Gene amplification followed by functional diversification is a major force in evolution. A typical example of this is seen in the WUSCHEL-RELATED HOMEOBOX （WOX） gene family, named after the ...Arabidopsis stem cell regulator WUSCHEL. Here we analyze functional divergence in the WOX gene family. Members of the WUS clade, except the cambium stem cell regulator WOX4, can substitute for WUS function in shoot and floral stem cell maintenance to different degrees. Stem cell function of WUS requires a canonical WUS-box, essential for interaction with TPL/TPR co-repressors, whereas the repressive EAR domain is dispensable and the acidic domain seems only to be required for female fertility. In contrast to the WUS clade, members of the ancient WOX13 and the WOX9 clades cannot support stem cell maintenance. Although the homeodomains are interchangeable between WUS and WOX9 clade members, a WUS- compatible homeodomain together with canonical WUS-box is not sufficient for stem cell maintenance. Our results suggest that WOX function in shoot and floral meristems of Arabidopsis is restricted to the modern WUS clade, suggesting that stem cell control is a derived function. Yet undiscovered functional domains in addition to the homeodomain and the WUS-box are necessary for this function.
Objectives
To evaluate the feasibility and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of hepatocellular carcinoma (HCC) unsuitable for standard loco-regional therapies.
...Materials and methods
Patients with 1–3 inoperable HCC lesions with diameter ≤6 cm were treated by SBRT. According to lesions size and liver function, two prescription regimens were adopted: 48–75 Gy in three fractions or 36–60 Gy in six fractions. SBRT was delivered using the volumetric modulated arc therapy technique with flattening filter-free photon beams. The primary end points of this study were in-field local control (LC) and toxicity. Secondary end points were overall survival (OS) and progression-free survival (PFS).
Results
Forty-three patients with 63 HCC lesions were irradiated. All patients had Child–Turcotte–Pugh class A or B disease. Thirty lesions (48 %) were treated with 48–75 Gy in three consecutive fractions, and 33 (52 %) received 36–60 Gy in six fractions. Median follow-up was 8 months (range 3–43 months). Actuarial LC at 6, 12 and 24 months was 94.2 ± 3.3, 85.8 ± 5.5 and 64.4 ± 11.5 %, respectively. A biological equivalent dose (BED) >100 Gy and GTV size were significant prognostic factors for LC in univariate analysis (
p
< 0.001 and
p
< 0.02). Median OS was 18.0 ± 5.8 months. Actuarial OS at 6, 12 and 24 months was 91.1 ± 4.9, 77.9 ± 8.2 and 45.3 ± 14.0 %, respectively. Univariate analysis showed that OS is correlated with LC (
p
< 0.04), BED >100 (
p
< 0.05) and cumulative gross tumor volume GTV <5 cm (
p
< 0.04). Median PFS was 8 months, with a 1-year PFS rate of 41 %. A significant (≥grade 3) toxicity was observed in seven patients (16 %) 2–6 months after the completion of the treatment. No classic radiation-induced liver disease was observed.
Conclusion
Stereotactic body radiation therapy is a safe and effective therapeutic option for HCC lesions unsuitable to standard loco-regional therapies, with acceptable local control rates and low treatment-related toxicity. The significant correlation between LC and higher doses and between LC and OS supports the clinical value of SBRT in these patients.
To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma.
A cohort of 100 patients was included in this ...retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index.
A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively.
A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to evaluate long-term efficacy and survival prognostic factors of stereotactic body radiation therapy (SBRT) for un-resectable liver metastases in patients enrolled in a ...prospective phase II trial.
5-year local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates were analyzed in patients with un-resectable liver metastases enrolled in a Phase II Trial on liver SBRT, with a prescription dose of 75Gy in 3 consecutive fractions.
