Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series.

Background: Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods: We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modified ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse effects were assessed. Results: Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. The mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). The most common adverse effects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. The metabolic strategy did not interfere with standard oncological treatments. Conclusion: This is the first study to observe the feasibility and safety of repeated, prolonged fasting combined with a modified ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse effects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: This study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. The study was registered on 4 December 2020.

MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication.

BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. RESULTS: Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M- (P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT-/M+ tumors (P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase (MGMT) status to predict improved patient survival (P < .05). CONCLUSIONS: Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival.

Hyperfractionated radiation therapy and concurrent chemotherapy for advanced head and neck cancer.

PURPOSE: To investigate the feasibility of combining hyperfractionated radiotherapy regimen with concomitant chemotherapy and to assess its toxicity in patients with advanced head and neck carcinoma (HNC). Progression free survival (PFS) and overall survival (OS) were set as secondary end points. PATIENTS AND METHODS: Between November 2003 and November 2007, 48 patients with stage III and IV HNC who met the eligibility criteria were enrolled in the study. Hyperfractionated Radiation consisted of 120 Gys twice daily, 6 hours apart, for a total of 69.6 Gys in 58 fractions over 6 weeks and boost of 6 Gys in 3 fractions in case of residual disease. Three cycles of concurrent chemotherapy in the form of Cisplatin 75 mg/ m² on day 1 and Fluorouracil 750 mg/m² 24 hour infusion on day 1-4 during weeks 1, 4 and 6 of irradiation. RESULTS: 48 patients have completed the treatment to date. The median radiation dose was 72 Gys including the boost to residual lymph node or primary site. The treatment was delivered in a median overall period of 54 days, with a recorded median delay of 7 days. Grade 4 skin toxicity was experienced by 4.1% of patients only. Therapy was well tolerated (grade 3 mucositis in 21%, grade 4 in 26%, grade 3 leukopenia in 10%). Weight loss of more than 10 kg was reported in 10 (16.7%) of the cases. The most common late toxicity was mild to moderate xerostomia which was encountered in 34 (70.8%) cases and improved thereafter. Hypothyroidism was encountered in 7 (14.6%) of the cases. Complete response (CR) was observed in 40 patients (83.3%). Partial response (PR) was achieved in the remaining 8 patients (16.7%). Disease relapse occurred in 9 patients (18.8%) after complete response and 2 patients developed progressive disease after partial response. 3 patients relapsed locally, 5 patients developed distant metastasis and 1 patient developed both local and distant metastasis. 2 patients (4.1%) died of treatment complications, 8 patients (16.7%) died with progressive locoregional, and metastatic disease. The 2- year disease free survival was 77% and the 2- year overall survival was 79%. CONCLUSION: Hyperfractionated radiotherapy and concurrent chemotherapy is tolerable. Results regarding LC and OS are encouraging as compared to conventional radiotherapy and concurrent chemotherapy.

Renal cell carcinoma: the experience of Kuwait Cancer Control Center, Kuwait.

OBJECTIVES: This retrospective study was undertaken to analyze the profile of patients presenting with renal cell carcinoma (RCC) and treatment outcomes. SUBJECTS AND METHODS: Records of 49 patients (36 male, 16 female, 21-75 years) treated at the Kuwait Cancer Control Center, Kuwait for RCC during the period 1993-1998 were analyzed. Forty-one patients had a nephrectomy, 18 postoperative radiotherapy and 1 patient also received adjuvant immunotherapy with interferon. Patients with metastatic disease were treated with a variety of agents including interferon, chemotherapy (vinblastine) or a hormonal agent (megestrol acetate). Data analysis was performed using SPSS statistical software package. Overall survival and disease-free survival were calculated using the Kaplan-Meier method. RESULTS: Twenty-nine patients presented with symptoms classically associated with RCC. Metastases at diagnosis were seen in 9 patients (18%), with lung being the most frequent site. The commonest tumor subtype was clear cell carcinoma (32.6%). Thirty-nine patients (80%) achieved a complete response to treatment and relapse was documented in 10 patients (26%). The majority of failures were distant, with lung metastases being the most common. Response to salvage treatment was poor. Overall survival was 83% at 2 years. The disease-free survival was 68 and 45% at 2 and 5 years, respectively. CONCLUSIONS: Although many patients presented with advanced local disease, a majority achieved complete response after radical surgery with or without postoperative radiation therapy. Salvage of metastatic disease proved difficult with interferon, chemotherapy.

Primary malignant tumors of the trachea - the Tata Memorial Hospital experience.

OBJECTIVE: Primary tumors of the trachea are extremely rare. Treatment methods vary considerably and few studies have sought to provide adequate guidelines. This study reviews the records of patients treated for tracheal cancer at the Tata Memorial Hospital (TMH), Mumbai, India. SUBJECTS AND METHODS: Fifteen patients with primary tracheal malignancies were identified in the TMH database during the period from 1983 to 2000. They were predominantly males (87%) belonging to an older age-group (67% above 40 years). Common presenting symptoms were cough, hoarseness, hemoptysis and indications of airway obstruction. Squamous cell carcinoma was the commonest histologic subtype (40%) followed by adenoid cystic carcinoma (27%). Ten patients received radical treatment. One patient underwent surgery (resection and anastomosis) and received postoperative radiotherapy. Another was explored but was found to be unresectable and was 1 of 2 patients treated with chemotherapy and radiotherapy. Laser resections and radiotherapy were used in 2 patients while 4 patients were managed with radiotherapy alone. One patient was treated elsewhere. The majority of patients (8/9) were treated with locoregional fields and doses ranging from 40 to 60 Gy (median 50 Gy). Two patients also received intraluminal brachytherapy, 1 as part of initial treatment and another for recurrence. RESULTS: Only 5 patients treated at TMH (5/9) achieved local control of their disease. Follow-up times ranged from 1 month to 134 months, median of 38 months. Distant metastases were identified in 4 patients (bone n = 1 and lung n = 3). Median survival was 38 months. Overall survival at 5 years was 37% by Kaplan-Meier method, but this figure should be treated with caution since only 6 patients had a follow-up of more than 2 years. CONCLUSION: Tracheal cancer is a rare malignancy. Radiation therapy is a reasonably effective modality for unresectable disease.