Toward uniform and controlled clinical pathways in cancer care: a qualitative description.

QUALITY ISSUE: The definition of clinical pathways (CPs) and their application are heterogeneous. Each center is used to choose whether to adopt this instrument or not and to variably conceive its features We consider CPs as the necessary description of the cancer patient journey and we emphasize their role as the user view of clinical processes rather than a local translation of guidelines. CHOICE OF SOLUTION: We proposed a unique CPs model for all the centers of our regional network, with the aim of making CPs accountable and comparable. We also established a central quality evaluation. IMPLEMENTATION: Through a multi-step process, the model was proposed to the 22 Regional centers. Landmark characteristics of the project were: the involvement of hospital administrations; reference to a unique set of guidelines; a peer-review and open evaluation. EVALUATION: Of the 374 expected CPs, 253 (68%) were received and evaluated. A median number of 131 items were the object of evaluation in each hub center and 77 in each spoke center. About 79.5% items were considered well described, 15.5% were absent and 5.0% partially described. The median percentage of fulfilled indicators was 85.6% in hub CPs and 82.2% in spoke CPs. Although, not all diseases were equally covered through the territory a high degree of homogeneity and a good quality of compilation were achieved. LESSONS LEARNED: The project was shown to be feasible and achieved its goal. We suggest this process as a functional way for building uniform cancer CPs.

Is Ovarian Cancer Being Managed According to Clinical Guidelines? Evidence From a Population-Based Clinical Audit.

BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.

Delineation of the larynx as organ at risk in radiotherapy: a contouring course within "Rete Oncologica Piemonte-Valle d'Aosta" network to reduce inter- and intraobserver variability.

AIMS: To evaluate the usefulness of a contouring course in reducing inter- and intraobserver variability in the definition of the larynx as organ at risk (OAR). METHODS: Within the "Rete Oncologica Piemonte-Valle d'Aosta" network, a contouring course focusing on larynx delineation was proposed. Twenty-six radiotherapist technicians (RTTs) experienced in delineating OARs were asked to contour larynx before and after the training. An expert radiation oncologist defined the reference volume for educational purpose. The contoured volumes obtained before and after the course were compared using descriptive statistics (mean value, standard deviation-SD, and coefficient of variation-COV) of volumes and maximum diameters. Conformity index (CI), dice coefficient (DC), and percentage of overlap were used to evaluate the spatial accuracy of the different volumes compared to the reference. Further analysis regarding the variation in the centre of mass (COM) displacement was performed. RESULTS: The mean volume was 40.4 cm3 before and 65.9 cm3 after the course, approaching the reference value. Mean anteroposterior, laterolateral, and craniocaudal diameters improved, getting each closer to the reference. Moreover, the COM moved approaching reference coordinates. Mean percentage of intersection and DC strongly increased after the course, rising from 57.76 to 93.83 % and from 0.68 to 0.89, respectively. CI enhanced from 0.06 to 0.31. CONCLUSIONS: This study shows an improvement in larynx definition after the contouring course with lower interobserver variability and major consistency compared to the reference volume. Other specific educational activities may further increase the quality of radiation therapy contouring in this setting.

Appropriateness and complications of androgen deprivation therapy for prostate cancer: Can we do better? A retrospective observational analysis from a referral center.

INTRODUCTION: Androgen deprivation therapy (ADT) is the key of medical treatment for advanced prostate cancer (PCa), especially in elderly patients. However, the adherence of ADT prescription to current guidelines is not optimal and must be balanced against possible side effects. Aim of this study was to evaluate the prescriptive appropriateness of ADT and ADT-related adverse events in a referral center for PCa. METHODS: Five hundred fifty six patients who received an outpatient prescription for ADT from 2014 to 2018 were retrospectively identified from an administrative database. Only standard ADT was considered, including GnRH agonists, GnRH antagonists, and antiandrogens. Prescriptive appropriateness was defined according to the last European Association of Urology (EAU) guidelines. Our cohort was stratified according to age categories and patient follow-up was updated. RESULTS: Four hundred twenty five patients were available for analysis. Mean age was 80 years; 96.3% of our patients fell in the "elderly" category. There was a predominance of GnRH agonists over the antagonists (84.9% vs 13%). 15.5% of ADTs did not have an appropriate indication according to guidelines. Patient compliance to ADT was evaluated as good in 372 (87.5%) cases. ADT-related complications were detected in 166 (39%) patients: bone, cardiovascular, and other complications were reported in 7.3%, 8.9%, and 19% of patients. Progression of disease was noted in 165 (38.8%) cases during ADT. At last follow-up, 124 (30.1%) patients were deceased. CONCLUSIONS: In a referral center, most ADT prescriptions followed EAU guidelines, but a non-negligible proportion still did not fall within these indications, exposing patients to unnecessary side effects. Compliance to ADT was generally good with a predominant use of GnRH agonists. Tolerance to ADT was fair, even if standardized reports were lacking.

