[Accessibility of home palliative care and place of death of cancer patients: data analysis of the Emilia-Romagna Region.] / Accessibilità di cure palliative domiciliari e luogo del decesso dei malati oncologici: analisi dei dati della Regione Emilia-Romagna.

INTRODUCTION: The ANT Foundation is one of the main non-profit organizations providing palliative care in Italy. For more than 30 years, it has developed a comprehensive home palliative care program for cancer patients predominately active in the Bologna province. One of its main achievements has allowed for the majority of patients to be assisted at home during the last weeks of their lives until time of death. The purpose of the present study is to evaluate the possible impact of the ANT program on health data relating to the location of where cancer patients die within the Local Health Care system area (AUSL) of Bologna, compared to what happens in the other AUSLs of the Emilia-Romagna Region (ERR) where it is not present. METHODS: Regional cancer mortality data in 2005, 2010 and 2015, according to place of death and AUSL, were obtained by consulting the RER database. Data on patients assisted in the same time periods by the ANT program in the Bologna AUSL area were extracted from the ANT Foundation database and analyzed for place of death. RESULTS: In the year 2015, 2965 cancer patients died in the Bologna AUSL area. Compared to other AUSL areas of the ERR, it presents with a lower hospital mortality rate (31.2% vs. 47.5%) and a higher home mortality rate (32.8% vs. 19.6%). On the other hand, in 2015 the ANT program had assisted almost 50% of the total number of cancer patients who died in the Bologna AUSL area. Out of these patients, 64.6% died at home, while only 18.7% and 16.6% died in hospital and hospice, respectively. Conversely, hospital and home mortality rates in patients of the Bologna AUSL area who were not assisted by the ANT program, did approximate the mean values of the other ERR AUSLs. Over the 2005-2015 time span, the home mortality rate in the ANT patient series remained about twice as high as those of the Bologna AUSL. CONCLUSIONS: The comprehensive home palliative care program of the ANT Foundation seems to have a strong impact in determining the reduced hospital mortality rate of the Bologna AUSL area when compared to the other AUSLs of the Emilia-Romagna Region. The extension of this model of comprehensive home-based palliative care to other areas could contribute to reduce the high hospital mortality rate of cancer patients in this Italian Region.

Impact of intervention aimed at improving the integration of oncology units and local palliative care services: results of the multicentre prospective sequential MIRTO study.

BACKGROUND: Chemotherapy (CT) in patients with advanced cancer (ACP) near the end of life is an increasing practice of oncology units. A closer integration with palliative care (PC) services could reduce the use of potentially harmful CT. This prospective study is aimed at assessing whether a more integrated care model could reduce CT use near the end of life and increase local PC service utilisation. METHODS: The study enrolled sequentially two cohorts of ACP with an estimated life expectancy of ≤6 months. In the first cohort, the usual oncologist's practice to prescribe CT and to activate local PC services were recorded. In cohort 2, the oncologist's decision was taken after an in-hospital consultation with the local PC teams. After patient death, a follow-back survey was carried out. RESULTS: The two cohorts included 109 and 125 evaluable patients, respectively. The oncologist's decision to prescribe CT occurred in 51.4% and 60%, respectively: the percentages of patients receiving the final CT administration in the last 30 days of life did not differ in the two cohorts (33.9% and 29.3%, respectively,p=0.83). Conversely, an increase in home PC service utilisation (from 56.9% to 82.4%, p=0.00), at home deaths (from 40.4% to 56.8%, p=0.01) and in-hospice deaths (from 8.3% to 19.2%, p=0.00) occurred in cohort 2. CONCLUSION: The implementation of an initial in-hospital consultation of oncologists and experienced home PC teams has not reduced the use of CT near the end of life but increased PC service utilisation and reduced in-hospital deaths.

18F-FDG PET/CT impact on testicular tumours clinical management.

