bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular and Clinical Pharmacokinetic/Pharmacodynamic Basis for Lack of Efficacy of 21-Day Continuous Topotecan in Patients with Untreated Advanced Adenocarcinoma of the Pancreas
Authors: August Mans Dennis Ricardo , Di Leone Luciane , Ferrary Caldas Ana Paula , Maino Marcelo , Almeida Leonardo , Cancela Anna Isabel , Grivicich Ivana , da Rocha Adriana Brondani , Schwartsmann Gilberto
Published: April 2018

Background

In a phase II study, topotecan was evaluated for response and toxicity in patients with advanced pancreatic carcinoma at the schedule of 0.7 mg/m2/day q 21 days q 28 days.

Methods

Responses were assessed after at least 2 courses using WHO criteria, and toxicity was evaluated after each course according to the CTC-NCI standards. Between December 1995 and September 1997, 15 assessable patients (median age, 55 years; range, 36-74; median ECOG performance, 1; range, 0-3) were included in the study. All had biopsy-proven and measurable disease, a life-expectancy of at least 3 months, and normal bone marrow, liver, and renal function. None of the patients had undergone prior cytotoxic or radiation therapy, and 10 were initially treated by surgery. Twenty-five cycles were assessable for toxicity. Plasma was collected from 7 patients who had received a total of 10 cycles and was, after extraction with methanol at −20°C, analyzed for total topotecan by an HPLC method. The thus determined steady-state concentrations were assessed for their capacity to affect growth and DNA integrity in the BxPC-3 human pancreatic carcinoma cell line after 21 days of continuous exposure. For these purposes, we used a sulforhodamine B staining assay, and agarose gel electrophoresis, respectively.

Results

Grades 3-4 leukopenia, thrombocytopenia, granulocytopenia, and anemia occurred in 8, 6, 8 and 8 cycles, respectively. Other mild to moderate side effects (grades 1-2) included malaise, nausea and vomiting, anorexia, and alopecia. No objective tumor response was documented. HPLC analysis of patients' plasma showed the attainment of constant steady-state levels of 1.0 ± 0.1 ng/mL during the entire infusion period. At such a concentration, topotecan did not significantly affect growth or DNA integrity in the BxPC-3 cells. Fifty percent cell growth inhibition and appreciable oligonucleosomal DNA fragmentation were only evident with 21 days topotecan ≥ 50 ng/mL.

Conclusions

Our data suggest that the lack of clinical activity of 0.7 mg/m2 daily topotecan for 21 days q 28 days in patients with advanced pancreatic carcinoma might be partially attributed to the achievement of non-tumoricidal plasma drug concentrations.
Intrathoracic Desmoid Tumor of the Posterior Mediastinum with Transdiaphragmatic Extension. Report of a Case
Authors: Kocak Zafer , Adli Mustafa , Erdir Ozlem , Erekul Selim , Cakmak Ahmet
Published: April 2018

We report on a de novo desmoid tumor of the posterior mediastinum with transdiaphragmatic extension in a 40-year-old man. The tumor was inoperable because of its location and the invasion of adjacent structures. Although extremely rare, desmoid tumors of the posterior mediastinum should be considered in the differential diagnosis of posterior mediastinal masses.
The Role of Somatostatin and Octreotide in Bowel Obstruction: Pre-Clinic Al and Clinical Results
Authors: Ripamonti Carla , Panzeri Cristina , Groff Liliana , Galeazzi Giordano , Boffi Roberto
Published: April 2018

Malignant bowel obstruction is a common complication in patients with advanced abdominal or pelvic cancer. Whereas surgery should be considered in all cases of malignant bowel obstruction, many advanced and terminal cancer patients are considered unfit for surgery. In such patients with a short life expectancy, gastrointestinal symptoms such as nausea, vomiting, continuous and/or colicky pain, can be controlled by using a pharmacologic approach made up of analgesics, antiemetics and antisecretory drugs, without the use of a venting nasogastric tube. Among the antisecretory drugs, octreotide has been shown to reduce nausea and vomiting in bowel-obstructed patients owing to a reduction of gastrointestinal secretions, thus allowing in most patients removal of the nasogastric tube and the associated distress. Preclinical and clinical studies that demonstrated the role of somatostatin and octreotide in bowel obstruction are reviewed.
Lack of a Time-Factor in Alternating Chemoradiotherapy for Advanced Head and Neck Squamous Cell Carcinoma
Authors: Sanguineti Giuseppe , Benasso Marco , Corvo Renzo , Marcenaro Michela , Ricci Isabella , D'Amico Mauro , Mora Francesco , Vitale Vito
Published: April 2018

Purpose

To assess whether a radiotherapy time factor exists also for patients affected by head and neck squamous cell carcinoma and receiving combined chemoradiotherapy.

Methods and materials

From 1989 to 1997, of 121 patients affected by stage III or IV head and neck squamous cell carcinoma who underwent alternating chemotherapy and radiotherapy according to the Merlano regimen at our institution, 59 were selected for time factor analysis. Until 1995, if chemotherapy had to be delayed because of bone marrow toxicity, radiotherapy was also delayed accordingly. Since January 1996 in order to avoid treatment-free gaps, radiotherapy was delivered continuously until it was possible to resume chemotherapy. Potential predictive factors of local-regional control were included in univariate and multivariate models. The median follow-up is 26 months (5-121 months).