Hospital factors and patient characteristics in the treatment of colorectal cancer: a population based study.

BACKGROUND: The present study focuses on the analysis of social, clinical and hospital characteristics that can lead to disparities in the management and outcome of care. To that end, indicators of the quality of initial treatment delivered to newly-diagnosed colorectal cancer patients in a North-Western Region of Italy, were investigated using administrative data. METHODS: The cohort includes all incident colorectal cancer patients (N = 24,187) selected by a validated algorithm from the Piedmont Hospital Discharge Record system over an 8-year period (2000-2007).Three indicators of quality of care in this population-based cohort were evaluated: the proportion of preoperative radiotherapy (RT) and of abdominoperineal (AP) resection in rectal cancer patients, and the proportion of postoperative in-hospital mortality in colorectal cancer patients. RESULTS: Among rectal cancers, older patients were less likely to have preoperative RT, and more likely to receive an AP resection compared to younger patients. The probability of undergoing preoperative RT and AP resection was reduced in females compared to males (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.64-0.93 and OR 0.78, 95%CI 0.69-0.89, respectively). However, there was a trend of increasing RT over time (p for trend <0.01). The probability of undergoing AP resection was increased in less-educated patients and in hospitals with a low caseload.A higher risk of postoperative in-hospital mortality was found among colorectal cancer patients who were older, male, (female versus male OR 0.71, 95%CI 0.60-0.84), unmarried (OR 1.32, 95%CI 1.09-1.59) or with unknown marital status. CONCLUSIONS: The study provides evidence of the importance of social, clinical and hospital characteristics on the equity and quality of care in a Southern European country with an open-access public health care system.

Effectiveness of Intensive Versus Minimalist Follow-Up Regimen on Survival in Patients With Endometrial Cancer (TOTEM Study): A Randomized, Pragmatic, Parallel Group, Multicenter Trial.

PURPOSE: In the absence of clear evidence from randomized trials, the intensity of follow-up regimens after surgical treatment of endometrial cancer is highly variable in clinical practice. To reduce this uncertainty, we conducted a randomized trial to test whether an intensive (INT) versus a minimalist (MIN) follow-up regimen improves overall survival (OS) in patients undergoing operation for endometrial cancer. METHODS: The TOTEM study was a large, pragmatic randomized trial, conducted in 42 hospitals (in Italy and France) including patients surgically treated for endometrial cancer, in complete clinical remission, International Federation of Gynecology and Obstetrics stage I-IV. After stratification by center and risk of relapse (low or high), patients were randomly assigned (1:1) to INT or MIN hospital-based follow-up regimens. The study was powered to demonstrate an absolute improvement of 5% of the 5-year OS with the INT regimen. RESULTS: In total, 1,871 patients were randomly assigned between November 2008 and July 2018, and 1,847 patients (98.7%) were available for the final analysis (60% low risk). After a median follow-up of 69 months, the 5-year OS was 90.6% in the INT and 91.9% in the MIN arms (hazard ratio, 1.13, 95% CI, 0.86 to 1.50, P = .380). No differences in OS were found in subgroup analyses considering age, cancer treatment, risk of relapse, and degree of adherence of the center to the scheduled follow-up. The probability of detecting a relapse was slightly higher in the INT arm (hazard ratio, 1.17; 95% CI, 0.92 to 1.48; P = .194). CONCLUSION: An INT follow-up in endometrial cancer-treated patients does not improve OS, even in high-risk patients. According to available evidence, there is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN regimens used in this trial.

