Bone texture analysis using CT-simulation scans to individuate risk parameters for radiation-induced insufficiency fractures.

This study deals with the role of texture analysis as a predictive factor of radiation-induced insufficiency fractures in patients undergoing pelvic radiation. INTRODUCTION: This study aims to assess the texture analysis (TA) of computed tomography (CT) simulation scans as a predictive factor of insufficiency fractures (IFs) in patients with pelvic malignancies undergoing radiation therapy (RT). METHODS: We performed an analysis of patients undergoing pelvic RT from January 2010 to December 2014, 24 of whom had developed pelvic bone IFs. We analyzed CT-simulation images using ImageJ macro software and selected two regions of interest (ROIs), which are L5 body and the femoral head. TA parameters included mean (m), standard deviation (SD), skewness (sk), kurtosis (k), entropy (e), and uniformity (u). The IFs patients were compared (1:2 ratio) with controlled patients who had not developed IFs and matched for sex, age, menopausal status, type of tumor, use of chemotherapy, and RT dose. A reliability test of intra- and inter-reader ROI TA reproducibility with the intra-class correlation coefficient (ICC) was performed. Univariate and multivariate analyses (logistic regression) were applied for TA parameters observed both in the IFs and the controlled groups. RESULTS: Inter- and intra-reader ROI TA was highly reproducible (ICC > 0.90). Significant TA parameters on paired t test included L5 m (p = 0.001), SD (p = 0.002), k (p = 0.006), e (p = 0.004), and u (p = 0.015) and femoral head m (p < 0.001) and SD (p = 0.001), whereas on logistic regression analysis, L5 e (p = 0.003) and u (p = 0.010) and femoral head m (p = 0.027), SD (p = 0.015), and sex (p = 0.044). CONCLUSIONS: In our experience, bone CT TA could be correlated to the risk of radiation-induced IFs. Studies on a large patient series and methodological refinements are warranted.

Assessment of response to chemoradiation therapy in rectal cancer using MR volumetry based on diffusion-weighted data sets: a preliminary report.

PURPOSE: This study evaluated the feasibility of magnetic resonance (MR) volumetry using a diffusion-weighted data set (V(DWI)) and compared it with conventional T2-weighted volumetry (V(C)) in patients affected by rectal cancer treated with chemoradiation therapy (CHRT). MATERIALS AND METHODS: Fourteen patients with a biopsy diagnosis of rectal cancer underwent MR examination before and after CHRT. T2-weighted images were used to extrapolate V(C). A diffusion-weighted (DW) sequence was acquired [spin-echo diffusion-weighted echo-planar imaging (SE-DW-EPI)] with a b-value of 800 s/mm(2) and volume (V(DWI)) was calculated by semiautomatic segmentation of tumour hyperintensity. Two radiologists independently assessed volumes and analysed data in order to establish interobserver agreement and compare and correlate volumes to tumour regression grade (TRG), as evaluable at pathological examination of the surgical specimen. RESULTS: Interobserver agreement was 0.977 [(95% confidence interval (CI) 0.954-0.989) and 0.956 (95% CI 0.905-0.980) for V(C) and V(DWI) and 0.964 (95% CI 0.896-0.988) and 0.271 (95% CI-0.267 to 0.686) between V(C) and V(DWI) before and after CHRT. The correlation between TRG and V(C) and V(DWI) was, respectively, rho = 0.597 (p<0.05) and r(2)=0.156 (p=0.162) and rho=0.847 (p<0.001). CONCLUSIONS: V(DWI) seems to be a promising tool for assessing response to CHRT in rectal cancer. Further studies on large series of patients are needed to refine the technique and evaluate its potential predictive value.

Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients.

The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects. For this reason, we performed an immunological monitoring in 59 out of 120 stage IIIb-IV NSCLC patients enrolled in the BEVA2007 phase II trial, who received fractioned cisplatin (30 mg/sqm days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE doublet) ±bevacizumab. In this group of patients, 12 received the mPE doublet alone and 47 the doublet in combination with bevacizumab (5 mg/kg on the day 3q21; mPEBev regimen). Blood cell counts, serum analysis, multiplex cytokine assay and immunocytofluorimetric analysis, performed on baseline and post-treatment on blood samples from these patients, revealed that bevacizumab addition to the doublet decreased levels of pro-angiogenic (VEGF, Angiostatin-1 and Follistatin) and inflammatory cytokines (interferon (IFN)γ, IL4 and IL17), improved in vivo and in vitro cytotoxic T-lymphocytes (CTL) response and promoted dendritic cell activation. These results suggest that the mPEBev regimen improve the micro-environmental conditions for an efficient antigen-specific CTL response, making it a feasible candidate regimen to be assessed in combination with immune-checkpoint inhibitors in NSCLC patients.

