Multifaceted Quadruplet of Low-Lying Spin-Zero States in

A search for shape isomers in the ^{66}Ni nucleus was performed, following old suggestions of various mean-field models and recent ones, based on state-of-the-art Monte Carlo shell model (MCSM), all considering ^{66}Ni as the lightest nuclear system with shape isomerism. By employing the two-neutron transfer reaction induced by an ^{18}O beam on a ^{64}Ni target, at the sub-Coulomb barrier energy of 39 MeV, all three lowest-excited 0^{+} states in ^{66}Ni were populated and their γ decay was observed by γ-coincidence technique. The 0^{+} states lifetimes were assessed with the plunger method, yielding for the 0_{2}^{+}, 0_{3}^{+}, and 0_{4}^{+} decay to the 2_{1}^{+} state the B(E2) values of 4.3, 0.1, and 0.2 Weisskopf units (W.u.), respectively. MCSM calculations correctly predict the existence of all three excited 0^{+} states, pointing to the oblate, spherical, and prolate nature of the consecutive excitations. In addition, they account for the hindrance of the E2 decay from the prolate 0_{4}^{+} to the spherical 2_{1}^{+} state, although overestimating its value. This result makes ^{66}Ni a unique nuclear system, apart from ^{236,238}U, in which a retarded γ transition from a 0^{+} deformed state to a spherical configuration is observed, resembling a shape-isomerlike behavior.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

First-line carboplatin/nab-paclitaxel in advanced ovarian cancer patients, after hypersensitivity reaction to solvent-based taxanes: a single-institution experience.

One of the major challenges related to solvent-based taxanes administration in clinical practice is the high rate of hypersensitivity reactions (HSRs). Nab-paclitaxel is a solvent-free, albumin-bound, paclitaxel, which minimize the risk of HSR occurrence. In this single-institution, retrospective analysis, we evaluated stage IIIc-IV epithelial ovarian cancer (EOC) patients, treated with first-line carboplatin/nab-paclitaxel (± bevacizumab), after the occurrence of an HSR with solvent-based paclitaxel (and/or docetaxel). Between April 2012 and December 2018, ten patients (20.8%) received carboplatin/nab-paclitaxel (± bevacizumab) after the occurrence of an HSR to solvent-based taxanes. Among the evaluable patients, ORR was 100%. At median follow-up of 28.5 months, median PFS was 16.7 months, and median OS was 65.4 months, respectively. Median received dose intensity (DI) was 86% and 80% of the projected DI for nab-paclitaxel and carboplatin, respectively. There were no treatment-related grade 4 adverse events. Most relevant treatment-related grade 3 adverse events were: asthenia (10%), hypertransaminasemia (10%), neutropenia (20%), thrombocytopenia (20%), and anemia (10%). No HSR recurrence was observed. The high rate of HSR occurrence could limit first-line treatment options in clinical practice. Carboplatin/nab-paclitaxel association could represent a valid treatment option in this setting.

Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes.

BACKGROUND: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed "non-drugable" progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. METHODS: We conducted a study on "post-progression" (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), "switched therapies" or best supportive care only (BSC). RESULTS: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35-0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33-0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68-1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52-1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). CONCLUSION: Our study confirmed that in clinical practice, in case of "non-druggable" disease progression, maintaining osimertinib beyond progression (with adjunctive LATs) is an effective option.

AMS assessment of U-contamination of structural materials of the Garigliano NPP under decommissioning.

