediate (42%) and high-risk (33%) disease, with 40% receiving androgen deprivation therapy as part of initial therapy. Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low-, intermediate-, and high-risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low-, intermediate-, and high-risk disease. The unadjusted overall survival was lower across increasing disease risk categories at 77%, 71%, and 62% for low-, intermediate-, and high-risk disease (p<.001). These data provide population-based 10-year benchmarks for clinically relevant end points, including metastasis-free survival, among patients with localized prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high-risk disease in particular suggest that outcomes have recently improved.

Neoadjuvant versus Concurrent Androgen Deprivation Therapy in Localized Prostate Cancer Treated with Radiotherapy: A Systematic Review of the Literature.

There is an ongoing debate on the optimal sequencing of androgen deprivation therapy (ADT) and radiotherapy (RT) in patients with localized prostate cancer (PCa). Recent data favors concurrent ADT and RT over the neoadjuvant approach. We conducted a systematic review in PubMed, EMBASE, and Cochrane Databases assessing the combination and optimal sequencing of ADT and RT for Intermediate-Risk (IR) and High-Risk (HR) PCa. Twenty randomized control trials, one abstract, one individual patient data meta-analysis, and two retrospective studies were selected. HR PCa patients had improved survival outcomes with RT and ADT, particularly when a long-course Neoadjuvant-Concurrent-Adjuvant ADT was used. This benefit was seen in IR PCa when adding short-course ADT, although less consistently. The best available evidence indicates that concurrent over neoadjuvant sequencing is associated with better metastases-free survival at 15 years. Although most patients had IR PCa, HR participants may have been undertreated with short-course ADT and the absence of pelvic RT. Conversely, retrospective data suggests a survival benefit when using the neoadjuvant approach in HR PCa patients. The available literature supports concurrent ADT and RT initiation for IR PCa. Neoadjuvant-concurrent-adjuvant sequencing should remain the standard approach for HR PCa and is an option for IR PCa.

Miniaturised dual-modality all-optical ultrasound probe for laser interstitial thermal therapy (LITT) monitoring.

All-optical ultrasound (OpUS) has emerged as an imaging paradigm well-suited to minimally invasive imaging due to its ability to provide high resolution imaging from miniaturised fibre optic devices. Here, we report a fibre optic device capable of concurrent laser interstitial thermal therapy (LITT) and real-time in situ all-optical ultrasound imaging for lesion monitoring. The device comprised three optical fibres: one each for ultrasound transmission, reception and thermal therapy light delivery. This device had a total lateral dimension of <1 mm and was integrated into a medical needle. Simultaneous LITT and monitoring were performed on ex vivo lamb kidney with lesion depth tracked using M-mode OpUS imaging. Using one set of laser energy parameters for LITT (5 W, 60 s), the lesion depth varied from 3.3 mm to 8.3 mm. In all cases, the full lesion depth could be visualised and measured with the OpUS images and there was a good statistical agreement with stereomicroscope images acquired after ablation (t=1.36, p=0.18). This work demonstrates the feasibility and potential of OpUS to guide LITT in tumour resection.

Clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with abiraterone with or without ongoing androgen deprivation therapy: A retrospective case-control study.

Abiraterone and concurrent androgen deprivation therapy (ADT) are used in the treatment of patients with metastatic castration-resistant prostate cancer. Recently, it has been suggested that the use of abiraterone alone (without ADT) may have comparable efficacy to abiraterone with ongoing ADT. Here, we sought to assess the impact of ADT cessation in patients beginning abiraterone for castration-resistant prostate cancer. We identified 39 patients at our institution who received abiraterone alone (with discontinuation of ADT) between 2011 and 2022. We then procured a comparable group of 39 patients (matched by age, Gleason score, and prostate-specific antigen [PSA] level) who received abiraterone with ongoing ADT during the same period. We assessed and compared clinical outcomes in the two groups (abiraterone-alone vs. abiraterone-ADT) with respect to PSA response rates, PSA progression-free survival, and overall survival. Results were adjusted using Cox proportional-hazards multivariable models. The median PSA before treatment initiation was 12.7 (range: 0.2-199) ng/mL in the abiraterone-alone group and 15.5 (range: 0.6-212) ng/mL in the abiraterone-ADT group. Use of abiraterone alone adequately suppressed testosterone levels in 35/37 (94.6%) patients. Patients receiving abiraterone alone had a median PSA reduction of 80.2% versus 79.5% in patients receiving abiraterone plus ADT. The median PSA progression-free survival in patients receiving abiraterone alone was 27.4versus 25.8 months in patients receiving abiraterone plus ADT (hazard ratio [HR] 1.10; 95% confidence interval [CI] 0.65-1.71; p = 0.82). In addition, abiraterone alone was associated with an overall survival of 3.6versus 3.1 years in patients receiving abiraterone plus ADT (HR 0.90; 95% CI 0.50-1.62; p = 0.72). There were no differences in PFS or OS between groups after performing Cox multivariable regression analyses. Use of abiraterone alone was associated with comparable clinical outcomes to patients who received abiraterone together with ADT. Further prospective studies are warranted to evaluate the impact of abiraterone alone on treatment outcomes and cost savings.