A total of 61 patients with 76 lesions were enrolled, with a median follow-up time of 6.1 years. One, three and 5 year LC rates were 94 ± 3.1%, 78.0 ± 5.9% and 78.0 ± 5.9%, without reaching the median LC time. Median OS was 27.6 months and the survival rates were 85.2 ± 4.5%, 31.1 ± 5.9% and 18.0 ± 4.9% at 1, 3 and 5-year after SBRT, respectively. Univariate analysis showed that favorable primary site (colorectal, breast and gynecological) of metastases (p = 0.001) improved survival. Toxicity was moderate. One patient experienced G3 late chest wall pain, which resolved within 1 year from SBRT. No cases of Radiation Induced Liver Disease (RILD) were detected.
Long-term results of this Phase II study suggest the efficacy and safety of SBRT for un-resectable liver metastases after 5-year of follow up. Selection of cases with positive prognostic factors may improve long-term survival of these oligo-metastastic patients and may confirm the role of SBRT as an effective alternative local therapy for liver metastases.
Introduction
The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The ...Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy.
Methods
Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1 month after radiation therapy and then every 3 months.
Results
Re-irradiation was performed at a median interval time (IT) of 16 months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9 Gy to 52.5 Gy, with a median biological effective dose of 43 Gy. The median, 1, 2 year OS were 9.7 months, 41% and 17.7%. Low grade glioma histology (p ≪ 0.01), IT > 12 months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival.
Conclusion
our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.
Small-cell lung cancer is an extremely chemo-sensitive disease; the addition of immunotherapy to chemotherapy has demonstrated a slight clinical benefit in pivotal trials, even with a statistically ...significant difference in terms of survival outcomes when compared to chemotherapy alone. In this scenario, the role of radiotherapy as a consolidation treatment in thoracic disease or as a prophylactic therapy in the brain should be clarified. In addition, due to the frailty and the poor prognostic characteristics of these patients, the need for predictive biomarkers that could support the use of immunotherapy is crucial. PD-L1 and TMB are not actually considered definitive biomarkers due to the heterogeneity of results in the literature. A new molecular classification of small-cell lung cancer based on the expression of key transcription factors seems to clarify the disease behavior, but the knowledge of this molecular subtype is still insufficient and the application in clinical practice far from reality; this classification could lead to a better understanding of SCLC disease and could provide the right direction for more personalized treatment. The aim of this review is to investigate the current knowledge in this field, evaluating whether there are predictive biomarkers and clinical patient characteristics that could help us to identify those patients who are more likely to respond to immunotherapy.
Purpose
The study aim was to compare the disease control in two groups of patients affected by liver metastases from CRC treated with microwave ablation (MWA) or stereotactic body radiation therapy ...(SBRT).
Methods
We extracted data of patients treated between 2009 and 2016. Inclusion criteria were: (1) maximum diameter of the liver lesions less than 4 cm; (2) no more than three liver lesions; (3) no evidence of progressive or untreated gross disease outside the liver; (4) adequate liver function; (5) no concurrent chemotherapy; (6) minimum age of 18. Tumour response was classified according to EORTC-RECIST criteria. Aim of the present study was to evaluate freedom from local progression (FFLP). To reduce indication bias, an inverse probability of treatment weighting was used to estimate treatment effect.
Results
A total of 135 patients with 214 lesions were included in the analysis. Median follow-up time was 24.5 months (range 2.4–95.8). The 1-year freedom from local progression (FFLP) was 88% (95%CI 80–92). In the SBRT group, FFLP was statistically longer than MWA group (
p
= 0.0214); the 1-year FFLP was 91% (95% CI 81–95) in SBRT group and 84% (95% CI 0.72–0.91) in MWA group. Patients treated with SBRT showed a reduce risk of local relapse compared to MWA (adjusted HR 0.31; 95%CI 0.13–0.70,
p
= 0.005). As expected, analogous result obtained in the inverse probability weighting analysis (HR 0.38; 95%CI 0.18–0.80;
p
= 0.011).
Conclusion
In conclusion, there seems to be an advantage of SBRT compared to MWA in treating CRC liver metastases, particularly for lesions bigger than 30 mm
To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer.
