Procarbazine, CCNU and vincristine (PCV) versus temozolomide chemotherapy for patients with low-grade glioma: a systematic review.

Low-grade gliomas (LGG) encompass a heterogeneous group of tumors that are clinically, histologically and molecularly diverse. Treatment decisions for patients with LGG are directed toward improving upon the natural history while limiting treatment-associated toxiceffects. Recent evidence has documented a utility for adjuvant chemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) or temozolomide (TMZ). We sought to determine the comparative utility of PCV and TMZ for patients with LGG, particularly in context of molecular subtype. A literature search of PubMed was conducted to identify studies reporting patient response to PCV, TMZ, or a combination of chemotherapy and radiation therapy (RT). Eligibility criteria included patients 16 years of age and older, notation of LGG subtype, and report of progression-free survival (PFS), overall survival (OS), and treatment course. Level I, II, and III data were included. Adjuvant therapy with PCV resulted in prolonged PFS and OS in patients with newly diagnosed high-risk LGG. This benefit was accrued most significantly by patients with tumors harboring 1p/19q codeletion and IDH1 mutation. Adjuvant therapy with temozolomide was associated with lower toxicity than therapy with PCV. In patients with LGG with an unfavorable natural history, such as with intact 1p/19q and wild-type IDH1, RT/TMZ plus adjuvant TMZ may be the best option. Patients with biologically favorable high-risk LGG are likely to derive the most benefit from RT and adjuvant PCV

Stereotactic Body Radiotherapy for Lung Oligo-metastases: Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines

PURPOSE A systematic review of treatment characteristics, outcomes, and treatment-related toxicities of stereotactic body radiation therapy (SBRT) for pulmonary oligometastases served as the basis for development of this International Stereotactic Radiosurgery Society (ISRS) practice guideline. METHODS In accordance with PRISMA guidelines, a systematic review was performed of retrospective series with ≥50 patients/lung metastases, prospective trials with ≥25 patients/lung metastases, analyses of specific high-risk situations, and all randomized trials published between 2012 and July 2022 in the MEDLINE or Embase database using the key words "lung oligometastases", "lung metastases", "pulmonary metastases", "pulmonary oligometastases", "stereotactic body radiation therapy (SBRT)" and "stereotactic ablative body radiotherapy (SBRT)". Weighted random effects models were used to calculate pooled outcomes estimates. RESULTS Of the 1884 articles screened, 35 analyses (27 retrospective-, 5 prospective, and 3 randomized trials) reporting on treatment of >3600 patients and >4650 metastases were included. The median local control was 90 % (Range: 57-100 %) at 1 year and 79 % (R: 70-96 %) at 5 years. Acute toxicity ≥3 was reported for 0.5 % and late toxicity ≥3 for 1.8 % of patients. A total of 21 practice recommendations covering the areas of staging & patient selection (n = 10), SBRT treatment (n = 10), and follow-up (n = 1) were developed, with agreements rates of 100 %, except for recommendation 13 (83 %). CONCLUSION SBRT represents an effective definitive local treatment modality combining high local control rates with low risk of radiation-induced toxicities

Progression-Free but No Overall Survival Benefit for Adult Patients with Bevacizumab Therapy for the Treatment of Newly Diagnosed Glioblastoma: A Systematic Review and Meta-Analysis.

Glioblastoma (GBM) is the most common high-grade primary brain tumor in adults. Standard multi-modality treatment of glioblastoma with surgery, temozolomide chemotherapy, and radiation results in transient tumor control but inevitably gives way to disease progression. The need for additional therapeutic avenues for patients with GBM led to interest in anti-angiogenic therapies, and in particular, bevacizumab. We sought to determine the efficacy of bevacizumab as a treatment for newly diagnosed GBM. We conducted a literature search using the PubMed database and Google Scholar to identify randomized controlled trials (RCTs) since 2014 investigating the safety and efficacy of bevacizumab in the treatment of adult patients (18 years and older) with newly diagnosed GBM. Only Level Ι data that reported progression-free survival (PFS) and overall survival (OS) were included for analysis. Random effects meta-analyses on studies with newly diagnosed glioblastoma were conducted in R to estimate the pooled hazard ratio (HR) for PFS and OS. Six RCTs met requirements for meta-analysis, revealing a pooled estimate of PFS HR suggesting a 33% decreased risk of disease progression (HR 0.67, 95% CI, 0.58-0.78; p \u3c 0.001) with bevacizumab therapy, but no effect on OS (HR = 1, 95% CI, 0.85-1.18; p = 0.97). A pooled estimate of the mean difference in OS months of -0.13 predicts little difference in time of survival between treatment groups (95% CI, -1.87-1.61). The pooled estimate for the mean difference in PFS months was 2.70 (95% CI, 1.89-3.50; p \u3c 0.001). Meta-analysis shows that bevacizumab therapy is associated with a longer PFS in adult patients with newly diagnosed glioblastoma, but had an inconsistent effect on OS in this patient population

