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Objective: The epidemiological evidence on soft-tissue sarcoma (STS) mortality is inconsistent in geographic and time coverage. This study provides mortality trends for STSs in selected countries worldwide over the last 2 decades, together with predicted figures for 2025., Methods: We extracted official numbers of certified deaths coded as C47 (i.e. malignant neoplasm of peripheral nerves and autonomic nervous system) and C49 (i.e. malignant neoplasm of other connective and soft tissue) according to the 10th Revision of the International Classification of Disease and population estimates from the WHO and the Pan American Health Organization databases. We computed age-standardized (world standard population) mortality rates (ASMRs). We used joinpoint regression analysis to identify significant changes in trends and to predict death numbers and rates for 2025., Results: The pattern emerging from the number of deaths and ASMRs up to 2018 shows an increase in most countries in both sexes. Around 2015 to 2018, ASMRs differed by 2.5-fold in both sexes with the highest rates being registered in Central-Eastern Europe, North America and Australia, while the lowest ones in Latin America, Japan, and Korea. In 2025, the number of STS deaths is predicted to increase in most countries and both sexes, and unfavourable rates are predicted in Central Europe in both sexes., Conclusion: In addition to improvements in STSs registration, unfavourable mortality rates reported in this study reflect inadequate referral of patients with STSs to high-volume multidisciplinary centres, as well as insufficient advancements in STS prevention, diagnosis, and treatments., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, Cancers 2021; ClinicalTrials.gov Identifier: NCT02793050)., Methods: A post-hoc analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety., Results: Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6)., Conclusions: Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile., Competing Interests: EP has served on an advisory board for Takeda, Amgen, Daiichi Sankyo, Lilly, Eusa Pharma, Deciphera, and SynOx Therapeutics and has received research support from Bristol Myers Squibb, Pfizer, PharmaMar, and Daiichi Sankyo. ABr is a consultant for Eli Lilly, Eisai, Glaxo-Smith Kline, Pharmamar and has received travel grants from PharmaMar, Takeda, and Ipsen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Palmerini, Sanfilippo, Grignani, Buonadonna, Romanini, Badalamenti, Ferraresi, Vincenzi, Comandone, Pizzolorusso, Brunello, Gelsomino, De Pas, Ibrahim, Gurrieri, Grosso, Zanelli, Pantaleo, Milesi, Ciuffreda, Ferrari, Marchesi, Quattrini, Righi, Setola, Carretta, Casali, Picci and Ferrari.)

Objective: To investigate the role of community pharmacists in the therapeutic process of oncological patients and to assess these patients' state of acceptance of their disease and their relationship with their therapies, we performed a survey in some oncological clinics in Turin (north-west of Italy)., Methods: The survey was carried out in a three months' period by means of a questionnaire. The questionnaire was administered on paper to oncological patients that attended 5 oncological clinics in Turin. The questionnaire was self-administered., Results: 266 patients filled out the questionnaire. More than half of patients reported that their cancer diagnosis interfered with normal life very much or extremely and almost 70% of patients reported that they were accepting of what happened and were trying to fight back. 65% of patients answered that it is important or very important that pharmacists are aware of their health status. About 3 out of 4 patients thought that pharmacists giving information on medicines purchased and on how to use them is important or very important and that it is important to receive information concerning health and the effects of medication taken., Conclusion: Our study underlines the role of territorial health units in the management of oncological patients. It can be said that the community pharmacy is certainly a channel of election, not only in cancer prevention but also in the management of those patients who have already been diagnosed with cancer. More comprehensive and specific pharmacist training is necessary for the management of this type of patient. Furthermore, it is necessary to improve the awareness of this issue in community pharmacists at the local and national levels by creating a network of qualified pharmacies developed in collaboration with oncologists, GPs, dermatologists, psychologists and cosmetics companies., (Copyright: © Pharmacy Practice.)