Results

As a result of change in treatment policy, mean radiotherapy duration was shorter for 25 patients treated after 1995 (group A, 8.4 weeks) than for those treated during 1995 or before (group B, 9.4 weeks) (t test, P = 0.0012). In contrast, as expected, mean chemotherapy duration remained relatively unchanged through the years (10.9 vs 10.7 weeks for groups B and A, respectively, t test, P = 0.77). At 2 years, the actuarial local-regional control rate was 53 ± 7% for the whole population. The estimated rates of local-regional control at 2 years were 49 ± 10% and 56 ± 9% for patients belonging to groups A and B, respectively. At univariate and multivariate analyses, treatment group was not predictive of local-regional control.

Conclusions

Our attempt to prospectively limit radiotherapy overall treatment time failed to improve outcome. The data, although obtained on a relatively limited number of patients, suggest that tumor cell repopulation during radiotherapy may not be clinically relevant when chemotherapy is part of the treatment for advanced head and neck squamous cell carcinoma.
Effective Penumbra and Scalloping Effect: A Dosimetric Study in Multifield Radiotherapy with Multileaf Collimator for Prostate Cancer Treatment
Authors: Stasi Michele , Baiotto Barbara , Palamara Federica , Gabriele Pietro , Scielzo Giuseppe
Published: April 2018

Aims and background

The aim of the study was to test whether the multileaf collimator can be used to replace divergent alloy blocks for field shaping and to evaluate the dosimetric impact of the scalloping effect and the effective penumbra in multifield isocentric configurations routinely used at our department to treat early stage prostate tumor in supine patients. Deviations between measurements and treatment planning system calculations are also discussed in order to estimate the accuracy of effective penumbra calculations carried out by the software in the presence of blocks or a multileaf collimator.

Methods

The multileaf collimator installed on a dual energy (6 and 18 MV) linear accelerator Varian CLINAC 2100 C/D is an add-on component positioned below the standard jaws, with 40 computer-controlled opposed pairs of tungsten leaves. Transmission, effective penumbra and scalloping measurements were performed with films placed at different depths in a (30 × 30 × 20 cm3) acrylic phantom. A laser scanning photo-densitometer was used to obtain the optical density and the relative dose profile. Effective penumbra and scalloping effect measured data were tested on a software phantom; the phantom, automatically performed with the treatment planning system, was a regular parallelepiped measuring 30 × 30 × 20 cm3 and the acrylic electronic density value.

Results

For one multileaf collimator-shaped field, the width of effective penumbra was about 2 mm wider than penumbra for cerrobend blocks, at a 45° angle between leaf motion direction and the field edge. Collimator rotation, automatically performed by the treatment planning system, by minimizing the sum of over- and underblocked areas, reduces the differences between the multileaf collimator and blocks. The differences between measured and treatment planning system calculated data were within the treatment planning system dose calculation accuracy limits, as recommended in ICRU Report No. 42.

Conclusions

Penumbra and, for the multileaf collimator, scalloping effect values seem to depend on the gantry angle, i.e., on the fields path of entry. The values for even fields are higher than the those for odd fields, because the dose gradient at the target edges is steeper for a single field than for two opposite fields, and the interplay of doses from the individual beams increases the distance between the isodose levels. Therefore, in order to reduce scalloping and effective penumbra values, it would be better to rotate the collimators, above all in even-number field techniques. In particular, the six-field technique, used mostly in prostate treatment, shows the same effective penumbra values with the multileaf collimator, with proper collimator rotation, and in blocked fields.
Implementation of an Integrated “Record and Verify” System for Data and Images in Radiotherapy
Authors: Schwarz Marco , Scielzo Giuseppe , Gabriele Pietro
Published: April 2018

In November 1999, new radiotherapy and medical physics departments began to operate in our institution. In the departments' project, considerable emphasis had been placed on the integration of the equipment through networking. In particular, a “record and verify” (R&V) system for data and images (Varian “Varis” and “Vision”) has been employed in the daily routine since the beginning of treatments. After one year, more than 600 patients have been treated, and a first evaluation of the system can be carried out. In clinical practice, the software required no significant changes in the already-established radiotherapy workflow and has been successfully configured in an acceptable time. On the other hand, the way information is exchanged and shared has dramatically changed towards a nearly paperless and filmless way of working. A good application reliability has been experienced, and the client-server structure has been proven useful by avoiding loss of data in critical situations. The staff time spent for the application to run is now well balanced by the increased safety in daily practice, and digital archiving of all the radiotherapy activity has increased the effectiveness of routine tasks and statistical researches. The critical aspects we have experienced in the application are the proper user rights definition and a minor rounding error in the daily dose accumulation. Future developments in implementation of the system will be aimed to a better integration with the Hospital Information System and to a further exploitation of the RT-PACS features of the “Vision” application.
Response of Metastatic Epidermoid Anal Cancer to Single Agent Irinotecan: A Case Report
Authors: Grifalchi Federico , Padovani Augusto , Romeo Fabio , Trinca Claudia , Moscetti Luca , Cortesi Enrico
Published: April 2018