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms.

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.

Telomerase activity, Ki-67, cyclin D1 and A expression, and apoptosis in solitary fibrous tumors: additional features of a predictable course?

Solitary fibrous tumors (SFTs) are infrequent soft tissue neoplasms which are usually benign and surgically curable. However, their behavior is not always predictable, although several clinical and pathological criteria of malignancy have been established. In many cancers, including some soft tissue tumors, telomerase activity (TA) has been shown to be a new reliable pathological marker of malignancy. Overexpression of some cyclins is associated with higher degrees of malignancy and predictive of the clinical course. In this study, we evaluated TA, mitotic and apoptotic indices (MI, AI), and the expression of Ki-67, cyclins D1 and A in five typical and two clinicopathologically atypical SFTs, the latter two of which had also recurred. High TA was demonstrated in the two atypical cases, which also showed a higher labeling index to Ki-67, as well as higher cyclin D1 and A expression, and either none or very few apoptoses. We suggest that TA, Ki-67, cyclin expression, and AI be evaluated in SFTs as possible adjunctive pathological criteria of behavior.

Unfavorable experience with hypofractionated radiotherapy in unresectable lung cancer.

The use of a reduced number of large-sized fractions in radiotherapy (hypofractionation) is usually associated with poor therapeutic results and severe adverse effects, in accord with radiobiologic concepts. However by some authors unresectable lung cancer patients have been treated with hypofractionated radiotherapy with the main aim of "convenience". Result and damage rates are reported to be comparable to those of conventional treatment. In our experience, based on palliative irradiation of 86 advanced-stage, nonmicrocytoma patients, objective remission rates, subjective and performance status improvement, and survival overall were as poor as could be expected in this kind of presentation, with no striking impact of this treatment modality. Severe adverse effects were shown by a large proportion of cases involving skin and soft tissues of the chest wall (40%) and lungs (55.5%). The incidence of severe damage was in agreement with BED (biologic effective dose) values, differently from other experiences of radiotherapeutic management of advanced lung cancer with large fractions.

Salvage with radiotherapy of postsurgical relapses of endometrial cancer.

From January 1960 to June 1974, 71 patients with a postsurgical relapse of endometrial adenocarcinoma have been referred to the Radiology Institute of the University of Florence. Eleven patients showed hematogenous metastases; the remaining 60 cases showed locoregional relapses and were treated with radiotherapy. Forty-eight patients, whose relapse was localized to the pelvis, vagina, inguinal nodes or perineal scar, were treated with a radical aim (4,500-6,000 rad in 5-6 weeks); the treatment was palliative in 12 cases with abdominal extrapelvic relapse. The therapeutic response was not evaluated in 8 patients lost to follow-up shortly after the treatment. In the cases treated with a radical scope, a complete regression was attained in 22 of 43 (51%); a survival rate of 16 of 43 (37%) was attained at 5 years. In 9 cases treated with a palliative aim, only subjective remission was attained, and no patient was alive one year after the therapy. The most favorable therapeutic response was attained in the vaginal relapses (50% survivors at 5 years) and the cases with a late recurrence (more than 3 years) after the initial surgery. No definite correlation was found between the prognosis of the relapse and the histological grading of the primary tumor.

Radiotherapy of seminoma of the testis. Report on 129 patients.

From 1958 to 1974, 129 patients with pure seminoma of the testis were admitted to the Institute of Radiology, University of Florence. Sixty-two were in Stage I, 36 in Stage II A, 23 in Stage II B, 3 in Stage III, and 5 in Stage IV, Para-aortic and ipsilateral iliac nodes were treated in all cases with doses ranging from 3000 to 4200 rads. In the treatment of the supradiaphragmatic area, uniform criteria were not adopted. Out of 124 cases in Stage I, II A and B, and III, 17 suffered a replase; aall relapsed cases died except for one. Site and cause of the failures were analyzed. Prophylactic irradiation of the mediastinum and supraclavicular area appears to lower the probability of recurrence in Stage II. Doses over 3500 rads may be necessary to destroy large metastases. The presence of nonseminomatous areas in the seminoma showing inadequate regression after radiotherapy must be suspected; an exploratory laparotomy should be indicated in such a case.