Angiogenesis has a direct stimulatory effect on tumor growth, duplication, invasion and metastatic development. A significant portion of conventional renal cell carcinomas are angiogenesis-dependent tumors and the pathways supporting this process have been thoroughly investigated over the last 20 years. As a consequence, many tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, pazopanib, axitinib, and cabozantinib), one monoclonal antibody (bevacizumab), and two mammalian target of rapamycin (mTOR) inhibitors (temsirolimus and everolimus) have been investigated and approved for the treatment of advanced or metastatic clear cell renal carcinoma (metastatic CCRC) in first-line, as well as second-line, therapy, with impressive results in progression-free survival and in the objective response rate compared with previously available therapies or placebo. Recently, a new type of drug has been approved for metastatic CCRC: immunomodulatory checkpoint inhibitors (ICIs), alone or in combination with TKIs. However, many questions and areas to be explored still remain with regard to clear cell renal carcinoma (CCRC) treatment: research on predictive biomarkers, the best patient selection, how to overcome the mechanisms of resistance, and the best sequence of therapies in daily clinical practice. This review focuses on the pharmacological properties and anticancer activities of these drugs. The toxicity profile and clinical limitations of these therapies are also discussed.

Introduction: The role of chemotherapy for patients with dedifferentiated chondrosarcoma (DDCS) is still under discussion. Here, we present the outcome in patients with DDCS treated with intensive chemotherapy from the EUROpean Bone Over 40 Sarcoma Study., Materials and Methods: The chemotherapy regimen included doxorubicin, ifosfamide and cisplatin. Postoperative methotrexate was added in case of poor histological response. Toxicity was graded based on the National Cancer Institute expanded common toxicity criteria, version 2.0, and survival was analysed using Kaplan-Meier curves, log-rank tests and univariate Cox regression models., Results: Fifty-seven patients with DDCS (localised, 34 [60%]; metastatic, 23 [40%]) aged 42-65 years were included. Surgical complete remission (SCR) was achieved in 36 (63%) patients. The median overall survival (OS) was 24 months (95% confidence interval, 22-25), and the 5-year OS was 39%. Patients with extremity localisation had a 5-year OS of 49% compared with 29% in patients with a central tumour (P = 0.08). Patients with localised disease had a 5-year OS of 46%, whereas patients with metastatic disease had a 5-year OS of 29% (P = 0.12). Patients in SCR had a 5-year OS of 49%, whereas patients not in SCR had a 5-year OS of 23% (P = 0.004). Chemotherapy toxicity was considerable but manageable. There was no treatment-related death, and 39 (70%) patients received ≥6 cycles of the planned nine chemotherapy cycles., Conclusions: Adding intensive chemotherapy to surgery for treatment of DDCS is feasible and shows favourable survival data compared with previous reports. With the limitations of data from a non-controlled trial, we conclude that chemotherapy could be considered in the management of patients aged >40 years., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.B. has reported grants from Deutsche Krebshilfe, Deutsche Forschungsgemeinschaft and the European Science Foundation and personal fees from Lilly, Bayer, Pfizer, Novartis, Isofol and Clinigen; E.P. has reported advisory roles for Amgen, Daiichi Sankyo, Eli Lilly, EUSA Pharma and Deciphera, received research support from Bristol Myers Squibb, Pfizer and PharmaMar and received travel support from Lilly, PharmaMar and Takeda; L.K. has reported honoraria from Bayer; P.R. has reported advisory roles for Exactech and Stryker; A.F. has reported honoraria from Ipsen Pharma, PharmaMar and Lilly; P.C. has reported honoraria for the speaker, consultancy or advisory role from Bayer, Deciphera, Eisai, Eli Lilly, Nektar Therapeutics and Pfizer and received research funds from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc., Glaxo, Karyopharm Pharmaceuticals, Novartis, Pfizer and PharmaMar; P.R. has reported honoraria from Bayer, Clinigen, BMS, Roche, MSD, Deciphera, Novartis, Pfizer, PharmaMar, Lilly and Amgen; I.H., S.F., K.S.H., P.P., S.H.-N., D.M.D., C.B., B.B., E.St., M.G., T.K., M.E., V.F., M.K., R.B., D.B., O.B., A.C., R.S., R.B., T.K., L.H., G.A., B.-N.H., E.Se., A.F., F.K., G.H.-W. and S.S. have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.

