Targeted Therapy After Brain Radiotherapy for BRAF-Mutated Melanoma With Extensive Ependymal Disease With Prolonged Survival: Case Report and Review of the Literature

Melanoma brain metastasis with ependymal spread/metastases is uncommon. These cases are frequently classified together with leptomeningeal disease. However, the commonalities and differences in the underlying pathophysiology and clinical outcomes between these two types of spread are not clear. Very few reports on long term outcome and durable central nervous system (CNS) disease control have been reported in the literature. Here, we report a case of a 45 year-old Caucasian lady with BRAF-V600E mutant metastatic melanoma to the brain who had whole brain radiotherapy followed by two Gamma knife radiosurgery treatments for localized disease progression. She then developed extensive ependymal disease progression with no evidence of leptomeningeal spread. She was treated with a repeat course of whole brain radiotherapy and maintained on BRAF and MEK inhibitors with durable CNS disease control for more than a year. This study reviews the management of BRAF-V600E mutant melanoma with ependymal involvement. Management using radiation therapy with maintenance targeted therapy seems to be a reasonable approach to this challenging disease

Arab Countries and Oncology Clinical Trials: A Bibliometric Analysis

The increasing cancer burden is a major health concern in Arab countries with cross-regional variations in cancer profiles. Given the limited oncology research output and scarce data on cancer trial participation in the Arab region, this study explored the therapeutic cancer trial landscape in Arab countries over the past 20 years. A bibliometric analysis of the PubMed database was conducted on primary publications of therapeutic trials with a participating Arab center. Arab countries participated in 320 published cancer-related therapeutic trials (2000–2021). During this period, there was a consistent increase in the number of trials, sample size, multiregional site participation, and number of randomized trials. However, most trials were small, did not receive external funding, and included a single Arab site. Compared with Arab-only trials, trials with joint non-Arab sites were larger (p = 0.003) and more likely to be externally funded (p p < 0.001, for both). Despite improving conduct and publication records of oncology trials with Arab centers, cancer trial participation remains limited in Arab countries. Concerted efforts are required to encourage sponsorship and international collaboration in this region

The Role of Pelvic Exenteration in the Management of Locally Advanced Prostate Cancer

Locally advanced prostate cancer poses a clinical challenge for physicians. Despite the established role of radiotherapy and androgen-deprivation therapy in these cases, some patients with locally advanced disease experience recurrent disease or persistent disease with debilitating local symptoms, such as intractable pain and urinary symptoms. In this narrative review, we sought to evaluate the role of exenterative surgery in the management of locally advanced prostate cancer. From our search, we found that total pelvic exenteration or cystoprostatectomy represents a viable therapeutic modality to manage prostate cancer directly invading the bladder, lower urinary tract symptoms, debilitating pain caused by locally advanced disease, and as salvage treatment after failure of primary treatment among other applications. Reports on minimally invasive pelvic exenteration for prostate cancer were also retrieved, as this represents a feasible and effective treatment option for experienced clinicians. Pelvic exenteration may be an effective tool for the treatment of locally advanced prostate cancer in the surgeon’s armamentarium; however, further studies are needed to establish its role in improving survival and overall patient outcomes

Nadir PSA is a strong predictor of treatment outcome in intermediate and high risk localized prostate cancer patients treated by definitive external beam radiotherapy and androgen deprivation

Abstract Background The aim of this study is to investigate the effect of tumor characteristics and parameters of treatment response in predicting biochemical disease-free survival (BFS) for patients with intermediate or high risk prostate cancer treated by combined definitive external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). Methods Between June 1995 and January 2015, 375 patients with localized prostate cancer and a National Comprehensive Cancer Network (NCCN) intermediate or high risk categories were treated by definitive EBRT and ADT. Median duration of androgen blockade was 10 months (range: 3–36 months); Median radiation dose was 72 Gy (Range: 70–78 Gy). Median follow-up time was 5.8 years (range: 0.8–16.39 years). The main study endpoint was biochemical disease free survival (BFS). Results Forty seven patients (12.5%) developed biochemical recurrence (BCR) during the observation period. Monovariate analysis identified baseline PSA (bPSA) (p = 0.024), T-stage (p = 0.001), Gleason’s score (GS) (p = 0.042), radiation dose (p = 0.045), PSA pre-radiation therapy (p = 0.048), and nadir PSA (nPSA), (p < 0.001) as significant variables affecting BCR. The receiver operating characteristic (ROC) curve identified a nPSA of 0.06 ng/ml as optimal cut-off value significantly predicting the patients’ risk of BCR (p < 0.001). Multivariate cox regression analysis revealed T-stage, GS, and nPSA as independent variable affecting BFS, while bPSA, age, and radiation dose were not. Conclusion Nadir PSA at 0.06 is a strong independent predictor of BFS in patients with intermediate or high risk prostate cancer treated by definitive EBRT and ADT

Intraoperative Radiation Therapy: A Promising Treatment Modality in Head and Neck Cancer

Every year, almost 62,000 are diagnosed with a head and neck cancer (HNC) and 13,000 will succumb to their disease. In the primary setting, intraoperative radiation therapy (IORT) can be used as a boost in select patients in order to optimize local control. Addition of external beam radiation to limited volumes results in improved disease control over surgery and IORT alone. In the recurrent setting, IORT can improve outcomes from salvage surgery especially in patients previously treated with external beam radiation. The use of IORT remains limited to select institutions with various modalities being currently employed including orthovoltage, electrons, and high-dose rate brachytherapy. Practically, execution of IORT requires a coordinated effort and careful planning by a multidisciplinary team involving the head and neck surgeon, radiation oncologist, and physicist. The current review summarizes common uses, outcomes, toxicities, and technical aspects of IORT in HNC patients

Benchmarking Outcomes after Ablative Radiotherapy for Molecularly Characterized Intrahepatic Cholangiocarcinoma

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted

Establishment of the First Comprehensive Adult and Pediatric Hematopoietic Stem Cell Transplant Unit in the United Arab Emirates: Rising to the Challenge

Hematopoietic stem cell transplantation (HSCT) is increasingly indicated for various malignant and non-malignant diseases. In the United Arab Emirates (UAE), patients that could benefit from the procedure commonly need to seek medical care abroad in view of the lack of a comprehensive HSCT facility that could offer the full spectrum of interventions and monitoring protocols. This comes with considerable challenges related to coverage and logistics of travel. It also limits the continuity of clinical care, and presents inconvenience to patients who come from a different cultural background. In this article, we share our experiences and lessons learned during the establishment of the first comprehensive adult and pediatric HSCT unit in the UAE that is designed to cater for local citizens and residents, as well as neighboring countries facing similar availability challenges