Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Palliative radiotherapy for gastric cancer: Is there a dose relationship between bleeding response and radiotherapy?

The aim of this study was to evaluate whether there is a relationship between bleeding response and radiotherapy dose to palliate patients with local recurrence or progression of gastric cancer (GC). To this end, we conducted a systematic review and meta-analysis of observational studies that evaluated the bleeding response in patients with GC with local recurrence or progression. A meta-regression analysis between biological effective dose (BED) and bleeding response was performed, as was subgroup analysis to evaluate the outcome by BED level and radiotherapy (RT) technique. A p-value <0.05 was considered significant. Ten non-comparative retrospective studies and one prospective study were included. In general, RT was effective at controlling tumor bleeding, and the bleeding response rate was 0.77 (95% confidence interval (CI), 0.73-0.81). Meta-regression analysis demonstrated a linear correlation between BED Gy 10 and bleeding response (p=0<0001). Studies using conformational RT had a significant bleeding response rate compared to those using 2D (0.79; 95%CI, 0.74-0.84 vs 0.65; 95%CI, 0.56-0.75; p=0.021). In terms of the BED level, a significant difference in BR was identified on comparing BED Gy10 ≥40 (0.79; 95%CI, 0.7-0.8), BED Gy10 30-39 (0.79, 95%CI, 0.71-0.86), and BED Gy10 <30 (0.64; 95%CI, 0.5-0.7; p=0.0001). The mean survival time was 3.31 months (95%CI, 2.73-3.9) months, and the responders had a significantly longer survival (longer by 2.5 months) compared to the non-responders (95%CI, 1.7-3.3; p<0.0001). Palliative RT is effective at controlling bleeding due to local recurrence/progression from GC. Our findings reveal a relationship between BR and BED. BED <30 Gy 10 should not be recommended, and 3DRT should be indicated instead in order to improve the result.

Intensity modulated radiotherapy (IMRT) or conformational radiotherapy (3D-CRT) with conventional fractionation for prostate cancer: Is there any clinical difference?

ABSTRACT Purpose: To compare the treatment outcomes of a cohort of prostate cancer patients treated with conventional schedule using IMRT or 3DRT technique. Materials and Methods: Between 2010-2017, 485 men with localized prostate cancer were treated with conventional radiotherapy schedule with a total dose ≥74Gy using IMRT (231) or 3DCRT (254). Late gastrointestinal (GI) and genitourinary (GU) toxicity were retrospectively evaluated according to modified RTOG criteria. The biochemical control was defined by the Phoenix criteria (nadir + 2ng/mL). The comparison between the groups included biochemical recurrence free survival (bRFS), overall survival (OS) and late toxicity. Results: With a median follow-up of 51 months (IMRT=49 and 3DRT=51 months), the maximal late GU for >=grade- 2 during the entire period of follow-up was 13.1% in the IMRT and 15.4% in the 3DRT (p=0.85). The maximal late GI ≥ grade- 2 in the IMRT was 10% and in the 3DRT 24% (p=0.0001). The 5-year bRFS for all risk groups with IMRT and 3D-CRT was 87.5% vs. 87.2% (p=0.415). Considering the risk-groups no significant difference for low-, intermediate- and high-risk groups between IMRT (low-95.3%, intermediate-86.2% and high-73%) and 3D-CRT (low-96.4%, intermediate-88.2% and high-76.6%, p=0.448) was observed. No significant differences for OS and DMFS were observed comparing treatment groups. Conclusion: IMRT reduces significantly the risk of late GI severe complication compared with 3D-CRT using conventional fractionation with a total dose ≥74Gy without any differences for bRFS and OS.

Salvage radiotherapy for biochemical recurrence after radical prostatectomy: does the outcome depend on the prostate cancer characteristics?

ABSTRACT Objective: To build a model to evaluate the impact of salvage radiotherapy (SRT) in men with PSA rise or persistent PSA after undergoing radical prostatectomy (RP). Materials and Methods: The study included 107 node-negative patients treated with SRT after RP at a single institution. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP. All patients received local radiation to the prostate / seminal vesicle bed. The primary measured outcome was the biochemical recurrence (BCR) free survival. Multivariable Cox regression analysis was used to develop a risk-stratification group to identify predictive factors associated with the probability of BCR at 5yr. Results: At a median follow-up of 52 months, the BCR free survival rate and overall survival in 5 years was 73% and 94%, respectively. At multivariable analysis, pre-SRT PSA level > 0.35ng / mL (p = 0.023), negative margins (p = 0.038), and seminal vesicles invasion (p = 0.001) were significantly associated with BCR free survival. Three risk groups using regression analysis for SRT administration was built. Low-, intermediate- and the high-risk groups had a BCR free survival in 5-years of 96%, 84%, and 44% (p = 0.0001), respectively. Conclusions: We developed a risk group stratification to show the impact of SRT based on prostate cancer characteristics. SRT showed to be extremely beneficial for patients with low- and intermediate-risk tumors. Moreover, the risk-group built could identify patients classified as high-risk who might benefit from more aggressive treatment for SRT.