Background and Objectives: Limb salvage surgery remains the standard treatment in bone and soft tissue tumors. Toronto Extremity Salvage Score (TESS) is the most used quality of life measure. Our objective was to perform cross-cultural adaptation and validation in Italian, testing test-retest reliability, construct validity, and responsiveness., Methods: We interviewed patients already treated for content validity. A total of 124 patients completed TESS and other questionnaires presurgery, at 3 months, 3 months + 2 weeks, and 6 months follow-up. We calculated intraclass correlation coefficients (ICCs) for reliability, associations with Pearson's r, and change over time with paired T tests., Results: A new item regarding touch-screen devices was added to the upper extremity (UE) questionnaire. ICC resulted of 0.99 for lower extremity (LE) and 0.98 for UE patients, Pearson's r between TESS and Musculoskeletal Tumor Society was .66 and .64, EuroQol-5D-5L r was .62 and .61, and r between TESS and short form-36 physical function subscale was .76 and .71 for LE and UE groups, respectively. Paired T test results were statistically significant to detect change over time (0.03, 0.04, and 0.04 for LE groups and 0.03, 0.01, and 0.04 for UE groups)., Conclusion: The Italian version of TESS can be used for the bone and soft tissue sarcoma population in clinical trials in Italy and with Italian speaking patients abroad to ensure patients' perspectives for efficacy and efficiency of treatments., (© 2020 Wiley Periodicals, Inc.)

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma., Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study., Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity., Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

Purpose: To evaluate whether apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) is able to investigate the histological features of soft tissue tumours., Methods: We reviewed MRIs of soft tissue tumours performed from 2012 to 2015 to calculate the average ADCs. We included 46 patients (27 male; mean age: 57 years, range 12-85 years) with histologically proven soft tissue tumours (10 benign, 2 intermediate 34 malignant) grouped into eight tumour type classes. An experienced pathologist assigned a semi-quantitative cellularity score (very high, high, medium and low) and tumour grading. The t test, ANOVA and linear regression were used to correlate ADC with clinicopathological data. Approximate receiver operating characteristic curves were created to predict possible uses of ADC to differentiate benign from malignant tumours., Results: There was a significant difference (p < 0.01) in ADCs between these three groups excluding myxoid sarcomas. A significant difference was also evident between the tumour type classes (p < 0.001), grade II and III myxoid lesions (p < 0.05), tumour grading classes (p < 0.001) and cellularity scores classes (p < 0.001), with the lowest ADCs in the very high cellularity. While the linear regression analysis showed a significant relationship between ADC and tumour cellularity (r = 0.590, p ≤ 0.05) and grading (r = 0.437, p ≤ 0.05), no significant relationship was found with age, gender, tumour size and histological subtype. An optimal cut-off ADC value of 1.45 × 10 -3 mm 2 /s with 76.8% accuracy was found to differentiate benign from malignant tumours., Conclusions: DWI may offer adjunctive information about soft tissue tumours, but its clinical role is still to be defined.

Aim: To investigate the possible role of imatinib, an inhibitor of the tyrosine kinase activity of PDGF-R, in desmoplastic small round cell tumor (DSRCT)., Patients & Methods: From August 2005 to June 2009, DSRCT patients refractory to conventional treatment were enrolled. Patients received imatinib 400 mg daily. Primary end point of this open label, prospective, Phase II trial was objective response rate., Results: Of the 13 enrolled patients, eight were evaluable for response. Median age was 20 years (range: 9-32). Objective responses at 3 months were: stable disease in one patient and progressive disease in seven patients., Conclusion: Imatinib showed no efficacy in the treatment of DSRCT unresponsive to conventional therapy, despite molecular-based selection of patients.

