Impact of age and co-morbidities in patients with newly diagnosed glioblastoma: a pooled data analysis of three prospective mono-institutional phase II studies

To analyse the impact of age and co-morbidities on compliance and outcomes in GBM patients enrolled in three prospective phase II trials. GBM patients (≥ 18 years) were treated with radiotherapy (60 Gy) or enrolled in a Fractionated Stereotactic Conformal-Radiotherapy Phase II trial (69.4 Gy). Concomitant and adjuvant chemotherapy with Temozolomide (TMZ) was administered. Charlson Index Co-morbidity (CCI) was used to assess co-morbidity. Toxicity was evaluated according to RTOG score. Survival analysis was performed by the Kaplan-Maier. Influence of age and co-morbidity was evaluated using log-rank test. From 2001 to 2008, 146 patients were enrolled: 56 (38.4 %) aged over 65 and 90 under 65. CCI ≥ 1 was observed in 41 % of elderly and 22 % of young group. Patients' compliance was 97.9 % for radio-chemotherapy. Acute toxicity was mild with no difference between the groups. Global median progression-free survival (PFS) and overall survival (OS) were 12 and 18 months, respectively. Age, surgery and radiation dose correlated with survival (p = 0.01, p = 0.04 and p = 0.03). CCI ≤ 2 did not show any influence on OS. Our data show that elderly with a good performance status and few co-morbidity may be treated as younger patients; moreover, age confirms a negative impact on survival while CCI ≤ 2 did not correlated with OS

Single-arm phase II study of conformal radiation therapy and temozolomide plus fractionated stereotactic conformal boost in high-grade gliomas: final report.

Abstract PURPOSE: To assess survival, local control and toxicity using fractionated stereotactic conformal radiotherapy (FSCRT) boost and temozolomide in high-grade gliomas (HGGs). PATIENTS AND METHODS: Patients affected by HGG, with a CTV(1)(clinical target volume, representing tumor bed \ub1 residual tumor + a margin of 5 mm) 64 8 cm were enrolled into this phase II study. Radiotherapy (RT, total dose 6,940 cGy) was administered using a combination of two different techniques: three-dimensional conformal radiotherapy (3D-CRT, to achieve a dose of 5,040 or 5,940 cGy) and FSCRT boost (19 or 10 Gy) tailored by CTV(1)diameter ( 64 6 cm and > 6 cm, respectively). Temozolomide (75 mg/m(2)) was administered during the first 2 or 4 weeks of RT. After the end of RT, temozolomide (150-200 mg/m(2)) was administered for at least six cycles. The sample size of 41 patients was assessed by the single proportion-powered analysis. RESULTS: 41 patients (36 with glioblastoma multiforme [GBM] and five with anaplastic astrocytoma [AA]) were enrolled; RTOG neurological toxicities G1-2 and G3 were 12% and 3%, respectively. Two cases of radionecrosis were observed. At a median follow-up of 44 months (range 6-56 months), global and GBM median overall survival (OS) were 30 and 28 months. The 2-year survival rate was significantly better compared to the standard treatment (63% vs. 26.5%; p < 0.00001). Median progression-free survival (PFS) was 11 months, in GBM patients 10 months. CONCLUSION: FSCRT boost plus temozolomide is well tolerated and seems to increase survival compared to the standard treatment in patients with HGG. PMID: 20936460 [PubMed - indexed for MEDLINE

Radiotherapy and concomitant temozolomide during the first and last weeks in high grade gliomas: long-term analysis of a phase II study

We tested the efficacy and safety of temozolomide (TMZ) when given concomitantly to radiotherapy only in the first and last weeks of treatment to patients affected by high grade gliomas. Conformal radiotherapy (CTV1: tumor bed + residual tumor if present + 1.5 cm, 5,940 cGy, 180 cGy/day; CTV2: oedema, 3,960 cGy, 180 cGy/day) was associated with TMZ, 75 mg/m(2) x 5 days, the first and last weeks of radiotherapy. Adjuvant chemotherapy with TMZ (150 mg/mq daily x 5 days, q28 on the first cycle, 200 mg/mq daily x 5 days, q28 for the following cycles) was given, after chemoradiation, until disease progression or up to 6 cycles. From October 2000 to December 2003, 29 patients (25 GBL, 86.2%; 4 AA, 13.8%) were enrolled in this study. Twenty-two patients (75.8%) received a median 6 cycles of adjuvant chemotherapy with TMZ (range 1-20). Hematological toxicity was absent during concomitant chemoradiation and mild in adjuvant therapy, while neurological toxicity (seizures) was observed only in one case. At a median follow-up of 66 months (range 3-96), median progression-free survival (PFS) was 8 months, with a 1- and 2-year PFS of 46.7 and 28.7%, respectively; median overall survival (OS) time was 21 months, with a 1- and 2-year OS of 69.2 and 42.3%, respectively. In our experience, TMZ proved to be effective even when given only during the first and the last week of radiotherapy, with lower hematological toxicity

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort

Background: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls. Methods: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger. Findings: We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1\ub754, 95% CI 1\ub702\u20132\ub733), including when analysis was restricted to patients aged 18 years or younger (1\ub780, 1\ub706\u20133\ub707). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1\ub760, 95% CI 1\ub705\u20132\ub744; p=0\ub704) and Asp294His (2\ub715, 1\ub705\u20134\ub740; p=0\ub704). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants. Interpretation: Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies. Funding: SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831