The assessment of the radiological impact of decommissioning activities at a Nuclear Power Plant requires a detailed mapping of the distribution of radionuclides both in the environment surrounding the NPP and in its structural material. The detection of long-lived actinide isotopes and possibly the identification of their origin is particularly interesting and valuable if ultrasensitive measurement of the relative abundance of U isotopes is performed via Accelerator Mass Spectrometry (AMS). In this paper we present an investigation carried out on the structural materials of the Garigliano NPP aiming to determine the abundance of 235,236,238U in the various compartments of the plant buildings under decommissioning. Since the expected values both for isotopic ratios and total U concentrations range over different orders of magnitude, we have developed a novel methodology for the measurement of 234,235U/238U isotopic ratios in low U concentration samples. This allowed a systematic investigation of the distribution of all U isotopes in concrete and metal matrices of the NPP. The behavior of 235,236U/238U isotopic ratios in the different compartments of the NPP is discussed. The correlation of these ratios with 60Co and 137Cs specific activities is also studied to show a different behavior for concrete and metal samples. These data represent a very valuable information to direct the decommissioning procedures under course.

[Health promotion and computer science in radiation protection]. / Promozione della salute e applicazione informatica nella sorveglianza medica della radioprotezione.

An automatic system of clinical-diagnostic information has been applied to workers exposed to ionising radiation at the University of Naples Federico II with reference to the last 5 years. For every person exposed a computerized case sheet was elaborated recording clinical, biological, dosimetric and other preventive data. In the localized risk, capillaroscopic monitoring was used. This research has highlighted the role of medical surveillance in developing health promotion criteria and the planning of the interventions with the complete control of all data in real time.

From adjuvant to preventive breast cancer treatment: bridging the gap over troubled waters.

Recently, chemoprevention trials have demonstrated the efficacy of preventive medical treatment (PMT) in reducing breast cancer (BC) detection rates in at-risk affected and unaffected women selected according to clinical and/or familial risk criteria, particularly with the use of tamoxifen (TAM). Major concerns limiting the routine use of TAM are the questionable benefit/risk ratio and poor patient compliance, which justify the studies undertaken to determine the efficacy of aromatase inhibitors (AIs) with respect to TAM. Issues such as therapy duration, impact on survival, incidence of side-effects and which subsets benefit most from treatment, still remain unsolved. Therefore, only ER+ BC patients are routinely subjected to PMT, independently of their BRCA1/2 status, using adjuvant hormonal therapy. More attention must be focused towards BRCA1/2 carriers as they are probably the women at highest risk of developing BC, in which available data remain controversial and in which hormone-therapy might be important. Hence, at-risk women (affected patients or unaffected women) should be carefully evaluated for inclusion into highly selected preventive clinical trials aimed at evaluating PMT independently of, or according to, BC predisposition status (unknown, positive or negative BRCA1/BRCA2 status) and with respect to menopausal status. BC patients, harboring a BRCA1/2 predisposition, may represent the best subset for extended adjuvant treatment, useful as PMT, simultaneously. Only the evolving differentiation of categories of at-risk women will allow physicians to discriminate PMT in a highly selective manner.

Increased tolerability of bimonthly 12-hour timed flat infusion 5-fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding study.

A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.

Progressive form of multiple pterygium syndrome in association with nemalin-myopathy: report of a female followed for twelve years.

We report on a girl with progressive multiple pterygium syndrome in association with gluteal muscle fibrosis and nemalin-myopathy. This girl has been followed for 12 years. Clinical findings, natural history, and the presence of nemalin myopathy suggest the possibility of a distinct form of multiple pterygium syndrome in this patient.

P16 hypermethylation contributes to the characterization of gene inactivation profiles in primary gastric cancer.

The objective of this study was to investigate the contribution of p16 inactivation in gastric cancer and to compare it with p53. A cohort of 34 primary GCs were analyzed for p16 mutations and transcriptional silencing of the gene due to hypermethylation of the promoter. SSCP analysis and direct sequencing of exons 1 and 2 of the p16 gene were performed to detect any structural alterations. The methylation specific PCR (MSP) assay was applied to reveal hypermethylation of the 'CpG' island in the regulatory region using specific primer pairs for methylated and unmethylated nucleotides after a chemical reaction converting cytosines into uracile when unmethylated. SSCP and direct sequencing analysis did not detect any p16 mutations. The MSP assay showed 4 MSP(+) variants (11.8%). Three MSP(+) were stage III-IV disease and 1 MSP(+) was detected in an early stage disease (IB). All MSP(+) were diffuse type adenocarcinomas. The MSP(+) samples were different from previously reported samples harboring p53 mutations in the same cohort. These data increase the number of gastric cancers showing alterations of either p53 or p16 to 29.4% (10/34). Functional inactivation by hypermethylation of the p16 locus and p53 mutations could play a significant, complementary role in the pathogenesis of sporadic gastric cancer.