During the last decades, much effort has been made to develop and test treatments for advanced/metastatic breast cancer (MBC) able to prolong survival and improve patients' quality of life. In this regard, eribulin represents one of the most recent and interesting discoveries. This tubulin-targeting chemotherapy demonstrated a survival benefit in MBC women who progressed after at least two prior lines of chemotherapy for the treatment of metastatic disease (prior therapies should have included an anthracycline and a taxane, in either adjuvant or metastatic setting). Here, we described five cases of heavily pretreated MBC patients who experienced long-lasting control of disease with eribulin.

Introduction: Musculoskeletal Soft Tissue Tumours (STT) are frequent heterogeneous lesions. Guidelines consider a mass larger than 5 cm and deep with respect to the deep fascia potentially malignant. Contrast Enhanced Ultrasound (CEUS) can detect both vascularity and tumour neoangiogenesis. We hypothesised that perfusion patterns and vascularisation time could improve the accuracy of CEUS in discriminating malignant tumours from benign lesions., Materials and Methods: 216 STT were studied: 40% benign lesions, 60% malignant tumours, 56% in the lower limbs. Seven CEUS perfusion patterns and three types of vascularisation (arterial-venous uptake, absence of uptake) were applied. Accuracy was evaluated by comparing imaging with the histological diagnosis. Univariate and multivariate analysis, Chi-square test and t-test for independent variables were applied; significance was set at p<0.05 level, 95% computed CI., Results: CEUS pattern 6 (inhomogeneous perfusion), arterial uptake and location in the lower limb were associated with high risk of malignancy. CEUS pattern has PPV 77%, rapidity of vascularisation PPV 69%; location in the limbs is the most sensitive indicator, but NPV 52%, PPV 65%. The combination of CEUS-pattern and vascularisation has 74% PPV, 60% NPV, 70% sensitivity. No correlation with size and location in relation to the deep fascia was found., Conclusion: US with CEUS qualitative analysis could be an accurate technique to identify potentially malignant STT, for which second line imaging and biopsy are indicated in Referral Centers. Intense inhomogeneous enhancement with avascular areas and rapid vascularisation time could be useful in discriminating benign from malignant SST, overall when the lower limbs are involved., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

GIST (gastrointestinal stromal tumor) are the most common mesenchymal tumors in gastrointestinal tract and are thought to derive from the cells of Cajal or their precursors that have a constitutional mutation in KIT and PDGFRA genes. There are KIT and PDGFRA genes mutations detected before the start of therapy that are believed to be related to GIST pathogenesis and some secondary mutations causing drug resistance and progression of disease. The most common KIT mutations are detected in exon 11 (66-71%), exon 9 (10-13%), exon 13,14,17 (1% each). PDGFRA mutations (8%) are described in exon 18 (5-6%), 12 (1%) and 14 (1%). No mutations are detected in 5-10% of tumors and those subtypes are called wild type GIST (WT). Imatinib mesilate is a selective inhibitor of KIT and PDGFRA with an antityrosine kinase activity (TKI) used in advanced or metastatic GIST as well as in adjuvant setting after complete resection of neoplasm. Imatinib has radically changed the therapy and prognosis of GIST, but sensitivity of the disease is different on the basis of leading mutations. GIST KIT exon 11 mutated manifests response rate in 80% of cases, exon 9 in 40% and GIST WT in 14%. PDGFRA shows a mild sensitivity to drug (66%) except the exon 18 D842 V mutation which is totally resistant. Unfortunately up to 15% of GIST have a primary resistance to imatinib that means progression of the disease within 6-12 months after the start of therapy. Another 40-50% of GIST develops a secondary resistance after >24 months of TKI treatment. Biopsy of progressing GIST shows multiple clonal origins with distinct mutational changes. Secondary resistance occurs almost exclusively in KIT mutated GIST with the appearances of T670I gatekeeper secondary mutation and less common in 14, 17, 18 exons. After progression of disease second line therapy is represented by sunitinib malate that overcomes the most common resistant mutations excepted PGDFRA D842V. Again, after few months of treatment, new different mutations appear and the disease progresses. Regorafenib is the third line therapy but too few data relates mutational status and regorafenib activity. In adjuvant setting only imatinib has a role. Two important studies (the USA ACOSOG Z 9001 and the German-Scandinavian study) fail to demonstrate that a specific mutation can predict a better DFS and OS in treated patients. On the contrary, volume of the tumor, number of mitosis and site of GIST are strong prognostic and predictive factors. In conclusion mutational analysis in GIST is at present more useful in metastatic setting than in adjuvant therapy. The insurgence of primary and secondary mutations during therapy is a fundamental step for disease progression.