Molecular profiling of advanced non-small cell lung cancer in the era of immunotherapy approach: a multicenter Italian observational prospective study of biomarker screening in daily clinical practice.

AIMS: Heterogeneous implementation of molecular tests in current diagnostic algorithm at a European and international level is emerging as a major issue for efficient lung cancer molecular profiling. METHODS: From May 2017 until October 2017, N=1612 patients referring to 13 Italian institutions were selected, at advanced stage non-small cell lung cancer (NSCLC), and prospectively evaluated. Principal endpoints were: the percentage of diagnoses performed on cytological and histological material, the proportion of requests for epidermal growth factor receptor (EGFR) mutational status, and resistance mutations detected on tissue and/or liquid biopsy samples after first-generation or second-generation tyrosine kinase inhibitors, the proportion of requests for anaplastic lymphoma kinase (ALK) gene rearrangements, ROS proto-oncogene 1 (ROS1) and Kirsten Rat Sarcoma (KRAS) determinations, the proportion of requests for programmed death-ligand1 (PD-L1) evaluation and, finally, the different assays used for the detection of EGFR mutations, ALK and ROS1 gene rearrangements and PD-L1 expression. RESULTS: Of 1325 patients finally included, only 50.8% requests were related to driver mutations with target agents already available in first-line at that preplanned time, while 49.2% were associated with PD-L1, ROS1, KRAS and others. Multiplex genomic assays (such as next-generation sequencing) were considered by all participating centres. CONCLUSIONS: To the best of our knowledge, this is the first study in a 'real-life daily practice' involving both pathologists and oncologists evaluating routinely workflow and trends towards improvements in molecular requests. Collected data aim to describe the applied algorithms and evolution of molecular screening for stage IV NSCLC in clinical practice.

[The psychological taking charge of the oncological patient: a 3 years study on the activities of psychologists of the Piedmont and Aosta Valley Oncology Network.] / La presa in carico psicologica del paziente oncologico: uno studio di 3 anni sulle attività degli psiconcologi della Rete Oncologica Piemonte e Valle d'Aosta.

INTRODUCTION: Tumor pathology is a bio-psycho-social event that has consequences for a person's life from all points of view, physical, psychological, relational and social. The mental discomfort that chronic pain and neoplastic pathology brings with it is present in 25-40% of cases, but the request for help to a psychologist, where not provided for by a specific diagnostic therapeutic assistance path, is in the case of medical pathologies less than 3%. The Piedmont and Valle d'Aosta Oncology Network has the role of coordinating the network of services that deal with the care of the cancer patient, including those relating to psycho-oncology. The article presents data relating to the activities of psycho-oncologists of the Network in the years 2017, 2018 and 2019. METHODS: A shared tool is used to collect the data, a database, made up of various variables deemed necessary to be able to photograph the activities carried out by the psycho-oncologists belonging to the Network. The database has been the subject of comparison between psychologists and has led to continuous revisions of the tool from 2017 to 2019, more accurate version. RESULTS: The 3-year study involved 2188 (2017), 3341 (2018) and 3457 (2019) adult patients or their families treated by psycho-oncologists. Patients are predominantly female with breast cancer, married/cohabiting, whose pre-eminent discomfort is anxiety, combined with the depressive component. The psychological intervention is mainly psychological support (level 2). DISCUSSION AND CONCLUSIONS: Psychological management is an important intervention in the path of the cancer patient. The systematic collection of data made it possible to detect an increase in patients who accessed the psycho-oncology service, from an estimate of 1/3% in 2009 to 4.6% in 2018/2019.

Population-based analyses of radical cystectomy and urinary diversion for bladder cancer in northern Italy.

