A multicenter LArge retrospectIve daTabase on the personalization of stereotactic ABlative radiotherapy use in lung metastases from colon-rectal cancer: The LaIT-SABR study.

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD). MATERIAL AND METHODS: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC). RESULTS: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035). CONCLUSION: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization.

Role of perfusion CT in the evaluation of metastatic nodal tumor response after radiochemotherapy in head and neck cancer: preliminary findings.

OBJECTIVE: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence. PATIENTS AND METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment. RESULTS: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistically significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters. CONCLUSIONS: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RT-CT are predictive of nodal tumor persistence.

The role of clinicopathologic and molecular prognostic factors in the post-mastectomy radiotherapy (PMRT): a retrospective analysis of 912 patients.

OBJECTIVE: To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT). PATIENTS AND METHODS: We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model. RESULTS: A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078). CONCLUSIONS: After mastectomy ECE, a cut off of Ki-67>30% and triple negative status were strictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes.

Association between RAD 51 rs1801320 and susceptibility to glioblastoma.

Glioblastoma is the most common and aggressive malignant primary brain tumor. Despite decades of research and the advent of new therapies, patients with glioblastoma continue to have a very poor prognosis. Radiation therapy has a major role as adjuvant treatment for glioblastoma following surgical resection. Many studies have shown that polymorphisms of genes involved in pathways of DNA repair may affect the sensitivity of the cells to treatment. Although the role of these polymorphisms has been investigated in relation to response to radiotherapy, their role as predisposing factors to glioblastoma has not been clarified yet. In the present study, we evaluated the association between polymorphisms in DNA repair genes, namely: XRCC1 rs25487, XRCC3 rs861539 and RAD51 rs1801320, with the susceptibility to develop glioblastoma. Eighty-five glioblastoma patients and 70 matched controls were recruited for this study. Data from the 1000 Genomes Project (98 Tuscans) were also downloaded and used for the association analysis. Subjects carrying RAD51 rs1801320 GC genotype showed an increased risk of glioblastoma (GC vs GG, χ(2) = 10.75; OR 3.0087; p = 0.0010). The C allele was also significantly associated to glioblastoma (χ(2) = 8.66; OR 2.5674; p = 0.0032). Moreover, RAD51 rs1801320 C allele increased the risk to develop glioblastoma also when combined to XRCC1 rs25487 G allele and XRCC3 rs861539 C allele (χ(2) = 6.558; p = 0.0053).

New approaches for imaging and therapy of solid cancer.

Radionuclide therapy is a systemic treatment that aims to deliver cytotoxic radiation to cancer cells. Due to their properties, antibodies have been considered as suitable agent for the delivery of therapeutic radioisotopes, radioimmunotherapy (RIT). This article gives an overview of new approaches for imaging and therapy of solid cancer with particular attention to strategies to enhance treatment success. Examples of increased antibody uptake by targeting stromal constituent of tumor microenvironment such as fibronectin (FN) an important tumor-associated angiogenesis targeting agent, with specifically designed antibody format will be provided. Strategies oriented to identify patients most likely to benefit from RIT including identification of radiosensitivity profiles, in vivo target identification by teragnostic approach and better prediction of dosimetric estimates would be presents. Combination regimens such as with chemo-radiotherapy and immunotherapy would be also discussed as an approach to enhance RIT success.

Comparison of various diffraction formulas in a study of open resonators.

Modes and losses of the planar Fabry-Perot and confocal resonators have been computed using various kernels obtained by different approximations of diffraction theory. For Fabry-Perot resonators no practical influence was found of the shape of the kernel on the results, at least for Fresnel numbers ranging up to 42.25. For the confocal resonator large differences were found even at small Fresnel numbers N greater, similar 1. In particular, a qualitative difference was found between the results obtained by the so-called parabolic approximation and the kernel of Rayleigh-Luneberg diffraction theory. These differences confirm the influence of the amplitude in the approximations.

Resonances and resonant fields in a fabry-perot resonator illuminated by a line source.

In the present paper, the field internal to an infinite-strip plane-parallel mirror resonator is evaluated in the case when the structure is illuminated by a cylindrical primary wave. The feeder where the primary wave originates constitutes a perturbation of the resonator and is assumed to scatter a cylindrical wave proportional to the field impinging on it. The quasi-stationary field pattern internal to the structure is evaluated for several values of the efficiency of the scatterer, that is, of the factor relating the wave scat- tered by the feeder to the wave impinging on the feeder. Resonant frequencies and fields are compared with the resonant frequencies and fields of a Fabry-Perot resonator not perturbed by the presence of the feeder. The effect of the persistent primary wave alone is analyzed by considering the case of a feeder with vanishing efficiency.

Quasi-stationary wave patterns inside infinite-strip open resonators.

The quasi-stationary wave patterns inside a two-mirror optical resonator are evaluated as the sum of a progressive and a regressive wave by assuming the mirrors to be illuminated by the fundamental mode of the resonator at a resonance frequency. The progressive and the regressive waves are also evaluated in the case of the first-order mode. Calculations are made for an infinite-strip Fabry-Perot resonator, as well as for a cylindrical and a confocal resonator, with Fresnel number N = 1.