We report a case of a patient affected by epidermoid anal cancer who had hepatic progression after standard therapy with the Nigro regimen (fluorouracil and mitomycin C plus radiotherapy). This is an uncommon neoplasm against which only few chemotherapeutic agents have been tested. In our patient salvage treatment with low dose irinotecan resulted in a partial response.
Tumor Microenvironment: What have we Learned Studying the Immune Response in this Puzzling Battlefield?
Authors: Mocellin Simone , Panelli Monica , Wang Ena , Rossi Carlo Riccardo , Marincola Francesco M
Published: April 2018

Recent developments hallmark the progress in the understanding of tumor immunology and related therapeutic strategies. The administration of interleukin-2 (IL-2) to patients with cancer has shown that immune manipulation can mediate the regression of established cancers. The identification of the genes encoding cancer antigens and the development of means for effectively immunizing against these antigens has opened new avenues for the development of active immunization of patients with cancer. However, an efficient immune response against tumor comprises an intricate molecular network still poorly understood. Only when the code governing immune responsiveness of cancer will be deciphered, new therapeutic strategies could be designed to fit biologically defined mechanisms of immune rejection of cancer.

In this review, we propose that the mechanisms regulating tumor rejection in response to vaccination will be more efficiently identified by following the evolution of treatment induced events within the tumor microenvironment taking advantage of recently developed technological tools. As a model, we will discuss the observed immune response to tumor antigen -specific immunization and its relationship with the systemic administration of IL-2.
Radiotherapy after Prostatectomy
Authors: Sanguineti Giuseppe , Franzone Paola , Culp Laura , Marcenaro Michela , Barra Salvina , Vitale Vito
Published: April 2018

Aims and background

The role of radiotherapy after prostatectomy is controversial. This paper tries to give some guidelines for everyday practice through an analysis of literature data.

Methods

The potential role of radiotherapy in the adjuvant and salvage setting is discussed. We also report and interpret available literature data for both settings.

Results

As regards an increase in or detectable prostate-specific antigen (PSA) after radical prostatectomy, about 40–50% of patients are rendered bNED with local salvage radiotherapy, but only 10–50% are long-term (5 years) biochemically controlled. A timely salvage treatment is crucial to optimize control probability. As regards adjuvant radiotherapy for undetectable postoperative PSA in patients at high risk of failure as judged on pathology, results are more encouraging. Recent data report bNED rates ≥70% at 5 years.

Conclusions

Although results are far from satisfactory, salvage radiotherapy should be considered for every patient with an increased or detectable PSA after surgery. Adjuvant radiotherapy seems preferable to salvage radiotherapy for patients at high (>30%) risk of failure.
Smoking in Italy, 2002
Authors: Gallus Silvano , Colombo Paolo , Scarpino Vilma , Zuccaro Piergiorgio , Apolone Giovanni , La Vecchia Carlo
Published: April 2018

Aims and background

To update estimates of smoking prevalence in Italy to the year 2002.

Methods

Population-based, face-to-face survey conducted by the DOXA (the Italian Branch of the Gallup International Association) in March-April 2002 on 3,238 individuals aged 15 or over, representative of the whole Italian population.

Results

Overall, 26.6% of Italian adults were current cigarette smokers (31.1% of men, 22.3% of women); 19.9% of men and 10.4% of women smoked 15 or more cigarettes per day. Ex-smokers were 15.2% (21.9% of men, 9.0% of women). There was no appreciable difference with reference to geographic area or education in men, but more educated women were more frequently smokers (28%). Compared to 2001, reported smoking prevalence declined by 3.7% in men and 1.3% in women, and the fall was evident in various age groups, including the youngest one (15–24 years). However, part of the fall is likely due to increased underreporting, since these survey figures are appreciably underestimated as compared to sale data. Among ex-smokers, 84% had stopped without support. Among smokers, 37% had tried at least once to stop. Using the Fagerström questionnaire, 69.5% of smokers were classified as low or very low dependent, whereas only 20.0% of smokers were classified as high or very high dependent. Women, younger and elderly, as well as more educated smokers of both sexes tended to be less dependent.

Conclusions

Self-reported smoking prevalence tends to decline in Italy, although the overall figure (26.6% of Italian adults) remains considerably higher than the USA and several Western European countries.
Pancreatic Involvement from Heavily Pretreated Small Cell Lung Cancer Successfully Treated with Transcatheter Intra-Arterial Chemotherapy: A Case Report with Local and Systemic Disease Control
Authors: Ottaiano Alessandro , Barletta Emiddio , Maione Paolo , Fiore Francesco , Pisano Carmela , Di Maio Massimo , laffaioli Vincenzo Rosario , Gridelli Cesare
Published: April 2018

This is a case report on pancreatic metastases from small cell lung cancer successfully treated by transcatheter arterial infusion of chemotherapy. The patient showed partial regression of pancreatic and thoracic disease. To our knowledge this is the first reported case of small cell lung cancer with pancreatic involvement treated with the transcatheter arterial infusion procedure; it represents an example of integrated treatments that may be considered for patients with pancreatic involvement from small cell lung cancer even if heavily pretreated.
A Clinical Case Report of Priapism Treated with External RT
Authors: Barone Vincenzo , Ferrera Giuseppe , Romeo Nando
Published: April 2018