PURPOSE: Testicular tumour is the most common malignancy in young men. The diagnostic work-up is mainly based on morphological imaging. The aim of our study was to evaluate the clinical impact of (18)F-FDG PET/CT in patients with testicular tumour. METHODS: We retrospectively evaluated all patients studied by (18)F-FDG PET/CT at our centre. Inclusion criteria were: pathological confirmation of testicular tumour, contrast-enhanced CT scan performed within a month of the PET/CT scan, and clinical/imaging follow-up performed at the Oncology Unit of our hospital. Overall, 56 patients were enrolled and 121 PET/CT scans were evaluated. (18)F-FDG PET/CT was performed following standard procedures and the results were compared with clinical, imaging and follow-up data. Clinicians were contacted to inquire whether the PET/CT scan influenced the patient's management. Answers were scored as follows: start/continue chemotherapy or radiotherapy, indication for surgery of secondary lesions, and clinical surveillance. RESULTS: On a scan basis, 51 seminoma and 70 nonseminoma (NS) cases were reviewed. Of the 121 cases. 32 were found to be true-positive, 74 true-negative, 8 false-positive and 6 false-negative by PET/CT. PET/CT showed good sensitivity and specificity for seminoma lesion detection (92% and 84%, respectively), but its sensitivity was lower for NS forms (sensitivity and specificity 77% and 95%, respectively). The PET/CT scan influenced the clinical management of 47 of 51 seminomas (in 6 chemotherapy was started/continued, in 3 radiotherapy was started/continued, in 2 surgery of secondary lesions was performed, and in 36 clinical surveillance was considered appropriate), and 59 of 70 NS (in 18 therapy/surgery was started/continued, and in 41 clinical surveillance was considered appropriate). CONCLUSION: Our preliminary data demonstrate the potential usefulness of PET/CT for the assessment of patients with testicular tumour. It provides valuable information for the clinical management, particularly for clinical surveillance, post-therapy assessment and when relapse is suspected.

Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a phase III trial of the AGO OVAR, COGI, GINECO, and GEICO--the MIMOSA study.

PURPOSE: To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. RESULTS: Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35 U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. CONCLUSION: Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.

Peritoneal cystic mesothelioma: are surgery and HIPEC optimal first-line treatments?

BACKGROUND: Peritoneal cystic mesothelioma (PCM) is an uncommon clinical pathology. Its high rate of recurrence following partial or total resection as well as its spontaneous onset of malignancy have been well documented in a series of case studies. The medical community has yet to define standardized treatment guidelines for PCM. CASE REPORTS: This study reviews the case of 2 patients admitted and treated for PCM. Recent studies have reported improved recurrence and survival rates achieved by means of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), especially when used as first-line treatments. However, whether or not the use of CRS and HIPEC is more effective than a surgical regimen of multiple debulking procedures, is still the subject of debate. CONCLUSION: CRS and HIPEC as first-line treatments have lower morbidity and mortality rates than regimens of multiple back-to-back surgical procedures, and as such, the CRS/HIPEC method appears to be the more successful approach.

Solitary Internal Mammary Lymph Node Metastases Detected by F-FDG-PET/CT in Ovarian Cancer.

Internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described. In this case report, 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented. (18)F-FDG-PET/CT allowed the diagnosis which was suspected by the increase of the serum CA-125 level in 2 out of 3 cases. Local treatment, consisting of surgery (in 2 patients) and radiation therapy (in 1 patient), permitted an optimal long-term disease control.

Long-term results of a pilot study on an intensive induction regimen for unresectable stage III non-small-cell lung cancer.

BACKGROUND: In 1995, we designed and carried out a pilot study on the combination of cisplatin + high dose epirubicin + vinorelbine with granulocyte-colony-stimulating factor support for the induction treatment of unresectable stage IIIAN2 and wet IIIB non-small-cell lung cancer. The present report concerns the long-term results. METHOD: Eligible patients received cisplatin, 75 mg/m(2), and epirubicin, 120 mg/m(2), on day 1, vinorelbine, 25 mg/m(2), on days 1 and 15, and granulocyte-colony-stimulating factor, 300 microg s.c., from days 3 to 12. The cycle was repeated every 3 weeks for 3 times. Subsequently, all the patients were re-evaluated for surgical resection. RESULTS: Twenty-six patients were enrolled: 21 males and 5 females; median age, 55 years (range, 31-64); median performance status, 90% (range, 80-100); 16 stage IIIA and 10 IIIB. After the 3 cycles, objective response was as follows: 2 complete (8%), 18 partial (69%), 5 no change (19%) and 1 progressive disease (4%). Ten patients were not operated (9 unresectable and 1 refusal) and received radiotherapy. Sixteen patients (61%) underwent surgery and 14 were completely resected (54%). After a median follow-up of 84 months (range, 12-120), the median overall progression-free survival was 17 months (range, 2-104+): 47 months for resected and 8 months for nonresected patients. The median overall survival was 40 months (range, 4-123+): 87 months for resected and 13 months for nonresected patients. One-year, 3-year and 5-year survival rates were 73%, 42% and 37%, respectively. CONCLUSIONS: These intensive cytotoxic regimen enabled us to obtain favorable long-term results in a selected series of inoperable stage III non-small-cell lung cancer patients.

Multimodal sequential approach in colorectal cancer liver metastases: hepatic resection after yttrium-90 selective internal radiation therapy and cetuximab rescue treatment.