OBJECTIVE: •To provide updated figures on urinary diversion, length of stay and mortality after cystectomy in two regions of northern Italy. PATIENTS AND METHODS: •Discharge records of patients undergoing cystectomy for bladder cancer in 2000-2008 were extracted from the regional archives of hospital discharges. •Data on partial vs radical cystectomy and type of urinary diversion were obtained from intervention codes. •The influence of demographic characteristics, year of intervention, presence of comorbidities and hospital cystectomy volume on the adoption of a continent diversion and on in-hospital mortality was assessed through multilevel models. RESULTS: •The crude cystectomy rate was close to 10 per 100,000. •The share of partial cystectomies declined from 5.5% in 2000-2002 to 3.0% in 2006-2008. •A continent diversion was adopted in 35% of radical cystectomies, with higher rates in young male patients treated in high-volume hospitals. •Median length of stay declined from 20 days in 2000-2002 to 18 in 2006-2008; in-hospital mortality decreased from 3.2% to 2.2%. CONCLUSION: •This first population-based report on cystectomies for bladder cancer from continental Europe evidences a limited role of partial cystectomy, a high proportion of continent diversion and a decreasing trend of length of stay and in-hospital mortality.

How uro-oncology has been affected by COVID-19 emergency? Data from Piedmont/Valle d'Aosta Oncological Network, Italy.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic has dramatically hit all Europe and Northern Italy in particular. The reallocation of medical resources has caused a sharp reduction in the activity of many medical disciplines, including urology. The restricted availability of resources is expected to cause a delay in the treatment of urological cancers and to negatively influence the clinical history of many cancer patients. In this study, we describe COVID-19 impact on uro-oncological management in Piedmont/Valle d'Aosta, estimating its future impact. METHODS: We performed an online survey in 12 urological centers, belonging to the Oncological Network of Piedmont/Valle d'Aosta, to estimate the impact of COVID-19 emergency on their practice. On this basis, we then estimated the medical working capacity needed to absorb all postponed uro-oncological procedures. RESULTS: Most centers (77%) declared to be "much"/"very much" affected by COVID-19 emergency. If uro-oncological consultations for newly diagnosed cancers were often maintained, follow-up consultations were more than halved or even suspended in around two out of three centers. In-office and day-hospital procedures were generally only mildly reduced, whereas major uro-oncological procedures were more than halved or even suspended in 60% of centers. To clear waiting list backlog, the urological working capacity should dramatically increase in the next months; delays greater than 1 month are expected for more than 50% of uro-oncological procedures. CONCLUSIONS: COVID-19 emergency has dramatically slowed down uro-oncological activity in Piedmont and Valle d'Aosta. Ideally, uro-oncological patients should be referred to COVID-19-free tertiary urological centers to ensure a timely management.

Implementation of the ERAS (Enhanced Recovery After Surgery) protocol for colorectal cancer surgery in the Piemonte Region with an Audit and Feedback approach: study protocol for a stepped wedge cluster randomised trial: a study of the EASY-NET project.

INTRODUCTION: The ERAS protocol (Enhanced Recovery After Surgery) is a multimodal pathway aimed to reduce surgical stress and to allow a rapid postoperative recovery. Application of the ERAS protocol to colorectal cancer surgery has been limited to a minority of hospitals in Italy. To promote the systematic adoption of ERAS in the entire regional hospital network in Piemonte an Audit and Feedback approach (A&F) has been adopted together with a cluster randomised trial to estimate the true impact of the protocol on a large, unselected population. METHODS: A multicentre stepped wedge cluster randomised trial is designed for comparison between standard perioperative management and the management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: incidence of postoperative complications, time to patients' recovery, control of pain and patients' satisfaction. With an A&F approach the adherence to the ERAS items is monitored through a dedicated area in the study web site. The study includes 28 surgical centres, stratified by activity volume and randomly divided into four groups. Each group is randomly assigned to a different activation period of the ERAS protocol. There are four activation periods, one every 3 months. However, the planned calendar and the total duration of the study have been extended by 6 months due to the COVID-19 pandemic.The expected sample size of about 2200 patients has a high statistical power (98%) to detect a reduction of LOS of 1 day and to estimate clinically meaningful changes in the other endpoints. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethical Committee of the coordinating centre and by all participating centres. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04037787.

Cytokine Profiling of End Stage Cancer Patients Treated with Immunotherapy.