Background/aim: Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma., Patients and Methods: Thirty-four patients received NPLD 40 mg/m(2) (d1) and ifosfamide 3 g/m(2)/day (d1-3) every three weeks as first-line therapy of metastatic soft tissue sarcoma. The treatment was planned for a maximum of six cycles., Results: The objective response (OR) rate among response-assessable patients was 55.9%. The median progression-free survival (PFS) was 4.2 months and the median overall survival (OS) was 11.2 months. Symptomatic grade 3 cardiotoxicity occurred in one patient (3%)., Conclusion: The combination of NPLD and ifosfamide reported in a population of metastatic soft tissue sarcoma patients at risk for developing heart failure encourage antitumour activity, similar to that of classical doxorubicin., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Irinotecan (IRI) is a topoisomerase I inhibitor active as first- or second-line chemotherapy in advanced colorectal cancer (ACRC). Its combination with fluorouracil (FU) increases the response rate and prolongs survival. In order to identify a new effective and less toxic schedule of administration, we planned this phase II study with weekly IRI and protracted venous infusion of FU (WI-FI regimen). The primary endpoint was the objective response rate. Secondary aims were to detect toxicity, progression-free survival (PFS) and overall survival (OS) of patients (pts)., Materials and Methods: On May 2000, a monoinstitutional study commenced with the following schedule of administration: IRI 80 mg/m2 on days 1, 8, 15, 22, 29 plus a 28-day protracted venous infusion of FU 200 mg/m2/day. The treatment was repeated every 35 days. Cycles were administered until a maximum of 6 courses, disease progression or unacceptable toxicity., Results: By March 2005, 52 patients (30 males and 22 females) had entered the study. Their median age was 61.5 years and the median ECOG PS was 1. In total, 223 courses were administered (median 5 cycles/patient). Toxicity was low: neutropenia G3 and asthenia G3 were the most observed toxicities (5 pts each). No other grade 3-4 toxic side-effects were seen. Weekly IRI was interrupted in 11 pts, mostly related to problems with the central venous catheter. Following RECIST criteria, we observed 5 complete responses, 15 partial responses, 17 pts had stable disease, while in 15 disease progressed. The overall response rate was 38.5% and the disease control rate was 71.2%. Thirteen pts underwent surgical resection of their relapsing disease. The median PFS was 8.2 months and the median OS was 16.3 months., Conclusion: The WI-FI regimen is an active treatment with a good safety profile in patients with CRC. The low incidence of grade 3-4 toxicities justifies further evaluation of this combination.

Gastrointestinal stromal tumours (GISTs) are a precise oncogenetic entity that has started the new era of targeted therapies in solid tumours. GISTs are now a model to understand the role of oncogenic kinase mutation in tumourigenesis, duplication, cell regulation, apoptosis and drug resistance. Ninety-five percent of GISTs have some activacting mutation of c-KIT or PDGFRA tyrosine kinase. The studies of the last two years have found concrete correlations between mutations and anatomical locations of GISTs, prognosis, response to therapy and resistance to therapy. Genotyping has increased of importance in the last years as a new field for translational researches. The important advances made in molecular studies are now a practical tool in diagnosis and therapy of GISTs.