The aim of this short communication is to present an extremely uncommon case of penile metastases from rectal adenocarcinoma treated with an external beam radiotherapy technique. A 76-year-old man affected by very painful priapism from penile metastases was treated with radiotherapy (30 Gy) for symptom relief. In the course of the radiotherapy treatment the patient reported gradual and continuous pain reduction. One month after the end of radiotherapy both the priapism and the pain had disappeared. Although the long-term prognosis remains poor, good quality of life was achieved in this patient.
Reflux Esophagitis as a Possible Risk Factor in the Development of Pharyngolaryngeal Squamous Cell Carcinoma
Authors: Bacciu Andrea , Mercante Giuseppe , Ingegnoli Anna , Bacciu Salvatore , Ferri Teore
Published: April 2018

Aims and background

To determine the role of reflux esophagitis in the development of pharyngolaryngeal squamous cell carcinoma in non-smoking and non-drinking patients.

Methods

The study population consisted of 92 consecutive non-smoking and non-drinking patients with histologically confirmed squamous cell carcinoma of the pharynx and the larynx. As a control, a group of 125 lifetime non-smoking and non-drinking cancer-free subjects was selected.

Results

Patients with pharyngolaryngeal cancer had a higher prevalence of reflux esophagitis than the control subjects (P <0.0001).

Conclusions

Our results confirm that reflux esophagitis in itself is associated with an increased risk of upper aerodigestive tract cancer.
The Molecular Basis of Thyroid Epithelial Tumorigenesis
Authors: Bongarzone Italia , Pierotti Marco A
Published: April 2018

Significant alterations in gene sequences, expression levels and protein structures have been associated with specific types of thyroid epithelial tumorigenesis. Recent revolutionary changes in molecular biology have spanned the disciplines of genomics and proteomics, which systematically generate and analyze the information about genomes, gene transcripts, proteins and their functions in a global, comprehensive manner. The application of these approaches will better discriminate between thyroid tumor subtypes that are not recognizable when traditional pathological criteria are used.
RET/PTC Oncoproteins: Molecular Targets of New Drugs
Authors: Lanzi Cinzia , Cassinelli Giuliana , Cuccuru Giuditta , Zanchi Chiara , Laccabue Diletta , Zunino Franco
Published: April 2018

Ret oncoproteins expressed in thyroid carcinomas represent possible targets for therapeutic intervention. Oncogenic activation of the receptor tyrosine kinase encoding RET gene occurs typically by gene rearrangement in papillary thyroid carcinomas (PTC) and by missense mutation in medullary thyroid carcinomas (MTC). These genetic alterations lead to the expression of deregulated products characterized by ligand-independent activation of the intrinsic tyrosine kinase of Ret. Such features suggest the possibility of using specific tyrosine kinase inhibitors to block the Ret oncoproteins signaling. The present report summarizes the cellular effects of the arylidene 2-indolinone Ret inhibitor RPI-1 (formerly Cpd1) on the human PTC cell line TPC-1 which spontaneously harbors the RET/PTC1 oncogene. The results provide evidence that RPI-1 is able to inhibit cell growth and to interfere with Ret/ptc1-driven signaling. These findings support a role for Ret oncoproteins as therapeutic targets and the pharmacological interest of RPI-1 as a candidate drug for preclinical evaluation on thyroid tumors expressing RET oncogenes.
Hürthle Cell Carcinoma: Clinic-Pathological and Biological Aspects
Authors: Carcangiu Maria Luisa
Published: April 2018

Despite its structural simplicity the thyroid gland can give rise to a wide variety of tumor types.

Although a substantial amount of work has been done in the past twenty-five years to redefine the clinic-pathological features of most types of thyroid tumors of follicular cell origin, some aspects of thyroid tumors composed of oncocytes, generally known as Hürthle cell tumors, are still matter of discussion. The major issues concern their very existence as a bona fide tumor type, the occurrence of benign and malignant forms and their relative frequency, the predictive value of morphologic parameters, the natural history of the malignant forms and the classification of Hürthle cell tumors with a papillary growth pattern. The definition of oncocytic cell, oncocytic neoplasm and oncocytic carcinoma as well as the pathologic characteristics and clinical behavior of neoplasms composed of oncocytes will be discussed.
Recombinant Human Thyrotropin (rhTSH) in the Follow-Up and Treatment of Patients with Thyroid Cancer
Authors: Bombardieri Emilio , Seregni Ettore , Villano Carlo , Aliberti Gianluca , Mattavelli Franco
Published: April 2018

The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen™). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.
The Role of Radionuclide Therapy in Medullary Thyroid Cancer
Authors: Castellani Maria Rita , Alessi Alessandra , Savelli Giordano , Bombardieri Emilio
Published: April 2018