Stereotactic Body Radiotherapy (SBRT) for Oligometastatic Spine Metastases: An Overview

The oligometastatic state is hypothesized to represent an intermediary state of cancer between widely metastatic disease and curable, localized disease. Advancements in radiotherapy have allowed for delivery of high precision, dose escalated treatment known as stereotactic body radiotherapy (SBRT) to targets throughout the body with excellent rates of local control. Recently, the first phase II randomized trial comparing conventional radiotherapy to comprehensive SBRT of oligometastatic disease demonstrated an overall survival and progression free survival advantage. The spine is a common site of metastasis, and a complex site for SBRT given the adjacent spinal cord and the tumor embedded within the bone tissue putting the patient at risk of fracture. Although there are expert spine SBRT guidelines for practice, there are as yet no reported randomized trials that proves superiority as compared to conventional radiation. The use of SBRT in patients with oligometastatic disease and spinal metastases is the focus of this review

Patterns of Pain and Functional Improvement in Patients with Bone Metastases after Conventional External Beam Radiotherapy and a Telephone Validation Study

Patients experiencing lower body pain resulting from bone metastases have greater levels of functional interference than those with upper body pain. The purpose of this study was to assess the levels of interference caused by pain after treatment with conventional radiotherapy using the Brief Pain Inventory (BPI) and to validate this tool for telephone use. After radiotherapy, a total of 159, 129, and 106 patients completed the BPI over the telephone at months 1, 2, and 3, respectively. Cronbach's alpha, confirmatory factor analysis, and discriminant validity tests were performed to assess the validity of the BPI. One-way ANOVA was used to compare BPI scores. There was no statistically significant difference in functional interference among patients after treatment. Internal consistency of the BPI was high. Functional interference may be inherently higher in patients with pain in the lower body. Telephone use of the BPI is reliable and recommended in this population

Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines

BACKGROUND Stereotactic body radiotherapy (SBRT) is an effective and safe modality for early-stage lung cancer and lung metastases. However, tumors in an ultra-central location pose unique safety considerations. We performed a systematic review and meta-analysis to summarize the current safety and efficacy data and provide practice recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS We performed a systematic review using PubMed and EMBASE databases of patients with ultra-central lung tumors treated with SBRT. Studies reporting local control (LC) and/or toxicity were included. Studies with <5 treated lesions, non-English language, re-irradiation, nodal tumors, or mixed outcomes in which ultra-central tumors could not be discerned were excluded. Random-effects meta-analysis was performed for studies reporting relevant endpoints. Meta-regression was conducted to determine the effect of various covariates on the primary outcomes. RESULTS 602 unique studies were identified of which 27 (one prospective observational, the remainder retrospective) were included, representing 1183 treated targets. All studies defined ultra-central as the planning target volume (PTV) overlapping the proximal bronchial tree (PBT). The most common dose fractionations were 50 Gy/5, 60 Gy/8, and 60 Gy/12 fractions. The pooled 1- and 2-year LC estimates were 92 % and 89 %, respectively. Meta-regression identified biological effective dose (BED10) as a significant predictor of 1-year LC. A total of 109 grade 3-4 toxicity events, with a pooled incidence of 6 %, were reported, most commonly pneumonitis. There were 73 treatment related deaths, with a pooled incidence of 4 %, with the most common being hemoptysis. Anticoagulation, interstitial lung disease, endobronchial tumor, and concomitant targeted therapies were observed risk factors for fatal toxicity events. CONCLUSION SBRT for ultra-central lung tumors results in acceptable rates of local control, albeit with risks of severe toxicity. Caution should be taken for appropriate patient selection, consideration of concomitant therapies, and radiotherapy plan design