Weekly epirubicin in advanced breast cancer.

Twenty-nine advanced breast cancer patients, considered unable to tolerate conventional cytotoxic chemotherapy, were treated with a weekly schedule of epirubicin (15 mg/m2 i.v.). All patients were fully evaluable. A remission of 34.5% was observed (2 CR; 8 PR), with a median duration of response of 9 months (range, 3-24 months). Side effects were mild, and on the whole the toxicity was negligible. This regimen showed a favorable therapeutic ratio in our series and seems active and well tolerated even in elderly and/or poor performance status patients.

Chemo-radiotherapeutic management of advanced head and neck cancer.

Stage III and IV head and neck cancer patients usually achieve poor therapeutic results after radiotherapy. The search for more effective treatment modalities is justified, provided that tolerance is not lower than that of the usual radiation therapy schedules. Chemotherapy has been shown to be effective, and cis-platinum and bleomycin based treatments are reported to result in objective remissions in a substantial proportion of cases. There is also experimental evidence of a radiosensitizing activity of cis-platinum. Thirty-five locally advanced head and neck cancer patients were given combined chemo-radiotherapeutic treatment consisting of a cis-platinum and bleomycin induction followed by a standard radiotherapy course integrated with weekly administrations of cis-platinum. Before radiotherapy, an overall 48.5% objective remission rate was achieved, that rose to 85.8% after completion of the entire treatment, with a 31.5% complete response rate. Incidence and severity of radiation mucositis seem not to be increased, and systemic toxicity is very low, with the adopted drug administration schedule. Overall results do not show any obvious superiority over those of radiotherapy alone.

Postoperative radiation therapy after vaginal surgery for endometrial cancer.

From 1958 to 1978, 88 consecutive patients affected by endometrial cancer were referred to the Radiology Institute of the University of Florence, for radiation therapy after vaginal hysterectomy and bilateral salpingo-oophorectomy. Five and ten-year actuarial survival rates are 71% and 62%. In the evaluable patients, results are analysed according to: extension of the tumor, as assessed by pathological evaluation (60 pats.), histologic grade of differentiation (44 pats.), and neoplastic infiltration of myometrium (32 pats.). When the tumor is limited to the uterine body, a 5-year actuarial survival is achieved in 89% of the cases; when the cervix or the adnexa and other pelvic structures are involved, this percentage decreases to 62.5% and 37.5%. The prognosis is also affected by the histological grade of differentiation and the depth of myometrial infiltration.

Radio-chemotherapeutic management of bone diffusion from breast carcinoma.

A combined modality therapy (irradiation plus low-dose Adriamycin and Cyclophosphamide) was delivered to 41 patient affected by extensive bone diffusion from breast carcinoma. A 36% (15/41) objective response rate was obtained, no change was also detectable in 36%, while progressive disease in 28% (11/41). A subjective response was achieved in 37/41 patients, i.e. 90%. The Authors remark the difficulties in evaluating the objective response of metastatic bone to therapy and confirm the keystone role of radiation therapy in the palliative treatment of breast cancer skeletal diffusion.

Postoperative radiation therapy after vaginal surgery for endometrial cancer.

From 1958 to 1978, 88 consecutive patients affected by endometrial cancer were referred to the Radiology Institute of the University of Florence, for radiation therapy after vaginal hysterectomy and bilateral salpingo-oophorectomy. Five and ten-year actuarial survival rates are 71% and 62%. In the evaluable patients, results are analysed according to: extension of the tumor, as assessed by pathological evaluation (60 pats.), histologic grade of differentiation (44 pats.), and neoplastic infiltration of myometrium (32 pats.). When the tumor is limited to the uterine body, a 5-year actuarial survival is achieved in 89% of the cases; when the cervix or the adnexa and other pelvic structures are involved, this percentage decreases to 62.5% and 37.5%. The prognosis is also affected by the histological grade of differentiation and the depth of myometrial infiltration.

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

Lymphoepithelioma-like carcinoma of the endometrium.

Only three cases of lymphoepithelioma-like carcinoma of the endometrium have been reported to date. We present a new case in a 67-year-old woman involving an exophytic mass that caused postmenopausal bleeding. Histologically, undifferentiated carcinomatous areas were intermingled with abundant lymphoid tissue. Epstein-Barr virus was not detected in either neoplastic or lymphoid cells.