In medullary thyroid carcinoma (MTC) the detection of occult metastases is difficult and the prognosis of widespread disease is poor. In recent years several radiopharmaceuticals have become available for the diagnosis of this tumor. None of these tracers, however, has satisfactory diagnostic sensitivity and specificity. Furthermore, only few radiopharmaceutical compounds proved to have clinical value in therapeutic applications. Radionuclide therapy utilizes unsealed radioactive sources in order to deliver selective irradiation to the target organs or cancer lesions. This approach is only clinically indicated when there is a scintigraphic evidence of sufficient tumor uptake and a favorable biodistribution. When these conditions are present, radionuclide therapy can be adopted in MTC patients. Due to the low incidence of this tumor, the poor sensitivity of the available radiopharmaceuticals and their limited indications, the clinical experience in radionuclide therapy of MTC is still limited and there is general agreement among experts that it has only a palliative role. Here we briefly report the main experiences in radionuclide therapy in the past and in recent years. In addition, we summarize the results obtained with 131I-MIBG therapy at the Istituto Nazionale Tumori of Milan, as well as the most important ongoing preclinical and phase I/II trials.
Evaluation of Circulating Calcitonin: Analytical Aspects
Authors: Martinetti Antonia , Seregni Ettore , Ferrari Leonardo , Pallotti Federica , Aliberti Gianluca , Coliva Angela , Fracassi Silvia , Bombardieri Emilio
Published: April 2018

Background and aim

Calcitonin (hCT) is a useful serum marker for the diagnosis and monitoring of medullary thyroid carcinoma (MTC). However, hCT values provided by different methods may differ, leading to difficulties in the interpretation of hCT results. In this study we compared four immunoradiometric (IRMA) and radioimmunometric (RIA) assays for hCT determination.

Material and methods

hCT was measured in 35 patients by means of the following commercially available IRMA or RIA kits: CT US (Biosource), IRMA hCT (Schering-CIS bio international), ultra-sensitive calcitonin (DSL), and calcitonin assay (Scantibodies). A comparison of the distribution of the hCT values measured by the tested IRMA-RIAs and a correlation analysis were performed.

Results

The hCT values were widely dispersed and the classification of the patients according to the hCT cutoff value varied depending on the assay used.

Conclusion

Despite efforts to develop new, highly specific antibodies, the evaluation of this marker is still flawed by analytical inaccuracy. hCT values are widely dispersed depending on the method used for marker measurement; as a consequence, patient classification according to the hCT cutoff value is still dependent on the assay used.
Radiation-Induced Osteosarcoma Arising 20 years after the Treatment of Ewing's Sarcoma
Authors: Longhi Alessandra , Barbieri Enza , Fabbri Nicola , Macchiagodena Michele , Favale Leonardo , Lippo Cataldo , Salducca Nicola , Bacci Gaetano
Published: April 2018

We report the case of a 17 years old female with a Ewing's sarcoma of the left femur treated with limb sparing surgery followed by local radiotherapy of 45 Gy and adjuvant chemotherapy with vincristine, doxorubicine, cyclophosphamide, actinomycin D. The patient received neoadjuvant chemotherapy for osteosarcoma and a left femur resection with endoprosthesis replacement. The patient is alive and free of disease 4 years after the treatment of this second malignant neoplasm (SMN). This case shows that radioinduced SMN can occurr with relatively low doses of RT («50Gy) and that it may occurr very late.
Outbreak of Infusion-Related Septicemia by Ralstonia Pickettii in the Oncology Department
Authors: Marroni Massimo , Pasticci Maria Bruna , Pantosti Annalisa , Colozza Maria Antonietta , Stagni Giuliano , Tonato Maurizio
Published: April 2018

Hospital acquired blood stream infection by Ralstonia pickettii in 9 cancer patients related to the heparin solution contamination used to flush the central venous catheter.
Efficacy of Epoetin Alfa in a Retrospective Non-stratified Subgroup Analysis of a Breast Cancer Cohort Receiving Non-platinum Chemotherapy
Authors: Bajetta Emilio , Vercammen Els , Reinhardt Uwe , Janmohamed Riaz , Da Costa Ricardo Marques , Matulonis Ursula , Guastalla Jean-Paul ,   for the Epoetin Alfa Study Group
Published: April 2018

Aims and Background

More than 60% of patients with metastatic breast cancer receiving non-platinum-based chemotherapy experience anemia, which is associated with fatigue and impaired quality of life. Epoetin alfa treatment in patients with a variety of malignancies has been shown to decrease transfusion requirements and improve hemoglobin levels and quality-of-life efficacy parameters.

Patients

Retrospective subgroup analyses were performed in patients with breast cancer who were part of a multinational, randomized (2:1), double-blind, placebo-controlled trial of anemic cancer patients (n = 375) undergoing non-platinum-based chemotherapy.

Results

In the breast cancer subpopulation (n = 114, 48% with stage IV disease at baseline), the hemoglobin increase was greater for epoetin alfa patients than placebo patients (2.3 versus 0.9 g/dL). Epoetin alfa patients had lower transfusion requirements (28.2% versus 33.3%), improvement or preservation versus deterioration of quality of life, and a higher proportion of responders (patients achieving a ≥2 g/dL increase in hemoglobin levels unrelated to transfusion) (68.0% versus 22.9% for placebo). The results were similar to those observed in the full study cohort, where statistical analyses showed the differences to be significant (P <0.05 for all). Epoetin alfa treatment was well tolerated. Although the study was not designed or powered for survival as an endpoint, Kaplan-Meier estimates for the full cohort showed a trend in overall survival favoring epoetin alfa treatment (P= 0.13, log rank test); a similar benefit was seen in the breast cancer subpopulation.