Published data suggest that immunotherapy plays a role even in patients with very advanced tumours. We investigated the immune profile of end-stage cancer patients treated with immunotherapy to identify changes induced by treatment. Breast, colon, renal and prostate cancer patients were eligible. Treatment consisted of metronomic cyclophosphamide, low-dose interleukin-2 (IL-2) and a single radiation shot. A panel of 16 cytokines was assessed using automated ELISA before treatment (T0), after radiation (RT; T1), at cycle 2 (T2) and at disease progression (TPD). Receiving operating characteristic (ROC) analysis was used to identify cytokine cut-off related to overall survival (OS). Principal component analysis (PCA) was used to identify the immune profile correlating better with OS and progression-free survival. Twenty-three patients were enrolled. High IL-2, low IL-8 and CCL-2 correlated with OS. The PCA identified a cluster of patients, with high IL-2, IL-12 and IFN-γ levels at T0 having longer PFS and OS. In all cohorts, IL-2 and IL-5 increased from T0 to T2; a higher CCL-4 level compared to T2 and a higher IL-8 level compared to T0 were found at TPD. The progressive increase of the IL-10 level during treatment negatively correlated with OS. Our data suggested that baseline cytokine levels may predict patients' outcome and that the treatment may affect their kinetic even in end-stage patients. Cytokine profiling of end-stage patients might offer a tool for medical decisions (EUDRACT: 2016-000578-39).

Use of Electronic Administrative Databases to Measure Quality Indicators of Breast Cancer Care: Experience of Five Regional Oncology Networks in Italy.

PURPOSE: Assuring quality of care, while maintaining sustainability, in complex conditions such as breast cancer (BC) is an important challenge for health systems. Here, we describe a methodology to define a set of quality indicators, assess their computability from administrative data, and apply them to a large cohort of BC cases. MATERIALS AND METHODS: Clinical professionals from the Italian Regional Oncology Networks identified 46 clinically relevant indicators of BC care; 22 were potentially computable using administrative data. Incident cases of BC diagnosed in 2016 in five Italian regions were identified using administrative databases from regional repositories. Each indicator was calculated through record linkage of anonymized individual data. RESULTS: A total of 15,342 incident BC cases were identified. Nine indicators were actually computable from administrative data (two structure and seven process indicators). Although most indicators were consistent with guidelines, for one indicator (blood tumor markers in the year after surgery, 44.2% to 64.5%; benchmark ≤ 20%), deviation was evident throughout the five regions, highlighting systematic overlooking of clinical recommendations. Two indicators (radiotherapy within 4 months after surgery if no adjuvant chemotherapy; 42% to 83.8%; benchmark ≥ 90%; and mammography 6 to 18 months after surgery, 55.1% to 72.6%; benchmark ≥ 90%) showed great regional variability and were lower than expected, possibly as result of an underestimation in indicator calculation by administrative data. CONCLUSION: Despite highlighting some limitations in the use of administrative data to measure health care performance, this study shows that evaluating the quality of BC care at a population level is possible and potentially useful for guiding quality improvement interventions.

Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte oncology network.

BACKGROUND: Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. METHODS: Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. RESULTS: Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. CONCLUSION: Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. TRIAL REGISTRATION: NCT00953394.

Multicentric, randomized phase III trial of two different adjuvant chemotherapy regimens plus three versus twelve months of trastuzumab in patients with HER2- positive breast cancer (Short-HER Trial; NCT00629278).

Trastuzumab, a monoclonal antibody against the HER2 receptor, is currently approved as a part of adjuvant therapy for patients with HER2-overexpressing breast tumors. The Short-HER study is a phase III randomized, multicentric Italian trial aimed at testing the optimal duration of adjuvant trastuzumab. In this trial, 2500 patients with HER2-positive breast cancer will be randomized to receive the following: (arm A, long) 4 courses of anthracycline- based chemotherapy (doxorubicin/cyclophosphamide or epidoxorubicin/cyclophosphamide) followed by 4 courses of docetaxel or paclitaxel in combination with trastuzumab, followed by 14 additional courses of trastuzumab administered every 3 weeks (for a total of 18 3-weekly doses of trastuzumab); or (arm B, short) 3 courses of 3-weekly docetaxel in combination with weekly trastuzumab (for a total of 9 weekly doses of trastuzumab) followed by 3 courses of 5-fluorouracil/epirubicin/cyclophosphamide. The primary objective is disease-free survival.

Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes' C colon cancer : economic evaluation in an Italian NHS setting.

BACKGROUND AND OBJECTIVE: In the recent X-ACT (Xeloda in Adjuvant Colon cancer Therapy) trial, oral capecitabine (Xeloda) demonstrated superior efficacy and an improved safety profile compared with infused fluorouracil + leucovorin (folinic acid) [FU+LV] in patients with Dukes' C colorectal cancer. We used the X-ACT results to determine the cost effectiveness of capecitabine compared with FU+LV from the perspective of the Italian National Health Service (NHS). METHODS: Medical resource use data were collected throughout the treatment period. Unit costs for drug administration, hospitalization, emergency room visits and concomitant medications were obtained using Italian published sources. A health-state transition model was used to estimate the incremental cost-effectiveness ratio per quality-adjusted life-month (QALM) gains in the intent-to-treat population (1004 and 983 patients in the capecitabine and FU+LV arms, respectively). Costs and effectiveness were discounted at 3.5%. Costs were calculated in euros (2005 values). RESULTS: Administration of capecitabine required fewer clinic visits per patient than FU+LV (7.35 vs 28.0, respectively). Mean acquisition costs per patient for capecitabine were higher than for FU+LV (euro 2533 vs euro 231, respectively), but this difference was offset by the difference in mean chemotherapy administration costs per patient for FU+LV (euro 4338, compared with euro 152 for capecitabine). Mean total hospital days and medication costs for treatment-related adverse events were higher for FU+LV than for capecitabine (euro 352 vs euro 78, respectively). The cost of emergency room visits for the treatment of adverse events did not differ between the treatment groups. With respect to the lifetime horizon, compared with FU+LV, capecitabine is projected to increase QALMs by a mean 6.5 months, with overall cost savings of euro 2234 over the treatment period. These findings show that capecitabine is an economically dominant treatment in this setting. CONCLUSIONS: Adjuvant capecitabine for patients with Dukes' C colon cancer has the same activity in terms of outcome when compared with FU+LV but is a lower cost option from the economic perspective of the Italian NHS.

Predicting gefitinib responsiveness in lung cancer by fluorescence in situ hybridization/chromogenic in situ hybridization analysis of EGFR and HER2 in biopsy and cytology specimens.

In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutational analysis is an excellent predictor of responsiveness to treatment with tyrosine kinase inhibitors, such as gefitinib. In up to 80% of NSCLCs, cytologic samples or endoscopic biopsies are the only specimens available for molecular analysis, but PCR amplification of DNA from small fixed and paraffin-embedded samples may create artifactual mutations. Fluorescence in situ hybridization (FISH) of EGFR and HER2 has been proposed as an alternative method of analysis. This project aimed to determine the optimal scoring method for FISH or chromogenic in situ hybridization (CISH) assays when analyzing small NSCLC samples to predict response. FISH or CISH analysis of EGFR and HER2 genes was done on 42 small samples derived from NSCLC patients treated with gefitinib. EGFR mutational analysis was done after quantity and quality controls of DNA. In seven of seven cases, a balanced increase in EGFR gene and chromosome 7 number was found to correlate with the presence of specific EGFR mutations. In addition, seven of seven cases with balanced EGFR/HER2 polysomy and two of three cases with balanced EGFR/HER2 trisomy responded to gefitinib (75% of responders). Instead, the EGFR mutations predicted only 7 of 12 (58%) of gefitinib-responsive patients. When only endoscopic biopsies or cytologic specimens are available, we propose using FISH/CISH for EGFR and HER2 as the test of choice for selecting patients for treatment with gefitinib and to consider as negative predictive factor the absence of EGFR/HER2 gene gain.

Different quality of treatment in retroperitoneal sarcomas (RPS) according to hospital-case volume and surgeon-case volume: a retrospective regional analysis in Italy.