A phase II study of concurrent involved-field radiotherapy and intrathecal chemotherapy for leptomeningeal metastasis from solid tumors

BackgroundThe role of involved-field radiation therapy (IFRT) and intrathecal chemotherapy (IC) in leptomeningeal metastasis (LM) from solid tumors was gradually underestimated in the era of targeted therapy. This study was aimed to investigate the safety and effectiveness of concurrent IFRT and intrathecal methotrexate (MTX)/cytarabine (Ara-C) for LM, particularly for those who developed LM while receiving targeted therapy. Materials and MethodsEnrolled patients were given induction IC first and then concurrent treatment, which consisted of IFRT (40 Gy total; 2 Gy/f) and IC (MTX 15 mg or Ara-C 50 mg, once per week). Primary endpoint was clinical response rate (RR). Secondary endpoints were safety and overall survival (OS). ResultsFifty-three patients received induction intrathecal MTX (n = 27) or Ara-C (n = 26). Forty-two patients completed concurrent therapy. Total RR was 34% (18/53). The improvement rate of neurological symptoms and KPS scores were 72% (38/53) and 66% (35/53) respectively. Adverse events (AEs) rate was 28% (15/53). Eight patients (15%, 8/53) showed grade 3–4 AEs, including myelosuppression (n = 4) and radiculitis (n = 5). Median OS was 6.5 months (95% CI, 5.3–7.7 months). Median survival for 18 patients who had clinical response was 7.9 months (95% CI, 4.4–11.4 months), and 0.8 months (95% CI, 0.08–1.5 months) for 6 patients who had LM progression. The median survival in 22 patients who received prior targeted therapy was 6.3 months (95% CI, 4.5–8.1 months). ConclusionConcurrent IFRT and intrathecal MTX or Ara-C was proved to be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity.

Evaluation of Three-Year Overall and Disease-Free Survival in Iranian Patients with Nasopharyngeal Carcinoma Treated by Intensity-Modulated Radiotherapy (IMRT): A Historical Cohort Single Center Study

Background: The aim of this study was to evaluate and analyze disease-free survival (DFS) and overall survival (OS) after intensity-modulated radiotherapy (IMRT) for Iranian patients with nasopharyngeal carcinoma (NC). Methods: In this historical cohort study, 65 non-metastatic patients treated for NC with IMRT were selected and reviewed at the Shohadai-e-Tajrish Hospital between October 2017 and October 2019. Chemotherapy was given either as induction, concurrent, or adjuvant therapy in all cases. Three years of DFS and OS were calculated according to Kaplan-Meier and compared with the Pearson Correlation Test. Results: The mean age of patients was 43.38 years. The three-year DFS and OS rates were 95.72%, 92.32%, 72.73%, 73.26%, and 100%, 84.61%, 90.90%, and 79.41% in stage I, II, III, and IV patients, respectively (P = 0.119, P = 0.155). The total three-year DFS rate and the total three-year OS rate were 76.47% and 84.60% in all cases. Based on the Pearson Correlation Test, it was a significant correlation between the duration of IMRT time and three-year DFS (correlation=0.138, P = 0.017) and the number of concurrent cycles of chemotherapy with IMRT (correlation=0.375, P = 0.002). It was not a significant correlation between total time duration, MRI response, induction chemotherapy, age, sex, and the three-year DFS. There was a significant correlation between total time duration and three-year OS (correlation=0.263, P = 0.040) and the number of concurrent cycles of chemotherapy with IMRT and three-year OS (correlation=0.334, P = 0.007). It was not a significant correlation between the duration of IMRT time, MRI response, induction chemotherapy, age, sex, and the three-year OS. Conclusions: Our findings showed that IMRT with concurrent chemo-radiotherapy has the three-year DFS and OS, which were comparable with the other published results. We emphasize the number of concurrent cycles of chemotherapy with IMRT, which have an important role in both three-year DFS and OS. The duration of IMRT time has also an important role in the three-year DFS but not in the three-year OS. A longer follow-up for the patients to evaluate 10-year DFS and OS is recommended.