Objective: To develop a method for adapting the best available cancer practice guidelines (CPGs) to the regional oncology network in Piedmont (NW of Italy, with about 4.3 million residents)., Methods: Four CPG were developed by multidisciplinary working groups, involving local opinion leaders, coordinated by the same team (including epidemiologists and health economists). The major features of these guidelines were: (a) to cover all the phases ofthe disease (from diagnosis to palliative care); (b) to satisfy common standards for evidence based guidelines; (c) to be coherent with the local health organization and resource availability. In the first three CPGs, regarding common cancers (colon-rectum, breast, lung), recommendations were graded according to the underlying level of evidence, from A to C, and treatment was organized by specialty. In the last guideline, regarding a rare condition (soft tissue sarcomas, STS), a grading system reflecting also the clinical importance of the decision was adopted and treatment recommendations were organized by clinical scenarios. In each guideline, some implementation tools, including a set of process and outcome indicators for audit monitoring, were provided., Results: The four CPGs have been published between 2001 and 2004. The number ofrecommendations ranged between 38 (STS) and 103 (colon-rectum), with some differences in the distribution by specialty and grading. The CPGs have been disseminated through the oncology network and local health coordinators have been involved in the implementation. The impact of the CPGs is being evaluated by different approaches (analyses of administrative data, sample surveys and user's interviews)., Conclusions: To adapt evidence based guidelines to a specific regional health organization is feasible and may be usefil for diseases requiring a multidisciplinary approach and continuity of care.

Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.

Gastrointestinal stromal tumours (GIST) are the most common form of mesenchymal tumour of the intestinal tract. The incidence in Italy is approximately 800-1,400 new cases/year; the most common localization is the stomach (50-60%), small bowel (20-30%), rectum (10%) and esophagus (5%). Extra-abdominal localizations are very rare. GIST characteristically express the Kit protein, a transmembrane tyrosine kinase receptor for the specific ligand. Most GIST have a mutation in kit receptor which becomes constitutive for the neoplasm. Kit mutation is a early tumorogenesis event. The disease clinically can present as an occasionally finding or can be diagnosed after hemorrhage, perforation or obstruction of the gastrointestinal tract. Surgery is the mainstay of the therapy mainly in primary tumour. More debated is its role in metastatic disease. In this situation imatinib mesilate, a tyrosine kinase inhibitor, is the drug of choice which has changed the natural history of the disease. Metastatic GIST before imatinib mesilate discovery had 6 months survival, now in the 3 published studies after 3 years of follow-up, median survival has not already reached. New drugs are now under evaluation in order to prolong the pharmacological activity of tyrosine kinase inhibition after progression of the disease.

Soft tissue tumors, involving the vascular bundle, require a particular surgical approach: oncological and vascular surgical techniques must be integrated in order to perform a limb-saving surgery with adequate margins. Thirty-six soft tissue sarcomas of the thigh and popliteal region were treated from June 1999 to September 2002. Nineteen cases involving the vascular bundle were analysed and placed in two groups according to imaging and clinical information: Group A, 14 patients, with tumors close to femoral vessels without adventitial infiltration, and Group B, 5 patients, with vascular infiltration. Group A was treated with vascular blunt dissection performing adventitial excision. Group B was treated with vascular "en-bloc" resection and reconstruction. Imaging and clinical information together with surgical techniques, strategies and complications were analysed in order to plan the surgical approach in neoplastic vascular bundle involvement.