Synchronous or metachronous liver metastases occur in up to one-third of patients with colorectal cancer and are associated with a poor prognosis. Many evidences have shown that surgical resection can be curative, with 5-year survival rates ranging from 37% to 50%, but many patients are ineligible for surgery because of multiple liver lesions, bilobar distribution of liver metastases, or the presence of widespread extrahepatic disease. The management of unresectable liver metastases includes many therapeutic options such as systemic chemotherapy, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90), targeted therapy, and surgery. These treatments can be integrated into a sequential multimodal approach to increase the resection rate. We present a case in which such an approach was put into practice. The favorable result suggests that SIRT, along with systemic chemotherapy and surgery, is a valid treatment option for unresectable colorectal liver metastases.

Early (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapy.

BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (Delta-SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the Delta-SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty-six patients (76%) had a Delta-SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a Delta-SUV < or =50% had a pNR. All 8 of those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early evaluation of metabolic response by (18)F-FDG-PET during PCT was able to identify 30% of patients, all with estrogen receptor-positive tumors, who would not obtain pR after completion of chemotherapy program.

Anticancer drugs and cardiotoxicity: Insights and perspectives in the era of targeted therapy.

Drug-induced cardiotoxicity is emerging as an important issue among cancer survivors. For several decades, this topic was almost exclusively associated with anthracyclines, for which cumulative dose-related cardiac damage was the limiting step in their use. Although a number of efforts have been directed towards prediction of risk, so far no consensus exists on the strategies to prevent and monitor chemotherapy-related cardiotoxicity. Recently, a new dimension of the problem has emerged when drugs targeting the activity of certain tyrosine kinases or tumor receptors were recognized to carry an unwanted effect on the cardiovascular system. Moreover, the higher than expected incidence of cardiac dysfunction occurring in patients treated with a combination of old and new chemotherapeutics (e.g. anthracyclines and trastuzumab) prompted clinicians and researchers to find an effective approach to the problem. From the pharmacological standpoint, putative molecular mechanisms involved in chemotherapy-induced cardiotoxicity will be reviewed. From the clinical standpoint, current strategies to reduce cardiotoxicity will be critically addressed. In this perspective, the precise identification of the antitarget (i.e. the unwanted target causing heart damage) and the development of guidelines to monitor patients undergoing treatment with cardiotoxic agents appear to constitute the basis for the management of drug-induced cardiotoxicity.

Clinically-staged T3N0 rectal cancer: is preoperative chemoradiotherapy the optimal treatment?

BACKGROUND: Preoperative chemoradiotherapy has been widely adopted as the standard of care for stage II-III rectal cancers. However, patients with T3N0 lesions had been shown to have a better prognosis than other categories of locally advanced tumor. Thus, neoadjuvant chemoradiation is likely to be overtreatment in this subgroup of patients. Nevertheless, the low accuracy rate of preoperative staging techniques for detection of node-negative tumors does not allow to check this hypothesis. We analyzed a group of patients with cT3N0 low rectal cancer who underwent neoadjuvant chemoradiotherapy with the purpose of evaluating the incidence of metastatic nodes in the resected specimens. METHODS: Between January 2002 and February 2008, 100 patients with low rectal cancer underwent clinical staging by means of endorectal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging. All patients received preoperative 5-fluorouracil-based chemoradiotherapy and surgical resection with curative aim. RESULTS: Of 100 patients with locally advanced rectal cancer, 32 were clinically staged as T3N0M0. Pathological analysis showed the presence of lymph node metastases in nine patients (28%) (node-positive group). In the remaining 23 cases, clinical N stage was confirmed at pathology (node-negative group). Node-positive and node-negative groups differ only in the number of ypT3 tumors (P < .01). CONCLUSIONS: Our results indicate that immediate surgery for patients with cT3N0 rectal cancer represents an undertreatment risk in at least 28% of cases, making necessary the use of postoperative chemoradiotherapy. Preoperative chemoradiotherapy should be the therapy of choice on the grounds of the principle that overtreatment is less hazardous than undertreatment for cT3N0 rectal cancers.

Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.

Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.

Estrogen receptor 1 mRNA is a prognostic factor in ovarian carcinoma: determination by kinetic PCR in formalin-fixed paraffin-embedded tissue.