Internet-Delivered Dialectical Behavioral Therapy Skills Training for Chronic Pain: Protocol for a Randomized Controlled Trial.

Emotion dysregulation is key to the development and maintenance of chronic pain, feeding into a cycle of worsening pain and disability. Dialectical behavioral therapy (DBT), an evidence-based treatment for complex transdiagnostic conditions presenting with high emotion dysregulation, may be beneficial to manage and mitigate the emotional and sensory aspects of chronic pain. Increasingly, DBT skills training as a key component of standard DBT is being delivered as a stand-alone intervention without concurrent therapy to help develop skills for effective emotion regulation. A previous repeated-measure single-case trial investigating a novel technologically driven DBT skills training, internet-delivered DBT skills training for chronic pain (iDBT-Pain), revealed promising findings to improve both emotion dysregulation and pain intensity. This randomized controlled trial aims to examine the efficacy of iDBT-Pain in comparison with treatment as usual to reduce emotion dysregulation (primary outcome) for individuals with chronic pain after 9 weeks and at the 21-week follow-up. The secondary outcomes include pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, posttraumatic stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. The trial also examines the acceptability of the iDBT-Pain intervention for future development and testing. A total of 48 people with chronic pain will be randomly assigned to 1 of 2 conditions: treatment and treatment as usual. Participants in the treatment condition will receive iDBT-Pain, consisting of 6 live web-based group sessions led by a DBT skills trainer and supervised by a registered psychologist and the iDBT-Pain app. Participants in the treatment-as-usual condition will not receive iDBT-Pain but will still access their usual medication and health interventions. We predict that iDBT-Pain will improve the primary outcome of emotion dysregulation and the secondary outcomes of pain intensity, pain interference, anxiety symptoms, depressive symptoms, perceived stress, harm avoidance, social cognition, sleep quality, life satisfaction, and well-being. A linear mixed model with random effects of individuals will be conducted to investigate the differences between the baseline, 9-week (primary end point), and 21-week (follow-up) assessments as a function of experimental condition. Recruitment started in February 2023, and the clinical trial started in March 2023. Data collection for the final assessment is planned to be completed by July 2024. If our hypothesis is confirmed, our findings will contribute to the evidence for the efficacy and acceptability of a viable intervention that may be used by health care professionals for people with chronic pain. The results will add to the chronic pain literature to inform about the potential benefits of DBT skills training for chronic pain and will contribute evidence about technologically driven interventions. Australian New Zealand Clinical Trials Registry ACTRN12622000113752; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383208&isReview=true. PRR1-10.2196/41890.

Safety of Concurrent Radiation Therapy With Brentuximab Vedotin in the Treatment of Lymphoma

Purpose: Radiation therapy (RT) and the antibody-drug conjugate brentuximab vedotin (BV) are standard-of-care treatment options for patients with certain B and T-cell lymphomas; however, there are limited data exploring the safety of concurrent BV and RT (BVRT). We performed a single institutional retrospective review of 44 patients who received BVRT. Twenty percent of patients (9/44) developed new grade 2 or higher (G2+) hematologic toxicity (HT) after BVRT, which was associated with radiation dose (median dose of 35 Gy in those with new G2+ HT compared with 15 Gy in those without; P < .001). Acute G2+ elevation in aspartate transaminase or alanine transaminase level was associated with administration of concurrent chemotherapy with BVRT (57% vs 21%; P=.047) but was not associated with any RT factors. Local control (LC) was achieved in 24 of 42 patients (57%) with available follow-up. Ten patients (23%) proceeded to stem cell transplant or cellular therapy after BVRT at a median of 48 days (interquartile range, 27-188 days). At last follow-up, 10 patients (23%) remained without evidence of disease. Our analysis demonstrates that the combination of BV and RT is well tolerated, though care should be taken during RT planning to reduce the risk of HT. This combination can be considered for patients in need of both local and systemic disease control.