82 patients with 1-3 inoperable metastases confined to one organ ...(liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity.
Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with ≥ 60 Gy (n = 58) and those irradiated with <60 Gy (n = 52) was statistically significant, with a 1, 2 and 3 yrs LC of 97%,92% and 83% for the higher dose, compared to 85%,70% and 70% for the lower dose (p < 0.04). Median OS was 32 months. Actuarial OS rate at 1, 2 and 3 yrs was 85%,65% and 43%. Univariate analysis showed a correlation only between OS and cumulative GTV > 3 cm (p < 0.02). Median PFS was 14 months, with a PFS rate of 56% at 1 yr and 40% at 2-3 yrs, without correlation with the site and prescription dose (p < 0.48 and p < 0.56). No patients experienced radiation-induced liver disease or grade >3 toxicity.
SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular carcinoma (HCC) is the most frequent liver malignancy and a leading cause of cancer death in the world. In unresectable HCC patients, transcatheter arterial (chemo-) embolization ...(TAE/TACE) has shown a disease response in 15-55% of cases. Though multiple TAE/TACE courses can be administered in principle, Stereotactic Body Radiotherapy (SBRT) has emerged as an alternative option in the case of local relapse following multiple TAE/TACE courses.
This is a single-center, prospective, randomized, controlled, parallel-group superiority trial of SBRT versus standard TAE/TACE for the curative treatment of the intermediate stage of HCC after an incomplete response following TAE/TACE (NCT02323360). The primary endpoint is 1-year local control (LC): 18 events were needed to assess a 45% difference (HR: 0.18) in favor of SBRT. The secondary endpoints are 1-year Progression-Free Survival (PFS), Distant Recurrence-Free Survival (DRFS), Overall Survival (OS) and the incidence of acute and late complications.
At the time of the final analysis, 40 patients were enrolled, 19 (49%) in the TAE/TACE arm and 21 (51%) in the SBRT arm. The trial was prematurely closed due to slow accrual. The 1- and 2-year LC rates were 57% and 36%. The use of SBRT resulted in superior LC as compared to TAE/TACE rechallenge (median not reached versus 8 months,
= 0.0002). PFS was 29% and 16% at 1 and 2 years, respectively. OS was 86% and 62% at 1 year and 2 years, respectively. In the TAE arm, PFS was 13% and 6% at 1 and 2 years, respectively. In the SBRT arm, at 1 and 2 years, PFS was 37% and 21%, respectively. OS at 1 and 2 years was 75% and 64% in the SBRT arm and 95% and 57% in the TACE arm, respectively. No grade >3 toxicity was recorded.
SBRT is an effective treatment option in patients affected by inoperable HCC experiencing an incomplete response following ≥1 cycle of TAE/TAC.
Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase ...III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A).
Adults patients with 1-4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2-3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS).
A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9-7.4%) in Arm-B, and 9.3% (95% CI 6.2-13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p << 0.001; HR 1.36 95% CI 1.25-1.48). Symptomatic RN occurred in 56 cases at a median time of 10.3 months (range 1.15-54.8 months), 27 in the Arm-B at a median time of 15.9 months (range 4.9-54.8 months), and 29 in the Arm-A at a median time of 6.9 months (1.2-32.3 months), without statistically significant differences between the two arms. No statistically significant differences were recorded between the two arms in CILP, BDF, DFS or OS. The mean beam-on time to deliver SRS was 49.0 ± 36.2 min in Arm-A, and 3.1 ± 1.6 min in Arm-B.
Given the technical differences between the treatment platforms investigated in this single-institution study, linac-based SRS (Arm-B) did not lead to significantly lower grade 2-3 RN rates versus the multi-source gamma-ray system (Arm-A) in a population of patients with limited brain metastases of small volume. No significant difference in local control was observed between both arms. For Arm-B, the treatment delivery time was significantly lower than for Arm-A.
ClinicalTrials.gov Identifier NCT02355613.
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