Short-term weekly neoadjuvant chemotherapy in the treatment of locally advanced cervical cancer.

Twenty patients with locally advanced cervical cancer (FIGO stage Ib-IIa "bulky"/IIb) were treated with three courses of weekly PVB (day 1: cisplatin, 50 mg/m2; vincristin, 1 mg/m2; bleomycin, 30 IU over 24-hr) in a neoadjuvant setting. Toxicity was generally mild (no grade 3-4 toxicity was observed), and the treatment was well tolerated without reduction of programmed dose intensity. Fourteen patients (70%) experienced a clinical response and underwent surgery within 20 days after the third course of chemotherapy. Six patients (30%) with stable disease were treated with salvage radiotherapy. Two of the 14 responders experienced a pathologic complete response (14.2%); microscopic disease was detected in one patient with clinical complete response. Pelvic node metastases were found in 4/14 patients (28.5%) and microscopic parametrium involvement in 3/14 (21.4%). All 14 patients had free margins of resection. A short-term weekly platinum-based chemotherapy is highly effective, has little toxicity, and allows a prompt salvage therapy for nonresponding patients.

[Can analysis of the molecular status of the p53 gene contribute to improving the therapeutic strategy for breast carcinoma?]. / L'analisi dello stato molecolare del gene p53 può contribuire ad innovare le strategie terapeutiche nel carcinoma della mammella?

The occurrence of mutations in the p53 tumor suppressor gene is a specific and recurring genetic event in solid tumors. P53 plays a pivotal role in multiple cellular processes such as cell growth control, DNA repair and programmed cell death. Genotoxic damage, also induced by chemotherapy or radiotherapy, induces p53 overexpression in order to control the rate of proliferating damaged cells, thus triggering the mismatch repair or apoptotic pathways. P53 inactivation determines a condition of genetic instability, justifying the subsequent susceptibility to acquire mutations of different other genes. P53 mutations are associated with worse prognosis and with chemo/radioresistance, due to the inability to trigger p53-dependent programmed cell death. Molecular diagnostic strategies show 32% p53 mutations in breast cancer. The analysis of the p53 gene performed by FAMA (Fluorescence Assisted Mismatch Analysis) in high-risk breast cancer patients with > or = 10 involved axillary nodes may help identify a subset of very high risk BC patients (vHR-BC) with poorer prognosis and a subset with better prognosis, potentially responsive to medical treatments. The accurate evaluation of the p53 status can predict prognosis and sensitivity to chemotherapy, thus representing the first step toward better definition of therapeutic strategies according to the molecular characterization of the individual patient.

Pelvic relapses in ovarian cancer. Role of CA-125, transvaginal ultrasound and color Doppler.

From January 1995 to January 2001, 40 patients with epithelial ovarian cancer were treated at our Institution. Fourteen of these, with a clinical CR after surgery and platinum-based chemotherapy, were evaluated monthly by gynecological examination, Ca-125 RIA assay, pelvic ultrasound with transabdominal and transvaginal probe and color Doppler. Six pelvic relapses, from 1.5 to 3.0 cm, were detected by transvaginal ultrasound (US). They showed a rich neovascularization with low resistance, high flow, PI from 0.3 to 1.0 and RI < 0.5 in all cases. US did not reveal any sign of relapse in the remaining eight patients. In all cases of pelvic relapses ultrasonic signs of recurrence preceded the increase of Ca-125 by one to six months (average 3.8).

Cervical sarcoma botryoides treated with conservative surgery and adjuvant chemotherapy: a case report.