Conclusions

In the full study cohort and the breast cancer subpopulation, epoetin alfa effectively treated anemia (increased hemoglobin levels and decreased transfusion requirements) and improved or preserved quality of life. Results concerning potential survival benefits support further study of epoetin alfa in anemic cancer patients.
Prognostic Significance of Serum Lactate Dehydrogenase in Osteosarcoma of the Extremity: Experience at Rizzoli on 1421 Patients Treated over the Last 30 Years
Authors: Bacci Gaetano , Longhi Alessandra , Ferrari Stefano , Briccoli Antonio , Donati Davide , De Paolis Massimiliano , Versari Michela
Published: April 2018

Aims

The study evaluated the correlation between pretreatment serum lactate dehydrogenase (LDH) levels with the stage of disease and its clinical prognostic value.

Methods

Pretreatment serum LDH of 1421 patients with osteosarcoma of the extremity were assessed to investigate whether the enzyme correlates with the stage of the tumor. In 860 assessable patients with localized disease, treated according to 10 different protocols of adjuvant (four) and neoadjuvant chemotherapy (six), we also evaluated the correlation between the serum levels of LDH and outcome.

Results

According to the stage of disease, the rate of high serum level of LDH was significantly higher in 199 patients with metastatic disease at presentation than in 1222 patients with localized disease (36.6% vs 18.8%; P <0.0001). In these patients, the 5-year disease-free survival was 39.5% for patients with high LDH levels and 60% for those with normal values. The 5-year disease-free survival correlated with serum level of LDH at univariate and multivariate analysis, although it lost its significance when histologic response to chemotherapy was also considered in the multivarite analysis.

Conclusions

Serum LDH has a prognostic value and it should be considered in evaluating the results of therapeutic trials of chemotherapy, as well as defining a category of patients at high-risk of relapse to be treated with a more aggressive regimen.
Differential Tumor Microenvironment in Human Ovarian Cystic Tumors
Authors: Murta Beatriz Martins Tavares , De Queiróz Cunha Fernando , Miranda Rodrigo , Adad Sheila Jorge , Murta Eddie Fernando Candido
Published: April 2018

Aims and Background

Cells and soluble mediators obtained from tumor effusions are useful in evaluating the tumor microenvironment. Our aim was to examine cytologically and to quantify the leukocyte infiltrate, nitric oxide, cytokines and tumor markers in the intracystic fluid from patients with a cystic adnexal mass, for a possible differentiation between benign and malignant findings.

Methods and Study Design

Sixty-six women who had their cystic fluids collected were prospectively divided into benign tumor (22, 33.3%), malignant tumor (10, 15.2%) or other gynecological alterations (34, 51.5%). Cytology, total and differential leukocyte counts were determined by light microscopy. Tumor markers, cytokines and nitric oxide were assayed in the supernatants using the Immutile system, ELISA and Griess reaction, respectively.

Results

The sensitivity and specificity of the cytological analysis was 66.7% and 97.7%, respectively. The levels of CA 19.9, CA 15.3, α-fetoprotein, carcinoembryonic antigen, progesterone and β-HCG were significantly higher in the benign and/or malignant group than in the other gynecological alterations. Also, the local concentrations of CA 15.3 and β-HCG were significantly higher in malignant than in benign tumors. In malignant tumors, increased leukocyte counts and higher concentrations of IL-6, IL-10 and nitric oxide were detected than in benign tumors or other gynecological alterations.

Conclusions

In malignant tumors, the microenvironment could be differentiated from benign tumors or other gynecological alterations by cystic fluid analysis.
Unusual Breast Tumors: Primary Lymphoma. A Case Report
Authors: Pasta Vittorio , Midulla Cecilia , Monti Massimo , Martelli Maurizio , Torcasio Angelo , Stella Salvatore
Published: April 2018

An 82-year-old woman presented with a right breast lump with erythematous reaction of the overlying skin and corresponding lymph nodes. Cytological examination of the breast lesion and lymph nodes suggested a lymphoid proliferation. Frozen section revealed carcinoma with lymphoid stroma. Simple mastectomy was performed because of the extent of the lesion. Histological diagnosis was non-Hodgkin type B large-cell lymphoma. Primary breast lymphomas behave similarly to lymphomas of similar histologic types occurring in other sites. The authors illustrate the diagnostic difficulties and the usefulness of complementary techniques in the diagnosis of an unusual breast mass.
Treatment Options in Hormone-refractory Metastatic Prostate Carcinoma
Authors: Fusi Alberto , Procopio Giuseppe , Torre Silvia Della , Ricotta Riccardo , Bianchini Gianpaolo , Salvioni Roberto , Ferrari Leonardo , Martinetti Antonia , Savelli Giordano , Villa Sergio , Bajetta Emilio
Published: April 2018