Purpose: Echocolor Power Doppler with contrast medium forms a non-invasive vascular image; the purpose of the study is to evaluate the effectiveness in differentiating benign and malignant tumors in the soft tissues of the limbs., Material and Method: Echocolor Power Doppler with contrast medium was used to study 80 patients with swelling in the soft tissues of the limbs: there were 54 benign lesions, 22 sarcomas, and 4 aggressive desmoid fibromatoses., Results: Were identified 4 patterns of wash-in and wash-out curves that could be correlated to the histological diagnosis: type I was present in 85% of benign lesions, type III in 91% of malignant lesions and in 3.7% of the benign ones, type II in aggressive fibromatoses, anomalous type in 4 benign lesions and 2 sarcomas; the curve was absent in 2 benign lesions., Conclusions: Power Doppler Echocolor with contrast medium can become a useful method to be associated with traditional imaging methods in the differential diagnosis of swelling of the soft tissues of the limbs.

Background: Soft tissue sarcomas are infrequent tumors (up to 1% of all neoplasms) in adult patients. Treatment of advanced disease is largely unsatisfactory. Only a few drugs are active agents and combination regimens offer limited and short-lived activity. High dose chemotherapy may be administered only to limited groups of patients., Patients and Methods: We evaluated, in a phase II study, the adriamycin and ifosfamide combination regimen. The drugs were administered at 60 mg/sqm and 6 g/sqm dosage, respectively. The total number of treated patients was 42 of which 40 were evaluable., Results: We observed 6 complete responses (14% response rate) and 6 partial responses (14%). The mean survival was 6 months (median 7.6 months). Toxicity was limited and reversible., Conclusion: While high dose chemotherapy may be reserved for selected groups of patients, an adriamycin and ifosfamide combination regimen at conventional doses can be administered to the great majority of patients with suboptimal performance status or with advanced age.

Purpose: To evaluate the maximum tolerated doses (MTD) of ifosfamide when given as a continuous infusion and in combination with fixed doses of bolus 4'-epidoxorubicin in advanced previously untreated adult soft tissue sarcoma patients., Methods: Treatment consisted of epidoxorubicin, 60 mg/m2 days one and two, and ifosfamide, 1.5 g/m2 every 12 hrs as a 72-hr infusion, at the first level. Further levels of ifosfamide were defined as increments of 12 hrs of the same infusion program. G-CSF 300 microg/die was administered from days +7 to +14. Dose-limiting toxicity (DLT) was defined as: G4 leukopenia or thrombocytopenia of > or =5 days; any G3 neuro or nephrotoxicity; G4 toxicity of any kind. Patients had to complete at least 2 consecutive cycles, and MTD was defined as the level in which 20% of patients developed a DLT; 10-15 patients were entered in each level., Results: First level: overall, 13 patients entered, 3 were not assessable for MTD, and only one developed a DLT. Second level: 18 patients entered, 3 were not assessable for MTD. Hematologic DLT was observed in 3/15 assessable patients. Therefore, the MTD was found at the ifosfamide level of 10.5 g/m2 given in 84 hrs. Eight patients of 29 assessable for response achieved an objective response: 1 complete and 7 partial. The overall response rate was 28% (95% CI: 13-47%)., Conclusions: If we accept 4-day G4 leukopenia as a reliable cutoff for safety, ifosfamide intensification cannot be substantially exploited over already available schedules with the combination of ifosfamide and anthracyclines.

Combined radiation therapy and chemotherapy have been reported to produce a high incidence of complete regression of epithelial cancer of the anal canal. Our group has treated 25 patients since June 1986. Treatment included chemotherapy (first period: Mitomycin C + 5-Fluorouracil; second period: Carboplatin + 5-Fluorouracil) and simultaneous whole-pelvis irradiation (50.40 Gy). Our results confirm that radiochemotherapy can achieve good local control: all patients were in complete clinical remission three months after the completion of combined therapy. Seven, patients developed recurrences; the actuarial survival rate was 78.5% and the disease free survival rate 67%. Acute toxicity was tolerable, but a relatively high number of patients exhibited chronic treatment-related symptoms. In order to reduce late side effects, other studies are necessary to explore if, in patients with small tumors, less extensive locoregional treatment can be effective without reducing the survival rate.

