Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer

BackgroundBrain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions.Materials and methodsAt a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period.ResultsA total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1–14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%.ConclusionIn patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.     

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot‘em all!

BackgroundAbout 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients.Materials and methodsPatients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel.ResultsBetween 2015–2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52–84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1–6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3–65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27–56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded.ConclusionsSimultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.     

食管癌三维适形放疗和常规放疗比较

目的对比研究三维适形放疗（3DCRT）和常规模拟机定位放疗两种不同方法在食管癌放射治疗中的优缺点。方法 20例食管癌患者采用3DCRT方法进行治疗,应用同一治疗计划系统,制定适形放疗和常规模拟机定位放疗方案。结果与常规模拟定位机定位放疗相比,食管癌照射中3DCRT有最好的剂量分布,既可明显提高靶区的剂量,同时能较好地保护正常组织。结论食管癌的适形放疗技术能降低正常组织的放射损伤和并发症,提高放疗治疗的适形度,改善靶区的剂量分布。     

Whole abdominal radiotherapy in ovarian cancer

Objectives

The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer.

Material and methods

Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40–70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42–45 Gy in the pelvis.

Results

The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery.

Conclusions

Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.     

Predictions of protein flexibility: first-order measures

The normal modes of a molecule are utilized, in conjunction with classical conformal vector field theory, to define a function that measures the capability of the molecule to deform at each of its residues. An efficient algorithm is presented to calculate the local chain deformability from the set of normal modes of vibration. This is done by considering each mode as an off-grid sample of a deformation vector field. Predictions of deformability are compared with experimental data in the form of dihedral angle differences between two conformations of ten kinases by using a modified correlation function. Deformability calculations correlate well with experimental results and validate the applicability of this method to protein flexibility predictions.     

An efficient targeted radiotherapy/gene therapy strategy utilising human telomerase promoters and radioastatine and harnessing radiation-mediated bystander effects

BACKGROUND: Targeted radiotherapy achieves malignant cell-specific concentration of radiation dosage by tumour-affinic molecules conjugated to radioactive atoms. Combining gene therapy with targeted radiotherapy is attractive because the associated cross-fire irradiation of the latter induces biological bystander effects upon neighbouring cells overcoming low gene transfer efficiency. METHODS: We sought to maximise the tumour specificity and efficacy of noradrenaline transporter (NAT) gene transfer combined with treatment using the radiopharmaceutical meta-[(131)I]iodobenzylguanidine ([(131)I]MIBG). Cell-kill was achieved by treatment with the beta-decay particle emitter [(131)I]MIBG or the alpha-particle emitter [(211)At]MABG. We utilised our novel transfected mosaic spheroid model (TMS) to determine whether this treatment strategy could result in sterilisation of spheroids containing only a small proportion of NAT-expressing cells. RESULTS: The concentrations of [(131)I]MIBG and [(211)At]MABG required to reduce to 0.1% the survival of clonogens derived from the TMS composed of 100% of NAT gene-transfected cells were 1.5 and 0.004 MBq/ml (RSV promoter), 8.5 and 0.0075 MBq/ml (hTR promoter), and 9.0 and 0.008 MBq/ml (hTERT promoter), respectively. The concentrations of radiopharmaceutical required to reduce to 0.1% the survival of clonogens derived from 5% RSV/NAT and 5% hTERT/NAT TMS were 14 and 23 MBq/ml, respectively, for treatment with [(131)I]MIBG and 0.018 and 0.028 MBq/ml, respectively, for treatment with [(211)At]MABG. CONCLUSIONS: These results indicate that the telomerase promoters have the capacity to drive the expression of the NAT. The potency of [(211)At]MABG is approximately three orders of magnitude greater than that of [(131)I]MIBG. Spheroids composed of only 5% of cells expressing NAT under the control of the RSV or hTERT promoter were sterilised by radiopharmaceutical treatment. This observation is indicative of bystander cell-kill.     

Modeling the time dependent distribution of a new 153Sm complex for targeted radiotherapy purpose

BackgroundFor radioimmunotherapy purposes, a chemical complex with high absorption in cancer tumor is required. New chemicals are to be examined for their concentration in tumor and healthy organs. These are labeled with β-emitting radioisotopes to irradiate the tumor while deposited inside it.AimTo study the capability of recently developed chemical complex in targeting cancer tumor and investigate the distribution of ¹⁵³Sm-TPTTC in rat organs as function of time.Materials and methodsThe chemical complex – [Tris(1,10-phenanthroline)Samarium(III)] trithiocyanate was prepared and labeled with ¹⁵³Sm radioisotope. The labeled complex was injected to a population of tumor bearing mice. In 2, 4, 24, 48, 96 h after injection the animals were sacrificed and the concentration of Samarium complex was measured in various organs such as blood, heart, intestine, colon, liver, spleen, kidney, sternum and bone.ResultsThe concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of ¹⁵³Sm-TPTTC was modeled and drawn as function of time.ConclusionIt is shown that ¹⁵³Sm-TPTTC is concentrated in tumor tissue and liver much more than in other organs. The variation of pharmaceutical concentration in all organs is described with summation of eight exponential terms and it approximates our experimental data with precision better than 2%.     