Prostate cancer represents one of the most important health problems in industrialized countries. It is the second leading cause of cancer-related death in the United States. Therapeutic options are different according to the stage of the disease at the diagnosis. Patients with localized disease may be treated with surgery or radiation, whereas the treatment for patients with a metastatic disease is purely palliative. Hormonal treatment represents the standard therapy for stage IV prostate cancer, but patients ultimately become unresponsive to androgen ablation and are classified as hormone-refractory prostate cancer patients. The molecular mechanisms involved in progression in hormone resistance are characterized by mutations, down and up-regulation in the androgen receptor gene, mutations in p53 and over-expression of Bcl2 and other alterations in genes and in gene expression. The important thing is that we understand these mechanisms to define potential therapeutic agents for the treatment of hormone-refractory prostate cancer patients. Conventional options for patients with hormone-refractory prostate cancer include secondary hormone therapy, radiotherapy and cytotoxic chemotherapy. The commonest antineoplastic agents are mitoxantrone, estramustine and taxanes. Despite an improvement In the palliative benefit, none of these agents has demonstrated a beneficial impact on the overall survival of patients. Therefore, there is no standard therapy for these patients, thus we need new approaches which should be studied in clinical trials. The evaluation and incorporation of new agents into current treatment regimens could have a role in the treatment of hormone-refractory prostate cancer, but their efficacy has not yet been demonstrated.
Epidemiology of Primary Central Nervous System Tumors in the Coast and Gorski Kotar County, Croatia, 1977-2000
Authors: Tuškan-Mohar Lidija , Materljan Eris , Jurjević Anton , Weiner-Črnja Mima , Willheim Ksenija , Antončić Igor , Bučuk Mira , Sepčić Juraj
Published: April 2018

Aim and Background

To establish the incidence of primary tumors of the central nervous system (CNS) in the resident population of the Coast and Gorski Kotar County, Croatia, in the period 1977-2000.

Methods

A retrospective descriptive epidemiological study. Tumors were classified according to the World Health Organization's scheme. A total of 911 cases was identified. Information about patient gender and age at diagnosis, tumor location and histologic type was obtained from case histories, autopsy protocols and pathology reports. Age- and sex-adjusted incidence were determined by a direct standardization method.

Results

Histologic confirmation was obtained in 84.5% of cases. The most frequent tumors were glioblastoma in men (30.2%) and meningioma in women (29.5%). The average annual crude and world-standardized incidence was 11.2 (95% CI, 10.1-12.3) and 8.2/100,000/year (95% CI, 7.4-9.0), respectively. The highest specific age incidence was detected in the seventh decade of life, 24.7/100,000/year (95% CI, 21.4-28.8). The tumors occurred equally in each sex. The lowest incidence was detected on the islands, 7.4/100,000/year (95% CI, 5.9-9.2) and the highest along the coast, 12.7/100,000/year (95% CI, 11.4-14.0). The survey showed the highest incidence of these neoplasms in the coastal municipality of Senj, 14.7/100,000/year (95% CI, 10.3-20.5).

Conclusion

The descriptive epidemiological incidence of primary CNS tumors in the Coast and Gorski Kotar County, Croatia, especially those of neuroepithelial and meningeal origin, correspond to the data reported in similar studies elsewhere in the world. The incidence of these neoplasms in the area investigated is uneven. Limitations in study design preclude definitive conclusions about the causes of these differences.
A Phase II Study of Liposomal Doxorubicin in Recurrent Epithelial Ovarian Carcinoma
Authors: Arcuri Carmela , Sorio Roberto , Tognon Germana , Gambino Angela , Scalone Simona , Lucenti Antonio , Caffo Orazio , Valduga Francesco , Arisi Emilio , Galligioni Enzo
Published: April 2018

Background

We conducted a phase II trial to evaluate the efficacy and safety of liposomal formulation of doxorubicin in recurrent ovarian carcinoma patients.

Methods

Thirty patients were included in the study after having obtained an informed consent. Their main characteristics were: median age, 64 years (range, 45-80), ECOG performance status 0 in 17 patients (56%), 1 in 11 patients (36%) and 2 in 2 patients (6.6%). Eighteen patients had metastatic disease and 12 locally advanced disease. All patients were pretreated with a platinum-based chemotherapy: 3 were considered refractory to platinum (progression or stable disease), 2 were platinum resistant (relapse <12 months), and 7 were platinum sensitive (relapse ≥12 months). Treatment consisted of liposomal doxorubicin, 50 mg/m2 every 4 weeks.

Results

The overall response rate was 26.6%, with 2 complete responses and 6 partial responses lasting 3.5 months. The incidence of grade 3-4 toxicity was 23.3% for neutropenia, 10% for mucositis and 10% for plantar-palmar erythrodysesthesia. Median survival was 12+ months (range, 2-26+).

Conclusions

Liposomal doxorubicin appears to be a moderately active drug in pretreated patients, and its activity seems to be similar to that reported for other active regimens in terms of response rate. The toxicological profile of liposomal doxorubicin suggests that it may be combined with other drugs in the treatment of patients with ovarian cancer.
Which Role for Radiation Therapy in Ethmoid Cancer? A Retrospective Analysis of 84 Cases from a Single Institution
Authors: Magrini Stefano M , Nicolai Piero , Somensari Andrea , Scheda Antonella , Bignardi Mario , Bonetti Bartolomea , Frata Paolo , Huscher Alessandra , La Face Beniamino , Tonoli Sandro
Published: April 2018

Purpose

To define the results of radiotherapy for the treatment of ethmoid carcinoma in a large, retrospective, substantially unselected series from a single institution.