Non small cell lung cancer is one of the leading causes of death in the industrial countries and some 70% of patients have non surgically eradicable disease. Platinum based combined regimens can achieve 35-40% objective responses, but advanced age, low performance status and concurrent diseases can exclude up to 60% of patients from an adequate poliychemotherapy treatment.

A total of 48 patients with non-metastatic osteosarcoma of the extremities were treated with a new neoadjuvant chemotherapy protocol which, prior to surgery, included the use of high dose methotrexate, cisplatin, adriamycin and ifosfamide. Cisplatin was administered intra-arterially, whereas the other drugs were given intravenously. In all of the cases response to this chemotherapy protocol was very good, allowing for conservative treatment in 46 out of 48 patients. Histological evaluation of chemotherapy response showed good (> 90%) and total necrosis in 87 and 54% of the cases, respectively. Drug toxicity was acceptable. Results were significantly better than those previously obtained in our and in other institutes when only three drugs were used (methotrexate, cisplatin, and adriamycin) in the preoperative treatment scheme. Since it has been demonstrated that grade of histological response to preoperative chemotherapy, and prognosis are closely related in osteosarcoma of the extremities treated with neoadjuvant chemotherapy, in addition to allowing for the use of conservative surgery in the majority of cases, this new protocol may also lead to a significant increase in the patient cure rate.

Palmar-Plantar Erythrodysestasia Syndrome (PPES) or Hand-Foot Syndrome (H&F S) is an underestimated adverse reaction to chemotherapeutic agents, mainly related to 5-Fluorouracil. From March 1991 to February 1992, at the San Giovanni Oncologic Hospital of Torino, we observed 12 out of 163 patients (7.3%) displaying PPES while being treated with 5-FU containing regimens. No correlation with type of neoplastic disease, sex, age and total dose of administered 5FU was observed. Dose reductions or drug suspension achieved PPES reversal. The etiopathogenesis remains unclear. Both an idiosyncratic pattern and cutaneous drug accumulation are suggested.

A phase II trial aiming to verify the effectiveness of a regimen including carboplatin and vindesine was performed. From November 1989 to September 1990, nineteen patients with advanced small cell lung cancer entered this study. Polychemotherapy treatment included: carboplatin 400 mg/sm, on day 1 and vindesine 3 mg/sm, on days 1 and 15, repeated every 4 weeks, as an outpatient regimen. Observed toxicity was mild; myelodepression, and nausea and vomiting were the main adverse events. No objective response was obtained; 14 no changes in the disease and 4 progressions were detected. The low objective response rate observed in this study is strongly influenced by a set of unfavourable prognostic factors. The median overall survival time [32 weeks] is comparable with the results of other studies.

Penile metastases are extremely uncommon, with less than 300 reported cases. The primary sites of the responsible carcinoma have been bladder, rectum, prostate, kidney, testis, lung, nasopharynx and melanoma in that order. We report a case confirming the same data: no therapy has been shown to be helpful, the prognosis is very poor, with an average survival of less than one year. On the other hand we pointed out the importance of CT scan as a diagnostic tool for assessing the spread of neoplasm.

Seventy-two patients with tumor and ten with non-neoplastic colon disease were studied for the presence of estrogen receptors (ER) by three different methods. Only seven specimens (six primary adenocarcinomas and one recurrent cancer) had an ER concentration above 3 fm/mg of cytosolic protein, with no sex, age and tumor stage correlation. Our results suggest that the large bowel does not contain a cytosolic receptor for estradiol.

The importance of sexual hormones in the development of cancers of the large bowel is strongly supported experimentally and epidemiologically. The clinical search for the presence of hormonal receptors in the cells of patients operated for tumours of the colon and rectum has been common since 1975. This investigation ought to have opened up new diagnostic and therapeutic prospects for these tumours which have given such a little curative satisfaction. The present review considered reported data. Unfortunately the emerging picture is irregular in cases and results. It is personally considered that these studies are not for the moment likely to produce important novelties for the treatment of tumours of the large bowel tract.