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BACKGROUND: Management of elderly patients with glioblastoma (GBM) is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols vs short-course radiotherapy without chemotherapy. METHODS: We evaluated treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the secondary endpoint is progression-free survival (PFS); patients were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS. RESULTS: Fifty-nine patients were recruited in our study with median age 66 (range: 60-81) years, and 47 (80%) were males. Thirty-seven patients (62.7%) had ECOG performance status (PS) ≥2, and 22 patients (37.3%) had PS <2. Gross total resection (GTR) and subtotal resection (STR) were done in 49 (82.9%) patients, and the median follow-up was 12 months. Thirty-eight (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions). The median OS was 12 months (95%CI: 9.52-14.48). Receiving conventional Rth and completion of six months adjuvant CTR were significant factors for O.S (P=0.043 and 0.026), respectively. The median PFS was nine months (95%CI: 6.13-11.87). For univariate analysis, PS, time to start adjuvant treatment, and completion of six months CTR were significant factors for PFS. CONCLUSION: Conventional Rth and completion of adjuvant CTR lead to better OS, while earlier start of adjuvant treatment and the completion of adjuvant CTR were associated with a better PFS.

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OBJECTIVE:  To evaluate the outcomes of radical intent radiation therapy in early glottic carcinoma (EGC), including local control rate (LCR), disease-free survival (DFS), death specific free survival (DSFS), and overall survival (OS) rates, in Saudi patients treated at a single institution.  Materials and methods: This is an institutional review board (IRB) approved, retrospective study of 27 patients with T1-2 N0 M0, early glottic carcinoma (EGC) who were treated from 2010 to 2015 at our institution with different radiotherapy (RT) fractionation regimens. The regimens included six different fractionation schedules of radiotherapy (RT): 50 Gy (20 x 2.5 Gy) dose prescribed to 95% isodose line, 52.4 Gy (20 x 2.52 Gy), 63 Gy (28 x 2.25 Gy), 66 Gy (33 x 2 Gy), and 70 Gy (35 x 2 Gy). The cohort was stratified into two groups, ≤ 52.5 Gy (n=15) and > 52.5 Gy (n=12). The median follow-up of all patients was 31.7 months (range 7-82). RESULTS: The mean age of the cohort was 64.5 years (median 65, range: 41-83). Eleven patients (40.7%) had a history of smoking. The majority of the cohort was with T1a EGC (70.4%, n=19), and anterior commissure invasion was seen in three patients (11.1%). The mean RT doses were 55.6 Gy (range: 50-70). The five-year LCR, DFS, DSFS, and OS rates were 83.1%, 80.0%, 96.2%, and 92.6%, respectively. The LCR rates for those receiving a dose of 52.5 Gy or less were 61.3 months compared to 89.5 months for those who received more than 52.5 Gy (p=0.994). Non-smokers and patients with an unknown smoking history achieved a five-year LCR of 100%, while patients with a positive smoking history achieved a five-year LCR of 60.6% (p=0.044). CONCLUSION:  Radiation therapy for EGC in our patients showed reasonable five-year LCR with larynx preservation at 83.1%, DFS 80.0%, five-year OS rate 92.6%, and DSFS rate 96.2%. We found that smoking had a significant correlation with LCR. However, large prospective trials are warranted to evaluate the efficacy of overall treatment time, dose per fraction of above 2 Gy, and smoking effect.

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Primary brain tumors are a leading cause of cancer-related morbidity and mortality in children. Glioblastoma (GBM) is a high-grade astrocytoma that occurs in both children and adults and is associated with a poor prognosis. Despite extensive study in recent years, the clinical management of these tumors has remained largely unchanged, consisting of surgical resection, conventional chemotherapy, and radiotherapy. Although the etiology and genomic drivers in GBM are diverse, constitutional mismatch repair-deficiency (CMMRD) syndrome is a rare, recessively inherited disease with a predisposition to gliomagenesis. CMMRD results from biallelic mutations in one of the mismatch repair genes including mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this report, we present the case of a 5-year-old female with GBM and CMMRD due to an MSH6 homozygous c.1883G>A mutation, who continues to experience an exceptional and durable response (9 months) to the immune checkpoint inhibitor (ICPI) nivolumab. Our patient presented with acute neurologic decline and increased intracranial pressure. Neuroimaging studies revealed a large left frontoparietal mass requiring neurosurgical decompression and resection. Histopathologic analyses resulted in a diagnosis of de novo GBM that was BRAF wild type and negative for programmed death-ligand 1 protein expression. She received standard-of-care treatment with surgery, radiation therapy, and temozolomide; however, the tumor recurred 3 months after the initial diagnosis. Molecular analyses of tumor and blood tissues revealed an MSH6 homozygous c.1883G>A mutation consistent with CMMRD. Given her CMMRD status, she was treated with nivolumab (3 mg/kg doses every 2 weeks for 36 weeks) and showed a 60% reduction in tumor size, improved clinical symptoms, and an ongoing durable response lasting 10 months to date. Our study highlights a durable response to the ICPI nivolumab in a pediatric patient with recurrent/refractory CMMRD-associated GBM. We show that incorporating genomic and/or molecular testing for CMMRD into routine pediatric oncology clinical care can identify a subset of patients likely to benefit from ICPI. KEY POINTS: Constitutional mismatch repair-deficiency (CMMRD) syndrome, alternatively known as biallelic mismatch repair deficiency syndrome, occurs in subset of pediatric cancer patients, including those with primary brain tumors.Patients from Arab and other developing countries are predicted to have higher incidence of CMMRD due to high prevalence of consanguinity.Integration of molecular and/or genomic testing into routine clinical care for pediatric cancer patients is important to identify patients with CMMRD syndrome.Patient with CMMRD-associated cancers may show increased responsiveness to immune checkpoint inhibitors.To the authors' knowledge, this is the first report in the Arab world of a durable response to immune checkpoint inhibitors in a pediatric glioblastoma patient.

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Introduction Bone metastasis (BM) is a major complication of many solid tumors like breast, prostate, lung and renal cancers. BM leads to serious sequelae of pain, fractures, spinal cord compression and hypercalcemia. Radiotherapy has an established role in relieving pain caused by BM. Worldwide different radiotherapy schedules are being used for BM. The aim of this study is to determine the efficacy of single fraction palliative radiotherapy for painful bone metastases. Methods Between April 2014 and April 2017, single fraction radiotherapy was used to treat 73 patients in our institution. They had pathologically proven breast, prostate, lung or renal cancer with radiological evidence of bone metastases. There were 39 males (53%) and 34 females (47%). The median age was 58 years (range 33-87 years). 39% patients (n = 28) had breast cancer, 35% had prostate cancer (n = 26), 23% had lung cancer (n = 17), and 3% had renal cancer (n = 2). On presentation, all the patients had a pain score of more than five on Brief Pain Inventory (BPI). Results Response assessment to pain after three months from single fraction radiotherapy was found to be complete response (CR) in 23% patients (n = 17), partial response (PR) in 38% patients (n = 28), stable disease (SD) in 26% patients (n = 19) and progressive disease (PD) in 12% patients (n = 9). The overall efficacy of treatment was 62%, with CR 23% and PR 38%. Pre-treatment mean pain score was 8.15 compared to 4.68 post-treatment (p < 0.001). Conclusions Single fraction palliative radiotherapy of 8 Gy showed significant efficacy in painful bone metastases in our setting and merits further investigation in our population.