Methods and Materials

A relatively large series of 84 consecutive patients treated at our Institution over a 30-year period (1970-2000) was retrospectively analyzed. Sixteen more patients treated in the same period were affected by a relapse of disease at presentation and were therefore excluded from the analysis. Most of the patients had T3 or T4 disease (76%), and half of them had undifferentiated (G3-G4) tumors. Radical surgery preceded radiotherapy in 60 patients, the remaining had only biopsy or incomplete surgery. Average ICRU dose varied according to the extent of postsurgical residual disease.

Results

The 5-year actuarial overall survival of the entire series was 48.6%, 5-year disease-specific survival 58%, and 5-year relapse-free survival 54.6%. Overall, disease-specific and relapse-free survival were significantly better (logrank test) for early stage patients (T1-T2) and for those with low-grade disease; relapse-free and disease-specific survival were also significantly (or almost significantly) better for patients who had radical surgery and for those with less extended postsurgical residue. Patients treated with radiotherapy after biopsy only or grossly incomplete surgery had 5-year relapse-free, disease-specific and overall survival of 22%, 42% and 37%, respectively. Higher cumulative doses (>60 Gy) were related to a not significantly lower recurrence probability in patients with micro- or macroscopic residual disease after surgery (54% vs 62%). Multivariate analysis (Cox model) showed that only T stage and grading were independent prognostic factors for overall and disease-specific survival, whereas the prognostic impact of radical surgery was limited to relapse-free survival.

Conclusions

Radical radiation therapy alone is able to cure about 25% of the unfavorably selected cases, after biopsy only or partial surgery. Radical surgery is associated with better relapse-free survival rates, but the contribution of postoperative radiotherapy to the primary treatment of these patients cannot be eliminated.
The Impact of 18F-deoxyglucose Positron Emission Tomography on Tumor Staging, Treatment Strategy and Treatment Planning for Radiotherapy in a Department of Radiation Oncology
Authors: Gabriele Pietro , Malinverni Giuseppe , Moroni Gian Luca , Gatti Marco , Regge Daniele , Versari Annibale , Serafini Desiderio , Fraternali Alessandro , Salvo Diana
Published: April 2018

Aims and Background

The study analyzed the potential contribution of positron emission tomography (PET) in patient selection for radiotherapy and in radiation therapy planning.

Methods

Eighty-seven patients with a histological cancer diagnosis were accrued for the study from December 2000 to December 2001. Demographic characteristics included a median age of 54 years and male/female ratio of 51/36. All patients staged by conventional workup who were candidates for radiotherapy had PET imaging and were allocated to a conventional “pre/post-PET stage”. The treatment protocol and the shape and/or size of the portals was directly related to PET results. We examined 26 lung cancers, 15 gastrointestinal tumors, 22 genitourinary cancers and 24 hematologic malignancies.

Results

In the lung cancer group, the stage was modified in 10/26 patients (38.5%) by PET, with a change in management in 13 (50%) and a change in radiotherapy planning in 6 (23.1%). In the hematological group, stage was modified by PET in 8/24 cases (33.3%), with a change in treatment strategy in 9 (37.5%) and a change in radiotherapy planning in 3 (12.5%). In the gastrointestinal group, the stage was modified by PET in 2/15 cases (13.4%), with a change inn treatment strategy in 4 (26.7%) and a change in the decision for radiotherapy in 8 (no radiotherapy in 53.3%). In the mixed group (genitourinary, breast and other), the stage was modified by PET in 6/22 cases (27.3%), with a change in treatment strategy in 11 (50%) and a very low rate of change in radiotherapy planning.

Conclusions

PET contributed to a modification of stage in 26/87 patients (30%), to a changing in treatment strategy in 37/87 (42.5%), and to a substantial change of the shape and/or size of radiotherapy portals in 13/43 (30%) who underwent radiotherapy.
P53 Expression, Dna Ploidy and Mitotic Index as Prognostic Factors in Patients with Epithelial Ovarian Carcinoma
Authors: Ceccaroni Marcello , Chieco Pasquale , Alboni Carlo , De Iaco Pierandrea , Pagano Katia , Ceccarelli Claudio , Santini Donatella , Taroni Beatrice , Pelusi Giuseppe
Published: April 2018

Aims and Background

Biological variables linked to genomic instability were examined and related to survival in 52 patients affected by ovarian carcinoma and nine patients with low malignant potential tumors (LMP).

Methods

DNA ploidy was measured by image cytometry in isolated neoplastic cells; the mitotic index was measured in Feulgen-toluidine blue-stained sections and p53 was investigated by immunohistochemistry.

Results

Twenty-five tumors (4 LMP) were peridiploid (ploidy <2.25c), 22 tumors (4 LMP) were hyperdiploid (2.25c>ploidy<2.9c) and 14 (1 LMP) had high ploidy (≥2.9c). Ml ranged from 0.3 to 24.2 with a mean of 1.8 for LMP and 6.8 for carcinomas (P <0.001). Widespread p53 overexpression was detected in 49% of carcinomas and in none of the LMP tumors.

Conclusions

Survival analysis performed in patients with carcinomas indicated that, of the examined biological variables, only Ml was moderately associated with survival in a subgroup of early-stage patients.