A case of cervical sarcoma botryoides treated with conservative surgery and adjuvant monochemotherapy is presented.

Surgical treatment of invasive carcinoma of the vulva. Our experience.

OBJECTIVE: The purpose of this study was to investigate the clinical findings, treatment and outcome of patients with vulvar carcinoma in the L'Aquila area. METHODS: Fifteen cases of vulvar carcinoma seen between September 1991 and December 1999 at the Department of Obstetrics and Gynecology of the University of L'Aquila were reviewed. Clinical, pathologic, surgical and follow-up data were collected from patient records. Mean age at diagnosis was 66.4 years. All patients were evaluated through a careful medical history and physical examination, vulvoscopy, abdomino-pelvic CT or MR, urethrocystoscopy, rectocolonscopy and SCC, and CEA determination. Radical surgery included six patients treated by the Taussig-Way operation. Modified radical surgery accounted for nine patients treated by the Byron three-incision approach. RESULTS: The major early complication was groin wound breakdown which occurred in four cases. The major late complication was chronic leg edema which was reported in six patients. The average number of nodes removed per patient was 19.5. Seven patients (46.7%) had a T2N0M0 pathologic stage, four (26.7%) were T2N1M0, four (26.7%) T1N0M0. Five patients died of local and distant recurrences within 37 months after surgical treatment; ten patients are alive, nine are apparently free from disease whereas one presented local and systemic recurrence within 18 months after surgery. CONCLUSIONS: Vulvar carcinoma predominantly affects older women. Most patients in our series (11/15) had tumors more than 2 cm in diameter. Although the vulva is an external organ and early detection should be achieved, many patients presented with extensive primary lesions due to both patient and physician delay. Stage of disease, tumor size, and nodal metastases are potential prognostic factors useful in selecting patients for a more conservative surgical approach.

Hypersensitivity reaction to carboplatin: successful resolution by replacement with cisplatin.

Hypersensitivity reactions caused by carboplatin rarely occur. These reactions can cause lethal complications and make subsequent therapeutic approaches difficult. To date, only a few cases of successful resolution of hypersensitivity by replacement of carboplatin with cisplatin have been reported. We report on a patient with serous papillary extra-ovarian peritoneal carcinoma who developed a hypersensitivity reaction after the 10th weekly administration of carboplatin. Two weeks after reaction, intradermal skin testing with paclitaxel, carboplatin, cisplatin, and mannitol showed intense reaction only to carboplatin. On the basis of these results, the patient was changed to a chemotherapy with cisplatin and paclitaxel. A further eight courses of chemotherapy were administered without evidence of hypersensitivity reactions. Carboplatin seems to be successfully replaceable by cisplatin in case of hypersensitivity reactions.

Cerebral metastasis from ovarian cancer treated with a multidisciplinary approach. Case report and review of literature.

Brain metastases from ovarian cancer are rare. A review of five autopsy studies reported brain metastases in 4% of 712 patients who died with a diagnosis of ovarian cancer. The prognosis is very poor and a consensus on the standard treatment is not available. We report the case of a patient who developed a solitary brain metastasis as single evidence of relapse, 26 months after the first diagnosis of ovarian cancer. A temporo-parietal craniotomy with excision of the mass and whole brain radiotherapy were performed. The patient is free of disease five months after radiotherapy completion. Also in patients suffering from neoplasms that rarely metastasize to CNS, a careful clinical examination may help to diagnose uncommon sites of disease relapse.

[Synchronous associations of tumors in the pelvic organs of the female genital tract]. / Associazioni sincrone di tumori degli organi pelvici dell'apparato genitale femminile.

The Authors report their findings concerning the synchronous associations of tumours involving pelvic organs in the female genital tract observed at the Gynecological Clinic, Aquila. From January 1980 to December 1991, 9 cases (4.28%) of synchronous tumours were found in a total of 210 cases of womb, ovary and vagina tumours. The paper examines the clinical problems and questions of anatomopathological characterisation raised by these associations.