Epidemiological and cell culture studies indicate that ovarian carcinoma growth is dependent on estrogen stimulation. However, possibly due to the lack of a reliable biomarker that helps to select patients according to prognostically relevant estrogen receptor (ER) levels, clinical trials using anti-estrogenic therapeutics in ovarian carcinoma have had inconsistent results. Therefore, we tested if ER expression analysis by a quantitative method might be useful in this regard in formalin-fixed paraffin-embedded (FFPE) tissue. In a study group of 114 primary ovarian carcinomas expression of estrogen receptor 1 (ESR1) mRNA was analyzed using a new method for RNA extraction from FFPE tissue that is based on magnetic beads, followed by kinetic PCR. The prognostic impact of ESR1 mRNA expression was investigated and compared to ERalpha protein expression as determined by immunohistochemistry. In univariate survival analysis the expression level of ESR1 mRNA was a significant positive prognostic factor for patient survival (hazard ratio (HR) 0.230 (confidence interval (CI) 0.102-0.516), P=0.002). ERalpha protein expression was correlated to ESR1 mRNA expression (P=0.0001); however, ERalpha protein expression did not provide statistically significant prognostic information. In multivariate analysis, ESR1 mRNA expression emerged as a prognostic factor, independent of stage, grade, residual tumor mass, age, and ERalpha protein expression (HR 0.227 (CI 0.078-0.656), P=0.006). Our results indicate that the determination of ESR1 levels by kinetic PCR may be superior to immunohistochemical methods in assessment of biologically relevant levels of ER expression in ovarian carcinoma, and is feasible in routinely used FFPE tissue.

Does stent placement for advanced colon cancer increase the risk of perforation during bevacizumab-based therapy?

BACKGROUND & AIMS: Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case series of patients with SEMS for occlusive colon cancer. METHODS: Patients with occlusive symptoms caused by colon cancer received a colonic stent under endoscopic and radiologic guidance. RESULTS: Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS: Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.

Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials.

PURPOSE: Six randomized phase II and III trials have investigated the role of oxaliplatin (OX) in combination with capecitabine (CAP) or infusional fluorouracil (FU) in metastatic colorectal cancer. This meta-analysis compared the efficacy of CAP/OX compared with infusional FU/OX. PATIENTS AND METHODS: This analysis compared all published CAP/OX versus infusional FU/OX regimens. A total of 3,494 patients (FU, n = 1,737; CAP, n = 1,757) were analyzed for response rate (RR), progression-free (PFS), overall survival (OS), and toxicity. RESULTS: The fixed-effect pooled estimate for RR showed higher RR for FU-based regimens (Odds ratio [OR] = 0.85; 95% CI, 0.74 to 0.97; P = .02) whereas the analysis of chemotherapy-only trials, excluding the bevacizumab containing NO16966 and TREE 2 trials, led to an OR of 0.74 (95% CI, 0.60 to 0.92; P = .007). However, for PFS (hazard ratio [HR] = 1.04; 95% CI, 0.96 to 1.12; P = .17) and OS (HR = 1.04; 95% CI, 0.95 to 1.12; P = .41) all models suggested similar outcome within the range of noninferiority. Grade 3/4 toxicities (thrombocytopenia-HR = 2.07, 95% CI, 1.42 to 3.03; P < .0002; diarrhea-HR = 1.34; 95% CI, 1.08 to 1.66; P < .0009; and grade 2/3 hand-foot-syndrome [HFS]-HR = 3.54; 95% CI, 2.07 to 6.05; P < .00001) were less prominent with FU-based regimens whereas neutropenia (HR = 0.15; 95% CI, 0.11 to 0.19; P < .00001) was lower in the CAP regimens. CONCLUSION: The combination of CAP and OX resulted in lower RR, but this did not affect PFS and OS, which were similar in both treatment arms. The toxicity analysis showed the characteristic toxicity of each of the different FU schedules, with thrombocytopenia and HFS consistently more prominent in the CAP regimens.

The predictive value of 18F-FDG-PET early evaluation in patients with metastatic gastric adenocarcinoma treated with chemotherapy plus cetuximab.

BACKGROUND: The aim of the study was to evaluate whether the therapy-induced reduction of the (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) maximum standardized uptake value in patients with advanced gastric adenocarcinoma treated with chemotherapy plus cetuximab could predict the objective response and outcome early during the treatment. METHODS: The study was performed as a part of a phase II trial evaluating cetuximab plus the leucovorin/5-fluorouracil/irinotecan (FOLFIRI) regimen. The objective response was evaluated according to the response evaluation criteria in solid tumors (RECIST) every 6 weeks. The early metabolic response evaluated by 18F-FDG-PET was assessed according to our own evaluated cutoff value (<35%) after receiver operating characteristic (ROC) analysis. RESULTS: Twenty of 22 patients had positive baseline 18F-FDG-PET. The best RECIST response was: complete response (CR), 3; partial response (PR), 9; stable disease (SD), 8. Twelve patients (60%) were classified as metabolic responders and 8 (40%) as nonresponders. At the median follow-up time of 11 months, median time to disease progression (TTP) and overall survival (OS) for early metabolic responders versus nonresponders were 11 versus 5 months (P = 0.0016) and 16 versus 6 months (P = 0.1493), respectively. CONCLUSION: The early metabolic response evaluated by 18F-FDG-PET predicted the clinical outcome in this series of patients with advanced gastric cancer treated with chemotherapy plus cetuximab.