VMAT-like plans for magnetic resonance guided radiotherapy: Addressing unmet needs

PurposeVMAT delivery technique is currently not applicable to Magnetic Resonance-guided radiotherapy (MRgRT) hybrid systems. Aim of this study is to evaluate an innovative VMAT-like (VML) delivery technique.Material and methodsFirst, planning and dosimetric evaluation of the MRgRT VML treatment have been performed on 10 different disease sites and the results have been compared with the corresponding IMRT plans. Then, in the second phase, 10 of the most dosimetrically challenging locally advanced pancreas treatment plans have been retrospectively re-planned using the VML approach to explore the potentiality of this new delivery technique. Finally, VML robustness was evaluated and compared with the IMRT plans, considering a lateral positioning error of ± 5 mm.ResultsIn phase one, all VML plans were within constraint for all OARs. When PTV coverage is considered, in the 50% of the cases VML PTV coverage is equal or higher than in IMRT plan. In the remaining 50%, the highest target under coverage difference in comparison with IMRT plan is −1.71%. The mean and maximum treatment time differences (VML-IMRT) is 0.2 min and 3.1 min respectively. In phase two, the treatment time variation (VML-IMRT), shows a mean, maximum and minimum variations of 1.3, 4.6 and −0.6 min respectively. All VML plans have a better target coverage if compared with IMRT plans, keeping in any case the OARs constraints within tolerance. VML doesn’t increase plan robustness.ConclusionVMAT-like treatment approach appeared to be an efficient planning solution and it was decided to clinically implement it in daily practice, especially in the frame of hypo fractionated treatments.     

Long noncoding RNA LINC00958 regulates cell sensitivity to radiotherapy through RRM2 by binding to microRNA-5095 in cervical cancer

Long noncoding RNAs (lncRNAs) have been implicated in the regulation of resistance to radiotherapy in cervical cancer, which is a type of gynecological disease with high mortality in women around the world. Hence, our purpose is to delineate the involvement of LINC00958 in regulating cell sensitivity to radiotherapy in cervical cancer. LINC00958 expression in cervical cancer was assayed, followed by verification of the relationship among LINC00958, microRNA-5095 (miR-5095) and ribonucleotide reductase subunit M2 (RRM2). Hela cells were transduced with up-/downregulation of miR-5095 or RRM2, or LINC00958 silencing, respectively, and then treated with or without a 6 Gy dose of X-ray irradiation. Then the cell proliferation, apoptosis, survival fraction rate, as well as sensitivity to radiotherapy, were assessed. Finally, xenograft tumor in nude mice was established by transplanting Hela cells transfected with sh-LINC00958 and irradiated with 6 Gy of X-ray. High expression of LINC00958 was revealed in The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis, as well as in radiation-resistant patients, which was associated with lower sensitivity to radiotherapy in cervical cancer. Moreover, cervical cancer patients with higher LINC00958 expression exhibited a shorter overall survival according to Kaplan–Meier analysis. In addition, LINC00958 could regulate the expression of RRM2 by competing for miR-5095. A combination of radiotherapy with LINC00958 silencing, RRM2 downregulation or miR-5095 overexpression was found to inhibit cervical cancer cell proliferation and tumor growth, while promoting cell apoptosis both in vitro and in vivo. Collectively, our results suggest that LINC00958 could regulate RRM2 by competing to miR-5095, which regulates cell sensitivity to radiotherapy in cervical cancer.     

Stereotactic radiation therapy for skull base recurrences: Is a salvage approach still possible?

AimA literature review was performed to analyse the role of stereotactic radiotherapy given in a single shot or in a fractionated fashion for recurrent skull base tumours in order to ascertain if it can be a real salvage approach.BackgroundThe management of recurrent skull base tumours can have a curative or palliative intent and mainly includes surgery and RT.Materials and methodsOne-thousand-ninety-one articles were found in the search databases and the most relevant of them were analysed and briefly described.ResultsData on recurrences of meningioma, pituitary adenoma, craniopharyngioma, chordoma and chondrosarcoma, vestibular schwannoma, glomus jugulare tumours, olfactory neuroblastoma and recurrences from head and neck tumours invading the base of skull are reported highlighting the most relevant results in terms of local control, survival, side effects and complications.ConclusionsIn conclusion, it emerges that SRS and FSRT are effective and safe radiation modalities of realize real salvage treatment for recurrent skull base tumours.