BACKGROUND: Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV) or by Surgeon Case Volume (SCV). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the quality of surgery in a wide region of Northern Italy. METHODS: We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (< 100 sarcomas observed per year). RESULTS: Data regarding 138 patients were collected. Patients coming from LCV hospitals (66) were excluded from the analysis as prognostic data were frequently not available. Among the 72 remaining cases of HCV hospitals 60% of cases had R0/R1 margins, with a more favorable distribution of R0/R1 versus R2 in HVCCC compared to HVTCA. CONCLUSIONS: In HCV hospitals, sarcoma SCV may significantly influence RPS treatment quality. In low-volume centers surgical reports can often miss important prognostic issues and surgical quality is generally poor.

Variability of clinical target volume delineation for rectal cancer patients planned for neoadjuvant radiotherapy with the aid of the platform Anatom-e.

OBJECTIVE: Delineation of treatment volumes is a major source of uncertainties in radiotherapy (RT). This is also true for rectal cancer patients undergoing neoadjuvant RT, with a potential impact on treatment quality. We investigated the role of the digital platform Anatom-e (Anatom-e Information Sytems Ltd., Houston, Texas) in increasing the compliance to follow a specific treatment protocol in a multicentric setting. MATERIALS AND METHODS: Two clinical cases of locally advanced rectal cancer were chosen. Participants were instructed to follow the 2009 Radiation Therapy Oncology Group consensus atlas and asked to manually segment clinical target volumes (CTVs), for both patient 1 and 2, on day 1 with and without the use of Anatom-e. After one week (day 2), the same radiation oncologist contoured again, with and without Anatom-e, the same CT series. Intraobserver (Intra-OV) and interobserver (Inter-OV) variability were evaluated with the Dice similarity coefficient (DSC), the Hausdorff distance (HD) and mean distance to agreement (MDA). RESULTS: For clinical case 1, no significant difference was found for Intra-OV and Inter-OV. For clinical case 2, no significant difference was found for Intra-OV but a statistically significant difference was found for Inter-OV in DSC when using or not the platform. Mean DCS was 0.65 (SD: ±0.64; range: 0.58-0.79) for day 1 vs reference volume without Anatom-e and 0.72 (SD: ±0.39; range: 0.67-0.77) (p = 0.03) with it. Mean MDA was lower with Anatom-e (3.61; SD: ±1.33; range: 2.85-4.78) than without (4.14; SD: ±2.97; range: 2.18-5.21), with no statistical significance (p = 0.21) The use of Anatom-e decreased the SD from 2.97 to 1.33. Mean HD was lower with Anatom-e (26.06; SD: ±2.05; range: 24.08-32.62), with no statistical significance (p = 0.14) compared to that without (31.39; SD: ±1.31; range: 26.14-48.72). CONCLUSIONS: The use of Anatom-e decreased the Inter-OV in the CTV delineation process for locally advanced rectal cancer with complex disease presentation planned for neoadjuvant RT. This system may be potentially helpful in increasing the compliance to follow shared guidelines and protocols.

Accessibility as a major determinant of radiotherapy underutilization: a population based study.

BACKGROUND AND PURPOSE: A survey was conducted of radiotherapy (RT) resources and utilization in a northwestern Italian Region in order to assess geographical variations in radiotherapy utilization rates, and the effects of infrastructure supply on accessibility. MATERIALS AND METHODS: The survey was conducted by analysing standardized utilization rates based on administrative records. The data were analysed at both Regional and Local Health Unit (LHU) level. RESULTS: Wide variation was found among LHUs RT utilization rates--the sex- and age-standardized rates varied from 1.8/1000 inhabitants to more than 3/1000 inhabitants. Patients resident in LHUs with no RT service showed a lower probability of accessing RT (standardized rate ratio (SRR), 0.82; 95%IC, 0.80-0.85). The utilization rate decreased in relation to the distance between a patient's residence and the nearest RT service; the reduction was greater for patients > or =70 years of age. CONCLUSION: The wide geographic variation implies lack of equity in access to services. Utilization levels decreased significantly with increasing distance from the nearest RT service, distance being a barrier to access particularly for older persons. The heterogeneous distribution of services on the Regional territory seems a relevant explanation of differences in utilization rates.